권호 표지

Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (APOCP)

  • Monthly
  • /
  • 1513-7368(pISSN)
  • /
  • 2476-762X(eISSN)

Domain

  • Health Sciences ＞ Development of Pharmaceutical

Aim & Scope

Cancer is a very complex disease. While many aspects of carcinoge-nesis and oncogenesis are known, cancer control and prevention at the community level is however still in its infancy. Much more work needs to be done and many more steps need to be taken before effective strategies are developed. The multidisciplinary approaches and efforts to understand and control cancer in an effective and efficient manner, require highly trained scientists in all branches of the cancer sciences, from cellular and molecular aspects to patient care and palliation. The Asia Pacific Organization for Cancer Prevention (APOCP) and its official publication, the Asia Pacific Journal of Cancer Prevention (APJCP), have served the community of cancer scientists very well and intends to continue to serve in this capacity to the best of its abilities. One of the objectives of the APOCP is to provide all relevant and current scientific information on the whole spectrum of cancer sciences. They aim to do this by providing a forum for communication and propagation of original and innovative research findings that have relevance to understanding the etiology, progression, treatment, and survival of patients, through their journal. The APJCP with its distinguished, diverse, and Asia-wide team of editors, reviewers, and readers, ensure the highest standards of research communication within the cancer sciences community across Asia as well as globally. The APJCP publishes original research results under the following categories: - Epidemiology, detection and screening. - Cellular research and bio-markers. - Identification of bio-targets and agents with novel mechanisms of action. - Optimal clinical use of existing anti-cancer agents, including combination therapies. - Radiation and surgery. - Palliative care. - Patient adherence, quality of life, satisfaction. - Health economic evaluations. All research and manuscript published by the Asia Pacific Journal of Cancer Prevention, are under the terms of the Creative Commons Attribution License. This permits anyone to copy, distribute, transmit and adapt the published work, provided the original work and source are appropriately cited. The APJCP strongly supports the Open Access initiative. Each published article is assigned a Crossref Digital Object Identifier (DOI), and full texts (HTML, PDF and XML format) of all articles published by the Asia Pacific Journal of Cancer Prevention, are freely accessible to everyone immediately after publication. Asia Pacific Journal of Cancer Prevention supports the Bethesda Statement on Open Access Publishing.

KSCI

Volume 16 Issue 4

  1. Mathema, Vivek Bhakta;Na-Bangchang, Kesara 1307
    https://doi.org/10.7314/APJCP.2015.16.4.1307 PDF KSCI
    Colangiocarcinoma (CCA) is a progressively fatal disease which generally occurs due to malignant transformation of hepatic biliary cholangiocytes. The incidence of CCA has been increasing worldwide and there is an urgent requirement for effective diagnosis and treatment strategies against this devastating disease. Different factors including liver-fluke infestation, viral hepatitis, exogenous nitrosamine-mediated DNA damage, and chronic inflammation have been linked to CCA genesis. However, the risk factors and underlying complex mechanisms leading to development of CCA are not sufficiently understood to devise an effective targeted treatment therapy. In this review, we summarize currently known epidemiological and pathological aspects of the disease and briefly describe various potential biomarkers and experimental anticancer phytochemicals related to CCA research. In addition, we also sum up recent findings that link chronic inflammation of hepatic biliary cholangiocytes with CCA. The collective information concisely presented in this article would provide useful insights into the current understanding of this cancer.
  2. Hagiwara, Tadashi;Mukaisho, Ken-Ichi;Nakayama, Takahisa;Hattori, Takanori;Sugihara, Hiroyuki 1315
    https://doi.org/10.7314/APJCP.2015.16.4.1315 PDF KSCI
    The fact that long-term use of proton pump inhibitors (PPIs) aggravates corpus atrophic gastritis in patients with Helicobacter pylori infection has been proven clinically and experimentally. Corpus atrophic gastritis is a known risk factor for gastric cancer. Therefore, gastric neoplasia might be associated with the long-term use of PPIs. One of the causes of worsening corpus atrophic gastritis, leading to the development of adenocarcinoma, might be bacterial overgrowth under conditions of hypochlorhydria. The production of potentially carcinogenic N-nitrosocompounds by nitrosating organisms under conditions of hypochlorhydria might be associated with carcinogenesis. Interactions between bile acids, pH, and H. pylori might also contribute to carcinogenicity, especially in patients with gastro-esophageal reflux disease (GERD). The concentration of soluble bile acids, which have bactericidal or chemorepellent properties toward H. pylori, in gastric contents is considerably higher in patients undergoing continuous PPI therapy than in healthy individuals with normal acid production. Under these circumstances, H. pylori might colonize the stomach body rather than the pyloric antrum. Hypergastrinemia induced by PPI administration might promote the development of gastric cancer. Because the main cause of corpus atrophic gastritis is H. pylori infection, and not PPI administration, H. pylori infection should be eradicated before starting long-term PPI therapy.
  3. Azadmanjir, Zahra;Safdari, Reza;Ghazisaeidi, Marjan 1321
    https://doi.org/10.7314/APJCP.2015.16.4.1321 PDF KSCI
    Self-care to prevent cancer and self-management to cope with the disease are two discrete effective mechanisms for improving of control and management of neoplasia. Both them have certain strategies and practices. Often the two are used interchangeably despite their different approaches. Strategies of self-care usually refer to prevention at different levels include primary, secondary and tertiary. In contrast, strategies of self-management are related to management and alleviation of unpleasant cancer-related symptoms and treatment-related side effects for improving the quality of life of cancer survivors. Successful promoting of self-care and self-management strategies need people and survivor empowerment. Within this context, innovative approaches open a new window. In this paper after a brief review of related strategies and practices, we provide an explanation of how cancer portals may play an important role in the empowerment process and what are key potentials for implementing of self-care and self-management strategies for cancer.
  4. Lotfi, Alireza;Mohammadi, Ghodrat;Tavassoli, Atena;mousaviagdas, Mehrnoosh;Chavoshi, Hadi;Saniee, Lale 1327
    https://doi.org/10.7314/APJCP.2015.16.4.1327 PDF KSCI
    Background: Squamous cell carcinoma (SCC) is the most common cancer in the oral area. Matrix metalloproteinases (MMPs) and especially MMP-2 and MMP-9 are increased in malignancy and lymph node involvement in oral SCCs. We aimed to evaluate the serum levels of MMP-2 and MMP-9 in patients with oral SCC compared to normal subjects and their relation with clinicopathological findings. Materials and Methods: In this case control study, 20 patients with oral SCC and 20 healthy subjects were included and serum levels of MMP-2 and MMP-9 were compared between groups. Also, the correlation between these markers with clinicopathological findings including grade (T) and node (N) were evaluated. Results: Patients with oral SCC had significantly higher serum levels of MMP-2 (p=0.01) and MMP-9 (p<0.001) compared to healthy subjects. With increase in grade T, MMP-2 was significantly increased (p=0.001), but in the MMP-9 case this was not significant (p=0.27). The levels of MMP-2 (p=0.002) and MMP-9 (p=0.01) in cases with lymph node involvement and that of MMP-2 in subjects with smoking history (p=0.001) were significantly high. There was significantly positive correlation between MMP-2 with grade T tumor (r=0.598, p=0.005), lymph node involvement (r=0.737, p<0.001) and smoking (r=0.674, p=0.001) and also between MMP-9 and lymph node involvement (r=0.474, p=0.03). Conclusions: Both markers are significantly increased in oral SCC compared to healthy subjects. However, MMP-2 was better for evaluating lymph node involvement and tumor grade.
  5. Yuan, Hong-Liang;Liu, Xiao-Lei;Dai, Qi-Chang;Song, Hui 1331
    https://doi.org/10.7314/APJCP.2015.16.4.1331 PDF KSCI
    Natural glycoproteins can induce apoptosis of tumor cells and exert anti-tumor activity by immunomodulatory functions, cytotoxic and anti-inflammation effects, and inhibition of endothelial growth factor. Given their prospects as novel agents, sources of natural antitumor glycoproteins have attracted attention and new research directions in glycoprotein biology are gradually shifting to the direction of cancer treatment and prevention of neoplastic disease. In this review, we summarize the latest findings with regard to the tumor suppressor signature of glycoproteins and underlying regulatory mechanisms.
  6. Akhtari-Zavare, Mehrnoosh;Ghanbari-Baghestan, Abbas;Latiff, Latiffah A.;Khaniki, Hadi 1337
    https://doi.org/10.7314/APJCP.2015.16.4.1337 PDF KSCI
    Background: Breast cancer is the most common cancer and the second principal cause of cancer deaths among women worldwide, including Malaysia. This study focused on media choice and attempted to determine the communication channels mostly used and preferred by women in seeking information and knowledge about breast cancer. Materials and Methods: A cross sectional study was carried out to examine the breast cancer prevention information seeking behavior among 450 students at one private university in Malaysia. Results: The mean age of respondents was $25{\pm}4.3years$. Common interpersonal information sources were doctors, friends, and nurses and common channel information sources were television, brochure, and internet. Overall, 89.9% used cell phones, 46.1% had an interest in receiving cell phone breast cancer prevention messages, 73.9% used text messaging, and 36.7% had an interest in receiving text breast cancer prevention messages. Bivariate analysis revealed significant differences among age, eduation, nationality and use of cell phones. Conclusions: Assessment of health information seeking behavior is important for community health educators to target populations for program development.
  7. Yan, Feng;Shao, Li-Jia;Hu, Xiao-Ya 1343
    https://doi.org/10.7314/APJCP.2015.16.4.1343 PDF KSCI
    Human UHRF1 (ubiquitin-like PHD and RING finger domain-containing 1) has been reported to be over-expressed in many cancers, but its role in ovarian cancer remains elusive. Here, we determined whether knockdown of UHRF1 by lentivirus-mediated shRNA could inhibit ovarian cancer cell growth. Lentivirus-mediated short hairpin RNAs (lv-shRNAs-UHRF1) were designed to trigger the gene silencing RNA interference (RNAi) pathway. The efficiency of lentivirus-mediated shRNA infection into HO-8910 and HO-8910 PM cells was determined using fluorescence microscopy to observe lentivirus-mediated GFP expression and was confirmed to be over 80 percent. UHRF1 expression in infected HO-8910 and HO-8910 PM was evaluated by real-time PCR and Western blot analysis. The Cell Counting Kit-8 (CCK-8) assay was used to measure cell viability; flow cytometry and Hoechst 33342 assay was applied to measure cell cycle arrest and apoptosis. Cell invasion was assessed using transwell chambers. Our results demonstrated that the loss of UHRF1 promoted HO-8910 and HO-8910 PM cell apoptosis, while inhibiting cell proliferation. In addition, UHRF1 knockdown significantly inhibited the invasion of human ovarian cancer cells. In the present study, we also showed that depleting HO-8910 cells of UHRF1 caused activation of the DNA damage response pathway, with the cell cycle arrested in G2/M-phase. The DNA damage response in cells depleted of UHRF1 was illustrated by phosphorylation of CHK (checkpoint kinase) 2 on Thr68, phosphorylation of CDC25 (cell division control 25) on Ser 216 and phosphorylation of CDK1 (cyclin-dependent kinase 1) on Tyr 15.
  8. Gonzalez-Herrera, A.L.;Salgado-Bernabe, M.;Velazquez-Velazquez, C.K.;Salcedo-Vargas, M.;Andrade-Manzano, A.;Avila-Moreno, F.;Pina-Sanchez, P. 1349
    https://doi.org/10.7314/APJCP.2015.16.4.1349 PDF KSCI
    Background: Cervical cancer (CeCa) is the second most common cancer in women in developing countries, and human papilloma virus (HPV) is the primary etiological factor. Aberrant expression of HOX transcription factors has been observed in several types of cancer. To date, however, no reports exist on the expression of HOXB2 and HOXB13 proteins during neoplastic progression in CeCa and its correlation with HPV infection. Materials and Methods: Expression of HOXB2 and HOXB13 proteins was assessed in tissue microarrays from normal cervical epithelium, cervical intraepithelial neoplasias grade 1-3, and CeCa. HPV was detected by PCR and sequencing. Expression of HOX-positive cells was determined in each diagnostic group. Results: Percentage of HOXB2- and HOXB13-positive cells gradually increased from means of 10.9% and 16.7%, respectively, in samples from healthy women, to 75.2% and 88.6% in those from CeCa patients. Frequency of HPV infection also increased from 13% in healthy tissue samples to 92.3% in CeCa. Both HOXB2 and HOXB13 proteins were preferentially expressed in HPV+ samples. Conclusions: The present study represents the first report on the expression of both HOXB2 and HOXB13 proteins through cervix tumorigenesis, providing evidence that increased expression of such proteins is a common event during progression to CeCa.
  9. Shin, Hyun-Young;Linton, John A.;Shim, Jae-Yong;Kang, Hee-Taik 1355
    https://doi.org/10.7314/APJCP.2015.16.4.1355 PDF KSCI
    Background: The number of cancer survivors is increasing globally and recently, higher rates of comorbidities in cancer survivors have been reported. However, no studies have investigated whether cancer survivors have a higher risk of chronic kidney disease (CKD). Accordingly, our study evaluated the association between cancer survivors and the risk of CKD using the 2010-2012 Korean National Health and Nutrition Examination Survey. Materials and Methods: A total of 11,407 participants aged 40 years and over were categorized into two groups according to cancer experience. Multiple variables were compared and the odds ratios (ORs) for CKD prevalence were calculated using a weighted logistic regression analysis between the two groups. Results: Cancer survivors were older than were those in the non-cancer group, on average, the percentages of glomerular filtration rate(GFR) lower than $60mL/min/1.73m^2$, proteinuria, and CKD were significantly higher in cancer survivors when compared to controls. Weighted logistic regression analyses demonstrated that cancer survivors had a higher risk for CKD after adjusting for multiple variables (OR (95% confidence interval), 2.88 (1.48-5.59)). Conclusions: Our study demonstrated a possible association between CKD and cancer survival in Korean adults. Identifying and correcting risk factors for cancer survivors would positively affect prevention of CKD and result in a better cancer prognosis.
  10. Wang, Da-Guang;Chen, Guang;Wen, Xiao-Yu;Wang, Dan;Cheng, Zhi-Hua;Sun, Si-Qiao 1361
    https://doi.org/10.7314/APJCP.2015.16.4.1361 PDF KSCI
    Background: We aimed to discover potential gene biomarkers for gastric cancer (GC) diagnosis. Materials and Methods: Genechips of 10 GC tissues and 10 gastric mucosa (GM, para-carcinoma tissue, normal control) tissues were generated using an exon array of Affymetrix containing 30,000 genes. The differentially expressed genes (DEGs) between GC tissues and normal control were identified by the Limma package and analyzed by hierarchical clustering analysis. Gene ontology (GO) and pathway enrichment analyses were performed for investigating the functions of DEGs. Receiver operating characteristics (ROC) analysis was performed to measure the effects of biomarker candidates for diagnosis of GC. Results: Totals of 896 up-regulated and 60 down-regulated DEGs were identified to be differentially expressed between GC samples and normal control. Hierarchical clustering analysis showed that DEGs were highly differentially expressed and most DEGs were up-regulated. The most significantly enriched GO-BP term was revealed to be mitotic cell cycle and the most significantly enriched pathway was cell cycle. The intersection analysis showed that most significant DEGs were cyclin B1 (CCNB1) and cyclin B2 (CCNB2). The sensitivities and specificities of CCNB1 and CCNB2 were both high (p<0.0001). Areas under the ROC curve for CCNB1 and CCNB2 were both greater than 0.9 (p<0.0001). Conclusions: CCNB1 and CCNB2, which were involved in cell cycle, played significant roles in the progression and development of GC and these genes may be potential biomarkers for diagnosis and prognosis of GC.
  11. Sombattheera, Sutthikan;Proungvitaya, Tanakorn;Limpaiboon, Temduang;Wongkham, Sopit;Wongkham, Chaisiri;Luvira, Vor;Proungvitaya, Siriporn 1367
    https://doi.org/10.7314/APJCP.2015.16.4.1367 PDF KSCI
    Diagnosis of cholangiocarcinoma (CCA) is difficult when patients do not show jaundice. The aim of this study was to examine the feasibility of using the total serum bile acid (TSBA) level as an aid for the diagnosis of CCA in patients without jaundice. For this purpose, TSBA of the following groups were measured using a Beckman Synchron CX4 clinical chemistry analyzer: 60 cases of CCA with total serum bilirubin ${\leq}2mg/dL$ (low total bilirubin group, LTB); 32 cases of CCA with total serum bilirubin >2 mg/dL (high total bilirubin group, HTB); and 115 healthy controls. Liver function parameters such as serum cholesterol, albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were also examined. The results showed that the TSBA of both LTB and HTB groups of the CCA patients were significantly higher than that of the healthy controls. Also, significant correlation was observed between TSBA and total bilirubin levels in the HTB group of CCA patients. However, no such correlation was seen in the LTB group. The cut-off value of TSBA was determined for the LTB group of CCA patients using the receiver operating characteristic curve analysis, and it was $6.05{\mu}mol/L$ with the sensitivity and specificity of 46.7% and 84.4%, respectively. In addition, the ALP level was correlated well with the TSBA level and ALP in HTB group was significantly higher than that of LTB group. Moreover, the combination of high TSBA and high ALP levels gave higher specificity up to 97.4%. TSBA might be useful for the diagnosis of CCA patients without jaundice.
  12. Krishnatreya, Manigreeva;Nandy, Pintu;Rahman, Tashnin;Sharma, Jagannath Dev;Das, Anupam;Kataki, Amal Chandra;Das, Ashok Kumar;Das, Rajjjyoti 1371
    https://doi.org/10.7314/APJCP.2015.16.4.1371 PDF KSCI
    Background: Tongue cancer is one of the leading sites of cancer in our population. Aim: To evaluate the socio-demographic profiles and stages at diagnosis of oral tongue (OT) and base of tongue (BT) cancers, and identify any possible variations in characteristics. Materials and Methods: A retrospective analysis was conducted on tongue cancer cases, divided into OT and BT, registered at the hospital cancer registry of North-East India during January 2010 to May 2013. Cases were analyzed for age, gender, residential status and different levels of education for patients, the stage at diagnosis and presence of distant metastasis. Results: A total of 1,113 cases of tongue cancers were registered, 846(76.1%) of BT and 267(23.9%) of OT. While 33.9% of BT cancer patients were above 65 years of age, the figure for OT cancers was 18.4%, stages III and IV accounting for 90.8% and 77%, respectively. The relative risk for distant metastasis in OT cancers was 3.3 (95% CI 1.08-10.1, p=0.03). Conclusions: In the subsites of tongue cancers in our population, the majority arose from the base of tongue, these tending to occur in older individuals and presenting at late stage.
  13. Jiang, Yong 1375
    https://doi.org/10.7314/APJCP.2015.16.4.1375 PDF KSCI
    Background: Objective Myocardin-related transcription factor (MRTF)-A is a Rho signaling-responsive co-activator of serum response factor (SRF). The purpose of this study is to investigate the role of MRTF-A and AQP1 (aquaporin 1) in pathological vascular remodeling. Materials and Methods: MRTF-A, AQP1 and neointima expression was detected both in the wire injured femoral arteries of wild-type mice and the atherosclerotic aortic tissues of $ApoE^{-/-}$ mice. Expression of ICAM-1, matrix metallopeptidase 9 (MMP-9) and integrin ${\beta}1$ were also assayed. The intercourse relationship between the molecules were investigated by interfering RNA and inhibitor assay. Results: MRTF-A and AQP1 expression were significantly higher in the wire injured femoral arteries of wild-type mice and in the atherosclerotic aortic tissues of $ApoE^{-/-}$ mice than in healthy control tissues. Both in wire-injured femoral arteries in MRTF-A knockout ($Mkl1^{-/-}$) mice and atherosclerotic lesions in $Mkl1^{-/-}$; $ApoE^{-/-}$ mice, neointima formation were significantly attenuated and the expression of AQP1 were significantly decreased. Expression of ICAM-1, matrix metallopeptidase 9 (MMP-9) and integrin ${\beta}1$, three SRF targets and key regulators of cell migration, and AQP1 in injured arteries was significantly weaker in $Mkl1^{-/-}$ mice than in wild-type mice. In cultured vascular smooth muscle cells (VSMCs), knocking down MRTF-A reduced expression of these genes and significantly impaired cell migration. Underlying the increased MRTF-A expression in dedifferentiated VSMCs were the down-regulation of microRNA-300. Moreover, the MRTF-A inhibitor CCG1423 significantly reduced neointima formation following wire injury in mice. Conclusions: MRTF-A could be a novel therapeutic target for the treatment of vascular diseases.
  14. Pengpid, Supa;Peltzer, Karl 1385
    https://doi.org/10.7314/APJCP.2015.16.4.1385 PDF KSCI
    The aim of this study was to investigate the sun protection use behaviour among university students from 25 low, middle income and emerging economy countries. Using anonymous questionnaires, data were collected from 18,687 undergraduate university students aged 18-30 years (mean age 20.8, SD=2.8) from 26 universities in 25 countries across Asia, Africa and the Americas. Overall, 57.2% of university students reported liking to sunbathe and of those only 48.1% used sun protection when sunbathing. In multivariate logistic regression, younger age, being female, coming from a wealthy or quite well off economic family background, living in an upper middle or high income country, lighter skin tone, and other health behaviours were found to be associated with sun protection use behaviour. Low sun protection use calls for health promotion programmes to prevent unprotected sun exposure.
  15. Altun, Ahmet;Saraydin, Serpil Unver;Soylu, Sinan;Inan, Deniz Sahin;Yasti, Cinar;Ozdenkaya, Yasar;Koksal, Binnur;Duger, Cevdet;Isbir, Cemil;Turan, Mustafa 1391
    https://doi.org/10.7314/APJCP.2015.16.4.1391 PDF KSCI
    Breast cancer is one of the most common and letal cancers in all over the world. Since there have been significant improvements in treatment of breast cancer, there is still a big need for alternative approaches. In this study, we aimed to investigate protective role of hydatid disease against breast cancer. Twenty Wistar rats were divided into two groups of 10 rats each Group I (control) and Group II. In Group II intraperitoneal hydatidosis was performed. Then DMBA was applied to mammary tissues of all rats. Immunohistochemistry studies for Ki-67 and S-100 in the tumoral tissue sections of DMBA induced mammary tumor in rats were performed. TUNEL Assay was used to detect apoptotic cells of tumoral tissue. In vivo anticancer activity testing was carried out by preventing the tumorigenesis by DMBA in mammary tissue of rats. The expressions of the Ki-67 and S-100 protein decreased in rats who had Hydatid Disease (HD) (Group II), compared with the control rats (Group I). TUNEL positive cells were higher in rats with HD (Group II), compared with the control rats (Group I). In vivo studies showed that HD prevented the tumorigenesis by DMBA in mammary tissue of rats with 50 percent.In the light of the evidence the present study showed that HD may have chemopreventive effects on DMBA induced breast cancer.
  16. Wang, Hong-Cheng;Meng, Qing-Cai;Shan, Ze-Zhi;Yuan, Zhou;Huang, Xin-Yu 1397
    https://doi.org/10.7314/APJCP.2015.16.4.1397 PDF KSCI
    Background: To determine the expressions of Tbx3, a member of subgroup belonging to T-box family, and its prognostic value in pancreatic carcinoma. Materials and Methods: We determined the expression levels of Tbx3 on both mRNA and protein levels in 30 pairs of fresh tumor tissues and paratumor tissues by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting, respectively. In addition, protein level of Tbx3 were identified using immunochemistry in 80 pairs of paraffin-embedded specimen. The correlations between Tbx3 expression and various clinicopathological parameters as well as overall survival were evaluated. Results: Tbx3 mRNA and protein levels in tumor tissues were significantly higher than in the paratumor tissues by qRT-PCR ($0.05{\pm}0.007$ vs. $0.087{\pm}0.001$, p<0.001) and western blotting ($1.134{\pm}0.043$ vs. $0.287{\pm}0.017$, p<0.001). The statistical analysis based on immunohistochemical evaluation suggested that Tbx3 aberrant expression was significantly associated with several conventional clinicopathological variables, such as gender, age, tumor position, preoperative CA19-9 level, pathological T staging and N staging. Univariate and multivariate analyses revealed that Tbx3 expression was an independent prognostic factor for overall survival (<0.001). Conclusions: Our results suggest that overexpression of Tbx3 is associated with poor prognosis of pancreatic cancer patients. However, additional clinical trials are needed to accurately validate this observation.
  17. Kaya, Halide;Demir, Melike;Taylan, Mahsuk;Sezgi, Cengizhan;Tanrikulu, Abdullah Cetin;Yilmaz, Sureyya;Bayram, Mehmet;Kaplan, Ibrahim;Senyigit, Abdurrahman 1403
    https://doi.org/10.7314/APJCP.2015.16.4.1403 PDF KSCI
    Background: New tumour biomarkers are being intensely investigated for malignant mesothelioma (MM). Fibulin-3 is produced in MM but its role remains uncertain. The aim of this study was to evaluate the validity of measuring serum fibulin-3 in the diagnosis and prognosis of MM. Materials and Methods: This prospective study was performed on 43 patients and 40 healthy controls who were admitted to our hospital between January 2012 and January 2014. Data from MM patients, including demographic and clinical features, routine laboratory data, levels of serum fibulin-3, and treatment outcomes were defined as potential prognostic factors. The receiver operating characteristic (ROC) curve for fibulin-3 was used to detect the cut-off value with highest sensitivity and specificity. Univariate survival analysis was performed using the Kaplan-Meier method in patients with MM. Afterwards, the possible factors identified with univariate analyses were entered into the cox regression analysis. Results: Our results revealed that patients with MM had significantly higher serum levels of fibulin-3 than controls. The results showed that the best cut-off point was 36.6 ng/ml with an AUC (area under the curve)=0.976, sensitivity=93.0% and specificity=90.0. In our study, the initial significant poor prognostic factors were advanced stage, high white blood cell count, high platelet count, high C-reactive protein (p<0.05 for each variable). Later, according to multivariate analysis the results showed only advanced stage as significant parameter (p=0.040). Conclusions: We determined that real use for serum fibulin-3 was not for prognosis but for diagnosis in MM. Also advanced stage was associated with poor MM prognosis.
  18. Keyghobadi, Naeimeh;Rafiemanesh, Hosein;Mohammadian-Hafshejani, Abdollah;Enayatrad, Mostafa;Salehiniya, Hamid 1409
    https://doi.org/10.7314/APJCP.2015.16.4.1409 PDF KSCI
    Background: According to increase in elderly populations, and change in lifestyle and cancer-causing behavior, the global burden of cancer is increasing. For prevention and control of disease, knowledge of population statistics of cancers and their trends is essential. This study aimed to investigate the epidemiology and trends of cancer in the province of Kerman: southeast of Iran. Materials and Methods: This analytical and cross-sectional study was carried out based on cancer registry data at the Disease Management Center of the Health Ministry from 2004 to 2009 in the province of Kerman in Iran. Common cancers were defined as the number of reported cases and standardized incidence rates. To compute the annual percentage change (APC), joinpoint 4.1.1.1 software was applied. Results: Of 10,595 registered cases, 45.3% (4802 cases) were in women and 56.7% (5,793 cases) occurred in men. The standardized incidence rates for both females and males were increasing during the six years studied. The most common cancers in both sexes during six years of studied were skin (13.4%), breast (9.35%), bladder (7.8%), stomach (7.45%), leukemia (7.05%), colorectal(5.57%), lung(4.92%), trachea(3.51%) and prostate(2.48%). Conclusions: Our findings revealed that the cancer incidence is demonstrating increasing trends in both sexes in the province of Kerman. This may be because of changes in lifestyle, increasing exposure to risk factors for cancer and increase of life expectancy. If this is the case, increasing public awareness of cancer risk factors is a high priority, together with introduction of large-scale screening techniques.
  19. Chun, Sung-Youn;Park, Hyeki;Lee, Tae Hoon;Park, Eun-Cheol 1415
    https://doi.org/10.7314/APJCP.2015.16.4.1415 PDF KSCI
    Background: We compared the health-promoting behavior of long-term cancer survivors with those of the general population to identify necessary behavioral interventions to reduce the health risk among cancer patients. Materials and Methods: We used data from the 2007 and 2012 Korea National Health and Nutrition Examination Surveys (KNHANES IV [2007~2009] and KNHANES V [2010~2012]) on smoking status, alcohol use, physical exercise, and disease screening. We compared long-term cancer survivors with members of the general population; the controls were matched by propensity score matching. A multiple logistic regression model was used to investigate the association between cancer status and health-promoting behavior. Results: Long-term cancer survivors had a lower risk of smoking than the general population controls (OR: 0.42, 95%CI: 0.25-0.71). In addition, the long-term cancer survivors had a lower risk of alcohol use than the general population controls (OR: 0.70, 95%CI: 0.50-0.98). However, in terms of physical exercise and disease screening, no statistically significant differences were detected (physical exercise OR: 1.01, 95%CI: 0.75-1.35; disease screening OR: 1.27, 95%CI: 0.93-1.74). All covariates were adjusted. Conclusions: The long-term cancer survivors had a much lower risk of smoking and alcohol use than the general population controls. However, almost no differences in physical exercise and screening for cancer recurrence or secondary disease were detected between the long-term cancer survivors and general population controls. To reduce the health risks and challenges facing long-term cancer survivors, interventions to encourage physical exercise and screening for cancer recurrence and secondary disease should be implemented.
  20. Du, Zi-Yan;Shi, Min-Hua;Ji, Cheng-Hong;Yu, Yong 1421
    https://doi.org/10.7314/APJCP.2015.16.4.1421 PDF KSCI
    Aims: Pleiotrophin (PTN), an angiogenic factor, is associated with various types of cancer, including lung cancer. Our aim was to investigate the possibility of using serum PTN as an early indicator regarding disease diagnosis, classification and prognosis, for patients with non-small cell lung cancer (NSCLC). Methods: Significant differences among PTN levels in patients with small cell lung cancer (SCLC, n=40), NSCLC (n=136), and control subjects with benign pulmonary lesions (n=21), as well as patients with different pathological subtypes of NSCLC were observed. Results: A serum level of PTN of 300.1 ng/ml, was determined as the cutoff value differentiating lung cancer patients and controls, with a sensitivity and specificity of 78.4% and 66.7%, respectively. Negative correlations between serum PTN level and pathological differentiation level, stage, and survival time were observed in our cohort of patients with NSCLC. In addition, specific elevation of PTN levels in pulmonary tissue in and around NSCLC lesions in comparison to normal pulmonary tissue obtained from the same subjects was also observed (n=2). Conclusion: This study suggests that the serum PTN level of patients with NSCLC could be an early indicator for diagnosis and prognosis. This conclusion should be further assessed in randomized clinical trials.
  21. Jerachotechueantaveechai, Tanut;Charoenkwan, Kittipat;Wongpaka, Nahathai 1427
    https://doi.org/10.7314/APJCP.2015.16.4.1427 PDF KSCI
    Aim: To compare prevalence of anxiety in women with abnormal cervical cytology (Pap) undergoing colposcopy to that of women attending the outpatient clinic for check-up and to examine predicting factors. Materials and Methods: In this cross-sectional analytical study, 100 women with abnormal cervical cytology (abnormal Pap group) and 100 women who attended our outpatient clinic for check-up (control group) were recruited from June 2013 to January 2014. The Hospital Anxiety and Depression Scale (HADS) was employed to determine anxiety in the participants with the score of ${\geq}11$ suggestive of clinically significant anxiety. The prevalence of anxiety and the mean HADS scores for anxiety were compared between the groups. For those with abnormal Pap, association between clinical factors and anxiety was assessed. A p-value of < 0.05 was considered significant. Results: Median age was different between the groups, 44.0 years in the abnormal Pap group and 50.0 years in the control group (p=0.01). The proportion of participants who had more than one sexual partner was higher in the abnormal Pap group, 39.2% vs. 24.7% (p=0.03) and the prevalence of anxiety was significantly higher 14/100 (14.0%) vs. 3/100 (3.0%) (p < 0.01). The prevalence of depression was comparable between the groups. The mean HADS scores for anxiety and depression subscales were significantly higher in the abnormal Pap group, 6.6 vs. 4.8 (P < 0.01) and 3.9 vs. 3.1 (p=0.05), respectively. For the abnormal Pap group, no definite association between clinical factors and anxiety was demonstrated. Conclusions: The prevalence of anxiety in women with abnormal Pap awaiting colposcopy was significantly higher than that of normal controls. Special attention including thorough counselling, with use of information leaflets and psychological support, should be directed to these women.
  22. Hedayatizadeh-Omran, Akbar;Rafiei, Alireza;Alizadeh-Navaei, Reza;Tehrani, Mohsen;Valadan, Reza;Moradzadeh, Kambiz;Panbechi, Mohammad;Taghavi, Seyed Mehdi 1431
    https://doi.org/10.7314/APJCP.2015.16.4.1431 PDF KSCI
    Background: Breast cancer is one of the most common cancers among women worldwide and the HER2 receptor plays an important role in its development and progression. This systematic review aimed to summarize the role of HER2 in brain metastasis in patients with breast cancer. Materials and Methods: We conducted a literature search by advanced search in title field using the Scopus, Pubmed, and Google scholar databases until the end of June 2014. With metastasis, metastatic, HER2, brain, and breast cancer, as terms of search we selected 31 articles, which were reviewed by two independent and blinded expert reviewers. The studies were first selected according to their titles and abstracts. Quality of the studies were then assessed using the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) protocol for observational studies and CONSORT(Consolidation of Standards for Reporting Trials) protocol for clinical trials. For statistical analyses, we used STATA, version 11.0 software. Forest and funnel diagrams were drawn and for heterogeneity, index was also considered. Also we used meta regression analysis. Results: Finally, we reviewed 10 studies. The prevalence of brain metastasis in HER2-positive breast cancer patients was 24.9%. There was publication bias in the reviewed studies. Meta regression analysis showed that follow up time had no significant effect (p=0.396) on the prevalence of brain metastasis. Conclusions: The results showed a high prevalence of brain metastasis in HER2 positive breast cancer patients.
  23. Phungrassami, Temsak;Sriplung, Hutcha 1435
    https://doi.org/10.7314/APJCP.2015.16.4.1435 PDF KSCI
    Purpose: To study the patient load, treatment pattern, survival outcome and its predictors in patients with brain metastases treated by radiotherapy. Materials and Methods: Data for patients with brain metastases treated by radiotherapy between 2003 and 2007 were collected from medical records, the hospital information system database, and a population-based tumor registry database until death or at least 5 years after treatment and retrospectively reviewed. Results: The number of treatments for brain metastases gradually increased from 48 in 2003 to 107 in 2007, with more than 70% from lung and breast cancers. The majority were treated with whole brain radiation of 30 Gy (3 Gy X 10 fractions) by cobalt-60 machine, using radiation alone. The overall median survival of the 418 patients was 3.9 months. Cohort analysis of relative survival after radiotherapy was as follows: 52% at 3 months, 18% at 1 year and 3% at 5 years in males; and 66% at 3 months, 26% at 1 year and 7% at 5 years in females. Multivariate analysis demonstrated that the patients treated with combined modalities had a better prognosis. Poor prognostic factors included primary cancer from the lung or gastrointestinal tract, emergency or urgent consultation, poor performance status (ECOG 3-4), and a hemoglobin level before treatment of less than 10 g/dl. Conclusions: This study identified an increasing trend of patient load with brain metastases. Possible over-treatment and under-treatment were demonstrated with a wide range of survival results. Practical prognostic scoring systems to assist in decision-making for optimal treatment of different patient groups is absolutely necessary; it is a key strategy for balancing good quality of care and patient load.
  24. Liu, Hong-Bin;Gao, Xiang-Xiang;Zhang, Qing;Liu, Jian;Cui, Yuan;Zhu, Yan;Liu, Yi-Fei 1443
    https://doi.org/10.7314/APJCP.2015.16.4.1443 PDF KSCI
    To investigate the significance of FOXO3a and Ki67 in human lung adenocarcinomas. Envision immunohistochemical staining and Western blotting were used to examine the protein expression of FOXO3a in 127 cases of human lung adenocarcinoma specimens. The positive rate in lung adenocarcinoma (55.9%) was lower than that in normal tissues (80%). We found that the expression of FOXO3a was closely related with the degree of differentiation, TNM staging, lymph node metastasis and survival. In addition, significant differences in the different pathological types of lung adenocarcinoma cases (P<0.01). The FOXO3a positive rate of the acini as the main type (APA) (86.7%) and the lepidic as the main type (LPA) (82.4%) was higher than the solid as the main type (SPA) (50.0%), the papilla as the main type (PPA) (42.9%) and the micropapilla as the main type (MPA) (9.4%). Moreover, the expression of FOXO3a was negatively related with Ki67 expression. Our results suggested that the expression of FOXO3a is closely correlated with the aggressiveness of lung adenocarcinoma. It was indicated that disregulation of FOXO3a might play key roles in the occurrence and development of lung a denocarcinoma and joint detection of the two markers might play an important role in diagnosing tumors.
  25. Phua, Vincent Chee Ee;Wong, Wei Quan;Tan, Pei Lin;Bustam, Anita Zarina;Saad, Marniza;Alip, Adlinda;Ishak, Wan Zamaniah Wan 1449
    https://doi.org/10.7314/APJCP.2015.16.4.1449 PDF KSCI
    Background: Oral capecitabine is increasingly replacing intravenous 5-fluorouracil in many chemotherapy regimens. However, data on the risk of febrile neutropaenia (FN) and treatment related death (TRD) with the drug remain sparse outside of clinical trial settings despite its widespread usage. This study aimed to determine these rates in a large cohort of patients treated in the University of Malaya Medical Centre (UMMC). Materials and Methods: We reviewed the clinical notes of all patients prescribed with oral capecitabine chemotherapy for any tumour sites in University Malaya Medical Centre (UMMC) from $1^{st}$ January 2009 till $31^{st}$ June 2010. Information collected included patient demographics, histopathological features, treatment received including the different chemotherapy regimens and intent of treatment whether the chemotherapy was given for neoadjuvant, concurrent with radiation, adjuvant or palliative intent. The aim of this study is to establish the pattern of usage, FN and TRD rates with capecitabine in clinical practice outside of clinical trial setting. FN is defined as an oral temperature > $38.5^{\circ}C$ or two consecutive readings of > $38.0^{\circ}C$ for 2 hours and an absolute neutrophil count < $0.5{\times}10^9/L$, or expected to fall below $0.5{\times}10^9/L$ (de Naurois et al., 2010). Treatment related death was defined as death occurring during or within 30 days of last chemotherapy treatment. Results: Between $1^{st}$ January 2009 and $30^{th}$ June 2010, 274 patients were treated with capecitabine chemotherapy in UMMC. The mean age was 58 years (range 22 to 82 years). Capecitabine was used in 14 different tumour sites with the colorectal site predominating with a total of 128 cases (46.7%), followed by breast cancer (35.8%). Capecitabine was most commonly used in the palliative setting accounting for 63.9% of the cases, followed by the adjuvant setting (19.7%). The most common regimen was single agent capecitabine with 129 cases (47.1%). The other common regimens were XELOX (21.5%) and ECX (10.2%). The main result of this study showed an overall FN rate of 2.2% (6/274). The overall TRD rate was 5.1% (14/274). The FN rate for the single agent capecitabine regimen was 1.6% (2/129) and the TRD rate was 5.4% (7/129). All the TRDs were with single agent capecitabine regimen were used for palliative intent. Conclusions: Oral capecitabine is used widely in clinical practice in a myriad of tumour sites and bears a low risk of febrile neutropaenia. However, capecitabine like any other intravenous chemotherapeutic agent carries a significant risk of treatment related death.
  26. Acevedo, Francisco;Camus, Mauricio;Sanchez, Cesar 1455
    https://doi.org/10.7314/APJCP.2015.16.4.1455 PDF KSCI
    Background: Young onset breast cancer (BC) has a worse outcome as compared to in the elderly. However, some studies have shown that BC in the elderly, despite indolent features, does also cause increase in mortality. In an attempt to compare clinic-pathological characteristics, BC subtypes and survival in patients with BC presenting at extremes of age, we performed a retrospective study. Materials and Methods: Patients were either ${\leq}40$ or ${\geq}70$ years old. Subtypes were defined using immunohistochemistry and histological grade. Chi-Square test was used for evaluation of categorical variables, and Kaplan-meier and log-rank for disease-specific survival (DSS) and disease free survival (DFS). Results: We analyzed 256 patients ${\leq}40$ and 366 patients ${\geq}70$. Younger patients presented with more aggressive disease, with less luminal A but more luminal B and triple negative (TN) subtype. With a median follow-up of 57.5 months, DFS at 5 years in younger patients was 72.3% vs 84.6% in the elderly (p=0.007). Luminal A and B disease presented with worse DFS in younger patients. The opposite was seen in the TN subgroup. Although we found no significant differences in DSS, older patients with TN tumors died of BC more frequently. This group also received less chemotherapy. Conclusions: Young patients present with more aggressive disease, this translating into worse DFS. However, elderly patients with TN disease represent a particular subpopulation with worse DFS and DSS, suggesting that chemotherapy should not be withheld only because of age.
  27. Li, Xue;Zhao, Lu-Jun;Liu, Ning-Bo;Zhang, Wen-Cheng;Pang, Qing-Song;Wang, Ping;Yuan, Zhi-Yong 1463
    https://doi.org/10.7314/APJCP.2015.16.4.1463 PDF KSCI
    Background: To evaluate the safety and efficacy of combined chemoradiotherapy or radiotherapy alone in elderly patients with esophageal carcinoma to identify the best method of treatment. Materials and Methods: One hundred and sixteen patients with esophageal carcinoma aged 70 and older who received definitive radiotherapy or chemoradiotherapy entered the study. Overall survival (OS), disease-free survival (DFS) and treatment-related toxicities were assessed. Results: The median OS of the overall population was 17.9 months. For patients treated with cCRT, sCRT and radiotherapy alone, the median OS was 22.3 months, 18.0 months and 12.4 months respectively(P=0.044). Median OS for patients treated with radiotherapy dose ${\geq}60Gy$ and <60Gy was 20.2 months and 10.9 months respectively (p=0.017). By univariate analysis, Chemoradiotherapy (include cCRT and sCRT) and radiotherapy dose ${\geq}60Gy$ were found to achieve higher survival rates compared with radiotherapy alone and radiotherapy dose <60Gy (P=0.015, P=0.017). By multivariate analysis, chemoradiotherapy (HR=1.645, P=0.022) and radiotherapy dose ${\geq}60Gy$ (HR=1.642, P=0.025) were identified as independent prognostic factors of OS. Conclusions: Definitive concurrent chemoradiotherapy could be considered as a feasible and effective treatment in esophageal carcinoma patients aged 70 and older. Radiotherapy dose 60Gy is an effective treatment option compared with standard dose radiotherapy, while higher doses are not beneficial to improve survival.
  28. Yazilitas, Dogan;Sendur, Mehmet Ali Nahit;Karaca, Halit;Ozdemir, Nuriye;Aksoy, Sercan;Berk, Veli;Yazici, Ozan;Ozturk, Banu;Ozkan, Metin;Zengin, Nurullah;Altundag, Kadri 1471
    https://doi.org/10.7314/APJCP.2015.16.4.1471 PDF KSCI
    Background: Adding taxanes to adjuvant antracycline and cyclophosphamide (AC) in combination may provide significant improvement in node-positive and high risk node-negative breast cancer (BC) patients. However, the optimal dose and the role of dose-dense (DD) chemotherapy have yet to be determined. The aim of this study was to compare the efficacy of a DD paclitaxel (P)-AC combination with conventional weekly P-AC or docetaxel D-AC combinations in patients with node-positive breast cancer. Materials and Methods: Newly diagnosed 280 node-positive BC patients diagnosed from 1998 to 2013 in three clinics were retrospectively analyzed. Demographic and medical data were collected from the medical charts. Patients were categorized to 3 groups according to treatment arms: arm A, ddAC-P; arm B, weekly P and AC combination; and arm C; T and AC combination. Adjuvant trastuzumab was added for HER2-positive patients. Kaplan-Meier survival analysis was carried out for disease free survival (DFS) and overall survival (OS). The log-rank test was used to examine the statistical significance of the differences observed between the groups. Two-sided P values <0.05 were considered statistically significant. Results: Of the total of 280 patients, 101 were in arm A, 114 in arm B and 65 in arm C.The median ages were 49, 50 and 46, respectively (p=0.11). Median follow-up was 39 (3-193) months. Stage, lymphovascular and perineural invasion, receptor patern, and menopausal status were similar in the 3 treatment arms, but HER2 positivity was significantly lower in arm A, compared to arms B and C (25.7%, 53.1%, 41.5% in arms A, B and C, respectively; p<0.001). Also grade 3 tumors were significantly less frequent in treatment arm A compared to arm B and C (27.3%, 56.8% and 49.2%, respectively, p=0.01). Afterunivariate and multivariate analysis were performed, 3-year DFS rates were 89%, 81%, and 75%, respectively (p=0.12) and three year OS rates were 96.6%, 89%, and 75% (p=0.62). Conclusions: In this study, no significant difference was found between adjuvant dose dense and conventional taxane treatment regimens.
  29. Ramadas, Amutha;Qureshi, Ahmad Munir;Dominic, Nisha Angela;Botross, Nevein Philip;Riad, Amgad;Arasoo, Valliammai Jayanthi Thirunavuk;Elangovan, Soman 1479
    https://doi.org/10.7314/APJCP.2015.16.4.1479 PDF KSCI
    Background: Even after completion of conventional treatment, breast cancer survivors continue to exhibit a variety of psychological and physical symptoms, affecting their quality of life. The study aimed to investigate the relationship between socio-demography, medical characteristics and health-related quality of life (HR-QOL) of a sample of breast cancer survivors in Malaysia. Materials and Methods: This pilot cross-sectional survey was conducted among breast cancer survivors (n=40) who were members of Breast Cancer Support Group Centre Johor Bahru. A validated self-administered questionnaire was used to identify the relationships between socio-demography, medical characteristics and HR-QOL of the participants. Results: Living with family and completion of treatment were significant predictive factors of self-rated QOL, while living with family and ever giving birth significantly predicted satisfaction with health and physical health. Psychological health had moderate correlations with number of children and early cancer stage. Survivors' higher personal income (>MYR4,500) was the only significant predictor of social relationship, while age, income more than MYR4,500 and giving birth significantly predicted environment domain score. Conclusions: The findings suggested the survivors coped better in all four HR-QOL domains if they were married, lived with family, had children and were employed.
  30. Zhang, Guo-Qing;Li, Fang;Sun, Sheng-Jie;Hu, Yi;Wang, Gang;Wang, Yu;Cui, Xiao-Xia;Jiao, Shun-Chang 1487
    https://doi.org/10.7314/APJCP.2015.16.4.1487 PDF KSCI
    Background: To investigate the clinical efficacy of expanded activated autologous lymphocytes (EAAL) in patients with small cell lung cancer (SCLC). Materials and Methods: A total of 32 SCLC patients were selected and randomly divided into EAAL treatment and control groups, 16 cases in each. EAAL were obtained by proliferation of peripheral blood mononuclear cells (PBMCs) of patients followed by phenotype determination. Clinical data of all patients were recorded. Patients of both groups were followed up and the overall survival (OS) were compared retrospectively. Results: After culture and proliferation in vitro, the percentages of $CD3^+$, $CD3^+CD8^+$, $CD45RO^+$, $CD28^+$, $CD29^+$, $CD8^+CD28^+$ and $CD3^+CD16^+/CD56^+$ cells increased markedly (p<0.05). The OS of the EAAL treatment group was longer than that of control group, but the difference was not statistically significant (p=0.060, HR=0.487, 95%CI 0.228~1.037). 1- to 3-year survival rates in EAAL treatment group were longer than those in control group, but there was still no significant difference (p>0.05). COX multivariate regression analysis showed that the number of chemotherapy cycles and the application of EAAL immunotherapy were independent prognostic factors for SCLC patients. The OS in females and chemotherapy${\leq}6$ cycles were obviously prolonged after EAAL immunotherapy. Conclusions: In vitro induction and proliferation of EAAL is easy and biologically safe. Generally, EAAL adoptive immunotherapy can evidently prolong the OS of SCLC patients.
  31. Sehitoglu, Ibrahim;Bedir, Recep;Ural, Ulku Mete;Gucer, Hasan;Yurdakul, Cuneyt;Cure, Medine Cumhur;Cure, Erkan;Yuce, Suleyman;Sahin, Figen Kir 1495
    https://doi.org/10.7314/APJCP.2015.16.4.1495 PDF KSCI
    Background: c-Kit is a proto-oncogene that encodes a tyrosine kinase receptor (CD117). Mean platelet volume (MPV) is a useful marker for demonstrating thrombocyte function. We aimed to investigate whether c-kit is expressed in benign, preneoplastic and neoplastic endometrial tissues and whether MPV has a relation with c-kit expression and its intensity. Materials and Methods: c-Kit expression was investigated immunohistochemically in 10 samples of normal endometrium (n=10), simple endometrial hyperplasia (5 cases with atypia and 10 cases without atypia), complex endometrial hyperplasia (10 cases with atypia and 10 cases without atypia) and endometrial cancer (EC) (10 cases grade I and 10 cases grade II) and MPV of all cases was checked. Results: c-Kit expression was observed at very low rates in cases with normal endometrial tissues (NE) and in hyperplasia without atypia. c-Kit expression and immunostaining were strong in endometrial atypia and EC. MPV levels of complex atypical endometrial hyperplasia (CAEH) (p:0.002), EC grade I (ECG I) (p<0.001) and EC grade II (ECG II) (p<0.001) were significantly elevated when compared with the NE group. Both c-kit expression and intensity of immunostaining had a positive correlation with MPV level. Conclusions: While c-kit expression and intensity of immunostaining were mildly positive in NE and hyperplasia without atypia, they were clearly observed in EC and hyperplasia with atypia. As c-kit expression is related to the mutagenesis a long-term followup may be needed in these cases. A high MPV level may be a good test for demonstrating c-kit expression and intensity of immunostaining.
  32. Alanazi, Khalid Mashay 1501
    https://doi.org/10.7314/APJCP.2015.16.4.1501 PDF KSCI
    Gemcitabine is an anti-cancer drug with clinically uses in the treatment of various neoplasms, including breast, ovarian, non-small cell lung, pancreaticand cervical cancers, T-cell malignancies, germ cell tumours, and hepatocellular carcinomas. However, it has also been reported to have many adverse effects. Naturally occurring anti-mutagenic effects, especially those of plant origin, have recently become a subject of intensive research. The present study was therefore designed to investigate the anti-mutagenic effects of Salvia merjamie (Family: Lamiaceae) plant extracts against the mutagenic effects of gemcitabine. The anti-mutagenic properties of Salvia merjamie were tested in Inbred SWR/J male and female mice bone marrow cells. The mice were treated in four groups; a control group treated with 30 mg/kg body weight gemcitabine and three treatment groups, each with 30 mg/kg body weight gemcitabine together with, respectively, 50, 100 and 150 mg/kg body weight Salvia merjamie extract. Chromosomal aberration and mitotic index assays were performed with the results demonstrating that Salvia merjamie extract protects bone marrow cells in mice against gemcitabine induced mutagenicity. This information can be used for the development of a potential therapeutic anti-mutagenic agents.
  33. Wu, Dong-Ming;Zhang, Peng;Xu, Guang-Chao;Tong, Ai-Ping;Zhou, Cong;Lang, Jin-Yi;Wang, Chun-Ting 1507
    https://doi.org/10.7314/APJCP.2015.16.4.1507 PDF KSCI
    Pemetrexed is an antifolate agent which has been used for treating malignant pleural mesothelioma and non small lung cancer in the clinic as a chemotherapeutic agent. In this study, pemetrexed inhibited cell growth and induced G1 phase arrest in the A549 cell line. To explore the molecular mechanisms of pemetrexed involved in cell growth, we used a two-dimensional polyacrylamide gel electrophoresis (2-DE) proteomics approach to analyze proteins changed in A549 cells treated with pemetrexed. As a result, twenty differentially expressed proteins were identified by ESI-Q-TOF MS/MS analysis in A549 cells incubated with pemetrexed compared with non-treated A549 cells. Three key proteins (GAPDH, HSPB1 and EIF4E) changed in pemetrexed treated A549 cells were validated by Western blotting. Accumulation of GAPDH and decrease of HSPB1 and EIF4E which induce apoptosis through inhibiting phosphorylation of Akt were noted. Expression of p-Akt in A549 cells treated with pemetrexed was reduced. Thus, pemetrexed induced apoptosis in A549 cells through inhibiting the Akt pathway.
  34. Kumar, Surendra;Muniyandi, Malaisamy 1515
    https://doi.org/10.7314/APJCP.2015.16.4.1515 PDF KSCI
    Background: Leukoplakia is an asymptomatic and potentially malignant change in the oral mucosa and high frequencies have been reported among smokers. The present study concerned the prevalence of tobacco use and leukoplakia and also associations between the two. Study design: This cross sectional survey was conducted amongst the Gond tribal population of Kundam Block, Jabalpur district, Madhya Pradesh state, Central India during 2007 to 2009. Screening for leukoplakia was conducted by a medical officer with two mouth mirrors. It is only based on visual inspection and oral pathology was not performed. A semi-structured questionnaire was used to collect information on socio-demographic and smoking habits. Prevalence of leukoplakia among users and non-users of tobacco was calculated in terms of percentages. Results: Of 1,552 individuals aged more than 12 years of age who were screened, 144 (9.3%) were found to have oral leukoplakia. The prevalence of leukoplakia was significantly elevated among tobacco users as compared to non-users (11% vs 2.5%; p<0.001). The percentage of leukoplakia was almost similar in both tobacco smokers and chewers (9% vs 11%; p=0.304). However, the percentage of leukoplakia was especially high among those chewers who also smoked tobacco (21.9%). Conclusions: The findings of the present study showed a positive effect of tobacco use and prevalence of leukoplakia. Also the prevalence was very high among Gond tribe, a marginalized population living in central India. There is a need for effective screening and treatment of leukoplakia in this area.
  35. Sarma, Usha;Mahanta, Jagadish;Borkakoty, Biswajyoti;Sarmah, Bidula 1519
    https://doi.org/10.7314/APJCP.2015.16.4.1519 PDF KSCI
    Infection of the uterine cervix by human papilloma viruses (HPV) may be associated with cervical pre-cancer and invasive cervical carcinoma if left untreated. With advance in molecular techniques, it has become easier to detect the resence of HPV DNA long before the appearance of any lesion. This study concerned cervical scrape samples of 310 married non-pregnant women attending a gynecology outpatient department for both Pap and PCR testing to detect HPV DNA. Nested PCR using primers for L1 consensus gene with My9/My11 and GP6+/GP5+followed by multiplex PCR were carried out to detect HPV 16 and HPV18. Result: HPV prevalence was 11.9% out of which 3.67% cases of negative for intra-epithelial lesion or malignancy (NILM) and in 71.1% (27/38) of atypical cervical smears were HPV positive. There was increasing trend of high-risk-HPV positivity (HR HPV 16 and 18), from 20% in benign cytology (NILM) to 42.9 % in LSIL, 71.41% in HSIL and 100% in SCC. There was highly significant association of HPV infection with cervical lesion ($x^2=144.0$, p<0.01) and also with type specific HPV prevalence ($x^2=7.761^*$, p<0.05).
  36. Shen, Kang;Huang, Xin-En 1525
    https://doi.org/10.7314/APJCP.2015.16.4.1525 PDF KSCI
    Objective: To investigate the clinical effect of riboflavin sodium phosphate on prevention of radiotherapy related esophagitis (RRE). Methods: This retrospective study involved 55 patients with middle and advanced esophageal cancer who were divided into an experimental group of 28 and a control group of 27 patients. Those in the experimental group were treated with riboflavin sodium phosphate combined with conventional symptomatic treatment during radiotherapy; while patients in control group received the latter alone. The incidence and degree of RRE were compared after radiotherapy. Results: The incidences of RRE in experimental and control group were 53.5% and 81.4%, respectively (p<0.05); the incidence of stages III and IV RRE in the experimental group was 17.8%, while in the control group it was 44.4% (p<0.05). Conclusion: Riboflavin sodium phosphate could significantly prevent RRE and reduce the incidence of stage III and IV disease. These results were worthy of further confirmation by randomized controlled trials.
  37. Saridi, Maria Ioannis;Toska, Aikaterini George;Rekleiti, Maria Dimitrios;Tsironi, Maria;Geitona, Maria;Souliotis, Kyriakos 1529
    https://doi.org/10.7314/APJCP.2015.16.4.1529 PDF KSCI
    Introduction: Overexposure to sun radiation and particularly its accumulation during childhood and adolescence is a significant risk factor for skin cancer development. The sun burn is particularly important. Aim: To estimate sun burn incidence in young pupils in a coastal area of Greece. Materials and Methods: Two surveys were conducted in a school population in the same district in Greece, over different periods of time, in young people 9 to 18 years old (n=2 977). Anonymous questionnaires were completed. Levels of significance were two-tailed and statistical significance was set at p=0.05. SPSS 17.0 software was used for statistical analysis. Results: From the individual characteristics of the participants it was shown that the majority of them had dark hair and fair skin, whereas a significant percentage reported the existence of moles on face and their body (83.4% vs 68.1%). The sun burn incidence was high in adolescents and the younger pupils (41.9% vs 55.6%). The younger aged children who were living in an urban area had significantly higher rates of sun burn than those living in semi-urban areas (33.8% vs 24.8%, p=0.020). As far as the knowledge of pupils about the risks of sun radiation it was shown that the elementary school pupils had better knowledge than those at high school. Finally, those with better knowledge had the fewer sun burns (Mean 2.83 SD 0.87, p<0.001). Conclusions: The contribution of knowledge to the decrease of sun burn incidence is important as long as this is continuous. Therefore, the education should concern not only children but also teachers and parents in the context of continuous and systematic programs of health education.
  38. Tayeb, Muhammad;Rauf, Fozia;Ahmad, Khurshid;Khan, Faiz Muhammad 1535
    https://doi.org/10.7314/APJCP.2015.16.4.1535 PDF KSCI
    Background: The objectives of the study were to: 1) determine the frequency of incidental malignancy in unsuspected/grossly normal looking gall bladders; 2) determine the frequency of malignancy in suspected/grossly abnormal looking gall bladders. Materials and Methods: This prospective, cross sectional study was carried out at a tertiary care hospital in Pakistan, during a four year period (Jan 2009-dec2012). All the cholecystectomy cases performed for gallstone diseases were examined initially by a surgeon and later on by a pathologist for macroscopic abnormalities and accordingly assigned to one of the three categories i.e. grossly normal, suspicious, abnormal/malignant. Frequency of incidental carcinoma in these categories was observed after receiving the final histopathology report. Results: A total of 426 patients underwent cholecystectomy for cholelithiasis, with a 1:4 male: female ratio. Mean age of the patients was 45 years with a range of 17-80 years. The frequency of incidental gallbladder carcinoma was found to be 0.70 %(n=3). All the cases of gallbladder carcinoma were associated with some macroscopic abnormality. Not a single case of incidental carcinoma gallbladder was diagnosed in 383 'macroscopically normal looking' gallbladders. Conclusions: Incidental finding of gall bladder cancer was not observed in any of macroscopically normal looking gall bladders and all the cases reported as carcinoma gallbladder had some gross abnormality that made them suspicious. We suggest histopathologic examination of only those gall bladders with some gross abnormality.
  39. Tsumura, Hideyasu;Matsumoto, Kazumasa;Ikeda, Masaomi;Yanagita, Kengo;Hirano, Shuhei;Hagiwara, Masahiro;Nagashio, Ryo;Fujita, Tetsuo;Sato, Yuichi;Iwamura, Masatsugu 1539
    https://doi.org/10.7314/APJCP.2015.16.4.1539 PDF KSCI
    Background: Uroplakins have been widely investigated as potential markers in patients with bladder cancer because these proteins are specific to the urothelium. However, the role of uroplakin proteins in bladder cancer remains unknown. In this study, preoperative serum levels of uroplakin III were measured in patients with urothelial carcinoma of the urinary bladder and examined for possible association with clinicopathological features and clinical outcomes. Materials and Methods: This study included 52 bladder cancer patients at various stages and 28 healthy controls. Uroplakin III levels were detected in preoperative sera using an automated dot blot system and a micro-dot blot array. Results: There was a significant increase in serum uroplakin III levels in patients with bladder cancer as compared to healthy controls (p<0.05). In addition, serum uroplakin III levels were associated with muscle-invasive status, high grade and lymphovascular invasion (p<0.02). Log-rank tests indicated high serum uroplakin III to be significantly associated with cancer-specific mortality. Conclusions: Determination of serum uroplakin III level could be valuable for identifying patients with biologically aggressive bladder cancer.
  40. Yang, Liu;Sun, Yan;Huang, Xin-En;Yu, Dong-Sheng;Zhou, Jian-Nong;Zhou, Xin;Li, Dong-Zheng;Guan, Xin 1545
    https://doi.org/10.7314/APJCP.2015.16.4.1545 PDF KSCI
    Purpose: Rectal cancers with high microsatellite-instable have clinical and pathological features that differentiate them from microsatellite-stable or low-frequency carcinomas, which was studied rarely in stage II rectal cancer, promoting the present investigation of the usefulness of microsatellite-instability status as a predictor of the benefit of adjuvant chemotherapy with fluorouracil in stage II rectal cancer. Patients and Methods: Data of 460 patients who underwent primary anterior resection with a double stapling technique for rectal carcinoma at a single institution from 2008 to 2012 were retrospectively collected. All patients experienced a total mesorectal excision (TME) operation. Survival analysis were analyzed using the Cox regression method. Results: Five-year rate of disease-free survival (DFS) was noted in 390 (84.8%) of 460 patients with stage II rectal cancer. Of 460 tissue specimens, 97 (21.1%) exhibited high-frequency microsatellite instability. Median age of the patients was 65 (50-71) and 185 (40.2%) were male. After univariate and multivariate analysis, microsatellite instability (p= 0.001), female sex (p<0.05) and fluorouracil-based adjuvant chemotherapy (p<0.001), the 3 factors were attributed to a favorable survival status independently. Among 201 patients who did not receive adjuvant chemotherapy, those cancers displaying high-frequency microsatellite instability had a better 5-year rate of DFS than tumors exhibiting microsatellite stability or low-frequency instability (HR, 13.61 [95% CI, 1.88 to 99.28]; p= 0.010), while in 259 patients who received adjuvant chemotherapy, there was no DFS difference between the two groups (p= 0.145). Furthermore, patients exhibiting microsatellite stability or low-frequency instability who received adjuvant chemotherapy had a better 5-year rate of DFS than patients did not (HR, 5.16 [95% CI, 2.90 to 9.18]; p<0.001), while patients exhibiting high-frequency microsatellite instability were not connected with increased DFS (p= 0.696). It was implied that female patients had better survival than male. Conclusion: Survival status after anterior resection of rectal carcinoma is related to the microsatellite instability status, adjuvant chemotherapy and gender. Fluorouracil-based adjuvant chemotherapy benefits patients of stage II rectal cancer with microsatellite-stable or low microsatellite-instable, but not those with high microsatellite-instable. Additionally, free of adjuvant chemotherapy, carcinomas with high microsatellite-instable have a better 5-year rate of DFS than those with microsatellite-stable or low microsatellite-instable, and female patients have a better survival as well.
  41. Misron, Nurul Akmar;Looi, Lai-Meng;Mustapha, Nik Raihan Nik 1553
    https://doi.org/10.7314/APJCP.2015.16.4.1553 PDF KSCI
    Background: COX-2 has been shown to play an important role in the development of breast cancer and increased expression has been mooted as a poor prognostic factor. The purpose of this study was to investigate the relationship between COX-2 immunohistochemical expression and known predictive and prognostic factors in breast cancer in a routine diagnostic histopathology setting. Materials and Methods: Formalin-fixed paraffin-embedded tumour tissue of 144 no special type (NST) invasive breast carcinomas histologically diagnosed between January 2009 and December 2012 in Hospital Sultanah Bahiyah, Alor Setar, Kedah were immunostained with COX-2 antibody. COX-2 overexpression was analysed against demographic data, hormone receptor status, HER2-neu overexpression, histological grade, tumour size and lymph node status. Results: COX-2 was overexpressed in 108/144 (75%) tumours and was significantly more prevalent (87%) in hormone receptor-positive tumours. There was no correlation between COX-2 overexpression and HER2/neu status. Triple negative cancers had the lowest prevalence (46%) (p<0.05). A rising trend of COX-2 overexpression with increasing age was observed. There was a significant inverse relationship with tumour grade (p<0.05), prevalences being 94%, 83% and 66% in grades 1, 2 and 3 tumours, respectively. A higher prevalence of COX-2 overexpression in smaller size tumours was observed but this did not reach statistical significance. There was no relationship between COX-2 expression and lymph node status. Conclusions: This study did not support the generally held notion that COX-2 overexpression is linked to poor prognosis, rather supporting a role in tumorigenesis. Larger scale studies with outcome data and basic studies on cancer pathogenetic pathways will be required to cast further light on whether COX-2 inhibitors would have clinical utility in cancer prevention or blockage of cancer progression. In either setting, the pathological assessment for COX-2 overexpression in breast cancers would have an important role in the selection of cancer patients for personalized therapy with COX-2 inhibitors.
  42. Jamy, Omer;Rafiq, Ammar;Laghari, Altaf;Chawla, Tabish 1559
    https://doi.org/10.7314/APJCP.2015.16.4.1559 PDF KSCI
    Background: Male breast cancer accounts for less than 1% of all cancers found in men. It usually presents at a later age and stage as compared to female breast cancer. Treatment strategies are extrapolated from the management of female breast cancer. Our study here looked at 18 patients diagnosed with and treated for male breast cancer at The Aga Khan University Hospital in Pakistan. We compared our findings with the existing data from Asian and Western countries. Materials and Methods: A retrospective study was conducted looking at patients with male breast cancer between January 1986 and December 2009. Patient and disease characteristics were analyzed and 5 year overall survival was calculated using Microsoft Excel and SPSS. Results: The average age at diagnosis was 52 years (38-67 years). Twelve (66.7%) patients had axillary lymphadenopathy. Stage II disease was the most common stage at presentation (9 patients, 50%). Infiltrating ductal carcinoma was seen in 16 patients (88.8%). Seven lesions were positive for both estrogen and progesterone receptors. Sixteen patients had surgery in the form of either modified radical mastectomy or radical mastectomy. Radiation was used in 7 patients in an adjuvant setting. The five year overall survival for stage I, II, III and IV disease was 100% vs 78% vs 50% vs 0%( p<0.05). Five year overall survival was 61%. None of the other prognostic factors were statistically significant. Median follow up was 15 months (3-202 months). Conclusions: Male breast cancer may be on a slow rise but is still an uncommon disease. Tumor stage and lymph node status are important prognostic markers. Public awareness and screening may help in detecting the disease at an earlier stage. Prospective trials are needed to improve the management of this disease.
  43. Foliaki, Sunia;Matheson, Anna 1565
    https://doi.org/10.7314/APJCP.2015.16.4.1565 PDF KSCI
    Background: In Aotearoa/New Zealand cervical screening programmes have reduced cervical cancer; however, half of cervical cancer cases among Pacific women are found among clients who had not attended cervical screening. Hence, we set out to determine health provider perspectives on barriers that prevent their services reaching Pacific women within Aotearoa/New Zealand. Materials and Methods: Twenty semi-structured interviews were conducted with health care providers, Pap smear takers and community workers in the Wellington region. Participants were asked their views on factors that enabled and/or constrained the participation of Pacific women in their cervical screening services. Results: Six interrelated themes influencing participation in cervical screening among Pacific women in the Wellington region were apparent: the funding and practice of service delivery; family always coming first; the cost of screening services; type of employment; the appropriateness of information; and attitudes to self and screening. Conclusions: Determining specific ethnic group actual health needs and meeting them contributes to overall improvement in New Zealand's health status. The results identified the need for improvements to the delivery of screening services including adapting cervical screening services to the requirements of Pacific women through more outreach services at alternate clinic hours; culturally appropriate practitioners; the ability to take up opportunities for health checks and foster long-term relationships; as well as appropriate monitoring and evaluation of approaches. Funding and reporting relationships also need to be compatible with the goal of improving outcomes for Pacific women. Further research into client voices for their particular needs to compliment the service provider perspective as well as minority groups is called for.
  44. Mansour-Ghanaei, Fariborz;Joukar, Farahnaz;Mojtahedi, Kourosh;Sokhanvar, Homayoon;Askari, Kourosh;Shafaeizadeh, Ahmad 1571
    https://doi.org/10.7314/APJCP.2015.16.4.1571 PDF KSCI
    Background: Treatment of Helicobacter pylori (H. pylori) decreases the prevalence of gastric cancer, and may inhibit gastric precancerous lesions progression into gastric cancer. The aim of this study was to determine the effect of treatment on subsequent gastric precancerous lesion development. Materials and Methods: We prospectively studied 27 patients who had low grade dysplasia at the time of enrollment, in addition to dysplasia atrophic gastritis and intestinal metaplasia observed in all patients. All were prescribed quadruple therapy to treat H. Pylori infection for 10 days. Patients underwent endoscopy with biopsy at enrollment and then at follow up two years later. Biopsy samples included five biopsies from the antrum of lesser curvature, antrum of greater curvature, angularis, body of stomach and fundus. Results of these biopsies were compared before and after treatment. Results: Overall, the successful eradication rate after two years was 15/27 (55.6%). After antibiotic therapy, the number of patients with low grade dysplasia decreased significantly (p=0.03), also with reduction of the atrophic lesions (p=0.01), but not metaplasia. Conclusions: Treatment of H. pylori likely is an effective therapy in preventing the development of subsequent gastric premalignant lesions.
  45. Li, Jing-Rong;Wang, Jian-Qin;Gong, Qing;Fang, Rui-Hua;Guo, Yun-Long 1575
    https://doi.org/10.7314/APJCP.2015.16.4.1575 PDF KSCI
    Some microRNAs (miRNAs) have been shown to act as oncogenes or tumor suppressor genes in human melanomas. miR-328 is upregulated in blood cells of melanoma patients compared to in healthy controls. This suggests a role for miR-328 in melanoma that warrants investigation. In this study, we demonstrated miR-328 levels to be dramatically decreased in human melanoma cell lines. Moreover, forced expression of miR-328 inhibited proliferation and induced G1-phase arrest of the SK-MEL-1 melanoma cell line. We identified TGFB2 as a direct target gene for miR-328 using a fluorescent reporter assay and western blotting. Levels of TGFB2 were dramatically increased in human melanoma cell lines and were inversely correlated with the miR-328 expression level. Our findings provide new insights into the mechanisms of human melanoma development, indicating that miR-328 has therapeutic potential for this disease.
  46. Gichki, Abdul Samad;Buajeeb, Waranun;Doungudomdacha, Sombhun;Khovidhunkit, Siribang-On Pibooniyom 1581
    https://doi.org/10.7314/APJCP.2015.16.4.1581 PDF KSCI
    Human papillomaviruses (HPVs) remain a serious world health problem due to their association with cervical and head and neck cancers. While over 100 HPV types have been identified, only a few subtypes are associated with malignancies. HPV 16 and 18 are the most prevalent oncogenic types in head and neck cancers. Although it has been proven that some subsets of benign and malignant head and neck lesions are associated with HPV, the general population have very little awareness and knowledge of their association with HPV. Therefore, the purpose of this study was to determine the knowledge of HPV and its links with head and neck benign and malignant lesions in a group of Pakistani dental patients who attended the Dental Department of the Sandeman provincial hospital in Quetta, Pakistan. One hundred and ninety-two patients were recruited and requested to answer a questionnaire. It was revealed that there was a low level of knowledge about HPV and its association with head and neck benign and malignant lesions among the participants. This result suggested that more education regarding the relationship of HPV in inducing head and neck benign and malignant lesions is required in this group of patients.
  47. Zeeshan, Rozina;Irfan, Syed Mohammed;Sultan, Sadia;Bhimani, Sanjana 1587
    https://doi.org/10.7314/APJCP.2015.16.4.1587 PDF KSCI
    Background: Chronic lymphoid leukemia (CLL) is the most frequent type of adult leukemia. The Rai and Binet staging systems have been well recognized as standards for assessing the treatment requirements and overall survival in CLL patients. However, there is a need to seek newer prognostic markers to identify stable or progressive forms of CLL that will facilitate risk-adapted treatment strategies. Currently a molecular biomarker ZAP-70 has attracted interest as providing prognostic information in CLL patients. Objective: To determine the frequency of ZAP-70 positivity in B-CLL patients at disease presentation. Materials and Methods: From January 2011 to September 2014, 89 patients were diagnosed to have chronic lymphoid leukemia. Complete blood count was done on an automated analyzer (Cell Dyne, Abott Architect, USA), while immunophenotyping was conducted for each patient to establish the diagnosis of the disease. ZAP-70 expression was evaluated by flow cytometry. Data were compiled and analyzed by SPSS version 21. Results: Out of the total of 89 B-CLL patients, 62 (69.7%) were male and 27 (30.3%) were females with a male to female ratio of 2:1. The mean age was $57.5{\pm}12.1years$. The frequency of ZAP-70 positivity in our B-CLL patients was found to be 13.5%. ZAP-70 positivity was significantly correlated with stage III disease and high absolute lymphocytic count (P<0.05). No correlation of ZAP-70 could be established with age and gender (p>0.05). Conclusions: The frequency of ZAP-70 in our patients appears low. It is approximately half that in international data. We would recommend to screen all the newly diagnosed patients with CLL for ZAP-70 protein expression for risk stratification, family counseling and to predict overall survival.
  48. Health Examinees (HEXA) Study Group 1591
    https://doi.org/10.7314/APJCP.2015.16.4.1591 PDF KSCI
    Background: Korea has experienced rapid economic development in a very short period of time. A mixture of traditional and modern risk factors coexists and the rapid change in non-genetic factors interacts with genetic constituents. With consideration of these unique aspects of Korean society, a large-scale genomic cohort study-the Health Examinees (HEXA) Study-has been conducted to investigate epidemiologic characteristics, genomic features, and gene-environment interactions of major chronic diseases including cancer in the Korean population. Materials and Methods: Following a standardized study protocol, the subjects were prospectively recruited from 38 health examination centers and training hospitals throughout the country. An interview-based questionnaire survey was conducted to collect information on socio-demographic characteristics, medical history, medication usage, family history, lifestyle factors, diet, physical activity, and reproductive factors for women. Various biological specimens (i.e., plasma, serum, buffy coat, blood cells, genomic DNA, and urine) were collected for biorepository according to the standardized protocol. Skilled medical staff also performed physical examinations. Results: Between 2004 and 2013, a total of 167,169 subjects aged 40-69 years were recruited for the HEXA study. Participants are being followed up utilizing active and passive methods. The first wave of active follow-up began in 2012 and it will be continued until 2015. The principal purpose of passive follow-up is based on data linkages with the National Death Certificate, the National Cancer Registry, and the National Health Insurance Claim data. Conclusions: The HEXA study will render an opportunity to investigate biomarkers of early health index and the chronological changes associated with chronic diseases.
  49. Reddy, Vijaya Ramakrishna;Annamalai, Thangavelu;Narayanan, Vivek;Ramanathan, Arvind 1599
    https://doi.org/10.7314/APJCP.2015.16.4.1599 PDF KSCI
    Background: Epigenetic silencing of tumor suppressor genes due to promoter hypermethylation is one of the frequent mechanisms observed in cancers. Hypermethylation of several tumor suppressor genes involved in cell cycle regulation has been reported in many types of tumors including oral squamous cell carcinomas. LATS1 (Large Tumor Suppressor, isoform 1) is a novel tumor suppressor gene that regulates cell cycle progression by forming complexes with the cyclin dependent kinase, CDK1. Promoter hypermethylation of the LATS1 gene has been observed in several carcinomas and also has been linked with prognosis. However, the methylation status of LATS1 in oral squamous cell carcinomas is not known. As oral cancer is one of the most prevalent forms of cancer in India, the present study was designed to investigate the methylation status of LATS1 promoter and associate it with histopathological findings in order to determine any associations of the genetic status with stage of differentiation. Materials and Methods: Tumor chromosomal DNA isolated from biopsy tissues of thirteen oral squamous cell carcinoma biopsy tissues were subjected to digestion with methylation sensitive HpaII enzyme followed by amplification with primers flanking CCGG motifs in promoter region of LATS1 gene. The PCR amplicons were subsequently subjected to agarose gel electrophoresis along with undigested amplification control. Results: HpaII enzyme based methylation sensitive PCR identified LATS1 promoter hypermethylation in seven out of thirteen oral squamous cell carcinoma samples. Conclusions: The identification of LATS1 promoter hypermethylation in seven oral squamous cell carcinoma samples (54%), which included one sample with epithelial dysplasia, two early invasive and one moderately differentiated lesions indicates that the hypermethylation of this gene may be one of the early event during carcinogenesis. To the best of our knowledge, this is the first study to have explored and identified positive association between LATS1 promoter hypermethylation with histopathological features in oral squamous cell carcinomas.
  50. Zhou, Yuan;Jiang, Hong-Gang;Lu, Ning;Lu, Bo-Hao;Chen, Zhi-Heng 1605
    https://doi.org/10.7314/APJCP.2015.16.4.1605 PDF KSCI
    Purpose: To investigate the expression of Ki67 protein in papillary thyroid microcarcinoma(PTMC), and to analyze its clinical significance. Materials and Methods: Ki67 protein expression was evaluated in the tissues of 108 human PTMC and 50 other benign papillary hyperplasia of thyroid specimens using immunohistochemistry. Results: The expression intensity of Ki67 in PTMC and benign papillary hyperplasia of thyroid specimens were $1.45{\pm}1.83%$ and $0.46{\pm}0.46%$.The positive expression rates were 46.3% and 14%. There were significant differences between these two groups (p<0.01). There was no significant variation of the expression intensity and positive expression rates of Ki67 in PTMC with gender, age, position of the tumor and the level of TSH pre-operation (p>0.05), but these parameters varied with tumor size, invasion by membrane and cervical lymph node metastasis (p<0.05 or p<0.01). Conclusions: The expression of Ki67 in PTMC was related to tumor size, invasion by membrane and cervical lymph node metastasis, and could be the important indicator for judging clinical progress and estimating prognosis.
  51. Chatchotikawong, Usanee;Ruengkhachorn, Irene;Leelaphatanadit, Chairat;Phithakwatchara, Nisarat 1609
    https://doi.org/10.7314/APJCP.2015.16.4.1609 PDF KSCI
    Purpose: To determine the rate of lymph node metastasis, oncologic and pregnancy outcomes in apparent early-stage malignant ovarian germ cell tumor (MOGCT). Materials and Methods: Medical records of apparent early-stage MOGCT patients undergoing primary surgical treatment at Siriraj Hospital, Bangkok, Thailand, between January 2006 and December 2013, were retrospectively reviewed. Results: Thirty-eight patients had apparent stage I-II MOGCT. The mean age was $22.1{\pm}7.7years$ (median, 20.8 years; range, 7.7-35.6 years). The mean tumor size was $17.8{\pm}6.5cm$ with a median of 20 (range 4-30) cm. Three most common histopathologies were dysgerminoma (12 patients, 31.6%), immature teratoma (12 patients, 31.6%), and endodermal sinus tumor (6 patients, 15.8%). Twenty-seven of 38 patients underwent lymphadenectomy; 13 patients (48.2%) were stage IA and 8 patients (29.6%) were stage IC. The rate of retroperitoneal nodes metastasis was 7.4% (2/27 patients). At 26.1 months of median follow-up time (range 1.9-88.5 months), 9 patients retained fertility functions, with uneventful pregnancies in 3 of these. Only one patient (2.6%) had progression of disease at 4.9 months after surgery. The 5-year survival rate was 97.4%. Conclusion: As the rate of pelvic or para-aortic node metastasis in MOGCT is considerable, lymphadenectomy should be incorporated in surgical staging procedures.
  52. Balasubramanian, Anandh;Subramaniam, Ramkumar;Narayanan, Vivek;Annamalai, Thangavelu;Ramanathan, Arvind 1615
    https://doi.org/10.7314/APJCP.2015.16.4.1615 PDF KSCI
    Background: Promoter hypermethylation mediated gene silencing of tumor suppressor genes is considered as most frequent mechanism than genetic aberrations such as mutations in the development of cancers. BRD7 is a single bromodomain containing protein that functions as a subunit of SWI/SNF chromatin-remodeling complex to regulate transcription. It also interacts with the well know tumor suppressor protein p53 to trans-activate genes involved in cell cycle arrest. Loss of expression of BRD7 has been observed in breast cancers and nasopharyngeal carcinomas due to promoter hypermethylation. However, the genetic status of BRD7 in oral squamous cell carcinomas (OSCCs) is not known, although OSCC is one of the most common among all reported cancers in the Indian population. Hence, in the present study we investigated OSCC samples to determine the occurrence of hypermethylation in the promoter region of BRD7 and understand its prevalence. Materials and Methods: Genomic DNA extracted from biopsy tissues of twenty three oral squamous cell carcinomas were digested with methylation sensitive HpaII type2 restriction enzyme that recognizes and cuts unmethylated CCGG motifs. The digested DNA samples were amplified with primers flanking the CCGG motifs in promoter region of BRD7 gene. The PCR amplified products were analyzed by agarose gel electrophoresis along with undigested amplification control. Results: Methylation sensitive enzyme technique identified methylation of BRD7 promoter region seventeen out of twenty three (74%) well differentiated oral squamous cell carcinoma samples. Conclusions: The identification of BRD7 promoter hypermethylation in 74% of well differentiated oral squamous cell carcinomas indicates that the methylation dependent silencing of BRD7 gene is a frequent event in carcinogenesis. To the best of our knowledge, the present study is the first to report the occurrence of BRD7and its high prevalence in oral squamous cell carcinomas.
  53. Fathollahzade, Abazar;Rahmani, Azad;Dadashzadeh, Abbas;Gahramanian, Akram;Esfahani, Ali;Javanganji, Leila;Nabiolahi, Leila 1621
    https://doi.org/10.7314/APJCP.2015.16.4.1621 PDF KSCI
    Background: Financial distress due to the cost of cancer treatments is prevalent among cancer patients. Identifying the level of financial distress and its affecting factors has an important role in providing supportive services. Accordingly, the aims of this study were to determine these parameters among Iranian cancer patients. Materials and Methods: This descriptive-correlational study was undertaken among 262 cancer patients admitted to both private and public hospitals in East Azerbaijan province, Iran. The financial distress/financial well being scale was used to determine financial distress. The data were analyzed using SPSS software using descriptive and inferential statistics (multiple linear regression). Results: Among the 262 cancer patients, 57.3% were male and their mean age was 47.0 years. The mean score for financial distress was 4.12 (2.01). The final regression model demonstrated that the independent variables (predictors) of income less than living expenses, income equal to living expenses, having an employed spouse in governmental job and living with parents, with regression coefficients of -1.029, -0.515, 0.198, and 0.096, respectively, were predictors of financial distress among cancer patients. These variables accounted for 50% of changes in variance of financial distress. Conclusions: Iranian cancer patients have moderate to high levels of financial distress. Considering policies for managing direct and indirect costs of cancer treatments must be followed.
  54. Mohaghegh, Pegah;Yavari, Parvin;Akbari, Mohammad Esmail;Abadi, Alireza;Ahmadi, Farzane 1627
    https://doi.org/10.7314/APJCP.2015.16.4.1627 PDF KSCI
    Background: Stage at diagnosis is one of the most important prognostic factors of breast cancer survival. Because in the breast cancer case this may vary with socioeconomic characteristics, this study was performed to recognize the relationship between demographic and socioeconomic factors with stage at diagnosis in Iran. Materials and Methods: This cross-sectional, descriptive study conducted on 526 patients suffering from breast cancer and registered in Cancer Research Center of Shahid Beheshti University of Medical Sciences from 2008 to 2013. A reliable and valid questionnaire about family levels of socioeconomic status filled in by interviewing the patients via phone. For analyzing the data, Multinomial logistic regression, Kendal tau-b correlation coefficient and Contingency Coefficient tests were executed by SPSS22. Economic status, educational attainment of patient and household head and/or a combination of these were considered as parameters for socioeconomic status. First, the relationship between stage at diagnosis and demographic and socioeconomic status was assessed in univariate analysis then these relationships assessed in two different models of multinomial logistic regression. Results: The mean age of the patients was 48.3 (SD=11.4). According to the results of this study, there were significant relationships between stage at diagnosis of breast cancer with patient education (p=0.011), living place (p=0.044) and combined socioeconomic status (p=0.024). These relationships persisted in multiple multinomial logistic regressions. Other variables, however, had no significant correlation. Conclusions: Patient education, combined socioeconomic status and living place are important variables in stage at diagnosis of breast cancer in Iranian women. Interventions have to be applied with the aim of raising women's accessibility to diagnostic and medical facilities and also awareness in order to reducing delay in referring. In addition, covering breast cancer screening services by insurance is recommended.
  55. Ekambaram, Varadharajan;Velayudham, Ramasubramanian;Swaminathan, Shiyama;Loganathan, Padmanabhan;Swaminathan, Vijaya 1633
    https://doi.org/10.7314/APJCP.2015.16.4.1633 PDF KSCI
    Background: The advantages of Rapid Arc plans versus Intensity modulated radiotherapy plans for Carcinoma left breast were analyzed. Materials and Methods: In this study 20 Post mastectomy carcinoma left breast patients were analyzed. Both Intensity modulated Radiotherapy and Rapid Arc plans were generated for these patients. IMRT plans with 7 beams in an arc fashion and VMAT plans with two semi arcs were made to achieve 95% dose coverage to 100% volume. The plans were evaluated using Dose volume Histograms. Results: The mean Conformity and Homogeneity index in VMAT is found to be 1.05 and 0.065 respectively whereas in IMRT it was 1.07 and 0.069. The 20% volume of Heart received a mean dose of 960cGy in VMAT and 1300cGy in IMRT. The mean dose was 1236cGy in VMAT and 1870cGy in IMRT. The ipsilateral Lung received 3395cGy to 5% volume and 1840cGy to 20% volume on an average and the mean dose was 1205cGy in VMAT, while the same were found to be 3525cGy, 2012cGy and 1435cGy respectively in IMRT. The Contralateral Lung received a mean dose of 505cGy in VMAT and 553cGy in IMRT. The mean Monitor units in VMAT were 512MU and 1170MU in IMRT. The NTID in VMAT is $108.8{\times}10^5Gycm^3$ and $110.1{\times}10^5Gycm^3$ in IMRT. Conclusions: The target coverage, homogeneity and Conformity index were better in VMAT plans. The Ipsilateral Lung and heart dose were very less in VMAT plans. The Contralateral Lung dose and the Normal Tissue Integral Dose were also lesser in VMAT plans however the difference is not very appreciable. The MU in VMAT plans is almost 50% that of the IMRT plans which results in the reduction of treatment time. On the whole VMAT proves to be a better modality for treating Ca. Left Breast Patients.
  56. Ma, Long;Zhu, Wen-Zhen;Liu, Ting-Ting;Fu, Hui-Ling;Liu, Zhao-Jun;Yang, Bing-Wu;Song, Tai-Yu;Li, Guo-Rong 1637
    https://doi.org/10.7314/APJCP.2015.16.4.1637 PDF KSCI
    Background: RhoGTPase-activating proteins (RhoGAPs) regulate RhoGTPases in cells, but whether individual reactive oxygen species (ROS) regulate RhoGAPs is unknown. Our previous published papers have shown that deleted in liver cancer 1 (DLC1) inhibits cancer cell migration by its RhoGAP activity. The present study was designed to explore the role of $H_2O_2$ in regulation of DLC1. Materials and Methods: We treated cells with $H_2O_2$ for 24h and phenotypic changes were analyzed by MTT, RT-PCR, Western blotting, immunofluorescence staining and wound healing assays. Results: $H_2O_2$ downregulated cyclin D1 and cyclin E to inhibit proliferation, and upregulated BAX to induce apoptosis in MCF-7 cells. Compared with non-tumorigenic cells, $H_2O_2$ increased expression of DLC1 and reduced activity of RhoA in cancer cells. Stress fiber production and migration were also suppressed by $H_2O_2$ in MDA-MB-231 cells. Conclusions: Our study suggests that $H_2O_2$ inhibits proliferation through modulation of cell cycle and apoptosis-related genes, and inhibits migration by decreasing stress fibers via DLC1/RhoA signaling.
  57. Ulas, Arife;Kos, Tugba;Avci, Nilufer;Cubukcu, Erdem;Olmez, Omer Fatih;Bulut, Nilufer;Degirmenci, Mustafa 1643
    https://doi.org/10.7314/APJCP.2015.16.4.1643 PDF KSCI
    Background: The aim of the present study was to evaluate clinicopathological characteristics of our early stage breast cancer patients who are epidermal growth factor receptor 2 (HER2) overexpressed/amplified (HER2+), the efficacy of trastuzumab treatment and survival results. Materials and Methods: Patients with HER2-positive early stage breast cancer receiving adjuvant trastuzumab were investigated retrospectively. Clinicopathological features of 210 patients and treatment outcome were analysed. To evaluate survival rates, the Kaplan-Meier method was used. Univariate and multivariate analyses were conducted with the Cox regression model. Results: Mean age of the patients was 51.8, 71.9% being postmenopausal. Some 37.6% of patients were node negative, and 31% had T1 tumor size and 52.4% were positive for estrogen receptor. Of 210 patients, 89.5% completed planned 52 weeks adjuvant trastuzumab treatment. The median follow up was 27.5 months (6.0-86.0). Relapse free survival (RFS) was 68.0 months (95% CI: 62.1-74.0) and overall survival (OS) was 74.8 months (95% CI: 69.5-80.1). The 3 year OS for all patients was 92.0% and RFS was 79.6%. During follow up, relapse was detected at the rate of 14.3%. Trastuzumab associated cardiotoxicity was found at the rate of 3.3%. In univariate analyses, larger tumor size and grade III were significantly associated (p<0.05) with RFS. Multivariate analyses of covariates displaying p<0.05 identified grade III as an independent prognostic factor. Conclusions: In the present study, it was established that trastuzumab had a satisfactory safety profile and treatment efficacy as in other clinical studies and that among clinicopathological factors evaluated, only being grade 3 had a significant effect on RFS. The occurrence of relapse with adjuvant trastuzumab makes it necessary to identify molecular predictors, which will define this group better and help explain resistance to anti HER2 based therapies.
  58. Yilmaz, Latif;Borazan, Ersin;Aytekin, Turkan;Baskonus, Ilyas;Aytekin, Alper;Oztuzcu, Serdar;Bozdag, Zehra;Balik, Ahmet 1651
    https://doi.org/10.7314/APJCP.2015.16.4.1651 PDF KSCI
    UGT1A play important roles in the glucuronidation of a variety of endogenous and exogenous compounds. UGT1A isoforms are expressed tissue specifically. The aim of this study was to examine the relationship between UGT1A3 and UGT1A7 mRNA expression and pancreatic cancer. Paired healthy and tumor tissue samples of 43 patients with pancreatic cancer were included in this study. UGT1A3 and UGT1A7 mRNA expressions were analyzed by real time-PCR. In the result of study, UGT1A3 and UGT1A7 mRNA expressions were significantly higher in tumor tissue than normal tissue of pancreatic cancer patients (p<0.05). In addition, high mRNA expression of UGT1A3 and UGT1A7 was significantly associated with larger tumor size (p<0.05). The data suggested that UGT1A3 and UGT1A7 may play roles in the progression of pancreatic cancer. Consequently, UGT1A3 and UGT1A7 are potential prognostic indicators.
  59. Ismail, Saber;Mayah, Wael;Battia, Hassan El;Gaballah, Hanaa;Jiman-Fatani, Asif;Hamouda, Hala;Afifi, Mohamed A.;Elmashad, Nehal;Saadany, Sherif El 1657
    https://doi.org/10.7314/APJCP.2015.16.4.1657 PDF KSCI
    Background: Early diagnosis of hepatocellular carcinoma (HCC) is the most important step in successful treatment. However, it is usually rare due to the lack of a highly sensitive specific biomarker so that the HCC is usually fatal within few months after diagnosis. The aim of this work was to study the role of plasma nuclear factor kappa B (NF-${\kappa}B$) and serum peroxiredoxin 3 (PRDX3) as diagnostic biomarkers for early detection of HCC in a high-risk population. Materials and Methods: Plasma nuclear factor kappa B level (NF-${\kappa}B$) and serum peroxiredoxin 3 (PRDX3) levels were measured using enzyme linked immunosorbent assay (ELISA), in addition to alpha-fetoprotein (AFP) in 72 cirrhotic patients, 64 patients with HCC and 29 healthy controls. Results: NF-${\kappa}B$ and PRDX3 were significantly elevated in the HCC group in relation to the others. Higher area under curve (AUC) of 0.854 (for PRDX3) and 0.825 (for NF-${\kappa}B$) with sensitivity of 86.3% and 84.4% and specificity of 75.8% and 75.4% respectively, were found compared to AUC of alpha-fetoprotein (AFP) (0.65) with sensitivity of 72.4% and specificity of 64.3%. Conclusions: NF-${\kappa}B$ and PRDX3 may serve as early and sensitive biomarkers for early detection of HCC facilitating improved management. The role of nuclear factor kappa B (NF-${\kappa}B$) as a target for treatment of liver fibrosis and HCC must be widely evaluated.
  60. Liu, Qian;Bi, Jian-Jun;Tian, Yan-Tao;Feng, Qiang;Zheng, Zhao-Xu;Wang, Zheng 1665
    https://doi.org/10.7314/APJCP.2015.16.4.1665 PDF KSCI
    Background: The optimal surgical strategy for the treatment of synchronous resectable gastric cancer liver metastases remains controversial. The aims of this study were to analyze the outcome and overall survival of patients presenting with gastric cancer and liver metastases treated by simultaneous resection. Materials and Methods: Between January 1990 and June 2009, 35 patients diagnosed with synchronous hepatic metastases from gastric carcinoma received simultaneous resection of both primary gastric cancer and synchronous hepatic metastases. The clinicopathologic features and the surgical results of the 35 patients were retrospectively analyzed. Results: The 5-year overall survival rate after surgery was 14.3%. Five patients survived for more than 5 years after surgery. No mortality has occurred within 30 days after resection, although two patients (5.7%) developed complications during the peri-operative course. Univariate analysis revealed that patients with the presence of lymphovascular invasion of the primary tumor, bilateral liver metastasis and multiple liver metastases suffered poor survival. Lymphovascular invasion by the primary lesion and multiple liver metastases were significant prognostic factors that influenced survival in the multivariate analysis (p=0.02, p=0.001, respectively). Conclusions: The presence of lymphovascular invasion of the primary tumor and multiple liver metastases are significant prognostic determinants of survival. Gastric cancer patients without lymphovascular invasion and with a solitary synchronous liver metastasis may be good candidates for hepatic resection. Simultaneous resection of both primary gastric cancer and synchronous hepatic metastases may effectively prolong survival in strictly selected patients.
  61. Qureshi, Muhammad Zahid;Romero, Mirna Azalea;Attar, Rukset;Javed, Zeeshan;Farooqi, Ammad Ahmad 1671
    https://doi.org/10.7314/APJCP.2015.16.4.1671 PDF KSCI
    Cancer genomics and proteomics have undergone considerable broadening in the past decades and increasingly it is being realized that solid/liquid phase microarrays and high-throughput resequencing have provided platforms to improve our existing knowledge of determinants of cancer development, progression and survival. Loss of apoptosis is a widely and deeply studied process and different approaches are being used to restore apoptosis in resistant cancer phenotype. Modulating the balance between pro-apoptotic and anti-apoptotic proteins is essential to induce apoptosis. It is becoming more understood that pharmacological inhibition of the proteasome might prove to be an effective option in improving TRAIL induced apoptosis in cancer cells. Keeping in view rapidly accumulating evidence of carcinogenesis, metastasis, resistance against wide ranging therapeutics and loss of apoptosis, better knowledge regarding tumor suppressors, oncogenes, pro-apoptotic and anti-apotptic proteins will be helpful in translating the findings from benchtop to bedside.
  62. Caramel, Simone;Marchionni, Marco;Stagnaro, Sergio 1675
    https://doi.org/10.7314/APJCP.2015.16.4.1675 PDF KSCI