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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 15 Issue 10

  1. Cihan, Yasemin Benderli;Ozturk, Ahmet;Arslan, Alaettin;Deniz, Kemal;Baran, Munevver;Karaca, Halit 4117
    https://doi.org/10.7314/APJCP.2014.15.10.4117 PDF KSCI
    Background: To determine prognostic value of excision repair cross-complementation 1 (ERCC1) in patients with malignant pleural mesothelioma (MPM). Materials and Methods: The study included 60 patients with MPM who were diagnosed and treated in the Radiation Oncology Department of Kayseri Teaching Hospital and Medical Oncology Department of Erciyes University, Medicine School between 2005 and 2013. By using immunohistochemical methods, ERCC1 expression in biopsy specimens was evaluated. We retrospectively assessed whether there is a correlation between ERCC1 and response to anti-neoplastic therapy or survival. Results: There were 50 men and 10 women with median age of 62 years (range: 39-83). Histological type was epithelial mesothelioma in the majority of the cases (85%), most commonly presenting in stage four. Of the cases, 20 (33%) received radiotherapy, 60 (%100) received first-line chemotherapy and 15 (%25) received second-line chemotherapy. In the assessment after therapy, it was found that there was partial response in 12 cases (20%), stable disease in 19 cases (31.4%) and progression in 25 cases (41.7%). ERCC1 was positive in 43% of the cases. Mean OS was 11.7 months and mean DFS was 9.5 months in ERCC1-positive cases regardless of therapy, while they were 19.2 months and 17.1 months in ERCC1-negative cases, respectively. The difference was found to be significant (p<0.05). In univariate analysis, stage, comorbidity, response to treatment and ERCC1 expression were found to be significantly associated with OS (p=0.083; p=0.043; p=0.041; p=0.050). In multivariate analysis, response to treatment remained to be significant for OS (p=0.005). In univariate and multivariate analyses, response to treatment and ERCC1 were found to be significantly associated with DFS (p=0.049; p=0.041). Conclusions: ERCC1 was identified as poor prognostic factor in patients with MPM.
  2. An, Wan-Xin;Fan, Ya-Xin;Liang, Xiao-Hua;Liu, Hui 4125
    https://doi.org/10.7314/APJCP.2014.15.10.4125 PDF KSCI
    The median ages at death from cancers between 1985 and 2005 were calculated to demonstrate that inherent anticancer mechanisms may be a common pathway for different cancers. Seventy-eight patients with gastric, liver and lung cancers, were recruited in the solid cancer group. The leukemia group consisted of 31 patients with three main types of leukemia. The controls were 100 healthy individuals. The samples were typed using an HLA-DR/DQ PCR-SSP typing kit. The results showed that the median ages at death from all causes were 64.7 years in 1985 and 70.1 years in 2005. The range of the median ages at death from all cancers was similar to the corresponding value for deaths attributed to all causes. The frequency of $DRB1^*03$ was 9.6% in the solid cancer group and 3.0% in the control group (p<0.05). The frequency of $DRB1^*04$ in the leukemia group were significantly lower than that of the control (p<0.05). $DRB1^*13$ and $DRB1^*06$ frequencies in the leukemia group were significantly higher than those of the controls (p<0.05). It is suggested that inherent anti-cancer mechanisms may be a common pathway for different cancers and are associated with the immune system and HLA.
  3. Peng, Yong;Guo, Cong-Shan;Li, Pan-Xia;Fu, Zhan-Zhao;Gao, Li-Ming;Di, Ya;Ju, Ya-Kun;Tian, Ru;Xue, Jia-Jia 4129
    https://doi.org/10.7314/APJCP.2014.15.10.4129 PDF KSCI
    Background: The objective was to study the effect of Scutellaria baicalensis Georgi ethanol extracts (SBGE) on immune and anti-oxidant function in U14 tumor-bearing mice. Materials and Methods: U14 tumor-bearing mice were randomly divided into eight groups: a control group, a cyclophosphamide (CTX) group, three dose groups of SBGEI (high, medium, low), and three dose groups of SBGEII (high, medium, low). After two weeks, the thymus and spleen weight indices of mice bearing U14 cervical cancer were calculated. Enzyme linked immunosorbent assays (ELISA) was used to determine the levels of serum IL-2, TNF-${\alpha}$, IL-8, and PCNA. MDA activity and SOD activity in plasma were measured with detection kits. Results: In the SBGE groups, thymus weight and spleen weight indices of U14 tumor-bearing mice were significantly higher than in the control group or CTX group (p<0.05). Compared to control group, the levels of serum IL-2 and TNF-${\alpha}$ in U14 tumor-bearing mice increased significantly, whereas the contents of serum IL-8 and PCNA decreased (p<0.05). The activity of SOD increased with the growing dose of SBGE, while the activity of MDA decreased significantly in the highe-rdose groups of SBGE. Conclusions: These findings suggested that SBGE, especially at high dose, 1000 mg/kg, showed significant immune and anti-oxidant effects infU14 tumor-bearing mice, which might be the mechanisms of SBGE inhibition of tumor growth.
  4. Rushatamukayanunt, Pradit;Morita, Kei-Ichi;Matsukawa, Sho;Harada, Hiroyuki;Shimamoto, Hiroaki;Tomioka, Hirofumi;Omura, Ken 4135
    https://doi.org/10.7314/APJCP.2014.15.10.4135 PDF KSCI
    Background: Human papillomaviruses (HPV) may play an important role as one of the possible etiologies of oral squamous cell carcinoma (OSCC). The present study aimed to investigate the association between HPV and OSCC in young Japanese patients by examining the presence of HPV DNA and surrogate markers in OSCC tissues. Materials and Methods: Forty young patients with OSCC whose surgical specimens were available were analyzed and compared with 40 patients randomly recruited from a pool of patients aged >40 years. HPV DNA was detected using the polymerase chain reaction-based AMPLICOR$^{(R)}$ HPV test, and surrogate markers of HPV infection were analyzed using immunohistochemical techniques to detect $p16^{INK4a}$ and p53. Results: Only two (5%) young patients and one (2.5%) older patient were positive for HPV DNA. $p16^{INK4a}$ overexpression was identified in six (15%) young patients. p53 staining levels were not high in tissues of most young patients (27 patients, 67.5%). HPV DNA status did not significantly correlate with $p16^{INK4a}$ expression levels. Profiles of increased levels of $p16^{INK4a}$ expression with diminished levels of p53 staining were not associated with the presence of HPV DNA. The combined p53 with $p16^{INK4a}$ profiles were significantly correlated with alcohol consumption in younger patients (p=0.006). Conclusions: Results of the present study indicate that HPV is less likely to cause OSCC in young Japanese patients, and the $p16^{INK4a}$ expression level is not an appropriate surrogate marker for HPV infection in OSCC.
  5. Cheung, Min Rex 4143
    https://doi.org/10.7314/APJCP.2014.15.10.4143 PDF KSCI
    Background: This study used receiver operating characteristic curve to analyze Surveillance, Epidemiology and End Results (SEER) Ewing sarcoma (ES) outcome data. The aim of this study was to identify and optimize ES-specific survival prediction models and sources of survival disparities. Materials and Methods: This study analyzed socio-economic, staging and treatment factors available in the SEER database for ES. 1844 patients diagnosed between 1973-2009 were used for this study. For the risk modeling, each factor was fitted by a Generalized Linear Model to predict the outcome (bone and joint specific death, yes/no). The area under the receiver operating characteristic curve (ROC) was computed. Similar strata were combined to construct the most parsimonious models. Results: The mean follow up time (S.D.) was 74.48 (89.66) months. 36% of the patients were female. The mean (S.D.) age was 18.7 (12) years. The SEER staging has the highest ROC (S.D.) area of 0.616 (0.032) among the factors tested. We simplified the 4-layered risk levels (local, regional, distant, un-staged) to a simpler non-metastatic (I and II) versus metastatic (III) versus un-staged model. The ROC area (S.D.) of the 3-tiered model was 0.612 (0.008). Several other biologic factors were also predictive of ES-specific survival, but not the socio-economic factors tested here. Conclusions: ROC analysis measured and optimized the performance of ES survival prediction models. Optimized models will provide a more efficient way to stratify patients for clinical trials.
  6. Lasrado, Savita;Moras, Kuldeep;Pinto, George Jawahar Oliver;Bhat, Mahesh;Hegde, Sanath;Sathian, Brijesh;Luis, Neil Aaron 4147
    https://doi.org/10.7314/APJCP.2014.15.10.4147 PDF KSCI
    Standard therapy for advanced head and neck cancer consists of a combination of surgery and radiation. However, survival of this patient population has not improved during the past 20 years. Many different multimodality treatment schedules have been proposed, and chemotherapy is often used with the intent of organ preservation. The present study was intended to establish the efficacy of concomitant chemoradiation with a single agent carboplatin in advanced head and neck cancers.The objectives were to investigate the feasibility of concomitant administration of carboplatin, monitor acute toxicity during radiotherapy, and determine subacute side effects, such as wound healing following surgery after chemoradiotherapy. A prospective study was conducted wherein a total of 40 patients with stage III and IV squamous cell carcinomas of oral cavity, oropharynx, hypopharynx and larynx were enrolled. All patients were treated with external beam radiotherapy and weekly carboplatin area under curve (AUC of 5). Radiotherapy was given in single daily fractions of 1.8-2 grays (Gy) to a total dose of 66-72 Gy. Salvage surgery was performed for any residual or recurrent locoregional disease. Neck dissection was recommended for all patients with neck disease showing less than a complete response after chemoradiation. A total of 40 patients were enrolled of whom 32 were males and 8 were females. Highest incidence of cancer was seen in the 5th-6th decades of life with a median age of 47.7 years. Oropharyngeal tumours constituted a maximum of 21 patients followed by hypopharynx in 10, larynx in 7 and oral cavity in 2. 80% of the patients had a neck node on presentation of which 40% had N2-N3 nodal status. TNM staging revealed that 58% of patients were in stage III and 43% in stage IV. Evaluation of acute toxicity revealed that 50% had grade II mucositis, 25% grade III mucositis, 2.5% grade IV mucositis. 50% of patients had grade I skin reactions, 65% of patients had grade I thrombocytopenia, and 24% of patients had grade I anaemia. After completion of treatment 65% of patients had complete response at the primary and regional sites, and 35% of patients had a partial response of whom 23% underwent neck dissection and 5% of them underwent salvage surgery at the primary site. At the end of one year there were six deaths and four recurrences and 70% were free of disease. Concurrent chemoradiation with carboplatin provided good locoregional control for locally advanced head and neck cancers. This regimen, although toxic, is tolerable with appropriate supportive intervention. Primary site conservation is possible in many patients. Chemoradiotherapy appears to have an emerging role in the primary management of head and neck cancers.
  7. Wu, Guo-Qiu;Liu, Nan-Nan;Xue, Xiu-Lei;Cai, Li-Ting;Zhang, Chen;Qu, Qing-Rong;Yan, Xue-Jiao 4153
    https://doi.org/10.7314/APJCP.2014.15.10.4153 PDF KSCI
    Background: This study was aimed to establish a novel method to simultaneously detect expression of four genes, ribonucleotide reductase subunit M1(RRM1), X-ray repair cross-complementing gene 1 (XRCC1), thymidylate synthase (TS) and class III ${\beta}$-tubulin (TUBB3), and to assess their application in the clinic for prediction of response of non-small cell lung cancer (NSCLC) to chemoradiotherapy. Materials and Methods: We have designed four gene molecular beacon (MB) probes for multiplex quantitative real-time polymerase chain reactions to examine RRM1, XRCC1, TUBB3 and TS mRNA expression in paraffin-embedded specimens from 50 patients with advanced or metastatic carcinomas. Twenty one NSCLC patients receiving cisplatin-based first-line treatment were analyzed. Results: These molecular beacon probes could specially bind to their target genes in homogeneous solutions. Patients with low RRM1 and XRCC1 mRNA levels were found to have apparently higher response rates to chemoradiotherapy compared with those with high levels of RRM1 and XRCC1 expression (p<0.05). The TS gene expression level was not significantly associated with chemotherapy response (p>0.05). Conclusions: A method of simultaneously detecting four molecular markers was successfully established and applied for evaluation of chemoradiotherapy response. It may be a useful tool in personalized cancer therapy.
  8. Zhang, Jie;Qi, Hui-Wei;Zheng, Hui;Chen, Mo;Zhu, Jun;Xie, Hui-Kang;Ni, Jian;Xu, Jian-Fang;Zhou, Cai-Cun 4159
    https://doi.org/10.7314/APJCP.2014.15.10.4159 PDF KSCI
    Background: The aim of this study was to evaluate the efficacy of alternating etoposide-cisplatin and vinorelbine-cisplatin (EP-NP) compared with an etoposide-cisplatin (EP) regimen for advanced combined small cell carcinomas. Materials and Methods: Histologically confirmed combined small cell carcinoma patients who met the inclusion criteria were randomly assigned (1:1) into either the EP-NP setting (group A) or the EP setting (group B). The primary endpoint was progression-free survival in patients who received at least one dose of treatment. Results: Eighty-two patients entered into this trial, 42 in group A and 40 in group B. The objective response rates in group A and group B were 42.9% and 32.5%, respectively (p=0.334). Survival analysis showed that median progression-free survival was 6.1 months in group A, which was significantly longer than the 4.1 months in group B (p=0.041). However, as to overall survival, no significant difference was found between the two groups (11.0 vs 10.1 months in groups A and B, respectively, p=0.545). No unexpected side effects were observed in either group. Conclusions: The EP-NP regimen for combined small cell carcinomas prolonged progressio-nfree survival compared with the EP regimen. Further clinical investigations are warranted.
  9. Mutlu, Hasan;Akca, Zeki;Erden, Abdulsamet;Aslan, Tuncay;Ucar, Kadir;Kaplan, Bunyamin;Buyukcelik, Abdullah 4165
    https://doi.org/10.7314/APJCP.2014.15.10.4165 PDF KSCI
    Background: The prognosis of primary glioblastoma (GBM) is poor. Approximately 2/3 of primary brain tumor diagnoses are GBM, of which 95% are primary lesions. In this study, we aimed to evaluate whether more sunlight exposure has an effect on survival of patients with primary GBM. Materials and Methods: A total of 111 patients with primary GBM were enrolled from Kayseri in inner Anatolia which has a cold climate (n: 40) and Mersin in Mediterranean region with a warm climate and more sunlight exposure (n: 71). The patients with primary GBM were divided into two groups as Kayseri and Mersin and compared for progression free survival (PFS) and overall survival (OS).Results: The PFS values were 7.0 and 4.7 months for Kayseri and Mersin groups, respectively (p=0.10) and the repsective OS values were 13.3 and 9.4 months (p=0.13). We did not found any significant difference regarding age, sex, comorbidity, smoking, surgery, resurgery, adjuvant chemoradiotherapy and palliative chemotherapy between the groups. Conclusions: We found that more sunlight exposure had no impact on prognosis of patients with primary GBM, adding inconsistency to the literature about the relationship between sunlight and GBM.
  10. Senturk, Aysegul;Babaoglu, Elif;Kilic, Hatice;Hezer, Habibe;Dogan, Hayriye Tatli;Hasanoglu, Hatice Canan;Bilaceroglu, Semra 4169
    https://doi.org/10.7314/APJCP.2014.15.10.4169 PDF KSCI
    Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is highly accurate in diagnosing mediastinal lymphadenopathies of lung cancer and benign disorders. However, the utility of EBUS-TBNA in the diagnosis of mediastinal lymphomas is unclear. The aim of this study was to determine the diagnostic value of EBUS-TBNA in patients with suspected lymphoma. Materials and Methods: Sixty-eight patients with isolated mediastinal lymphadenopathy and suspected of lymphoma were included in the study. EBUS-TBNA was performed on outpatients under moderate sedation. The sensitivity, specificity, negative predictive value and diagnostic accuracy of EBUS-TBNA were calculated. Results: Sixty-four patients were diagnosed by EBUS-TBNA, but four patients with non-diagnostic EBUS-TBNA required surgical procedures. Thirty-five (51.5%) patients had sarcoidosis, six (8.8%) had reactive lymphadenopathy, nine (13.3%) had tuberculosis, one (1.5%) had squamous cell carcinoma, two (2.9%) had sarcoma and fifteen (22%) had lymphoma (follicular center cell, large B-cell primary, and Hodgkin lymphomas in three, two, and ten, respectively). Of the 15 lymphoma patients, thirteen were diagnosed by EBUS and two by thoracotomy and mediastinoscopy. The sensitivity, specificity, negative predictive value, and diagnostic accuracy of EBUS-TBNA for the diagnosis of lymphoma were calculated as 86.7%, 100%, 96.4%, and 97%, respectively. Conclusions: EBUS-TBNA can be employed in the diagnosis of mediastinal lymphoma, instead of more invasive surgical procedures.
  11. Albasri, Abdulkader;El-Siddig, Abeer;Hussainy, Akbar;Mahrous, Mervat;Alhosaini, Abdulaziz Abdullah;Alhujaily, Ahmed 4175
    https://doi.org/10.7314/APJCP.2014.15.10.4175 PDF KSCI
    Aims: To delineate the histopathological pattern of prostate diseases and to highlight age variations in prostate specific antigen (PSA) values and histopathological features. Materials and Methods: A retrospective review was made of all prostate biopsy reports seen between January 2006 and December 2013 at the King Fahad Hospital, Madinah, Saudi Arabia. Prostate lesions were tabulated and classified into benign and malignant groups. Histological scoring of adenocarcinomas was accomplished using the Gleason system. PSA values were correlated with Gleason scores. Results: Of 417 prostate lesions reviewed, 343 (82.3%) were benign and 74 (17.7%) were malignant, giving a benign to malignant ratio of 4.6:1. Benign prostatic hyperplasia (both with and without inflammation) was the commonest prostatic lesion and accounted for 80.3% of all cases and 97.6% of all benign cases. The age range was 20 to 97 years with a mean of 69.2 years and a peak age group at 70-79 years. Seventy one cases of adenocarcinoma accounted for 95.9% of the total of 74 malignant tumors. It showed an age range of 44 to 95 years, a mean age of 70.9 years and peak prevalence in the 80-89 year age group. Gleason score seven was the most frequent (39.4%) in occurrence. Most adenocarcinomas, 41 cases (57.7%), were moderately differentiated (Gleason score of 5-7). PSA values ranged widely between 16-1,865ng/ml with a mean of 363.4ng/ml. Elevated PSA (>100ng/ml) levels were found in 53 (81.6%) patients. There was a statistically significant positive correlation between serum PSA level and Gleason score (p=0.0304). Conclusions: Prostatic lesions constitute a significant source of morbidity among adult males in Madinah. Benign prostatic hyperplasia was the commonest benign prostatic lesion and adenocarcinoma was the commonest histological subtype of prostatic cancer.
  12. Zhu, Ping;Fu, Ju-Fang;Wang, Bo;Lin, Jing;Wang, Yan;Fang, Ning-Ning;Wang, Dan-Dan 4181
    https://doi.org/10.7314/APJCP.2014.15.10.4181 PDF KSCI
    Background: The aim of this study was to describe the characteristics of male spouse caregivers of breast cancer patients in China, assess their quality of life (QOL), and investigate the influencing factors. Materials and Methods: A total of 243 breast cancer patient-spouse caregiver dyads were recruited from four hospitals in Shanxi and Anhui province of China. A cross-sectional design was applied to collect data and the Chinese version of the Medical Outcomes Study 36-item Short Form (SF-36) was used to measure caregivers' QOL, and the Chinese version of M.D. Anderson Symptom Inventory (MDASI-C) was applied to measure patient symptom severity and interference. Pearson's correlation was used to examine the correlations between caregiver burden and QOL. The multiple regression analysis was used to determine the most predictive factors influencing QOL. Results: The scores of all SF-36 scales were above 50.0, which were much lower than that of general mainland Chinese males. Mental QOL was significantly worse than physical QOL. Spouses demographic characteristics, caregiving-related variables and patient symptoms were related to spouse QOL. Caregiver burden has a negative relationship with QOL. Conclusions: A decrease in life events and patient symptoms, as well as increase in spouse sleeping time and family income, ought to improve QOL.
  13. Wang, Chao;Ma, Hong-Xi;Jin, Mei-Shan;Zou, Ya-Bin;Teng, Yong-Liang;Tian, Zhuang;Wang, Hai-Ying;Wang, Yin-Ping;Duan, Xiu-Mei 4187
    https://doi.org/10.7314/APJCP.2014.15.10.4187 PDF KSCI
    Matrix metalloproteinase (MMP)-2 and MMP-9 are important proteases involved in invasion and metastasis of various tumors. Extra-gastrointestinal stromal tumors (EGISTs) are rare neoplasms. This study was performed to assess MMP-2 and MMP-9 expression in EGIST tissue samples for association with clinicopathological data from the patients. Twenty-one surgical EGIST tissue specimens were collected for analysis of MMP-2 and MMP-9 expression using immunohistochemistry. MMP-2 and MMP-9 proteins were expressed in all of the epithelial cell types of EGISTs, whereas they were only expressed in 75% of the spindle cell type, although there was no statistically significant difference (p>0.05). Expression of MMP-2 and MMP-9 proteins was associated with tumor size, mitotic rate, tumor necrosis, and distant metastasis (p<0.05). MMP-2 expression was linked with MMP-9 levels (p<0.05). However, there was no correlation between MMP-9 expression and age, sex, primary site, or cell morphology in any of these 21 EGIST patients (p>0.05). Moreover, expression of MMP-2 and MMP-9 proteins increased with the degree of EGIST risk. This study provided evidence of an association of MMP-2 and MMP-9 expression with advanced EGIST behavior.
  14. Suprasert, Prapaporn;Apichartpiyakul, Chatchawann;Sakonwasun, Choompone;Nitisuwanraksa, Pimonphan;Phuackchantuck, Rochana 4193
    https://doi.org/10.7314/APJCP.2014.15.10.4193 PDF KSCI
    Lingzhi or Ganoderma lucidum is a popular medicinal mushroom used as a health promotion herb in China and other Asian countries for thousands of years. There have many previous studies about the anti-cancer effects of lingzhi especially in vitro. The present study reports the clinical data of 5 gynecologic cancer patients who achieved stability in the disease after ingestion of lingzhi in the form of fruit body water extract and spores in a salvage setting. This report has been written to enhance the data describing the effect of lingzhi in cancer patients.
  15. Ekalaksananan, Tipaya;Malat, Praphatson;Pientong, Chamsai;Kongyingyoes, Bunkerd;Chumworathayi, Bandit;Kleebkaow, Pilaiwan 4197
    https://doi.org/10.7314/APJCP.2014.15.10.4197 PDF KSCI
    Minor trauma to the uterine cervix is supposed to induce local immunity to prevent cervical lesions caused by human papillomavirus (HPV) infection. This study aimed to investigate the local cervical immunity in women with low grade squamous intraepithelial lesion (LSIL) and effects of abrasion after cryosurgery or Pap smear. One hundred women with LSIL and known results of HPV detection were recruited. HPV positive women were randomly divided according to abrasion into cryotherapy and Pap smear observation groups. Cervical tissues and cervico-vaginal lavage (CVL) were collected at 6 and 12 months after allocation. The levels of cytokines at first recruitment were compared with cytokine levels at 6 months after abrasions. The mRNA of IFN-${\gamma}$, TNF-${\alpha}$ and IL-10 in cervical tissues and these cytokines secreted in CVL were determined using real time PCR and ELISA, respectively. Anti-HPV16 IgG and IgA antibodies in CVL were assessed by western blotting. At first recruitment of women with LSIL (100 cases), IL-10 mRNA and cytokine in HPV positive group (60 cases) was significantly higher than negative group (40 cases). IFN-${\gamma}$ and TNF-${\alpha}$ mRNA level in both groups were comparable but their secretions in CVL were significantly increased in HPV negative group. After abrasion for 6 months in HPV-positive women, all mRNA and secreted cytokines were changed, but no significant difference was observed between cryotherapy and observation groups. When individuals were compared between first recruitment and after abrasion for 6 months, IFN-${\gamma}$ mRNA and anti-HPV16 L1 IgA antibodies were significantly increased in the cryotherapy group. The results suggest that modulation of local cervical immunities by abrasion might promote different effects in clearance of HPV-related cytological abnormalities.
  16. Guzel, Ali Irfan;Kokanali, Mahmut Kuntay;Erkilinc, Selcuk;Topcu, Hasan Onur;Oz, Murat;Ozgu, Emre;Erkaya, Salim;Gungor, Tayfun 4203
    https://doi.org/10.7314/APJCP.2014.15.10.4203 PDF KSCI
    Purpose: The objective of this study was to assess the predictive role of the neutrophil/lymphocyte ratio (NLR) for invasion of gestational trophoblastic disease (GTD). Materials and Methods: A retrospective analysis was conducted on 127 women who were managed at our clinic for GTD. Of all patients, 8 showed invasion according to histological examination. The clinical parameters of patients with invasive GTD (Group 1; n=8) were compared with patients who showed no invasion (Group 2; n=119). All underwent a prior uterine evacuation and followed up by regular assessment of ${\beta}$-hCG titers. Results: Demographic and obstetric history and pre-evacuation hCG levels of the patients showed no statistically significantly difference between the groups (p>0.05). The mean gestational weeks (GW), size of the GTD and NLR levels were statistically significantly higher in the invasive GTD group (p<0.05). Correlations between invasion and gestational weeks, size of GTD, post-evacuation chemotherapy and NLR were evident. ROC curve analysis demonstrated that GW, size of GTD and NLR may be discriminative parameters in predicting invasion of GTD. Conclusions: To the best of our knowledge, this is the first study evaluating the predictive role of NLR in invasion of GTD. In conclusion, we think that pretreatment NLR can be used as a biomarker of invasion in GTD.
  17. Zhou, Cheng-Jiang;Zhang, Liu-Wei;Gao, Fang;Zhang, Bin;Wang, Ying;Chen, Da-Fang;Jia, Yan-Bin 4207
    https://doi.org/10.7314/APJCP.2014.15.10.4207 PDF KSCI
    Several lines of evidence suggest that genetic variation in MUC5AC gene might contribute to the risk of gastric cancer. We conducted a case-control study to evaluate the relationship between common genetic variations in MUC5AC gene and non-cardia gastric cancer using an LD-based tagSNP approach in Baotou, north-western China. We genotyped 12 tagSNPs by TaqMan method among 288 cases with non-cardia gastric cancer and 281 normal controls. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for non-cardia gastric cancer risk in association with alleles, genotypes and haplotypes. We observed that the frequencies of rs3793964 C allele and rs11040869 A allele were significantly lower in cases than in controls. Meanwhile, minor allele homozygotes of rs3793964 and rs11040869 were significantly associated with a decreased risk of non-cardia gastric cancer when compared with their major allele homozygotes. Furthermore, a statistically significantly protective effect of rs885454 genotypes on non-cardia gastric cancer was also observed (for CT vs. CC: OR=0.581, 95%CI=0.408-0.829; for CT/TT vs. CC: OR=0.623, 95%CI=0.451-0.884). Our results indicated that some common genetic variations in the MUC5AC gene might have effects on the risk of non-cardia gastric cancer in our studied population.
  18. Mu, Hui-Jun;Zou, Jian;Xie, Ping;Xu, Zhuo-Qun;Ruan, Jun;Yang, Shu-Dong;Yin, Ying 4211
    https://doi.org/10.7314/APJCP.2014.15.10.4211 PDF KSCI
    Background: Although roles of genetic polymorphisms of leptin receptor (LEPR) gene in several cancers have been documented, the association between polymorphisms of LEPR and clear cell renal cell carcinoma (CC-RCC) remains unknown. The aim of this study was to explore any relation. Materials and Methods: The study population consisted of 77 patients with CC-RCC and 161 healthy control subjects. Polymorphism analyses of Lys109Arg and Gln223Arg were performed by direct DNA sequencing and PCR-restriction fragment length polymorphism approaches respectively. Results: Comparisons of allelic and genotypic frequencies in Lys109Arg and Gln223Arg showed no significant difference between the cases and controls. However, when evaluating the combined genotype of Lys109Arg and Gln223Arg, risk with GG/GG was increased (OR=1.85, 95%CI=1.04-3.30) and with GA/GG or GG/GA was decreased (OR=0.07, 95%CI=0.01-0.54; OR and 95%CI of the latter could not be calculated for a value of zero). Furthermore, the G-G haplotype frequency of Lys109Arg and Gln223Arg in the cases was higher (OR=1.68; 95%CI=1.02-2.76). In contrast, the A-G and G-A haplotype frequencies in the cases were lower than those in the controls (OR=0.06; 95%CI=0.01 to 0.47; OR and 95%CI of the latter could not be calculated for a value of zero). In addition, the Lys109Arg A allele was in LD with the Gln223Arg A allele (d'=0.9399) in the CC-RCC subjects, but not in the controls. Conclusions: Our data suggest that the GG/GG combined genotype and G-G haplotype of Lys109Arg and Gln223Arg can act as evaluating factors for CC-RCC risk.
  19. Subimerb, Chutima;Wongkham, Chaisiri;Khuntikeo, Narong;Leelayuwat, Chanvit;McGrath, Michael S.;Wongkham, Sopit 4217
    https://doi.org/10.7314/APJCP.2014.15.10.4217 PDF KSCI
    Cholangiocarcinoma (CCA), a slow growing but highly metastatic tumor, is highly prevalent in Northeast Thailand. Specific tests that predict prognosis of CCA remain elusive. The present study was designed to investigate whether peripheral blood leukocyte (PBL) transcriptional profiles might be of use as a prognostic test in CCA patients. Gene expression profiles of PBLs from 9 CCA and 8 healthy subjects were conducted using the Affymetrix HG_U133 Plus 2.0 GeneChip. We indentified informative PBLs gene expression profiles that could reliably distinguish CCA patients from healthy subjects. Of these CCA specific genes, 117 genes were up regulated and 60 were down regulated. The molecular and cellular functions predicted for these CCA specific genes according to the Gene Ontology database indicated differential PBL expression of host immune response and tumor progression genes (EREG, TGF ${\beta}1$, CXCL2, CXCL3, IL-8, and VEGFA). The expression levels of 9 differentially expressed genes were verified in 36 CCA vs 20 healthy subjects. A set of three tumor invasion related genes (PLAU, CTSL and SERPINB2) computed as "prognostic index" was found to be an independent and statistically significant predictor for CCA patient survival. The present study shows that CCA PBLs may serve as disease predictive clinically accessible surrogates for indentifying expressed genes reflective of CCA disease severity.
  20. Cihan, Yasemin Benderli;Arslan, Alaettin;Cetindag, Mehmet Faik;Mutlu, Hasan 4225
    https://doi.org/10.7314/APJCP.2014.15.10.4225 PDF KSCI
    Aim: To determine prognostic value of blood parameters on overall and progression-free survival in cases received adjuvant radiotherapy and chemotherapy with diagnosis of stage I-III breast cancer. Materials and Methods: We retrospectively reviewed files of 350 patients with non-metastatic breast cancer who were treated in the Radiation Oncology Department of Kayseri Teaching Hospital between 2005 and 2010. Pretreatment white blood cell (WBC), neutrophil, monocyte, basophil and eosinophil counts, and the neutrophil/lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) were recorded. The relationship between clinicopathological findings and blood parameters was assessed. Results: Overall, 344 women and 6 men were recruited. Median age was $55.3{\pm}0.3$ years (range: 22-86). Of the cases, 243 (61.4%) received radiotherapy while 329 (94.3%), received chemotherapy and 215 (61.4%) received hormone therapy. Mean overall survival (OS) and progression-free survival (PFS) was 84.4 and 78.8 months, respectively. During follow-up, 48 patients died due to either disease-related or non-related causes. Local recurrence was detected in 14 cases, while distant metastasis was noted in 45 cases. In univariate analysis, age, pathology, perinodal invasion were significantly associated with overall survival, whereas gender, stage and hormone therapy were significantly associated with progression-free survival. In multivariate analysis, histopathological diagnosis (OR: 0.3; 95%: 0.1-0.7; p=0.006) and perinodal invasion (OR: 0.1; 95% CI: 0.1-1.3; p=0.026) were significantly associated with overall survival, whereas tumor stage (OR: 2.1; 95% CI: 0.0-0.7; p=0.014) and hormone therapy (OR: 2.1; 95%: 1.2-3.8; p=0.010) were significantly associated with progression-free survival. Conclusions: It was found that serum inflammatory markers including WBC, neutrophil, lymphocyte and monocyte counts, and NLR and PLR had no effect on prognosis in patients with breast cancer who underwent surgery and received adjuvant radiotherapy and chemotherapy.
  21. Cihan, Yasemin Benderli 4233
    https://doi.org/10.7314/APJCP.2014.15.10.4233 PDF KSCI
    Background: The aim of this study was to investigate the relationship of body mass index with overall and progression-free survival as well as other prognostic factors of breast cancer in patients with non-metastatic breast cancer. Materials and Methods: We retrospectively reviewed 456 patients diagnosed with breast cancer in the Radiation Oncology department of Kayseri Teaching Hospital between 2005 and 2013. We investigated relationship of body mass index with prognosis and other prognostic factors. Results: The study included 456 patients (447 women and 9 men). Mean age at presentation was 55.6 years. Of the cases, 96.9% underwent modified radical mastectomy and 95.0% received chemotherapy, while 82.4% received radiotherapy and 60.0% were given hormone therapy. Body mass index was >25 mg/kg2 in 343 cases. Five- and 10-years overall survival rates were 77% and 58% whereas progression-free survival rates were 65% and 49%, respectively. In univariate analyses, factors including stage (p=0.046), tumor diameter (p=0.001), lymph node metastasis (p=0.006) and body mass index (p=0.030) were found to be significantly associated with overall survival, while perinodal involvement was found to be significantly associated with progression-free survival (p=0.018). In multivariate analysis, stage (p=0.032; OR: 3.8; 95% CI: 1.1-13), tumor diameter (p<0.000; OR: 0.0; 95% CI: 0.0-0.3), lymph node metastasis (p=0.005; OR: 0.0; 95% CI: 0.0-0.5) and BMI (p=0.027; OR: 0.02; 95% CI: 0.0-0.8) remained as significantly associated with OS. Conclusions: In our study, it was seen that overall survival time was shorter in underweight and obese patients when compared to normal weight patients.
  22. Pei, Chang-Song;Wu, Hong-Yan;Fan, Fan-Tian;Wu, Yi;Shen, Cun-Si;Pan, Li-Qun 4239
    https://doi.org/10.7314/APJCP.2014.15.10.4239 PDF KSCI
    Background: This study investigated the influence of curcumin on HOX transcript antisense RNA (HOTAIR)-mediated migration of cultured renal cell carcinoma (RCC) cells. Materials and Methods: Five RCC cell lines (769-P, 769-P-vector, 769-P-HOTAIR, 786-0, and Kert-3 ) were maintained in vitro. The expression of HOTAIR mRNA was determined by quantitative real-time PCR and cell migration was measured by transwell migration assay. The effects of different concentrations of curcumin (0 to $80{\mu}mol/L$) on cell proliferation was determined by the CCK-8 assay and influence of non-toxic levels (0 to $10{\mu}M$) on the migration of RCC cells was also determined. Results: Comparison of the 5 cell lines indicated a correlation between HOTAIR mRNA expression and cell migration. In particular, the migration of 769-P-HOTAIR cells was significantly higher than that of 769-P-vector cells. Curcumin at $2.5-10{\mu}M$ had no evident toxicity against RCC cells, but inhibited cell migration in a concentration-dependent manner. Conclusions: HOTAIR expression is correlated with the migration of RCC cells, and HOTAIR may be involved in the curcumin-induced inhibition of RCC metastasis.
  23. Sun, Pan;Hu, Jun-Wei;Xiong, Wu-Jun;Mi, Jun 4245
    https://doi.org/10.7314/APJCP.2014.15.10.4245 PDF KSCI
    Emerging evidence has suggested that glycolysis is enhanced in cancer-associated fibroblasts (CAF), and miR-186 is downregulated during the CAF formation. However, it is not clear whether miR-186 is involved in the regulation of glycolysis and what the role of miR-186 plays during the CAF formation. In this study, quantitative PCR analysises show miR-186 is downregulated during the CAF formation. Moreover, miR-186 targets the 3' UTR of Glut1, and its overexpression results in the degradation of Glut1 mRNA, which eventually reduces the level of Glut1 protein. On the other hand, knockdown of miR-186 increased the expression of Glut1. Both time course and dose response experiments also demonstrated that the protein and mRNA levels of Glut1 increase during CAF formation, according to Western blot and quantitative PCR analyses, respectively. Most importantly, besides the regulation on cell cycle progression, miR-186 regulates glucose uptake and lactate production which is mediated by Glut1. These observations suggest that miR-186 plays important roles in glycolysis regulation as well as cell cycle checkpoint activation.
  24. Goksu, Sema Sezgin;Gunduz, Seyda;Unal, Dilek;Uysal, Mukremin;Arslan, Deniz;Tatli, Ali Murat;Bozcuk, Hakan;Ozdogan, Mustafa;Coskun, Hasan Senol 4251
    https://doi.org/10.7314/APJCP.2014.15.10.4251 PDF KSCI
    Background: Treatment of anemia is an important issue in the palliative care setting. Blood transfusion is generally used for this purpose in supportive care. However the place of blood transfusion in terminally ill cancer cases is less far established. Objective: We aimed to outline the use of transfusions and to find the impact of blood transfusion on survival in patients with advanced cancer and very near to death. Design: Patients dying in 2010-2011 with advanced cancer were included in the study. We retrospectively collected the data including age, type of cancer, the duration of last hospitalisation, ECOG performance status, Hb levels, transfusion history of erythrocytes and platelets, cause and the amount of transfusion. The anaemic patients who had transfusion at admission were compared with the group who were not transfused. Survival was defined as the time between the admission of last hospitalisation period and death. Results: Three hundred and ninety eight people with solid tumours died in 2010-2011 in our clinic. Ninety percent of the patients had anemia at the time of last hospitalisation. One hundred fifty three patients had erythrocyte transfusion at admission during the last hospitalisation period (38.4%). In the anaemic population the duration of last hospitalisation was longer in patients who had erythrocyte transfusion (15 days vs 8 days, p<0.001). Conclusions: Patients who had blood transfusion at the end of life lived significantly longer than the anaemic patients who were not transfused. This study remarks that blood transfusions should not be withheld from terminal cancer patients in palliative care.
  25. Azam, Rosa;Ghafouri-Fard, Soudeh;Tabrizi, Mina;Modarressi, Mohammad-Hossein;Ebrahimzadeh-Vesal, Reza;Daneshvar, Maryam;Mobasheri, Maryam Beigom;Motevaseli, Elahe 4255
    https://doi.org/10.7314/APJCP.2014.15.10.4255 PDF KSCI
    Lactobacilli are probiotics shown to have antitumor activities. In addition, they can regulate gene expression through epigenetic mechanisms. In this study, we aimed to assess anti tumor activities of Lactobacillus acidophilus and Lactobacillus crispatus on the MDA-MB-231 breast cancer cell line. The effects of culture supernatants were determined by MTT [3-(4,5-dimethylthiazol-2-y-2,5-diphenyltetrazolium bromide] assay. Changes in expression of 5 cancer-testis antigens (CTAs), namely AKAP4, ODF4, PIWIL2, RHOXF2 and TSGA10, were analyzed by quantitative real time RT-PCR. The culture supernatants of the 2 lactobacilli inhibited MDA-MB-231 cell proliferation. In addition, transcriptional activity of all mentioned CTAs except AKAP4 was significantly decreased after 24 hour treatment with culture supernatants. This study shows that Lactobacillus acidophilus and Lactobacillus crispatus have antiproliferative activity against MDA-MB-231 cells. In addition, these lactobacilli could decrease transcriptional activity of 4 CTAs. Previous studies have shown that expression of CTAs is epigenetically regulated, so it is possible that lactobacilli cause this expression downregulation through epigenetic mechanisms. As expression of CTAs in cancers is usually associated with higher grades and poor prognosis, downregulation of their expression by lactobacilli may have clinical implications.
  26. Ng, Chong Guan;Mohamed, Salina;Wern, Tai Yi;Haris, Azwa;Zainal, Nor Zuraida;Sulaim, Ahmad Hatim 4261
    https://doi.org/10.7314/APJCP.2014.15.10.4261 PDF KSCI
    Objective: To examine the prescription rates in cancer patients of three common psychotropic drugs: anxiolytic/hypnotic, antidepressant and antipsychotic. Materials and Methods: In this retrospective cohort study, data were extracted from the pharmacy database of University Malaya Medical Center (UMMC) responsible for dispensing records of patients stored in the pharmacy's Medication Management and Use System (Ascribe). We analyzed the use of psychotropics in patients from the oncology ward and cardiology from 2008 to 2012. Odds ratios (ORs) were adjusted for age, gender and ethnicity. Results: A total of 3,345 oncology patients and 8,980 cardiology patients were included. Oncology patients were significantly more often prescribed psychotropic drugs (adjusted OR: anxiolytic/hypnotic=5.55 (CI: 4.64-6.63); antidepressants=6.08 (CI: 4.83-7.64) and antipsychotics=5.41 (CI: 4.17-7.02). Non-Malay female cancer patients were at significantly higher risk of anxiolytic/hypnotic use. Conclusions: Psychotropic drugs prescription is common in cancer patients. Anxiolytic/hypnotic prescription rates are significantly higher in non-Malay female patients in Malaysia.
  27. Tong, Gui-Xian;Cheng, Jing;Chai, Jing;Geng, Qing-Qing;Chen, Peng-Lai;Shen, Xin-Rong;Liang, Han;Wang, De-Bin 4265
    https://doi.org/10.7314/APJCP.2014.15.10.4265 PDF KSCI
    Purpose: This study aimed at summarizing epidemiological evidence of the association between gestational diabetes mellitus (GDM) and subsequent risk of cancer. Materials and Methods: We searched Medline, Embase, Cancer Lit and CINAHL for epidemiological studies published by February 1, 2014 examining the risk of cancer in patients with history of GDM using highly inclusive algorithms. Information about first author, year of publication, country of study, study design, cancer sites, sample sizes, attained age of subjects and methods used for determining GDM status were extracted by two researchers and Stata version 11.0 was used to perform the meta-analysis and estimate the pooled effects. Results: A total of 9 articles documented 5 cohort and 4 case-control studies containing 10,630 cancer cases and 14,608 women with a history of GDM were included in this review. Taken together, the pooled odds ratio (OR) between GDM and breast cancer risk was 1.01 (0.87-1.17); yet the same pooled ORs of case-control and cohort studies were 0.87 (0.71-1.06) and 1.25 (1.00-1.56) respectively. There are indications that GDM is strongly associated with higher risk of pancreatic cancer (HR=8.68) and hematologic malignancies (HR=4.53), but no relationships were detected between GDM and other types of cancer. Conclusions: Although GDM increases the risk of certain types of cancer, these results should be interpreted with caution becuase of some methodological flaws. The issue merits added investigation and coordinated efforts between researchers, antenatal clinics and cancer treatment and registration agencies to help attain better understanding.
  28. Han, Rong-Fei;Ji, Xiang;Dong, Xing-Gao;Xiao, Rui-Jing;Liu, Yan-Ping;Xiong, Jie;Zhang, Qiu-Ping 4271
    https://doi.org/10.7314/APJCP.2014.15.10.4271 PDF KSCI
    The epithelial to mesenchymal transition (EMT) is a key step during embryonic morphogenesis and plays an important role in drug resistance and metastasis in diverse solid tumors. We previously reported that 48 h treatment of anti-cancer drug doxorubicin could induce EMT in human gastric cancer BGC-823 cells. However, the long term effects of this transient drug treatment were unknown. In this study we found that after 48 h treatment with $0.1{\mu}g/ml$ doxorubicin, most cells died during next week, while a minor population of cells survived and formed colonies. We propagated the surviving cells in drug free medium and found that these long term cultured drug survival cells (abbreviated as ltDSCs) retained a mesenchymal-like cell morphology, and expressed high levels of EMT-related molecules such as vimentin, twist and ${\beta}$-catenin. The expression of chromatin reprogramming factors, Oct4 and c-myc, were also higher in ltDSCs than parental cells. We further demonstrated that the protein level of p300 was upregulated in ltDSCs, and inhibition of p300 by siRNA suppressed the expression of vimentin. Moreover, the ltDSCs had higher colony forming ability and were more drug resistant when compared to parental cells. Our results suggested that an epigenetic mechanism is involved in the EMT of ltDSCs.
  29. Shawky, Abd El-Aty;El-Hafez, Amal Abd;El-Tantawy, Dina;Hamdy, Rasha 4275
    https://doi.org/10.7314/APJCP.2014.15.10.4275 PDF KSCI
    Background: The aim of this work is to assess the frequency of BRCA1 protein immunohistochemical (IHC) expression in epithelial ovarian cancer (EOC) and to evaluate the association of BRCA1 expression with clinical and pathological characteristics and the overall survival (OS) of patients treated with postoperative platinum-based chemotherapeutic agents. Materials and Methods: This retrospective study was conducted on 35 cases of epithelial ovarian cancer selected from the files of the Pathology Department, Faculty of Medicine, Mansoura University, Egypt. Immunohistochemistry (IHC) was performed for BRCA1 gene protein. BRCA1 expression was compared to patient's age, tumor histology, grade, stage and OS time. Statistical analysis was carried out with the SPSS version 16.0 to assess significant associations. Results: BRCA1 nuclear expression was detected in 40% of EOC, in which a mild increase in the percentage of positive cases was observed with serous histology, stage IV, and grade 3 carcinomas. There was a significant statistical difference in BRCA1 expression with regard to histological subtypes of EOC (p=0.048), but not grade or stage. Mean OS and survival rate were slightly better for BRCA1 expressing group, but there was no statistically significant difference (p=0.528). Conclusions: No association between BRCA1 immunohistochemical expression and tumor grade, stage or overall survival was noted in platinum-treated epithelial ovarian cancer patients.
  30. Haroun, Riham Abdel-Hamid;Zakhary, Nadia Iskandar;Mohamed, Mohamed Ragaa;Abdelrahman, Abdelrahman Mohamed;Kandil, Eman Ibrahim;Shalaby, Kamal Ali 4281
    https://doi.org/10.7314/APJCP.2014.15.10.4281 PDF KSCI
    Background: Methylation of tumor suppressor genes has been investigated in all kinds of cancer. Tumor specific epigenetic alterations can be used as a molecular markers of malignancy, which can lead to better diagnosis, prognosis and therapy. Therefore, the aim of this study was to evaluate the association between gene hypermethylation and expression of fragile histidine triad (FHIT), glutathione S-transferase P1 (GSTP1) and p16 genes and various clinicopathologic characteristics in primary non-small cell lung carcinomas (NSCLC). Materials and Methods: The study included 28 primary non-small cell lung carcinomas, where an additional 28 tissue samples taken from apparently normal safety margin surrounding the tumors served as controls. Methylation-specific polymerase chain reaction (MSP) was performed to analyze the methylation status of FHIT, GSTP1 and p16 while their mRNA expression levels were measured using a real-time PCR assay with SYBR Green I. Results: The methylation frequencies of the genes tested in NSCLC specimens were 53.6% for FHIT, 25% for GSTP1, and 0% for p16, and the risk of FHIT hypermethylation increased among patients with NSCLC by 2.88, while the risk of GSTP1 hypermethylation increased by 2.33. Hypermethylation of FHIT gene showed a highly significant correlation with pathologic stage (p<0.01) and a significant correlation with smoking habit and FHIT mRNA expression level (p<0.05). In contrast, no correlation was observed between the methylation of GSTP1 or p16 and smoking habit or any other parameter investigated (p>0.05). Conclusions: Results of the present study suggest that methylation of FHIT is a useful biomarker of biologically aggressive disease in patients with NSCLC. FHIT methylation may play a role in lung cancer later metastatic stages while GSTP1 methylation may rather play a role in the early pathogenesis.
  31. Kurtuncu, Meltem;Akhan, Latife Utas;Celik, Sevecen;Alkan, Isin 4289
    https://doi.org/10.7314/APJCP.2014.15.10.4289 PDF KSCI
    Background: One of the most important reasons for the high mortality rates of cancer is the low level of awareness, which can lead to a late diagnosis and treatments starting too late. Therefore, it is necessary for individuals, especially at younger age, to gain awareness and integrate taking the necessary precautions into their lifestyle in order to prevent cancer and ensure early diagnosis. The aim of this study was to assess the levels of awareness of factors for major cancers among students studying in two different campuses of a university in the Western Black Sea Region. Materials and Methods: This descriptive/cross-sectional study was performed between January-March 2014. Students studying in the 2013-2014 academic year in a university in the Western Black Sea Region in two separate campuses were the subjects. Results: The mean age was $21.01{\pm}3.63$. While female students (51.2%) were the majority in the health sciences campus (74.8%), male students (48.8%) were the majority in the social sciences campus (76.5%). Some 9.6% of the students from the health sciences campus and 12.4% of the students from the social sciences campus thought that cancer was communicable, while most of the students from both campuses knew that smoking caused cancer. It can also be seen that the rate of answering questions regarding cancer correctly was higher among students studying in the health sciences campus. Conclusions: It was determined that students who do not study at the health sciences campus have insufficient information on cancer, cancer symptoms, and the possibility of breast cancer in males and approximately half of them regarded obesity as a risk factor for cancer.
  32. Zhang, Xing-Mao;Wang, Zheng;Ma, Sheng-Hui;Zhou, Zhi-Xiang 4295
    https://doi.org/10.7314/APJCP.2014.15.10.4295 PDF KSCI
    Background: Surgery offers the only potential for cure and long-term survival of recurrence of rectal cancer. Few studies about laparoscopic recurrent lesion resection have been reported. This study was designed to evaluate the safety and feasibility of laparoscopic abdomino-perineal resection for anastomotic recurrence of rectal cancer. Materials and Methods: Data for 42 patients with recurrence of rectal cancer were collected retrospectively. Of the 42 patients, 22 underwent laparoscopic surgery (LR group) and 20 received open surgery (OR group). Outcomes between the two groups were compared. Results: Operation time in LR group was shorter compared with the OR group ($164.6{\pm}27.7min$ vs $203.0{\pm}45.3min$); intra-operative blood loss was $119.7{\pm}44.4ml$ and $185.0{\cdot}94.0ml$ in LR group and OR group, respectively (p<0.001); time to first flatus in LR group was shorter than in OR group, and the difference was statistically significant ($2.6{\pm}0.8$ days vs $3.1{\pm}0.8$ days, p=0.013); hospital stay in the LR and OR groups was $8.6{\pm}1.3$ days and $9.8{\pm}2.2$ days; 3-year survival rates in the LR and OR groups were 44.4% and 42.8% (p=0.915) and the 3-year disease-free survival rates were 36.4% and 30.0%, respectively (p=0.737). Conclusions: Laparoscopic abdomino-perineal resection is safe and feasible for anastomotic recurrence of rectal cancer.
  33. Chen, Shao-Jun 4301
    https://doi.org/10.7314/APJCP.2014.15.10.4301 PDF KSCI
    Tanshinone IIA is a pharmacologically active ingredient extracted from Danshen, a Chinese traditional medicine. Its molecular mechanisms are still unclear. The present study utilized computational approaches to uncover the potential targets of this compound. In this research, PharmMapper server was used as the inverse docking tool andnd the results were verified by Autodock vina in PyRx 0.8, and by DRAR-CPI, a server for drug repositioning via the chemical-protein interactome. Results showed that the retinoic acid receptor alpha ($RAR{\alpha}$), a target protein in acute promyelocytic leukemia (APL), was in the top rank, with a pharmacophore model matching well the molecular features of Tanshinone IIA. Moreover, molecular docking and drug repurposing results showed that the complex was also matched in terms of structure and chemical-protein interactions. These results indicated that $RAR{\alpha}$ may be a potential target of Tanshinone IIA for APL. The study can provide useful information for further biological and biochemical research on natural compounds.
  34. Yuan, Ping;Chen, Tie-Hui;Chen, Zhong-Wu;Lin, Xiu-Quan 4307
    https://doi.org/10.7314/APJCP.2014.15.10.4307 PDF KSCI
    Purpose: To calculate the probability of one person's life-time death caused by a malignant tumor and provide theoretical basis for cancer prevention. Materials and Methods: The probability of one person's death caused by a tumor was calculated by a probability additive formula and based on an abridged life table. All data for age-specific mortality were from the third retrospective investigation of death cause in China. Results: The probability of one person's death caused by malignant tumor was 18.7% calculated by the probability additive formula. On the same way, the life-time death probability caused by lung cancer, gastric cancer, liver cancer, esophageal cancer, colorectal and anal cancer were 4.47%, 3.62%, 3.25%, 2.25%, 1.11%, respectively. Conclusions: Malignant tumor is still the main cause of death in one's life time and the most common causes of cancer death were lung, gastric, liver, esophageal, colorectal and anal cancers. Targeted forms of cancer prevention and treatment strategies should be worked out to improve people's health and prolong life in China. The probability additive formula is a more scientific and objective method to calculate the probability of one person's life-time death than cumulative death probability.
  35. El-Kassas, Hala Yassin;El-Sheekh, Mostafa M. 4311
    https://doi.org/10.7314/APJCP.2014.15.10.4311 PDF KSCI
    Background: Nano-biotechnology is recognized as offering revolutionary changes in the field of cancer therapy and biologically synthesized gold nanoparticles are known to have a wide range of medical applications. Materials and Methods: Gold nanoparticles (GNPs) were biosynthesized with an aqueous extract of the red alga Corallina officinalis, used as a reducing and stabilizing agent. GNPs were characterized using UV-Vis spectroscopy, transmission electron microscopy (TEM), energy dispersive analysis (EDX) and Fourier transform infra-red (FT-IR) spectroscopy and tested for cytotoxic activity against human breast cancer (MCF-7) cells cultured in Dulbecco's modified Eagle medium supplemented with 10% fetal bovine serum, considering their cytotoxicty and effects on cellular DNA. Results: The biosynthesized GNPs were $14.6{\pm}1nm$ in diameter. FT-IR analysis showed that the hydroxyl functional group from polyphenols and carbonyl group from proteins could assist in formation and stabilization. The GNPs showed potent cytotoxic activity against MCF-7 cells, causing necrosis at high concentrations while lower concentrations were without effect as indicated by DNA fragmentation assay. Conclusions: The antitumor activity of the biosynthesized GNPs from the red alga Corallina officinalis against human breast cancer cells may be due to the cytotoxic effects of the gold nanoparticles and the polyphenolcontent of the algal extract.
  36. Malik, Manzoor Ahmad;Umar, Meenakshi;Gupta, Usha;Zargar, Showkat Ali;Mittal, Balraj 4319
    https://doi.org/10.7314/APJCP.2014.15.10.4319 PDF KSCI
    Background: Phospholipase C epsilon 1 (PLCE1) encodes a member of the phospholipase family of proteins that play crucial roles in carcinogenesis and progression of several cancers including esophageal cancer (EC). In two large scale genome-wide association studies (GWAS) single nucleotide polymorphisms (SNP, rs2274223A>G, rs3765524C>T) in PLCE1 were identified as novel susceptibility loci of esophageal cancer (EC) in China. The aim of the present study was to investigate this finding in Kashmir Valley, a high risk area. Materials and Methods: We determined genotypes of three potentially functional SNPs (rs2274223A>G, rs3765524C>T and rs7922612C>T) of PLCE1 in 135 EC patients, and 195 age and gender matched controls in Kashmiri valley by PCR RFLP method. Risk for developing EC was estimated by binary logistic regression using SPSS. Results: The selected PLCE1 polymorphisms did not show independent association with EC. However, the $G_{2274223}T_{3765524}T_{7922612}$ haplotype was significantly associated with increased risk of EC (OR=2.92; 95% CI=1.30-6.54; p=0.009). Smoking and salted tea proved to be independent risk factors for EC. Conclusions: Genetic variations in PLCE1 modulate risk of EC in the high risk Kashmiri population.
  37. Kavarodi, Abdul Majeed;Thomas, Mary;Kannampilly, Johnny 4325
    https://doi.org/10.7314/APJCP.2014.15.10.4325 PDF KSCI
    Background: The expatriate population in Qatar largely comprises workers from the Indian subcontinent which has a very high rate of oral malignancy. Social and cultural habits and as well premalignant risk factors in this population remain prevalent even after migration. Materials and Methods: This cross sectional study assessed the prevalence of risk factors and occurrence of oral precancerous lesions in a low income group expatriate community from the Indian subcontinent residing in Qatar. Results: Among the 3,946 participants screened for oral premalignant lesions 24.3% (958) were smokers and 4.3 % (169) were pan chewers while 6.3% (248) were users of both smoked and smokeless forms of tobacco. Significantly higher proportion of industrial laborers (49.9%) followed by drivers (24.1%) were found to be smokers (p=0.001). The prevalence of white lesions was higher in smokers versus non-smokers 3.5% versus 2.3% (p=0.111), however this difference was statistically non-significant. Red and white lesions were highly significant (i.e. 1.2 % and 10.9% respectively) in the subjects with pan chewing and smoking habits (p=0.001). A significant proportion (8.9%) of the subjects with pan chewing habit showed evidence of oral precancerous lesions (p=0.001). Conclusions: Even though smoking and pan chewing were two significant risk factors detected in this population, their prevalence and occurrence of premalignant lesions are low as compared to the studies conducted in their home countries.
  38. Zhang, Song;Huang, Wei-Bin;Wu, Li;Wang, Lai-You;Ye, Lian-Bao;Feng, Bing-Hong 4331
    https://doi.org/10.7314/APJCP.2014.15.10.4331 PDF KSCI
    $N^1$-(2, 5-dimethoxyphenyl)-$N^8$-hydroxyoctanediamide (N25) is a novel SAHA cap derivative of HDACi, with a patent (No. CN 103159646). This invention is a hydroxamic acid compound with a structural formula of $RNHCO(CH_2)6CONHOH$ (wherein R=2, 5dimethoxyaniline), a pharmaceutically acceptable salt which is soluble. In the present study, we investigated the effects of N25 with regard to drug distribution and molecular docking, and anti-proliferation, apoptosis, cell cycling, and $LD_{50}$. First, we designed a molecular approach for modeling selected SAHA derivatives based on available structural information regarding human HDAC8 in complex with SAHA (PDB code 1T69). N25 was found to be stabilized by direct interaction with the HDAC8. Anti-proliferative activity was observed in human glioma U251, U87, T98G cells and human lung cancer H460, A549, H1299 cells at moderate concentrations ($0.5-30{\mu}M$). Compared with SAHA, N25 displayed an increased antitumor activity in U251 and H460 cells. We further analyzed cell death mechanisms activated by N25 in U251 and H460 cells. N25 significantly increased acetylation of Histone 3 and inhibited HDAC4. On RT-PCR analysis, N25 increased the mRNA levels of p21, however, decreased the levels of p53. These resulted in promotion of apoptosis, inducing G0/G1 arrest in U251 cells and G2/M arrest in H460 cells in a time-dependent and dose-dependent manner. In addition, N25 was able to distribute to brain tissue through the blood-brain barrier of mice ($LD_{50}$: 240.840mg/kg). In conclusion, our findings demonstrate that N25 will provide an invaluable tool to investigate the molecular mechanism with potential chemotherapeutic value in several malignancies, especially human glioma.
  39. Feng, Rui;Wang, De-Bin;Chai, Jing;Cheng, Jing;Li, Hui-Ping 4339
    https://doi.org/10.7314/APJCP.2014.15.10.4339 PDF KSCI
    Purpose: This study aimed at exploring treatment delay (TD) among cancer patients in China with an attempt to develop a practical methodology facilitating frontline Chinese clinicians in promoting earlier cancer diagnosis and treatment. Materials and Methods: The study comprised framework development, qualitative interviews and paired factor rating. Framework development utilized systematic literature review, soft systems thinking and consensus groups. Qualitative interviews employed a checklist of open questions soliciting information about all the domains included the framework from cancer patients drawn via stratified randomized sampling of inpatients at 10 hospitals in Hefei, China. Paired factor rating used a self-developed computer aid and the interviewed patients as referring cases to weigh the relative importance of the factors listed in the framework in terms of their contributions to specific components of total delay (TD). Results: a) A conceptual framework was proposed consisting of a 6-step path to TD and 36 category determinants. b) A total of 227 patients were interviewed; their TD was 267.3 mean or 108 median days ranging from 0 to 2475 days; average appraisal, illness, behavioral, preparation and treatment delay accounted for 52.1%, 9.4%, 0.30%, 8.8% and 29.4% of the TD respectively. Individual side factors were rated substantially more important than environmental side factors (60% vs. 40%); most influential TD factors included cancer symptoms, overall health, family relations and knowledge about cancer and health. Conclusions: The framework proposed together with the interviewing and rating approaches used provide a potential new methodology for understanding cancer patients' TD and promoting earlier cancer treatment.
  40. Hadizadeh, Mohammad;Padashi, Maryam;Alizadeh, Amir Houshang Mohammad;Zali, Mohammad Reza 4349
    https://doi.org/10.7314/APJCP.2014.15.10.4349 PDF KSCI
    Background: Pancreatic cancer has a high mortality rate because it is usually diagnosed late. Since little is known about this cancer in Iran, with the aim of improving this knowledge deficiency, we evaluated clinical, laboratory biomarkers, imaging findings and treatment modalities in Iranian patients with pancreatic adenocarcinoma. Materials and Methods: 131 cases of pancreatic adenocarcinoma in 2010-2013 were obtained from the Taleghani Hospital Record Department. Cases confirmed by histopathology from CT-guided biopsy, EUS-FNA and surgery examination were included. We excluded those with incomplete medical records. Results: The study included 131 subjects between 24 and 97 years of age and a mean age of $63{\pm}13.4$ years. Eighty (61.1%) were male and 51 (38.9%) female. Previous history included diabetes mellitus in 36 (27.5%), alcohol drinking in 5 (3.9%), smoker in 28 (21.4%) and opium addiction in 13 (10%). The common presenting history included weight loss in 79 (60.3%), abdominal pain in 77 (58.8%), fever in 11 (8.4%), nausea in 30 (22.9%), jaundice in 72 (55%), pruritus in 52 (39.7) and anemia in 33 (25.2%). CA19-9 levels with cut offs of 50, 100 and 200 U/ml were increased in 81%, 72% and 66% of patients, respectively. Tumor staging was: stage I, 3 (2.3%); stage II, 10 (7.6%); stage III, 58 (44.3%); and stage IV, 60 (45.8%). From 45 patients, 17 received ERCP inserted metallic stents and 22 plastic stents, the remaining 6 failed that PTC was done. Whipple surgery and chemotherapy were conducted for 10 and 29 patients, respectively. Conclusions: This disease affected older people and there was a male preponderance. The commonest risk factors were diabetes mellitus, smoking and cholelithiasis. The majority of patients presented with loss of appetite, loss of weight, jaundice, abdominal pain and discomfort. Almost all presented at late stages of the disease so that curative surgery was impossible. Also chemotherapy was only performed in a few patients as a neoadjuant treatment.
  41. Davoudi, Zahra;Akbarzadeh, Abolfazl;Rahmatiyamchi, Mohammad;Movassaghpour, Ali Akbar;Alipour, Mohsen;Nejati-Koshki, Kazem;Sadeghi, Zohre;Dariushnejad, Hassan;Zarghami, Nosratollah 4353
    https://doi.org/10.7314/APJCP.2014.15.10.4353 PDF KSCI
    Background: PI3/AKT and NF-kB signaling pathways are constitutively active in acute myeloid leukemia and cross-talk between the two has been shown in various cancers. However, their role in acute myeloid leukemia has not been completely explored. We therefore used cell penetrating inhibitor peptides to define the contributions of AKT and NF-kB to survival and multi drug resistance (MDR) in HL-60 cells. Materials and Methods: Inhibition of AKT and NF-kB activity by AKT inhibitor peptide and NBD inhibitor peptide, respectively, resulted in decreased expression of mRNA for the MDR1 gene as assessed by real time PCR. In addition, treatment of HL-60 cells with AKT and NBD inhibitor peptides led to inhibition of cell viability and induction of apoptosis in a dose dependent manner as detected by flow cytometer. Results: Finally, co-treatment of HL-60 cells with sub-optimal doses of AKT and NBD inhibitor peptides led to synergistic apoptotic responses in AML cells. Conclusions: These data support a strong biological link between NF-kB and PI3-kinase/AKT pathways in the modulation of antiapoptotic and multi drug resistant effects in AML cells. Synergistic targeting of these pathways using NF-kB and PI3-kinase/AK inhibitor peptides may have a therapeutic potential for AML and possibly other malignancies with constitutive activation of these pathways.
  42. Hock, Lim Kuang;Ghazali, Sumarni Mohamad;Cheong, Kee Chee;Kuay, Lim Kuang;Li, Lim Hui;Huey, Teh Chien;Ying, Chan Ying;Yen, Yeo Lay;Ching, Fiona Goh Swee;Yi, Khoo Yi;Lin, Chong Zhuo;Ibrahim, Normala;Mustafa, Amal Nasir 4359
    https://doi.org/10.7314/APJCP.2014.15.10.4359 PDF KSCI
    Intention to smoke is a valid and reliable factor for predicting future smoking habits among adolescents. This factor, however, has received inadequate attention in Malaysia. The present paper elaborates the prevalence and factors associated with intent to initiate or to cease smoking, among adolescent nonsmokers and smokers in Kota Tinggi, Johor, Malaysia. A total of 2,300 secondary school students aged 13-16 years were selected through a two-stage stratified sampling method. A set of standardized questionnaires was used to assess the smoking behavior among adolescents and the inter-personal and intra-personal factors associated with smoking intention (intention to initiate smoking or to cease smoking). Multivariable logistic regression was used to identify factors related to smoking intention. The prevalence of intention to smoke in the future or to cease smoking among non-smoking adolescents and current smokers were 10.7% and 61.7% respectively. Having friends who smoke, social influence, and poor knowledge about the ill effects on health due to smoking showed significant relationships with intention to smoke in the future among non-smokers. Conversely, perceived lower prevalence of smoking among peers, weak contributory social influence, and greater awareness of the ill effects of smoking are factors associated with the intention to cease smoking sometime in the future. The study found that prevalence of intention to initiate smoking is low among non-smokers while the majority of current smokers intended to cease smoking in the future. Existing anti-smoking programmes that integrate the factors that have been identified in the current study should be put in motion to reduce the prevalence of intention to initiate smoking and increase the intention to cease smoking among adolescents.
  43. Lu, Li-Rong;Liu, Jing;Xu, Zhen;Zhang, Geng-Lin;Li, De-Chang;Lin, Chao-Shuang 4367
    https://doi.org/10.7314/APJCP.2014.15.10.4367 PDF KSCI
    We here document discovery of expression profile of myeloid derived suppressor cells (MDSCs) in chronic hepatitis B (CHB) patients and changes in the course of disease. The study population was composed of 75 outpatient HBV cases and 15 healthy control cases. Peripheral blood samples were collected for separation of mononuclear cells. Levels of MDSCs labeled with Lin-DR-CD11b+CD33+ obtained from peripheral blood mononuclear cells (PBMC), were revealed to have significant differences between the CHB and other groups. They were 0.414% for health control cases and 0.226% for CHB cases (Z=-2.356, p=0.0189). It also observed that the group of HBeAg positive cases had significant difference in MDSCs/PBMC median ($X^2=11.877$, p=0.003), compared with group of HBeAg negative cases and the healthy control group. It suggested considerable MDSCs might be involved in HBeAg immune tolerance. In addition, negative correlations between MDSCs/PBMC and parameters of ALT, AST and TBil, while positive correlation between MDSCs/PBMC and ALB parameter were found. Multiple comparisons between the four phases and health control phase again, there was a statistically sifnificant difference ($X^2=17.198$, p=0.002). Taken together, these findings may provide a new immunotherapy strategy for reduced the expression levels of MDSCs in CHB patients, through induction of an autoimmune response to virus removal.
  44. Tanoglu, Alpaslan;Yiyit, Nurettin;Berber, Ufuk;Karagoz, Ergenekon 4373
    https://doi.org/10.7314/APJCP.2014.15.10.4373 PDF KSCI
  45. Balta, Ahmet Ziya;Berber, Ufuk;Tanoglu, Alpaslan;Ozdemir, Yavuz;Demirel, Dilaver 4375
    https://doi.org/10.7314/APJCP.2014.15.10.4375 PDF KSCI