• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5749-5754
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• 2015

Cervical carcinoma is the main cause of cancer-related mortality in women and is correlated with more than 15 risk cofactors, including infection of cervical cells with high-risk types of HPV (hrHPV). Indeed, both aberrant methylation of the RASSF1A promoter and hrHPV infection are often observed in cervical carcinomas. The purpose of our meta-analysis was to evaluate the role of RASSF1A promoter methylation and hrHPV infection in cervical cancer. Our meta-analysis involved 895 cervical cancer patients and 454 control patients from 15 studies. Our results suggested that RASSF1A promoter hypermethylation increased the risk of cervical cancer (OR=9.77, 95%CI=[3.06, 31.26], P=0.0001, $I^2=78%$). By grouping cases according to cancer subtypes, we found that HPV infection was higher in cervical squamous cell carcinomas (SCCs) than in cervical adenocarcinomas/adenosquamous cancers (ACs/ASCs) (OR=4.00, 95%CI=[1.41, 11.30], P=0.009, $I^2=55%$). Interestingly, HPV infection tended to occur in cervical cancers with relatively low levels of RASSF1A promoter methylation (OR=0.59, 95%CI=[0.36, 0.99], P=0.05, I2=0%). Our study provides evidence of a possible interaction between HPV infection and RASSF1A promoter methylation in the development of cervical cancers.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.4863-4867
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• 2015

Background: Triple negative breast cancer (TNBC), characterized as estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 Her2 negative and accounting for 10-17% of all breast carcinomas, is only partially responsive to chemotherapy and suffers from a lack of clinically established targeted therapies. The aim of the current study was to evaluate the patterns of treatment and clinicopathology figures in Kurdish patients with triple-negative breast cancer, and to compare these to other reports. Materials and Methods: Between 2001 and 2014, 950 breast cancer patients were referred to our clinic. There were 74 female patients with TNBC, including 70 patients was invasive ductal carcinoma entered into our study. ER and PR positivity was defined as positive immunohistochemical staining in more than 10% of tumor cells. Immunohistochemistry assay with anti-HER2 antibodies was used to identify HER negative (0 and 1+) or positive (2+ and 3+). HER2 gene amplification was determined by fluorescent in situ hybridization (FISH). Overall survival (OS) was plotted with GraphPad Prism 5 Software using Kaplan-Meier and log-rank tests for comparison of results. Results: The mean age in the first diagnosis for 70 patients with triple TNBC and invasive ductal carcinoma was 49.6 years that range of age was 27-82 years. All of the patients were female. Of 70 patients, 23 patients had metastasis. Thirty-two patients (45.7%) were treated with tamoxifen and 39 (55.7%) with radiotherapy. Three-year, 5-year and 10-year OS rates for all patients were 82%, 72% and 64%, respectively. Conclusions: The OS in our West Iran TNBC patients is less than reported elsewhere. However, treatment with combination of tamoxifen plus radiation increases the OS and reduces the mortality rate.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5817-5822
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• 2015

The developing countries have higher mortality rates for breast cancer. A reason for this is presentation at advanced stages due to low levels of public awareness. Activities are arranged by health authorities of developing countries to increase the knowledge of women but their effectiveness has not been evaluated in detail. A multiple choice questionnaire with questions about socio-demographic profile and questions about breast cancer knowledge was designed in local language Urdu, to evaluate the knowledge of the participants before and after an audio visual educational activity in Lahore, Pakistan. Scores of 0-2, 3-5 and 6-8 were ranked as poor, fair and good, respectively. Among 146 participants these scores were achieved by 1%, 55% and 45% before activity and 0%, 16% and 84% after the activity. Overall 66% of participants increased their knowledge score. Younger age, higher education, reliance on television as source of information and being a housewife were associated with better impact of the awareness activity. For the six knowledge related questions 3%, 5%, 11%, 23%, 33% and 44% more participants gave correct answers after the activity. However 6% and 7% fewer participants answered correctly for 2 questions related to the cause and the best prevention for breast cancer. The study indicated that awareness activities are effective to increase the knowledge of women and better impact is associated with higher education and younger age of women. The component analysis showed that the questions and related presentations using medical terms have a negative impact and should not therefore be used. Analysis of activity therefore leads to identification of deficiencies which can be remedied in future.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.1
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• pp.169-174
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• 2015

Cervical cancer (CxCa) is the most common cancer in women and a prominent cause of cancer mortality worldwide. The primary cause of CxCa is human papillomavirus (HPV). Radiation therapy and chemotherapy have been used as standard treatments, but they have undesirable side effects for patients. It was reported that gallic acid has antioxidant, antimicrobial, and anticancer activities. Gold nanoparticles are currently being used in medicine as biosensors and drug delivery agents. This study aimed to develop a drug delivery agent using gold nanoparticles conjugated with gallic acid. The study was performed in uninfected (C33A) cervical cancer cells, cervical cancer cells infected with HPV type 16 (CaSki) or 18 (HeLa), and normal Vero kidney cells. The results showed that GA inhibited the proliferation of cancer cells by inducing apoptosis. To enhance the efficacy of this anticancer activity, 15-nm spherical gold nanoparticles (GNPs) were used to deliver GA to cancer cells. The GNPs-GA complex had a reduced ability compared to unmodified GA to inhibit the growth of CxCa cells. It was interesting that high-concentration ($150{\mu}M$) GNPs-GA was not toxic to normal cells, whereas GA alone was cytotoxic. In conclusion, GNPs-GA could inhibit CxCa cell proliferation less efficiently than GA, but it was not cytotoxic to normal cells. Thus, gold nanoparticles have the potential to be used as phytochemical delivery agents for alternative cancer treatment to reduce the side effects of radiotherapy and chemotherapy.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.1
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• pp.9-21
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• 2015

Cancer, a serious public health problem in worldwide, results from an excessive and uncontrolled proliferation of the body cells without obvious physiological demands of organs. The gastrointestinal tract, including the esophagus, stomach and intestine, is a unique organ system. It has the highest cancer incidence and cancer-related mortality in the body and is influenceed by both genetic and environmental factors. Among the various chemical elements recognized in the nature, some of them including zinc, iron, cobalt, and copper have essential roles in the various biochemical and physiological processes, but only at low levels and others such as cadmium, lead, mercury, arsenic, and nickel are considered as threats for human health especially with chronic exposure at high levels. Cadmium, an environment contaminant, cannot be destroyed in nature. Through impairment of vitamin D metabolism in the kidney it causes nephrotoxicity and subsequently bone metabolism impairment and fragility. The major mechanisms involved in cadmium carcinogenesis could be related to the suppression of gene expression, inhibition of DNA damage repair, inhibition of apoptosis, and induction of oxidative stress. In addition, cadmium may act through aberrant DNA methylation. Cadmium affects multiple cellular processes, including signal transduction pathways, cell proliferation, differentiation, and apoptosis. Down-regulation of methyltransferases enzymes and reduction of DNA methylation have been stated as epigenetic effects of cadmium. Furthermore, increasing intracellular free calcium ion levels induces neuronal apoptosis in addition to other deleterious influence on the stability of the genome.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.1
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• pp.185-189
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• 2015

Background: Due to the increase in morbidity and mortality rate, cancer has become an alarming threat to the human population worldwide. Since cancer is a progressive disorder, timely diagnosis is necessary to prevent/stop cancer from progressing to a severe stage. In Khyber Paktunkhwa, Pakistan, many tumors are diagnosed with endoscopy and biopsy; rare studies exist regarding the diagnosis and evaluation of ovarian cancer, based on tumor markers like CA-125. Objectives: The objectives of this study were to investigate and evaluate levels of CA-125 in hospitalized ovarian cancer patients. Materials and Methods: In this study, a total of 63 admitted patients having ovarian cancer by biopsy were included. The level of CA-125 was determined in the blood of these patients using ELISA technique. Results: Out of 63 patients, the level of CA-125 was high in 52%. The affected individuals were more in the group of 40-60 and the level of CA-125 was comparatively higher in patients having moderately differentiated histology than those having well differentiated and poorly differentiated tumor histology. Moreover, the highest level of CA-125 was present among the patients having serous subtype of carcinoma and the common stage of carcinoma was stage II followed by stage III, I and IV. Conclusions: CA-125 level was high in more than 50% of the total patients. Moreover, CA-125 elevation was more common in serous subtype and stage II cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.5983-5991
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• 2014

Introduction: Upper aero-digestive tract cancer is a multidimensional problem, international trends showing complex rises and falls in incidence and mortality across the globe, with variation across different cultural and socio-economic groups. This paper seeks some explanations and identifies some research and policy needs. Methodological Approach: The literature illustrates the multifactorial nature of carcinogenesis. At the cellular level, it is viewed as a multistep process involving multiple mutations and selection for cells with progressively increasing capacity for proliferation, survival, invasion, and metastasis. Established and emerging risk factors, in addition to changes in incidence and prevalence of cancers of the upper aero-digestive tract, were identified. Risk Factors: Exposure to tobacco and alcohol, as well as diets inadequate in fresh fruits and vegetables, remain the major risk factors, with persistent infection by particular so-called "high risk" genotypes of human papillomavirus increasingly recognised as also playing an important role in a subset of cases, particularly for the oropharynx. Chronic trauma to oral mucosa from poor restorations and prostheses, in addition to poor oral hygiene with a consequent heavy microbial load in the mouth, are also emerging as significant risk factors. Conclusions: Understanding and quantifying the impact of individual risk factors for these cancers is vital for health decision-making, planning and prevention. National policies and programmes should be designed and implemented to control exposure to environmental risks, by legislation if necessary, and to raise awareness so that people are provided with the information and support they need to adopt healthy lifestyles.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.1931-1936
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• 2014

Background: Gastric cancer (GC) ranks as one of the major causes of mortality due to cancer worldwide. In Chile, it is currently the leading cause of cancer death. Identification of novel molecular markers that may help to improve disease diagnosis at early stages is imperative. Materials and Methods: Using whole-genome DNA microarrays we determined differential mRNA levels in fresh human GC samples compared to adjacent healthy mucosa from the same patients. Genes significantly overexpressed in GC were validated by RT-PCR in a group of 14 GC cases. Results: The genes CD248, NSD1, RAB17, ABCG8, Ephb1 and P2RY2 were detected as the top overexpressed in GC biopsies. P2RY2, Ephb1 and CD248 showed the best sensitivity for GC detection with values of 92.9%, 85.7% and 64.3% (p<0.05), respectively. Specificity was 85.7%, 71.4% and 71.4% (p<0.05), for each respectively.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1947-1959
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• 2016

Background: Colorectal cancer (CRC) is a major cause of morbidity and mortality, being the second most common type of cancer worldwide in both men and women. It accounts yearly for approximately 9% of all new cases of cancers. Furthermore, the current chemotherapeutic regimens seem unsatisfactory, so that exploration of novel therapeutic modalities is needed. The present study was undertaken to investigate the inhibitory effects of a crude alkaloid extract (CAERS) of a medicinal herb, Rhazya stricta, on proliferation of CRC HCT116 cells and to elucidate mechanisms of action. To achieve these aims, we utilized MTT, comet, DNA laddering and gene reporter assays, along with Western blot and RT-PCR analyses. Results: We found that CAERS inhibited cell proliferation and induced apoptotic cell death in HCT116 cells. Hallmarks of morphological and biochemical signs of apoptosis were clearly evident. CAERS down-regulated DNA-binding and transcriptional activities of NF-${\kappa}B$ and AP-1 proteins, while up-regulating expression of the Nrf-2 protein. It also down-regulated expression levels of the ERK MAPK, Bcl-2, cyclin D1, CDK-4, survivin and VEGF and up-regulated levels of Bax, caspase-3/7 and -9, p53, p21, Nrf-2. Markedly, it promoted mRNA expression levels of cytoprotective genes including the hemeoxygenase-1, NAD(P)H quinine oxidoreductase 1 and UDP-glucuronyltransferase. Conclusions: These findings indicate that CAERS exerts antiproliferative action on CRC cells through induction of apoptotic mechanisms, and suggest CAERS could be a promising agent for studying and developing novel chemotherapeutic agents aimed at novel molecular targets for the treatment of CRC.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1917-1921
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• 2012

Background: Colorectal cancer is one of the leading causes of mortality worldwide. Genome wide analysis studies have identified sequence mutations causing loss-of-function that are associated with disease occurrence and severity. Epigenetic modifications, such DNA methylation, have also been implicated in many cancers but have yet to be examined in the East Asian population of colorectal cancer patients. Methods: Biopsies of tumors and matched non-cancerous tissue types were obtained and genomic DNA was isolated and subjected to the bisulphite conversion method for comparative DNA methylation analysis on the Illumina Infinium HumanMethylation27 BeadChip. Results: Totals of 258 and 74 genes were found to be hyper- and hypo-methylated as compared to the individual's matched control tissue. Interestingly, three genes that exhibited hypermethylation in their promoter regions, CMTM2, ECRG4, and SH3GL3, were shown to be significantly associated with colorectal cancer in previous studies. Using heatmap cluster analysis, eight hypermethylated and 10 hypomethylated genes were identified as significantly differentially methylated genes in the tumour tissues. Conclusions: Genome-wide methylation profiling facilitates rapid and simultaneous analysis of cancerous cells which may help to identify methylation markers with high sensitivity and specificity for diagnosis and prognosis. Our results show the promise of the microarray technology in identification of potential methylation biomarkers for colorectal cancers.