bluuebunny/crossref_metadata_2025 huggingface dataset:
Voltage-Gated K+ Channels Promote BT-474 Breast Cancer Cell Migration
Authors: Chow L.W.C. , Cheng K.S. , Wong K.L. , Leung Y.M.
Published: September 2018

Objective: A variety of ion channels have been implicated in breast cancer proliferation and metastasis. Voltage-gated K+ (Kv) channels not only cause repolarization in excitable cells, but are also involved in multiple cellular functions in nonexcitable cells. In this study we investigated the role of Kv channels in migration of BT474 breast cancer cells. Methods: Transwell technique was used to separate migratory cells from nonmigratory ones and these 2 groups of cells were subject to electrophysiological examinations and microfluorimetric measurements for cytosolic Ca2+. Cell migration was examined in the absence or presence of Kv channel blockers. Results: When compared with nonmigratory cells, migratory cells had much higher Kv current densities, but rather unexpectedly, more depolarized membrane potential and reduced Ca2+ influx. PCR analysis revealed the presence of Kv1.4, Kv1.5, Kv1.6, Kv2.1 and Kv3.1 channels. Cell migration was markedly inhibited by tetraethylammonium, a delayed rectifier Kv channel blocker, but not by 4-aminopyridine, an A-type Kv blocker. Conclusion: Taken together, our results show that increased Kv channel expression played a role in BT474 cell migration, and Kv channels could be considered as biomarkers or potential therapeutic targets for breast cancer metastasis. The mechanism(s) by which Kv channels enhanced migration appeared unrelated to membrane hyperpolarization and Ca2+ influx.
Cannabis Smoking and Risk of Cancer: A Meta-Analysis of Observational Studies
Authors: Park S. , Myung S.-K.
Published: September 2018

Background: Cannabis (also called marijuana or marihuana) is 1 of the most widely used illicit substances in the world. While cigarette smoking is a well-known risk factor of many cancers, effects of cannabis smoking on risk of developing cancer have remained unclear. Aim: This study is conducted to evaluate the association between cannabis smoking and cancer risk. Methods: We searched PubMed, Embase and the bibliographies of relevant articles to locate additional publications in October 2017. Two evaluators independently reviewed and selected eligible studies based on predetermined selection criteria. Observational studies such as cross-sectional, case-control, and cohort studies reporting odd ratios (ORs) or relative risk (RRs) for association between cannabis smoking and any kind of cancer risk were included. Subgroup analysis also was performed by cancer type (lung, oral, testicular, head and neck and others) and by smoking duration (<5 years, 5-10 years, >10 years). Results: We included 18 observational studies with 2 cohort studies and 16 case-controls studies, which involved a total of 13,646 cancer patients and 151,572 participants without cancer in final analysis. The random-effects meta-analysis of all 20 studies showed marginally statistically significant association between cannabis smoking and risk of lung cancer (OR = 1.76, 95% CI 1.00-3.08; I2 = 82.0%). Subgroup analysis by type of cancer shows that cannabis smoking more than 10 years increased risk of testicular cancer (OR = 1.50; 95% CI, 1.02-2.09; I2 = 00.0%). Conclusion: The current meta-analysis of observational studies found an overall significant increased risk of lung cancer and cannabis. Further, an increased risk of testicular cancer when duration of cannabis smoking exceeded 10 years also was found.
National Study of Opium and Cancer in Iran (IROPICAN): Study Protocol and Results of the Pilot Phase
Authors: Hadji M. , Marzban M. , Gholipour M. , Rashidian H. , Naghibzadeh-Tahami A. , Haghdoost A.A. , Rezaianzadeh A. , Rahimi-Movaghar A. , Moradi A. , Seyyedsalehi M. , Poustchi H. , Eghtesad S. , Ghiasvand R. , Boffetta P. , Veierød M. B. , Weiderpass E. , Kamangar F. , Zendehdel K.
Published: September 2018

Background: Several epidemiologic studies have reported that opium consumption is associated with higher risk of cancer and may indeed cause cancer. However, most of these studies were not primarily designed to study the effect of opium on cancer. Therefore, control selection and data collections methods were not optimized for this purpose. Aim: We designed a large multicenter case-control study to specifically investigate the association between opium use and risk of 4 cancer types (i.e., lung, bladder, head and neck and colorectal cancers). We will recruit 800 cases and 800 controls for each cancer in this project. Methods: So far we have collected 70% of the cases and controls. We report here the study protocol and results of the pilot phase. Results: During the pilot phase, we determined that hospital visitors are the most appropriate type of controls; 185 cases and 176 controls were enrolled. Controls are matched to cases for sex, age and place of residence. Collection of data using a comprehensive questionnaire, focused on measuring use of opium and its derivatives, was feasible. Underreporting of opium was estimated to be 30% among controls. Collection of other data, including data tobacco and alcohol use, and nutritional data using a food frequency questionnaire, was feasible. Biologic samples including blood and saliva sample were collected from cancer cases and controls. Results of the pilot phase and validation study were used to optimize the full study protocol and questionnaires. Conclusion: The pilot phase of the study showed that the study is feasible, the best method of control selection is from hospital visitors, and both questionnaire and biologic samples can be collected. In addition of the results from pilot phase, preliminary results from the main phase of this study will be presented.
Regulatory Compliance: A Challenge for Unbranded Smokeless Tobacco Products
Authors: Chandra A. , Yadav A. , Chandan K. , Mehrotra R.
Published: September 2018

Background: Smokeless tobacco (SLT) is available in many forms in India and is widely used by all social groups. SLT market in India is the world largest market. Over the last 2 decades, the SLT industry in India has grown immensely, mostly in cottage industry sector and unorganized sector. Several SLT products are self-made or mixed by users themselves. This presents a great challenge for regulation of such unbranded and loose products. Cancer of the oral cavity and the pharynx are a major public health problem in India. At least 90% of these cancers are caused by SLT products use. Aim: To study the challenges for unbranded SLT products in implementing the mandated regulatory compliances under the Indian Tobacco Control Law that applies to all tobacco products. Methods: The information on unbranded/loose SLT products was collected through literature search, field trips, discussions with SLT product vendors and with community members of different age group. Results: Several types of unbranded SLT products are sold both in urban and rural India. These unbranded products vary from state to state. In some cases they vary from 1 place to another within a state. Most of the unbranded products do not comply with the legal mandates of the Indian tobacco control (COTPA) and food safety (FSSA) laws that regulate sale of tobacco products. The biggest fall-out of unbranded sale is that there is no pictorial health warnings to warn the users about the ill effects of these SLT products as required under section 7 of COTPA. In addition these products also do not mention the minimum requirement of the packaging and labeling under the legal metrology law. In absence of the pictorial health warnings these SLT products become more accessible and affordable to minors. The FSSA prohibits use of tobacco and nicotine as ingredient in any food item, however, most of the unbranded SLT products are sold with added flavorings, condiments and spices which are classified as food. Conclusion: Strict implementation of the mandated regulatory provisions is needed to check the unrestricted sale of unbranded products. Noncompliant unbranded/loose SLT products should be confiscated as per the prescriptions of the existing tobacco control and food safety laws. Findings from this paper calls for development of policies that will prevent sale of unbranded/loose SLT products in India to protect the unsuspecting youth and other vulnerable group of population from these cancer traps.
Unbranded Carcinogenic Products From Indian Terrain
Authors: Chandra A. , Sharma V. , Nandan A. , Mehrotra R.
Published: September 2018

Background: The burden of cancers caused due to tobacco-related carcinogenic products is increasing at an alarming rate in India. Unlike the western world, where cancer-causing products are mostly smoked (such as cigarettes), in India it is mostly consumed as such without combustion. Such products are produced for self-consumption or for selling in the local markets within specific geographical locations. There is very little information available in the public search engines (PubMed) about such products (i.e., dohra [mixture of areca nut, catechu, edible lime, peppermint, cardamom, and some flavoring agents], tuibur [tobacco water sipped and retained in mouth for 5-10 minutes and then spit out], kaddipudi [fine powder of tobacco plant used as such, or in processed form, as bricks and blocks made with jaggery and water], and hogesoppu [tobacco leaf used by women either as such or with betel]). Aim: To study the (i) geographical distribution, (ii) varieties, (iii) production and (iv) adverse health effects of unbranded chewable or drinkable carcinogenic products from India. Methods: The information on unbranded carcinogenic products was collected via study tour to different geographical areas of India, via group discussions or telephonic talks with community members of different age groups. Results: Dohra is found in the state of Uttar Pradesh, India. It majorly contains areca nut which contains a carcinogenic compound - arecoline known for causing histologic changes in the oral mucosa. Tuibur is found in the state of Manipur and Mizoram. Evidence suggests that it contains tobacco which is rich in N-nitroso compounds known for causing systemic tumors. Kaddipudi and hogesoppu are found in the state of Karnataka. Both of them contain tobacco. Conclusion: Dohra, Tuibur, kaddipudi and hogesoppu are unbranded cancer-causing products used at specific geographical locations in India. Since these products contain carcinogenic compounds, their use should be avoided.
Biochemical Profiling of Smokeless Tobacco Product Kiwam at Different Processing Steps
Authors: Chandra A. , Sharma V. , Nandan A. , Kaushik R. , Mehrotra R.
Published: September 2018

Introduction: Kiwam (qiwam) is a partially fermented tobacco product consumed with betel quid (paan). The major constituents of this product are tobacco, saffron (zaffrani) and some other additives. It contains tobacco-specific nitrosamines (TSNA) which is considered as a cancer causing agent. To elucidate the carcinogenic property of kiwam, biochemical profiling of its constituents at different stages of processing is needed. The major processing steps involved in the formation of kiwam and biochemical profiling/changes at each processing step is still unknown. Aim: To describe the major processing steps and biochemical changes that occur at each processing step during the preparation of kiwam. Methods: Tobacco leaves and stems were washed with Millipore water so as to remove the dirt particles from the leaves and stems. It is then boiled in water followed by filtering of the constituents to remove the leaves and stem residues. The filtrate was again boiled to form a thick paste residue. The resultant paste was partially fermented through sun curing, and lastly, saffron along with specific additives was added. The samples from each step were analyzed for biochemical profiling through Continuous Flow Autoanalyzer using Flow View Solution 3700 Analyzer (version 1.2.2) software. Results: The biochemical changes at TSNA levels were observed at each processing steps. The detailed chemical profiling will be presented during the meeting. Conclusion: Kiwam is rich in TSNA and hence its use should be avoided.
Less PMMA Injection as an Independent Factor for Poor Neurologic Recovery in Malignant Vertebral Compression Fractures With Symptoms of Neurologic Compression Following Percutaneous Vertebroplasty
Authors: Li E.-S. , Mu J.-X.
Published: September 2018

Background: Recent years, percutaneous vertebroplasty (PVP) has gained wide clinical acceptance as an effective treatment option for patients with intractable pain related to compression fractures of the spine. But little is known about PVP for spinal malignant lesions with epidural involvement in patients with neurologic deficit. Aim: To evaluate the efficacy of PVP for malignant vertebral compression fractures with symptoms of neurologic compression following percutaneous vertebroplasty (PVP), and evaluate the predictive factors for poor outcomes following PVP. Methods: Forty-three patients with malignant vertebral compression fractures with symptoms of neurologic compression were treated with PVP. Patients were classified into 2 groups according to the American Spinal Injury Association (ASIA) impairment scale at the last follow-up. Data were collected and the patients followed-up at 1, 3, 6 and 12 months and yearly after the procedure. Univariate and multivariate analysis was performed to evaluate factors predictive of poor neurologic compression symptoms recovery. Results: PVP were successful in all patients. Full recovery from (n = 2) or improvement of (n = 16) neurologic compression symptoms were achieved in 18 patients (Group A), and no improvement of neurologic compression symptoms in 25 patients (Group A). Univariate analysis showed more PMMA leakage ( P = 0.038) and less PMMA volume injection ( P < 0.001) was associated with the poor symptoms of neurologic compression recovery, and multivariate analysis showed that less PMMA volume injection ( P = 0.004) was an independent predictor for poor symptom of neurologic compression recovery. Conclusion: Our results indicated PVP should not be served as an effective treatment of malignant compression fractures with symptoms of neurologic compression, and less PMMA volume injection was an independent predictor of poor symptom of neurologic compression recovery.
Differential Immune Responses in Epidemic and Endemic Tanzanian Kaposi Sarcoma Patients
Authors: Mwaiselage J.D. , Lidenge S. , Ngowi J.R. , Haynatzki G. , Wood C. , West J.
Published: September 2018

Background: Mechanisms underlying Kaposi sarcoma (KS) development are unclear. The high incidence of KS in HIV-1+ individuals implicates immune dysregulation in epidemic KS (EpKS) development. In African endemic KS (EnKS), the immune response is uncharacterized. Aim: The aim was to assess a comparative quantification between newly diagnosed Tanzanian EpKS and EnKS patients, and asymptomatic controls. We also report the first comparison of KSHV NAb prevalence and titer between EpKS and EnKS patients. Methods: To compare innate and adaptive immune responses, we recruited histologically confirmed Tanzanian EpKS and EnKS patients, as well as noncancer controls. After differential detection of KSHV nucleic acids in tissues, neutralizing antibody (NAb), levels of cytokines/chemokines, and T-cell differentiation subsets were quantified. The Mann-Whitney U-test was used to assess median differences between groups. All tests were 2-tailed and P-values < 0.05 were considered significant. Results: A total of 180 patients have been recruited in this study. In addition, a comparable 25 EpKS and 10 EnKS as well as 10 noncancer controls were recruited for this study. KSHV was significantly more frequently detected in EpKS patients than in EnKS. While all EpKS, and some EnKS patients mounted NAb responses, the EpKS patients had higher prevalence and titer of NAb compared with EnKS patients ( P = 0.001). Levels of the cytokines IP-10 and IL-10 were higher in EpKS vs EnKS patients ( P = 0.006 and P = 0.005 respectively), whereas, IL-4 was lower in EpKS vs EnKS patients ( P = 0.004). The levels of all 14 cytokines/chemokines measured were comparable between EnKS patients and HIV− controls ( P < .05 ). The distribution of CD4+ and CD8+ T-cells was similar between EpKS and EnKS such as naive and effector T-cells were depleted while central memory T-cells were elevated in both KS forms. Conclusion: The detection of similar abnormalities in T-cell differentiation subsets in both EpKS and EnKS as compared with controls, suggests that KSHV-induced T-cell dysfunction plays a major role in the disease, and that HIV-1 coinfection is only exacerbating and accelerating KSHV pathogenesis and KS development.
Combined Treatment of 5-Fluorouracil and Delta-Tocotrienol Induce of Apoptosis and Autophagy in Colorectal Cancer Cells
Authors: Tham S.Y. , Mai C.W. , Fu J.Y. , Loh H.-S.
Published: September 2018

Background: 5-fluorouracil (5-FU) has been a first choice chemotherapeutic drug used to treat colorectal cancer. However, its therapeutic outcome often be limited by high-dose toxicities and drug resistance development. Hence, the current research advocates combined application of delta-tocotrienol (δ-T3), as a natural chemosensitizer, with 5-FU as a novel treatment approach for colorectal cancer. Aim: To investigate the combinatorial anticancer effects of δ-T3 and 5-FU on colorectal cancer cell lines. Methods: Cell viability assay was performed to investigate the individual and combined effects of δ-T3 (0.1-100 µM) and 5-FU (0.1-100 µM) on HCT116, HCC2998, Caco-2 and SW48 colorectal cancer cells at 72 h. Subsequently, the synergistic combination were evaluated for the effects on clonogenicity, apoptosis and autophagy. Morphologic assessment was conducted by bright-field and fluorescence microscopy. The protein expression profiles of programmed cell death and survival markers were determined by Western blotting. Results: Combined treatment of subeffective dose of δ-T3 significantly lowered the IC50 of 5-FU in Caco-2 and SW48 colorectal adenocarcinomas for 16-fold and fourfold respectively, signifying a chemosensitising effect. Clonogenic survival assay showed that the combined treatment profoundly hampered the cell survival as compared with the individual single treatments. Apoptosis was induced by the combined treatment as confirmed by flow cytometry. Interestingly, both apoptotic and autophagic morphologies were observed, including nuclear condensation, cell shrinkage, cytoplasmic vacuolation and extension. The presence of autophagy was further confirmed by increase LC3A/B ratio and high volume of acidic vesicular organelles. The combined treatment were found to upregulate prodeath proteins such as Bax, caspase-8, caspase-3, PARP and downregulate prosurvival proteins such as cIAP, XIAP and survivin. Conclusion: The enhanced cell death induced by 5-FU and δ-T3 combined treatment involved both apoptosis and autophagy, suggesting a novel and effective treatment approach for colorectal cancer.
Identification of New Molecular Targets for Treatment of Endometrial Cancers
Authors: Lim W.M. , Nalliah S. , Chung F.F.L. , Chan K.K. , Leong C.O.
Published: September 2018

Background: Current approaches using molecularly targeted drug alone or in combination with cytotoxic agents are associated with varying degrees of response rates and adverse effects. Clearly, there is a need to identify new molecular targets with more selectivity against the endometrial cancer cells. Aim: To perform high throughput screening to identify and validate new molecular targets for treatment of endometrial cancers. Methods: Kinome-wide shRNA library screen was performed on endometrial cancer cell line. The results were validated using viability and apoptosis assay. Immunoblotting assay was conducted to identify the target protein. Results: We identified that the knock-down of endogenous cyclin-dependent kinases regulatory subunit 1B (CKS1B) induced significant cell death in a panel of endometrial cancer cell lines (AN3CA, HEC-1A, HEC-1B, RL-95 and Ishikawa). In contrast, no significant cytotoxicity was observed in the THESC nontransformed endometrial epithelial cells suggesting that CKS1B is mediating a tumor-specific survival pathway. Analysis by immunoblotting assay revealed an increased of p27 protein expression following depletion of endogenous CKS1B in the type 2 endometrial cancer cells (AN3CA and HEC-1A), while no changes was observed in the type 1 (Ishikawa and RL95-2) endometrial cancer cells. These results suggest that CKS1B might regulate the survival of type I and type II endometrial cancer cells through distinct mechanisms. Conclusion: The results demonstrated that inhibition of CKS1B induced significant tumor-specific cell death in endometrial cancer cells. We found that the response is significant in type 2 endometrial cancer cell line and is p27 dependent. This finding suggests that CKS1B could be a potential target for therapeutic intervention and warrant further investigation.
Long-Term Breast Cancer Survival Affected by Overdiagnosis
Authors: Fann C.
Published: September 2018

Background: Overdetected breast cancers (BCs) via mammography screening that are biologically nonprogressive and unnecessary to receive treatment is of great concern for population-based screening. Most previous studies estimated overdiagnosis by excess incidence due to the introduction of screening compared with background incidence derived from randomized control trial, which require population incident-based BC data and the strong assumption of lead-time distribution, few studies have been adopted by using merely follow-up data on BCs. Aim: To assess respective independent contributions of overdiagnosis and curation to long-term breast cancer survival by the application of the novel zero-inflated statistical model to a longitudinal follow up empirical data with sufficient information based on patient-based data. Methods: We designed a retrospective cohort composed of 1346 patients diagnosed with invasive breast cancer in Falun Central Hospital of Dalarna County, Sweden, through international collaboration. A novel zero-inflated cured or overdiagnosis regression model was conducted. The zero part represents both types of nonprogressive cancer without potential of dying from BC, the cured due to treatment and the overdiagnosed due to mammography screening. These 2 types would be distinguished by detection modes (screen-detected cases and interval cancer plus cancers from nonparticipants). The count part represents the progressive breast cancer with potential of dying from BC associated with prognostic factors during follow-up. Results: The probability for nonprogressive BC (the zero part) was 56.14%. The probability of zero due to curation resulting from early detection and effective treatment was 44.34%. Overdiagnosis resulting from mammography screening program was 8.94% and high awareness was 2.86%. Among 43.86% progressive BC (the count part), 32.11% patients undergoing subsequent adjuvant therapies still remained alive after 15-year follow-up when adjusting for significant prognostic factors. The 15-year prognosis-adjusted cumulative survival of BC was dropped from 88.25% to 74.80% after correcting for the zero-inflated part of overdiagnosis. Conclusion: The proposed zero-inflated model with 15 years of follow-up data revealed 12% due to overdiagnosis after taking out the probability of zero due to curation as a result of early detection and effective treatment from the total zero part.
Quantitative Assessment on Waiting Time in Quality Assurance of Screening Program With Application to Taiwanese Population-Based Organized Service Colorectal Cancer Screening
Authors: Jen H.-H.
Published: September 2018

Background: In a population-based organized service colorectal cancer (CRC) screening program, waiting time for confirmatory diagnosis for those who screened as positive test would be affected by coverage rate, positive rate, and compliance rate given clinical capacity of different settings. Long waiting time might cause the anxiety of patient and affect the quality of life. It is an essential index in the quality assurance of screening program. Aim: We aim to project the waiting time in different scenarios by changing the joint effect of these 3 factors (coverage rate, positive rate, and compliance rate). Methods: We proposed a stochastic process for modeling a complicated structure of screening data containing arrival rate for attending screening (coverage rate), positive rate, compliance rate, and waiting time for confirmatory diagnosis. It was applied to Taiwanese nationwide CRC screening program during the period of 2004 to 2009. The estimated parameters were used to project the waiting time by changing different scenarios. Results: Given positive rate and compliance rate, the waiting time was lengthened with increasing coverage rate. Under the similar scenario with Taiwanese nationwide population-based screening (7% of positive rate and 60% of compliance), the waiting time expanded from 10 days to 101 days as the coverage rate increased by 10-fold (from 5% to 50%). If the referral policy allows 2 months of waiting time for follow-up confirmatory, a 3-year CRC screening program can reach to 90% of coverage rate. If positive rate increases as a result of the cutoff value or compliance rate is enhanced, the waiting time can be prolonged in a quantitative manner. Conclusion: Waiting time for confirmatory examination usually plays an important role in the assessment of the quality assurance of screening program. After considering the change of 3 joint effects on coverage rate, positive rate, and compliance rate, we can project the waiting time and provide a quantitative assessment on referral policy to improve the quality of service for decision-maker.
Reduction of Colorectal Cancer Mortality and Advanced Stage Cancer Incidence After 10 Years of Fecal Immunochemical Test Screening
Authors: Chen R.-C. , Chiu H.-M. , Wang Y.-W. , Fann J.C.-Y. , Yen A.M.-F. , Chiu S.Y.-H. , Chen S.L.-S. , Lee Y.-C. , Wu C.-Y. , Jou Y.-Y. , Chen H.-H.
Published: September 2018

Background and aims: Colorectal cancer (CRC) is a leading cause of cancer deaths worldwide, and fecal immunochemical testing (FIT) is most widely used for population-based screening. Reduced long-term CRC mortality has been reported only scarcely in response to early detection with FIT screening. We aimed to elucidate whether and how FIT screening led to overall and site-specific reduction of advanced stage CRC incidence and mortality after the first decade of Taiwan's screening program, which offers biennial FIT screening for people aged 50-69 years. Method: The study cohort comprised eligible subjects who did (screened group) and did not (unscreened group) participate in FIT screening during the inaugural 5 years (2004-2009) with follow up until 2014. FIT-positive subjects were offered colonoscopy as a confirmatory exam. The primary outcome was incidence of advanced stage CRC and CRC mortality. Results: Among 5,417,699 eligible subjects, 3,072,164 (56.6%) had at least once FIT screening, and 1,605,200 (52.3%) received 2 or more screenings during the study period. During mean follow-up of 9.78 years, 5716 screened and 20,962 unscreened subjects developed incident advanced stage cancers [adjusted relative risk (aRR) = 0.76; 95% CI, 0.72-0.79] after controlling for self-selection to attend screening and increasing CRC incidence. CRC deaths during follow-up included 3077 screened and 15,550 unscreened subjects (aRR = 0.56, 95% CI, 0.53-0.59). Effectiveness was greater for distal cancers (advanced cancer incidence aRR = 0.68, 95% CI, 0.65-0.71); mortality aRR = 0.52 95% CI, 0.49-0.55) than for proximal cancers (advanced cancer incidence aRR = 0.99 95% CI, 0.92-1.07; mortality aRR = 0.69 95% CI, 0.63-0.75). Conclusion: FIT screening effectively reduces risk of advanced stage CRC and CRC mortality, with effectiveness consistently stronger for distal CRC than proximal CRC.
Geographical Variations in the Clinical Management of Colorectal Cancer in Australia: A Systematic Review
Authors: Crawford-Williams F. , March S. , Ireland M. , Rowe A. , Goodwin B. , Chambers S. , Aitken J. , Dunn J.
Published: September 2018

Background: Colorectal cancer (CRC) presents considerable health, economic, and societal burden, and Australia has one of the highest incidence rates of this disease. Over a third of the Australian population live in nonmetropolitan areas and research has shown that they experience a range of health disadvantages that result in a higher disease burden and lower life expectancy. One of the main contributors of poorer CRC outcomes in rural Australia may be limited access to treatment facilities and optimal care; however, the extent to which geographical disparities exist in CRC management has not been systematically explored. Aim: To understand the nature of geographical variations in the clinical management and treatment of CRC (including surgery, chemotherapy, and radiotherapy) in Australia, incorporating clinical reports as well as peer-reviewed literature. Methods: A systematic review of published and gray literature was conducted. Five databases (CINAHL, PubMed, Embase, ProQuest, and Informit) were searched for articles published in English from 1990 to 2018. Studies were included if they assessed differences in clinical management according to geographical location; focused on CRC patients; and were conducted in Australia. Included studies were critically appraised using a modified Newcastle-Ottawa Scale. PRISMA systematic review reporting methods were applied. Results: Only 17 articles met inclusion criteria. All were of high (53%) or moderate (47%) quality. The evidence available may suggest that patients in nonmetropolitan areas are more likely to experience delays in surgery and are less likely to receive chemotherapy for stage III colon cancer and adjuvant radiotherapy for rectal cancer. Conclusion: The present review found limited information on clinical management across geographic regions in Australia and the synthesis highlights significant issues both for data collection and reporting at the population level. Where geographical disparities exist, these may be due to a combination of patient and system factors reflective of location. Population-level data regarding clinical management and treatment of CRC needs to be routinely collected to better understand geographical variations and inform future guidelines and policy.
Development of Assessment Tool for Psychological Effect of Thyroid Cancer Screening
Authors: Oh S.-E. , Lee H.J. , Hwang J.Y. , Lim J.T. , Oh S.W. , Lee E.S. , Chang Y. , Lee C.W. , Kim Y.
Published: September 2018

Background: Nation cancer screening program is provided to all population who reached a certain age in Korea. Also individualized cancer screening also widely conducted in private screening units. The harms associated with cancer screening have rarely been reported. Moreover there have been few studies on the psychological effects associated with cancer screening. Aim: This study aimed to evaluate the psychological effects occurring in thyroid cancer screening which is frequently conducted in Korea. We evaluate the validity and reliability of developing measuring tools. Methods: The psychological effects on cancer screening were classified into 3 domains (quality of life, stress response and anxiety) through the review of previous studies and expert discussion. Four assessment tools were selected for measuring quality of life (WHOQOL-BREF), stress level (PSS, SRI), anxiety level (GAD-7). We conducted 2-step of survey. First step was conducted on the day of cancer screening. And second step survey was conducted after reporting cancer screening results. Inclusion criteria of participation is subjects who received thyroid cancer screening for the first time or who has not had thyroid cancer screening for the past 3 years. Based on the survey results, the final assessment tool for psychological effect of thyroid cancer screening was developed through the second expert meeting. The final assessment tool was verified the reliability and the validity through 2-step surveys before and after screening. Results: The new Assessment tool for Psychological Effect of Cancer Screening (APECS) was developed in 4 domains (quality of life, stress-anxiety level, stress responses, and thyroid cancer screening related psychological problems). A total of 143 patients were surveyed on the day of thyroid cancer screening using the developed assessment tool. Second survey was conducted for 99 patients who visited the hospital for counseling the screening results. Test-retest reliability showed high internal consistency with 0.859, P < 0.001, and Cronbach's alpha showed high value with 0.918 in all domains. The reliability of the stress-reaction level domain was the highest in the all domains (0.878). Factor analysis identified 5 factors, including quality of life, stress-anxiety level/response, and thyroid cancer screening–related psychological problems domain were combined. Conclusion: Both of reliability and validity of the newly developed assessment tool for psychological effect of thyroid cancer screening were measured high in all domains. In the future, a strategy for minimizing psychological harms could be suggested from the results of a large scale survey with the new assessment tool on the psychological impact of thyroid cancer screening.
Disparity Between Metro-Centric Cancer Care and Rural Outreach in India: Situational Analysis and Future Trends in Context of Developing Countries
Authors: Chaudhuri S. , Goel A. , Awasthi A. , Gupta S.K. , Rastogi S. , Panda D. , Kumar N. , Aneesh P.
Published: September 2018

Background: Radiation therapy is used in two-third of all patients diagnosed with cancer in any form and it has become an integral part of modern treatment strategies for many types of cancers in recent decade. Semi-urban and rural places in India lack healthcare facilities and so as the cancer care facilities. Aim: To identify the propensity of a metro-centric oncologic care in developing countries undermining the need of availability of facilities in smaller towns and cities. Methods: Data for state-wise population for 2016 and 2026 was projected using cohort component method. For the projection of cancer incidence and prevalence in 2016 and 2026, we assumed that the state-level prevalence and incidence of cancer in the year 2015 will not change over time in 2016. Data collected through telephonic interviews from the radiotherapy centers listed by Atomic Energy Regulatory Board (AERB), India. Further, we assumed few scenarios of cancer incidence and prevalence increase and projected state wise cancer burden in 2026. Results: With almost 70% population of India residing in districts and cities lacking quality health care, the situation of cancer care is much grave. India is currently equipped with only 394 RTU (Radiation Therapy Unit) against requirement of almost 1300 RTU, amounting to 0.38 RTU per million populations as per World Health Organization. The public sponsored healthcare infrastructure for cancer treatment, and research is centralized with all the resources centered in metro/major cities. Eight metro cities of India with a combined population of 140.6 million hold control of 188 RTU under their boundaries. Thus, while habitants of these eight metro cities, constituting only 10.9% of the national population, avail treatment benefit from 38% of total RTU capacity of India, rest of Indian population at 1143.8 million strengths is left prey to the wrath of cancer with just 306 machines at disposal. In comparison, the developed nations as the United States of America, Australia, and the United Kingdom fare far better in RTU availability for treatment of diagnosed cancer patients, with RTU per million population density of 12.45, 10.12 and 5.04 respectively. Similar scenario has been seen in other LMICs in world like Congo, Mongolia, Sudan, Nigeria, Nepal etc. Conclusion: We observed that wide disparity exists in India concerning RTU and cancer facility availability and density per million populations in between metro cities and rest of India and a dire need of improvement to fight against cancer which is very similar to the situation in developing countries.
Radiotherapy With Continued EGFR-TKIs for Oligoprogressive Disease in Non–Small Cell Lung Cancer: A Real-World Study
Authors: Hu C. , Wu S. , Wu F.
Published: September 2018

Introduction: Almost all epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) will develop tyrosine kinase inhibitors (TKIs) resistance. The treatment of oligoprogression is debatable after TKIs resistance. We conducted a real-world retrospective study to evaluate the efficacy of radiotherapy and continuation of TKIs in advanced NSCLC patients with oligoprogressive disease after EGFR-TKIs. Methods: From January 2011 to January 2018, we retrospectively analyzed EGFR-mutated NSCLC patients with oligoprogression in our institution. 33 patients were treated by radiotherapy and continuation of TKIs. We used Kaplan-Meier and Cox regression model to analyze the prognostic factors of progression-free survival (PFS) and overall survival (OS) from the time of oligoprogression. Variables we selected for analyses included gender, age, smoking status, performance status (PS) score, stage at initial diagnosis, initial resectable, radiotherapy dose, EGFR mutation type, number of metastasis, sites of radiation, T790M status, time of oligometastasis to radiotherapy. Results: 33 patients develop resistance to EGFR TKIs at a median time of 11.0 months. The mPFS and mOS were 6.5 and 21.0 months, respectively. T790M mutation was tested in 8 patients. The mPFS was 11.3 months in T790M mutation positive patients and 6.0 months in negative patients. The mPFS of patients with brain, lung, and bone metastases were 5.7, 6.0, and 13.0 months, respectively. The mPFS in patients who started radiotherapy within or beyond 1 month after oligometastasis was 11.0 months and 5.3 months. The mPFS of patients with postoperative recurrence and initial unresectable were 13.0 and 6.0 months, respectively. Patients with 1 or more than 1 metastatic site showed a mPFS of 11.0 and 4.4 months, respectively. Those who had EGRF exon 21 mutation achieved a mPFS of 11.3 months, whereas those with EGRF exon 19 mutation did worse with a mPFS of 6.5 months. Cox regression model showed no variables significantly correlated with PFS difference. Univariate analysis identified age and smoking status were significantly associated with OS. The results of multivariate analysis indicated that there was no OS-related prognostic factors. Conclusion: Radiotherapy with continued TKIs is an efficacious treatment option in our patients. Age and smoking status were prognostic factors for OS. Our research showed that there was a better survival in patients with T790M mutation, EGRF exon 21 mutation, radiotherapy within 1 month after oligometastasis and bone metastases. However, this was not statistically significant. Prospective studies are needed to validate these clinical results.
Development of a National Cancer Registry in a Low Resourced Country: The Case of Kenya National Cancer Registry Programme
Authors: Korir A. , Gakunga R. , Okerosi N. , Karagu A. , Buziba N. , Chesumbai G. , Gathere S. , Manduku V. , Rochford R. , Parkin D.
Published: September 2018

Background: Population-based cancer registration represents the gold standard for the provision of information on cancer incidence in a defined population (Bray F, et. al, IARC Technical Report No. 43). In Kenya, the incidence and prevalence of cancer has not been well documented. The existing population-based cancer registries (PBCRs) cover less than 10% of Kenya's population. Kenya is made up of 47 administrative counties and has a population of over 45 million people. Aim: To establish a National Cancer Registry Program that will compile national data on incidence, mortality and trends of cancer in Kenya over time. Methods: Three functional PBCRs have been in existence covering 3 counties: Nairobi, Eldoret and Kisumu. Needs assessment was conducted in the 3 registries. Additional support and resources were provided. New registries were set up in different geographical regions of Kenya. A centralized office to host the national registry was established and equipped at the Centre for Clinical Research, Kenya Medical Research Institute. Sensitization and awareness activities targeting the leaders in the selected counties were undertaken. Similarly trainings and technical support of the regional registries were conducted. Data were collected on to case registration forms, coded using the International Classification of Diseases for Oncology (ICD-O); data entry, validation and analysis done using IARC software CanReg5. Results: Variations in cancer occurrence in the different counties were noted. However the leading cancers were somewhat similar in the 8 counties with prostate and esophageal cancers being the leading in men while breast and cervical cancer being top among women. These variations could provide understanding on causation of certain types of cancers. Data highlights the need to develop and expand intervention programs like HPV vaccination, screenings, early detection and early treatment. Governments' allocation of resources to cancer registries and surveillance programs is important as well as building partnerships. Conclusion: In countries with limited resources it is expensive to develop a national cancer registry covering the entire country. Our program demonstrates that a national cancer registry program can be established by setting up regional population-based cancer registries that covers a reasonable population of the entire country and aggregating the data in a centralized system. Population-based cancer registries are critical in generating data on burden of cancer in specified populations. These data should be used to inform effective cancer control programs and research.
Predictors of Uptake of Cervical Cancer Screening Among Nurses in Ogbomoso, Oyo State, Nigeria
Authors: Oyekale R. , Oluwatosin A. , Edet B.
Published: September 2018

Background: Globally, cervical cancer cause a significant death rate annually and Nigeria is not an exception. Routine cervical cancer screening has been shown to greatly reduce the number of new cases and deaths accrued to the disease. The researcher´s interaction with nurses showed many nurses with adequate knowledge of cervical cancer and screening still display some form of nonchalant attitude toward the screening. Nurses who form a majority of healthcare providers in all settings often carried away by the care they render to patients to the extent that they neglect there own health. Previous studies have focused on knowledge and attitude to cervical cancer screening among women while no study known to the researcher has been carried out on predictors of cervical cancer screening among nurses particularly in Ogbomoso. Aim: To determine the predictors of cervical cancer screening among nurses in Ogbomoso, Oyo State. Methods: This is a descriptive cross sectional study that used a structured pretested questionnaire with a reliability score of 0.814 to collect data from 230 nurses who are randomly selected from Lautech Teaching Hospital and Bowen University Teaching Hospital in Ogbomoso. Data were collected after approval from the ethical review board of the facilities. Descriptive statistics were used to analyzed sociodemographic characteristics, knowledge of participants, attitudes of participants toward screening and association of factors with utilization of cervical cancer screening among participants while inferential statistics were analyzed with χ2 and Student t test using Statistical Package For Social Sciences (SPSS) software version 21 for Windows. Results: The mean age of participants was 38.7, SD=10.724, (72.2%) were married, (49.6%) were graduate and earn a minimum of #45,000 as monthly income. The respondents reported several factors such as level of education (71.7%), financial status (76.5%), marital status (64.8%), lack of facilities (77%), lack of awareness (75.5%), long distance to place of screening (68.7%), inconvenient screening time (75.7%) and age (65.2%) as influencing utilization of cervical cancer screening. Marital status was shown to be significantly related with utilization of cervical cancer screening with p value=0.047. Conclusion: Conclusively, the study has shown that marital status is a significant predictor of cervical cancer screening. Female nurses generally are therefore encouraged to use screening services more regularly and the hospital can help by subsidizing the cost of screening and make it more easily available and accessible for nurses. For the married nurses who utilizes screening services, they are encouraged to do it according to the guideline recommended for screening.
EBV-BZLF1 Promotes Gastric Cancer Growth Through Activating the PI3K/AKT Pathway
Authors: Li B. , Zhang M. , Zhang C. , Shen L. , Gao J.
Published: September 2018

Background: EBVaGC (EBV associated gastric cancer) had been paid much attentions once classified by TCGA and were considered as the suitable group for immunotherapy, which hold distinguishing characteristics with EBVnGC (EBV nonassociated gastric cancer). This study aims to explore the biologic behavior and its possible mechanisms to provide treatment options for EBVaGC. Methods: Lentiviral infection system was used to construct the control and BZLF1 stably expressing gastric cancer cell lines (AGS and HGC27). The cell-derived xenografts (CDX) were constructed to detect the tumor growth and functional experiment including CCK8 assay, cell cycle assay, apoptosis assay, cell migration and invasion assay were implemented to detect the proliferation and transfer ability in vitro. Western blot and immunohistochemistry were used to detect the expression of related molecules. Results: The BZLF1 overexpression cells and the corresponding xenografts grew faster than control groups with enhanced pAKT and pS6 expression. BZLF1 induced “G0/1 phase” arrest in AGS and “S phase” arrest in HGC27 cell, inhibited cell apoptosis through upregulating bcl-2 protein, meanwhile, slightly increased P53 and p-P53 expression in both BZLF1 overexpression cells. However, no significant effects were observed on the malignant biologic behaviors in terms of migration and invasion ability. Conclusion: BZLF1 may promote the growth of gastric cancer through activating the PI3K/AKT pathway, regulating the cell cycle especially regarding P53 signaling network. PI3K/AKT pathway inhibitor probably become promising treatment options for EBVaGC.