bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinicopathological Features and Treatment Outcomes in Parotid Malignancies at Ocean Road Cancer Institute, Dar-es-Salaam, Tanzania
Authors: Adatia A.
Published: September 2018

Background: Neoplasms that arise in the salivary glands are relatively rare, yet they represent a wide variety of both benign and malignant histologic subtypes. Tumors of the salivary glands form one of the most heterogeneous groups of oncological pathology. Head and neck tumors represent ∼5% of human neoplasms, and out of these, salivary gland neoplasms constitute 10%. Aim: The challenges faced for parotid gland malignancy are numerous and these factors determine the treatment modality, prognosis and outcome, overall survival, sociodemographic features affecting Tanzanian residents and there is very little knowledge on clinicopathological aspects of parotid gland malignancies diagnosed at a tertiary health center and this study can compare the findings with epidemiologic data from different geographic locations. Methods: A Retrospective study design was used among all patients who had been diagnosed and confirmed histologically with malignant Parotid tumor referred to and treated at Ocean Road Cancer Institute (ORCI) from January 2009-December 2016. Analysis of this retrospective study determined the sociodemographic factors, clinico-pathologic features, treatment outcomes of surgery, radiotherapy, chemotherapy and assessment of 2 years overall survival of parotid malignancies from January 2009 to December 2014. The study was conducted at ORCI in Dar es Salaam. Results: Out of 94 patients with histologically confirmed parotid gland malignancy, more males were affected compared with females with the ratio of 1.18:1 and the mean SD age of patients was 51.9 years. Adenocarcinoma was the most common malignant tumor n = 37 (40%) followed by squamous cell carcinoma n = 18 (19.1%) and the left parotid gland being the most affected site. 44 cases (46.8%) had pathologic grading, grade IV accounting for majority of the grades (27.3%). Stage IV was presented the most n=72 (76.5%) and 8.5% presented with metastasis at diagnosis. 31% of patients were subjected to surgery while 69.1% were deemed to be unfit for surgery due to advanced disease. Radiotherapy was received by n = 82 (95.2%) with 13 patients (14%) subjected to curative intent and 69 patients (86%) subjected to palliative intent. 2 year overall survival for the curative cohort from 2009-2014 is 23% and 11% for the palliative arm. The 2 year overall survival of parotid gland malignancy treated at ORCI is 12%. Conclusion: Clinico-pathologic presentation of parotid gland malignancy seen in this study differs from other studies probably due to geographical variations. More males are affected than women, especially in the middle ages. Adenocarcinoma was the most frequent histology. Two years overall survival from 2009 to 2014 was 12%. Late stage presentation was seen as a problem that needs to addressed to maximize the effectiveness of the treatment, and improve the overall survival. Treatment modalities need to be standardized across health facilities in Tanzania.
Benzo(a)pyrene, an Active Product of Cigarette Smoke, Role in PLA2 Isoforms Activation in Colon Cancer
Authors: Sharma S. , Yadav S. , Rana S. , Avti P. , Khanduja K.L.
Published: September 2018

Background and aim: One of the active combustion product of cigarette smoke, Benzo[a]pyrenes, role in pulmonary cancer is clearly understood. However, its role in gastrointestinal cancer including colon cancer is not clearly understood. Methods: In this study, benzo(a)pyrenes was treated to colon cells to evaluate its role in cell viability, cellular ROS, and gene expression of various PLA2 isoforms was evaluated by FACS and PCR. The identified PLA2 was silenced at the gene level to evaluate its role in cell viability and ROS generation. Results: B(a)P treatment at 1 µg/mL for 48 h to HCT-15 male colon cells significantly reduced the cell viability without affecting HT-29 female colon cells. Higher doses and longer treatment duration with B(a)P showed that female colon cells were highly sensitive than male colon cells. Annexin-V/PI staining for preapoptotic detection showed that B(a)P treatment increased the apoptosis in both the cell types in a concentration and time-dependent manner. The cytosolic ROS (cROS) and superoxide radical (SOR) formation in the female colon cells was significantly higher than male colon cells unlike the mitochondrial ROS (mtROS) production which was significantly higher in male colon cells. Treatment with B(a)P significantly upregulated the IID and IVA PLA2 isoform groups in HCT-15 male colon cells, whereas IB was upregulated in HT-29 female colon cells among the various PLA2 isozyme gene studied (IB, IID, III, IVA, IVB, IVC, VI, X, aiPLA2 and iPLA2). Gene silencing experiments targeting PLA2 IID and IVA in the HCT-15 male colon cells and IB in HT-29 female colon cells showed no effect with B(a)P treatment on the cell proliferation, apoptosis, membrane integrity and free radicals (ROS, mtROS, and SOR) generation. Conclusion: Targeting specific PLA2 isozymes in a cell-specific manner abolished the B(a)P-induced PLA2-mediated oxidative damage–related signaling pathways.
Status of Bone Mineral Density Mammographic Breast Density and Serum Oestrogen and Calcium Levels: A Case-Control Study
Authors: Chelliah K.
Published: September 2018

Background: Mammographic breast density (MBD) is a predictor of breast cancer while bone mineral density (BMD) is a marker of estrogen and calcium level. Aim: The objective of the study is to compare MBD, BMD, estrogen and calcium level between the cancer and control groups. Method: This case-control study was done on 40 women in each control and cancer group. The women had mammography and dual energy x-ray absorptiometry at Kuala Lumpur Hospital. Respondents were chosen using purposive sampling and women who had commenced cancer treatment were excluded from the study. Blood samples were taken to analyze serum estrogen and calcium level of the subjects. Results: The demographic characteristic of the control and cancer patients were similar in age, body mass index and menarche age. The mean of selected variables were compared between groups using independent t test and Mann-Whitney for continuous and categorical data respectively. There was significant difference for estrogen between the groups. Person correlation showed moderate correlation between estrogen level and BMD. Women with scattered fibroglandular breasts and dense breast were the most affected by cancer, multiple logistic regression showed significant difference between the groups for breast density ( P = 0.047) and estrogen level ( P = 0.002). Conclusion: There is significant difference between cancer and control group for MBD and estrogen level.
Targeting the Tumour-Specific Spliceosome Through In Silico Virtual Screening for Discovery of New SF3B1 Small Molecule Inhibitors
Authors: Wong L.Z.
Published: September 2018

Background: The coding (exon) and noncoding (intron) eukaryotic genes are expressed as precursor messenger RNA (premRNA). mRNA splicing defines the process by which introns are excised from premRNA and flanking exons are ligated together. This process is catalyzed by the spliceosome in which combination of small nuclear ribonucleoproteins (U1, U2, U4, U5, U6) forms a spliceosome. The SF3B1 protein is a core component of the U2 snRNP that binds to the branch site and facilitate RNA splicing. Recent studies have identified mutations and dysregulation of in SF3B1 activities in subsets of human cancers including chronic lymphocytic leukemias (CLLs), uveal melanomas, pancreatic cancers and breast cancers. Despite promising in vivo results indicating the potential of spliceosome modulators in targeting the refractory breast cancers, the preclinical and clinical development of such modulators will take several years to complete. Aim: In the current study, we sought to identify new SF3B1 modulators using massive virtual screening of FDA-approved drugs or novel agents for drug repurposing. Methods: A total of 3000 compounds were screened and the hits were identified based on the binding free energy (kcal/mol) of the molecules to the predicted binding sites. Of the 90 hits, vitamin D3 and its analogs (calcipotriol and calcitriol) were identified as a putative SF3B1 modulators. Results: Further in vitro testing revealed that vitamin D3 and its analogs induced significant mRNA misplicing and tumor-specific cell death in MCF7 and MDA-MB-468. Further analyses revealed that vitamin D3 and its analogs significantly reduce SF3B1 protein expression with no changes in its mRNA expression. Conclusion: These results suggest that vitamin D3 and its analogs might interact with SF3B1 to induce protein degradation rather than transcriptional activation.
Mouse Avatar Models of Colorectal Cancer Liver Metastasis: The Molecularly Annotated Platforms for Preclinical Evaluation of Novel Therapeutics
Authors: Jingyuan W. , Wei L. , Jing G. , Baocai X. , Lin S.
Published: September 2018

Background: Liver is the most common metastatic site in advanced colorectal cancer. Most patients with colorectal cancer liver metastasis (CRLM) could not benefit from the current treatment. Patient-derived xenograft (PDX) models with definite molecular signature are attractive preclinical models and essential for development of novel drugs. Aim: This study was designed to focus on the establishment, characterization of pathologic and molecular features of PDX models. Furthermore, we also validate potential therapeutic targets and explore novel drug therapies guided by genotyping or expression profiling, leading to potential implications for precision medicine. Methods: CRLM PDX models were established and elucidated their possible implications for preclinical research and personalized treatment from their fidelity of clinicopathologic characteristics, genomic landscape, and antitumor activities of novel targeted drugs. Response biomarkers were also explored. Results: A total of 56 PDX models from CRLM were successfully established (transplantation success 76.7%, 56/73). The transplantation rate was higher than that of primary specimens (61.5%, 16/26). No differences were observed between latency period and characteristics except the level of CEA. Along with the passaging, latency period became shorter and shorter. PDXs from CRLM recapitulated the pathologic, genetic, and protein properties of corresponding parental tumors. Frequent altered genes showed high consistency compared with patients' genomic alterations, and were enriched in MAPK, ErbB, cell cycle, focal adhesion, adherence junction pathways. Several potential drug targets, such as KRAS, HER2 and FGFR2, were selected and validated by corresponding inhibitors. In addition, PDX models could also used for patients with no druggable alterations identified to screen the efficient regimen. Conclusion: In this study, we have successfully established and validated a large panel of molecularly annotated CRLM platforms for preclinical evaluation of novel therapeutics and biomarker discovery.
Applying of Technique for Assessing Occupational Cancerogenic Risks for Workers Used in Metallurgical Shops With Different Methods of Blister Copper Production
Authors: Adrianovskii V. , Lipatov G. , Kuzmina E. , Zlygosteva N.
Published: September 2018

Background: Exposure to carcinogens at workers used in the enterprises of copper metallurgy making urgent the task of assessing carcinogenic risks in the nonferrous metallurgy. In particular, melting and conversion of copper are characterized by the exposure of arsenic, cadmium, lead, nickel, benz(a)pyrene. Aim: Assessment of professional carcinogenic risks for workers used in shops with a shaft and reflective copper smelting ore, compared with one of the modern methods of producing blister copper. Carcinogenic risk was estimated from each of the substances and in total from their combination for 25 years of work experience. When inappropriate carcinogen risk calculated duration time of operation, at which the allowable upper limit of occupational risk. Methods: A hygienic assessment of the contribution of the working environment to the formation of a carcinogenic risk for workers engaged in reverberatory and blast smelting of copper-bearing ores in comparison with autogenous processes was carried out. To calculate the carcinogenic risks, we used 8 hours concentration in the working air as well as slope factors for inhalation exposure (SFi) of arsenic, cadmium, lead, nickel, and benz(a)pyrene. Results: It is shown that when copper is smelted, inorganic arsenic compounds are the main factor that forms a carcinogenic risk: reverberatory smelting - 67.8%; shaft smelting - 88.9%; melting furnaces in “molten bath” - 96.2%. The highest predicted values of carcinogenic risk for similar occupations of metallurgical shops are observed with reverberatory (2.9 × 10−2) and blast smelting (1.8 × 10−2), rather than with bath smelting (5.2 × 10−3). It is due to the difference in the used equipment. The highest values of carcinogenic risks identified in the batch loader, working conditions which are characterized by exposure to high concentrations of dust in the workplace area, and the least - for the metal spiller. Among the professions of the copper smelting shop, in which reflective smelting is used, the values of the length of service in contact with carcinogenic substances were in the range from 6.5 to 1.1 years. A little more was the duration of the maximum work experience in mine melting - from 1.38 to 1.56 years. In the smelting shop with smelting furnaces in a “liquid bath” the amount of acceptable work experience varied from 3.13 to 6.41 years. Conclusion: When all the existing methods for producing blister copper carcinogenic risk due to exposure to arsenic, cadmium, lead, chromium (VI), and benzo(a)pyrene is in an unacceptable range (>1.0 × 10−3). The main measure to reduce the carcinogenic risk of blister copper production should be the technical re-equipment of smelter shops with the introduction of autogenous processes (melting furnaces in “molten bath”).
Quantitative Models for Modeling Overdetection in Population-Based Screening for Colorectal Cancer
Authors: Lin T.-Y.
Published: September 2018

Background: Overdetection resulting from population-based cancer screening has been debatable over the past decade. However, a systematic approach for quantitative estimation of overdetection has been barely addressed. Contextually, mass screening for breast cancer and prostate cancer has been well documented, but colorectal cancer (CRC) has been scarcely highlighted. Aim: The aim of this study is to develop a systematic approach for quantitative estimation of overdetection and elucidating the mechanism of overdetection in population-based colorectal cancer screening. Methods: The graphic method was first proposed by comparing cumulative incidence curves of advanced and nonadvanced cancers. Then, the modeling approaches used for quantitative methods were developed. We proposed the standardized overdetection ratio (SOR), the index including expected and observed which are simulated by a 3-state Markov model (normal, preclinical detectable phase, clinical phase) based on screened group and control group, respectively. Moreover, we developed the 5-state Markov model in conjunction with SOR to quantify the extent of overdetection. Two randomized controlled trials on guaiac–fecal occult blood test (gFOBT) in U.K. and Denmark and population-based service screening using fecal immunochemical test (FIT) in Taiwan were applied to assess the proposed methods to quantify overdetection in population-based cancer screening. Results: Using the graphic method, the average of overdetection was 31.1% and 24.9% for the UK trial and the Denmark trial, respectively. However, the estimated proportion of overdetection may be biased because the graphic method did not take the natural history of adenoma and high awareness in the routine clinical practice into account. According to the proposed 3-state Markov model, the overdetection of CRC was 9% with gFOBT based on the 2 randomized controlled trials in Europe and 7% with FIT based on a nationwide screening program in Taiwan. The estimated overdetection by the 5-state Markov model were 6.1% and 9.2% for the U.K. and Denmark trial, respectively. Moreover, the main pathway for overdetection in population-based CRC screening is from nonadvanced in the preclinical phase to advanced in the preclinical phase which is supported by the evidence that SOR decreases from 1.29 to 1.16 and 1.16 to 0.97 for the U.K. and Denmark trial, respectively. Conclusion: This study developed the graphic method and the disease natural progression model for quantitative assessment of overdetection in colorectal cancer. The index, SOR, was proposed not only to assess the extent of overdetection but also to elucidate the mechanism to know how overdetection affects the progression of colorectal cancer from the preclinical phase to the clinical phase with information of cancer stage.
Personalized Prediction Model for Hepatocellular Carcinoma With a Bayesian Clinical Reasoning Approach
Authors: Wang W.-C.
Published: September 2018

Background: Predictive models for the risk of hepatocellular carcinoma (HCC) are often appropriate for average-risk population but not tailored for a personalized prediction model for individual risk of hepatocellular carcinoma (HCC), namely personalized prediction model. Aim: The objective of this study is to build up an individually tailored predictive model for HCC by using a Bayesian clinical reasoning algorithm to stratify risk groups of the underlying population. Methods: Data were derived from a community-based screening cohort consisting of 98,552 subjects between 1999 and 2007. Information on HBV and HCV infection status, liver function test, AFT, family history of liver cancer, demographic characteristics, lifestyle variables and relevant biomarkers were collected. The occurrence of HCC was ascertained by the linkage of the nationwide cancer registry till the end of 2007. Bayesian clinical reasoning model was adopted by constructing the basic model taken as the prior model for average-risk subject. We then updated the basic model by sequentially incorporating other risk factors for HCC encrypted in the likelihood ratio to form posterior probability that was used for predicting individual risk of HCC. Results: By dint of Bayesian clinical reasoning model with a step-by-step update of the risk of HCC for the sequentially obtained information, a 57-year-old man was predicted to yield 0.69% of HCC risk with the prior model. After history-taking of having hepatitis B carrier (likelihood ratio [LR]: 3.65), family history (LR: 1.43), and no alcohol drinking (LR: 0.89), the posterior risk for HCC was enhanced up to 3.13%. After further biochemical examination, the updated risk of HCC for a man [the following biomarkers [ALT = 30 IU/L (LR: 0.78), AST = 56 IU/L (LR: 8.99), platelets = (203 × /μL) (unit cube of ten) (LR: 0.55)] was increase to 11.07%. Conclusion: We proposed a individually tailored prediction model for HCC by incorporating routine information with a sequential Bayesian clinical reasoning approach.
A Study Utilizing Mobile E-Health and Self-Acquired Cervical Screening in Health Clinics
Authors: Woo Y.L. , Nasir N.H. , Kanapathy J. , Said Z. Mohd
Published: September 2018

Background: Malaysia continues to have a high incidence of cervical cancer with a relatively high mortality rate due to late presentation. Pilot Project R.O.S.E was a cross-sectional study to assess acceptability, feasibility and reach of a cervical screening strategy that utilizes self-collected, point-of-care HPV testing in primary care settings. Within this study, mobile SMS technology was used to register patients into a cervical screening registry and to deliver the HPV test results. Aim: To assess the feasibility, acceptability, advantages and limitations of the use of mobile SMS technology to deliver HPV screening test results. Methods: Invitation for cervical screening was offered to women aged 30 to 65 years who are presenting to these clinics for care, or accompanying another individual. Upon agreeing to do the test, the nurse registered the woman's details and mobile number. A mobile phone verification SMS is triggered at this point. HPV results were delivered to women via mobile SMS within 3 working days. Phone-based surveys were conducted on randomly selected screened positives and screened negative women to ascertain acceptability of the screening and the usage of mobile technology. Results: Ninety percent of participants received their SMS results without any hitches. Ten percent of participants experienced problems with receiving their results SMS. Further investigations revealed that there were various reasons for message delivery failure. Posttest surveys revealed that majority of participants were satisfied with the use of mobile technology to receive HPV screening test results. Conclusion: This study suggests that the use of mobile SMS technology for delivery of HPV screening test results is feasible and acceptable. However, measures should be taken to overcome technology related failures. The findings of this implementation research may help to inform the design of future mobile SMS technology usage within health settings in Malaysia.
Understanding Barriers to Cervical Screening Follow-Up and Treatment Compliance in Malaysia: A Qualitative Study of Provider Perspectives
Authors: Hong L.L. , Yong J.C. , Lee K.Y. , Nasir N.H. Binti , Gravitt P. , Lee Y.K. , Woo Y.L.
Published: September 2018

Background: Cervical cancer is a leading cause of women mortality in Malaysia. In Malaysia, system of care remain fragmented despite the increased uptake of cervical screening. Thus, it is important to better understand factors that affect loss to follow-up and treatment along the care continuum. The ability of a patient to attend a cervical screening clinic, to return for possible treatment, and to return to clinic for follow-up evaluation (“the patient factor”) is a major component to the success of a screening program. Women diagnosed with early or local (stage 1) cervical cancer have a 92% chance of survival 5 years after diagnosis whereas survival rates decrease to 17% for women with late cancer diagnoses. Due to this, a better understanding of barriers to cervical cancer treatment can inform initiatives to address therapeutic delays, which is vitally important to providing optimal care. Aim: To explore, from the perspectives of healthcare professionals, the perceived barriers of cervical screening follow-up and treatment compliance in Malaysia. Methods: In-depth semistructured interviews with 45 government health clinic staffs comprise of clinicians, nurses, front desk staffs, medical laboratory technicians and IT support engineers were conducted from 5 government health clinics in Petaling District. Qualitative content analysis through an inductive approach was used to identify barriers of cervical cancer care continuum and treatment compliance in public health clinics settings. Results: Participants identified various potential barriers to seeking follow-up care and treatment after receiving a positive Pap test results or invalid test results at 2 levels: the structural level, and the patient level. Long waiting time, lack of transport to healthcare providers, fear of treatment, poor documentation, absence of cervical screening registry, as well as unsystematic referral or treatment procedures are some of the major reasons affecting follow-up and treatment compliance. Conclusion: The results highlight the need of structural and personal interventions that eliminate barriers to follow-up and treatment compliance along the care continuum.
Cancer Care in Small Pacific Island States
Authors: Dyer R. , Tafuna'i M. , Meredith I. , Sarfati D.
Published: September 2018

Background: Like other LMICs, many Pacific Island countries and territories (PICTs) have fragile and overburdened health systems with which to combat an increasing burden of cancer. Additionally, a combination of small geographically dispersed populations, limited resources, isolation and frequent natural disasters make cancer control in Pacific Islands also significantly different to elsewhere in the world. No prior work has provided a stocktake of current capacity for diagnosis and treatment of cancer across the region to date. Aim: To describe the specialized health services available for cancer control in the Pacific region, and show the complexity associated with accessing cancer care for Pacific Islanders. Methods: A cross-sectional review of medical services and human resources available for cancer control was undertaken for 21 Pacific Community (SPC) member countries and territories in April-May 2018 , specifically diagnosis (pathology and radiology) and treatment (chemotherapy, radiotherapy and surgical modalities and overseas referrals for services not available on-island) by contacting individual countries and territories. Common travel routes were mapped individually for 4 PICTs; Papua New Guinea, Solomon Islands, Kiribati and Tokelau; as examples of the unique challenges faced by rural dwelling Pacific Islanders when accessing the highest level of care available in-country. Results: Capacity for cancer diagnosis and care is extremely limited in the Pacific region. The exceptions are the 2 French territories (French Polynesia and New Caledonia) and Guam where a near full complement of services for diagnosis and treatment are operational. Some pathology services are generally available in the larger PICTs, while specimens are sent to affiliated off island laboratories for the rest. Plain x-ray and ultrasound are available at 1 or more locations in all PICTs. General and gynecologic surgery is the most widespread treatment modality available. Some to full chemotherapy administered in 7 and radiotherapy in 3 (formerly 4) PICTs. Overseas referrals for medical services not available in-country are a common feature to all PICTs health systems. A need to travel long distances to access health care is a challenged faced by Pacific Islanders on outer islands and rural villages. Examples will be presented. Conclusion: Cancer control services are few and far between in the Pacific region, and PICTs will always likely rely on overseas referrals for care not available. Access barriers exist for those on outer islands and in villages, and an unknown number seek treatment late or not at all for these reasons. Governments need to invest into strengthening primary and secondary care services, making them an option that is more easily accessible to remote populations. Collaboration between transport and health sectors to look at ways to improve frequency, regulation and safety of modes of transportation to outer islands to improve current systems.
Identifying the Barriers of Delayed Presentation in Pakistani Breast Cancer Patients Undergoing Care at Tertiary Hospital
Authors: Gulzar F.
Published: September 2018

Background: Breast cancer is the most frequently diagnosed cancer in females worldwide and second leading cause of cancer related death among women. In Pakistan, 1 in 8 women would develop breast cancer at some stage of their life. Aim: Delay in seeking health care by breast cancer patients is associated with advanced stage of disease and poor survival rate. This study aimed at identifying the barriers of delayed presentation and their association with various sociodemographic variables. Methods: A total of 200 female patients with abnormal breast finding were randomly selected. Delay was defined as, consultation with health care provider by more than 3 months from the appearance of first symptoms. Sociodemographic variables, symptoms, time interval between seeking medical attention and appearance of symptoms and causes of the delayed presentation were inquired. Data were statistically evaluated by χ2 and logistic regression tests for significance and association. Results: Among 125 breast cancer women fulfilling inclusion criteria, aged 24-75 years, 88.8% (n = 111) of patients presented late (>3 months) and 59% of them were presented advanced stage (stage III/IV) of disease. Majority of them were older than 40 years (65.6%) age, 99.2% married, 60.8% under matriculation, 67.2% had poor social status, 64.8% had a negative family history of any cancer type. 96% of patients complained presence of a painless lump in their breast. Ignorance of disease or presence of painless lumps in the breast and low financial resources for therapy (81.1%) were the main causes of delayed presentation. Moreover, educational factor ( P < 0.000, OR, 4.682) and social status ( P < 0.001, OR, 95% CI) were also associated with delayed presentation. Conclusion: Our study highlighted the reasons of delayed presentation in Pakistani breast cancer patients. The significant number of patients presented late due to misconceptions and poor knowledge about the disease and its symptoms while illiteracy and poor social status were the major contributing factors toward delayed presentation which lead to advanced stage of disease and ultimately decreased survival rate.
Effects and Mechanism of Dihydroartemisinin on Malignant Behavior of Cisplatin-Resistant Gastric Cancer Cells
Authors: Zhang S. , Feng R. , Yuan F. , Chen X. , Li N. , Yang S.
Published: September 2018

Background: Studies showed that dihydroartemisinin (DHA) has significant antitumor effects. However, there have been no relevant reports on gastric cancer resistance to DHA. Aim: To investigate the influence of DHA on the malignant behavior of cisplatin (DDP)-resistant gastric cancer cells SGC7901/DDP and the possible molecular mechanism. Methods: The IC50 of DHA against SGC7901/DDP cells at 48 h was obtained with CCK-8. DHA was used against SGC7901/DDP, with IC50 concentration at 0 µmol/L, 0.5-fold, onefold, and twofold respectively. Then the proliferation activity of SGC7901/DDP from day 1 to day 5 was detected by CCK-8. At 48 h after DHA treatment, we observed apoptosis, invasion, and migration, evaluated autophagy, and detected the expression level of protein related to the regulation of autophagy, apoptosis, angiogenesis and lymphangiogenesis with Western blot. The influence of DHA on cisplatin resistance of SGC7901/DDP was detected through sensitization test and the evaluation of p-gp expression level. Results: The IC50 concentration of DHA against SGC7901/DDP cells at 48 h is 70 µmol/L. DHA significantly inhibited the proliferation of SGC7901/DDP, which was time- and concentration-dependent (all P < 0.05). After having been treated for 48 h by increasing concentrations of DHA (0, 35, 70 and 140 µmol/L), the apoptosis rate increased and the penetrating cell number and scratch healing rate significantly decreased (all P < 0.05). The expression levels of Beclin1 and LC3-II/LC3-I which were corrected with autophagy, and the formation of autophagosomes and autophagous vacuoles increased in a concentration-dependent manner (all P < 0.05). The total PI3K, Akt, and mTOR expression levels did not significantly change, but their phosphorylated products (PI3P, p-Akt [Ser473], and p-mTOR) showed concentration-dependent decreases (all P < 0.05). The expression of caspases-8/9/3 protein significantly increased while the expression of VEGF-A、VEGF-C protein decreased (all P < 0.05). DHA could reverse the resistance of SGC7901/DDP cells to cisplatin after DHA treatment at a nontoxic dose (15.23 µg/mL) with a reversal rate of 2.95. After DHA treatment at different concentrations for 48 h, the expression of p-gp was significantly reduced in a concentration-dependent manner ( P < 0.05). Conclusion: DHA significantly inhibited proliferation, promoted programmed death, and had anti-invasion and antimetastatic effects on SGC7901/DDP cells, probably by upregulating autophagy-related Beclin1 and LC3-II expression and by inhibiting the antiautophagy signaling pathway PI3K/AKT/mTOR, thus promoting autophagic death. In addition, DHA induced caspase-dependent and mitochondrial pathway apoptosis in SGC7901/DDP cells, and reduced VEGF-A and VEGF-C activity to promote antiangiogenesis and antilymphangiogenesis. Furthermore, DHA effectively reversed the cisplatin resistance of gastric cancer cell by inhibiting p-gp expression.
Using Hospital-Based Cancer Registry Data to Inform Establishment of Population-Based Cancer Registries in Western Kenya
Authors: Chesumbai G.C. , Koskei A.C. , Buziba N.G. , Chite F.A.
Published: September 2018

Background: Eldoret Cancer Registry (ECR) is both a population-based cancer registry (PBCR) and hospital-based cancer registry (HBCR) located in Uasin Gishu County, western region of Kenya. As HBCR, it collects data on cancer cases seen at the Moi Teaching and Referral Hospital (M.T.R.H.), which is the second largest public referral hospital in Kenya and has a robust cancer diagnosis, treatment facilities and medical specialists. The catchment population of MTRH is estimated at 24 million. Aim: The aim of this study is to determine the number of cancer patients seen at MTRH by county and determine which counties will benefit most from establishment of a PBCR, based on their high incidence. Methods: Case finding is an active process. The E.C.R seeks clearance to collect data from the various data sources within MTRH. Trained cancer registrars visit the units on a regular basis to abstract and update cancer data into CanReg5. Quality checks and analysis of data are mainly done using CanReg5. Results: 16 years of HBCR data were analyzed. Out 20,423 cancer cases, Uasin Gishu county registered 39%. Nandi, Bungoma, Kakamega and Trans-Nzoia counties each registered 8%, 7%, 6% and 6% respectively. E-Marakwet and Busia both had 4% while other counties had below 2% of cancers cases registered for the period of analysis. Conclusion: Notably, there were high numbers of cancer patients registered from counties bordering Uasin Gishu. There is a high likelihood that there are more cases in these areas for patients who did not make it to MTRH due to preference, distance, SES, traditional/cultural beliefs etc. Establishing PBCRs will ensure a more comprehensive capture and reporting of cancer incidence and therefore necessitate proper planning for cancer control programs in those areas to reduce cancer burden and improve services for cancer patients and their families.
Increasing Trend in the Incidence of Colorectal Cancer on Malaysia
Authors: Ali N. , Manan A. Ab
Published: September 2018

Background: Colorectal cancer (CRC) is the second most common cancer in Malaysia (13.2%). Aim: To study the epidemiologic trend of colorectal cancer in Malaysia and to suggest the strategy in reducing the incidence of CRC in Malaysia. Methods: Total of 13,693 cases of colorectal cancer diagnosed in 2007-2011 were extracted from the Malaysian National Cancer Registry (MNCR). MNCR is a population-based cancer registry which collects data from all government and private facilities (hospitals, clinics, laboratories, National Registration Department and Health Informatics, MOH) by passive notification and active case findings. The registry registers all new cancer cases among Malaysian citizen diagnosed in Malaysia into CanReg4 software. Data were explored using IARC tools and analyzed using CanReg4 software. Results: 55.8% of the colorectal cancer cases were in male and 44.2% in female. ASR was 14.6 per 100,000 population for male and 11.1 per 100,000 populations for female. The male to female ASR ratio was 1.3:1. The 5-years trend shows increasing incidence for both gender. The age-specific incidence rates of the cases were between 45 to 75 years old. The lifetime risk for males was 1 in 56 and in females was 1 in 74. Majority of the cancer were detected among Chinese followed by Malays and Indians. 66% of the colorectal cancer presented at advanced stage (stage 3 and 4) in males and 65% in female. Conclusion: The trend of colorectal cancer is increasing in Malaysia and most of the cancer cases were diagnosed at late stage. To increase the detection rate of CRC at early stage, Ministry of Health Malaysia has introduce screening program using immunochemical fecal occult blood test (iFOBT) since 2013. Tremendous campaigns also being carry out in the community to create awareness on the importance of colorectal cancer screening for early detection and treatment hence improved the survival.
A 30 Years’ Experience in Cancer Prevention From Alexandria, Egypt
Authors: Elkhwsky F.
Published: September 2018

Background: Cancer registration is a systematic process of data collection of adequate data about patient with confirmed cancer, followed by processing and dissemination of reports to allow understanding of magnitude and pattern of cancer in certain covered population. Alexandria Cancer Registry (ACR) is a well-established central hospital based cancer registry from university hospitals, hospitals of ministry of public health, medical care organization and health insurance hospitals to cover more than 90% of diagnosed cases with cancer. Data are collected active and passive ways. Data abstracts include: age, gender, residence, occupation, date of first diagnosis and contact address of the patient together with items about mode of diagnosis, site, laterality, topography, histology, lymph node affections, modality of treatment and health status during the last visit. Cancer registrars in ACR attended several continuous training activities in abstracting, case ascertainment and TNM coding to allow competence, reliability and accuracy of data through intimate supervision from pathologists, oncologists, surgeons and radiologists in the registry board. Data manipulation and analysis are routinely by CanReg5.0 software. The last report in 2015, shows a total of 4550 confirmed cases have been registered, with a male to female ratio 1:1.1. The report adopted the guidelines of IACR-WHO. The report shows the frequency of cases by systems, age and gender, followed by affected organs within each system. The most affected system was connective tissues and soft tissue including female breast cancer. The second most affected system was gastrointestinal system. Primary hepatocellular carcinoma replaced urinary bladder as the first most frequent cancer among males with young age presentation. As a data bank, several research activities has been done in ACR in the form of case control studies in collaboration with IARC and Mario Negri Institute, Milan, Italy. Screening for colorectal cancer started with University of Alabama at Birmingham. Several interesting findings will be displayed, discussed and explained during the presentation. Conclusion: The appropriate data quality of cancer patients in cancer registry along with the catalog guided biologic repositories are considered as initial pillar to establish a biobank and allowed us to join International Biobank (IBB) and BCNet in IARC to accelerate global understanding of causes of cancer and joining a framework of other members will allow exchange of knowledge and upscale levels of cancer prevention.
EUS-Guided FNA Biopsy of Solid Pancreatic Lesions: A Review of 111 Cases and Comparative Study of Diff-Quik/PAP/Thin Prep Staining Techniques
Authors: Lad D.L. , Lad L.K.V. , Jhala N.C. , Toha A.
Published: September 2018

Background: Pancreatic cancer is the fourth leading cause of cancer associated deaths in the United States and ranks ninth in its incidence. EUS-guided FNA cytology has emerged as an important diagnostic tool since Vilman and Grimm (1992) made the first reports of endoscopic guided fine needle aspiration. Currently, EUS-guided FNA biopsy of the pancreas is a standard practice for the diagnosis and staging of pancreatic malignancy. Aim: The current study was carried out with the following objectives. 1. To find out the diagnostic accuracy, sensitivity, and specificity of EUS-guided FNA of the pancreatic malignancy by correlating cytologic diagnosis with histologic diagnosis and other investigations. 2. To know the diagnostic accuracy of air-dried smears using Diff-Quik Stain. 3. To compare the diagnosis obtained by Diff-Quik, conventional PAP Stain smears/cytospin preparation and Thin Prep (liquid-based media). Methods: 111 cases of EUS-guided FNA biopsy of the pancreas performed during the year January 2008 to December 2009 having solid pancreatic mass/lesion on the USG/CT and suspicious for the malignancy or malignant on clinical and radiologic investigations were reviewed in August 2011 at the Department of Pathology and Laboratory Medicine, Hospital of University of Pennsylvania. Results: There was an 83.9% correlation between Diff-Quick diagnosis and the final cytologic diagnosis. The overall diagnostic accuracy for the malignancy was 89.7%, sensitivity 90.6%, and specificity 100% of the cases where the cytologic diagnosis was correlated with histologic diagnosis and the other investigations. The positive predictive value for the malignancy was 100%. The false negative diagnosis was encountered in 10.3% cases. 51% of the cases showed intranuclear vacuoles, in the malignant cases on Diff-Quik stain. Conclusion: EUS FNA of the pancreas is a safe and reliable technique with high diagnostic accuracy, sensitivity, and specificity. The Diff-Quik stain smear is a useful technique for the rapid on-site cytologic evaluation for the detection of malignancy of the pancreas. Thin Prep was found superior to the PAP/Diff-Quik stain for the diagnosis of the malignancy. The EUS FNA samples processed by multiple staining techniques help to improve the diagnostic accuracy and sensitivity.
Clinical Outcome of Dose-Adjusted R-Epoch in Frontline Therapy of Primary Mediastinal B-Cell Lymphoma in Hospital Melaka
Authors: Dang C.C. , Lau N.S. , Gan W.F.
Published: September 2018

Background: Primary mediastinal B-cell lymphoma (PMBCL) is a unique and uncommon form of aggressive NHL that is potentially curable with combination chemotherapy and radiation therapy. A phase II study from the National Cancer Institute (NCI) demonstrated the effectiveness of a chemotherapy alone approach using the dose-adjusted DA-R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin) regimen in the treatment of PMBCL. Given the excellent outcomes seen in this study, many hematologists adopted this regimen without consolidative radiation therapy as a front-line option for PMBCL. Aim: In our case series, we evaluate the outcomes by frontline regimen DA-R-EPOCH for the treatment of PMBCL as well as the treatment-related complications. Methods: We reported a cohort of 3 primary mediastinal large B-cell lymphoma (PMLBL) patients who had completed 8 cycles of DA-R-EPOCH by February 2018 in Hospital Melaka, Malaysia. Results: These 3 PMBCL patients were diagnosed in 2017 and all had bulky disease (>10 cm). DA-R-EPOCH treatment with an escalation dose of level 3, representing a 144% of the starting dose, were given and 40 mg of doxorubicin per square meter of body surface area were received for at least 1 cycle. Cumulative doses of anthracycline were range from 416 to 424 mg per square meter; which falls between the range in other reported studies. The 3 patients in our cohort were able to achieve partial response (PR) at the end of treatment. The average of mediastinal residual disease size was 7.13 cm. All the patients had been scheduled for radiotherapy consolidation. Hospitalization due to treatment-related complications was reported for 2 patients. One of the patients admitted to ICU due to infected chemoport. Another patient reported acquired Varicella zoster virus during the chemotherapy. He also had sinus tachycardia probably related to anthracycline with prolonged QTC and was able to be controlled by tablet carvedilol during treatment. Toxicity was assessed during administration of all the cycles of DA-R-EPOCH. Absolute neutrophil counts of less than 500 cells per cubic milliliter occurred in 30% of the cycles compared with the reported 50% in other study. The use of neutrophil-based dose adjustment maximized the delivered dose and limited the incidence of febrile neutropenia to 26% of the total cycles. Conclusion: PMBCL is a potential curable disease with combination of chemotherapy. There is no established standard treatment of PMBCL although R-CHOP chemotherapy has become a de facto standard. In fact, DA-R-EPOCH are getting more popular among treating hematologists. Our results indicated that PMBCL patients on DA-R-EPOCH regimen had a partial response and may not necessary obviate the need for radiotherapy. This is a preliminary result as 4 more patients are ongoing DA-R-EPOCH treatment.
Identification of Inhibitors Synergizing Chemotherapeutic Sensitivity in the Breast Cancer Stem Cells and Non-Stem Breast Cancer Cells
Authors: Hii L.W. , Chung F.F.L. , Tan B.S. , Lim Y.M. , Cheong S.K. , Leong C.O.
Published: September 2018

Background: Breast cancer stem cells (BCSCs), as a subset of cancer cells with enriched capacity to generate breast tumors, have recently been attributed to driving chemoresistance, cancer recurrence and metastasis. Although the importance of developing strategies to target BCSCs has been recently highlighted, it is conceivable that the depletion of BCSCs within a breast tumor would not lead to complete regression since non-BCSCs might still be capable of sustaining tumor growth or regaining BCSC potential. As conventional chemotherapeutics have been well-established and known to eradicate non-BCSCs, potentially it is preferable to develop BCSC-targeting agents in combination with chemotherapy, to overcome any of the possibilities that would confound the effectiveness of therapeutic agents that exclusively target BCSCs. Aim: This study aimed to rapidly identify and develop BCSC-targeting agents that could pair synergistically with conventional chemotherapeutic agents to produce desired tumor-specific cell death in both BCSCs and non-BCSCs. Methods: By exploiting the capability of enriching BCSCs from breast cancer cell lines, we performed high-throughput screening of a well-characterized chemical library consisting of 1672 diverse bioactive small molecules to identify agents that effective against BCSCs and non-BCSCs. The candidate hit molecules were then paired with chemotherapeutic agents to evaluate the drug combinatory effects on BCSCs and non-BCSCs. Results: Through our comprehensive chemical library screening against BCSCs and non-BCSCs, we identified a total of 193 candidate molecules, including 45 FDA approved drugs, which could target both BCSCs and non-BCSCs. Subsequent analysis suggested histone deacetylase (HDAC) inhibitors as a potential class of anticancer agents targeting both BCSCs and non-BCSCs. When combined with conventional chemotherapeutics, HDAC inhibitors were found to synergise DNA-damaging chemotherapeutics, namely doxorubicin and cisplatin, in killing both BCSCs and non-BCSCs. Moreover, the dose reduction potentials of these combinatory regimens that revealed in this study may be exploited to reduce the dose-limited toxicities in clinical oncology. Conclusion: In summary, our data suggests that HDAC inhibitors represent a class of therapeutic options, either as monotherapy or combination therapy, for refractory breast cancer treatment which warrants detailed investigations.