bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased PD-1 MRNA Expression in Peripheral Blood Cells of ER+ and PR+ Breast Cancer Patients and Its Unfavorable Prognostic Value
Authors: Liu C. , Yu Y. , Sun Y. , Guo D. , Sun B. , Wu S. , Yu J.
Published: September 2018

Background: The clinical significance of programmed cell death 1 (PD-1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) expression on tumor infiltrating lymphocytes in breast cancer patients has been confirmed, while that of peripheral blood cells derived immune molecules remain unclear. Aim: We aimed to investigate the clinical importance of immune molecules, including PD-1 and CTLA-4, expression in peripheral blood cells of breast cancer patients, especially in terms of the relationship between immune molecules and estrogen receptor (ER)/progesterone receptor (PR) status, as well as their prognostic values. Methods: We enrolled 109 breast cancer patients, including 52 cases before surgery and neoadjuvant treatment (PreS group), 18 cases postsurgery and adjuvant chemoradiotherapy (PostS group), 39 metastatic cases presalvage treatment (Met group), and 21 age- and sex-matched healthy volunteers). The mRNA abundance of PD-1, CTLA-4, IL-2 receptor alpha (IL-2Rα), and cluster of differentiation 28 (CD28), forkhead box P3 (FOXP3), transforming growth factor beta (TGF-β), and interleukin-10 (IL-10) in pretreatment peripheral blood were analyzed by quantitative real-time PCR. Results: ER+ breast cancer patients showed significant higher mRNA levels of PD-1, CTLA-4, IL-2Rα, and CD28 with fold changes of 10.8, 2.4, 5.0, and 3.8, respectively ( P < 0.05) than that of ER− cases. Similarly, PR+ patients showed increased levels of PD-1, CTLA-4, and CD28 with fold changes of 6.7, 2.0, and 2.5, respectively ( P < 0.05) comparing to that of PR− cases. Patients in PreS group and Met group showed higher mRNA levels of PD-1, CTLA-4, IL-2Rα, CD28, FOXP3, TGF-β, and IL-10 than PostS group and healthy volunteers. Univariable analysis revealed that high PD-1 expression was associated with poorer progression-free survival (PFS) in metastatic breast cancer patients (5.9 vs 14.6 months, HR: 2.47, 95% CI: 1.22-5.02, P = 0.046). Meanwhile, the prognostic value of PD-1 was remained in multivariate analyses (HR: 2.22, 95% CI: 1.04-4.73, P = 0.039). Conclusion: Increased PD-1, CTLA-4, and CD28 mRNA abundance were showed in breast cancer patients and ER+/PR+ cases, which may provide the rationale for combining checkpoint inhibitors with endocrine therapy for breast cancer treatment. Furthermore, PD-1 is a promising prognostic biomarker for metastatic breast cancer.
NGS-Based BRCA1, BRCA2, and PALB2 Mutation Testing in Iranian Population With Breast Cancer
Authors: Ebrahimi E. , Sellars E. , Shirkoohi R. , Harirchi I. , Ghiasvand R. , Mohebbi E. , Zendehdel K. , Akbari M.R.
Published: September 2018

Background: Identification of individuals who have a pathogenic mutation in breast cancer susceptibility genes is an important step to take advantage of genetic counseling, screening, and potentially life-saving prevention strategies. Based on the National Comprehensive Cancer Network (NCCN) guideline, genetic testing is deemed suitable for breast cancer patients with young age at onset, positive family history of cancers, male breast cancer, or diagnosis with a multifocal or triple negative breast cancer. Aim: Since, it is not known what proportion of breast cancers in Iran is hereditary and related to mutations in BRCA1/2 and PALB2 genes, therefore, we screened these 3 genes in multiethnic Iranian population to determine the spectrum of the breast cancer susceptibility gene mutations and to further assess the predictive value of the hereditary breast cancer risk criteria for genetic testing. Methods: Next generation sequencing (NGS) was conducted on a population consisted of 299 and 125 breast cancer patients, with and without hereditary cancer risk criteria for genetic testing, respectively. Results: Pathogenic mutation rate was 10.36% in patients with hereditary criteria for breast cancer vs 1.6% in no criteria group ( P = 0.002). All the patients who only met the young age at onset (<40) criterion tested negative for a gene mutation. This is while patients who had only 1 hereditary criterion (OR: 5.48, 95% CI: 1.09, 52.90, P = 0.017) and patients with multiple hereditary criteria (OR: 22.5, 95% CI: 5.19, 201.31, P < 0.0001) had a significantly higher probability of finding a mutation compared with no risk-criteria group. Conclusion: The first application of NGS on Iranian breast cancer population added to the cumulative evidence that BRCA1/2 mutations are seen commonly among Iranian breast cancer patients especially those with hereditary breast cancer criteria and indicated that PALB2 should be concerned in hereditary breast cancer screening alongside BRCA1/2. Investigating the predictive potential of hereditary breast cancer risk criteria our results suggest that offering genetic testing to women with early age at onset of <40 with no other hereditary criteria, may not be cost effective and should be considered for optimization of genetic counseling and genetic testing of the Iranian population.
An Eye Opener: Lessons Learnt in Retinoblastoma Awareness and Screening Program
Authors: Nair S. , Desai S. , Gupta H. , Dhamankar V.
Published: September 2018

Background: Retinoblastoma is most common intraocular malignancy of infancy. Globally screening is recommended for ‘at risk’ children. Despite knowing this, Indian Cancer Society undertook general screening at behest of a corporate donor. Scenario in India is challenging as children at rural, urban slums are not routinely screened for any of eye disease. ICS implemented the pilot project among underprivileged children with primary aim of spreading awareness and improve the ocular health. Though expected outcome was zero retinoblastoma suspect cases; based on past projects it was expected that other eye conditions like squint, cataract etc. would be identified in a few. Aim: To screen 4500 children below 4 years of age at Indian rural and suburban slum areas. To create awareness about retinoblastoma and other eye conditions in community. Methods: Locations were identified where literacy, awareness, immunization coverage were low. Partners were selected a team of experts (ocular oncologists, pediatric ophthalmologists, optometrists, paramedical staff) were deployed for implementation. For awareness, all parents coming for the immunization, Aaganwadis and preschools etc. were given a talk on the importance of child eye screening and various disease which can be detected and prevented through simple eye examination. Special community level programs planned to create awareness about retinoblastoma and early childhood eye screening. Brochures and pamphlets were to be given in the vernacular language of the region. Screening for retinoblastoma was planned in 2 phases, those found to have positive red reflex in stage 1 are subjected to dilation, after obtaining consent from the parents. Proformas were filled in and treatment was given as per the pediatric eye disease identified. Results: In 5 months 2450 children were screened, at tribal area and in suburban slum areas. Awareness sessions were conducted for 348 mothers in batches at the tribal area and similarly for mothers and teachers at Anganwadi, schools. None of the parents/teachers were aware about cancer of eye. A thorough eye check-up was done based on the suggestions of the American Association of Pediatric eye diseases and special attention was given to tests such as Bruckners test. Number of children suspected of retinoblastoma was nil, however, 6% children were found to have other eye conditions such as congenital cataract, corneal opacity, refractive errors, squints and ptosis in the tribal area and project is ongoing in suburban area. Treatment was given as per the protocol for same. Conclusion: Screening for retinoblastoma for not at risk children is not recommended. Main aim for implementing retinoblastoma awareness program is to integrate it with immunization or nutritional program in India. This would ensure standardized ocular care. Challenges are numerous, such as lack of infrastructure, poor literacy rates, low income levels. Yet, innovative strategies are needed for better impact of awareness programs.
Long-Term Evaluation of Outcomes for Abdominal Ultrasound Screening for Hepatocellular Carcinoma
Authors: Yeh Y.-P.
Published: September 2018

Background: Mass screening for hepatocellular carcinoma (HCC) with abdominal ultrasound (AUS) has been demonstrated in short-term follow-up in Taiwan, but long-term effectiveness and cost-effectiveness of AUS have not been well studied particularly when the recently emerging antiviral therapy has been introduced. The aim of this study is therefore to evaluate long-term outcomes of population-based organized service screening program without control group. Methods: AUS screening based on a risk score–guided invitation has been launched since October 2008 in Changhua. A total of 85,147 subjects aged 40-74 years attended the Changhua community-based integrated screening (CHCIS) program were targeted. Those with high score based on hepatitis virus infection, ALT, AST, type 2 diabetes, platelet count were invited to receive ultrasonography screening performed by board-certified gastroenterologists in town-based health center to identify liver cirrhosis, and suspected HCC cases. We developed a pseudo-control group by building up the disease natural history for HCC embedded with the risk prediction model and the survival by detection modes. The pseudo-control model was further used to the development of health economic decision model for cost-effectiveness of various preventive strategies. Results: We observed a 61% (RR = 0.39, 95% CI: 0.32-0.46) HCC mortality reduction with AUS by risk groups together with ∼30% coverage rate of antiviral therapy in an 8-year period. The simulated results indicates the additional contribution of 30% compliance rate of antiviral therapy (empirical estimate) to HCC mortality reduction was ∼22%. The corresponding figures were raised to 30% and 35% when the compliance rate of antiviral therapy was enhanced to 50% and 70%, respectively. The results of cost-effectiveness analysis shows the incremental cost-effectiveness ratio was $22,849 for the administration of AUS, and $101,849 for the administration of AUS plus 30% compliance to antiviral therapy. The corresponding figures for 50% and 70% compliance rate to antiviral therapy were $141,805 and $181,919, respectively. Conclusion: The population-based screening program for HCC together with antiviral therapy achieved HCC mortality reduction by 60%. The computer study design with a pseudo-control group on the basis of disease natural history of HCC embedded with the predictive model, and the survival part of HCC enables us to quantify the attributable proportion from different preventive regimes, and to estimate long-term effectiveness of the overall and marginal effectiveness and cost-effectiveness of AUS and antiviral therapy under different scenarios. Such approach provides the health policy-makers a reference for resource allocation.
Long-Term Effect of Breast Symptoms Reported at Mammography Screening Visit on Cancer Incidence and Mortality
Authors: Singh D. , Anttila A. , Malila N. , Pitkaniemi J. , Miettinen J.
Published: September 2018

Background: Efforts to reduce mortality through early detection and diagnosis has intensified in the recent decade. An important risk factor, 'breast symptoms' reported by women during screening visit, is still overlooked. Aim: To study the association between breast symptoms reported at screening visit and the risk of cancer incidence and mortality in a prospective manner over a period of 24-years. Methods: This population based matched cohort study was based on the follow-up of the ongoing Finnish National Breast Cancer Screening Program (FNBCSP) that began in 1987. Symptomatic subjects who attended screening with symptoms (lump, 39,965 visits; retraction, 24,190 visits; nipple discharge, 7882 visits) were identified from the Finnish Cancer Registry database. For each visit with symptoms, nonsymptomatic controls were matched (1:1 for lump and retraction; 1:2 for nipple discharge) based on age at screening visit (within 2 years), year of invitation (2 years band), number of invited visits, and municipality of invitation. The primary outcomes were incidence of breast cancer and incidence-based mortality, including all-cause mortality. Results: Women who reported lump or retraction had about twofold risk of breast cancer incidence, threefold risk of breast cancer mortality and all-cause mortality respectively as compared with women without respective symptoms. We found a substantial difference in mortality rates throughout the follow-up period between symptomatic and asymptomatic group. In absolute terms, for lump, in every 1000 screening visits, 20 women died of breast cancer as compared with 7 women without lump, and 30 vs 11 all-cause deaths in women with and without lump, respectively after 24 years of follow-up. We also found difference in the number of deaths in women who reported retraction or nipple discharge. Conclusion: This study provides comprehensive evidence that women with breast symptoms remain in a higher risk of dying over a very long period. Guidelines to reduce these inequalities needs to be developed.
Similar Effect of P16 Hydroxymethylation and True Methylation on Prediction of Malignant Transformation of Oral Epithelial Dysplasia: A Prospective Study
Authors: Liu H. , Liu Z. , Liu X. , Xu S. , Wang L. , Liu Y. , Zhou J. , Gu L. , Gao Y. , Liu X. , Sun Z. , Deng D.
Published: September 2018

Background: Total P16 methylation (P16M), including P16 hydroxymethylation (P16H) and true-P16M, correlates with malignant transformation of oral epithelial dysplasia (OED). Both true-P16M and P16H are early events in carcinogenesis. Aim: The aim of this study is to prospectively determine if discrimination of true-P16M from P16H similarly is necessary for prediction of cancer development from OEDs. Methods: Patients (n = 265) with mild or moderate OED were recruited into the double-blind 2-center cohort. Total-P16M and P16H were analyzed using the 115-bp MethyLight, TET-assistant bisulfite (TAB) methylation-specific PCR (MSP), and TAB-sequencing. Total-P16M-positive and P16H-negative samples were defined as true-P16M-positive. Progression of OEDs was monitored for a minimum 24 months follow-up period. Results: P16H was detected in 23 of 73 (31.5%) total-P16M-positive OEDs. Follow-up information was obtained from 247 patients with an ultimate compliance of 93.2%. OED-derived squamous cell carcinomas were observed in 13.0% (32/247) patients during the follow-up (median, 41.0 months). The cancer progression rate for total-P16M-positive patients was significantly increased when compared with total-P16M-negative patients (23.3% vs 8.6%; adjusted odds ratio = 2.67 [95% CI: 1.19-5.99]). However, the cancer progression rate was similar between P16H- and true-P16M-positive OEDs (26.1% [6/23] vs 22.0% [11/50]; odds ratio = 0.80 [95% CI: 0.22-2.92]). The progression-free survival was also similar for these patients. Conclusion: P16H and true-P16M are similar biomarkers for determining malignant potential of OEDs. Discrimination of P16H from true-P16M, at least in OED, may be not necessary in clinical applications.
Combinatorial Characterization of Saliva for Oral Precancer Diagnostics
Authors: Sharma N. , Bag S. , Biswas K. , Pal M. , Paul R.R. , Chatterjee J.
Published: September 2018

Background: Saliva based diagnostic can play an important role in the translational research related to cancer diagnostics and treatment. It is easily available, noninvasive, low storage cost, has less contamination chances with simple collection procedure. Cancers related to tobacco use, including oral cancer account for about 30% of all cancers in males and females. Five years' survival rate remains the same even after decades of advancement of detection, prevention, and treatment of OSCC (oral squamous cell carcinoma) mainly due to late diagnosis of oral potentially malignant disorders (OPMDs). Aim: Combinatorial characterization of saliva, endorsing multidimensional spectroscopic signatures using suitably designed biochamber. Methods: Eighteen saliva samples (6 normal, 6 OSF [oral submucous fibrosis, a type of OPMD] and 6 confirmed OSCC) were collected from GNIDSR (Guru Nanak Institute of Dental Science and Research) Kolkata. Ethical approval was obtained for the study and all the participants were explained the objectives of the study and a written informed consent was obtained from them. Participant's demographic detail and clinical characteristics were also recorded. The participants were asked not to consume food 1 hour before sample collection and were suggested to rinse their mouth 30 minutes prior to saliva expectoration to minimize the contamination of food in saliva. Empty, sterile, graded tubes were used for this purpose. The subjects were asked not to clear nose or throat during the process of saliva expectoration to avoid forced phlegm from other part of the respiratory tract. The saliva samples were then immediately transferred to −20 degrees and later in −80 degrees for long storage. The electrical impedance (EI) of saliva was measured in custom made biochambers with copper electrodes. The EI was measured for the frequency sweep from 20 Hz to 2 MHz using an impedance analyzer. Apart from EI measurement, the corresponding samples were subjected to FTIR (Fourier-transform IR spectroscopy) analysis. SPSS and OMNIC software were used for the data analysis of EI and FTIR respectively. Results: [Table: see text][Table: see text][Table: see text][ Table A , B & C represents descriptive statistics, correlation matrix and component matrix respectively. The multivariate analysis of the FTIR data indicates the significant differences ( P < 0.005) among the different study groups such as normal, OSF and OSCC. The eigen values (normal 0.917, OSF 0.962, OSCC 0.975) from component matrix analysis also indicate the same. Conclusion: The spectroscopic characterization (EI and FTIR) of saliva was effective in evaluating normal and OPMD condition. This noninvasive paradigm can serve as a complimentary technique to the existing gold standard methods for the early detection of oral cancer.
Increasing Breast and Cervical Cancer Screening Uptake in Women of Child-Bearing Age in Niger State, Nigeria
Authors: Kolo H.T.
Published: September 2018

Background: Prevalence of breast and cervical cancer are on the increase in the developing countries despite the knowledge of how these diseases can be prevented through screening. Reproductive rights, Advocacy, Safe space and Empowerment Foundation (RAISE) initiated breast and cervical cancer screening program in Niger State as part of its reproductive health services. The program is hereby evaluated with the aim of improving its performance toward reducing burden of these diseases in Niger State. Aim: To evaluate the breast and cervical cancer screening program, to report the experience from the program, and to recommend necessary changes and scaling up of best practices. Methods: Audit of the breast and cervical cancer screening program was conducted. The basic components of cervical cancer screening programs; screening uptake, screening services, treatment of screen positives, follow-up and referrals were audited against previously set standards for the program. The difference in screening uptake for breast and cervical cancer was evaluated for better understanding of factors determining screening uptake in Niger state. Results: Between 18 July 2016 and 30 April 2018, 2035 women between the age of 15-75 years were screened for breast cancer and 1258 women between the age of 20-55 years were screened for cervical cancer, representing about 38% higher uptake of breast cancer screening compared with cervical cancer. The parity range of these women is 0-20. The mean age and parity for women screened during the audit period were; 35 years and 8 for breast cancer, while 29 years and 7 for cervical cancer. Fifty-two (2.56%) of the 2035 women screened for breast cancer had a palpable lump in either 1 or both breasts, while 4 (0.3%) of the 1258 women screened for cervical cancer had a positive result (aceto-white lesions) treated with cryotherapy. The women have low socioeconomic status with predominantly farmers, petty traders and housewives earning less than $2 per day. Most of the women are illiterate with little or no form of education. Other possible barriers for low uptake of breast and cervical cancer screening is lack of transportation, religious and cultural beliefs, shyness and lack of sensitization. Conclusion: Screening uptake is still very poor despite massive awareness campaign. The current awareness creation strategy has not been able to create needed demand for the available screening services. A total overhaul of awareness creation strategies is therefore advocated.
Measurement of Salivary pH Using Litmus Paper as a Screening Tool of Smoking Behavior in Adolescents
Authors: Jessica A. , Handy F.
Published: September 2018

Background: Cigarettes are the biggest threat in the world, including Indonesia. According to The Health Ministry of Indonesia 2017 , Indonesia is one the country with the highest number of smokers. More than one-third (36.3%) of Indonesia's population, 20% are adolescents aged 13-15 years old. In Indonesia, cigarettes caused more than 200,000 deaths per year. It has been recorded that the amount of cigarettes consumed in Indonesia increases from 182 billion in 2001 to 260.8 billion in 2009. In addition to the increasing number of the smokers and the age of smoking, there is another factor which is adolescents deceit for their smoking behavior, therefore screening is necessary to prevent the complications from smoking. Aim: To find out changes in salivary pH as a smoking behavior screening tool in adolescents. Methods: : Results: Distribution of data in 85 samples with 50 nonsmokers and 35 smokers, got the youngest age of smoking is in fourth year of elementary school, with the highest number of cigarettes consumed per day is more than 2 boxes. The salivary pH in smokers was significantly ( P < 0.005) lower than nonsmokers. This can be seen also through since the smoke, the last time smoking and the number of cigarettes consumed per day. The younger age of smoking, the last time smoking (<24 hour) and the more the number of cigarettes consumed per day, that all can significantly decrease salivary pH. Conclusion: Salivary pH measurement using litmus paper is a potential screening for smoking behavior in adolescents.
Mitochondrial Dysfunction–Induced Apoptosis in Breast Carcinoma Cells Through pH-Dependent Intracellular Quercetin NDDS of PVPylated-TiO2NPs
Authors: Ponraj T. , Kannan S.
Published: September 2018

Background: The conventional chemotherapy has some noticeable drawbacks, such as lack of specificity, the requirement of high drug-dose, adverse effects, and gradual development of multidrug resistance (MDR), that reduce the efficacy of cancer therapy. Aim: To achieve intracellular drug delivery, strategies for overcoming various biologic barriers from the system level to the organ level, to the cellular level. To win through over these challenges in chemotherapy is to be achieving high drug loading combination with low leakage at physiologic pH, minimal toxicity toward healthy cells, and tunable controlled release at the site of action is an ongoing challenge. Methods: To assist drug delivery, we have prepared PVPylated-TiO2NPs consisting of Qtn with high loading efficiency (26.6% w/w) for NDDS. Qtn-PVPylated-TiO2NPs uptake via endocytosed by cancer cells able to generate intracellular ROS, to decrease the mitochondrial membrane potential loss (Δψm) to release cytochrome- c, Bcl-2 dysregulation into the cytosol and then activating caspase-3 to induce cancer cell apoptosis. Results: These novel nanocombinations can be used to improve cancer nanotherapy by induction of apoptosis in vitro. Analysis at molecular level revealed that Qtn-PVPylated-TiO2NPs nanocombination induced Δψm-mediated apoptotic signaling pathway. Conclusion: To our knowledge, this is a novel report using Qtn-PVPylated-TiO2NPs nanocombinations to study the pH-dependent intracellular NDDS to cancer cells. This new nanoformulations of this study may further advance the use of Qtn-PVPylated-TiO2NPs based nanotherapeutic of biomaterials for various biomedical applications, especially cancer nanotherapy.
Mismatch Repair Status as a Predictor of Benefit From Platinum-Based Adjuvant Therapy in Ovarian Clear Cell Carcinoma
Authors: Zhu J. , Wu X. , Ju X.
Published: September 2018

Background: Previous studies have indicated that patients with colorectal cancer who demonstrate defective DNA mismatch repair (dMMR) have clinical and pathologic features that distinguish them from patients who have proficient mismatch repair (pMMR) tumors. However, the influence of mismatch repair (MMR) status in ovarian clear cell carcinoma (OCCC) is still unknown. Aim: To evaluate the MMR statuses in OCCC and its correlation with clinicopathological and prognostic characteristics. Methods: MMR statuses were measured by tissue microarray–based immunohistochemistry from 120 OCCC patients. The associations of clinicopathologic features with progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier method and multivariate analysis was further performed by Cox regression model. Results: Overall, 120 OCCC patients met the entry criteria and their MMR status were detected, consisting of 24 patients with dMMR and 96 patients with pMMR. Tumors with dMMR were strongly associated with platinum-sensitive disease ( P = 0.008) and large tumor volume ( P = 0.028). Among all the patients who have received surgery, tumors with dMMR had a better progression-free survival and overall survival (OS) than those with pMMR (hazard ratio [HR] for recurrence, 0.459 [95% confidence interval (95% CI), 0.224-0.940]; P = 0.029; HR for death, 0.381 [95% CI, 0.170-0.853]; P = 0.015). In subgroup analysis, dMMR patients experienced a better PFS (HR, 0.242; P = 0.055) and OS (HR, 0.141; P = 0.039) than pMMR cases among early stages (I-II), but this difference was not observed in advanced stage (III-IV) patients. Meanwhile, pMMR was associated with more favorable prognosis than dMMR in platinum-resistant patients (PFS, HR: 0.317, P = 0.052; OS, HR: 0.370, P = 0.046). Multivariate analysis revealed that only advanced stages (III-IV) were adverse independent prognosticators for both PFS (HR, 5.938; [95% CI, 2.804-12.574], P < 0.001) and OS (HR, 6.209; [95% CI, 2.724-14.156], P < 0.001). Conclusion: MMR status in ovarian clear cell carcinoma is not only a prognostic indicator, but also appears to be a possible predictor for the use of platinum-based adjuvant chemotherapy.
Assessment of Traditional Treatment Modality in the Management of Adenocarcinoma of Prostate: A Case Report Based on Cytokine Expression
Authors: Umayangani L.H.S. , Jayathilake N. , Kaluthotage S. , Amarasinghe A.P.G. , Chandana E.P.S.
Published: September 2018

Background: Adenocarcinoma of prostate is one of the most common cancers in Sri Lanka. It is developed in the prostate gland which is in a male reproductive system. Aim: This clinical case report was conducted from September to November 2016 in the out patient department of Bandaranaike Memorial Ayurveda Research Institute (BMARI), Navinna, Sri Lanka to assess antitumor activity of the traditional treatment modality. Methods: A patient 65 years old who was attended with symptoms of competence of urination, flatulence, anorexia and diagnosed as adenocarcinoma of prostate with the evidence of early metastatic in 7th 8th ribs and L2 vertebra. Detailed history, clinical examinations and relevant investigations were conducted at BMARI and the Department of Zoology, Faculty of Science, University of Ruhuna, Sri Lanka. Five traditional herbal powder formulae namely C1 Choorna, KY Choorna, A1 Choorna, IM Choorna and SG Choorna were administered throughout period of study. Tumor marker expression and biochemical analysis were tested before and after treatments (after 45 days and 90 days of treatment). Further serum IL-2, IL-5, IFN-γ, PUMA were quantified using ELISA before and after the treatments (after 45 days and 90 days of treatment) as these cytokines play a significant role in tumor growth control. Results: Symptoms of adenocarcinoma of prostate were significantly improved and PSA was decreased. As the results of the ELISA, IL-2, IL-5, IFN-γ and PUMA concentrations were increased after the treatment. Conclusion: Expression level increased in all 4 cytokines over time indicating the possible control of adenocarcinoma of prostate growth by the 5 drug formulae. Further investigations are required to evaluate the efficacy of this drug modality in controlling adenocarcinoma of prostate.
Combinatory Effect of Jerantinine A and Chemotherapeutic Agent in Regulating Spliceosome in Breast Cancer Stem Cells and Non-Stem Breast Cancer Cells
Authors: Tan C.H. , Mai C.W. , Leong C.O.
Published: September 2018

Background: Breast cancer is the second most common cancer and is afflicting women globally. Current standard regimen of chemotherapy includes 2 main classes of drug anthracycline (e.g., doxorubicin) and taxane (e.g., paclitaxel). Two main issues are associated with these drugs: toxicity and recurrence. The former issue warrants for search of novel compounds which preferably synergize with the existing chemotherapeutic agents. Whereas the latter prompts researchers to test their anticancer compounds against breast cancer stem cells (BCSCs), which is the culprit behind tumorigenesis. In a preliminary study, an indole alkaloid compound named Jerantinine A (JA) was found to have anticancer effect on breast cancer cells. The effect was mediated by disruption of splicing in the cancer cells. The key spliceosome component involved was splicing factor 3b subunit 1 (SF3b1). Aim: In current study, we further investigated whether JA had similar inhibitory effect on BCSCs. Also, if such inhibitory effect was mediated by SF3b1 too. Lastly, we explored the drug combination effect of doxorubicin and JA. Methods: Cell proliferative assay was used to determine viability of BCSCs, which would indicate the inhibitory effect of JA. On the other hand, quantitative polymerase chain reaction (qPCR) was used in detection of disrupted spliceosome activity, especially that associated with SF3b1. With respect to drug combination effect, the Chou and Talalay method was used in the relevant analysis. Results: Results showed that JA had inhibitory effect on BCSCs in vitro. Such effect was mediated by SF3b1, as shown by accumulation of 4 associated unspliced premRNAs (e.g., RIOK3, BRD2, DNAJB1, CDKN1B) in quantitative-PCR (qPCR). Lastly, based on the combined index (CI) and drug reduction index (DRI), we concluded that JA not only could synergize with doxorubicin but also sensitized BCSCs to the effect of doxorubicin. Conclusion: There was a main caveat, which was the ratio of JA against doxorubicin; only at certain ratios did the combinatory effect therefor hold promising. Nonetheless, our findings provided basis for future studies to look further into the potential of JA in alleviating cardiotoxicity issue of doxorubicin and the roles of spliceosome in breast cancer.
Wound Complications After Multimodal Treatment of Soft Tissue Sarcomas
Authors: Khanevich M. , Khazov A.
Published: September 2018

Background: Surgical removal of the tumor remains the only 1 radical treatment of patients with soft tissue sarcomas of the extremities. However, the parameters of total and disease-free survival after this type of treatment cannot be considered satisfactory. Currently the active search and introduction into clinical practice of additional impact methods that can improve the immediate and long-term results of treatment of such patients is being conducted. Aim: To evaluate the risk of the wound process complications after surgical treatment of soft tissue sarcomas using endovascular embolization and cryosurgery. Methods: We have assessed the quantity and quality of postoperative complications of wound process in 199 patients with soft tissue sarcomas and their recurrences. The study group consisted of 53 patients, who underwent radical surgery with selective preoperative endovascular embolization and intraoperative cryosurgery. The control group consisted of 146 patients who had radical surgery without any additional methods. Preoperative embolization and cryosurgery on the wound bed after tumor removal was used to prevent local recurrence of soft tissue sarcomas. Preoperative angiography with selective embolization of vessels feeding the tumor was performed 1-1.5 hours before the main surgical treatment. Cryosurgery was carried out by the method of “Olympic rings” with 3 minutes duration. The temperature of exposure was −186°C. In the course of cryosurgery we adhere to the principle of “quick freezing - an independent slow thawing”. All postoperative wounds tightly sutured with silicone drains by Redon, if necessary. Results: Complications of wound healing have been diagnosed in 15 (28.3%) patients of the main group and in 34 (23.3%) control group patients. Inflammatory-suppurative complications were observed in the remaining 8 (15.1%) patients of the main group and in 18 (12.3%) control group patients ( P > 0.05). Long lymphorrhea was observed in 6 (11.3%) patients of the main group and 11 (7.5%) control group patients. Bleeding in the postoperative period was observed in 1 (1.9%) case of main group patients and in 5 (3.4%) cases of control group. Conclusion: The additional using of selective preoperative endovascular embolization and cryosurgery is safe and does not worsen immediate results of surgical treatment of soft tissue sarcomas.
Not Just a Pretty Picture: The U.S. Cancer Statistics Data Visualization Tool
Authors: Senkomago V. , Singh S. , O'Neil M.E. , Pollack L. , Kolli A. , Benard V. , Lisa R. , Wu M.
Published: September 2018

Background: The United States Centers for Disease Prevention and Control (CDC) National Program of Cancer Registries (NPCR) works to disseminate cancer surveillance data to multiple audiences in accessible, discoverable, and usable formats. To this end, CDC released the official federal cancer statistics, U.S. Cancer Statistics (USCS), in a data visualization tool available at www.cdc.gov/cancer/dataviz . We made further enhancements to the online tool since its initial release in 2017. Aim: We describe the process and enhancements made to the USCS data visualization tool's content, graphical displays, and sharing capabilities. Methods: CDC partnered with Agency for Toxic Substances and Disease Registry's Geospatial Research, Analysis, and Services Program to further work initiated by a group of cancer registrars, program planners, epidemiologists, computer programmers, and communication specialists to improve the visual presentation of USCS cancer incidence and mortality data. We conducted usability testing and implemented changes to the Web site's layout and added content, including county-level data, survival data, and prevalence estimates. Results: New features include county statistics, survival, prevalence, Puerto Rico data, and tobacco-, alcohol-, and obesity-related cancers data displays. The tool was also enhanced to better display on mobile devices. Data displays on national and state incidence, mortality and trends are available as maps and bar charts with interpretive text when users scroll over each graphic. Users can customize displays of overall and cancer-specific statistics, download data tables, and share each page via social media. Conclusion: Surveillance data are fundamental to measure progress and target action. CDC's interactive USCS data visualization tool is designed to make cancer data more accessible and usable to multiple users, including the general public, media, policy makers and planners. We will continue to improve the tool's accessibility and usefulness to facilitate the interpretation and sharing of cancer data.
Therapeutic Potential of Cytosolic PLA2 Isoform–Specific Inhibitor Arachidonyl Trifluromethyl Ketone in Cigarette Smoke Condensate–Induced Pathological Conditions in Alveolar Type I and II Epithelial Cells
Authors: Kumar S. , Sharma S.K. , Medhi B. , Khanduja K.L.
Published: September 2018

Background: Cigarette smoking is responsible for various lung pathologies including chronic lung inflammation, emphysema, chronic obstructive pulmonary disease (COPD), cancer, and annually causes almost 10 million deaths globally. During smoke exposure, most affected cells are the alveolar epithelial cells where as a repair mechanism, activation of cytosolic phospholipase A2 enzymes takes place. High free radicals and cPLA2 activity due to continuous exposure of smoke exposure leads to elevated levels of secondary metabolites and various pathophysiologic conditions such as chronic inflammation, oxidative stress and cancer. To reduce the burden of chronic inflammation as well as oxidative stress, and higher levels of secondary metabolites whose role is well defined in progression of cancer, we checked the therapeutic potential of cPLA2 inhibitor arachidonyl trifluromethyl ketone (ATK) by pharmacologically targeting the most expressible cPLA2 during continuous exposure of cigarette smoke. Aim: To check the therapeutic potential of cytosolic PLA2 isoform specific inhibitor arachidonyl trifluromethyl ketone in cigarette smoke condensate–induced pathologic conditions in alveolar type I and II epithelial cells. Methods: Effect of cPLA2 inhibitor on CSC-induced cPLA2 activity were checked using colorimetric assay, cell viability using MTT assay, FDA uptake assay using fluorescence microscopy, ROS levels and apoptosis markers through flow cytometry, and ERK levels using ELISA, in both type of alveolar epithelial cells. Results: ATK significantly mimicked CSC-induced cPLA2 activity, free radicals, primary apoptosis, ratio of apoptotic/apoptotic proteins and levels of ERK whereas protected cells from loss of cell viability and membrane integrity. Conclusion: Current observations revealed cPLA2s as a potential therapeutic target and their inhibitor ATK as a potential therapeutic agent in Cigarette smoke induced pathological conditions in alveolar type I and II epithelial cells.
TET2 Loss Dysregulates the Behavior of Mesenchymal Stem Cells and Increases Their Ability to Promote TET2−/−-Driven Myeloid Malignancy Progression
Authors: Zhao Z.
Published: September 2018

Background: TET2 is a methylcytosine dioxygenase that regulates cytosine hydroxymethylation. Although there are extensive data implicating a pivotal role of TET2 in hematopoietic stem/progenitor cell (HSPCs), the importance of TET2 in bone marrow mesenchymal stromal cells (BMSCs) remains unknown. Aim: Tet2 loss may dysregulate the integrity of bone marrow niche, by which affects the malignant progression. Methods: Generation and maintenance of Tet2 conditional knockout MiceAnalysis of 5-hmC and 5-mC levels using dot blotFlow cytometry analysis, cell sorting, and hematopoietic progenitor cell (HPC) assayMSC Culture and long-term coculture with HSPCsReal-time PCR and RAN-Seq AnalysisMeDIP-seq to profile the genome-wide distribution of 5hmC. Results: Here, we show that while both Tet2 f/f ;Mx1Cre (conditional Tet2-inactivation in hematopoietic cells) and Tet2 f/f ;MxfCre (germ line Tet2-inactivation) developed myeloid malignancies in mice, Tet2 f/f ;MxfCre mice had a significantly shortened survival compared with Tet2 f/f ;Mx1Cre mice. Interestingly, Tet2 −/− recipient mice exhibited a higher incident of myeloid malignancies and a significantly reduced survival rate compare with WT recipient mice. These data indicate that Tet2 −/− bone marrow niche might promote the progression of myeloid malignancies in Tet2 −/− mice. Strikingly, deletion of Tet2 in mesenchymal stem cells (MSCs) using Prx1-cre is associated with a significantly accelerated malignancy progression and shortened survival, suggesting that MSCs are the cell components in Tet2 −/− mice play a role in the initiation/progression of Tet2 −/−-driven myeloid malignancies. Furthermore, Tet2 −/− MSCs displayed a significantly increased self-renewal, proliferating and differentiation capability as assayed by the frequency of CFU-F and commitment toward osteoblasts. In addition, Tet2 −/− but not WT MSCs exhibited a significantly increased supportive capacity to Tet2 −/− HSC/HPC proliferation. RNA-sequencing analysis revealed that Tet2 −/− MSCs exhibited a distinct gene expression profiles with 468 dysregulated genes as compared with WT MSCs. Furthermore, the number of 5-hmC peaks were significantly decreased in Tet2 −/− MSCs compared with WT MSCs based on whole genomic 5-hmC profiling. The majority of TET2-dependent 5hmC modifications in MSCs are located within genes. We then examined TET2 gene expression in MSCs derived from human myeloproliferative neoplasms (MPN) patients and healthy individuals and found that TET2 and 5-hmC was moderately down-regulated in MPN MSCs as compared with healthy controls. Conclusion: These results highlight the critical role of TET2 in the maintenance of BMSC functions and osteoblast differentiation, and provide evidence that dysregulation of epigenetic modifier in BMSCs contributes to the progression of myeloid malignancies.
Developing a Nurse-Led Intervention for Men With Advanced Prostate Cancer: A Preimplementation Study
Authors: Ralph N. , Chambers S. , Pomery A. , Dunn J.
Published: September 2018

Background: Men with advanced prostate cancer can experience poor life quality and health outcomes compared with men with localized disease. Closely matching men's needs and identifying barriers and facilitators to implementation were critical first steps for ensuring the feasibility of our nurse-led telephone-based supportive care intervention for men with advanced prostate cancer. Aim: The aim of this study is to understand the context for implementing ProsCare from PCSNs, and in doing so, further develop the intervention and implementation strategy. Methods: A total of 30 Prostate Cancer Specialist Nurses (PCSNs) participated in 4 semistructured focus groups. Data were coded into the Consolidated Framework for Implementation Research (CFIR) to evaluate the ProsCare program content and guide the implementation and evaluation of this targeted program for men with advanced prostate cancer. Results: Participants validated ProsCare components of (1) decision support; (2) treatment education with self-management and skills training for symptom effects, including exercise prescription; (3) routine screening for psychological distress with referral; (4) psycho-education with tailored distress management strategies; and (5) communicating with health professionals. Data supported a revised treatment schedule and a comprehensive implementation plan including professional education and centralised administration. Conclusion: ProsCare is a valid supportive care nurse-led intervention. The CFIR framework is useful for the structured identification of implementation factors.
Improvement in Infection Prevention and Control Measures at The Children Hospital, Lahore. A My Child Matters Collaborative Project
Authors: Faizan M. , Anwar S. , Kashif R.U.A. , Saleem R. , Javed H. , Zafar A. , Hameed A. , Taj M. , Maysam H. , Miguela C. , Rathore A.W. , Sadiq M. , Gonzalez M. , Zaidi A.
Published: September 2018

Background: Overcrowding, lack of operational funds, and healthcare associated infections are major challenges at the Children Hospital Lahore, a public healthcare facility in Pakistan with 900 new pediatric cancer admissions annually. In 2014, a collaboration between My Child Matters (MCM), St. Jude Global Infectious Diseases Program (SJ-GID), and our institution was established to address these issues. Aim: To describe the effect of a collaborative improvement strategy on the infection prevention and control (IPC) standards in a pediatric oncology unit in a resource-limited setting. Methods: Our study was a prospective before-and-after study. We compare the WHO Hand Hygiene Self-Assessment Framework (HHSAF) and 4 modules of the St. Jude modified Infection Control Assessment Tool (ICAT) scores. Our strategy included: (1) creating a multidisciplinary team of pediatric hematology-oncology, infectious disease physicians, nurses, microbiologist, and a data manager, (2) engaging on monthly online IPC mentoring sessions with the SJ-GID and MCM mentors, (3) performing daily inpatient healthcare associated (HAI) surveillance rounds, and (4) providing regular hand hygiene training and compliance audits. Results: Our hand hygiene facility level per WHO scores increased from “Inadequate” during the baseline assessment to “Intermediate/Consolidation” by the end of 3-year implementation (122 vs 352 HHSAF scores). The sink: bed and hand sanitizer: bed ratios improved to 1:6 and 1:1 respectively. Six washrooms were added to our unit. ICAT general infection control module increased by 40% (45 vs 78 ICAT score) and hygiene compliance improved by 20% from baseline. Identification of HAI increased from baseline (4.07 vs 8.7 infections per 1000 patient days). A 25% of the isolates were multidrug-resistant microorganisms. Conclusion: Implementing a collaborative improvement strategy improved the IPC standards in our pediatric cancer center. The increase of HAI might be a result of a better surveillance and laboratory identification. Further targeted interventions should be develop to decrease HAI rates and infection-related morbidity and mortality in our population.