Co-prevalence of Epstein-Barr virus and high-risk human papillomaviruses in Syrian women with breast cancer.

ABSTRAT We recently performed 2 studies viewing the presence of Epstein-Barr virus (EBV) and high-risk human papillomaviruses (HPVs) types 16, 18, 31, 33 and 35 in human breast cancer in the Syrian population. Herein, we report that EBV and high-risk HPVs are co-present in breast cancer in Syrian women. Therefore, and based on our previous studies and present data, we reveal that 35 (32%) of 108 cancer samples are positive for both EBV and high-risk HPVs and their co-presence is associated with high grade invasive ductal carcinomas (IDCs) with at least one positive lymph nodes, in comparison with EBV and high-risk HPVs-positive samples, which are low to intermediate grade IDCs, respectively. Future studies are needed to confirm the co-presence and the cooperation effect of these onco-viruses in human breast carcinogenesis and metastasis.This work was supported by the Canadian Institutes for Health Research (CIHR) and the Fonds de la Recherche en Santé du Québec (FRSQ- Réseau du Cancer). The new research lab of Dr. Al Moustafa is supported by the College of Medicine at Qatar University

Co-Incidence of Epstein–Barr Virus and High-Risk Human Papillomaviruses in Cervical Cancer of Syrian Women

Epstein–Barr virus (EBV) has been recently shown to be co-present with high-risk human papillomaviruses (HPVs) in human cervical cancer; thus, these oncoviruses play an important role in the initiation and/or progression of this cancer. Accordingly, our group has recently viewed the presence and genotyping distribution of high-risk HPVs in cervical cancer in Syrian women; our data pointed out that HPVs are present in 42/44 samples (95%). Herein, we aim to explore the co-prevalence of EBV and high-risk HPVs in 44 cervical cancer tissues from Syrian women using polymerase chain reaction, immunohistochemistry, and tissue microarray analyses. We found that EBV and high-risk HPVs are co-present in 15/44 (34%) of the samples. However, none of the samples was exclusively EBV-positive. Additionally, we report that the co-expression of LMP1 and E6 genes of EBV and high-risk HPVs, respectively, is associated with poorly differentiated squamous cell carcinomas phenotype; this is accompanied by a strong and diffuse overexpression of Id-1 (93% positivity), which is an important regulator of cell invasion and metastasis. These data imply that EBV and HPVs are co-present in cervical cancer samples in the Middle East area including Syria and their co-presence is associated with a more aggressive cancer phenotype. Future investigations are needed to elucidate the exact role of EBV and HPVs cooperation in cervical carcinogenesis

Co-Incidence of Epstein-Barr Virus and High-Risk Human Papillomaviruses in Cervical Cancer of Syrian Women.

Epstein-Barr virus (EBV) has been recently shown to be co-present with high-risk human papillomaviruses (HPVs) in human cervical cancer; thus, these oncoviruses play an important role in the initiation and/or progression of this cancer. Accordingly, our group has recently viewed the presence and genotyping distribution of high-risk HPVs in cervical cancer in Syrian women; our data pointed out that HPVs are present in 42/44 samples (95%). Herein, we aim to explore the co-prevalence of EBV and high-risk HPVs in 44 cervical cancer tissues from Syrian women using polymerase chain reaction, immunohistochemistry, and tissue microarray analyses. We found that EBV and high-risk HPVs are co-present in 15/44 (34%) of the samples. However, none of the samples was exclusively EBV-positive. Additionally, we report that the co-expression of LMP1 and E6 genes of EBV and high-risk HPVs, respectively, is associated with poorly differentiated squamous cell carcinomas phenotype; this is accompanied by a strong and diffuse overexpression of Id-1 (93% positivity), which is an important regulator of cell invasion and metastasis. These data imply that EBV and HPVs are co-present in cervical cancer samples in the Middle East area including Syria and their co-presence is associated with a more aggressive cancer phenotype. Future investigations are needed to elucidate the exact role of EBV and HPVs cooperation in cervical carcinogenesis.We would like to thank Mrs. A. Kassab for her critical reading of the manuscript. This work was supported by Qatar University grants # GCC-2017-002 QU/KU and QUCG-CMED-2018\2019-3

Participation of older newly-diagnosed cancer patients in an observational prospective pilot study: an example of recruitment and retention

<p>Abstract</p> <p>Background</p> <p>There have been few prospective observational studies which recruited older newly-diagnosed cancer patients, and of these only some have reported information on the number needed to screen to recruit their study sample, and the number and reasons for refusal and drop-out. This paper reports on strategies to recruit older newly-diagnosed cancer patients prior to treatment into an observational prospective pilot study and to retain them during a six-month period.</p> <p>Methods</p> <p>Medical charts of all patients in the Segal Cancer Centre aged 65 and over were screened and evaluated for inclusion. Several strategies to facilitate recruitment and retention were implemented. Reasons for exclusion, refusal and loss to follow-up were recorded. Descriptive statistics were used to report the reasons for refusal and loss to follow-up. A non-response analysis using chi-square tests and t-tests was conducted to compare respondents to those who refused to participate and to compare those who completed the study to those who were lost to follow-up. A feedback form with open-ended questions was administered following the last interview to obtain patient's opinions on the length of the interviews and conduct of this pilot study.</p> <p>Results</p> <p>3060 medical charts were screened and 156 eligible patients were identified. Of these 112 patients participated for a response rate of 72%. Reasons for refusal were: feeling too anxious (40%), not interested (25%), no time (12.5%), too sick (5%) or too healthy (5%) or other reasons (5%). Ninety-one patients participated in the six-month follow-up (retention 81.3%), seven patients refused follow-up (6.2%) and fourteen patients died (12.5%) during the course of the study. The median time to conduct the baseline interview was 45 minutes and 57% of baseline interviews were conducted at home. Most patients enjoyed participation and only five felt that the interviews were too long.</p> <p>Conclusion</p> <p>It was feasible to recruit newly-diagnosed cancer patients prior to treatment although it required considerable time and effort. Once patients were included, the retention rate was high despite the fact that most were undergoing active cancer treatment.</p

A simplified interventional mapping system (SIMS) for the selection of combinations of targeted treatments in non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is a leading cause of death worldwide. Targeted monotherapies produce high regression rates, albeit for limited patient subgroups, who inevitably succumb. We present a novel strategy for identifying customized combinations of triplets of targeted agents, utilizing a simplified interventional mapping system (SIMS) that merges knowledge about existent drugs and their impact on the hallmarks of cancer. Based on interrogation of matched lung tumor and normal tissue using targeted genomic sequencing, copy number variation, transcriptomics, and miRNA expression, the activation status of 24 interventional nodes was elucidated. An algorithm was developed to create a scoring system that enables ranking of the activated interventional nodes for each patient. Based on the trends of co-activation at interventional points, combinations of drug triplets were defined in order to overcome resistance. This methodology will inform a prospective trial to be conducted by the WIN consortium, aiming to significantly impact survival in metastatic NSCLC and other malignancies

Treatment Access, Health Economics, and the Wave of a Magic Wand

New drugs are expensive, in part due to excessive drug development costs. Governments are trying to reduce drug prices. This can delay access to effective agents. A country&rsquo;s access to new drugs correlates with prices they agree to pay. After Health Canada approves a drug, the Canadian Agency for Drug and Technologies in Health (CADTH) assesses it. CADTH&rsquo;s approval is usually contingent on it costing &le;CAD 50,000 per quality adjusted life year (QALY) gained. This value (unchanged from the 1970s) is inappropriately low. An inflation-adjusted CAD 50,000 1975 QALY should translate into a CAD 250,000 2021 QALY. CADTH&rsquo;s target also does not consider that drug development costs have risen much faster than inflation or that new precision therapies may only be used in small populations. In a separate process, proposals from the Patented Medicines Price Review Board (PMPRB) would decrease initial Canadian drug prices by 20%, but prices would fall further as sales increased, with ultimate price reductions of up to 80%. PMPRB claims its proposal would not reduce drug access, but multiple analyses strongly suggest otherwise. Government price controls target the symptom (high prices), not the disease. They translate into shortages without solving the problem. CADTH and PMPRB approaches both threaten access to effective drugs