tbuckley/cabot-search huggingface dataset:
Risks of ischaemic heart disease and stroke in meat eaters, fish eaters, and vegetarians over 18 years of follow-up: results from the prospective EPIC-Oxford study
Authors: Tammy Y N Tong, Paul N Appleby, Kathryn E Bradbury, Aurora Perez-Cornago, Ruth C Travis, Robert Clarke, Timothy J Key
Journal: BMJ (2019)

Abstract Objective To examine the associations of vegetarianism with risks of ischaemic heart disease and stroke. Design Prospective cohort study. Setting The EPIC-Oxford study, a cohort in the United Kingdom with a large proportion of non-meat eaters, recruited across the country between 1993 and 2001. Participants 48 188 participants with no history of ischaemic heart disease, stroke, or angina (or cardiovascular disease) were classified into three distinct diet groups: meat eaters (participants who consumed meat, regardless of whether they consumed fish, dairy, or eggs; n=24 428), fish eaters (consumed fish but no meat; n=7506), and vegetarians including vegans (n=16 254), based on dietary information collected at baseline, and subsequently around 2010 (n=28 364). Main outcome measures Incident cases of ischaemic heart disease and stroke (including ischaemic and haemorrhagic types) identified through record linkage until 2016. Results Over 18.1 years of follow-up, 2820 cases of ischaemic heart disease and 1072 cases of total stroke (519 ischaemic stroke and 300 haemorrhagic stroke) were recorded. After adjusting for sociodemographic and lifestyle confounders, fish eaters and vegetarians had 13% (hazard ratio 0.87, 95% confidence interval 0.77 to 0.99) and 22% (0.78, 0.70 to 0.87) lower rates of ischaemic heart disease than meat eaters, respectively (P&lt;0.001 for heterogeneity). This difference was equivalent to 10 fewer cases of ischaemic heart disease (95% confidence interval 6.7 to 13.1 fewer) in vegetarians than in meat eaters per 1000 population over 10 years. The associations for ischaemic heart disease were partly attenuated after adjustment for self reported high blood cholesterol, high blood pressure, diabetes, and body mass index (hazard ratio 0.90, 95% confidence interval 0.81 to 1.00 in vegetarians with all adjustments). By contrast, vegetarians had 20% higher rates of total stroke (hazard ratio 1.20, 95% confidence interval 1.02 to 1.40) than meat eaters, equivalent to three more cases of total stroke (95% confidence interval 0.8 to 5.4 more) per 1000 population over 10 years, mostly due to a higher rate of haemorrhagic stroke. The associations for stroke did not attenuate after further adjustment of disease risk factors. Conclusions In this prospective cohort in the UK, fish eaters and vegetarians had lower rates of ischaemic heart disease than meat eaters, although vegetarians had higher rates of haemorrhagic and total stroke.
Optimizing medication management: The pharmacists’ role and the cancer patients’ view
Authors: K. Meier, W. Wagner, S. Thor-Wiedemann, G. J. Wiedemann
Journal: Journal of Clinical Oncology (2009)

e20684 Background: The safety of cancer patients given antineoplastic drugs as an outpatient treatment strictly depends on patients’ compliance to the information given by physicians and other health care professionals. On that note, pharmacists play an important part because they supply the cancer patients with the prescribed drugs and influence the actual intake of the medication. It has been shown in several large-scale studies that at least one third of all cancer patients do not take their vital medication. Is this missing compliance partially caused by insufficient or lacking information by the pharmacists? The patients‘ view. Methods: 312 (out of 514 invited) cancer patients from all parts of Germany undergoing cancer treatment filled in a questionnaire (Picker Institute, Germany) asking about the use of pharmacist services in 47 pharmacies and their satisfaction with the information received. Results: In pharmacies with an oncological focus 50% of the cancer patients received specific counselling. Other pharmacies provided oncology-specific information to 6%. 18% of the surveyed patients would have liked counselling but did not receive any. 17% were not interested in further information. Patients were disappointed about the lack of information regarding medication (25% of the patients), nutrition (43%), supportive therapy (35%), complementary medicine (51%). Complete satisfication with the information given was achieved in counselling regarding medication (30%), nutrition (22%), supportive therapy (28%), and complementary medicine (10%). Conclusions: The majority of the surveyed cancer patients were not satisfied with the information regarding medication, supportive therapy, nutrition, and complementary treatments provided by pharmacists. Our data have implications for pharmacist education and may help to improve patient support and compliance by ameliorating consulting skills. No significant financial relationships to disclose.
Effect of microRNA-124 on homologous recombination protein RAD51 and glioblastoma cells undergoing radiation.
Authors: Henning S Schäfer, Reuven Agami, Gijs van Haaften
Journal: Journal of Clinical Oncology (2012)

e13515 Background: The DNA damage repair (DDR) pathways are an essential cell survival mechanism to preserve genomic integrity. In tumor cells, DDR pathways have a huge impact in cell survival, response to therapy and thus prognosis. Our objective is to investigate whether microRNAs (miRs) can influence specific DNA repair pathways. For our studies we focussed on double-strand break (DSB) repair by homologous - (HR) or non-homologous recombination (NHEJ). DSBs are the main lethal lesions induced by ionizing radiation. Methods: A retroviral miR expression library of ~500 miRs was transduced into a HR reporter cell line. For less abundant miRs found in this analysis in silico analysis was performed to detect potential targets. Regulation of HR protein RAD51 by miR-124 could be shown by luciferase assays and immunoblotting. Overexpression of miR-124 in glioblastoma cell line U87 was done by lentiviral constructs. Effect of miR-124 overexpression was revealed by colony – and competetive growth assays. Results: In an unbiased screen we found that miR-124 is less abundantly expressed in a reporter cell population sufficient for HR, suggesting a negative role for these miRs in DSB repair via HR. Reporter assays revealed a negative regulation of RAD51, a key protein of HR pathway, by miR-124. This regulation was specific to a conserved binding motif at the 3` UTR of RAD51. This regulation could also be detected in vivo whereas overexpression of miR-124 leads to downregulation of RAD51 protein levels. Functional experiments in glioblastoma cell line (U87), that express hardly no miR-124, revealed increased sensitivity to ionizing radiation if miR-124 is (re)-expressed. Conclusions: In this work we uncover miRs influencing the cellular DNA-repair machinery. We show that miR-124 influences the repair of DSBs by HR. This effect is specific and mediated by the regulation of RAD51 protein level, an essential component of the HR pathway. Re-expression of miR-124 sensitizes glioblastoma cell line (U87) to radiation in functional experiments. We propose that (re)-expressing miR-124 in glioblastomas could be a new treatment strategy to sensitize this tumors to radiation therapy.
Neoadjuvant Therapy of Pancreatic Ductal Adenocarcinoma With Vascular Involvement Shows Promise
Authors: Roxanne L. Massoumi, O. Joe Hines
Journal: JAMA Surgery (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Critical evaluation of MRI-targeted TRUS-guided transperineal fusion biopsy for detection of prostate cancer.
Authors: Timur H. Kuru, Matthias Roethke, Tobias Simpfendoerfer, Silvan Boxler, Jonas Seidenader, Heinz-Peter Schlemmer, Markus Hohenfellner, Boris Hadaschik
Journal: Journal of Clinical Oncology (2013)

e16063 Background: Precise staging of prostate cancer (PC) is essential for individualized treatment decisions. However, the majority of transrectal biopsies are negative for prostate cancer or show imprecise results. Additionally, the rate of upgrading in Gleason scores between biopsy and prostatectomy specimen is around 30-40%. MRI/TRUS fusion has shown encouraging results for detecting clinically significant prostate cancer. Methods: 412 consecutive patients with suspicion of PC were prospectively included in our database. The median age of patients was 65 years (range 42-84). Mean PSA level was 9.56 ng/ml (± 7.9ng/ml, SD). 55% of men had previous TRUS-guided biopsies, 45% underwent primary biopsy. Imaging data and biopsy results were analyzed and a self-designed questionnaire was send to all men regarding further clinical history and adverse effects of the biopsy. Results: In 236 of 412 (57.3%) biopsy samples showed PC. 71.6% of biopsy proven PC were clinically significant (D’Amico criteria). On multiparametric (mp)-MRI, 120 men were reported as highly suspicious for PC and in these tumor detection rate was 83.3% (100/120). In patients without cancer-suspicious MRI-lesions, 31,8% (42/132) men were diagnosed with significant disease (Table 1). Regarding adverse effects, 152 patients (49%) reported hematuria after biopsy. 9 patients (2%) needed temporary catheterization after biopsy due to prostate swelling. In three patients (0.7%) febrile urinary tract infection occurred after biopsy. Major limitation is the limited follow-up of 12-months of biopsy-negative patients. Conclusions: MRI-targeted TRUS-guided transperineal fusion biopsy provides high detection rates of clinically significant tumors. mp-MRI still has its limitations, and therefore systematic biopsies should currently not be omitted. The morbidity of the transperineal saturation approach is reasonable and mainly self-limiting. [Table: see text]
RNA-silencing nanoprobes for effective activation and dynamic imaging of neural stem cell differentiation
Authors: Ruili Zhang, Zhe Wang, Zuo Yang, Linlin Wang, Zhongdi Wang, Baihang Chen, Zhongliang Wang, Jie Tian
Journal: Theranostics (2019)

To achieve the clinical potential of neural stem cells (NSCs), it is crucial to activate NSC differentiation into neurons and simultaneously monitor the process of NSC differentiation.However, there are many challenges associated with regulating and tracking NSC differentiation.Methods: We developed a redox-responsive multifunctional nanocomplex with a disulfide bond-cvNC-for the delivery of siRNAs to induce NSC differentiation through sequence-specific RNA interference (RNAi) and real-time imaging of sequential mRNA expression during differentiation.The stability and specificity of cvNCs were studied in vitro.Controlled release of siRNA, gene silencing efficiency, as well as real-time imaging of cvNCs on Tubb3 and Fox3 mRNAs during NSC differentiation were evaluated. Results:The introduction of a redox-sensitive disulfide bond not only ensures the remarkable performance of cvNC, such as high stability, controlled siRNA release, and enhanced gene silencing efficiency, but also effectively stimulates NSC differentiation into neurons.More importantly, the cvNC can track NSC differentiation in real-time by monitoring the sequential expression of mRNAs. Conclusion:Our study indicates that cvNC can serve as a robust system for exploring NSCs differentiation process as well as other biological events in living cells.
Distinct Colorectal Cancer–Associated APC Mutations Dictate Response to Tankyrase Inhibition
Authors: Emma M. Schatoff, Sukanya Goswami, Maria Paz Zafra, Miguel Foronda, Michael Shusterman, Benjamin I. Leach, Alyna Katti, Bianca J. Diaz, Lukas E. Dow
Journal: Cancer Discovery (2019)

Abstract The majority of colorectal cancers show hyperactivated WNT signaling due to inactivating mutations in the adenomatous polyposis coli (APC) tumor suppressor. Genetically restoring APC suppresses WNT and induces rapid and sustained tumor regression, implying that reengaging this endogenous tumor-suppressive mechanism may be an effective therapeutic strategy. Here, using new animal models, human cell lines, and ex vivo organoid cultures, we show that tankyrase (TNKS) inhibition can control WNT hyperactivation and provide long-term tumor control in vivo, but that effective responses are critically dependent on how APC is disrupted. Mutant APC proteins truncated within the mutation cluster region physically engage the destruction complex and suppress the WNT transcriptional program, while APC variants with early truncations (e.g., ApcMin) show limited interaction with AXIN1 and β-catenin, and do not respond to TNKS blockade. Together, this work shows that TNKS inhibition, like APC restoration, can reestablish endogenous control of WNT/β-catenin signaling, but that APC genotype is a crucial determinant of this response. Significance: This study reveals how subtle changes to the mutations in a critical colorectal tumor suppressor, APC, influence the cellular response to a targeted therapy. It underscores how investigating the specific genetic alterations that occur in human cancer can identify important biological mechanisms of drug response and resistance. This article is highlighted in the In This Issue feature, p. 1325
Renal impairment after chemotherapy in lung (LC), colorectal (CRC), and breast cancer (BC) patients (pts) from the Henry Ford Health System (HFHS) tumor registry.
Authors: Laura Chu, Marianne Ulcickas Yood, Mahmoud Loghman-Adham, Karen Wells, Deborah Casso, Susan A. Oliveria, Wei Dong
Journal: Journal of Clinical Oncology (2012)

1590 Background: Renal impairment is a common comorbidity in cancer pts. It can delay excretion and alter metabolism of anticancer drugs leading to further renal toxicity. The objective of this study was to determine the proportion of pts with renal impairment, defined as the presence of proteinuria (PR), acute kidney injury (AKI), or chronic kidney disease (CKD), after chemotherapy (chemo) initiation. Methods: LC, CRC, and BC pts newly diagnosed between 2000 and 2007 (regardless of prior renal status) were identified using the HFHS tumor registry, with follow-up through Mar 2009. AKI was defined based on RIFLE (severity categories only) using lab data within 1 to 7 days after chemo initiation. CKD was defined based on NKF-KDOQI criteria and lab data up to 1 year after chemo initiation. Proteinuria was defined as protein/creatinine &gt;30 mg/g within 3 months after chemo initiation. Descriptive statistics include proportions stratified by renal impairment status (yes, no) at cancer diagnosis. Results: We identified 1,896 LC, 1,088 CRC, 1,611 BC chemo treated pts. Median age for all pts was 66 years. For LC and CRC, 56% and 51% were men, respectively. The proportion of pts with renal impairment after chemo by tumor type was the following: LC (AKI=23.4%; CKD=48.2%; PR=0.4%); CRC (AKI=20.3%; CKD=55.7%; PR=0.1%); BC (AKI=7.8%; CKD=63.9%; PR=0.6%). Pts with pre-existing renal impairment at cancer diagnosis were more likely to have impairment after chemo (Table). Conclusions: In LC, CRC, and BC pts, the proportion of pts with renal impairment after chemo initiation was high. Extent of renal impairment, especially AKI, appears to be associated with tumor type. Older age, as in this HFHS cohort, is associated with higher prevalence of CKD. Renal function should be closely monitored, particularly among pts with pre-existing renal impairment, and preventive measures implemented to minimize further toxicity after treatment.
Phase II study of bevacizumab in combination with docetaxel and carboplatin in patients with metastatic non-small cell lung cancer (NSCLC)
Authors: W. N. William, M. S. Kies, F. V. Fossella, G. Gladish, J. V. Heymach, B. S. Glisson, W. H. Tse, D. Liu, R. S. Herbst, S. M. Lippman
Journal: Journal of Clinical Oncology (2007)

18098 Background: The combination of bevacizumab, paclitaxel and carboplatin has been recently shown to increase response rates and survival in patients (pts) with untreated, metastatic, non-squamous, NSCLC and is currently FDA-approved for this indication. However, there are limited data on the safety and efficacy of bevacizumab in combination with other widely used chemotherapy doublets for NSCLC. This is a single-arm, open-labeled, phase II trial of bevacizumab, docetaxel and carboplatin for pts with NSCLC. Methods: Eligibility criteria included chemotherapy-naïve stage IIIB or IV incurable NSCLC of non-squamous cell histology, PS 0–1, no brain metastases, no history of hemoptysis, no cavitation, stable cardiac condition and no full dose anticoagulation. Treatment consisted of docetaxel 75 mg/m 2 , carboplatin AUC 6, and bevacizumab 15 mg/kg IV on day 1 every 3 weeks for up to 6 cycles followed by bevacizumab 15 mg/kg alone every 3 weeks until progression. The primary endpoint was progression-free survival. Results: 20 pts (12 females) have been enrolled with a planned sample size of 50 pts. Baseline characteristics were: median age 66 years old (37–77), PS 0 (6 pts) or 1 (14 pts), stage IIIB (1 pt) or IV (19 pts). 19 pts are evaluable for response and toxicity at this time. Severe adverse events (SAEs) included: 4 pts with neutropenia (2 febrile neutropenias), mild hemoptysis in 2 pts (treated with radiotherapy), 1 pt with peritoneal perforation (who had a history of diverticula), 1 pt with pulmonary embolism, and 1 pt with grade 3 hypertension. Partial responses by RECIST have been observed in 14 pts (74%, 13 confirmed), and stable disease in 5 pts (26%, 4 confirmed). Disease control rate (PR+SD) was 100% after 4 cycles of therapy. 9/20 pts are off treatment (3 progressions, 5 SAEs, 1 maximal benefit). Progression-free survival will be reported at the completion of the trial. Conclusions: The combination of bevacizumab, docetaxel and carboplatin appears to be efficacious and tolerable for the first-line treatment of metastatic NSCLC. No significant financial relationships to disclose.
Prescribing decision drivers in patients with recurrent gastrointestinal stromal tumor (GIST) previously treated with adjuvant imatinib: A retrospective chart extract-based approach.
Authors: Annie Guérin, Medha Sasane, Geneviève Gauthier, Frances Annelies Schwiep, Christopher Hunt Keir, Matt Magestro, Eric Q. Wu, Anthony Paul Conley
Journal: Journal of Clinical Oncology (2013)

e21515 Background: Adjuvant imatinib (IM) is the standard of care for primary resectable GIST. However, little is known about prescribing habits following disease recurrence. This study identifies main prescribing decision drivers in recurrent GIST pts following completion of adjuvant IM treatment. Methods: Using an online data collection system, clinical information was retrieved on 410 pts treated with adjuvant IM for ≥6 months for primary resectable KIT+GIST, who discontinued IM treatment, had a recurrence (while off IM), and subsequently restarted IM or initiated sunitinib. Pt-level data were collected at primary diagnosis and at first recurrence. Prescribing decision drivers were identified using logistic regression models. Physicians were also surveyed to identify factors that influence their prescribing decisions. Results: Following initial disease recurrence, 77% of pts restarted IM and 23% initiated sunitinib. IM duration at primary diagnosis was the main prescribing decision driver; pts treated with IM for a shorter period of time (≤18 months) were 7.0 times more likely to restart IM than pts with longer IM duration (p&lt;.01). Pts who took longer (≥12 months) to develop recurrence after IM discontinuation (Odds ratio [OR]=3.4; p=&lt;.01 ), had a low mitotic rate at recurrence (OR=2.8; p=&lt;.01), or had a recurrence inside the gastrointestinal system (OR=2.7; p=&lt;.01) were also more likely to be prescribed IM following recurrence. These findings were consistent with the top survey responses on factors influential to prescribing decisions after recurrence: time to develop recurrence (55%), pt risk profile (53%), and IM duration prior to recurrence (51%). Conclusions: Based on information of pts who restarted IM or initiated sunitinib, IM treatment duration at primary diagnosis, time to develop recurrence after IM discontinuation, tumor location and mitotic rate at recurrence seem to be the main prescribing decision drivers. These findings were consistent with physicians’ main factors reported to influence their prescribing decisions following recurrence.
Sustained Progression-Free Survival Benefit of Rituximab Maintenance in Patients With Follicular Lymphoma: Long-Term Results of the PRIMA Study
Authors: Emmanuel Bachy, John F. Seymour, Pierre Feugier, Fritz Offner, Armando López-Guillermo, David Belada, Luc Xerri, John V. Catalano, Pauline Brice, François Lemonnier, Alejandro Martin, Olivier Casasnovas, Lars M. Pedersen, Véronique Dorvaux, David Simpson, Sirpa Leppa, Jean Gabarre, Maria G. da Silva, Sylvie Glaisner, Loic Ysebaert, Anne Vekhoff, Tanin Intragumtornchai, Steven Le Gouill, Andrew Lister, Jane A. Estell, Gustavo Milone, Anne Sonet, Jonathan Farhi, Harald Zeuner, Hervé Tilly, Gilles Salles
Journal: Journal of Clinical Oncology (2019)

PURPOSE The PRIMA study (ClinicalTrials.gov identifier: NCT00140582 ) established that 2 years of rituximab maintenance after first-line immunochemotherapy significantly improved progression-free survival (PFS) in patients with follicular lymphoma compared with observation. Here, we report the final PFS and overall survival (OS) results from the PRIMA study after 9 years of follow-up and provide a final overview of safety. METHODS Patients (&gt; 18 years of age) with previously untreated high–tumor-burden follicular lymphoma were nonrandomly assigned to receive one of three immunochemotherapy induction regimens. Responding patients were randomly assigned (stratified by induction regimen, response to induction treatment, treatment center, and geographic region) 1:1 to receive 2 years of rituximab maintenance (375 mg/m 2 , once every 8 weeks), starting 8 weeks after the last induction treatment, or observation (no additional treatment). All patients in the extended follow-up provided their written informed consent (data cutoff: December 31, 2016). RESULTS In total, 1,018 patients completed induction treatment and were randomly assigned to rituximab maintenance (n = 505) or observation (n = 513). Consent for the extended follow-up was provided by 607 patients (59.6%) of 1,018 (rituximab maintenance, n = 309; observation, n = 298). After data cutoff, median PFS was 10.5 years in the rituximab maintenance arm compared with 4.1 years in the observation arm (hazard ratio, 0.61; 95% CI, 0.52 to 0.73; P &lt; .001). No OS difference was seen in patients randomly assigned to rituximab maintenance or observation (hazard ratio, 1.04; 95% CI, 0.77 to 1.40; P = .7948); 10-year OS estimates were approximately 80% in both study arms. No new safety signals were observed. CONCLUSION Rituximab maintenance after induction immunochemotherapy provides a significant long-term PFS, but not OS, benefit over observation.