tbuckley/cabot-search huggingface dataset:
Lurbinectedin (PM01183) with doxorubicin (DOX), an active treatment as second-line therapy in small cell lung cancer (SCLC).
Authors: Martin Forster, Emiliano Calvo, Maria Eugenia Olmedo Garcia, M. Pilar Lopez Criado, Victor Moreno, Arturo Soto-Matos, Esther Holgado, Nicholas F. Brown, Michael Flynn, Valentina Boni, Eva Guerra Alia, Sergio A. Szyldergemajn
Journal: Journal of Clinical Oncology (2015)

7509 Background: PM01183 inhibits transactivated transcription and acts on the tumor microenvironment. It lacks cross-resistance with platinum. PM01183 and DOX are synergistic in vitro. Recommended dose (RD): 4 mg (or 2 mg/m2) + 50 mg/m2, respectively, both on day (D) 1 every 3 weeks. Compelling activity was observed earlier in 2nd line SCLC patients (pts), leading to a cohort expansion. The historical response rate (RR) of DOX-based combinations is around 20%. Methods: SCLC pts ≤ 75 years with ECOG PS 0-1, adequate organ function and 1 prior chemotherapy-containing line were included. Stable asymptomatic brain metastases were allowed. DOX was discontinued before reaching 450 mg/m2, non-progressing pts could continue on PM01183 alone. CSF prophylaxis was not mandatory. Results: 21 pts were treated and evaluable for efficacy [response rate (RR) by RECIST v1.1]. Male: 76%; median age: 62 y (r, 48-73); ECOG PS = 0/1 in 43%/57%; 29% had brain metastases, 62% had bulky disease and 81% responded to 1st line, 5% CRs. Median chemotherapy-free interval (CTFI) was 3.1 months; 48% were resistant (R = CTFI ≤ 90 d). Confirmed RR was 67% (95%CI: 43-85%), including ~10% CRs. CTFI was predictive of RR (100% vs. 30% in R pts; p = 0.001). Grade (G) 4 neutropenia, thrombocytopenia or anemia occurred in 86%/19%/5%, respectively and febrile neutropenia (G3/4) in 29%. Other toxicities were generally mild: fatigue (G3 = 14%), anorexia, nausea/vomiting, alopecia, stomatitis (G3 = 10%), dysgeusia, constipation and pneumonia (10%). Three pts discontinued due to toxicity (myelosuppression in 2), no cardiac toxicity or G5 events occurred. As of January 2015, 5 pts (24%) are still ongoing. Progression-free survival (PFS) is 4.7 months (95%CI: 3.5-not reached). Conclusions: The PM01183 and DOX combination showed compelling clinical activity as 2nd line treatment in SCLC. RR could be comparable to those achieved in 1st line. Reversible myelosuppression was the most frequent and expected side effect; DOX dose adjustment and/or CSF prophylaxis might be appropriate to improve tolerance. A randomized study is planned to help define the role of this combination in relapsed SCLC pts. Updated results will be presented. Clinical trial information: NCT01970540.
A Novel MPEG-PDLLA-PLL Copolymer for Docetaxel Delivery in Breast Cancer Therapy
Authors: Liwei Tan, Jinrong Peng, Qian Zhao, Lan Zhang, Xichuan Tang, Lijuan Chen, Minyi Lei, Zhiyong Qian
Journal: Theranostics (2017)

Satisfactory drug loading capacity and stability are the two main factors that determine the anti-cancer performance. In general, the stability of the micelles is reduced when the drug loading (DL) is increased. Therefore, it was a challenge to have high drug loading capacity and good stability. In this study, we introduced a hydrophilic poly (L-Lysine) (PLL) segment with different molecular-weights into the monomethoxy poly (ethylene glycol)-poly (D, L-lactide) (MPEG-PDLLA) block copolymer to obtain a series of novel triblock MPEG-PDLLA-PLL copolymers. We found that the micelles formed by a specific MPEG
Enteropathogen detection in children with diarrhoea, or vomiting, or both, comparing rectal flocked swabs with stool specimens: an outpatient cohort study
Authors: Stephen B Freedman, Jianling Xie, Alberto Nettel-Aguirre, Bonita Lee, Linda Chui, Xiao-Li Pang, Ran Zhuo, Brendon Parsons, James A Dickinson, Otto G Vanderkooi, Samina Ali, Lara Osterreicher, Karen Lowerison, Phillip I Tarr, Anderson Chuck, Gillian Currie, Mohamed Eltorki, Tim Graham, Jason Jiang, David Johnson, James Kellner, Martin Lavoie, Marie Louie, Judy MacDonald, Shannon MacDonald, Kimberley Simmonds, Larry Svenson, Raymond Tellier, Steven Drews, James Talbot
Journal: The Lancet. Gastroenterology & hepatology (2017)
Pretreatment anti-mullerian hormone to predict for resumption of mense in one year after chemotherapy in premenopausal hormone-receptor positive early breast cancer.
Authors: Yanxia Shi, Ye Cao, Cong Xue, Cui Shao, Zhongyu Yuan, Shusen Wang, Xin An, Roujun Peng, Fei Xu, Jia Jia Huang, Wen Xia, Xi Wang, Weidong Wei, Jun Tang, Peng Liu
Journal: Journal of Clinical Oncology (2016)

e12032 Background: Postchemotherapy ovarian function is very important in relation to adjuvant endocrine therapy decisions of hormone receptor-positive (HR+) early breast cancer (eBC). Although menses status is commonly used to measure ovarian function after chemotherapy, its retrospective pattern limited the prospective application in endocrine therapy plan making. Anti-mullerian hormone (AMH) is now the gold standard to measure ovarian reserve function in reproductive medicine. The purpose of this study was to evaluate the association of prechemotherapy AMH, follicle-stimulating hormone (FSH) and estrogen (E) with resumption of menses in one year after chemotherapy. Methods: This is a retrospective study. From August 2013 to December 2014, a total of 120 premenopausal patients younger than 50 years old with HR+ eBC were included in this study. We tested the relationship between prechemotherapy AMH, FSH and E with one year menses status. Results: After a median follow up of 446 days (range, 182-790 days) after chemotheapy, 38 patients (31.7%) experienced resumption of menses in one year after chemotherapy. Pretreatment AMH was significantly lower in women with amenorrhoea than those with menses at one year (1.17±1.68ng/ml vs 3.06±2.62, p< 0.0001), but not E or FSH. In adjusted analyses, AMH levels was associated with the one year resumption of menses, independent of age. AMH levels under detection ( < 0.08 ng/ml) resulted in correct classification of resumption of menses in one year with sensitivity 97.4% and specificity 84.1%. Conclusions: In premenopausal patients with HR+ eBC, prechemothearpy AMH were associated the one year resumption of menses, independent of age. This study supports using prechemotherapy AMH to predict future recovery of menses. The prespective observational study is now conducting.
Behavioral Counseling to Promote a Healthful Diet and Physical Activity for Cardiovascular Disease Prevention in Adults Without Known Cardiovascular Disease Risk Factors
Authors: Carrie D. Patnode, Corrine V. Evans, Caitlyn A. Senger, Nadia Redmond, Jennifer S. Lin
Journal: JAMA (2017)

Unhealthful dietary patterns, low levels of physical activity, and high sedentary time increase the risk of cardiovascular disease.To systematically review the evidence on the benefits and harms of behavioral counseling for the primary prevention of cardiovascular disease in adults without known cardiovascular risk factors to inform the US Preventive Services Task Force.MEDLINE, PubMed, Cochrane Central Register of Controlled Trials, and PsycINFO for studies published in the English language between January 1, 2013, and May 25, 2016, and ongoing surveillance in targeted publications through March 24, 2017. Studies included in the previous review were reevaluated for inclusion.Randomized clinical trials of behavioral interventions targeting improved diet, increased physical activity, decreased sedentary time, or a combination of these among adults without known hypertension, dyslipidemia, diabetes, or impaired fasting glucose.Independent critical appraisal and data abstraction by 2 reviewers.Cardiometabolic health and intermediate outcomes, behavioral outcomes, and harms related to interventions.Eighty-eight studies (N = 121 190) in 145 publications were included. There was no consistent benefit of the interventions on all-cause or cardiovascular mortality or morbidity (4 trials [n = 51 356]) or health-related quality of life (10 trials [n = 52 423]). There was evidence of small, statistically significant between-group mean differences for systolic blood pressure (-1.26 mm Hg [95% CI, -1.77 to -0.75]; 22 trials [n = 57 953]), diastolic blood pressure (-0.49 mm Hg [95% CI, -0.82 to -0.16]; 23 trials [n = 58 022]), low-density lipoprotein cholesterol level (-2.58 mg/dL [95% CI, -4.30 to -0.85]; 13 trials [n = 5554]), total cholesterol level (-2.85 mg/dL [95% CI, -4.95 to -0.75]; 19 trials [n = 9325]), and body mass index (-0.41 [95% CI, -0.62 to -0.19]; 20 trials [n = 55 059]) at 6 to 12 months as well as small-to-modest associations with dietary and physical activity behaviors. There was no evidence of greater incidence of serious adverse events, injuries, or falls in intervention vs control participants.Diet and physical activity behavioral interventions for adults not at high risk for cardiovascular disease result in consistent modest benefits across a variety of important intermediate health outcomes across 6 to 12 months, including blood pressure, low-density lipoprotein and total cholesterol levels, and adiposity, with evidence of a dose-response effect, with higher-intensity interventions conferring greater improvements. There is very limited evidence on longer-term intermediate and health outcomes or on harmful effects of these interventions.
Posing Causal Questions When Analyzing Observational Data
Authors: Shilpa N. Bhupathiraju, Meir J. Stampfer, JoAnn E. Manson
Journal: JAMA (2017)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
A Combination of DNA-peptide Probes and Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS): A Quasi-Targeted Proteomics Approach for Multiplexed MicroRNA Quantification
Authors: Feifei Xu, Weixian Zhou, Jianxiang Cao, Qingqing Xu, Dechen Jiang, Yun Chen
Journal: Theranostics (2017)

The distorted and unique expression of microRNAs (miRNAs) in cancer makes them an attractive source of biomarker.There is much evidence indicating that a panel of miRNAs, termed "miRNA fingerprints", is more specific and informative than an individual miRNA as biomarker.Thus, multiplex assays for simultaneous quantification of multiple miRNAs could be more potent in clinical practice.However, current available assays normally require pre-enrichment, amplification and labeling steps, and most of them are semi-quantitative or lack of multiplexing capability.In this study, we developed a quasi-targeted proteomics assay for multiplexed miRNA quantification by a combination of DNA-peptide probes and liquid chromatography-tandem mass spectrometry (LC-MS/MS).Specifically, the signal of target miRNAs (i.e., miR-21, miR-let7a, miR-200c, miR-125a and miR-15b) was converted into the mass response of reporter peptides by hybridization of miRNAs with DNA-peptide probes and subsequent tryptic digestion to release the peptides.After a careful optimization of conditions related to binding, conjugation, hybridization and multiple reaction monitoring (MRM) detection, the assay was validated for each miRNA and the limit of quantification (LOQ) for all the miRNAs can achieve 1 pM.Moreover, crosstalk between DNA-peptide probes in multiplex assay was sophisticatedly evaluated.Using this quasi-targeted proteomics assay, the level of target miRNAs was determined in 3 human breast cell lines and 36 matched pairs of breast tissue samples.Finally, simplex assay and qRT-PCR were also performed for a comparison.This approach grafts the strategy of targeted proteomics into miRNA quantification and may offer a new way for multiplexed miRNA profiling.
Prevalence of Discrepancy Between the Results of One-Stage and Chromogenic Factor VIII:C Assays in Iranian Patients with Mild / Moderate Hemophilia A
Authors: Minoo Ahmadinejad, Fatemeh Vossough, Kataioon Karimi, Mohammad Reza Tabatabaei, Sanaz Homayoun, Mehran Karimi, Gholamreza Toogeh
Journal: Blood (2016)
Comprehensive assessment of <i>ATRX</i> mutation, protein expression, and alternative lengthening of telomeres (ALT) phenotype in grade II and III gliomas.
Authors: Aline P. Becker, Erica Hlavin Bell, Jessica Fleming, Joseph P McElroy, Denise Fabian, Sasha Beyer, Andrea L Salavaggione, Mindy K Graham, Christopher M Heaphy, Oliver Oehlke, Ori Staszewski, Marco Prinz, Anca Grosu, Arnab Chakravarti
Journal: Journal of Clinical Oncology (2017)

2064 Background: ATRX mutations are key molecular markers for classification of gliomas. We aimed to evaluate ATRXmutations and protein expression and the ALT phenotype as potential biomarkers for grade II and III gliomas. Methods: Retrospective analysis of 156 adult gliomas, with long-term follow up. Gene sequencing ( IDH1/2 and ATRX), Oncoscan array (1p19q co-deletion), FISH assays (1p19q co-deletion and ALT phenotype) and immunohistochemistry (IDH1 R132H and ATRX) were performed and the results were correlated with OS and PFS. Results: Twenty-six out of 94 samples (27.7%) had ATRX mutations, commonly related to IDH1/2 mutant-1p/19q intact tumors (22/26 cases – p &lt; 0.0001), however, 3 (11.5%) mutant tumors had concurrent 1p/19q co-deletions. ATRX loss of expression occurred in 66/150 cases (44%), consistently related to ATRX mutations (p &lt; 0.0001). Intriguingly, 4/25 ATRX mutant tumors (2 frameshift and 2 point mutations with low/medium functional impact) showed weak/heterogeneous expression, while 18/65 (27.7%) ATRX wild type tumors had loss of protein expression. ALT phenotype was detected in 50/150 cases (33.3%), strongly related to ATRX mutations (23/32 cases), loss of protein expression (45/50 cases), and to IDH1/2 mutant-1p/19q intact tumors (35/41 cases). Two ATRX mutant tumors were ALT negative, while nine ATRX wild type tumors with loss of expression had ALT phenotype. ATRXmutations, loss of protein expression, and ALT phenotype were strongly related to longer OS in grade III gliomas (p = 0.006, 0.023 and 0.003, respectively). Further subset analyses were not completed due to small sample sizes. Conclusions: ATRX mutations and loss of protein expression as well as ALT phenotype are potential prognostic factors for grade III gliomas. Importantly, this study highlights possible discrepancies (although infrequent) between ATRX sequencing, immunohistochemistry, and FISH (ALT). In addition, other mechanisms of ATRX gene silencing should be further investigated in grade II and III gliomas. FUNDING: R01CA108633, R01CA169368, RC2CA148190, U10CA180850-01 (NCI), Brain Tumor Funders Collaborative Grant, and The Ohio State University CCC (all to AC).
Survival benefit of statin use in ankylosing spondylitis: a general population-based cohort study
Authors: Amar Oza, Na Lu, Sara R Schoenfeld, Mark C Fisher, Maureen Dubreuil, Sharan K Rai, Yuqing Zhang, Hyon K Choi
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> Recent studies have shown an increase in both cardiovascular and all-cause mortality in ankylosing spondylitis (AS). We examined the potential survival benefit of statin use in AS within a general population context. <h3>Methods</h3> We performed an incident user cohort study with time-stratified propensity score matching using a UK general population database between 1 January 2000 and 31 December 2014. To account for potential confounders, we compared propensity score-matched cohorts of statin initiators and non-initiators using 1-year cohort accrual blocks. The variables used to create the propensity score model included disease duration, body mass index, lifestyle factors, comorbidities and medication use. <h3>Results</h3> Using unmatched AS cohorts, statin initiators (n=1430) showed a 43% higher risk of mortality than non-initiators (n=1430) (HR=1.43; 95% CI 1.12 to 1.84). After propensity score matching, patients with AS who initiated statins (n=1108) had 96 deaths, and matched non-initiators (n=1108) had 134 deaths over a mean follow-up of 5.3 and 5.1 years, respectively. This corresponded to mortality rates of 16.5 and 23.8 per 1000 person-years (PY), respectively, resulting in an HR of 0.63 (95% CI 0.46 to 0.85) and an absolute mortality rate difference of 7.3 deaths per 1000 PY (95% CI 2.1 to 12.5). <h3>Conclusion</h3> This general population-based cohort study suggests that statin initiation is associated with a substantially lower risk of mortality among patients with AS. The magnitude of the inverse association appears to be larger than that observed in randomised trials of the general population and in population-based cohort studies of patients with rheumatoid arthritis.
Erratum: Paclitaxel induces significant changes in epidoxorubicin distribution in mice (Ann. Oncol. 1996; 7: 801-805)
Authors: T. Colombo, O. Gonzalez Paz, M. Zucchetti, A. Maneo, C. Sessa, A. Goldhirsch, M. D'Incalci
Journal: Annals of Oncology (1997)
Outcomes and renal function trajectory after acute kidney injury: the narrow road to perdition
Authors: Steven G. Coca
Journal: Kidney International (2017)

Analyses of the Grampian Laboratory Outcomes Morbidity and Mortality Study-II cohort support the notion that acute kidney injury (AKI) increases the risk of progression of glomerular filtration rate after recovery from AKI to a new baseline. However, the findings have to be considered in the bigger context of the absolute event rates for de novo progression versus nonrecovery and the competing risk of death after AKI. Examination of the data raises important implications for the design and implementation of clinical trials with interventions that target the AKI-to-chronic kidney disease transition.
A phase 1 dose-escalation trial of intratumoral TTI-621, a novel immune checkpoint inhibitor targeting CD47, in subjects with relapsed or refractory percutaneously-accessible solid tumors and mycosis fungoides.
Authors: John A. Thompson, Oleg Akilov, Christiane Querfeld, Matthew H. Taylor, Lisa Johnson, Tina Catalano, Penka S. Petrova, Robert A. Uger, Meghan Irwin, Eric L. Sievers
Journal: Journal of Clinical Oncology (2017)

TPS3101 Background: CD47 is an immune checkpoint that binds to signal regulatory protein alpha (SIRPα) and delivers a "do not eat" signal to suppress macrophage phagocytosis. Tumor cells frequently overexpress CD47 and exploit this pathway to evade macrophage-mediated destruction. CD47 blockade promotes both innate (macrophage phagocytosis) and adaptive immunity (T cell responses). TTI-621 (SIRPαFc) is an immune checkpoint inhibitor designed to bind human CD47 and block the “do not eat” signal. The IgG1 region of TTI-621 engages Fcγ receptors on macrophages, converting the inhibitory signal to one that activates, thereby enhancing phagocytosis, and antitumor activity. A Phase 1 study is ongoing to evaluate the safety/tolerability and preliminary efficacy of IV administered TTI-621 in subjects with relapsed/refractory hematologic malignancies. It is hypothesized that employing direct intratumoral injections will result in very high local target engagement, promoting the development of innate and adaptive immune responses. Methods: A Phase 1 multicenter, open-label study was initiated to characterize the safety and tolerability of delivering TTI-621 directly into cancer lesions to achieve high local CD47 engagement to increase phagocytosis of tumor cells (NCT02890368). Subjects are being enrolled in sequential cohorts that gradually increase in dose and dosing frequency to characterize the feasibility of intratumoral TTI-621 injections and their safety, PK, pharmacodynamics, and preliminary antitumor activity. Eligible subjects are adults with relapsed or refractory percutaneously-accessible solid tumors or mycosis fungoides (MF), which have progressed on standard anticancer therapy or for which no other approved therapy exists. TTI-621 is delivered by intratumoral injection at protocol-defined doses and dosing regimens starting at 1 mg/injection. Serial biopsies are being collected to characterize local anti-tumor responses and assess the impact of TTI-621 on the tumor microenvironment. Clinical trial information: NCT02890368.
Replication of Candidate SNP Survival Analyses and Gene-Based Tests of Association with Survival Outcomes after an Unrelated Donor Blood or Marrow Transplant: Results from the Discovery-BMT Study
Authors: Ezgi Karaesmen#, Abbas Rizvi#, Qianqian Zhu, Li Yan, Qian Liu, Qiang Hu, Leah Preus, Alyssa I. Clay, Song Liu, Daniel O. Stram, Loreall C. Pooler, Xin Sheng, Christopher A. Haiman, Xiaochun Zhu, Stephen R. Spellman, Marcelo C. Pasquini, Philip L. McCarthy, Theresa Hahn, Lara E. Sucheston-Campbell
Journal: Blood (2016)
Duration of androgen deprivation therapy in high risk prostate cancer: Final results of a randomized phase III trial.
Authors: Abdenour Nabid, Marie-Pierre Garant, André-Guy Martin, Jean-Paul Bahary, Celine Lemaire, Sylvie Vass, Boris Bahoric, Robert Archambault, Francois Vincent, Redouane Bettahar, Nathalie Carrier, Marie Duclos, Luis Souhami
Journal: Journal of Clinical Oncology (2017)

5008 Background: Long-term androgen deprivation therapy (ADT) combined with radiotherapy (RT) is a standard treatment for patients with high-risk prostate cancer (HRPC). However, the optimal duration of ADT is not yet defined. The aim of this randomized trial (Clinical Trials.gov, #NCT00223171) was to compare outcomes of RT combined with either 36 or 18 months of ADT. Methods: Patients with HRPC were randomized to pelvic and prostate RT combined with 36 (arm 1) or 18 months (arm 2) of ADT. Overall survival (OS) and quality of life (QoL) were primary end points. OS rates were compared with Cox Regression model and QoL data were analyzed through mixed linear model. Results: 630 patients were randomized, 310 to arm 1 and 320 to arm 2. With a median follow-up of 9.4 years, 290 patients had died (147 arm 1 vs. 143 arm 2). The 10-year OS rate was 62.4% (95% confidence interval [CI] 56.4%, 67.8%) for arm 1 and 62.0% (95% CI 56.1%, 67.3%) for arm 2 (p = 0.8412) with a global hazard ratio (HR) of 1.024 (95% CI 0.813-1.289, p = 0.8411). QoL analysis showed a significant difference (p &lt; 0.001) in 6 scales and 13 items favoring 18 months ADT with two of them presenting a clinically relevant difference in mean scores of ≥10 points. Conclusions: In HRPC, ADT combined with RT can be safely reduced from 36 to 18 months without compromising outcomes or QoL. 18 months of ADT represents a new standard of care in HRPC. Funded by AstraZeneca Pharmaceuticals Clinical trial information: NCT00223171.