tbuckley/cabot-search huggingface dataset:
Androgen receptor dependent and independent signal transduction pathways leading to proliferation in androgen-independent prostate cancer
Authors: Margarita Mikhailova, Roble G. Bedolla, Yu Wang, Naveen K. Krishnegowda, Jeffrey I. Kreisberg, Paramita M. Ghosh
Journal: Cancer Research (2006)

934  Prostate cancer is initially dependent on androgens for growth and thus responsive to androgen ablation. However, many patients treated with hormonal therapy ultimately progress to an androgen independent (AI) state. The LNCaP cell line has been widely used as a model for androgen-dependent (AD) prostate cancer. This cell line can be induced to progress to androgen independence by prolonged androgen deprvation and two AI prostate tumor cell lines cloned from LNCaP cells, LNCaP-AI (developed in vitro) and C4-2 (developed in vivo), are often used as models to study androgen independence. Both these LNCaP clones express the androgen receptor (AR), and hence, in this study, we evaluate the role of the AR in their proliferation. Proliferation was determined by MTT assay and by flow cytometry in propidium iodide stained ethanol fixed cells. Protein expression was determined by immunoblotting while AR transcriptional activity was determined by luciferase assay in cells transfected with a human prostate specific antigen (PSA) promoter tagged to a luciferase construct (hPSA-luc). We used siRNA technology and a pharmacological inhibitor to downregulate the expression and activation of the AR, respectively. Both LNCaP-AI and C4-2 cells showed increased proliferation rates compared to LNCaP cells. LNCaP cells were growth arrested by 10 μM Casodex, a competitive inhibitor of androgen binding to the AR, whereas LNCaP-AI and C4-2 cells were not, reflecting their AI nature. C4-2 cells exhibited lower AR expression and higher endogenous express of the AR target gene PSA compared to LNCaP. In contrast, LNCaP-AI cells showed higher AR expression compared to LNCaP but did not express endogenous PSA. Despite this, in LNCaP-AI cells, AR transcriptional activity on hPSA-luc was increased compared to LNCaP and C4-2 cells and was androgen-sensitive, showing that the AR in these cells remained active. Next, we determined whether AR expression mediated AI cell proliferation. Transfection with AR-specific siRNA duplexes downregulated the AR and inhibited proliferation in LNCaP and LNCaP-AI, but not in C4-2 cells. These results indicated that the AR mediated the growth of LNCaP-AI but not C4-2 cells. Despite AR-independent proliferation in C4-2 cells, the AR in this cell line was capable of regulating cell cycle proteins. However, we provide evidence that proliferation in C4-2 cells exhibited increased dependence on an alternate signaling pathway involving Akt, a serine/threonine kinase downstream of phosphatidylinositol 3-kinase. Our data suggest that LNCaP-AI and C4-2 cells represent two different forms of AI prostate cancer - while the LNCaP-AI cells are AR-dependent, the C4-2 cells are AR-independent.
Retracted: Diffuse midline glioma with H3 K27M mutation: a comparison integrating the clinical, radiological, and molecular features between adult and pediatric patients
Authors: Haihui Jiang, Kaiyuan Yang, Xiaohui Ren, Yong Cui, Mingxiao Li, Yifei Lei, Song Lin
Journal: Neuro-Oncology (2019)

Diffuse midline glioma (DMG), H3 K27M mutant, occurs in both adult and pediatric populations. The characteristics of the 2 DMG groups were systematically explored in this study.
Opioid policies: scientists advising US government had commercial ties, BMJ investigation finds
Authors: Abi Rimmer
Journal: BMJ (2019)

An investigation by The BMJ has found that a scientific body advising the US Food and Drug Administration on opioid policies did not publicly disclose that one of its presidents had recent links to industry.1

As a result of The BMJ ’s investigation into the National Academies of Sciences, Engineering and Medicine (NASEM), a number of journal articles by Victor Dzau, president of the National Academy of Medicine, were updated to disclose his financial ties to several companies including Medtronic, which sells an implantable device to deliver pain medicine.

Dzau joined NASEM in 2014 and continued to own shares in Medtronic until 2018. He told The BMJ that he had resigned from all commercial relationships and divested his holdings before taking up the …
Prenatal oxidative balance and risk of asthma and allergic disease in adolescence
Authors: Joanne E. Sordillo, Sheryl L. Rifas-Shiman, Karen Switkowski, Brent Coull, Heike Gibson, Mary Rice, Thomas A.E. Platts-Mills, Itai Kloog, Augusto A. Litonjua, Diane R. Gold, Emily Oken
Journal: Journal of Allergy and Clinical Immunology (2019)
A simplified frailty scale predicts outcomes in transplant-ineligible patients with newly diagnosed multiple myeloma treated in the FIRST (MM-020) trial
Authors: Thierry Facon, Meletios A. Dimopoulos, Nathalie Meuleman, Andrew Belch, Mohamad Mohty, Wen-Ming Chen, Kihyun Kim, Elena Zamagni, Paula Rodriguez-Otero, William Renwick, Christian Rose, Adrian Tempescul, Eileen Boyle, Salomon Manier, Michel Attal, Philippe Moreau, Margaret Macro, Xavier Leleu, Marie Lorraine Chretien, Heinz Ludwig, Shien Guo, Michael Sturniolo, Antoine Tinel, Mara Silvia Monzini, Bruno Costa, Vanessa Houck, Cyrille Hulin, Jean Yves Mary
Journal: Leukemia (2019)

Patients with multiple myeloma are generally older and vary in fitness levels, which may influence the clinical benefit of treatment. Patients from the large, phase 3 FIRST trial in newly diagnosed multiple myeloma (NDMM) were retrospectively investigated to determine outcomes based on frailty using scores for age, Charlson Comorbidity Index (CCI), and Eastern Cooperative Oncology Group performance status (ECOG PS), instead of the EQ-5D quality-of-life questionnaire, as previously reported. ECOG PS (n = 1618) was investigated in frailty groups: frail (49%) and nonfrail (51%). Frail patients experienced worse progression-free and overall survival vs nonfrail patients. Prognostic assessment was improved when combining frailty and International Staging System stage (I/II vs III). Frail patients had a higher risk of developing grade 3/4 treatment-emergent adverse events. Treatment effects observed in the FIRST trial were confirmed per frailty group and per frailty and ISS group. The use of this ECOG PS-containing frailty scale as a predictive measure of clinical outcomes in patients with transplant-ineligible NDMM is supported by data from the FIRST trial. This score, based on age, CCI, and ECOG PS, can be easily replicated and may help design future myeloma studies in frail or nonfrail elderly patients.
A practical decision-making strategy based on clinical triple features for EGFR-TKIs to treat advanced non-small cell lung cancer patients with unknown EGFR mutation status.
Authors: Di Zheng, Jiying Wang, Bing Lu
Journal: Journal of Clinical Oncology (2013)

e19082 Background: EGFR mutated lung cancers are strongly associated with clinical characteristics of never- smoking history and adenocarcinoma histology type, and tended to develop multiple pulmonary metastases.Whether multiple pulmonary metastatic lung adenocarcinomas with never-smoking history would respond to EGFR-TKIs as those harboring EGFR active mutation remains unclear. Methods: 223 consecutive metastatic non-small cell lung cancer (NSCLC) patients with unknown EGFR status who received EGFR-TKIs as salvage therapy after failure of previous platinum-based chemotherapy in Shanghai Pulmonary hospital between 2009 and 2011 were included to the study. Available CT scans, routinely performed at baseline and one month after the start of EGFR-TKIs therapy, were reviewed independently by two investigators. For the purposes of this study, diffuse pulmonary metastatic nodules were defined as multiple nodules distributed diffusely throughout the whole lung with at least 20 nodules within the unilateral lung field. Paraffin embedded tissues were available for 45 of 223 patients for EGFR gene mutation test. Results: Of 134 never-smokers with lung adenocarcinoma,70 patients responded to EGFR-TKIs with an objective response rate (ORR) of 52.2% (70/134), and the ORR for the 62 patients with diffuse pulmonary metastatic nodules was 79% (49/62). Among the 20 patients with confirmed EGFR mutation (based on the available 45 archived specimen), the ORR was 75% (15/20). The multivariate analyses showed that the presence of diffused multiple pulmonary metastatic nodules, activating EGFR mutation and female are independent predictive factors of the response to EGFR-TKIs. Conclusions: Patient selection based on specific clinical features to recieve EGFR-TKI treatment yield high response rate comparable to that selected by EGFR mutation status. It is practical to consider EGFR-TKI as salvage therapy in non-smoking patients with lung adenocarcinoma characterized by diffuse pulmonary nodules when EGFR mutation testing is a challenge.
Association of Maternal Age With Severe Maternal Morbidity and Mortality in Canada
Authors: Kazuyoshi Aoyama, Ruxandra Pinto, Joel G. Ray, Andrea D. Hill, Damon C. Scales, Stephen E. Lapinsky, Michelle A. Hladunewich, Gareth R. Seaward, Robert A. Fowler
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Over the past 2 decades, there has been a trend toward increasing maternal age in many high-income countries. Maternal age may lead to greater attendant morbidity and mortality for Canadian mothers. <h3>Objective</h3> To investigate the association of maternal age, adjusting for patient-level and hospital-level factors, with severe maternal morbidity (SMM) and maternal death in Canada. <h3>Design, Setting, and Participants</h3> A nationwide population-based cohort study of all antepartum, peripartum, and postpartum women and adolescents seen at Canadian acute care hospitals from April 1, 2004, to March 31, 2015. All analyses were completed on September 13, 2018. <h3>Exposures</h3> Maternal age at the index delivery. <h3>Main Outcomes and Measures</h3> Severe maternal morbidity and maternal death during pregnancy and within 6 weeks after termination of pregnancy. <h3>Results</h3> During the study period, there were 3 162 303 new pregnancies (mean [SD] maternal age, 29.5 [5.6] years) and 3 533 259 related hospital admissions. There were 54 219 episodes of SMM (17.7 cases per 1000 deliveries) in the entire study period, with a 9.8% relative increase from 2004-2005 to 2014-2015, in addition to an increasing proportion of pregnancies to older mothers. Independent patient-level factors associated with SMM included increasing Maternal Comorbidity Index; maternal age 19 years or younger and 30 years or older, with the greatest risk experienced by women 45 years or older (odds ratio [OR], 2.69; 95% CI, 2.34-3.06 compared with maternal age 20-24 years); and lowest income quintile (OR, 1.19; 95% CI, 1.14-1.22 compared with highest income quintile). Hospital-level factors associated with SMM included specific provinces. Independent patient-level factors associated with maternal mortality included increasing Maternal Comorbidity Index, age 40 to 44 years (OR, 3.39; 95% CI, 1.68-6.82 compared with age 20-24 years), age 45 years or older (OR, 4.39; 95% CI, 1.01-19.10 compared with age 20-24 years), and lowest income quintile (OR, 4.14; 95% CI, 2.03-8.50 compared with highest income quintile). Hospital-level factors associated with maternal mortality included lowest hospital pregnancy volume. <h3>Conclusions and Relevance</h3> In Canada, maternal age and SMM have increased over the past decade. Results of this study suggest that province of residence, maternal comorbidity, residence income quintile, and extremes of maternal age, especially those 45 years or older, were associated with SMM and mortality. These findings are relevant to prospective parents, their health care team, and public health planning.
Is Hyperselection of Patients the Right Strategy?
Authors: Barbara Casolla, Charlotte Cordonnier
Journal: JAMA Neurology (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 Neurology 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 Neurology journal
Efficacy and safety of metronomic capecitabine and gefitinib in heavily pretreated metastatic triple-negative breast cancer.
Authors: Anantbhushan Ranade, Kanaka Govind Babu, Purvish M. Parikh, Jk Singh, Manisha Singh, Gouri Shankar Bhattacharyya
Journal: Journal of Clinical Oncology (2013)

1071 Background: Metronomic chemotherapy regimens have shown efficacy in patients with metastatic breast cancer by antiangiogenic mechanisms. When used metronomically the toxicity profile of capecitabine is low. Triple negative breast cancer is a common problem in India and developing countries. Approximately 30% of triple negative breast cancer express EGFR and its mutation. Methods: Since October 2003 to December 2011 we objectively tested response rates, clinical benefit, and safety of gefitinib and capecitabine administered with a metronomic schedule of 500 mg thrice daily in heavily pretreated metastatic breast cancer patients with gefitinib 250 mg once daily. 300 patients were screened for EGFR expression. Among 85 enrolled patients with EGFR positivity, 76 were evaluable. ECOG performance status (PS) was 0-2, median age 52 years (range 36-65), bone plus visceral metastasis in 40% of patients. Rest had only visceral metastasis. All the patients were pretreated with anthracyclines and taxanes. The combination was administered for a median duration of 32 weeks (range 12-166). Results: We observed 18 partial responses (PR: 24%), 42 (55%) stable disease (SD). Median time to progression was 53 weeks, (95% CI, range 12-166 weeks). Safety of metronomic capecitabine with gefitinib was excellent. Neither grade 2-4 haematological or clinical side effects were recorded. Only 12 patients experienced grade I (WHO) hand-foot syndrome. Conclusions: Treatment with metronomic capecitabine and gefitinib was effective and minimally toxic in heavily pretreated breast cancer patients.
Bacteriophage Therapy of Ventilator-associated Pneumonia and Empyema Caused by <i>Pseudomonas aeruginosa</i>
Authors: Susan Maddocks, Aleksandra Petrovic Fabijan, Josephine Ho, Ruby C. Y. Lin, Nouri L. Ben Zakour, Chris Dugan, Ivana Kliman, Steven Branston, Sandra Morales, Jonathan R. Iredell
Journal: American Journal of Respiratory and Critical Care Medicine (2019)
Surgical Lung Biopsy and Cryobiopsy in Fibrosing Interstitial Lung Diseases: One Swallow Does Not Make a Summer
Authors: Elisabeth Bendstrup, Sissel Kronborg-White, Line Bille Madsen, Torben R. Rasmussen, Birgitte Folkersen, Nina Voldby, Janne Møller, Venerino Poletti
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

However, when we analyze Table E3 in the online supplement of their study, this seems to be the case for only eight of 21 cases (38%).Finally, the most striking result of the study is that neither SLB nor TBLC analysis by the blinded pathologist achieved good agreement with the final diagnosis (62% and 48%, respectively, with a wide confidence interval).This point illustrates the fact that we should consider the pathologist as one actor, among others, in the multidisciplinary assessment of ILD (7).In this regard, it would have been interesting to have the agreement between the final diagnosis and TBLC or SLB analyzed by the local pathologist, and to compare the diagnostic performance of the local pathologist (taking part in the multidisciplinary discussion) with that of the blinded expert pathologist.In conclusion, although the study demonstrates low agreement between blinded analyses of SLB and TBLC and the final diagnosis, the results should not prevent specialists from performing TBLC in the setting of specialized multidisciplinary management of ILD.We also think that this important work by Romagnoli and colleagues paves the way for future trials comparing SLB and TBLC in a multidisciplinary setting.
The long term surgical outcome of spinal giant cell tumor.
Authors: Joonho Yoon, Chun Kee Chung, Sunho Lee, Chiheon Kim
Journal: Journal of Clinical Oncology (2019)

e22510 Background: GCT is a benign and locally aggressive tumor that occur infrequently in the mobile spine. The radical excision is generally agreed for treatment of GCTs. Methods: We performed retrospective analysis of 20 GCTs in the mobile spine from 2005 to 2013. Verteberal involvement was classified with Weinstein-Boriani-Biagini grading system. Surgery types were classified into 3 groups; partial excision, gross total removal (GTR), and en-bloc resection. We analysis by GTR versus non-GTR group, and enbloc versus non-enbloc group in GTR group. The log rank test was used for comparison of factors, and a P value of less than 0.05 was deemed significant. Results: After first surgery of the 20 patients, 17 additional surgery performed for 10 (50%) patients. There were 7 (35%) local recurrences and 3 (15%) distant metastasis. The time to recurrence or progression of tumor ranged from 5 months to 39 months. Two (10%) patients had additional surgery for instrument failure. One (5%) patient died from the complication of the surgery. The follow up duration ranged from 24 months to 141 months. The local recurrence was associated with partial resection (P &lt; 0.01) and history of recurrence (P = 0.39). There was no significant difference between non-en bloc GTR and en bloc GTR in local recurrence (p = 0.101). Conclusions: Gross total resection should be considered for GCTs of the mobile spine. The choice of en bloc resection must be balanced with risks of the procedure. En bloc resection or radical excision could be challenging in many cases. In that cases, the gross total removal by intralesional resection is considerable for local control.
Interim analyses of the efficacy of a collaborative care intervention for patients diagnosed with comorbid cancer and depression.
Authors: Jennifer Lynne Steel, Jessica Miceli, Carol Lynn Hecht, Allan Tsung, Wallis Marsh, Michael Antoni, Yoram Vodovotz, Shaymal Peddada, Michael Spring, Heather Jackson, Yanet Vanegas, Donna Olejniczak, Qi Chen, David A. Geller
Journal: Journal of Clinical Oncology (2019)

11599 Background: There is an urgent need for evidence-based and scalable interventions to reduce depression, pain, and fatigue and improve quality of life in patients diagnosed with cancer. The aims of this study were to share the interim analyses of testing the efficacy of a stepped collaborative care intervention for patients diagnosed with cancers affecting the hepatobiliary and pancreatic system. Methods: Patients were screened for clinical levels of depression, pain, or fatigue and were enrolled in the study if they screened positive for depression, pain, and/or fatigue. After completing a baseline battery of instruments, patients were randomized to the stepped collaborative care intervention or the screening and referral arm. Post-treatment data was collected at 6 months and 12 months to assess efficacy and maintenance of change in depressive symptoms. Results: A total of 100 patients have completed the post-treatment assessment. Interim data analyses revealed that the mean age of patients was 64.0 years (SD = 10.3) and the majority of patient were male (51%), Caucasian (89%), diagnosed with liver cancer (47%) and stage III and IV (60%). Patients randomized to the stepped collaborative care intervention reported significant reductions in depressive symptoms (F(1,92) = 6.22, p = 0.014) and improvements in quality of life (F(1,92) = 7.36, p = 0.008) with moderate effect sizes (Cohen’s d = 0.547 and 0.652, respectively) at 6-months. The mean change in depressive symptoms from randomization to 6-month post- treatment was -4.3 (SD = 9.7) for the patients randomized to the collaborative care intervention and +0.71 (SD = 9.4) for the patients randomized to the screening and referral arm of the study. The mean change in quality of life from randomization to 6-month post-treatment was +4.5 (SD = 16.2) for the patients randomized to the collaborative care intervention and -4.4 (SD = 15.2) for the patients randomized to the screening and referral arm of the study. Conclusions: This promising evidence-based, scalable intervention to treat comorbid cancer and depression was shown to be effective in reducing depressive symptoms and improving quality of life in patients with cancer. Clinical trial information: NCT02939755.
Before Freezing Out Cryobiopsy, We Need to Thaw Out Flaws in the Diagnosis of Interstitial Lung Disease
Authors: Fabien Maldonado, Athol Wells, Sonye Danoff, Thomas Colby, Jay Ryu, Venerino Poletti, Otis Rickman, Felix Herth, Momen Wahidi, Juergen Hetzel, Moishe Liberman, Lonny Yarmus
Journal: American Journal of Respiratory and Critical Care Medicine (2019)
Addressing Limitations in Case-Control Study of Patients Undergoing Resuscitative Endovascular Balloon Occlusion of the Aorta
Authors: Jeremy W. Cannon, Todd E. Rasmussen
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
Quantum Dots: Application of Ti<sub>3</sub>C<sub>2</sub> MXene Quantum Dots for Immunomodulation and Regenerative Medicine (Adv. Healthcare Mater. 16/2019)
Authors: Alireza Rafieerad, Weiang Yan, Glen Lester Sequiera, Niketa Sareen, Ejlal Abu‐El‐Rub, Meenal Moudgil, Sanjiv Dhingra
Journal: Advanced Healthcare Materials (2019)

Ti3C2 MXene quantum dots (MQDs) are immunomodulatory and can be loaded into an injectable chitosan (CS)-based hydrogel for tissue engineering applications. In article number 1900569, Sanjiv Dhingra and co-workers show that injection of a CS-MQD hydrogel to an infarct site after coronary artery occlusion may reduce recruitment of immune cells and limit secondary injury to the heart.