tbuckley/cabot-search huggingface dataset:
Free Fatty Acids Rewire Cancer Metabolism in Obesity-Associated Breast Cancer via Estrogen Receptor and mTOR Signaling
Authors: Zeynep Madak-Erdogan, Shoham Band, Yiru C. Zhao, Brandi P. Smith, Eylem Kulkoyluoglu-Cotul, Qianying Zuo, Ashlie Santaliz Casiano, Kinga Wrobel, Gianluigi Rossi, Rebecca L. Smith, Sung Hoon Kim, John A. Katzenellenbogen, Mariah L. Johnson, Meera Patel, Natascia Marino, Anna Maria V. Storniolo, Jodi A. Flaws
Journal: Cancer Research (2019)

Obesity is a risk factor for postmenopausal estrogen receptor alpha (ERα)-positive (ER+) breast cancer. Molecular mechanisms underlying factors from plasma that contribute to this risk and how these mechanisms affect ERα signaling have yet to be elucidated. To identify such mechanisms, we performed whole metabolite and protein profiling in plasma samples from women at high risk for breast cancer, which led us to focus on factors that were differentially present in plasma of obese versus nonobese postmenopausal women. These studies, combined with in vitro assays, identified free fatty acids (FFA) as circulating plasma factors that correlated with increased proliferation and aggressiveness in ER+ breast cancer cells. FFAs activated both the ERα and mTOR pathways and rewired metabolism in breast cancer cells. Pathway preferential estrogen-1 (PaPE-1), which targets ERα and mTOR signaling, was able to block changes induced by FFA and was more effective in the presence of FFA. Collectively, these data suggest a role for obesity-associated gene and metabolic rewiring in providing new targetable vulnerabilities for ER+ breast cancer in postmenopausal women. Furthermore, they provide a basis for preclinical and clinical trials where the impact of agents that target ERα and mTOR signaling cross-talk would be tested to prevent ER+ breast cancers in obese postmenopausal women. SIGNIFICANCE: These findings show that obesity-associated changes in certain blood metabolites rewire metabolic programs in cancer cells, influence mammary epithelial cell tumorigenicity and aggressiveness, and increase breast cancer risk.
Characteristics of statuses of thyroid hormones and cortisol in patients with primary tumors and cerebral metastases from them.
Authors: Margarita Kozlova, Elena Mikhaylovna Frantsiyants, Alexey N. Shevchenko, Dmitry Aleksandrovich Shvyrev, Ayna Mayerbekovna Salatova, Yulia A. Pogorelova, Lyudmila Gennadiyevna Sergostyants
Journal: Journal of Clinical Oncology (2015)

e15608 Background: Neoplasms are similar in their damaging effect on metabolic processes, and study of the effect of primary and metastatic tumors on an organism is an important aspect of the problem. The purpose of this study was to assess statuses of the main hormones regulating metabolism in patients with primary tumors and cerebral metastases from them. Methods: Levels of total and free Т3 and Т4, thyroid-stimulating hormone (TSH) and cortisol were determined by radioimmunoassay in blood of 90 patients with primary lung cancer (LC), breast cancer (BC), kidney cancer (KC) and skin melanoma (SM) st. T2-3N0M0 and in 74 patients with brain metastases (MLC, MBC, MKC, MSM). Results: Free T3 level was increased by 1.3-1.8 times in LC, BC, KC and SM patients, total T3 level was decreased in BC, KC and SM by 1.4-1.5 times and was unchanged in LC. Normal free Т3 content and reduced total Т3 (by 1.9-2.2 times) were observed in all metastatic cancers. Free T4 level was decreased in KC only (by 1.2 times) and was equal to the norm in all metastases; abnormalities in total T4 level could be similar (KC and MKC, SM and MSM) or opposite (LC and MLC, BC and MBC). TSH secretion was decreased in patients with MLC only. Hypercortisolemia was detected in 44.35% of patients with primary tumors, hypocortisolemia – in 11.29%; in patients with metastases cortisol exceeded the norm in 16.38% of patients and was sharply reduced in 62.5% (by 2.5-5.4 times). Conclusions: Paraneoplastic abnormalities in structure of thyroid and glucocorticoid homeostasis were revealed to have a number of peculiarities in development of primary tumors and metastases from them, with a more pronounced inhibiting and impoverishing metabolic status of patients influence of metastatic processes.
Abstract P337: CardioClick an Innovative Telehealth Approach to Lifestyle Intervention in High Risk South Asians
Authors: Vijaya Parameswaran, Kiranbir Josan, Jennifer Winterbottom, Jenny Shearer, Abha Khandelwal, Shriram Nallamshetty, Rajesh Dash, Fatima Rodriguez
Journal: Circulation (2019)

Introduction: Exercise &amp; nutritional intervention programs are effective in lowering cardiovascular events in randomized control trials but success in real world settings may be limited by resource constraints. We describe the implementation &amp; preliminary effectiveness of a comprehensive telehealth lifestyle approach that provides culturally relevant lifestyle interventions, recognizing the role of acculturative stressors &amp; behavior patterns unique to South Asians. Methods: CardioClick was introduced in the Stanford South Asian Translational Heart Initiative on 11/1/2017 to deliver care via video visits. Patients ages 20-60 were offered enrollment. Those who did not consent were followed in the traditional in-person program. Both programs included a comprehensive risk assessment &amp; personalized treatment plan focused on aggressive risk reduction, with a set of 3 cardiologist &amp; 3 dietitian visits over 6 months. CardioClick patients received a lifestyle questionnaire &amp; satisfaction survey at each visit. Based on responses &amp; online dialog, culturally tailored nutrition, exercise recommendations &amp; resources to address sleep deficiencies &amp; perceived stress, were provided. Results: Out of 110 currently enrolled 23 have completed CardioClick. These patients were similar in age (44 vs 43 years) BMI (27.1 vs 26.7) &amp; cardiovascular risk (ASCVD 4.8 vs 4.5) but had more dietitian visits (3 vs 1), more likely to lose weight 83% (19/23) vs 54% (44/82) &amp; lost more weight (9lbs vs 0.7lbs) compared to traditional program patients. In the CardioClick group QDiabetes score (9.2 to 7.2) &amp; TG/HDL ratio (2.3 to 1.8) dropped. Questionnaire 100% (23/23) &amp; survey 57%(13/23) responses showed improved lifestyle behaviors &amp; patient satisfaction. Conclusion: Early results from a novel telemedicine preventive cardiology program showed improved patient engagement, lifestyle behaviors &amp; cardiometabolic benefits in high risk South Asians.
Tumor biopsies in high grade ovarian cancer: Clinical utility and challenges for biomarker-directed therapy.
Authors: Michelle K. Wilson, Kevin Lin, Iain A. McNeish, Elizabeth M. Swisher, Heidi Giordano, Elaina Mann, Mitch Raponi, Lara Maloney, Scott Yerganian, Murtaza Mehdi, Roman Yelensky, Lindsey Rolfe, Andrew R. Allen, Amit M. Oza
Journal: Journal of Clinical Oncology (2015)

5539 Background: Molecular profiling of tissue obtained with a biopsy aids detection of predictive and pharmacodynamic biomarkers to guide patient (pt) selection and treatment. This study assesses the safety and success rate of obtaining FFPE tissue for profiling in ARIEL2 - a large multi-center Phase II trial of rucaparib (oral PARP inhibitor) in high grade serous or endometrioid ovarian cancer (HGOC). Methods: Screening biopsy and archival tissue samples were required at study entry. Success was defined as the ability to obtain tissue with minimal pt risk and to complete Foundation Medicine’s next generation sequencing-based comprehensive genomic profiling (NGS-based CGP), which requires tissue specimens with tumor nuclei ≥ 20% and volume ≥ 0.2 mm3. Usability of tissue was assessed by biopsy site. Results: 201 pts were enrolled, with results available for 189 screening and 195 archival specimens. 8 pts had insufficient/inaccessible tissue at the time of biopsy. No serious biopsy-related adverse events were seen, with grade 1 pain in only 4 pts (2%). Omental/peritoneal disease was the most common site biopsied (table). Overall NGS-based CGP success rate was 83%. Greater success was seen with archival tissue (179; 92%) than screening biopsies (141; 75%). Unsuccessful profiling on biopsies was due to insufficient tumor nuclei in 36 pts (75%; med tumor nuclei 5%), inadequate volume in 10 (21%; med 0.08mm3), and insufficient DNA yield in 2 (4%). Success was higher in nodal biopsies (84%) but lower in omental/peritoneal samples (63%). No pt tumors failed profiling on both screening biopsy and archival tissue. Conclusions: Research biopsies in HGOC are safe, feasible, and can be profiled with a NGS-based assay. Nodal biopsies had higher success rates compared to peritoneal/omental samples. Algorithms to guide biopsy site choice should be developed considering primary disease, radiologic appearance, and test in question. Clinical trial information: NCT01891344. Site of biopsy Overall n Sufficient tumor nuclei and volume Successful NGS-based CGP n Success % n Success % p* Liver 25 18 72 18 72 0.81 Lymph node 45 38 84 38 84 0.12 Omentum/peritoneum 57 37 65 36 63 0.03 Other 62 50 81 49 79 0.38 * Fisher’s exact of success/fail rate for each biopsy site vs all other sites
Plasma copeptin levels predict disease progression and tolvaptan efficacy in autosomal dominant polycystic kidney disease
Authors: Ron T. Gansevoort, Maatje D.A. van Gastel, Arlene B. Chapman, Jaime D. Blais, Frank S. Czerwiec, Eiji Higashihara, Jennifer Lee, John Ouyang, Ronald D. Perrone, Katrin Stade, Vicente E. Torres, Olivier Devuyst
Journal: Kidney International (2019)
Oesophageal and scaly skin lesions associated with chronic cholestatic liver disease
Authors: Philipp Kasper, Tobias Goeser, Dirk Nierhoff
Journal: Gut (2019)

A 29-year-old man presented to the hospital with progressive dysphagia and nausea. He also claimed recurrent episodes of nyctalopia (night blindness) in the past. His medical history includes a hepatocyte nuclear factor-1β gene mutation causing a chronic cholestatic liver disease.

On physical examination, epigastric tenderness was detected and there were multiple scaly plaques at the extensor sides of the upper and lower extremities (figure 1A).



Figure 1 
(A) Skin lesions on the left lower leg. (B) Endoscopic view of the distal oesophagus. (C) Endoscopic view of the distal oesophagus. (D) Histology findings of distal oesophagus biopsies. …
Abstract P196: Mississippi Delta Health Collaborative Community and Faith Based Programs to Screen Hypertension
Authors: Masoumeh Karimi, Cassandra Dove, Tameka Walls, Monique Hopkins
Journal: Circulation (2019)

Introduction: The Mississippi Delta Health Collaborative (MDHC) provides leadership in the Delta region to implement heart disease and stroke prevention interventions. Barbers Reaching Out To Educate on Routine Screenings (BROTHERS) is an innovative community based program whereby MDHC partners with existing barbershops to provide routine blood pressure screenings and referrals. The faith-based Delta Alliance for Congregational Health (DACH) supports the mission of its member churches to minister to their communities with regular cardiovascular health screenings and include community outreach events. The MDHC program started in 2008 and has devoted the last 2 years to screen residents’ blood pressure and help them to control it as a risk factor for cardiovascular disease. The aim of this study is to track the community base initiatives outcomes. Methods: From October 2016 to March 2018, from all 18 counties of the Mississippi Delta region, 33 barbers participated in the BROTHERS program and completed a total of 4,926 blood pressure screening encounters of 4,301 individuals (97.6% (n= 3943) black; 71.14% (n=3060) male; mean age= 35.67, SD=13.92). Also 26 churches participated in the DACH program and completed a total of 2,658 blood pressure screening encounters of 1,987 individuals (94.5% (n=1877) black; 65.2% (n=1295) female; mean age= 52.62, SD=16.43). Results: Barbers screenings showed that 51.84% (n=1688) of men were pre-hypertensive while only 10.81% (n=352) had normal blood pressure. Among all, 16.2% (n=738) participants reported never having their blood pressure checked. Among men, 1,216 (37.34%) had hypertension while 26.8% (n=326) were currently taking blood pressure medications, 37.9% (n=459) were current smokers, 31% (n=375) had no insurance coverage and 46.7% (n=566) had no personal doctor. DACH screenings showed that 42.3% (n=842) of participants were pre-hypertensive and 40.46% (n=804) had hypertension. Among hypertensive participants, 63.8% (n=513) were aware of the high blood pressure status and 58.3% (n=469) were currently taking medications for high blood pressure. Conclusion: Health is determined in part by access to social and economic opportunities as well as the resources and support in communities. Because of the innovative health initiatives underway in the Mississippi Delta region, a new story is unfolding. Community based screenings help people to become familiar with their health status, educate them on various methods of prevention and intervention and help them to change their life style to have a healthier life. Each healthy step taken is one towards improved health and prosperity not only for our state, but for the entire country.
Oversight of Supplements
Authors: Feyza Sancar
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Phase II study of concurrent chemoradiotherapy with weekly CDDP/PTX in patients with locally advanced uterine cervical cancer: JACCRO-GY-01 trial.
Authors: Munetaka Takekuma, Yasuyuki Hirashima, Kenji Umayahara, Shin-ei Noda, Tatsuya Ohno, Etsuko Miyagi, Fumiki Hirahara, Eiji Hirata, Eiji Kondo, Tsutomu Tabata, Yutaka Nagai, Yoichi Aoki, Masaru Wakatsuki, Masahiro Takeuchi, Takafumi Toita, Nobuhiro Takeshima, Ken Takizawa
Journal: Journal of Clinical Oncology (2015)

5587 Background: A multicenter phase II trial was conducted to assess the efficacy and toxicity of concurrent chemoradiotherapy (CCRT) with weekly CDDP/PTX in patients with locally advanced uterine cervical cancer. Methods: The patients with FIGO stages III-IVA uterine cervical cancer who had no para-aortic lymphadenopathy ( > 10 mm) assessed by CT were enrolled. Patients received definitive radiotherapy (RT) consisting of external beam whole pelvic RT and HDR-ICBT. The cumulative linear quadratic equivalent dose (EQD2) was 62-65 Gy prescribed at point A. Cisplatin 30 mg/m(2) and Paclitaxel 50 mg/m(2) weekly was administered concurrently with RT for 5 courses. Results: Of the 70 patients registered, 68 were eligible. The Compete response rate was 76.5% (95%CI, 66.4% to 86.6%). With a median follow-up of 27 months(range: 7.9-33.5), the 2-year progression-free survival rate and pelvic disease progression-free rate were 83.8% (95% CI, 75.1% to 92.6%) and 89.6% (95% CI, 82.3% to 96.9%), respectively. The 2-year overall survival rate was 92.7% (95% CI, 86.4% to 98.9%). The 2-year cumulative late complication rates were 25% for all grades, 13.2% for grade 1, 5.9% for grade 2, 2.9% for grade 3, and 2.9% for grades 4. Conclusions: Concurrent chemoradiotherapy with weekly CDDP/PTX for locally advanced cervical cancer demonstrated favorable antitumor activity, and is feasible and safe with respect to the protocol-specified SAEs and AEs. Evaluation of this regimen in phase III trials is warranted. Clinical trial information: UMIN000002937.
Systemic Treatment for Advanced Hepatocellular Carcinoma
Authors: Mohamed Bouattour, Neil Mehta, Aiwu R. He, Emil I. Cohen, Jean-Charles Nault
Journal: Liver Cancer (2019)

Patients with advanced hepatocellular carcinoma (HCC) have a poor prognosis. First-line sorafenib has been the standard of care for a decade, but the treatment landscape is expanding. This review provides a practical overview of current and future systemic treatment options for advanced HCC and their place in clinical practice.First-line sorafenib and lenvatinib have shown to improve the survival of patients with advanced HCC. In the second line, regorafenib provides benefit for patients who previously tolerated sorafenib. Anti-PD1 antibodies, nivolumab and pembrolizumab, recently became available for second-line use in the US. Ramucirumab (for patients with α-fetoprotein [AFP] levels ≥400) and cabozantinib present potential future second-line treatment options. Combinations of systemic and locoregional treatment, such as radiofrequency ablation or selective internal radiotherapy, require further research. Precision medicine has not yet been translated into clinical practice, as the most common driver mutations (TERT promoter, CTNNB1, TP53, and ARID1A mutations) have not yet been shown to be suitable therapeutic targets. However, our growing understanding of signaling pathways and efforts in drug development are expected to pave the way for precision medicine in HCC in the future. Evaluating the place for the current and novel systemic treatment options in clinical practice can be challenging due to the diverse toxicity profiles of the treatment options and characteristics of the patient population. Sorafenib data elucidate the effect patient characteristics (such as the performance score, Child-Pugh class, AFP, etiology of the underlying disease, and level of macrovascular invasion and extrahepatic spread) may have on outcomes in advanced stages.Lenvatinib is expected to join sorafenib as a preferred first-line treatment in advanced HCC. In the second line, the treatment of choice, regorafenib, is soon expected to be accompanied by cabozantinib and ramucirumab in patients with AFP ≥400 ng/mL, whereas nivolumab and pembrolizumab present second-line alternatives in the US.
Research wastage: industry versus academic sponsorship
Authors: Nadarajah Sreeharan
Journal: BMJ (2019)

The commentary by Glasziou and Chalmers1 raises many issues2 that need tackling to prevent the effects of poor and wasted research on patient safety and medical training, as well as the colossal drainage of societal funds. Academic research now seems to be more culpable than industry sponsored research.

Research sponsored by the drug industry has rightly received considerable scrutiny over the years, …
Characterization and survival of patients presenting with PSA values 100 or greater.
Authors: Andrew Kuiwai Leung, Lee Hugar, Dattatraya Patil, Lisa Wong, Bradley Curtis Carthon, Kelvin A Moses, Viraj A. Master
Journal: Journal of Clinical Oncology (2015)

e16127 Background: Inconsistent guidelines exist among medical groups regarding PSA screening, including recommendation against routine screening by the United States Preventive Services Task Force. This may expose certain populations, such as African-American men, to increased risk or burden of advanced disease. This study aims to characterize men presenting with PSA values 100 ng/mL or greater in terms of stage and survival. Methods: Retrospective chart review (IRB approved) was conducted on 100 patients from a total of 206 who presented to Grady Memorial Hospital from 2004-2011 with initial PSA ≥ 100 ng/mL. Demographics, disease characteristics, and survival status were obtained via the Tumor Registry and a combination of electronic medical records and older paper charts, with missing data from paper charts excluded on analyses. Results: Sixty-five patients were newly diagnosed with prostate cancer on presentation and 35 previously diagnosed. Median PSA at presentation was 405.5 ng/mL (min 100, max 7805), 81% had AJCC Stage 4 cancer, and 94% were Gleason ≥ 7. Median UCSF CAPRA score was 8. Median age at presentation was 67.4 years (min 40.8, max 90.6). Eighty-nine percent of patients were African-American, 36.7% in a partnership, 63% lived with family/friends, 24% lived alone, 12% homeless or incarcerated, 21% employed, 51% insured by Medicare/Medicaid, and 47% were uninsured. Only 1% had HIV, 19% had diabetes, 13% had chronic kidney disease, and 66% history of hypertension. Of the 65 newly diagnosed patients, only 23% had ever been screened and 9% previously biopsied. As of 12/31/2014, 71% of all patients were deceased with median time from presentation to death of 17.7 months (min 0.16, max 107). Conclusions: At a safety-net tertiary care hospital, African-American race was the only defining demographic of patients presenting with PSA ≥ 100 ng/mL. Patients were otherwise relatively healthy and in stable housing situations with access to social support. When considering the low levels of PSA screening history among newly diagnosed men, these data demonstrate the potential heavy burden of advanced disease and potential negative impact of existing guidelines on vulnerable populations if routine screening recommendations are ended.
Another Look at the Baby-Friendly Hospital Initiative—Reply
Authors: Joel L. Bass
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
Widespread Thickened, Verrucous, Hyperpigmented Plaques in a Woman With Weight Loss
Authors: Chen Yuan, Lingling Liu, Mingyue Wang
Journal: JAMA Oncology (2019)

A 30-year-old woman presented with a history of thickened, verrucous, hyperpigmented plaques distributed symmetrically over her body. She also had recent weight loss and an enlarged thyroid. What is your diagnosis?