tbuckley/cabot-search huggingface dataset:
Single nucleotide polymorphisms (SNPs) of hypoxia-related and DNA repair genes associated with toxicity and clinical outcome in head and neck squamous cell carcinoma patients treated with cetuximab plus radiotherapy.
Authors: Juan J. Grau, Camen Munoz-Garcia, Luis R Feliz, Miguel Caballero, Aaron R Sosa, Verónica Pereira
Journal: Journal of Clinical Oncology (2013)

6072 Background: One of the standard therapy in inoperable head and neck squamous cell carcinoma (HNSCC) patients is cetuximab plus radiotherapy. However, the efficacy of this treatment varies greatly among individuals. In an attempt to identify predictive markers to determine the patients most likely to benefit from this treatment, we examined the potential effect on outcome and skin toxicity according to single SNPs in hypoxia-related genes and DNA repair genes. Methods: Sixty-one patients enrolled between May 2006 and August 2011 and diagnosed with HNSCC were included. Data on epithelitis, mucositis and folliculitis were collected in accordance with WHO criteria. SNPs were analyzed in HIF-1α, HIF-2α, HIF-1β, VHL, FIH-1, XRCC1 and XRCC5 in DNA obtained from paraffin-embedded tumor tissues by allelic discrimination in an ABI PRISM 7500 Sequence detection system. Results were correlated with time to progression (TTP), overall survival (OS) and toxicity. Results: The median of TTPand OSwere better in patients with mucositis severe vs mild (17 vs 7 months, p=0.03, and 26 vs 12 months, p=0.016, respectively) and in those with folliculitis severe vs mild (10 versus 7 months, p=0.01, and 26 vs 10 months, p&lt;0.001, respectively). Patients withHIF-1α CT/TT had better OS than those with HIF-1α CC or wild type (28 versus 13 months, p=0.035). Patients with XRCC5 GG/AA genotypes had longer TTP than patients with XRCC5 AG (11 versus 7 months, p=0.035). Conclusions: Our findings indicate that the presence of severe skin toxicities, as well as SNPs in HIF-1α and XRCC5, are associated with interindividual differences in outcome among HNSCC patients.
Abstract C28: Platelet-derived growth factor receptor-β (PDGFRβ) in the breast metastatic tumor microenvironment
Authors: Gina Sizemore, Anisha Mathur, Katie Thies, Chelsea Bolyard, Steven Sizemore, Raleigh Kladney, Anthony Trimboli, Balveen Kaur, Gustavo Leone, Michael Ostrowski
Journal: Cancer Research (2016)

Abstract A role for the tumor microenvironment (TME) in cancer progression is irrefutable and our laboratory has been at the forefront of this field providing evidence for both tumor suppressive and oncogenic roles of the TME. The PDGF pathway is an exemplar for the study of tumor-stroma interaction as PDGF receptors (PDGFR) are frequently expressed in the fibroblasts and pericytes within the tumor-associated stroma of epithelial tumors including breast cancer. In contrast, PDGF ligands are expressed by the epithelial tumor cells themselves. However, beyond a few descriptive studies, the role of interactive PDGFRβ signaling in the TME during breast cancer initiation, progression and metastases is not understood. This can be attributed in part to limited in vivo models to study the complex TME, especially for breast cancer associated metastases. To overcome this limitation, we have established a transgenic knock-in mouse model that expresses constitutively active PDGFRβ in the stroma of the mammary gland as well in the lung and the brain, two common sites of metastatic breast cancer dissemination. We have found that these mice develop mammary gland hyperplasia highlighting the importance of PDGFRβ in the TME in driving mammary epithelial cell growth. To test whether activation of mutant PDGFRβ in either the lung or the brain increases metastatic growth at either site, two experimental metastases assays were performed: (1) tail vein and (2) intracranial injections to test for lung and brain metastatic outgrowth, respectively. Tail vein injection of the non-metastatic murine mammary cancer cell line DB7 cells led to pronounced lung metastases in PDGFRβ knock-in mice in less than 4 weeks. No macrometastases were seen in the control at this same time point. Similar to the surge in lung metastasis, intracranial injection of DB7 cells led to an increase in tumor growth in brains of the mutant versus wild type controls, revealing an important role for PDGFRβ signaling in the breast cancer metastatic microenvironment. In addition, knockdown of PDGF-B in mammary cancer cells represses intracranial growth in wild type animals. Combined these data support a role for PDGFRβ signaling in the breast cancer metastatic microenvironment. Ongoing investigation is aimed to delineate how activated PDGF-B to PDGFRβ signaling primes the metastatic niche. Citation Format: Gina Sizemore, Anisha Mathur, Katie Thies, Chelsea Bolyard, Steven Sizemore, Raleigh Kladney, Anthony Trimboli, Balveen Kaur, Gustavo Leone, Michael Ostrowski. Platelet-derived growth factor receptor-β (PDGFRβ) in the breast metastatic tumor microenvironment. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr C28.
Mucocutaneous Engraftment and Type VII Collagen (C7) Replacement after Allogeneic Hematopoietic Cell Transplantation (HCT) in Patients with Recessive Dystrophic Epidermolysis Bullosa (RDEB)
Authors: Jakub Tolar, John A McGrath, Mark J. Osborn, Douglas R Keene, Kristen Hook, Maria Hordinsky, David Woodley, Mei Chen, Alain Hovnanian, Katsuto Tamai, Bruce R. Blazar, John E Wagner
Journal: Blood (2015)
Аналіз ефективності лікувального комплексу у хворих гастроентерологічного профілю з кандидозом слизової оболонки верхнього відділу травного тракту
Authors: I.V. Kushnirenko
Journal: GASTROENTEROLOGY (2016)

Проблема лікування кандидозу слизової оболонки верхнього відділу травного тракту залишається актуальною у зв’язку з необхідністю як проведення етіотропної терапії, так і врахування варіабельності імунної відповіді при взаємодії макроорганізму й Candida albicans. Зниження імунореактивності в цьому випадку потребує проведення коригуючого лікування. Мета дослідження — вивчити вплив лікувального комплексу з включенням поліпептидного імуномодулятора імунофан на показники вродженого та адаптивного імунітету у хворих означеної групи. Згідно з отриманими результатами, пацієнтів з інвазією грибів у слизову оболонку відрізняє наявність імунодефіциту за співвідношенням лейкоцити/CD3+, що в 1,3 раза вище, ніж у хворих з орофарингеальним та поверхневим кандидозом (р &lt; 0,01). Після проведеного лікування у групі хворих з інвазією кандид у слизову оболонку первинно підвищене значення НСТ-тесту і цитохімічного показника активності нейтрофілів знизилося на 40,40 % (р &lt; 0,05) і 29,03 % (р &lt; 0,05) відповідно. Ці зміни в сукупності з підвищенням рівня циркулюючих імунних комплексів у 1,4 раза порівняно зі значеннями до лікування (р &lt; 0,05) та у 1,5 раза — порівняно з конт­ролем (р &lt; 0,01) свідчать про більш глибокі дефекти в системи вродженого імунітету, що, очевидно, зумовлюють як більш тяжкий перебіг захворювання, так і труднощі в лікуванні. У цілому застосування лікувального комплексу призводить до відновлення Т-клітинної ланки імунітету хворих обох груп з нормалізацією співвідношення Т-хелпери/Т-супресори, до підвищення рівня лактоферину в ротовій порожнині та підвищення концентрації IgA та IgG у пацієнтів з інвазією. Отже, комплексний підхід до лікування хворих з кандидозом слизової оболонки верхнього відділу шлунково-кишкового тракту та визначення стратегії й тактики подальшого спостереження є необхідними для ефективного надання медичної допомоги даній групі пацієнтів.
Expression of the Transcription Factor Lymphoid Enhancer Binding Factor-1 (LEF-1) Is Correlated to Aberrantly Increased Fibromodulin Transcripts in Chronic Lymphocytic Leukemia (CLL).
Authors: Felix Erdfelder, Iris Gehrke, Rajesh Kumar Gandhirajan, Magdalena Hertweck, Regina Razavi, Julian Paesler, Alexandra Filipovich, Sabrina Uhrmacher, Simon Jonas Poll-Wolbeck, Michael Hallek, Karl Anton Kreuzer
Journal: Blood (2009)
In Vitro Cytotoxicity of Alemtuzumab on B-CLL Cells: Differential Effect on B and T Lymphocytes.
Authors: Salvatore Berretta, Annalisa Chiarenza, Luana Adamo, Laura Parrinello, Daniela Buglio, Fabio Stagno, Daniele Tibullo, Concetta Conticello, Giuseppe A. Palumbo, Francesco Di Raimondo
Journal: Blood (2006)
Inhibition of mammalian target of rapamycin (mTOR) in advanced pancreatic cancer: The results of two prospective phase II studies
Authors: M. M. Javle, H. Xiong, S. Reddy, P. Bhosale, D. Davis, G. Varadhachary, D. Fogelman, A. Kaseb, R. A. Wolff, J. L. Abbruzzese
Journal: Journal of Clinical Oncology (2009)

4621 Background: PI3-kinase/ Akt pathway is constitutively activated in pancreatic cancer and is mediated by mTOR kinase. Our in vitro studies suggest that prolonged exposure to mTOR inhibitors can promote insulin receptor substrate-PI3-kinase interactions and paradoxically increase Akt phosphorylation and cyclin D1 expression in pancreatic cancer cells (negative feedback loop). The addition of erlotinib to rapamycin down-regulates rapamycin-stimulated Akt in preclinical models. Methods: Study A: CCI-779 (Temsirolimus), Study B: RAD001 (Everolimus) + Erlotinib. Inclusions: Adult patients with gemcitabine-refractory pancreatic cancer, ECOG PS 0–1, adequate laboratories and measurable disease. Dose and schedule: CCI-779 25 mg IV weekly; RAD001 30 mg weekly + erlotinib 150 mg daily. Primary endpoint: overall survival at 6 months. Secondary endpoints: time-to-progression, response and toxicity. Tumor biopsies analyzed by immunofluorescence and laser scanning cytometry analysis for expression of pmTOR/mTOR, pAkt/Akt, pErk/Erk, pS6, p4EBP-1, PTEN and for k-ras mutations. Results: Study A: 5 patients enrolled, 4 patients received 2–4 doses. 2 patients died within a month; one from rapid progression other from hemorrhagic stroke. 2 developed SAEs: dehydration and asthenia. Study B: 16 patients enrolled; 12 males, all ECOG PS=1. Median cycles=1 (range 1–2). Grade 4 toxicity: hyponatremia (n=1), Grade 3: diarrhea (n=1), cholangitis (n=3), hyperglycemia (n=1), fatigue (n=1). Grade 2: pneumonia (n=2), dehydration (n=2), neutropenia (n=1), mucositis (n=2) &amp; rash (n=2); hospitalizations=4. Progressive disease occurred in 15 and 1 was non-evaluable. Pretreatment biopsies revealed increased pAkt/ Akt ratio in tumor specimens as compared with non malignant pancreatic tissue. No such trends occurred for pErk/Erk or pmTOR/ mTOR. K-ras mutations occurred in 2/7 patient samples. Conclusions: Neither study with mTOR inhibitors demonstrated objective responses or disease stability. Negative feedback loop seen preclinically may account for the rapid progression noted with mTOR inhibitors in pancreatic cancer. The addition of erlotinib may not counter this effect in the clinical setting. [Table: see text]
Poorest urban areas face highest rates of psychosis, study finds
Authors: Jacqui Wise
Journal: BMJ (2016)

People who live in poorer urban communities are more likely to experience a first episode of psychosis than people in rural wealthier areas, a study in the east of England shows.1

The research, published in the American Journal of Psychiatry , shows that the risk of a psychotic disorder such as schizophrenia is also higher in young people, men, and black …
Incidence and risk factors of bisphosphonate associated osteonecrosis of the jaws
Authors: M. Stumpe, R. Chandra, F. Yunus, S. Samant
Journal: Journal of Clinical Oncology (2007)

9074 Background: Intravenous bisphosphonate therapy has been used for treatment of various benign and malignant bone diseases, including bony metastasis. Recent single case reports have described osteonecrosis (ON) of the mandible or maxilla as a previously unknown complication of this therapy. Methods: Records of 638 patients treated with intravenous pamidronate or zoledronic acid were reviewed to determine the incidence of jaw ON. Number of infusions, dosing interval, dosage administered, and duration of treatment were analyzed to determine risk factors for the development of this complication. Results: Mean age of the study group was 67 years and 61% were female. The most common primary malignancies included prostate, lung, breast, and multiple myeloma. The overall incidence of osteonecrosis was 6/638 (0.94%). Patients treated with pamidronate (n=336), zoledronic acid (n=169), and both agents (n=133) had an incidence of ON of 1.2%, 0%, and 1.5% respectively (p=NS). No significant relationship was observed between the incidence of ON and demographic parameters, primary tumor, cumulative drug dose, or dosing interval. However, patients who developed ON had a significantly greater mean number of infusions (20.7 versus 10.7, p=0.016) and significantly greater mean hours of infusion time (42.7 versus 17.7, p=0.0036) than those who did not develop the complication. Underlying dental disease appears to be associated with ON. Conclusions: This review represents the largest single series to date of patients treated with IV bisphosphonate therapy. The findings suggest positive correlation between the development of ON and drug exposure as measured by number of infusions and total infusion hours. However, this data must be interpreted with caution as the overall incidence of the complication was low (&lt;1%), precluding rigorous statistical analysis. Dental comorbidity should be addressed prior to initiation of bisphosphonate therapy. No significant financial relationships to disclose.
Hypercalcemia and Elevated 1,25-(OH)<sub>2</sub>D Levels in a Patient with End-Stage Renal Disease and Active Tuberculosis
Authors: M Fuss, R Karmali, P Bergman, C Gillet, T Prigogine, J Schmerber, H Brauman, J Corvilain, P Dierckx
Journal: New England Journal of Medicine (1985)
Sluggish Progress in Improving Breastfeeding Practices
Authors: M.J. Friedrich
Journal: JAMA (2016)

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
Bile acid excess induces cardiomyopathy and metabolic dysfunctions in the heart
Authors: Moreshwar S. Desai, Bhoomika Mathur, Zeena Eblimit, Hernan Vasquez, Heinrich Taegtmeyer, Saul J. Karpen, Daniel J. Penny, David D. Moore, Sayeepriyadarshini Anakk
Journal: Hepatology (2016)

Cardiac dysfunction in patients with liver cirrhosis is strongly associated with increased serum bile acid concentrations. Here we show that excess bile acids decrease fatty acid oxidation in cardiomyocytes and can cause heart dysfunction, a cardiac syndrome that we term cholecardia. Farnesoid X receptor; Small Heterodimer Partner double knockout mice, a model for bile acid overload, display cardiac hypertrophy, bradycardia, and exercise intolerance. In addition, double knockout mice exhibit an impaired cardiac response to catecholamine challenge. Consistent with this decreased cardiac function, we show that elevated serum bile acids reduce cardiac fatty acid oxidation both in vivo and ex vivo. We find that increased bile acid levels suppress expression of proliferator-activated receptor-γ coactivator 1α, a key regulator of fatty acid metabolism, and that proliferator-activated receptor-γ coactivator 1α overexpression in cardiac cells was able to rescue the bile acid-mediated reduction in fatty acid oxidation genes. Importantly, intestinal bile acid sequestration with cholestyramine was sufficient to reverse the observed heart dysfunction in the double knockout mice.Decreased proliferator-activated receptor-γ coactivator 1α expression contributes to the metabolic dysfunction in cholecardia so that reducing serum bile acid concentrations may be beneficial against the metabolic and pathological changes in the heart. (Hepatology 2017;65:189-201).
Risk Factors Associated with the Development of Pneumonitis After High-Dose Chemotherapy with Cyclophosphamide, BCNU, and Etoposide (CBV) Followed by Autologous Stem Cell Transplant
Authors: Andrew A. Lane, Philippe Armand, Yang Feng, Donna Neuberg, Jeremy S. Abramson, Jennifer R. Brown, David C. Fisher, Ann S. LaCasce, Eric D. Jacobsen, Steven L. McAfee, Thomas R. Spitzer, Arnold S. Freedman, Yi-Bin Chen
Journal: Blood (2010)
Preclinical Efficacy of TGF-Beta Receptor I Kinase Inhibitor, Galunisertib, in Myelofibrosis
Authors: Lanzhu Yue, Matthias Bartenstein, Wanke Zhao, Wan-Ting Ho, Ling Zhang, Franck Rapaport, Ross L. Levine, Zonghong Shao, Zhizhuang Joe Zhao, Amit Verma, Pearlie K Epling-Burnette
Journal: Blood (2015)
Upregulation of CD20 on Human Acute Lymphoblastic Leukemia Cells by IL-4 and CpG Motif Containing Oligonucleotides Increases Susceptibility to Rituximab.
Authors: Bart Nijmeijer, Marianke L.J. Van Schie, Roelof Willemze, J.H. Frederik Falkenburg
Journal: Blood (2006)
UK government is urged to end recruitment of “children” into armed forces
Authors: Anne Gulland
Journal: BMJ (2016)

The UK’s armed forces are facing a call to stop recruiting 16 and 17 year olds, who are not yet physiologically or emotionally mature enough to make such a life changing decision.

The campaign group Medact said in a report that the UK is one of few countries in the world to recruit 16 year olds into the military, despite calls from human rights organisations such as the United Nations Committee on the Rights of the Child and the …
Massage and postexercise recovery: the science is emerging
Authors: Thomas M Best, Scott K Crawford
Journal: British Journal of Sports Medicine (2016)

Athletes use a variety of postexercise recovery techniques with the belief that they are effective at enhancing return to competition and training. Common modalities include massage, cold water immersion, compression, electrical stimulation, vibration therapy and a combination of one or more of these strategies. Other approaches include diet and hydration protocols, active recovery and sleep. Despite their popularity, the evidence for the effectiveness of most of these modalities is rather limited, although recent efforts are advancing their science which should help in the recommendation of optimal indications and protocols.

The scientific literature on postexercise massage has accelerated in the last decade. A number of clinical and animal studies have addressed biological plausibility. Clinical studies have investigated the long-held claims that massage mediates leucocyte migration and attenuates the inflammatory response to exercise,1 as well as decreases pain, muscle tone and hyperactivity.2 These reports suggest that massage mediates molecular processes linked to inflammation, specifically by …
A multicenter phase I study of adenoviral p53 in Japanese patients with advanced non-small cell lung cancer
Authors: S. Kagawa, T. Fujiwara, Y. Saijo, T. Nukiwa, K. Yoshimura, H. Nakamura, H. Kato, S. Chada, N. Tanaka
Journal: Journal of Clinical Oncology (2006)

2564 Adenovirus expressing p53 gene, Advexin (A), has shown antitumor activity in a variety of human cancer in preclinical and clinical studies. The goals of this study were to determine the feasibility, safety, humoral immune response, and biological activity of multiple intratumoral injections of A and to characterize the pharmacokinetics of A in Japanese patients with advanced non-small cell lung cancer (NSCLC). Fifteen patients with histologically confirmed NSCLC and p53 mutations were enrolled into this phase I trial. Nine patients received escalating dose levels of A (1 × 109 to 1 × 1011 plaque-forming units [PFU]) as monotherapy once every 4 weeks. Six patients were treated on a 28-day schedule with A in combination with intravenous administration of cisplatin (80 mg/m 2 ). Patients were monitored for toxicity, tumor response, antibody formation, and vector distribution. Fifteen patients received a total of 63 intratumoral injections of A without dose-limiting toxicity. The most common treatment-related toxicity was a transient fever. Thirteen of 15 patients were assessable for efficacy; one patient had a partial response (squamous cell carcinoma at the carina), 10 patients had stable disease, with three lasting &gt; 9 months, and 2 patients had progressive disease. Distribution studies revealed that the vector was detected in the gargle and plasma, but rarely in the urine. Despite of the presence of neutralizing anti-adenovirus antibody, specific p53 transgene expression was detected in biopsied tumor tissues throughout the period of treatment using reverse-transcriptase polymerase chain reaction We conclude that multiple courses of intratumoral A injection alone or in combination with intravenous administration of cisplatin were feasible and well tolerated in advanced NSCLC patients, and appeared to provide clinical benefit. [Table: see text]