tbuckley/cabot-search huggingface dataset:
Unleashing the power of anti-tumor CD4+ T cells: novel insights into the curative mechanisms of chemoimmunotherapy for cancer
Authors: Tsadik G Habtetsion, Gang Zhou
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts CD4+ T cells are critical mediators of anti-tumor immunity and orchestrate a broad range of immune responses against cancer. Previous studies from our lab and others have demonstrated that, adoptive transfer of tumor specific CD4+ T cells to lymphopenic hosts led to eradication of
Bronchoprovocation challenge testing – The estimation of FEV1 decline
Authors: Bronislava Balkova, Beata Dlouha, Pavlina Klusackova, Jindriska Lebedova, Lenka Hurtova
Journal: European Respiratory Journal (2011)

Background: Methacholine and histamine bronchoprovocation challenge (BPC) is an important tool in the diagnosis of bronchial hyperreactivity (BHR). Some patients respond to BPC by a significant and fast drop in forced expiratory volume in one second (FEV1). The aim of the study was to evaluate which baseline anamnestic data correlates with a fast and severe drop in FEV1.

Methods: BPC was performed in each of 1375 patients presenting with suspected bronchial asthma (BA) of either occupational (OA) - 207 patients (15%) or non-occupational origin (1168 patients - 85%). The consequential impact of the following parameters on FEV1 drop was also checked: age, sex, respiratory difficulties (dyspnoea, irritating cough, wheezing and allergic rhinitis symptoms), atopy, past medical history (PMH) of respiratory infection, smoking, chronic bronchitis. A 30% or higher FEV1 drop at bronchoprovocant dosages or concentrations lower than the planned cumulative dose or a 40% or higher FEV1 drop after inhalation of the whole bronchoprovocant dose was considered as severe.

Results: A severe FEV1 drop was found in 248 persons (18%), of which 201 patients (14.6%) were finally diagnosed with BA (52 patients with OA, 149 with non OA origin). Statistically significant FEV1 drop was found in both subgroups among patients with a PMH of whistling, among patients with atopy and smokers.

Conclusion: Caution is recommended when performing BPC in some patients, particularly in those with suspected asthma who are smokers, diagnosed with atopy and those with a PMH of wheezing. These patients may experience greater discomfort from bronchial obstruction and therefore, the provocational dose may need to be increased at a slower rate.
Setting Up a Lung Cancer Screening Program
Authors: Douglas Arenberg, Ella A. Kazerooni
Journal: Journal of the National Comprehensive Cancer Network (2012)

This article summarizes what is known about the best practices of lung cancer screening and provides suggestions for the proper structure for institutions considering offering lung cancer screening services. Important points of emphasis include the need to confine screening to patients at highest risk, the presence of multidisciplinary teams capable of managing the high number of false-positive findings, the need for additional research on biomarkers and risk models for lung cancer, and the currently unknown cost-effectiveness of lung cancer screening on a societal level.
Lipoprotein-Associated Phospholipase A 2 Loss-of-Function Variant and Risk of Vascular Diseases in 90,000 Chinese Adults
Authors: Iona Y. Millwood, Derrick A. Bennett, Robin G. Walters, Robert Clarke, Dawn Waterworth, Toby Johnson, Yiping Chen, Ling Yang, Yu Guo, Zheng Bian, Alex Hacker, Astrid Yeo, Sarah Parish, Michael R. Hill, Stephanie Chissoe, Richard Peto, Lon Cardon, Rory Collins, Liming Li, Zhengming Chen
Journal: Journal of the American College of Cardiology (2016)
Treatment options for chronic hepatitis
Authors: A J Zuckerman, D Lavanchy
Journal: BMJ (1999)

Over two billion people alive today have been infected with the hepatitis B virus and over 350 million of them are chronically infected carriers, of whom more than 75% are from South East Asia and the Western Pacific region. Although not all carriers are infectious, they represent an important reservoir of infection. Persistent carriers are at high risk of long term complications of infection, including chronic hepatitis, cirrhosis, and hepatocellular carcinoma Hepatitis B infection claims the lives of 1-2 million people every year and thus represents an important public health challenge The recent licensing of a new class of drugs may offer much help to the infected populations of South East Asia, but it also poses a set of problems.

Hepatitis B vaccines, introduced in 1982 and incorporated into universal infant immunisation programmes, have proved successful in preventing infection and have reduced significantly the pool of carriers in several countries. Nevertheless, there remains a need for a treatment for persistent carriers to prevent them developing progressive liver disease. Cirrhosis and hepatocellular carcinoma are caused by active replication of hepatitis B virus in the hepatocytes. Hence, the primary goal of treatment is to eliminate the virus or stop its …
Expression of the Multidrug Resistance-Associated Protein Gene in Refractory Lymphoma: Quantitation by a Validated Polymerase Chain Reaction Assay
Authors: Zhirong Zhan, Victor A. Sandor, Erick Gamelin, Joanna Regis, Bruce Dickstein, Wyndham Wilson, Antonio T. Fojo, Susan E. Bates
Journal: Blood (1997)
A randomized phase II study of FOLFOX or FOLFIRI.3 as second-line therapy in patients with advanced pancreatic cancer previously treated with gemcitabine-based chemotherapy
Authors: J. Y. Hwang, C. Yoo, T. Kim, J. Lee, D. Park, D. Seo, S. Lee, M. Kim, D. Han, S. Kim, J. Lee
Journal: Journal of Clinical Oncology (2009)

4618 Background: Only few clinical trials have been conducted in patients with advanced pancreatic cancer after failure of first-line gemcitabine-based chemotherapy. We conducted a randomized phase II trial of modified FOLFOX vs. modified FOLFIRI.3 as second-line regimen for the patients with gemcitabine refractory pancreatic cancer ( NCT00786006 ). Methods: Patients with advanced pancreatic adenocarcinoma previously treated with gemcitabine were randomly assigned to FOLFOX or FOLFIRI.3 stratifying by age (≤ 65 vs. &gt;65), performance status (0–1 vs. 2) and prior response to gemcitabine (PR/SD vs. PD). FOlFIRI.3 regimen consisted of Irinotecan 70 mg/m 2 (over 60 min) D1, leucovorin 400 mg/m 2 (over 2h) D1, 5-FU 2000 mg/m 2 (over 46 hours) from D1, then irinotecan 70 mg/m 2 (over 60 min) at the end of the 5-FU infusion every two week. FOLFOX regimen is composed of oxaliplatin 85 mg/m 2 (over 120 min) D1, LV 400 mg/m 2 D1, 5-FU 2,000 mg/m 2 (over 46 hours) every two week. The primary end-point was 6-month overall survival (P 0 =20%) and Simon-Wittes-Ellenberg design was used to calculate the sample size (29 evaluable patients for each treatment arm). Results: From January 2007 to December 2008, sixty patients were enrolled and randomized to FOLFOX (N=30) or FOLFIRI.3 (N=30). Baseline characteristics were well balanced between each arm; median age 56 (35–60) vs. 56 yo (37–73); ECOG PS 0/1/2, 5/24/1 vs. 5/25/0; prior response to gemcitabine-based chemotherapy PR/SD/PD 10/13/7 vs. 10/11/9. With a median follow-up period of 6.0 months (95% CI, 4.7–7.3) the median overall survival was 4.0 months in both group (HR=0.95, 95% CI 0.52–1.75) with 6-month survival rates of 25% and 20%, respectively. The median PFS was 1.4 months for FOLFOX and 1.9 months for FOLFIRI.3 (HR=1.11, 95% CI, 0.64–1.92). Disease control (PR+SD) was achieved in 20% (5/25 in FOLFOX) and 28% (7/25 in FOLFIRI.3) of patients with measurable disease. The incidences of grade 3/4 toxicities were similar in both groups. Conclusions: Both FOLFOX and FOLFIRI.3 were tolerated with manageable toxicity, offering modest activity as second-line treatment of patients with advanced or metastatic pancreatic cancer, previously treated with gemcitabine. No significant financial relationships to disclose.
A phase II study of a novel oral isotype-selective histone deacetylase (HDAC) inhibitor in patients with relapsed or refractory Hodgkin lymphoma
Authors: A. Younes, M. Fanale, B. Pro, P. McLaughlin, S. Neelapu, L. Fayad, A. Wedgwood, M. Dubay, J. Backstrom, R. E. Martell
Journal: Journal of Clinical Oncology (2007)

8000 Background: MGCD0103 is a non-hydroxamate, isotype-selective, inhibitor of human HDACs. Abnormal regulation of HDAC activity is associated with malignant disease in humans, and small molecule HDAC inhibitors are a novel drug class with anticancer potential. Their proposed anti-Hodgkin activity is through regulation of aberrant gene expression at the transcriptional level by inhibiting proliferation, inducing apoptosis, and/or initiating differentiation in cancer cells. Methods: A phase II trial of MGCD0103 (110 mg 3x/week in 4- week cycles) is ongoing in patients (pts) with relapsed/refractory Hodgkin Lymphoma (RRHL). The primary endpoint is a composite of objective response and stable disease. Results: As of Dec 15 th , 2006, 18 pts out of a planned 12–35 have been enrolled; median age 28 (range: 21–62). All pts were previously treated with autologous and/or allogeneic stem cell transplant. The median number of cycles received to date is 2 (range: 1–4). Seven pts have completed =8 weeks (2 cycles) of therapy and are evaluable for response analysis; 5 of these had tumor reduction ranging between 21% and 70% by CT, which is associated with a significant reduction in FDG-PET activity in 4 pts. Of the 18 pts, 5 have had dose reductions/discontinuations due to: mucositis (n=1); fatigue/nausea/diarrhea (n=1); nausea/vomiting (n=1); fatigue (n=1) and pancreatitis/hypotension (n=1). Significant HDAC inhibition (&gt;20% of total activity), was seen in PBMCs from 7/9 pts with samples. Treatment is ongoing in 14 pts; including those with tumor reduction. Criteria have been met to expand to the second stage of the study (&gt;1 response demonstrated in the first 12 patients). Conclusions: Preliminary results suggest that single-agent MGCD0103 demonstrates significant anti-tumor activity in RRHL and is well tolerated at a Phase II dose of 110mg in this ongoing trial. No significant financial relationships to disclose.
Inhibition of diacylglycerol kinase α restores restimulation-induced cell death and reduces immunopathology in XLP-1
Authors: Elisa Ruffo, Valeria Malacarne, Sasha E. Larsen, Rupali Das, Laura Patrussi, Christoph Wülfing, Christoph Biskup, Senta M. Kapnick, Katherine Verbist, Paige Tedrick, Pamela L. Schwartzberg, Cosima T. Baldari, Ignacio Rubio, Kim E. Nichols, Andrew L. Snow, Gianluca Baldanzi, Andrea Graziani
Journal: Science Translational Medicine (2016)

DGKα inhibition restores apoptosis in SAP-deficient lymphocytes, decreasing immunopathology in XLP-1 patients.
Relation of Dietary Fat Level to Fatty Livers in Several Strains of Mice&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: Paul F. Fenton, Marian T. Dowling, Jeanne S. Mershon
Journal: JNCI Journal of the National Cancer Institute (1954)

Relation of Dietary Fat Level to Fatty Livers in Several Strains of Mice Get access Paul F. Fenton, Paul F. Fenton Department of Biology, Brown University, Providence, R. I. Search for other works by this author on: Oxford Academic PubMed Google Scholar Marian T. Dowling, Marian T. Dowling Department of Biology, Brown University, Providence, R. I. Search for other works by this author on: Oxford Academic PubMed Google Scholar Jeanne S. Mershon Jeanne S. Mershon Department of Biology, Brown University, Providence, R. I. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 15, Issue 3, December 1954, Pages 429–432, https://doi.org/10.1093/jnci/15.3.429 Published: 01 December 1954 Article history Received: 21 July 1954 Published: 01 December 1954
Mavoglurant in fragile X syndrome: Results of two randomized, double-blind, placebo-controlled trials
Authors: Elizabeth Berry-Kravis, Vincent Des Portes, Randi Hagerman, Sébastien Jacquemont, Perrine Charles, Jeannie Visootsak, Marc Brinkman, Karin Rerat, Barbara Koumaras, Liansheng Zhu, Gottfried Maria Barth, Thomas Jaecklin, George Apostol, Florian von Raison
Journal: Science Translational Medicine (2016)

In contrast to previous studies, targeting the mGluR pathway in fragile X syndrome patients did not improve behavior independent of FMR1 methylation.
Abstract 15155: Acidic Fibroblast Growth Factor Delivered by Ultrasound Targeted Microbubble Destruction Increases Microvascular Densities and Improves Left Ventricular Systolic and Diastolic Function in Diabetic Cardiomyopathy in Rats
Authors: Xinqiao Tian, Ao Ru, Yingzheng Zhao, Lei Zheng, Xing Li, Jianmin Li, Keke Jin, Chao Zhang, Shuping Ge
Journal: Circulation (2012)

BACKGROUND AND OBJECTIVES: We sought to pursue enhancing angiogenesis and tissue growth and repair to improve microcirculation and left ventricular (LV) function to treat diabetic cardiomyopathy (D...
Cdx2 Expression and Intestinal Metaplasia Induced by <i>H. pylori</i> Infection of Gastric Cells Is Regulated by NOD1-Mediated Innate Immune Responses
Authors: Naoki Asano, Akira Imatani, Tomohiro Watanabe, Jun Fushiya, Yutaka Kondo, Xiaoyi Jin, Nobuyuki Ara, Kaname Uno, Katsunori Iijima, Tomoyuki Koike, Warren Strober, Tooru Shimosegawa
Journal: Cancer Research (2016)

Abstract Chronic infection with the bacterial Helicobacter pylori is a major cause of gastric and duodenal ulcer disease, gastric mucosal atrophy, and cancer. H. pylori–induced expression of the intestinal epithelial–specific transcription factor caudal-related homeobox 2 (Cdx2) contributes to intestinal metaplasia, a precursor event to gastric cancer. Given a role for the bacterial pattern recognition molecule nucleotide-binding oligomerization domain 1 (NOD1) in the innate immune response to bacterial infection, we investigated mechanisms used by NOD1 to regulate H. pylori infection and its propensity towards the development of intestinal metaplasia. We found that Cdx2 was induced by H. pylori infection in both normal and neoplastic gastric epithelial cells in a manner that was inversely related to NOD1 signaling. Mechanistic investigations revealed that Cdx2 induction relied upon activation of NF-κB but was suppressed by NOD1-mediated activation of TRAF3, a negative regulator of NF-κB. In vivo, prolonged infection of NOD1-deficient mice with H. pylori led to increased Cdx2 expression and intestinal metaplasia. Furthermore, gastric epithelial cells from these mice exhibited increased nuclear expression of the NF-κB p65 subunit and decreased expression of TRAF3. Overall, our findings illuminated a role for NOD1 signaling in attenuating H. pylori–induced Cdx2 expression in gastric epithelial cells, suggesting a rationale to augment NOD1 signaling in H. pylori–infected patients to limit their risks of accumulating precancerous gastric lesions. Cancer Res; 76(5); 1135–45. ©2016 AACR.
<i>CCR</i> 20th Anniversary Commentary: Bevacizumab in the Treatment of Glioblastoma—The Progress and the Limitations
Authors: Nataliya Mar, Annick Desjardins, James J. Vredenburgh
Journal: Clinical Cancer Research (2015)

Abstract Vredenburgh and colleagues conducted the first phase II study of bevacizumab plus irinotecan in recurrent malignant glioma, confirming the safety and efficacy of bevacizumab. This study, which was published in the February 15, 2007, issue of Clinical Cancer Research, was a stepping stone for subsequent research, leading to regulatory approval of bevacizumab for recurrent glioblastoma. Clin Cancer Res; 21(19); 4248–50. ©2015 AACR. See related article by Vredenburgh et al., Clin Cancer Res 2007;13(4) February 15, 2007;1253–9
Predicting breast cancer risk in <i>BRCA1</i> and <i>BRCA2</i> carriers: Methylation studies using intraductal fluid
Authors: Y. C. Antill, G. Mitchell, S. A. Johnson, L. Devereux, A. Milner, A. Sridhar, J. A. Kirk, K. Phillips, G. Lindeman, I. G. Campbell
Journal: Journal of Clinical Oncology (2007)

10537 Background: Genomic alterations are likely to precede the phenotypic changes of breast cancer (BC) and include hyper- methylation of tumour suppressor genes. An intraductal approach, such as ductal lavage (DL), is an attractive means of accessing ductal epithelial and other cells in a prospective fashion. Methods: Women with at least one breast unaffected by BC, with a germline BRCA1 or BRCA2 mutation, attended for 6-monthly DL collection for up to 3 years. Standard methods were used for DNA extraction and bisulfite conversion. Hyper-methylation of p16, RASSF1A, twist and RARβ genes was investigated using a qualitative, real-time, nested PCR assay. Associations between methylation status and categorical variables were tested using Fisher's exact test including cytological findings and BC incidence. Logistic regression was used to examine the relationship between methylation status and patient age, and to examine the effects of multiple variables. Analyses were performed at three levels; samples from a single breast over time and from a single duct over time and each sample in isolation. Results: A total of 173 DL samples from 98 ducts in 56 breasts were analysed in 34 women (16 BRCA1 and 18 BRCA2 mutation carriers) with a median age of 43 years (range 27- 60). DL fluid was collected from all women on at least one occasion (median 2.5 visits, range 1–5). Five women developed BC on study. Methylation of p16 was strongly associated with a known BRCA1 mutation (p=0.0003, p&lt;0.0001 and p&lt;0.0001 at the breast, duct and sample levels respectively) and was also more likely in women with a previous history of contralateral BC (p=0.0008 and p&lt;0.0001 at the duct and sample level respectively). Independent associations were seen for women who developed BC on study and methylation of p16 and RASSF1A (p16: p=0.0023 at the sample level only) and (RASSF1A: p=0.0760, p=0.0178 and p&lt;0.0001- at the breast, duct and sample level respectively). Conclusions: The methylation pattern in a panel of genes could be used as a biomarker for risk of future breast cancer. In addition p16 methylation may be a predictor of BRCA1 mutation status. Further research is required to corroborate these findings as the numbers recruited for this study are small with a short duration of clinical follow up. No significant financial relationships to disclose.
Cycling Status of CD34+ Cells Mobilized Into Peripheral Blood of Healthy Donors by Recombinant Human Granulocyte Colony-Stimulating Factor
Authors: Roberto M. Lemoli, Agostino Tafuri, Alessandra Fortuna, Maria Teresa Petrucci, Maria Rosaria Ricciardi, Lucia Catani, Damiano Rondelli, Miriam Fogli, Giuliana Leopardi, Cristina Ariola, Sante Tura
Journal: Blood (1997)
Endothelial β-Catenin Signaling Is Required for Maintaining Adult Blood–Brain Barrier Integrity and Central Nervous System Homeostasis
Authors: Khiem A. Tran, Xianming Zhang, Dan Predescu, Xiaojia Huang, Roberto F. Machado, Joachim R. Göthert, Asrar B. Malik, Tibor Valyi-Nagy, You-Yang Zhao
Journal: Circulation (2015)

The blood-brain barrier (BBB) formed by brain endothelial cells interconnected by tight junctions is essential for the homeostasis of the central nervous system. Although studies have shown the importance of various signaling molecules in BBB formation during development, little is known about the molecular basis regulating the integrity of the adult BBB.Using a mouse model with tamoxifen-inducible endothelial cell-restricted disruption of ctnnb1 (iCKO), we show here that endothelial β-catenin signaling is essential for maintaining BBB integrity and central nervous system homeostasis in adult mice. The iCKO mice developed severe seizures accompanied by neuronal injury, multiple brain petechial hemorrhages, and central nervous system inflammation, and all had postictal death. Disruption of endothelial β-catenin induced BBB breakdown and downregulation of the specific tight junction proteins claudin-1 and -3 in adult brain endothelial cells. The clinical relevance of the data is indicated by the observation of decreased expression of claudin-1 and nuclear β-catenin in brain endothelial cells of hemorrhagic lesions of hemorrhagic stroke patients.These results demonstrate the prerequisite role of endothelial β-catenin in maintaining the integrity of adult BBB. The results suggest that BBB dysfunction secondary to defective β-catenin transcription activity is a key pathogenic factor in hemorrhagic stroke, seizure activity, and central nervous system inflammation.
HLA class I molecules associated with microvesicles in sera of patients with cancer induce apoptosis of activated T cells
Authors: Eva U. Wieckowski, Jeong-Whun Kim, Torsten E. Reichert, Soldano Ferrone, Theresa L. Whiteside
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

5308 

The presence of apoptosis-inducing membraneous microvesicles (MV) in sera of patients with cancer has been linked to death of immune cells. We and others have shown that MV-mediated T-cell apoptosis involves the Fas/FasL pathway. However, among 27 MV initially isolated from sera of patients with head and neck cancer (HNC), 7 did not express FasL in Western blots, yet all induced DNA fragmentation in activated T lymphocytes and in Fas-resistant Jurkat cells. In Western blots, these MV were found to contain various levels of HLA class I molecules (HLA-I), and their biologic activity was blocked by anti-HLA-I mAbs, TP25.99 and W6/32. MV obtained from other HNC patients’ sera and co-incubated with activated T cells induced DNA fragmentation and caspase 3 cleavage, which were completely blocked by anti-Fas and anti-HLA-I Abs but only partially (e.g., 40-50%) by TP25.99 Ab alone. Thus, MV-associated FasL and/or HLA-I antigens mediated apoptosis of T cells. We have reported that CD8+ effector T cells are especially sensitive to MV-mediated apoptosis in patients with cancer. Pre-incubation of activated T cells with Abs to the CD8 molecule inhibited MV-induced apoptosis, while Abs to TcR did not. This finding implicates the CD8 complex signaling in MV-mediated apoptosis, possibly through mechanisms involving an interaction of MV-associated HLA-I antigens with CD8. We consider this molecular mechanism to be particularly relevant to tumor escape from immune cells in patients with cancer.
Abstract 11021: Akt1-mediated Skeletal Muscle Growth Attenuates Renal Interstitial Fibrosis and Inflammation in Obstructive Nephropathy
Authors: Shinsuke Hanatani, Yasuhiro Izumiya, Satoshi Araki, Taku Rokutanda, Kenneth Walsh, Hisao Ogawa
Journal: Circulation (2012)

Introduction:  Muscle wasting is a common complication in chronic kidney disease (CKD), and contributes to poor outcomes. It is unknown whether the reverse is true; will an increase in lean muscle mass can improve renal damages in the setting of CKD?   Hypothesis:  Skeletal muscle growth attenuates pathological renal damages after mouse model of CKD.   Methods:  We utilized skeletal muscle-specific, conditional Akt1 transgenic mice, that can induce the growth of functional skeletal muscle by switching Akt1 signaling on in muscle fibers. Seven days after Akt1 activation in skeletal muscle, renal injury was induced by unilateral ureteral obstruction (UUO) in Akt1 transgenic and wild type (WT) mice. Renal damages were examined by histological and gene expression analysis at 3, 7 and 14 days after UUO.   Results:  Activation of Akt1 signaling in myofibers led to an increase in skeletal muscle mass, assessed by gastrocnemius muscle weight/tibial length ratio, at 7 and 14 days after surgery (15.0 vs. 9.5 mg/mm; p   Conclusions:  Akt1-mediated skeletal muscle growth attenuates renal interstitial fibrosis and inflammation after UUO, suggesting clinical utility of exercise lead to a skeletal muscle growth, such as resistance training in kidney diseases.
Defining AML and MDS second cancer risk dynamics after diagnoses of first cancers treated or not with radiation
Authors: T Radivoyevitch, R K Sachs, R P Gale, R J Molenaar, D J Brenner, B T Hill, M E Kalaycio, H E Carraway, S Mukherjee, M A Sekeres, J P Maciejewski
Journal: Leukemia (2015)