tbuckley/cabot-search huggingface dataset:
Green tea extract and (-) epigallocatechin-3-gallate inhibit hypoxia- and serum-induced HIF-1 α protein accumulation and VEGF expression in HeLa and HepG2cells
Authors: Qunzhou Zhang, Xudong Tang, Qingyi Lu, Zuofeng Zhang, Jianyu Rao, Jimmy Brown, Anh Le
Journal: Cancer Research (2006)

2257   Green tea extract (GTE) and its major component (-)epigallocatechin-3-gallate (EGCG) have been shown to have antiangiogenic effects in various experimental tumor models. A growing body of evidence has demonstrated that hypoxia-inducible factor (HIF)-1α-mediated vascular endothelial growth factor (VEGF) expression plays a critical role in tumor angiogenesis. In this study, we investigated the effect of GTE and EGCG on HIF-1α and VEGF expressions induced by hypoxia or serum in human cervical carcinoma (HeLa) and hepatoma (HepG2) cells. Our results showed that GTE and EGCG significantly inhibited hypoxia- and serum-induced HIF-1α protein accumulation in the cancer cells, but had no effects on HIF-1α mRNA expression. Meanwhile, GTE and EGCG also drastically inhibited VEGF expressions at both mRNA and protein levels in HeLa and HepG2 cells in response to hypoxia or serum stimulation. Mechanistically, we found that GTE and EGCG inhibited hypoxia- induced HIF-1α protein accumulation via blocking the activation of PI-3K/AKT and ERK1/2 signaling pathways and substantially promoting HIF-1α protein degradation through the proteasome system. In addition, we demonstrated that GTE and EGCG inhibited serum- induced HIF-1α protein expression through the inhibition of AKT activation and the phosphorylation of two protein translational regulators, Mr 70,000 ribosomal protein S6 kinase (p70S6K) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1). Our data suggested that HIF-1α/VEGF may serve as a promising target for GTE and EGCG in the context of cancer chemoprevention and anticancer therapy.
Combination therapy of 2-methoxyantimycin-A3 with bortezomib in mesothelioma
Authors: Lidong Zhang, Charles Rodarte, Xiaobo Cao, James Littlejohn, W. Smythe
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

3263 

Malignant pleural mesothelioma (MPM) is a solid neoplasm that is highly unresponsive to conventional therapy. Therefore, there is urgent need for development of new strategies of therapy. Previously, we and others have demonstrated that MPM overexpresses anti-apoptotic cellular protein Bcl-xL. Furthermore, we have demonstrated that the functional inhibition of Bcl-xL by its specific inhibitor 2-methoxyantimycin-A3 induces apoptosis and increases chemosensitivity in MPM cell lines in vitro and in vivo. In this study, we investigated the combination effects of 2-methoxyantimycin-A3 with bortezomib, a specific proteasome pathway inhibitor, on MPM in vitro. Our results showed that the both MPM cell lines, I-45 and REN, displayed synergistically enhanced cell viability reduction after treatment with a sub IC50 dose of bortezomib (12.5 nM) and 10, 20, or 40μg/mL of 2-methoxyantimycin-A3 for 48 hours. Combination treatment with bortezomib at 12.5 nM and 2-methoxyantimycin-A3 at 20 μg/mL showed a significant increase in sub-G1 population in REN cell lines (28.25%) compared with treatment of either drug alone (6.74-7.23%). However, the same combination treatment only resulted in a slight increase in sub-G1 population in I-45 cell line (7.65%) when compared with treatment of either drug alone (1.6-3.9%), indicating that apoptosis induction is the main reason for the combination effect in REN cell line, while cell growth inhibition is major contribution to the combination effect in I-45 cell lines. For mechanism study, Noxa, a pro-apoptotic member of Bcl-2 protein family, displayed 500-600% increases in the both MPM cell lines treated with combined drugs when compared with treatment without either drugs. However, knockdown of Noxa gene expression by its siRNA did not protect REN cells from the combined therapy-induced apoptosis. Overall, our results provide a potential combination therapy for patients with MPM.
Characterization of novel c-erbB2 regulated genes using massively parallel signature sequencing (MPSS)
Authors: Ana Paula Medeiros Silva, Dirce Maria Carraro, Lilian Campos Pires, Victor C. Jongeneel, Sandro José De Souza, Anamaria Aranha Camargo
Journal: Cancer Research (2006)

83   Overexpression of the proto-oncogene c-erbB2 is observed in 30% of breast tumors and is considered an adverse prognostic factor for breast cancer. However, the molecular mechanisms associated with c-erbB2 overexpression are not yet understood. In this work, transcriptional changes associated with c-erbB2 overexpression were investigated using Massively Parallel Signature Sequencing (MPSS). MPSS is a powerful technique for genome-wide gene expression analysis, which relies on the production and quantification of short tags proximal to the 3′ end of transcripts. Over 24 million MPSS tags, representing aproximately 17,000 different genes were generated for a immortalized mammary luminal epithelial cell line (HB4a) and for a variant cell line (C5.2) transfected with c-erbB2. After establishing reliable correlations between tags and known human transcripts, 9% of the tags could not be associated with a known transcripts and were designated orphan tags. Among the orphan tags there were many that showed differential expression between HB4a and C5.2 cell lines and probably represent novel genes regulated by c-erbB2. In order to further characterize these novel genes, we have extended 83 tags orphan tags towards the 3′ end of the corresponding mRNA molecule using a methodology named GLGI (Generation of Longer cDNA fragments for Gene Identification). Forty one 3′ cDNA fragments were obtained and similarity analysis of these fragments using BLAST allowed the identification of 10 transcripts putativelly regulated by c-erB2. Differential expression in the C5.2 cell line of 3 out of the 10 transcripts putativelly regulated by c-erbB2 was confirmed by Real-Time PCR. We are currently investigating the effects of Herceptin treatment on gene expression patterns in HER2-amplified and nonamplified breast cancer cell lines in order to elucidate the molecular consequences of blocking the HER pathway.
A Phase II Trial Of Eltrombopag For Patients With Chronic Lymphocytic Leukemia (CLL) and Thrombocytopenia
Authors: Nitin Jain, Michael J. Keating, Jan A. Burger, Alessandra Ferrajoli, Gautam Borthakur, Charles Koller, Srdan Verstovsek, Susan O'Brien, William G. Wierda
Journal: Blood (2013)
Predictive Significance of Serum Beta 2-Microglobulin Levels and M-Protein Velocity for Symptomatic Progression of Smoldering Multiple Myeloma
Authors: Tsuyoshi Muta, Shinsuke Iida, Kosei Matsue, Kazutaka Sunami, Jun Isoda, Naoko Harada, Yoshio Saburi, Seiichi Okamura, Kyouya Kumagae, Junichi Watanabe, Junya Kuroda, Kenichi Aoki, Ryosuke Ogawa, Toshihiro Miyamoto, Koichi Akashi, Yasushi Takamatsu
Journal: Blood (2014)
Committee's action has compromised continuing studies
Authors: M W. L Davis, M. Lewis, L. De Caestecker, R. Mann
Journal: BMJ (1995)

using the pill early because they had had a thrombo- embolic event).The users of products containing levonorgestrel and norethisterone might then comprise, in effect, a population of survivors who are less at risk of the condition under study.I understand that further analyses are in progress to test this hypothesis in various ways.The same model, however, has important implications for prescribers now.A first time user could
The prognostic significance of obsessive-compulsive symptoms in schizophrenia
Authors: W S Fenton, T H McGlashan
Journal: American Journal of Psychiatry (1986)

Obsessive-compulsive symptomatology has been described in schizophrenia for more than 60 years, but its clinical significance has yet to be explored systematically. This report details the clinical characteristics and long-term course of a group of 21 schizophrenic patients with prominent obsessive-compulsive symptoms from the Chestnut Lodge Follow-Up Study. While this group differed on admission only minimally from schizophrenic patients without obsessive-compulsive symptoms, their long-term outcome in the areas of social relations, employment, psychopathology, and global functioning was significantly, and almost uniformly, poorer. Persistent obsessive-compulsive symptoms thus appear to be a powerful predictor of poor prognosis in schizophrenia.
Report of the Committee on Infectious Diseases.
Authors: Earl M. Cooperman
Journal: Annals of Internal Medicine (1986)

histories.The chapters in section 6 on the evaluation of primary medical care, by Cassell, Hulka and Ibrahim, and those on research in general practice by John Fry are outstanding.Section 7 contains a discussion of the health care team, the familyoriented medical record, patterns of morbidity in family practice, and the knowledge and skills needed for family practice.Extensive use is made of case histories, charts and tables.The content of each chapter is brief, to the point and well organized for easy understanding.This book should be in the libraries of all medical schools and all departments of family medicine.It should be required reading for all family physician-teachers and medical students who are contemplating a career in family medicine.
Are Complicated Forms of Celiac Disease Cryptic T-Cell Lymphomas?
Authors: Franck Carbonnel, Laurence Grollet-Bioul, Jean Claude Brouet, Marie Françoise Teilhac, Jacques Cosnes, Régis Angonin, Marie Deschaseaux, François-Patrick Châtelet, Jean Pierre Gendre, François Sigaux
Journal: Blood (1998)
Statistics Notes: Measurement error proportional to the mean
Authors: J M. Bland, D. G Altman
Journal: BMJ (1996)

We often need to know the error with which measurements are made—for example, so that we can decide whether the change in a clinical observation represents a real change in a patient's condition. We have discussed previously the within-subject standard deviation as a practical index of measurement error.1 We said that this approach should be used when the measurement error was not related to the magnitude of the measurement and recommended that we plot the subject standard deviation against the subject mean to check this. Table 1 shows some duplicate salivary cotinine measurements taken from a larger study. Figure 1 shows absolute subject difference against subject mean, which is equivalent to a standard deviation versus mean plot when we have only two measurements per subject.1 If we are to use the within-subject standard deviation as an index of measurement error we need the subject standard deviation to be …
SS8885 (Raloxifene diphosphate): A prodrug enhancing anti-tumor potential of raloxifene.
Authors: Yoshinori Okamoto, Xiaoping Liu, Naomi Suzuki, Kanako Okamoto, Santosh Laxmi, Shinya Shibutani
Journal: Cancer Research (2008)

3303   Raloxifene (RAL) significantly reduced the incidence of breast cancer in women at high risk of developing the disease and unlike tamoxifen, did not promote endometrial cancer in women. RAL has recently been approved by the Food and Drug Administration for use of breast cancer prevention. However, RAL, having two hydroxyl moieties, can be conjugated rapidly through phase II metabolism and excreted, making it difficult to achieve adequate bioavailability by oral administration in humans. As a result, higher doses must be administered to obtain an efficacy equivalent to that achieved with tamoxifen. To improve oral bioavailability and antitumor potential, SS8885 (RAL diphosphate) was prepared as a prodrug. RAL diphosphate showed several orders of magnitude lower binding potential to both ERα and ERβ and weak antiproliferative potency on cultured human MCF-7 and ZR-75-1 breast cancer cells, as compared with RAL. Therefore, RAL diphosphate itself has only weak ER binding and antiproliferative potency. Since RAL diphosphate was dephosphorylated by rat intestinal cytosol and microsomes, but not by the serum, the phosphate-derivatives may be cleaved primarily during transportation in the intestine. When rats were treated orally with an equimolar dose of RAL or RAL diphosphate, RAL diphosphate was absorbed more rapidly in the body and kept concentrated in the blood longer than RAL. RAL diphosphate has a higher bioavailability than RAL, endowing it with higher antitumor potential than RAL against both 7,12-dimethylbenz( a )anthracene-induced mammary carcinoma in rats and human MCF-7 breast cancer implanted in athymic nude mice. The use of a low dose of RAL diphosphate may reduce several side-effects such as venous thrombo-embolic events and liver dysfunction while maintaining the antitumor potency of RAL. The RAL prodrug may provide greater clinical benefit for breast cancer therapy and prevention.
Variations in Coronary Artery Disease Secondary Prevention Prescriptions Among Outpatient Cardiology Practices
Authors: Thomas M. Maddox, Paul S. Chan, John A. Spertus, Fengming Tang, Phil Jones, P. Michael Ho, Steven M. Bradley, Thomas T. Tsai, Deepak L. Bhatt, Pamela N. Peterson
Journal: Journal of the American College of Cardiology (2013)
Abstract 2736: Mutations In The Nonpore Region of The HERG Gene Are at Risk of Acquired Long QT Syndrome
Authors: Yuichiro Sakamoto, Hidekazu Ino, Noboru Fujino, Katsuharu Uchiyama, Kenshi Hayashi, Kenji Sakata, Eiichi Masuta, Akira Funada, Toshinari Tsubokawa, Keisuke Nakasima, Haruhiro Higasida, Masakazu Yamagishi
Journal: Circulation (2007)

Introduction : Mutations involving the KCNH2 gene in HERG channel are responsible for type2 LQTS. Previous study showed patients with mutations in the pore region of the HERG gene are markedly increased risk for arrhythmia-related cardiac events compared with patients with nonpore mutations. However, a few data exist regarding mode of onset and frequency in arrhythmic events of mutations in the nonpore regions of the HERG channel. Hypothesis :We hypothesized that patients with mutations in the nonpore regions of the HERG gene increase risk for cardiac events under a specific condition. Methods: We examined 104 unrelated subjects with LQTS. Genetic analysis of KCNH2 gene was performed using standard genetic tests for probands and families of genotyped ones.Between subjects with and without pore mutations,difference in clinical characteristics such as QTc intervals, LQT score and major cardiac events are evaluated by standard statistical methods. Result: We identified 7 LQT2 patients with 3 pore mutations and 17 patients with 7 nonpore mutation, and evaluated clinical characteristics and characterized the electrophysiological properties of these mutations. The baseline QTc intervals were significantly longer with pore than with nonpore mutations (513 ± 60ms vs. 479 ± 21ms, p&lt;0.01). The LQTS scores determined by Schwartz’s criteria were also significantly higher with pore mutations (4.5 ± 1.2 vs. 2.9 ± 1.2, p&lt;0.01). However the frequency of LQTS-related cardiac events with nonpore mutaion was as high as with pore mutations (57 % vs. 30 %, N.S). Significantly 4 of 5 cardiac events with nonpore mutations occurred under medications (Probucol) or conditions (Hypokalemia) known to favor QT prolongation, although only 1 of 4 cardiac events with pore mutations did. Electrophysiological study revealed that the tail current amplitude through one nonpore mutant channel(M124T)was significantly decreased as compared that of WT HERG channel and Probucol significantly inhibited M124T HERG channels. Conclusions: These data demonstrate that LQT2 patients with nonpore mutations are also at high risk of arrhythmia-related events in the presence of drugs or other environmental stressors.
Monoclonal Antibodies Progress To the Next Generation
Authors: C. McNeil
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Monoclonal Antibodies Progress To the Next Generation Get access Caroline McNeil Caroline McNeil Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 23, 6 December 1995, Pages 1738–1739, https://doi.org/10.1093/jnci/87.23.1738 Published: 06 December 1995
Abstract 13941: Non Viral Reprogramming of Skeletal Myoblasts to Stemness by Single Small Molecule: miR Profiling and Cardiac Regeneration
Authors: Zeeshan Pasha, Khawaja H Haider, Muhammad Ashraf
Journal: Circulation (2011)

Background Reprogramming somatic cells into induced pluripotent stem cells typically require the enforced expression of several pluripotency determinant transcription factors, posing mutagenesis ri...
Demographics and survivial of a cohort of blood and breast cancer patients who developed heart failure following cancer treatment
Authors: Robyn A. Clark, Alexandra L. McCarthy, Munir H. Chowdhury, Narelle Berry, Shahid Ullah, Bogda Koczwara, John Atherton, David Roder
Journal: Circulation (2014)

Background/Aim: Cardiotoxicity resulting in heart failure is a devastating complication of cancer therapy. It is possible that a patient may survive cancer only to develop heart failure (HF), which is more deadly than cancer. The aim of this project was to profile the characteristics of patients at risk of cancer treatment induced heart failure. 

Methods: Linked Health Data Analysis of Queensland Cancer Registry (QCR) from 1996-2009, Death Registry and Hospital Administration records for HF and chemotherapy admissions were reviewed. Index heart failure admission must have occurred after the date of cancer registry entry. 

Results: A total of 15,987 patients were included in this analysis; 1,062 (6.6%) had chemotherapy+HF admission (51.4% Female) and 14,925 (93.4%) chemotherapy_no HF admission. Median age of chemotherapy+HF patients was 67 years (IQR 58 to 75) vs. 54 years (IQR 44 to 64) for chemotherapy_no HF admission. Chemotherapy+HF patients had increased risk of all cause mortality (HR 2.79 [95% CI 2.58-3.02] and 1.67 [95% CI, 1.54 to 1.81] after adjusting for age, sex, marital status, country of birth, cancer site and chemotherapy dose). Index HF admission occurred within one year of cancer diagnosis in 47% of HF patients with 80% of patinets having there index admission with 3 years. The number of chemotherapy cycles was not associated with significant reduction in survival time in chemotherapy+HF patients. Mean survival for heart failure patients was 5.3 years (95% CI, 4.99 - 5.62) vs.9.57 years (95% CI, 9.47-9.68) for chemotherapy_no HF admission patients. 

Conclusion: All-cause mortality was 67% higher in patients diagnosed with HF following chemotherapy in adjusted analysis for covariates. Methods to improve and better coordinate of the interdisciplinary care for cancer patients with HF involving cardiologists and oncologists are required, including evidence-based guidelines for the comprehensive assessment, monitoring and management of this cohort.
Abstract P266: The Local Food Environment and Obesity: A Systematic Review
Authors: Laura K Cobb, Lawrence J Appel, Manuel Franco, Jessica C Jones-Smith, Cheryl A Anderson
Journal: Circulation (2015)

Introduction: Numerous studies have explored the relationship of the local food environment and obesity. However, results have been inconsistent, and existing literature reviews have not taken into account study quality or the heterogeneity of measures of the local food environment. Methods: We used systematic keyword searches in Pubmed and Scopus to identify studies conducted in the US and Canada that assessed the relationship of obesity to the local availability of supermarkets, grocery stores, convenience stores, fast food restaurants or indices combining these measures. We developed a quality metric based on study design, exposure and outcome measurement and analysis, and then assigned each study a score. Results: We identified 71 studies representing 65 cohorts. Overall, study quality was low; 60 studies were cross-sectional. The approach to measuring local food environments varied: fast food availability was measured 31 ways in 44 studies. Associations between food outlet availability and obesity were predominantly null. In adults, we saw a trend among the non-null associations toward inverse associations between supermarket availability and obesity (22 inverse, 4 direct, 67 null) and direct associations between fast food and obesity (29 direct, 6 inverse, 71 null). In children, we saw robust direct associations between fast food availability and obesity in lower income populations only (12 direct, 7 null). In adults, indices made up of multiple types of outlets had resulted in the most consistent associations with obesity (18 expected, 23 null). Limiting analyses to higher quality studies did not affect results. Conclusions: We found limited evidence for associations between the local food environment and obesity. Quality issues, however, make causal inference difficult. Absent compelling direct evidence linking local food environments to obesity, policy makers will need to rely on other types of evidence as they address the environmental changes that contribute to the steep increase in obesity in the US.
Effect of hyperthermia on the cytotoxicity of gemcitabine in cultured human pancreatic cell lines
Authors: Satoko Adachi, Satoshi Kokura, Takeshi Ishikawa, Tetsuro Yamane, Tomohisa Takagi, Osamu Handa, Yuji Naito, Norimasa Yoshida, Toshikazu Yoshikawa
Journal: Cancer Research (2007)

4582    Background and Aim:  The transcription factor NF-κB is constitutively activated in many human cancers, and induces the expression of multiple genes including COX-2, VEGF, and IAP. Therefore, the blocking of NF-κB activity may be associated with the suppression of angiogenesis, and induction of apoptosis. It is also reported that NF-κB is further activated by chemotherapy in some cancer cell lines and NF-κB activation is one of mechanisms by which tumors are induced to become resistant to chemotherapy. Thus, it is expected that the blocking of NF-κB could attenuate the tumor growth, and enhance the anti-tumor effect of chemotherapeutic compounds. In this study, we examined the relevance of NF-κB in the resistance of pancreatic carcinoma cell lines against for gemcitabine. We and other groups reported that hyperthermia-induced Hsp70 could inhibit Ikk, resulting in the inhibition of NF-κB activation. Therefore, we speculated that the activated NF-κB in pancreatic cell line might be inhibited by hyperthermia, resulting in the enhancement of gemcitabine-induced cytotoxicity.  Methods:  We used human pancreatic carcinoma cell lines, AsPC-1 and MIAPaCa-2. AsPC-1 and MIAPaCa-2 were treated with various concentration (0, 5, 10, 20 and 30μM) of gemcitabine for 24 hours. Hyperthermia (43 degrees Celsius 1hr) was combined with gemcitabine at the various timing. The effect of gemcitabine and heat treatment on cell survival was determined by WST-8 assay. The status of NF-κB in carcinoma cells exposed to gemcitabine was investigated by EMSA and immunocytochemistry. We analyzed apoptosis and necrosis in AsPC-1 and MIAPaCa-2 by flow cytometry. Furthermore the levels of Hsp70, cyclin D1, caspase-3, VEGF in each treatment group were detected by Western bloting.   Results:   1) A significant cytotoxicity was observed with gemcitabine. 2) Gemcitabine activated NF-κB binding activity in both cell lines. 3) Hyperthermia inhibited the gemcitabine-induced activation of NF-κB. 4) Hyperthermia enhanced the cytotoxicity of gemcitabine especially when hyperthermia was performed 24hr before the treatment of gemcitabine.5) The levels of Hsp70 was increased by hyperthermia. Gemcitabine did not affect the protein level of Hsp70. The levels of pre-caspase-3 were decreased by hyperthermia combined with gemcitabine.   Conclusions:  Hyperthermia inhibited gemcitabine-induced activation of NF-κB, resulting in the enhancement of the cytotoxicity of gemcitabine. It is important to investigate the schedule-dependency of hyperthermia combined with gemcitabine.