tbuckley/cabot-search huggingface dataset:
Abstract 450: Smad interacting protein 1 (SIP1) is associated with peritoneal carcinomatosis in intestinal type gastric cancer
Authors: Yoshinaga Okugawa, Koji Tanaka, Yasuhiro Inoue, Mikio Kawamura, Kouhei Matsushita, Aya Kawamoto, Junichro Hiro, Susumu Saigusa, Yuji Toiyama, Masaki Ohi, Keiichi Uchida, Yasuhiko Mohri, Hiroki Hori, Masato Kusunoki
Journal: Cancer Research (2012)

Abstract Purpose. Smad interacting protein 1 (SIP1) encodes a transcription factor and is one of the epithelial-mesenchymal transition (EMT)-inducible genes that play a key role in tumor progression in various cancers. The aim of this study is to clarify the clinical significance of SIP1 expression in gastric cancer patients, and to clarify its biological function especially in intestinal type gastric cancer. Methods. We studied one hundred thirty-four patients undergoing surgery for gastric cancer. We analyzed SIP1 mRNA levels by real-time reverse transcription PCR in gastric cancer tissue and adjacent normal mucosa, and in gastric cancer cell lines. SIP1 protein expression in primary cancer and in peritoneal dissemination samples was measured using immunohistochemical analysis. Knockdown of the SIP1 gene by siRNA transfection was performed to evaluate SIP1 function in gastric cancer cell. Results. Expression of the SIP1 gene was significantly higher in cancerous tissue than in adjacent normal mucosa (p&amp;lt;0.05). Increased SIP1 expression was significantly associated with peritoneal dissemination (p&amp;lt;0.05), and was an independent prognostic factor (risk ratio, 2.17; 95% confidence interval, 1.26-3.74; p&amp;lt;0.05). Logistic regression analysis revealed that increased SIP1 expression was an independent risk factor for peritoneal dissemination (odds ratio, 3.43; 95% confidence interval, 1.25-9.43; p&amp;lt;0.05). Especially in intestinal type gastric cancer, elevated SIP1 expression was significantly correlated with peritoneal dissemination and poor prognosis (p&amp;lt;0.05). Immunohistochemical analysis indicated that SIP1 was intensely expressed in both primary cancer and peritoneal dissemination samples. In vitro, cell proliferation, migration and invasion were inhibited by SIP1 knockdown, while resistance to anoikis was decreased after knockdown of SIP1 in the intestinal type gastric cancer cell line MKN7. Conclusion: High SIP1 expression is associated with poor prognosis especially in intestinal type gastric cancer patients and enhanced malignant potential in terms of proliferation, migration, invasion and anoikis inhibition in intestinal type gastric cacner cell. These results indicate that SIP1 plays an important role in progression to peritoneal carcinomatosis in intestinal type gastric cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 450. doi:1538-7445.AM2012-450
Epidemiology and long term prognosis of hepatitis C virus infection in Japan.
Authors: M Yano, H Yatsuhashi, O Inoue, K Inokuchi, M Koga
Journal: Gut (1993)

In Japanese blood donors, positivity for antibodies to hepatitis C virus (HCV) ranges from 0.2% in subjects under 20 to 3.9% in those over 50 years. It is estimated that at least 2.3 million Japanese have contracted HCV infection through contaminated blood. HCV carrier state was confirmed by polymerase chain reaction for HCV-RNA in subjects positive for antibodies to more than one viral protein (70% of cases). Subjects positive for core antibody alone, however, were found to be HCV-RNA negative with normal liver function, and are considered to have only a past history of HCV infection (30% of cases). Acute hepatitis C progresses to chronic infection in about 90% of cases. In comparison with hepatitis B, chronic hepatitis C leads more frequently to cirrhosis and liver cancer, and rarely remits spontaneously. In typical HCV infection, aminotransferase activities fluctuate markedly in the early stages, then become relatively stable for 10 years or more, with chronic persistent hepatitis shown by histological examination. Thereafter, aminotransferase activities may change dramatically, with progression to chronic active hepatitis and rapid development of cirrhosis and hepatocellular carcinoma. On average, it takes about 30 years for chronic hepatitis C to progress from initial infection to cirrhosis and cancer, but the disease progresses much more rapidly in elderly patients.
Benefits of omalizumab as add‐on therapy in patients with severe persistent asthma who are inadequately controlled despite best available therapy (GINA 2002 step 4 treatment): INNOVATE
Authors: M. Humbert, R. Beasley, J. Ayres, R. Slavin, J. Hébert, J. Bousquet, K.‐M. Beeh, S. Ramos, G. W. Canonica, S. Hedgecock, H. Fox, M. Blogg, K. Surrey
Journal: Allergy (2004)

Patients with severe persistent asthma who are inadequately controlled despite Global Initiative for Asthma (GINA) 2002 step 4 therapy are a challenging population with significant unmet medical need. We determined the effect of omalizumab on clinically significant asthma exacerbations (requiring systemic corticosteroids) in the first omalizumab study to exclusively enrol patients from this difficult-to-treat patient population.Following a run-in phase, patients (12-75 years) inadequately controlled despite therapy with high-dose inhaled corticosteroids (ICS) and long-acting beta(2)-agonists (LABA) with reduced lung function and a recent history of clinically significant exacerbations were randomized to receive omalizumab or placebo for 28 weeks in a double-blind, parallel-group, multicentre study.A total of 419 patients were included in the efficacy analyses. The clinically significant asthma exacerbation rate (primary efficacy variable), adjusted for an observed relevant imbalance in history of clinically significant asthma exacerbations, was 0.68 with omalizumab and 0.91 with placebo (26% reduction) during the 28-week treatment phase (P = 0.042). Without adjustment, a similar magnitude of effect was seen (19% reduction), but this did not reach statistical significance. Omalizumab significantly reduced severe asthma exacerbation rate (0.24 vs 0.48, P = 0.002) and emergency visit rate (0.24 vs 0.43, P = 0.038). Omalizumab significantly improved asthma-related quality of life, morning peak expiratory flow and asthma symptom scores. The incidence of adverse events was similar between treatment groups.In patients with inadequately controlled severe persistent asthma, despite high-dose ICS and LABA therapy, and often additional therapy, omalizumab significantly reduced the rate of clinically significant asthma exacerbations, severe exacerbations and emergency visits. Omalizumab is effective and should be considered as add-on therapy for patients with inadequately controlled severe persistent asthma who have a significant unmet need despite best available therapy.
Pallidotomy relieves some symptoms of Parkinson's disease
Authors: D. Josefson
Journal: BMJ (2000)

Posteroventral medial pallidotomy can provide long term relief from many of the debilitating symptoms of Parkinson's disease, but it does not improve others and is not without side effects, according to a study by physicians at the University of Toronto, Canada (New England Journal of Medicine 2000:342;1708-14).

Pallidotomy is a surgical procedure in which overactive dopaminergic neurons in a portion of the basal ganglia, the globus pallidus, are ablated in an effort to reduce the tremors and dyskinesias of Parkinson's …
Flavonoids as aryl hydrocarbon receptor agonists/antagonists: effects of structure and cell context.
Authors: Shu Zhang, Chunhua Qin, Stephen H Safe
Journal: Environmental Health Perspectives (2003)

Chemoprotective phytochemicals exhibit multiple activities and interact with several cellular receptors, including the aryl hydrocarbon (Ah) receptor (AhR). In this study we investigated the AhR agonist/antagonist activities of the following flavonoids: chrysin, phloretin, kaempferol, galangin, naringenin, genistein, quercetin, myricetin, luteolin, baicalein, daidzein, apigenin, and diosmin. We also investigated the AhR-dependent activities of cantharidin and emodin (in herbal extracts) in Ah-responsive MCF-7 human breast cells, HepG2 human liver cancer cells, and mouse Hepa-1 cells transiently or stably transfected with plasmids expressing a luciferase reporter gene linked to multiple copies of a consensus dioxin-responsive element. The AhR agonist activities of the compounds (1 and 10 micro M) were as high as 25% of the maximal response induced by 5 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and their potencies were dependent on cell context. Galangin, genistein, daidzein, and diosmin were active only in Hepa-1 cells, and cantharidin induced activity only in human HepG2 and MCF-7 cells. Western blot analysis confirmed that baicalein and emodin also induced CYP1A1 protein in the human cancer cell lines. The AhR antagonist activities of four compounds inactive as agonists in MCF-7 and HepG2 cells (kaempferol, quercetin, myricetin, and luteolin) were also investigated. Luteolin was an AhR antagonist in both cell lines, and the inhibitory effects of the other compound were dependent on cell context. These data suggest that dietary phytochemicals exhibit substantial cell context-dependent AhR agonist as well as antagonist activities. Moreover, because phytochemicals and other AhR-active compounds in food are present in the diet at relatively high concentrations, risk assessment of dietary toxic equivalents of TCDD and related compounds should also take into account AhR agonist/antagonist activities of phytochemicals.
Enflurane Hepatotoxicity
Authors: JAMES H. LEWIS
Journal: Annals of Internal Medicine (1983)

Analysis of 24 cases of enflurane anesthesia-associated hepatic injury shows that the clinical, biochemical, and histologic features are similar to those seen with halothane- and methoxyflurane-related hepatitis. Postoperative fever was the presenting symptom in 19 patients. Jaundice occurred in 19 patients after a mean latent period of 8 days. Sixteen patients had been previously exposed to enflurane or halothane, and the latent period from exposure to the onset of symptoms or jaundice was shortened in these patients. There were five fatalities among the entire group. Liver biopsy most characteristically showed centrilobular necrosis, occasionally with ballooning degeneration and fatty change. The presumed mechanism of injury is metabolic idiosyncracy, and prior exposure to a haloalkane anesthetic may increase the risk of hepatic injury after enflurane administration.
REPORT OF PROGRESS IN DEVELOPING A MENTAL HYGIENE COMPONENT OF A CITY HEALTH DISTRICT
Authors: PAUL LEMKAU, CHRISTOPHER TIETZE, MARCIA COOPER
Journal: American Journal of Psychiatry (1941)

1. Progress in attaining the objectives of a mental hygiene component in a city health district is reported. 2. The 1933 survey indicates that 25 per cent of all psychotics in the district are not hospitalized. 3. Personality disorder of varying severity but sufficient to attract attention by the community is present in about two per cent of the population. 4. Methods of prophylactic work in connection with a well baby clinic of a city health department are outlined. 5. The properly educated public health nurse can be an excellent agent for the dissemination of knowledge of mental hygiene principles.
Abstract 705: HER2 assessment to define outcomes for breast cancer patients treated with neoadjuvant therapy
Authors: Huan Cheng, Yalai Bai, Willliam Sikov, Natalie Sinclair, Maysa Abu-Khalaf, Lyndsay N. Harris, David L. Rimm
Journal: Cancer Research (2012)

Abstract Background: HER2 expression or amplification is now an established companion diagnostic test. Now, as HER2-targeting neoadjuvant therapy for breast cancer increases, the accuracy of the companion diagnostic tests are revisited. Specifically, we seek to determine with the level of expression of the target (HER2 protein) is associated with pathologic response. In this study, we quantitatively assess HER2 expression both before and after the neoadjuvant therapies to breast cancer in the BrUOG BR-211B (NCT00617942) trial. Methods: We evaluated core biopsy samples from breast cancer patients enrolled in a preoperative clinical trial using trastuzumab, nab-paclitaxel and carboplatin combination therapy. Tumor core biopsies were taken before and after 10 days of either trastuzumab or nab-paclitaxel treatment. Combination chemotherapy was given for 6 cycles. Automated quantitative analysis (AQUA), a fluorescent-based method for analysis of in situ protein expression, was used to assess HER2 and phospho-HER2 expression in the BruOG Cohort, a study where patients who serially received Herceptin and Abraxane were biopsied both before and after treatment. This study assesses the HER2 positive patient subset (n=27) Results: Of 18 evaluable patients, the 8 with a PathCR showed a mean HER2 levels of 10251 compared with 4766 in the patients without PathCR (p=0.0047). This is notable in that a HER2 score of 2000 is equivalent to HER2 2+ in previous studies. Measurement of Phospho-HER2 showed no difference in PathCR vs Non-PathCR groups. A small subset (9) cases were measured for HER2 immediately after treatment, but the study has accrued an insufficient number of cases to statistically determine if there is a reduction in HER2 immediately following treatment. Conclusions: High levels of HER2 are associated with PathCR in the neoadjuvant setting. Levels of Phospho-HER2 are not associated with response. Further studies are underway to determine changes in levels of HER2 immediately after treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 705. doi:1538-7445.AM2012-705
Mechanism of Improved Cardiac Function After Bone Marrow Mononuclear Cell Therapy
Authors: Chang-Hwan Yoon, Masamichi Koyanagi, Kazuma Iekushi, Florian Seeger, Carmen Urbich, Andreas M. Zeiher, Stefanie Dimmeler
Journal: Circulation (2010)

Cell therapy is a promising option to improve functional recovery after ischemia. Several subsets of bone marrow-derived cells were shown to reduce infarct size and increase ejection fraction in experimental models of ischemia. The mechanisms underlying the functional improvement are diverse and have been shown to include paracrine effects of the injected cells, as well as a variable degree of differentiation to endothelial cells, pericytes, smooth muscle, and cardiac muscle.To elucidate the true nature of such plasticity and contribution to recovery, we engineered vectors that encoded inducible suicide genes under the control of endothelium (endothelial nitric oxide synthase)-, smooth muscle (SM22alpha)-, and cardiomyocyte (alpha-MHC)-specific promoters, thereby allowing selective depletion of the individual cell lineage acquired by the transplanted undifferentiated bone marrow-derived cells. Lentivirally delivered thymidine kinase, which converts the prodrug ganciclovir into a cytotoxic agent, was used to selectively eliminate cells 2 weeks after transplantation of bone marrow mononuclear cells in an acute myocardial infarction model. We demonstrate that elimination of transplanted endothelium-committed or SM22alpha-expressing cells, but not cardiac-committed cells, induced a significant deterioration of ejection fraction. Moreover, elimination of endothelial nitric oxide synthase-expressing cells 2 weeks after injection reduced capillary and arteriole density.This study demonstrates that elimination of bone marrow mononuclear cells reexpressing endothelial nitric oxide synthase particularly induced a deterioration of cardiac function, which indicates a functional contribution of the vascular cell fate decision of human bone marrow-derived mononuclear cells in vivo.
Insulin Resistance Is Highly Prevalent and Is Associated With Reduced Exercise Tolerance in Nondiabetic Patients With Heart Failure
Authors: Matlooba A. ALZadjali, Valerie Godfrey, Faisel Khan, AnnaMaria Choy, Alexander S. Doney, Aaron K. Wong, John R. Petrie, Allan D. Struthers, Chim C. Lang
Journal: Journal of the American College of Cardiology (2009)
Resistance to Store Depletion–induced Endothelial Injury in Rat Lung after Chronic Heart Failure
Authors: Diego F. Alvarez, Judy A. King, Mary I. Townsley
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

In chronic heart failure, the lung endothelial permeability response to angiotensin II or thapsigargin-induced store depletion is ablated, although the mechanisms are not understood.To determine whether the ablated permeability response to store depletion during heart failure was due to impaired expression of store operated Ca2+ channels in lung endothelium.Heart failure was induced by aortocaval fistula in rats. Permeability was measured in isolated lungs using the filtration coefficient and a low Ca2+/Ca2+ add-back strategy to identify the component of the permeability response dependent on Ca2+ entry.In fistulas, right ventricular mass and left ventricular end diastolic pressure were increased and left ventricular shortening fraction decreased compared with shams. Thapsigargin-induced store depletion increased lung endothelial permeability in shams, but not in fistulas. Permeability increased in both groups after the Ca2+ ionophore A23187 or 14,15-epoxyeicosatrienoic acid, independent of store depletion. A diacylglycerol analog had no impact on permeability. Increased distance between the endoplasmic reticulum and the plasmalemmal membrane was ruled out as a mechanism for the loss of the permeability response to store depletion. Endothelial expression of the endoplasmic reticulum Ca2+ ATPase was not altered in fistulas compared with shams, whereas the store-operated canonical transient receptor potential channels 1, 3, and 4 were downregulated in extraalveolar vessel endothelium.We conclude that the adaptive mechanism limiting store depletion-induced endothelial lung injury in the aortocaval model of heart failure involves downregulation of store-operated Ca2+ channels.
Safety and Immunogenicity of Tyrosinase DNA Vaccines in Patients with Melanoma
Authors: Jedd D Wolchok, Jianda Yuan, Alan N Houghton, Humilidad F Gallardo, Teresa S Rasalan, Jian Wang, Yan Zhang, Rajaram Ranganathan, Paul B Chapman, Susan E Krown, Philip O Livingston, Melanie Heywood, Isabelle Riviere, Katherine S Panageas, Stephanie L Terzulli, Miguel A Perales
Journal: Molecular Therapy (2007)

Immunity to self antigens on cancer is constrained by tolerance/ignorance. DNA vaccines encoding xenogeneic differentiation antigens, such as tyrosinase (TYR), mediate tumor protection and regression in implantable mouse models, and dogs with spontaneous melanoma. We conducted a trial of mouse and human TYR DNA vaccines in stage III/IV melanoma patients. Eighteen human leukocyte antigen (HLA)-A*0201(+) melanoma patients were randomized as follows: one group received three mouse TYR DNA injections followed by three human TYR DNA injections; the other group received the same vaccines in opposite sequence. The study was conducted at three dose levels: 100, 500, and 1,500 microg DNA/injection, administered intramuscularly (IM) every 3 weeks. Most toxicities were grade 1 injection site reactions. Seven patients developed CD8(+) T-cell responses, defined by a >3 SD increase in baseline reactivity to TYR peptide in tetramer or intracellular cytokine staining (ICS) assays. There was found to be no relationship between dose, assigned schedule, and T-cell response. At a median of 42 months follow-up, median survival has not been reached. Mouse and human TYR DNA vaccines were found safe and induced CD8(+) T-cell responses in 7 of 18 patients. T cells recognizing a native TYR peptide had a phenotype consistent with that of effector memory cells.
Clinical Significance of Microscopic Melanoma Metastases in the Nonhottest Sentinel Lymph Nodes
Authors: Su Luo, Alice Z. C. Lobo, Kenneth K. Tanabe, Alona Muzikansky, Tyler Durazzo, Arthur Sober, Hensin Tsao, A. Benedict Cosimi, Donald P. Lawrence, Lyn M. Duncan
Journal: JAMA Surgery (2015)

A practice gap exists in the surgical removal of sentinel lymph nodes, from removal of only the most radioactive (hottest) lymph node to removal of all lymph nodes with radioactivity greater than 10% of the hottest lymph node.To determine the clinical significance of melanoma in sentinel lymph nodes that are not the hottest sentinel node and to determine the risk for disease progression based on sentinel lymph node status and primary tumor characteristics.Consecutive patients with cutaneous melanoma with sentinel lymph nodes resected from January 5, 2004, to June 30, 2008, with a mean follow-up of 59 months, at Massachusetts General Hospital were included in this retrospective review. The last year of follow-up was 2012. The operative protocol led to resection of all sentinel lymph nodes with radioactivity greater than 10% of the hottest lymph node. The number of lymph nodes removed, technetium-99m counts for each sentinel lymph node, presence or absence of sentinel lymph node metastases, primary tumor characteristics, disease progression, and melanoma-specific survival were recorded.Microscopic melanoma metastases in the hottest and nonhottest sentinel lymph nodes and factors that correlate with disease progression and mortality.A total of 1575 sentinel lymph nodes were analyzed in 475 patients. Ninety-one patients (19%) had positive sentinel lymph nodes. Of these, 72 (79%) had metastases in the hottest sentinel lymph node. Of 19 cases with tumor present, but not in the hottest sentinel lymph node, counts ranged from 26% to 97% of the hottest node. Progression occurred in 43% of patients with sentinel node metastasis, regardless of whether the hottest lymph node was positive. In patients with negative sentinel lymph nodes, 11% developed metastases beyond the sentinel lymph node basin and 3.4% recurred in the basin. Mitogenicity of the primary tumor was associated with mortality (odds ratio, 2.435; 95% CI, 1.351-4.391; P < .001). Removing only the hottest sentinel lymph node would have led to false-negative results in 19 of 475 (4%) of all patients and 19 of 91 patients (21%) with positive sentinel lymph nodes. The 8-year survival in patients with at least 1 positive sentinel lymph node was less than 55%. The presence of more than 1 mitosis per square millimeter in the primary cutaneous melanoma was associated with decreased survival.Microscopic melanoma metastases was associated with disease progression and mortality, whether present in the hottest sentinel lymph node or not. These observations emphasize the importance of removing the less hot nodes, addressing a practice gap in the surgical approach to patients with melanoma.