tbuckley/cabot-search huggingface dataset:
Trends in the Risks and Benefits to Patients With Cancer in Phase 1 Clinical Trials—Reply
Authors: Thomas G. Roberts, Bernardo H. Goulart, Jeffrey W. Clark, Bruce A. Chabner
Journal: JAMA (2005)

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Re: Alcohol Dehydrogenase 3 Genotype and Risk of Oral Cavity and Pharyngeal Cancers
Authors: C. Bouchardy, C. Coutelle, P. J. Ward, P. Dayer, S. Benhamou
Journal: JNCI Journal of the National Cancer Institute (1998)

eters (1).Any one of these devices can be combined with the transjugular intrahepatic portal vein catheter technique.This hypothesis seems to us worthy of testing in clinical trials.
959 HEPATIC ADENOMAS AND OBESITY: PRESENTATION, CLINICAL SPECTRUM, AND MANAGEMENT
Authors: C. Bunchorntavakul, R. Bahirwani, D. Drazek, M. Soulen, E. Siegelman, E. Furth, K. OlthofP, A. Shaked, R.K. Reddy
Journal: Journal of Hepatology (2011)
Pioglitazone Enhances Cytokine-Induced Apoptosis in Vascular Smooth Muscle Cells and Reduces Intimal Hyperplasia
Authors: Yoshiaki Aizawa, Jun-ichi Kawabe, Naoyuki Hasebe, Naohumi Takehara, Kenjiro Kikuchi
Journal: Circulation (2001)

Background Cytokines induce apoptosis in vascular disease lesions through enhancement of inducible nitric oxide (NO) synthase (iNOS) activation. The thiazolidinediones, novel insulin-sensitizing agents, have been demonstrated to modulate cytokine-induced NO production. We have investigated the role of pioglitazone in the apoptosis of vascular smooth muscle cells (VSMCs) in vitro and developed intimal hyperplasia in vivo. Methods and Results Pioglitazone (0.1 to 10 μmol/L) significantly enhanced cytokine-induced expression of iNOS and NO production in a dose-dependent manner in rat VSMCs, but 15-deoxy-Δ 12,14 -prostaglandin J2 (up to 10 μmol/L), a native peroxisome proliferator-activated receptor-γ ligand, showed no effect. Pioglitazone also significantly enhanced reduction of cell viability, as evidenced by the increase in the number of TUNEL-positive cells. All of these effects of pioglitazone were blocked by treatment with N -monomethyl- l -arginine, an NO synthesis inhibitor. In an in vivo study with a balloon-injured rat carotid artery, neointimal thickness had reached maximum levels at 2 weeks after injury. Then, rats were fed with or without pioglitazone (3 mg · kg −1 · d −1 ) for an additional week. The ratio of intima to media area of carotid artery was significantly decreased by 30%, and the ratio of apoptotic cells in neointima was significantly increased in pioglitazone-treated rats compared with vehicle-treated control rats. Conclusions Pioglitazone enhanced apoptosis in an NO-dependent manner in cytokine-activated VSMCs and induced significant regression of intimal hyperplasia in balloon-injured rat carotid artery. It appears that pioglitazone is a potent apoptosis inducer in vascular lesions, providing a novel pharmacological strategy to prevent restenosis after vascular intervention.
Expression of Adipose Differentiation-Related Protein: A Predictor of Cancer-Specific Survival in Clear Cell Renal Carcinoma
Authors: Masahiro Yao, Ying Huang, Koichi Shioi, Keiko Hattori, Takayuki Murakami, Noboru Nakaigawa, Takeshi Kishida, Yoji Nagashima, Yoshinobu Kubota
Journal: Clinical Cancer Research (2007)

Abstract Purpose: We recently found that adipose differentiation-related protein (ADFP) is a potential diagnostic and prognostic biomarker for clear cell subtype renal cell carcinoma (RCC). To further evaluate the correlation between ADFP expression levels and clinicopathologic characteristics and patient outcome, we retrospectively examined patients with clear cell RCC. Experimental Design: A series of 432 consecutive patients with sporadic clear cell RCC who underwent nephrectomy between March 1986 and June 2004 were enrolled in the study. ADFP expression levels in the primary tumors and in 18 metastases were measured by real-time quantitative PCR. The clinicopathologic and prognostic data were collected, as well as the von Hippel-Lindau disease (VHL) gene alteration status in selected cases. Results: ADFP expression was apparently high in cases without a symptomatic presentation, as well as in cases of low-stage, low-grade, or VHL alteration–positive clear cell RCC, whereas it was down-regulated in undifferentiated tumors with a spindle/pleomorphic component or metastatic lesions. Univariate analyses showed that high ADFP expression was associated with better cancer-specific survival and cancer-free survival. Further Cox multivariate analyses combined with the split-sample validation method showed that ADFP expression still remains an independent predictor for cancer-specific survival in all tumor stages and in advanced metastatic cases, whereas the predictive value of ADFP expression for cancer recurrence is rather weak. Conclusions: The ADFP expression may represent the tumor differentiation status, and the detection of the expression levels provides useful prognostic information for cancer-specific survival in patients with clear cell RCC.
Onward and upward
Authors: John Collins, Felice Petraglia
Journal: Human Reproduction Update (2013)

As Human Reproduction Update changes its Editor-in-Chief with the first issue of 2013, it is an apt time to reflect on the history of this journal and project plans for a strong future. Human Reproduction Update is a review journal which is owned by ESHRE, a large professional society, and published by Oxford University Press (OUP), a highly respected academic publisher. As a review journal it aims to provide comprehensive, authoritative, up-to-date and balanced information, primarily for the scientific community. Another task for a review journal which is owned by a professional society is to provide an educational service to its members and other readers. The Journal scope covers basic, transitional and clinical topics related to reproduction. This includes all the relevant areas of reproductive genetics, epidemiology, endocrinology and immunology. Reviews on mechanisms of action of hormones and regulatory molecules in female and male reproductive axis functions and pathologies, as well as on diagnostic and therapeutic topics in reproductive medicine, are welcome. In 2005 the types of reviews in the journal were summarized by two former Editors as follows:
Randomized Phase III Trial of Paclitaxel, Etoposide, and Carboplatin Versus Carboplatin, Etoposide, and Vincristine in Patients With Small-Cell Lung Cancer
Authors: Martin Reck, Joachim von Pawel, Hans-Nicolas Macha, Eckhard Kaukel, Karl-Matthias Deppermann, Reiner Bonnet, Kurt Ulm, Sybill Hessler, Ulrich Gatzemeier
Journal: JNCI Journal of the National Cancer Institute (2003)

Background: Paclitaxel administered in combination with a topoisomerase-II inhibitor (such as etoposide) and carboplatin is an effective and safe first-line treatment for patients with small-cell lung cancer (SCLC). We conducted a randomized phase III multicenter trial to determine whether paclitaxel plus etoposide plus carboplatin improves the outcome of patients with primary SCLC relative to standard chemotherapy (carboplatin, etoposide, and vincristine). Methods: Between January 1998 and December 1999, 614 patients with SCLC stages I–IV were randomly assigned to the standard arm (309 patients) or the experimental arm (305 patients). Treatment courses were repeated every 21 days for a maximum of six courses. All patients were evaluated for response rate, survival, and toxicities every two courses. The primary endpoint was survival. Survival curves were estimated with the Kaplan–Meier method and compared using the log-rank test. All statistical tests were two-sided. Results: A total of 608 patients were evaluable for all endpoints (standard arm 307 patients, experimental arm 301 patients). The hazard ratio [HR] of death for patients receiving the standard treatment was statistically significantly higher than that for patients receiving the experimental treatment (HR = 1.22, 95% confidence interval [CI] = 1.03 to 1.45; P = .024). Progression-free survival was also statistically significantly shorter for patients in the standard arm relative to that of patients in the experimental arm (HR = 1.21, 95% CI = 1.03 to 1.42). There were no differences in the response rates (complete and partial combined) to the treatments (standard arm: 69.4%, 95% CI = 63.9% to 74.5%; experimental arm: 72.1%, 95% CI = 66.7% to 77.1%; difference = 2.7%, 95% CI = 4.5% to 9.9%). Rates of severe grade of anemia, leukocytopenia, neutropenia, and thrombocytopenia were lower in the experimental arm than in the standard arm. Conclusion: Patients with previously untreated SCLC who received paclitaxel, etoposide, and carboplatin showed improved overall and progression-free survival and less frequent hematologic toxicities than those who received the standard therapy.
Enhanced Expression of Asparagine Synthetase under Glucose-Deprived Conditions Protects Pancreatic Cancer Cells from Apoptosis Induced by Glucose Deprivation and Cisplatin
Authors: Hongyan Cui, Stephanie Darmanin, Mitsuteru Natsuisaka, Takeshi Kondo, Masahiro Asaka, Masanobu Shindoh, Fumihiro Higashino, Junji Hamuro, Futoshi Okada, Masataka Kobayashi, Koji Nakagawa, Hideyuki Koide, Masanobu Kobayashi
Journal: Cancer Research (2007)

Although hypovasculature is an outstanding characteristic of pancreatic cancers, the tumor cells survive and proliferate under severe hypoxic, glucose-deprived conditions caused by low blood supply. It is well known that the hypoxia-inducible factor-1 pathway is essential for the survival of pancreatic cancer cells under hypoxic conditions. To discover how pancreatic cancer cells adapt to glucose deprivation as well as hypoxia, we sought glucose deprivation-inducible genes by means of a DNA microarray system. We identified 63 genes whose expression was enhanced under glucose-deprived conditions at >2-fold higher levels than under normal glucose conditions. Among these genes, asparagine synthetase (ASNS) was studied in detail. Although it is known to be associated with drug resistance in leukemia and oncogenesis triggered by mutated p53, its function is yet to be determined. In this study, we found that glucose deprivation induced the overexpression of ASNS through an AMP-activated protein kinase-independent and activating transcription factor-4-dependent manner and that ASNS protects pancreatic cancer cells from apoptosis induced by glucose deprivation itself. ASNS overexpression also induced resistance to apoptosis triggered by cisplatin [cis-diammine-dichloroplatinum (CDDP)] and carboplatin, but not by 5-fluorouracil, paclitaxel, etoposide, or gemcitabine. We show that glucose deprivation induces the activation of c-jun NH(2)-terminal kinase (JNK)/stress-activated protein kinase (SAPK) in a mock transfectant but not in an ASNS transfectant. Consequently, an inhibitor of JNK/SAPK decreased the sensitivity of pancreatic cancer cells to apoptosis by glucose deprivation and CDDP. These results strongly suggest that ASNS is induced by glucose deprivation and may play a pivotal role in the survival of pancreatic cancer cells under glucose-deprived conditions.
IMMUNOFLUORESCENCE PATTERNS IN DERMATITIS HERPETIFORMIS.
Authors: K. HOLUBAR, MAJA DORALT, G. EGGERTH
Journal: British Journal of Dermatology (1971)

Summary.— An attempt has been made to detect Ig deposits in skin and upper intestinal mucosa, and circulating antibodies in the serum, of patients with dermatitis herpetiformis. Deposits containing IgA and complement (C3’) were traced in the lesional skin of 11 of 12 patients. One patient wbo was free of skin symptoms failed to exhibit similar findings. Specimens of upper intestinal mucosa (9 patients), did not show a similar pattern of junctional IF; however a marked flattening of the mucosal relief was observed in 6 patients. Circulating antibodies against junctional antigens of skin or jejunal tissue were not demonstrated.
Spontaneous hypoglycaemia and pleural fibroma: role of insulin like growth factors.
Authors: N E Moat, J D Teale, R E Lea, A W Matthews
Journal: Thorax (1991)

Spontaneous hypoglycaemia was the presenting feature of a man with a large subpleural fibroma. Preoperative and postoperative studies support the view that the tumour induced hypoglycaemia was due to the secretion of peptide hormones by the tumour.
Origin of Colorectal Cancers in Hyperplastic Polyps and Serrated Adenomas: Another Truism Bites the Dust
Authors: S. R. Hamilton
Journal: JNCI Journal of the National Cancer Institute (2001)

After considerable debate in the medical literature about the existence of de novo cancer and the classification of colorectal polyps and their relationship to cancer (4), the concept of the adenoma–carcinoma sequence emerged in the 1970s as the dominant morphogenetic explanation of colorectal cancer (5). The hyperplastic polyp was recognized as a frequently occurring lesion, but common knowledge held that its only importance resided in the need to distinguish it from the adenoma because the hyperplastic polyp was regarded as having no malignant
Gall bladder function after endoscopic sphincterotomy.
Authors: L A Desa, P A Grace, M N Vipond, B Henderson, J N Thompson
Journal: BMJ (1990)

Endoscopic sphincterotomy with extraction of the stones is often the only treatment for stones in the bile duct in patients considered unfit for surgery.Most of these patients fare well even when they have stones in the gall bladder; cholecystectomy for biliary colic, acute cholecystitis, or jaundice was necessary in less than 15% followed up for up to seven years. 2 After the procedure patients retain their gall bladder and have an incompetent lower bile duct sphincter; little is known
Sodium taurocholate cotransporting polypeptide is a serine, threonine phosphoprotein and is dephosphorylated by cyclic adenosine monophosphate
Authors: Sunil Mukhopadhyay, M. Ananthanarayanan, Bruno Stieger, Peter J. Meier, Frederick J. Suchy, Sawkat M. Anwer
Journal: Hepatology (1998)

Na + /taurocholate (Na + /TC) cotransport in hepatocytes is mediated primarily by Na + /TC cotransporting polypeptide (Ntcp), and cyclic adenosine monophosphate (cAMP) stimulates Na + /TC cotransport by inducing translocation of Ntcp to the plasma membrane. The aim of the present study was to determine if Ntcp is a phosphoprotein and if cAMP alters Ntcp phosphorylation. Freshly prepared hepatocytes from rat livers were incubated with carrier–free 32 PO 4 for 2 hours, followed by incubation with 10 μmol/L 8–chlorophenylthio adenosin 3′:5′–cyclic monophosphate (CPT–cAMP) for 15 minutes. Subcellular fractions isolated from 32 P–labeled hepatocytes were subjected to immunoprecipitation using Ntcp antibody, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS–PAGE) and autoradiography to determine if Ntcp is phosphorylated. Ntcp immunoprecipitated from plasma membranes isolated from nonlabeled hepatocytes was subjected to immunoblot analysis using anti–phosphoserine, anti–phosphothreonine, or anti–phosphotyrosine antibody to determine whether Ntcp is a serine, threonine, or tyrosine phosphoprotein. Hepatocytes were loaded with bis–(2–amino–5–methylphenoxy)–ethane– N , N , N ′, N ′–tetraacetic acid (MAPTA), a Ca 2+ buffering agent, and the effect of CPT–cAMP on TC uptake, cytosolic [Ca 2+ ], and ntcp phosphorylation and translocation was determined. In addition, the effect of cAMP on protein phosphatases 1 and 2A (PP1/2A) was determined in homogenates and plasma membranes obtained from CPT–cAMP-treated hepatocytes. Phosphorylation study showed that phosphorylated Ntcp is detectable in plasma membranes, and cAMP treatment resulted in dephosphorylation of Ntcp. Immunoblot analysis with phosphoamino antibodies revealed that Ntcp is a serine/threonine, and not a tyrosine, phosphoprotein, and cAMP inhibited both serine and threonine phosphorylation. In MAPTA–loaded hepatocytes, CPT–cAMP failed to stimulate TC uptake, failed to increase cytosolic [Ca 2+ ], and failed to induce translocation and dephosphorylation of Ntcp. cAMP did not alter the activity of PP1/2A in either homogenates or in plasma membranes. Taken together, these results suggest that Ntcp is a serine/threonine phosphoprotein and is dephosphorylated by cAMP treatment. Activation of PP1/2A is not involved in cAMP–mediated dephosphorylation of Ntcp. Both translocation and dephosphorylation of Ntcp may be involved in the regulation of hepatic Na + /TC cotransport.
Development and Applications of Lectins as Biological Tools in Biomedical Research
Authors: Xiuli Dan, Wenlong Liu, Tzi Bun Ng
Journal: Medicinal Research Reviews (2015)

Abstract As a new and burgeoning area following genomics and proteomics, glycomics has become a hot issue due to its pivotal roles in many physiological and pathological processes. Glycans are much more complicated than genes or proteins since glycans are highly branched and dynamic. Antibodies and lectins are the two major molecular tools applied for glycan profiling. Though the study of antibodies and lectins started at almost the same time in 1880s, lectins gained much less attention than the antibodies until recent decades when the importance and difficulties of glycomics were realized. The present review summarizes the discovery history of lectins and their biological functions with a special emphasis on their various applications as biological tools. Both older techniques that had been developed in the last century and new technologies developed in recent years, especially lectin microarrays and lectin‐based biosensors, are included in this account.
Colchicine alters the quantitative and qualitative display of selectins on endothelial cells and neutrophils.
Authors: B N Cronstein, Y Molad, J Reibman, E Balakhane, R I Levin, G Weissmann
Journal: Journal of Clinical Investigation (1995)

Since colchicine-sensitive microtubules regulate the expression and topography of surface glycoproteins on a variety of cells, we sought evidence that colchicine interferes with neutrophil-endothelial interactions by altering the number and/or distribution of selectins on endothelial cells and neutrophils. Extremely low, prophylactic, concentrations of colchicine (IC50 = 3 nM) eliminated the E-selectin-mediated increment in endothelial adhesiveness for neutrophils in response to IL-1 (P < 0.001) or TNF alpha (P < 0.001) by changing the distribution, but not the number, of E-selectin molecules on the surface of the endothelial cells. Colchicine inhibited stimulated endothelial adhesiveness via its effects on microtubules since vinblastine, an agent which perturbs microtubule function by other mechanisms, diminished adhesiveness whereas the photoinactivated colchicine derivative gamma-lumicolchicine was inactive. Colchicine had no effect on cell viability. At higher, therapeutic, concentrations colchicine (IC50 = 300 nM, P < 0.001) also diminished the expression of L-selectin on the surface of neutrophils (but not lymphocytes) without affecting expression of the beta 2-integrin CD11b/CD18. In confirmation, L-selectin expression was strikingly reduced (relative to CD11b/CD18 expression) on neutrophils from two individuals who had ingested therapeutic doses of colchicine. These results suggest that colchicine may exert its prophylactic effects on cytokine-provoked inflammation by diminishing the qualitative expression of E-selectin on endothelium, and its therapeutic effects by diminishing the quantitative expression of L-selectin on neutrophils.
STUDIES ON RENAL JUXTAGLOMERULAR CELLS
Authors: Phyllis Merritt Hartroft, W. Stanley Hartroft
Journal: The Journal of Experimental Medicine (1953)

Accumulation of granules in the juxtaglomerular cells occurred in rats which were maintained for 5 to 6 weeks on a diet low in sodium, chloride. Cytological evidence suggests that this was probably a storage phase of secretion following a decrease in the rate of liberation of the granules. Administration of DCA (desoxycorticosterone acetate) to salt-deficient rats did not alter this appearance of the juxtaglomerular cells. Two per cent sodium chloride taken in the drinking water consumed for 4 weeks by similar animals caused degranulation of the juxtaglomerular cells. This effect was enhanced by DCA. DCA administered to animals on a normal salt intake produced a lesser degree of degranulation. Cytological changes in degranulated cells suggested that these represent a stage of hyperactivity in the secretory cycle produced by an increase in the rate of liberation of granules. A hypothesis is suggested that the juxtaglomerular cells are involved in the hormonal regulation of sodium metabolism and/or blood pressure.
CD4+CD25+ Regulatory T Cells Can Mediate Suppressor Function in the Absence of Transforming Growth Factor β1 Production and Responsiveness
Authors: Ciriaco A. Piccirillo, John J. Letterio, Angela M. Thornton, Rebecca S. McHugh, Mizuko Mamura, Hidekazu Mizuhara, Ethan M. Shevach
Journal: The Journal of Experimental Medicine (2002)

CD4(+)CD25(+) regulatory T cells inhibit organ-specific autoimmune diseases induced by CD4(+)CD25(-) T cells and are potent suppressors of T cell activation in vitro. Their mechanism of suppression remains unknown, but most in vitro studies suggest that it is cell contact-dependent and cytokine independent. The role of TGF-beta1 in CD4(+)CD25(+) suppressor function remains unclear. While most studies have failed to reverse suppression with anti-transforming growth factor (TGF)-beta1 in vitro, one recent study has reported that CD4(+)CD25(+) T cells express cell surface TGF-beta1 and that suppression can be completely abrogated by high concentrations of anti-TGF-beta suggesting that cell-associated TGF-beta1 was the primary effector of CD4(+)CD25(+)-mediated suppression. Here, we have reevaluated the role of TGF-beta1 in CD4(+)CD25(+)-mediated suppression. Neutralization of TGF-beta1 with either monoclonal antibody (mAb) or soluble TGF-betaRII-Fc did not reverse in vitro suppression mediated by resting or activated CD4(+)CD25(+) T cells. Responder T cells from Smad3(-/-) or dominant-negative TGF-beta type RII transgenic (DNRIITg) mice, that are both unresponsive to TGF-beta1-induced growth arrest, were as susceptible to CD4(+)CD25(+)-mediated suppression as T cells from wild-type mice. Furthermore, CD4(+)CD25(+) T cells from neonatal TGF-beta1(-/-) mice were as suppressive as CD4(+)CD25(+) from TGF-beta1(+/+) mice. Collectively, these results demonstrate that CD4(+)CD25(+) suppressor function can occur independently of TGF-beta1.