tbuckley/cabot-search huggingface dataset:
Polymorphisms and Clinical Outcome in Recurrent Ovarian Cancer Treated with Cyclophosphamide and Bevacizumab
Authors: Anne M. Schultheis, Georg Lurje, Katrin E. Rhodes, Wu Zhang, Dongyun Yang, Agustin A. Garcia, Robert Morgan, David Gandara, Sidney Scudder, Amit Oza, Hal Hirte, Gini Fleming, Lynda Roman, Heinz-Josef Lenz
Journal: Clinical Cancer Research (2008)

Abstract Purpose: This study was designed to evaluate the associations between angiogenesis gene polymorphisms and clinical outcome in ovarian cancer patients treated with low-dose cyclophosphamide and bevacizumab. Experimental Design: Seventy recurrent/metastatic epithelial ovarian cancer patients were enrolled in a phase II clinical trial. Genomic DNA was available from 53 blood samples. Polymorphisms were analyzed using the PCR-RFLP protocol. A 5′ end 33P γATP-labeled PCR protocol was used to analyze dinucleotide repeats. Results: Patients genotyped A/A or A/T for the IL-8 T-251A gene polymorphism had a statistically significant lower response rate (19%; 0%) than those homozygous T/T (50%; P = 0.006, Fisher's exact test). Patients carrying a minimum one C allele (C/C; C/T) of the CXCR2 C+785T polymorphism showed a median progression-free survival (PFS) of 7.4 months compared with the PFS of 3.7 months for those homozygous T/T (P = 0.026, log-rank test). Patients with the VEGF C+936T polymorphism C/T genotype had a longer median PFS of 11.8 months, compared with those with the C/C and T/T genotype, which had median PFS of 5.5 months and 3.2 months, respectively (P = 0.061, log-rank test). Patients carrying both AM 3′end alleles &amp;lt;14 CA repeats had the shortest median PFS of 3.4 months; patients with at least one allele &amp;gt;14 repeats or both alleles &amp;gt;14 repeats showed a median PFS of 6.4 months and 7.2 months, respectively (P = 0.008, log-rank test). Conclusion: Our data suggest that the IL-8 A-251T polymorphism may be a molecular predictor of response to bevacizumab-based chemotherapy. The CXCR2 C+785T, VEGF C+936T single nucleotide polymorphisms and the AM 3′ dinucleotide repeat polymorphisms may be molecular markers for PFS in ovarian cancer patients.
Vorapaxar in Acute Coronary Syndrome Patients Undergoing Coronary Artery Bypass Graft Surgery
Authors: David J Whellan, Pierluigi Tricoci, Edmond Chen, Zhen Huang, David Leibowitz, Pascal Vranckx, Gregary D Marhefka, Claes Held, Jose C Nicolau, Robert F Storey, Witold Ruzyllo, Kurt Huber, Peter Sinnaeve, A Teddy Weiss, Jean-Pierre Dery, David J Moliterno, Frans Van de Werf, Philip E Aylward, Harvey D White, Paul W Armstrong, Lars Wallentin, John Strony, Robert A Harrington, Kenneth W Mahaffey
Journal: Journal of the American College of Cardiology (2013)
Effect of Human Papillomavirus-16 Infection on CD8+ T-Cell Recognition of a Wild-Type Sequence p53264–272 Peptide in Patients with Squamous Cell Carcinoma of the Head and Neck
Authors: Nicky Sirianni, Patrick K. Ha, Mattias Oelke, Joseph Califano, William Gooding, William Westra, Theresa L. Whiteside, Wayne M. Koch, Jonathan P. Schneck, Albert DeLeo, Robert L. Ferris
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Wild-type sequence (wt) p53 peptides are attractive candidates for broadly applicable cancer vaccines, currently considered primarily for patients whose tumors overexpress p53. Circumstances exist, however, where increased p53 degradation may result in appreciable presentation of p53-derived peptides, despite low p53 expression. Squamous cell carcinoma of the head and neck is associated with oncogenic human papillomavirus (HPV) subtypes, which inactivate p53 through proteasomal degradation. The criterion of p53 overexpression would exclude these individuals from wt p53-based immunotherapy. Experimental Design: We tested the correlation of HPV infection with enhanced antigenicity of the p53 protein and postulated that removal of HPV-16+ tumors with enhanced p53264-272 peptide presentation might lead to a drop in T cells specific for this peptide in vivo. Circulating frequencies of T cells specific for the HLA A*0201:p53264-272 complex were measured ex vivo using dimeric HLA:peptide complexes in 15 head and neck cancer patients before and 6 months after tumor excision. Results: CD8+ T-cell recognition of HLA A*0201restricted wt p53264-272 peptide presented by HPV-16− squamous cell carcinoma of the head and neck lines was enhanced by HPV-16 E6 expression, sometimes exceeding that of a naturally transformed, HPV-16+ wt p53 expressing squamous cell carcinoma of the head and neck cell line. In patients with HPV-16− tumors, the frequency of wt p53264–272–specific T cells remained largely unchanged after tumor removal. However, a significant decline in frequency of anti-p53264–272 T cells was observed postoperatively in HPV-16+ patients (P &amp;lt; 0.005). Conclusions: Recognition of HPV-associated squamous cell carcinoma of the head and neck appears associated with levels of wt p53-specific T cells and inversely with p53 expression. p53 peptides may be useful tumor antigens for squamous cell carcinoma of the head and neck immunotherapy in addition to viral gene products.
Changes in Forelimb Weight and Segmental Vascular Resistances Following Severe Hemorrhage
Authors: George J. Grega, James M. Schwinghamer, Francis J. Haddy
Journal: Circulation Research (1971)

The forelimb was used to study capillary fluid fluxes following hemorrhage in dogs anesthetized with sodium pentobarbital. Arterial hemorrhage (48 ml/kg) and 4 hours of hypovolemia produced decreases in forelimb weight, arterial and venous pressures, and skin and skeletal muscle blood flows. Segmental resistances (large artery, small vessel, large vein) in both skin and skeletal muscle increased markedly, and the increase was either completely or largely maintained throughout the hypovolemic period. The large arteries and large veins constricted proportionately more than the small vessels following hemorrhage. In animals that survived the hypovolemic period, the large arteries and large veins constricted almost proportionately, whereas in the animals that died, the large veins constricted proportionately more than the large arteries. The weight loss exceeded forelimb vascular volume, indicating that net extravascular fluid reabsorption occurred. In fact, the weight loss from 60-240 minutes after hemorrhage began appears to be largely attributable to extravascular fluid reabsorption, since resistance and, inferentially, blood volume were relatively constant in the forelimb capacitance vessels. These data fail to support the hypothesis that fluid filtration is a determinant of irreversibility but rather suggest that the compensatory responses to blood loss in the forelimb, i.e., vasoconstriction and net extravascular fluid reabsorption, persist during severe prolonged hemorrhagic hypotension.
Low holotranscobalamin II is the earliest serum marker for subnormal vitamin B<sub>12</sub> (cobalamin) absorption in patients with AIDS
Authors: Victor Herbert, Warren Fong, Veronica Gulle, Tracy Stopler
Journal: American Journal of Hematology (1990)

Abstract In AIDS, as previously found in pernicious anemia (PA), the earliest serum marker of subnormal vitamin B 12 (cobalamin) absorption, and therefore of negative B 12 balance, is low serum holotranscobalamin II (holo‐TC II; B 12 ‐TC II) despite normal total serum B 12 level, normal serum homocysteine, and normal classic (oral free radio‐B 12 ) Schilling test. This may be accompanied by subtle and insidious damage to hematopoietic, immunologic, neuropsychiatric, nutritional and alimentary systems, confirmed by correction on therapeutic trial with B 12 therapy. Our studies suggest such selective B 12 deficiency occurs in about half of the HIV‐1 infected, in part due to frequent depression of B 12 absorption by HIV‐1 attack on the gastric mucosa and/or opportunistic infection attack on the small bowel, and in part due to a telescoping of the continuum of the stages of negative B 12 balance in relation to damage to B 12 delivery by the infective and/or systemic disease process. In AIDS, when total serum B 12 is normal despite tissue depletion of B 12 , if the classic Schilling test does not reveal subnormal food B 12 absorption, the food Schilling test does. We hypothesize that DNA‐synthesizing cells of the hematopoietic, immunologic, neurologic and other systems which have surface receptors solely for holo‐TC II, and which have low B 12 stores, rapidly become dysfunctional due to B 12 deficiency when holo‐TC II is low, while cells (such as liver cells) which also have surface receptors for holohaptocorrin (B 12 ‐haptocorrin) remain B 12 ‐replete. We believe this to be another example of the concept of selective nutrient deficiency in one cell line but not another.
The β -Adrenoceptor
Authors: MALCOLM JOHNSON
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Section:ChooseTop of pageAbstract <<THE β-ADRENOCEPTORβ-RECEPTOR COUPLING: AIRW...β22-RECEPTOR AGONISTSβ-RECEPTOR DESENSITIZATIO...POLYMORPHISM OF THE β-ADR...ReferencesCITING ARTICLES
Short- and long-term effects of cytochalasin D, paclitaxel and rapamycin on wall thickening in experimental porcine vein grafts
Authors: G MURPHY, T JOHNSON, M CHAMBERLAIN, S RIZVI, M WYATT, S GEORGE, G ANGELINI, K KARSCH, M OBERHOFF, A NEWBY
Journal: Cardiovascular Research (2006)

Neointima formation and wall thickening caused by smooth muscle cell proliferation compromise long-term patency of human aorto-coronary vein-grafts. We investigated short- and long-term effects of anti-proliferative pharmacological agents on experimental pig vein-grafts with similar dimensions and kinetics to human coronary grafts.Saphenous veins were treated for 1 h ex vivo with vehicle or concentrations of cytochalasin D, paclitaxel or rapamycin found to be anti-proliferative in preliminary studies. Vehicle and treated veins were implanted contralaterally, end-to-end into the carotid arteries of pigs. Cytochalasin D 2.5 mug/ml non-significantly reduced neointima formation in 4-week vein-grafts (mean+/-standard error, 2.5+/-0.6 vs. 3.3+/-0.6 mm2, n = 10, p = NS), whilst paclitaxel 10 microM produced significant inhibition (1.7+/-0.2 vs. 3.0+/-0.3 mm2, n = 8, p < 0.01) as did rapamycin 0.1 mg/ml (0.6+/-0.3 vs. 1.7+/-0.5 mm(2), n = 8, p < 0.02). Similar effects were found on total wall cross-sectional area but medial area was unaffected. PCNA staining of 1-week vein grafts confirmed in vivo anti-proliferative effects of paclitaxel (21+/-2 vs. 36+/-3%, n = 5, p < 0.01) and rapamycin (32+/-1 vs. 57+/-6%, n = 6, p < 0.005); neither agent stimulated loss of endothelium at these concentrations. Neointima and total wall area increased significantly between 4- and 12-weeks in all vein-grafts such that there was no longer a significant effect on neointima formation of either paclitaxel (7.5+/-1.3 vs. 8.9+/-1.9 mm2 in control, n = 5, p = NS) or rapamycin (6.0+/-0.9 vs. 7.9+/-1.1 mm2 in control, n = 9, p = NS) or on total wall area in 12-week grafts.Pre-treatment of saphenous vein with anti-proliferative agents paclitaxel or rapamycin reduced neointima and total wall area after 4 weeks but continued growth abolished differences by 12 weeks. These results may help to understand the failure of clinical studies using anti-proliferative treatments in vein-grafts.
FLAVINE IN PERINEAL DRESSINGS
Authors: M. A. D. Crawford
Journal: BMJ (1930)

There is still muclh to be learnt about all abnoriialities of carbohydrate nietabolism, and particularly about those asso- ciated witlh ani ullusually low blood -sugar level, but opportunities for investig.ationare by no means rare, as the nunuber of cases I have met with in a comparatively short period indicates.I hope this paper miiay be the means of directing the attention of others to what is, I believe, a matter of considerable clinical importance.REFERENs.
Significance of Immunohistochemical Expression of Estrogen Receptors α and β in Squamous Cell Carcinoma of the Esophagus
Authors: Tadahiro Nozoe, Tsunehiro Oyama, Mitsuhiro Takenoyama, Takeshi Hanagiri, Kenji Sugio, Kosei Yasumoto
Journal: Clinical Cancer Research (2007)

Possible significance of sex hormone estrogen as an antitumor therapeutic arm toward esophageal squamous cell carcinoma (ESCC) cells has been suggested. The aim of the current study was to clarify the clinicopathologic significance of an immunohistochemical expression of estrogen receptors alpha and beta (ER alpha and ER beta) in ESCC.Expression of ER alpha and ER beta were examined using an immunohistochemical methods in 73 paraffin-embedded sections collected from patients with ESCC who had been subjected to esophageal resection and digestive reconstruction without any preoperative induction therapy.Forty-seven (64.4%) ESCCs had a positive cytoplasmic expression of ER alpha and 21 (28.8%) ESCCs had a positive nuclear expression of ER beta. Univariate analysis showed that both positive ER alpha expression (P=0.0001) and negative ER beta expression (P=0.026) were unfavorable prognostic indicators in ESCC. Moreover, multivariate analysis showed that ER alpha-positive/ER beta-negative expression (P=0.003) and progression of tumor stage (P=0.014) were found to be independent unfavorable prognostic indicators in ESCCs.Immunohistochemical expression of ER alpha and ER beta were found to be observed in ESCC. Positive expression of ER alpha in addition to negative expression of ER beta proved to be an unfavorable independent prognostic indicator in ESCC.
A Computer Model of Normal Conduction in the Human Atria
Authors: None David M. Harrild, Craig S. Henriquez ;
Journal: Circulation Research (2000)

Although considerable progress has been made in understanding the process of wavefront propagation and arrhythmogenesis in human atria, technical concerns and issues of patient safety have limited experimental investigations. The present work describes a finite volume-based computer model of human atrial activation and current flow to complement these studies. Unlike previous representations, the model is three-dimensional, incorporating both the left and right atria and the major muscle bundles of the atria, including the crista terminalis, pectinate muscles, limbus of the fossa ovalis, and Bachmann's bundle. The bundles are represented as anisotropic structures with fiber directions aligned with the bundle axes. Conductivities are assigned to the model to give realistic local conduction velocities within the bundles and bulk tissue. Results from simulations demonstrate the role of the bundles in a normal sinus rhythm and also reveal the patterns of activation in the septum, where experimental mapping has been extremely challenging. To validate the model, the simulated normal activation sequence and conduction velocities at various locations are compared with experimental observations and data. The model is also used to investigate paced activation, and a mechanism of the relative lengthening of left versus right stimulation is presented. Owing to both the realistic geometry and the bundle structures, the model can be used for further analysis of the normal activation sequence and to examine abnormal conduction, including flutter. The full text of this article is available at http://www.circresaha.org.
MCP-1 induces activation of MAP-kinases ERK, JNK and p38 MAPK in human endothelial cells
Authors: M WERLE, U SCHMAL, K HANNA, J KREUZER
Journal: Cardiovascular Research (2002)

Activation of vascular endothelial cells (ECs) plays an important pathogenic role in the development of atherosclerosis. Monocyte chemoattractant protein-1 (MCP-1) is a potent chemoattractant of monocytes. Besides induction of monocyte recruitment, it has been suggested that MCP-1 can also affect the cellular responses of ECs. We investigated whether MCP-1 activated the three major mitogen activated protein (MAP)-kinases extracellular signal-regulated kinase (ERK), c-Jun amino terminal kinase (JNK) and p38 MAPK. Stimulation of ECs with MCP-1 induced a time- and concentration-dependent activation of all three MAP-kinases, concentrations as low as 0.1 ng/ml were sufficient for this mechanism. MCP-1 also induced secretion of matrix metalloproteinase (MMP)-2 which along with ERK activation was inhibited by PD098059. The results demonstrate that MCP-1 can lead to direct activation of MAP kinases together with induction of MMP2 in ECs. Our data thus propose a new mechanism for the proatherogenic effect of MCP-1.
Depressive Symptoms, Insulin Resistance, and Risk of Diabetes in Women at Midlife
Authors: Susan A. Everson-Rose, Peter M. Meyer, Lynda H. Powell, Dilip Pandey, Javier I. Torréns, Howard M. Kravitz, Joyce T. Bromberger, Karen A. Matthews
Journal: Diabetes Care (2004)

OBJECTIVE—To examine depression and 3-year change in insulin resistance and risk of diabetes and whether associations vary by race. RESEARCH DESIGN AND METHODS—We analyzed data from 2,662 Caucasian, African-American, Hispanic, Japanese-American, and Chinese-American women without a history of diabetes from the Study of Women’s Health Across the Nation. We estimated regression coefficients and odds ratios to determine whether depression (Center for Epidemiological Studies Depression Scale score ≥16) predicted increases in homeostasis model assessment of insulin resistance (HOMA-IR) and greater risk of incident diabetes, respectively, over 3 years. RESULTS—Mean baseline HOMA-IR was 1.31 (SD 0.86) and increased 0.05 units per year for all women (P &amp;lt; 0.0001). A total of 97 incident cases of diabetes occurred. Depression was associated with absolute levels of HOMA-IR (P &amp;lt; 0.04) but was unrelated to changes in HOMA-IR; associations did not vary by race. The association between depression and HOMA-IR was eliminated after adjustment for central adiposity (P = 0.85). Depression predicted a 1.66-fold greater risk of diabetes (P &amp;lt; 0.03), which became nonsignificant after adjustment for central adiposity (P = 0.12). We also observed a depression-by-race interaction (P &amp;lt; 0.05) in analyses limited to Caucasians and African Americans, the only groups with enough diabetes cases to reliably test this interaction. Race-stratified models showed that depression predicted 2.56-fold greater risk of diabetes in African Americans only, after risk factor adjustment (P = 0.008). CONCLUSIONS—Depression is associated with higher HOMA-IR values and incident diabetes in middle-aged women. These associations are mediated largely through central adiposity. However, African-American women with depression experience increased risk of diabetes independent of central adiposity and other risk factors.
Limb-reduction defects and chorion villus sampling
Authors: Pierpaolo Mastroiacovo, Denise Pontes Cavalcanti, Giovanni Monni, Rosa Maria Ibba, Rosalba Lai, Giovanni Olla, Antonio Cao, Fon-Jou Hsieh, Dar Chen, Li-Hui Tseng, Chien-Nan Lee, Tsang-Ming Ko, Sou-Ming Chuang, Hsi-Yao Chen, ThomasH. Shepard, RajP. Kapur, AlanG. Fantel
Journal: The Lancet (1991)
Antagonism of Inhibitor of Apoptosis Proteins Increases Bone Metastasis via Unexpected Osteoclast Activation
Authors: Chang Yang, Jennifer L. Davis, Rong Zeng, Paras Vora, Xinming Su, Lynne I. Collins, Suwanna Vangveravong, Robert H. Mach, David Piwnica-Worms, Katherine N. Weilbaecher, Roberta Faccio, Deborah Veis Novack
Journal: Cancer Discovery (2012)

Inhibitor of apoptosis (IAP) proteins play a central role in many types of cancer, and IAP antagonists are in development as anticancer agents. IAP antagonists cause apoptosis in many cells, but they also activate alternative NF-κB signaling through NF-κB-inducing kinase (NIK), which regulates osteoclasts. In bone metastasis, a positive feedback loop between tumors and osteoclasts promotes tumor growth and osteolysis. We therefore tested the effect of IAP antagonists on the bone microenvironment for metastasis. In both drug-sensitive and drug-resistant tumors, growth in bone was favored, as compared with other sites during IAP antagonist treatment. These drugs also caused osteoporosis and increased osteoclastogenesis, mediated by NIK, and enhanced tumor-associated osteolysis. Cotreatment with zoledronic acid, a potent osteoclast inhibitor, reduced IAP antagonist-enhanced tumor growth in bone and osteolysis. Thus, IAP antagonist-based cancer treatment may be compromised by osteoporosis and enhanced skeletal metastasis, which may be prevented by antiresorptive agents.Although IAP antagonists are a class of anticancer agents with proven efficacy in multiple cancers, we show that these agents can paradoxically increase tumor growth and metastasis in the bone by stabilizing NIK and activating the alternative NF-κB pathway in osteoclasts. Future clinical trials of IAP antagonist-based therapy may require detailed examination of this potential for enhanced bone metastasis and osteoporosis, as well as possible combination with antiresorptive agents.
Impairment of Glucose Tolerance Over 10 Years in Middle-Aged Normal Glucose Tolerant Indians
Authors: Chittaranjan S. Yajnik, Kishore M. Shelgikar, Sadanand S. Naik, Mehmood G. Sayyad, Kondiram N. Raut, Dattatraya S. Bhat, Jyoti A. Deshpande, Shailaja D. Kale, Derek Hockaday
Journal: Diabetes Care (2003)

We followed 191 normal glucose tolerant (NGT; 1985 World Health Organization criteria) nondiabetic subjects (115 men) as control subjects in the Wellcome Diabetes Study (1). Their mean age was 41 years (SD 11.2), BMI 23.6 kg/m2 (34% >25 kg/m2), and 31% had a first-degree relative with diabetes.

During the next 10 years, 8 (7 men) died, 40 were lost to follow up, 14 men and 8 women became impaired glucose tolerant (IGT), and 2 men and 4 women developed diabetes. Men whose glucose tolerance deteriorated were heavier at entry …
Preoperative evaluation of gastric cancer by endoscopic ultrasound.
Authors: K Akahoshi, T Misawa, H Fujishima, Y Chijiiwa, A Maruoka, A Ohkubo, H Nawata
Journal: Gut (1991)

The preoperative use of endoscopic ultrasound was evaluated in 74 patients with confirmed gastric cancer. It was used in diagnosing the depth of invasion in the gastric wall, the infiltration to the adjacent organs, and the involvement of the perigastric lymph nodes. Results were compared with histological findings in resected specimens. Accuracy in staging gastric cancer using the T grade of the 1987 TNM system was 81.1% (60 of 74 patients). Endoscopic ultrasound provided excellent results compared with computed tomography and conventional ultrasound, particularly in evaluating perigastric lymph node metastasis and direct infiltration to the adjacent organs. The success rate in detecting lymph node metastasis was 50% (11 of 22 patients); the accuracy in diagnosing direct infiltration to the adjacent organs was 60% (three of five patients). This technique is useful in diagnosing malignant invasion and lymph node metastasis of gastric carcinomas but requires further refinement for use in diagnosing the disease itself. Its preoperative use is recommended for establishing surgical and other treatment plans, as well as in predicting the prognosis of gastric cancer.