tbuckley/cabot-search huggingface dataset:
Durable Complete Responses With High-Dose Bolus Interleukin-2 in Patients With Metastatic Melanoma Who Have Experienced Progression After Biochemotherapy
Authors: Ahmad A. Tarhini, John M. Kirkwood, William E. Gooding, Chao Cai, Sanjiv S. Agarwala
Journal: Journal of Clinical Oncology (2007)

Purpose We conducted a phase II trial of high-dose bolus (HDB) interleukin-2 (IL-2) in patients with metastatic melanoma who had experienced progression after biochemotherapy (BCT). Patients and Methods Eligible patients had experienced progression on or after BCT (cisplatin, vinblastine, dacarbazine, IL-2 9 MU/m 2 /d for 4 days, and interferon alfa-2b). HDB IL-2 was administered at 600,000 U/kg per dose for a maximum of 14 doses per cycle with a 1-week rest period between cycles. Stable or responding patients were offered an additional course (two cycles) after 6 to 8 weeks. Results Twenty-six patients (12 men and 14 women), age 28 to 70 years (median, 45 years), have been treated. All but three patients received at least two cycles of HDB IL-2; 10 patients received a second course of therapy. Disease stage was American Joint Committee on Cancer (AJCC) stage M1a (n = 5), M1b (n = 5), and M1c (n = 16). Grade 3 and 4 toxicities included hyperbilirubinemia (n = 10), thrombocytopenia (n = 6), oliguria (n = 3), diarrhea (n = 1), infection (n = 2), and neurologic toxicity (n = 2). Overall response rate was 19.2% (four complete responses, lasting 4, 4, 26+, and 41+ months; and one partial response, lasting 3 months). Five patients (19%) had stable disease lasting 1 to 3 months, but all eventually experienced progression. All four complete responders had AJCC stage M1a disease. At a median follow-up time of 10 months, median survival time was 42 weeks (95% CI, 19.1 to 86.6 weeks), and median progression-free survival time was 10 weeks (95% CI, 8 to 16.1 weeks). An initial response to BCT was not found to be predictive for response to HDB IL-2. Conclusion HDB IL-2 is active therapy for patients who experience progression on BCT. This observation has implications regarding the importance of dose-intensity for IL-2 therapy.
Thermoregulatory observations in soccer match play: professional and recreational level applications using an intestinal pill system to measure core temperature
Authors: A M Edwards, N A Clark
Journal: British Journal of Sports Medicine (2006)

Technological limitations associated with oesophageal and rectal temperature probes have previously limited match play observations of body temperature.To investigate the application of an intestinal pill system to measure core temperature during dynamic, field based, soccer matches.Core temperature (T(c)) was assessed using the intestinal pill system (CorTemp 2000) and changes in plasma volume were calculated using the values for haemoglobin and packed cell volume obtained before and after recreational (n = 8) and the professional soccer (n = 7) matches.In the recreational match, there were significant post-match reductions in body mass (-1.6%, p<0.05) and plasma volume (-7.2%, p<0.01). Significant increases were observed in T(c) from rest to half time (p<0.01) and from half time to full time (p<0.05). In the professional match, body mass decreased by 1.9% (p<0.05) and plasma volume by 11.6% (p<0.01). T(c) increased from rest to half time (p<0.01) but was unchanged from half time to full time. Significant associations were observed between maximum oxygen consumption and match play heart rates in the second half of each match but these were not related to changes in plasma volume or T(c).Intestinal temperature proved a useful method of recording core temperature during soccer match play and assisted in the measurement of alterations in thermoregulatory variables in response to both professional and recreational level soccer matches; however, technological limitations still restrict the wider application of this method, especially at a competitive level.
Nonmyeloablative transplantation with or without alemtuzumab: comparison between 2 prospective studies in patients with lymphoproliferative disorders
Authors: José A. Pérez-Simón, Panagiotis D. Kottaridis, Rodrigo Martino, Charles Craddock, Dolores Caballero, Raj Chopra, Javier Garcı́a-Conde, Don W. Milligan, Stephen Schey, Alvaro Urbano-Ispizua, Anne Parker, Angel Leon, Kwee Yong, Ana Sureda, Ann Hunter, Jordi Sierra, Anthony H. Goldstone, David C. Linch, Jesus F. San Miguel, Stephen Mackinnon
Journal: Blood (2002)
Molecular Profiling Diagnosis in Unknown Primary Cancer: Accuracy and Ability to Complement Standard Pathology
Authors: F Anthony Greco, Wayne J Lennington, David R Spigel, John D Hainsworth
Journal: JNCI Journal of the National Cancer Institute (2013)

Molecular tumor profiling (MTP) is a potentially powerful diagnostic tool for identifying the tissue of origin in patients with cancer of unknown primary (CUP). However, validation of the accuracy and clinical value of MTP has been difficult because the anatomic primary site in most patients is never identified. From March 2008 through January 2010, clinicopathologic data from 171 CUP patients who had MTP (CancerTYPE ID; bioTheranostics, Inc, San Diego, CA) performed on archived material were evaluated. The accuracy of MTP diagnoses was evaluated by comparison with 1) latent primary tumor sites found months/years later; 2) initial single diagnoses by immunohistochemistry (IHC); and 3) additional directed IHC and/or clinicopathologic findings evaluated after MTP diagnoses. A single MTP diagnosis was made in 144 of 149 patients with adequate tumor specimens. Eighteen of 24 patients with latent primaries discovered months to years later had correct diagnoses by MTP (75%), and these diagnoses compared favorably with IHC. Single IHC diagnoses matched MTP diagnoses in 40 of 52 patients (77%). IHC predictions of 2 or more possible primaries compared poorly with MTP diagnoses. However, additional targeted IHC and clinical/histologic evaluation supported the MTP diagnosis in 26 of 35 patients (74%). Clinical features were usually consistent with MTP diagnoses (70%). The diagnostic accuracy of this MTP assay was supported by a high level of agreement with identified latent primaries (75%), single IHC diagnoses (77%), and additional directed IHC and/or clinical/histologic findings (74%) prompted by the MTP diagnoses. MTP complements standard pathologic evaluation in determining the tissue of origin in patients with CUP, particularly when IHC is inconclusive.
Protein kinase Cδ amplifies ceramide formation via mitochondrial signaling in prostate cancer cells
Authors: Makoto Sumitomo, Motoi Ohba, Junichi Asakuma, Takako Asano, Toshio Kuroki, Tomohiko Asano, Masamichi Hayakawa
Journal: Journal of Clinical Investigation (2002)

We studied the role of protein kinase C isoform PKCdelta in ceramide (Cer) formation, as well as in the mitochondrial apoptosis pathway induced by anticancer drugs in prostate cancer (PC) cells. Etoposide and paclitaxel induced Cer formation and apoptosis in PKCdelta-positive LNCaP and DU145 cells but not in PKCdelta-negative LN-TPA or PC-3 cells. In contrast, these drugs induced mitotic cell cycle arrest in all PC cell lines. Treatment with Rottlerin, a specific PKCdelta inhibitor, significantly inhibited drug-induced Cer formation and apoptosis in LNCaP cells, as did overexpression of dominant negative-type PKCdelta. Overexpression of wild-type PKCdelta had an opposite effect in PC-3 cells. Notably, etoposide induced biphasic Cer formation in LNCaP cells. The early and transient Cer increase resulted from de novo Cer synthesis, while the late and sustained Cer accumulation was derived from sphingomyelin hydrolysis by neutral sphingomyelinase (nSMase). Cer, in turn, induced mitochondrial translocation of PKCdelta and stimulated the activity of this kinase, promoting cytochrome c release and caspase-9 activation. Furthermore, the specific caspase-9 inhibitor LEHD-fmk significantly inhibited etoposide-induced nSMase activation, Cer accumulation, and PKCdelta mitochondrial translocation. These results indicate that PKCdelta plays a crucial role in activating anticancer drug-induced apoptosis signaling by amplifying the Cer-mediated mitochondrial amplification loop.
A chart of failure risk for noninvasive ventilation in patients with COPD exacerbation
Authors: M. Confalonieri, G. Garuti, M. S. Cattaruzza, J. F. Osborn, M. Antonelli, G. Conti, M. Kodric, O. Resta, S. Marchese, C. Gregoretti, A. Rossi
Journal: European Respiratory Journal (2005)

Knowing the likelihood of failure of noninvasive positive pressure ventilation (NPPV) in patients with exacerbation of chronic obstructive pulmonary disease (COPD) could indicate the best choice between NPPV and endotracheal intubation instituted earlier. For this purpose, two risk charts were designed (at admission and after 2 h of NPPV) that included all relevant measurable clinical prognostic indicators derived from a population representing the patients seen routinely in clinical practice. Risk stratification of NPPV failure was assessed in 1,033 consecutive patients admitted to experienced hospital units, including two intensive care units, six respiratory intermediate care units, and five general wards. NPPV was successful in 797 patients. Patients with a Glasgow Coma Score <11, acute physiology and chronic health evaluation (APACHE) II > or =29, respiratory rate > or =30 breaths x min(-1) and pH at admission <7.25 have a predicted risk of failure >70%. A pH <7.25 after 2 h greatly increases the risk (>90%). The risk charts were validated on an independent group of 145 consecutive COPD patients treated with NPPV due to an acute ventilatory failure episode. To identify patients with a probability of failure >50%, the sensitivity and specificity were 33% and 96.7% on admission and 52.9% and 94.1% after 2 h of NPPV, respectively. The prediction chart, based on data from the current study, can function as a simple tool to predict the risk of failure of noninvasive positive pressure ventilation and thus improve clinical management of patients tailoring medical intervention.
Increased Risk of Cognitive Impairment in Patients With Diabetes Is Associated With Metformin
Authors: Eileen M. Moore, Alastair G. Mander, David Ames, Mark A. Kotowicz, Ross P. Carne, Henry Brodaty, Michael Woodward, Karyn Boundy, Kathryn A. Ellis, Ashley I. Bush, Noel G. Faux, Ralph Martins, Cassandra Szoeke, Christopher Rowe, David A. Watters
Journal: Diabetes Care (2013)

To investigate the associations of metformin, serum vitamin B12, calcium supplements, and cognitive impairment in patients with diabetes.Participants were recruited from the Primary Research in Memory (PRIME) clinics study, the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging, and the Barwon region of southeastern Australia. Patients with Alzheimer disease (AD) (n=480) or mild cognitive impairment (n=187) and those who were cognitively intact (n=687) were included; patients with stroke or with neurodegenerative diseases other than AD were excluded. Subgroup analyses were performed for participants who had either type 2 diabetes (n=104) or impaired glucose tolerance (n=22).Participants with diabetes (n=126) had worse cognitive performance than participants who did not have diabetes (n=1,228; adjusted odds ratio 1.51 [95% CI 1.03-2.21]). Among participants with diabetes, worse cognitive performance was associated with metformin use (2.23 [1.05-4.75]). After adjusting for age, sex, level of education, history of depression, serum vitamin B12, and metformin use, participants with diabetes who were taking calcium supplements had better cognitive performance (0.41 [0.19-0.92]).Metformin use was associated with impaired cognitive performance. Vitamin B12 and calcium supplements may alleviate metformin-induced vitamin B12 deficiency and were associated with better cognitive outcomes. Prospective trials are warranted to assess the beneficial effects of vitamin B12 and calcium use on cognition in older people with diabetes who are taking metformin.
Prevalence and Clinical Significance of Papillary Muscle Infarction Detected by Late Gadolinium-Enhanced Magnetic Resonance Imaging in Patients With ST-Segment Elevation Myocardial Infarction
Authors: Takashi Tanimoto, Toshio Imanishi, Hironori Kitabata, Nobuo Nakamura, Keizo Kimura, Takashi Yamano, Kohei Ishibashi, Kenichi Komukai, Yasushi Ino, Shigeho Takarada, Takashi Kubo, Kumiko Hirata, Masato Mizukoshi, Atsushi Tanaka, Takashi Akasaka
Journal: Circulation (2010)

Background— The frequency of papillary muscle infarction (PapMI) without rupture has not been fully investigated in vivo. Furthermore, the relationship between papillary muscle dysfunction and mitral regurgitation (MR) has been controversial in patients with ST-segment elevation myocardial infarction. Therefore, the aim of this study was to assess the frequency and clinical characteristics of PapMI without rupture using late gadolinium-enhanced magnetic resonance imaging (MRI) in patients with ST-segment elevation myocardial infarction. Methods and Results— One hundred eighteen ST-segment elevation myocardial infarction patients with primary percutaneous coronary intervention underwent cardiac MRI twice 9±4 days and 8±1 months (n=104) after myocardial infarction. MR was categorized by echocardiography. Of these patients, 40% were found to have late gadolinium enhancement of papillary muscle, in which the posterior papillary muscle was involved more frequently than the anterior papillary muscle (77% versus 26%; P &lt;0.001). PapMI was encountered more frequently in patients with left circumflex and right coronary artery lesions compared with left anterior descending artery lesion (78%, 48%, and 13%; P &lt;0.001). By multiple logistic regression analysis, only coaptation height was identified as an independent predictor of the presence of MR. The second cardiac magnetic resonance imaging showed that the infarct size had a positive correlation with left ventricular end-diastolic volume ( r =0.41, P &lt;0.001) and that PapMI was not associated with left ventricular remodeling ( P =0.31). Deterioration of MR was not observed in patients with PapMI. Conclusions— PapMI is more frequent than previously thought yet appears to have significant clinical latency. The size of the myocardial infarction, but not the presence of PapMI, seems to affect left ventricular remodeling, and PapMI is not obligatorily associated with MR.
Accuracy of Revised Bethesda Guidelines, Microsatellite Instability, and Immunohistochemistry for the Identification of Patients With Hereditary Nonpolyposis Colorectal Cancer
Authors: Virgínia Piñol, Antoni Castells, Montserrat Andreu, Sergi Castellví-Bel, Cristina Alenda, Xavier Llor, Rosa M Xicola, Francisco Rodríguez-Moranta, Artemio Payá, Rodrigo Jover, Xavier Bessa
Journal: JAMA (2005)

The selection of individuals for hereditary nonpolyposis colorectal cancer (HNPCC) genetic testing is challenging. Recently, the National Cancer Institute outlined a new set of recommendations, the revised Bethesda guidelines, for the identification of individuals with HNPCC who should be tested for microsatellite instability.To establish the most effective and efficient strategy for the detection of MSH2/MLH1 gene carriers.A prospective, multicenter, nationwide study (the EPICOLON study) in 20 hospitals in the general community in Spain of 1222 patients with newly diagnosed colorectal cancer between November 1, 2000, and October 31, 2001.Microsatellite instability testing and MSH2/MLH1 immunostaining in all patients regardless of age, personal or family history, and tumor characteristics. Patients whose tumors exhibited microsatellite instability and/or lack of protein expression underwent MSH2/MLH1 germline testing.Effectiveness and efficiency of both microsatellite instability testing and immunostaining, either directly or previous selection of patients according to the revised Bethesda guidelines, were evaluated with respect to the presence of MSH2/MLH1 germline mutations.Two hundred eighty-seven patients (23.5%) fulfilled the revised Bethesda guidelines. Ninety-one patients (7.4%) had a mismatch repair deficiency, with tumors exhibiting either microsatellite instability (n = 83) or loss of protein expression (n = 81). Germline testing identified 11 mutations (0.9%) in either MSH2 (7 cases) or MLH1 (4 cases) genes. Strategies based on either microsatellite instability testing or immunostaining previous selection of patients according to the revised Bethesda guidelines were the most effective (sensitivity, 81.8% and 81.8%; specificity, 98.0% and 98.2%; positive predictive value, 27.3% and 29.0%, respectively) to identify MSH2/MLH1 gene carriers. Logistic regression analysis confirmed the revised Bethesda guidelines as the most discriminating set of clinical parameters (odds ratio, 33.3; 95% confidence interval, 4.3-250; P = .001).The revised Bethesda guidelines constitute a useful approach to identify patients at risk for HNPCC. In patients fulfilling these criteria, both microsatellite instability testing and immunostaining are equivalent and highly effective strategies to further select those patients who should be tested for MSH2/MLH1 germline mutations.
Psoriasis and stress *
Authors: R.H. SEVILLE
Journal: British Journal of Dermatology (1977)

132 psoriasis patients who had been completely cleared with dithranol were assessed and then followed up over a 3-year period. The incubation time from specific incidents of stress to the development of psoriasis was between 2 days and 1 month. Specific stress within a month before the first attack was recalled by 51 patients (39%); chance association was excluded by studying a control group where there was significantly less specific stress. The prognosis for the psoriasis patients who recollected specific stress a month prior to the onset was significantly better than for the rest of the patients where none had been recalled.
Human uterine lymphocytes
Authors: A King
Journal: Human Reproduction Update (1998)

During the luteal phase and the early months of pregnancy, there is a dense mucosal infiltration of CD56+ natural killer (NK) cells. These uterine NK cells have a phenotype (CD56bright, CD16-, mCD3-) which distinguishes them from peripheral blood NK cells (CD56dim, CD16bright, mCD3-). The uterine NK cells are in close association with extravillous trophoblast (EVT) cells which infiltrate into the decidua and maternal spiral arteries. This subpopulation of trophoblast expresses two human leukocyte antigen (HLA) class I molecules, HLA-G and HLA-C. Circulating NK cells express receptors for HLA class I molecules. We have recently found evidence that similar receptors are present on decidual NK cells belonging to both the Killer Inhibitory Receptor (KIR) and CD94 families. The repertoire of NK receptors expressed varies between different women. The findings indicate that decidual NK cells do have receptors for trophoblast HLA class I molecules. Experiments are underway to determine the effects of this interaction on NK cell function.
Prospective Approach to Breast Cancer Risk Prediction in African American Women: The Black Women's Health Study Model
Authors: Deborah A. Boggs, Lynn Rosenberg, Lucile L. Adams-Campbell, Julie R. Palmer
Journal: Journal of Clinical Oncology (2015)

Breast cancer risk prediction models have underestimated risk for African American women, contributing to lower recruitment rates in prevention trials. A model previously developed for African American women was found to underestimate risk in the Black Women's Health Study (BWHS).We developed a breast cancer risk model for African American women using relative risks derived from 10 years of follow-up of BWHS participants age 30 to 69 years at baseline. Using the subsequent 5 years of follow-up data, we evaluated calibration as the ratio of expected to observed number of breast cancers and assessed discriminatory accuracy using the concordance statistic.The BWHS model included family history, previous biopsy, body mass index at age 18 years, age at menarche, age at first birth, oral contraceptive use, bilateral oophorectomy, estrogen plus progestin use, and height. There was good agreement between predicted and observed number of breast cancers overall (expected-to-observed ratio, 0.96; 95% CI, 0.88 to 1.05) and in most risk factor categories. Discriminatory accuracy was higher for women younger than age 50 years (area under the curve [AUC], 0.62; 95% CI, 0.58 to 0.65) than for women age ≥ 50 years (AUC, 0.56; 95% CI, 0.53 to 0.59). Using a 5-year predicted risk of 1.66% or greater as a cut point, 2.8% of women younger than 50 years old and 32.2% of women ≥ 50 years old were classified as being at elevated risk of invasive breast cancer.The BWHS model was well calibrated overall, and the predictive ability was best for younger women. The proportion of women predicted to meet the 1.66% cut point commonly used to determine eligibility for breast cancer prevention trials was greatly increased relative to previous models.
COX-2 suppresses tissue factor expression via endocannabinoid-directed PPARδ activation
Authors: Mallika Ghosh, Haibin Wang, Youxi Ai, Elisa Romeo, James P. Luyendyk, Jeffrey M. Peters, Nigel Mackman, Sudhansu K. Dey, Timothy Hla
Journal: The Journal of Experimental Medicine (2007)

Although cyclooxygenase (COX)-2 inhibitors (coxibs) are effective in controlling inflammation, pain, and tumorigenesis, their use is limited by the recent revelation of increased adverse cardiovascular events. The mechanistic basis of this side effect is not well understood. We show that the metabolism of endocannabinoids by the endothelial cell COX-2 coupled to the prostacyclin (PGI2) synthase (PGIS) activates the nuclear receptor peroxisomal proliferator–activated receptor (PPAR) δ, which negatively regulates the expression of tissue factor (TF), the primary initiator of blood coagulation. Coxibs suppress PPARδ activity and induce TF expression in vascular endothelium and elevate circulating TF activity in vivo. Importantly, PPARδ agonists suppress coxib-induced TF expression and decrease circulating TF activity. We provide evidence that COX-2–dependent attenuation of TF expression is abrogated by coxibs, which may explain the prothrombotic side-effects for this class of drugs. Furthermore, PPARδ agonists may be used therapeutically to suppress coxib-induced cardiovascular side effects.