tbuckley/cabot-search huggingface dataset:
Array CGH analysisin neoadjuvant chemotherapy for breast cancer
Authors: J. Y. Kim, H. Kwak, K. U. Choi, J. Chung, Y. T. Bae, M. K. Lee, H. W. Kim, D. Y. Park, C. H. Lee, K. Y. Huh, M. Y. Sol
Journal: Journal of Clinical Oncology (2005)

786 Background: To assess a potential and common pattern of genetic alterations in Korean women’s breast cancer correlated with clinicopathologic parameters and to assess the potential genes which may be helpful to predict the response of neoadjuvant chemotherapy, we analyzed 13 tumors from breast cancer patients by microarray-based CGH. Methods: Array CGH(including 350 cancer-related genes and 1,090 STS) was performed with fresh frozen tumor tissue from the breast cancer patients. Ten cases of them received neoadjuvant chemotherapy(cyclophosphamide 600 mg/m2, adriamycin 50 mg/m2(CA); cyclophosphamide 600 mg/m2, adriamycin 50 mg/m2, 5-FU 500 mg/m2(CAF); cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2, 5-FU 500 mg/m2(CMF); CA and Taxol; Nabelvine), 2 cases adjuvant chemotherapy and 1 case had no history of chemotherapy. Immunohistochemical study for ER, PR, p53, and Her-2 were also done. Results: In array CGH analysis, the patients showed typical imbalances for breast cancer; gain of 8q(84.6%), 11q13(69.2%), 16p(84.6%), 22q(69.2%), 3p(61.5%) and losses of 1p(61.5%), 18q(38.5%) and 2q(38.5%). Other recurrent imbalance of newly recognized pattern for breast cancer was gain of 1p(92.3%). One patient, died within 5 months with pulmonary metastasis after diagnosis, displayed gains of 20q13, 8q and losses of 13q21, 18p and 18q which were known as chromosomal changes related with adverse prognosis in previous reports. Genetic alterations in the “progress” group after neoadjuvant chemotherapy showed gain of MAFG(v-maf musculoaponeurotic fibrosarcoma oncogene homolog G; 17q25) which was related to cellular stress response and loss of DCC(18q21.3) whose function was induction of apoptosis. Genetic alterations in the “stable” and “partial remission” group were gain of p73(1p36), which was p53-related protein, and activated by chemotherapy and thereafter contributed to the reduction of the tumor size. Conclusions: These data suggest that gains of 1p might be a newly identified CGH finings which characterize the Korean women breast cancer. These findings suggest that loss of DCC and gain of MAFG and p73 might be a possible predictor for the response of neoadjuvant chemotherapy. No significant financial relationships to disclose.
Optimization and simplification of the Allergic and Hypersensitivity conditions classification for the ICD-11
Authors: L. K. Tanno, M. A. Calderon, P. Demoly
Journal: Allergy (2016)

Background Since 2013, an international collaboration of Allergy Academies, including first the World Allergy Organization (WAO), the American Academy of Allergy Asthma and Immunology (AAAAI), and the European Academy of Allergy and Clinical Immunology (EAACI), and then the American College of Allergy, Asthma and Immunology (ACAAI), the Latin American Society of Allergy, Asthma and Immunology (SLAAI), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology (APAAACI), has spent tremendous efforts to have a better and updated classification of allergic and hypersensitivity conditions in the forthcoming International Classification of Diseases (ICD)-11 version by providing evidences and promoting actions for the need for changes. The latest action was the implementation of a classification proposal of hypersensitivity/allergic diseases built by crowdsourcing the Allergy Academy leaderships. Methods Following bilateral discussions with the representatives of the ICD-11 revision, a face-to-face meeting was held at the United Nations Office in Geneva and a simplification process of the hypersensitivity/allergic disorders classification was carried out to better fit the ICD structure. Results We are here presenting the end result of what we consider to be a model of good collaboration between the World Health Organization and a specialty. Conclusion We strongly believe that the outcomes of all past and future actions will impact positively the recognition of the allergy specialty as well as the quality improvement of healthcare system for allergic and hypersensitivity conditions worldwide.
Abstract 192: Does Neighborhood Matter? How Location Influences Cardiac Arrest Outcomes and Predictability of the Utstein Factors
Authors: Jason E Buick, Joel G Ray, Alex Kiss, Laurie J Morrison
Journal: Circulation (2012)

Introduction: The Utstein factors only predict 72% of out-of-hospital cardiac arrest (OHCA) survival variability (AUC: 0.86). Previous studies demonstrated geographical variations in both OHCA incidence and outcomes, while others have related these differences to ethnic and socioeconomic measures. The objective of this study was to determine the role of neighborhoods in OHCA survival and predictability in a Canadian setting. Hypothesis: We hypothesized that there are neighbourhood factors associated with survival and variability in cardiac arrest outcomes. Methods: All treated OHCA between April 2006 and March 2010 were mapped into census tracts (CT) using Geographic Information System analysis. Based on their home address, patients were assigned neighborhood factors extracted from the 2005 Canadian Census and include: instability, dependency, deprivation, ethnic diversity, crime rate and density of family physicians. Hierarchical logistic modeling was performed to assess which factors were associated with survival. Results: A total of 4,626 OHCA were eligible for enrollment and contained the required information for geographic mapping. Survival to hospital discharge was 4.3%. The CT survival varied between 0 - 50% (IQR: 0.0 - 7.7), where 68.4% had 0% survival. The Utstein factors predicted 85.4% (95% CI: 81.0 - 89.6%) of survival variability. After adjusting for the Utstein factors, only the ethnic concentration of the CT was associated with survival. Inclusion of CT variables increased the predictability of the Utstein factors to 87.2% (95% CI: 83.4 - 91.2%, p = 0.12). Conclusions: In conclusion, although neighborhood differences in OHCA outcomes exist, this difference contributes minimally to the Utstein factors prediction of survival. Since bystander resuscitation efforts are the most powerful predictors of survival perhaps neighborhood differences in bystander resuscitation efforts may address the gap in the Utstein predictability.
A validation study of preventing oxaliplatin-induced hypersensitivity reactions by dexamethasone: The AVOID trial.
Authors: Keiji Hirata, Yoichiro Yoshida, HIroshi Matsuoka, Shigeyoshi Iwamoto, Masahito Kotaka, Hideto Fujita, Naoya Aisu, Seiichiro Hoshino, Takeo Kosaka, Kotaro Maeda, Yuichi Yamashita
Journal: Journal of Clinical Oncology (2015)

727 Background: Patients treated with oxaliplatin are at risk for hypersensitivity reactions. The incidence of hypersensitivity reactions in clinical practice is estimated to be 12% to 20%. Prescribing information says that oxaliplatin is incompatible in solution with alkaline medications or media and must not be mixed these or administered simultaneously through the same infusion line. Because steroid is alkaline, the coinfusion of steroids and oxaliplatin can make oxaliplatin unstable due to the elevation of pH; further, the effectiveness of steroid in this therapy is unknown. Therefore, dexamethasone is routinely given to patients before they receive chemotherapy. However, we have reported that the pH after the addition of DEX (6.6 mg) to oxaliplatin was less than 7.4, and there is possibility that hypersensitivity reactions to oxaliplatin could have been prevented by coinfusion of dexamethasone (DEX) (Yoshida et al.2012 ASCO-GI) but just in a retrospective study. This prospective study was undertaken to evaluate the effectiveness of coinfusion of DEX to oxaliplatin for controlling hypersensitivity reactions caused by oxaliplatin. Methods: The AVOID trial is a prospective, multicenter, open-label, single-arm, phase II trial investigating hypersensitivity reactions to oxaliplatin could have been prevented by coinfusion of DEX. The study included 73 patients who received XELOX or XELOX +bevacizumab therapy for colorectal cancer. In all the patients, oxaliplatin (130mg/m²) was administered in combination with DEX (6.6 mg). Results: Hypersensitivity reactions developed in 3 patients (4.1%). Respiratory symptoms, ocular symptoms and anaphylaxis were not observed in 73 patients. The three patients experienced cutaneous reaction (erythema: grade1). Grade 3 or higher hemotoxicity was noted in 13.7% of the patients, and grade 3 or higher nonhematological toxicity was noted in 13.7%. The response rate was 58.1%. Conclusions: This trial supports coinfusion of dexamethasone and oxaliplatin reduced oxaliplatin-related hypersensitivity reactions. This effective approach should be considered for all patients who receive oxaliplatin, allowing treatment to be completed as planned. Clinical trial information: UMIN000009742.
Abstract P261: Skeletal Muscle Density: A Novel Risk Factor for Hypertension in Aging African Ancestry Men
Authors: Iva Miljkovic, Allison Kuipers, Clareann Bunker, Alan Patrick, Joseph Zmuda
Journal: Circulation (2015)

Background: Intramuscular fat is greater in African compared with European ancestry men and is now recognized as a major risk factor for cardio-metabolic diseases, independent of general obesity. However, prospective studies examining health consequences of this important ectopic fat depot are lacking, particularly in high-risk African ancestry populations. Therefore, we sought to determine if change in skeletal muscle density, a measure of intramuscular fat, predicts subsequent development of hypertension in African ancestry men. Methods: We measured at two time points calf skeletal muscle density (MD; mg/cm 3 ) using computed tomography in 1504 Afro-Caribbean men aged 40-92 years (mean, 59 years), who were recruited without regard to their health status. Hypertension was defined as having a systolic blood pressure of 140 mm Hg or greater, having a diastolic blood pressure of 90 mm Hg or greater, or taking antihypertensive medications. Logistic regression was used to estimate the association between change in MD and incident hypertension adjusting for follow-up time, baseline age and muscle density, and covariates known to be associated with hypertension and intramuscular fat (baseline body weight, body weight change, waist circumference, waist circumference change, current smoking, alcohol intake, physical activity, and baseline type 2 diabetes status). Results were expressed as the odds (95% CI) of hypertension per one standard deviation decrease in muscle density. Results: During the 6.2 years follow-up (range of follow-up years: 4.9-9.1 years), we observed a significant annualized percent decrease in muscle density (-0.43 %/yr; P&lt;0.0001). Among the 777 men who were normotensive at the baseline visit, 224 (28.8%) developed hypertension during follow-up. Decreased MD during follow-up was associated with an increased risk of hypertension (odds ratio [95% CI] per SD decrease in MD: 1.31 [1.03, 1.67]). This association remained significant after additional adjustment for baseline waist circumference and change in waist circumference in a separate model (odds ratio [95% CI] per SD decrease in MD: 1.27 [1.02, 1.59]). Conclusions: Our novel findings show that ectopic intramuscular fat increases with advancing age, and support a causal role of intramuscular fat in hypertension risk among middle-aged and elderly African ancestry men. Additional studies are needed to elucidate the mechanisms behind this association, and to confirm our findings in other populations.
P47 CLEVER-1 mediates T regulatory cell recruitment via hepatic sinusoidal endothelium by transcellular migration
Authors: S Shetty, C Weston, Y Oo, N Westerlund, Z Stamataki, J Youster, S Hubscher, M Salmi, S Jalkanen, P Lalor, D H Adams
Journal: Gut (2010)

Introduction  Lymphocytes are recruited via the unique hepatic sinusoidal channels during chronic inflammatory liver diseases. This low shear vascular bed is lined by hepatic sinusoidal endothelium (HSEC) which lacks certain conventional adhesion molecules leading us to look for novel receptors involved in lymphocytes recruitment. HSEC express several receptors found on lymphatic endothelium including the scavenger receptor CLEVER-1 which has been implicated in lymphocyte migration to lymph nodes.  Aim  We now show that CLEVER-1 is upregulated on human hepatic sinusoidal endothelium where it is involved in lymphocyte transendothelial migration.  Method  We studied the expression of CLEVER-1 in normal and diseased human liver tissue and on isolated human sinusoidal endothelial cells. We used isolated HSEC in flow adhesion assays to study the functional role of CLEVER-1 in lymphocyte subset recruitment. Immunofluorescent staining and confocal microscopy were used to characterise the transmigration of lymphocytes across HSEC under conditions of flow.  Results  CLEVER-1 was expressed at high levels within the sinusoids of chronically inflamed livers and hepatocellular carcinomas as well as at other sites of lymphocyte recruitment including neo-vessels and portal associated lymphoid tissue. Flow-based adhesion assays using human HSEC demonstrated that CLEVER-1 mediates transmigration of CD4 but not CD8T cells with strong preferential activity for FoxP3+regulatory T cells. Confocal microscopy demonstrated that a large proportion of CD4 Treg transmigrated via the transcellular route through CLEVER-1 lined channels within the endothelial cell.  Conclusion  This is the first report to implicate a specific adhesion molecule in the recruitment of T regulatory cells to tissue. CLEVER-1 appears to mediate the transcellular migration of Tregs through hepatic sinsuoids and is an organ specific target for therapy aimed at modulating Treg recruitment to the liver.
Karnofsky memorial lecture. Conceptual and practical advances in the management of breast cancer.
Authors: G Bonadonna
Journal: Journal of Clinical Oncology (1989)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1989.7.10.1380 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2674330 Karnofsky memorial lecture. Conceptual and practical advances in the management of breast cancer. G BonadonnaxG BonadonnaSearch for articles by this author Show More Division of Medical Oncology, Istituto Nazionale Tumori, Milan, Italy. https://doi.org/10.1200/JCO.1989.7.10.1380 First Page PDF © 1989 by American Society of Clinical Oncology
SYNERGISM AND POTENTIATION
Authors: H. VELDSTRA
Journal: Pharmacological Reviews (1956)

In the article by H. Veldstra on Synergism and Potentiation which appeared in Pharmacological Reviews, volume 8, number 3, September 1956, the left half of figure 1 on page 344 was inadvertently omitted.

The complete figure 1 and its legend, reproduced below, should be substituted for the incomplete figure which appeared in the Journal.
Low serum cholesterol level and attempted suicide
Authors: J A Golier, P M Marzuk, A C Leon, C Weiner, K Tardiff
Journal: American Journal of Psychiatry (1995)

Several studies suggest that a low cholesterol concentration is associated with a greater than normal risk of mortality from suicide. The authors sought to determine whether a low cholesterol level is associated with a history of serious suicide attempts among psychiatric inpatients.Lifetime history of attempted suicide of 650 patients, aged 18-59 years, consecutively admitted to a psychiatric hospital was assessed by semistructured interview. The seriousness of an attempt was rated on the basis of the resulting medical injury. Serum cholesterol levels, obtained from the admission biochemical profiles, were divided into quartiles.Compared to men with low cholesterol levels (defined as less than or equal to the 25th percentile), men with cholesterol levels above the 25th percentile were less likely to have ever made a serious suicide attempt when age, weight, race, socioeconomic status, alcohol use, and depression were controlled for. There was no association between cholesterol level and attempted suicide in women.Male psychiatric patients with low cholesterol levels were twice as likely to have ever made a medically serious suicide attempt than men with cholesterol levels above the 25th percentile. Low cholesterol concentration should be further investigated as a potential biological marker of suicide risk.
Effects of social deprivation in whole population should be addressed
Authors: H M P Fielder, J G Avery, D Wright
Journal: BMJ (1996)

more closely.A study of awareness ofthe "reduce the risk" campaign in a socially deprived area in south Wales in 1994 showed that a third of 250 mothers with children born before the introduction of the campaign said that they checked their babies more often than they had done previously.5For babies to endure increasingly long periods of solitude after birth is biologically unreason- able.In 1991 in Cardiff we included another fac- tor to lower the risk of the syndrome: we encouraged mothers to have their babies in their room at night for the first six to nine months and to keep the cot in which the babies slept by day close by.To focus only on posture, heating, and smoking and not to consider where a baby sleeps could detract from other factors in the care giving environment that might be protective.Any intervention programme aiming to reduce the incidence of the sudden infant death syndrome must also consider the broad range of care prac- tices that could reduce the risk.
Efficacy and safety of pemetrexed (P) in elderly cancer patients (pts)
Authors: P. M. Kulkarni, R. Chen, M. Monberg, C. K. Obasaju
Journal: Journal of Clinical Oncology (2006)

8544 Background: P, a novel multitargeted antifolate, has demonstrated antitumor activity in a broad range of tumor types. Approximately 60% of all new cases of cancer and 70% of all cancer-related deaths occur in the elderly population. However, few studies have specifically analyzed the utility of chemotherapy in this population. The objective of this posthoc analysis was to understand the efficacy and tolerability of pemetrexed (alone or in combination) when used in the elderly cancer population. Methods: Data from three pemetrexed registration trials conducted between April 1999 and February 2003 were pooled together. Pts in these studies were diagnosed with malignant pleural mesothelioma, NSCLC, or advanced pancreatic cancer. Pts receiving P as monotherapy or in combination with another drug (gemcitabine or cisplatin) who received at least one cycle of therapy were included in this analysis (n=764). In all studies, P 500 mg/m 2 was administered every 21 days. Demographics, efficacy, and safety data from pts receiving P were stratified by age ± 65 years. Kaplan-Meier method was used to estimate survival and time to PD. Cox regression model was also used to test the survival effect of pemetrexed on age after adjusting for disease stage, performance status, gender, and type of tumors, the prognostic factors considered to influence survival. Results: * P&lt;.05 from fisher’s exact test. The adjusted hazard ratio of elderly patients over younger patients was 1.074 with p-value 0.42. Conclusions: P produced similar treatment effects in older and younger patients and appeared to be well tolerated in the elderly population. CTC grade 3/4 Lab and Non-Lab toxicity between two age groups were similar except, as expected, the elderly group had modestly higher myelosuppression. Non-hematologic toxicities were similar between the two age groups. [Table: see text] [Table: see text]
A phase II clinical trial of MK-0646, an insulin-like growth factor-1 receptor inhibitor (IGF-1R), in patients with metastatic well-differentiated neuroendocrine tumors (NETs).
Authors: D. L. Reidy, E. Hollywood, M. Segal, L. Saltz
Journal: Journal of Clinical Oncology (2010)

4163 Background: Preclinical studies have implicated the IGF-1 receptor in the progression of neuroendocrine tumors. A therapy directed at IGFR mediated signaling pathways has potential for conferring enhanced anti-tumor activity. We evaluated the safety and efficacy of MK-0646, a monoclonal antibody (mab) that blocks the insulin-like growth factor receptor (IGF-1R), as monotherapy in metastatic well differentiated neuroendocrine patients. Methods: A phase II study was performed in which patients received MK-0646 at a dose of 10 mg/kg iv over 1 hour weekly. Archived pretreatment tumor tissue was obtained for putative biomarkers. Results: A total of 25 patients were treated (15 carcinoid, 10 islet cell carcinoma) female, 40%; median age, 61 years, (range 36-82). No antitumor activity was seen in these 25 patients treated with MK-0646 monotherapy. Five patients achieved stable disease for 24 weeks or longer defined by RECIST criteria (range 6.25-10.5 months). The most common serious adverse event (SAE) thought to be potentially related to MK-0646 was hyperglycemia (7 patients, 25%). Other SAEs included one grade 2 infusion-related reaction (4%), and 2 patients with grade 3 fatigue (8%). Conclusions: MK-0646 alone was well tolerated with the exception of hyperglycemia that was manageable with antihyperglycemic medications, however, the degree of activity seen was insufficient to warrant further study as a monotherapy in well differentiated neuroendocrine tumors. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Alchemia, Biothera, Delcath, ImClone Systems, Merck, Novartis, Roche Pfizer Amgen, Biothera, Bristol-Meyers Squibb, Curetech, Genentech, ImClone Systems, Lilly, Merck, Pfizer, Roche, Tercica
Early response to induction therapy as a predictor of disease-free survival and late recurrence of childhood acute lymphoblastic leukemia: a report from the Childrens Cancer Study Group.
Authors: D R Miller, P F Coccia, W A Bleyer, J N Lukens, S E Siegel, H N Sather, G D Hammond
Journal: Journal of Clinical Oncology (1989)

The Childrens Cancer Study Group (CCSG) CCG-160 protocol series was designed to evaluate prognostic factors in acute lymphoblastic leukemia (ALL). Patients were assigned to one of three prognostic groups based upon initial WBC count and age. To determine the optimal duration of therapy, CCG-160 patients completing 2 years of treatment in continuous remission were randomized ("late randomization") to discontinue therapy or receive another year of maintenance therapy. The prognostic significance of early response to induction therapy, as measured by the percentage of lymphoblasts in the day-14 bone marrow (d14 BM) aspirate, was evaluated in 2,516 children. For 1,490 patients with complete data, the status of the d 14 BM was a highly significant predictor of disease-free survival (DFS) by univariate and multivariate analysis (P less than .0001). The observed/expected (O/E) failure rate in patients with d14 M1 (less than 5% blasts), M2 (4% to 25% blasts), or M3 (greater than 25% blasts) BM rating who were subsequently M1 on day 28 or day 42, was .87, 1.59, and 2.30, respectively (P less than .0001). Patients with M2 or M3 d14 BM were more likely to have L2 ALL (modified French-American-British [FAB] morphologic classification), P less than .001. The significance of the d14 BM rating persisted after correction was made for WBC count and clinical prognostic groups using current CCSG criteria, except in infants less than 12 months of age. The d14 BM was also the most significant predictor of DFS in 975 patients after late randomization at 2 years following diagnosis. The O/E failure rate in patients with d14 M1, M2, or M3 BM was .88, 1.78, and 2.02, respectively (P = .0002, trend). Other significant predictors of late relapse were prognostic groups (P = .0003, trend) and initial WBC count (P = .004, trend). Predictive for both early and late relapse of ALL, early response should be monitored closely and alternative treatment regimens should be considered for slow responders.