tbuckley/cabot-search huggingface dataset:
A proposed staging system for diffuse malignant peritoneal mesothelioma patients undergoing cytoreductive surgery and perioperative intraperitoneal chemotherapy
Authors: P. H. Sugarbaker, T. Yan, D. Yoo, E. Brun, C. Cerruto, D. Chang
Journal: Journal of Clinical Oncology (2006)

4150 Background: There is no staging system available for diffuse malignant peritoneal mesothelioma (DMPM). This study evaluated seven clinical, seven radiological and twelve histopathologic prognostic parameters for survival of patients with DMPM. Methods: Between September 1989 and September 2005, sixty-two DMPM patients who were treated in a uniform fashion utilizing cytoreductive surgery combined with heated intraoperative intraperitoneal chemotherapy, with cisplatin and doxorubicin, followed by early postoperative intraperitoneal paclitaxel from postoperative day 1 to day 5 were included in this study. All prognostic parameters were analyzed in univariate and multivariate analyses using overall survival as the endpoint. The clinical and radiological data were obtained prospectively. A review of the histopathological features of DMPM was performed by two experienced pathologists, who individually evaluated each case. The mean number of specimens taken from separate anatomic sites was 11 ± 4 per patient. The mean number of slides studied was 20 ± 8 per patient. Results: The median follow-up was 37 months (range 8 to 143 months). The overall survival was 79 months (range 1 to 143 months) and 5-year survival was 50%. The following 14 prognostic variables were significant for survival in the univariate analysis: gender (p = 0.045), peritoneal cancer index (p = 0.038), completeness of cytoreduction score (p = 0.010), interpretive CT findings of the small bowel (p = 0.001), histologic type (p &lt; 0.001), nuclear size (p &lt; 0.001), nuclear/cytoplasmic ratio (p &lt; 0.001), mitotic count (p &lt; 0.001), atypical mitosis (p &lt; 0.001), chromatin pattern (p &lt; 0.001), cellular necrosis (p &lt; 0.001), perineural invasion (p = 0.037), stroma pattern (p &lt; 0.001) and depth of invasion (p = 0.014). In the multivariate analysis, the only factor that was independently associated with an improved survival was nuclear size. The 3-year survival rates with nuclear size of 10–20 μm, 21–30 μm, 31–40 μm and &gt; 40 μm were 100%, 87%, 27% and 0%, respectively. Conclusions: Nuclear size was the dominant factor determining overall survival in patients with DMPM. A histopathological staging system based on measurement of the nuclear size was proposed. No significant financial relationships to disclose.
DOUBLE BLIND RANDOMISED CONTROLLED TRIAL: INJECTION OF AUTOLOGOUS BLOOD IN THE TREATMENT OF CHRONIC PATELLA TENDINOPATHY—A PILOT STUDY
Authors: T Khanbhai, P Resteghini, S Mughal, Z Sivardeen
Journal: British Journal of Sports Medicine (2015)

Aim Patella tendinopathy is a common cause of knee pain in athletes, with limited treatment options once rehabilitation methods have failed. We conducted a double blind randomised controlled study to assess the efficacy of Autologous Blood Injections (ABI) against saline in patients with chronic recalcitrant patella tendinopathy. Methods Patients with a diagnosis of refractory patellar tendinopathy were recruited between March 2010 and March 2012. Diagnosis was confirmed on ultrasound. All patients completed the Short-form McGill pain questionnaire (MPQ), a visual analogue scale (VAS) and a VISA-P scale. Using two practitioners, patients were randomised to either receive autologous blood or saline injections. All patients were followed up for 12 months with repeat assessments. Results 22 patients completed the final review at 12-months and were included in the study. Subjects ranged in age from 22 and 61 years and were randomised to 11 in each autologous blood (ABI) and saline groups. ABI group had a mean duration of symptoms of 16.7 months whilst that of the saline group was 19.2 months. The saline group mean VAS score was reduced from 7.9 to 4.5 at 1 month (p=0.003) and 3.3 (p=0.005) at one year. With ABI, the score was reduced from 7.5 to 4.5 (p=0.005) at 1 month and 3.1 (p=0.003) at one year. VISA-P, MPQ and VAS scores were all significant in both groups. Conclusions This study demonstrated that both the ABI and saline groups experienced a significant improvement in symptoms. However, when the results were compared there was no statistical difference between the two groups. This research provided an argument that it is the tendon fenestration that provides the therapeutic effect rather than the substance being injected.
Abstract P129: FTO Genotype and 2-year Change in Body Composition and Fat Distribution in Response to Weight-loss Diets: The Pounds Lost Trial
Authors: Xiaomin Zhang, Qibin Qi, Frank Hu, Frank Sacks, Lu Qi
Journal: Circulation (2012)

OBJECTIVE The fat mass and obesity-associated gene (FTO) variant has shown the strongest association with obesity. Recent studies suggest that dietary intake may modify the genetic effects of FTO. We tested the effect of FTO variant on long-term weight loss and change in body composition in a 2-year randomized intervention trial. RESEARCH DESIGN AND METHODS FTO SNP rs1558902 was genotyped in 742 overweight or obese adults who were randomly assigned to one of four diets differing in the percentages of energy derived from fat, protein and carbohydrate (20, 15, and 65%; 20, 25, and 55%; 40, 15, and 45%; and 40, 25, and 35%) in the Pounds Lost Trial for 2 years. Body composition and fat distribution were measured in 424 and 195 participants by Dual-energy X-ray absorptiometry (DXA) and computed tomography (CT), respectively. RESULTS We found significant modification effects for diet intervention varying in protein (low vs high), but not in fat, on 2-year changes in total fat, fat free mass (FFM), fat mass% (FM%), trunk fat%, total adipose tissue mass (TAT), visceral adipose tissue mass (VAT) and superficial adipose tissue mass (SAT) (P for interactions=0.045, 0.036, 0.033, 0.048, 0.001, 0.008 and 0.002, respectively). Carriers of the risk allele (A allele) had a greater loss of weight and regional fat in response to high protein diet, while an opposite genetic effect was observed on changes in TAT and SAT in response to low protein diet at 2 years. Significant gene by diet interventions (low vs high protein) were also observed at 6 months of intervention, when the maximum of weight-loss was achieved, for changes in FFM, TAT, VAT and SAT (P for interactions=0.007, 0.019, 0.036 and 0.041, respectively). Patterns of change in body composition and fat distribution by diet intervention were similar at 6 month and 2 year. CONCLUSIONS Our data suggest that a high-protein diet may be beneficial for weight loss in individuals with the risk allele of the FTO variant rs1558902.
Association of sTNF-R1 and the development of treatment-related symptoms in patients undergoing concurrent chemoradiation therapy for colorectal or esophageal cancer
Authors: X. S. Wang, L. A. Williams, V. E. Johnson, L. Mao, S. Krishnan, Z. Liao, G. Mobley, C. S. Cleeland
Journal: Journal of Clinical Oncology (2009)

3041 Background: Cancer-treatment-induced dysregulation of proinflammatory cytokines may be a common mechanism underlying the development of symptom burden (e.g., pain, fatigue, distress, and disturbed sleep) during concurrent chemoradiation therapy (CXRT). Methods: Patients undergoing CXRT for locally advanced colorectal or esophageal cancer (N=97) reported symptoms weekly via the M. D. Anderson Symptom Inventory (MDASI). Serum samples were tested weekly during therapy for changes in concentration levels of inflammatory cytokines (interleukin [IL]-6, IL-8, IL-10, IL-1 receptor antagonist [IL-1RA], vascular endothelial growth factor [VEGF], and soluble tumor necrosis factor receptor type 1 [sTNF-R1]) via enzyme-linked immunosorbent assay (ELISA). Symptom responses were modeled using longitudinal ordinal probit regression functions that included these serum cytokine values, along with age, cancer type, prechemotherapy status, and race (non-Hispanic white vs. others), as explanatory variables. Results: The severity of multiple symptoms significantly increased at week 4 and peaked around the end of CXRT (weeks 5–7). We found that an increase in the serum level of sTNF-R1 was significantly associated with an increase in the severity of 14 of the 16 MDASI symptoms individually over the course of CXRT, as well as with each of the 6 interference items (all p&lt;.001). Even when week of observation was added as a variable to account for concurrent systematic trends in symptom reports and cytokine levels, sTNF-R1 retained a significant positive association with 14 of 16 symptoms, and IL-6 also showed a significant positive association with 6 of 16 symptoms. Conclusions: Longitudinal analysis identified temporal associations between increases in level of serum sTNF-R1 (and, to a lesser degree, IL-6) and the development of multiple symptoms in patients undergoing CXRT for colorectal and esophageal cancer. The results may be indicative of these cytokines as potential intervention targets of reducing aggressive chemoradiation-induced symptom burden. No significant financial relationships to disclose.
Association of MDR-1 gene polymorphism 2677G/T(A) and 3435C/T with clinical outcomes of paclitaxel monotherapy in metastatic breast cancer patients
Authors: H. Chang, S. Rha, H. Jeung, C. Im, J. Ahn, W. Kwon, N. Yoo, J. Roh, H. Chung
Journal: Journal of Clinical Oncology (2008)

14654
Hypothermic modulation of human cortical neurons to explore a role for tau protein in neuroprotection
Authors: Nina M Rzechorzek, Peter Connick, Matthew R Livesey, Shyamanga Borooah, Rickie Patani, Karen Burr, David Story, David J A Wyllie, Giles E Hardingham, Siddharthan Chandran
Journal: The Lancet (2016)
A phase 2 study to evaluate the efficacy and safety of SU11248 in patients (pts) with unresectable neuroendocrine tumors (NETs)
Authors: M. Kulke, H. J. Lenz, N. J. Meropol, J. Posey, D. P. Ryan, J. Picus, E. Bergsland, K. Stuart, C. M. Baum, C. S. Fuchs
Journal: Journal of Clinical Oncology (2005)

4008 Background: Standard cytotoxic chemotherapy has limited efficacy in pts with metastatic NETs. SU11248 is an oral multitargeted tyrosine kinase inhibitor with antiangiogenic and antitumor activity that specifically inhibits VEGFR, PDGFR, and c-KIT. NETs are known to be highly vascular, and both pancreatic NETs and carcinoid tumors have been shown to express high levels of both VEGF and VEGFR. In addition, evidence of clinical activity was seen in phase 1 studies. Methods: In this ongoing phase 2 study, pts with advanced, unresectable NETs were treated with repeated 6-wk cycles of SU11248, 50 mg po qd for 4 wks, followed by a 2-wk break. Treatment with prior cytotoxic chemotherapy was allowed, and pts receiving octreotide were allowed to continue treatment while on study. Pts were followed for adverse events, response, and overall survival. Pt-reported outcomes were compiled across four of the 6-week cycles using the EQ-5D and the FACIT-Fatigue subscale. Results: 106 pts were enrolled. Preliminary results are presented on 93 pts with the following characteristics: islet cell/carcinoid = 52/41; median age = 56 (range 32–81); M/F = 52/40; ECOG PS 0/1 = 50/41; prior systemic therapy: 53%; median days on treatment: 204 (range 26–543). Treatment-related toxicities were observed in 86 pts. Grade 3/4 toxicities included diarrhea (n=3, 3%), fatigue (n=23, 26%), glossodynia (n=3, 3%), nausea (n=6, 7%), neutropenia (n=12, 13%), thrombocytopenia (n=8, 9%), and vomiting (n=5, 6%). Other toxicities were infrequent. Response to therapy is shown in Table 1. There were no significant changes in quality of life over the first four treatment cycles. Conclusions: SU11248 is well tolerated and is associated with modest RRs and a high level of SD when used as a single agent in pts with advanced unresectable NET. Additional studies to explore the clinical benefit of SU11248 in pts with NET are warranted. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, Novartis, Pfizer, Sanofi Pfizer
Genotyping and strain distribution of Mycobacterium avium subspecies hominissuis isolated from humans and pigs in Belgium, 2011–2013
Authors: Christelle Vluggen, Karine Soetaert, Lucille Duytschaever, Joseph Denoël, Maryse Fauville-Dufaux, François Smeets, Nicolas Bruffaerts, Kris Huygen, David Fretin, Leen Rigouts, Claude Saegerman, Vanessa Mathys
Journal: Eurosurveillance (2016)

Mycobacterium avium represents a health concern for both humans and pigs. The characterisation of its subspecies is an important step improving the understanding of the epidemiology and the control of this pathogen. Ninety-two human M. avium strains were selected for a retrospective study. Subspecies determination by rpoB sequencing and IS 1245 /IS 901 analysis showed that 98.9% of Belgian human M. avium strains belong to the subspecies hominissuis (MAH). Some of these MAH strains present particular IS 1245 /IS 901 profiles (absence of IS 1245 and false IS901 detection provoked by the presence of IS Mav6 ). In addition, 54 MAH strains isolated from submandibular lymph nodes of Belgian pigs with lymphadenitis were included in this study. Genotyping of human and porcine isolates was performed using multispacer sequence typing (MST). In total, 49 different MST types were identified among pig (n = 11) and human (n = 43) MA isolates, with only five shared by both hosts. Among these MST types, 34 were newly identified. Our findings demonstrate the extensive genetic diversity among MAH isolates. Some genotypes were more prevalent in human or pigs but no correlation was observed between MST type and place of residence or the farm of origin for human and porcine isolates respectively, suggesting an environmental source of infection.
&lt;sc&gt;l&lt;/sc&gt;-Histidinol Protection Against Cytotoxic Action of Cytosine Arabinoside and 5-Fluorouracil in Cultured Mouse Spleen Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: R C Warrington, W D Fang
Journal: JNCI Journal of the National Cancer Institute (1982)

The effects of L-histidinol, a structural analog of the essential amino acid L-histidine, on the proliferative responses and anticancer drug vulnerability of cultured spleen cells from male C57BL/6J mice exposed to optimal mitogenic doses of concanavalin A (Con A) or E. coli lipopolysaccharide (LPS) were investigated. By means of tritiated thymidine ([3H]dThd) incorporation into acid-insoluble material as the criterion for proliferation. L-histidinol was shown to provide a dose-dependent inhibition of mitogenic responses elicited by Con A and LPS. Total (apparent) inhibition was provided by 1-mM concentrations of the analog and, at this concentration, [3H]dThd incorporation was totally reversible even after 72 hours of sustained exposure. Simultaneous addition of L-histidinol and either of the mitogens provide a Go-like arrest for 24 hours. Thereafter, the cells appeared to begin slow cell cycle transit but did not traverse the G1/S boundary within 96 hours of incubation. These responses of cultured murine lymphocytes to L-histidinol provided dramatic and extended protection from the cell cycle phase-specific drug cytosine arabinoside and dramatic but transient protection from the cell cycle-specific drug 5-fluorouracil. In principle, these findings extend the L-histidinol anticancer drug approach for improving the therapeutic index of antineoplastic agents, not only to both cycle- and phase-specific drugs, but also to primary cells of myeloid origin.
Abstract 18889: Higher Serum Interieukin-6 is a Strong Postoperative Predictor of Delirium After Isolated Coronary Artery Bypass Graft Surgery
Authors: Li Sun, Shu Ding, Xinwei Feng, Fangqin Wu, Pixiong Su, Yuzhi Shen, Haibo Zhao, Ying Wu
Journal: Circulation (2014)

Introduction: Postoperative delirium (POD) is a common neuropsychiatric complication after coronary artery bypass graft (CABG) surgery and contributes to the morbidity and mortality. Although the pathogenesis of POD is largely unknown, surgery induced systemic inflammation might play a role. We examined the predictive values of serum interieukin-6 (sIL-6) level in predicting the occurrence of POD. Methods: Ninety nine patients undergoing the first time elective isolated CABG were consecutively recruited. All enrolled patients were assessed for POD twice a day for 5 days using the Confusion Assessment Method for Intensive Care Unit, and divided into either POD or non-POD groups. IL-6 levels were measured by ELISA (R&amp;D Human IL-6 Quantikine) before operation (T0) and 6 (T6), 12 (T12) and 18 (T18) hours after operation. One-way repeated ANOVA was used to test the differences in trends and patterns of sIL-6 changes over time between the two groups. Logistic regression and ROC were performed to determine the predictive values of IL-6. Results: POD developed in 42.4% (42 of 99) patients. Among them, 90.4% POD occurred within the first 2 days after CABG. Patients with POD were older and more likely to be female. The sIL-6 levels were significantly higher in POD group than those in non-POD group with the highest levels at T6 and T12 (Figure 1). One-way ANOVA for repeated measures revealed interaction effects between time and group (with p values of &lt;0.001 and 0.019). Logistic regression showed that sIL-6 level ≥491.37 pg/mL at T18 was a strong predictor of POD (OR=4.706, 95%CI 1.998-11.082, p&lt;0.001) even after adjusting for age and female gender (OR=10.220, 95%CI 2.465-42.365, p=0.001), with a sensitivity and specificity of 66.7% and 68.4%, respectively. Conclusions: Higher sIL-6 level is an independent predictor of POD, and the sIL-6 level above 491.37pg/mL at 18 hours after CABG has a higher specificity in predicting the occurrence of POD.
Efficacy and toxicity of vinblastine, bleomycin, and methotrexate with involved-field radiotherapy in clinical stage IA and IIA Hodgkin's disease: a British National Lymphoma Investigation pilot study.
Authors: N P Bates, M V Williams, E M Bessell, G Vaughan Hudson, B Vaughan Hudson
Journal: Journal of Clinical Oncology (1994)

PURPOSE To assess the efficacy and toxicity of vinblastine, bleomycin, and methotrexate (VBM) chemotherapy with involved-field radiotherapy in clinical stage IA and IIA Hodgkin's disease. PATIENTS AND METHODS Thirty eligible patients with clinical stage IA or IIA Hodgkin's disease, at intermediate risk of relapse, were enrolled into a prospective multicenter pilot study. They received two cycles of VBM chemotherapy, followed by involved-field radiotherapy and then four further cycles of VBM. The median follow-up duration from the start of treatment is 30 months. RESULTS All 26 patients with assessable disease showed an objective response after two cycles of VBM (nine complete responses, 17 partial responses). By the completion of treatment, 27 patients were in complete remission; two had stable residual masses, which have not progressed at 26 and 34 months of follow-up; and one patient who died of treatment-related sepsis was in complete remission at that time. Two relapses have occurred, 19 and 28 months after starting VBM. Cough and dyspnea developed in 14 of 30 patients, and were associated with impairment of pulmonary function tests. Three episodes of neutropenic sepsis were recorded. CONCLUSION VBM with involved-field radiotherapy is an effective treatment for early Hodgkin's disease. However, the associated toxicity, both pulmonary and hematologic, is severe, making the regimen unsuitable for routine use.
Megestrol acetate therapy for advanced breast cancer.
Authors: E J Gregory, S C Cohen, D W Oines, C H Mims
Journal: Journal of Clinical Oncology (1985)

One hundred twenty-four patients with metastatic breast cancer were treated with 40 mg of megestrol acetate four times daily. Complete responses (CR) or partial responses (PR) were seen in 29 patients (23%). CR, PR, or stable disease (S) was seen in 80 patients (65%). The median duration of response was 22 months for CR and PR and ten months for S. A significantly higher response rate (CR + PR) was seen in estrogen-receptor-positive (ER-positive) patients (26%) and in patients who had not received prior therapy (39%). A significant relationship to response could not be established for menopausal status, progesterone-receptor (PrR) status, dominant site of disease, or prior administration of chemotherapy. Median survival was 66+ months for responders, 35 months for patients with stable disease, and 9 months for nonresponders. These differences are all statistically significant (P less than .001). Toxicity was minimal, and side effects consisted primarily of weight gain, which was seen in 18 patients (14.5%). Megestrol acetate can provide effective palliation in patients with advanced breast cancer.
MLL-AF9– and HOXA9-mediated acute myeloid leukemia stem cell self-renewal requires JMJD1C
Authors: Nan Zhu, Mo Chen, Rowena Eng, Joshua DeJong, Amit U. Sinha, Noushin F. Rahnamay, Richard Koche, Fatima Al-Shahrour, Janna C. Minehart, Chun-Wei Chen, Aniruddha J. Deshpande, Haiming Xu, S. Haihua Chu, Benjamin L. Ebert, Robert G. Roeder, Scott A. Armstrong
Journal: Journal of Clinical Investigation (2016)

Self-renewal is a hallmark of both hematopoietic stem cells (HSCs) and leukemia stem cells (LSCs); therefore, the identification of mechanisms that are required for LSC, but not HSC, function could provide therapeutic opportunities that are more effective and less toxic than current treatments. Here, we employed an in vivo shRNA screen and identified jumonji domain-containing protein JMJD1C as an important driver of MLL-AF9 leukemia. Using a conditional mouse model, we showed that loss of JMJD1C substantially decreased LSC frequency and caused differentiation of MLL-AF9- and homeobox A9-driven (HOXA9-driven) leukemias. We determined that JMJD1C directly interacts with HOXA9 and modulates a HOXA9-controlled gene-expression program. In contrast, loss of JMJD1C led to only minor defects in blood homeostasis and modest effects on HSC self-renewal. Together, these data establish JMJD1C as an important mediator of MLL-AF9- and HOXA9-driven LSC function that is largely dispensable for HSC function.