tbuckley/cabot-search huggingface dataset:
Nutritional deterioration in colorectal cancer: New insights in the pathogenesis
Authors: P. Ravasco, M. Camilo, I. Monteiro Grillo, R. Pinto
Journal: Journal of Clinical Oncology (2004)

3682 Background: Cancer related wasting and the relative role of cytokines is still unknown. The aim of this prospective study in 35 colorectal cancer (CRC) patients was to explore potential inter-relationships between patients' nutritional deterioration, cancer/treatment-related factors, and IL-1ra and IL-10 cytokines. Methods: Data: cancer histology differentiation and stage, prior chemotherapy/surgery, resting energy expenditure (indirect calorimetry), weight loss, dietary intake (diet history), IL-1ra and IL-10 serum concentrations (ELISA). Results: Mann-Whitney U test univariate analysis: greater weight loss and diet intake reduction were associated with higher IL-1ra (p<.006), low histology grade (p<.03) and advanced stage (p<.04); weight loss and diet intake reduction were also associated (p=.05). The general linear model multivariate analysis was then used to calculate estimates of effect size attributed to each variable: weight loss was significantly (p<.03) determined in 18% by low histology grade, in 17% by n° positive nodes, in 16% by advanced stage, in 15% by higher serum IL-1ra and in 13% by intake reduction. Diet intake reduction was attributed (p<.02) in 21% to higher serum IL-1ra, in 19% to low histology grade, in 19% to advanced stage and in 18% to n° positive nodes. The remaining variables did not achieve statistical significance. Conclusions: CRC histological aggressiveness and burden, in conjunction with overproduction of pro-inflammatory IL-1ra appear to be key for patients' nutritional deterioration. No significant financial relationships to disclose.
Carcinogenic Effects of Intragastric 3-Methylcholanthrene and 7,12-Dimethylbenz[&lt;italic&gt;a&lt;/italic&gt;]anthracene in Wistar and Sprague-Dawley Rats&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: M. Gruenstein, D. R. Meranze, D. Thatcher, M. B. Shimkin
Journal: JNCI Journal of the National Cancer Institute (1966)

In 2 experiments involving 384 rats of the Wistar (W) and Sprague-Dawley (SD) strains, the carcinogenic effects of repeated intragastric instillations of 3-methylcholanthrene (MCA) were compared with those of single intragastric doses of 7,12-dimethylbenz[a]anthracene (DMBA). Mammary carcinomas appeared in a higher proportion and earlier in SO than in W rats exposed to either carcinogen (during 36 weeks, 90 vs. 50% with MCA in SD and W rats, at an average of 12 and 15 weeks, respectively, and 80 vs. 64% with DMBA in SO and W rats, at an average of 16 and 22 weeks, respectively). Fibroadenomas of the breast were seen in 20 percent of SD rats by 36 weeks. In W rats observed for 1 year following DMBA administration, fibroadenomas occurred in 64 percent and adenosis in 49 percent, at an average of 45 to 51 weeks, whereas after MCA administration these reactions occurred in less than 10 percent. Intraluminal secretion indicative of lactation was noted in approximately 20 percent of Fibroadenomas and adenoses. Nine W rats developed lymphoma, 5 following DMBA and 4 following MCA administration. Uterine papillary formations were observed in 1 W and 2 SD rats, and uterine carcinomas in 2 SD rats; 3 animals had received DMBA and 2, MCA.
Single-agent and combination activity of suberoylanilide hydroxamic acid (SAHA, vorinostat) in small cell lung cancer (SCLC) cell lines
Authors: C. Cubitt, S. Zhang, A. Chiappori
Journal: Journal of Clinical Oncology (2009)

e14586 Background: SCLC represents a major therapeutic challenge. Histone deacetylase inhibitors (HDAC-I) are a new class of drugs. Exposure to HDAC-Is results in hyperacetylation of core histone proteins, with subsequent chromatin decondensation, and increased topoisomerase inhibitor (TI) DNA binding, with potentiation of DNA damage and apoptosis. This synergy is only observed when the HDAC-I precedes the TI. We investigated the activity of SAHA, an HDAC-I with broad activity in different cancer cell lines, and the potential synergy between SAHA and TIs, in SCLC cell lines. Methods: TIs were obtained from chemical supply companies and SAHA from Merck. Four different cell lines (DMS-114, NCI-H69, NCI-H82, and NCI-H526) were grown and cryopreserved in the recommended media. Drug activity was determined by a high-throughput CellTiter-Blue cell viability assay. A luciferase based assay (Caspase-Glo 3/7) was used to confirm apoptosis as the cause of cell viability reductions. The Chou and Talalay method was used to optimize the drug doses to use in a combination, and to determine the influence of drug sequencing on any additive or synergistic anti- tumor effect. Results: The 72 hours inhibitory concentration 50 (IC50) values corresponding to each drug and cell line is reported in the Table . Using the CellTiter-Blue cell viability assay, the combination index (CI) for SAHA with each of 2 TIs (topotecan and etoposide) was calculated concurrently and sequentially. The strongest synergism was always detected when SAHA and the TI were combined sequentially (SAHA first). This observation was reproduced when the CI was calculated using the Caspase-Glo 3/7 luciferase based assay. Conclusions: The anti-tumor activity of SAHA in SCLC cell lines is comparable to that of common TIs. The synergism observed between SAHA and TIs is sequence specific and highest when drugs are used sequentially (SAHA first). Clinical confirmation of this synergism is warranted in patients with SCLC. [Table: see text] No significant financial relationships to disclose.
Clinicopathological, endoscopic, and molecular characteristics of the “skirt” – a new entity of lesions at the margin of laterally spreading tumors
Authors: Shozo Osera, Satoshi Fujii, Hiroaki Ikematsu, Hideaki Miyamoto, Yasuhiro Oono, Tomonori Yano, Atsushi Ochiai, Takayuki Yoshino, Atsushi Ohtsu, Kazuhiro Kaneko
Journal: Endoscopy (2016)

A slightly elevated flat lesion with wide pits has occasionally been observed at the margin of laterally spreading tumors (LSTs) and is known as a "skirt." The aim of this study was to evaluate the clinicopathological, endoscopic, and genetic characteristics of a skirt.Consecutive LSTs were examined to evaluate the pathological, endoscopic, and genetic characteristics. Pathological characteristics, including the dimension of the cryptic opening (DCO), width of the individual gland (WIG), DCO to WIG ratio, and microvessel diameter were elucidated and compared with those of hyperplastic polyps, low grade dysplasia (LGD), and normal mucosa. The endoscopic findings of pit and microvascular patterns were assessed. Gene mutation analyses were performed for the KRAS, BRAF, NRAS, and PIK3CA genes.A skirt was identified in 35 of 1023 LSTs, and 80 % of lesions with a skirt had a component of either intramucosal or submucosal adenocarcinoma. The DCO, WIG, and DCO to WIG ratio of the skirt were significantly larger than those of other lesions. The microvessel diameters in skirts were significantly smaller than those in LGDs. Regarding the endoscopic findings, 30 skirts showed pits with a coral reef-like appearance, and all skirt regions were found to have a type I capillary pattern. KRAS mutation at codon 146 was found in the nodular part in one of five LSTs with a skirt.The skirt is a newly identified lesion distinct from hyperplastic polyps and LGDs, suggesting the presence of a novel pathway for rectal carcinogenesis from LSTs with a skirt.
Outbreak of Clostridium histolyticum infections in injecting drug users in England and Scotland
Authors: J  S Brazier, M Gal, V Hall, T E Morris
Journal: Eurosurveillance (2004)

Clostridial infections in injecting drug users in the United Kingdom are a relatively new phenomenon that came to light in 2000 when cases of serious illness and deaths due to Clostridium novyi were recorded. In the period December 2003 to April 2004, the Anaerobe Reference Laboratory received twelve referrals of an extremely rare isolate, Clostridium histolyticum, from cases of infection in injecting drug users submitted from nine different hospitals in England and Scotland. Molecular typing of these isolates by two different methods of pulsed-field gel electrophoresis and PCR ribotyping revealed they are all indistinguishable, indicating a common source of the infections, most probably a batch of heroin that was recently distributed across the UK.
Effect of cyclosporine on endothelial albumin leakage in rats.
Authors: L C Moore, J Mason, L Feld, J B Van Liew, F J Kaskel
Journal: Journal of the American Society of Nephrology (1992)

Short-term treatment of rats with cyclosporine (cyclosporine A [CsA]; Sandimmune) results in a marked reduction in intravascular plasma volume, a factor that might contribute to the renal dysfunction associated with this potent immunosuppressant. To examine the role of plasma extravasation in CsA-induced hypovolemia, intravascular plasma volumes (PV), blood volumes, [125I]albumin disappearance, and changes in hematocrit (Hct) were measured in Inactin-anesthetized rats subjected to minimal surgery. The rats were treated for 3 wk with either 25 mg/kg/day of CsA s.c. or vehicle. Plasma creatinine and urea were significantly elevated, and magnesium was reduced in the CsA group (N = 6) as compared with controls (CON) (N = 6). CsA treatment had no effect on urinary protein and albumin excretion. Blood volume was significantly lower in CsA than in CON (8.4 +/- 0.5 versus 10.6 +/- 0.3 mL/100 g body wt) as was PV (4.3 +/- 0.2 versus 5.5 +/- 0.2 mL/100 g body wt). Two hours after injection, plasma [125I]albumin concentration had fallen by 41 +/- 4% in CsA versus 23 +/- 5% in CON. Because Hct, and, hence PV, was unchanged in both groups during these 2 h, these data indicate enhanced endothelial albumin leakage in the CsA group. In two additional groups of six rats each, acute volume expansion with fresh whole blood (2 mL/100 g body wt) resulted in extravasation of plasma. Hct rose by 8.0 +/- 0.2% in CsA versus 3.8 +/- 0.2% in CON after 150 min, corresponding to 27 +/- 3 and 15 +/- 2% decreases in total PV, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Bronchial hyperresponsiveness using mannitol in morbid obesity before and after bariatric surgery
Authors: Ebymar Arismendi, Eva Rivas, Yolanda Torralba, Felip Burgos, Josep Roca, Josep Vidal, Roberto Rodriguez-Roisin
Journal: European Respiratory Journal (2012)

Introduction: The association between bronchial hyperresponsiveness (BHR) and morbid obesity (MO) is common.

Objective: To investigate the prevalence of BHR using mannitol (MAN) in patients with MO before and one year after bariatric surgery (BS).

Methods: We determined BHR in 70 patients with MO (46±11 yr; BMI, 46±6 kg/m2; 53 females; smokers, [33±26 pack-yr] 59%). BHR(+) was defined as a PD15<635mg. Severe OSA (apnea/hypopnea Index [AHI] ≥ 30 events/h) was present in 31 patients.

Results: Before BS, patients had FEV1, 93±15%; FEV1/FVC, 0.83±0.05; bronchodilator test, +4.9±0.7%. Twenty two had BHR(+) (PD15=78 mg) with an FEV1 fall of -20±2%. BMI and central obesity (abdominal circumference and waist-hip-ratio) were higher in patients with BHR(+) than in those BHR(-) (p<0.05 each). Likewise, the AHI was higher (53±10 vs 29±5 events/h) in patients with BHR(+) than in those BHR(-) (p<0.05).

The ratio-dose-response (RDR) to MAN was positively associated with BMI (r=0.30, p<0.05). There were also associations between AHI and TNF-α, and between the abdominal circumference and TNF-α (r=0.40, p<0.05 each).

After BS, all but one BHR(+) patient, reverted their BHR (PD15 ≥ 635 mg) with an FEV1 fall of -8±2%, and IL-8 levels decreased in all patients (p<0.05).

Conclusions: In MO the prevalence of BHR with MAN is elevated, which is associated with increased BMI, central obesity and AHI. Our findings suggest that obstructive sleep apnea and central obesity can in MO share a similar pathogenic mechanism related to development of BHR.

Supported by FIS PI080311 CIBERES, Almirall and Esteve.
Quality of life (QoL) correlates with the rest/activity circadian rhythm (RAR) in patients (pts) with metastatic colorectal cancer (MCC) on first line chemotherapy with 5-fluorouracil, leucovorin and oxaliplatin: An international multicenter study (EORTC 05963)
Authors: P. F. Innominato, C. Focan, G. A. Bjarnason, C. Garufi, S. Iacobelli, M. C. Mormont, J. Waterhouse, T. Gorlia, S. Marreaud, F. A. Lévi
Journal: Journal of Clinical Oncology (2005)

8029 Background: The assessment of quality of life with questionnaires is limited by their subjective nature. Actigraphy monitoring is non invasive and provides quantitative parameters of the RAR that correlate with QoL items and can complement QoL questionnaires (Clin Cancer Res, 2000: 6; 3038). In this multicenter trial, we prospectively investigated the correlation between QoL and RAR parameters in previously untreated MCC pts. Methods: Before the first chemotherapy course, 94 MCC pts completed the EORTC QLQ-C30 and had RAR assessment for 3 days using a small wrist-watch (actigraph), which records the number of arm movements per minute. Three validated RAR parameters were calculated: mean activity (mAct), autocorrelation coefficient at 24h (r24), indicating the robustness of the activity pattern over a period of 24-h, and dichotomy index (I<O), quantifying the differences in activity distribution between the rest span and the active phase. QoL items were correlated with RAR parameters by the Spearman rank 2-sided test. Results: Global QoL correlated positively with mAct (r = 0.36, p = 0.0005), r24 (r = 0.35, p = 0.0006) and I<O (r = 0.40, p < 0.0001). I<O was negatively correlated with fatigue (r = -0.39, p < 0.0001), appetite loss (r = -0.38, p < 0.0001) and pain (r = -0.37, p = 0.0002). A positive correlation was found between r24 and social functioning (r = 0.35, p = 0.0006) as well as I<O and physical functioning (r = 0.36, p = 0.0004). Conversely, RAR parameters were poorly or not correlated with insomnia, cognitive and emotional functioning. Conclusions: This prospective multicenter study has established the correlation between the RAR and global QoL, several symptom scores and functioning scales in chemotherapy-naïve MCC pts. The circadian timing system, that generates the RAR, can be disrupted in cancer. Monitoring this system gives an objective and quantitative estimate of QoL and symptom clusters in cancer pts. The strength of the relation between RAR output and QoL is being further assessed during interventions targeted at the circadian system. No significant financial relationships to disclose.
Abstract 230: Gender Differences in the Development of Experimental Pulmonary Hypertension and Associated Right Ventricular Remodeling: The Role of Estrogen Rescue
Authors: Soban Umar, Rangarajan Nadadur, Mansoureh Eghbali
Journal: Circulation Research (2012)

17-beta estradiol or Estrogen (E2) pre-treatment has been shown to attenuate the development of pulmonary hypertension (PH). Here, we aim to investigate the gender differences and the effect of ovariectomy on the development of experimental PH and adverse right ventricular (RV) remodeling. We also evaluate the therapeutic potential of E2 in rescuing PH and adverse RV remodelling in male and female rats. Male and female (intact and ovariectomized (OVX)) rats were treated with a single injection of monocrotaline (MCT, 60mg/kg, s.c.) to induce PH. Twenty one days after MCT, rats developed severe PH. At this point, one set of rats from each group was left untreated to develop PH-induced right ventricular failure (RVF), whereas the other set received E2 (42.5 ug/kg/day, 10-day slow release s.c. pellets). E2-treated rats were observed for an additional 12 days after cessation of therapy to check whether the effects of therapy were long-lived. Saline treated rats served as control (CTRL). Serial echocardiography was performed to monitor cardiopulmonary hemodynamics. Direct RV catheterization was terminally performed to record RV peak systolic pressure (RVPSP). The expression of novel extracellular matrix (ECM) enzymes A Disintegrin And Metalloproteinase (ADAM15 and 17) and Osteopontin (OPN) were assessed by RT-PCR. Intact females developed less severe PH than males and OVX females at day 30 (RVPSP: Females=62±3, Males=74±3, OVX=77±3 mm Hg, p&lt;0.05 vs. respective CTRL). E2 therapy resulted in rescue of PH in all groups (RVPSP: Females=36±4, Males=38±2, OVX=44±2 mm Hg, p&lt;0.05 vs. respective PH-RVF). Intact females also developed less severe RV remodeling compared to males and OVX females. Expression of OPN increased ∼7-9-fold in PH-RVF males and OVX but only ∼2-fold in intact females, (p&lt;0.05 vs. CTRL for all). E2 reversed OPN upregulation in all groups (p&lt;0.05 vs. PH-RVF). Novel ECM-degrading Disintegrin-Metalloproteinases ADAM15 and ADAM17 transcripts were also elevated ∼2-fold in all PH-RVF animals (p&lt;0.05 vs. CTRL). E2-therapy reversed RV remodeling in all groups (p&lt;0.05 vs. PH-RVF). In conclusion, intact females are more protected against the development of PH compared to males and OVX females. E2 rescues PH and adverse RV remodeling in all groups.
Release of Virus Infectious to Chickens by RBI Rat Sarcoma in Tissue Culture and by Its Ascites Form Into the Ascitic Fluid
Authors: J. Svec, E. Hlavay, F. Svec
Journal: JNCI Journal of the National Cancer Institute (1968)

Induced by the B77 variant of Rous sarcoma virus, the RBI rat sarcoma, which was adapted to growth in tissue culture, released a virus infectious to chickens into the culture fluid. A 100% take in chickens was obtained with the dilution 1:2, when the number of cells in culture was at least 1 × 104/ml. An ascites form was developed from the RBI tumor. The ascites sarcoma cells released infectious virus into the ascitic fluid. The titer varied between 120 and 1,280 ID50/ml of cell-free ascitic fluid. Chromosome analysis of the ascites form of RBI sarcoma confirmed the rat origin of the cells. The number of chromosomes was hyperdiploid, with 35.4% of cells having a stemline of 59–60 chromosomes. No marker chromosome was found.
대한간학회지 제2차 춘계학술대회 초록집 : 간경변성 복수의 조절에 있어서 Transtubular Potassium Concentration Gradient (TTKG) 및 임의요 전해질 농도의 유용성
Authors: 임영석 ( Im Yeong Seog ), 이효석 ( Lee Hyo Seog ), 송인성 ( Song In Seong ), 김정룡 ( Kim Jeong Lyong )
Journal: Clinical and Molecular Hepatology (1996)
Randomized multicenter phase III study in patients with locally advanced adenocarcinoma of the pancreas: Gemcitabine with or without chemoradiotherapy and with or without erlotinib—LAP 07 study.
Authors: P. Hammel, F. Huguet, J. Van Laethem, D. Goldstein, B. Glimelius, M. J. Moore, B. Chibaudel, F. Bonnetain, C. Louvet
Journal: Journal of Clinical Oncology (2011)

e14619 Background: Administration of chemoradiotherapy (CRT) in patients with LAP cancer stable after induction CT could be superior to continue CT alone (Huguet, JCO 2007;25:326-31). Role of erlotinib in LAP cancer is unknown. This international multicenter randomized study assess whether CRT could increase OS vs continuation CT in patients whose LAP cancer is controlled after 4 months, and the role of erlotinib on overall survival (main objectives). Methods: Randomizations: 1) R1: gemcitabine (Burris) vs gemcitabine plus erlotinib (100 mg/d). Stratification: center, PS. 2) R2 (tumor controlled after 4 months CT): continuation CT vs CRT (54 Gy, capecitabine 1,600 mg/m2). Stratification: center, initial arm. Patients in the arm erlotinib will continue the drug as maintenance therapy (150 mg/d) after completing CT or CRT. To test hypotheses, 600 patients should achieve R2 (902 patients required). Duration of study: 47 months. Intermediate analysis: superiority of RCT: 257 deaths, erlotinib: 400 deaths. Ancillary studies: predictive markers; circulating tumor cells (France only). Quality assurance for RT: validation a dummy run and CD-ROM with defined items provided after completion of treatment. Major eligibility criteria: tumor stage III, usual clinico-biochemical criteria, no ophthalmic disease. Clinical trial registry number: EUDRACT 2007-001174-87. Results: First inclusion: February 2008. Current enrollment on 1-2-2011: 323 patients included. Participating countries: France (271), Belgium (32), Australia-New Zealand (12), Sweden (8). Conclusions: LAP 07 is the largest randomized study dedicated to LAP cancer. We aim to address the role of CRT with quality control in patients whose tumor has been firstly controlled by CT, and the role of erlotinib in this disease.
Abstract P186: Quality of Total Heart Adipose Tissue May Contribute to the Presence and Extent of Coronary Artery Calcification in Women at Midlife: The Study of Women’s Health Across the Nation
Authors: Carrie L Hanley, Karen Matthews, Maria M Brooks, Imke Janssen, Matthew J Budoff, Akira Sekikawa, Suresh Mulukutla, Samar R El Khoudary
Journal: Circulation (2015)

Background: The location and quantity of specific adipose tissue depots have been shown to be independent predictors of subclinical atherosclerosis. Most recently, attention has been focused on the quality of these fat depots as a novel marker of CVD risk. Adipose tissue attenuation, measured via radiodensity in computed tomography (CT) Hounsfield units (HU), is one such marker of fat quality. Our objective was to determine the cross-sectional association between total heart adipose tissue (TAT) radiodensity and coronary artery calcification (CAC) in women at midlife, a time period marked with an increase in CVD risk. Methods: Participants from the Study of Women’s Health Across the Nation (SWAN) Ectopic Cardiovascular Fat Ancillary Study were evaluated. CAC and TAT were measured using electron-beam CT. CAC was evaluated as 1) presence of CAC (CAC Agatston score &gt;10), and 2) extent of CAC (continuous Agatston score). TAT radiodensity was evaluated as tertiles of HU (lowest tertile, -91 to -81 HU; middle tertile, -80 to -78 HU; highest tertile -77 to -67 HU). Logistic (for CAC presence) and Tobit regression (for CAC extent) were used for statistical analyses. Results: A total of 495 women with a mean age of 51 years were examined. This sample of women was 63% white, 37% black, 54% pre-/early peri-menopausal, 35% late peri-/postmenopausal, and 11% used hormones. In unadjusted logistic and Tobit regression models ( Table 1 ), the tertiles of TAT were significantly and inversely associated with the presence and extent of CAC. In fully adjusted models, the middle tertile remained significantly inversely associated with the presence and extent of CAC compared to the lowest tertile, but the adjusted estimates for the highest tertile were attenuated and non-significant ( Table 1 ). Conclusions: There appears to be an inverse relationship between TAT radiodensity and CAC which is more pronounced for those with mid-range radiodensity values. These results merit further investigation.