tbuckley/cabot-search huggingface dataset:
Streptozocin plus fluorouracil versus doxorubicin therapy for metastatic carcinoid tumor.
Authors: P F Engstrom, P T Lavin, C G Moertel, E Folsch, H O Douglass
Journal: Journal of Clinical Oncology (1984)

EST 5275 is a phase II and III study of fluorouracil plus streptozocin (5-FU plus STZ) or doxorubicin in patients with measurable progressive carcinoid tumor. Among one hundred seventy-two cases with no prior chemotherapy and no heart disease, the response rate was 22% for 5-FU plus STZ and 21% for doxorubicin, while the median response duration and median survival were 31 weeks and 64 weeks for the combination and 26 weeks and 48 weeks for doxorubicin. Thirty-three patients who failed 5-FU plus STZ crossed over to doxorubicin and achieved an 18% response. Of the thirty-five patients who failed on doxorubicin, 29% responded to 5-FU plus STZ. Hematologic toxicity was similar for both treatments; however, the 5-FU plus STZ patients experienced more vomiting but acceptable renal toxicity. Both chemotherapy regimens have antitumor activity in carcinoid tumors.
Constitutive HOXA5 Expression Inhibits Erythropoiesis and Increases Myelopoiesis From Human Hematopoietic Progenitors
Authors: Gay M. Crooks, John Fuller, Denise Petersen, Parvin Izadi, Punam Malik, Paul K. Pattengale, Donald B. Kohn, Judith C. Gasson
Journal: Blood (1999)
Specific knockdown of versican 1 ameliorated the impairment of elastin deposit in pulmonary fibroblasts co-cultured with cigarette smoke
Authors: Jing Zhang, Lian Wu, Chun-xue Bai, Jie-ming Qu
Journal: European Respiratory Journal (2013)

Background Loss of elastin is a feature of emphysema. After secretion from cells, tropoelastin assembles into functional insoluble elastin. In our previous study, despite the increased expression of tropoelastin by the COPD fibroblasts this did not translate into increased elastin deposit, which was accompanied by an increased production of versican 1 (V1). We hypothesized that down-regulation of V1 could improve elastin repair. Methods Pulmonary fibroblasts CCL-210 were cultured and treated with or without cigarette smoke (CS). Expression of mRNA for tropoelastin and V1 were measured by qPCR. Supernatant protein levels for V1 and soluble elastin were measured by ELISA. Insoluble elastin in lysates was measured by Fastin Elastin assay. Specific siRNA was used to knockdown V1 expression. Results CS inhibited elastin mRNA expression at 3 days and 14 days after treatment (p<0.01); levels of tropoelastin and insoluble elastin were both decreased as compared to untreated cells at 14 days (p<0.01). mRNA and protein levels of V1 were increased after CS insult (p<0.01), which was diminished by V1 siRNA. V1 siRNA did not alter the decreased tropoelastin after CS treatment, but attenuated the decreased elastin deposit.

![Figure][1] 



Conclusions V1 played a role in the impaired elastin deposit in pulmonary fibroblasts after CS exposure. Specific knockdown of V1 can alleviate the elastin loss.

 [1]: pending:yes
Phase III trial comparing initial chemoradiotherapy (intermittent cisplatin and infusional 5-FU) followed by gemcitabine vs. gemcitabine alone in patients with locally advanced non metastatic pancreatic cancer: A FFCD-SFRO study
Authors: B. Chauffert, F. Mornex, F. Bonnetain, J. P. Triboulet, O. Bouche, P. Rougier, J. F. Bosset, T. Aparicio, F. Masskouri, L. Bedenne
Journal: Journal of Clinical Oncology (2006)

4008 Background: The GITSG studies have shown a greater survival after 5 FU-based chemoradiotherapy (CHRT) than radiotherapy or polychemotherapy alone in patients (pts) with locally advanced non metastatic pancreatic cancer. This randomized trial evaluated whether initial CHRT adds to modern gemcitabine in term of Overall Survival (OS). Methods: Pts with WHO status 0–2, proven adenocarcinoma of the pancreas, without metastasis at CT-scan, and deemed non resectable, were randomized 1:1 between CHRT ( 60 Gy in 6 weeks, 2 Gy/fraction, concomitant with 5-FU, 300 mg/m 2 /24 h as a continuous infusion, day 1–5 every week and cisplatin, 20 mg/m 2 /d, day 1–5 at week 1 and 5) or gemcitabine (G) (1000 mg/m 2 weekly 7q8w) as induction treatment. Maintenance treatment was G (1000 mg/ m2 weekly 3q4w) in both arms until progression or limiting toxicity. Stratification criteria were: center, WHO status and initial surgery. It was required to include 176 pts to detect an expected change in median OS from 6 to 12 months (bilateral α = 1% and β = 10%). Intent to treat survival analysis used the Logrank test. Results: Between 03/00 and 07/05, 59 pts were randomized to CHRT and 60 to G. Median follow-up at the 05/05 was 16 months. Pt characteristics were well balanced (CHRT/G) with mean age (60.1/62.7 year), sex ratio (1/ 1.4) and WHO status ( 0–1: 88%/73%, 2: 9%/23%). During the induction phase, more than 75% of the planned dose was completed in 81.4% of pts for radiotherapy, 52.5% for 5-FU and 50.8% for cisplatin and 76.7% of pts in the G arm. In CHRT and G arms, OS at 6 and 12 months were respectively 78/82% and 24/51%, with a median survival of 8.4/14.3 months (stratified log-rank p = 0.014). CHRT or G related toxicities during induction phase were grade 3/4 leukopenia (17%/10%), thrombopenia (8.5%/0%), non-haematological toxicity (37%/ 17%) with diarrhea (7%/0% ), cutaneous toxicity (0%/3%). One treatment-related death was observed in the CHRT arm (aplasia). Conclusion: Study was stopped before the planned inclusion due to lower survival with initial CHRT when compared to G alone. Reasons explaining this difference are under investigation. No significant financial relationships to disclose.
Capacity for science in sub-Saharan Africa
Authors: Alison Elliott, Barbara Nerima, Bernard Bagaya, Andrew Kambugu, Moses Joloba, Stephen Cose, Guiseppe Pantaleo, Maria Yazdanbakhsh, David Mabey, David Dunne, Ashley Moffett, Eli Katunguka Rwakishaya, Pontiano Kaleebu, Edward Katongole Mbidde
Journal: The Lancet (2015)
Creativity and mental illness: prevalence rates in writers and their first-degree relatives
Authors: N C Andreasen
Journal: American Journal of Psychiatry (1987)

Rates of mental illness were examined in 30 creative writers, 30 matched control subjects, and the first-degree relatives of both groups. The writers had a substantially higher rate of mental illness, predominantly affective disorder, with a tendency toward the bipolar subtype. There was also a higher prevalence of affective disorder and creativity in the writers' first-degree relatives, suggesting that these traits run together in families and could be genetically mediated. Both writers and control subjects had IQs in the superior range; the writers excelled only on the WAIS vocabulary subtest, confirming previous observations that intelligence and creativity are independent mental abilities.
Phase II trial of paclitaxel and granulocyte colony-stimulating factor in patients with pancreatic carcinoma: a Southwest Oncology Group study.
Authors: R P Whitehead, J Jacobson, T D Brown, S A Taylor, G R Weiss, J S Macdonald
Journal: Journal of Clinical Oncology (1997)

PURPOSE Pancreatic cancer is difficult to treat, with most patients surgically unresectable at the time of diagnosis. Radiotherapy and chemotherapy can offer palliation, but more effective therapy is needed. This trial evaluated the effects of an aggressive schedule of paclitaxel given with granulocyte colony-stimulating factor (G-CSF) to patients with advanced pancreatic cancer. PATIENTS AND METHODS All patients were required to have a histologic diagnosis of pancreatic adenocarcinoma with measurable disease and no prior chemotherapy or radiation therapy. Patients had to have performance status of 0 to 2, pretreatment absolute granulocyte count &gt; or = 1,500/microL, and platelet count greater than or equal to the institutional lower limit of normal. Following pretreatment with dexamethasone, diphenhydramine, and cimetidine, patients received paclitaxel at a dose of 250 mg/m2 by 24-hour infusion on day 1, repeated every 21 days. G-CSF was given at a dose of 5 microg/kg/d on days 3 to 18 or until two consecutive absolute neutrophil counts (ANCs) &gt; or = 10,000/microL were obtained. Doses of paclitaxel were modified depending on nadir counts. RESULTS Forty-five patients were entered onto this study, with six ineligible. For the 39 eligible patients, there was one complete response (CR) and two partial responses (PRs), five stable/no responses, 23 increasing disease, two early deaths, and six patients whose assessment was inadequate to determine response. The response rate was therefore three of 39 or 8% (95% confidence interval [CI], 2% to 21%). The median survival time for the 39 eligible patients was 5 months. The most common toxicities were anemia, leukopenia/granulocytopenia, malaise/fatigue, nausea/vomiting, alopecia, thrombocytopenia, paresthesias, and liver function abnormalities. There was one death due to sepsis. CONCLUSION Single-agent paclitaxel in this dose and schedule has minimal activity in pancreatic adenocarcinoma patients.
Immunohistochemical Quantitation of Thymidylate Synthase Expression in Colorectal Cancer Metastases Predicts for Clinical Outcome to Fluorouracil-Based Chemotherapy
Authors: Carlo Aschele, Domizia Debernardis, Stefania Casazza, Giovanna Antonelli, Gianni Tunesi, Chiara Baldo, Rita Lionetto, Frank Maley, Alberto Sobrero
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To determine whether immunohistochemical thymidylate synthase (TS) quantitation predicts for clinical outcome in patients with advanced colorectal cancer treated by fluorouracil (FUra)-based chemotherapy. PATIENTS AND METHODS: TS levels were measured immunohistochemically on archival specimens of colorectal cancer metastases from 48 patients homogenously treated by bolus FUra plus methotrexate alternating with continuous-infusion FUra plus leucovorin. These measurements were retrospectively correlated with patient characteristics and clinical outcome. RESULTS: A significant correlation was found between intratumoral TS expression and all the parameters of clinical outcome analyzed. In patients whose tumors had low (n = 27) and high (n = 21) TS levels, the overall response rates were 67% and 24%, respectively (P = .003). The percentage of tumor shrinkage after chemotherapy was linearly related to TS immunoreactivity (r = .56, P = .00004), and its mean values were 65% and 14% with low and high TS levels, respectively (P = .0001). By logistic regression analysis, low TS expression was the single best predictor of response to chemotherapy (relative probability, 5.0). In patients with low and high TS expression, the median time to progression was 9.6 months v 6.2 months (P = .005) and the median survival time 18.4 months v 15.4 months (P = .02), respectively. Two- and 3-year survival rates were 41% v 15% and 19% v 0% (P = .02), respectively. CONCLUSION: In this cohort of homogenously treated patients, intratumor TS content was a major predictor of clinical outcome. Immunohistochemical TS quantitation provides a convenient, low-cost technique for identifying patients unresponsive to TS inhibitors who may be candidates for alternative chemotherapy regimens.
INHIBITION OF KERATINIZING STRUCTURES BY SYSTEMIC DRUGS
Authors: PETER FLESCH
Journal: Pharmacological Reviews (1963)

A variety of systemically administered chemical agents interferes with the development of human hair, horny layer, or both. These agents include vitamin A, thallium, antineoplastic compounds, hypocholesteremic drugs, chloroprene dimers, mimosine, and anticoagulants. As a general rule, the hair root is more easily affected by these compounds than the epidermis. Only the growing hairs are attacked; hence the scalp is the most commonly involved area. Disturbed epidermal differentiation follows mainly the administration of hypocholesteremic drugs.

The mechanisms of action of these compounds are incompletely understood. Vitamin A may divert cytoplasmic metabolic processes from keratin formation to mucopolysaccharide synthesis or may act by releasing a protease. Thallium interferes with the utilization or incorporation of cystine. The antineoplastic drugs inhibit mitoses in the rapidly proliferating hair matrix in a variety of ways. Hypocholesteremic drugs possibly prevent the synthesis of a proteohipid cement, while the modes of action of the chioroprene dimers, mimosine, and anticoagulants are essentially unknown. It is obvious, therefore, that hair loss and disturbed epidermal differentiation are nonspecific effects, resulting from a variety of mechanisms.

Few attempts have been made to correlate cutaneous effects or disease conditions with other pharmacologic actions of these compounds. The specific influence of vitamin A and especially of its derivatives should be studied in greater depth. Inhibition of hair growth has been used as a measure of the toxicity of cancer chemotherapeutic drugs. On the whole, however, the potentialities of these agents for pharmacologic and dermatologic research have not been sufficiently exploited.

Abnormal developments of horny structures are easily observable, accessible, and essentially harmless side-effects of drugs. Broadening of their study would enlarge our understanding not only of the biology of these processes, but also of the effects of a number of drugs. Such investigations could make important contributions to the therapy of many essentially incurable scaling skin diseases which affect a large proportion of the population, and could help in the fight against neoplastic diseases.
Abstract 869: Evaluate breast cancer diagnostic antibody specificity by using high density protein microarray technology
Authors: Donghui Ma, Jian Chen, Wei Fu, Julie McDowell, Kehu Yuan
Journal: Cancer Research (2014)

Abstract Detection sensitivity and target specificity are the two key features for a good diagnostic monoclonal antibody. There are a number of well-established technology platforms to quantitatively measure antibody affinity. However, there is no complete technology solution to evaluate antibody target specificity. Antibody cross-reactivity could lead to false diagnostic reports. Currently, high density protein microarray technology is the best technology platform available for antibody specificity evaluation. Here we will showcase how we utilized protein microarray technology to evaluate target specificity for a couple of commonly used breast cancer IHC diagnostic antibodies. Our data suggested that cross-reactivity is one of the reasons to create off-target staining for breast cancer diagnostics. We will also show how we can utilize OriGene protein microarray chip technology to develop UltraMABs, the Ultra-specific monoclonal antibodies for anatomic pathology application. Citation Format: Donghui Ma, Jian Chen, Wei Fu, Julie McDowell, Kehu Yuan. Evaluate breast cancer diagnostic antibody specificity by using high density protein microarray technology. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 869. doi:10.1158/1538-7445.AM2014-869
Abstract 2847: Presence of Spouses Impacts Positively Survival in Patients with Heart Failure Regardless of Presence of Depressive Symptoms
Authors: Misook L Chung, Terry A Lennie, Barbara Riegel, Rebecca D Dekker, Jia-Rong Wu, Seongkum Heo, Debra K Moser
Journal: Circulation (2007)

Background:  Positive spousal support is associated with improved long-term outcomes in heart failure (HF) patients. Depressive symptoms are a well-known predictor of mortality and morbidity. However, the impact of having a spouse on survival in the context of patient depressive symptoms is unknown.   Purpose : To determine the impact of a spouse on event-free survival in depressed and non-depressed patients.   Methods:  Depressive symptoms were assessed using the Beck Depression Inventory-II (BDI-II) in HF patients who were followed for 3-years to collect data on cardiac related mortality and hospitalizations. Patients were grouped into presence and absence of depressive symptom using a cut-point score of 14 on the BDI-II. The Kaplan-Meier survival analysis with a log rank test was used to obtain survival curves for married and non married groups who were stratified by presence or absence of depressive symptoms.   Results:  Of a total of 165 patients (68.7% male, 61 years, 62% NYHA class III/IV), 56% were married and 33% had depressive symptoms. Levels of depressive symptom were similar between married and non-married patients (10.9 vs. 12.1, p = 0.39). Married patients experienced longer event-free survival than non-married patients (p   Conclusion:  Regardless of depressive symptoms, patients with a spouse had longer event-free survival than patients without a spouse. Intervention aimed at improving clinical outcomes should identify and reinforce alternative social support networks for non-married patient.
Likelihood ratios should have been given
Authors: S. Sanderson
Journal: BMJ (1996)

EDITOR,—A P Davie and colleagues examine the role of electrocardiography in identifying left ventricular systolic dysfunction.1 While electrocardiography is a useful first line investigation in patients deemed suitable for open access echocardiography, it would be a mistake to recommend it as a useful investigation for all patients with suspected chronic heart failure in, for example, general practice. The problem is not with the validity of Davie and colleagues' …
XDR and MDR-TB genetic markers of M. tuberculosis strains circulating in Kyrgyz Republic
Authors: Jainagul Isakova, Nurmira Sovhozova, Barchynay Kabylova, Almaz Aldashev
Journal: European Respiratory Journal (2011)

In Kyrgyz Republic multidrug-resistant tuberculosis (MDR-TB) is a real public health problem. For treatment of MDR-TB the second-line drug fluoroquinolone (FQ) is used. The use of this drug has led to the emergence of fluoroquinolone-resistant M.Tuberculosis (M.tb).   Aim:  The aim of this study was to asses the fluroquinolone resistance in MDR-TB cases and to reveal the main mutations of gyrA gene associated with FQ resistance in Kyrgyz Republic.   Materials and methods:  DNA samples of M. tb were collected from 70 adult patients with primary MDR-TB. From all samples the 33 sputum samples were taken from patients from the penitentiary system and 37 sputum samples were taken from patients from the civilian sector. The resistance to rifampicin, isoniazid and fluoroquinolone were analyzed by biochip assay.   Results:  70 selected samples of M.tb strains carried mutations leading to MDR and including 5 cases with FQ resistance. The most prevalent mutations of gyrA gene was Asp94Gly, the second was Ala90Val. One case had the combination of both mutations Asp94Gly and Ala90Val of gyrA gene. These mutations of gyrA gene were coexisting in the same samples with Ser531Leu mutation of rpoB, Ser315Thr of katG and inhA T_15 mutation of inhA gene.   Conclusion:  In XDR-TB cases mutations of gyrA gene leading to FQ resistance of M.tuberculosis are mostly associated with presence of Ser531Leu mutation of rpoB, Ser315Thr mutation of katG gene and inhA T_15 mutation of inhA gene.
Abstract P024: Blood Pressure Levels, Aggressiveness of Antihypertensive Therapy, and Prevalence of Left Ventricular Hypertrophy
Authors: Sindhu Lakkur, Sayed Soliman, Suzanne Oparil, Suzanne Judd, George Howard
Journal: Circulation (2015)

A major cause of left ventricular hypertrophy (LVH) is an excessive hemodynamic load, making LVH more common among people with hypertension. Clinical trials of antihypertensive medication have found that treatment reduces left ventricular mass among those with hypertension, but little is known about the prevalence of LVH in the general population that are taking, and not taking, antihypertensive medication. We examined the cross-sectional association between blood pressure control and LVH among 28,106 participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, to test the hypotheses that: 1) within strata of blood pressure control, LVH will be more prevalent in those requiring more intensive treatment, and 2) that within strata of intensiveness of blood pressure treatment, that LVH will be more prevalent at higher blood pressure levels. The REGARDS study enrolled black and white participants, aged 45 and older, from 2003-2007. Systolic blood pressure was defined as normal (&lt;120 mmHg), prehypertension (120 mmHg - 139 mmHg), stage 1 (140 mmHg - 159 mmHg), and stage 2 hypertension (&gt;160 mmHg). Classes of antihypertensive medications at baseline were defined as 0, 1, 2, or 3 or more. LVH by electrocardiogram was detected in 2,803 participants. Multivariable-adjusted odds ratios (ORs) for LVH and 95% confidence intervals (CIs) were calculated using logistic regression models. The ORs (95% CIs) for each additional medication class were 1.31 (1.20-1.43) for normal blood pressure, 1.21 (1.14-1.27) for prehypertension, 1.07 (0.98-1.16) for stage 1, and 1.02 (0.88-1.17) for stage 2. The ORs (95% CIs) for each additional increase in blood pressure category were 1.57 (1.41-1.75) for no medications, 1.47 (1.33-1.63) for 1, 1.30 (1.18-1.43) for 2, and 1.21 (1.10-1.34) for 3 medications. We observed that successful blood pressure control by medication is still associated with elevated odds of LVH compared to untreated normotensive participants, emphasizing the importance of hypertension prevention.
GIST specific overall survival data of patients diagnosed in Scotland from 1995 to 1999 using the AFIP prognostic system.
Authors: S. A. Nowicki, J. Graham, G. Calman, F. Cowie, C. Dick, S. Walsh, J. D. White
Journal: Journal of Clinical Oncology (2010)

e14671 Background: The most commonly used prognostic criteria over the last few years has been the NIH criteria. However, there have been limitations specifically in the heterogeneity of tumors in the high-risk category and overlap in overall survival between low and intermediate-risk groups. Emphasis has changed to an alternative prognostic system devised by the Armed Forces Institute of Pathology (AFIP). Its main difference is that it includes the addition of tumour site as a prognostic factor. Our population study aims to provide overall survival data in relation to AFIP criteria. Methods: Patients with suspected GIST between 1995 to 1999 were included. C-kit positive and C-kit negative but CD34 positive tumours were included. GIST specific overall survival was estimated by the Kaplan-Meier method using Statistics Package for Social Sciences (SPSS Version 12.0). Results: 75 patients were analysed with a median follow up time of 11.7 years. We analysed our data, according to AFIP prognostic groups, in relation to GIST specific overall survival. Sixty percent were classified in the three low-risk groups, 13% in the moderate-risk group, and 26% in the high-risk group. Due to the lack of events, only the high-risk group achieved a median survival time (24.1 months 95%CI 0-73.7) The three low-risk categories had similar mean survival times (no risk 114.2 mths 95%CI 89.1-139.4, very low risk 126.2 mths 95%CI 107.8-144.5, low risk 116.3 mths 95%CI 94.2-138.4) but the moderate-risk group (mean 91.4 mths 95%CI 54.1-128.7) and high-risk group (mean 56.5 mths 95%CI 33.3-79.7) had lower mean survival times as predicted. Kaplen-Meier curves showed divergence of the moderate and high-risk groups from the low-risk groups (p < 0.0001). Conclusions: In relation to the AFIP criteria this population study is the first to relate the prognostic criteria to GIST specific overall survival. It confirms a significant difference between prognostic groups. However there seems close overlap been the low and very low-risk groups. This may be related to the small number of patients in this study but does raise the possibility of further refinements to the AFIP criteria. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis