tbuckley/cabot-search huggingface dataset:
Different types of mutations in GISTs: Different clinical implications?
Authors: C. Braconi, I. Bearzi, F. Bianchi, R. Bracci, A. Costagliola, F. Arduini, A. Mandolesi, R. Cellerino
Journal: Journal of Clinical Oncology (2007)

20505 Background: Mutations of KIT or PDGFRa are associated with the pathogenesis of gastrointestinal stromal tumors (GISTs). The prognostic significance of these mutations is still controversial. Methods: We examined 125 patients diagnosed with GISTs. Genomic DNA was extracted from paraffin-embedded tumor tissues and analysed for the presence of KIT exon 9 and 11 mutations and PDGFRa exon 12 and 18 mutations. DFS (Disease Free Survival) was analysed in 92 radically resected patients. The relation between mutations and clinico-pathological factors was analysed using Fisher's exact test and Kaplan-Meyer analysis. Results: KIT mutations occurred in exon 9 in 15 cases and in exon 11 in 78 cases. PDGFRa mutations have been detected mainly in exon 18 (10 cases) and less frequently in exon 12 (3 cases). Exon 11 mutations were as follows: deletions in 58%, point mutations in 30%, insertions and duplications respectively in 4 and 5 cases. Although type of mutations within exon 11 KIT didn't correlate with DFS, a better trend was evident for duplicated and point mutated GISTs. Exon 9 KIT mutated GISTs were associated with intestinal location and higher grade. There was significant association between PDGFRa mutations, gastric location and lower mitotic index. Moreover, PDGFRa mutated and wild type GISTs seemed to have a better outcome. Conclusions: Point mutations and duplications in exon 11 KIT were associated with a better clinical trend in DFS. Exon 9 KIT mutations significantly correlated with intestinal location and higher mitotic count. PDGFRa mutated GISTs were localized in the stomach and seemed to have a favorable clinical behavior. No significant financial relationships to disclose.
Two Turkish doctors who went to aid of protesters are sentenced to prison
Authors: Ingrid Torjesen
Journal: BMJ (2015)

Two doctors who gave first aid to people injured during the Gezi Park demonstrations in Istanbul in 2013 have been given a 10 month prison sentence by a Turkish court.

The convictions of Yasemin Erenc and Sercan Yuksel for “denigrating a mosque” while delivering healthcare services have been condemned by human rights organisations and the World Medical Association. The doctors are currently not in prison and are expected to appeal the sentences.

The charges against them were brought in an action against 255 people caught up in the 2013 Gezi Park protests. The protests began in late May 2013 against plans to build a shopping centre on the central park, one of the few green spaces left in the …
From Mice to Men and Back: An Assessment of Preclinical Model Systems for the Study of Lung Cancers
Authors: Adi F. Gazdar, Fred R. Hirsch, John D. Minna
Journal: Journal of Thoracic Oncology (2015)

Studies of preclinical models are essential for determining the biology of lung cancers and testing new and novel therapeutic approaches. We review the commonly used preclinical models for lung cancers and evaluate their strengths and weaknesses.We searched the MEDLINE database via PubMed using combinations of the following medical subject headings: lung cancer; animal models, mice; cell line, tumor; cell culture, mice; transgenic, mice; SCID, transplantation; heterologous; and genetic engineering. We reviewed the relevant published articles.Multiple examples of the three major preclinical models-tumor cell lines, patient-derived xenografts, and genetically engineered mouse models-exist and have been used by investigators worldwide, with more than 15,000 relevant publications. Each model has its strengths and actual or potential weaknesses. In addition, newer forms of these models have been proposed or are in use as potential improvements over the conventional models.A large number and variety of models have been developed and extensively used for the study of all major types of lung cancer. While they remain the cornerstone of preclinical studies, each model has its individual strengths and weaknesses. These must be carefully evaluated and applied to the proposed studies to obtain the maximum usefulness from the models.
CORRESPONDENCE
Authors: D. SPICER, D. SHOUPE, M. PIKE
Journal: JNCI Journal of the National Cancer Institute (1991)

The authors point out an error in a news article about their research on a contraceptive containing a gonadotropin-releasing hormone antagonist and 0.6-0.9 mg conjugated equine estrogens taken 6 days/week and progestogens for 13 days every 4 months.  The article erroneously stated that the women taking the drug had no sex steroids.  They were actually replacing estrogens at a dose equivalent to what is given to menopausal women a dose much lower than the steroids in oral contraceptives.  The GnRH antagonist effectively inhibits ovulation but without added sex hormones women would suffer symptoms of estrogen deficiency such as bone demineralization and cardiovascular risks.  This new contraceptive regimen should prevent ovarian and endometrial cancer as oral contraceptives do by inhibiting ovulation but also lower risk of breast cancer by providing a lower total steroid dose.
In older adults with treatment-resistant depression, adding aripiprazole to venlafaxine increased remission at 12 wk
Authors: Ana Hategan
Journal: Annals of Internal Medicine (2016)

Source Citation Lenze EJ, Mulsant BH, Blumberger DM, et al. Efficacy, safety, and tolerability of augmentation pharmacotherapy with aripiprazole for treatment-resistant depression in late life: a randomised, double-blind, placebo-controlled trial. Lancet. 2015;Sep 24. [Epub ahead of print.] 26423182
A randomized phase II trial of mitoxantrone, estramustine and vinorelbine or 13-cis retinoic acid, interferon and paclitaxel in patients with metastatic hormone refractory prostate cancer: results of ECOG 3899
Authors: R. S. Dipaola, J. Manola, S. Li, D. Vaughn, B. Roth, G. Wilding
Journal: Journal of Clinical Oncology (2004)

4594 Background: Additional options of chemotherapy are limited for hormone refractory prostate cancer (HRPC), making the study of novel agents and combinations critical. We tested two novel regimens in HRPC. Given data demonstrating that retinoids and interferon reduce Bcl-2 expression, the effect of therapy on Bcl-2 was tested in peripheral blood mononuclear cells (PBMC). Methods: Patients (pts) received 10 mg/m2 mitoxantrone on d2, 280 mg bid estramustine on d1–5 and 25 mg/m2 vinorelbine on d2 and 9 (MEN) q3 wks (Arm A), or 1 mg/kg 13 cis-retinoic acid, 6 million U/m2 alpha interferon on d1 and 2, and 75 mg/m2 paclitaxel on d2 (RIT) weekly for 6 out of 8 weeks (Arm B). PBMCs were obtained on day 1 and 3 to assess the effect on Bcl-2 by immunoblot. Results: Seventy pts with HRPC, without prior chemotherapy, were entered. PSA at entry was 165 ng/ml in arm A and 234 ng/ml in arm B. In arm A, grade > 2 toxicities included neutropenia in 77%, with only 3% febrile neutropenia, thrombosis in 16%, and fatigue in 22%. In arm B, grade > 2 toxicities included neutropenia in 13%, with no pts having febrile neutropenia, thrombosis in 3%, and fatigue in 23%. Biochemical response, defined as a decrease in PSA >/= 50%, occurred in 50% (13/26) and 17% (4/24) of evaluable pts in arm A and B respectively. Partial tumor response was documented in 2/10 pts in arm A and 2/12 pts in B with measurable disease. Stable measurable disease occurred in 5/10 and 6/12 pts in arm A and B respectively. Median overall survival was 18.4 and 11.5 months in arm A and B respectively. Bcl-2 expression in PBMCs deceased significantly during therapy only in arm B (p=0.03). There was no association with the decreased expression of Bcl-2 and response, but power is limited for comparison. Assessment of Bax is ongoing. Conclusion: MEN and RIT are well tolerated in pts with HRPC. Therapy with MEN offers an active non-taxane combination that may warrant further study in pts after progression on taxane therapy. The activity of RIT is not enough to warrant study in phase III trials. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Glaxo Aventis; Bristol-Myers Squibb
Comparative Effects of Mare, Stallion, Gelding Horse, and Fetal Bovine Sera on Neoplastic Transformation &lt;italic&gt;In Vitro&lt;/italic&gt;
Authors: Virginia J. Evans, Floyd M. Price, Katherine K. Sanford, Harold A. Kerr, Sandra L. Handleman
Journal: JNCI Journal of the National Cancer Institute (1972)

This study compares the effects of several sera on the spontaneous neoplastic transformation of C3Hf mouse embryo cells in vitro. These sera would differ in hormonal content and included fetal bovine, mare, stallion, and gelding horse sera. AHempts also were made to diagnose the neoplastic potential of the cells by means of cytologic criteria developed for similar cell culture systems. The 3 different pools of embryo cells used to initiate cell lines were found to vary in their potential for neoplastic transformation. The reason for this variation is still unclear. From results of animal assays and cytologic observations, mare serum, like fetal bovine serum, appeared to delay or inhibit spontaneous neoplastic transformation as compared with the 2 male sera, stallion and gelding. This effect on neoplastic transformation appeared to be unrelated to the growth-stimulating capacity of the sera.
Psychogenic cough: Clinical and laboratory characteristics
Authors: Vasiliki Avramidou, Elpis Hatziagorou, Fotis Kirvassilis, Dimos Gidaris, John Tsanakas
Journal: European Respiratory Journal (2011)

Background:  A bizarre loud and honking cough which increases with increased attention and is absent at night in an otherwise well child suggests a psychogenic origin.   Aim – method:  Clinical and laboratory characteristics of children with psychogenic cough were analyzed retrospectively. Children were followed up in a Paediatric Respiratory clinic, over a nine year period.   Results:  114 children with psychogenic cough (46% boys) aged 4.5 - 18 years were evaluated. Mean duration of the cough was 8.66±11.1 months. Clinical characteristics of cough were: harsh and explosive (85%), croupy and barking (14%), exacerbating in the presence of medical staff (62%), disappearing with sleep (98%), not exacerbated with exercise (82%), not accompanied with wheeze (98%). Fifty-three children (46%) appeared to be under psychological stress, including school phobias, attention seeking, or anxiety (28%) and parental strife (18%). Sixty-three children (55%) had been prescribed antitussive medication, salbutamol, inhaled and oral steroids, or anti-histamines, with no response. Physical examination and lung function tests were normal. Among 21% of the children flexible bronchoscopy was normal. Explanation and discussion of the problems that appeared to be associated with the cough were beneficial for 81% of the patients. 6% of cases with persistent symptoms despite reassurance were referred for psychiatric consultation.   Conclusions:  In children with chronic cough, the characteristics of the cough may be suggestive of psychogenic cough. The physician9s awareness of the possibility of psychogenic factors in the aetiology of persistent cough may help in early diagnosis and thus unnecessary and expensive investigations may be avoided.
Hormone treatment may help prevent premature menopause in cancer patients
Authors: Jacqui Wise
Journal: BMJ (2015)

Young women with breast cancer who are given a luteinising hormone releasing hormone (LHRH) analogue, triptorelin, alongside chemotherapy are more likely to retain ovarian function, a study in JAMA shows.1

Early menopause and impaired fertility are possible consequences of cancer treatment. This can add to a patient’s distress and may also affect treatment decisions. Freezing eggs or embryos is the standard procedure for fertility preservation in patients with cancer. Administering LHRH analogues during chemotherapy to …
Anal cancer incidence in relation to HIV epidemiology
Authors: E. Y. Chiao, D. Schrag
Journal: Journal of Clinical Oncology (2004)

4080 Background: Like cervical cancer, squamous cell carcinoma of the anal canal (SCCA) is etiologically linked to Human Papilloma Virus (HPV). HIV-related immunosupression likely contributes to the increased incidence of SCCA. We sought to describe secular trends in SCCA in relation to the HIV epidemic. Methods: We used data from the Surveillance, Epidemiology and End Results (SEER) database to calculate trends in age-adjusted incidence of SCCA from 1973–2000. We analyzed the data according to three separate periods during the HIV epidemic: Pre-HIV (cases reported from 1973–1984), Pre-Highly Active Antiretroviral Therapy (HAART) (cases reported from 1985–1995), and Post-HAART (cases reported from 1996–2000). Results: A total of 6,061 cases of SCCA were reported from 1973–2000. The incidence per 100,000 of SCCA increased from 0.8 (0.8,0.9) pre-HIV to 1.1 (1.0,1.1) pre-HAART to 1.4 (1.3,1.5) with HAART. The gap between SCCA incidence in women compared to men decreased from 1.7:1 Pre-HIV to 1.1:1 in the HAART era. The gap between SCCA incidence in cases > age 60 compared to ages 20–59 has also decreased from 4:1 Pre-HIV to 3:1 in the HAART era. Percentage of cases diagnosed early (In situ or Localized disease) increased from 44% pre-HIV to 50% pre-HAART and to 60% with HAART. Percentage of advanced disease (Regional Lymph Node involvement, and Distant metastases) decreased from 47% pre-HIV to 35% pre-HAART and to 30% with HAART. Five-year relative survival increased from 63% pre-HIV to 64% pre-HAART to 68% with HAART. Conclusions: Despite the advent of HAART therapy for HIV, the incidence of SCCA continues to increase. The incidence of SCCA has particularly increased in men and in cases age 20–59 which suggests an association with the HIV epidemic. No significant financial relationships to disclose.
Abstract P322: Reproducibility, Validity, and Responsiveness of the 200-Meter Fast Walk Test in Patients Undergoing Cardiac Rehabilitation
Authors: Vincent Gremeaux, Armelle Hannequin, Gaelle Deley, Julien Duclay, Davy Laroche, Jean-Marie Casillas
Journal: Circulation (2012)

Introduction: The 200-Meter Fast Walk Test (200-mFWT) has recently been designed to assess functional capacities at a higher intensity level than does the 6-Minute Walk Test in healthy elderly people and in coronary artery disease (CAD) patient. Objective: to investigate the reliability, validity, and responsiveness of the 200-mFWT in coronary artery disease CAD patients engaged in a cardiac rehabilitation program. Design: Descriptive study. Setting: tertiary care hospital. Subjects: Thirty stable CAD patients (51.9±8.7 yrs), referred to the cardiac rehabilitation department after an acute coronary syndrom (ACS). Main measures: 6MWT distance, time to perform the 200-mFWT, peak power output of the graded maximal exercise test (GMET), before and after the program; SF-36 quality of life questionnaire at baseline. Walk tests were performed twice at baseline to assess reliability. Results: The 200-mFWT was highly reliable (ICC=0.97). It was significantly correlated with the GMET peak power and the 6-MWT at baseline (r=-0.417; p&lt;0.05; and r=-0.566; p&lt;0.01, respectively) and after the training program (r=-0.460, p&lt;0.05; and r=-0.926; p&lt;0.01respectively). At baseline, there was a strong correlation between the 200-mFWT time and the physical component score of the SF-36 (r=-0.77; P&lt;0.01), but not between the 200-mFWT time and the SF-36 mental component score. Mean 200-mFWT time was significantly different between the patients performing ≤ 90Watts (n=11) or ≥ 100Watts (n=19) at the baseline GMET (121.7±13.6 vs 115.5±10.1 sec; P&lt;0.05). The responsiveness was strong with a standardized response mean at 1.11. Conclusion: the 200-mFWT is a reliable, valid, discriminant, and responsive high-intensity walk test in CAD patients after an ACS. It can thus give additional information to those given by the 6-MWT and the GMET.
Dual VEGF inhibition with sorafenib and bevacizumab (BEV) as salvage therapy in metastatic colorectal cancer (mCRC): Results of the phase II North Central Cancer Treatment Group study N054C.
Authors: A. Grothey, J. M. Lafky, B. W. Morlan, P. J. Stella, S. R. Dakhil, P. D. Steen, W. S. Loui, B. M. Bot, S. R. Alberts, J. T. Reynolds
Journal: Journal of Clinical Oncology (2010)

3549
Epidemiologic Studies of Childhood Leukemia in Green Bay, Wisconsin&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: J W Flynt, I L Doto, R J McCollough, T D Chin
Journal: JNCI Journal of the National Cancer Institute (1970)

A cluster of 5 cases of acute lymphocytic leukemia in children under 15 years of age in Green Bay, Wisconsin, in 1963 and 1964 led to the study of leukemia, lymphoma, and congenital malformations in the metropolitan area of Green Bay. A threefold increase in the observed number of leukemia cases above expected was found in the age group of 0–4 years of western Green Bay in 1963–64 and 1958–62. The preponderance of leukemia cases in western Green Bay could not be attributed to any significant differences between the eastern and western sections. A peak in the incidence of congenital defects coincided with the month of onset of 2 of the cases of leukemia clustering.
Etoricoxib demonstrates similar efficacy and improved gastrointestinal safety compared to naproxen in two 138-week randomized studies of osteoarthritis patients
Authors: Jean-Yves Reginster, C. L. Fischer, A. Beualieu, K. Malmstrom, S. P. Curtis, E. R. Miller, G. Bergman, J. Smolar, A. S. Reicin
Journal: Annals of the Rheumatic Diseases (2004)
Chromosome Banding Patterns of Rat Fibrosarcomas Induced by In Vitro Transformation of Embryo Cells or In Vivo Injection of Rats by 7,12-Dimethylbenz[a] anthracene
Authors: C. D. Olinici, J. A. DiPaolo
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Chromosome Banding Patterns of Rat Fibrosarcomas Induced by In Vitro Transformation of Embryo Cells or In Vivo Injection of Rats by 7,12-Dimethylbenz[a] anthracene Get access C. D. Olinici, C. D. Olinici Cytogenetics and Cytology Section, Biology Branch, Division of Cancer Cause and Prevention, National Cancer Institute, National Institutes of Health, Public Health Service, U.S. Department of Health, Education, and Welfare, Bethesda, Md. 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar J. A. DiPaolo J. A. DiPaolo 4 Cytogenetics and Cytology Section, Biology Branch, Division of Cancer Cause and Prevention, National Cancer Institute, National Institutes of Health, Public Health Service, U.S. Department of Health, Education, and Welfare, Bethesda, Md. 20014 4Address reprint requests to: J. A. DiPaolo, National Cancer Institute, Bldg. 37, Room 2A13, Bethesda, Md. 20014. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 52, Issue 5, May 1974, Pages 1627–1634, https://doi.org/10.1093/jnci/52.5.1627 Published: 01 May 1974 Article history Received: 07 December 1973 Accepted: 01 February 1974 Published: 01 May 1974
TGFβ Signaling Intersects with CD103 Integrin Signaling to Promote T-Lymphocyte Accumulation and Antitumor Activity in the Lung Tumor Microenvironment
Authors: Marie Boutet, Ludiane Gauthier, Marine Leclerc, Gwendoline Gros, Vincent de Montpreville, Nathalie Théret, Emmanuel Donnadieu, Fathia Mami-Chouaib
Journal: Cancer Research (2016)

Abstract Homing of CD8+ T lymphocytes to the tumor microenvironment is an important step for mounting a robust antitumor immune response. TGFβ is responsible for CD103 (αEβ7) integrin induction in activated intraepithelial CD8+ T lymphocytes. However, the interplay between TGFβ and CD103 and their contribution to T-cell infiltration and antitumor activity remain unknown. Here, we used viable human lung tumor slices and autologous tumor antigen-specific T-lymphocyte clones to provide evidence that CD103 is directly involved in T-lymphocyte recruitment within epithelial tumor islets and intratumoral early T-cell signaling. Moreover, TGFβ enhanced CD103-dependent T-cell adhesion and signaling, whereas it inhibited leukocyte function-associated antigen (LFA)-1 (αLβ2) integrin expression and LFA-1-mediated T-lymphocyte functions. Mechanistic investigations revealed that TGFβ bound to its receptors (TGFBR), which promoted the recruitment and phosphorylation of integrin-linked kinase (ILK) by TGFBR1. We further show that ILK interacted with the CD103 intracellular domain, resulting in protein kinase B (PKB)/AKT activation, thereby initiating integrin inside-out signaling. Collectively, our findings suggest that the abundance of TGFβ in the tumor microenvironment may in fact engage with integrin signaling pathways to promote T-lymphocyte antitumor functions, with potential implications for T-cell-based immunotherapies for cancer. Cancer Res; 76(7); 1757–69. ©2016 AACR.
The Myrmecia
Authors: A. Lyell, J. A. R. Miles
Journal: BMJ (1951)

Understanding the relationship between dendritic excitability and synaptic plasticity is vital for determining how dendrites regulate the input–output function of the neuron. Dendritic calcium spikes have been associated with the induction of long-term changes in synaptic efficacy. Here we use direct recordings from cerebellar Purkinje cell dendrites to show that synaptically activated local dendritic calcium spikes are potent triggers of cannabinoid release, producing a profound and short-term reduction in synaptic efficacy at parallel fiber synapses. Enhancing dendritic excitability by modulating dendritic large-conductance calcium-activated potassium (BK) channels improves the spread of dendritic calcium spikes and enhances cannabinoid release at the expense of spatial specificity. Our findings reveal that dendritic calcium spikes provide a local and tunable coincidence detection mechanism that readjusts synaptic gain when synchronous activity reaches a threshold, and they reveal a tight link between the regulation of dendritic excitability and the induction of synaptic plasticity.