tbuckley/cabot-search huggingface dataset:
Integrating Tumor and Stromal Gene Expression Signatures With Clinical Indices for Survival Stratification of Early-Stage Non–Small Cell Lung Cancer
Authors: Andrew J Gentles, Scott V Bratman, Luke J Lee, Jeremy P Harris, Weiguo Feng, Ramesh V Nair, David B Shultz, Viswam S Nair, Chuong D Hoang, Robert B West, Sylvia K Plevritis, Ash A Alizadeh, Maximilian Diehn
Journal: JNCI Journal of the National Cancer Institute (2015)

Accurate survival stratification in early-stage non–small cell lung cancer (NSCLC) could inform the use of adjuvant therapy. We developed a clinically implementable mortality risk score incorporating distinct tumor microenvironmental gene expression signatures and clinical variables. Gene expression profiles from 1106 nonsquamous NSCLCs were used for generation and internal validation of a nine-gene molecular prognostic index (MPI). A quantitative polymerase chain reaction (qPCR) assay was developed and validated on an independent cohort of formalin-fixed paraffin-embedded (FFPE) tissues (n = 98). A prognostic score using clinical variables was generated using Surveillance, Epidemiology, and End Results data and combined with the MPI. All statistical tests for survival were two-sided. The MPI stratified stage I patients into prognostic categories in three microarray and one FFPE qPCR validation cohorts (HR = 2.99, 95% CI = 1.55 to 5.76, P < .001 in stage IA patients of the largest microarray validation cohort; HR = 3.95, 95% CI = 1.24 to 12.64, P = .01 in stage IA of the qPCR cohort). Prognostic genes were expressed in distinct tumor cell subpopulations, and genes implicated in proliferation and stem cells portended poor outcomes, while genes involved in normal lung differentiation and immune infiltration were associated with superior survival. Integrating the MPI with clinical variables conferred greatest prognostic power (HR = 3.43, 95% CI = 2.18 to 5.39, P < .001 in stage I patients of the largest microarray cohort; HR = 3.99, 95% CI = 1.67 to 9.56, P < .001 in stage I patients of the qPCR cohort). Finally, the MPI was prognostic irrespective of somatic alterations in EGFR, KRAS, TP53, and ALK. The MPI incorporates genes expressed in the tumor and its microenvironment and can be implemented clinically using qPCR assays on FFPE tissues. A composite model integrating the MPI with clinical variables provides the most accurate risk stratification.
Abstract 1529: Ovarian low grade serous cancer: Mutation analysis with a comprehensive 409 cancer gene panel
Authors: Yvonne T. Tsang, Daisy Izaguirre, Suet-Yan Kwan, Samuel C. Mok, David Gershenson, Kwong-Kwok Wong
Journal: Cancer Research (2014)

Abstract Patients with ovarian serous cancer are usually younger and survive longer than patients with high-grade serous cancer. Unfortunately, most low-grade serous cancer patients eventually die of the disease because recurrent low-grade serous carcinoma is relative chemoresistant. So far, the known mutations identified in low-grade ovarian serous carcinomas and their putative precursor ovarian serous borderline tumors are BRAF and KRAS mutations. BRAF and KRAS mutations together have been identified in approximately 60% of serous borderline tumors and early stage low-grade serous carcinomas. However, BRAF mutation is rare in advanced-stage low-grade serous carcinomas. To further investigate the molecular pathogenesis of low-grade serous carcinoma, mutation analyses of 409 cancer related genes were performed in 21 low-grade ovarian serous carcinoma, 8 ovarian serous borderline tumors and one ovarian cystadenoma using next generation sequencer. A total of nineteen missense mutations were identified in 20 samples but ten samples had no detectable mutations. BRAF mutation was detected in 3 serous borderline tumors and one low-grade serous carcinoma. KRAS mutations were detected in three low-grade serous carcinomas. Other than BRAF and KRAS mutations, we also detected other prevalent mutations: ATRX mutations were detected in 3 low-grade ovarian serous carcinomas and a cystadenoma; KMT2C mutations were detected in 3 low-grade ovarian serous carcinomas; ATM mutations were detected in 2 low-grade ovarian serous carcinomas. Interestingly, both ATRX and MLL3 genes are involved in the chromatin remodeling. Moreover, both ATRX and ATM are involved in DNA damaging response. Thus, the pathogenesis of low-grade serous carcinoma may involve de-regulation of chromatin remodeling pathway and DNA damaging response. Further analysis of a large cohort of low-grade serous carcinomas for these prevalent mutations is ongoing. Citation Format: Yvonne TM Tsang, Daisy Izaguirre, Suet-Yan Kwan, Samuel C. Mok, David Gershenson, Kwong-Kwok Wong. Ovarian low grade serous cancer: Mutation analysis with a comprehensive 409 cancer gene panel. [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 1529. doi:10.1158/1538-7445.AM2014-1529
Evidence incidence of cystic fibrosis: A 30-year study in Krasnoyarsk, Russia
Authors: Vladimir Chikunov, Natalya Ilienkova, Tatyana Elizareva
Journal: European Respiratory Journal (2013)

Monitoring of CF incidence is essential to be able to make reliable predictions for disease management in the future.

Methods. This study enrolled CF patients born in Krasnoyarsk region (Siberia, Russia) between January 1st 1981 and December 31st 2012. Patients born before the set up of NBS were retrieved through active diagnosis high-risk groups. In July 2006 NBS for CF was added to the routine screening programme in Krasnoyarsk region. We using the neoIRT-IRT-sweet test protocol. For this protocol, neonates with an neoIRT 70 ng/mL and IRT 40 ng/mL were considered positive, and the standard sweat test was administered to determine CF status. Macroduct or Nanoduct (Wescor, USA) screening systems was use. Patients born since the implementation of NBS were collected by data from genetic centre as well as data from the genetics laboratories of our area. The birth incidence rate of CF (with its 95% confidence interval-95% CI) was determined for the whole study period, by 5-year periods and by year. The incidence rate of a given year was calculated by dividing the number of CF children born over that year by: 1) Prior to the implementation of NBS (1981-July 2006) (n=500, children from group risk), 2) After the implementation of NBS (July 2006-2012) (n=242453).

Results. A total of 65 CF children in Krasnoyarsk region between January 1st 1981 and December 31st 2012 were recorded. Half of them (n = 40; 61,5%) were born since the implementation of the NBS program in July 2006. The CFTR genotype could be fully determined in 89,2% of the patients and 56,0% of them were homozygous for the main F508del mutation. The resulting estimate of incidence relative to live births is 1:6061.
Biomass smoke exposure is the main risk factor for COPD in non smoking women in a developing country
Authors: Lalita Fernandes, Anthony Mesquita
Journal: European Respiratory Journal (2013)

Background: COPD is an important non communicable disease with rising mortality and morbidity. Tobacco smoking is the biggest risk factor for COPD in developed countries. In a developing country like India, where the prevalence of smoking is low in women (3.6% in women and 26.25% in men), the prevalence of COPD is equal in both sexes (2-22% in men and 1.2-19% in women). Biomass smoke exposure is the biggest risk factor for COPD in women,however the awareness of COPD in non smoking women is low.  Aim: To evaluate the differences in risk factors,respiratory symptoms, lung function,BMI and exercise capacity in men and women with COPD.  Methods: We included males and females≥40 years of age and excluded patients with COPD exacerbation within 4 weeks of enrollment and other lung diseases. BOLD questionnaire captured symptoms,COPD defined by GOLD guideline 2009 and 6MWD performed per ATS guidelines.  Results:  Conclusions: Biomass smoke exposure is the biggest risk factor for COPD in women and women have similar clinical presentation of COPD as men.
Induction of Tumors by Direct Injection of &lt;italic&gt;N&lt;/italic&gt;-Ethyl-&lt;italic&gt;N&lt;/italic&gt;-nitrosourea Into the Amniotic Space of the Mouse Fetus&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: L Rossi, T Mollner, A Munhall, P Shubik
Journal: JNCI Journal of the National Cancer Institute (1979)

An N-ethyl-N-nitrosourea (ENU) solution was injected into the amniotic space of Swiss mouse fetuses. Embryos 9 days old were exposed to 2 and 4 μg ENU and died within the first 4 weeks of life. Injection of 4 μg ENU into 11-day-old fetuses induced a 10% lung tumor incidence, whereas 16 μg injected at 12, 15, or 16 days resulted in lung tumor incidences of 42, 100, and 84%, respectively. A mortality rate of 50% and a lung tumor incidence of 89% in survivors resulted after exposure of 16-day-old fetuses to 64 μg ENU. Histologic examination revealed that the tumors were alveologenic adenomas 1–7 mm in diameter. Two saline-treated control groups had no tumors. The possible utilization of this biologic model in testing chemical alkylating agents similar to ENU is discussed.
Loco-Regional Recurrence and Survival after Wide Local Excision, Radiotherapy and Axillary Clearance for Early Breast Cancer
Authors: R Carpenter, G T Royle, M Cross C Hamilton, R Buchanan, I Taylor
Journal: Journal of the Royal Society of Medicine (1992)

After breast conservation for early breast cancer which comprised wide local excision, axillary clearance and radiotherapy to the breast, 145 women have been followed prospectively for a median of 42 months. Local recurrence occurred in 11 (7%) and axillary recurrence in three (2%). Distant recurrence has occurred in 32 and accounted for 80% of all first recurrences. Local treatment failure has occurred in three women and would not have been prevented by mastectomy. Loco-regional recurrence in the absence of preceding or synchronous distant disease was unusual and did not pose a significant clinical problem.
Conservative Treatment for Girls With Nonmetastatic Rhabdomyosarcoma of the Genital Tract: A Report From the Study Committee of the International Society of Pediatric Oncology
Authors: Hélène Martelli, Odile Oberlin, Annie Rey, Jan Godzinski, Richard D. Spicer, Nathalie Bouvet, Christine Haie-Meder, Marie-Josée Terrier-Lacombe, José Sanchez de Toledo, David Spooner, Danielle Sommelet, Françoise Flamant, Michaël C.G. Stevens
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To report the results of a conservative multimodal approach in girls with nonmetastatic rhabdomyosarcoma (RMS) of the genital tract, treated in International Society of Pediatric Oncology (SIOP) Malignant Mesenchymal Tumors 84 and 89 protocols. PATIENTS AND METHODS: From 1984 to 1994, 38 girls with RMS of the genital tract (vulva, vagina, uterus) were treated in SIOP protocols. With the exception of patients with rare small tumors, which were resected at the start of the studies, all patients received initial chemotherapy (CHT) (ifosfamide, vincristine, and actinomycin D). Local treatment including surgery, brachytherapy (BT), and external-beam radiotherapy (ERT) was given only to girls who did not achieve complete remission (CR) with CHT or who subsequently relapsed. RESULTS: The primary tumor originated in the vulva or vagina in 27 girls and in the uterus in 11. The overall survival rate (± SE) was 91% ± 6% at 5 years, and the event-free survival rate was 78% ± 7%. At a median follow-up of 5 years, 30 girls were alive and in first CR and five were alive and in second CR. Four patients treated with complete resection of the tumor at diagnosis received less CHT. Thirteen patients were treated with CHT alone. In 17 patients, local treatment was necessary to achieve complete local control, for a residual mass after initial CHT (10 patients), for viable tumor on biopsy (three patients), or for local relapse (four patients). The local treatment used was radiotherapy (RT) (ERT in three patients, BT in seven), radical surgery with uterine ablation (three patients), RT and radical surgery (three patients), and conservative surgery with RT (one patient). CONCLUSION: Girls with nonmetastatic RMS of the genital tract have an excellent prognosis. We found no difference in outcome between uterine and vulvovaginal RMS. Local treatment does not seem necessary in patients who have a complete response to CHT. When a local treatment is needed, BT may be an alternative to radical surgery or ERT.
Methylphenidate therapy improves cognition, mood, and function of brain tumor patients.
Authors: C A Meyers, M A Weitzner, A D Valentine, V A Levin
Journal: Journal of Clinical Oncology (1998)

PURPOSE Patients with malignant glioma develop progressive neurobehavioral deficits over the course of their illness. These are caused both by the effects of the disease and the effects of radiation and chemotherapy. We sought to determine whether methylphenidate treatment would improve these patients' neurobehavioral functioning despite their expected neurologic deterioration. PATIENTS AND METHODS Thirty patients with primary brain tumors underwent neuropsychologic assessment before and during treatment with methylphenidate. Ability to function in activities of daily living and magnetic resonance imaging (MRI) findings were also documented. Patients were assessed on 10, 20, and 30 mg of methylphenidate twice daily. RESULTS Significant improvements in cognitive function were observed on the 10-mg twice-daily dose. Functional improvements included improved gait, increased stamina and motivation to perform activities, and in one case, increased bladder control. Adverse effects were minimal and immediately resolved when treatment was discontinued. There was no increase in seizure frequency and the majority of patients on glucocorticoid therapy were able to decrease their dose. Gains in cognitive function and ability to perform activities were observed in the setting of progressive neurologic injury documented by MRI in half of the subjects. CONCLUSION This study demonstrated improved patient function in the setting of a progressive neurologic illness. Methylphenidate should be more widely considered as adjuvant brain tumor therapy.
Mammary Nodules in Dogs During Four Years' Treatment With Megestrol Acetate or Chlormadinone Acetate
Authors: L. W. Nelson, J. H. Weikel, F. E. Reno
Journal: JNCI Journal of the National Cancer Institute (1973)

A 7 year study of megestrol and chlormadinone in female dogs is in progress. This report characterized histopathologically 60 mammary nodules during the first 4 years of the study. 100 purebred female beagles, 6-12 months of age, were randomly assigned to 5 equal groups. One group was used as a control. Oral doses were .01, .10, and .25 mg/kg/day of megestrol acetate in coconut oil in capsules and of chlormadinone acetate .25 mg/kg/day in lactose tablets. These doses were 1, 10, and 25 times the projected dose of megestrol for humans and about 25 times the human dose of chlormadinone. After 2 years 4 dogs from each group were necropsied. One high-dose megestrol-treated and 1 chlormadinone-treated dog had benign mixed mammary tumors. Palpable nodules were first observed at 16 months in the chlormadinone-treated dogs, at 18 months in dogs given the high dose megestrol and at 27 months in the dogs treated with middle-dose megestrol. Transitory nodules were found in 4 control dogs after 21 months and in low dose megestrol-treated dogs at 26 months. Of 38 grossly detected nodules evaluated microscopically from the megestrol-treated dogs 27 were nodular hyperplasia, 5 were benign mixed mammary tumors, 3 were ductal dialatations, 1 was a lymph node, 1 was fat necrosis and 1 was the umbilicus. Of 22 nodules from the chlormadinone-treated dogs 12 were nodular hyperplasia, 4 benign mixed mammary tumors, 1 chondromucoid degeneration and 1 adenocarcinoma with widespread metastases. 3 nodules were lymph nodes and 1 other had no mammary tissue. Involutions, regression and sclerosis of many areas of nodular hyperplasia were evident at 4 years. Thus of the 60 nodules evaluated during the first 4 years of the study 50 were non-neoplastic and 10 were neoplastic. It is considered that the 1 adenocarcinoma may have been spontaneous and not a treatment-related neoplasm. A precursor stage through nodular hyperplasia apparently did not occur.
Predictors of length of stay in hospitalized patients with community acquired pneumonia
Authors: Shiva Bikmalla, Masood Khalil, Muhammed Ganaie
Journal: European Respiratory Journal (2013)

Introduction:  The proportion of patients with community acquired pneumonia (CAP) requiring hospitalisation range from 22-42%. In our centre the median length of stay was high compared to national average. This has major impact on the utilisation of health care resources. Therefore we aimed to identify the predictors of length of stay in patients with CAP.  Methods:  A prospective data collection over a period of 60 days (Dec 2012- Jan 2013) in a single tertiary centre. We included all patients admitted with symptoms of lower respiratory tract infection and has confirmation of pneumonia based on new infiltrates on the chest radiograph.  Results:  Data was collected on 50 patients who were consecutively selected based on the inclusion criteria. The median age was 72 years (range 23-98) and 54% were women. The median length of stay was 9 (range 2-35). Eleven patients (22%) who died during the stay had median age of 86 years. Patients with chronic lung conditions have higher length of stay (relative risk of 1.65). In our cohort hypoxia on admission, high CURB65 score, female sex, sputum production and pyrexia above 38c have shown increase in the length of stay.  Discussion:  Through our study we have been able to identify predictive markers of length of stay in hospital. However large, multi-centred studies are required to describe the parameters with high significance, which would help in organising effective and safe early discharge planning.
Sexual dysfunction (SD) in obese women: Is there a role for obstructive sleep apnea?
Authors: Francesco Fanfulla, Antonella Camera, Paola Fulgoni, Luca Chiovato, Rossella E. Nappi
Journal: European Respiratory Journal (2011)

SD in premenopausal obese women is frequent but the association with OSA has not been well recognized. We enrolled 35 women (age 41.4±7.7 yrs; BMI 42.8±5 kg/m2, waist circumference 130.6±10.3 cm) that were evaluated by means of Female Sexual Function Index (FSFI), Female Sexual Distress Scale (FSDS), General Health Questionnaire (GHQ), Perceived Stress Scale (PSS), as well as hormonal and metabolic assessment. The presence of OSAS was assessed by a full standard polysomnography. The FSFI total score was 24.2±11.1 with 10 women scoring   15. Mean GHQ score was 4.3±3.7 and PSS median score 21.3±8.4, suggesting psychological distress. Mean LH, FSH and Estradiol values were in the normal range for the age. 22 women meet the criteria for OSAS diagnosis and 15 showed excessive daytime sleepiness. A statistically significant difference between women with abnormal or normal FSDS score was found for AHI (39.4±38 vs 18.8±15, p=0.03), GHQ (5.9±3.5 vs 2.9±3.3, p<0.01) and PSS (25.1±8.4 vs 18.1±7, p<0.01), respectively. A statistically significant correlations was found between AHI and FSDS (r=0.48, p=0.003), GHQ (r=0.42, p=0.01), or PSS score (0.39, p=0.02) but not with FSFI score that was only correlated to BMI (r=0.4, p=0.01). We conclude that obese women with OSAS showed an high prevalence of SD. Sexual function seems to be related to obesity itself while the sexual distress to the severity of OSA.
Vibration response imaging (VRIxp) for calculation of predictive postoperative lung function. Comparison to lung perfusion scintigraphy
Authors: Michael Westhoff, Schoch Gernot, Axel Kempa, Merav Gat
Journal: European Respiratory Journal (2011)

Introduction:  Radionuclide studies of regional perfusion (Tc) together with lung function tests (FEV1, TLCO) are established methods for predicting pulmonary function after lung resection. The VRIxp (DeepBreeze, Or-Akiva, Israel) records lung sounds, calculates quantitative lung data representing the regional acoustic energy contributed by each lung area. We compared VRIxp with perfusion scintigraphy.   Methods:  30 patients (6 F, 24 M age=67±9yrs) with lung cancer (24 lobectomies and 6 pneumonectomies) were enrolled. VRIxp was scheduled the same day as the perfusion tests. Predicted postoperative FEV1 (FEV1-ppo) was calculated by subtracting the percent blood uptake or percent acoustic energy of the lung to be resected from the total. VRIxp and perfusion results were compared by Pearson correlation.   Results:  There was a good correlation between VRIxp and perfusion scintigraphy (R=0.91). In 80% the difference between both methods was    Conclusion:  Prediction of postoperative lung function by VRIxp demonstrated a high accuracy compared to perfusion scintigraphy and postoperative lung function. VRIxp can play an important role in prediction of post-operative lung function.  VRIxp is non-invasive and radiation free, thus posing no risk to patients. The method needs further evaluation because of possible intraindividual variation (> 10%) of the results.
Efficacy of roflumilast with concomitant cardiovascular medication in patients with COPD
Authors: Peter Calverley, Leonardo Fabbri, Fernando Martinez, Udo-Michael Goehring, Manja Brose, Klaus Rabe
Journal: European Respiratory Journal (2013)

Background   Cardiovascular disease is common in patients with COPD and systemic inflammation has been proposed as a link between the two. Roflumilast, a phosphodiesterase 4 inhibitor, has shown efficacy in reducing exacerbation frequency in patients with severe COPD. Here we investigate whether the efficacy of roflumilast is influenced by concomitant treatment with cardiovascular medication.   Methods   Data were pooled from two identically designed randomized studies. Patients with severe COPD, chronic bronchitis and a history of exacerbations received either roflumilast 500µg o.d. (n=1537) or placebo (n=1554) for 52 weeks and were classified by concomitant treatment with statins or ACE inhibitors.   Results   In the roflumilast group, statins or ACE inhibitors were used by 225 (15%) and 301 (20%) patients, respectively; in the placebo group they were used by 241 (16%) and 323 (21%), respectively. In the overall population the exacerbation rate was significantly lower in the roflumilast group compared with placebo (–16.9% [95% CI –25,–8], p=0.0003). This difference remained significant independent of treatment with statins (–37.4% [95% CI –52,–18], p=0.0008) or not (–14.1% [95% CI –23,–4], p=0.0064) or treatment with ACE inhibitors (–23.0% [95% CI –39,–3], p=0.0278) or not (–16.8% [95% CI –26,–7], p=0.0013). There was a trend for greater reduction of exacerbations induced by roflumilast in subjects treated with statins. Roflumilast significantly improved FEV 1  in the overall population and in each subgroup.   Conclusions   Roflumilast reduces the rate of moderate or severe exacerbations and improves lung function in patients with severe COPD, independent of concomitant treatment with statins or ACE inhibitors.
Epigenetic silencing of a long non-coding RNA KIAA0495 in multiple myeloma
Authors: Kwan Yeung Wong, Zhenhai Li, Xiaoqin Zhang, Gilberto Ka Kit Leung, Godfrey Chi-fung Chan, Chor Sang Chim
Journal: Molecular Cancer (2015)

In multiple myeloma, a long non-coding RNA, KIAA0495 (alias PDAM/TP73-AS1), had been found progressively downregulated from normal plasma cell to benign monoclonal gammopathy of undetermined significance to symptomatic myeloma. Herein, by methylation-specific PCR, the putative KIAA0495 promoter was found unmethylated in all healthy controls (N = 14) but methylated in 50 % of myeloma cell lines (N = 10). KIAA0495 methylation was shown inversely correlated with KIAA0495 expression. However, KIAA0495 methylation was detected in none of both primary myeloma samples at diagnosis (N = 61) and at relapse/progression (N = 16). Collectively, despite frequently methylated in cell lines, KIAA0495 methylation appeared unimportant in the pathogenesis or progression of myeloma.