tbuckley/cabot-search huggingface dataset:
Immunophenotypic characterization of breast cancers in carriers of BRCA1/BRCA2 mutations
Authors: S. D. Simon, C. E. Bacchi, A. L. Molina, C. A. Moreira-Filho
Journal: Journal of Clinical Oncology (2004)

9641 Background: About 6% of breast cancers are due to mutations in the BRCA1/2 genes. Partial phenotypic characterization of these tumors has shown that BRCA1-related tumors are often Estrogen Receptor (ER) and Progesterone Receptor (PR) negative; this is usually not seen in BRCA2-related tumors. HER-2/neu has been found to be frequently negative in both BRCA1and BRCA2 tumors. We have examined 24 breast cancer specimens in patients with BRCA1/2 mutations in order to assess the expression of ER, PR, HER-2/neu, EGFR, Cyclin D1, p27KIP1, p53, bcl-2 and Ki-67 antigen. Methods: Mutations were identified by D-HPLC screening and confirmed by reverse and forward base sequencing of abnormal exons . Paraffin blocks were retrieved on 24 tumors of 20 patients. Avidin-biotin immunoperoxidase was performed and analysed by one pathologist (C.E.B.) Results: Our series show that BRCA1 tumors are usually ER negative, PR negative, HER-2/neu negative and have increased expression of abnormal p53 protein and bcl-2; protein p27KIP1 was low in 77% of the samples; EGFR was strongly expressed in none of these patients; Ki-67 was elevated (>25%) in 62% and Cyclin D1 was low or absent in 62% of BRCA1 patients. The BRCA2-related tumors had a less specific profile; absence of HER-2/neu in all but one patient was the only distinctive finding in this group. Conclusions: BRCA-1 related tumors seem to have a relatively specific immunophenotypic profile that distinguishes them from sporadic breast cancer. No specific findings were found in the BRCA2-related tumors. No significant financial relationships to disclose.
Sex-specific features of emphysema among current and former smokers with COPD
Authors: Megan Hardin, Marilyn Foreman, Mark T. Dransfield, Nadia Hansel, MeiLan K. Han, Michael H. Cho, Surya P. Bhatt, Joe Ramsdell, David Lynch, Jeffrey L. Curtis, Edwin K. Silverman, George Washko, Dawn DeMeo
Journal: European Respiratory Journal (2015)

Recent studies suggest that males with chronic obstructive pulmonary disease (COPD) have more emphysema than females. It is not known if these differences persist across degrees of COPD severity. Our aim was to identify sex-specific differences in quantitative emphysema within COPD subgroups based on COPD severity. We included non-Hispanic white and African-American subjects from the COPDGene study with at least 10 pack-years of smoking and COPD Global Initiative for Chronic Obstructive Lung Disease (GOLD) spirometry grade II or greater. We examined sex-specific differences in log-transformed emphysema (log per cent low-attenuation area (%LAA)) by GOLD spirometry grade among subjects with early-onset COPD (&lt;55 years old) and advanced emphysema (&gt;25% emphysema). Compared with females, males had higher log %LAA: overall (1.97±1.4 versus 1.69±1.6, β=0.32 (0.04), p=1.34×10 −14 ), and among non-Hispanic white (p=8.37×10 −14 ) and African-American subjects (p=0.002). Females with early-onset COPD, severe emphysema and GOLD grade IV COPD had similar emphysema as males, but markedly fewer pack-years smoking (early-onset, p=0.01; severe emphysema and GOLD grade IV, p&lt;0.001). This study identifies subsets of female smokers with COPD who are particularly susceptible to parenchymal destruction.
Studies on the Nature of the Proximal Bladder Carcinogens&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;
Authors: Walter Troll, Sidney Belman, Frank Mukai
Journal: JNCI Journal of the National Cancer Institute (1969)

Bladder cancer is caused by urinary metabolites of certain aromatic amines serving as proximal carcinogens. Bis(2-amino-1 -naphthyl) phosphate and its N-hydroxy derivative are unique metabolites of the bladder carcinogen 2-naphthylamine. The appearance of these metabolites with the carcinogen 2-naphthylamine and their absence with the virtually inactive compound 1-naphthylamine, as well as their ether solubility, have made them promising candidates for the proximal carcinogen.
Comparison of characteristics of COPD patients with an established diagnosis, with those newly identified through case-finding – The Birmingham COPD cohort study
Authors: Peymane Adab, Andy Dickens, Alexandra Enocson, David Fitzmaurice, Rachel Jordan
Journal: European Respiratory Journal (2014)

Introduction   There is increasing effort to identify people with undiagnosed COPD. However there is insufficient data on the profile of such patients to determine whether their characteristics and trajectory differ from those with established disease.   Aim   We compare the clinical characteristics of patients identified from a primary care COPD case-finding trial, with established cases on practice registers.   Methods   Interim baseline data from a primary care cohort of COPD patients from 71 UK practices were used. Patients with established COPD, as well as newly identified cases were invited. Baseline assessment includes spirometry, anthropometry, exercise capacity as well as questionnaires to obtain socio-demographic, occupational, lifestyle and health data   Results   1,071 patients with spirometry confirmed COPD (LLN criteria) were included; 89 identified through case-finding. Compared with established cases, the newly identified were more likely to be female (47 vs 37%), younger (mean age 63.2 vs 68.9) and current smokers (42.0 vs 31.3%). They had less severe obstruction (55.1% vs 17.2% GOLD stage I), lower CAT score (mean 15.4 vs 20.2) and fewer comorbidities (10.1 vs 15.6% had ≥3 comorbidities). Restricting analyses to 812 with moderate/severe disease (GS II-III), newly identified patients still had lower CAT (p=0.04), fewer exacerbations (p≤0.01) and lower BODE (p≤0.01). All analyses adjusted for age, sex, smoking and disease severity.   Conclusions   Patients identified through case finding have milder disease. Longitudinal studies are needed to assess prognosis and longer term benefits of early diagnosis.
Lung function values as predictors for outcome during non-invasive ventilation in COPD patients
Authors: Dora Bartusek, Judit Varga, Andras Bikov, Tamas Komaromi, Gyorgy Losonczy
Journal: European Respiratory Journal (2011)

Introduction:  The use of non-invasive ventilation (NIV) has markedly increased over the past two decades, and has now become an integral tool in the management of respiratory failure. Although several predictive factors have been suggested for successful NIV treatment, it is still unclear which clinical baseline variable should be used to predict the outcome of the therapy in COPD patients with respiratory failure.   Objective:  The aim of the study was to determine predictive factors for COPD patients with acute exacerbation receiving NIV.   Methods:  38 patients with COPD (mean age: 64.05±11.26, GOLD III-IV) participated in our study. Lung function, blood gas test and blood sampling for CRP and white cell count measurement were performed, as well as smoking history was recorded and APACHE II score was determined at the day of admission to the respiratory care unit. We accepted NIV to be successful, if no additional invasive methods were needed. The clinical data underwent principal component analysis and receiver operating characteristic (ROC) curve was performed to determine the variables for successful NIV treatment. A principal component having an area under the curve (AUC) more than 0.7 was suggested predictive.   Results:  NIV was successful in 68% of patients. We found principal component capturing the baseline FVC and FEV 1  to be the best predictive variable for failure of treatment (AUC=0.9, sensitivity 90%, specificity 80%), however the other parameters were less useful (AUC   Conclusion:  Baseline lung function may be helpful to predict which patient is susceptible to receive additional endotracheal intubation.
Passive smoking and lung cancer
Authors: P. Lee, G. Scherer, W.-D. Heller, F. Nyberg, G. Pershagen, A K Hackshaw, M R Law, N J Wald
Journal: BMJ (1998)

Editor—Hackshaw et al estimate a 26% excess risk of lung cancer (95% confidence interval 7% to 47%) in non-smokers who live with a smoker.1 This estimate may be too high. 

Their adjustment for smoking misclassification bias is inadequate for two reasons. Firstly, it is based on the comparatively low misclassification rates seen in American and British populations and ignores evidence of far higher rates in Asian women (table).2–4 Secondly, it uses a new adjustment technique that takes no account of the varying relative risks from smoking in the 37 studies. Despite the fact that lung cancer has many known causes and the evidence that smoking and passive smoking are associated with higher exposure to many adverse lifestyle risk factors,5 the authors’ consideration of confounding is limited to fruit and vegetable consumption. The authors dismiss publication bias, using an argument that addresses only whether such bias might explain the whole observed association. They do not even mention recall bias, and they do not discuss implications of specific weaknesses of the studies. After their inadequate downward adjustment for bias and confounding, they adjust upwards for effects of non-spousal passive exposure to smoke. Such effects are inferred indirectly from cotinine data, and the direct evidence that exposure to smoke in the workplace, in social situation, and during childhood is not associated with risk of lung cancer is ignored. 

Hackshaw et al also estimate an excess risk of 19% from passive smoking, by extrapolating from the risk in current smokers, and this may also be too high. The use of particulate matter rather than cotinine to calculate the relative exposure of passive and active smokers would reduce the excess risk estimate at least tenfold; allowance for a quadratic component to the dose-response would reduce it further. 

Hackshaw et al also create a false impression of precision by using confidence limits that take no account of the many uncertainties in the adjustment procedures used, and by emphasising the similarity of their estimates of 26% and 19%. If more appropriate adjustments were used for bias and confounding and different assumptions were made in the dose-response extrapolation, both estimates could remain similar but be an order of magnitude or more lower. Indeed, bearing in mind the possibility of a zero threshold for carcinogenesis, one might even argue that the authors have not conclusively demonstrated that passive smoking has any effect on risk of lung cancer.
Characterization and prognostic significance of circulating tumor cells in the peripheral blood of patients with metastatic pancreatic cancer.
Authors: B. P. Negin, N. J. Meropol, R. K. Alpaugh, K. Ruth, C. McAleer, T. Halbherr, C. Bingham, P. Fittipaldi, S. J. Cohen
Journal: Journal of Clinical Oncology (2010)

4127 Background: Increased numbers of circulating tumor cells (CTC) are associated with worse survival in patients (pts) with metastatic prostate, breast, and colorectal cancer. We initiated the current pilot study to evaluate the clinical significance and characteristics of CTC in pts with metastatic pancreatic cancer (mPC). Methods: The CellSearch immunomagnetic separation system was used to quantify CTC from the peripheral blood of pts with mPC on first-line systemic therapy. Samples were evaluated at baseline, 7 days, and first disease evaluation (6-10 weeks). CTC were further analyzed for epidermal growth factor receptor (EGFR) and human mucin 1 (MUC1) expression utilizing immunofluorescent markers. Results: 40 pts were enrolled. Pt characteristics: M/F (24/16), age range 39-86 years (median 61). 50% of pts at baseline (median 0.5, range 0-20), 39% at 7 days, and 28% at 6-10 weeks had ≥ 1 CTC/7.5mL peripheral blood. Median progression-free survival (PFS) and overall survival (OS) were 113 and 232 days (d) respectively for the entire group. Those pts at baseline with any CTC had a trend toward shorter OS than those without CTC (125 d. vs. 298 d., p = 0.12). A similar trend was seen with baseline CTC and PFS (84.5 d. for those with any CTC v 137 d. without CTC; p = 0.19). OS and PFS also trended shorter in patients with any CTC at 7 days and at first disease evaluation compared to those without CTC. EGFR expression was not associated with PFS or OS. Those pts with MUC1+ CTC (10/20 with any CTC) had a shorter median OS than those with MUC1-CTC (85.5 vs. 293 days; p = 0.08). Conclusions: CTC can be isolated and enumerated from the blood of pts with mPC, although yield is less than with other epithelial malignancies. The presence of any CTC at baseline and follow-up time points is associated with a trend toward worse survival. MUC1+ CTC appear to correlate with worse clinical outcome in this exploratory analysis. Larger study to expand these initial results is warranted. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Veridex Veridex
Adoptive transfer of activated marrow-infiltrating lymphocytes induces measurable antitumor immunity in the bone marrow in multiple myeloma
Authors: Kimberly A. Noonan, Carol A. Huff, Janice Davis, M. Victor Lemas, Susan Fiorino, Jeffrey Bitzan, Anna Ferguson, Amy Emerling, Leo Luznik, William Matsui, Jonathan Powell, Ephraim Fuchs, Gary L. Rosner, Caroline Epstein, Lakshmi Rudraraju, Richard F. Ambinder, Richard J. Jones, Drew Pardoll, Ivan Borrello
Journal: Science Translational Medicine (2015)

Marrow-infiltrating lymphocytes (MILs) may be used as adoptive cell therapy for multiple myeloma.
A randomized, phase II ECOG trial of two dose levels of temsirolimus (CCI-779) in patients with extensive stage small cell lung cancer in remission after induction chemotherapy. A preliminary report
Authors: K. J. Pandya, D. E. Levy, M. Hidalgo, R. B. Cohen, M. W. Lee, J. H. Schiller, D. H. Johnson
Journal: Journal of Clinical Oncology (2005)

7005 Background: Temsirolimus (CCI-779), an ester of sirolimus, is an inhibitor of mTOR, shown to inhibit tumor cell proliferation in non-clinical models. Standard chemotherapy typically results in a 9 month median survival in extensive stage small cell lung cancer (SCLC-ES). A Phase II study was initiated in patients (pts) with SCLC-ES in remission (CR, PR, SD) following 4–6 cycles of carboplatin or cisplatin+etoposide or irinotecan, to determine the effects of temsirolimus on progression-free and overall survival. Methods: Between January 2002 and December 2003, 87 pts were randomized to 2 dose levels of temsirolimus (86 pts are eligible for this analysis): 44 pts to 25 mg (Arm A); 42 pts to 250 mg (Arm B), both given IV over 30 minutes weekly until progression. Pts were entered 4–8 weeks after completing induction therapy.Their characteristics are: male 42 (49%), female 44(51%); PS0: 38(44%), 1: 41(48%), 2: 4(5%); brain metastases 5(6%). Median follow up time is 33.8 months. Results: Toxicity: There were no treatment related grade (G) 5 toxicities on either arm. Worst G3/4 degree reported: 21 pts on Arm A and 26 pts in Arm B. G3/4 neutropenia: 4 in each arm; thrombocytopenia: 3 in Arm A, 9 in Arm B; hypercholesterolemia/triglyceridemia: 1/1 in Arm A, 3/3 in Arm B; hypophosphatemia: 2 in Arm A, 6 in Arm B. G3 allergic reaction: 1 in each arm; urticaria: 2 in Arm B. Survival: 8/44 pts (18%) are alive on Arm A, and 16/42 (38%) are alive on Arm B at the time of analysis. The median survival for all pts is 19.8 months (95% CI: 16.3 -22.9 months): Arms A 16.5 months and Arm B, 22.9 months. The median progression free survival for all pts is 5.5 months (95% CI: 4.4 - 7.7 months): Arm A 4.7 months and Arm B, 6.3 months. By comparison, the post randomization median survival was 8.9 months in 242 pts with CR, PR, SD following cisplatin+etoposide induction in ECOG phase III study E7593 (JCO 19:2114,2001). Conclusion: Temsirolimus appears to have significant activity in extensive stage small cell lung cancer and should be studied further in this setting. No significant financial relationships to disclose.
Cetuximab + FOLFOX 6 as first line therapy for metastatic colorectal cancer
Authors: J. Scott, S. Dakhil, T. Cosgriff, C. Pink, B. Butler, R. V. Boccia
Journal: Journal of Clinical Oncology (2005)

3705 Background: This phase II trial was designed to evaluate the safety and efficacy of cetuximab, an EGFR targeting monoclonal antibody recently approved for 2nd line therapy of advanced colorectal cancer (CRC) combined with FOLFOX6, a regimen which is now widely used as first line therapy in this patient population. This report presents preliminary safety information demonstrating the safety and tolerability of this combination. Methods: Eligibility: Age ≥ 18, locally advanced or metastatic CRC, no prior therapy for advanced disease. Regimen: Cetuximab 400 mg/M2 (2 hour infusion) day 1; 250 mg/M2 day 8 (and 250 mg/M2 for all subsequent doses); and modified FOLFOX 6 consisting of oxaliplatin 85 mg/M2 (2 hour infusion) day 1; leucovorin (LV) 400 mg/M2 (2 hour infusion); and 5-FU bolus 400 mg/M2 day 1 followed by FU-CI 2400 mg/M2 over 46 hours (days 1 and 2). Cycles were repeated every 14 days. Results: Preliminary results are available for 26 patients who have been treated with this regimen. EGFR expression was positive in 25. The median number of treatment cycles administered was 3 (range 1–12). One patient died (acute M.I.) on study and 2 had therapy discontinued for toxicity (hypersensitivity to cetuximab, oxaliplatin induced diarrhea). No patient has been discontinued for disease progression. The most frequently observed toxicity was neutropenia, with 5 patients having GR4 and 3 patients having GR3. Severe thrombocytopenia or anemia was not observed. Other selected grade 3/4 toxicities are shown in the table below. Conclusion: These preliminary data suggest that cetuximab may be safely combined with FOLFOX6 for the first line treatment of patients with metastatic CRC. Conclusions concerning the efficacy of this combination await further treatment information. No significant financial relationships to disclose.
Structure of extrapulmonary tuberculosis forms in Romania among 2007–2009
Authors: Constantin Marica, Cristian Didilescu, Mihaela Tanasescu, Mara Popescu-Hagen, Nicoleta Cioran
Journal: European Respiratory Journal (2011)

Tuberculosis represents a major matter of public health in Romania and as a result the antituberculosis activities provided by NTP take into account also to point out all the aspects and tendencies of TB endemy.   Objective:  In the context of an increased TB endemy (notification rate 99,9% 000 meaning 21457 cases in 2009) but with a decrease tendency in the last 7 years, we intended to determine extrapulmonary TB weight and structure by locations among 2007 – 2009.   Material and method:  We have used information in the national data basis within the service of NTP epidemiologic supervision.   Results:  Among 2007 – 2009, extrapulmonary TB weight from all sites was chronologically the following: 13,49% =3351 cases (2007), 13,41% = 3310 (2008) and 14,51% =3378 (2009). TB pleuresies represented 62,1% (2007), 62,1% (2008) and 58,1% (2009) of the extrapulmonary sites. In absolute figures, the other extrapulmonary sites were 1263 cases in 2007, 1252 in 2008 and 1381in the last year, 2009. The most frequent extrapulmonary localizations (without pleuresies), whole values during the three studied years, were: intra and extra thoracic adenopathies (1804 cases), osteoarticular localizations (816), meningoencefalites (348), renal and urinary tracks (204) and pericarditis (152) etc. During this period, there were only 2 TB tiroidian cases and no surrenal case.   Conclusions:  Extrapulmonary TB forms among 2007-2009 keep a constant weight level within the structure of TB sites. The high level of pleuresies (with phtisiogenic risk) and also the high frequency of TB meningities (severe prognosis, element of epidemiologic gravity) involve an increased responsibility in TB control.
Osteosarcoma: Experience at Instituto Especializado de Enfermedades Neoplásicas (1985–2000)
Authors: T. Vidaurre, S. Neciosup, J. Pinto, C. Torrico, H. Gómez, L. Mas, J. León, L. León, C. Carracedo, C. Vallejos
Journal: Journal of Clinical Oncology (2005)

9081 Background: Osteosarcoma is a malignant tumor of the bone arising from osteoblastic cells, being more frequent in long bones; this cancer affects usually to teenagers. Mutations on TP53 and rb genes may be present. The aim of this study was to determine the clinical characteristics of Peruvian patients with osteosarcoma. Methods: A retrospective clinical study of 296 patients with diagnosis of osteosarcoma from Instituto Especializado de Enfermedades Neoplásicas (Lima-Perú) treated between 1985 to 2000 was performed. Clinical characteristics as hystologic type, metastasis at diagnosis, and clinical response were evaluated. Disease-free survival to five years was estimated by Kaplan-Meier and survival curves were compared by Longrank test. Results: The median age was 19 years (range 14–77 years), with a median of 19 years; 61.5% of patients (182/296) were male; femur was more frequent site of involvement (49%\(\frac{145}{296}\)), followed by tibia (22%\(\frac{66}{296}\)). Conventional osteosarcoma subtype was more frequent. 30.4% of patients (90/296) had metastasis at diagnosis. Disease-free survival was 26%; 43.9% had progression of disease; was observed a lower rate of overall survival in patients with pulmonary metastasis (35%) than patients without metastasis at diagnosis (52%). Conclusions: Osteosarcoma is usually frequent in young patients and more frequent in male than female; femur is the site of more frequent involvement; the overall survival is related with metastasis at diagnosis. No significant financial relationships to disclose.
DANGERS OF PHOSPHORUS IN FIREWORKS
Journal: JAMA (1921)

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