tbuckley/cabot-search huggingface dataset:
CT screening for lung cancer: Risk of dying of “competing” causes of death
Authors: R. Yip, C. I. Henschke, D. Yankelevitz
Journal: Journal of Clinical Oncology (2005)

7185 Background: Enrollment into a screening program should be limited to those with a reasonable life expectancy as otherwise they will not live long enough to have the benefit of screening. Thus it is necessary to determine the risk of dying of ’competing’ causes of death when enrolled in a program of CT screening for lung cancer. Methods: We reviewed the records of all 4,827 people enrolled in the Early Lung Cancer Action Project between 1993–2004. Death records were obtained from all who had not returned for screening in the past 2 years and included all causes other than lung cancer. Kaplan-Meier analysis was used to determine the 10-year death rate by age categories (40–49, 50 74, 75+) years of age and smoking categories (1–29, 30–59, 60+) pack years of smoking. Results: For those of age 40–49, the 10-year death rate was 0%, regardless of smoking history. For those of age 50–74, it was 0%, 2%, and 7%, respectively for the 3 smoking history categories of 1–29, 30–59, 60+. For those of age 75+, it was 0%, 7%, 11%, respectively for the 3 smoking history categories. Conclusions: The results showed that for smokers and former smokers, the risk of dying of competing causes of death depends on the age and smoking history. No significant financial relationships to disclose.
Phase I study of gefitinib in combination with irinotecan in patients with fluoropyrimidine refractory advanced colorectal cancer (CRC)
Authors: I. Chau, A. Massey, L. Higgins, N. Botwood, D. Cunningham
Journal: Journal of Clinical Oncology (2004)

3572 Background: Gefitinib (Iressa, ZD1839) is an orally active epidermal growth factor receptor tyrosine kinase inhibitor that potentiates the effects of irinotecan in preclinical models. This study aims to establish the maximum tolerated dose (MTD) of administering gefitinib in combination with irinotecan and to assess safety and efficacy. Methods: Patients with advanced CRC progressing on or within 12 weeks of fluoropyrimidine-based chemotherapy were recruited. In cohort 1, patients were treated with irinotecan 250mg/m2 once every 3 weeks and gefitinib 250mg daily starting on day 1. Two dose limiting toxicities (DLTs), prolonged grade 4 neutropenia and grade 3 diarrhoea with neutropenic sepsis, were seen at this starting level. Thus two lower dose levels were explored in cohort 2 (irinotecan 200mg/m2 day 1) and cohort 3 (irinotecan 225mg/m2 day 1) both given with gefitinib 250mg daily starting on day 3. Pharmacokinetic (PK) studies were instigated in cohorts 2 and 3. Results: Eighteen patients were treated with ≥1 cycle in total. Baseline demographics and maximum grade toxicity in any cycle are shown in the table. One patient in cohort 2 developed grade 4 vomiting before starting gefitinib and was not considered a DLT. Another patient in cohort 3 developed febrile neutropenia in cycle 2. So far, 4 patients had disease stabilization of ≥12 weeks, all of whom developed a skin rash during treatment, with 1 patient having stable disease for 17 months. Conclusions: Dose limiting toxicities, especially neutropenia, occurred at an unexpectedly low dose of irinotecan in combination with gefitinib and on-going PK analysis may provide further insight. Irinotecan 225mg/m2 and gefitinib 250mg daily is recommended as the MTD and this dose level is being expanded in a phase II study. 'Iressa' is a trademark of the AstraZeneca group of companies Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca AstraZeneca AstraZeneca (UK)
Impact on disease-free survival of adjuvant erlotinib or gefitinib in patients with resected lung adenocarcinomas that harbor epidermal growth factor receptor (EGFR) mutations
Authors: Y. Y. Janjigian, B. J. Park, M. G. Kris, V. A. Miller, G. J. Riely, J. Zheng, J. P. Dycoco, R. Shen, C. G. Azzoli
Journal: Journal of Clinical Oncology (2009)

7523 Background: Patients with stage IV adenocarcinoma whose tumors harbor EGFR mutations have high rates of response (∼ 75%) and prolonged progression free survival after EGFR tyrosine kinase inhibitor (TKI) treatment. Adjuvant cisplatin-based chemotherapy improves disease free survival (DFS) and overall survival (OS) in patients with resected stages IB-IIIA NSCLC. To see if adjuvant treatment with EGFR TKI (gefitinib or erlotinib) improves DFS in patients with EGFR mutation NSCLC, we conducted a retrospective review of patients with resected lung adenocarcinoma harboring EGFR mutations, some of whom received EGFR TKIs postoperatively. Methods: With Institutional Review Board approval, clinical information was obtained on all patients with stage I-III lung adenocarcinoma harboring EGFR exon 19 or 21 mutations that underwent resection at MSKCC between May 2002 and August 2008. Age, gender, type of surgery, histology, EGFR mutation status (exon 19 deletions and exon 21 L858R), stage, perioperative therapy and survival were recorded. Kaplan-Meier analysis and Cox regression analysis were performed. Results: We studied 150 patients (112 women, 38 men) with completely resected stage I-III lung adenocarcinoma whose resection specimens contained EGFR activating mutations in exon 19 or 21. Median age was 69. Forty two patients (28%) received cytotoxic chemotherapy. Forty eight (32%) received either erlotinib (n=26) or gefitinib (n=22) postoperatively. The median time on TKI was 16 months. The median DFS was 43 months in the group that received a TKI vs. 31 months for those that did not. After controlling for stage, individuals who received adjuvant gefitinib or erlotinib had a better DFS (HR=0.38, 95%CI: 0.16–0.90) than the non-TKI group (p=0.03). The median overall survival has not been reached. Conclusions: These data indicate that the adjuvant use of either gefitinib or erlotinib improves DFS in patients with completely resected stage I -III lung adenocarcinomas with mutations in EGFR exons 19 and 21. These data justify a randomized trial in similar patients. [Table: see text]
P0119 : Validation Of The NACSELD Infection-Related Acute-on-Chronic Liver Failure (I-ACLF) score in an independent multicenter cohort
Authors: J.G. O’Leary, K.R. Reddy, G. Garcia-Tsao, S.W. Biggins, F. Wong, M.B. Fallon, R. Subramanian, P.S. Kamath, P. Thuluvath, B. Maliakkal, H. Patton, P. Tandon, L.R. Thacker, J.S. Bajaj
Journal: Journal of Hepatology (2015)
Differential Distribution of Mouse Mammary Tumor Virus-Related Sequences in the DNA’s of Rats2
Authors: W. Drohan, J. Schlom
Journal: JNCI Journal of the National Cancer Institute (1979)

Abstract Radioactively labeled mouse mammary tumor virus (MuMTV) 60-70S RNA, obtained from virions grown In both murine and feline cells, was employed In molecular hybridization experiments to detect MuMTV-related sequences In the DNA’s of rats (Rattus norveglcus). With the use of relaxed conditions of hybridization and assay for RNA-DNA duplexes, all strains of laboratory rats and feral rats examined were shown to possess endogenous MuMTV-related DNA sequences In the low repetitive range. These sequences were related to approximately 20% of the MuMTV genome and exhibited a melting temperature (Tm) approximately 5° C lower than MuMTV-specific proviral sequences In murine (Mus musculus) DNA’s. Certain colonies of the F344 strain of rat (Fischer) contained animals whose DNA’s possessed additional MuMTV-related sequences. These sequences were related to the non-germ-line-transmitted, tumorassociated (TA) sequences of the highly oncogenic MuMTV (C3H). They were found In the DNA of some F344 rats and a cloned established F344 rat embryo cell line at a frequency of approximately one copy per haploid genome and exhibited a Tm 9° C lower than that of hybrid duplexes formed between radioactive MuMTV TA-sequence RNA and C3H mouse mammary tumor DNA. The DNA’s of rats, therefore, contained two sets of sequences that were related to sequences of the MuMTV genome: One set was germ-line transmitted, whereas the other set appeared to be transmitted in some rats via a non-germ line or infectious process.
Benefit, Risk, and Outcomes in Drug Development: A Systematic Review of Sunitinib
Authors: Benjamin Carlisle, Nadine Demko, Georgina Freeman, Amanda Hakala, Nathalie MacKinnon, Tim Ramsay, Spencer Hey, Alex John London, Jonathan Kimmelman
Journal: JNCI Journal of the National Cancer Institute (2015)

Little is known about the total patient burden associated with clinical development and where burdens fall most heavily during a drug development program. Our goal was to quantify the total patient burden/benefit in developing a new drug.
The involucrin gene of the owl monkey: origin of the early region.
Authors: H Tseng, H Green
Journal: Molecular Biology and Evolution (1989)

A large part of the coding region of the hominoid involucrin gene is of recent origin. This part of the gene, which we have called the modern segment, contains numerous repeats of a sequence of 10 codons, created by multiple duplications some of which consist of 3-12 repeats. We have sequenced two alleles of the involucrin gene in the owl monkey and found that the involucrin gene of this species also possesses a modern segment. By comparing the modern segment of the owl monkey with that of the hominoids, we find that only a part of this segment is shared by the two species. We call this part the early region because it must have originated in a common ancestor of the anthropoids. The rest of the hominoid modern segment does not correspond to any groups of repeats in the owl monkey and was therefore created after divergence of the two lineages. As in the hominoids, the latest additions to the modern segment of the owl monkey have been in its 5' half, which possesses different duplication patterns in the two alleles. Lineage divergences within the anthropoids can be detected at different sites within the modern segment.
Carboplatin (C), paclitaxel (P) and gemcitabine (G) induction therapy followed by thoracic conformal radiation therapy (TCRT) with or without concurrent CP in stage IIIA/B non-small cell lung cancer (NSCLC)
Authors: J. R. Casal, M. Q. Lazaro, S. E. Vazquez, J. L. P. Firvida, C. M. Almanza, J. Garcia, M. Amenedo, J. Castellanos, G. Quintero, C. Grande
Journal: Journal of Clinical Oncology (2005)

7241 Background: Combined thoracic radiation and chemotherapy has become the treatment of choice for unresectable stage III NSCLC, but the optimal strategy remain undefined. Methods: 94 patients (pts) with unresectable locally advanced NSCLC, stage IIIAN2/IIIB (no pleural T4), were included in a phase II study with a scheme of induction with CPG and, if no surgery, followed by TCRT with (Group-1/concomitant) or without (Gr-2) CP. The CPG scheme is: C AUC-5 mgr/iv d1, P 175 mgr/m2/iv d1, and G 1000 mgr/m2/iv on d 1 and 8 every 3 weeks through 2 (Gr1) or 3 (Gr2) cycles; if no surgery, treatment in Gr-1 consisted of TCRT (60Gys, 180 cGy/day) with concomitant C AUC-2 mgr/iv and P 45 mgr/m2/ iv weekly during 7 weeks and in Gr-2 only TCRT (60 Gys, 200 cGy/day over 6 weeks). The primary objective: overall survival; secondary: progression free survival, response rate (RR) and toxicity. Results: The pts characteristics were: mean age 58.9 yrs (37–74); ECOG 0/1 in 23/71 pts; stage IIIAN2: 30 pts and stage IIIB 64 pts. 85 pts were evaluables for response and 91 pts for toxicity. Induction CPG response: 5 CR and 44 PR (RR 57.5%), 27 SD (31.8%) and 9 PD (10.7%). 15 pts went to surgery: 3 pCR, 11 pPR and 1 pSD. 33 pts in Gr-1 completed treatment with 6 CR, 20 PR, 2 SD and 5 PD (RR 78.7%) and 12 pts in Gr-2 with 1 CR, 7 PR and 4 PD (RR 57.1%). The median time to progression was 9 mo (9 mo in Gr-1 and 8 mo in Gr-2) and median overall survival was 16 mo (15 mo in Gr-1 and 17 mo in Gr-2). A total of 239 cycles of CPG were administered (2.3 per pts), with the hematologic toxicity (NCI-CTC) per pts Grade (g) 1–2/3–4 (%) as follows: neutropenia 28.5/17.5; anemia 40.6/3.2; thrombocytopenia 9.8/6.5; neutropenic fever in 5 pts.The main toxicities (RTOG) in consolidation treatment were in Gr-1: g1–2 neutropenia/anemia/ thrombocytopenia 40/60/11.5% of pts; g1–2/3 esophagitis in 45.7/8.5% and g1–2 pneumonitis in 17% of pts; hospitalizations was necessary in 6 pts with 1 toxic death. Conclusions: CPG is active against stage III NSCLC with moderate toxicity and overall survival is not improved by concomitant CP and TCRT, to expense of a higger toxicity. No significant financial relationships to disclose.
Obesity and chronic intermittent hypoxia are independent risk factors for clinical decompensation in patients with cirrhosis and OSAS
Authors: Aliae Mohamed-Hussein, Mohamed-Eltaher Ibrahim
Journal: European Respiratory Journal (2014)

Obesity and chronic intermittent hypoxia are closely associated with OSAS and may cause aggressive deterioration in the course of chronic viral hepatitis. However, their impact in the development of clinical decompensation (CD) in patients with cirrhosis with OSAS is uncertain. Patients and Methods: 34 patients with OSAS and compensated cirrhosis (group A) as well as 30 compensated cirrhotic patients (group B) were included. Body mass index (BMI), polysomnography, abdominal sonography, liver functions and portal pressure were assessed on inclusion. Parameters of CD within one year were recorded (ascites, hepatic encephalopathy or variceal hemorrhage). Results: BMI was significantly higher in group A (p=0.01), CD occurred in 32.3% of cases in group A vs 10% in group B (p=0.01). Positive correlations were recorded between BMI, desaturation index, sleep duration SpO2l90% and predictors of CD. Multivariable analysis showed that BMI, AHI, sleep duration SpO2l 90%, desaturation index were independent predictors of CD, together with high portal venous pressure and serum albumin. Conclusion: Obesity and hypoxemia in OSAS may have deleterious effect on the natural history of compensated cirrhosis independent of portal pressure and liver function. Treatment of OSAS and weight reduction may decrease considerable burden on cirrhosis.
Pathological features of advanced gastric cancer (GC): Relationship to human epidermal growth factor receptor 2 (HER2) positivity in the global screening programme of the ToGA trial
Authors: Y. Bang, H. Chung, J. Xu, F. Lordick, A. Sawaki, N. Al-Sakaff, O. Lipatov, C. See, J. Rueschoff, E. Van Cutsem
Journal: Journal of Clinical Oncology (2009)

4556 Background: HER2 positivity is thought to be a negative prognostic factor in GC, correlating with poor survival rates. Reported HER2-positivity rates in GC have varied widely (6–35%). The ToGA trial is evaluating the addition of trastuzumab (Herceptin) to chemotherapy in HER2-positive advanced GC. It is the first randomised Phase III trial to provide prospective information on HER2-positivity rates in GC. Enrollment is complete, with 3,883 patients screened in 24 countries. The pathological features of GC and the relationship with HER2 positivity will be examined. Methods: Advanced GC tumour samples were centrally screened by immunohistochemistry (IHC; HercepTest) and fluorescence in situ hybridisation (FISH; PharmDx) in parallel. A HER2-scoring system modified from the protocol in breast cancer (BC) was used: a score of IHC 3+ and/or FISH positive was defined as HER2 positive. Results: Final data showed an overall HER2-positivity rate of 22.1% evaluated from 3807 patients. The HER2-positivity rate was similar between Europe (23.6%) and Asia (23.5%). HER2-positivity rates were higher in gastro-oesophageal junction (GEJ) than stomach cancer (33.2% vs 20.9%; p&lt;0.001) and in intestinal than diffuse/mixed cancer (32.2% vs 6.1%/20.4%; p&lt;0.001). This is reflected in above-average HER2-positivity rates in countries with the highest GEJ:stomach cancer ratios (France 0.56 [HER2 positivity 26.9%]; Germany 0.53 [23.7%]; UK 0.33 [25.8%]) and intestinal:diffuse cancer ratios (UK 3.4 [HER2 positivity 25.8%]; Australia 2.6 [32.8%]; Japan 2.8 [27.8%]). The modified HER2-scoring system showed concordance between IHC and FISH results of 87.5%. In BC most IHC 0/1 samples are FISH negative but, in ToGA, the frequency of IHC 0/1 samples testing FISH positive was almost as high as IHC 2/FISH-positive samples (23% vs 26%). Conclusions: The overall HER2-positivity rate in advanced GC in ToGA is 22.1%. Variations in tumour location and type mostly explain the difference in HER2-positivity rates between countries. Efficacy data will enable further evaluation of the clinical significance of HER2 IHC and FISH scoring patterns. [Table: see text]
Dermatomyositis and breast cancer.
Authors: S Daryanani
Journal: Journal of Clinical Oncology (1998)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1998.16.8.2890 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 9704744 Dermatomyositis and breast cancer. S DaryananixS DaryananiSearch for articles by this author Show More Hospital de Clinicas Caracas, Venezuela. https://doi.org/10.1200/JCO.1998.16.8.2890 PDF "Dermatomyositis and breast cancer.." Journal of Clinical Oncology, 16(8), pp. 2890–2891© 1998 by American Society of Clinical Oncology
Abstract 13824: Role for DNA Damage in the Etiology of Pulmonary Arterial Hypertension
Authors: Jolyane Meloche, Aude Pflieger, Mylene Vaillancourt, Sandra Breuils-Bonnet, Eve Tremblay, Caroline Lambert, Roxane Paulin, Evangelos D Michelakis, Steeve Provencher, Sebastien Bonnet
Journal: Circulation (2013)

Background: Pulmonary arterial hypertension (PAH) is associated with sustained inflammation known to promote DNA damage. Despite these unfavorable environmental conditions, PAH pulmonary arterial s...
Enhancing Effect of Vitamin E on Murine Intestinal Tumorigenesis by 1 ,2-Dimethylhydrazine Dihydrochloride&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Bela Toth, Kashinath Patil
Journal: JNCI Journal of the National Cancer Institute (1983)

The effect of the antioxidant vitamin E on the tumor-inducing ability of 1,2-dimethylhydrazine dihydrochloride (1,2-DMH) was investigated in randomly bred Swiss mice. Three groups of mice that were 6 weeks of age at the beginning of the experiment received the following treatments: a) vitamin E acetate [DL-alpha-tocopheryl acetate (TA)] at a 4% dose level in a powdered diet for life; b) 1,2-DMH, 10 weekly sc injections at 20 micrograms/g body weight; c) combination of a and b treatments. The administration of TA enhanced the tumorigenicity of 1,2-DMH, as evidenced by statistically significant incidences of tumors in the duodenum, cecum, colon, rectum, and anus. The present finding apparently is in contrast with the reported inhibitory effect of TA on colon carcinogenesis by 1,2-DMH.
Reversal of central sleep apnoea with change from methadone to buprenorphine-naloxone: a case report
Authors: David Wang, Nicholas Lintzeris, Stefanie Leung, Paul S. Haber, Brendon J. Yee, Ronald R. Grunstein
Journal: European Respiratory Journal (2015)

Preventing prescription opioid poisoning deaths is a major public health priority in Western societies. Deaths from these medications exceed deaths from all illicit drugs combined [1]. Methadone (for pain treatment) is involved in one third of US prescription opioid overdose deaths despite accounting for only 5% of dispensed opioids [2]. There is a dose-dependent increase in the severity of central sleep apnoea (CSA) with methadone [3–5] and sleep disordered breathing is a contributing factor in methadone-related deaths [2]. The partial μ-agonist buprenorphine is putatively safer than methadone with a ceiling effect upon respiratory depression [6]. However, the effect of buprenorphine on breathing during sleep remains unclear. The only relevant report from a cross-sectional observational study suggested that buprenorphine-naloxone therapy may induce significant CSA and hypoxaemia [7]. Methadone-using patients with central sleep apnoea may reverse symptoms with switch to buprenorphine-naloxone therapy <http://ow.ly/NilUq>
Anticipating missing reference standard data when planning diagnostic accuracy studies
Authors: Christiana A Naaktgeboren, Joris A H de Groot, Anne W S Rutjes, Patrick M M Bossuyt, Johannes B Reitsma, Karel G M Moons
Journal: BMJ (2016)

Results obtained using a reference standard may be missing for some participants in diagnostic accuracy studies. This paper looks at methods for dealing with such missing data when designing or conducting a prospective diagnostic accuracy study
Enhanced Liver Uptake of Opsonized Red Blood Cells After In Vivo Transfer of FcγRIIA cDNA to the Liver
Authors: Petr Bezdicek, Stefan Worgall, Imre Kovesdi, Moo-Kyung Kim, Jong-Gu Park, Theresa Vincent, Philip L. Leopold, Alan D. Schreiber, Ronald G. Crystal
Journal: Blood (1999)
Over half of English general practices report unmanageable workload
Authors: Gareth Iacobucci
Journal: BMJ (2016)

More than half of GP surgeries in England say that their patient care has “deteriorated” in the past 12 months because of an increasing workload, a new survey by the BMA has found.

Some 2840 of 7962 practices in England responded to the survey (a 36% response rate), the latest in a string of polls by the BMA1 designed to draw attention to the pressures facing GPs and to encourage government action to support the profession.

More than half of the practices that responded (1564; 55%) …
Inhibition of DNA Synthesis by a Small-Cell Lung Carcinoma-Derived Protein
Authors: W K Funkhouser, L M Neckers, R S Ames, D N Carney, J A Roth
Journal: JNCI Journal of the National Cancer Institute (1986)

A tumor-derived factor that inhibits cellular DNA synthesis was identified. The factor was extractable from a small-cell lung carcinoma cell line grown in either chemically defined medium ornu/nu mice and inhibited tritiated thymidine ([3H]dThd) incorporation by tumor cell lines of autologous, allogeneic, and xenogeneic origins. The viability of nonproliferating cells from normal tissue was not affected. Tumor extract inhibitory activity was trypsin labile but was resistant to other proteases, neuraminidase, lipase, DNase, RNase, glucosidase, extremes of pH-temper-ature, and reducing conditions. Inhibitory activity was reversibly bound to helix pomatia lectin but not to lentil, wheat germ, or concanavalin A lectins. Purification by size-exclusion high-performance liquid chromatography yielded a bioactive unimodal 12-kilodalton (kd) peak. The bioactive 12-kd moiety could be eluted from sodium dodecyl sulfate-polyacrylamide gels. Redosing of populations of the T-lymphoblastoid cell line CEM achieved an early (24 hr) sustained depression of pulse [3H]dThd incorporation and ultimately led to decreased population density of factor-treated populations. DNA histogram analysis demonstrated no change in cell cycle phase distribution after factor treatment. 5-Bromo-2′-deoxyuridine (BrdUrd) vs. propidium iodide with the two-parameter Fluorescence-Activated Cell Sorter analysis showed relative inhibition of non-S-phase BrdUrd uptake at 24 hours. A cell-free DNA polymerase assay demonstrated significant inhibition of non-α-polymerase-associated DNA synthesis in factor-treated cells. These studies suggest that this tumor-derived inhibitor of DNA synthesis represents a class of cellular products involved in the autoregulation of growth by regulation of DNA synthetic activity.