tbuckley/cabot-search huggingface dataset:
Epidermal growth factor receptor (EGFR) inhibition in triple-negative breast cancer (BrCa)
Authors: B. Corkery, N. O’Donovan, M. Clynes, J. Crown
Journal: Journal of Clinical Oncology (2007)

14071 Background: Triple-negative BrCa lacks expression of hormone receptors and HER-2 but does express EGFR. It is associated with early relapse and poor survival. There is no targeted therapy for triple-negative BrCa. We are studying the potential role of EGFR inhibition. Methods: EGFR expression was examined in triple-negative BrCa cell lines, (BT20, HCC1937, and MDA-MB-231) by western blot. IC 50 assays were determined for three EGFR inhibitors, gefitinib (G) and erlotinib (T), which are small-molecule tyrosine kinase inhibitors, and cetuximab (E) which is a monoclonal antibody against EGFR, and chemotherapy (CRx) drugs docetaxel (D) and carboplatin (P)), using the acid phosphatase assay. The controls were HER2+ BrCa cell lines, BT474 and SKBR3 which express low levels of EGFR. Results: The three triple-negative cell lines over-express EGFR. IC 50 values for G and T were significantly higher in the triple-negative than in the HER2+ cell lines. E did not cause significant inhibition in any cell line (max inhibition 20% at 100 μg/ml E). IC 50 values for G were lower than for T in the triple-negative cell lines (IC 50 s for HCC1937: G - 8.4 ± 1.5 μM; T - 26.2 ± 9.3 μM). Combined EGFR inhibition with CRx was tested in HCC1937 cells. G combined with P or with D for 5 days showed an additive effect on inhibition of proliferation ( Table 1 ). Alternate scheduling of the drugs did not significantly influence response. Conclusions: Our results suggest that triple-negative BrCa cells over-express EGFR but are not as sensitive to EGFR inhibition as HER2+ BrCa cells. However, EGFR inhibition may enhance response to CRx in triple-negative BrCa. [Table: see text] No significant financial relationships to disclose.
Cell Kinetics In Vivo and In Vitro for C3H/He Spontaneous Mammary Tumors 2
Authors: Paul G. Braunschweiger, Lawrence Poulakos, Lewis M. Schiffer
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Cell Kinetics In Vivo and In Vitro for C3H/He Spontaneous Mammary Tumors Get access Paul G. Braunschweiger, Paul G. Braunschweiger 3Cancer Research Unit, Division of Radiation Oncology, Allegheny General Hospital, 320 East North Ave., Pittsburgh, Pa. 15212. Search for other works by this author on: Oxford Academic PubMed Google Scholar Lawrence Poulakos, Lawrence Poulakos 3Cancer Research Unit, Division of Radiation Oncology, Allegheny General Hospital, 320 East North Ave., Pittsburgh, Pa. 15212. 4Present address: Biomedical Division, L-523, Lawrence Livermore Laboratory, University of California, Livermore, Calif. 94550. Search for other works by this author on: Oxford Academic PubMed Google Scholar Lewis M. Schiffer Lewis M. Schiffer 3Cancer Research Unit, Division of Radiation Oncology, Allegheny General Hospital, 320 East North Ave., Pittsburgh, Pa. 15212. 5We thank Linda Fisher, Tamara Hamilton, Debra Iannuzzi, and Kathleen Klueber for their technical assistance and Paula Banachoski for preparation of the manuscript. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 59, Issue 4, October 1977, Pages 1197–1204, https://doi.org/10.1093/jnci/59.4.1197 Published: 01 October 1977 Article history Received: 29 July 1976 Revision received: 02 December 1976 Accepted: 25 April 1977 Published: 01 October 1977
Prospective study with combined low-dose chemotherapy and zidovudine in 37 patients with poor-prognosis AIDS-related non-Hodgkin's lymphoma
Authors: U. Tirelli, D. Errante, E. Oksenhendler, M. Spina, E. Vaccher, D. Serraino, R. Gastaldi, L. Repetto, G. Rizzardini, A. Carbone, G. Bertola, E. Mandelli, S. Monfardini, C. Gisselbrecht
Journal: Annals of Oncology (1992)
Results of allogeneic bone marrow transplants for leukemia using donors other than HLA-identical siblings.
Authors: R Szydlo, J M Goldman, J P Klein, R P Gale, R C Ash, F H Bach, B A Bradley, J T Casper, N Flomenberg, J L Gajewski, E Gluckman, P J Henslee-Downey, J M Hows, N Jacobsen, H J Kolb, B Lowenberg, T Masaoka, P A Rowlings, P M Sondel, D W van Bekkum, J J van Rood, M R Vowels, M J Zhang, M M Horowitz
Journal: Journal of Clinical Oncology (1997)

PURPOSE To compare outcomes of bone marrow transplants for leukemia from HLA-identical siblings, haploidentical HLA-mismatched relatives, and HLA-matched and mismatched unrelated donors. PATIENTS A total of 2,055 recipients of allogeneic bone marrow transplants for chronic myelogenous leukemia (CML), acute myelogenous leukemia (AML), and acute lymphoblastic leukemia (ALL) were entered onto the study. Transplants were performed between 1985 and 1991 and reported to the International Bone Marrow Transplant Registry (IBMTR). Donors were HLA-identical siblings (n = 1,224); haploidentical relatives mismatched for one (n = 238) or two (n = 102) HLA-A, -B, or -DR antigens; or unrelated persons who were HLA-matched (n = 383) or mismatched for one HLA-A, -B, or -DR antigen (n = 108). HLA typing was performed using serologic techniques. RESULTS Transplant-related mortality was significantly higher after alternative donor transplants than after HLA-identical sibling transplants. Among patients with early leukemia (CML in chronic phase or acute leukemia in first remission), 3-year transplant-related mortality (+/-SE) was 21% +/- 2% after HLA-identical sibling transplants and greater than 50% after all types of alternative donor transplants studied. Among patients with early leukemia, relative risks of treatment failure (inverse of leukemia-free survival), using HLA-identical sibling transplants as the reference group, were 2.43 (P &lt; .0001) with 1-HLA-antigen-mismatched related donors, 3.79 (P &lt; .0001) with 2-HLA-antigen-mismatched related donors, 2.11 (P &lt; .0001) with HLA-matched unrelated donors, and 3.33 (P &lt; .0001) with 1-HLA-antigen-mismatched unrelated donors. For patients with more advanced leukemia, differences in treatment failure were less striking: 1-HLA-antigen-mismatched relatives, 1.22 (P = not significant [NS]); 2-HLA-antigen-mismatched relatives, 1.81 (P &lt; .0001); HLA-matched unrelated donors, 1.39 (P = .002); and 1-HLA-antigen-mismatched unrelated donors, 1.63 (P = .002). CONCLUSION Although transplants from alternative donors are effective in some patients with leukemia, treatment failure is higher than after HLA-identical sibling transplants. Outcome depends on leukemia state, donor-recipient relationship, and degree of HLA matching. In early leukemia, alternative donor transplants have a more than twofold increased risk of treatment failure compared with HLA-identical sibling transplants. This difference is less in advanced leukemia.
Synergistic Antitumor Effects of Rat γ-Interferon and Human Tumor Necrosis Factor α against Androgen-dependent and -independent Rat Prostatic Tumors
Authors: R. J. A. Van Moorselaar, B. T. Hendriks, P. Van Stratum, P. H. Van Der Meide, F. M. J. Debruyne, J. A. Schalken
Journal: Cancer Research (1991)

We have examined the antitumor effects of rat gamma-interferon (IFN-gamma) and human tumor necrosis factor alpha (TNF) against androgen-dependent and -independent Dunning rat prostatic tumors. In vitro studies, using the double layer soft agar assay, showed a very limited antiproliferative activity of the drugs in the dose range tested (1-1000 units IFN-gamma and/or 1-1000 ng TNF/dish). For in vivo studies IFN-gamma and TNF were administered s.c., peritumorally. IFN-gamma was given 3 times/week, 8,000 or 80,000 units/rat, and TNF 5 times/week, 10 or 100 micrograms/rat. IFN-gamma and TNF monotherapy were not significantly effective in inhibiting tumor growth, except for IFN-gamma against the androgen-independent MatLyLu tumor. Combinations of IFN-gamma and TNF had synergistic antiproliferative effects against all four tumor lines tested; however, complete growth inhibitions could not be achieved. Survival studies showed significant increase in survival of tumor-bearing rats.
Small neuroretinal rim and large parapapillary atrophy as predictive factors for progression of glaucomatous optic neuropathy 1 1The authors have no proprietary interest in the products or devices mentioned herein.
Authors: Jost B Jonas, Peter Martus, Wido M Budde, Anselm Jünemann, Jochen Hayler
Journal: Ophthalmology (2002)
Effects of socioeconomic status on severity, treatment and outcomes in patients with pleural infection
Authors: Hsiu-Nien Shen, Chin-Li Lu, Chung-Yi Li
Journal: European Respiratory Journal (2013)

Background: Whether and how socioeconomic status (SES) influences severity, treatment and outcomes in patients with pleural infection remains unknown.  Methods: We analyzed 24,864 adults with pleural infection, treated between 1997 and 2008, from Taiwan’s National Health Insurance Research Database. The SES, measured by monthly incomes, was categorized into four levels: no, low, middle and high incomes. Primary outcome was 30-day mortality. Secondary outcomes were development of new organ failure (as a measure of disease severity) and surgery for pleural infection. The effect of SES on outcomes was assessed using sequential multivariable logistic regression models.  Results: The risks of new organ failure were 34%, 30%, and 12% higher in patients with no (OR 1.34, 95% CI 1.20-1.49), low (OR 1.30, 95% CI 1.19-1.42) and middle incomes (OR 1.12, 95% CI 1.03-1.21), respectively, than in those with high income after adjusting for baseline covariates. Surgery was 23% and 22% less likely to be performed in patients with no (OR 0.77, 95% CI 0.65-0.91) and low incomes (OR 0.78, 95% CI 0.66-0.91) than in those with high income after adjusting for the baseline covariates, disease severity and uses of life-supports. The 30-day mortality was 17.1%, 15.5%, 14.8% and 10.4% in patients with no, low, middle and high incomes, respectively (p for trend   Conclusions: Lower SES patients with pleural infection are more severe and less likely to undergo surgery. Their higher mortality is largely explained by higher severity of illness.
Lung cancer symptoms with cetuximab/taxane/carboplatin in first-line advanced NSCLC: Analysis of the BMS099 trial
Authors: T. Patel, L. Dreisbach, M. McCleod, W. J. Heim, R. C. Hermann, D. Woytowitz, H. Lu, M. R. Weber, T. J. Lynch
Journal: Journal of Clinical Oncology (2009)

e19011 Background: The phase III BMS099 trial investigated cetuximab (C) added to taxane/carboplatin (TC) for 1st line treatment of advanced NSCLC. Progression-free survival (PFS) was not significantly different with C; response rate (RR) was significantly higher. Median overall survival (OS) was longer, with a difference not statistically significant, but similar in magnitude to the significant OS improvement from the FLEX trial (cisplat/vinorelb±C). A secondary objective of the BMS099 study was to assess the effect of C on Lung Cancer Symptoms (LCS). Methods: Chemonaïve patients (pts) with stage IIIB/IV NSCLC (any histology or EGFR expression status) were randomized to TC±C. LCS were measured using the functional assessment of cancer treatment-lung cancer subscale questionnaire (FACT-LCS), given at baseline and before each therapy cycle until disease progression (scoring 7 symptoms: breath loss, weight loss, clear thinking, coughing, appetite, chest tightness, breath ease, on a 0–4 scale). The main endpoints were rates of symptom response/progression (≥ 2 point improvement/decrease from baseline in 2 consecutive assessments), compared between arms with a stratified Cochran-Mantel-Haenszel (CMH) test; a stratified log-rank test was used to compare time to symptomatic progression. A Wei-Lachin test was used to compare between arms the changes from baseline in LCS score, and a longitudinal model was constructed to measure treatment effect on those score changes. Results: With 676 patients randomized, the baseline compliance rates for the FACT-LCS questionnaire were 99.4% and 99.1% for CTC and TC respectively, decreasing by week 18 to 74.0% and 66.4%. Baseline FACT-LCS scores were similar across treatment arms (median, 19.0). Symptom response rates were similar with CTC vs TC (32.6% vs 28.5%, CMH P=0.26), and time to symptomatic progression was not significantly different (log-rank P=0.58). Changes from baseline in FACT-LCS scores did not differ significantly between arms (Wei Lachin P=0.912; longitudinal model P=0.81). Conclusions: The addition of C to TC for the 1 st treatment of advanced NSCLC resulted in similar symptom response/progression rates and did not affect trends in LCS score changes throughout treatment. [Table: see text]
Evaluation of the effect of appropriate antimicrobial therapy on mortality associated with Acinetobacter nosocomialis bacteraemia
Authors: S.-C. Kuo, Y.-T. Lee, S.-P. Yang, M.-C. Chiang, Y.-T. Lin, F.-C. Tseng, T.-L. Chen, C.-P. Fung
Journal: Clinical Microbiology and Infection (2012)
Hormone replacement therapy and the breast
Authors: A. H MacLennan
Journal: BMJ (2002)

Editor—As active members of the Australasian Menopause Society, we are disappointed at the conclusions that Dixon drew in his editorial on hormone replacement therapy and the breast.1 Although it may be true that hormone replacement therapy makes mammograms harder to interpret, it is far from clear that it causes breast cancer.

A recent overview by Bush et al emphasises the weakness of Dixon's argument, based, as it is, almost entirely on level three observational studies.2 Unlike Dixon's selection of studies with the highest odds ratio, Bush et al's review was of 45 studies assessing the association between use of hormone replacement therapy and risk of breast cancer. It found that risk was reduced (relative risk<0.9) in 20% of the studies, did not change in 47% (0.9-1.1), and increased in 33% (1.1-2.0). In no study did relative risk increase above 2.0, and in the 20 studies where the relation between risk of breast cancer and combined oestrogen and progestin therapy was studied only four reported a significant difference in relative risk, with two showing an increased and two a decreased risk.

The heterogeneity of these data is in stark contrast to the homogeneity of the data on mortality from breast cancer in users of hormone replacement therapy that were reviewed: all 11 of the studies reported a reduction in risk. Unlike Dixon, the authors concluded that the likelihood of an adverse effect of hormone replacement therapy on breast cancer must be small.

The Australasian Menopause Society is a sponsor of the women's international study of long duration oestrogen use after the menopause (the WISDOM trial), a large prospective 15 year randomised placebo controlled trial. The results of this trial, together with those of the women's health initiative in the United States, will be needed to answer the question of whether hormone replacement therapy has any effect (beneficial or adverse) on breast cancer.

Until then strong opinions will continue to be held about hormone replacement therapy and its relation to risk of breast cancer, often derived from selective quoting of the available literature. These opinions heighten the anxiety of women who have valid reasons for taking hormone replacement therapy and do not afford them the opportunity of informed choice.
Quality Improvement Targets for Regional Variation in Surgical End-Stage Renal Disease Care
Authors: Devin S. Zarkowsky, Caitlin W. Hicks, Isibor Arhuidese, Joseph K. Canner, Tammam Obeid, Umair Qazi, Eric Schneider, Christopher J. Abularrage, James H. Black, Julie A. Freischlag, Mahmoud B. Malas
Journal: JAMA Surgery (2015)

Arteriovenous fistula (AVF) access improves survival in patients with end-stage renal disease (ESRD) compared with other modalities when used at first hemodialysis. Use varies between locations, but, to our knowledge, no study has related this finding to mortality on a national scale.To quantify regional variation in AVF access at first hemodialysis, as well as the associated effect on mortality in the US Renal Data System.The US Renal Data System tracks all patients with ESRD in the United States. A retrospective analysis of the population from January 1, 2006, to December 31, 2010, was performed. Univariate analyses (χ² test; 2-tailed, unpaired t test; and analysis of variance) as well as multivariable logistic regressions were carried out to compare patient characteristics, incident AVF frequencies, and corrected mortality hazards between ESRD Network Programs, which comprise 18 states, commonwealths, and protectorates in which residents receive hemodialysis. Of the patients receiving hemodialysis in these networks, the data on 464,547 individuals who were beginning renal replacement therapy were analyzed. Analysis was started April 1, 2013, and ended August 3, 2014.Mortality hazard variation between ESRD Network Programs in the United States and incident AVF frequency.Of the 464,547 patients beginning hemodialysis in this cohort, first hemodialysis with an AVF ranged from 11.1% to 22.2% depending on the ESRD Network in which they maintained residency (P < .001). Similarly, corrected mortality hazard varied by 28% (hazard ratios from 0.99 [95% CI, 0.96-1.03] to 1.27 [95% CI, 1.22-1.31]; P < .001). Logistic regression determined nephrology care to increase the odds of a patient beginning hemodialysis using an AVF by 11-fold (odds ratio, 11.42 [95% CI, 10.93-11.93]; P < .001); congestive heart failure was a negative correlatefold (odds ratio, 0.65 [95% CI, 0.64-0.67]; P < .001). No region achieved the 50% Fistula First Breakthrough Initiative (now known as Fistula First Catheter Last) target for incident AVF access.Marked regional variation in functional incident AVF frequency and risk-adjusted ESRD mortality exists across the United States. Differences in access to preoperative nephrology care and patient comorbidities may explain some of these variations, but an opportunity to implement best-practice guidelines exists.
Interruption of the enterohepatic circulation of digitoxin by cholestyramine
Authors: James H. Caldwell, Norton J. Greenberger
Journal: Journal of Clinical Investigation (1971)

Previous studies have demonstrated that considerable amounts of parenterally administered cardiac glycosides are excreted in the bile and reabsorbed across the intestinal mucosa in several species. It is currently believed that the more prolonged action of nonpolar digitalis glycosides is due to their retention and recycling in the enterohepatic circulation. This report describes studies carried out to evaluate the effects of pharmacologic interruption of this enterohepatic cycle with the intraluminal sequestering agent cholestyramine. Cholestyramine was found to bind substantial quantities of digitoxin-(3)H and digoxin-(3)H in vitro and this binding was only modestly inhibited by the presence of bile. Administration of cholestyramine to rats by intragastric catheter before the subcutaneous injection of the LD(100) dose of digitoxin (10 mg/kg) resulted in a 70% survival rate. Further, oral administration of cholestyramine to rats before the subcutaneous injection of digitoxin-(3)H resulted in accelerated fecal excretion of radioactivity and lower levels of digitoxin-(3)H and metabolites in brain tissue compared to controls. Similarly, pretreatment of guinea pigs with cholestyramine orally before the injection of digitoxin in dosages of 10.0 and 4.0 mg/kg resulted in a 25 and 70% survival rate respectively as compared to survival rates of 0 and 30% in control animals. Cholestyramine pretreatment of guinea pigs was also accompanied by lower levels of digitoxin-(3)H and metabolites in heart and liver 90 min after injection of digitoxin-(3)H. Cholestyramine therapy did not result in significant changes in serum potassium levels excluding the possibility that drug-induced hyperkalemia might have affected the cardiac uptake of digitoxin. The data obtained in this study indicate that cholestyramine treatment affords a significant degree of protection against lethal digitoxin intoxication in rats and guinea pigs. It is suggested that cholestyramine binds appreciable amounts of digitoxin in the intestinal lumen resulting in reduced reabsorption, increased fecal excretion, and lower tissue levels of glycoside in critical organs. The protective effects of cholestyramine appear to be mediated by interruption of the enterohepatic circulation of digitoxin.
Purging of bone marrow in autologous bone marrow transplantation for non-Hodgkin's lymphoma: a case-matched comparison with unpurged cases by the European Blood and Marrow Transplant Lymphoma Registry.
Authors: C D Williams, A H Goldstone, R M Pearce, T Philip, O Hartmann, P Colombat, G Santini, L Foulard, N C Gorin
Journal: Journal of Clinical Oncology (1996)

PURPOSE The use of in vitro purging of bone marrow in autologous bone marrow transplantation (ABMT) for non-Hodgkin's lymphoma (NHL) has been a controversial issue; its benefit is as yet unproven. Its effect on the clinical outcome of ABMT in these patients is still unclear. We look at this issue using data from the European Blood and Marrow Transplant (EBMT) Lymphoma Registry. PATIENTS AND METHODS Seventeen hundred twenty-six patients with NHL have been reported to the EBMT registry, of whom 270 had bone marrow purged at transplant. Two hundred twenty-four of these patients were compared with a case-matched group of 224 unpurged patients who had undergone the same procedure. The case matching was made following selection of the main prognostic factors for progression-free survival (PFS) by multivariate analysis. Response, complications, and outcome in ABMT were analyzed. RESULTS Time to hematologic engraftment, response to ABMT, and number of procedure-related deaths were similar in purged and unpurged patients. The overall survival (OS) rate was 54% at 5 years in purged patients and 48.3% in unpurged patients (P = .1813). The PFS rate was 44.3% and 44.6%, respectively (P = .1961). Patterns of relapse, including bone marrow relapse, were similar in both groups. Patients with low-grade lymphoma did not have a significantly improved PFS if the bone marrow was purged (P = .1757); however, they did have a significantly improved OS (P = .00184). This increased OS was found to be associated with non-totalbody irradiation (TBI) conditioning and also with the purged patients undergoing transplantation at large transplant centers (P = .0016). CONCLUSION Purging of bone marrow in ABMT for NHL does not affect the rate of hematologic engraftment or risk of procedure-related death (PRD). There is no significant difference in PFS for patients whose bone marrow is purged as compared with unpurged.