tbuckley/cabot-search huggingface dataset:
Expression of CD24 and CD44 tumor cells in breast cancer patients who received neoadjuvant therapy.
Authors: R. Reid, A. Muslimani, L. Downing, S. M. Wills, T. Fennell, B. Marples, D. Decker
Journal: Journal of Clinical Oncology (2010)

e21051 Background: Current research suggests that the presence of stem-cell like progenitor cells confer a poorer prognosis in patients with breast cancer. CD24-/CD44+ cells have been described as putative progenitor cells in breast cancer. The purpose of this study was to determine if clinical outcome of ER-/Her2- breast cancer patients corresponded with expression of progenitor cells. Methods: Histological analysis of the breast was carried out on mounted tissue sections which were stained for both CD24 and CD44 and subsequently counterstained. Sections were analyzed microscopically to determine the percentage of cells that stained positively for both CD24 (CD24+/CD44-) and CD44 (CD24-/CD44+) alone as well as the percentage of cells that were positive for both markers (CD24+/CD44+). The following ranges of percentages were assigned: <10, 10-25, 26-50, 51-75 and 76-100. Samples were blinded to the scores. Results: Slides (n=31) from 17 patients who had received neoadjuvant chemotherapy were stained for CD24/CD44. Of these, 9 were ER-/HER2- and 8 were ER+/HER2-. Eight patients were found to have the presence of both CD24 and CD44, 6 of these were ER-/HER2- and 2 were ER+/HER2-. Those patients with the greatest degree of positive staining were all ER-/HER2-. One ER-/HER2- patient had tissue stained from both residual tumor and residual normal parenchyma. The tissue from residual tumor was markedly positive for CD24/CD44 whereas the tissue from normal parenchyma did not stain for either CD24 or CD44. Tissue staining CD44+/CD24- was found in 5 patients (3 ER-/HER2-; 2 ER+/HER2-). No particular distribution was observed for tissue that was CD24+/CD44-. Five patients were known to have had recurrent disease 3 of these patients were notably CD44+/CD24-, and one patient was CD24+/CD44+. Conclusions: In patients who received neoadjuvant chemotherapy, CD24+/CD44+ positive staining was most commonly linked with ER- /HER2- status. Recurrence was more common in patients that were CD44+/CD24-, and no pattern for recurrence was seen in CD44+/CD24+ patients. We are in progress of expanding this limited study to validate the results from a larger group of patients. No significant financial relationships to disclose.
Utility of pre-chemotherapy echocardiographical assessment of cardiac abnormalities.
Authors: N. V. Karanth, A. Roy, M. Joseph, C. Depasquale, C. S. Karapetis, B. Koczwara
Journal: Journal of Clinical Oncology (2010)

9049 Background: Echocardiography provides both morphological and functional information offering a potential advantage over nuclear medicine gated blood pool scans which only estimate ejection fraction. This additional information may be relevant to management of patients receiving potentially cardiotoxic cancer treatment. Methods: We retrospectively audited all pre-chemotherapy echocardiograms (ECHO) ordered by medical oncologists at our institution over a 36 months period. The primary objective was to determine the frequency of cardiac abnormality detection on the initial ECHO. We also looked at the frequency of clinically relevant cardiac abnormalities other than ejection fraction abnormalities including diastolic dysfunction, intracardiac shunts, moderate-severe valvular abnormalities, pulmonary hypertension, ventricular hypertrophy, pericardial effusion, wall motional abnormalities, ventricular dysfunction/dilatation, cardiac tumours and congenital anomalies. Results: Baseline ECHOs were analyzed in 217 consecutive patients. Female patients comprised 89% of population and the majority had breast cancer (75.5%). The median age of the patients at the time of ECHO was 55 years (range 16 to 87). 13.4% of patients had at least one clinically relevant abnormality on ECHO. Systolic and moderate diastolic dysfunctions were seen in 5% and 2.7% respectively. Aortic stenosis was seen in 5 (2.3%) patients. Atrial septal defects were seen in 2 patients, moderate mitral regurgitations in 2 patients and left atrial tumour in 1 patient. A total of 7.4% of patients had abnormalities, which would not have been detected by gated blood pool scan (GBPS). The ECHO resulted in change in chemotherapy plan in 2.8% and referral to cardiology in 3.7%. Conclusions: Our retrospective analysis suggests that pre-chemotherapy ECHO can provide more useful clinical information than the GBPS, which may impact on clinical management of cancer patients. No significant financial relationships to disclose.
Electron microscopy in small cell lung carcinomas: clinical correlation.
Authors: B Copple, S E Wright, F Moatamed
Journal: Journal of Clinical Oncology (1984)

In order to investigate the relationship of subcellular differentiation of small cell lung carcinomas (SCLC) and clinical response, we reviewed the electron microscopic (EM) features of tumor biopsy specimens from 33 patients with SCLC diagnosed by light microscopy (LM). These tumors were divided by EM into four groups according to the ultrastructural features. Group I (13 patients) had tumors with only neurosecretory granules on EM. Group II (11 patients) had tumors with neurosecretory granules and other subcellular features of non-SCLC. Group III (five patients) had tumors that lacked neurosecretory granules but contained subcellular features of non-SCLC. Group IV (four patients) had tumors that lacked all of these features. The complete and partial response rate to systemic chemotherapy with or without radiation therapy was 88% in the total population studied. The response rates were not statistically different in any of the four groups based on EM findings. The results of this study suggest that the LM diagnosis of SCLC alone adequately identifies lung cancer patients with a high response rate to systemic therapy.
The protective role of erythropoietin against doxorubicin-induced cardiomyopathy
Authors: K.-H. Kim, P. Backx
Journal: Journal of Clinical Oncology (2005)

9555 Background: The clinical usage of antineoplastic drug doxorubicin (DOX) is limited due to apoptosis-related cardiotoxic side effects. The cytokine erythropoietin (EPO) is critical for the production of mature red blood cells and is commonly used to treat anemia in cancer therapy. Recent experimental data report that EPO contributes to anti-apoptosis in neuronal, vascular smooth muscle, and vascular endothelial cells. Methods: To assess whether EPO protects the heart against DOX-induced cardiomyopathy, EPO (1U/mL) was applied to cultured neonatal mouse ventricular myocytes (NMVM). Results: EPO protected (P<0.05) NMVMs against DOX application (0.1, 0.5 & 1.0μM) - induced cytotoxic cell death (by ≈50%) and apoptosis as measured by DNA fragmentation and caspase-3 activity (reduced from 44.5±6.2 nmol pNA/mg to 31.5±6.1). This protection by EPO correlated with increased (P<0.05) phosphorylation of PI3K-dependent survival pathways, Akt/PKB (∼2-fold) and GSK-3β (∼1.3-fold), which was blocked by the PI3K inhibitor LY294002. LY294002 also diminished EPO’s protective effects on cell survival and caspase-3 activity (45.5±8.9 nmol pNA/mg in DOX+EPO+LY294002), suggesting that EPO’s protection is mediated by PI3K-dependent pathways. These protective actions of EPO (2,000U/kg/wk) were also observed in mice administered DOX (3 weekly i.p. injections of 5mg/kg) wherein cardiac function, as assessed by fractional shortening (FS) using echocardiography (FS = 50.9±5% for DOX+EPO vs. 33.0±0.2% for DOX+Placebo). Conclusions: This study suggests that EPO protects myocardium against DOX-induced cell death and apoptosis via PI3K-dependent pathways as well as impaired heart function. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration University of Toronto
Evidence-based treatment protocol (ETP) usage in community oncology clinics
Authors: P. W. Cobb, R. Hermann, H. Lebos, H. Tamim, M. S. Walker, E. J. Stepanski, L. S. Schwartzberg
Journal: Journal of Clinical Oncology (2008)

6621 Background: Clinical outcomes for patients (pts) treated in non-clinical trial settings have not been compared to clinical trial participant outcomes. Moreover, the degree to which reference regimens (Ref Reg) are utilized in actual clinical settings is not known. We created ETPs based on trial reports and guidelines and measured clinician compliance with regimens, degree of variance from Ref Reg, and outcomes in heterogenous community oncology practice settings. Methods: ETPs including Ref Reg were created for 1st and 2nd line therapy in metastatic colorectal cancer (CRC), non-small cell lung cancer (NSCLC) and prostate cancer (PRC) based on review of published and presented Phase III trials and supplemented by NCCN guidelines when phase III data were not available. A range of acceptable regimens and a preferred regimen for each disease were identified, but clinicians were free to utilize any regimen of their choice after pt prospective registration with IRB approved informed consent on the ETP. Results: Five community oncology clinics with median (range) 13 (8–26) medical oncologists enrolled 169 pts as of 12/1/07: 64 CRC, 85 NSCLC, and 20 PRC. Pt demographics: 43% female, 14% African American, 50% Medicare primary payer, ECOG PS 0 31%, PS 1, 47% and > 2, 17%. Of 160 evaluable pts 67(41.9%) were treated identically to Ref Reg, 57 (35.6%) received a standard regimen with dose variation, 20 (12.5%) were enrolled on a research protocol and 11% received a non-ETP regimen. From time to event analysis, the estimated median (95%CI) duration of first line regimen ETP was 210 (98–322) days for CRC, 111 (86–135) days for NSCLC and 225 (181–268) days for PRC. There was no statistically significant difference in the duration of 1st line therapy for Ref Reg compared to dose variation/non-standard regimens. The ETP preferred regimen (± dose variation) was used in 30/54 CRC, 47/70 NSCLC, and 10/16 PRC pts. Accruals to all three ETPs are ongoing. Conclusions: ETPs can be created and utilized successfully in community oncology practice. Most patients received a Ref Reg although a priori dose modifications were common. Initial analysis indicates duration of 1st line therapy is similar in patients receiving clinical trial derived Ref Reg or alternative doses or regimens. No significant financial relationships to disclose.
Genes involved in radiation response in fibroblasts, studied by whole genome microarray
Authors: Geza Safrany, Eniko Kis, Katalin Lumniczky, Marton Keszei, Olga Esik, Andras Falus, Egon J. Hidvegi
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4402 

The authors wished to identify the radiation-induced early transcriptional responses and genes related to individual radiation sensitivity. Seven normal and three radiation sensitive primary human fibroblast cell lines were irradiated with 2 Gy gamma-radiations and RNA isolated 2 h later. Radiation-induced transcriptional alterations and differences in basal gene expression profiles were investigated using Agilent’s Whole Human Genome Oligo Microarray (44000 features) system. Statistically significant (P<0.001) alterations was determined using Agilent’s Feature extraction Image Analysis software. Limited number of genes showed significant radiation-induced responses in normal cells: 109 were up-regulated and 114 were down-regulated. In radiation sensitive fibroblasts 144 genes were up- and 56 genes were down-regulated. When radiation-induced responses were compared in normal and sensitive cells, 28 genes were up- and 2 were down-regulated in all fibroblasts. The radiation-response genes were functionally categorized into the following groups: cell cycle, DNA repair, stress response, energy metabolism, signal transduction and function unknown. When basal gene expression profiles of radiation sensitive strains were compared to normal fibroblasts 60 genes were up- and 150 genes were down-regulated in all sensitive cell lines. We suggest that genes responding to radiation both in normal and sensitive fibroblasts have an inevitable function in radiation response. Genes responding to radiation either only in normal or sensitive cells, and genes whose basal expression profile was altered in all sensitive fibroblasts might contribute to individual radiation sensitivity. The data presented here could contribute to the better understanding of early radiation responses and the development of biomarkers to identify radiation susceptible individuals.
A long-term open-label extension study examining the steroid-sparing effects of corticorelin acetate in patients with cerebral tumors
Authors: L. Mechtler, E. T. Wong, A. Hormigo, S. Pannullo, V. Hines, R. Milsted, P. C. O'Connor, R. P. Ryan, L. Recht
Journal: Journal of Clinical Oncology (2009)

2079 Background: Corticorelin acetate (CrA) is a synthetic peptide formulation of corticotropin-releasing factor, which is undergoing clinical trials as a treatment for peritumoral edema. The objective of this study was to evaluate long-term safety, tolerability and steroid-sparing potential of CrA in patients with primary or secondary brain tumors and peritumoral edema. Methods: Patients from two randomized double-blind controlled studies who received either CrA (CrA-CrA group) or placebo (PLA) (PLA-CrA group) were permitted to receive open-label CrA 1 mg SC bid after participation in the initial studies. Treating physicians were requested to attempt and maintain the maximum possible reduction of the dexamethasone (dex) dose without knowledge of their patients’ prior treatment regimen in the controlled feeder studies. During this extension study, patients’ dex doses and adverse events were monitored monthly; neurologic function and clinical status were recorded 3 monthly. For this analysis, data up to October 17, 2008, are reported from this ongoing study. Results: Of the 110 patients enrolled, 47 (43%) reduced their dex dose to zero and 67 (61%) were able to reduce their dose to ≤1 mg/day. At entry to this extension study, the daily baseline dex dose was lower for patients who had previously received CrA (3.9 mg; n = 59) than for those who had previously received PLA (6.2 mg; n = 51). The PLA-CrA group showed a greater percent decrease in dex dose than the CrA-CrA group at Week 4 (24.0% vs. 12.6%). At week 8 the mean prescribed dex dose was similar in the two groups (PLA-CrA 3.7 mg vs. CrA-CrA 3.4 mg). Long-term treatment with CrA has been well tolerated with no reported safety concerns. To date, 48 patients remained on study for ≥6 months, 27 patients for ≥12 months, 5 patients for &gt;2 years; 31 patients remain on study. Conclusions: These findings indicate that CrA is safe and well-tolerated, and may enable substantial reduction or cessation of dex therapy for many patients with cerebral tumors. [Table: see text]
A phase I trial of the heat shock protein 90 (HSP90) inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17- DMAG, alvespimycin) administered weekly
Authors: S. C. Pacey, R. Wilson, M. Walton, M. Eatock, J. Moreno-Farre, E. Gallerani, V. Davergne, F. Raynaud, P. Workman, I. Judson
Journal: Journal of Clinical Oncology (2007)

3568 Background: The geldanamycin analogue 17-DMAG inhibits the ATPase activity of HSP90, thus altering client protein &amp; chaperone interactions and targeting client proteins for degradation. The plethora of oncogenic HSP90 client proteins offers the potential of combinatorial blockade across multiple, cancer causing signalling pathways in cancer. Methods: 17-DMAG was administered weekly to patients with advanced, solid tumours using a dose-doubling 3 + 3 Phase I design. The pharmacokinetic (PK) and pharmacodynamic (PD) analyses undertaken were validated to comply with U.K clinical trial legislation. Results: 10 patients, 7 male and 3 female with a mean age of 60 years (range 38 - 78) have received 107 infusions (mean 10.7 weeks, range 2 - 30) at dose levels of 2.5mg/m 2 , 5mg/m 2 &amp; 20mg/m 2 . No dose-limiting or drug related grade 3 or 4 toxicity has occurred in 9 patients eligible for toxicity assessment. A linear relationship exists between dose and AUC and C max (see table ). Hsp72 induction and CDK4 depletion (consistent with HSP90 inhibition) have been detected at doses of 20mg/m 2 in peripheral blood mononuclear cells. A confirmed partial response (by PSA and RECIST) has occurred in a patient with hormone refractory prostate cancer (HRPC). Conclusions: We have shown linear PK for 17-DMAG up to 20mg/m 2 . No dose-limiting toxicity has been encountered. A robust biologically active dose has not been reached but evidence of the pharmacological signature of HSP90 inhibition has been detected in surrogate tissue and a confirmed PR seen in a patient with HRPC. These data support dose escalation to 40mg/m 2 and paired tumor biopsies will be taken to further define the PK-PD-clinical relationships. [Table: see text] [Table: see text]
Outcomes of patients (pts) receiving emetogenic chemotherapy (CT): How do oncologist's (MD's) practice patterns of antiemetic prescribing change after pts experience acute or delayed CINV?
Authors: E. B. Rubenstein, C. De Moor, L. Cohen, C. Klahn, P. Eisenberg
Journal: Journal of Clinical Oncology (2004)

8256 BackgroundIn order to understand MD's practice patterns & pt outcomes of AE therapy we conducted an observational study at 10 US sites. Methods 114 pts receiving emetogenic CT (90% Hesketh 4 or 5) recorded emetic episodes (EE) & nausea scores during 1st (C1) & 2nd (C2) cycles of CT. MD prescriptions & pt diaries were used to determine compliance (Comp) w/ ASCO or MASCC AE guidelines (AEG). CINV = either EE or nausea > 5mm on VAS. ResultsPts were mostly women (80.7 %), mean age 56 yrs. Cancer diagnoses: breast (55%), lung (13%) & lymphoma (12%). For C1 +C2, acute AE were 5HT3 RA + steroids ± other agents (191), 5HT3 RA w/o steroids ± other agents (31) & other (4). Delayed AE included 5HT3 RA + D2 receptor blockers (112), D2 receptor blockers alone (27), none (9), steroid-based AE (40) & single-agent 5HT3 RA (9). Failure rates & compliance w/ G are shown below. A-CINV Comp D-CINV Comp Of the 37 pts w/ A-CINV in C1,6 didn't receive G-based care & only 1 of these received G-based AE in C2. Of the 67 pts in C1who had D-CINV, 15 did not receive G-based AE & only 3 of these pts received G-based care in C2.ConclusionsDespite high Comp w/ AEG, acute & delayed CINV are still major problems for pts. Steroids are underutilized. Pts who don't respond to AE may not have changes to their AE regimens in subsequent cycles. These findings suggest that educational programs & systems approaches incorporating pt outcomes into daily practice may be needed in order for pts to realize the benefits of newer AE agents that enhance control of acute & delayed CINV. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck; MGI Pharma MGI Pharma Merck Merck
Randomized phase II trial of three gemcitabine (GEM)-taxane combinations in metastatic breast cancer (MBC
Authors: K.-S. Khoo, M. Zaidi, V. Srimuninnimit, Z. F. Jiang, P. Prem Kumar, A. Bustam, A. H. Villalon, M. Lehnert
Journal: Journal of Clinical Oncology (2004)

710 Background: Two-drug combinations of GEM and paclitaxel (P) or docetaxel (D) have shown promising efficacy in MBC. This study evaluated efficacy and safety of GEM plus single or split dose taxanes. Methods: Major eligibility criteria: tissue diagnosis of breast carcinoma; stage IV; prior anthracycline therapy; KPS ≥70; age ≥18; adequate bone marrow, liver and kidney function; written informed consent. Patients (pts) were randomized to receive: GEM 1250 mg/m2 D1+8 and P 175 mg/m2 as 3-hr infusion D1 (GP1); GEM 1000 mg/m2 D1+8 and P 100 mg/m2 as 1-hr infusion D1+8 (GP2); GEM 1000 mg/m2 D1+8 and D 40 mg/m2 as 1-hr infusion D1+8 (GD) in a 3-week cycle (8 cycles max). Primary endpoint was response rate; secondary endpoints were time to progression (TTP), time to treatment failure (TTTF), response duration and toxicity. Results: 210 pts were enrolled, 208 qualified for safety and time-to-event efficacy analysis, 204 for response assessment. Baseline variables were balanced across arms. Dominant site of disease was visceral in 70%; >50% had ≥3 organ sites of disease; all but 1 pt had previously received anthracyclines, 46% for MBC. Efficacy outcomes were similar in the 3 arms. Neutropenia was the main toxicity in each arm. Grade 4 neutropenia, Grade 3+4 anemia, febrile neutropenia, infection and diarrhea were higher for GD as were use of G-CSF, IV antibiotics and blood transfusions. There were 6 drug-related deaths (2.9%; 2 pts on GP1, 3 on GP2, 1 on GD), mostly from myelotoxicity complications. Conclusions: The three GEM-taxane regimens appear to have high efficacy and manageable toxicity in MBC after prior anthracycline therapy. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Asian Operations Eli Lilly & Co. Eli Lilly & Co. Eli Lilly Singapore Pty Ltd. Eli Lilly and Company
A hypothetical model of host-pathogen interaction of<i>Streptococcus suis</i>in the gastro-intestinal tract
Authors: Maria Laura Ferrando, Constance Schultsz
Journal: Gut Microbes (2016)

Streptococcus suis (SS) is a zoonotic pathogen that can cause systemic infection in pigs and humans. The ingestion of contaminated pig meat is a well-established risk factor for zoonotic S. suis disease. In our studies, we provide experimental evidence that S. suis is capable to translocate across the host gastro-intestinal tract (GIT) using in vivo and in vitro models. Hence, S. suis should be considered an emerging foodborne pathogen. In this addendum, we give an overview of the complex interactions between S. suis and host-intestinal mucosa which depends on the host origin, the serotype and genotype of S. suis, as well as the presence and expression of virulence factors involved in host-pathogen interaction. Finally, we propose a hypothetical model of S. suis interaction with the host-GIT taking in account differences in conditions between the porcine and human host.