tbuckley/cabot-search huggingface dataset:
MnSOD and GPx-1 polymorphisms in relation to local recurrence in patients with rectal cancer treated with chemoradiation
Authors: M. A. Gordon, W. Zhang, D. Y. Yang, J. Gil, J. Yun, O. Press, N. Mallik, H. J. Lenz
Journal: Journal of Clinical Oncology (2004)

3604 Background: Manganese superoxide dismutase (MnSOD) and Glutathione peroxidase-1 (GPx-1) are two enzymes that scavenge ROS (reactive oxygen species) such as superoxide and hydrogen peroxide and protect cells from oxidative damage. MnSOD reduces superoxide to oxygen and hydrogen peroxide, and GPx-1 reduces hydrogen peroxide to water. Radiation therapy produces an excess of ROS, which results in DNA damage, cellular destruction, and tumor degradation. In vitro and in vivo studies show that increasing the levels of MnSOD and GPx-1 lowers the level of ROS in the cell. Therefore, the activity levels of MnSOD and GPx-1 may be directly related to the efficacy of chemoradiation treatment and hence may influence risk of local recurrence. We tested whether two functional polymorphisms, an Ala-9Val SNP in the mitochondrial targeting sequence of the MnSOD gene and a Pro/Leu SNP at codon 197 near the C-terminus of the GPx-1 protein will correlate with local recurrence in chemoradiation-treated rectal cancer patients. Methods: DNA was extracted from rectal tissue and blood from 92 patients with locally advanced rectal cancer treated with neoadjuvant or adjuvant chemoradiation, of which 38 had local recurrence and 54 had no recurrence. MnSOD Ala-9Val polymorphism and GPx-1 Pro-198Leu polymorphism were tested using PCR-RFLP method. Results: A combined analysis of the genotypes showed patients carrying at least one unfavorable genotype (homozygous Ala for MnSOD and homozygous Leu for GPx-1) had a greater risk of recurrence (relative risk: 2.36, 95% CI) when compared to patients possessing no unfavorable genotypes (p=0.01). Individually, MnSOD and GPx-1 showed trends for tumor recurrence (p=0.087 for GPx-1 and p=0.13 for MnSOD). Conclusions: The data suggest that polymorphisms in free radical scavengers MnSOD and GPx-1 are potential prognostic markers for local recurrence in rectal cancer and may predict chemoradiation efficacy. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Chiron NCI; NIH; Roche; Lilly; Pharmacia; Bayer; Bristol-Myers Squibb; Chiron; Aventis; Genentech; ImClone; Cellpathway; Newbiotics; Sanofi
Thy 1.2&lt;sup&gt;+&lt;/sup&gt; Leukemia Cells Eradicated From In Vitro Leukemia-Bone Marrow Cell Mixtures by Antibody-Toxin Conjugates&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: M Colombatti, A Colombatti, H E Blythman, C Bron
Journal: JNCI Journal of the National Cancer Institute (1984)

Journal Article Thy 1.2+ Leukemia Cells Eradicated From In Vitro Leukemia-Bone Marrow Cell Mixtures by Antibody-Toxin Conjugates Get access Marco Colombatti, Marco Colombatti Search for other works by this author on: Oxford Academic PubMed Google Scholar Alfonso Colombatti, Alfonso Colombatti Search for other works by this author on: Oxford Academic PubMed Google Scholar Hildur E. Blythman, Hildur E. Blythman Search for other works by this author on: Oxford Academic PubMed Google Scholar Claude Bron Claude Bron Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 72, Issue 5, May 1984, Pages 1095–1099, https://doi.org/10.1093/jnci/72.5.1095 Published: 01 May 1984 Article history Received: 06 June 1983 Revision received: 18 October 1983 Accepted: 13 December 1983 Published: 01 May 1984
Late relapse in early-stage Hodgkin's disease patients enrolled on European Organization for Research and Treatment of Cancer protocols.
Authors: S Bodis, M Henry-Amar, J Bosq, J M Burgers, W A Mellink, P Y Dietrich, N Dupouy, E M Noordijk, J M Raemaekers, J Thomas
Journal: Journal of Clinical Oncology (1993)

PURPOSE The great majority of relapses after the treatment for early-stage Hodgkin's disease are observed within 4 to 5 years after treatment completion. This study describes the characteristics and outcome of patients who had late relapses, which was defined as relapses that occurred 5 or more years after initial treatment start. PATIENTS AND METHODS A total of 1,082 adult patients with early clinical stage Hodgkin's disease were enrolled on three consecutive European Organization for Research and Treatment of Cancer (EORTC) protocols (H1, H2, and H5 trials) from 1964 to 1981. Of these, 1,044 patients satisfied the eligibility criteria with a supradiaphragmatic localization, age greater than 15 years, and initial complete remission. Overall, 341 patients (32.6%) relapsed, 304 (29.1%) early and 37 (3.5%) late. For each of these 37 late relapsers, questionnaires were sent to the participating centers and detailed information for 34 relapses was obtained. Cumulative probabilities for developing a late relapse were estimated using the Kaplan and Meier method. Quantification of the relationship between late relapse and several confounding variables was performed using the Cox's proportional hazards model. RESULTS The 10- and 15-year cumulative probabilities of late relapse in patients who were disease-free at 5 years were 4.8% and 8.3%, respectively. Patients treated on more recent protocols had a higher incidence of late relapse, possibly due to an attempt to tailor therapy to the specific prognostic factors (10-year cumulative probabilities, 4.6%, 2.6%, and 7.5% in trials H1, H2, and H5, respectively). Incidence of late relapses significantly correlated with male sex, B symptoms, mediastinal involvement, and treatment modality. Salvage treatment induced a complete response in 27 patients (79%) and a prolonged complete remission in 24 patients (71%). Twenty years after initial treatment start, similar overall survival rates were observed for late relapsing (72%) and nonrelapsing patients (75%). CONCLUSION Late relapses of Hodgkin's disease are uncommon, but may be more frequent with recent protocols tailored to specific prognostic factors. If treated, their outcome is favorable. Late relapse is therefore another factor indicating that careful, long-term follow-up is needed for patients with Hodgkin's disease.
The cytomegalovirus-antigenemia assay in the diagnosis of posttransplant cytomegalovirus infection.
Authors: B M Murray, J Brentjens, D Amsterdam, J Myers, V Gray, I Pawlowski, K Schewegler, J P Singh, R C Venuto
Journal: Journal of the American Society of Nephrology (1994)

Cytomegalovirus (CMV) infection continues to be a major cause of morbidity and mortality in transplant recipients, yet prompt diagnosis remains a problem. A new assay has been developed that detects CMV antigens in peripheral blood leukocytes (CMV-AG). A retrospective analysis of the experience with this assay was performed, and its usefulness in the diagnosis of CMV infection in renal transplant recipients with unexplained fever was compared with that of conventional modalities (buffy coat culture, detection of circulating anti-CMV immunoglobulin M). The results suggest that the CMV-AG assay is a more rapid and sensitive test than existing modalities in the early diagnosis of CMV infection. When expressed quantitatively, it can discriminate between CMV infection and CMV disease, and it is useful in monitoring the course of infection and the response to therapy.
Differentiation of anxious patients by two-dimensional echocardiographic evaluation of the mitral valve
Authors: S R Dager, K A Comess, D L Dunner
Journal: American Journal of Psychiatry (1986)

Forty-four anxious patients with a history of panic attacks had a significantly higher prevalence of mitral valve abnormalities than 20 patients with generalized anxiety only. The higher number of mitral valve abnormalities was not correlated with the frequency of panic attacks.
Marked synergism of cytotoxic agents with either a prenylation inhibitor or M-TOR inhibitor in acute leukemia cell lines: Potential clinical implications
Authors: D. R. Budman, A. Calabro
Journal: Journal of Clinical Oncology (2006)

13103 Background: The most combinations of anticancer drugs are based upon empiricism. The potential permutations of drugs overwhelm the clinical trials system. Acute leukemia is sensitive to a variety of agents but relapses are common. Targeted agents are attractive new venues of therapy both as single agents and in combination with older agents. Isobologram median effect analysis allows up to three agents to be studied together in vitro to identify interesting combinations. We evaluated a commercially available statin, fluvastatin, to block prenylation which affects a variety of pathways, rapamycin and its experimental analogue RAD001 as M-TOR inhibitors to block downstream of the AKT pathway, and cytotoxic agents. Methods: The human leukemia cell lines AML-193 and KG-1 were obtained from ATTC (Rockville, MD), fluvastatin and RAD001 from Novartis Pharma, and the other agents from Sigma-Aldrich (St. Louis, MO). The IC 50 of the single agent was determined by a 72 hr incubation of log growth cells using a MTT assay and the EZ-ED50 program (Perrella Scientific, Conyers, CA). The dosages of all agents were at clinically achievable concentrations. All reported values were the means of at least 3 experiments with each study using 4 wells per point. For isobologram analysis, a minimum of 8 concentrations of drug mixtures were studied above and below the IC 50 . Median effect CI values less than 1 are synergistic. Results: Doublets of fluvastatin with Ara-C (0.7), daunomycin (0.4), idarubicin (0.7), RAD001 (0.5), or rapamycin (0.3) demonstrated synergy. Doublets of RAD001 with Ara-C (0.3), daunomycin (0.7), or idarubicin (0.5) demonstrated synergy. Triplets of RAD001/daunorubicin/Ara-C, RAD001/daunomycin/fluvastatin, and RAD001/Ara-C/idarubicin all demonstrated marked synergy in both cell lines. Conclusion: A new potential non classical combination for further investigation is RAD001 or rapamycin with an inhibitor of prenylation such as fluvastatin. Additional potential combinations include cytotoxics with either fluvastatin or RAD001, and triplet combinations. No significant financial relationships to disclose.
Expression of a Putative Tumor-Associated Surface Antigen on Normal Versus Marek's Disease Virus-Transformed Lymphocytes&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: K A McColl, B W Calnek, W V Harris, K A Schat, L F Lee
Journal: JNCI Journal of the National Cancer Institute (1987)

Various avian tumor cell lines and normal spleen cells from 3 genetic strains of specific-pathogen-free (SPF) chickens were examined for expression of Marek's disease (MD) tumor-associated surface antigen (MATSA). Two anti-MATSA monoclonal antibodies (RPH 6 and EB 29) and a rabbit anti-MATSA antiserum were used in indirect fluorescent antibody tests, and cells were examined by fluorescence microscopy and with a fluorescence-activated cell sorter (FACS). Less than 5% MATSA-positive cells were observed in 2 non-MD tumor cell lines (LSCC-RP 9 and RECC-CU 60) with RPH 6, but 7–82% positive cells were observed with EB 29 or the rabbit antiserum. Five MD tumor cell lines (MDCC-CU 2, -CU 14, -CU 25, -CU 32, and -CU 41) had 12–72% positive cells detected with one or both monoclonals and 31–99% positive cells detected with the rabbit antiserum. Over 90% of cells in all MD lines were la and T3 positive, while values for the same parameters in LSCC-RP 9 were 100 and 3% and for RECCCU 60, 48 and 51%, respectively. Evidence for cell-cycle-dependent expression of MATSA on MDCC-CU 2 was obtained from cell sorting experiments with the FACS and from examination of the MATSA-staining characteristics of 3 clones derived from the parent culture. Less than 5% MATSA-positive cells were observed in uncultured spleen cells from SPF chickens or in spleen cells stimulated for 48 hours with concanavalin A or phytohemagglutinin-M. However, with one exception, 10–53% of normal spleen cells were MATSA positive with RPH 6, after stimulation by mitogen for 24 or 48 hours followed by maintenance in conditioned medium (CM) for various times or after culture directly in CM for 3 days. More limited experiments with rabbit anti-MATSA antiserum yielded 55–85% MATSA-positive cells. From 60 to 97% of these MD virusfree, MATSA-positive cells were la-positive; and, in 2 cases, 89 and 90% were T3 positive.
Predicting prostate biopsy outcome: An international prospective multicenter model involving 4,788 men
Authors: C. R. Porter, D. Crawford, G. Bartsch, J. Presti, E. Gamito
Journal: Journal of Clinical Oncology (2004)

4618 Background: Diagnosis of prostate cancer (CAP) requires prostate needle biopsy (PNB). Objective: To develop a model to predict PNB outcome. Methods:3,814 men in the European Tyrol, screening project 1993 -2001 were used to develop the model. In the US, Virginia Mason Clinic [VM], Seattle and Stanford University [SU], were used to validate the model. A feed forward, back error-propagation Artificial Neural Network (ANN) model using Tyrol data was developed and compared to a logistic regression model (LR). The Tyrol data was split randomly into three (N=1200) cross validation sets. The ANN was alternately trained on 2 of these data sets and validated on the remaining data set . Similarly 3 LR models were produced and validated, using cross validation, from identical Tyrol data sets. The Tyrol model with the average Area Under Receiver Operating Characteristic Curve (AUROC) was validated with VM (N=491) & SU (N=483) data sets. Prospectively collected model input variables were age, prostate specific antigen (PSA), PSA density (PSAD), prostate volume (PV), digital rectal exam (DRE), and transrectal ultrasound (TRUS) findings. Results:Patients characteristics are listed in table1. Univariate analysis (Tyrol) identified age (p<0.00001), PSAD (p<0.00001),PSA (p<0.00005), abnormal DRE (p<0.0001), and lesion on TRUS (p<0.0001) to be predictive of positive biopsy. Accuracy of prediction is reported as AUROC. Tyrol models (A, B, C) had AUROC's of 0.74, 0.76and 0.75 for ANN, and 0.75, 0.76, and 0.75 for LR models. Mean AUROC for both ANN and LR was 0.75 with standard deviation 0.009 (ANN) and.006 (LR). Tyrol C model validation with VM and SU data demonstrated AUROC's of 0.74 (both ANN & LR) and 0.73 (ANN) and 0.72 (LR) respectively. Conclusions:The ANN designed to predict PNB outcome performs accurately on both European and US populations.. Models such as this may be useful in evaluating the need for PNB. No significant financial relationships to disclose.
Establishment of human primary colorectal tumor xenograft models to test anticancer drugs.
Authors: C. Liui, W. Li, B. Li, W. Huang, H. Yang, B. Lou
Journal: Journal of Clinical Oncology (2010)

e14121 Background: Human xenograft tumor models established by transplantation of human tumor cell lines into immunodeficient mice have been routinely used for preclinical testing anticancer agents. However, such tumor models have a relatively low transplantability and limited correlation with clinical findings. Recently, we have developed human primary colorectal tumor xenograft models by transplanting fresh human colorectal tumor tissues into nude mice, which is being used to test standard chemotherapeutic drugs and to screen effectiveness of novel compounds. Methods: The fresh colorectal tumor fragments of 2-3 mm were subcutaneously implanted in the flanks of nude mice. Sixteen tumor fragments were grafted into four mice from one patient tumor tissue. In the first passage, tumors derived from male patients were implanted into male mice, and tumors from women were inoculated into female mice. All therapeutic efficacy experiments used female mice. The test drugs included 5-FU, irinotecan, and oxaliplatin. Results: A total of 36 human colorectal tumor samples were initially implanted with 14 successful xenograft tumors (39%) from the first passage. The rate of tumor formation was higher in the second and third passages, ranging from approximately 80%-100%. The three anticancer drugs' efficacy data showed that 5-FU produced 35%-48% tumor growth inhibition, irinotecan 57%-86%, and oxaliplatin 68%-89%, which are consistent with clinical findings. The human primary colorectal tumor xenografts' architecture, biomarker profile and histopathologic morphology from three generations reproduced biological activity and response to therapy of the original tumors. Conclusions: Human primary colorectal tumor models have been used to test current chemotherapeutic agents. Future studies testing effectiveness of novel compounds against human colon cancer tumors are under way using this experimental model. This strategy may predict more relevant clinical response rates and higher correlation with clinical findings than use of traditional xenograft models established from long-term cultured cancer cell lines. Furthermore, they have advantages for test of target-oriented therapeutics in new drugs development programs. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pharmaron
In the idiopathic inflammatory myopathies, reactive oxygen species are at the crossroad between immune and non-immune cell-mediated mechanisms
Authors: Alain Meyer, Jean Sibilia, Bernard Geny
Journal: Annals of the Rheumatic Diseases (2015)

In the idiopathic inflammatory myopathies, reactive oxygen species are at the crossroad between immune and non-immune cell-mediated mechanisms Dear editor, We read with great interest the article by Lightfoot et al 1 who suggested that in the idiopathic inflammatory myopathies (IIM), reactive oxygen species (ROS) contribute to muscle weakness.The authors opposed immune and non-immune cell-mediated mechanisms in IIM and reviewed ROS as part of the latter.Here, we would like to point out recent data that reconcile this dichotomy and stress the interplay between ROS and immune cell-mediated processes during IIM.In accordance with the authors' hypothesis, we recently observed high ROS formation, along with mitochondrial respiratory chain dysfunctions, in muscle of patients with dermatomyositis. 2 Furthermore, in muscle cells cultured in the absence of immune cells, interferon-β-induced mitochondrial dysfunctions in a ROS-dependent manner.Finally, in an antigen-induced mouse model of IIM, ROS scavenging with N-acetyl cysteine prevented muscle weakness and mitochondrial dysfunctions and immunize cell infiltrate in muscle. 2 Thus, ROS and immune cells are not independent actors in IIM.Indeed, ROS participate in immune cell infiltrate, which in turn can further increase ROS formation and mediated damages in the muscle. 3This definitely places ROS as central actors and potential therapeutic targets in IIM.
No evidence of acute cardiovascular complications of chemotherapy for testicular cancer: an analysis of the Testicular Cancer Intergroup Study.
Authors: C R Nichols, B J Roth, S D Williams, I Gill, F M Muggia, D M Stablein, R B Weiss, L H Einhorn
Journal: Journal of Clinical Oncology (1992)

PURPOSE The purpose of this study is to evaluate the risk of acute vascular events in patients receiving cisplatin-based chemotherapy for testicular cancer. PATIENTS AND METHODS A questionnaire assessing cardiovascular toxicity was distributed to all participants in the Testicular Cancer Intergroup study and details of toxicity from the chemotherapy flow sheets were reviewed. Patients with pathologic stage I testicular cancer were registered on to the study and observed after retroperitoneal lymphadenectomy. Patients with pathologic stage II disease were randomized to receive two postoperative courses of adjuvant cisplatin-based chemotherapy or observation. Any patient who had disease recurrence after observation or adjuvant therapy was given four cycles of cisplatin-based chemotherapy. RESULTS Review treatment-related toxicity for those patients receiving adjuvant chemotherapy (n = 97) or chemotherapy for recurrent disease (n = 83) showed no cases of acute cardiovascular toxicity. The median follow-up period after study enrollment was 5.1 years; 459 questionnaires were mailed and 270 were returned. The percent return was equal among the observed adjuvant and recurrent groups (59%, 54%, and 64%). There was a significant increase in the incidence of extremity paresthesias in the two groups receiving chemotherapy. Fatal myocardial infarction was reported in two patients in the observation group and one nonfatal infarction was reported in the adjuvant treatment group. No patient in any group reported an incidence of stroke. Three patients in the observation group and one patient in the recurrent group experienced a thromboembolic event. CONCLUSION Despite sporadic case reports suggesting a causal association between chemotherapy for testicular cancer and acute vascular events, this retrospective analysis provides no evidence of an increased risk for subsequent cardiovascular disease in this patient population.
Increasing risk for venous thromboembolism among hospitalized cancer patients
Authors: A. A. Khorana, C. W. Francis, E. Culakova, N. M. Kuderer, G. H. Lyman
Journal: Journal of Clinical Oncology (2007)

9009 Background: Venous thromboembolism (VTE) contributes to morbidity and mortality in cancer patients and is a frequent complication of anti-cancer therapy. We examined the frequency, risk factors and trends associated with VTE among hospitalized US cancer patients. Methods: We conducted a retrospective cohort study using the discharge database of the University Health System Consortium. This included all 1,824,316 hospitalizations of cancer patients between 1995 and 2003 at 133 United States medical centers. To avoid overestimation, only a single randomly chosen hospitalization was included for patients with multiple admissions. Results: Among 1,015,598 individual cancer patients, 34,357 (3.4%) were diagnosed with deep venous thrombosis and 11,515 with pulmonary embolism (PE) (1.1%) for an overall VTE rate of 4.1%. Subgroups of cancer patients with highest rates included Black ethnicity (5.1% per hospitalization) and those on chemotherapy (4.9%). Sites of cancer with the highest rates of VTE included pancreas (8.2%), kidney (5.7%), ovary (5.6%), lung (5.1%) and stomach (4.9%). Amongst hematologic malignancies, myeloma (5%), non-Hodgkin’s lymphoma (4.8%) and Hodgkin’s disease (4.6%) had the highest rates of VTE. The rate of VTE rose from 3.6% per hospitalization in 1995–96 to 4.6% in 2002–03, an increase of 28%, including a near-doubling of PE rates from 0.8% to 1.5% (P&lt;0.0001). Among patients receiving chemotherapy, rates of VTE rose from 3.9% per hospitalization to 5.7%, an increase of 47% (P&lt;0.0001). In contrast, patients undergoing surgery for breast, head and neck, pancreatic or spinal cancers, experienced no significant change in the rate of VTE. Use of diagnostic procedures for VTE also did not increase over the study period. Conclusions: The rate of VTE, including PE, among hospitalized cancer patients has increased significantly in recent years. Black patients, those on chemotherapy and those with certain types of cancer are disproportionately at increased risk. The rise in VTE does not appear to be attributable to an increased utilization of diagnostic procedures. Further efforts to increase thromboprophylaxis compliance during hospitalization are needed. No significant financial relationships to disclose.