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Bryan Schneider, MD

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Hematology/Oncology

Associate Professor of Medicine; Vera Bradley Investigator in Oncology; Associate Professor of Medical & Molecular Genetics

Academic Office

Indiana Cancer Pavilion, Suite 473
535 Barnhill Dr
Indianapolis IN 46202-5289 Map

Contact Information

Phone: (317) 274-6473
Fax: 317-944-3646
Email:

Bio

Dr. Schneider is an Assistant Professor of Medicine at the Indiana University Melvin and Bren Simon Cancer Center. He holds appointments in the Divisions of Hematology/Oncology and Clinical Pharmacology in the Department of Medicine with a secondary appointment in the Department of Medical and Molecular Genetics. Dr. Schneider completed his Medical School, Internal Medicine Residency and Hematology/Oncology Fellowship at Indiana University. Dr. Schneider devotes his clinical time caring for breast cancer patients as a Medical Oncologist and has a special interest in novel therapeutic agents. He is the model example of a translational scientist as his lab work is both an extension of and complimentary to his clinical interest. His laboratory focus is on pharmacogenetics of breast cancer therapeutics. His biomarker work to date has opened the door for the potential enrichment of patient selection for bevacizumab. Based on his early work he has designed correlative trials in collaborations with multiple groups to better guide proper patient selection for these agents. He is extensively published in the area of therapeutic individualization (i.e. "finding the right drug for each patient"). He is a recipient of the prestigious Komen Promise Award and a member of the Komen Scientific Advisory Council. Dr. Schneider is the Chair of the Educational Symposium for the Developmental Therapeutics Committee, the Vice-Chair of the Pharmacogenetics Committee, and a member of the Breast Cancer Committee for the Eastern Cooperative Oncology Group (ECOG). He is also a member of the Consortium on Breast Cancer Pharmacogenetics (CoBRA) and the Pharmacogenetics Research Network (PGRN).

Research Interests

My major research goal is translational in nature. I hope to identify critical genetic and pharmacogenetic differences that predict for etiology, aggressiveness, and therapeutic responsiveness as it relates to cancer. My current research focus is primarily involved with polymorphisms of angiogenesis as it relates to breast cancer. I also wish to participate in multiple clinical trials testing therapies in breast cancer.

Clinical Interests

Breast cancer

Education and Training

Fellowship Indiana University School of Medicine, Indianapolis, IN
Residency Indiana University School of Medicine, Indianapolis, IN
Medicine (M.D.) Indiana University
Biology, General Evansville, University Of

Publications (53)¹

A large microRNA cluster on chromosome 19 is a transcriptional hallmark of WHO type A and AB thymomas.
Journal: British journal of cancer
Authors: Radovich M; Solzak JP; Hancock BA; Conces ML; Atale R; Porter RF; Zhu J; Glasscock J; Kesler KA; Badve SS; Schneider BP; Loehrer PJ;
Publication Date: 2016 Jan 14

Abstract

Thymomas are one of the most rarely diagnosed malignancies. To better understand its biology and to identify therapeutic targets, we performed next-generation RNA sequencing.
View details for PubMedID 26766736
Pilot trial of paclitaxel-trastuzumab adjuvant therapy for early stage breast cancer: a trial of the ECOG-ACRIN cancer research group (E2198).
Journal: British journal of cancer
Authors: Schneider BP; O'Neill A; Shen F; Sledge GW; Thor AD; Kahanic SP; Zander PJ; Davidson NE;
Publication Date: 2015 Dec 1

Abstract

Blockade of human epidermal growth factor receptor type 2 (HER2) has dramatically improved outcome for patients with HER2-positive breast cancer. Trastuzumab, an anti-HER2 monoclonal antibody, has previously demonstrated improvement in overall survival (OS) in patients with metastatic and early stage HER2-positive breast cancer. However, trastuzumab can cause congestive heart failure (CHF) with an increased frequency for patients who have also received an anthracycline. The current trial was designed to evaluate the impact of the duration of trastuzumab on CHF.
View details for PubMedID 26625004
Cerebral Perfusion and Gray Matter Changes Associated With Chemotherapy-Induced Peripheral Neuropathy.
Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Authors: Nudelman KN; McDonald BC; Wang Y; Smith DJ; West JD; O'Neill DP; Zanville NR; Champion VL; Schneider BP; Saykin AJ;
Publication Date: 2015 Nov 2

Abstract

To investigate the longitudinal relationship between chemotherapy-induced peripheral neuropathy (CIPN) symptoms (sx) and brain perfusion changes in patients with breast cancer. Interaction of CIPN-sx perfusion effects with known chemotherapy-associated gray matter density decrease was also assessed to elucidate the relationship between CIPN and previously reported cancer treatment-related brain structural changes.
View details for PubMedID 26527786
Genome-Wide Association Studies for Taxane-Induced Peripheral Neuropathy in ECOG-5103 and ECOG-1199.
Journal: Clinical cancer research : an official journal of the American Association for Cancer Research
Authors: Schneider BP; Li L; Radovich M; Shen F; Miller KD; Flockhart DA; Jiang G; Vance G; Gardner L; Vatta M; Bai S; Lai D; Koller D; Zhao F; O'Neill A; Smith ML; Railey E; White C; Partridge A; Sparano J; Davidson NE; Foroud T; Sledge GW Jr;
Publication Date: 2015 Jul 2

Abstract

Taxane-induced peripheral neuropathy (TIPN) is an important survivorship issue for many cancer patients. Currently, there are no clinically implemented biomarkers to predict which patients might be at increased risk for TIPN. We present a comprehensive approach to identification of genetic variants to predict TIPN.
View details for PubMedID 26138065
Effect of Unblinding on Participants' Perceptions of Risk and Confidence in a Large Double-Blind Clinical Trial of Chemotherapy for Breast Cancer.
Journal: JAMA oncology
Authors: Partridge AH; Sepucha K; O'Neill A; Miller KD; Motley C; Swaby RF; Schneider BP; Dang CT Jr; Northfelt DW; Sledge GW Jr;
Publication Date: 2015 Jun

Abstract

Blinding patients to treatment regimen is an important component of high-quality randomized clinical trials, although concern exists about how receipt of a placebo will affect participants' views, particularly among patients with cancer.
View details for PubMedID 26114161
Incremental Prognostic Value of Echocardiographic Strain and Its Association With Mortality in Cancer Patients.
Journal: Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography
Authors: Rhea IB; Uppuluri S; Sawada S; Schneider BP; Feigenbaum H;
Publication Date: 2015 Mar 12

Abstract

Left ventricular global longitudinal systolic strain (GLS) has been shown to be superior to ejection fraction in detecting subclinical dysfunction in patients with cancer and predicting mortality in patients with cardiovascular disease. Cancer-related fatigue is common in the later stages of neoplastic malignancies and may be indicative of nonovert heart failure. The aim of this study was to determine whether reduced strain by echocardiography was associated with all-cause mortality in a cancer cohort.
View details for PubMedID 25770665
Symptoms: Chemotherapy-Induced Peripheral Neuropathy.
Journal: Advances in experimental medicine and biology
Authors: Schneider BP; Hershman DL; Loprinzi C;
Publication Date: 2015

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is a problematic, treatment-induced toxicity that has the potential to impact quality of life and limit the doses of curative intent therapy. This therapy-induced side effect is one of the most troublesome in oncology clinical practices, considering the morbidity, the frequency, and the potential irreversibility of this problem. Patients with breast cancer are particularly impacted by this side effect as multiple agents commonly used for this disease can cause neuropathy. In this chapter, we provide an overview of CIPN, including: clinical predictors, frequency, and its impact on quality of life. Further, we highlight the pathophysiology and review the literature to date for agents designed to prevent or treat CIPN. We also highlight the most important ongoing clinical and translational research questions that hope to help better predict and prevent this toxicity. This includes optimizing the methods of assessment, using host specific factors (Race and genetics) to predict those more likely to experience CIPN, and determining how CIPN might impact clinical decisions toward therapy.
View details for PubMedID 26059930
Symptoms: Aromatase Inhibitor Induced Arthralgias.
Journal: Advances in experimental medicine and biology
Authors: Hershman DL; Loprinzi C; Schneider BP;
Publication Date: 2015

Abstract

Recent clinical trials have demonstrated that aromatase inhibitors (AIs) are slightly more effective than tamoxifen at reducing breast cancer recurrences. However, breast cancer patients receiving AIs have a higher incidence of musculoskeletal symptoms, particularly joint pain and stiffness. Musculoskeletal pain and stiffness can lead to noncompliance and increased utilization of health care resources. There is a suggestion that the syndrome is the result of estrogen deprivation and may share components with autoimmune diseases such as Sjögren's syndrome. Several factors may increase the likelihood of developing AI arthralgia, such as prior chemotherapy, prior hormone replacement therapy, and increased weight; there are inconsistencies with regard to the data on genetic predispositions to this syndrome. While several studies have been done to evaluate interventions to treat or prevent AI arthralgia, no clear treatment has emerged as being particularly beneficial. Much of the research has been limited by small sample size, difficulty blinding patients to placebo, inconsistent definitions of the syndrome, multiple patient reported outcomes, lack of objective outcome measures and heterogeneous patient populations. We are at the early stages of research in characterizing, understanding etiology, preventing and treating AI arthralgias; however much work is being done in this area which, hopefully, will ultimately improve the lives of women with breast cancer.
View details for PubMedID 26059931
Integrated and convenient procedure for protein extraction from formalin-fixed, paraffin-embedded tissues for LC-MS/MS analysis.
Journal: Proteomics
Authors: Lai X; Schneider BP;
Publication Date: 2014 Sep 5

Abstract

Because fresh-frozen tissue samples associated with long-term clinical data and of rare diseases are often unobtainable at the present time, formalin-fixed paraffin-embedded (FFPE) tissue samples are considered a highly valuable resource for researchers. However, protein extraction from FFPE tissues faces challenges of deparaffinization and cross-link reversion. Current procedures for protein extraction from FFPE tissue require separate steps and toxic solvents, resulting in inconvenience in protein extraction. To overcome these limitations, an integrated method was developed using nontoxic solvents in four types of FFPE tissues. The average amount of proteins from three replicates of bladder, kidney, liver, and lung FFPE tissues were 442.6, 728.9, 736.4, and 694.7 µg with CVs of 7.5, 5.8, 2.4, and 4.5%, respectively. Proteomic analysis showed that 348, 417, 607, and 304 unique proteins were identified and quantified without specification of isoform by a least two peptides from bladder, kidney, liver, and lung FFPE tissue samples, respectively. The analysis of individual protein CV demonstrated that 97-99% of the proteins were quantified with a CV = 30%, verifying the reproducibility of the integrated protein extraction method. In summary, the developed method is high-yield, reproducible, convenient, simple, low cost, nonvolatile, nonflammable, and nontoxic.
View details for PubMedID 25091982
Genetic variant predicts bevacizumab-induced hypertension in ECOG-5103 and ECOG-2100.
Journal: British journal of cancer
Authors: Schneider BP; Li L; Shen F; Miller KD; Radovich M; O'Neill A; Gray RJ; Lane D; Flockhart DA; Jiang G; Wang Z; Lai D; Koller D; Pratt JH; Dang CT; Northfelt D; Perez EA; Shenkier T; Cobleigh M; Smith ML; Railey E; Partridge A; Gralow J; Sparano J; Davidson NE; Foroud T; Sledge GW;
Publication Date: 2014 Aug 12

Abstract

Bevacizumab has broad anti-tumour activity, but substantial risk of hypertension. No reliable markers are available for predicting bevacizumab-induced hypertension.
View details for PubMedID 25117820
Nodular Regenerative Hyperplasia After Treatment With Trastuzumab Emtansine.
Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Authors: Force J; Saxena R; Schneider BP; Storniolo AM; Sledge GW Jr; Chalasani N; Vuppalanchi R;
Publication Date: 2014 May 12
Altered cerebral blood flow one month after systemic chemotherapy for breast cancer: a prospective study using pulsed arterial spin labeling MRI perfusion.
Journal: PloS one
Authors: Nudelman KN; Wang Y; McDonald BC; Conroy SK; Smith DJ; West JD; O'Neill DP; Schneider BP; Saykin AJ;
Publication Date: 2014 May 9

Abstract

Cerebral structural and functional alterations have been reported after chemotherapy for non-CNS cancers, yet the causative mechanism behind these changes remains unclear. This study employed a novel, non-invasive, MRI-based neuroimaging measure to provide the first direct longitudinal measurement of resting cerebral perfusion in breast cancer patients, which was tested for association with changes in cognitive function and gray matter density. Perfusion was measured using pulsed arterial spin labeling MRI in women with breast cancer treated with (N?=?27) or without (N?=?26) chemotherapy and matched healthy controls (N?=?26) after surgery before other treatments (baseline), and one month after chemotherapy completion or yoked intervals. Voxel-based analysis was employed to assess perfusion in gray matter; changes were examined in relation to overall neuropsychological test performance and frontal gray matter density changes measured by structural MRI. Baseline perfusion was not significantly different across groups. Unlike control groups, chemotherapy-treated patients demonstrated significantly increased perfusion post-treatment relative to baseline, which was statistically significant relative to controls in the right precentral gyrus. This perfusion increase was negatively correlated with baseline overall neuropsychological performance, but was not associated with frontal gray matter density reduction. However, decreased frontal gray matter density was associated with decreased perfusion in bilateral frontal and parietal lobes in the chemotherapy-treated group. These findings indicate that chemotherapy is associated with alterations in cerebral perfusion which are both related to and independent of gray matter changes. This pattern of results suggests the involvement of multiple mechanisms of chemotherapy-induced cognitive dysfunction. Additionally, lower baseline cognitive function may be a risk factor for treatment-associated perfusion dysregulation. Future research is needed to clarify these mechanisms, identify individual differences in susceptibility to treatment-associated changes, and further examine perfusion change over time in survivors.
View details for PubMedID 24816641
Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline.
Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Authors: Hershman DL; Lacchetti C; Dworkin RH; Lavoie Smith EM; Bleeker J; Cavaletti G; Chauhan C; Gavin P; Lavino A; Lustberg MB; Paice J; Schneider B; Smith ML; Smith T; Terstriep S; Wagner-Johnston N; Bak K; Loprinzi CL; American Society of Clinical Oncology;
Publication Date: 2014 Apr 14

Abstract

To provide evidence-based guidance on the optimum prevention and treatment approaches in the management of chemotherapy-induced peripheral neuropathies (CIPN) in adult cancer survivors.
View details for PubMedID 24733808
Phase 1 pharmacogenetic and pharmacodynamic study of sorafenib with concurrent radiation therapy and gemcitabine in locally advanced unresectable pancreatic cancer.
Journal: International journal of radiation oncology, biology, physics
Authors: Chiorean EG; Schneider BP; Akisik FM; Perkins SM; Anderson S; Johnson CS; DeWitt J; Helft P; Clark R; Johnston EL; Spittler AJ; Deluca J; Bu G; Shahda S; Loehrer PJ; Sandrasegaran K; Cardenes HR;
Publication Date: 2014 Apr 11

Abstract

To define the safety, efficacy, and pharmacogenetic and pharmacodynamic effects of sorafenib with gemcitabine-based chemoradiotherapy (CRT) in locally advanced pancreatic cancer.
View details for PubMedID 24726286
Biomarker prediction of chemotherapy-related amenorrhea in premenopausal women with breast cancer participating in E5103.
Journal: Breast cancer research and treatment
Authors: Ruddy KJ; O'Neill A; Miller KD; Schneider BP; Baker E; Sparano JA; Dang C; Northfelt DW; Sledge GW Jr; Partridge AH;
Publication Date: 2014 Mar 2

Abstract

This study aimed to investigate whether pre-chemotherapy anti-mullerian hormone (AMH) is a biomarker for chemotherapy-related amenorrhea (CRA) in breast cancer patients. A multicenter randomized controlled trial, ECOG5103, assigned patients with early stage breast cancer to standard doxorubicin-cyclophosphamide followed by paclitaxel with either placebo or one of two durations of bevacizumab therapy. Five hundred ninety-one patients were part of the decision-making/quality of life substudy, in which there were surveys from baseline through 18-month follow-up. One hundred twenty-four women were included in this analysis of menses data because they were premenopausal at enrollment, responded to the 12-month survey, had not undergone bilateral oophorectomy or ovarian function suppression before that survey, and had serum banked for research before chemotherapy. One hundred of the 124 also responded to the 18-month survey. Median age was 45 years (range 25-55), and median serum AMH level was 0.11 ng/mL (range 0.01-8.63) prior to treatment. Eighty-two percent had CRA at 12 months, and 81 % at 18 months. In multivariate analyses, older age (p = 0.0003) was the only statistically significant predictor of 12-month CRA, but at 18-months, lower pre-chemotherapy AMH (p = 0.04) and older age (p = 0.008) were both statistically significant predictors of CRA. Race, bevacizumab therapy, and tamoxifen use were not statistically significantly associated with CRA after adjustment for AMH and age. Pre-chemotherapy AMH level is a potential novel biomarker for CRA in premenopausal women with early stage breast cancer. Further research to evaluate the clinical utility of AMH testing is warranted.
View details for PubMedID 24584876
Characterizing the heterogeneity of triple-negative breast cancers using microdissected normal ductal epithelium and RNA-sequencing.
Journal: Breast cancer research and treatment
Authors: Radovich M; Clare SE; Atale R; Pardo I; Hancock BA; Solzak JP; Kassem N; Mathieson T; Storniolo AM; Rufenbarger C; Lillemoe HA; Blosser RJ; Choi MR; Sauder CA; Doxey D; Henry JE; Hilligoss EE; Sakarya O; Hyland FC; Hickenbotham M; Zhu J; Glasscock J; Badve S; Ivan M; Liu Y; Sledge GW; Schneider BP;
Publication Date: 2013 Nov 29

Abstract

Triple-negative breast cancers (TNBCs) are a heterogeneous set of tumors defined by an absence of actionable therapeutic targets (ER, PR, and HER-2). Microdissected normal ductal epithelium from healthy volunteers represents a novel comparator to reveal insights into TNBC heterogeneity and to inform drug development. Using RNA-sequencing data from our institution and The Cancer Genome Atlas (TCGA) we compared the transcriptomes of 94 TNBCs, 20 microdissected normal breast tissues from healthy volunteers from the Susan G. Komen for the Cure Tissue Bank, and 10 histologically normal tissues adjacent to tumor. Pathway analysis comparing TNBCs to optimized normal controls of microdissected normal epithelium versus classic controls composed of adjacent normal tissue revealed distinct molecular signatures. Differential gene expression of TNBC compared with normal comparators demonstrated important findings for TNBC-specific clinical trials testing targeted agents; lack of over-expression for negative studies and over-expression in studies with drug activity. Next, by comparing each individual TNBC to the set of microdissected normals, we demonstrate that TNBC heterogeneity is attributable to transcriptional chaos, is associated with non-silent DNA mutational load, and explains transcriptional heterogeneity in addition to known molecular subtypes. Finally, chaos analysis identified 146 core genes dysregulated in >90 % of TNBCs revealing an over-expressed central network. In conclusion, use of microdissected normal ductal epithelium from healthy volunteers enables an optimized approach for studying TNBC and uncovers biological heterogeneity mediated by transcriptional chaos.
View details for PubMedID 24292813
A pharmacogenetics study to predict outcome in patients receiving anti-VEGF therapy in age related macular degeneration.
Journal: Clinical ophthalmology (Auckland, N.Z.)
Authors: Kitchens JW; Kassem N; Wood W; Stone TW; Isernhagen R; Wood E; Hancock BA; Radovich M; Waymire J; Li L; Schneider BP;
Publication Date: 2013 Oct 10

Abstract

To ascertain whether single nucleotide polymorphisms (SNPs) in the Vascular Endothelial Growth factor (VEGFA), Complement Factor H (CFH), and LOC387715 genes could predict outcome to anti-VEGF therapy for patients with age related macular degeneration (AMD).
View details for PubMedID 24143065
Paced respiration for vasomotor and other menopausal symptoms: a randomized, controlled trial.
Journal: Journal of general internal medicine
Authors: Carpenter JS; Burns DS; Wu J; Otte JL; Schneider B; Ryker K; Tallman E; Yu M;
Publication Date: 2013 Feb

Abstract

Paced respiration has been internationally recommended for vasomotor symptom management, despite limited empirical evidence.
View details for PubMedID 22936289
Potential roles of microRNAs in regulating long intergenic noncoding RNAs.
Journal: BMC medical genomics
Authors: Juan L; Wang G; Radovich M; Schneider BP; Clare SE; Wang Y; Liu Y;
Publication Date: 2013 Jan 23

Abstract

Over 10,000 long intergenic non-coding RNAs (lincRNAs) have been identified in the human genome. Some have been well characterized and known to participate in various stages of gene regulation. In the post-transcriptional process, another class of well-known small non-coding RNA, or microRNA (miRNA), is very active in inhibiting mRNA. Though similar features between mRNA and lincRNA have been revealed in several recent studies, and a few isolated miRNA-lincRNA relationships have been observed. Despite these advances, the comprehensive miRNA regulation pattern of lincRNA has not been clarified.
View details for PubMedID 23369519
Prognostic and predictive value of tumor vascular endothelial growth factor gene amplification in metastatic breast cancer treated with paclitaxel with and without bevacizumab; results from ECOG 2100 trial.
Journal: Clinical cancer research : an official journal of the American Association for Cancer Research
Authors: Schneider BP; Gray RJ; Radovich M; Shen F; Vance G; Li L; Jiang G; Miller KD; Gralow JR; Dickler MN; Cobleigh MA; Perez EA; Shenkier TN; Vang Nielsen K; Müller S; Thor A; Sledge GW Jr; Sparano JA; Davidson NE; Badve SS;
Publication Date: 2013 Jan 22

Abstract

Clinically validated biomarkers for anti-angiogenesis agents are not available. We have previously reported associations between candidate VEGFA single-nucleotide polymorphisms (SNP) and overall survival (OS) in E2100. The associations between tumor VEGFA amplification and outcome are evaluated here.
View details for PubMedID 23340303
Functional microRNAs in Alzheimer's disease and cancer: differential regulation of common mechanisms and pathways.
Journal: Frontiers in genetics
Authors: Holohan KN; Lahiri DK; Schneider BP; Foroud T; Saykin AJ;
Publication Date: 2013 Jan 17

Abstract

Two of the main research priorities in the United States are cancer and neurodegenerative diseases, which are attributed to abnormal patterns of cellular behavior. MicroRNAs (miRNA) have been implicated as regulators of cellular metabolism, and thus are an active topic of investigation in both disease areas. There is presently a more extensive body of work on the role of miRNAs in cancer compared to neurodegenerative diseases, and therefore it may be useful to examine whether there is any concordance between the functional roles of miRNAs in these diseases. As a case study, the roles of miRNAs in Alzheimer's disease (AD) and their functions in various cancers will be compared. A number of miRNA expression patterns are altered in individuals with AD compared with healthy older adults. Among these, some have also been shown to correlate with neuropathological changes including plaque and tangle accumulation, as well as expression levels of other molecules known to be involved in disease pathology. Importantly, these miRNAs have also been shown to have differential expression and or functional roles in various types of cancer. To examine possible intersections between miRNA functions in cancer and AD, we review the current literature on these miRNAs in cancer and AD, focusing on their roles in known biological pathways. We propose a pathway-driven model in which some molecular processes show an inverse relationship between cancer and neurodegenerative disease (e.g., proliferation and apoptosis) whereas others are more parallel in their activity (e.g., immune activation and inflammation). A critical review of these and other molecular mechanisms in cancer may shed light on the pathophysiology of AD, and highlight key areas for future research. Conclusions from this work may be extended to other neurodegenerative diseases for which some molecular pathways have been identified but which have not yet been extensively researched for miRNA involvement.
View details for PubMedID 23335942
Survival in patients with metastatic recurrent breast cancer after adjuvant chemotherapy: little evidence of improvement over the past 30 years.
Journal: Cancer
Authors: Tevaarwerk AJ; Gray RJ; Schneider BP; Smith ML; Wagner LI; Fetting JH; Davidson N; Goldstein LJ; Miller KD; Sparano JA;
Publication Date: 2012 Oct 12

Abstract

Population-based studies have shown improved survival for patients diagnosed with metastatic breast cancer over time, presumably because of the availability of new and more effective therapies. The objective of the current study was to determine whether survival improved for patients who developed distant recurrence of breast cancer after receiving adjuvant therapy.
View details for PubMedID 23065954
Pharmacogenetic biomarkers for the prediction of response to antiangiogenic treatment.
Journal: The Lancet. Oncology
Authors: Schneider BP; Shen F; Miller KD;
Publication Date: 2012 Oct

Abstract

Antiangiogenic treatments have shown activity across multiple tumour types and in various settings. Despite having been approved on the basis of efficacy, the therapeutic index varies substantially in different settings for many of these agents. A major limitation is the current inability to personalise treatment a priori according to findings on measurement of a predictive biomarker. The roles of germline single-nucleotide polymorphisms have been investigated as potential biomarkers for antiangiogenic treatments. The rationale is founded on the understanding that the drugs target the vasculature rather than the tumour, which could mean that much of the variability is regulated by the host. Several single-nucleotide polymorphisms have been associated with differential outcomes and toxic effects in clinical trials. In this Review we provide an overview of available data with particular attention paid to the pitfalls and strengths of potential biomarkers. We also highlight continuing work and plans for confirmatory studies.
View details for PubMedID 23026828
Advanced cognitive training for breast cancer survivors: a randomized controlled trial.
Journal: Breast cancer research and treatment
Authors: Von Ah D; Carpenter JS; Saykin A; Monahan P; Wu J; Yu M; Rebok G; Ball K; Schneider B; Weaver M; Tallman E; Unverzagt F;
Publication Date: 2012 Aug 24

Abstract

The purpose of this study was to evaluate the preliminary efficacy and satisfaction/acceptability of training in memory or speed of processing versus wait-list control for improving cognitive function in breast cancer survivors. 82 breast cancer survivors completed a three-group randomized, controlled trial. Primary outcomes were objective neuropsychological tests of memory and speed of processing. Secondary outcomes were perceived cognitive functioning, symptom distress (mood disturbance, anxiety, and fatigue), quality of life, and intervention satisfaction/acceptability. Data were collected at baseline, post-intervention, and 2-month follow-up. Using repeated-measures mixed-linear ANCOVA models, each intervention was compared to wait-list control while adjusting for age, education, and baseline measures. The effect sizes for differences in means and the reliable improvement percentage were reported. The results show that domain-specific effects were seen for both interventions: memory training improved memory performance at 2-month follow-up (p = 0.036, d = 0.59); speed of processing training improved processing speed post-intervention (p = 0.040, d = 0.55) and 2-month follow-up (p = 0.016; d = 0.67). Transfer effects to non-trained domains were seen for speed of processing training with improved memory post-intervention (p = 0.007, d = 0.75) and 2-month follow-up (p = 0.004, d = 0.82). Both interventions were associated with improvements in perceived cognitive functioning, symptom distress, and quality of life. Ratings of satisfaction/acceptability were high for both interventions. It was concluded that while both interventions appeared promising, speed of processing training resulted in immediate and durable improvements in objective measures of processing speed and verbal memory. Speed of processing training may have broader benefits in this clinical population.
View details for PubMedID 22918524
Neuropathy is not associated with clinical outcomes in patients receiving adjuvant taxane-containing therapy for operable breast cancer.
Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Authors: Schneider BP; Zhao F; Wang M; Stearns V; Martino S; Jones V; Perez EA; Saphner T; Wolff AC; Sledge GW Jr; Wood WC; Davidson NE; Sparano JA;
Publication Date: 2012 Jul 30

Abstract

Neuropathy is a common and potentially disabling complication of adjuvant taxane therapy. Recent studies have identified candidate single nucleotide polymorphisms associated with taxane-induced neuropathy. Therefore, we sought to determine whether neuropathy was associated with breast cancer recurrence in a clinical trial population who received adjuvant taxane therapy.
View details for PubMedID 22851566
A phase I dose-escalation trial of trastuzumab and alvespimycin hydrochloride (KOS-1022; 17 DMAG) in the treatment of advanced solid tumors.
Journal: Clinical cancer research : an official journal of the American Association for Cancer Research
Authors: Jhaveri K; Miller K; Rosen L; Schneider B; Chap L; Hannah A; Zhong Z; Ma W; Hudis C; Modi S;
Publication Date: 2012 Jul 10

Abstract

We conducted a phase I dose-escalation study to define the maximum tolerated dose (MTD), pharmacokinetics (PK), and pharmacodynamics of alvespimycin (17-DMAG), a heat shock protein 90 (Hsp90) inhibitor, given in combination with trastuzumab.
View details for PubMedID 22781552
Cancer-associated alteration of pericentromeric heterochromatin may contribute to chromosome instability.
Journal: Oncogene
Authors: Slee RB; Steiner CM; Herbert BS; Vance GH; Hickey RJ; Schwarz T; Christan S; Radovich M; Schneider BP; Schindelhauer D; Grimes BR;
Publication Date: 2011 Nov 28

Abstract

Many tumors exhibit elevated chromosome mis-segregation termed chromosome instability (CIN), which is likely to be a potent driver of tumor progression and drug resistance. Causes of CIN are poorly understood but probably include prior genome tetraploidization, centrosome amplification and mitotic checkpoint defects. This study identifies epigenetic alteration of the centromere as a potential contributor to the CIN phenotype. The centromere controls chromosome segregation and consists of higher-order repeat (HOR) alpha-satellite DNA packaged into two chromatin domains: the kinetochore, harboring the centromere-specific H3 variant centromere protein A (CENP-A), and the pericentromeric heterochromatin, considered important for cohesion. Perturbation of centromeric chromatin in model systems causes CIN. As cancer cells exhibit widespread chromatin changes, we hypothesized that pericentromeric chromatin structure could also be affected, contributing to CIN. Cytological and chromatin immunoprecipitation and PCR (ChIP-PCR)-based analyses of HT1080 cancer cells showed that only one of the two HORs on chromosomes 5 and 7 incorporate CENP-A, an organization conserved in all normal and cancer-derived cells examined. Contrastingly, the heterochromatin marker H3K9me3 (trimethylation of H3 lysine 9) mapped to all four HORs and ChIP-PCR showed an altered pattern of H3K9me3 in cancer cell lines and breast tumors, consistent with a reduction on the kinetochore-forming HORs. The JMJD2B demethylase is overexpressed in breast tumors with a CIN phenotype, and overexpression of exogenous JMJD2B in cultured breast epithelial cells caused loss of centromere-associated H3K9me3 and increased CIN. These findings suggest that impaired maintenance of pericentromeric heterochromatin may contribute to CIN in cancer and be a novel therapeutic target.
View details for PubMedID 22081068
Cytochrome P450 polymorphisms and their relationship with premature ovarian failure in premenopausal women with breast cancer receiving doxorubicin and cyclophosphamide.
Journal: The breast journal
Authors: Wessels AM; Flockhart DA; Carpenter JS; Radovich M; Li L; Miller KD; Sledge GW; Storniolo AM; Otte JL; Lemler SM; Schneider BP;
Publication Date: 2011 Aug 9
A large, consistent plasma proteomics data set from prospectively collected breast cancer patient and healthy volunteer samples.
Journal: Journal of translational medicine
Authors: Riley CP; Zhang X; Nakshatri H; Schneider B; Regnier FE; Adamec J; Buck C;
Publication Date: 2011 May 27

Abstract

Variability of plasma sample collection and of proteomics technology platforms has been detrimental to generation of large proteomic profile datasets from human biospecimens.
View details for PubMedID 21619653
Anti-vascular endothelial growth factor therapy for breast cancer: can we pick the winners?
Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Authors: Schneider BP; Sledge GW Jr;
Publication Date: 2011 May 9
Evaluating the role of serotonin on neuropsychological function after breast cancer using acute tryptophan depletion.
Journal: Biological research for nursing
Authors: Von Ah D; Skaar T; Unverzagt F; Yu M; Wu J; Schneider B; Storniolo AM; Moser L; Ryker K; Milata J; Carpenter JS;
Publication Date: 2010 Dec 30

Abstract

Although cognitive dysfunction is a prevalent and disruptive problem for many breast cancer survivors (BCSs), little research has examined its etiology. One potential mechanism that remains to be explored is serotonin. Serotonin has been implicated in normal and dysfunctional cognitive processes, and serotonin levels are significantly affected by estrogen withdrawal, a common side effect of breast cancer treatment. However, no study has evaluated serotonin's role on cognitive dysfunction in BCSs. The purpose of this study was to examine the role of serotonin in cognitive dysfunction in survivors by lowering central serotonin concentrations via acute tryptophan depletion (ATD). Based on previous research in noncancer populations, we hypothesized that alterations in central serotonin levels would induce cognitive dysfunction in these women controlling for confounding characteristics such as fluctuating mood and glucose levels. Secondarily, we explored whether genetic variations in serotonin genes would partly explain ATD. Participants included 20 female BCSs, posttreatment for nonmetastatic breast cancer, who received ATD or control in a double-blind, crossover design. Cognitive performance was measured at the 5-hr tryptophan/serotonin nadir on each test day using standardized neuropsychological tests. Specific impairment was noted in episodic memory (delayed recall) and motor speed during ATD versus control. ATD did not alter new learning (immediate recall), working memory, verbal fluency, or information processing speed. Findings suggest that serotonin may play a critical role in memory consolidation and motor functioning in BCSs.
View details for PubMedID 21196424
Paclitaxel plus bevacizumab in patients with chemosensitive relapsed small cell lung cancer: a safety, feasibility, and efficacy study from the Hoosier Oncology Group.
Journal: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
Authors: Jalal S; Bedano P; Einhorn L; Bhatia S; Ansari R; Bechar N; Koneru K; Govindan R; Wu J; Yu M; Schneider B; Hanna N;
Publication Date: 2010 Dec

Abstract

Bevacizumab when combined with carboplatin and paclitaxel improves response rates (RRs) and overall survival in patients with advanced non-small cell lung cancer. Paclitaxel has single-agent activity in relapsed small cell lung cancer (SCLC). Angiogenesis seems to play an important role in the pathogenesis of SCLC. This study evaluated the safety and efficacy of paclitaxel plus bevacizumab in patients with chemosensitive relapsed SCLC.
View details for PubMedID 21102263
Compliance differences between patients with breast cancer in university and county hospitals.
Journal: Clinical breast cancer
Authors: Komenaka IK; Pennington RE Jr; Schneider BP; Hsu CH; Norton LE; Clare SE; Zork NM; Goulet RJ Jr;
Publication Date: 2010 Oct 1

Abstract

Compliance with recommended breast cancer treatments outside the context of a clinical trial differs from that in study populations. The purpose of this study was to examine differences in compliance of breast cancer treatments.
View details for PubMedID 20920983
Resequencing of the vascular endothelial growth factor promoter reveals haplotype structure and functional diversity.
Journal: Angiogenesis
Authors: Radovich M; Hancock BA; Kassem N; Mi D; Skaar TC; Schneider BP;
Publication Date: 2010 Jun 16

Abstract

Our group has previously reported that SNPs in the VEGF promoter are strongly associated with efficacy and toxicity to the anti-VEGF antibody bevacizumab in breast cancer. In order to better understand the biologic mechanism for our previously reported biomarkers, we embarked on a comprehensive evaluation of genetic variation in the VEGF promoter coupled with a study of its intrinsic function. We resequenced 48 Caucasians and 48 African-Americans for the VEGF promoter to identify SNPs and elucidate its haplotype structure. We further cloned the haplotypes into reporter constructs and assessed the role of SNPs on promoter function in breast cancer cell lines. SNPs that were identified included twenty previously reported SNPs/insertions/deletions, one novel SNP, and one novel deletion. Among these variants, we identified five SNPs that tag six haplotypes capturing 74% of the genetic variation of the promoter. Subsequently, assessment of the haplotypes in reporter constructs demonstrates significant variation in promoter induced expression among the haplotypes. In particular, two haplotypes had higher expression and one haplotype had lower expression across cell lines. Haplotypes containing SNPs previously reported to be associated with increased survival with the use of bevacizumab are high-expressing haplotypes, thus lending putative functional evidence to the prior clinical finding.
View details for PubMedID 20552269
A phase I dose escalation and pharmacokinetic study of vatalanib (PTK787/ZK 222584) in combination with paclitaxel in patients with advanced solid tumors.
Journal: Cancer chemotherapy and pharmacology
Authors: Chiorean EG; Malireddy S; Younger AE; Jones DR; Waddell MJ; Sloop MI; Yu M; Hall SD; Schneider B; Sweeney CJ;
Publication Date: 2009 Nov 29

Abstract

To define the maximum-tolerated dose (MTD) for weekly paclitaxel administered in combination with daily vatalanib (PTK787/ZK 222584, PTK/ZK) and assess for a drug-drug interaction.
View details for PubMedID 20091169
Intrinsic subtype-associated changes in the plasma proteome in breast cancer.
Journal: Proteomics. Clinical applications
Authors: Nakshatri H; Qi G; You J; Kerry B; Schneider B; Zon R; Buck C; Regnier F; Wang M;
Publication Date: 2009 Nov

Abstract

Breast cancers are classified into five intrinsic subtypes: Luminal subtype A, Luminal subtype B, HER2+, Basal, and Normal-like. In this study, we compared the plasma proteome of patients with Luminal A, Luminal B, HER2+, and Basal subtype with plasma from healthy individuals. Protein changes were considered significant if q-value (false discovery rate) was less than 5%. The highest number of changes in the plasma proteome was observed in patients with Luminal type B followed by Basal type breast cancers. The plasma proteome of Luminal A and HER2+ breast cancer patients did not differ significantly from healthy individuals. In Basal breast cancer, a significant number of plasma proteins were downregulated compared with healthy individuals. Acute phase-response proteins a-glycoprotein orosomucoid 1 and serum amyloid protein P were specifically upregulated in the plasma of Luminal B breast cancer patients, suggesting prevalence of low-grade inflammation. Proteins involved in immune response and free radical scavenging were downregulated in the plasma of Luminal B patients, which is in agreement with defective immune system observed in cancer patients. These results reveal intrinsic subtype specific changes in the plasma proteome that may influence tumor progression as well as the systemic effects of cancer.
View details for PubMedID 21136952
The role of vascular endothelial growth factor genetic variability in cancer.
Journal: Clinical cancer research : an official journal of the American Association for Cancer Research
Authors: Schneider BP; Radovich M; Miller KD;
Publication Date: 2009 Aug 25

Abstract

Angiogenesis is a hallmark of tumor pathogenesis. Vascular endothelial growth factor (VEGF) is a critical regulator of angiogenesis and its inhibition has become a successful approach to antitumor therapy across tumor types. The VEGF gene is highly polymorphic with multiple common single nucleotide polymorphisms (SNPs) in the promoter, 5' untranslated region and 3' untranslated region. There is evidence that these SNPs in the regulatory regions can affect VEGF expression. In vitro and in vivo data show that genetic variability affects the activity and expression of VEGF. Case-control and cohort studies suggest that genetic variability may affect risk and outcome of a variety of disease states that are tightly regulated by angiogenesis. Recently, genetic variability in VEGF has been studied as a potential predictive biomarker for bevacizumab. The VEGF-1154 AA and -2578 AA genotypes predicted an improved median overall survival, whereas the VEGF-634 CC and -1498 TT genotypes predicted protection from grade 3-4 hypertension in the pivotal trial, E2100. If validated, these finding could help direct which subgroup of patients should receive bevacizumab.
View details for PubMedID 19706811
Anti-VEGF therapy as adjuvant therapy: clouds on the horizon?
Journal: Breast cancer research : BCR
Authors: Schneider BP; Sledge GW Jr;
Publication Date: 2009 May 18

Abstract

Anti-angiogenic therapies have demonstrated their value in the setting of advanced cancer, and are being explored for use in micrometastatic disease. Recent preclinical studies suggest that adjuvant anti-vascular endothelial growth factor (VEGF) therapies may increase the risk of metastasis. How concerning are these preclinical studies, and should they affect our willingness to explore anti-VEGF therapy in the adjuvant setting?
View details for PubMedID 19519950
Triple-negative breast cancer: risk factors to potential targets.
Journal: Clinical cancer research : an official journal of the American Association for Cancer Research
Authors: Schneider BP; Winer EP; Foulkes WD; Garber J; Perou CM; Richardson A; Sledge GW; Carey LA;
Publication Date: 2008 Dec 15

Abstract

Triple-negative breast cancer has recently been recognized as an important subgroup of breast cancer with a distinct outcome and therapeutic approach when compared with other subgroups of breast cancer. Triple-negative breast cancer comprises primarily, but not exclusively, a molecularly distinct subtype of breast cancer, the basal-like subtype. We do not yet have an assay to identify basal-like breast cancer in clinical samples, so triple-negative breast cancer has become a commonly used proxy for this subtype. The molecular biology and pathophysiology of triple-negative breast cancer are not completely understood, but understanding is improving rapidly with the advent of sophisticated molecular biology platforms. Moreover, the established risk factors of breast cancer as a whole may not apply to this unique subgroup of patients. Finally, because triple-negative breast cancer is defined by the absence of a target, there are currently limitations to using a tailored therapeutic approach, leaving conventional cytotoxic therapies as the mainstay. Active preclinical and clinical research programs focus on defining the clinical behavior, delineating the risk factors, and more completely understanding the molecular biology of triple-negative breast cancer to improve prevention, optimize conventional agents, and unveil novel therapeutic targets. This CCR focus article will review the current state of the art on triple-negative breast cancer.
View details for PubMedID 19088017
Association of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 genetic polymorphisms with outcome in a trial of paclitaxel compared with paclitaxel plus bevacizumab in advanced breast cancer: ECOG 2100.
Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Authors: Schneider BP; Wang M; Radovich M; Sledge GW; Badve S; Thor A; Flockhart DA; Hancock B; Davidson N; Gralow J; Dickler M; Perez EA; Cobleigh M; Shenkier T; Edgerton S; Miller KD; ECOG 2100;
Publication Date: 2008 Oct 1

Abstract

No biomarkers have been identified to predict outcome with the use of an antiangiogenesis agent for cancer. Vascular endothelial growth factor (VEGF) genetic variability has been associated with altered risk of breast cancer and variable promoter activity. Therefore, we evaluated the association of VEGF genotype with efficacy and toxicity in E2100, a phase III study comparing paclitaxel versus paclitaxel plus bevacizumab as initial chemotherapy for metastatic breast cancer.
View details for PubMedID 18824714
Exploratory study evaluating the association of polymorphisms of angiogenesis genes with hot flashes.
Journal: Breast cancer research and treatment
Authors: Schneider BP; Radovich M; Flockhart DA; Carpenter JS; Li L; Robarge JD; Storniolo AM; Hancock BA; Skaar TC; Sledge GW;
Publication Date: 2008 Sep 11

Abstract

Hot flashes are a common symptom and an important cause of decreased quality of life in women with breast cancer. Hot flashes involve vasodilatation and flushing, however, their complex etiology is not fully understood. We evaluated the association between germline polymorphisms in genes important to angiogenesis and subjective reporting of hot flashes.
View details for PubMedID 18785001
A 25-year single institution experience with surgery for primary mediastinal nonseminomatous germ cell tumors.
Journal: The Annals of thoracic surgery
Authors: Kesler KA; Rieger KM; Hammoud ZT; Kruter LE; Perkins SM; Turrentine MW; Schneider BP; Einhorn LH; Brown JW;
Publication Date: 2008 Feb

Abstract

The treatment of primary mediastinal nonseminomatous germ cell tumors (PMNSGCT) with cisplatin-based chemotherapy, followed by surgical resection of residual disease, has been established. We reviewed our institution's 25-year experience in the cisplatin era to determine surgical risks and predictors of survival after surgery for PMNSGCT.
View details for PubMedID 18222228
Association of polymorphisms of angiogenesis genes with breast cancer.
Journal: Breast cancer research and treatment
Authors: Schneider BP; Radovich M; Sledge GW; Robarge JD; Li L; Storniolo AM; Lemler S; Nguyen AT; Hancock BA; Stout M; Skaar T; Flockhart DA;
Publication Date: 2007 Sep 20

Abstract

Few studies have systematically explored a pathway approach: to test the association of multiple polymorphisms from multiple genes important to angiogenesis simultaneously with risk of breast cancer. We report our preliminary data evaluating the association of polymorphisms from seven genes known to influence angiogenesis with the likelihood of having breast cancer.
View details for PubMedID 17891484
Is the blood-brain barrier relevant in metastatic germ cell tumor?
Journal: International journal of radiation oncology, biology, physics
Authors: Azar JM; Schneider BP; Einhorn LH;
Publication Date: 2007 Sep 1

Abstract

Germ cell tumors are uniquely chemosensitive and curable, even with advanced metastatic disease. Central nervous system recurrence can terminate a complete remission in other chemosensitive tumors, such as small cell lung cancer, because of the blood-brain barrier (BBB). We propose to document that the BBB is also relevant in germ cell tumors despite their dramatic chemosensitivity.
View details for PubMedID 17707269
Drug insight: VEGF as a therapeutic target for breast cancer.
Journal: Nature clinical practice. Oncology
Authors: Schneider BP; Sledge GW Jr;
Publication Date: 2007 Mar

Abstract

Angiogenesis is implicated in the pathogenesis of malignancy and metastasis. Inhibition of angiogenesis has demonstrated clinically significant improvements in outcomes in a variety of malignancies, including breast cancer. The humanized monoclonal antibody against VEGF, bevacizumab, is the clinically most mature of the antiangiogenic agents and has recently been shown to improve outcome when combined with chemotherapy in the first-line metastatic setting of breast cancer. A variety of other antiangiogenic agents are currently under investigation, including drugs that inhibit the VEGF receptor 2, the cognate receptor for VEGF found on endothelial cells. The combination of antiangiogenic drugs with one another and with other biologic agents is also being explored in an attempt to improve efficacy and to overcome the drug resistance seen with the initial studies of antiangiogenic agents. This Review will focus on the current state of therapeutics designed to inhibit this angiogenic process in breast cancer.
View details for PubMedID 17327858
Breast cancer treatment and ovarian failure: risk factors and emerging genetic determinants.
Journal: Nature reviews. Cancer
Authors: Stearns V; Schneider B; Henry NL; Hayes DF; Flockhart DA;
Publication Date: 2006 Oct 12

Abstract

Most premenopausal women diagnosed with primary breast cancer receive adjuvant chemotherapy, and many experience chemotherapy-induced ovarian failure (CIOF). CIOF is associated with menopausal symptoms, fertility concerns and long-term implications including bone loss. Ironically, CIOF might confer a disease-specific benefit to women whose breast cancers express hormone receptors. Risk factors of CIOF include the woman's age at the time of therapy, and the type, dose and schedule of chemotherapy. Because inherited genetic factors have an important role in determining who will experience CIOF, genetic testing has the potential to provide optimal counselling about risks and possible interventions.
View details for PubMedID 17036039
A phase I, pharmacokinetic and pharmacodynamic dose escalation trial of weekly paclitaxel with interferon-alpha2b in patients with solid tumors.
Journal: Cancer chemotherapy and pharmacology
Authors: Schneider B; Fukunaga A; Murry D; Yoder C; Fife K; Foster A; Rosenberg L; Kelich S; Li L; Sweeney C;
Publication Date: 2006 May 30

Abstract

Paclitaxel and interferon have demonstrated anti-angiogenic activity in vitro and in vivo. The toxicity, pharmacokinetics, and pharmacodynamics of paclitaxel with interferon-alpha2b (IFN-alpha2b) were assessed in patients with solid tumors to assess the feasibility of this novel anti-angiogenic regimen.
View details for PubMedID 16733646
Analysis of angiogenesis genes from paraffin-embedded breast tumor and lymph nodes.
Journal: Breast cancer research and treatment
Authors: Schneider BP; Skaar TC; Sledge GW; Badve S; Li L; Flockhart DA;
Publication Date: 2006 Feb 28

Abstract

Angiogenesis is important in tumor growth and metastasis. Germ-line polymorphisms critical to the angiogenesis pathway have been shown to confer prognostic information in multiple tumor types. These genes include vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS).
View details for PubMedID 16505966
Angiogenesis of breast cancer.
Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Authors: Schneider BP; Miller KD;
Publication Date: 2005 Mar 10
Outcome of patients with residual germ cell or non-germ cell malignancy after resection of primary mediastinal nonseminomatous germ cell cancer.
Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Authors: Schneider BP; Kesler KA; Brooks JA; Yiannoutsos C; Einhorn LH;
Publication Date: 2004 Apr 1

Abstract

To identify prognostic variables and outcomes in patients with primary mediastinal nonseminomatous germ cell tumor (PMNSGCT) with postchemotherapy resection of persistent cancer.
View details for PubMedID 15051766
Phase II study of gemcitabine plus docetaxel in advanced pancreatic cancer: a Hoosier Oncology Group study.
Journal: Oncology
Authors: Schneider BP; Ganjoo KN; Seitz DE; Picus J; Fata F; Stoner C; Calley C; Loehrer PJ;
Publication Date: 2003

Abstract

To determine the response rate, duration of response and survival with weekly gemcitabine plus docetaxel in metastatic or unresectable pancreatic cancer.
View details for PubMedID 14657595
Isosteric analogues of nicotinamide adenine dinucleotide derived from furanfurin, thiophenfurin, and selenophenfurin as mammalian inosine monophosphate dehydrogenase (type I and II) inhibitors.
Journal: Journal of medicinal chemistry
Authors: Franchetti P; Cappellacci L; Perlini P; Jayaram HN; Butler A; Schneider BP; Collart FR; Huberman E; Grifantini M;
Publication Date: 1998 May 7

Abstract

Dinucleotides TFAD (6), FFAD (7), and SFAD (8), isosteric NAD analogues derived, respectively, from C-nucleosides 5-beta-d-ribofuranosylthiophene-3-carboxamide (thiophenfurin, 1), 5-beta-d-ribofuranosylfuran-3-carboxamide (furanfurin, 2), and 5-beta-d-ribofuranosylselenophene-3-carboxamide (selenophenfurin, 5), were synthesized as human inosine monophosphate dehydrogenase (IMPDH) type I and II inhibitors. The synthesis was carried out by imidazole-catalyzed coupling of the 5'-monophosphate of 1, 2, and 5 with AMP. These dinucleotides, which are also analogues of thiazole-4-carboxamide adenine dinucleotide (TAD) and selenazole-4-carboxamide adenine dinucleotide (SAD), the active metabolites of the oncolytic C-nucleosides 2-beta-D-ribofuranosylthiazole-4-carboxamide (tiazofurin) and 2-beta-D-ribofuranosylselenazole-4-carboxamide (selenazofurin), were evaluated for their inhibitory potency against recombinant human IMPDH type I and II. The order of inhibitory potency found was SAD > SFAD = TFAD = TAD > FFAD for both enzyme isoforms. No significant difference was found in inhibition of IMPDH type I and II.
View details for PubMedID 9572896
Synthesis, structure, and antiproliferative activity of selenophenfurin, an inosine 5'-monophosphate dehydrogenase inhibitor analogue of selenazofurin.
Journal: Journal of medicinal chemistry
Authors: Franchetti P; Cappellacci L; Sheikha GA; Jayaram HN; Gurudutt VV; Sint T; Schneider BP; Jones WD; Goldstein BM; Perra G; De Montis A; Loi AG; La Colla P; Grifantini M;
Publication Date: 1997 May 23

Abstract

The synthesis and biological activity of selenophenfurin (5-beta-D-ribofuranosylselenophene-3-carboxamide, 1), the selenophene analogue of selenazofurin, are described. Glycosylation of ethyl selenophene-3-carboxylate (6) under stannic chloride-catalyzed conditions gave 2- and 5-glycosylated regioisomers, as a mixture of alpha- and beta-anomers, and the beta-2,5-diglycosylated derivative. Deprotected ethyl 5-beta-D-ribofuranosylselenophene-3-carboxylate (12 beta) was converted into selenophenfurin by ammonolysis. The structure of 12 beta was determined by 1H- and 13C-NMR, crystallographic, and computational studies. Selenophenfurin proved to be antiproliferative against a number of leukemia, lymphoma, and solid tumor cell lines at concentrations similar to those of selenazofurin but was more potent than the thiophene and thiazole analogues thiophenfurin and tiazofurin. Incubation of K562 cells with selenophenfurin resulted in inhibition of IMP dehydrogenase (IMPDH) (76%) and an increase in IMP pools (14.5-fold) with a concurrent decrease in GTP levels (58%). The results obtained confirm the hypothesis that the presence of heteroatoms such as S or Se in the heterocycle in position 2 with respect to the glycosidic bond is essential for both cytotoxicity and IMP dehydrogenase inhibitory activity in this type of C-nucleosides.
View details for PubMedID 9171883