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Full-Text Articles in Medicine and Health Sciences

Reciprocal Interaction Of Wnt And Rxr-Alpha Pathways In Hepatocyte Development And Hepatocellular Carcinoma, J. Li, M. Chanrion, E. Sawey, T. Wang, E. Chow, A. Tward, Y. Su, W. Xue, R. Lucito, L. Zender, +3 Additional Authors Jan 2015

Reciprocal Interaction Of Wnt And Rxr-Alpha Pathways In Hepatocyte Development And Hepatocellular Carcinoma, J. Li, M. Chanrion, E. Sawey, T. Wang, E. Chow, A. Tward, Y. Su, W. Xue, R. Lucito, L. Zender, +3 Additional Authors

Journal Articles

Genomic analysis of human hepatocellular carcinoma (HCC) is potentially confounded by the differentiation state of the hepatic cell-of-origin. Here we integrated genomic analysis of mouse HCC (with defined cell-of-origin) along with normal development. We found a major shift in expression of Wnt and RXR-alpha pathway genes (up and down, respectively) coincident with the transition from hepatoblasts to hepatocytes. A combined Wnt and RXR-alpha gene signature categorized HCCs into two subtypes (high Wnt, low RXR-alpha and low Wnt, high RXR-alpha), which matched cell-of-origin in mouse models and the differentiation state of human HCC. Suppression of RXR-alpha levels in hepatocytes increased Wnt …


A Quantitative Proteomics-Based Signature Of Platinum Sensitivity In Ovarian Cancer Cell Lines, G. Fan, K. O. Wrzeszczynski, C. Fu, G. Su, D. J. Pappin, R. Lucito, N. K. Tonks Jan 2015

A Quantitative Proteomics-Based Signature Of Platinum Sensitivity In Ovarian Cancer Cell Lines, G. Fan, K. O. Wrzeszczynski, C. Fu, G. Su, D. J. Pappin, R. Lucito, N. K. Tonks

Journal Articles

Although DNA encodes the molecular instructions that underlie the control of cell function, it is the proteins that are primarily responsible for implementing those instructions. Therefore quantitative analyses of the proteome would be expected to yield insights into important candidates for the detection and treatment of disease. We present an iTRAQ (isobaric tag for relative and absolute quantification)-based proteomic analysis of ten ovarian cancer cell lines and two normal ovarian surface epithelial cell lines. We profiled the abundance of 2659 cellular proteins of which 1273 were common to all 12 cell lines. Of the 1273, 75 proteins exhibited elevated expression …


Effusive-Constrictive Tuberculous Pericarditis In The Setting Of Penetrating Abdominal Trauma, V. Meytes, S. Docimo, D. Elkowitz, A. Kopatsis Jan 2015

Effusive-Constrictive Tuberculous Pericarditis In The Setting Of Penetrating Abdominal Trauma, V. Meytes, S. Docimo, D. Elkowitz, A. Kopatsis

Journal Articles

Tuberculous pericarditis is rare in developed nations and is most commonly associated with effusive-constrictive pericarditis. We present the case of a 33-year-old man with a self-inflicted mid-abdominal stab wound. The patient underwent an exploratory laparotomy, revealing a grade IV pancreatic transection and injuries to the portal vein, right renal vein, inferior vena cava and the superior mesenteric vein. Repair of the vessels was performed and a pancreaticojejunostomy with a gastrojejunostomy was created for the pancreatic injury. The patient's hospital course was complicated by tuberculous effusive-constrictive pericarditis requiring emergent median sternotomy with opening of the pericardial sac and eventual expiration. The …


Early Toxicity In Patients Treated With Postoperative Proton Therapy For Locally Advanced Breast Cancer, J. J. Cuaron, B. Chon, H. Tsai, A. Goenka, D. Deblois, A. Ho, S. Powell, E. Hug, O. Cahlon Jan 2015

Early Toxicity In Patients Treated With Postoperative Proton Therapy For Locally Advanced Breast Cancer, J. J. Cuaron, B. Chon, H. Tsai, A. Goenka, D. Deblois, A. Ho, S. Powell, E. Hug, O. Cahlon

Journal Articles

PURPOSE: To report dosimetry and early toxicity data in breast cancer patients treated with postoperative proton radiation therapy. METHODS AND MATERIALS: From March 2013 to April 2014, 30 patients with nonmetastatic breast cancer and no history of prior radiation were treated with proton therapy at a single proton center. Patient characteristics and dosimetry were obtained through chart review. Patients were seen weekly while on treatment, at 1 month after radiation therapy completion, and at 3- to 6-month intervals thereafter. Toxicity was scored using Common Terminology Criteria for Adverse Events version 4.0. Frequencies of toxicities were tabulated. RESULTS: Median dose delivered …


Medically Inoperable Peripheral Lung Cancer Treated With Stereotactic Body Radiation Therapy, K. D. Kelley, D. L. Benninghoff, J. S. Stein, J. Z. Li, R. T. Byrnes, L. Potters, J. P. Knisely, H. D. Zinkin Jan 2015

Medically Inoperable Peripheral Lung Cancer Treated With Stereotactic Body Radiation Therapy, K. D. Kelley, D. L. Benninghoff, J. S. Stein, J. Z. Li, R. T. Byrnes, L. Potters, J. P. Knisely, H. D. Zinkin

Journal Articles

BACKGROUND: Lung cancer is the most frequent cause of cancer-related death in North America. There is wide variation between patients who are medically inoperable and those managed surgically. The use of stereotactic body radiotherapy (SBRT) has narrowed the gap in survival rates between operative and non-operative management for those with early stage disease. This retrospective study reports outcomes for the treatment of peripheral non-small cell lung carcinoma (NSCLC) with SBRT from a single community practice. METHODS: Sixty-seven consecutive patients (pts) with inoperable, untreated peripheral lung tumors were treated from 2010 through 2012 and included in this study. Stereotactic targeting was …


Humoral Immune Response Against Nontargeted Tumor Antigens After Treatment With Sipuleucel-T And Its Association With Improved Clinical Outcome, D. Guhathakurta, N. A. Sheikh, L. Q. Fan, H. Kandadi, T. C. Meagher, S. J. Hall, J. B. Whitmore, M. W. Frohlich, J. B. Trager, C. G. Drake, +7 Additional Authors Jan 2015

Humoral Immune Response Against Nontargeted Tumor Antigens After Treatment With Sipuleucel-T And Its Association With Improved Clinical Outcome, D. Guhathakurta, N. A. Sheikh, L. Q. Fan, H. Kandadi, T. C. Meagher, S. J. Hall, J. B. Whitmore, M. W. Frohlich, J. B. Trager, C. G. Drake, +7 Additional Authors

Journal Articles

PURPOSE: Antitumor activity of cancer immunotherapies may elicit immune responses to nontargeted (secondary) tumor antigens, or antigen spread. We evaluated humoral antigen spread after treatment with sipuleucel-T, an immunotherapy for asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC), designed to target prostatic acid phosphatase (PAP; primary antigen). EXPERIMENTAL DESIGN: Serum samples from patients with mCRPC enrolled in the placebo-controlled phase III IMPACT study (evaluable n = 142) were used to assess humoral antigen spread after treatment with sipuleucel-T. Immunoglobulin G (IgG) responses to self-antigens (including tumor antigens) were surveyed using protein microarrays and confirmed using Luminex xMAP. IgG responses …


Prc2 Is Recurrently Inactivated Through Eed Or Suz12 Loss In Malignant Peripheral Nerve Sheath Tumors, W. Lee, S. Teckie, T. Wiesner, A. Viale, S. Singer, D. Zheng, M. F. Berger, Y. Chen, C. R. Antonescu, P. Chi, +11 Additional Authors Jan 2014

Prc2 Is Recurrently Inactivated Through Eed Or Suz12 Loss In Malignant Peripheral Nerve Sheath Tumors, W. Lee, S. Teckie, T. Wiesner, A. Viale, S. Singer, D. Zheng, M. F. Berger, Y. Chen, C. R. Antonescu, P. Chi, +11 Additional Authors

Journal Articles

Malignant peripheral nerve sheath tumors (MPNSTs) represent a group of highly aggressive soft-tissue sarcomas that may occur sporadically, in association with neurofibromatosis type I (NF1 associated) or after radiotherapy. Using comprehensive genomic approaches, we identified loss-of-function somatic alterations of the Polycomb repressive complex 2 (PRC2) components (EED or SUZ12) in 92% of sporadic, 70% of NF1-associated and 90% of radiotherapy-associated MPNSTs. MPNSTs with PRC2 loss showed complete loss of trimethylation at lysine 27 of histone H3 (H3K27me3) and aberrant transcriptional activation of multiple PRC2-repressed homeobox master regulators and their regulated developmental pathways. Introduction of the lost PRC2 component in a …


B Cells Populating The Multiple Sclerosis Brain Mature In The Draining Cervical Lymph Nodes, J. N. Stern, G. Yaari, J. A. Vander Heiden, G. Church, W. F. Donahue, R. Q. Hintzen, A. J. Huttner, J. D. Laman, R. M. Nagra, K. C. O’Connor, +7 Additional Authors Jan 2014

B Cells Populating The Multiple Sclerosis Brain Mature In The Draining Cervical Lymph Nodes, J. N. Stern, G. Yaari, J. A. Vander Heiden, G. Church, W. F. Donahue, R. Q. Hintzen, A. J. Huttner, J. D. Laman, R. M. Nagra, K. C. O’Connor, +7 Additional Authors

Journal Articles

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) characterized by autoimmune-mediated demyelination and neurodegeneration. The CNS of patients with MS harbors expanded clones of antigen-experienced B cells that reside in distinct compartments including the meninges, cerebrospinal fluid (CSF), and parenchyma. It is not understood whether this immune infiltrate initiates its development in the CNS or in peripheral tissues. B cells in the CSF can exchange with those in peripheral blood, implying that CNS B cells may have access to lymphoid tissue that may be the specific compartment(s) in which CNS-resident B cells encounter antigen and …


Transcriptional Diversity Of Long-Term Glioblastoma Survivors, N. K. Gerber, A. Goenka, S. Turcan, M. Reyngold, V. Makarov, K. Kannan, K. Beal, C. W. Brennan, J. T. Huse, T. A. Chan, +3 Additional Authors Jan 2014

Transcriptional Diversity Of Long-Term Glioblastoma Survivors, N. K. Gerber, A. Goenka, S. Turcan, M. Reyngold, V. Makarov, K. Kannan, K. Beal, C. W. Brennan, J. T. Huse, T. A. Chan, +3 Additional Authors

Journal Articles

BACKGROUND: Glioblastoma (GBM) is a highly aggressive type of glioma with poor prognosis. However, a small number of patients live much longer than the median survival. A better understanding of these long-term survivors (LTSs) may provide important insight into the biology of GBM. METHODS: We identified 7 patients with GBM, treated at Memorial Sloan-Kettering Cancer Center (MSKCC), with survival >48 months. We characterized the transcriptome of each patient and determined rates of MGMT promoter methylation and IDH1 and IDH2 mutational status. We identified LTSs in 2 independent cohorts (The Cancer Genome Atlas [TCGA] and NCI Repository for Molecular Brain Neoplasia …


Defining Internal Target Volume Using Positron Emission Tomography For Radiation Therapy Planning Of Moving Lung Tumors, A. C. Riegel, M. K. Bucci, O. R. Mawlawi, M. Ahmad, D. Luo, A. Chandler, T. S. Pan Jan 2014

Defining Internal Target Volume Using Positron Emission Tomography For Radiation Therapy Planning Of Moving Lung Tumors, A. C. Riegel, M. K. Bucci, O. R. Mawlawi, M. Ahmad, D. Luo, A. Chandler, T. S. Pan

Journal Articles

Substantial disagreement exists over appropriate PET segmentation techniques for non-small cell lung cancer. Currently, no segmentation algorithm explicitly considers tumor motion in determining tumor borders. We developed an automatic PET segmentation model as a function of target volume, motion extent, and source-to-background ratio (the VMSBR model). The purpose of this work was to apply the VMSBR model and six other segmentation algorithms to a sample of lung tumors. PET and 4D CT were performed in the same imaging session for 23 patients (24 tumors) for radiation therapy planning. Internal target volumes (ITVs) were autosegmented on maximum intensity projection (MIP) of …


Loss Of Dok2 Induces Carboplatin Resistance In Ovarian Cancer Via Suppression Of Apoptosis, E. Lum, M. Vigliotti, N. Banerjee, N. Cutter, K. O. Wrzeszczynski, S. Khan, S. Kamalakaran, D. A. Levine, N. Dimitrova, R. Lucito Jan 2013

Loss Of Dok2 Induces Carboplatin Resistance In Ovarian Cancer Via Suppression Of Apoptosis, E. Lum, M. Vigliotti, N. Banerjee, N. Cutter, K. O. Wrzeszczynski, S. Khan, S. Kamalakaran, D. A. Levine, N. Dimitrova, R. Lucito

Journal Articles

Objective. Ovarian cancers are highly heterogeneous and while chemotherapy is the preferred treatment many patients are intrinsically resistant or quickly develop resistance. Furthermore, all tumors that recur ultimately become resistant. Recent evidence suggests that epigenetic deregulation may be a key factor in the onset and maintenance of chemoresistance. We set out to identify epigenetically silenced genes that affect chemoresistance. Methods. The epigenomes of a total of 45 ovarian samples were analyzed to identify epigenetically altered genes that segregate with platinum response, and further filtered with expression data to identify genes that were suppressed. A tissue culture carboplatin resistance screen was …


The Immune Cell Infiltrate Populating Meningiomas Is Composed Of Mature, Antigen-Experienced T And B Cells, L. Fang, D. E. Lowther, M. L. Meizlish, R. C. Anderson, J. N. Bruce, J. N. Stern, G. Yaari, L. Lovato, K. M. Cronk, K. C. O'Connor, +4 Additional Authors Jan 2013

The Immune Cell Infiltrate Populating Meningiomas Is Composed Of Mature, Antigen-Experienced T And B Cells, L. Fang, D. E. Lowther, M. L. Meizlish, R. C. Anderson, J. N. Bruce, J. N. Stern, G. Yaari, L. Lovato, K. M. Cronk, K. C. O'Connor, +4 Additional Authors

Journal Articles

BACKGROUND: Meningiomas often harbor an immune cell infiltrate that can include substantial numbers of T and B cells. However, their phenotype and characteristics remain undefined. To gain a deeper understanding of the T and B cell repertoire in this tumor, we characterized the immune infiltrate of 28 resected meningiomas representing all grades. METHODS: Immunohistochemistry was used to grossly characterize and enumerate infiltrating lymphocytes. A molecular analysis of the immunoglobulin variable region of tumor-infiltrating B cells was used to characterize their antigen experience. Flow cytometry of fresh tissue homogenate and paired peripheral blood lymphocytes was used to identify T cell phenotypes …


Protein-Tyrosine Phosphatase 1b Antagonized Signaling By Insulin-Like Growth Factor-1 Receptor And Kinase Brk/Ptk6 In Ovarian Cancer Cells, G. F. Fan, G. Lin, R. Lucito, N. K. Tonks Jan 2013

Protein-Tyrosine Phosphatase 1b Antagonized Signaling By Insulin-Like Growth Factor-1 Receptor And Kinase Brk/Ptk6 In Ovarian Cancer Cells, G. F. Fan, G. Lin, R. Lucito, N. K. Tonks

Journal Articles

Ovarian cancer, which is the leading cause of death from gynecological malignancies, is a heterogeneous disease known to be associated with disruption of multiple signaling pathways. Nevertheless, little is known regarding the role of protein phosphatases in the signaling events that underlie the disease; such knowledge will be essential to gain a complete understanding of the etiology of the disease and how to treat it. We have demonstrated that protein-tyrosine phosphatase 1B (PTP1B) was underexpressed in a panel of ovarian carcinoma-derived cell lines, compared with immortalized human ovarian surface epithelial cell lines. Stable restoration of PTP1B in those cancer cell …


Two Distinct Categories Of Focal Deletions In Cancer Genomes, M. Rajaram, M. Kato, L. Myeroff, S. D. Markowitz, S. W. Lowe, M. Zhang, A. Krasnitz, R. Lucito, D. Mu, R. S. Powers, +13 Additional Authors Jan 2013

Two Distinct Categories Of Focal Deletions In Cancer Genomes, M. Rajaram, M. Kato, L. Myeroff, S. D. Markowitz, S. W. Lowe, M. Zhang, A. Krasnitz, R. Lucito, D. Mu, R. S. Powers, +13 Additional Authors

Journal Articles

One of the key questions about genomic alterations in cancer is whether they are functional in the sense of contributing to the selective advantage of tumor cells. The frequency with which an alteration occurs might reflect its ability to increase cancer cell growth, or alternatively, enhanced instability of a locus may increase the frequency with which it is found to be aberrant in tumors, regardless of oncogenic impact. Here we've addressed this on a genome-wide scale for cancer-associated focal deletions, which are known to pinpoint both tumor suppressor genes (tumor suppressors) and unstable loci. Based on DNA copy number analysis …