Jan Geliebter

New York Medical College, New York, New York, United States

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Publications (61)343.26 Total impact

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    ABSTRACT: Purpose: The emergence of prostate cancer as a major health issue and the absence of curative treatment for metastatic disease requires the development of new treatment modalities. Prostate specific antigen (PSA) and prostate-specific membrane antigen (PSMA) are possible targets for prostate cancer immunotherapy. We have previously shown that PSA and PSMA can be expressed in recombinant bacille Calmette-Guérin (BCG) strains. Methods: The in vivo immunogenicity of the prostate-specific proteins produced by this recombinant BCG strain were examined by detection of specific antibody responses and delayed-type hypersensitivity (DTH) responses in mice vaccinated with these strains. These immune responses were compared with those of control mice vaccinated with phosphate buffered saline diluent or soluble PSA or PSMA. Results: Mice vaccinated with rBCG-PSA developed low levels of anti-PSA antibodies and strong DTH to PSA. Mice vaccinated with rBCG-PSMA developed strong DTH to PSMA and no anti-PSMA antibodies. Conclusions: We conclude that recombinant BCG expressing PSA or PSMA induce strong cellular immune responses to these antigens. We propose that the innate adjuvant capacity of BCG could help stimulate a specific immune response against prostate-specific proteins produced by the bacteria, which in turn, could lead to the eradication of undetected metastatic prostate cancer cells in post-surgical patients.
  • Cancer Research 10/2014; 74(19 Supplement):1107-1107. DOI:10.1158/1538-7445.AM2014-1107 · 9.28 Impact Factor
  • Cancer Research 10/2014; 74(19 Supplement):2122-2122. DOI:10.1158/1538-7445.AM2014-2122 · 9.28 Impact Factor
  • Cancer Research 10/2014; 74(19 Supplement):641-641. DOI:10.1158/1538-7445.AM2014-641 · 9.28 Impact Factor
  • Cancer Research 10/2014; 74(19 Supplement):3709-3709. DOI:10.1158/1538-7445.AM2014-3709 · 9.28 Impact Factor
  • TCGA Third Annual Scientific Symposium; 05/2014
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    ABSTRACT: Background: Prostate cancer progression is a complex process in which chemokines and their receptors play an important role related to tumor survival, growth, and metastasis. Objectives: 1) To determine the expression profiles of proinflammatory chemokines in prostate cancer cell line supernatants and their association with the metastatic phenotype, and 2) To determine whether these chemokines are present in the exosomes released from prostate cancer cell lines examined. Methods: Prostate cancer lines investigated included PWR-1E (non-tumorigenic), LNCaP (low metastatic potential) and PC-3 (high metastatic potential). The Human Common Chemokines Multi-Analyte ELISArray Kit (Qiagen) was used to evaluate the expression profiles of several proinflammatory chemokines in the supernatant and in the exosomal fraction of prostate cancer cells in culture. Chemokine profiles were correlated with the metastatic abilities of the cell lines analyzed. Chemokines evaluated were CCL2, CCL3, CCL4, CCL5, CCL11, CCL17, CCL22, CXCL1, CXCL8, CXCL9, CXCL10 and CXCL11. Results: Differential chemokine profiles in the cell lines were observed in the supernatant and in the exosomal fractions. Conclusions: Prostate cancer cell lines with different phenotypes have different chemokine profiles, both in supernatant and in the exosomal fraction of these cells in culture. These results may be useful for the design of diagnostic, prognostic and/ or therapeutic strategies.
    AACR Annual Meeting 2014, San Diego; 04/2014
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    ABSTRACT: Thyroid cancer is the most common endocrine-related cancer in the United States and its incidence is rising rapidly. Since among various genetic lesions identified in thyroid cancer, the BRAFV600E mutation is found in 50% of papillary thyroid cancers and 25% of anaplastic thyroid cancers, this mutation provides an opportunity for targeted drug therapy. Our laboratory evaluated cellular phenotypic effects in response to treatment with PLX4032, a BRAFV600E-specific inhibitor, in normal BRAF-wild-type thyroid cells and in BRAFV600E-positive papillary thyroid cancer cells. Normal BRAF-wild-type thyroid cells and BRAFV600E-mutated papillary thyroid cancer cells were subjected to proliferation assays and analyzed for cell death by immunofluorescence. Cell cycle status was determined using an EdU uptake assay followed by laser scanning cytometry. In addition, expression of proteins within the MAPK signal transduction pathway was analyzed by Western blot. PLX4032 has potent anti-proliferative effects selectively in BRAF-mutated thyroid cancer cells. These effects appear to be mediated by the drug's activity of inhibiting phosphorylation of signaling molecules downstream of BRAF within the pro-survival MAPK pathway. Interestingly, PLX4032 promotes the phosphorylation of these signaling molecules in BRAF-wild-type thyroid cells. These findings support further evaluation of combinational therapy that includes BRAFV600E inhibitors in thyroid cancer patients harboring the BRAFV600E mutation.
    BMC Research Notes 03/2014; 7(1):187. DOI:10.1186/1756-0500-7-187
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    ABSTRACT: Estrogen aids in neo-vascularization of various tumors during hypoxic conditions, however the role of estrogen within the hypoxic environment of thyroid cancer is not known. In a series of experimentations, using human thyroid cancer cells, we observed that estrogen and hypoxia modulate the hypoxia inducible factor-1 (HIF-1) signaling which is abrogated by the anti-estrogen fulvestrant and the HIF-1 inhibitor YC-1 (3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole). Furthermore, we found that the conditioned medium from estrogen treated thyroid cancer cells lead to enhanced migration and tubulogenesis of human umbilical vein endothelial cells (HUVECs) which is abrogated by HIF-1 inhibitor. These findings, in addition to our previous and other scientific literature data, lead us to conclude that estrogen and hypoxia are interlinked in thyroid cancer and can equally modulate epithelial-endothelial cell interactions by mediating key cellular, metabolic and molecular processes of thyroid cancer progression. We believe that the hormonal component and cellular adaptation to oxygen tension of cancer cells are functionally equivalent with a cellular transition that can be exploited clinically for a combinational approach for thyroid cancer treatment involving antiestrogens as well as anti-hypoxic agents.
    Current Medicinal Chemistry 12/2013; DOI:10.2174/0929867321666131201142434 · 3.72 Impact Factor
  • K. Wong, N. A. Patel, J. Geliebter, E. J. Shin
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    ABSTRACT: Objectives: Thyroid cancer is the most common endocrine malignancy in the United States. The objective of this study was to examine regional trends in thyroid cancer in New York (NY) and compare results with national trends in the Surveillance, Epidemiology, and End Results (SEER) database.
    Otolaryngology Head and Neck Surgery 08/2013; 149(2 Suppl):P150-P150. DOI:10.1177/0194599813496044a25 · 1.72 Impact Factor
  • Cancer Research 08/2013; 73(8 Supplement):1048-1048. DOI:10.1158/1538-7445.AM2013-1048 · 9.28 Impact Factor
  • Cancer Research 08/2013; 73(8 Supplement):3559-3559. DOI:10.1158/1538-7445.AM2013-3559 · 9.28 Impact Factor
  • Cancer Research 08/2013; 73(8 Supplement):96-96. DOI:10.1158/1538-7445.AM2013-96 · 9.28 Impact Factor
  • Cancer Research 08/2013; 73(8 Supplement):2829-2829. DOI:10.1158/1538-7445.AM2013-2829 · 9.28 Impact Factor
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    ABSTRACT: Development of a melanoma-specific vaccine is of clinical necessity. Therefore, a phase III, randomized, double-blind trial was performed (June 1988-June 1991) to assess the clinical effectiveness of our vaccinia melanoma oncolysate (VMO) vaccine in stage III melanoma patients. Patient data were collected from 11 institutions, as well as from the Social Security Death Index and were analyzed from April through August 2008 for disease-free interval (DFI) and overall survival (OS). The median OS for patients who were administered the VMO vaccine was 7.71 years, compared to 7.95 years for patients administered the vaccinia virus vaccine (V) (p=0.70). The median DFI for the VMO group was six years, while the median DFI for the V group has not yet been reached. This analysis demonstrated a statistically significant difference in OS in females in both groups (VMO, 79%; V, 92%), as compared to males (VMO, 57%; V, 68%) (p=0.0473). This follow-up analysis demonstrated that females had a survival advantage over males, thus warranting further investigation. This significant observation may facilitate the recruitment of patients for future clinical trials, as well as determine which patients are more likely to benefit from receiving the VMO vaccine.
    Molecular and Clinical Oncology 05/2013; 1(3):466-472. DOI:10.3892/mco.2013.97
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    ABSTRACT: Background: Prostate cancer (PCa) is the second most common worldwide neoplasm in men [1]. Proliferative inflammatory atrophy (PIA) is proposed as a "risk factor lesion" as it has an important inflammatory component and the associated oxidative stress has been suggested to have a role in prostatic carcinogenesis [2,3] Objectives: To determine correlations between pathological findings of inflammation and proliferative inflammatory atrophy (PIA), in prostate biopsy specimens and to compare their prevalence in biopsies with and without prostate adenocarcinoma. Methods: A prospective study was conducted between December 2010 and June 2012 in the Hospital Universitario del Caribe, Cartagena, Colombia. Patients referred for transrectal ultrasound-guided prostate needle biopsy for suspected PCa were invited to participle and signed an informed consent. Initial prostate biopsies were examined for the presence of PCa, chronic inflammation and atrophy. The inflammation was scored for grade, localization and extension using the classification system of the CPCRN and IPCN consensus [4]. Atrophy was classified according to "Working Group Classification of Focal Prostate Atrophy Lesions" [5], and grade of atrophy was graduated using categories described by Postma [6]. For statistical analysis we compared parameters between groups with and without PCa. This study was approved for the Ethical Review Board of the participating institutions. Results: 97 patients were included, between the ages of 47 and 87 years (mean age: 68.32, SD: 8.9). Adenocarcinoma was identified in 50 of the 97 (51.5%) biopsies examined. There was a significant age difference between the PCa and benign groups (p=0.0031) and PSA levels were significantly higher in patients with cancer. Inflammation was detected in 95.87% of biopsies. Inflammation grade was significantly different between PCa and benign samples (p=0.038) but extension and localization of inflammation was not different between the groups. PIA was observed in 61 cases (62.8%) of which 23 had PCa. Atrophy grade and type were not different between groups and simple atrophy was the most frequently observed type. Morphological transition PIA-HGPIN was significantly more frequent in PCa group (p=0.0002) Conclusions: Our data provide evidence for a role of PIA as a PCa precursor lesion as we observed a strong association between morphological transition PIA-HGPIN and PCa. As inflammation was observed in the vast majority of patient samples, our analysis did not detect an association with PCa. Likewise, a clear association between atrophy and PCa was not observed.
    Cancer Research 04/2013; 73(8). DOI:10.1158/1538-7445.AM2013-2870 · 9.28 Impact Factor
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    ABSTRACT: Background: Metastatic spread poses the greatest challenge for the management of Prostate Cancer (PCa). Although its frequency at diagnosis of PCa cases is only 4%, it is associated with poor prognosis, with five year survival rates of only 30%. Molecular mechanisms involved in metastatic progression are not completely understood; however, it has been noted that chemokines and their receptors play a key role in the establishment of metastatic lesions. Objective: To compare the mRNA expression profiles of chemokines and their receptors in two human PCa cell lines with different metastatic phenotypes (LNCaP, PC-3) and in a control, normal prostate epithelial cell line (PWR-1E). Methods: We evaluated the expression profiles at the transcript level of chemokines and their receptors in LNCaP, PC-3 and PWR-1E human cell lines using a commercial primer panel (Chemokines SensiMix qPCR Primers Panel©,Origene Technologies), as well as a custom primer panel. The relative quantification of gene expression was determined using the {Delta}{Delta}Ct method with the normal PWR-1E cell line as the reference cell line and normalizing the expression to β-actin, HPRT1 and GAPDH housekeeping genes. Results: Sixteen gene transcripts were overexpressed in PC-3, 13 of which were exclusively overexpressed in this cell line and 3 other genes were up-regulated in both PC-3 and LNCaP cell lines. Of the 13 genes overexpressed in PC-3, 12 were found under-expressed in LNCaP cell line, compared to PWR-1E (CCL2, CCL26, CCL28, CXCL2, CXCL3, CXCL4, CXCL4V1, CXCL6, IL8, CXCL12, CCR10, and CCRL2). Chemokine transcript under-expression was more frequently found in LNCaP than in PC-3 (11 vs 8) and transcripts for genes CCL3, CCL3L1, CCL3L3, CCL27 and DARC were underexpressed in both cell lines. Discussion: Here we describe the differential chemokine expression profile between PCa cell lines with different metastatic potentials. In addition to chemokines/receptors known to play a role in PCa, we have identified the differential expression of chemokine gene transcripts not previously associated with PCa. Conclusions: Differential chemokine expression at the mRNA level was found in association with metastatic phenotypes of PCa cell lines. Additional research is needed to determine mechanisms involved in genic regulation of this profiles and to determine their roles in tumorigenesis and cancer progression in the prostate.
    Cancer Research 04/2013; 73(8). DOI:10.1158/1538-7445.AM2013-2691 · 9.28 Impact Factor
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    ABSTRACT: Transformation of the pigment producing melanocytes into melanoma is a complex multi-step process involving the enhanced expression of various antigens considered as immunotherapeutic targets. Significant progress in melanoma research has been made over the years and has resulted in the identification of various antigens over expressed in melanoma as well as advances in immunotherapeutic treatments, which focus on modulating the immune systems response to melanoma. Despite these advances, incidences of melanoma are still on the rise thus warranting additional research in identifying new therapeutic treatments. Our focus is on developing a multivalent immunotherapeutic vaccine that targets various melanoma associated antigens. The approach focuses on the use of five primary patient derived melanoma cells (MEL-2, MEL-V, 3MM, KFM, and GLM-2, which have been characterized in this study. These cells express differential amounts of various melanoma associated antigens such as MART-1, gp100 (Pmel17), MAGE-A1 and tyrosinase as well a cell surface antigens essential for melanoma cell metastasis, such as CD146 and CD71. In addition these cells display differential in vitro migratory and invasive properties as well as have the ability to form solid tumors when implanted into BALB/c nude mice. The retention of the innate phenotype of these primary patient derived cells together with the expression of a multitude repertoire of melanoma associated antigens offers a novel opportunity to target melanoma so as to avoid immune evasion.
    01/2013; 4(5):371-82. DOI:10.7150/jca.6625
  • Cancer Research 06/2012; 72(8 Supplement):1520-1520. DOI:10.1158/1538-7445.AM2012-1520 · 9.28 Impact Factor
  • Cancer Research 06/2012; 72(8 Supplement):1569-1569. DOI:10.1158/1538-7445.AM2012-1569 · 9.28 Impact Factor