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Search Results: 1 - 10 of 500 matches for " Marvin Rubenstein "
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Following Inhibition of BCL-2 by Antisense Oligonucleotides Compensatory Suppression of Apoptosis Involves the Direct Signal Transduction Pathway of LNCaP Cells  [PDF]
Marvin Rubenstein, Courtney M. P. Hollowell, Patrick Guinan
Open Journal of Apoptosis (OJApo) , 2015, DOI: 10.4236/ojapo.2015.41001
Abstract: Previously we have shown that when LNCaP cells are treated with antisense oligonucleotides (oligos) directed against BCL-2, compensatory changes in non-targeted genes take place in attempts to restore apoptosis and promote tumor aggressiveness. In addition to the inhibition of BCL-2, we find that the apoptosis promoter caspase-3 activity is suppressed, the transcription activity of STAT-3 is enhanced, while other regulators (bax, clusterin, AKT-1) associated with mitochondrial regulated apoptosis and caspase cascade are either unchanged or undetectable. We now evaluate proteins associated with the second pathway of apoptosis activation mediated by direct signal transduction involving fas, fas-ligand (a tumor necrosis factor-like cell surface receptor aka CD95), as well as the similar programmed death cell surface receptor (PD-1) and its respective ligand (PD-1L). This study evaluates the growth inhibition of in vitro propagating LNCaP cells employing mono- and bispecific oligos directed against BCL-2 [the second binding site was directed against the epidermal growth factor receptor (EGFR)]; and employing RT-PCR. The expression of these four proteins was evaluated. Expression of fas-ligand, PD-1 and PD-L1 were all significantly enhanced, whereas fas itself was undetectable. This suggests that in addition to pathways associated with the mitochondrial pathway of apoptosis, compensatory changes occur in the direct signal transduction pathway of this process. In addition to alterations in androgen sensitivity, growth factor expression and oncogene expression, these data suggest that suppressive BCL-2 therapy involves multiple pathways, including those involved with immune targeting and cytotoxicity and must be taken into account to make gene therapy more efficacious.
Altered Oncogene Activity Contributes to Compensation for Antisense Suppression of Bcl-2 and Tumor Resistance  [PDF]
Marvin Rubenstein, Courtney M. P. Hollowell, Patrick Guinan
Open Journal of Apoptosis (OJApo) , 2015, DOI: 10.4236/ojapo.2015.43007
Abstract: Antisense oligonucleotides (oligos) have targeted growth regulatory proteins in prostate cancer models. To identify compensatory alterations in the expression of non-targeted genes we evaluate mono- and bispecific oligos targeting and equally suppressing the expression of the apoptosis inhibitory protein bcl-2. Bcl-2 is chosen because oligos directed towards it have entered clinical trials to restore apoptosis in cancer patients. Treated LNCaP cells compensate for the diminished bcl-2 by suppressing caspase-3 (an apoptosis promoter) while enhancing expression of AKT-1 (another apoptosis inhibitor), androgen receptor (AR) and its (p300 and IL-6) coactivators. Additional proteins are enhanced including PD-1, its ligand PD-L1 (immune checkpoint blockade markers) and fas-ligand, which activate apoptosis through the signal transduction, along with suppressor protein p53, polymerase transcription mediator MED-12 and signal transducer STAT-3. These alterations in expression may contribute to a greatly enhanced expression of the proliferation marker KI-67. This suggests that therapeutic approaches to restore apoptosis through suppression of bcl-2 lead to an altered expression in non-targeted genes involving apoptosis, androgen sensitivity, transcriptional activity and immune responsiveness, leads to an increase in proliferation (and a more androgen driven aggressive phenotype). In this study we evaluate the expression of two oncogenes (v-myc and K-ras) and find a large and significant enhancement of v-myc activity, which is produced by oligos targeting bcl-2 at the 5’ position. For K-ras, although significant suppression is produced by the bispecific targeting bcl-2 at the 3’ position, the percent change is relatively small compared with other compensatory alterations we have measured, and much less than in v-myc. Therefore, for the two oncogenes being evaluated, only increased v-myc activity is probably large enough to contribute to increased tumor aggressiveness in compensation for bcl-2 suppression.
Correlation Between PSMA and VEGF Expression as Markers for LNCaP Tumor Angiogenesis
Paulus Tsui,Marvin Rubenstein,Patrick Guinan
Journal of Biomedicine and Biotechnology , 2005, DOI: 10.1155/jbb.2005.287
Abstract: Our aim is the identification and correlation of changes in tumor-associated protein expression which results from therapy. LNCaP tumors, excised from nude mice treated either by orchiectomy or with the chemotherapeutic agent paclitaxel, were evaluated for the expression of proteins and receptors associated with growth, differentiation, and angiogenesis using immunohistologic procedures. Compared to untreated control tumors, both treatments reduced the expression of vascular endothelial growth factor (VEGF), prostate-specific membrane antigen (PSMA), prostate-specific antigen (PSA), androgen receptor (AR), and epidermal growth factor receptor (EGFR). The effect of paclitaxel treatment on AR expression was the most significant (P=.005). Of particular interest was identifying a significant correlation (P<.000801) between PSMA and VEGF expression regardless of treatment modality. These altered expressions suggest that PSMA may also be a marker for angiogenesis and could represent a target for deliverable agents recognizing either prostatic tumors or endothelial development. Cell surface PSMA would then present a unique target for treatment of patients early in their development of prostatic metastases.
Correlation Between PSMA and VEGF Expression as Markers for LNCaP Tumor Angiogenesis
Tsui Paulus,Rubenstein Marvin,Guinan Patrick
Journal of Biomedicine and Biotechnology , 2005,
Abstract: Our aim is the identification and correlation of changes in tumor-associated protein expression which results from therapy. LNCaP tumors, excised from nude mice treated either by orchiectomy or with the chemotherapeutic agent paclitaxel, were evaluated for the expression of proteins and receptors associated with growth, differentiation, and angiogenesis using immunohistologic procedures. Compared to untreated control tumors, both treatments reduced the expression of vascular endothelial growth factor (VEGF), prostate-specific membrane antigen (PSMA), prostate-specific antigen (PSA), androgen receptor (AR), and epidermal growth factor receptor (EGFR). The effect of paclitaxel treatment on AR expression was the most significant ( P = .005 ) . Of particular interest was identifying a significant correlation ( P < .000801 ) between PSMA and VEGF expression regardless of treatment modality. These altered expressions suggest that PSMA may also be a marker for angiogenesis and could represent a target for deliverable agents recognizing either prostatic tumors or endothelial development. Cell surface PSMA would then present a unique target for treatment of patients early in their development of prostatic metastases.
A law of nature?  [PDF]
Marvin Chester
Open Journal of Ecology (OJE) , 2011, DOI: 10.4236/oje.2011.13011
Abstract: Is there an overriding principle of nature, hitherto overlooked, that governs all population behavior? A single principle that drives all the regimes observed in nature exponential-like growth, saturated growth, population decline, population extinction, oscillatory behavior? In current orthodox population theory, this diverse range of population behaviors is described by many different equations each with its own specific justification. The signature of an overriding principle would be a differential equation which, in a single statement, embraces all the panoply of regimes. A candidate such governing equation is proposed. The principle from which the equation is derived is this: The effect on the environment of a population’s success is to alter that environment in a way that opposes the success.
La conversión de los shuar
Rubenstein , Steve
Iconos : Revista de Ciencias Sociales , 2005,
Abstract:
Coping with cannabis in a Caribbean country : from problem formulation to going public
Hymie Rubenstein
New West Indian Guide , 1998,
Abstract: Analyzes the dialectic between problem discovery and formulation, ethical considerations, and the public dissemination of research results. Author describes his personal experience of fieldwork, the moral-ethical dilemmas it involved, and the circulation of research findings on cannabis production and consumption in St. Vincent. He became frustrated that his academic publications were only accessible to a tiny portion of St. Vincent's population and therefore decided to publish about cannabis in the local media.
Re-Assessment of PrPSc Distribution in Sporadic and Variant CJD
Richard Rubenstein, Binggong Chang
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0066352
Abstract: Human prion diseases are fatal neurodegenerative disorders associated with an accumulation of PrPSc in the central nervous system (CNS). Of the human prion diseases, sporadic Creutzfeldt-Jakob disease (sCJD), which has no known origin, is the most common form while variant CJD (vCJD) is an acquired human prion disease reported to differ from other human prion diseases in its neurological, neuropathological, and biochemical phenotype. Peripheral tissue involvement in prion disease, as judged by PrPSc accumulation in the tonsil, spleen, and lymph node has been reported in vCJD as well as several animal models of prion diseases. However, this distribution of PrPSc has not been consistently reported for sCJD. We reexamined CNS and non-CNS tissue distribution and levels of PrPSc in both sCJD and vCJD. Using a sensitive immunoassay, termed SOFIA, we also assessed PrPSc levels in human body fluids from sCJD as well as in vCJD-infected humanized transgenic mice (Tg666). Unexpectedly, the levels of PrPSc in non-CNS human tissues (spleens, lymph nodes, tonsils) from both sCJD and vCJD did not differ significantly and, as expected, were several logs lower than in the brain. Using protein misfolding cyclic amplification (PMCA) followed by SOFIA, PrPSc was detected in cerebrospinal fluid (CSF), but not in urine or blood, in sCJD patients. In addition, using PMCA and SOFIA, we demonstrated that blood from vCJD-infected Tg666 mice showing clinical disease contained prion disease-associated seeding activity although the data was not statistically significant likely due to the limited number of samples examined. These studies provide a comparison of PrPSc in sCJD vs. vCJD as well as analysis of body fluids. Further, these studies also provide circumstantial evidence that in human prion diseases, as in the animal prion diseases, a direct comparison and intraspecies correlation cannot be made between the levels of PrPSc and infectivity.
Molecular Chaperones as Targets to Circumvent the CFTR Defect in Cystic Fibrosis
Ronald C. Rubenstein
Frontiers in Pharmacology , 2012, DOI: 10.3389/fphar.2012.00137
Abstract: Cystic Fibrosis (CF) is the most common autosomal recessive lethal disorder among Caucasian populations. CF results from mutations and resulting dysfunction of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). CFTR is a cyclic AMP-dependent chloride channel that is localized to the apical membrane in epithelial cells where it plays a key role in salt and water homeostasis. An intricate network of molecular chaperone proteins regulates CFTR’s proper maturation and trafficking to the apical membrane. Understanding and manipulation of this network may lead to therapeutics for CF in cases where mutant CFTR has aberrant trafficking.
Superflares and Giant Planets
Eric P Rubenstein
Physics , 2001, DOI: 10.1511/2001.1.38
Abstract: Stellar flares 100-10^7 times more energetic than the most powerful solar flares have been detected from 9 normal F and G main sequence stars (Schaefer, King & Deliyannis 2000). Although these stars are not in close binary systems, their superflares show a remarkable similarity to the large stellar flares observed on RS Canum Venaticorum binary systems. Such flares are caused by magnetic reconnection events associated with the tangling of magnetic fields between the two stars. The superflare stars are certainly not of this class, although the mechanism may be similar. The superflares may be caused by magnetic reconnection between fields of the primary star and a close-in Jovian planet. This scenario explains the energies, durations, and spectra of superflares, as well as explain why our Sun does not have such events. Only known planetary properties and reconnection scenarios are required by this mechanism.
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