Marvin Rubenstein - Academia.edu (original) (raw)

Papers by Marvin Rubenstein

Research paper thumbnail of Effect of Antisense Oligonucleotides Directed Against BCL-2 on Immunotherapy Markers PD-1, PD-L1 and CDK-12 IN LNCaP Cells - A Human Derived Prostate Cancer Line Likely Susceptible to Immunotherapy is Altered by Treatment

Cancer science & research, 2019

Research paper thumbnail of In LNCaP cells enhanced expression of the androgen receptor compensates for Bcl-2 suppression by antisense oligonucleotides

Therapeutic Advances in Urology, Mar 24, 2011

Research paper thumbnail of Increased expression of the androgen receptor with p300 and interleukin-6 coactivators compensate for oligonucleotide suppression of bcl-2: no increased CREB binding protein or interleukin-4 expression

Therapeutic Advances in Urology, Nov 8, 2012

Research paper thumbnail of Synthesis of branched antisense oligonucleotides having multiple specificities

Research paper thumbnail of siRNA directed against EGFR has comparable efficacy to a first generation antisense oligonucleotide in combination therapy against the PC-3 prostate tumor line

Cancer Research, May 1, 2005

Research paper thumbnail of Treatment of MCF-7 breast cancer cells with mono- and bispecific antisense oligonucleotides

Journal of Clinical Oncology, May 20, 2008

14660 Background: Antisense against TGF-α (MR1) and EGFR (MR2), is efficacious against UACC 897 b... more 14660 Background: Antisense against TGF-α (MR1) and EGFR (MR2), is efficacious against UACC 897 breast, PC-3 and LNCaP prostate, and T98G glioblastoma tumors in vitro and in vivo, and oligos agains...

Research paper thumbnail of Effect of Tumor Necrosis Factor on a Prostate Tumor Model

Elsevier eBooks, 1987

ABSTRACT Copenhagen X Fischer F1 rats bearing palpable Dunning R3327 MAT-LyLu prostatic adenocarc... more ABSTRACT Copenhagen X Fischer F1 rats bearing palpable Dunning R3327 MAT-LyLu prostatic adenocarcinomas were treated by intraperitoneal (I.P.) intratumor (I.T.) injection with either human serum albumin (HuSA) alone or in combination with recombinant tumor necrosis factor (rTNF). The dose administered (30 mg) was previously determined to be the maximum amount tolerated with minimal toxicity. At weekly intervals tumors were measured and survivals noted. Those treated I.T. with rTNF survived significantly longer and ultimately developed significantly smaller tumors than untreated controls. Those groups administered rTNF by the I.P. route had less statistically significant increases in survival when compared to the I.T. route of therapy.

Research paper thumbnail of Oligonucleotide suppression of bcl-2 in LNCaP cells is compensated by increased androgen sensitivity, p53 and oncogene activity, and suppressed caspase-3

Medical Oncology, May 16, 2013

Research paper thumbnail of Differentiated prostatic antigen expression in LNCaP cells following treatment with bispecific antisense oligonucleotides directed against BCL-2 and EGFR

Medical Oncology, May 15, 2011

Research paper thumbnail of Inhibition of BCL-2 by Antisense Oligonucleotides is Followed by a Compensatory Suppression of Caspase-3 in LNCaP Cells

Research paper thumbnail of Combination therapy using polyamine synthesis inhibitor alpha-difluoromethylornithine and adriamycin in treatment of rats carrying the dunning R3327 MAT-LyLu prostatic adenocarcinoma

The Prostate, 1987

Prostate cells of human and rat origin produce polyamines in high content, whose apparent functio... more Prostate cells of human and rat origin produce polyamines in high content, whose apparent functions relate to cellular proliferation and secretory activities. Formation is dependent on the enzyme ornithine decarboxylase (ODC) which is irreversibly inhibited by alpha‐difluoromethylomithine (DFMO). It has been postulated that pretreatment with DFMO may render cells more susceptible to subsequent chemotherapy. Copenhagen X Fischer F1 rats bearing the Dunning R3327 MAT‐LyLu prostatic adenocarcinoma were given DFMO or adriamycin (ADR), alone or in combination. Those receiving DFMO were continuously provided the drug ad libitum, in water (2.5 %), for the duration of the experiment, beginning 2 days prior to ADR administration. At intervals, tumor sizes were measured, animal survivals noted and comparisons made to nontreated, tumor‐bearing controls. The results indicate that ADR alone or in combination with DFMO significantly reduced tumor progression, but that only combination therapy significantly prolonged survivals. Decreased tumor progression produced by DFMO alone was not statistically significant. Differences produced with combined use were additive and suggest that DFMO may augment ADR chemotherapy.

Research paper thumbnail of Treatment of prostate and breast tumors employing mono- and bi-specific antisense oligonucleotides targeting apoptosis inhibitory proteins clusterin and bcl-2

Medical Oncology, Jun 16, 2009

Antisense oligonucleotides (oligos) have demonstrated their efficacy in inhibiting the growth of ... more Antisense oligonucleotides (oligos) have demonstrated their efficacy in inhibiting the growth of prostate and breast tumor cells. Previous studies employed first generation, phosphorothioated, cDNA oligos synthesized complimentary to mRNA encoding transforming growth factor-alpha (TGF-alpha), epidermal growth factor receptor (EGFR), the anti-apoptosis protein bcl-2, and the androgen receptor (AR). In an effort to construct oligos with greater than one mRNA binding site, bi-specifics have been developed which target combinations of the above proteins, and these have been shown at least as effective as the mono-specific oligos from which their sequences were derived. While all bi-specifics have inhibitory effects, which can be enhanced by the combined administration of an additional chemotherapeutic agent, those bi-specifics which target bcl-2 and EGFR were reported to be the most effective. The experiments presented here are an effort to evaluate a new group of bi-specifics whose targets include the chaperone protein clusterin, whose expression is up regulated in many tumors and activity is known to inhibit apoptosis. Of particular interest were those bi-specifics constructed to target both clusterin and bcl-2 (also an apoptosis inhibitory protein). Cell lines targeted included both prostate LNCaP and PC-3, as well as the breast derived MCF-7. In order to identify agents which enhance oligo activity, but contribute less toxicity, oligos were tested both alone and in combination with either the immune inhibitor Rapamycin, or the chemotherapeutic (and more toxic) Taxol. Results indicate that bi-specifics targeting clusterin are statistically effective, and are similarly enhanced by Rapamycin, or Taxol. When bi-specifics including clusterin as a target, were tested against LNCaP and MCF-7 cells, the level of activity was intermediate between that of the mono-specific compounds tested separately. In experiments which compared both, bi-specifics which included a target for clusterin had inhibitory activity similar to the previously described bi-specifics directed towards bcl-2 and EGFR.

Research paper thumbnail of The effect of androgen deprivation on malignant and benign prostate tissue

Medical Oncology, Sep 1, 1997

Research paper thumbnail of In vivo establishment of T98G human gliobastoma

Methods and Findings in Experimental and Clinical Pharmacology, 1999

ABSTRACT Human derived T98G glioblastoma has long been utilized as an in vitro model for epiderma... more ABSTRACT Human derived T98G glioblastoma has long been utilized as an in vitro model for epidermal growth factor receptor (EGFR)-mediated growth regulation. Recently, T98G has been employed to develop new types of therapy directed at limiting EGFR expression such as by administration of antisense oligonucleotides directed against EGFR encoding mRNA. A major limitation to extending this model for in vivo application is that T98G implanted s.c. or intracerebrally has been reported not to grow in nude mice. In an effort to extend this model to permit in vivo studies, we evaluated the use of Matrigel and orthotopic (intracranial) implantation techniques. When equal volumes of Matrigel were mixed with T98G cell suspensions, tumors developed at both flank and orthotopic locations. Four groups of nude mice were inoculated into the flanks with either 10(5), 10(6), 4 x 10(6) or 10(7) T98G cells in a 150 microliters total volume with Matrigel. In 1/5, 3/5, 1/5 and 1/3 mice receiving 10(5), 10(6), 4 x 10(6) and 10(7) cells, respectively, tumors developed 11, 15, 15 and 15 weeks, respectively, following inoculation. Out of 4 mice inoculated orthotopically (intracranially into the frontal lobe) with only 4 x 10(4) cells and Matrigel, 2 developed tumors. However, all mice (4/4) inoculated orthotopically with 4 x 10(5) cells in a 10 microliters total volume with Matrigel developed tumors. Two were identified histologically following a scheduled sacrifice at 36 and 60 days and two more at 103 and 118 days after sacrifice following abnormal behavior. The best tumor establishment efficacy combined orthotopic implantation of 4 x 10(5) T98G cells with Matrigel. These techniques permit the use of T98G glioblastoma as an in vivo model for new forms of therapy.

Research paper thumbnail of An evaluation of the markers p53 and Ki-67 for their predictive value in prostate cancer

Journal of Surgical Oncology, 1998

p53 and Ki-67 are but two markers being evaluated for their predictive value in prostate cancer. ... more p53 and Ki-67 are but two markers being evaluated for their predictive value in prostate cancer. The purpose of this study was to compare p53 and Ki-67 with age, stage, Gleason score, and ploidy for their prognostic abilities in prostate cancer. Prostate cancer specimens from 134 patients were immunohistochemically stained for p53 and Ki-67 expression and differences evaluated by SPSS analysis of variance (ANOVA) methods. The dependent variable was patient survival and the independent variables were age, stage, Gleason score, and ploidy. In decreasing order of prediction of survival were stage (P < 0.001), Gleason score (P < 0.001), age (P = 0.1869), Ki-67 (P = 0.2284), p53 (P = 0.4282) and ploidy (P = 0.8141). It is concluded that stage and Gleason score are significant predictors of survival while p53, Ki-67, age and ploidy are not.

Research paper thumbnail of Involvement of compensatory CD44+ stem cells following BCL-2 suppression by antisense oligonucleotides

Journal of Clinical Oncology, May 20, 2013

2590 Background: Gene therapy is in theory specific but encounters difficulties in practice. Suit... more 2590 Background: Gene therapy is in theory specific but encounters difficulties in practice. Suitable targets are found in many pathways and tumors do express altered patterns of expression. However the actual activity of most regulatory genes are similar to normal. Resistance develops because biochemical pathways are complex, regulated by stimulatory and inhibitory factors, each possibly affected by therapy. It’s suggested that tumors alter dependence on targeted gene products for growth by relying upon others, through compensation. Antisense oligos have targeted regulatory proteins in both in vivo and in vitro prostate cancer models. Cells treated with antisense directed against bcl-2 compensated by suppressing caspase-3 (an apoptosis promoter) and enhancing androgen receptor (AR), (co-activating) p300 and IL-6 expression. This suggests that in LNCaP a progression to increased androgen sensitivity accompanies bcl-2 suppression with a pattern of co-activation associated with more advanced prostate tumors. Methods: We evaluated mono- and bispecific oligos which targeted and equally suppressed bcl-2 expression in LNCaP cells. To further evaluate compensatory mechanisms related to tumor resistance we evaluated the level of CD44 expression employing RT-PCR and agarose gel quantification. Bands representing pcr product were photographed, converted to black and white and assessed by MIPAV software. Results: Comparable amounts of RNA from LNCaP cells treated with either mono- or bispecific oligos directed against bcl-2 (and EGFR in the bispecifics) were evaluated by RT-PCR using primers directed against CD44. When background intensity was subtracted, the relative intensity of the bands corresponding to CD44, and representing cells treated with MR4, MR24 and MR42 (compared to controls) were respectively increased 3.0% ± 33.6 (NS), suppressed 16.4% ± 49.1 (NS) and suppressed 9.2% ± 26.5 (NS). These results were pooled from both duplicate PCR runs and gels, and indicate no significant changes in CD44 expression was produced by any oligo type. Conclusions: Stem cells expressing this marker were unaffected by treatment, suggesting this population is not altered by suppressive bcl-2 therapy.

Research paper thumbnail of Racial differences in prostate cancer incidence and mortality

Journal of Clinical Oncology, May 20, 2012

e15119 Background: Prostate cancer is the second leading cause of male cancer deaths in the U.S. ... more e15119 Background: Prostate cancer is the second leading cause of male cancer deaths in the U.S. There are significant racial differences in prostate cancer incidence and mortality. Methods: The SEER Database for 2008 was analysed for designated areas: Connecticut, Detroit, and Hawaii, assuming that these areas are surrogates for whites, blacks, and Asians, respectively. Results: Incidence and mortality (see Table). Conclusions: Assuming that the geographic SEER areas (Conn, Det, Ha) are surrogates for whites, blacks, and Oriental populations, we conclude that the incidence and mortality rates for blacks are higher than those for whites and Orientals. [Table: see text]

Research paper thumbnail of Ethnic belief differences in the incidence and mortality of prostate cancer

Journal of Clinical Oncology, May 20, 2014

e16108 Background: One of the leading causes of male death worldwide is prostate cancer. Although... more e16108 Background: One of the leading causes of male death worldwide is prostate cancer. Although many databases evaluate disease incidence, mortality and diverse contributory influences, few evalu...

Research paper thumbnail of Compensatory regulatory mechanisms that restore apoptosis following bcl-2 suppression

Journal of Clinical Oncology, May 20, 2014

e13536 Background: Gene therapy, in theory, is specific. However, in practice, it encounters diff... more e13536 Background: Gene therapy, in theory, is specific. However, in practice, it encounters difficulties. In the apoptosis pathway there are many regulatory proteins which either promote or inhibi...

Research paper thumbnail of Immunopriming of Tumor Infiltrating Lymphocytes with Neoadjuvant Cyclophosphamide

Immunological Investigations, 1993

Tumor infiltrating lymphocytes (TIL) are increasingly employed in immunotherapy protocols. When m... more Tumor infiltrating lymphocytes (TIL) are increasingly employed in immunotherapy protocols. When modified and expanded they can be utilized in new therapeutic protocols. TIL augmentation can be in vitro and in vivo. The purpose of this article is to review the various methods of TIL augmentation and report our experience with a neoadjuvant technique of cyclophosphamide immunopriming of TILs.

Research paper thumbnail of Effect of Antisense Oligonucleotides Directed Against BCL-2 on Immunotherapy Markers PD-1, PD-L1 and CDK-12 IN LNCaP Cells - A Human Derived Prostate Cancer Line Likely Susceptible to Immunotherapy is Altered by Treatment

Cancer science & research, 2019

Research paper thumbnail of In LNCaP cells enhanced expression of the androgen receptor compensates for Bcl-2 suppression by antisense oligonucleotides

Therapeutic Advances in Urology, Mar 24, 2011

Research paper thumbnail of Increased expression of the androgen receptor with p300 and interleukin-6 coactivators compensate for oligonucleotide suppression of bcl-2: no increased CREB binding protein or interleukin-4 expression

Therapeutic Advances in Urology, Nov 8, 2012

Research paper thumbnail of Synthesis of branched antisense oligonucleotides having multiple specificities

Research paper thumbnail of siRNA directed against EGFR has comparable efficacy to a first generation antisense oligonucleotide in combination therapy against the PC-3 prostate tumor line

Cancer Research, May 1, 2005

Research paper thumbnail of Treatment of MCF-7 breast cancer cells with mono- and bispecific antisense oligonucleotides

Journal of Clinical Oncology, May 20, 2008

14660 Background: Antisense against TGF-α (MR1) and EGFR (MR2), is efficacious against UACC 897 b... more 14660 Background: Antisense against TGF-α (MR1) and EGFR (MR2), is efficacious against UACC 897 breast, PC-3 and LNCaP prostate, and T98G glioblastoma tumors in vitro and in vivo, and oligos agains...

Research paper thumbnail of Effect of Tumor Necrosis Factor on a Prostate Tumor Model

Elsevier eBooks, 1987

ABSTRACT Copenhagen X Fischer F1 rats bearing palpable Dunning R3327 MAT-LyLu prostatic adenocarc... more ABSTRACT Copenhagen X Fischer F1 rats bearing palpable Dunning R3327 MAT-LyLu prostatic adenocarcinomas were treated by intraperitoneal (I.P.) intratumor (I.T.) injection with either human serum albumin (HuSA) alone or in combination with recombinant tumor necrosis factor (rTNF). The dose administered (30 mg) was previously determined to be the maximum amount tolerated with minimal toxicity. At weekly intervals tumors were measured and survivals noted. Those treated I.T. with rTNF survived significantly longer and ultimately developed significantly smaller tumors than untreated controls. Those groups administered rTNF by the I.P. route had less statistically significant increases in survival when compared to the I.T. route of therapy.

Research paper thumbnail of Oligonucleotide suppression of bcl-2 in LNCaP cells is compensated by increased androgen sensitivity, p53 and oncogene activity, and suppressed caspase-3

Medical Oncology, May 16, 2013

Research paper thumbnail of Differentiated prostatic antigen expression in LNCaP cells following treatment with bispecific antisense oligonucleotides directed against BCL-2 and EGFR

Medical Oncology, May 15, 2011

Research paper thumbnail of Inhibition of BCL-2 by Antisense Oligonucleotides is Followed by a Compensatory Suppression of Caspase-3 in LNCaP Cells

Research paper thumbnail of Combination therapy using polyamine synthesis inhibitor alpha-difluoromethylornithine and adriamycin in treatment of rats carrying the dunning R3327 MAT-LyLu prostatic adenocarcinoma

The Prostate, 1987

Prostate cells of human and rat origin produce polyamines in high content, whose apparent functio... more Prostate cells of human and rat origin produce polyamines in high content, whose apparent functions relate to cellular proliferation and secretory activities. Formation is dependent on the enzyme ornithine decarboxylase (ODC) which is irreversibly inhibited by alpha‐difluoromethylomithine (DFMO). It has been postulated that pretreatment with DFMO may render cells more susceptible to subsequent chemotherapy. Copenhagen X Fischer F1 rats bearing the Dunning R3327 MAT‐LyLu prostatic adenocarcinoma were given DFMO or adriamycin (ADR), alone or in combination. Those receiving DFMO were continuously provided the drug ad libitum, in water (2.5 %), for the duration of the experiment, beginning 2 days prior to ADR administration. At intervals, tumor sizes were measured, animal survivals noted and comparisons made to nontreated, tumor‐bearing controls. The results indicate that ADR alone or in combination with DFMO significantly reduced tumor progression, but that only combination therapy significantly prolonged survivals. Decreased tumor progression produced by DFMO alone was not statistically significant. Differences produced with combined use were additive and suggest that DFMO may augment ADR chemotherapy.

Research paper thumbnail of Treatment of prostate and breast tumors employing mono- and bi-specific antisense oligonucleotides targeting apoptosis inhibitory proteins clusterin and bcl-2

Medical Oncology, Jun 16, 2009

Antisense oligonucleotides (oligos) have demonstrated their efficacy in inhibiting the growth of ... more Antisense oligonucleotides (oligos) have demonstrated their efficacy in inhibiting the growth of prostate and breast tumor cells. Previous studies employed first generation, phosphorothioated, cDNA oligos synthesized complimentary to mRNA encoding transforming growth factor-alpha (TGF-alpha), epidermal growth factor receptor (EGFR), the anti-apoptosis protein bcl-2, and the androgen receptor (AR). In an effort to construct oligos with greater than one mRNA binding site, bi-specifics have been developed which target combinations of the above proteins, and these have been shown at least as effective as the mono-specific oligos from which their sequences were derived. While all bi-specifics have inhibitory effects, which can be enhanced by the combined administration of an additional chemotherapeutic agent, those bi-specifics which target bcl-2 and EGFR were reported to be the most effective. The experiments presented here are an effort to evaluate a new group of bi-specifics whose targets include the chaperone protein clusterin, whose expression is up regulated in many tumors and activity is known to inhibit apoptosis. Of particular interest were those bi-specifics constructed to target both clusterin and bcl-2 (also an apoptosis inhibitory protein). Cell lines targeted included both prostate LNCaP and PC-3, as well as the breast derived MCF-7. In order to identify agents which enhance oligo activity, but contribute less toxicity, oligos were tested both alone and in combination with either the immune inhibitor Rapamycin, or the chemotherapeutic (and more toxic) Taxol. Results indicate that bi-specifics targeting clusterin are statistically effective, and are similarly enhanced by Rapamycin, or Taxol. When bi-specifics including clusterin as a target, were tested against LNCaP and MCF-7 cells, the level of activity was intermediate between that of the mono-specific compounds tested separately. In experiments which compared both, bi-specifics which included a target for clusterin had inhibitory activity similar to the previously described bi-specifics directed towards bcl-2 and EGFR.

Research paper thumbnail of The effect of androgen deprivation on malignant and benign prostate tissue

Medical Oncology, Sep 1, 1997

Research paper thumbnail of In vivo establishment of T98G human gliobastoma

Methods and Findings in Experimental and Clinical Pharmacology, 1999

ABSTRACT Human derived T98G glioblastoma has long been utilized as an in vitro model for epiderma... more ABSTRACT Human derived T98G glioblastoma has long been utilized as an in vitro model for epidermal growth factor receptor (EGFR)-mediated growth regulation. Recently, T98G has been employed to develop new types of therapy directed at limiting EGFR expression such as by administration of antisense oligonucleotides directed against EGFR encoding mRNA. A major limitation to extending this model for in vivo application is that T98G implanted s.c. or intracerebrally has been reported not to grow in nude mice. In an effort to extend this model to permit in vivo studies, we evaluated the use of Matrigel and orthotopic (intracranial) implantation techniques. When equal volumes of Matrigel were mixed with T98G cell suspensions, tumors developed at both flank and orthotopic locations. Four groups of nude mice were inoculated into the flanks with either 10(5), 10(6), 4 x 10(6) or 10(7) T98G cells in a 150 microliters total volume with Matrigel. In 1/5, 3/5, 1/5 and 1/3 mice receiving 10(5), 10(6), 4 x 10(6) and 10(7) cells, respectively, tumors developed 11, 15, 15 and 15 weeks, respectively, following inoculation. Out of 4 mice inoculated orthotopically (intracranially into the frontal lobe) with only 4 x 10(4) cells and Matrigel, 2 developed tumors. However, all mice (4/4) inoculated orthotopically with 4 x 10(5) cells in a 10 microliters total volume with Matrigel developed tumors. Two were identified histologically following a scheduled sacrifice at 36 and 60 days and two more at 103 and 118 days after sacrifice following abnormal behavior. The best tumor establishment efficacy combined orthotopic implantation of 4 x 10(5) T98G cells with Matrigel. These techniques permit the use of T98G glioblastoma as an in vivo model for new forms of therapy.

Research paper thumbnail of An evaluation of the markers p53 and Ki-67 for their predictive value in prostate cancer

Journal of Surgical Oncology, 1998

p53 and Ki-67 are but two markers being evaluated for their predictive value in prostate cancer. ... more p53 and Ki-67 are but two markers being evaluated for their predictive value in prostate cancer. The purpose of this study was to compare p53 and Ki-67 with age, stage, Gleason score, and ploidy for their prognostic abilities in prostate cancer. Prostate cancer specimens from 134 patients were immunohistochemically stained for p53 and Ki-67 expression and differences evaluated by SPSS analysis of variance (ANOVA) methods. The dependent variable was patient survival and the independent variables were age, stage, Gleason score, and ploidy. In decreasing order of prediction of survival were stage (P < 0.001), Gleason score (P < 0.001), age (P = 0.1869), Ki-67 (P = 0.2284), p53 (P = 0.4282) and ploidy (P = 0.8141). It is concluded that stage and Gleason score are significant predictors of survival while p53, Ki-67, age and ploidy are not.

Research paper thumbnail of Involvement of compensatory CD44+ stem cells following BCL-2 suppression by antisense oligonucleotides

Journal of Clinical Oncology, May 20, 2013

2590 Background: Gene therapy is in theory specific but encounters difficulties in practice. Suit... more 2590 Background: Gene therapy is in theory specific but encounters difficulties in practice. Suitable targets are found in many pathways and tumors do express altered patterns of expression. However the actual activity of most regulatory genes are similar to normal. Resistance develops because biochemical pathways are complex, regulated by stimulatory and inhibitory factors, each possibly affected by therapy. It’s suggested that tumors alter dependence on targeted gene products for growth by relying upon others, through compensation. Antisense oligos have targeted regulatory proteins in both in vivo and in vitro prostate cancer models. Cells treated with antisense directed against bcl-2 compensated by suppressing caspase-3 (an apoptosis promoter) and enhancing androgen receptor (AR), (co-activating) p300 and IL-6 expression. This suggests that in LNCaP a progression to increased androgen sensitivity accompanies bcl-2 suppression with a pattern of co-activation associated with more advanced prostate tumors. Methods: We evaluated mono- and bispecific oligos which targeted and equally suppressed bcl-2 expression in LNCaP cells. To further evaluate compensatory mechanisms related to tumor resistance we evaluated the level of CD44 expression employing RT-PCR and agarose gel quantification. Bands representing pcr product were photographed, converted to black and white and assessed by MIPAV software. Results: Comparable amounts of RNA from LNCaP cells treated with either mono- or bispecific oligos directed against bcl-2 (and EGFR in the bispecifics) were evaluated by RT-PCR using primers directed against CD44. When background intensity was subtracted, the relative intensity of the bands corresponding to CD44, and representing cells treated with MR4, MR24 and MR42 (compared to controls) were respectively increased 3.0% ± 33.6 (NS), suppressed 16.4% ± 49.1 (NS) and suppressed 9.2% ± 26.5 (NS). These results were pooled from both duplicate PCR runs and gels, and indicate no significant changes in CD44 expression was produced by any oligo type. Conclusions: Stem cells expressing this marker were unaffected by treatment, suggesting this population is not altered by suppressive bcl-2 therapy.

Research paper thumbnail of Racial differences in prostate cancer incidence and mortality

Journal of Clinical Oncology, May 20, 2012

e15119 Background: Prostate cancer is the second leading cause of male cancer deaths in the U.S. ... more e15119 Background: Prostate cancer is the second leading cause of male cancer deaths in the U.S. There are significant racial differences in prostate cancer incidence and mortality. Methods: The SEER Database for 2008 was analysed for designated areas: Connecticut, Detroit, and Hawaii, assuming that these areas are surrogates for whites, blacks, and Asians, respectively. Results: Incidence and mortality (see Table). Conclusions: Assuming that the geographic SEER areas (Conn, Det, Ha) are surrogates for whites, blacks, and Oriental populations, we conclude that the incidence and mortality rates for blacks are higher than those for whites and Orientals. [Table: see text]

Research paper thumbnail of Ethnic belief differences in the incidence and mortality of prostate cancer

Journal of Clinical Oncology, May 20, 2014

e16108 Background: One of the leading causes of male death worldwide is prostate cancer. Although... more e16108 Background: One of the leading causes of male death worldwide is prostate cancer. Although many databases evaluate disease incidence, mortality and diverse contributory influences, few evalu...

Research paper thumbnail of Compensatory regulatory mechanisms that restore apoptosis following bcl-2 suppression

Journal of Clinical Oncology, May 20, 2014

e13536 Background: Gene therapy, in theory, is specific. However, in practice, it encounters diff... more e13536 Background: Gene therapy, in theory, is specific. However, in practice, it encounters difficulties. In the apoptosis pathway there are many regulatory proteins which either promote or inhibi...

Research paper thumbnail of Immunopriming of Tumor Infiltrating Lymphocytes with Neoadjuvant Cyclophosphamide

Immunological Investigations, 1993

Tumor infiltrating lymphocytes (TIL) are increasingly employed in immunotherapy protocols. When m... more Tumor infiltrating lymphocytes (TIL) are increasingly employed in immunotherapy protocols. When modified and expanded they can be utilized in new therapeutic protocols. TIL augmentation can be in vitro and in vivo. The purpose of this article is to review the various methods of TIL augmentation and report our experience with a neoadjuvant technique of cyclophosphamide immunopriming of TILs.

Research paper thumbnail of Is Immune Checkpoint Blockade Altered By Specific Gene Therapy Directed Against Bcl-2

Antisense oligonucleotides (oligos) [1,2] have been administered against prostatic LNCaP cells in... more Antisense oligonucleotides (oligos) [1,2] have been administered against prostatic LNCaP cells in both in vivo and in vitro models. In spite of advances in early detection, the treatment of prostate cancer has not improved and it is estimated that 233,000 new cases will be diagnosed and 29,450 men will die from it this year in the United States [3]. Gene therapy and immune checkpoint blockade could provide some improvement. However, our studies indicate that gene therapy employing oligos directed towards bcl-2 (in LNCaP cells) frequently are compensated for by altered regulation of apoptosis, increased androgen sensitivity and enhanced oncogene activity [4]. In addition, we found that certain oligo conformations induce interferon [5], enhance cell surface antigen expression [prostate specific membrane antigen (PSMA)] [6] and potentially increase tumor recognition and targeting by the immune system. We hypothesized that immunologic recognition is an additional pathway for compensation which follows suppressive bcl-2 treatment and suggest that this type of gene therapy could influence proteins associated with immune checkpoint blockade [7,8] now the " standard for care " treatment of melanoma and currently being evaluated for kidney and other solid tumors (including the prostate). Therefore, markers targeted by these new agents should be evaluated to identify changes in expression produced by previous therapy.