The Experts below are selected from a list of 136182 Experts worldwide ranked by ideXlab platform
Ruiwen Zhang - One of the best experts on this subject based on the ideXlab platform.
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FBA-TPQ, a novel marine-derived compound as Experimental Therapy for prostate cancer
Investigational New Drugs, 2010Co-Authors: Feng Wang, Wei Wang, Elizabeth R Rayburn, Scharri J. Ezell, Yong Zhang, Dwayaja H. Nadkarni, Srinivasan Murugesan, Sadanandan E. Velu, Ruiwen ZhangAbstract:We recently synthesized a series of novel makaluvamine compounds, and found that the most potent was FBA-TPQ. The effects of FBA-TPQ on human (LNCaP and PC3) and murine (TRAMP C1) prostate cancer cells were evaluated. Potential mechanisms of action of the compound were also determined. FBA-TPQ exhibited dose-dependent cytotoxicity in the low micromolar range, inhibited proliferation, caused cell cycle arrest, and induced apoptosis in prostate cancer cell lines. The compound also decreased the expression of the androgen receptor and PSA. The results presented herein support the further development of FBA-TPQ as a novel agent for prostate cancer.
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novel ginsenosides 25 oh ppd and 25 och3 ppd as Experimental Therapy for pancreatic cancer anticancer activity and mechanisms of action
Cancer Letters, 2009Co-Authors: Wei Wang, Elizabeth R Rayburn, Yuqing Zhao, Hui Wang, Ruiwen ZhangAbstract:We recently isolated and characterized two novel ginsenosides, 25-OH-PPD and 25-OCH3-PPD. We investigated whether these ginsenosides could represent safe and effective therapeutic agents for pancreatic cancer. In vitro and in vivo studies demonstrated that both compounds inhibited proliferation, caused cell cycle arrest, and induced apoptosis. They also both inhibited the growth of xenograft tumors without any host toxicity. Preliminary investigations into the mechanisms of action of the compounds suggest that their effects may be partially mediated by their inhibition of the MDM2 oncogene and related pathways. The data presented here support further evaluation of the ginsenosides for pancreatic cancer Therapy.
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Experimental Therapy of hepatoma with artemisinin and its derivatives in vitro and in vivo activity chemosensitization and mechanisms of action
Clinical Cancer Research, 2008Co-Authors: Disong Wang, Ruiwen Zhang, Hui WangAbstract:PURPOSE: ART and its derivatives, clinically used antimalarial agents, have recently shown antitumor activities. However, the mechanisms underlying these activities remain unclear. This study was designed to determine their antitumor efficacy and underlying mechanisms of action in human hepatoma cells. Experimental DESIGN: The in vitro cytotoxicities of ART, DHA, artemether, and artesunate were compared in human hepatoma cells, HepG2 (p53 wild-type), Huh-7 and BEL-7404 (p53 mutant), and Hep3B (p53 null), and a normal human liver cell line, 7702. Based on their activity and specificity, ART and DHA were further investigated for their in vitro and in vivo antitumor effects and their effects on the protein expression of genes associated with cell proliferation and apoptosis. RESULTS: ART and DHA exerted the greatest cytotoxicity to hepatoma cells but significantly lower cytotoxicity to normal liver cells. The compounds inhibited cell proliferation, induced G(1)-phase arrest, decreased the levels of cyclin D1, cyclin E, cyclin-dependent kinase 2, cyclin-dependent kinase 4, and E2F1, and increased the levels of Cip1/p21 and Kip1/p27. They induced apoptosis, activated caspase-3, increased the Bax/Bcl-2 ratio and poly(ADP-ribose) polymerase, and down-regulated MDM2. In mice bearing HepG2 and Hep3B xenograft tumors, ART and DHA inhibited tumor growth and modulated tumor gene expression consistent with in vitro observations. DHA increased the efficacy of the chemotherapeutic agent gemcitabine. CONCLUSIONS: ART and DHA have significant anticancer effects against human hepatoma cells, regardless of p53 status, with minimal effects on normal cells, indicating that they are promising therapeutics for human hepatoma used alone or in combination with other therapies.
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Experimental Therapy of prostate cancer with novel natural product anti cancer ginsenosides
The Prostate, 2008Co-Authors: Wei Wang, Elizabeth R Rayburn, Miao Hao, Yuqing Zhao, Donald L Hill, Ruiwen Zhang, Hui WangAbstract:BACKGROUND Ginseng and its components exert various biological effects, including antioxidant, anti-carcinogenic, anti-mutagenic, and anti-tumor activity, and recent research has focused on their value in human cancer prevention and treatment. We recently isolated 25-hydroxyprotopanaxadiol (25-OH-PPD) and 25-hydroxyprotopanaxatriol (25-OH-PPT) from Panax ginseng and evaluated their anti-cancer activity in vitro. METHODS We compared the effects of the two compounds on human prostate cancer LNCaP and PC3 cells in vitro and in a mouse PC3 xenograft tumor model. We also accomplished a preliminary determination of the mechanisms of action of the compounds. RESULTS 25-OH-PPD, but not 25-OH-PPT, inhibited prostate cancer cell growth and proliferation, induced apoptosis, and led to arrest in the G1 phase of the cell cycle. In nude mice bearing PC3 xenograft tumors, 25-OH-PPD inhibited tumor growth in a dose-dependent manner and could be safely combined with chemotherapeutic agents (taxotere and gemcitabine) and radiation Therapy to improve the anti-tumor effects. Further, in both PC3 and LNCaP cell lines, 25-OH-PPD increased expression of p21, p27, and Bax, induced PARP cleavage and activated caspases. The compound also reduced expression of MDM2, E2F1, Bcl2, cdk2/4/6, and cyclin D1, which correlated with the cell cycle arrest in G1 and the decrease in proliferation. Moreover, 25-OH-PPD demonstrated low toxicity to non-cancer cells and no observable host toxicity in animals either alone or in combination with conventional therapies. CONCLUSIONS The newly identified ginsenoside 25-OH-PPD may have potential as a novel prostate cancer therapeutic agent. Prostate 68:809–819, 2008. © 2008 Wiley-Liss, Inc.
Walter L. Miller - One of the best experts on this subject based on the ideXlab platform.
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DEXAMETHASONE TREATMENT OF CONGENITAL ADRENAL HYPERPLASIA IN UTERO: AN Experimental Therapy OF UNPROVEN SAFETY
The Journal of urology, 1999Co-Authors: Walter L. MillerAbstract:Congenital adrenal hyperplasia (CAH) due to steroid 21-hydroxylase deficiency is a common cause of genital virilization in female infants resulting from inappropriate fetal adrenal androgen secretion. Some investigators have advocated treating pregnant women who are at risk for carrying a CAH fetus with dexamethasone to suppress fetal adrenal androgen synthesis. Experience to date shows that this treatment can be effective in ameliorating the genital virilization in female fetuses. However, the doses used are supraphysiological, the mechanism of dexamethasone action in the fetus is unclear and no long-term followup studies have been done. To be effective the treatment would need to be started by week 6 of gestation but the genetic diagnosis cannot be made until week 12. If the mother has had a previous CAH child, only 1 in 4 pregnancies will be affected and only the female fetuses stand to benefit from treatment, thus, 7 of 8 fetuses will be treated needlessly. In view of these and other concerns, the prenatal treatment of CAH remains an Experimental Therapy and, hence, must only be done with fully informed consent in controlled prospective trials approved by human experimentation committees at centers that see enough of these patients to collect meaningful data.
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Prenatal Treatment of Congenital Adrenal Hyperplasia: A Promising Experimental Therapy of Unproven Safety
Trends in endocrinology and metabolism: TEM, 1998Co-Authors: Walter L. MillerAbstract:The long-term safety of the prenatal treatment of congenital adrenal hyperplasia (CAH) has not been established, and it remains an Experimental Therapy that raises unique ethical questions. Prenatal treatment should be performed only according to controlled, prospective, peer-reviewed protocols carried out according to strict scientific and ethical standards. Such studies must incorporate detailed, decades-long follow-up to permit accurate appraisal of its efficacy and safety, especially among the seven of eight fetuses who receive unneeded treatment.
Hui Wang - One of the best experts on this subject based on the ideXlab platform.
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novel ginsenosides 25 oh ppd and 25 och3 ppd as Experimental Therapy for pancreatic cancer anticancer activity and mechanisms of action
Cancer Letters, 2009Co-Authors: Wei Wang, Elizabeth R Rayburn, Yuqing Zhao, Hui Wang, Ruiwen ZhangAbstract:We recently isolated and characterized two novel ginsenosides, 25-OH-PPD and 25-OCH3-PPD. We investigated whether these ginsenosides could represent safe and effective therapeutic agents for pancreatic cancer. In vitro and in vivo studies demonstrated that both compounds inhibited proliferation, caused cell cycle arrest, and induced apoptosis. They also both inhibited the growth of xenograft tumors without any host toxicity. Preliminary investigations into the mechanisms of action of the compounds suggest that their effects may be partially mediated by their inhibition of the MDM2 oncogene and related pathways. The data presented here support further evaluation of the ginsenosides for pancreatic cancer Therapy.
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Experimental Therapy of hepatoma with artemisinin and its derivatives in vitro and in vivo activity chemosensitization and mechanisms of action
Clinical Cancer Research, 2008Co-Authors: Disong Wang, Ruiwen Zhang, Hui WangAbstract:PURPOSE: ART and its derivatives, clinically used antimalarial agents, have recently shown antitumor activities. However, the mechanisms underlying these activities remain unclear. This study was designed to determine their antitumor efficacy and underlying mechanisms of action in human hepatoma cells. Experimental DESIGN: The in vitro cytotoxicities of ART, DHA, artemether, and artesunate were compared in human hepatoma cells, HepG2 (p53 wild-type), Huh-7 and BEL-7404 (p53 mutant), and Hep3B (p53 null), and a normal human liver cell line, 7702. Based on their activity and specificity, ART and DHA were further investigated for their in vitro and in vivo antitumor effects and their effects on the protein expression of genes associated with cell proliferation and apoptosis. RESULTS: ART and DHA exerted the greatest cytotoxicity to hepatoma cells but significantly lower cytotoxicity to normal liver cells. The compounds inhibited cell proliferation, induced G(1)-phase arrest, decreased the levels of cyclin D1, cyclin E, cyclin-dependent kinase 2, cyclin-dependent kinase 4, and E2F1, and increased the levels of Cip1/p21 and Kip1/p27. They induced apoptosis, activated caspase-3, increased the Bax/Bcl-2 ratio and poly(ADP-ribose) polymerase, and down-regulated MDM2. In mice bearing HepG2 and Hep3B xenograft tumors, ART and DHA inhibited tumor growth and modulated tumor gene expression consistent with in vitro observations. DHA increased the efficacy of the chemotherapeutic agent gemcitabine. CONCLUSIONS: ART and DHA have significant anticancer effects against human hepatoma cells, regardless of p53 status, with minimal effects on normal cells, indicating that they are promising therapeutics for human hepatoma used alone or in combination with other therapies.
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Experimental Therapy of prostate cancer with novel natural product anti cancer ginsenosides
The Prostate, 2008Co-Authors: Wei Wang, Elizabeth R Rayburn, Miao Hao, Yuqing Zhao, Donald L Hill, Ruiwen Zhang, Hui WangAbstract:BACKGROUND Ginseng and its components exert various biological effects, including antioxidant, anti-carcinogenic, anti-mutagenic, and anti-tumor activity, and recent research has focused on their value in human cancer prevention and treatment. We recently isolated 25-hydroxyprotopanaxadiol (25-OH-PPD) and 25-hydroxyprotopanaxatriol (25-OH-PPT) from Panax ginseng and evaluated their anti-cancer activity in vitro. METHODS We compared the effects of the two compounds on human prostate cancer LNCaP and PC3 cells in vitro and in a mouse PC3 xenograft tumor model. We also accomplished a preliminary determination of the mechanisms of action of the compounds. RESULTS 25-OH-PPD, but not 25-OH-PPT, inhibited prostate cancer cell growth and proliferation, induced apoptosis, and led to arrest in the G1 phase of the cell cycle. In nude mice bearing PC3 xenograft tumors, 25-OH-PPD inhibited tumor growth in a dose-dependent manner and could be safely combined with chemotherapeutic agents (taxotere and gemcitabine) and radiation Therapy to improve the anti-tumor effects. Further, in both PC3 and LNCaP cell lines, 25-OH-PPD increased expression of p21, p27, and Bax, induced PARP cleavage and activated caspases. The compound also reduced expression of MDM2, E2F1, Bcl2, cdk2/4/6, and cyclin D1, which correlated with the cell cycle arrest in G1 and the decrease in proliferation. Moreover, 25-OH-PPD demonstrated low toxicity to non-cancer cells and no observable host toxicity in animals either alone or in combination with conventional therapies. CONCLUSIONS The newly identified ginsenoside 25-OH-PPD may have potential as a novel prostate cancer therapeutic agent. Prostate 68:809–819, 2008. © 2008 Wiley-Liss, Inc.
Wei Wang - One of the best experts on this subject based on the ideXlab platform.
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FBA-TPQ, a novel marine-derived compound as Experimental Therapy for prostate cancer
Investigational New Drugs, 2010Co-Authors: Feng Wang, Wei Wang, Elizabeth R Rayburn, Scharri J. Ezell, Yong Zhang, Dwayaja H. Nadkarni, Srinivasan Murugesan, Sadanandan E. Velu, Ruiwen ZhangAbstract:We recently synthesized a series of novel makaluvamine compounds, and found that the most potent was FBA-TPQ. The effects of FBA-TPQ on human (LNCaP and PC3) and murine (TRAMP C1) prostate cancer cells were evaluated. Potential mechanisms of action of the compound were also determined. FBA-TPQ exhibited dose-dependent cytotoxicity in the low micromolar range, inhibited proliferation, caused cell cycle arrest, and induced apoptosis in prostate cancer cell lines. The compound also decreased the expression of the androgen receptor and PSA. The results presented herein support the further development of FBA-TPQ as a novel agent for prostate cancer.
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novel ginsenosides 25 oh ppd and 25 och3 ppd as Experimental Therapy for pancreatic cancer anticancer activity and mechanisms of action
Cancer Letters, 2009Co-Authors: Wei Wang, Elizabeth R Rayburn, Yuqing Zhao, Hui Wang, Ruiwen ZhangAbstract:We recently isolated and characterized two novel ginsenosides, 25-OH-PPD and 25-OCH3-PPD. We investigated whether these ginsenosides could represent safe and effective therapeutic agents for pancreatic cancer. In vitro and in vivo studies demonstrated that both compounds inhibited proliferation, caused cell cycle arrest, and induced apoptosis. They also both inhibited the growth of xenograft tumors without any host toxicity. Preliminary investigations into the mechanisms of action of the compounds suggest that their effects may be partially mediated by their inhibition of the MDM2 oncogene and related pathways. The data presented here support further evaluation of the ginsenosides for pancreatic cancer Therapy.
-
Experimental Therapy of prostate cancer with novel natural product anti cancer ginsenosides
The Prostate, 2008Co-Authors: Wei Wang, Elizabeth R Rayburn, Miao Hao, Yuqing Zhao, Donald L Hill, Ruiwen Zhang, Hui WangAbstract:BACKGROUND Ginseng and its components exert various biological effects, including antioxidant, anti-carcinogenic, anti-mutagenic, and anti-tumor activity, and recent research has focused on their value in human cancer prevention and treatment. We recently isolated 25-hydroxyprotopanaxadiol (25-OH-PPD) and 25-hydroxyprotopanaxatriol (25-OH-PPT) from Panax ginseng and evaluated their anti-cancer activity in vitro. METHODS We compared the effects of the two compounds on human prostate cancer LNCaP and PC3 cells in vitro and in a mouse PC3 xenograft tumor model. We also accomplished a preliminary determination of the mechanisms of action of the compounds. RESULTS 25-OH-PPD, but not 25-OH-PPT, inhibited prostate cancer cell growth and proliferation, induced apoptosis, and led to arrest in the G1 phase of the cell cycle. In nude mice bearing PC3 xenograft tumors, 25-OH-PPD inhibited tumor growth in a dose-dependent manner and could be safely combined with chemotherapeutic agents (taxotere and gemcitabine) and radiation Therapy to improve the anti-tumor effects. Further, in both PC3 and LNCaP cell lines, 25-OH-PPD increased expression of p21, p27, and Bax, induced PARP cleavage and activated caspases. The compound also reduced expression of MDM2, E2F1, Bcl2, cdk2/4/6, and cyclin D1, which correlated with the cell cycle arrest in G1 and the decrease in proliferation. Moreover, 25-OH-PPD demonstrated low toxicity to non-cancer cells and no observable host toxicity in animals either alone or in combination with conventional therapies. CONCLUSIONS The newly identified ginsenoside 25-OH-PPD may have potential as a novel prostate cancer therapeutic agent. Prostate 68:809–819, 2008. © 2008 Wiley-Liss, Inc.
Matthew H. Samore - One of the best experts on this subject based on the ideXlab platform.
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Empirical Consequences of Current Recommendations for the Design and Interpretation of Noninferiority Trials
Journal of General Internal Medicine, 2018Co-Authors: Scott K. Aberegg, Andrew M. Hersh, Matthew H. SamoreAbstract:Background Noninferiority trials are increasingly common, though they have less standardized designs and their interpretation is less familiar to clinicians than superiority trials. Objective To empirically evaluate a cohort of noninferiority trials to determine 1) their interpretation as recommended by CONSORT, 2) choice of alpha threshold and its sidedness, and 3) differences between methods of analysis such as intention-to-treat and per-protocol. Design We searched MEDLINE for parallel-group randomized controlled noninferiority trials published in the five highest-impact general medical journals between 2011 and 2016. Main Measures Data abstracted included trial design parameters, results, and interpretation of results based on CONSORT recommendations. Key Results One hundred sixty-three trials and 182 noninferiority comparisons were included in our analysis. Based on CONSORT-recommended interpretation, 79% of Experimental therapies met criteria for noninferiority, 13% met criteria for superiority, 20% were declared inconclusive, and 2% met criteria for inferiority. However, for 12% of trials, the Experimental Therapy was statistically significantly worse than the active control, but CONSORT recommended an interpretation of inconclusive or noninferior. A two-sided alpha equivalent of greater than 0.05 was used in 34% of the trials, and in five of these trials, the use of a standard two-sided alpha of 0.05 led to changes in the interpretation of results that disfavored the Experimental Therapy. In four of the five comparisons where different methods of analysis (e.g., intention-to-treat and per-protocol) yielded different results, the intention-to-treat analysis was the more conservative. In 11% of trials, a secondary advantage of the new Therapy was neither reported nor could it be inferred by reviewers. Conclusions In this cohort, the design and interpretation of noninferiority trials led to significant and systematic bias in favor of the Experimental Therapy. Clinicians should exercise caution when interpreting these trials. Future trials may be more reliable if design parameters are standardized.
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Empirical Consequences of Current Recommendations for the Design and Interpretation of Noninferiority Trials
Journal of General Internal Medicine, 2017Co-Authors: Scott K. Aberegg, Andrew M. Hersh, Matthew H. SamoreAbstract:Noninferiority trials are increasingly common, though they have less standardized designs and their interpretation is less familiar to clinicians than superiority trials. To empirically evaluate a cohort of noninferiority trials to determine 1) their interpretation as recommended by CONSORT, 2) choice of alpha threshold and its sidedness, and 3) differences between methods of analysis such as intention-to-treat and per-protocol. We searched MEDLINE for parallel-group randomized controlled noninferiority trials published in the five highest-impact general medical journals between 2011 and 2016. Data abstracted included trial design parameters, results, and interpretation of results based on CONSORT recommendations. One hundred sixty-three trials and 182 noninferiority comparisons were included in our analysis. Based on CONSORT-recommended interpretation, 79% of Experimental therapies met criteria for noninferiority, 13% met criteria for superiority, 20% were declared inconclusive, and 2% met criteria for inferiority. However, for 12% of trials, the Experimental Therapy was statistically significantly worse than the active control, but CONSORT recommended an interpretation of inconclusive or noninferior. A two-sided alpha equivalent of greater than 0.05 was used in 34% of the trials, and in five of these trials, the use of a standard two-sided alpha of 0.05 led to changes in the interpretation of results that disfavored the Experimental Therapy. In four of the five comparisons where different methods of analysis (e.g., intention-to-treat and per-protocol) yielded different results, the intention-to-treat analysis was the more conservative. In 11% of trials, a secondary advantage of the new Therapy was neither reported nor could it be inferred by reviewers. In this cohort, the design and interpretation of noninferiority trials led to significant and systematic bias in favor of the Experimental Therapy. Clinicians should exercise caution when interpreting these trials. Future trials may be more reliable if design parameters are standardized.
