The Experts below are selected from a list of 43299 Experts worldwide ranked by ideXlab platform
A Böhle - One of the best experts on this subject based on the ideXlab platform.
-
Basics of Antisense Oligonucleotide therapy and current therapeutical strategies in urology
Aktuelle Urologie, 2003Co-Authors: I Kausch, A BöhleAbstract:Antisense Oligonucleotides are short DNA sequences designed to modulate the information transfer from gene to protein. Sequence-related hybridisation with the mRNA of a specific protein results in selective inhibition of gene expression and downregulation of protein expression. This allows the study of gene function and therapy on a molecular level. Antisense Oligonucleotide inhibitors can be designed directly from genomic sequence information by simply making the reversed complement of the desired sequence. In this review, we focus on the mechanisms of action of Antisense Oligonucleotides and summarize the progress in urological Antisense therapy. The ability to inhibit individual gene expression with Antisense Oligonucleotides has been promising in preclinical cancer models. Current clinical studies test Antisense compounds targeted against various cancer related genes. Although some of these studies comprise patients with urological tumors, such as advanced prostate cancer, experimental Antisense therapy in urology is still in its infancy.
-
Antisense Oligonucleotide therapy for urologic tumors.
Current urology reports, 2003Co-Authors: I Kausch, A BöhleAbstract:Modulation of gene expression using Antisense Oligonucleotides has advanced from the laboratory to the clinic. Numerous companies can, at least partially, attribute their success to the development of Antisense techniques, and one Antisense drug is currently on the market. Antisense compounds have been used in clinical trials that included patients with urologic tumors, mostly directed at proliferation- or apoptosis-related targets. Furthermore, therapeutic inhibition of many new identified genes is being investigated in preclinical tests. This review provides a contemporary overview of current preclinical and clinical Antisense Oligonucleotide concepts for the treatment of urologic tumors.
-
Antisense Oligonucleotide Therapy in Urology
The Journal of urology, 2002Co-Authors: I Kausch, A BöhleAbstract:Purpose: Antisense Oligonucleotides are short modified DNA or RNA molecules designed to bind selectively messenger RNA and inhibit synthesis of the encoded protein. In the last 20 years Antisense technology has emerged as an exciting and promising strategy, especially for treating cancer. We provide urologists with a contemporary review of relevant background information and outline current treatment strategies and clinical trials of Antisense Oligonucleotide therapy for urological tumors.Materials and Methods: We comprehensively reviewed the literature, including PubMed and recent abstract proceedings from international meetings, on preclinical and clinical studies of Antisense Oligonucleotide therapy in urology.Results: Current preclinical Antisense strategies in urological cancer research include the inhibition of proliferation and induction of tumor cell differentiation, reversal of immunosuppression by tumor secreted molecules and induction of apoptosis. The use of phosphorothioate Oligonucleotides a...
I Kausch - One of the best experts on this subject based on the ideXlab platform.
-
Basics of Antisense Oligonucleotide therapy and current therapeutical strategies in urology
Aktuelle Urologie, 2003Co-Authors: I Kausch, A BöhleAbstract:Antisense Oligonucleotides are short DNA sequences designed to modulate the information transfer from gene to protein. Sequence-related hybridisation with the mRNA of a specific protein results in selective inhibition of gene expression and downregulation of protein expression. This allows the study of gene function and therapy on a molecular level. Antisense Oligonucleotide inhibitors can be designed directly from genomic sequence information by simply making the reversed complement of the desired sequence. In this review, we focus on the mechanisms of action of Antisense Oligonucleotides and summarize the progress in urological Antisense therapy. The ability to inhibit individual gene expression with Antisense Oligonucleotides has been promising in preclinical cancer models. Current clinical studies test Antisense compounds targeted against various cancer related genes. Although some of these studies comprise patients with urological tumors, such as advanced prostate cancer, experimental Antisense therapy in urology is still in its infancy.
-
Antisense Oligonucleotide therapy for urologic tumors.
Current urology reports, 2003Co-Authors: I Kausch, A BöhleAbstract:Modulation of gene expression using Antisense Oligonucleotides has advanced from the laboratory to the clinic. Numerous companies can, at least partially, attribute their success to the development of Antisense techniques, and one Antisense drug is currently on the market. Antisense compounds have been used in clinical trials that included patients with urologic tumors, mostly directed at proliferation- or apoptosis-related targets. Furthermore, therapeutic inhibition of many new identified genes is being investigated in preclinical tests. This review provides a contemporary overview of current preclinical and clinical Antisense Oligonucleotide concepts for the treatment of urologic tumors.
-
Antisense Oligonucleotide Therapy in Urology
The Journal of urology, 2002Co-Authors: I Kausch, A BöhleAbstract:Purpose: Antisense Oligonucleotides are short modified DNA or RNA molecules designed to bind selectively messenger RNA and inhibit synthesis of the encoded protein. In the last 20 years Antisense technology has emerged as an exciting and promising strategy, especially for treating cancer. We provide urologists with a contemporary review of relevant background information and outline current treatment strategies and clinical trials of Antisense Oligonucleotide therapy for urological tumors.Materials and Methods: We comprehensively reviewed the literature, including PubMed and recent abstract proceedings from international meetings, on preclinical and clinical studies of Antisense Oligonucleotide therapy in urology.Results: Current preclinical Antisense strategies in urological cancer research include the inhibition of proliferation and induction of tumor cell differentiation, reversal of immunosuppression by tumor secreted molecules and induction of apoptosis. The use of phosphorothioate Oligonucleotides a...
Shili Xu - One of the best experts on this subject based on the ideXlab platform.
-
an hk2 Antisense Oligonucleotide induces synthetic lethality in hk1 hk2 multiple myeloma
Cancer Research, 2019Co-Authors: Shili Xu, Nicholas A Bayley, Art Catapang, Reiko E Yamada, Alex Vasuthasawat, Joshua Sasine, Tianyuan Zhou, Daniel Braas, Ryan K. Trinh, John M TimmermanAbstract:Although the majority of adult tissues express only hexokinase 1 (HK1) for glycolysis, most cancers express hexokinase 2 (HK2) and many coexpress HK1 and HK2. In contrast to HK1+HK2+ cancers, HK1−HK2+ cancer subsets are sensitive to cytostasis induced by HK2shRNA knockdown and are also sensitive to synthetic lethality in response to the combination of HK2shRNA knockdown, an oxidative phosphorylation (OXPHOS) inhibitor diphenyleneiodonium (DPI), and a fatty acid oxidation (FAO) inhibitor perhexiline (PER). The majority of human multiple myeloma cell lines are HK1−HK2+. Here we describe an Antisense Oligonucleotide (ASO) directed against human HK2 (HK2-ASO1), which suppressed HK2 expression in human multiple myeloma cell cultures and human multiple myeloma mouse xenograft models. The HK2-ASO1/DPI/PER triple-combination achieved synthetic lethality in multiple myeloma cells in culture and prevented HK1−HK2+ multiple myeloma tumor xenograft progression. DPI was replaceable by the FDA-approved OXPHOS inhibitor metformin (MET), both for synthetic lethality in culture and for inhibition of tumor xenograft progression. In addition, we used an ASO targeting murine HK2 (mHK2-ASO1) to validate the safety of mHK2-ASO1/MET/PER combination therapy in mice bearing murine multiple myeloma tumors. HK2-ASO1 is the first agent that shows selective HK2 inhibition and therapeutic efficacy in cell culture and in animal models, supporting clinical development of this synthetically lethal combination as a therapy for HK1−HK2+ multiple myeloma. Significance: A first-in-class HK2 Antisense Oligonucleotide suppresses HK2 expression in cell culture and in in vivo, presenting an effective, tolerated combination therapy for preventing progression of HK1−HK2+ multiple myeloma tumors. Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/10/2748/F1.large.jpg.
-
an hk2 Antisense Oligonucleotide induces synthetic lethality in hk1 hk2 multiple myeloma
Cancer Research, 2019Co-Authors: Shili Xu, Nicholas A Bayley, Art Catapang, Reiko E Yamada, Alex Vasuthasawat, Joshua Sasine, Tianyuan Zhou, Daniel Braas, Ryan K. Trinh, John M TimmermanAbstract:Although the majority of adult tissues express only hexokinase 1 (HK1) for glycolysis, most cancers express hexokinase 2 (HK2) and many coexpress HK1 and HK2. In contrast to HK1+HK2+ cancers, HK1−HK2+ cancer subsets are sensitive to cytostasis induced by HK2shRNA knockdown and are also sensitive to synthetic lethality in response to the combination of HK2shRNA knockdown, an oxidative phosphorylation (OXPHOS) inhibitor diphenyleneiodonium (DPI), and a fatty acid oxidation (FAO) inhibitor perhexiline (PER). The majority of human multiple myeloma cell lines are HK1−HK2+. Here we describe an Antisense Oligonucleotide (ASO) directed against human HK2 (HK2-ASO1), which suppressed HK2 expression in human multiple myeloma cell cultures and human multiple myeloma mouse xenograft models. The HK2-ASO1/DPI/PER triple-combination achieved synthetic lethality in multiple myeloma cells in culture and prevented HK1−HK2+ multiple myeloma tumor xenograft progression. DPI was replaceable by the FDA-approved OXPHOS inhibitor metformin (MET), both for synthetic lethality in culture and for inhibition of tumor xenograft progression. In addition, we used an ASO targeting murine HK2 (mHK2-ASO1) to validate the safety of mHK2-ASO1/MET/PER combination therapy in mice bearing murine multiple myeloma tumors. HK2-ASO1 is the first agent that shows selective HK2 inhibition and therapeutic efficacy in cell culture and in animal models, supporting clinical development of this synthetically lethal combination as a therapy for HK1−HK2+ multiple myeloma. Significance: A first-in-class HK2 Antisense Oligonucleotide suppresses HK2 expression in cell culture and in in vivo, presenting an effective, tolerated combination therapy for preventing progression of HK1−HK2+ multiple myeloma tumors. Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/10/2748/F1.large.jpg.
-
An HK2 Antisense Oligonucleotide Induces Synthetic Lethality in HK1−HK2+ Multiple Myeloma
Cancer Research, 2019Co-Authors: Shili Xu, Nicholas A Bayley, Art Catapang, Reiko E Yamada, K. Ryan Trinh, Tianyuan Zhou, Daniel Braas, Alex VasuthasawatAbstract:Although the majority of adult tissues express only hexokinase 1 (HK1) for glycolysis, most cancers express hexokinase 2 (HK2) and many coexpress HK1 and HK2. In contrast to HK1+HK2+ cancers, HK1−HK2+ cancer subsets are sensitive to cytostasis induced by HK2shRNA knockdown and are also sensitive to synthetic lethality in response to the combination of HK2shRNA knockdown, an oxidative phosphorylation (OXPHOS) inhibitor diphenyleneiodonium (DPI), and a fatty acid oxidation (FAO) inhibitor perhexiline (PER). The majority of human multiple myeloma cell lines are HK1−HK2+. Here we describe an Antisense Oligonucleotide (ASO) directed against human HK2 (HK2-ASO1), which suppressed HK2 expression in human multiple myeloma cell cultures and human multiple myeloma mouse xenograft models. The HK2-ASO1/DPI/PER triple-combination achieved synthetic lethality in multiple myeloma cells in culture and prevented HK1−HK2+ multiple myeloma tumor xenograft progression. DPI was replaceable by the FDA-approved OXPHOS inhibitor metformin (MET), both for synthetic lethality in culture and for inhibition of tumor xenograft progression. In addition, we used an ASO targeting murine HK2 (mHK2-ASO1) to validate the safety of mHK2-ASO1/MET/PER combination therapy in mice bearing murine multiple myeloma tumors. HK2-ASO1 is the first agent that shows selective HK2 inhibition and therapeutic efficacy in cell culture and in animal models, supporting clinical development of this synthetically lethal combination as a therapy for HK1−HK2+ multiple myeloma. Significance: A first-in-class HK2 Antisense Oligonucleotide suppresses HK2 expression in cell culture and in in vivo, presenting an effective, tolerated combination therapy for preventing progression of HK1−HK2+ multiple myeloma tumors. Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/10/2748/F1.large.jpg.
John M Timmerman - One of the best experts on this subject based on the ideXlab platform.
-
an hk2 Antisense Oligonucleotide induces synthetic lethality in hk1 hk2 multiple myeloma
Cancer Research, 2019Co-Authors: Shili Xu, Nicholas A Bayley, Art Catapang, Reiko E Yamada, Alex Vasuthasawat, Joshua Sasine, Tianyuan Zhou, Daniel Braas, Ryan K. Trinh, John M TimmermanAbstract:Although the majority of adult tissues express only hexokinase 1 (HK1) for glycolysis, most cancers express hexokinase 2 (HK2) and many coexpress HK1 and HK2. In contrast to HK1+HK2+ cancers, HK1−HK2+ cancer subsets are sensitive to cytostasis induced by HK2shRNA knockdown and are also sensitive to synthetic lethality in response to the combination of HK2shRNA knockdown, an oxidative phosphorylation (OXPHOS) inhibitor diphenyleneiodonium (DPI), and a fatty acid oxidation (FAO) inhibitor perhexiline (PER). The majority of human multiple myeloma cell lines are HK1−HK2+. Here we describe an Antisense Oligonucleotide (ASO) directed against human HK2 (HK2-ASO1), which suppressed HK2 expression in human multiple myeloma cell cultures and human multiple myeloma mouse xenograft models. The HK2-ASO1/DPI/PER triple-combination achieved synthetic lethality in multiple myeloma cells in culture and prevented HK1−HK2+ multiple myeloma tumor xenograft progression. DPI was replaceable by the FDA-approved OXPHOS inhibitor metformin (MET), both for synthetic lethality in culture and for inhibition of tumor xenograft progression. In addition, we used an ASO targeting murine HK2 (mHK2-ASO1) to validate the safety of mHK2-ASO1/MET/PER combination therapy in mice bearing murine multiple myeloma tumors. HK2-ASO1 is the first agent that shows selective HK2 inhibition and therapeutic efficacy in cell culture and in animal models, supporting clinical development of this synthetically lethal combination as a therapy for HK1−HK2+ multiple myeloma. Significance: A first-in-class HK2 Antisense Oligonucleotide suppresses HK2 expression in cell culture and in in vivo, presenting an effective, tolerated combination therapy for preventing progression of HK1−HK2+ multiple myeloma tumors. Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/10/2748/F1.large.jpg.
-
an hk2 Antisense Oligonucleotide induces synthetic lethality in hk1 hk2 multiple myeloma
Cancer Research, 2019Co-Authors: Shili Xu, Nicholas A Bayley, Art Catapang, Reiko E Yamada, Alex Vasuthasawat, Joshua Sasine, Tianyuan Zhou, Daniel Braas, Ryan K. Trinh, John M TimmermanAbstract:Although the majority of adult tissues express only hexokinase 1 (HK1) for glycolysis, most cancers express hexokinase 2 (HK2) and many coexpress HK1 and HK2. In contrast to HK1+HK2+ cancers, HK1−HK2+ cancer subsets are sensitive to cytostasis induced by HK2shRNA knockdown and are also sensitive to synthetic lethality in response to the combination of HK2shRNA knockdown, an oxidative phosphorylation (OXPHOS) inhibitor diphenyleneiodonium (DPI), and a fatty acid oxidation (FAO) inhibitor perhexiline (PER). The majority of human multiple myeloma cell lines are HK1−HK2+. Here we describe an Antisense Oligonucleotide (ASO) directed against human HK2 (HK2-ASO1), which suppressed HK2 expression in human multiple myeloma cell cultures and human multiple myeloma mouse xenograft models. The HK2-ASO1/DPI/PER triple-combination achieved synthetic lethality in multiple myeloma cells in culture and prevented HK1−HK2+ multiple myeloma tumor xenograft progression. DPI was replaceable by the FDA-approved OXPHOS inhibitor metformin (MET), both for synthetic lethality in culture and for inhibition of tumor xenograft progression. In addition, we used an ASO targeting murine HK2 (mHK2-ASO1) to validate the safety of mHK2-ASO1/MET/PER combination therapy in mice bearing murine multiple myeloma tumors. HK2-ASO1 is the first agent that shows selective HK2 inhibition and therapeutic efficacy in cell culture and in animal models, supporting clinical development of this synthetically lethal combination as a therapy for HK1−HK2+ multiple myeloma. Significance: A first-in-class HK2 Antisense Oligonucleotide suppresses HK2 expression in cell culture and in in vivo, presenting an effective, tolerated combination therapy for preventing progression of HK1−HK2+ multiple myeloma tumors. Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/10/2748/F1.large.jpg.
Alex Vasuthasawat - One of the best experts on this subject based on the ideXlab platform.
-
an hk2 Antisense Oligonucleotide induces synthetic lethality in hk1 hk2 multiple myeloma
Cancer Research, 2019Co-Authors: Shili Xu, Nicholas A Bayley, Art Catapang, Reiko E Yamada, Alex Vasuthasawat, Joshua Sasine, Tianyuan Zhou, Daniel Braas, Ryan K. Trinh, John M TimmermanAbstract:Although the majority of adult tissues express only hexokinase 1 (HK1) for glycolysis, most cancers express hexokinase 2 (HK2) and many coexpress HK1 and HK2. In contrast to HK1+HK2+ cancers, HK1−HK2+ cancer subsets are sensitive to cytostasis induced by HK2shRNA knockdown and are also sensitive to synthetic lethality in response to the combination of HK2shRNA knockdown, an oxidative phosphorylation (OXPHOS) inhibitor diphenyleneiodonium (DPI), and a fatty acid oxidation (FAO) inhibitor perhexiline (PER). The majority of human multiple myeloma cell lines are HK1−HK2+. Here we describe an Antisense Oligonucleotide (ASO) directed against human HK2 (HK2-ASO1), which suppressed HK2 expression in human multiple myeloma cell cultures and human multiple myeloma mouse xenograft models. The HK2-ASO1/DPI/PER triple-combination achieved synthetic lethality in multiple myeloma cells in culture and prevented HK1−HK2+ multiple myeloma tumor xenograft progression. DPI was replaceable by the FDA-approved OXPHOS inhibitor metformin (MET), both for synthetic lethality in culture and for inhibition of tumor xenograft progression. In addition, we used an ASO targeting murine HK2 (mHK2-ASO1) to validate the safety of mHK2-ASO1/MET/PER combination therapy in mice bearing murine multiple myeloma tumors. HK2-ASO1 is the first agent that shows selective HK2 inhibition and therapeutic efficacy in cell culture and in animal models, supporting clinical development of this synthetically lethal combination as a therapy for HK1−HK2+ multiple myeloma. Significance: A first-in-class HK2 Antisense Oligonucleotide suppresses HK2 expression in cell culture and in in vivo, presenting an effective, tolerated combination therapy for preventing progression of HK1−HK2+ multiple myeloma tumors. Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/10/2748/F1.large.jpg.
-
an hk2 Antisense Oligonucleotide induces synthetic lethality in hk1 hk2 multiple myeloma
Cancer Research, 2019Co-Authors: Shili Xu, Nicholas A Bayley, Art Catapang, Reiko E Yamada, Alex Vasuthasawat, Joshua Sasine, Tianyuan Zhou, Daniel Braas, Ryan K. Trinh, John M TimmermanAbstract:Although the majority of adult tissues express only hexokinase 1 (HK1) for glycolysis, most cancers express hexokinase 2 (HK2) and many coexpress HK1 and HK2. In contrast to HK1+HK2+ cancers, HK1−HK2+ cancer subsets are sensitive to cytostasis induced by HK2shRNA knockdown and are also sensitive to synthetic lethality in response to the combination of HK2shRNA knockdown, an oxidative phosphorylation (OXPHOS) inhibitor diphenyleneiodonium (DPI), and a fatty acid oxidation (FAO) inhibitor perhexiline (PER). The majority of human multiple myeloma cell lines are HK1−HK2+. Here we describe an Antisense Oligonucleotide (ASO) directed against human HK2 (HK2-ASO1), which suppressed HK2 expression in human multiple myeloma cell cultures and human multiple myeloma mouse xenograft models. The HK2-ASO1/DPI/PER triple-combination achieved synthetic lethality in multiple myeloma cells in culture and prevented HK1−HK2+ multiple myeloma tumor xenograft progression. DPI was replaceable by the FDA-approved OXPHOS inhibitor metformin (MET), both for synthetic lethality in culture and for inhibition of tumor xenograft progression. In addition, we used an ASO targeting murine HK2 (mHK2-ASO1) to validate the safety of mHK2-ASO1/MET/PER combination therapy in mice bearing murine multiple myeloma tumors. HK2-ASO1 is the first agent that shows selective HK2 inhibition and therapeutic efficacy in cell culture and in animal models, supporting clinical development of this synthetically lethal combination as a therapy for HK1−HK2+ multiple myeloma. Significance: A first-in-class HK2 Antisense Oligonucleotide suppresses HK2 expression in cell culture and in in vivo, presenting an effective, tolerated combination therapy for preventing progression of HK1−HK2+ multiple myeloma tumors. Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/10/2748/F1.large.jpg.
-
An HK2 Antisense Oligonucleotide Induces Synthetic Lethality in HK1−HK2+ Multiple Myeloma
Cancer Research, 2019Co-Authors: Shili Xu, Nicholas A Bayley, Art Catapang, Reiko E Yamada, K. Ryan Trinh, Tianyuan Zhou, Daniel Braas, Alex VasuthasawatAbstract:Although the majority of adult tissues express only hexokinase 1 (HK1) for glycolysis, most cancers express hexokinase 2 (HK2) and many coexpress HK1 and HK2. In contrast to HK1+HK2+ cancers, HK1−HK2+ cancer subsets are sensitive to cytostasis induced by HK2shRNA knockdown and are also sensitive to synthetic lethality in response to the combination of HK2shRNA knockdown, an oxidative phosphorylation (OXPHOS) inhibitor diphenyleneiodonium (DPI), and a fatty acid oxidation (FAO) inhibitor perhexiline (PER). The majority of human multiple myeloma cell lines are HK1−HK2+. Here we describe an Antisense Oligonucleotide (ASO) directed against human HK2 (HK2-ASO1), which suppressed HK2 expression in human multiple myeloma cell cultures and human multiple myeloma mouse xenograft models. The HK2-ASO1/DPI/PER triple-combination achieved synthetic lethality in multiple myeloma cells in culture and prevented HK1−HK2+ multiple myeloma tumor xenograft progression. DPI was replaceable by the FDA-approved OXPHOS inhibitor metformin (MET), both for synthetic lethality in culture and for inhibition of tumor xenograft progression. In addition, we used an ASO targeting murine HK2 (mHK2-ASO1) to validate the safety of mHK2-ASO1/MET/PER combination therapy in mice bearing murine multiple myeloma tumors. HK2-ASO1 is the first agent that shows selective HK2 inhibition and therapeutic efficacy in cell culture and in animal models, supporting clinical development of this synthetically lethal combination as a therapy for HK1−HK2+ multiple myeloma. Significance: A first-in-class HK2 Antisense Oligonucleotide suppresses HK2 expression in cell culture and in in vivo, presenting an effective, tolerated combination therapy for preventing progression of HK1−HK2+ multiple myeloma tumors. Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/10/2748/F1.large.jpg.