Telomerase Inhibition And Sensitization Of Breast Tumor Cells

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Telomerase Inhibition and Sensitization of Breast Tumor Cells

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Author : Ann Kennon Rigby Poynter
Publisher :
ISBN 13 :
Total Pages : 294 pages
Book Rating : 4.:/5 (276 download)

Book Synopsis Telomerase Inhibition and Sensitization of Breast Tumor Cells by : Ann Kennon Rigby Poynter

Download or read book Telomerase Inhibition and Sensitization of Breast Tumor Cells written by Ann Kennon Rigby Poynter and published by . This book was released on 2007 with total page 294 pages. Available in PDF, EPUB and Kindle. Book excerpt: Telomerase, a ribonucleoprotein enzyme minimally composed of an RNA template (hTR) and a catalytically active protein subunit (hTERT), synthesizes telomeric repeats onto chromosome ends and is obligatory for continuous tumor cell proliferation, as well as malignant progression of breast cancer cells. Telomerase is an attractive anticancer therapeutic target because its activity is present in over 90% of human cancers, including more than 95% of breast carcinomas, but undetectable in most somatic cells. Traditions chemo- and radio-therapies lack the ability to effectively control and cure breast cancer, in part because residual cells are or become resistant to DNA damaging modalities. While various telomerase inhibition strategies cause cancer cells to undergo apoptosis car senescence, there is often a lag period between administration and biologic effect (Corey, 2002). Our goal in this study was to compare the efficacy of different telomerase inhibition strategies in concert with standard chemotherapeutic agents at triggering senescence and/or apoptosis in cultures of breast cancer cells. We hypothesized that telomerase inhibition strategies will sensitize breast cancer cells to traditional chemotherapies, potentially reducing the lag phase, allowing for more potent anti-tumor effects at lower doses, and therefore ultimately imparting less toxicity to the patient. We blocked telomerase by targeting hTR and hTERT, individually and collectively utilizing synthetic short interfering RNA (siRNA), short hairpin RNA (siRNA), and a dominant negative form of hTERT (DN-hTERT) in MCF-7 breast cancer cells. We analyzed the efficiency of telomerase inhibition for each strategy alone and then treated the cells with two mainstay chemotherapeutic agents, Adriamycin (AdR) and Taxol. The most effective telomerase inhibition strategies were synthetic siRNA and DN-hTERT, individually. After treatment with various concentrations of AdR or Taxol, breast cancer cells with inhibited telomerase grew significantly slower and exhibited widespread senescence or apoptosis within a much shorter time period and at a dose that is insufficient to trigger cytostasis. In addition, we provide evidence that cells in which telomerase was inhibited were more sensitive to anti-cancer agents, whether the drug inhibited topoisomerase II resulting in DNA damage (AdR) or blocked mitosis via protracted microtubule stabilization (Taxol). Collectively, our data indicate that alone, anti-telomerase inhibition strategies differ in their efficacy. However, when used in the adjuvant setting with diverse acting chemotherapeutic agents, there is a potent synergy resulting in chemotherapeutic sensitization characterized in part by widespread senescence and/or apoptosis.

Mechanism of Telomerase Inhibition Using Small Inhibitory RNAs and Induction of Breast Tumor Cell Sensitization

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Author :
Publisher :
ISBN 13 :
Total Pages : 15 pages
Book Rating : 4.:/5 (742 download)

Book Synopsis Mechanism of Telomerase Inhibition Using Small Inhibitory RNAs and Induction of Breast Tumor Cell Sensitization by :

Download or read book Mechanism of Telomerase Inhibition Using Small Inhibitory RNAs and Induction of Breast Tumor Cell Sensitization written by and published by . This book was released on 2005 with total page 15 pages. Available in PDF, EPUB and Kindle. Book excerpt: Telomerase, a ribonucleoprotein enzyme composed of an RNA template (hTR) and a catalytically active protein subunit (hTERT), synthesizes telomeres after cell divisions and is obligatory for continuous tumor cell proliferation as well as malignant progression of breast cancer cells. Telomerase is an attractive anti-cancer therapeutic agent because telomerase activity is present in over 90% of human breast cancers but is undetectable in most normal somatic cells. Traditional therapies (surgery, chemotherapy, radiotherapy, etc.) lack the ability to effectively control and cure breast cancer, primarily because residual cells are or become resistant to DNA damaging modalities including standard chemo- and radio-therapies. Since telomerase requires its associated hTR for repeat synthesis, we have chosen to use RNA interference as a method to inactivate hTR and hence telomerase. RNA interference (RNAI) has become a powerful tool for the analysis of gene function in that RNAI allows sequence specific inhibition of gene expression. Another protein we targeted is p21, which has long been established as a requirement for senescence. We wanted to further examine its relationship to senescence and apotosis, in an attempt to sensitize breast tumor cells more effectively.

Mechanism of Telomerase Inhibition Using a Small Inhibitory RNAs and Induction of Breast Tumor Cell Sensitization

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Author :
Publisher :
ISBN 13 :
Total Pages : 53 pages
Book Rating : 4.:/5 (15 download)

Book Synopsis Mechanism of Telomerase Inhibition Using a Small Inhibitory RNAs and Induction of Breast Tumor Cell Sensitization by :

Download or read book Mechanism of Telomerase Inhibition Using a Small Inhibitory RNAs and Induction of Breast Tumor Cell Sensitization written by and published by . This book was released on 2007 with total page 53 pages. Available in PDF, EPUB and Kindle. Book excerpt: Telomerase, a ribonucleoprotein enzyme minimally composed of an RNA template (hTR) and a catalytically active protein subunit (hTERT), synthesizes telomeric repeats onto chromosome ends and is obligatory for continuous tumor cell proliferation, as well as malignant progression of breast cancer cells. Telomerase is an attractive anti-cancer therapeutic target because its activity is present in over 90% of human cancers, including more than 95% of breast carcinomas, but undetectable in most somatic cells. Traditional chemo- and radiotherapies lack the ability to effectively control and cure breast cancer, in part because residual cells are or become resistant to DNA damaging modalities. While various telomerase inhibition strategies cause cancer cells to undergo apoptosis or senescence, there is often a lag period between administration and biologic effect (Corey, 2002). Our goal in this study was to compare the efficacy of different telomerase inhibition strategies in concert with standard chemotherapeutic agents at triggering senescence and/or apoptosis in cultures of breast cancer cells. We hypothesized that telomerase inhibition strategies will sensitize breast cancer cells to traditional chemotherapies, potentially reducing the lag phase, allowing for more potent anti-tumor effects at lower doses, and therefore ultimately imparting less toxicity to the patient.

Mechanism of Telomerase Inhibition Using Small Inibitory RNAs and Induction of Breast Tumor Cell Sensitivity

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Author :
Publisher :
ISBN 13 :
Total Pages : 21 pages
Book Rating : 4.:/5 (227 download)

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Download or read book Mechanism of Telomerase Inhibition Using Small Inibitory RNAs and Induction of Breast Tumor Cell Sensitivity written by and published by . This book was released on 2007 with total page 21 pages. Available in PDF, EPUB and Kindle. Book excerpt: Telomerase, a ribonucleoprotein enzyme composed of an RNA template (hTR) and a catalytically active protein subunit (hTERT), synthesizes telomeres after cell divisions and is obligatory for continuous tumor cell proliferation as well as malignant progression of breast cancer cells. Telomerase is an attractive anti-cancer therapeutic agent because telomerase activity is present in over 90% of human breast cancers but is undetectable in most normal somatic cells. Traditional therapies (surgery, chemotherapy, radiotherapy, etc.) lack the ability to effectively control and cure breast cancer, primarily because residual cells are or become resistant to DNA damaging modalities including standard chemo- and radio-therapies. Since telomerase requires its associated hTR for repeat synthesis, we have chosen to use RNA interference as a method to inactivate hTR and hence telomerase. RNA interference (RNAi) has become a powerful tool for the analysis of gene function in that RNAi allows sequence specific inhibition of gene expression. Another protein we targeted is p21, which has long been established as a requirement for senescence. We wanted to further examine its relationship to senescence and apotosis, in an attempt to sensitize breast tumor cells more effectively.

Telomerase Inhibition and Chemosensitization of Prostate Cancer Cells

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Author :
Publisher :
ISBN 13 :
Total Pages : 17 pages
Book Rating : 4.:/5 (742 download)

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Download or read book Telomerase Inhibition and Chemosensitization of Prostate Cancer Cells written by and published by . This book was released on 2004 with total page 17 pages. Available in PDF, EPUB and Kindle. Book excerpt: We hypothesize that telomerase inhibition (telomere shortening) can sensitize human tumor cells to existing anticancer drugs. During the period of the grant we made the following findings-: 1) 2'-methoxy ethyl oligonucleotides inhibit - -telomerase in prostate cancer cells, cause telomeres to shorten, and cause cell- proliferation to decrease; -2) Cell proliferation in culture is -more pronounced when cells are grown under conditions that mimic tumor growth; 3) Cell proliferation is dramatically reduced in a xenograft model using LNCAP cells, and 4) We did not observe significant synergy with standard chemotherapy agents. The ability of relatively short-term treatments with telomerase inhibitors to slow tumor growth in vivo suggests that telomerase inhibitors are a reasonable approach to prostate cancer therapy.

Telomeres and Telomerase in Cancer

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Author : Keiko Hiyama
Publisher : Springer Science & Business Media
ISBN 13 : 1603278796
Total Pages : 375 pages
Book Rating : 4.6/5 (32 download)

Book Synopsis Telomeres and Telomerase in Cancer by : Keiko Hiyama

Download or read book Telomeres and Telomerase in Cancer written by Keiko Hiyama and published by Springer Science & Business Media. This book was released on 2009-03-18 with total page 375 pages. Available in PDF, EPUB and Kindle. Book excerpt: Telomerase, an enzyme that maintains telomeres and endows eukaryotic cells with immortality, was first discovered in tetrahymena in 1985. In 1990s, it was proven that this enzyme also plays a key role in the infinite proliferation of human cancer cells. Now telomere and telomerase are widely accepted as important factors involved in cancer biology, and as promising diagnostic tools and therapeutic targets. Recently, role of telomerase in “cancer stem cells” has become another attractive story. Until now, there are several good books on telomere and telomerase focusing on biology in ciliates, yeasts, and mouse or basic sciences in human, providing basic scientists or students with updated knowledge.

Development of a Novel In-Situ Telomere Length Qualification System to Address Suitability of Telomerase Inhibitor Therapy to Breast Cancer Following Corrective Surgery

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Author :
Publisher :
ISBN 13 :
Total Pages : 17 pages
Book Rating : 4.:/5 (742 download)

Book Synopsis Development of a Novel In-Situ Telomere Length Qualification System to Address Suitability of Telomerase Inhibitor Therapy to Breast Cancer Following Corrective Surgery by :

Download or read book Development of a Novel In-Situ Telomere Length Qualification System to Address Suitability of Telomerase Inhibitor Therapy to Breast Cancer Following Corrective Surgery written by and published by . This book was released on 2003 with total page 17 pages. Available in PDF, EPUB and Kindle. Book excerpt: Normal breast epithelial cells undergo progressive telomeric shortening throughout their replicative lifespan culminating in critically short telomeres, which trigger replicative senescence. Breast cancer cells are able to bypass this growth-arrest mechanism through deregulated expression of telomerase, which maintains telomeres above the minimal critical length. Based on this observation the suitability of these tumors to telomerase inhibitors as direct or adjuvant therapy needs to be determined. To do this we have developed a novel 3-D quantitative fluorescence in-situ hybridization system to analyze total nuclear telomeric signal from normal and tumor-derived breast epithelial cells in tissue culture. This technique has been applied to tumor-derived breast epithelial cells successfully and will be applied to two normal Human Mammary Epithelial Cell (HMEC) lines, HME13 and HME17. Collection of regular cell and DNA samples has enabled us to determine the mean telomere lengths and rate of shortening for these HMEC lines. We will use Q-FISH to determine a per nuclei telomere dynamic. These findings will then be applied to 3-D models before finally generating predictions of telomere lengths within resected breast tumor samples. This will allow us to determine the suitability of telomerase inhibitors in vivo.

Development of a Novel In-situ Telomere Length Quantification System to Address Suitability of Telomerase Inhibitor Therapy to Breast Cancer Following Corrective Surgery

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Author :
Publisher :
ISBN 13 :
Total Pages : 11 pages
Book Rating : 4.:/5 (946 download)

Book Synopsis Development of a Novel In-situ Telomere Length Quantification System to Address Suitability of Telomerase Inhibitor Therapy to Breast Cancer Following Corrective Surgery by :

Download or read book Development of a Novel In-situ Telomere Length Quantification System to Address Suitability of Telomerase Inhibitor Therapy to Breast Cancer Following Corrective Surgery written by and published by . This book was released on 2002 with total page 11 pages. Available in PDF, EPUB and Kindle. Book excerpt: Normal breast epithelial cells undergo progressive telomeric shortening throughout their replicative lifespan culminating in critically short telomeres, which trigger replicative senescence. Breast cancer cells are able to bypass this growth-arrest mechanism through deregulated expression of telomerase, which maintains telomeres above the minimal critical length. Based on this observation the suitability of these tumors to telomerase inhibitors as direct or adjuvant therapy needs to be determined. To do this we have developed a novel quantitative fluorescence in-situ hybridization system to analyze total nuclear telomeric signal from normal and tumor-derived breast epithelial cells in tissue culture. This technique has been applied to normal human fibroblasts (W138) successfully and will be applied to two normal Human Mammary Epithelial Cell (HMEC) lines, HMEl3 and HME 17%. Through collection of regular cell and DNA samples we will determine the mean telomere lengths and rate of shortening for each HMEC line and use Q-FISH to determine a per nuclei telomere dynamic. These findings will then be applied to 3-D matrigel models before finally generating predictions of telomere lengths within resected breast tumor samples. This will allow us to determine the suitability of telomerase inhibitors in vivo.

Holland-Frei Cancer Medicine

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Author : Robert C. Bast, Jr.
Publisher : John Wiley & Sons
ISBN 13 : 111900084X
Total Pages : 2004 pages
Book Rating : 4.1/5 (19 download)

Book Synopsis Holland-Frei Cancer Medicine by : Robert C. Bast, Jr.

Download or read book Holland-Frei Cancer Medicine written by Robert C. Bast, Jr. and published by John Wiley & Sons. This book was released on 2017-03-10 with total page 2004 pages. Available in PDF, EPUB and Kindle. Book excerpt: Holland-Frei Cancer Medicine, Ninth Edition, offers a balanced view of the most current knowledge of cancer science and clinical oncology practice. This all-new edition is the consummate reference source for medical oncologists, radiation oncologists, internists, surgical oncologists, and others who treat cancer patients. A translational perspective throughout, integrating cancer biology with cancer management providing an in depth understanding of the disease An emphasis on multidisciplinary, research-driven patient care to improve outcomes and optimal use of all appropriate therapies Cutting-edge coverage of personalized cancer care, including molecular diagnostics and therapeutics Concise, readable, clinically relevant text with algorithms, guidelines and insight into the use of both conventional and novel drugs Includes free access to the Wiley Digital Edition providing search across the book, the full reference list with web links, illustrations and photographs, and post-publication updates

Heat Shock Proteins in Cancer

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Author : Stuart K. Calderwood
Publisher : Springer Science & Business Media
ISBN 13 : 1402064012
Total Pages : 399 pages
Book Rating : 4.4/5 (2 download)

Book Synopsis Heat Shock Proteins in Cancer by : Stuart K. Calderwood

Download or read book Heat Shock Proteins in Cancer written by Stuart K. Calderwood and published by Springer Science & Business Media. This book was released on 2007-09-09 with total page 399 pages. Available in PDF, EPUB and Kindle. Book excerpt: Heat shock proteins are emerging as important molecules in the development of cancer and as key targets in cancer therapy. These proteins enhance the growth of cancer cells and protect tumors from treatments such as drugs or surgery. However, new drugs have recently been developed particularly those targeting heat shock protein 90. As heat shock protein 90 functions to stabilize many of the oncogenes and growth promoting proteins in cancer cells, such drugs have broad specificity in many types of cancer cell and offer the possibility of evading the development of resistance through point mutation or use of compensatory pathways. Heat shock proteins have a further property that makes them tempting targets in cancer immunotherapy. These proteins have the ability to induce an inflammatory response when released in tumors and to carry tumor antigens to antigen presenting cells. They have thus become important components of anticancer vaccines. Overall, heat shock proteins are important new targets in molecular cancer therapy and can be approached in a number of contrasting approaches to therapy.

Role of Nutraceuticals in Cancer Chemosensitization

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Author :
Publisher : Academic Press
ISBN 13 : 0128123745
Total Pages : 400 pages
Book Rating : 4.1/5 (281 download)

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Download or read book Role of Nutraceuticals in Cancer Chemosensitization written by and published by Academic Press. This book was released on 2017-10-18 with total page 400 pages. Available in PDF, EPUB and Kindle. Book excerpt: Role of Nutraceuticals in Chemoresistance to Cancer, Volume Two, focuses on nutraceuticals, the compounds derived from natural sources, which are usually multi-targeted as a means to overcome chemoresistance. This book discusses the role of several compounds related to nutraceuticals and chemoresistance, such as curcumin, resveratrol, indole 3-carbinol, tocotrienols, ursolic acid, fisetin, celastrol, gambogic, butein, catechins and silymarin. It is a valuable resource for cancer researchers, oncologists and members of several areas of the biomedical field who are interested in understanding how to use nutraceuticals as a sensitizing agent for chemotherapy. Brings updated information on natural compounds used as specific inhibitors of cell signaling pathways as reviewed by experts in the field Presents experts analysis and summary of reported and novel findings and potential translational application in cancer patients Describes molecular mechanisms with new and helpful approaches for the readers to use in their own investigations

Cancer Cell Chemoresistance and Chemosensitization

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Author : Ajaikumar B. Kunnumakkara
Publisher : World Scientific
ISBN 13 : 9813208570
Total Pages : 682 pages
Book Rating : 4.8/5 (132 download)

Book Synopsis Cancer Cell Chemoresistance and Chemosensitization by : Ajaikumar B. Kunnumakkara

Download or read book Cancer Cell Chemoresistance and Chemosensitization written by Ajaikumar B. Kunnumakkara and published by World Scientific. This book was released on 2018 with total page 682 pages. Available in PDF, EPUB and Kindle. Book excerpt: "Despite the significant advances in cancer therapy made through constant evaluation and analysis of treatment aftereffects, the disease still remains one of the foremost causes of mortality worldwide killing more than 12 million people annually. The prime reason behind the failure of conventional chemotherapeutics which are used as the chief regimen in the comprehensive treatment of cancers is the development of chemoresistance. It can be either intrinsic or acquired and is primarily mediated via different key regulators like MDR, MAPK, NF-κB, PI3K/Akt, Wnt signaling pathways etc. Thus, agents which can target these regulatory elements or pathways and in turn sensitize cancer cells to chemotherapy holds immense prospect. However, there is barely such comprehensive work available in scientific literature that explains how chemosensitization of cancer cells functions using different drug combinations and exhibit synergism. This book provides a detailed description of chemoresistance and chemosensitization, targets for chemosensitization and various approaches adapted in the process of chemosensitization. Furthermore, the book explicates the role of various chemosensitizers, both natural and synthetic in sensitizing cancer cells and also details the current research findings on chemosensitization of different cancer types in both pre-clinical and clinical settings."--Publisher's website

Mitochondria as Targets for Phytochemicals in Cancer Prevention and Therapy

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Author : Dhyan Chandra
Publisher : Springer Science & Business Media
ISBN 13 : 1461493269
Total Pages : 267 pages
Book Rating : 4.4/5 (614 download)

Book Synopsis Mitochondria as Targets for Phytochemicals in Cancer Prevention and Therapy by : Dhyan Chandra

Download or read book Mitochondria as Targets for Phytochemicals in Cancer Prevention and Therapy written by Dhyan Chandra and published by Springer Science & Business Media. This book was released on 2013-12-11 with total page 267 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book highlights the importance of phytochemicals and mitochondria in cancer prevention and therapy. Recent scientific discoveries have identified that naturally occurring biologically active compounds (i.e. phytochemicals) target multiple steps of tumorigenesis leading to the inhibition or delay in cancer progression. Mitochondria, organelles within a cell, are a critical target for phytochemicals in regulating the initiation, promotion, and progression of cancer. The book is divided into three parts to better communicate the important findings related to phytochemicals and mitochondria in cancer research. The first part describes updates on environmental and genetic factors causing cancer initiation and progression, the role of mitochondria function in regulating the process of tumorigenesis, and the role of mitochondria in regulating cell death such as apoptosis, autophagy, and necroptosis. The second part focuses on the elucidation of key target proteins that could be exploited for cancer prevention, an the role of phytochemicals in cancer prevention, updates on basic research related to phytochemicals action critical for cancer prevention, and updates on translational knowledge on cancer prevention by phytochemicals. The third part provides updates on phytochemicals targeting mitochondria for cancer therapy, an overview of action of phytochemicals on cancer stem cells, updates on the role of microRNA in phytochemicals-based therapy of cancer, and updates on phytochemicals-based translation research on therapy for metastatic cancer.

Breast Cancer

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Author : Phuc Van Pham
Publisher : BoD – Books on Demand
ISBN 13 : 9535129996
Total Pages : 570 pages
Book Rating : 4.5/5 (351 download)

Book Synopsis Breast Cancer by : Phuc Van Pham

Download or read book Breast Cancer written by Phuc Van Pham and published by BoD – Books on Demand. This book was released on 2017-04-05 with total page 570 pages. Available in PDF, EPUB and Kindle. Book excerpt: Breast Cancer - From Biology to Medicine thoroughly examines breast cancer from basic definitions, to cellular and molecular biology, to diagnosis and treatment. This book also has some additional focus on preclinical and clinical results in diagnosis and treatment of breast cancer. The book begins with introduction on epidemiology and pathophysiology of breast cancer in Section 1. In Section 2, the subsequent chapters introduce molecular and cellular biology of breast cancer with some particular signaling pathways, the gene expression, as well as the gene methylation and genomic imprinting, especially the existence of breast cancer stem cells. In Section 3, some new diagnostic methods and updated therapies from surgery, chemotherapy, hormone therapy, immunotherapy, radiotherapy, and some complementary therapies are discussed. This book provides a succinct yet comprehensive overview of breast cancer for advanced students, graduate students, and researchers as well as those working with breast cancer in a clinical setting.

Glucosinolates

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Author : J. M. Merillon
Publisher :
ISBN 13 : 9783319264790
Total Pages : pages
Book Rating : 4.2/5 (647 download)

Book Synopsis Glucosinolates by : J. M. Merillon

Download or read book Glucosinolates written by J. M. Merillon and published by . This book was released on with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Repurposed Drugs Targeting Cancer Signaling Pathways: Dissecting New Mechanisms of Action Through in vitro and in vivo Analyses

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Author : Alma D. Campos-Parra
Publisher : Frontiers Media SA
ISBN 13 : 288971716X
Total Pages : 326 pages
Book Rating : 4.8/5 (897 download)

Book Synopsis Repurposed Drugs Targeting Cancer Signaling Pathways: Dissecting New Mechanisms of Action Through in vitro and in vivo Analyses by : Alma D. Campos-Parra

Download or read book Repurposed Drugs Targeting Cancer Signaling Pathways: Dissecting New Mechanisms of Action Through in vitro and in vivo Analyses written by Alma D. Campos-Parra and published by Frontiers Media SA. This book was released on 2021-11-29 with total page 326 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Dissertation Abstracts International

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Author :
Publisher :
ISBN 13 :
Total Pages : 902 pages
Book Rating : 4.F/5 ( download)

Book Synopsis Dissertation Abstracts International by :

Download or read book Dissertation Abstracts International written by and published by . This book was released on 2008 with total page 902 pages. Available in PDF, EPUB and Kindle. Book excerpt: