Pub Date : 2010-01-01DOI: 10.2174/1876822901003010078
Benjamin M Johnson, Bently P Doonan, Faisal F Radwan, Azizul Haque
Prostate cancer is the most commonly diagnosed cancer in men and accounts for significant morbidity and mortality in the western world. While traditional therapies are effective at clearing early stage cancer, they often fail to treat late stage metastatic disease. Thus, an effective therapy that targets prostate tumor growth and metastasis is desired for alleviating the disease and improving patient outcomes. Natural extracts have been the focus of recent investigation, particularly those with reduced cellular toxicity to healthy tissue. In this review, we discuss one potential candidate, ganoderic acid, an extract from the Ganoderma lucidum mushroom that has been tested in multiple cancer models. Interestingly, ganoderic acid DM (GA-DM) has shown toxicity to both androgen-dependent and independent prostate cancer cells with reduced osteoclastogenesis in late stage metastatic disease. This review will discuss the current knowledge on this GA-DM extract and the potential benefit in treating advanced prostate cancer. We will also provide an overview on the targeted delivery of GA-DM through nanoparticles that would reduce bystander toxicity and improve the drug's effectiveness. An improved understanding of this drug and its uses will advance the field of natural chemotherapeutics, particularly in treating advanced prostate cancer.
{"title":"Ganoderic Acid DM: An Alternative Agent for the Treatment of Advanced Prostate Cancer.","authors":"Benjamin M Johnson, Bently P Doonan, Faisal F Radwan, Azizul Haque","doi":"10.2174/1876822901003010078","DOIUrl":"https://doi.org/10.2174/1876822901003010078","url":null,"abstract":"Prostate cancer is the most commonly diagnosed cancer in men and accounts for significant morbidity and mortality in the western world. While traditional therapies are effective at clearing early stage cancer, they often fail to treat late stage metastatic disease. Thus, an effective therapy that targets prostate tumor growth and metastasis is desired for alleviating the disease and improving patient outcomes. Natural extracts have been the focus of recent investigation, particularly those with reduced cellular toxicity to healthy tissue. In this review, we discuss one potential candidate, ganoderic acid, an extract from the Ganoderma lucidum mushroom that has been tested in multiple cancer models. Interestingly, ganoderic acid DM (GA-DM) has shown toxicity to both androgen-dependent and independent prostate cancer cells with reduced osteoclastogenesis in late stage metastatic disease. This review will discuss the current knowledge on this GA-DM extract and the potential benefit in treating advanced prostate cancer. We will also provide an overview on the targeted delivery of GA-DM through nanoparticles that would reduce bystander toxicity and improve the drug's effectiveness. An improved understanding of this drug and its uses will advance the field of natural chemotherapeutics, particularly in treating advanced prostate cancer.","PeriodicalId":22947,"journal":{"name":"The open prostate cancer journal","volume":"3 ","pages":"78-85"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4002166/pdf/nihms434200.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32309713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2009-01-01DOI: 10.2174/1876822900902010059
Isis C Sroka, Gerald D Pond, Raymond B Nagle, Frank Porreca, Tamara King, Gary Pestano, Bernard W Futscher, Jaime M Gard, Janice Riley, Anne E Cress
Existing clinical imaging procedures lack sensitivity and specificity in detecting early prostate cancer bone metastatic lesions. In this study, we developed a highly reproducible bone metastasis xenograft model and identified possible molecular imaging candidates for detecting early bone metastatic lesions. Bone trophic human prostate cells (PC-3B1) were isolated and characterized for their ability to reach bone after intracardiac injection into SCID mice. The appearances of skeletal metastases were evaluated using digital radiographic imaging and confirmed by necropsy and histology. The PC-3B1 cells retain a bone homing phenotype after long term propagation in tissue culture and exhibit progressive bone lesions within 3 weeks following intracardiac injection. Comparative transcription signatures of PC-3 and PC-3B1 cells were determined using a cancer specific microarray and confirmed by RT-PCR analysis. The analysis identified increased expression of four cell surface molecules in PC-3B1 cells that may be suitable as molecular imaging candidates to detect bone micro metastases.
{"title":"Human Cell Surface Receptors as Molecular Imaging Candidates for Metastatic Prostate Cancer.","authors":"Isis C Sroka, Gerald D Pond, Raymond B Nagle, Frank Porreca, Tamara King, Gary Pestano, Bernard W Futscher, Jaime M Gard, Janice Riley, Anne E Cress","doi":"10.2174/1876822900902010059","DOIUrl":"https://doi.org/10.2174/1876822900902010059","url":null,"abstract":"<p><p>Existing clinical imaging procedures lack sensitivity and specificity in detecting early prostate cancer bone metastatic lesions. In this study, we developed a highly reproducible bone metastasis xenograft model and identified possible molecular imaging candidates for detecting early bone metastatic lesions. Bone trophic human prostate cells (PC-3B1) were isolated and characterized for their ability to reach bone after intracardiac injection into SCID mice. The appearances of skeletal metastases were evaluated using digital radiographic imaging and confirmed by necropsy and histology. The PC-3B1 cells retain a bone homing phenotype after long term propagation in tissue culture and exhibit progressive bone lesions within 3 weeks following intracardiac injection. Comparative transcription signatures of PC-3 and PC-3B1 cells were determined using a cancer specific microarray and confirmed by RT-PCR analysis. The analysis identified increased expression of four cell surface molecules in PC-3B1 cells that may be suitable as molecular imaging candidates to detect bone micro metastases.</p>","PeriodicalId":22947,"journal":{"name":"The open prostate cancer journal","volume":"2 ","pages":"59-66"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3212735/pdf/nihms164369.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30107580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-03-05DOI: 10.1046/J.1525-1411.2001.32004.X
L. Brive, D. Agus, K. R. Ely
Background: Mutant androgen receptors (ARs) that arise in prostate cancer cells may contribute directly to the development of advanced disease in some patients. Therefore, a structural understanding of the altered receptors will provide new information about the molecular triggers that lead to androgen-independent disease or metastatic spread. Methods: Recognizing that molecular localization is required to understand the effect of AR mutations on receptor function, a structural model of the ligand-binding domain of AR was used to locate a comprehensive set of mutations in this domain that occur in prostate cancer. Substitutions were grouped into those that are likely to affect (1) ligand binding, (2) dimerization, or (3) coactivator binding/transactivation. Results: The results were tabulated and were used to develop a novel structure-based database linking molecular location with clinical observations for each mutant receptor expressed in the prostate cancer cells. Categories in the database can be cross-referenced to retrieve, for each mutation, molecular details of the substitution, clinical stage of the disease, treatment history, and functional phenotype of the mutant receptor. Conclusions: This database will be a resource for the development of therapeutics targeted to the AR and for understanding the role of ARs in androgen independence.
{"title":"Structure‐Based Androgen Receptor Gene Mutation Database: A Tool to Link Molecular Location and Receptor Function","authors":"L. Brive, D. Agus, K. R. Ely","doi":"10.1046/J.1525-1411.2001.32004.X","DOIUrl":"https://doi.org/10.1046/J.1525-1411.2001.32004.X","url":null,"abstract":"Background: Mutant androgen receptors (ARs) that arise in prostate cancer cells may contribute directly to the development of advanced disease in some patients. Therefore, a structural understanding of the altered receptors will provide new information about the molecular triggers that lead to androgen-independent disease or metastatic spread. \u0000 \u0000 \u0000 \u0000Methods: Recognizing that molecular localization is required to understand the effect of AR mutations on receptor function, a structural model of the ligand-binding domain of AR was used to locate a comprehensive set of mutations in this domain that occur in prostate cancer. Substitutions were grouped into those that are likely to affect (1) ligand binding, (2) dimerization, or (3) coactivator binding/transactivation. \u0000 \u0000 \u0000 \u0000Results: The results were tabulated and were used to develop a novel structure-based database linking molecular location with clinical observations for each mutant receptor expressed in the prostate cancer cells. Categories in the database can be cross-referenced to retrieve, for each mutation, molecular details of the substitution, clinical stage of the disease, treatment history, and functional phenotype of the mutant receptor. \u0000 \u0000 \u0000 \u0000Conclusions: This database will be a resource for the development of therapeutics targeted to the AR and for understanding the role of ARs in androgen independence.","PeriodicalId":22947,"journal":{"name":"The open prostate cancer journal","volume":"49 1","pages":"76-91"},"PeriodicalIF":0.0,"publicationDate":"2002-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77601801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-04-01DOI: 10.1046/J.1525-1411.2001.32008.X
G. Bubley, S. Balk, R. Joyce, M. Taplin
Objectives: To determine whether hormones derived from the adrenal gland affected the progression of androgen-independent (AI) prostate cancer for patients already receiving treatment with high-dose bicalutamide. This was accomplished by using a sequential trial design in which medically or surgically castrated patients with AI prostate cancer whose cancers were progressing while receiving bicalutamide were treated with adrenolytic therapy in the form of aminoglutethimide (AM) and hydrocortisone (HC). Materials and Methods: Sixteen patients with AI prostate cancer were enrolled into this trial. All patients had metastatic disease in the bone, and two patients had additional metastases at other sites. Using prostate specific antigen (PSA) level as an indicator of disease activity, patients initially received bicalutamide therapy, then AM and HC were added to the regimen, and then bicalutamide therapy was discontinued, with each documented PSA level increase (see Figure 1). Figure 1. Clinical Trial Study Design: Patients were treated with sequential hormonal interventions according to the scheme depicted above. Download figure to PowerPoint Results: Four (25%) patients demonstrated PSA level reductions of at least 50% after the initiation of bicalutamide, 150 mg/day. No patient demonstrated a PSA or obvious clinical response to the addition of AM and HC to the regimen. This includes the four patients who were initially sensitive to bicalutamide. Therapy with AM and HC was associated with fatigue and skin rashes. These side effects persisted after the withdrawal of bicalutamide therapy and were therefore attributed to AM and HC therapy. Conclusions: Bicalutamide at high doses seems to effectively block the androgen receptor (AR) from the growth stimulation derived from adrenal hormones. Therefore, the inhibition of adrenal hormone production by AM is not a useful therapeutic maneuver in this setting and is associated with moderate side effects. The activation of the AR pathway in these patients may occur by a mechanism other than stimulation by the androgens derived from the testes or adrenal gland.
{"title":"Lack of Effect of Aminoglutethimide and Hydrocortisone Added to High-Dose Bicalutamide for Androgen-Independent Prostate Cancer","authors":"G. Bubley, S. Balk, R. Joyce, M. Taplin","doi":"10.1046/J.1525-1411.2001.32008.X","DOIUrl":"https://doi.org/10.1046/J.1525-1411.2001.32008.X","url":null,"abstract":"Objectives: To determine whether hormones derived from the adrenal gland affected the progression of androgen-independent (AI) prostate cancer for patients already receiving treatment with high-dose bicalutamide. This was accomplished by using a sequential trial design in which medically or surgically castrated patients with AI prostate cancer whose cancers were progressing while receiving bicalutamide were treated with adrenolytic therapy in the form of aminoglutethimide (AM) and hydrocortisone (HC). \u0000 \u0000 \u0000 \u0000Materials and Methods: Sixteen patients with AI prostate cancer were enrolled into this trial. All patients had metastatic disease in the bone, and two patients had additional metastases at other sites. Using prostate specific antigen (PSA) level as an indicator of disease activity, patients initially received bicalutamide therapy, then AM and HC were added to the regimen, and then bicalutamide therapy was discontinued, with each documented PSA level increase (see Figure 1). \u0000 \u0000 \u0000 \u0000 \u0000Figure 1. Clinical Trial Study Design: Patients were treated with sequential hormonal interventions according to the scheme depicted above. \u0000 \u0000Download figure to PowerPoint \u0000 \u0000 \u0000 \u0000 \u0000Results: Four (25%) patients demonstrated PSA level reductions of at least 50% after the initiation of bicalutamide, 150 mg/day. No patient demonstrated a PSA or obvious clinical response to the addition of AM and HC to the regimen. This includes the four patients who were initially sensitive to bicalutamide. Therapy with AM and HC was associated with fatigue and skin rashes. These side effects persisted after the withdrawal of bicalutamide therapy and were therefore attributed to AM and HC therapy. \u0000 \u0000 \u0000 \u0000Conclusions: Bicalutamide at high doses seems to effectively block the androgen receptor (AR) from the growth stimulation derived from adrenal hormones. Therefore, the inhibition of adrenal hormone production by AM is not a useful therapeutic maneuver in this setting and is associated with moderate side effects. The activation of the AR pathway in these patients may occur by a mechanism other than stimulation by the androgens derived from the testes or adrenal gland.","PeriodicalId":22947,"journal":{"name":"The open prostate cancer journal","volume":"64 1","pages":"98-104"},"PeriodicalIF":0.0,"publicationDate":"2001-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86131595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-04-01DOI: 10.1046/J.1525-1411.2001.32006.X
D. Solit, D. Agus
{"title":"HER‐Kinase‐Directed Therapy of Prostate Cancer","authors":"D. Solit, D. Agus","doi":"10.1046/J.1525-1411.2001.32006.X","DOIUrl":"https://doi.org/10.1046/J.1525-1411.2001.32006.X","url":null,"abstract":"","PeriodicalId":22947,"journal":{"name":"The open prostate cancer journal","volume":"47 4 1","pages":"53-58"},"PeriodicalIF":0.0,"publicationDate":"2001-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76515999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}