Prostate Cancer
· 2013 · PMID 24396604
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Despite the clinical implication and high incidence of bone and spinal metastases, the molecular mechanisms behind prostate cancer metastasis to bone and spine are not well understood. In this review the molecular mechan...Despite the clinical implication and high incidence of bone and spinal metastases, the molecular mechanisms behind prostate cancer metastasis to bone and spine are not well understood. In this review the molecular mechanisms that may contribute to the highly metastatic phenotype of prostate cancer are discussed. Proangiogenic factors such as vascular endothelial growth factor (VEGF) have been shown to not only aid in the metastatic capabilities of prostate cancer but also encourage the colonization and growth of prostate tumour cells in the skeleton. The importance of VEGF in the complex process of prostate cancer dissemination to the skeleton is discussed, including its role in the development of the bone premetastatic niche, metastatic tumour cell recognition of bone, and bone remodeling. The expression of VEGF has also been shown to be upregulated in prostate cancer and is associated with clinical stage, Gleason score, tumour stage, progression, metastasis, and survival. Due to the multifaceted effect VEGF has on tumour angiogenesis, tumour cell proliferation, and bone destruction, therapies targeting the VEGF pathways have shown promising clinical application and are being investigated in clinical trials.
Chornokur G, Amankwah EK, Davis SN
… +4 more, Phelan CM, Park JY, Pow-Sang J, Kumar NB
Prostate Cancer
· 2013 · PMID 24386569
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Background. Prostate cancer (PCa) racial disparity is multifactorial, involving biological, sociocultural, and lifestyle determinants. We investigated the association between selected potentially functional polymorphisms...Background. Prostate cancer (PCa) racial disparity is multifactorial, involving biological, sociocultural, and lifestyle determinants. We investigated the association between selected potentially functional polymorphisms (SNPs) and prostate cancer (PCa) risk in Black (AAM) and White (EAM) men. We further explored if these associations varied by the body mass index (BMI) and height. Methods. Age-matched DNA samples from 259 AAM and 269 EAM were genotyped for 10 candidate SNPs in 7 genes using the TaqMan allelic differentiation analysis. The dominant, recessive, and additive age-adjusted unconditional logistic regression models were fitted. Results. Three SNPs showed statistically significant associations with PCa risk: in AAM, HNF1B rs7501939 (OR = 2.42, P = 0.0046) and rs4430796 (OR = 0.57, P = 0.0383); in EAM, CTBP2 rs4962416 (OR = 1.52, P = 0.0384). In addition, high BMI in AAM (OR = 1.06, P = 0.022) and height in EAM (OR = 0.92, P = 0.0434) showed significant associations. Interestingly, HNF1B rs7501939 was associated with PCa exclusively in obese AAM (OR = 2.14, P = 0.0103). Conclusion. Our results suggest that variation in the HNF1B may influence PCa risk in obese AAM.
Peltier A, Aoun F, El-Khoury F
… +5 more, Hawaux E, Limani K, Narahari K, Sirtaine N, van Velthoven R
Prostate Cancer
· 2013 · PMID 24349788
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Objectives. To compare prostate cancer detection rates of extended 2D versus 3D biopsies and to further assess the clinical impact of this method in day-to-day practice. Methods. We analyzed the data of a cohort of 220 c...Objectives. To compare prostate cancer detection rates of extended 2D versus 3D biopsies and to further assess the clinical impact of this method in day-to-day practice. Methods. We analyzed the data of a cohort of 220 consecutive patients with no prior history of prostate cancer who underwent an initial prostate biopsy in daily practice due to an abnormal PSA and/or DRE using, respectively, the classical 2D and the new 3D systems. All the biopsies were done by a single experienced operator using the same standardized protocol. Results. There was no significant difference in terms of age, total PSA, or prostate volume between the two groups. However, cancer detection rate was significantly higher using the 3D versus the 2D system, 50% versus 34% (P < 0.05). There was no statistically significant difference while comparing the 2 groups in term of nonsignificant cancer detection. Conclusion. There is reasonable evidence demonstrating the superiority of the 3D-guided biopsies in detecting prostate cancers that would have been missed using the 2D extended protocol.
Prostate Cancer
· 2013 · PMID 24327925
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Since the introduction of robot-assisted radical prostatectomy (RALP), robotics has become increasingly more commonplace in the armamentarium of the urologic surgeon. Robotic utilization has exploded across surgical disc...Since the introduction of robot-assisted radical prostatectomy (RALP), robotics has become increasingly more commonplace in the armamentarium of the urologic surgeon. Robotic utilization has exploded across surgical disciplines well beyond the fields of urology and prostate surgery. The literature detailing technical steps, comparison of large surgical series, and even robotically focused randomized control trials are available for review. RALP, the first robot-assisted surgical procedure to achieve widespread use, has recently become the primary approach for the surgical management of localized prostate cancer. As a result, surgeons are constantly trying to refine and improve upon current technical aspects of the operation. Recent areas of published modifications include bladder neck anastomosis and reconstruction, bladder drainage, nerve sparing approaches and techniques, and perioperative and postoperative management including penile rehabilitation. In this review, we summarize recent advances in perioperative management and surgical technique for RALP.
Mesko S, Kupelian P, Demanes DJ
… +3 more, Huang J, Wang PC, Kamrava M
Prostate Cancer
· 2013 · PMID 24222860
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BACKGROUND: Ki-67 is a robust predictive/prognostic marker in prostate cancer; however, tumor heterogeneity in prostate biopsy samples is not well studied. METHODS: Using an MRI/US fusion device, biopsy cores were obtain...BACKGROUND: Ki-67 is a robust predictive/prognostic marker in prostate cancer; however, tumor heterogeneity in prostate biopsy samples is not well studied. METHODS: Using an MRI/US fusion device, biopsy cores were obtained systematically and by targeting when indicated by MRI. Prostate cores containing cancer from 77 consecutive men were analyzed. The highest Ki-67 was used to determine interprostatic variation. Ki-67 range (highest minus lowest) was used to determine intraprostatic and intralesion variation. Apparent diffusion coefficient (ADC) values were evaluated in relation to Ki-67. RESULTS: Interprostatic Ki-67 mean ± standard deviation (SD) values for NCCN low (L), intermediate (I), and high (H) risk patients were 5.1 ± 3.8%, 7.4 ± 6.8%, and 12.0 ± 12.4% (ANOVA P = 0.013). Intraprostatic mean ± SD Ki-67 ranges in L, I, and H risk patients were 2.6 ± 3.6%, 5.3 ± 6.8%, and 10.9 ± 12.3% (ANOVA P = 0.027). Intralesion mean ± SD Ki-67 ranges in L, I, and H risk patients were 1.1 ± 0.9%, 5.2 ± 7.9%, and 8.1 ± 10.8% (ANOVA P = 0.22). ADC values at Ki-67 > and <7.1% were 860 ± 203 and 1036 ± 217, respectively (P = 0.0029). CONCLUSIONS: High risk patients have significantly higher inter- and intraprostatic Ki-67 heterogeneity. This needs to be considered when utilizing Ki-67 clinically.
Laderach DJ, Gentilini L, Jaworski FM
… +1 more, Compagno D
Prostate Cancer
· 2013 · PMID 24205440
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A better understanding of multimolecular interactions involved in tumor dissemination is required to identify new effective therapies for advanced prostate cancer (PCa). Several groups investigated protein-glycan interac...A better understanding of multimolecular interactions involved in tumor dissemination is required to identify new effective therapies for advanced prostate cancer (PCa). Several groups investigated protein-glycan interactions as critical factors for crosstalk between prostate tumors and their microenvironment. This review both discusses whether the "galectin-signature" might serve as a reliable biomarker for the identification of patients with high risk of metastasis and assesses the galectin-glycan lattices as potential novel targets for anticancer therapies. The ultimate goal of this review is to convey how basic findings related to galectins could be in turn translated into clinical settings for patients with advanced PCa.
El-Amm J, Freeman A, Patel N
… +1 more, Aragon-Ching JB
Prostate Cancer
· 2013 · PMID 24069538
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Majority of patients with metastatic castrate resistant prostate cancer (mCRPC) develop bone metastases which results in significant morbidity and mortality as a result of skeletal-related events (SREs). Several bone-tar...Majority of patients with metastatic castrate resistant prostate cancer (mCRPC) develop bone metastases which results in significant morbidity and mortality as a result of skeletal-related events (SREs). Several bone-targeted agents are either in clinical use or in development for prevention of SREs. Bisphosphonates were the first class of drugs investigated for prevention of SREs and zoledronic acid is the only bisphosphonate that is FDA-approved for this indication. Another bone-targeted agent is denosumab which is a fully humanized monoclonal antibody that binds to the RANK-L thereby inhibiting RANK-L mediated bone resorption. While several radiopharmaceuticals were approved for pain palliation in mCRPC including strontium and samarium, alpharadin is the first radiopharmaceutical to show significant overall survival benefit. Contemporary therapeutic options including enzalutamide and abiraterone have effects on pain palliation and SREs as well. Other novel bone-targeted agents are currently in development, including the receptor tyrosine kinase inhibitors cabozantinib and dasatinib. Emerging therapeutics in mCRPC has resulted in great strides in preventing one of the most significant sources of complications of bone metastases.
Badani KK, Shapiro EY, Berg WT
… +5 more, Kaufman S, Bergman A, Wambi C, Roychoudhury A, Patel T
Prostate Cancer
· 2013 · PMID 23862066
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Purpose. To report on the feasibility of a new Laparoscopic Doppler ultrasound (LDU) technology to aid in identifying and preserving arterial blood flow within the neurovascular bundle (NVB) during robotic prostatectomy...Purpose. To report on the feasibility of a new Laparoscopic Doppler ultrasound (LDU) technology to aid in identifying and preserving arterial blood flow within the neurovascular bundle (NVB) during robotic prostatectomy (RARP). Materials and Methods. Nine patients with normal preoperative potency and scheduled for a bilateral nerve-sparing procedure were prospectively enrolled. LDU was used to measure arterial flow at 6 anatomic locations alongside the prostate, and signal intensity was evaluated by 4 independent reviewers. Measurements were made before and after NVB dissection. Modifications in nerve-sparing procedure due to LDU use were recorded. Postoperative erectile function was assessed. Fleiss Kappa statistic was used to evaluate inter-rater agreement for each of the 12 measurements. Results. Analysis of Doppler signal intensity showed maintenance of flow in 80% of points assessed, a decrease in 16%, and an increase in 4%. Plane of NVB dissection was altered in 5 patients (56%) on the left and in 4 patients (44%) on the right. There was good inter-rater reliability for the 4 reviewers. Use of the probe did not significantly increase operative time or result in any complications. Seven (78%) patients had recovery of erections at time of the 8-month follow-up visit. Conclusions. LDU is a safe, easy to use, and effective method to identify local vasculature and anatomic landmarks during RARP, and can potentially be used to achieve greater nerve preservation.
Patel JC, Maughan BL, Agarwal AM
… +3 more, Batten JA, Zhang TY, Agarwal N
Prostate Cancer
· 2013 · PMID 23819055
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Androgen deprivation therapy (ADT) with medical or surgical castration is the mainstay of therapy in men with metastatic prostate cancer. However, despite initial responses, almost all men eventually develop castration r...Androgen deprivation therapy (ADT) with medical or surgical castration is the mainstay of therapy in men with metastatic prostate cancer. However, despite initial responses, almost all men eventually develop castration refractory metastatic prostate cancer (CRPC) and die of their disease. Over the last decade, it has been recognized that despite the failure of ADT, most prostate cancers maintain some dependence on androgen and/or androgen receptor (AR) signaling for proliferation. Furthermore, androgen independent molecular pathways have been identified as drivers of continued progression of CRPC. Subsequently, drugs have been developed targeting these pathways, many of which have received regulatory approval. Agents such as abiraterone, enzalutamide, orteronel (TAK-700), and ARN-509 target androgen signaling. Sipuleucel-T, ipilimumab, and tasquinimod augment immune-mediated tumor killing. Agents targeting classic tumorogenesis pathways including vascular endothelial growth factor, hepatocyte growth factor, insulin like growth factor-1, tumor suppressor, and those which regulate apoptosis and cell cycles are currently being developed. This paper aims to focus on emerging molecular pathways underlying progression of CRPC, and the drugs targeting these pathways, which have recently been approved or have reached advanced stages of development in either phase II or phase III clinical trials.
Prostate Cancer
· 2013 · PMID 23766912
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Purpose. To determine whether Ski-interacting protein (SKIP) regulates TGF- β 1-stimulated expression of urokinase-type plasminogen activator (uPA), matrix metalloproteinase-9 (MMP-9), and uPA Inhibitor (PAI-1) in the an...Purpose. To determine whether Ski-interacting protein (SKIP) regulates TGF- β 1-stimulated expression of urokinase-type plasminogen activator (uPA), matrix metalloproteinase-9 (MMP-9), and uPA Inhibitor (PAI-1) in the androgen-independent human prostate cancer cell model. Materials and Methods. PC-3 prostate cancer cell line was used. The role of SKIP was evaluated using synthetic small interference RNA (siRNA) compounds. The expression of uPA, MMP-9, and PAI-1 was evaluated by zymography assays, RT-PCR, and promoter transactivation analysis. Results. In PC-3 cells TGF- β 1 treatment stimulated uPA, PAI-1, and MMP-9 expressions. The knockdown of SKIP in PC-3 cells enhanced the basal level of uPA, and TGF- β 1 treatment inhibited uPA production. Both PAI-1 and MMP-9 production levels were increased in response to TGF- β 1. The ectopic expression of SKIP inhibited both TGF- β 1-induced uPA and MMP-9 promoter transactivation, while PAI-1 promoter response to the factor was unaffected. Conclusions. SKIP regulates the expression of uPA, PAI-1, and MMP-9 stimulated by TGF- β 1 in PC-3 cells. Thus, SKIP is implicated in the regulation of extracellular matrix degradation and can therefore be suggested as a novel therapeutic target in prostate cancer treatment.
Gnanasekar M, Kalyanasundaram R, Zheng G
… +3 more, Chen A, Bosland MC, Kajdacsy-Balla A
Prostate Cancer
· 2013 · PMID 23766911
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High mobility group box 1 (HMGB1) was originally discovered as a chromatin-binding protein several decades ago. It is now increasingly evident that HMGB1 plays a major role in several disease conditions such as atheroscl...High mobility group box 1 (HMGB1) was originally discovered as a chromatin-binding protein several decades ago. It is now increasingly evident that HMGB1 plays a major role in several disease conditions such as atherosclerosis, diabetes, arthritis, sepsis, and cancer. It is intriguing how deregulation of HMGB1 can result in a myriad of disease conditions. Interestingly, HMGB1 is involved in cell proliferation, angiogenesis, and metastasis during cancer progression. Furthermore, HMGB1 has been demonstrated to exert intracellular and extracellular functions, activating key oncogenic signaling pathways. This paper focuses on the role of HMGB1 in prostate cancer development and highlights the potential of HMGB1 to serve as a key target for prostate cancer treatment.
da Silva HB, Amaral EP, Nolasco EL
… +6 more, de Victo NC, Atique R, Jank CC, Anschau V, Zerbini LF, Correa RG
Prostate Cancer
· 2013 · PMID 23738079
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Prostate cancer (PCa) is one of the most common malignancies found in males. The development of PCa involves several mutations in prostate epithelial cells, usually linked to developmental changes, such as enhanced resis...Prostate cancer (PCa) is one of the most common malignancies found in males. The development of PCa involves several mutations in prostate epithelial cells, usually linked to developmental changes, such as enhanced resistance to apoptotic death, constitutive proliferation, and, in some cases, to differentiation into an androgen deprivation-resistant phenotype, leading to the appearance of castration-resistant PCa (CRPCa), which leads to a poor prognosis in patients. In this review, we summarize recent findings concerning the main deregulations into signaling pathways that will lead to the development of PCa and/or CRPCa. Key mutations in some pathway molecules are often linked to a higher prevalence of PCa, by directly affecting the respective cascade and, in some cases, by deregulating a cross-talk node or junction along the pathways. We also discuss the possible environmental and nonenvironmental inducers for these mutations, as well as the potential therapeutic strategies targeting these signaling pathways. A better understanding of how some risk factors induce deregulation of these signaling pathways, as well as how these deregulated pathways affect the development of PCa and CRPCa, will further help in the development of new treatments and prevention strategies for this disease.
Sorongon-Legaspi MK, Chua M, Sio MC
… +1 more, Morales M
Prostate Cancer
· 2013 · PMID 23589776
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Previous researches involving dietary methods have shown conflicting findings. Authors sought to assess the association of prostate cancer risk with blood levels of omega-3 polyunsaturated fatty acids (n-3 PUFA) through...Previous researches involving dietary methods have shown conflicting findings. Authors sought to assess the association of prostate cancer risk with blood levels of omega-3 polyunsaturated fatty acids (n-3 PUFA) through a meta-analysis of human epidemiological studies in available online databases (July, 2012). After critical appraisal by two independent reviewers, Newcastle-Ottawa Quality Assessment Scale (NOQAS) was used to grade the studies. Six case control and six nested case control studies were included. Results showed nonsignificant association of overall effect estimates with total or advanced prostate cancer or high-grade tumor. High blood level of alpha-linolenic acid (ALA) had nonsignificant positive association with total prostate cancer risk. High blood level of docosapentaenoic acid (DPA) had significant negative association with total prostate cancer risk. Specific n-3 PUFA in fish oil, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) had positive association with high-grade prostate tumor risk only after adjustment of interstudy variability. There is evidence that high blood level of DPA that is linked with reduced total prostate cancer risk and elevated blood levels of fish oils, EPA, and DHA is associated with high-grade prostate tumor, but careful interpretation is needed due to intricate details involved in prostate carcinogenesis and N-3 PUFA metabolism.
Prostate Cancer
· 2013 · PMID 23577261
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MicroRNAs are key regulators of gene expression and play critical roles in both normal physiology and pathology. Recent research has demonstrated that these molecules are present in body fluids, such as serum, plasma, an...MicroRNAs are key regulators of gene expression and play critical roles in both normal physiology and pathology. Recent research has demonstrated that these molecules are present in body fluids, such as serum, plasma, and urine, and can be readily measured using a variety of techniques. More importantly, emerging evidence suggests that circulating or urine miRNAs are useful indicators of disease. Here, we consider the potential utility of such miRNAs as noninvasive biomarkers of prostate cancer, a disease that would benefit substantially from novel diagnostic and prognostic tools. The studies aimed at identifying diagnostic, prognostic, and/or predictive miRNAs for prostate cancer are summarised and reviewed. Finally, practical considerations that will influence the translation of this recent research into clinical implementation are discussed.
Sazuka T, Imamoto T, Namekawa T
… +9 more, Utsumi T, Yanagisawa M, Kawamura K, Kamiya N, Suzuki H, Ueda T, Ota S, Nakatani Y, Ichikawa T
Prostate Cancer
· 2013 · PMID 23533779
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Background. The aim of this study was to determine concordance rates for prostatectomy specimens and transrectal needle biopsy samples in various areas of the prostate in order to assess diagnostic accuracy of the transr...Background. The aim of this study was to determine concordance rates for prostatectomy specimens and transrectal needle biopsy samples in various areas of the prostate in order to assess diagnostic accuracy of the transrectal biopsy approach, especially for presurgical detection of cancer in the prostatic apex. Materials and Methods. From 2006 to 2011, 158 patients whose radical prostatectomy specimens had been evaluated were retrospectively enrolled in this study. Concordance rates for histopathology results of prostatectomy specimens and needle biopsy samples were evaluated in 8 prostatic sections (apex, middle, base, and transitional zones bilaterally) from 73 patients diagnosed at this institution, besides factors for detecting apex cancer in total 118 true positive and false negative apex cancers. Results. Prostate cancer was found most frequently (85%) in the apex of all patients. Of 584 histopathology sections, 153 (49%) from all areas were false negatives, as were 45% of apex biopsy samples. No readily available preoperative factors for detecting apex cancer were identified. Conclusions. In Japanese patients, the most frequent location of prostate cancer is in the apex. There is a high false negative rate for transrectal biopsy samples. To improve the detection rate, transperitoneal biopsy or more accurate imaging technology is needed.
Prostate Cancer
· 2013 · PMID 23533778
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Prostate cancer (PC) is the principal malignancy affecting African descent men in the Caribbean and the USA. Disparities in incidence, prevalence, and mortality in these populations are poorly understood. We evaluated th...Prostate cancer (PC) is the principal malignancy affecting African descent men in the Caribbean and the USA. Disparities in incidence, prevalence, and mortality in these populations are poorly understood. We evaluated the urologic characteristics and sexual behaviors of men with histologically confirmed PC (cases) and age-matched controls in the nationwide Prostate Cancer in a Black Population (PCBP) study conducted in Barbados. Cases were around 1.5 to 3 times more likely to report symptoms of prostatic enlargement, hematuria/hematospermia, and previous prostatitis. Sexually transmitted infections (STIs) were similar among cases (24.5%) and controls (26.7%). First sexual intercourse before the age of 16 was associated with an increased likelihood of both low- (Gleason score < 7; OR 1.63; 95% CI: 1.03-1.66) and high-grade PC (Gleason score ≥ 7; OR 1.82; 1.11-2.99). PC risk decreased with later age of sexual debut (P-trend = 0.004). More lifetime sexual partners was associated with increased odds of high grade PC (P-trend = 0.02). The contribution of sexual behaviors to the development and the outcomes of PC is likely due to multiple mechanisms, and further study will be necessary to elucidate the underlying pathophysiologic mechanisms in this and similar populations.
Prostate Cancer
· 2013 · PMID 23533777
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There are radiobiological rationales supporting hypofractionated radiotherapy for prostate cancer. The recent advancements in treatment planning and delivery allow sophisticated radiation treatments to take advantage of...There are radiobiological rationales supporting hypofractionated radiotherapy for prostate cancer. The recent advancements in treatment planning and delivery allow sophisticated radiation treatments to take advantage of the differences in radiobiology of prostate cancer and the surrounding normal tissues. The preliminary results from clinical studies indicate that abbreviated fractionation programs can result in successful treatment of localized prostate cancer without escalation of late toxicity.
Rebbeck TR, Devesa SS, Chang BL
… +36 more, Bunker CH, Cheng I, Cooney K, Eeles R, Fernandez P, Giri VN, Gueye SM, Haiman CA, Henderson BE, Heyns CF, Hu JJ, Ingles SA, Isaacs W, Jalloh M, John EM, Kibel AS, Kidd LR, Layne P, Leach RJ, Neslund-Dudas C, Okobia MN, Ostrander EA, Park JY, Patrick AL, Phelan CM, Ragin C, Roberts RA, Rybicki BA, Stanford JL, Strom S, Thompson IM, Witte J, Xu J, Yeboah E, Hsing AW, Zeigler-Johnson CM
Prostate Cancer
· 2013 · PMID 23476788
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Prostate cancer (CaP) is the leading cancer among men of African descent in the USA, Caribbean, and Sub-Saharan Africa (SSA). The estimated number of CaP deaths in SSA during 2008 was more than five times that among Afri...Prostate cancer (CaP) is the leading cancer among men of African descent in the USA, Caribbean, and Sub-Saharan Africa (SSA). The estimated number of CaP deaths in SSA during 2008 was more than five times that among African Americans and is expected to double in Africa by 2030. We summarize publicly available CaP data and collected data from the men of African descent and Carcinoma of the Prostate (MADCaP) Consortium and the African Caribbean Cancer Consortium (AC3) to evaluate CaP incidence and mortality in men of African descent worldwide. CaP incidence and mortality are highest in men of African descent in the USA and the Caribbean. Tumor stage and grade were highest in SSA. We report a higher proportion of T1 stage prostate tumors in countries with greater percent gross domestic product spent on health care and physicians per 100,000 persons. We also observed that regions with a higher proportion of advanced tumors reported lower mortality rates. This finding suggests that CaP is underdiagnosed and/or underreported in SSA men. Nonetheless, CaP incidence and mortality represent a significant public health problem in men of African descent around the world.
Wang BD, Yang Q, Ceniccola K
… +6 more, Bianco F, Andrawis R, Jarrett T, Frazier H, Patierno SR, Lee NH
Prostate Cancer
· 2013 · PMID 23365759
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The incidence and mortality rates of prostate cancer (PCa) are higher in African American (AA) compared to Caucasian American (CA) men. To elucidate the molecular mechanisms underlying PCa disparities, we employed an int...The incidence and mortality rates of prostate cancer (PCa) are higher in African American (AA) compared to Caucasian American (CA) men. To elucidate the molecular mechanisms underlying PCa disparities, we employed an integrative approach combining gene expression profiling and pathway and promoter analyses to investigate differential transcriptomes and deregulated signaling pathways in AA versus CA cancers. A comparison of AA and CA PCa specimens identified 1,188 differentially expressed genes. Interestingly, these transcriptional differences were overrepresented in signaling pathways that converged on the androgen receptor (AR), suggesting that the AR may be a unifying oncogenic theme in AA PCa. Gene promoter analysis revealed that 382 out of 1,188 genes contained cis-acting AR-binding sequences. Chromatin immunoprecipitation confirmed STAT1, RHOA, ITGB5, MAPKAPK2, CSNK2A,1 and PIK3CB genes as novel AR targets in PCa disparities. Moreover, functional screens revealed that androgen-stimulated AR binding and upregulation of RHOA, ITGB5, and PIK3CB genes were associated with increased invasive activity of AA PCa cells, as siRNA-mediated knockdown of each gene caused a loss of androgen-stimulated invasion. In summation, our findings demonstrate that transcriptional changes have preferentially occurred in multiple signaling pathways converging ("transcriptional convergence") on AR signaling, thereby contributing to AR-target gene activation and PCa aggressiveness in AAs.
Smith DW, Stoimenova D, Eid K
… +1 more, Barqawi A
Prostate Cancer
· 2012 · PMID 23346405
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Prostate cancer is one of the most prevalent cancers among men in the United States, second only to nonmelanomatous skin cancer. Since prostate-specific antigen (PSA) testing came into widespread use in the late 1980s, t...Prostate cancer is one of the most prevalent cancers among men in the United States, second only to nonmelanomatous skin cancer. Since prostate-specific antigen (PSA) testing came into widespread use in the late 1980s, there has been a sharp increase in annual prostate cancer incidence. Cancer-specific mortality, though, is relatively low. The majority of these cancers will not progress to mortal disease, yet most men who are diagnosed opt for treatment as opposed to observation or active surveillance (AS). These men are thus burdened with the morbidities associated with aggressive treatments, commonly incontinence and erectile dysfunction, without receiving a mortality benefit. It is therefore necessary to both continue investigating outcomes associated with AS and to develop less invasive techniques for those who desire treatment but without the significant potential for quality-of-life side effects seen with aggressive modalities. The goals of this paper are to discuss the problems of overdiagnosis and overtreatment since the advent of PSA screening as well as the potential for targeted focal therapy (TFT) to bridge the gap between AS and definitive therapies. Furthermore, patient selection criteria for TFT, costs, side effects, and brachytherapy template-guided three-dimensional mapping biopsies (3DMB) for tumor localization will also be explored.