Malignant priapism secondary to metastatic prostate cancer: a case report and review of literature

Penile metastasis of cancers from other primary sites is a rare phenomenon that infrequently manifests as malignant priapism. We outline a case of an 84-year-old patient who presented with a 3-month history of painful priapism after radiation therapy for prostate adenocarcinoma. The patient underwent surgical penile exploration and cavernosal biopsy that revealed poorly differentiated cells suggestive of prostate cancer. Postoperative imaging demonstrated extensive regional and distal metastases. A review of the literature on penile metastases returned approximately 400 published cases, with priapism being the initial presentation in 20% to 50% of cases. Regardless of site of origin or subsequent management, most cases have shown very poor prognosis.     

Development of a synoptic MRI report for primary rectal cancer

As the recent collection of papers from the Quality Enhancement Research Initiative (QUERI) Series indicates, knowledge is leading to considerable action in the United States (U.S.) Department of Veterans Affairs (VA). The QUERI Series offers clinical researchers, implementation scientists, health systems, and health research funders from around the globe a unique window into the both the practice and science of implementation or knowledge translation (KT) in the VA. By describing successes and challenges as well as setbacks and disappointments, the QUERI Series is all the more useful. From the vantage point of Canadian KT researchers and officials at a national health research funding agency, we offer a number of observations and lessons that can be learned from QUERI. "Knowledge, if it does not determine action, is dead to us." Plotinus (Roman philosopher 205AD-270AD)     

Vaccination therapy in prostate cancer

Radical prostatectomy and radiation therapy provide excellent localized prostate cancer (PC) control. Although the majority of prostate carcinoma is nowadays diagnosed at early stages with favourable risk features, in patients up to 30–40% it recurs within 10 years. Furthermore, the lack of effective therapies, once prostate carcinoma becomes refractory to androgen deprivation, mandates the development of alternative therapeutic options. There is a growing interest in harnessing the potency and specificity of anti-tumour immunity through the generation of fully competent dendritic cells and tumour reactive effector lymphocytes. Several strategies to treat or prevent the development of metastatic PC have been explored in clinical trials and are summarized in this review, considering also the feasibility and safety of these approaches. In some cases clinical responses were achieved showing that vaccine-primed T cells induced anti-tumour activity in vivo. The present findings and perspectives of the immunologic interventions in PC patients will be discussed.     

A preliminary report on the use of transfer factor for treating stage D3 hormone-unresponsive metastatic prostate cancer

As conventional treatments are unsuccessful, the survival rate of stage D3 prostate cancer patients is poor. Reports have suggested the existence of humoral and cell-mediated immunity (CMI) against prostate cancer tumour-associated antigens (TAA). These observations prompted us to treat stage D3 prostate cancer patients with an in vitro produced transfer factor (TF) able to transfer, in vitro and in vivo, CMI against bladder and prostate TAA. Fifty patients entered this study and received one intramuscular injection of 2–5 units of specific TF monthly. Follow-up, ranging from 1 to 9 years, showed that complete remission was achieved in 2 patients, partial remission in 6, and no progression of metastatic disease in 14. The median survival was 126 weeks, higher than the survival rates reported in the literature for patients of the same stage.     

Development of a Listeria monocytogenes based vaccine against prostate cancer

Prostate specific antigen (PSA) is a likely immunotherapeutic target antigen for prostate cancer, the second leading cause of cancer-related death in American men. Previously, we demonstrated that attenuated strains of Listeria monocytogenes (Lm) can be used as effective vaccine vectors for delivery of tumor antigens causing regression of established tumors accompanied by strong immune responses toward these antigens in murine models of cancer. In the present study, we have developed and characterized a recombinant live attenuated L. monocytogenes/PSA (Lm–LLO–PSA) vaccine with potential use for the treatment of pCa. Human PSA gene was cloned into and expressed by an attenuated Lm strain. This recombinant bacterial vaccine, Lm–LLO–PSA was tested for stability, virulence, immunogenicity and anti-tumor effects in a murine model for pCa. Immunization with Lm–LLO–PSA was shown to lower the number of tumor infiltrating T regulatory cells and cause complete regression of over 80% of tumors formed by an implanted genetically modified mouse prostate adenocarcinoma cell line, which expressed human PSA. Lm–LLO–PSA was immunogenic in C57BL/6 mice and splenocytes from mice immunized with Lm–LLO–PSA showed significantly higher number of IFN-γ secreting cells over that of the naïve animals in response to a PSA H2Db-specific peptide, as measured by both, ELISpot and intracellular cytokine staining. In addition, using a CTL assay we show that the T cells specific for PSA were able to recognize and lyse PSA-peptide pulsed target cells in vitro. In a comparison study with two other PSA-based vaccines (a pDNA and a vaccinia vaccine), Lm–LLO–PSA was shown to be more efficacious in regressing established tumors when used in a homologues prime/boost regimen. Together, these results indicate that Lm–LLO–PSA is a potential candidate for pCa immunotherapy and should be further developed.     

Polymorphisms of MLH1 in benign prostatic hyperplasia and sporadic prostate cancer

Mismatch repair is one of several DNA repair pathways of which defects may lead to cancer. We hypothesize that polymorphisms of the MLH1 gene can be a risk factor for benign prostatic hyperplasia (BPH) and prostate cancer. The genetic distribution of MLH1 polymorphisms that lead to amino acid changes at codons 132, 219, 384, and 723 were analyzed in BPH and sporadic prostate cancer patients, and compared to healthy controls from an Asian population. These experiments demonstrate a protective role for the codon 384 variant allele against prostate cancer (P = 0.031) but not BPH when compared to normal controls and furthermore, an inverse association was observed with stage (P = 0.074) and grade (P = 0.056) of cancer. This is the first report that demonstrates a protective effect for the race-related MLH1 polymorphism at codon 384 against prostate cancer and these results are important in understanding their role in this disease.     

Ligand-dependent corepressor acts as a novel androgen receptor corepressor, inhibits prostate cancer growth, and is functionally inactivated by the Src protein kinase

The activated androgen receptor (AR) promotes prostate cancer (PCa) growth. AR antagonists repress the AR by recruitment of corepressors. Not much is known about the inactivation of AR by corepressors in the presence of agonists (androgens). Here we show that the corepressor LCoR acts as an androgen-dependent corepressor that represses human PCa growth in vivo. In line with this, progressive decrease of ligand-dependent corepressor expression was observed in the PCa TRAMP mouse model with increasing age. LCoR interacts with AR and is recruited to chromatin in an androgen-induced manner. Unexpectedly, the LXXLL motif of LCoR is dispensable for interaction with the AR. Rather, the data indicate that LCoR interacts with the AR DNA binding domain on DNA. Interestingly, the interaction of LCoR with AR is inhibited by signaling pathways that are associated with androgen-independent PCa. Here we also show that the Src kinase inactivates the corepressive function of LCoR. Interfering with endogenous Src function by a dominant negative Src mutant, the growth inhibitory activity of LCoR is enhanced in vivo in a xenograft mouse model system. Thus, our studies indicate a role of LCoR as an AR corepressor and a tumor suppressor. Further, the decreased expression or inactivation of LCoR is as an important step toward PCa carcinogenesis in vivo.     

LNCaP prostate cancer cells are insensitive to zinc-induced senescence

Prostate cancer is an age-related disease that is linked to the inability of prostate cells to accumulate zinc following transformation. It is shown in the present study that the basal percentage of normal prostate cells expressing senescence-associated beta-galactosidase (SA-beta-gal) is higher than that of the cancer cells. In the presence of high zinc in the cell culture medium, the percentage of normal prostate cells expressing the SA-beta-gal increased but not that of the cancer cells. Increased intracellular zinc occurs in the prostate cancer cells treated with supraphysiologic concentration of zinc but it does not induce senescence or decrease the telomerase activities in these cells. Senescence, however, occurred when the prostate cancer cells DNA is damaged by irradiation. These findings suggest that prostate cancer cells are insensitive to the senescence-inducing effects of zinc but the cancer cells retain the capacity to undergo senescence through other pathways.     

Proteomic analysis of cancer stem cells in human prostate cancer cells

Results from recent studies support the hypothesis that cancer stem cells (CSCs) are responsible for tumor initiation and formation. Here, we applied a proteome profiling approach to investigate the mechanisms of CSCs and to identify potential biomarkers in the prostate cancer cell line DU145. Using MACS, the DU145 prostate cancer cell line was isolated into CD44+ or CD44− cells. In sphere culture, CD44+ cells possessed stem cell characteristics and highly expressed genes known to be important in stem cell maintenance. In addition, they showed strong tumorigenic potential in the clonogenic assay and soft agar colony formation assay. We then analyzed and identified proteins that were differentially expressed between CD44+ and CD44− using two-dimensional gel electrophoresis and LC-MS/MS. Cofilin and Annexin A5, which are associated with proliferation or metastasis in cancer, were found to be positively correlated with CD44 expression. These results provide information that will be important to the development of new cancer diagnostic tools and understanding the mechanisms of CSCs although a more detailed study is necessary to investigate the roles of Cofilin and Annexin A5 in CSCs.     

山东早始新世五图组的一种古有蹄类Olbitherium millenariusum gen.et sp.nov.(哺乳动物纲,"伪齿兽集目")

记述了在山东省五图盆地下始新统发现的一种“伪齿兽集目”化石 :千禧福兽 (Olbither iummillenariusumgen.etsp .nov.)。千禧福兽其颊齿形态基本上与原始奇蹄类相似 ,同时也具有伪齿兽类的一些特征 ,如m1～ 2下次尖没有与下内尖直接连接的下次脊。千禧福兽的M3次尖具前、后棱 ,这一点似与原始的蹄兔Seggeurius相似。因此 ,新种在目一级的归类有困难 ,暂置于McKenna ( 1 975 )创立的“伪齿兽集目”(“MirorderPhenacodonta”)。千禧福兽的发现进一步证明了奇蹄类可能起源于亚洲和北非类似伪齿兽类 (phenacodontids)的古有蹄类 ,福兽仅是类似伪齿兽类的古新世古有蹄类向奇蹄类进化过程中的一叉支的代表。     

Fallout from the Chernobyl accident and overall cancer incidence in Finland

Aim: We studied whether incidence of all cancer sites combined was associated with the radiation exposure due to fallout from the Chernobyl accident in Finland. An emphasis was on the first decade after the accident to assess the suggested “promotion effect”. Methods: The segment of Finnish population with a stable residence in the first post-Chernobyl year (2 million people) was studied. The analyses were based on a 250 m × 250 m grid squares covering all of Finland and all cancer cases except cancers of the breast, prostate and lung. Cancer incidence in four exposure areas (based on first-year dose due to external exposure <0.1 mSv, 0.1–1.3, 0.3–0.5, or ≥0.5 mSv) was compared before the Chernobyl accident (1981–1985) and after it (1988–2007) taking into account cancer incidence trends for a longer period prior to the accident (since 1966). Results: There were no systematic differences in the cancer incidence in relation to radiation exposure in any calendar period, or any subgroup by sex or age at accident. Conclusion: The current large and comprehensive cohort analysis of the relatively low levels of the Chernobyl fallout in Finland did not observe a cancer promotion effect.     

Co-expression of interleukin-6 and human growth hormone in apparently normal prostate biopsies that ultimately progress to prostate cancer using low pH, high temperature antigen retrieval

Prostate cancer is the most common cancer in American men and the second leading cause of cancer deaths in this group. Both growth hormone (GH) and the inflammatory cytokine interleukin 6 (IL-6) have been implicated in prostate cancer progression. Studies in other systems have shown that an increase in GH results in an increase in IL-6 also. The current study demonstrated a parallel spatial and temporal expression of GH and IL-6 in cells in prostate cancer glandular acina cells. This study cannot determine if this expression is coincidental or causative, but it seems likely that the increase in GH could induce the expression of IL-6, since this is the case in other tissues. Optimal labelling for IL-6 in our study was achieved with low pH, high temperature antigen retrieval.     

Paleogenetics of the late Roman-early Byzantine cemeteries at Sayala,Egyptian Nubia

Out of the five late Roman-early Byzantine cemeteries at Sayala, the three large burial complexes CI-III were found to represent the same population not only on the basis of 76·6% of the metric features already studied, but also of 72·9% of the 48 non-metric features examined in the present paper. The remaining features, which show different frequencies, were most probably related to some social and/or genetic isolation of the three subgroups (“lineages”) of the same basic population.The left-right asymmetry of the frequencies was practically irrelevant; sex differences were however present in one-third of the features observed.Some of the traits showed unusually high frequencies, revealing a high rate of inbreeding within a homogeneous population.To evaluate the relationships among the CI-III people and the neighbouring populations, 22 discrete traits were compared with the same traits studied in 11 Ancient Egyptian samples by Berry, Berry & Ucko (1967) and in 6 contemporary African Negro samples by Rightmire (1972). It was shown that the Sayala CI-III population does not resemble either of these groups. The fourth contemporary Sayala sample from A cemetery was also found to be not related with the CI-III sample on the basis of the same traits. The fifth contemporary Sayala sample from N cemetery was too small to be tested. Moreover, the comparison between the CI-III population and the C-group population of Sayala also revealed the lack of genetic continuity. The isolated position found in the CI-III population of Sayala agrees with the hypothesis that it would represent the Blemmyes, people originating from the Eastern Desert.