Treatment Of Prostatic Carcinoma Research Articles

Previous inguinal hernia surgery does not limit the likelihood of choosing prostatectomy as primary prostate cancer therapy

We evaluated whether previous inguinal hernia repair may affect the choice of prostate carcinoma treatment in a population-based cohort. It has been suggested that previous laparoscopic inguinal hernia repair (LIHR) could limit the subsequent possibility of performing a prostatectomy. Several small studies have suggested otherwise. The study cohort included all new prostate cancer cases in Finland 1998–2015 identified through the Finnish cancer registry. Data on the treatment of prostate cancer and surgical inguinal hernia repairs in 1998–2016 was obtained from the HILMO hospital discharge registry. After linkage, the study cohort included 7206 men. Of these, 5500 had no history of inguinal hernia, 1463 had an open hernia repair, and 193 had a minimally invasive repair (LIHR). Compared to men with no history of hernia repair, those with previous hernia repairs were more likely to undergo prostatectomy over radiation therapy as the primary treatment for prostate cancer HR 1.34 (CI 95% 1.19–1.52). The association did not depend on the method of hernia repair, HR 1.58 (CI 95% 1.15–2.18), in men with previous LIHR. The increased likelihood of choosing prostatectomy over radiation therapy concerns all type prostatectomies. Previous hernia repair is not a limiting factor when choosing treatment for prostate cancer.

Monitoring Dual-Cancer Treatment in a Patient With Prostate and Hepatocellular Carcinoma Using Prostate-Specific Membrane Antigen-Directed PET/CT.

We report on a 70-year-old man affected with prostate carcinoma (PC) scheduled for prostate-specific membrane antigen (PSMA) PET/CT using 18 F-PSMA1007. Because of uptake in the liver and corresponding findings on magnetic resonance, diagnosis of hepatocellular carcinoma (HCC, G1) was established. The patient was then scheduled for antihormonal treatment for PC and locoregional therapy due to HCC. On follow-up PSMA-targeted PET/CT, we observed durable response to PC-associated therapy, whereas hepatic lesions showed progressive disease. As such, we herein report on a dual-cancer targeting molecular imaging strategy to determine disease extent in a patient affected with both PC and HCC, along with potential of monitoring both systemic and locoregional treatment.

Exploring Anticancer Potential of Camptothecin Isolated from Nothapodytes Nimmonianain the Treatment of Prostate and Lung Carcinoma

Background: Cancer is a life-threatening disease which is a major threat to global health which continues to affect predominantly in developing nations. Present research work has been oriented towards the determination of the anticancer potential of camptothecin (CPT) as herbal medicine for the treatment of prostate and lung carcinoma. Methods: Structural determination of camptothecin has been performed by different analytical techniques where anticancer potential was tested by MTT assay, Flow cytometry and DAPI on A549 and LNCaP cells lines. Results: FTIR spectra of camptothecin showed peaks related to specific structure which is nearly equal to standard structure of CPT. NMR spectra of camptothecin showed specific peaks in the region of delta 8.686 - 5.279, the signals of H-7 related to structural features similar to camptothecin. LCMS spectra of camptothecin showed mean retention time at 3.620 and covered 100 % area along with mass spectra gives precursor m/z peak at 349.2 [M+H]+ matches to standard molecular weight of camptothecin. CPT has been used as competent alternative to systemic chemotherapy to cure lung and prostate carcinoma having IC50 value 3.421 μg /ml and 5.253μg /ml respectively. CPT successfully induces apoptosis in A549 and LNCaP cell lines 72.12 ± 3.45 % and 66.41 ± 4.50 % as compared to control 4.28 ± 1.78 and 1.52 ± 0.58 respectively which was proved by DAPI and flow cytometry. Conclusions: Chemical fingerprinting and structural elucidation confirmed that isolated moiety was camptothecin and it has great potential in treatment of lung and prostate carcinoma as a competent alternative to chemotherapy in the form of herbal medicine.

The association of claudin-18 and androgen receptor expression in prostatic carcinoma: an immunohistochemical study

BackgroundClaudin-18 (CLDN18) is a recently identified anticancer therapeutic target with promising results for various gastrointestinal malignancies. The role of CLDN18 in prostatic carcinoma has not been investigated. The aim of this study was to investigate CLDN18 and androgen receptor (AR) expression in prostatic carcinoma and to link these findings with other clinicopathological characteristics. This retrospective study was carried out on 120 cases of prostatic lesions, including 100 cases of prostatic carcinoma and 20 cases of benign prostatic hyperplasia. The immunohistochemical staining technique was used to evaluate the expression of both CLDN18 and AR in prostatic carcinoma in relation to clinicopathological parameters.ResultsCLDN18 expression was completely absent in benign prostatic tissue, while it was detected in the membrane of 30 (30%) of studied carcinoma cases, with a statistically significant difference (p = 0.046). In contrast to other variables, a statistically significant relationship was identified between CLDN18 expression and Gleason Grade group (p = 0.000), stage (p = 0.03), and nodal metastasis (p = 0.000). The expression of the androgen receptor was detected in the nucleus of 96 (96%) of the cancer cases under study, with no statistically significant difference between the studied groups (p = 0.427). A statistically significant relation was found between AR expression and Gleason Grade group (p = 0.03) and stage (p = 0.01), while no relation with other variables was detected. AR expression and CLDN18 expression were shown to be statistically significantly correlated (p = 0.002).ConclusionsCLDN18 was expressed in prostatic carcinoma and correlated with an adverse tumor outcome. CLDN18 may be regulated by AR. CLDN18 could be a candidate therapeutic marker for the treatment of prostatic carcinoma.

An Updated Review Summarizing the Anticancer Efficacy of Melittin from Bee Venom in Several Models of Human Cancers.

Apitherapy (using bee products) has gained broad recognition in cancer therapeutics globally. Honeybee venom has a broad range of biological potential, and its utilization is rapidly emerging in apitherapy. Bee products have significant potential to strengthen the immune system and improve human health. Thus, this review is targeted toward recapitulating the chemo-preventive potential of melittin (MEL), which constitutes a substantial portion of honeybee venom. Honeybee venom (apitoxin) is produced in the venom gland of the honeybee abdomen, and adult bees utilize it as a primary colony defense mechanism. Apitoxin comprises numerous biologically active compounds, including peptides, enzymes, amines, amino acids, phospholipids, minerals, carbohydrates, and volatile components. We are mainly focused on exploring the potential of melittin (a peptide component) of bee venom that has shown promising potential in the treatment of several human cancers, including breast, stomach, lung, prostate, ovary, kidney, colon, gastric, esophageal, cervical cancers, melanoma, osteosarcoma, and hepatocellular carcinoma. This review has summarized all potential studies related to the anticancerous efficacy of melittin (apitoxin), its formulations, conjugates, and nano-formulations against several human carcinomas, which would further pave the way for future researchers in developing potent drugs for cancer management.

PSMC4 promotes prostate carcinoma progression by regulating the CBX3-EGFR-PI3K-AKT-mTOR pathway.

Proteasome 26S subunit ATPase 4 (PSMC4) could regulate cancer progression. However, the function of PSMC4 in prostate carcinoma (PCa) progression requires further clarification. In the study, PSMC4 and chromobox 3 (CBX3) levels were verified by TCGA data and tissue microarrays. Cell counting kit-8, cell apoptosis, cell cycle, wound healing, transwell and xenograft tumour model assays were performed to verify biological functions of PSMC4 in PCa. RNA-seq, PCR, western blotting and co-IP assays were performed to verify the mechanism of PSMC4. Results showed that PSMC4 level was significantly increased in PCa tissues, and patients with PCa with a high PSMC4 level exhibited shorter overall survival. PSMC4 knockdown markedly inhibited cell proliferation, cell cycle and migration in vitro and in vivo, and significantly promoted cell apoptosis. Then further study revealed that CBX3 was a downstream target of PSMC4. PSMC4 knockdown markedly reduced CBX3 level, and inhibited PI3K-AKT-mTOR signalling. CBX3 overexpression markedly promoted epidermal growth factor receptor (EGFR) level. Finally, PSMC4 overexpression showed reverse effect in DU145 cells, and the effects of PSMC4 overexpression on cell proliferation, migration and clonal formation were rescued by the CBX3 knockdown, and regulated EGFR-PI3K-AKT-mTOR signalling. In conclusion, PSMC4 could regulate the PCa progression by mediating the CBX3-EGFR-PI3K-AKT-mTOR pathway. These findings provided a new target for PCa treatment.

Preclinical Characterization of the 177Lu-Labeled Prostate Stem Cell Antigen (PSCA)-Specific Monoclonal Antibody 7F5.

Prostate specific membrane antigen (PSMA) is an excellent target for imaging and treatment of prostate carcinoma (PCa). Unfortunately, not all PCa cells express PSMA. Therefore, alternative theranostic targets are required. The membrane protein prostate stem cell antigen (PSCA) is highly overexpressed in most primary prostate carcinoma (PCa) cells and in metastatic and hormone refractory tumor cells. Moreover, PSCA expression positively correlates with tumor progression. Therefore, it represents a potential alternative theranostic target suitable for imaging and/or radioimmunotherapy. In order to support this working hypothesis, we conjugated our previously described anti-PSCA monoclonal antibody (mAb) 7F5 with the bifunctional chelator CHX-A″-DTPA and subsequently radiolabeled it with the theranostic radionuclide 177Lu. The resulting radiolabeled mAb ([177Lu]Lu-CHX-A″-DTPA-7F5) was characterized both in vitro and in vivo. It showed a high radiochemical purity (>95%) and stability. The labelling did not affect its binding capability. Biodistribution studies showed a high specific tumor uptake compared to most non-targeted tissues in mice bearing PSCA-positive tumors. Accordingly, SPECT/CT images revealed a high tumor-to-background ratios from 16 h to 7 days after administration of [177Lu]Lu-CHX-A″-DTPA-7F5. Consequently, [177Lu]Lu-CHX-A″-DTPA-7F5 represents a promising candidate for imaging and in the future also for radioimmunotherapy.

Evolution of the views on the role of testosterone in prostate cancer. Literature review

Background. Prostate cancer is one of the most common cancers in men. The views on the role of the main male hormone, testosterone, in the genesis of prostate carcinoma has changed dramatically over the last two centuries. Aim. To study the evolution of views on the relationship between testosterone and prostate cancer and to assess their impact on the organization of medical care. Materials and methods. Publications were searched in the National Library of Medicine of the United States and the Central Scientific Medical Library of the Russian Federation using the keywords: prostate cancer, testosterone. Only original publications and meta-analyses were considered. As a result, 59 publications were selected and their descriptive analysis was performed. Results. The information aboutthe doubtfulness ofthe negative role oftestosterone in genesis of prostate cancer is presented, taking into account the small number of observations and numerous methodological defects of the studies. The evidence for the theory of androgenic saturation in prostate carcinoma is outlined, which is based on publications with a sufficient number of publications. Studies confirming the absence of a carcinogenic effect of androgen replacement therapy in healthy individuals and progression of the tumor process on testosterone administration after treatment of the cancer process are described. Moreover, there is information on the use of this hormone in the treatment of castration-resistant prostate carcinoma. Conclusion. Over time, there is increasing evidence for the protective role of testosterone in the development and even treatment of prostate cancer. This raises the prospect of a global transformation in the organization of medical care in the management of patients with prostatic carcinoma, as well as older men in general. There is a clear need for new and better research on this issue.

Association between Prostate Carcinoma and Multiple Myeloma.

Synchronous or sequential development of multiple myeloma and prostate carcinoma is rare. It is not sure whether these two occur independently or if one influences the development of the other. We reviewed the cases published in the English literature; eight cases of myeloma developing after diagnosis and treatment for prostate carcinoma, five cases of simultaneous occurrence of myeloma and prostate carcinoma, and five cases where the patient with multiple myeloma later developed prostate carcinoma were found. This short review attempts to analyze the occurrence of these two diseases in the same patient and dissect whether there is a close association or it is just a mere coincidence.

Suppression of prostate cancer and amelioration of the immunosuppressive tumor microenvironment through selective immunoproteasome inhibition

ABSTRACT New treatment options to battle hormone-refractory prostate carcinoma (PC) are a pressing medical need. Chronic inflammation has been implicated in PC etiology. The pro-inflammatory cytokines IL-6, IL-23 and IL-17 are key mediators to promote growth of PC. Here, we evaluate the potential of immunoproteasome inhibition for anti-inflammatory and direct anti-tumorigenic therapy of PC. The anti-tumor effect of immunoproteasome inhibitor ONX 0914 was tested in mouse and human PC cells and the in vivo therapeutic efficacy of immunoproteasome inhibition was analyzed in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice in preventive and therapeutic settings and in castration-resistant (CR)PC after castration. Inhibition of the immunoproteasome subunit LMP7 induced apoptotic cell death in PC cell lines. In TRAMP mice, ONX 0914-treatment resulted in significant inhibition of PC growth with a decreased frequency of malignant prostatic lesions and inhibition of metastasis formation. The number of immunosuppressive myeloid cells in PC was greatly reduced in response to ONX 0914. Thus, immunoproteasome inhibition shows remarkable efficacy against PC progression in vivo and impedes tumor recurrence in CRPC-TRAMP mice by blocking the immunosuppressive inflammatory response in the tumor microenvironment. In conclusion, we show that the immunoproteasome is a promising drug target for the treatment of PC.

High dose rate brachytherapy – long term results

Introduction and objective: High-dose-rate brachytherapy with a temporary implant is one of the alternative methods for the treatment of localised prostate carcinoma, along with radical prostatectomy and external beam radiation therapy. The objective of this study is to analyze the long-term treatment results after definitive high-dose-rate brachytherapy for localised prostate carcinoma in USBALO. Material and methods: For the period from January 2011 to January 2019, 90 patients were treated with HDR-brachytherapy (with a temporary implant) in the Radiotherapy Department of USBALO. The average age is 66.5 years (53÷78 years). Patients are divided into low risk group – 54 (60%) and intermediate risk due to the presence of 1 negative factor – 36 (40%) patients. Follow-up ranged from 16 to 129 months (mean 84 months or 7 years). For the area of ​​the prostate and the base of the seminal vesicles, 20 (22.2%) patients received 3 fractions of 10.5 Gy over 14 days, and 70 (77.8%) received a dose of 3 x 11 Gy. Results: During the follow-up period, biochemical control was established in 78 patients (86.7%). Five-year biochemical control for all patients was 90%, and the 10-year biochemical control – 86.7%. Long-term follow-up of patients shows 5- and 10-year biochemical progression-free survival of 87.9% and 79.7%, respectively. Conclusions: Definitive high-dose-rate brachytherapy provides excellent long-term outcomes in low-risk and favorable intermediate-risk patients with localised prostate cancer in our data compared with those reported to date.

Clinical Significance of High Expression of tRF-Glu-TTC-2 in Prostate Carcinoma and its Effect on Growth.

The tRNA-derived fragments (tRFs) are a new class of regulatory noncoding RNAs and have different biological functions in cancer. This article investigated the expression and clinicopathological significance of tRF-Glu-TTC-2 in prostate carcinoma (PCa), and its effect on tumor growth. Expression profiles of tRFs and tiRNAs were analyzed by tRF and tiRNAs microarray in PCa samples, and then the expression was confirmed by qRT-PCR; RNA in situ hybridization was used to detect the positive expression of tRF-Glu-TTC-2 and to analyze the correlation between the expression level of tRF-Glu-TTC-2 and clinicopathological parameters. CCK-8 experiment was used to detect the effect of tRF-Glu-TTC-2 on the proliferation of PCa cells, and nude mice subcutaneous tumor model was used to detect the effect of tRF-Glu-TTC-2 on the growth of PCa cells. The results showed that tRF-Glu-TTC-2 was mainly positive and its expression level increased in PCa. The high expression was closely related to the tumor size (p < .05). Overexpression of tRF-Glu-TTC-2 promoted the proliferation of PCa cells, and decreased expression of tRF-Glu-TTC-2 inhibited the proliferation of PCa cells (p < .05). The results of subcutaneous tumor transplantation in nude mice showed that the tumor volume and weight of the knockdown group were smaller than those of the control group(all ps < .05). Ki-67 staining showed that the proportion of Ki-67-positive cells in the reduced tRF-Glu-TTC-2 group was lower than that in the control group (p < .05). The tRF-Glu-TTC-2 may be a new oncogene that can promote growth and proliferation of PCa. It provides a new idea for the treatment of PCa.

209P Efficacy and feasibility of long acting every three months goserelin for premenopausal breast cancer patients during COVID pandemic

Monthly Goserelin demonstrated safety and efficacy for treating pre-menopausal hormone receptor positive breast cancer patients in both adjuvant and metastatic settings. Although, every 3 months Goserelin 10.8 mg was already approved for the treatment of localized and metastatic prostatic carcinoma, it is not currently approved for use in breast cancer patients. The aim of this study is to evaluate safety and efficacy of goserelin 10.8 mg for breast cancer patients.

Hsa_circ_0102485 inhibits the growth of cancer cells by regulating the miR-188–3p/ARID5B/AR axis in prostate carcinoma

BackgroundStudies have shown that circular RNAs (circRNAs) have significant potential as novel molecular markers for the diagnosis, treatment, and prognosis of prostate carcinoma (PCa). However, the role and mechanism of circRNA hsa_circ_0102485 in PCa remains unclear. Materials & methodsThe real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to quantify hsa_circ_0102485 expression in PCa. The potential mechanisms and roles of hsa_circ_0102485 in tumor growth were explored using dual-luciferase-reporter and subcutaneous-xenograft assays, rescue experiments, and immunohistochemical staining. Clinical correlations were assessed by tissue-on-a-chip in-situ hybridization and Fisher’s exact test. ResultsHsa_circ_0102485 expression was decreased in PCa, and overexpression of hsa_circ_0102485 suppressed the proliferation, metastasis, invasion, and antiapoptotic abilities of PCa cells. MicroRNA 188–3p (MiR-188–3p) is a direct target of hsa_circ_0102485, and cotransfection of hsa_circ_0102485 in PCa cells overexpressing miR-188–3p inhibited its promotive effects. Hsa_circ_0102485 indirectly promotes the expression of AT-rich interaction domain 5B (ARID5B) and androgen receptor (AR) by sponging miR-188–3p and inhibiting PCa cell growth. Correlation analysis showed that hsa_circ_0102485 expression in PCa was not significantly correlated with the age, International Society of Urologic Pathologists (ISUP) grade, Gleason score, or lymph node metastasis status of PCa patients. ConclusionHsa_circ_0102485 plays an inhibitory role in PCa by regulating the Mir-188–3p/ARID5B/AR axis and may be a potential diagnostic biomarker and therapeutic target for PCa that requires further study.

What Is Your Choice for Androgen Deprivation Therapy in Metastatic Prostate Carcinoma: Surgical or Medical?

At the time of diagnosis, approximately 16.5% of prostate cancer patients are metastatic. The main framework of metastatic prostate cancer treatment is androgen deprivation therapy, which is performed surgically or medically. The aim of this study is to evaluate the attitudes of medical oncologists and urologists about orchiectomy as androgen deprivation therapy. A total of 387 physicians working in the Departments of Urology (n=217) and Medical Oncology (n=170) were included in this descriptive study. Data were collected through an electronic survey. Only 7.5% of participants indicated that they offered surgical castration to their patients. Urologists preferred surgical castration more than oncologists for the treatment of metastatic castration-sensitive prostate carcinoma (P=.003). The reasons why medical oncologists preferred surgical castration less are that it is an invasive procedure, has risk of morbidity and mortality, high cost of hospitalization, and may cause deterioration of the patient's body image (P < .05). This study showed that physicians were less likely to perform orchiectomy as an androgen deprivation therapy. Although the most important reason for this is the patient preference, the biased presentation of treatment options to patients, the lack of knowledge of physicians about orchiectomy, and the effect of the pharmaceutical industry should also be kept in mind.

Abstract CT141: CC-1, a bispecific PSMAxCD3 antibody for treatment of prostate carcinoma: Results of the ongoing phase I dose escalation trial

Abstract While highly efficient in hematological malignancies, bispecific antibodies (bsAbs), alike the closely related CAR T cells, are as of yet not successful in solid tumors. Moreover, all presently available T cell-mobilizing strategies cause substantial side effects that endanger patients and limit applicable doses and thus efficacy. Here we report on the development of CC-1, a PSMAxCD3 bsAb that is constructed in a novel IgG-based format (IgGsc) and contains a proprietary PSMA binder with extended reactivity. CC-1 displays a prolonged serum half-life, especially when compared to the BiTE bsAb format. Extensive in vitro and in vivo characterization demonstrated the potency of CC-1 to induce T cell activity in a highly target cell-restricted manner, resulting in profound antitumor activity, which among others allowed for elimination of large established tumors in humanized mice (Zekri et al, EMBO 2020). Exclusively funded by public resources, we conducted GMP production of CC-1 and in November 2019 initiated a first in human trial enrolling castration resistant prostate carcinoma patients (NCT04104607). The trial consists of two parts: a dose escalation phase with intra-individual dose escalation until the target dose of 826µg to determine overall safety, tolerability as well as the maximum tolerated dose (MTD), and a dose expansion phase, where patients are treated on the MTD level to detect possible efficacy. In August 2021, recruitment in the dose escalation phase was completed and the target dose was reached without DLT upon treatment of the 9th patient. A total of 14 patients were treated, with the most frequently observed toxicity being cytokine release syndrome (CRS) in 79% of patients. CRS did not exceed grade 2 according to the Lee et al. grading system (Lee et al., 2014) and resolved in most cases without additional application of tocilizumab. Besides hypertension (observed in 50% of patients), no further CC-1 related toxicities (i.e., Xerostomia, or anaphylactic reaction) were observed. As expected, after prophylactic tocilizumab application decreased neutrophile counts and elevated liver enzymes were observed in 86% and 43% of patients, respectively. In terms of efficacy, a rapid and profound decline of elevated PSA levels was observed in all the heavily pre-treated patients, with up to 60% reduction compared to baseline. Three patients of the dose escalation phase received multiple treatment cycles at the highest dose level, based on clinical tolerability, documented induction of potent T cell activation as well as rapid and profound decline of elevated PSA levels. Taken together, CC-1 is a promising compound with a favorable toxicity profile and promising clinical activity. Recruitment in the dose expansion phase is ongoing with the respective data to be presented at the meeting. Citation Format: Jonas S. Heitmann, Juliane S. Walz, Martin Pflügler, Maddalena Marconato, Christian M. Tegeler, Julia Reusch, Jannik Labrenz, Richard Schlenk, Gundram Jung, Helmut Salih. CC-1, a bispecific PSMAxCD3 antibody for treatment of prostate carcinoma: Results of the ongoing phase I dose escalation trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT141.

Systematic Development of Solid Lipid Nanoparticles of Abiraterone Acetate with Improved Oral Bioavailability and Anticancer Activity for Prostate Carcinoma Treatment.

In the present work, an attempt was undertaken to improve the oral bioavailability and anticancer activity of abiraterone acetate. Solid lipid nanoparticles (SLNs) were developed using the quality by design (QbD) principles and evaluated through in vitro, ex vivo, and in vivo studies. Solid lipid suitability was evaluated by equilibrium solubility study, while surfactant and cosurfactant were screened based on the ability to form microemulsion with the selected lipid. SLNs were prepared by emulsion/solvent evaporation method using glyceryl monostearate, Tween 80, and Poloxamer 407 as the solid lipid, surfactant, and cosurfactant, respectively. Box-Behnken design was applied for optimization of material attributes and evaluating their impact on particle size, polydispersity index, zeta potential, and entrapment efficiency of the SLNs. In vitro drug release study was evaluated in simulated gastric and intestinal fluids. Cell culture studies on PC-3 cells were performed to evaluate the cytotoxicity of the drug-loaded SLNs in comparison to the free drug suspension. Qualitative uptake was evaluated for Rhodamine B-loaded SLNs and compared with free dye solution. Ex vivo permeability was evaluated on Wistar rat intestine and in vivo pharmacokinetic evaluation on Wistar rats for SLNs and free drug suspension. Concisely, the SLNs showed potential for significant improvement in the biopharmaceutical performance of the selected drug candidate over the existing formulations of abiraterone acetate.

Combined intracavernous injection of prostaglandin E1 and a phosphodiesterase type 5 inhibitors in 5 cases after non-nerve sparing radical prostatectomy

ABSTRACT Introduction and Objectives Erectile dysfunction (ED) usually occurs in the surgical treatment of prostate cancer (PC). Since many patients are reluctant to discuss ED when facing PC treatment, some patients choose non-nerve sparing radical prostatectomy and later seek for ED treatment. We had 5 cases of patients who were treated with combination therapy of intracavernous injection (ICI) therapy of prostaglandin E1 (PGE1) and PDE5 inhibitors for ED after non-nerve sparing RP and retrospectively investigated the effectiveness of the combination therapy. Material and Methods The mean age when the patients had RP was 65.4 years. Following the 2016 National Comprehensive Cancer Network (NCCN) risk classification guidelines, 2 patients had high risk, and 3 had intermediate risk. The mean period up to the introduction of ICI from the date of RP was 40.2 months (12-120 months). All patients were given PDE5 inhibitors 3-4 weeks prior to ICI therapy. Erection was evaluated by the induction of ICI of 20 μg of prostaglandin E1 (PGE1), using Erection Hardness Score of 1 to 4; a score of 3 or 4 was classified as successful. Self-injection regimen was introduced by the physicians after the evaluation, and a total of 5 patients were tested. Results The response was Grade 1 in 1 patient, Grade 3 in 3 cases, Grade 4 in 1 case. The effectiveness rate was 80%. Penile self-injection therapy was adopted by 4 patients, and IIEF-5 and SHIM score improved from 5.3 to 17.5 and 4.3 to 14.8, respectively. No drug adverse effect was observed in the 4 cases. Conclusions Combination of ICI therapy and PDE5 inhibitors can be a candidate for ED patients who unluckily chose non-nerve sparing radical prostatectomy when treated prostate carcinoma. Disclosure Work supported by industry: no.

The risk of inguinal hernia repair after radical prostatectomy – a population-based cohort study

Objectives A nationwide population-based register study will evaluate the risk of postoperative inguinal hernia repair after primary curative-intent treatment of prostate carcinoma (PCa). Background Several previous studies have suggested an increased risk of inguinal hernia repair after prostatectomy. Only a few studies have compared the risk by PCa treatment modalities. Methods Data were collected between the years 1998 and 2016 from the national hospital discharge database HILMO and between the years 1998 and 2015 from the Finnish cancer registry to identify all men with prostate cancer with data on primary treatment available and information on inguinal hernia diagnoses and procedures among them. The risk of inguinal hernia repair among men managed with prostatectomy was compared to those treated with radiation therapy. Participants treated with prostatectomy were analyzed as a whole and separately stratified into subgroups managed with mini-invasive or open surgery. Multivariate Cox regression with adjustment for age and comorbidities was used for analysis. Results A total of 7207 cases of PCa were included in the study. 4595 men were treated with radical prostatectomy and 2612 with radiation therapy. Overall, the risk of hernia repair was higher among men treated with prostatectomy compared to men who received radiation therapy as the primary PCa treatment (HR 1.42, 95% CI 1.14–1.77). The risk did not differ markedly by the prostatectomy method. Conclusion Prostate cancer treatment with prostatectomy is associated with an increased risk of inguinal hernia surgery than external beam radiation therapy treatment. This risk should be taken into account when planning PCa treatment.

Target Protein for Xklp2 Functions as Coactivator of Androgen Receptor and Promotes the Proliferation of Prostate Carcinoma Cells.

The activation of the androgen receptor (AR) pathway is crucial in the progression of human prostate cancer. Results of the present study indicated that the target protein xenopus kinesin-like protein (TPX2) enhanced the transcription activation of AR and promoted the proliferation of LNCaP (ligand-dependent prostate carcinoma) cells. The protein-protein interaction between AR and TPX2 was investigated using coimmunoprecipitation assays. Results of the present study further demonstrated that TPX2 enhanced the transcription factor activation of AR and enhanced the expression levels of the downstream gene prostate-specific antigen (PSA). TPX2 did this by promoting the accumulation of AR in the nucleus and also promoting the recruitment of AR to the androgen response element, located in the promoter region of the PSA gene. Overexpression of TPX2 enhanced both the in vitro and in vivo proliferation of LNCaP cells. By revealing a novel role of TPX2 in the AR signaling pathway, the present study indicated that TPX2 may be an activator of AR and thus exhibits potential as a novel target for prostate carcinoma treatment.