Neuropilin‐2 (NRP2) is a member of the neuropilin receptor family and known to regulate autophagy and mTORC2 signaling in prostate cancer (PCa). Our study investigated the association of immunohistochemical NRP2 expression with clinicopathological data in PCa patients. For this purpose, we generated a tissue microarray with prostate tissue specimens from 400 PCa patients treated by radical prostatectomy. We focused on patients with high‐risk factors such as extraprostatic extension (pT ≥ 3), Gleason score ≥8 and/or the presence of regional lymph node metastases (pN1). Protein levels of NRP2, the vascular endothelial growth factor C (VEGFC) and oncogenic v‐ets avian erythroblastosis virus E26 oncogene homolog (ERG) gene as an indicator for TMPRSS2‐ERG fusion was assessed in relation to the patients' outcome. NRP2 emerged as an independent prognostic factor for cancer‐specific survival (CSS) (hazard ratio 2.360, 95% confidence interval = 1.2–4.8; p = 0.016). Moreover, the association between NRP2 expression and shorter CSS was also especially pronounced in patients at high risk for progression (log‐rank test: p = 0.010). We evaluated the association between NRP2 and the TMPRSS2‐ERG gene fusion status assessed by immunohistochemical nuclear ERG staining. However, ERG staining alone did not show any prognostic significance. NRP2 immunostaining is significantly associated with shorter CSS in ERG‐negative tumors (log‐rank test: p = 0.012). No prognostic impact of NRP2 expression on CSS was observed in ERG‐positive tumors (log‐rank test: p = 0.153). Our study identifies NRP2 as an important prognostic marker for a worse clinical outcome especially in patients with a high‐risk PCa and in patients with ERG‐negative PCa.

With improved prognosis due to advances in the diagnosis and therapy of breast cancer, physicians and therapists now focus on aspects such as quality of life and the management of side effects from breast cancer treatment. Therapy- and disease-related side effects often reduce the patient?s quality of life and can place a further burden on patients, with non-compliance or discontinuation of therapy a potential consequence. Study data have shown that therapy- and disease-related side effects can be reduced using the methods of integrative medicine. Reported benefits include improving patients? wellbeing and quality of life, reducing stress, and improving patients? mood, sleeping patterns and capacity to cope with disease. Examining the impact of integrative medicine on the side effects of cancer treatment would be beyond the scope of this review. This article therefore looks at short-term side effects of cancer treatment which are usually temporary and occur during or after local and systemic therapy. The focus is on mind-body medicine, acupuncture and classic naturopathic treatments developed by Sebastian Kneipp as complementary therapies. The latter includes hydrotherapy, phytotherapy, nutritional therapy, exercise therapy and a balanced lifestyle.

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Prostate cancer (PCa) is the most frequent malignancy in older men with a high propensity for bone metastases. Characteristically, PCa causes osteosclerotic lesions as a result of disrupted bone remodeling. Extracellular vesicles (EVs) participate in PCa progression by conditioning the pre-metastatic niche. However, how EVs mediate the cross-talk between PCa cells and osteoprogenitors in the bone microenvironment remains poorly understood. We found that EVs derived from murine PCa cell line RM1-BM increased metabolic activity, vitality, and cell proliferation of osteoblast precursors by >60%, while significantly impairing mineral deposition (−37%). The latter was further confirmed in two complementary in vivo models of ossification. Accordingly, gene and protein set enrichments of osteoprogenitors exposed to EVs displayed significant downregulation of osteogenic markers and upregulation of proinflammatory factors. Additionally, transcriptomic profiling of PCa-EVs revealed the abundance of three microRNAs, miR-26a-5p, miR-27a-3p, and miR-30e-5p involved in the suppression of BMP-2-induced osteogenesis in vivo, suggesting the critical role of these EV-derived miRNAs in PCa-mediated suppression of osteoblast activity. Taken together, our results indicate the importance of EV cargo in cancer-bone cross-talk in vitro and in vivo and suggest that exosomal miRNAs may contribute to the onset of osteosclerotic bone lesions in PCa.

Im Rahmen zweier klinischer Phase-II- bzw. -III-Studien wurden Patien-ten mit einem histologisch gesicherten metastasierendem Nierenkarzinom entweder mit γ-Interferon in zwei unterschiedlichen Dosierungen (100 μg/m² 3 × pro Woche über 4 h i.v. jede 2. Woche, oder 500 μg/m², 5 × pro Woche über 24 h i.v. jede 2. Woche) oder mit α-2-Interferon allein (18 × 10⁶ E 3 × pro Woche, jede Woche i.m.) oder in Kombination mit Vinblastin (0,1 mg/kg Körpergewicht i.v. jede 3. Woche) behandelt. Ziel dieser Studie war es, die Ansprechrate, die Ansprechdauer, die Überlebensrate, die Toxizität sowie die Verträglichkeit beider Therapie-formen zu eruieren. Die Ansprechrate lag in der γ-Interferonstudie beí beiden Dosierungen insgesamt bei 30%, in der Studie mit α-Interferon in Kombination mit Vinblastin bei insgesamt 31%. Die Ansprechdauer lag in der γ-Interferon-Studie bei 2–34+Monaten, bei der α-2-Interferon-Studie bei 2–24 + Monaten. Patienten, die unter der γ-Interferon-Therapie eine Tumorreaktion auf-wiesen, überlebten statistisch signifikant länger als diejenigen, die nicht auf die Therapie ansprachen (p = 0,0056). Die Behandlung mit der nie-drigen Dosis des γ-Interferon sowie mit α-2-Interferon war ambulant gut durchführbar. Die Interferon-Therapie stellt u. E. derzeit bei Patienten mit einem metastasierenden Nierenkarzinom die Therapie der Wahl dar.

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Prostate cancer (PCa) is a major cause of cancer-related death in men. Tumor-derived WNT5A plays an important role in primary and metastatic PCa. Surrounding stroma cells also produce WNT5A, which may modulate the biology of PCa. Here we assessed the role of stroma-derived WNT5A (stWNT5A) in primary PCa. A tissue microarray of samples obtained from 400 patients who underwent radical prostatectomy and control samples from 41 patients with benign prostate hyperplasia (BPH) was immunohistochemically assessed for expression of stWNT5A. The cores were scored for staining intensity: 0 (no staining), 1 (weak), 2 (moderate), or 3 (strong) and the stained stromal surface area: 0 (0%), 1 (1-25%), 2 (26-50%), 3 (51-75%), or 4 (76-100%). Gleason Score (GS) and TNM-stage were assessed by stratifying the cohort into high-risk (≥ pT3, pN1, GS ≥ 8) and non-high-risk patients. Ki67 and TUNEL assays were performed to assess proliferation and apoptosis. Expression of stWNT5A in BPH and tumor free control samples was 1.2-fold higher compared to tumor samples (p<0.001). Non-high-risk patients had a higher stWNT5A score than high-risk patients (p<0.05). stWNT5A expression was not correlated with overall and cancer-specific survival. Proliferation (r2=0.038, p<0.001) and apoptosis (r2=0.277, p<0.001) negatively correlated with stWNT5A expression. In summary, we show that expression of stWNT5A is higher in benign tissue and non-high-risk PCa. Stroma-derived Wnt signaling and tumor-derived Wnt may differentially impact on tumor behavior. Future studies are warranted to dissect the Wnt profile in tumor vs. surrounding stroma tissues.

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