Expression Levels of IL-17A, IL-17F, IL-17RA, and IL-17RC in Prostate Cancer with Taking into Account the Histological Grade according to Gleason Scale in Comparison to Benign Prostatic Hyperplasia: In Search of New Therapeutic Options.

Prostate cancer (PCa) is the second most commonly diagnosed malignant tumor and the fifth leading cause of cancer death in men in the world. The most common types of tumors are adenocarcinomas. Prostate cancer is a slow-growing cancer. The incidence increases with age. Evaluation of proinflammatory factors such as IL-17A, IL-17F, IL-17RA, and IL-17RC expression makes it possible to assess the impact of inflammatory process on progression of PCa. The aim of the study was to retrospectively assess the histological material of PCa divided into few groups using the Gleason score. Studies were carried out on archival tissue material in the form of paraffin blocks of 40 men with PCa after radical prostatectomy. The control group was composed of 10 men with benign prostatic hyperplasia (BPH). The material was obtained by the transurethral resection of the prostate (TURP). Immunohistochemistry was performed on prepared material using specific primary antibodies against IL-17A, IL-17F, IL-17RA, and IL-17RC. Expression of the antibody to be examined using light microscopy and the Remmele-Stegner score (IRS) in cancer staining was then evaluated. Expression of IL-17 RA was not shown in a group of patients with PCa and in the control group. In the group of patients with Gleason score 8 and 9 PCa, the expression of IL-17A was higher compared to that of IL-17F. In addition, in PCa with an increased grade of Gleason scale, a decrease in the expression of the study inflammatory parameters was found. The inflammatory process has an impact on PCa. A study on IL-17 may become a starting point for further research on an attempt to use, for example, immunotherapy in PCa.

Immunotherapy as a Promising Treatment for Prostate Cancer: A Systematic Review.

Prostate cancer treatment is currently based on surgical removal, radiotherapy, and hormone therapy. In recent years, another therapeutic method has emerged-immunological treatment. Immunotherapy modulates and strengthens one's immune responses against cancer. Neoplastic cells naturally escape from the control of the immune system, and the main goal of immune therapy is to bring the control back. Satisfying outcomes after treatment of advanced melanoma and lung cancer suggest a great potential of immunotherapy as an approach for other tumors' treatment, especially in patients primarily introduced to palliative care. After initial clinical trials, immunotherapy seems to have different side effects than chemotherapy. Prostate cancer was the first neoplasm in which a specific vaccine significantly improved survival. There is a tremendous potential for synergistic combinations of immunotherapy with conventional cancer treatments. A combination of several drugs or methods can be a key in radical treatment of metastatic prostate cancer as demonstrated by preliminary studies.

Expression of COX-2, IL-1ß, TNF-α and IL-4 in epithelium of serrated adenoma, adenoma and hyperplastic polyp.

INTRODUCTION: Colon polyps and inflammatory process play the key role in neoplasia of colorectal cancer. In recent years there have been many publications on the malignancy of hyperplastic polyp (HP) which according to the WHO classification is a non-neoplastic polyp. The aim of this study is to determine the expression of inflammatory proteins COX-2, IL-1ß, TNF-α and IL-4 in the epithelium of colorectal polyps. MATERIAL AND METHODS: In the study, 144 colorectal polyps were analyzed. The groups of HP, classical (A) and serrated adenomas (SA) and normal mucosa (control) according to histopathological studies were selected. Immunohistochemical examinations Rusing antibodies against COX-2, IL-1ß, TNF-α and IL-4 were performed. The expression of analyzed protein was evaluated using modified Remmele-Stegner scale (0-16). RESULTS: Statistical analysis revealed higher expression of TNF-α (16 ±3.87 vs. 1 ±5.06), IL-1ß (12 ±4 vs 8 ±2.72), COX-2 (9 ±2.54 vs. 8 ±3.14) and IL-4 (12 ±3.45 vs. 4 ±3.35) in SA polyps compared to the control (p < 0.001). The HP had an increased level of expression of TNF-α (12 ±3.72 vs. 1 ±5.06, p < 0.005), COX-2 (8.5 ±1.97 vs. 8 ±3.14, p < 0.012) and IL-4 (12 ±3.46 vs. 4 ±3.35, p < 0.001). Significantly higher expression of IL-4 (12 ±2.32 vs. 4 ±3.35, p < 0.001) and IL-1ß (16 ±4.32 vs. 8 ±2.72, p < 0.044) in A compared to the control were observed. CONCLUSIONS: Expression of inflammatory factors differed between polyps. Inflammation accompanied the serrated structures which occur in polyps. The inflammatory process affects the development of colorectal polyps. The HP may predispose to malignancy.

Large Bowel Genetic Background and Inflammatory Processes in Carcinogenesis--Systematic Review.

Colorectal cancer (CRC) has become the third most common cancer in developed countries. Each year more and more people die from CRC. CRC is also one of the most effectively studied topics in recent years. It has been found that the key phenomena in CRC development are genetic and inflammatory processes. Well-known genetic bases for the carcinogenesis of CRC include chromosomal changes characteristic of the chromosomal instability pathway which correlates with specific and well-defined genetic alterations (such as APC, K-RAS, DCC and p53) and genomic instability characteristics for the mutator pathway focused on KRAS and BRAF mutations. Recent studies have highlighted the impact of inflammation in CRC, especially elevated levels of pro-inflammatory cytokines. Among important risk factors of colon carcinogenesis are colorectal polyps, which are currently the subject of intense research. Recent studies have shown that different adenomas are characterized by different pathways of carcinogenesis as well as diverse COX-2 expression in various polyps. Understanding the mechanism of inflammatory processes in CRC parallel to basic genetic alterations might allow for effective and targeted treatment.

Serrated polyps and their alternative pathway to the colorectal cancer: a systematic review.

Colorectal cancer (CRC) is the third most frequently diagnosed cancer in the world. For a long time, only one pathway of colorectal carcinogenesis was known. In recent years, a new "alternative" pathway through serrated adenoma was described. Recent meta-analysis estimated these cancers as about 10% to 30% of all CRCs. Serrated polyps are the second most popular groups of polyps (after conventional adenomas) found during colonoscopy. Serrated polyps of the colon are clinically and molecularly diverse changes that have common feature as crypt luminal morphology characterized by glandular serration. Evidence suggests that subtypes of serrated polyps, particularly TSA and SSA/P, can lead to adenocarcinoma through the serrated pathway. Moreover, the data indicate that the SSA/P are the precursors of colorectal carcinoma by MSI and may be subject to rapid progression to malignancy. An important step to reduce the incidence of CRC initiated by the serrated pathway is to improve the detection of serrated polyps and to ensure their complete removal during endoscopy. Understanding of the so-called serrated carcinogenesis pathway is an important step forward in expanding possibilities in the prevention of CRC.

Impact of COX-2, IL-1ß, TNF-α, IL-4 and IL-10 on the process of carcinogenesis in the large bowel.

In recent years there have been many intensive studies on the molecular mechanisms involving the carcinogenesis of colorectal cancer (CRC). An inflammatory process and genetics play the key role in neoplasia of CRC. Currently, there are two known pathways of CRC carcinogenesis, such as the adenoma and the serrated adenoma, which are referred to as "classic" and "alternative", respectively. Among all the components of the inflammatory process, the proinflammatory and anti-inflammatory cytokines play a major role as a factor influencing the process of malignant transformation. In our study we focused on key inflammatory factors such as cytokines interleukin (IL)-10, IL-1ß, IL-4, tumor necrosis factor α (TNF-α) and cyclooxygenase-2 (COX-2) in adenomas, serrated adenomas, hyperplastic polyps, adenocarcinomas and normal mucosa. Our study confirmed the hypothesis that inflammation has a major effect on carcinogenesis of CRC. Our studies also showed the difference in carcinogenesis of CRC. It showed a greater effect of the inflammatory process in carcinogenesis of CRC by a "serrated" (alternative) way as compared to the classic way. In a serrated way all the inflammatory factors had a higher expression. It might suggest that effectiveness of cancer prevention with the use of NSAIDs has a greater impact in patients whose tumors were formed in an alternative way. Additionally, it also showed that the inflammatory process has no influence on the final form of cancer.