Therapeutic potency of heat-shock protein-70 in the pathogenesis of colorectal cancer: current status and perspectives.

Heat-shock protein-70 (HSP70) is critical to the folding, stability, and activity of several client proteins including many responsible for cancer cell proliferation, apoptosis, drug toxicity, and metastasis. Up-regulation of HSP70 is positively associated with increased tumorigenicity as well as poor survival in colon cancer patients, supporting the diagnostic, prognostic, and therapeutic potencies of HSP70 in colorectal cancer. The administration of specific pharmacological inhibitors or gene knock-down for HSP70 suppresses tumor progression and enhances tumor cell chemosensitivity. This review summarizes the different tumorigenic properties of HSP70 and the potential therapeutic potency of HSP70 inhibitors in terms of a novel strategy for colorectal cancer therapy, for a better understanding, and hence better management of this disease.

Comparison of Propofol-Fentanyl with Midazolam-Ketamine Combination in Pediatric Patients Undergoing Kidney Biopsy.

INTRODUCTION: Kidney biopsy is a procedure of choice for the diagnosis of many kidney diseases. In children it is performed with the use of sedatives. The aim of this study was to compare the combination of propofol/fentanyl with midazolam/ketamine for sedation in pediatric patients undergoing kidney biopsy. METHODS: In this double-blinded clinical trial, seventeen children, candidate of kidney biopsy were included and randomized into two groups. One group received Midazolam/Ketamine with doses of 30 to 50 µg/kg and 0.25 to 1 mg/kg, and the other group were sedated with propofol/fentanyl combination in doses of 0.5 to 1 mg/kg and 0.5 to 1 mg/kg, respectively. Administration time, medication doses, total procedure time, need for analgesic use after the procedure, and patient relaxation, with no agitation during and after the biopsy were recorded. RESULTS: Nine patients received midazolam/ketamine and eight received propofol/fentanyl. None of them experienced vomiting or itching after sedation. There were no meaningful differences in qualitative variables of the need for pain relief between two groups. Regarding the distribution of pain at the time of sedation, and 1, 3, 6, and 24 hours after sedation, there was no significant statistical difference between the two groups. There was also no significant statistical difference between the two groups, regarding patients' relaxation during, and 1, 3, 6, and 24 hours after biopsy. CONCLUSION: There was no statistically significant difference between the degree of sedation and the analgesic effect of the two regimens in the two groups.  DOI: 10.52547/ijkd.6982.

Prognostic Significance of Substance P and Neurokinin-1 Receptor in Bladder Cancer.

Background: Bladder cancer is one of the most common genitourinary cancers with significant mortality. Finding reliable tumor markers and potential drug targets can improve early diagnosis, prognosis, and more effective therapeutic protocols. Previous studies have reported the involvement of the substance P (SP)/neurokinin-1 receptor (NK-1R) system in cancers. The potential prognostic role and the interaction of SP and NK-1R in bladder tumor are yet to be elucidated. Methods: Serum samples from 22 primarily diagnosed patients with bladder cancer as well as 22 healthy controls were examined for SP level using ELISA method. Tissue distribution of NK-1R in tumor samples and their adjacent normal tissues was evaluated through immunohistochemistry. Results: Serum SP levels in patients with bladder cancer were higher than the healthy group (p< 0.001) and had a significant correlation with NK-1R staining intensity (p< 0.001), percentage of stained cells (p< 0.001), and NK-1R tissue distribution. Also, the immunoreactivity of NK-1R in cancer samples increased significantly without correlation with tumor characteristics. However, no significant association was found between SP and NK-1R levels with clinical characteristics including tumor size (p= 0.33), tumor stage (p= 0.29), grade (p= 0.93), NK-1R staining intensity (p= 0.53), and percentage of stained cells (p= 0.32). Discussion: According to our findings, despite the lack of association between SP and NK-1R with clinical characteristics of bladder cancer, their serum levels were higher in patients with bladder cancer. Further studies are needed to confirm the potential prognostic role of SP and NK-1R in bladder cancer.

The emerging role of substance P/neurokinin-1 receptor signaling pathways in growth and development of tumor cells.

Tachykinins (TKs) include an evolutionarily conserved group of small bio-active peptides which possess a common carboxyl-terminal sequence, Phe-X-Gly-Leu-Met-NH2. TKs also have been shown to have implications in different steps of carcinogenesis, such as angiogenesis, mitogenesis, metastasis, and other growth-related events. The biological actions of substance P (SP), as the most important member of the TK family, are mainly mediated through a G protein-coupled receptor named neurokinin-1 receptor (NK1R). More recently, it has become clear that SP/NK1R system is involved in the initiation and activation of signaling pathways involved in cancer development and progression. Therefore, SP may contribute to triggering a variety of effector mechanisms including protein synthesis and a number of transcription factors that modulate the expression of genes involved in these processes. The overwhelming insights into the blockage of NK1R using specific antagonists could suggest a therapeutic approach in cancer therapy. In this review, we focus on evidence supporting an association between the signaling pathways of the SP/NK1R system and cancer cell proliferation and development.