Ligand-dependent CD36 functions in cancer progression, metastasis, immune response, and drug resistance.

CD36, a multifunctional glycoprotein, has been shown to play critical roles in tumor initiation, progression, metastasis, immune response, and drug resistance. CD36 serves as a receptor for a wide range of ligands, including lipid-related ligands (e.g., long-chain fatty acid (LCFA), oxidized low-density lipoprotein (oxLDL), and oxidized phospholipids), as well as protein-related ligands (e.g., thrombospondins, amyloid proteins, collagens I and IV). CD36 is overexpressed in various cancers and may act as an independent prognostic marker. While it was initially identified as a mediator of anti-angiogenesis through its interaction with thrombospondin-1 (TSP1), recent research has highlighted its role in promoting tumor growth, metastasis, drug resistance, and immune suppression. The varied impact of CD36 on cancer is likely ligand-dependent. Therefore, we focus specifically on the ligand-dependent role of CD36 in cancer to provide a critical review of recent advances, perspectives, and challenges.

Immunotherapy with or without targeted therapy for metastatic upper tract urothelial carcinoma: case report and literature review.

Background: Immune checkpoint inhibitors (ICIs) have been proved having a better safety profile compared to platinum-based chemotherapy and have demonstrated encouraging anti-tumor therapeutic effects for patients with metastatic urothelial carcinoma (mUC). However, few studies have evaluated the efficacy of ICIs in patients with metastatic upper tract urothelial carcinoma (mUTUC). Case reports: Case 1 was a 71-year-old male patient diagnosed with left renal pelvic carcinoma, accompanied by a metastasis to the second lumbar spine. As the patient became refractory to chemotherapy, four cycles of camrelizumab, one of the ICIs, were administered, which helped to control the metastases and extend the patient's progression-free survival to five months. Case 2 was an 88-year-old female with middle and lower right ureter carcinoma with right iliac arteriovenous invasion. The patient received five cycles of camrelizumab plus vascular endothelial growth factor receptor 2 (VEGFR2) inhibitors and achieved stable disease. Conclusion: For patients who are ineligible for chemotherapy, immunotherapy might be a feasible treatment, regardless of whether or not they are given VEGFR2 inhibitors.

Single-port robot-assisted perineal radical prostatectomy with the da Vinci XI system: initial experience and learning curve using the cumulative sum method.

BACKGROUND: To evaluate the early functional and oncological outcomes of single-port robot-assisted perineal radical prostatectomy (sp-pRARP) using the da Vinci XI system and analyze its learning curve using the cumulative sum (CUSUM) method. METHODS: The clinical data of 50 patients who underwent sp-pRARP for localized prostate cancer between May 2020 and May 2022 in our center by a single surgeon were analyzed retrospectively. Demographic information, preoperative and postoperative variables, complications, early functional and oncological outcomes of patients were recorded. The CUSUM method was used to illustrate the learning curve based on operation time. RESULTS: All surgeries were completed without conversion. The median (interquartile range, IQR) operation time was 205.0 (82.5) min, whereas the median (IQR) docking time was 30.0 (15.0) min and the console time was 120.0 (80.5) min. The median (IQR) estimated blood loss (EBL) was 50.0 (137.5) mL. Positive surgical margins were detected in five patients (10.0%). The continence rate was 40.9%, 63.6%, 88.4%, and 97.7% at the 1, 3, 6, and 12 months after surgery. According to the CUSUM plot, the inflection points of the learning curve were 20 cases, splitting the case series into "early phase" and "late phase." In "late phase" cases, there was less time spent on each step of the operation and less EBL. CONCLUSIONS: Sp-pRARP using the da Vinci XI system was verified to be a feasible and reliable surgical approach. According to the CUSUM plot, 20 cases was considered the turning point for surgeons to master the novel technique.

N6-methyladenosine-modified TRAF1 promotes sunitinib resistance by regulating apoptosis and angiogenesis in a METTL14-dependent manner in renal cell carcinoma.

BACKGROUND: Sunitinib resistance can be classified into primary and secondary resistance. While accumulating research has indicated several underlying factors contributing to sunitinib resistance, the precise mechanisms in renal cell carcinoma are still unclear. METHODS: RNA sequencing and m6A sequencing were used to screen for functional genes involved in sunitinib resistance. In vitro and in vivo experiments were carried out and patient samples and clinical information were obtained for clinical analysis. RESULTS: We identified a tumor necrosis factor receptor-associated factor, TRAF1, that was significantly increased in sunitinib-resistant cells, resistant cell-derived xenograft (CDX-R) models and clinical patients with sunitinib resistance. Silencing TRAF1 increased sunitinib-induced apoptotic and antiangiogenic effects. Mechanistically, the upregulated level of TRAF1 in sunitinib-resistant cells was derived from increased TRAF1 RNA stability, which was caused by an increased level of N6-methyladenosine (m6A) in a METTL14-dependent manner. Moreover, in vivo adeno-associated virus 9 (AAV9) -mediated transduction of TRAF1 suppressed the sunitinib-induced apoptotic and antiangiogenic effects in the CDX models, whereas knockdown of TRAF1 effectively resensitized the sunitinib-resistant CDXs to sunitinib treatment. CONCLUSIONS: Overexpression of TRAF1 promotes sunitinib resistance by modulating apoptotic and angiogenic pathways in a METTL14-dependent manner. Targeting TRAF1 and its pathways may be a novel pharmaceutical intervention for sunitinib-treated patients.

Camrelizumab monotherapy leading to partial remission for relapsed upper tract urothelial carcinoma after radical nephroureterectomy: a case report.

Upper tract urothelial carcinoma (UTUC) is a rare malignant disease, and while locally advanced non-metastatic UTUC can be cured by radical nephroureterectomy (RNU), this procedure leaves patients at high risk of relapse and death from cancer. Though the FDA has currently approved five agents for the systemic immunotherapy treatment of urothelial carcinoma (UC) patients, the effect of immunotherapy in patients with recurrent UTUC still lacks specific evidence. Camrelizumab is a programmed cell death protein 1 (PD-1) inhibitor which has been approved for the treatment of recurrent or refractory classical Hodgkin lymphoma in China and have achieved improvement in a verity of solid tumors with manageable safety profile. We herein report a case of an 80-year-old woman diagnosed with localized UTUC (pT4N0M0) for which she underwent RNU but relapsed after 2 months. As the toxic effects of chemotherapy were intolerable for the patient, she received the PD-1 inhibitor Camrelizumab as a salvage treatment to stop tumor growth. The tumor shrank and the patient achieved partial response (PR) after eight cycles but progressed after 14 cycles. Based on the current evidence, our case indicated that Camrelizumab is a promising agent in treating locally advanced and recurrent UTUC patients with poor performance status and imparted renal function.

Transperineal single-port robot-assisted radical prostatectomy with Si da Vinci surgical system: initial experience and description of technique.

BACKGROUND: Single-port robotic-assisted radical laparoscopic prostatectomy has emerged as a novel robotic-assisted radical laparoscopic prostatectomy in recent years, arousing wide attention. However, single-port robotic-assisted radical laparoscopic prostatectomy using Si da Vinci surgical system has been rarely reported, especially via the transperineal approach. METHODS: We retrospectively collected 9 cases of prostate cancer patients who underwent transperineal single-port robot-assisted radical prostatectomy (t-spPARP) using Si da Vinci surgical system in our center from May 2020 to June 2020. The operation time, estimated blood loss (EBL), complications, changes in prostate-specific antigen (PSA) 3 months after surgery, and urinary continence recovery 6 months after surgery were analyzed. RESULTS: No perioperative complications were recorded. The median [interquartile range (IQR)] operation time was 350 [150] min and the median [IQR] EBL was 300 [100] mL. PSA levels were less than 0.01 ng/mL at 3 months postoperatively in all cases (undetectable in 8 cases). All the 9 patients recovered their urinary continence 6 months after surgery and merely two patients required pads during the day. CONCLUSIONS: t-spRARP was verified as a safe and feasible surgical alternative to treat patients with localized prostate cancer, especially for those whose prostate is small-volume or who had abdominal surgery history.

Early channel transurethral resection of the prostate for patients with urinary retention after brachytherapy.

OBJECTIVE: It is recommended that transurethral resection of the prostate (TURP) after brachytherapy should not be performed at an early stage after implantation. Herein we report our experiences and the results of channel TURP (cTURP) within six months post-implant for patients with refractory urinary retention. METHODS: One hundred and ninety patients with localized prostate cancer of clinical stages T1c to T2c were treated by brachytherapy as monotherapy at our institution from February 2009 to July 2013. Nine patients who developed refractory urinary retention and underwent cTURP within six months after brachytherapy were retrospectively reviewed and analyzed. RESULTS: The median interval between prostate brachytherapy and cTURP was three months (range 1.5 to 5.0 months). There were no intraoperative or postoperative complications and no incontinence resulting from the surgery. All urinary retention was relieved per the American Brachytherapy Society urinary symptom score. With a mean follow-up time of 16 months (range 6 to 26 months) after cTURP, no patient experienced biochemical recurrence. The mean serum prostate-specific antigen (PSA) of the patients who underwent cTURP was 0.42 ng/ml (range 0.08 to 0.83 ng/ml) at the end of their follow-up. CONCLUSIONS: Early cTURP was found to be safe and effective in relieving urinary retention after brachytherapy and could be performed without compromising its therapeutic efficacy.

[Protective effects of carnosine against closed head injury in mice].

OBJECTIVE: To investigate the protective effects of carnosine against experimental closed head injury (CHI) in mice. METHODS: The CHI model was established by free-falling weight-drop. Carnosine (250 mg/kg or 500 mg/kg) was administered intraperitoneally 30 min before brain trauma, then q.d for 7 d; while normal saline was administrated for control group. The neurological defect was evaluated by neurological severity score (NSS) within 7 d; the survival rate and the histological alternations were observed. RESULTS: Carnosine prevented the body weight loss of mice at dose of 500 mg/kg; significantly increased the survival rate, and reduced the neurological defect and histological damage at dose of 250 and 500 mg/kg. CONCLUSION: Carnosine can attenuate closed head injury in mice.