Search Results (1,322)

Background: This study aimed to investigate the polymorphic genotypes of MDM2 rs937282, rs937283, rs2279744, and rs769412, as well as the combined effects of MDM2 genotypes and environmental factors on RCC susceptibility. Methods: A total of 135 RCC patients and 590 controls were recruited for MDM2 genotyping using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Quantitative PCR was performed to assess MDM2 mRNA levels among 30 healthy individuals and 22 RCC patients. Results: MDM2 rs2279744, but not other polymorphisms, was significantly associated with an increased RCC risk (p = 0.0133). The MDM2 rs2279744 G allele was identified as a risk factor for RCC (odds ratio [OR] = 1.49, 95% confidence interval [CI] = 1.14–1.96, p = 0.0047). Among smokers (p = 0.0070), alcohol drinkers (p = 0.0233), individuals with hypertension (p = 0.0041), diabetes (p = 0.0225), and those with a family history of cancer (p = 0.0020), the MDM2 rs2279744 GT and GG genotypes exhibited increased RCC risks. However, this risk effect was not observed in non-smokers, non-drinkers, or individuals without hypertension, diabetes, or a family cancer history (all p > 0.05). Moreover, MDM2 mRNA levels were significantly higher in RCC patients compared to controls and varied among the rs2279744 genotypes, with GG genotype exhibiting the highest expression levels among both RCC patients and controls. Conclusions: This study highlights the association between MDM2 rs2279744 genotypes and RCC risk, suggesting that genotype-associated MDM2 mRNA levels could contribute to early RCC detection. Further studies are warranted to elucidate the detailed mechanisms underlying the role of MDM2 in RCC development. Full article

A thorough study of Clear Cell Renal Cell Carcinoma (ccRCC) shows that combining tyrosine kinase inhibitors (TKI) with immune checkpoint inhibitors (ICI) shows promising results in addressing the tumor-promoting influences of abnormal immunological and molecular biomarkers in metastatic Clear Cell Renal Cell Carcinoma (ccRCC). These abnormal biomarkers enhance drug resistance, support tumor growth, and trigger cancer-related genes. Ongoing clinical trials are testing new treatment options that appear more effective than earlier ones. However, more research is needed to confirm their long-term safety use and potential side effects. This study highlights vital molecular and immunological biomarkers associated with drug resistance in Clear Cell Renal Cell Carcinoma (ccRCC). Furthermore, this study identifies a number of promising drug candidates and biomarkers that serve as significant contributors to the enhancement of the overall survival of ccRCC patients. Consequently, this article offers pertinent insights on both recently completed and ongoing clinical trials, recommending further toxicity study for the prolonged use of this treatment strategy for patients with metastatic ccRCC, while equipping researchers with invaluable information for the progression of current treatment strategies. Full article

This study assessed the effectiveness of four competitive pasture species—Premier digit grass (Digitaria eriantha Steud. var. Premier), Rhodes grass (Chloris gayana Kunth.), sabi grass (Urochloa mosambicensis Hack.), and buffel grass (Pennisetum ciliare L.) against the toxic annual riceflower (Pimelea trichostachya Lindl.) at varying planting densities and ratios. At six plants pot⁻¹, with a 66:33 grass-to-weed ratio, riceflower biomass decreased by 73.7%, 82.5%, 73.7%, and 60.6% when grown alongside Premier digit, Rhodes, sabi, and buffel grasses, respectively. Similarly, with four plants pot⁻¹ at a 75:25 ratio, reductions were 69.1%, 79.8%, 71.0%, and 44.5%, respectively. Annual riceflower experienced the greatest suppression when grown with Rhodes grass, showing aggressivity index (AI) values of −60.2 and −67.2 and relative crowding coefficient (RCC) values of 0.4 for both six and four plants pot⁻¹. Premier digit grass also suppressed riceflower effectively, with riceflower AI values of −35.6 and −36.7 and RCC values of 0.5 and 0.6. Buffel grass had the least impact, with riceflower AI values of −41.1 and −27.9 and RCC values of 0.9 and 2.0. Sabi grass also demonstrated good suppressive effects, though slightly less than the top two species. Higher planting densities generally resulted in stronger riceflower suppression. The results highlight the importance of considering planting density, arrangement, and key plant traits when selecting pasture species for successful weed control. Based on these findings, we conclude that Premier digit grass and Rhodes grass show promising potential for effective suppression of annual riceflower growth. Full article

Background/Objectives: Renal cell carcinoma is an aggressive form of kidney cancer, contributing to an estimated 138,000 deaths globally in 2017. Traditional treatments like chemotherapy and radiation are generally considered ineffective. Additionally, CD47 has been identified as a crucial tumor antigen involved in the development and progression of various cancers, including renal cell carcinoma. The interaction of CD47 with SIRPα triggers a “don’t eat me” signal to the macrophages, inhibiting phagocytosis. Much progress has been made in targeting CD47 for cancer immunotherapy in solid tumors (STs) and hematological malignancies. This study aimed to evaluate CD47 expression in malignant and benign renal cell tumors and compare it with prognostic histopathological parameters. Methods: We included 160 malignant and 26 benign tumors. The malignant tumors consisted of renal cell carcinoma (RCC) subtypes including 37 clear cell, 30 chromophobe, 30 papillary type 1, 29 papillary type 2, and 34 unclassified RCC cases. As for the benign tumors, we included 26 oncocytoma cases. All samples were stained with anti-CD47 antibodies by immunohistochemistry methods. Results: The statistical analysis yielded a significant correlation between CD47 expression and survival, metastasis, and capsule invasion for the unclassified RCC cases. We did not find any further significant correlation between CD47 expression and the studied parameters. Conclusions: To the best of our knowledge, our study is the first to research CD47 expression in benign and malignant renal carcinoma subtypes. Further large-scale studies are needed to determine the expression profile of CD47 in renal cell tumors. Full article

Background: The RAVE-Renal study was conducted to evaluate the real-world efficacy and safety of avelumab plus axitinib as a first-line therapy for patients with metastatic renal cell carcinoma (mRCC). Methods: RAVE-Renal was a multicenter, noninterventional, ambispective study with both retrospective and prospective components. The study included adult patients with histologically confirmed mRCC, measurable disease per RECIST version 1.1, and no prior systemic therapy. Patients received avelumab (800 mg intravenously every 2 weeks) plus axitinib (5 mg orally twice daily). The primary endpoints were median progression-free survival (PFS) and objective response rate (ORR). The secondary endpoints included median OS, 1-year overall survival (OS) rate, and safety. Results: A total of 125 patients from 13 sites were enrolled, with a median follow-up of 16.1 months. The median age was 61.0 years. The study population comprised 35.3% favorable, 49% intermediate, and 15.7% poor IMDC risk patients. The median PFS was 14.9 months (95% CI, 11.72–19.08). The ORR was 44.3% (95% CI, 32.5–56.1). The clinical benefit rate was 93.4%. The 1-year OS rate was 71.2%, with the median OS not reached. Any-grade treatment-related adverse events (TRAEs) occurred in 99 (79.2%) cases, including grade ≥3 TRAEs in 24 (19.2%). Conclusions: Avelumab in combination with axitinib showed clinical benefits in a real-world setting, consistent with findings from a pivotal trial. The regimen was effective and well tolerated across various patient subgroups. Full article

Mutations of the von Hippel–Lindau (VHL) tumor suppressor gene occur frequently in clear cell renal cell carcinoma (RCC), the predominant histology of kidney cancer, and have been associated with its pathogenesis and progression. Alterations of VHL lead to impaired degradation of hypoxia-inducible factor 1α (HIF1α) and HIF2α promoting neoangiogenesis, which is pivotal for cancer growth. As such, targeting the VHL-HIF axis holds relevant potential for therapeutic purposes. Belzutifan, an HIF-2α inhibitor, has been recently indicated for metastatic RCC and other antiangiogenic drugs directed against HIF-2α are currently under investigation. Further, clinical and preclinical studies of combination approaches for metastatic RCC including belzutifan with cyclin-dependent kinase 4–6 inhibitors, tyrosine kinase inhibitors, or immune checkpoint inhibitors achieved promising results or are ongoing. This review aims to summarize the existing evidence regarding the VHL/HIF pathway, and the approved and emerging treatment strategies that target this pivotal molecular axis and their mechanisms of resistance. Full article

Background: N-succinimidyl-[¹⁸F]fluorobenzoate ([¹⁸F]SFB) is commonly prepared through a three-step procedure starting from [¹⁸F]fluoride ion. A number of methods for the single-step radiosynthesis of [¹⁸F]SFB have been introduced recently, including the radiofluorination of diaryliodonium salts and the Cu-mediated ¹⁸F-fluorination of pinacol aryl boronates and aryl tributyl stannanes, but they still have the drawbacks of lengthy product purification procedures. In the present work, two approaches for the direct labeling of [¹⁸F]SFB from diaryliodonium (DAI) salt (4) and pinacol aryl boronate (6) are evaluated, with a major focus on developing a fast and simple SPE-based purification procedure. Methods: DAI salt precursor 6 was labeled employing the common “minimalist” approach with a two-step reaction heating sequence. The Cu-mediated radiofluorination of 4 was accomplished using Bu₄NOTf as a phase transfer catalyst for the elution of [¹⁸F]fluoride, followed by radiofluorination in the same solvent. Several types of SPE cartridges were tested in the elution and SPE procedures. Results: The Cu-mediated ¹⁸F-fluorination of the pinacol aryl boronate precursor afforded a higher RCC of 56 ± 3% (n = 7), making it better suited for the one-pot synthesis of [¹⁸F]SFB. SPE-based purification was achieved using cation exchange and reverse-phase polymer resin cartridges, connected in series. In a full-batch test, [¹⁸F]SFB was obtained with an RCY of 30% (n. d. c.), RCP > 99%, A_m 96–155 GBq/µmol, and a synthesis time of ≤35 min. Conclusions: Compared to other published methods, [¹⁸F]SFB production via the Cu-mediated radiofluorination of pinacol aryl boronate precursor provides significant time and cost savings, coupled with an ease of implementation. Full article

Background: stereotactic ablative body radiotherapy (SABR) is a disruptive radiation therapy technique which is increasingly used for the treatment of urologic cancers. The aim of this narrative review is to provide an overview on the current landscape of SABR in urologic cancers and highlight advancements on the horizon. Methods: a narrative review of the contemporary role of SABR in urologic cancers is conducted. Results: in localised prostate cancer, SABR boasts excellent tumour control and biochemical control, with acceptable GU and GI toxicity. Its comparison to laparoscopic radical prostatectomy is currently ongoing. SABR appears to be practical for metastasis-directed therapy in metastatic prostate cancer, with good local control and a low toxicity profile, either alone or in combination with ADT. In localised RCC, SABR offers adequate local control with a modest impact on renal function in patients unfit for surgical management. Its role in metastatic RCC is much more established, where it has been shown to be superior to conventional radiotherapy. Emerging evidence suggests that SABR has a role in delaying systemic therapy whilst maintaining QOL and overall survival. Intriguingly, in metastatic prostate cancer and metastatic RCC, SABR results in a cytoreductive and immunomodulatory ‘abscopal effect’, a focus of current investigations. Conclusions: SABR has emerged as a safe, effective, and feasible treatment for urologic cancers. Urologists should be aware of its increasing use in localised prostate cancer and metastatic RCC, with good oncological outcomes combined with acceptable toxicity. In addition, SABR holds promise for both metastatic prostate cancer and localised RCC treatment in terms of toxicity and oncological outcomes. Full article

Background/Objectives: The purpose of this study was to develop the gemcitabine-loaded drug-eluting beads (G-DEBs) for transarterial chemoembolization (TACE) in rabbit renal tumors and to evaluate their antitumor effect using 2-deoxy-2-[(18)F]fluoro-D-glucose positron emission tomography/X-ray computed tomography (¹⁸F-FDG PET/CT). Methods: DEBs were prepared by polyvinyl alcohol-based macromer crosslinked with N-acryl tyrosine and N,N′-methylenebis(acrylamide). Gemcitabine was loaded through ion change to obtain G-DEBs. Their particle size and drug release profile were characterized. VX2 tumors were implanted in the right kidney of rabbits to establish the renal tumor model. The tumor-bearing rabbits received pre-scan by ¹⁸F-FDG PET/CT, followed by targeted transarterial injection of G-DEBs under digital subtraction angiography (DSA) guidance. The rabbits received another ¹⁸F-FDG PET/CT scan 10 or 14 days after the treatment. The therapeutic effect was further validated by histopathological analysis of the dissected tumors. Results: The average particle size of the microspheres was 58.06 ± 0.50 µm, and the polydisperse index was 0.26 ± 0.002. The maximum loading rate of G-DEBs was 18.09 ± 0.35%, with almost 100% encapsulation efficiency. Within 24 h, GEM was eluted from G-DEBs rapidly and completely, and more than 20% was released in different media. DSA illustrated that G-DEBs were delivered to rabbit renal tumors. Compared with the untreated control group with increased tumor volume and intense ¹⁸F -FDG uptake, the G-DEBs group showed significant reductions in tumor volume and maximum standard uptake value (SUV_max) 10 or 14 days after the treatment. Histopathological analysis confirmed that the proliferating area of tumor cells was significantly reduced in the G-DEBs group. Conclusions: Our results demonstrated that G-DEBs are effective in TACE treatment of rabbit VX2 renal tumors, and ¹⁸F-FDG PET/CT provides a non-invasive imaging modality to monitor the antitumor effects of TACE in renal tumors. Full article

Background and Objectives: The role of surgery in pancreatic metastases of renal cell carcinoma (PM_RCC) is highly controversial, particularly in the context of modern systemic therapies and the conflicting results of studies published so far. This study aims to explore a single surgical center experience (including mainly pancreatic resections) regarding the indications, the type of pancreatectomies, and early and long-term outcomes for PM_RCC. Materials and Methods: The data of all patients with surgery for PM_RCC (from 1 January 2002 to 31 December 2023) were retrospectively assessed, and potential predictors of survival were explored. Results: 20 patients underwent surgery for PM_RCC (pancreatectomies—95%). Metachronous PM_RCC was 90%, with a median interval between the initial nephrectomy and PM_RCC occurrence of 104 months. For elective pancreatectomies, the overall and severe morbidity and mortality rates were 24%, 12%, and 0%, respectively; 32% of patients underwent non-standardized pancreatic resections. The median survival of patients with negative resection margins was 128 months after pancreatectomies, with an 82% 5-year survival rate. Left kidney RCC and the body/tail PM_RCC were favorable prognostic factors for the overall survival after pancreatectomies for PM_RCC. Body/tail, asymptomatic PM_RCC, and an interval after initial nephrectomy > 2 were favorable prognostic factors for the overall survival after initial nephrectomy for RCC. Conclusions: Pancreatectomies for PM_RCC can achieve long-term survival whenever complete resection is feasible, with acceptable complication rates. Patients with left kidney RCC, body/tail, and asymptomatic PM_RCC and an interval of more than 2 years after nephrectomy exhibit the best survival rates. Full article

Aim: The purpose of the study was to identify potential differences between patients with right colon cancer and left colon cancer in epidemiological, clinical presentation, pathological, and surgical results in addition to the impact of the sidedness on disease-free survival (DFS) and overall survival (OS). Method: Patients with a diagnosis of colon cancer stages I-IV between 2010 and 2020 were identified from a prospective database in a tertiary single center. Right and left-sided cancer were compared regarding epidemiological, clinical presentation, pathological, and surgical results. Survival analysis was conducted using the Kaplan–Meier method and adjusted hazard ratios for mortality (OS) and disease-free survival (DFS) were obtained using Cox proportional hazards regression. Results: The right colon group included 82 (31%) patients and the left colon group 182 (69%). After adjusted analysis, RCC presented less bleeding (RP: 0.31; CI: 0.18–0.56; p: 0.0001) and change in bowel habits (RP: 0.60; CI: 0.41–0.87; p: 0.0069). A laparotomy approach was more performed in LCC (RP: 0.64; CI: 0.47–0.86; p: 0.0029). Regarding pathological results, RCC had more poorly differentiated tumors (RP: 0.81; CI: 0.70–0.94; p: 0.05). In the adjusted analysis, there was no difference in survival for right-sided compared to left-sided colon cancer: the hazard ratios were 1.36 (CI 95%: 0.61–3.01; p: 0.4490) for OS and 2.04 (CI: 0.91–4.59; p: 0.0814) for DFS. Conclusions: In this population-based cohort, we found no impact of colon cancer sidedness on OS and DFS. RCC presented less differentiated tumors and LCC presented more bleeding and change in bowel habits. Full article

Heat stress is a major environmental stressor that affects fish metabolism, growth, and death rates. This research examined the impact of dietary rutin addition (0, 100, 300, or 500 mg/kg) for 60 days on juvenile hybrid fish (Carassius auratus cuvieri, WCC, ♀ × Carassius auratus red var, RCC, ♂, WR) (27.97 ± 0.56 g) under heat stress conditions (32 ± 1 °C for 48 h). The analysis focused on blood parameters, oxidative stress biomarkers, and hepatic hsp70 and hsp90 gene expression in WR. The results demonstrated that rutin supplementation elevated blood glucose levels and the liver activities of glutathione reductase, glutathione peroxidase, catalase, and total superoxide dismutase in comparison to the control group. Additionally, rutin supplementation also significantly reduced serum cortisol and hepatic malondialdehyde levels while upregulating hepatic hsp70 and hsp90 gene expression. These findings suggest that rutin supplementation enhances antioxidant responses and alleviates the impact of heat stress on fish physiological and biochemical markers and heat shock protein gene expression. Full article

Background: Immunotherapy has transformed cancer treatment; however, predicting treatment response remains challenging. Serum biomarkers can help identify patients who are most likely to benefit from immunotherapy. Objective: This study evaluates the relationship between serum growth differentiation factor 15 (GDF-15) and interleukin-6 (IL-6) levels and treatment outcomes in cancer patients undergoing second-line immunotherapy. Methods: We conducted a prospective observational study involving 85 patients with non-small-cell lung cancer (NSCLC), renal cell carcinoma (RCC), or malignant melanoma treated with nivolumab. The baseline serum levels of GDF-15 and IL-6 were measured by using ELISA kits. The primary endpoints were progression-free survival (PFS) and overall survival (OS), with cachexia as a secondary outcome. Results: Elevated GDF-15 levels were significantly associated with shorter PFS (HR: 0.55, 95% CI: 0.32–0.96, p = 0.032) and OS (HR: 0.47, 95% CI: 0.25–0.90, p = 0.020). Higher IL-6 levels correlated with shorter PFS, though statistical significance was not achieved. Additionally, high GDF-15 levels were linked to increased cachexia incidence (p = 0.037). Conclusion: Our findings indicate that GDF-15 could serve as a prognostic biomarker for immunotherapy response and may also be a target for cachexia management. Further studies should explore its potential to guide clinical decision making in oncology. Full article

Background: Kidney cancer accounts for approximately 2% of all diagnosed cancers and fatalities worldwide, and a notable increase in its incidence has been observed in recent years. Previous studies have identified various risk factors for renal cell carcinoma (RCC), including age, gender, smoking, hypertension, overweight, and obesity. However, limited information is available regarding the correlation between RCC risk factors and tumor lateralization. Objectives: To investigate the relationship between body mass index (BMI) and the lateralization of kidney tumors in patients undergoing surgery for renal cell carcinoma. Moreover, we aim to evaluate the impact of lateralization of malignant kidney tumors on overall survival (OS) and cancer-specific survival (CSS). Materials and Methods: This single-center study included 287 patients who underwent surgical treatment for kidney tumors between January 2016 and December 2019. The patients were allocated into the following groups based on their BMI: normal (18.5–24.99 kg/m²), overweight (25–29.99 kg/m²), or obese (≥30 kg/m²). The study collected demographic and histopathological data, as well as patient history, including risk factors such as smoking and hypertension. Results: Right-sided kidney tumors occurred more frequently (55.05%, n = 158) than left-sided ones (44.95%, n = 129). A statistically significant relationship (p = 0.04731) was observed between BMI and the frequency of right-sided kidney tumors in the overweight group (70 vs. 43 cases). There was no correlation between BMI and the occurrence of kidney tumors in the normal BMI and obesity groups. Furthermore, the analysis revealed no association between the lateralization of kidney tumors, smoking, and hypertension. The 5-year survival rate was 62%, with a mean follow-up duration of 104 months (approximately 8.5 years). No statistically significant difference was observed between the right- and left-sided cancer groups, with survival rates of 58% and 66%, respectively (p = 0.652). Conclusions: This study highlighted that right-sided kidney tumors occurred significantly more frequently in overweight individuals in our cohort of patients. No association was observed between lateralization of kidney cancer and overall survival (OS) or cancer-specific survival (CSS). Full article

A combination of nivolumab and ipilimumab (NIVO + IPI) is the only approved combination of two immune checkpoint inhibitors for metastatic or advanced renal cell carcinoma (mRCC). Inadequate evidence of treatment with NIVO + IPI has been reported in Japanese cohorts. We evaluated the clinical efficacy of NIVO + IPI treatment. Patients with mRCC who received NIVO + IPI at nine Japanese facilities between August 2018 and March 2023 were enrolled in this study. The primary endpoint in this study was the assessment of oncological outcomes in patients with mRCC who received NIVO + IPI. Eighty-four patients with mRCC were enrolled. The median follow-up period was 18.3 months, and median progression-free and overall survival were 13.3 and 50.9 months, respectively. The objective response rate was 47.6%, and the disease control rate was 78.6%. To our knowledge, this is the largest study that evaluates Japanese patients with mRCC receiving NIVO + IPI treatment. In this study, the real-world oncological outcomes after NIVO + IPI treatment were comparable to those in the CheckMate 214 study. Full article