Role of Hb to RDW ratio in metastatic renal cell carcinoma patients treated with first-line immunotherapy combinations.

Background: The present study aimed to investigate the prognostic and predictive roles of Hb/RDW ratio in patients with mRCC treated with first-line immunotherapy combinations (TKI plus ICI or ICI plus ICI).

Materials And Methods: We performed a sub-analysis of a multicenter retrospective observational study (ARON-1 project) involving patients with mRCC treated with first-line immunotherapy combinations.

Results: Three hundred and twenty-nine patients were enrolled, 244 males and 85 females.

The Clinical Role of Hypoxia Inducible Factor (HIF) Inhibition in Renal Cancer: A Focus on Belzutifan.

Systemic therapy for metastatic Renal Cell Carcinoma (mRCC) has dramatical-ly improved in the last years because of the use of immunotherapy with checkpoint inhibi-tor combinations with or without targeted therapies against the Vascular Endothelial Growth Factor Receptors (VEGFR). As a result, patients with mRCC have prolonged sur-vival time, but they ultimately develop resistance and the disease progresses, which high-lights the critical need for novel treatment options. The Hypoxia-inducible Factor (HIF) pathway is central to the pathophysiology of ccRCC and von Hippel-Lindau (VHL) disease.

Identification and Reconstitution of the First Two Enzymatic Steps for the Biosynthesis of Bioactive Meroterpenoids from (Lion's Mane Mushroom).

(Lion's Mane mushroom) is widely consumed for its numerous reported benefits for brain health. A growing body of evidence suggests that these benefits are likely attributable to aromatic compounds contained in its fruiting bodies, including the meroterpenoids hericenones. Here, we report the identification and reconstitution of the first two steps of the biosynthetic pathway of hericenones via heterologous expression of the polyketide synthase HerA and the carboxylic acid reductase HerB in .

MIBiG 4.0: advancing biosynthetic gene cluster curation through global collaboration.

Specialized or secondary metabolites are small molecules of biological origin, often showing potent biological activities with applications in agriculture, engineering and medicine. Usually, the biosynthesis of these natural products is governed by sets of co-regulated and physically clustered genes known as biosynthetic gene clusters (BGCs). To share information about BGCs in a standardized and machine-readable way, the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard and repository was initiated in 2015.

Defining the Position of [Lu]Lu-PSMA Radioligand Therapy in the Treatment Landscape of Metastatic Castration-Resistant Prostate Cancer: A Meta-analysis of Clinical Trials.

Background: In recent years, theranostics has become a promising approach for treating metastatic castration-resistant prostate cancer (mCRPC), with trials investigating targeted radioligand therapy, particularly using prostate-specific membrane antigen labeled with lutetium-177 ([Lu]Lu-PSMA). The proper position of [Lu]Lu-PSMA in the therapeutic algorithm of mCRPC is yet to be identified.

Design, Setting, And Participants: We conducted a systematic review and meta-analysis of phase II/III randomized controlled trials to assess the efficacy of [Lu]Lu-PSMA in treating mCRPC.

Relationship Between Loss of Y Chromosome and Urologic Cancers: New Future Perspectives.

The Y chromosome (ChrY) is essential for male sex determination and spermatogenesis. However, recent studies have revealed its broader role in various physiological processes and disease susceptibility, including cancer. A comprehensive literature review was conducted using databases like MEDLINE, Scopus, Web of Science, and Google Scholar.

Discovery and Heterologous Expression of Functional 4--Dimethylallyl-l-tyrosine Synthases from Lichen-Forming Fungi.

Fungal aromatic prenyltransferases are a family of biosynthetic enzymes that catalyze the prenylation of a range of aromatic substrates during the biosynthesis of bioactive indole alkaloids, diketopiperazines, and meroterpenoids. Their broad substrate scope and soluble nature make these enzymes particularly adept for applications in biocatalysis; for example, the enzymatic derivatization of aromatic drugs improves their bioactivity. Here, we investigated four putative aromatic prenyltransferases from lichen-forming fungi, an underexplored group of organisms that produce more than 1,000 unique metabolites.

Belzutifan versus Everolimus for Advanced Renal-Cell Carcinoma.

Background: Belzutifan, a hypoxia-inducible factor 2α inhibitor, showed clinical activity in clear-cell renal-cell carcinoma in early-phase studies.

Methods: In a phase 3, multicenter, open-label, active-controlled trial, we enrolled participants with advanced clear-cell renal-cell carcinoma who had previously received immune checkpoint and antiangiogenic therapies and randomly assigned them, in a 1:1 ratio, to receive 120 mg of belzutifan or 10 mg of everolimus orally once daily until disease progression or unacceptable toxic effects occurred. The dual primary end points were progression-free survival and overall survival.

Highlights from the 2024 ASCO Genitourinary Symposium: focus on urothelial and prostate cancer.

The 2024 ASCO Genitourinary Cancer Symposium, this year celebrating the 20th anniversary, delved into key advancements in urothelial carcinoma (UC) and prostate cancer (PC). For UC, insights emerged from adjuvant pembrolizumab for muscle-invasive urothelial carcinoma, and from the efficacy of the EV-302 study of enfortumab vedotin +pembrolizumab in the metastatic setting. In PC, adjuvant therapy with high-dose radiotherapy schedules plus long-t erm ADT was explored.

2024 ASCO genitourinary cancers symposium: a focus on renal cell carcinoma.

In this article, we report the breakthrough acquisitions for renal cell carcinoma (RCC) management presented at the 2024 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium. The results from Keynote 564 showed an impressive overall survival (OS) advantage for pembrolizumab, in patients at higher risk of relapse after surgery and confirmed the benefit in terms of disease-free survival (DFS). Until now, pembrolizumab is the only immune checkpoint inhibitor (ICI) to prove a survival advantage.

The incidence and relative risk of major adverse cardiovascular events and hypertension in patients treated with immune checkpoint inhibitors plus tyrosine-kinase inhibitors for solid tumors: a systemic review and meta-analysis.

Introduction: Combinations of immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) can be responsible for major adverse cardiovascular events (MACEs). We performed a meta-analysis to assess the relative risk (RR) of MACEs and hypertension in cancer patients treated with ICI+TKI combinations.

Research Design And Methods: We selected prospective trials through MEDLINE/PubMed, Cochrane Library, and ASCOMeeting abstracts.

Clinical Outcomes and Prognostic Factors in Patients With Penile Carcinoma: A Sub-Analysis From Meet-URO 23 (I-RARE) Registry Study.

Introduction: Penile squamous cell carcinoma (PSCC) is a rare tumor with an aggressive behavior. The Meet-URO 23/I-RARE registry includes rare genitourinary malignancies. We extracted patients with PSCC to conduct a retrospective study aimed at assessing clinical outcomes and prognostic factors.

External validation of a red cell-based blood prognostic score in patients with metastatic renal cell carcinoma treated with first-line immunotherapy combinations.

Immunotherapy combinations with tyrosine-kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) had significantly improved outcomes of patients with mRCC. Predictive and prognostic factors are crucial to improve patients' counseling and management. The present study aimed to externally validate the prognostic value of a previously developed red cell-based score, including hemoglobin (Hb), mean corpuscular volume (MCV) and red cell distribution width (RDW), in patients with mRCC treated with first-line immunotherapy combinations (TKI plus ICI or ICI plus ICI).

Theranostics revolution in prostate cancer: Basics, clinical applications, open issues and future perspectives.

In the last years, theranostics has expanded the therapeutic options available for prostate cancer patients. In this review, we explore this dynamic field and its potential to revolutionize precision medicine for prostate cancer. We delve into the foundational principles, clinical applications, and emerging opportunities, emphasizing the potential synergy between radioligand therapy and other systemic treatments.

Comparison of PIV and Other Immune Inflammation Markers of Oncological and Survival Outcomes in Patients Undergoing Radical Cystectomy.

Unlabelled: Inflammation is widely acknowledged as a significant characteristic of cancer, playing a substantial function in both the initiation and advancement of cancers. In this research, we planned to compare pan-immune inflammation markers and other well-known markers (systemic immune inflammation index and neutrophil to lymphocyte ratio) to predict prognosis in individuals treated with radical cystectomy for bladder cancer.

Methods: In this retrospective analysis, we focused on preoperative PIV, systemic immune inflammation index (SII), and neutrophil-lymphocyte ratio (NLR) in 193 individuals managed with radical cystectomy for bladder cancer between January 2016 and November 2022.

Genome sequencing and molecular networking analysis of the wild fungus Anthostomella pinea reveal its ability to produce a diverse range of secondary metabolites.

Background: Filamentous fungi are prolific producers of bioactive molecules and enzymes with important applications in industry. Yet, the vast majority of fungal species remain undiscovered or uncharacterized. Here we focus our attention to a wild fungal isolate that we identified as Anthostomella pinea.

Is Systemic Immune-Inflammation Index a Real Non-Invasive Biomarker to Predict Oncological Outcomes in Patients Eligible for Radical Cystectomy?

: To assess the potential prognostic role of the systemic immune-inflammation index (SII) in predicting oncological outcomes in a cohort of patients treated with radical cystectomy (RC). : From 2016 to 2022, a retrospective monocentric study enrolled 193 patients who were divided into two groups based on their SII levels using the optimal cutoff determined by the Youden index. The SII was obtained from a preoperative blood test approximately one month before RC.

Heterologous Naringenin Production in the Filamentous Fungus .

Naringenin is a natural product with several reported bioactivities and is the key intermediate for the entire class of plant flavonoids. The translation of flavonoids into modern medicine as pure compounds is often hampered by their low abundance in nature and their difficult chemical synthesis. Here, we investigated the possibility to use the filamentous fungus as a host for flavonoid production.

Navigating the Rapidly Evolving Advanced Urothelial Carcinoma Treatment Landscape: Insights from Italian Experts.

Purpose Of Review: To discuss recent advances in the treatment of advanced urothelial carcinoma (UC) and how best to incorporate new therapies into clinical practice.

Recent Findings: There have been several recent practice-changing phase 2 and 3 trials of immune checkpoint inhibitors (ICIs), antibody-drug conjugates (ADCs), and targeted agents in advanced UC. Based on data from these trials, ICIs can be used as first-line maintenance therapy in patients who do not progress on platinum-based chemotherapy, second-line therapy for those with progression, and first-line therapy in cisplatin-ineligible patients with PD-L1 expression; ADCs and targeted agents provide later-line treatment options.