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Simple Summary: While treatments have expanded for advanced renal cell carcinoma (RCC), resistance emerges in the majority of patients. Novel alternative diagnostics and therapeutics are required to improve outcomes. Prostate membrane-specific antigen (PSMA) diagnostic and therapeutic strategies have emerged, and early studies highlight the relevance of PSMA in RCC tumors. These early observations have generated interest in targeting PSMA, which is encoded by the FOLH1 gene, as a diagnostic and therapeutic strategy in RCC. We aimed to investigate patterns of FOLH1 expression in RCC and their impact on outcomes. We identified differential FOLH1 expression based on RCC histology and metastatic sites. We observed a correlation between FOLH1 expression and an angiogenic gene signature, suggesting potential therapeutic implications for tumors with high FOLH1 expression. Consistent with our findings, high FOLH1 expression was associated with an increased time on cabozantinib. Ultimately, this analysis provides insights for designing diagnostic and therapeutic strategies that target FOLH1/PSMA. Purpose: Given the emergence of PSMA-targeted diagnostic agents and therapeutics, we sought to investigate patterns of FOLH1 expression in RCC and their impacts on RCC outcomes. Methods: We conducted a pooled multi-institutional analysis of patients with RCC having undergone DNA and RNA next-generation sequencing. FOLH1-high/low expression was defined as the ≥75th/<25th percentile of RNA transcripts per million (TPM). Angiogenic, T-effector, and myeloid expression signatures were calculated using previously defined gene sets. Kaplan–Meier estimates were calculated from the time of tissue collection or therapy start. Results: We included 1,724 patients in the analysis. FOLH1 expression was significantly higher in clear cell (71%) compared to non-clear cell RCC tumors (19.0 versus 3.3 TPM, p < 0.001) and varied by specimen site (45% primary kidney/55% metastasis, 13.6 versus 9.9 TPM, p < 0.001). FOLH1 expression was correlated with angiogenic gene expression (Spearman = 0.76, p < 0.001) and endothelial cell abundance (Spearman = 0.76, p < 0.001). While OS was similar in patients with FOLH1-high versus -low ccRCC, patients with FOLH1-high clear cell tumors experienced a longer time on cabozantinib treatment (9.7 versus 4.6 months, respectively, HR 0.57, 95% CI 0.35–0.93, p < 0.05). Conclusions: We observed differential patterns of FOLH1 expression based on histology and tumor site in RCC. FOLH1 was correlated with angiogenic gene expression, increased OS, and a longer duration of cabozantinib treatment. [ABSTRACT FROM AUTHOR]

Biosynthetic gold nanoparticles (bAuNPs) present a promising avenue for enhancing bio-compatibility and offering an economically and environmentally responsible alternative to traditional production methods, achieved through a reduction in the use of hazardous chemicals. While the potential of bAuNPs as anticancer agents has been explored, there is a limited body of research focusing on the crucial physicochemical conditions influencing bAuNP production. In this study, we aim to identify the optimal growth phase of Pseudomonas aeruginosa cultures that maximizes the redox potential and coordinates the formation of bAuNPs with increased efficiency. The investigation employs 2,6-dichlorophenolindophenol (DCIP) as a redox indicator. Simultaneously, we explore the impact of temperature, pH, and incubation duration on the biosynthesis of bAuNPs, with a specific emphasis on their potential application as antitumor agents. Characterization of the resulting bAuNPs is conducted using ATR-FT-IR, TEM, and UV-Vis spectroscopy. To gain insights into the anticancer potential of bAuNPs, an experimental model is employed, utilizing both non-neoplastic (HPEpiC) and neoplastic (PC3) epithelial cell lines. Notably, P. aeruginosa cultures at 9 h/OD600 = 1, combined with biosynthesis at pH 9.0 for 24 h at 58 °C, produce bAuNPs that exhibit smaller, more spherical, and less aggregated characteristics. Crucially, these nanoparticles demonstrate negligible effects on HPEpiC cells while significantly impacting PC3 cells, resulting in reduced viability, migration, and lower IL-6 levels. This research lays the groundwork for the development of more specialized, economical, and ecologically friendly treatment modalities. [ABSTRACT FROM AUTHOR]

Simple Summary: The present study demonstrates a high concordance between the immunohistochemistry (IHC) expression of HER2 and the RNA expression of ERBB2 in urothelial carcinoma. The genomic, transcriptomic, and immunologic landscapes of urothelial carcinoma based on ERBB2 expression were investigated. High-expressing ERBB2 tumors have an increased expression of antibody drug conjugate (ADC) target genes NECTIN4 and TACSTD2 versus the low-expressing ERBB2 tumor. Targeting ERBB2-high tumors with multiple ADCs should be investigated as a potential therapeutic strategy. Additionally, a positive association between ERBB2 expression and survival was observed and warrants further investigation. Background: Recent data suggests that HER2-targeted treatment is efficacious in urothelial carcinoma (UC). We investigated the genomic, transcriptomic, and immune landscapes and clinical outcomes in UC segmented by ERBB2 expression. Methods: NextGen DNA/RNA sequencing was performed for 4743 UC tumors. A total of 3% (124/4125) of tumors had HER2 IHC and whole transcriptome sequencing (WTS) data. ERRB2-high and -low tumors were defined by ≥75th and <25th percentiles of ERBB2 expression, respectively. PD-L1 (SP142) positive staining was defined as ≥2+ and ≥5%. HER2 (4B5) positive staining was defined as ≥3+ and >10% or 2+ and >10% with positive HER2 in situ hybridization (ISH). Results: Of the patients who were ERBB2-high, 79% (61/77) were HER2 positive via IHC. Tumors from lower tract UC had higher ERBB2 expression compared to upper tract UC (50 v 40 median TPM (mTPM), p < 0.001). ERBB2 expression was similar between primary and metastatic tumors (47 v 47 mTPM, p = 0.95). ERBB2-high tumors had a higher prevalence of pathogenic mutations in pTERT, ERBB2, and ELF3 versus ERBB2-low tumors, p < 0.001. ERBB2-high tumors had higher expressions of ADC target genes NECTIN4 (12 v 8 mTPM) and TACSTD2 (366 v 74 mTPM) versus ERBB2-low (p < 0.001), as well as better overall survival from time of tissue sampling than ERBB2-low (HR 1.71, p < 0.001). Conclusion: Our study demonstrated a high concordance between HER2 expression by IHC and ERBB2 gene expression by WTS in UC. Differences in ADC target expression between ERBB2-high vs. ERBB2-low UC may provide a rationale for combination treatment strategies with HER2-ADC. The association between high ERBB2 expression and survival advantage warrants further investigation. [ABSTRACT FROM AUTHOR]

Aptamers are short, single-stranded oligonucleotides synthesized in vitro from a randomized oligonucleotide library against a specific target. These molecules are capable of binding to a wide range of biological targets with high specificity and affinity. They present great advantages over antibodies with potential applications in research, diagnosis, and therapeutics. Specifically for tumors with late-stage identification and poor prognosis, like pancreatic cancer, the study of novel aptamers holds tremendous potential for cancer diagnosis and treatment. Along with cancer treatment, aptamers have also shown high potential in regulating the immune response and modulating several critical steps of signaling cascades, such as in immune checkpoints. In the context of microbiota and infection, aptamers are being studied to identify microbes and their metabolites. This assessment has the potential to improve the detection and management of infectious diseases while assisting us in better understanding health risks and treatment outcomes by tracking changes in the microbiota. In this review, the potential of aptamers is explored regarding their applications in cancer, immune, and microbiota therapy. [ABSTRACT FROM AUTHOR]

Background: Faecalibacterium prausnitzii, one of the most important bacteria of the human gut microbiota, produces butyrate (a short-chain fatty acid). Short-chain fatty acids are known to influence thyroid physiology and thyroid cancer's response to treatment. We aimed to analyze the relative abundance of Faecalibacterium prausnitzii on the gut microbiota of differentiated thyroid cancer patients compared to controls and its variation after radioiodine therapy (RAIT). Methods: Fecal samples were collected from 37 patients diagnosed with differentiated thyroid cancer before and after radioiodine therapy and from 10 volunteers. The abundance of F. prausnitzii was determined using shotgun metagenomics. Results: Our study found that the relative abundance of F. prausnitzii is significantly reduced in thyroid cancer patients compared to volunteers. We also found that there was a mixed response to RAIT, with an increase in the relative and absolute abundances of this bacterium in most patients. Conclusions: Our study confirms that thyroid cancer patients present a dysbiotic gut microbiota, with a reduction in F. prausnitzii's relative abundance. In our study, radioiodine did not negatively affect F. prausnitzii, quite the opposite, suggesting that this bacterium might play a role in resolving radiation aggression issues. [ABSTRACT FROM AUTHOR]

The therapeutic landscape of several genitourinary malignancies has been revolutionized by the development of immune checkpoint inhibitors (ICIs); however, the utility of immunotherapies in prostate cancer has been limited, partly due to the immunologically "cold" tumor terrain of prostate cancer. As of today, pembrolizumab is the only immune checkpoint inhibitor approved for the treatment of metastatic castration resistant prostate cancer (mCRPC) in a select group of patients with high microsatellite instability (MSI-H), deficient mismatch repair (dMMR), or high tumor mutational burden (TMB). Looking ahead, several combinatorial approaches with ICIs involving radioligands, radiotherapy, PARP inhibitors, interleukin inhibitors, and cancer vaccines are exploring a potential synergistic effect. Furthermore, B7-H3 is an alternative checkpoint that may hold promise in adding to the treatment landscape of mCRPC. This review aims to summarize previous monotherapy and combination therapy trials of ICIs as well as novel immunotherapy combination therapeutic strategies and treatment targets in mCRPC. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer treatments have significantly changed with the introduction of immunotherapy. Recently, the development of new agents that harness the redirection of T-cells against cancer is rapidly emerging in multiple tumor types. Since bispecific T-cell engager (BiTE) therapies have demonstrated clinical benefit in hematologic malignancies, their application to solid tumors has been an active area of investigation. However, in prostate cancer, due to the heterogeneous and immune-suppressive tumor microenvironment, the development of immunotherapy strategies remains a therapeutic challenge. In this review, we summarize the current development of BiTE therapies in solid tumors with a particular focus on clinical trials in advanced prostate cancer. Over the past decade, immunotherapy has demonstrated an impressive improvement in treatment outcomes for multiple cancers. Following the landmark approvals for use of immune checkpoint inhibitors, new challenges emerged in various clinical settings. Not all tumor types harbor immunogenic characteristics capable of triggering responses. Similarly, many tumors' immune microenvironment allows them to become evasive, leading to resistance and, thus, limiting the durability of responses. To overcome this limitation, new T-cell redirecting strategies such as bispecific T-cell engager (BiTE) have become attractive and promising immunotherapies. Our review provides a comprehensive perspective of the current evidence of BiTE therapies in solid tumors. Considering that immunotherapy has shown modest results in advanced prostate cancer to date, we review the biologic rationale and promising results of BiTE therapy in this clinical setting and discuss potential tumor-associated antigens that may be integrated into BiTE construct designs. Our review also aims to evaluate the advances of BiTE therapies in prostate cancer, illustrate the major obstacles and underlying limitations, and discuss directions for future research. [ABSTRACT FROM AUTHOR]

The gut microbiota refers to bacteria lodges in the gastrointestinal tract (GIT) that interact through various complex mechanisms. The disturbance of this ecosystem has been correlated with several diseases, such as neurologic, respiratory, cardiovascular, and metabolic diseases and cancer. Therefore, the modulation of the gut microbiota has emerged as a potential therapeutic tool; of the various forms of gut microbiota modulation, fecal microbiota transplantation (FMT) is the most approached. This recent technique involves introducing fecal material from a healthy donor into the patient's gastrointestinal tract, aiming to restore the gut microbiota and lead to the resolution of symptoms. This procedure implies a careful donor choice, fine collection and handling of fecal material, and a balanced preparation of the recipient and consequent administration of the prepared content. Although FMT is considered a biological therapy with promising effects, side effects such as diarrhea and abdominal pain have also been claimed, making this a significant challenge in the application of FMT. Bearing this in mind, the present review aims to summarize the recent advances in understanding FMT mechanisms, their impact across different pathological conditions, and the associated side effects, emphasizing the most recent published data. [ABSTRACT FROM AUTHOR]

This study aimed to determine the effect of three widely used radiopharmaceuticals with intestinal excretion on selected relevant bacteria that are part of the human gut microbiota, using an ex vivo approach. Fecal samples obtained from healthy volunteers were analyzed. Each sample was divided into four smaller aliquots. One served as the non-irradiated control. The other three were homogenized with three radiopharmaceutical solutions ([131I]NaI, [99mTc]NaTcO4, and [223Ra]RaCl2). Relative quantification of each taxa was determined by the 2−ΔΔC method, using the ribosomal gene 16S as an internal control (primers 534/385). Twelve fecal samples were analysed: three controls and nine irradiated. Our experiment showed fold changes in all analyzed taxa with all radiopharmaceuticals, but results were more significant with I-131, ranging from 1.87–83.58; whereas no relevant differences were found with Tc-99m and Ra-223, ranging from 0.98–1.58 and 0.83–1.97, respectively. This study corroborates limited existing research on how ionizing radiation changes the gut microbiota composition, providing novel data regarding the ex vivo effect of radiopharmaceuticals. Our findings justify the need for future larger scale projects. [ABSTRACT FROM AUTHOR]

Simple Summary: Pioglitazone is a potent activator of PPAR-γ, a transcriptional factor that is involved in insulin sensibilization and adipocyte differentiation. Here, we propose an optimized methodology for adipocyte differentiation that is critical for secretome release. To achieve this goal, different concentrations of pioglitazone (0–10 µM) were tested and the adipocyte lipidic accumulation was studied. The secretome was then incubated with prostatic cells and macrophages, and the aggressiveness and expression of the inflammatory cytokines were evaluated. We concluded that pioglitazone enhanced adipocyte differentiation and secretome production, making this secretome an excellent adiposity study model. Despite the primary function of pioglitazone in antidiabetic treatment, this drug is a potent inducer of PPAR-γ, a crucial receptor that is involved in adipocyte differentiation. In this work, we propose an optimized methodology to enhance the differentiation of 3T3-L1 fibroblasts into adipocytes. This process is crucial for adipocyte secretome release, which is fundamental for understanding the molecular mechanisms that are involved in obesity for in vitro studies. To achieve this, a pioglitazone dose-response assay was determined over a range varying from 0 to 10 µM. Lipid accumulation was evaluated using Oil-Red-O. The results showed that 10 µM pioglitazone enhanced differentiation and increased secretome production. This secretome was then added into two cell lines: PC3 and RAW264.7. In the PC3 cells, an increase of aggressiveness was observed in terms of viability and proliferation, with the increase of anti-inflammatory cytokines. Conversely, in RAW264.7 cells, a reduction of viability and proliferation was observed, with a decrease in the overexpression of pro-inflammatory cytokines. Overall, the present work constitutes an improved method for adipocyte secretome production that is suitable for experimental biology studies and that could help with our understanding of the molecular mechanisms underlying adiposity influence in other cells. [ABSTRACT FROM AUTHOR]

Simple Summary: Metastatic renal cell carcinoma continues to have a poor prognosis. Chemotherapies and immuno-oncologic therapies have garnered increasing importance in cancer therapy, with improvements in patient care and survival. However, a large proportion of patients present with tumors resistant to these treatments. Exosomes are small extracellular vesicles secreted by all nucleated cells that have proven to be key actors in this resistance. Exosomes carry bioactive oncogenic cargos that reprogram target cells to promote tumor growth, migration, metastasis, immune evasion, and chemotherapy resistance. Tipifarnib, in combination with standard therapy, decreased tumor growth in the setting of chemotherapeutic resistance through an exosome-mediated mechanism. After using a qNANO IZON system to compare tumor-derived exosomes collected from untreated and tipifarnib-treated cells, all cancerous cell lines displayed a reduction of vesicle concentration. Tipifarnib also directly inhibited PD-L1 protein expression in chemo-sensitive cell lines and resistant cell lines. Background: Tyrosine kinase inhibitors (TKI) were initially demonstrated as an efficacious treatment for renal cell carcinoma (RCC). However, after a median treatment length of 14 months, a vast majority of patients develop resistance. This study analyzed a combination therapy of tipifarnib (Tipi) + sunitinib that targeted exosome-conferred drug resistance. Methods: 786-O, 786-O-SR (sunitinib resistant), A498, A498-SR, Caki-2, Caki-2-SR, and 293T cells were cultured. Exosomes were collected using differential ultracentrifugation. Cell proliferation, Jurkat T cell immune assay, and immunoblot analysis were used for downstream analysis. Results: SR exosomes treatment displayed a cytotoxic effect on immune cells. This cytotoxic effect was associated with increased expression of PD-L1 on SR exosomes when compared to sunitinib-sensitive (SS) exosomes. Additionally, Tipi treatment downregulated PD-L1 expression on exosomes derived from SR cell lines. Tipi's ability to downregulate PD-L1 in exosomes has a significant application within patients. Exosomes collected from patients with RCC showed increased PD-L1 expression over subjects without RCC. Next, exosome concentrations were then compared after Tipi treatment, with all SS cell lines displaying an even greater reduction. On immunoblot assay, 293T cells showed a dose-dependent increase in Alix with no change in either nSMase or Rab27a. Conversely, all the SS and SR cell lines displayed a decrease in all three markers. After a cell proliferation employed a 48-h treatment on all SS and SR cell lines, the drug combination displayed synergistic ability to decrease tumor growth. Conclusions: Tipifarnib attenuates both the exosome endosomal sorting complex required for endosomal sorting complex required for transport (ESCRT)-dependent and ESCRT-independent pathways, thereby blocking exosome biogenesis and secretion as well as downregulating PD-L1 on SS and SR cells. [ABSTRACT FROM AUTHOR]

Simple Summary: CTX-M β-lactamases are a growing group among extended-spectrum β-lactamases (ESBLs), not only in number, diversity, and functional kinetics. Until now, it has been well-accepted five main clusters within CTX-M β-lactamases. These canonical clusters are CTX-M-1, CTX-M-2, CTX-M-8, CTX-M-9, and CTX-M-25. In the present study, we propose a new sixth cluster, CTX-M-151. The production of extended-spectrum β-lactamases (ESBLs) is the main defense mechanism found in Gram negative bacteria. Among all the ESBLs, the CTX-M enzymes appear as the most efficient in terms of dissemination in different epidemiological contexts. CTX-M enzymes exhibit a striking plasticity, with a large number of allelic variants distributed in several sublineages, which can be associated with functional heterogeneity of clinical relevance. This observational analytical study provides an update of this family, currently with more than 200 variants described, from a phylogenetic, molecular, and structural point of view through homology in amino acid sequences. Our data, combined with described literature, provide phylogenetic and structural evidence of a new group. Thus, herein, we propose six groups among CTX-M enzymes: the already stablished CTX-M-1, CTX-M-2, CTX-M-8, CTX-M-9, and CTX-M-25 clusters, as well as CTX-M-151 as the new cluster. [ABSTRACT FROM AUTHOR]

Simple Summary: Genitourinary malignancies include cancers along the urinary tract and the male reproductive tract, encompassing the adrenal glands, kidneys, bladder, prostate, and testicles. Immunotherapy, which treats cancer by using the immune system to attack malignant cells, has historically been successful in treating some types of genitourinary cancers, especially of the bladder and kidney. In the past decade, a more precise method of immunotherapy, known as immune checkpoint inhibition, has gained popularity as it enhances the immune system's ability to recognize and destroy tumor cells. Several immune checkpoint inhibitors have achieved success in patients with advanced genitourinary cancers. This review provides a brief overview of traditional immunotherapies, focuses on how immune checkpoint inhibitors have achieved success in patients with advanced cancers, and investigates the role for immunotherapy in genitourinary malignancies in the future. For decades, limited options existed to treat metastatic genitourinary cancers, including treatment options that could be classified as immunotherapy. Historically, immunotherapy centered on systemic cytokines for the treatment of metastatic kidney cancer, which had several adverse effects, as well as the Bacillus Calmette–Guérin vaccine for non-metastatic bladder cancer. Within the past decade, advances in immunotherapy have led to several approvals from the United States Food and Drug Administration, particularly in the field of immune checkpoint inhibition. Immune checkpoint inhibitors (ICIs) are now being used extensively to treat multiple solid tumors, including kidney and bladder cancers, and they are also being tested in many other cancers. Despite encouraging data from phase 2/3 clinical trials, less is known about biomarkers that may predict better response to ICIs. The effect of ICIs in genitourinary cancers is heterogeneous, with some tumor types having little clinical data available, or ICIs having limited activity in other tumors. In this review, we briefly discuss approved immunotherapy agents prior to the time of ICIs. Then, given the emergence of this class of agents, we summarize the several important ICIs and the clinical trials that led to their approval. Finally, we mention ongoing and future clinical trials. [ABSTRACT FROM AUTHOR]

Background: The human gut microbiota is defined as the microorganisms that collectively inhabit the intestinal tract. Its composition is relatively stable; however, an imbalance can be precipitated by various factors and is known to be associated with various diseases. Humans are daily exposed to ionizing radiation from ambient and medical procedures, and gastrointestinal side effects are not rare. Methods: A systematic search of PubMed, EMBASE, and Cochrane Library databases was conducted. Primary outcomes were changes in composition, richness, and diversity of the gut microbiota after ionizing radiation exposure. Standard methodological procedures expected by Cochrane were used. Results: A total of 2929 nonduplicated records were identified, and based on the inclusion criteria, 11 studies were considered. Studies were heterogeneous, with differences in population and outcomes. Overall, we found evidence for an association between ionizing radiation exposure and dysbiosis: reduction in microbiota diversity and richness, increase in pathogenic bacteria abundance (Proteobacteria and Fusobacteria), and decrease in beneficial bacteria (Faecalibacterium and Bifidobacterium). Conclusions: This review highlights the importance of considering the influence of ionizing radiation exposure on gut microbiota, especially when considering the side effects of abdominal and pelvic radiotherapy. Better knowledge of these effects, with larger population studies, is needed. [ABSTRACT FROM AUTHOR]

The Euterpe oleracea fruit (açaí) is a promising source of polyphenols with health-promoting properties. To our knowledge, few studies have focused on the influence of açaí phytochemicals on angiogenesis, with a significant impact on cancer. This study aimed at investigating the phytochemical profile of a purple açaí hydroethanolic extract (AHE) obtained from a commercial dietary powder supplement by high-performance liquid chromatography coupled to diode array detection and electrospray ionization mass spectrometry, and evaluate its in vitro effects on distinct angiogenic steps during vessel growth and on oxidative markers in human microvascular endothelial cells (HMEC-1). The phenolic profile of AHE revealed the presence of significant levels of anthocyanins, mainly cyanidin-3-O-rutinoside, and other flavonoids with promising health effects. The in vitro studies demonstrated that AHE exerts antiangiogenic activity with no cytotoxic effect. The AHE was able to decrease HMEC-1 migration and invasion potential, as well as to inhibit the formation of capillary-like structures. Additionally, AHE increased antioxidant defenses by upregulating superoxide dismutase and catalase enzymatic activities, accompanied by a reduction in the production of reactive oxygen species. These data bring new insights into the potential application of angiogenic inhibitors present in AHE on the development of novel therapeutic approaches for angiogenesis-dependent diseases. [ABSTRACT FROM AUTHOR]

Simple Summary: In recent years, the development of sequencing techniques to reveal the genomic information of prostate cancer tumors has allowed for the emergence of targeted therapies. Genomic aberrations in tumor cells have become popular due to the successful development of PARP inhibitors, which are particularly active in those tumors harboring DNA repair genomic defects. This review focuses on PARP inhibitors, two of which were approved for use by the US Food and Drug Administration in 2020 in metastatic castration-resistant prostate cancer. The article highlights the development of PARP inhibitors in the preclinical setting, summarizes the impactful clinical trials in the field, and discusses the need for continued research for further success in treating men with advanced prostate cancer. Metastatic castration-resistant prostate cancer (mCRPC) is an incurable malignancy with a poor prognosis. Up to 30% of patients with mCRPC have mutations in homologous recombination repair (HRR) genes. Poly (ADP-ribose) polymerase (PARP) inhibitors take advantage of HRR deficiency to kill tumor cells based on the concept of synthetic lethality. Several PARP inhibitors (PARPis) have been successful in various malignancies with HRR gene mutations including BRCA1/2, especially in breast cancer and ovarian cancer. More recently, olaparib and rucaparib were approved for mCRPC refractory to novel hormonal therapies, and other PARPis will likely follow. This article highlights the mechanism of action of PARPis at the cellular level, the preclinical data regarding a proposed mechanism of action and the effectiveness of PARPis in cancer cell lines and animal models. The article expands on the clinical development of PARPis in mCRPC, discusses potential biomarkers that may predict successful tumor control, and summarizes present and future clinical research on PARPis in the metastatic disease landscape. [ABSTRACT FROM AUTHOR]

Prostate-specific membrane antigen (PSMA) has been the subject of extensive investigation in the past two decades as a promising molecular target for prostate cancer (PCa). Its appealing molecular features have enabled the development of a novel diagnostic and therapeutic—thus "theranostic"—approach to PCa. There is now substantial evidence of the high sensitivity of PSMA-targeted imaging for PCa lesions and growing evidence of the therapeutic efficacy of PSMA radioligand therapy for metastatic castration-resistant prostate cancer. This article presents a broad overview of the current status of PSMA theranostics, including current evidence, potential clinical impact, and active areas of research. [ABSTRACT FROM AUTHOR]

Limited fitness for practice may result from a mismatch between education and practice. Aiming to meet the common interests of academics and practitioners, the Portuguese Pharmaceutical Society (PPS) developed the Education and Practice Platform (EPP). The EPP includes one representative from each pharmacy faculty, and all Councils of Speciality Boards of Practice. Brainstorming with involved parties enabled sharing of interests, concerns and identifying a common path. Aims, mission, vision and values were set. The EPP's mission is to: act as an enabler to foster the quality and adequacy of education through sharing best practices, ultimately leading to facilitate professional integration, and to foster quality development in teaching practices with recognition for autonomy in freedom to teach and to learn. Its vision is an alignment of education and practice with the PPS' statutes to ensure validation of the competences defined for each practice area, and compliance with international guidance. Key performance indicators (KPIs) were set. Activities developed include the creation of a national forum to discuss education and practice, development of workshops on teaching methods and pharmacy internships, enhanced representation in international events and response to global and national requests. Ongoing work focuses on the creation of a common training framework in hospital and community pharmacy practice adapted to Portugal. The EPP is a worldwide case study, encouraging the development of discussion contributing to an open climate of sharing best practices, indirectly leading to foster a better alignment between education and practice. Many of these results are so far intangible in scientific terms but worth describing. [ABSTRACT FROM AUTHOR]

Background: The gut microbiota is relatively stable; however, various factors can precipitate an imbalance that is known to be associated with various diseases. We aimed to conduct a systematic literature review of studies reporting the effects of ionizing radiation on the composition, richness, and diversity of the gut microbiota of animals., Methods: A systematic literature search was performed in PubMed, EMBASE, and Cochrane library databases. The standard methodologies expected by Cochrane were utilized., Results: We identified 3531 non-duplicated records and selected twenty-nine studies after considering the defined inclusion criteria. The studies were found to be heterogeneous, with significant differences in the chosen populations, methodologies, and outcomes. Overall, we found evidence of an association between ionizing radiation exposure and dysbiosis, with a reduction of microbiota diversity and richness and alterations in the taxonomic composition. Although differences in taxonomic composition varied across studies, Proteobacteria, Verrucomicrobia, Alistipes , and Akkermancia most consistently reported to be relatively more abundant after ionizing radiation exposure, whereas Bacteroidetes, Firmicutes, and Lactobacillus were relatively reduced., Conclusions: This review highlights the effect of ionizing exposure on gut microbiota diversity, richness, and composition. It paves the way for further studies on human subjects regarding gastrointestinal side effects in patients submitted to treatments with ionizing radiation and the development of potential preventive, therapeutic approaches.

Radium-223 (Ra-223) is a targeted nuclear medicine therapy for castration-resistant prostate cancer with bone metastases. Its major route of elimination is the intestine. There is overwhelming evidence that the gut microbiota is altered by ionizing radiation (IR) from radiotherapy treatments. Nevertheless, it is known that extrapolation of outcomes from radiotherapy to nuclear medicine is not straightforward. The purpose of this study was to prospectively determine the effect of Ra-223 on selected important bacteria from the gut microbiota. Stool samples from three prostate cancer patients and two healthy individuals were obtained, processed, and analysed. We specifically measured the relative change of the abundance of important bacteria, determined by the 2 -ΔΔC method. We found that Ra-223 influenced the gut microbiota composition. The most relevant changes were increases of Proteobacteria and Atopobacter; and decreases of Bacteroidetes, Prevotella , Lactobacillus , Bifidobacterium , Clostridium coccoides, and Bacteroides fragilis . Additionally, our experiment confirms that the composition of gut microbiota from prostate cancer patients is altered. No significant correlation was found between each subject's gut microbiome profile and their clinical indices. Despite its limited sample, the results of this pilot study suggest that ionizing radiation from Ra-223 alters the gut microbiota composition and that the gut microbiota of prostate cancer patients has an increase of the bacteria with known prejudicial effects and a decrease of the ones with favorable effects.