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JAMA Network Open Oct 2023Selenium and vitamin E have been identified as promising agents for the chemoprevention of recurrence and progression of non-muscle-invasive bladder cancer. (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Selenium and vitamin E have been identified as promising agents for the chemoprevention of recurrence and progression of non-muscle-invasive bladder cancer.
OBJECTIVE
To determine whether selenium and/or vitamin E may prevent disease recurrence in patients with newly diagnosed NMIBC.
DESIGN, SETTING, AND PARTICIPANTS
This multicenter, prospective, double-blinded, placebo-controlled, 2 × 2 factorial randomized clinical trial included patients with newly diagnosed NMIBC recruited from 10 secondary or tertiary care hospitals in the UK. A total of 755 patients were screened for inclusion; 484 did not meet the inclusion criteria, and 1 declined to participate. A total of 270 patients were randomly assigned to 4 groups (selenium plus placebo, vitamin E plus placebo, selenium plus vitamin E, and placebo plus placebo) in a double-blind fashion between July 17, 2007, and October 10, 2011. Eligibility included initial diagnosis of NMIBC (stages Ta, T1, or Tis); randomization within 12 months of first transurethral resection was required.
INTERVENTIONS
Oral selenium (200 μg/d of high-selenium yeast) and matched vitamin E placebo, vitamin E (200 IU/d of d-alfa-tocopherol) and matched selenium placebo, selenium and vitamin E, or placebo and placebo.
MAIN OUTCOME AND MEASURES
Recurrence-free interval (RFI) on an intention-to-treat basis (analyses completed on November 28, 2022).
RESULTS
The study randomized 270 patients (mean [SD] age, 68.9 [10.4] years; median [IQR] age, 69 [63-77] years; 202 male [75%]), with 65 receiving selenium and vitamin E placebo, 71 receiving vitamin E and selenium placebo, 69 receiving selenium and vitamin E, and 65 receiving both placebos. Median overall follow-up was 5.5 years (IQR, 5.1-6.1 years); 228 patients (84%) were followed up for more than 5 years. Median treatment duration was 1.5 years (IQR, 0.9-2.5 years). The study was halted because of slow accrual. For selenium (n = 134) vs no selenium (n = 136), there was no difference in RFI (hazard ratio, 0.92; 95% CI, 0.65-1.31; P = .65). For vitamin E (n = 140) vs no vitamin E (n = 130), there was a statistically significant detriment to RFI (hazard ratio, 1.46; 95% CI, 1.02-2.09; P = .04). No significant differences were observed for progression-free interval or overall survival time with either supplement. Results were unchanged after Cox proportional hazards regression modeling to adjust for known prognostic factors. In total, 1957 adverse events were reported; 85 were serious adverse events, and all were considered unrelated to trial treatment.
CONCLUSIONS AND RELEVANCE
In this randomized clinical trial of selenium and vitamin E, selenium supplementation did not reduce the risk of recurrence in patients with NMIBC, but vitamin E supplementation was associated with an increased risk of recurrence. Neither selenium nor vitamin E influenced progression or overall survival. Vitamin E supplementation may be harmful to patients with NMIBC, and elucidation of the underlying biology is required.
TRIAL REGISTRATION
isrctn.org Identifier: ISRCTN13889738.
Topics: Humans; Male; Aged; Vitamin E; Selenium; Non-Muscle Invasive Bladder Neoplasms; Prospective Studies; Neoplasm Recurrence, Local; Urinary Bladder Neoplasms
PubMed: 37847504
DOI: 10.1001/jamanetworkopen.2023.37494 -
Frontiers in Oncology 2023Urological tumors, such as prostate cancer, renal cell carcinoma, and bladder cancer, have shown a significant rise in prevalence in recent years and account for a... (Review)
Review
Urological tumors, such as prostate cancer, renal cell carcinoma, and bladder cancer, have shown a significant rise in prevalence in recent years and account for a significant proportion of malignant tumors. It has been established that metastasis to distant organs caused by urological tumors is the main cause of death, although the mechanisms underlying metastasis have not been fully elucidated. The fibronectin receptor integrin α5β1 reportedly plays an important role in distant metastasis and is closely related to tumor development. It is widely thought to be an important cancer mediator by interacting with different ligands, mediating tumor adhesion, invasion, and migration, and leading to immune escape. In this paper, we expound on the relationship and regulatory mechanisms of integrin α5β1 in these three cancers. In addition, the clinical applications of integrin α5β1 in these cancers, especially against treatment resistance, are discussed. Last but not least, the possibility of integrin α5β1 as a potential target for treatment is examined, with new ideas for future research being proposed.
PubMed: 37483505
DOI: 10.3389/fonc.2023.1165073 -
World Journal of Clinical Cases May 2024Neuroendocrine prostate cancer (NEPC) shows an aggressive behavior compared to prostate cancer (PCa), also known as prostate adenocarcinoma. Scanty foci in PCa can...
Neuroendocrine prostate cancer (NEPC) shows an aggressive behavior compared to prostate cancer (PCa), also known as prostate adenocarcinoma. Scanty foci in PCa can harbor genetic alternation that can arise in a heterogeneity of prostate cancer. NEPC may arise or develop following androgen deprivation therapy (ADT). NEPC that arise following ADT has the nomenclature "treatment-emerging/induced NEPC (t-NEPC)". t-NEPC would be anticipated in castration resistant prostate cancer (CRPC) and metastatic PCa. t-NEPC is characterized by low or absent androgen receptor (AR) expression, independence of AR signaling, and gain of neuroendocrine phenotype. t-NEPC is an aggressive metastatic tumor, develops from PCa in response to drug induced ADT, and shows very short response to conventional therapy. t-NEPC occurs in 10%-17% of patients with CRPC. NEPC is rare and is accounting for less than 2% of all PCa. The molecular mechanisms underlying the trans-differentiation from CRPC to t-NEPC are not fully elucidated. Sphingosine kinase 1 plays a significant role in t-NEPC development. Although neuroendocrine markers: Synaptophysin, chromogranin A, and insulinoma associated protein 1 () are expressed in t-NEPC, they are non-specific for diagnosis, prognosis, and follow-up of therapy. t-NEPC shows enriched genomic alteration in tumor protein P53 () and retinoblastoma 1 (). There are evidences suggest that t-NEPC might develop through epigenetic evolution. There are genomic, epigenetic, and transcriptional alterations that are reported to be involved in development of t-NEPC. Knock-outs of and were found to contribute in development of t-NEPC. PCa is resistant to immunotherapy, and at present there are running trials to approach immunotherapy for PCa, CRPC, and t-NEPC.
PubMed: 38808339
DOI: 10.12998/wjcc.v12.i13.2143 -
Frontiers in Oncology 2024Multiple cancer cell types are found in prostate tumors. They are either luminal-like adenocarcinoma or less luminal-like and more stem-like non-adenocarcinoma and small... (Review)
Review
Multiple cancer cell types are found in prostate tumors. They are either luminal-like adenocarcinoma or less luminal-like and more stem-like non-adenocarcinoma and small cell carcinoma. These types are lineage related through differentiation. Loss of cancer differentiation from luminal-like to stem-like is mediated by the activation of stem cell transcription factors (scTF) such as LIN28A, NANOG, POU5F1 and SOX2. scTF expression leads to down-regulation of β2-microglobulin (B2M). Thus, cancer cells can change from the phenotype of differentiated to that of of dedifferentiated in the disease course. In development, epithelial cell differentiation is induced by stromal signaling and cell contact. One of the stromal factors specific to prostate encodes proenkephalin (PENK). PENK can down-regulate scTF and up-regulate B2M in stem-like small cell carcinoma LuCaP 145.1 cells indicative of exit from the stem state and differentiation. In fact, prostate cancer cells can be made to undergo dedifferentiation or reprogramming by scTF transfection and then to differentiate by PENK transfection. Therapies need to be designed for treating the different cancer cell types. Extracellular anterior gradient 2 (eAGR2) is an adenocarcinoma antigen associated with cancer differentiation that can be targeted by antibodies to lyse tumor cells with immune system components. eAGR2 is specific to cancer as normal cells express only the intracellular form (iAGR2). For AGR2-negative stem-like cancer cells, factors like PENK that can target scTF could be effective in differentiation therapy.
PubMed: 38595814
DOI: 10.3389/fonc.2024.1321694 -
Cancers May 2024Over the years, our understanding of cribriform and intraductal prostate cancer (PCa) has evolved significantly, leading to substantial changes in their classification... (Review)
Review
Over the years, our understanding of cribriform and intraductal prostate cancer (PCa) has evolved significantly, leading to substantial changes in their classification and clinical management. This review discusses the histopathological disparities between intraductal and cribriform PCa from a diagnostic perspective, aiming to aid pathologists in achieving accurate diagnoses. Furthermore, it discusses the ongoing debate surrounding the different recommendations between ISUP and GUPS, which pose challenges for practicing pathologists and complicates consensus among them. Recent studies have shown promising results in integrating these pathological features into clinical decision-making tools, improving predictions of PCa recurrence, cancer spread, and mortality. Future research efforts should focus on further unraveling the biological backgrounds of these entities and their implications for clinical management to ultimately improve PCa patient outcomes.
PubMed: 38893122
DOI: 10.3390/cancers16112002 -
Romanian Journal of Morphology and... 2023Incidental prostate carcinoma (iPC) is a subject of debate concerning its definition, incidence, biology, diagnosis, staging, and treatment. The present study aimed to...
Incidental prostate carcinoma (iPC) is a subject of debate concerning its definition, incidence, biology, diagnosis, staging, and treatment. The present study aimed to assess the incidence and main clinical-morphological characteristics of iPC identified in radical cystoprostatectomy (RCP) specimens over a 5-year period. Using the database of the Urology and Pathology Departments, we identified all patients with bladder carcinomas (BCs) who underwent RCP within a 5-year frame time. We selected only those patients with synchronous BC and prostate carcinoma (PC). The following parameters were analyzed for these patients: age, type of bladder and prostate tumor, degree of differentiation, pathological stage, and other prognostic parameters. We identified 91 men with bladder tumors treated by RCP among whom 43, aged between 53 and 84 years (mean age: 69.2 years), presented synchronous PC. iPC was more prevalent in older individuals (>65 years: 30 patients, 69.8%), with only six out of the 43 (12.8%) patients with iPC being aged ≤60 years. All iPC cases were conventional adenocarcinoma. Well-differentiated prostate adenocarcinomas (grade group 1) predominated (65.1%). Among the 43 iPCs, 16 (37.2%) were clinically significant PCs. iPC is frequently identified in patients with BC when inclusion and evaluation of all or most of the prostate tissue are performed. Although more than half of iPCs were well-differentiated tumors confined to the prostate, a significant number of cases met the criteria of clinically significant PC. All men over the age of 50 who are candidates for RCP, should undergo evaluation through serum prostate specific antigen determination.
Topics: Aged; Aged, 80 and over; Humans; Male; Middle Aged; Carcinoma; Pelvis; Prostate; Prostatic Neoplasms; Urinary Bladder; Urinary Bladder Neoplasms
PubMed: 38184830
DOI: 10.47162/RJME.64.4.06 -
RoFo : Fortschritte Auf Dem Gebiete Der... Apr 2024Imaging biomarkers are quantitative parameters from imaging modalities, which are collected noninvasively, allow conclusions about physiological and... (Review)
Review
BACKGROUND
Imaging biomarkers are quantitative parameters from imaging modalities, which are collected noninvasively, allow conclusions about physiological and pathophysiological processes, and may consist of single (monoparametric) or multiple parameters (bi- or multiparametric).
METHOD
This review aims to present the state of the art for the quantification of multimodal and multiparametric imaging biomarkers. Here, the use of biomarkers using artificial intelligence will be addressed and the clinical application of imaging biomarkers in breast and prostate cancers will be explained. For the preparation of the review article, an extensive literature search was performed based on Pubmed, Web of Science and Google Scholar. The results were evaluated and discussed for consistency and generality.
RESULTS AND CONCLUSION
Different imaging biomarkers (multiparametric) are quantified based on the use of complementary imaging modalities (multimodal) from radiology, nuclear medicine, or hybrid imaging. From these techniques, parameters are determined at the morphological (e. g., size), functional (e. g., vascularization or diffusion), metabolic (e. g., glucose metabolism), or molecular (e. g., expression of prostate specific membrane antigen, PSMA) level. The integration and weighting of imaging biomarkers are increasingly being performed with artificial intelligence, using machine learning algorithms. In this way, the clinical application of imaging biomarkers is increasing, as illustrated by the diagnosis of breast and prostate cancers.
KEY POINTS
· Imaging biomarkers are quantitative parameters to detect physiological and pathophysiological processes.. · Imaging biomarkers from multimodality and multiparametric imaging are integrated using artificial intelligence algorithms.. · Quantitative imaging parameters are a fundamental component of diagnostics for all tumor entities, such as for mammary and prostate carcinomas..
CITATION FORMAT
· Bäuerle T, Dietzel M, Pinker K et al. Identification of impactful imaging biomarker: Clinical applications for breast and prostate carcinoma. Fortschr Röntgenstr 2024; 196: 354 - 362.
Topics: Humans; Male; Artificial Intelligence; Biomarkers; Carcinoma; Magnetic Resonance Imaging; Nuclear Medicine; Prostate; Prostatic Neoplasms; Female
PubMed: 37944934
DOI: 10.1055/a-2175-4446 -
PloS One 2023In a phase I dose escalation and safety study (NCT02555397), a replication-competent oncolytic adenovirus expressing yCD, TK and hIL-12 (Ad5-yCD/mutTKSR39rep-hIL-12) was...
In a phase I dose escalation and safety study (NCT02555397), a replication-competent oncolytic adenovirus expressing yCD, TK and hIL-12 (Ad5-yCD/mutTKSR39rep-hIL-12) was administered in 15 subjects with localized recurrent prostate cancer (T1c-T2) at increasing doses (1 × 1010, to 1 × 1012 viral particles) followed by 7-day treatment of 5-fluorocytosine (5-FC) and valganciclovir (vGCV). The primary endpoint was toxicity through day 30 while the secondary and exploratory endpoints were quantitation of IL-12, IFNγ, CXCL10 and peripheral blood mononuclear cells (PBMC). The study maximum tolerated dose (MTD) was not reached indicating 1012 viral particles was safe. Total 115 adverse events were observed, most of which (92%) were grade 1/2 that did not require any treatment. Adenoviral DNA was detected only in two patients. Increase in IL-12, IFNγ, and CXCL10 was observed in 57%, 93%, and 79% patients, respectively. Serum cytokines demonstrated viral dose dependency, especially apparent in the highest-dose cohorts. PBMC analysis revealed immune system activation after gene therapy in cohort 5. The PSA doubling time (PSADT) pre and post treatment has a median of 1.55 years vs 1.18 years. This trial confirmed that replication-competent Ad5-IL-12 adenovirus (Ad5-yCD/mutTKSR39rep-hIL-12) was well tolerated when administered locally to prostate tumors.
Topics: Humans; Male; Adenocarcinoma; Adenoviridae; Genetic Therapy; Interleukin-12; Leukocytes, Mononuclear; Prostate; Prostatic Neoplasms; Genes, Transgenic, Suicide; Oncolytic Virotherapy
PubMed: 37713401
DOI: 10.1371/journal.pone.0291315 -
Cancer Biology & Therapy Dec 2024The introduction of novel immunotherapies has significantly transformed the treatment landscape of genitourinary (GU) cancers, even becoming the standard of care in some... (Review)
Review
The introduction of novel immunotherapies has significantly transformed the treatment landscape of genitourinary (GU) cancers, even becoming the standard of care in some settings. One such type of immunotherapy, immune checkpoint inhibitors (ICIs) like nivolumab, ipilimumab, pembrolizumab, and atezolizumab play a pivotal role by disturbing signaling pathways that limit the immune system's ability to fight tumor cells. Despite the profound impact of these treatments, not all tumors are responsive. Recent research efforts have been focused on understanding how cancer cells manage to evade the immune response and identifying the possible mechanisms behind resistance to immunotherapy. In response, ICIs are being combined with other treatments to reduce resistance and attack cancer cells through multiple cellular pathways. Additionally, novel, targeted strategies are currently being investigated to develop innovative methods of overcoming resistance and treatment failure. This article presents a comprehensive overview of the mechanisms of immunotherapy resistance in GU cancers as currently described in the literature. It explores studies that have identified genetic markers, cytokines, and proteins that may predict resistance or response to immunotherapy. Additionally, we review current efforts to overcome this resistance, which include combination ICIs and sequential therapies, novel insights into the host immune profile, and new targeted therapies. Various approaches that combine immunotherapy with chemotherapy, targeted therapy, vaccines, and radiation have been studied in an effort to more effectively overcome resistance to immunotherapy. While each of these combination therapies has shown some efficacy in clinical trials, a deeper understanding of the immune system's role underscores the potential of novel targeted therapies as a particularly promising area of current research. Currently, several targeted agents are in development, along with the identification of key immune mediators involved in immunotherapy resistance. Further research is necessary to identify predictors of response.
Topics: Humans; Nivolumab; Antineoplastic Agents; Neoplasms; Urogenital Neoplasms; Immunotherapy; B7-H1 Antigen
PubMed: 38629578
DOI: 10.1080/15384047.2024.2342599 -
International Journal of Molecular... Jul 2023Prostate cancer (PCa) is one of the most prevalent cancers in men, yet its pathogenic pathways remain poorly understood. Transcriptomics and high-throughput sequencing...
Prostate cancer (PCa) is one of the most prevalent cancers in men, yet its pathogenic pathways remain poorly understood. Transcriptomics and high-throughput sequencing can help uncover cancer diagnostic targets and understand biological circuits. Using prostate adenocarcinoma (PRAD) datasets of various web-based applications (GEPIA, UALCAN, cBioPortal, SR Plot, hTFtarget, Genome Browser, and MetaCore), we found that upregulated dysbindin domain-containing 1 () expression in primary prostate tumors was strongly correlated with pathways involving the cell cycle, mitotic in KEGG, WIKI, and REACTOME database, and transcription factor-binding sites with the gene in prostate samples. gene expression was influenced by sample type, cancer stage, and promoter methylation levels of different cancers, such as PRAD, liver hepatocellular carcinoma (LIHC), and lung adenocarcinoma (LUAD). Regulation of glycogen synthase kinase (GSK)-3β in bipolar disorder and ATP/ITP/GTP/XTP/TTP/CTP/UTP metabolic pathways was closely correlated with the gene and its co-expressed genes in PCa. gene expression was positively associated with immune infiltration of B cells, Myeloid-derived suppressor cell (MDSC), M2 macrophages, andneutrophil, whereas negatively correlated with CD8 T cells, T follicular helper cells, M1 macrophages, and NK cells in PCa. These findings suggest that DBNDD1 may serve as a viable prognostic marker not only for early-stage PCa but also for immunotherapies.
PubMed: 37569304
DOI: 10.3390/ijms241511930