Publications by authors named "Tim Oliver"

Background/objectives: Several independent studies have associated prostate cancer (PCa) with specific groups of bacteria, most of them reporting the presence of anaerobic or microaerophilic species such as (). Such findings suggest a prostate cancer-related bacterial dysbiosis, in a manner similar to the association between infection and gastric cancer. In an earlier exploratory study looking for such dysbiosis events, using a culturomics approach, we discovered that the presence of obligate anaerobes (OAs) along with was associated with increased prostate-specific antigen (PSA) levels in 39 participants.

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Early epidemic reports have linked low average 25(OH) vitamin D levels with increased COVID-19 mortality. However, there has been limited updated research on 25(OH) vitamin D and its impact on COVID-19 mortality. This study aimed to update the initial report studying the link between vitamin D deficiency and COVID-19 mortality by using multi-country data in 19 European countries up to the middle of June 2023.

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Article Synopsis
  • Docetaxel enhances survival in advanced prostate cancer but not all patients respond due to resistance, highlighting the need for effective predictive tests.
  • This study explores the use of circulating tumor cells (CTCs) and their gene expression from blood samples to predict response to docetaxel treatment, overall survival (OS), and progression-free survival (PFS).
  • Findings indicate that pre-treatment CTC detection is linked to worse outcomes, with specific CTC metrics predicting lack of response, shorter OS, and diminished PFS in castration-resistant and metastatic hormone-sensitive prostate cancer patients.
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  • Castration-resistant prostate cancer (CRPC) is a leading cause of death from prostate cancer, and identifying biomarkers could improve early detection and treatment outcomes.
  • The study analyzed plasma exosomal miRNAs in 24 treatment-naive prostate cancer patients and 24 CRPC patients, ultimately identifying six differentially expressed miRNAs through RNA-sequencing and RT-qPCR.
  • Among these, miR-423-3p emerged as a significant biomarker for predicting CRPC, especially when combined with prostate-specific antigen (PSA), showing strong performance in validation cohorts with high area under the ROC curve (AUC) values.
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Article Synopsis
  • Prostate specific antigen (PSA) testing often leads to unnecessary biopsies and overtreatment, creating a need for more accurate, less invasive diagnostic methods for prostate cancer.
  • A study involving 155 patients with prostate cancer analyzed circulating tumor cells (CTCs) to predict clinically significant cases, using various statistical methods to assess their association with aggressive cancer features.
  • The results showed that detecting CTCs could improve prediction accuracy for clinically significant prostate cancer when combined with PSA levels and a 12-gene panel, potentially enhancing patient management and reducing unnecessary procedures.
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Testicular germ cell tumors (TGCTs) are the commonest tumors in young men. With the advancement of chemotherapies, most TGCTs are successfully cured, even when diagnosed at an advanced and metastatic stage. However, a proportion of often young patients, median age 35-40, with advanced disease are not cured and will inevitably die.

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The microaerophylic organism Propionibacterium acnes has shown consistent association with prostate cancer (PC). Studies linking circumcision with reduced PC further support anaerobes involvement as circumcision reduces anaerobe colonisation on the glans penis. A 1988 study linked anaerobes with PC but considered them as opportunists in necrotic tumour.

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Prostate cancer is the most common cancer among western men, with a significant mortality and morbidity reported for advanced metastatic disease. Current understanding of metastatic disease is limited due to difficulty of sampling as prostate cancer mainly metastasizes to bone. By analysing prostate cancer bone metastases using high density microarrays, we found a common genomic copy number loss at 6q16.

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To develop an approach for the investigation of different subtypes of circulating tumor cells (CTC) and other cells to evaluate their potential prognostic value of prostate cancer. Malignancy of CTCs undergoing epithelial-to-mesenchymal transition (EMT) was confirmed by repeated FISH. Subgroups of CTCs in 81 patients with prostate cancer (43 castration resistant and 38 untreated localized) were correlated to disease aggressiveness parameters.

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Prostate cancer predisposition has been extensively investigated in European populations, but there have been few studies of other ethnic groups. To investigate prostate cancer susceptibility in the under-investigated Chinese population, we performed single-nucleotide polymorphism (SNP) array analysis on a cohort of Chinese cases and controls and then meta-analysis with data from the existing Chinese prostate cancer genome-wide association study (GWAS). Genotyping 211,155 SNPs in 495 cases and 640 controls of Chinese ancestry identified several new suggestive Chinese prostate cancer predisposition loci.

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Genomic changes affecting tumour suppressor genes are fundamental to cancer. We applied SNP array analysis to a panel of testicular germ cell tumours to search for novel tumour suppressor genes and identified a frequent small deletion on 6q25.3 affecting just one gene, ZDHHC14.

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Background: Few randomised studies have compared antiandrogen intermittent hormonal therapy (IHT) with continuous maximal androgen blockade (MAB) therapy for advanced prostate cancer (PCa).

Objective: To determine whether overall survival (OS) on IHT (cyproterone acetate; CPA) is noninferior to OS on continuous MAB.

Design, Setting, And Participants: This phase 3 randomised trial compared IHT and continuous MAB in patients with locally advanced or metastatic PCa.

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Many human cancers present as multifocal lesions. Understanding the clonal origin of multifocal cancers is of both etiological and clinical importance. The molecular basis of multifocal prostate cancer has previously been explored using a limited number of isolated markers and, although independent origin is widely believed, the clonal origin of multifocal prostate cancer is still debatable.

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Background: Testicular cancer is the most common cancer in men under 35 years of age, and has the highest survival for adult male malignancies. Despite the fact that survival is very high, there is evidence that survival differs between socio-economic groups.

Methods: We analysed survival patterns for 1606 testicular cancer patients diagnosed during 1984-2001 and recruited to one of two clinical studies.

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The immunity-related GTPases (IRGs) are a family of proteins induced by interferon-γ that play a crucial role in innate resistance to intracellular pathogens. The M subfamily of IRG proteins (IRGM) plays a profound role in this context, in part because of the ability of its members to regulate the localization and expression of other IRG proteins. We present here evidence that IRGM proteins affect the localization of the guanylate-binding proteins (GBPs), a second family of interferon-induced GTP-binding proteins that also function in innate immunity.

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Background: Human respiratory epithelia function in airway mucociliary clearance and barrier function and have recently been implicated in sensory functions.

Objective: We investigated a link between chronic obstructive pulmonary disease (COPD) pathogenesis and molecular mechanisms underlying Ca2+ influx into human airway epithelia elicited by diesel exhaust particles (DEP).

Methods And Results: Using primary cultures of human respiratory epithelial (HRE) cells, we determined that these cells possess proteolytic signaling machinery, whereby proteinase-activated receptor-2 (PAR-2) activates Ca2+-permeable TRPV4, which leads to activation of human respiratory disease-enhancing matrix metalloproteinase-1 (MMP-1), a signaling cascade initiated by diesel exhaust particles (DEP), a globally relevant air pollutant.

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Fusion genes play important roles in tumorigenesis. The identification of the high-frequency TMPRSS2 fusion with ERG and other ETS family genes in prostate cancer highlights the importance of fusion genes in solid tumor development and progression. However, the mechanisms leading to these fusions are unclear.

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Aims: Treatment decisions are difficult in clinically localised prostate cancer and further biomarkers of aggressive behaviour are required. We investigated the hypothesis that the tissue expression of three cell cycle markers, Rb, p21 and p16, would provide helpful prognostic information in a well characterised series of prostate cancers which were clinically localised and treated conservatively.

Methods: The immunohistochemical staining expression of these markers was assessed in tissue microarrays and correlated with 10 year prostate cancer survival and overall survival and then compared with pathological data including contemporary Gleason score, age, measures of tumour extent and initial serum prostate specific antigen (PSA) level.

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Treatment decisions on prostate cancer diagnosed by trans-urethral resection (TURP) of the prostate are difficult. The current TNM staging system for pT1 prostate cancer has not been re-evaluated for 25 years. Our objective was to optimise the predictive power of tumor extent measurements in TURP of the prostate specimens.

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The optimal method for measuring cancer extent in prostate biopsy specimens is unknown. Seven hundred forty-four patients diagnosed between 1990 and 1996 with prostate cancer and managed conservatively were identified. The clinical end point was death from prostate cancer.

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