Optimising Extracellular Vesicle Metabolomic Methodology for Prostate Cancer Biomarker Discovery.

Conventional diagnostic tools for prostate cancer (PCa), such as prostate-specific antigen (PSA), transrectal ultrasound (TRUS), digital rectal examination (DRE), and tissue biopsy face, limitations in individual risk stratification due to invasiveness or reliability issues. Liquid biopsy is a less invasive and more accurate alternative. Metabolomic analysis of extracellular vesicles (EVs) holds a promise for detecting non-genetic alterations and biomarkers in PCa diagnosis and risk assessment.

Prostate cancer-derived extracellular vesicles metabolic biomarkers: Emerging roles for diagnosis and prognosis.

Prostate cancer (PCa) is a global health concern, ranking as the most common cancer among men in Western countries. Traditional diagnostic methods are invasive with adverse effects on patients. Due to the heterogeneous nature of PCa and their multifocality, tissue biopsies often yield false-negative results.

Proteomic Identification of Small Extracellular Vesicle Proteins LAMB1 and Histone H4 for Prostate Cancer Diagnosis and Risk Stratification.

Diagnosis and stratification of prostate cancer (PCa) patients using the prostate-specific antigen (PSA) test is challenging. Extracellular vesicles (EVs), as a new star of liquid biopsy, has attracted interest to complement inaccurate PSA screening and invasiveness of tissue biopsy. In this study, a panel of potential small EV (sEV) protein biomarkers is identified from PCa cell lines using label-free LC-MS/MS proteomics.

Ga-PSMA-PET/CT in addition to mpMRI in men undergoing biopsy during active surveillance for low- to intermediate-risk prostate cancer: study protocol for a prospective cross-sectional study.

Background: In active surveillance there is significant interest in whether imaging modalities such as multiparametric magnetic resonance imaging (mpMRI) or Gallium prostate-specific membrane antigen positron emission tomography/computerized tomography (Ga-PSMA-PET/CT) can improve the detection of progression to clinically significant prostate cancer (csPCa) and thus reduce the frequency of prostate biopsies and associated morbidity. Recent studies have demonstrated the value of mpMRI in active surveillance; however, mpMRI does miss a proportion of disease progression and thus alone cannot replace biopsy. To date, prostate-specific membrane antigen positron emission tomography (PSMA-PET) has shown additive value to mpMRI in its ability to detect prostate cancer (PCa) in the primary diagnostic setting.

Experimental and Theoretical Exploration of the Kinetics and Thermodynamics of the Nucleophile-Induced Fragmentation of Ylidenenorbornadiene Carboxylates.

Ylidenenorbornadienes (YNDs), prepared by [4 + 2] cycloadditions between fulvenes and acetylene carboxylates, react with thiol nucleophiles to yield mixtures of four to eight diastereomers depending on the symmetry of the YND substrate. The mixtures of diastereomers fragment via a retro-[4 + 2] cycloaddition with a large variation in rate, with half-lives ranging from 16 to 11,000 min at 80 °C. The diastereomer-enriched samples of propane thiol adducts [YND-propanethiol (PTs)] were isolated and identified by nuclear Overhauser effect spectroscopy (NOESY) correlations.

Differentiation of renal masses with multi-parametric MRI: the de Silva St George classification scheme.

Purpose: To develop a system for multi-parametric MRI to differentiate benign from malignant solid renal masses and assess its accuracy compared to the gold standard of histopathological diagnosis.

Methods: This is a retrospective analysis of patients who underwent 3 Tesla mpMRI for further assessment of small renal tumours with specific scanning and reporting protocol incorporating T2 HASTE signal intensity, contrast enhancement ratios, apparent diffusion coefficient and presence of microscopic/macroscopic fat. All MRIs were reported prior to comparison with histopathologic diagnosis and a reporting scheme was developed.

Ylidenenorbornadiene Carboxylates: Experimental Kinetic Analysis of a Nucleophile-Induced Fragmentation Reaction.

Ylidenenorbornadienes (YNDs), prepared by [4 + 2] cycloadditions between fulvenes and acetylene carboxylates, react with -mercaptoethanol to yield a mixture of four diastereomers. These four diastereomers fragment via a retro-[4 + 2] cycloaddition at differing rates. A simulated kinetics approach extrapolated the rate constants of the diastereomers from the observed rate data.

The diagnostic utility of diffusion weighted MRI imaging and ADC ratio to distinguish benign from malignant renal masses: sorting the kittens from the tigers.

Background: MRI is playing an increasing role in risk stratification and non-invasive diagnosis of the undifferentiated small renal mass. This study was designed to assess the reliability of MRI in diagnostic evaluation of renal masses, specifically characterising lesions with diffusion weighted imaging (DWI) and apparent diffusion coefficient (ADC) values.

Methods: This is a retrospective analysis of patients undergoing MRI as part of their clinical workup for a renal mass suspicious for renal cell carcinoma (RCC) on CT or ultrasound followed by biopsy and/or surgical excision.

Quality Assessment and Comparison of Plasma-Derived Extracellular Vesicles Separated by Three Commercial Kits for Prostate Cancer Diagnosis.

Introduction: Current standard biomarkers in clinic are not specific enough for prostate cancer (PCa) diagnosis. Extracellular vesicles (EVs) are nano-scale vesicles released by most mammalian cells. EVs are promising biomarker source for PCa liquid biopsy due to its minimal invasive approach, rich information and improved accuracy compared to the clinical standard prostate-specific antigen (PSA).

Bladder perforation: A rare complication of retention management.

A healthy 25 year old woman presented with acute urinary retention following alcohol ingestion. A 14 french foley catheter drained over 1 L of haematuria immediately. Due to worsening and persistent abdominal pain, CT and ultrasound imaging was performed, demonstrating only a small amount of free fluid.

Towards real time in-vivo rectal dosimetry during trans-rectal ultrasound based high dose rate prostate brachytherapy using MOSkin dosimeters.

Purpose: To compare the dose measured by MOSkin dosimeters coupled to a trans-rectal ultrasound (TRUS) probe to the dose predicted by the brachytherapy treatment planning system (BTPS) during high dose rate (HDR) prostate brachytherapy (pBT), and to examine the feasibility of performing real-time catheter-by-catheter analysis of in-vivo rectal dosimetry during TRUS based HDR pBT.

Method: Four MOSkin dosimeters were coupled to a TRUS probe during 20 TRUS-based HDR pBT treatment fractions. The measured MOSkin doses were retrospectively compared to those predicted by the BTPS for the total treatment fraction, as well as on a per catheter basis.

Chemical shift imaging in the identification of those renal tumours that contain microscopic fat and the utility of multiparametric MRI in their differentiation.

Introduction: The aim of this study was to assess the qualitative and MRI findings of renal tumours, to determine which lesions contain microscopic fat, one of the potential differentiating factors between tumour types.

Methods: 73 patients who underwent 3 Tesla MRI including chemical shift imaging, with subsequent biopsy or excision for histopathological diagnosis, were included in the study. The images were reviewed for a decrease in signal intensity (SI) on the opposed phase compared with the in-phase gradient echo T1 images, indicating the presence of microscopic fat.

What not to expect when you're expecting - Postpartum proximal ureteric rupture: A case report.

Introduction: Spontaneous ureteric rupture is an extremely rare cause of acute abdominal pain in the intrapartum and postpartum period. We present the case of a right ureteric rupture diagnosed immediately postpartum.

Case: A 23-year-old woman in her second pregnancy (who had had a previous caesarean section) developed acute-onset right-flank pain 12 h after vaginal delivery.

Extracellular vesicles: the next generation of biomarkers for liquid biopsy-based prostate cancer diagnosis.

Prostate cancer (PCa) is a leading cause of cancer death for males in western countries. The current gold standard for PCa diagnosis - template needle biopsies - often does not convey a true representation of the molecular profile given sampling error and complex tumour heterogeneity. Presently available biomarker blood tests have limited accuracy.

CD44 variant 6 is associated with prostate cancer growth and chemo-/radiotherapy response in vivo.

We have previously demonstrated that CD44 variant 6 (CD44v6) is associated with prostate cancer (CaP) growth and therapeutic resistance in vitro, however, the role of CD44v6 in CaP in vivo is not fully understood. The purpose of this study is to investigate the effect of CD44v6 on CaP growth and chemo-/radiotherapy response in NOD/SCID mouse models in vivo and to validate its role as a therapeutic target for CaP therapy. CD44v6 was knocked down in PC-3M CaP cell line using short hairpin RNA.

Exosomes in Cancer Radioresistance.

Radiation is a mainstay of cancer therapy. Radioresistance is a significant challenge in the treatment of locally advanced, recurrent and metastatic cancers. The mechanisms of radioresistance are complicated and still not completely understood.

Targeting MicroRNAs in Prostate Cancer Radiotherapy.

Radiotherapy is one of the most important treatment options for localized early-stage or advanced-stage prostate cancer (CaP). Radioresistance (relapse after radiotherapy) is a major challenge for the current radiotherapy. There is great interest in investigating mechanisms of radioresistance and developing novel treatment strategies to overcome radioresistance.

Frequency of Angiomyolipomas Among Echogenic Nonshadowing Renal Masses (> 4 mm) Found at Ultrasound and the Utility of MRI for Diagnosis.

Objective: The purpose of this study is to evaluate what percentage of echogenic nonshadowing renal lesions larger than 4 mm found at ultrasound are angiomyolipomas (AMLs) and to review how to diagnose AMLs, with particular emphasis on the increasing role played by MRI.

Materials And Methods: The study data were obtained at a single institution over a period of 45 months. Although some patients were being reviewed for specific symptoms, such as hematuria, pain, or recurrent urinary tract infections, most of the findings were incidental.

Identification of protein biomarkers and signaling pathways associated with prostate cancer radioresistance using label-free LC-MS/MS proteomic approach.

Identifying biomarkers and signaling pathways are important for the management of prostate cancer (CaP) radioresistance. In this study, we identified differential proteins and signaling pathways from parental CaP cell lines and CaP radioresistant (RR) sublines using a label-free LC-MS/MS proteomics approach. A total of 309 signaling pathway proteins were identified to be significantly altered between CaP and CaP-RR cells (p ≤ 0.

Proteomic identification of the lactate dehydrogenase A in a radioresistant prostate cancer xenograft mouse model for improving radiotherapy.

Radioresistance is a major challenge for prostate cancer (CaP) metastasis and recurrence after radiotherapy. This study aimed to identify potential protein markers and signaling pathways associated with radioresistance using a PC-3 radioresistant (RR) subcutaneous xenograft mouse model and verify the radiosensitization effect from a selected potential candidate. PC-3RR and PC-3 xenograft tumors were established and differential protein expression profiles from two groups of xenografts were analyzed using liquid chromatography tandem-mass spectrometry.

The risk of second malignancies after I prostate brachytherapy as monotherapy in a single Australian institution.

Purpose: To report the incidence of second primary cancer (SPC) after I brachytherapy (BT) for early prostate cancer in an Australian institution.

Methods And Materials: All the patients in our cohort had a cystoscopy before the implant. Data were prospectively collected on all subsequent SPC diagnoses.

Hemiablative Focal Low Dose Rate Brachytherapy: A Phase II Trial Protocol.

Background: The objective of focal brachytherapy (BT) is to provide effective prostate cancer control for low-risk disease but with reduced genitourinary, gastrointestinal and sexual side effects in a cost-effective way.

Objective: The aim of this study is to describe a phase II study examining technical and dosimetric feasibility and toxicity, quality of life changes, and local control with post-treatment biopsy outcomes in men with early stage low volume prostate cancer treated with focal iodine-125 seed BT.

Methods: The study design is a prospective, multicenter trial with a planned sample size of 20 patients including men with a minimum age of 60 years, a life expectancy estimated to be greater than 10 years, with low or low-tier intermediate risk prostate cancer, unilateral disease on the biopsy, and a Gleason score of ≤3+4 and <25% cores involved.

Cancer stem cells and signaling pathways in radioresistance.

Radiation therapy (RT) is one of the most important strategies in cancer treatment. Radioresistance (the failure to RT) results in locoregional recurrence and metastasis. Therefore, it is critically important to investigate the mechanisms leading to cancer radioresistance to overcome this problem and increase patients' survival.

Proteomics discovery of radioresistant cancer biomarkers for radiotherapy.

Radiotherapy (RT) is one of the most important strategies in cancer treatment. Radioresistance is a major challenge to RT and results in locoregional recurrence and metastasis. Thus, there is a great interest in investigating biomarkers to distinguish radiosensitive from radioresistant (RR) cancer patients.