Design and Prototyping of a Novel Triple Lumen Photo-Angioplasty Device: Lumi-Solve-T.

Purpose: A triple lumen iteration of the novel photo-angioplasty drug eluting balloon catheter (DEBc) Lumi-Solve may be compromised by guidewire shadow (GWS)-mediated attenuation of balloon surface drug activation. The current study aimed to design and evaluate a novel triple lumen prototype, designated Lumi-Solve-T, to circumvent these issues.

Methods: Effects of guidewire shadowing (GWS) on vascular smooth muscle cell (VSMC) proliferation was evaluated using the MTT assay.

Characterization of an Estrogen Receptor α-Selective F-Estradiol PET Tracer.

 Conventional imaging of cancer with modalities such as computed tomography or magnetic resonance imaging provides little information about the underlying biology of the cancer and consequently little guidance for systemic treatment choices. Accurate identification of aggressive cancers or those that are likely to respond to specific treatment regimens would allow more precisely tailored treatments to be used. The expression of the estrogen receptor α subunit is associated with a more aggressive phenotype, with a greater propensity to metastasize.

Prospective Evaluation of Serum Free Thiols in Inflammatory Bowel Disease: A Candidate to Replace C-Reactive Protein for Disease Activity Assessment?

Background: Serum free thiols (SFTs) reflecting oxidative stress appear to correlate with inflammatory bowel disease (IBD) activity. We aimed to evaluate the performance of SFTs concentrations vs endoscopic and histological activity, compare SFTs with established biomarkers, and identify clinical and laboratory parameters independently associated with SFT levels in IBD patients.

Methods: Patients with confirmed IBD undergoing routine ileocolonoscopy for activity assessment were prospectively recruited, with serum samples obtained concurrently for SFTs and routine bloods, plus fecal calprotectin and immunochemical tests were collected ±30 days from ileocolonoscopy.

Lytic effects of water on cancer cells: Implications for post-operative irrigation.

Background: Intraoperative tumour spillage can be concerning during cancer excisions, given it can lead to tumour-cell re-implantation and local recurrence. Examples include bladder tumour recurrences post-transurethral resection, or peritoneal spillage during laparotomy/laparoscopy for bowel and ovarian cancers. One approach to reducing implantation is mechanical wash out of free-floating tumour cells.

Effects of estrogen receptor signaling on prostate cancer carcinogenesis.

Management of advanced prostate cancer remains complex, with substantial changes in treatment options emerging in recent years having implications for treatment selection and sequencing. Recognition of the importance of androgen signaling has led to life-prolonging treatments, as well as "liquid biopsy" techniques to guide these treatments in some settings. Therapies that target estrogen receptor signaling are efficacious but infrequently used options for treatment of castration-resistant prostate cancer.

Circulating oestrogen receptor mutations and splice variants in advanced prostate cancer.

Objective: To characterize circulating oestrogen receptor ( ER) mutants and splice variants in men with advanced prostate cancer.

Materials And Methods: Sequential blood samples were obtained from men with advanced prostate cancer, and from healthy controls. Blood-derived RNA samples were analysed using droplet digital PCR for the presence of six ERα mutations (E380Q, L536Q, Y537C, Y537S, Y537N and D538G), and six ERα and ERβ splice variants (ERα-66, ERα-36, ERβ1, ERβ2, ERβ4 & ERβ5).

The intestinal vitamin D receptor in inflammatory bowel disease: inverse correlation with inflammation but no relationship with circulating vitamin D status.

Background: The intestinal vitamin D receptor (VDR) remains poorly characterized in patients with inflammatory bowel disease (IBD).

Methods: Colonoscopic biopsies and intestinal resection specimens from the terminal ileum, ascending and sigmoid colon, from patients with and without IBD, were analyzed for VDR mRNA quantification by polymerase chain reaction, and protein localization and semi-quantification by immunohistochemistry. The relationship between VDR and intestinal inflammation, serum 25(OH)D and oral vitamin D intake was elicited.

Vinorelbine Potently Induces Placental Cell Death, Does Not Harm Fertility and is a Potential Treatment for Ectopic Pregnancy.

Ectopic pregnancies complicate 1-2 pregnancies and are a leading cause of maternal death. An effective oral drug therapy that replaces surgery might make its treatment safer, cheaper, simpler and therefore more widely accessible. The only current medical treatment offered to women is intramuscular methotrexate, but this only reliably resolves smaller ectopic pregnancies.

Cell mates: paracrine and stromal targets for prostate cancer therapy.

After many years of limited treatment options for patients with metastatic castration-resistant prostate cancer (mCRPC), multiple systemic therapies are now available, providing patients with significant improvements in survival, symptom control and bone health. Most of the recent advances in this area have been based on better understanding of mCRPC biology, particularly with respect to the key role of androgen receptor signalling. However, most therapies are targeted towards the malignant epithelial cell component of the cancer and it should not be forgotten that cancer cells exist in close and symbiotic relationships with other components of the tumour.

Targeted nanoparticle delivery of doxorubicin into placental tissues to treat ectopic pregnancies.

Abnormal trophoblast growth can cause life-threatening disorders such as ectopic pregnancy, choriocarcinoma, and placenta accreta. EnGeneIC Delivery Vehicles (EDVs) are nanocells that can promote tissue-specific delivery of drugs and may be useful to medically treat such disorders. The objective of this study was to determine whether EDVs loaded with the chemotherapeutic doxorubicin and targeting the epidermal growth factor receptor (EGFR, very highly expressed on the placental surface) can regress placental cells in vitro, ex vivo, and in vivo.

Proteomic changes in rat spermatogenesis in response to in vivo androgen manipulation; impact on meiotic cells.

The production of mature sperm is reliant on androgen action within the testis, and it is well established that androgens act on receptors within the somatic Sertoli cells to stimulate male germ cell development. Mice lacking Sertoli cell androgen receptors (AR) show late meiotic germ cell arrest, suggesting Sertoli cells transduce the androgenic stimulus co-ordinating this essential step in spermatogenesis. This study aimed to identify germ cell proteins responsive to changes in testicular androgen levels and thereby elucidate mechanisms by which androgens regulate meiosis.

Cancer/testis antigens can be immunological targets in clonogenic CD133+ melanoma cells.

"Cancer stem cells" that resist conventional treatments may be a cause of therapeutic failure in melanoma. We report a subpopulation of clonogenic melanoma cells that are characterized by high prominin-1/CD133 expression in melanoma and melanoma cell lines. These cells have enhanced clonogenicity and self-renewal in vitro, and serve as a limited in vitro model for melanoma stem cells.

Application of laser-capture microdissection to analysis of gene expression in the testis.

The isolation and molecular analysis of highly purified cell populations from complex, heterogeneous tissues has been a challenge for many years. Spermatogenesis in the testis is a particularly difficult process to study given the unique multiple cellular associations within the seminiferous epithelium, making the isolation of specific cell types difficult. Laser-capture microdissection (LCM) is a recently developed technique that enables the isolation of individual cell populations from complex tissues.

Claudin-11 expression and localisation is regulated by androgens in rat Sertoli cells in vitro.

Claudin-11 and occludin are protein components in tight junctions (TJs) between Sertoli cells which are important for the maintenance of the blood-testis barrier. Barrier formation occurs during puberty, with evidence suggesting hormonal regulation of both claudin-11 and occludin. This study aimed to investigate the regulation of claudin-11 and occludin mRNA expression by testosterone (T) and FSH and their immunolocalisation at rat Sertoli cell TJs in vitro, and to correlate any steroid regulation with the functional capacity of TJs.

Stage-specific expression of genes associated with rat spermatogenesis: characterization by laser-capture microdissection and real-time polymerase chain reaction.

Spermatogenesis in the rat consists of 14 unique morphologic cellular associations between Sertoli cells and developing germ cells within the seminiferous epithelium. The complexity of the cellular associations leads to difficulty in the isolation of individual cells at a defined stage of development for the study of their unique patterns of gene or protein expression. Thus, laser-capture microdissection is an ideal technique to permit such analysis.