Cytotoxic Effects of the Therapeutic Radionuclide Rhenium-188 Combined with Taxanes in Human Prostate Carcinoma Cell Lines.

Objective: Rhenium-188-HEDP is an effective radiopharmaceutical for the treatment of painful bone metastases from prostate cancer. The effectiveness of the β-radiation emitted by Re might be enhanced by combination with chemotherapy, using the radiosensitization concept. Therefore, the authors investigated the combined treatment of the taxanes, docetaxel and cabazitaxel, with Re in prostate carcinoma cell lines.

Non‑invasive prostate cancer detection by measuring miRNA variants (isomiRs) in urine extracellular vesicles.

In many cancer types, the expression and function of ~22 nucleotide-long microRNAs (miRNA) is deregulated. Mature miRNAs can be stably detected in extracellular vesicles (EVs) in biofluids, therefore they are considered to have great potential as biomarkers. In the present study, we investigated whether miRNAs have a distinct expression pattern in urine-EVs of prostate cancer (PCa) patients compared to control males.

Protein Complexes in Urine Interfere with Extracellular Vesicle Biomarker Studies.

Urine exosomes (extracellular vesicles; EVs) contain (micro)RNA (miRNA) and protein biomarkers that are useful for the non-invasive diagnosis of various urological diseases. However, the urinary Tamm-Horsfall protein (THP) complex, which forms at reduced temperatures, may affect EV isolation and may also lead to contamination by other molecules including microRNAs (miRNAs). Therefore, we compared the levels of three miRNAs within the purified EV fraction and THP- protein-network.

miR-129-3p controls centrosome number in metastatic prostate cancer cells by repressing CP110.

The centrosome plays a key role in cancer invasion and metastasis. However, it is unclear how abnormal centrosome numbers are regulated when prostate cancer (PCa) cells become metastatic. CP110 was previously described for its contribution of centrosome amplification (CA) and early development of aggressive cell behaviour.

A prognostic classifier for patients with colorectal cancer liver metastasis, based on AURKA, PTGS2 and MMP9.

Background: Prognosis of patients with colorectal cancer liver metastasis (CRCLM) is estimated based on clinicopathological models. Stratifying patients based on tumor biology may have additional value.

Methods: Tissue micro-arrays (TMAs), containing resected CRCLM and corresponding primary tumors from a multi-institutional cohort of 507 patients, were immunohistochemically stained for 18 candidate biomarkers.

Molecular imaging of aurora kinase A (AURKA) expression: Synthesis and preclinical evaluation of radiolabeled alisertib (MLN8237).

Introduction: Survival of patients after resection of colorectal cancer liver metastasis (CRCLM) is 36%-58%. Positron emission tomography (PET) tracers, imaging the expression of prognostic biomarkers, may contribute to assign appropriate management to individual patients. Aurora kinase A (AURKA) expression is associated with survival of patients after CRCLM resection.

A cell-based high-throughput screening assay for radiation susceptibility using automated cell counting.

Background: Radiotherapy is one of the mainstays in the treatment for cancer, but its success can be limited due to inherent or acquired resistance. Mechanisms underlying radioresistance in various cancers are poorly understood and available radiosensitizers have shown only modest clinical benefit. There is thus a need to identify new targets and drugs for more effective sensitization of cancer cells to irradiation.

The ultimate radiochemical nightmare: upon radio-iodination of Botulinum neurotoxin A, the introduced iodine atom itself seems to be fatal for the bioactivity of this macromolecule.

Background: Botulinum neurotoxin A (BoNT-A) is a highly neurotoxic drug and frequently used in patients. Knowledge on the optimal way of administration of BoNT-A and its subsequent distribution is still rather limited. An accurate method for monitoring these processes might be the use of radiolabelled BoNT-A.

Glucose Transporter 1 (SLC2A1) and Vascular Endothelial Growth Factor A (VEGFA) Predict Survival After Resection of Colorectal Cancer Liver Metastasis.

Objective: To investigate the individual and combined prognostic value of HIF1α, SLC2A1, and vascular endothelial growth factor A (VEGFA) in a multi-institutional cohort of patients with resected colorectal cancer liver metastasis (CRCLM).

Background: In the majority of patients with CRCLM, resection seems not to be curative, despite its curative intent. Overexpression of hypoxia-inducible factor 1α (HIF1α), glucose transporter 1 (SLC2A1; also known as GLUT1), and VEGFA has been associated with tumor progression and poor prognosis of patients with colorectal cancer (CRC).

[18F]fluoromethylcholine as a chemotherapy response read-out in prostate cancer cells.

Purpose: The objective of the present study is to determine whether uptake of [(18)F]fluoromethylcholine ([(18)F]FCH) in comparison with 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) accurately reflects chemotherapy efficacy at the tumor cell level in prostate cancer (PC).

Procedures: The effects of docetaxel and cabazitaxel on viable tumor cell number were explored in four PC cell lines. Cellular uptake of [(18)F]FDG and [(18)F]FCH was compared with the effects measured using sulforhodamine B (SRB) assay, cell counting and colony formation assay (CFA), as proximators of viable tumor cell number.

Epidermal growth factor receptor (EGFR) and prostaglandin-endoperoxide synthase 2 (PTGS2) are prognostic biomarkers for patients with resected colorectal cancer liver metastases.

Background: Resection of colorectal cancer liver metastasis (CRCLM) with curative intent has long-term benefit in ~40% of cases. Prognostic biomarkers are needed to improve clinical management and reduce futile surgeries. Expression of epidermal growth factor receptor (EGFR) and prostaglandin-endoperoxide synthase 2 (PTGS2; also known as cyclooxygenase-2) has been associated with carcinogenesis and survival.

Inefficacy of therapeutic cancer vaccines and proposed improvements. Casus of prostate cancer.

Prophylactic vaccination is arguably the most effective medical preventative method. After local inoculation, vaccines induce antigen-specific systemic immunity, protecting the whole body. Systemic antitumour immunity can cure advanced cancer, but will therapeutic vaccination suffice? A vaccine for castration-refractory prostate cancer (CRPC) was approved by regulatory authority, but its evidence is disputed.

Development of an in vitro model to measure bioactivity of botulinum neurotoxin A in rat bladder muscle strips.

Background: Botulinum toxin A (BoNT-A) is a new treatment modality in various causes of bladder dysfunction; like neurogenic detrusor overactivity and overactive bladder. The best technique of administrating BoNT-A in patients is unknown. A validated in vitro model could be used to investigate newer intravesical administration techniques of BoNT-A.

Characterization of and protection from neurotoxicity induced by oxaliplatin, bortezomib and epothilone-B.

Aim: To characterize neurotoxicity induced by oxaliplatin, bortezomib, and epothilone-B as well as protection against their neurotoxicity using an in vitro model.

Materials And Methods: Neurotoxicity was evaluated using the neurite outgrowth method in PC12 rat pheochromo-cytoma cells differentiated towards a mature neuronal phenotype, while neuroprotection was explored by simultaneous exposure to 0.5 mM amifostine.

Exosomal ITGA3 interferes with non-cancerous prostate cell functions and is increased in urine exosomes of metastatic prostate cancer patients.

Background: Cancer cells are able to change the protein expression and behavior of non-cancerous surrounding cells. Exosomes, secreted by prostate cancer (PCa) cells, may have a functional role in cancer metastasis and present a promising source for protein biomarkers. The aim of the present study was to identify which proteins in exosomes can influence non-cancerous cells, and to determine whether we can use urine exosomal proteins to identify high-risk PCa patients.

Aurora kinase A (AURKA) expression in colorectal cancer liver metastasis is associated with poor prognosis.

Background: Five-year survival after resection of colorectal cancer liver metastasis (CRLCM) is <30%. We recently found that aurora kinase A (AURKA) drives 20q gain-associated tumour progression and is associated with disease recurrence. This study evaluates the prognostic value of AURKA expression in CRCLM of patients who underwent liver resection.

Profiling of the calcitonin-calcitonin receptor axis in primary prostate cancer: clinical implications and molecular correlates.

Expression of the neuroendocrine peptide calcitonin (CT) and its receptor (CTR) is frequently elevated in prostate cancers (PCs), and activation of the CT-CTR axis in non-invasive PC cells induces an invasive phenotype. We aimed to link CT/CTR expression in prostate specimens to clinicopathological parameters of PC. We analyzed CT and CTR expression in cohorts of benign prostates and primary PCs with/without metastatic disease by immunohistochemistry.

Decay of γ-H2AX foci correlates with potentially lethal damage repair in prostate cancer cells.

To determine the relationship between ionizing radiation-induced levels of γ-H2AX foci and cell survival in cultured prostate cancer cell lines, three prostate cancer cell lines: LNCaP (wt TP53), DU145 (mut TP53) and PC3 (TP53 null), were studied. For γ-H2AX foci induction, cells were irradiated with a single dose of 2 Gy and foci levels were studied at 30 min and 24 h after irradiation. Cell survival was determined by clonogenic assay, directly and 24 h after irradiation with doses ranging from 0 to 8 Gy.

Targeted radiosensitization in prostate cancer.

Radiotherapy is one of the treatment options for locally or regionally advanced prostate cancer, but radioresistance of prostate cancer cells is a practical limitation of radiotherapy. The identification of molecular targets of radioresistance in prostate cancer is important to improve therapeutic intervention. The aim of this review is to give more biological insight into some well known processes involved in radioresistance of prostate cancer especially Apoptotic pathway; DNA damage response; and NF- κB(nuclear factor kappalight- chain-enhancer of activated B cells) signaling pathway.

ABCC4 Decreases docetaxel and not cabazitaxel efficacy in prostate cancer cells in vitro.

Background: This study aimed to investigate cabazitaxel efficacy in a model for docetaxel-resistant prostate cancer cells and to evaluate the involvement of ATP-cassette binding protein 4 (ABCC4) with regard to multidrug resistance.

Materials And Methods: Docetaxel and cabazitaxel sensitivity was measured in PC3 and R3327-MATLyLu (MLL) cell lines, using the sulforhodamine B (SRB) assay. ABCC4 expression was examined by western blotting and its functional involvement in drug sensitivity by blocking with MK571 inhibitor.

A predictive role for noncancerous prostate cells: low connexin-26 expression in radical prostatectomy tissues predicts metastasis.

Background: It is important to identify markers that predict whether prostate cancer will metastasise. The adjacent noncancerous cells (influenced by the tumour cells) may also express potential markers. The objective of this study was to determine the influence of cancer cells on noncancerous cells and to assess the value of the cell-communication protein connexin-26 (Cx26) as a marker to predict the development of metastasis.

Serum testosterone plays an important role in the metastatic ability of castration resistant prostate cancer.

Purpose: Prostate cells are dependent on androgens for growth and proliferation. Androgen deprivation therapy is the recommended treatment for advanced/metastatic prostate cancer. Under this therapy, prostate cancer will inevitably progress to castration resistant prostate cancer (CRPC).

Longitudinal 3.0T MRI analysis of changes in lymph node volume and apparent diffusion coefficient in an experimental animal model of metastatic and hyperplastic lymph nodes.

Purpose: To perform a longitudinal analysis of changes in lymph node volume and apparent diffusion coefficient (ADC) in healthy, metastatic, and hyperplastic lymph nodes.

Materials And Methods: Three groups of four female Copenhagen rats were studied. Metastasis was induced by injecting cells with a high metastatic potential in their left hind footpad.

Evaluation of adenoviral oncolytic effect on glioma spheroids by 18F-DG positron-emission tomography.

Multicellular tumor spheroids are used as a model to assess the efficacy of replicating oncolytic adenoviruses. As most assays used to assess cellular viability are unsuitable for oncolytic viruses because of ongoing viral replication, we have used positron emission tomography (PET) to sequentially determine the incorporation of 18F-labeled deoxyglucose (18F-DG) as a measure of viability and compared the results to more commonly used assays for measuring the effect of oncolytic therapy. Glioma monolayer cultures and spheroids were infected with wild-type replicating adenovirus and viability was measured by 18F-DG incorporation, WST-1 assay, crystal violet assay, and spheroid volume 2 to 10 days following infection.

New experimental markers for early detection of high-risk prostate cancer: role of cell-cell adhesion and cell migration.

Today's treatment and diagnosis of prostate cancer still exhibit major limitations. The search for new and additional prognostic markers is therefore still an actual field of interest. Potential markers involved in numerous biological processes in the tumor cell have been investigated intensively.