The use of circulating tumor cells (CTCs) and circulating extracellular vesicles (EVs), such as exosomes, as liquid biopsy-derived biomarkers for cancers have been investigated. CTC enumeration using the CellSearch based platform provides an accurate insight on overall survival where higher CTC counts indicate poor prognosis for patients with advanced metastatic cancer. EVs provide information based on their lipid, protein, and nucleic acid content and can be isolated from biofluids and analyzed from a relatively small volume, providing a routine and non-invasive modality to monitor disease progression. Our pilot experiment by assessing the level of two subpopulations of small EVs, the CD9 positive and CD63 positive EVs, showed that the CD9 positive EV level is higher in plasma from patients with advanced metastatic prostate cancer with detectable CTCs. These data show the potential utility of a particular EV subpopulation to serve as biomarkers for advanced metastatic prostate cancer. EVs can potentially be utilized as biomarkers to provide accurate genotypic and phenotypic information for advanced prostate cancer, where new strategies to design a more personalized therapy is currently the focus of considerable investigation.
Objective Androgen deprivation therapy (ADT) reduces muscle and bone mass, increasing frailty in men with prostate cancer. The liver mediates the whole body anabolic effects of testosterone. Based on first-pass metabolism, liver-targeted testosterone treatment (LTTT) entails oral delivery of a small dose of testosterone that does not raise peripheral blood testosterone levels. LTTT reduces blood urea, stimulates protein anabolism in hypogonadal men and postmenopausal women. We investigated whether LTTT prevents loss of lean and bone mass during ADT. Method A 6 month double-blind placebo-controlled study of testosterone 40 mg/day in 50 men. Primary outcome measures were lean mass and bone mineral content (BMC). Testosterone, urea and PSA were monitored. Patients were withdrawn if PSA exceeded 4 ng/mL. Results 42 patients completed the study. Mean (95%CI) testosterone rose during LTTT but not placebo treatment (∆ 2.2 [1.3 – 3.0] vs -0.7 [-1.5 – 0.2] nmol/L; p<0.01). Mean PSA level did not change significantly during either treatment. Blood urea fell (∆-0.4 [-0.9 – -0.1] mmol/L) during LTTT but not placebo (∆ 0.05 [-0.8 – 0.9] mmol/L). BMC (∆ 49 [5 – 93] gm, p<0.02) and lean mass (∆ 0.8 [-0.1 – 1.7] kg; p=0.04) increased compared to placebo. Five patients on LTTT withdrew from increased PSA levels, all returning to baseline levels. Conclusion LTTT shows promise as simple therapy for preventing sarcopenia and bone loss during ADT. LTTT may induce reversible PSA rise in some patients. Further studies are required to optimize LTTT dose in ADT. LTTT has potential application in other catabolic states in men and women.
Background. Previous pre-clinical and clinical trials showed that distress experienced by cancer patients can activate the sympathetic nervous system, resulting in the elevation of the level of catecholamines in tumor tissue. catecholamines activate tumor neoangiogenesis via binding to the adrenergic receptors of tumor cells and cells of tumor microenvironment. Vascular endothelial growth factor a(VEgF a) plays a key role in tumor neoangiogenesis.Objective. To evaluate the correlation between serum VEgF alevel and distress in ovarian cancer patients.Material and methods. The prospective cross-sectional study included 100 patients with stage i–iV ovarian cancer. the median age of the patients was 56 ± 9,56 years. Enzym-linked immunosorbent assay was used for the assessment of serum VEgF alevel. distress thermometer (validated self-reported questionnaire) was used for distress diagnosis.Results. The median serum VEgF alevel was 325.77 pg/ml. aclinically significant distress was diagnosed in 54 % of patients. We found the correlation between the serum VEgF alevel and distress level in ovarian cancer patients (spearman’s rho=0.33; 95 % ci, 0.11–0.52; р< 0.004). We also found the correlation between the serum VEgR alevel and disease stage (rho=0.30; 95 % ci0.02–0.53; p<0.05). However, there was no correlation between distress and disease stage. the regression analysis method revealed that distress was an independent factor of serum VEgF aelevation in ovarian cancer patients (p<0.05).Conclusion. Assessment and early diagnosis of cancer-related distress was shown to be important for the appropriate management of ovarian cancer.
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