Decreased levels of cathepsin Z mRNA expressed by immune blood cells: diagnostic and prognostic implications in prostate cancer.

Cathepsin Z (CTSZ) is a cysteine protease responsible for the adhesion and migration of both immune and tumor cells. Due to its dual role, we hypothesized that the site of CTSZ expression could be determinant of the pro- or anti-tumorigenic effects of this enzyme. To test this hypothesis, we analyzed CTSZ expression data in healthy and tumor tissues by bioinformatics and evaluated the expression levels of CTSZ mRNA in the blood cells of prostate cancer (PCa) patients by qRT-PCR compared with healthy subjects, evaluating its diagnostic and prognostic implications for this type of cancer. Immune cells present in the blood of healthy patients overexpress CTSZ. In PCa, we found decreased CTSZ mRNA levels in blood cells, 75% lower than in healthy subjects, that diminished even more during biochemical relapse. CTSZ mRNA in the blood cells had an area under the curve for PCa diagnosis of 0.832, with a 93.3% specificity, and a positive likelihood ratio of 9.4. The site of CTSZ mRNA expression is fundamental to determine its final role as a protective determinant in PCa, such as CTSZ mRNA in the blood cells, or a malignant determinant, such as found for CTSZ expressed in high levels by different types of primary and metastatic tumors. Low CTSZ mRNA expression in the total blood is a possible PCa marker complementary to prostate-specific antigen (PSA) for biopsy decisions, with the potential to eliminate unnecessary biopsies.

Decreased levels of cathepsin Z mRNA expressed by immune blood cells: diagnostic and prognostic implications in prostate cancer

Cathepsin Z (CTSZ) is a cysteine protease responsible for the adhesion and migration of both immune and tumor cells. Due to its dual role, we hypothesized that the site of CTSZ expression could be determinant of the pro- or anti-tumorigenic effects of this enzyme. To test this hypothesis, we analyzed CTSZ expression data in healthy and tumor tissues by bioinformatics and evaluated the expression levels of CTSZ mRNA in the blood cells of prostate cancer (PCa) patients by qRT-PCR compared with healthy subjects, evaluating its diagnostic and prognostic implications for this type of cancer. Immune cells present in the blood of healthy patients overexpress CTSZ. In PCa, we found decreased CTSZ mRNA levels in blood cells, 75% lower than in healthy subjects, that diminished even more during biochemical relapse. CTSZ mRNA in the blood cells had an area under the curve for PCa diagnosis of 0.832, with a 93.3% specificity, and a positive likelihood ratio of 9.4. The site of CTSZ mRNA expression is fundamental to determine its final role as a protective determinant in PCa, such as CTSZ mRNA in the blood cells, or a malignant determinant, such as found for CTSZ expressed in high levels by different types of primary and metastatic tumors. Low CTSZ mRNA expression in the total blood is a possible PCa marker complementary to prostate-specific antigen (PSA) for biopsy decisions, with the potential to eliminate unnecessary biopsies.

Bisphosphonate therapy in patients under androgen deprivation therapy for prostate cancer: a systematic review and meta-analysis.

The objective of this study was to clarify the role of bisphosphonates in the treatment of osteoporosis in patients with prostate adenocarcinoma under androgen deprivation therapy (ADT). The Medline, EMBASE, Cancerlit and the American Society of Clinical Oncology abstract databases were searched for published randomized, placebo-controlled trials evaluating the usage of bisphosphonates in patients with prostate cancer (PC) under ADT. The outcomes assessed were fracture, osteoporosis, incidence of adverse events and changes in bone mineral density (BMD) during treatment. A total of 15 articles (2634 participants) were included in the meta-analysis. Treatment with bisphosphonates showed a substantial effect in preventing fractures (risk ratio (RR), 0.80; P = 0.005) and osteoporosis (RR, 0.39; P <0.00001). Zoledronic acid showed the best number needed to treat (NTT), compared with placebo, in relation to fractures and osteoporosis (NNT = 14.9 and NNT = 2.68, respectively). The between-group difference (bisphosphonates vs placebo) in the lumbar spine and femoral neck BMD were 5.18 ± 3.38% and 2.35 ± 1.16%, respectively. This benefit of bone loss prevention could be reached without major side effects (cardiovascular or gastrointestinal events). Bisphosphonates are effective in preventing bone loss in patients with PC who are under ADT.

[Androgen deprivation therapy and morbid obesity: do they share cardiovascular risk through metabolic syndrome?]. / Terapia de privación de andrógenos y obesidad mórbida: ¿tienenen común el riesgo cardiovascular por síndrome metabólico?

BACKGROUND: Although the use of androgen deprivation therapy (ADT) has resulted in improved survival in men with advanced prostate cancer, the resulting hypogonadism is associated with profound adverse effects comparable to those found in morbid obesity, being cardiovascular risk among the most lethal. OBJECTIVES: Evaluate metabolic syndrome, metabolic abnormalities and cardiovascular risk in patients with prostate cancer under ADT, not under ADT and morbid obese men. METHODS: This is a cross-sectional study that involves 79 men presenting prostate cancer, of whom 54 under ADT and 25 not under ADT and 91 morbidly obese patients paired by sex and age. To define metabolic syndrome, we used the International Diabetes Federation (IDF) criteria. Metabolic abnormalities, metabolic markers and Framingham score to predict the ten year coronary heart disease risk were compared among patients under ADT, not under ADT and morbid obese. RESULTS: Patients under ADT presented significantly greater occurrence of diabetes and central obesity and higher levels of total cholesterol and low density lipoprotein (LDL) compared to eugonadal men. The mean cardiovascular risk was significantly higher in patients under ADT (39.97±12.53% vs. 26.09±14.80%; p=0.021). Morbidly obese subjects had increased ten year coronary heart disease risk; comparable to patients under ADT (p=0.054). CONCLUSION: This study suggests that patients under ADT show higher prevalence of metabolic abnormalities and cardiovascular risk similar to those found in morbidly obese subjects. It is possible that both processes share cardiovascular risk through metabolic syndrome.