Blood-Derived Exosomal hTERT mRNA in Patients with Lung Cancer: Characterization and Correlation with Response to Therapy.

Background: Telomerase (human telomerase reverse transcriptase (hTERT) is considered a hallmark of cancer, being active in cancer cells but repressed in human somatic cells. As such, it has the potential to serve as a valid cancer biomarker. Exosomal hTERT mRNA can be detected in the serum of patients with solid malignancies but not in healthy individuals. We sought to evaluate the feasibility of measuring serum exosomal hTERT transcripts levels in patients with lung cancer. Methods: A prospective analysis of exosomal hTERT mRNA levels was determined in serum-derived exosomes from 76 patients with stage III-IV lung cancer (11 SCLC and 65 NSCLC). An hTERT level above RQ = 1.2 was considered "detectable" according to a previous receiver operating characteristic curve (ROC) curve. Sequential measurements were obtained in 33 patients. Demographic and clinical data were collected retrospectively from patients' charts. Data on response to systemic therapy (chemotherapy, immunotherapy, and tyrosine kinase inhibitors) were collected by the treating physicians. Results: hTERT was detected in 53% (40/76) of patients with lung cancer (89% of SCLC and 46% of NSLCC). The mean hTERT levels were 3.7 in all 76 patients, 5.87 in SCLC patients, and 3.62 in NSCLC patients. In total, 25 of 43 patients with sequential measurements had detectable levels of hTERT. The sequential exosomal hTERT mRNA levels reflected the clinical course in 23 of them. Decreases in hTERT levels were detected in 17 and 5 patients with partial and complete response, respectively. Eleven patients with a progressive disease had an increase in the level of exosomal hTERT, and seven with stable disease presented increases in its exosomal levels. Another patient who progressed on the first line of treatment and had a partial response to the second line of treatment exhibited an increase in exosomal hTERT mRNA levels during the progression and a decrease during the response. Conclusions: Exosomal hTERT mRNA levels are elevated in over half of patients with lung cancer. The potential association between hTERT levels and response to therapy suggests its utility as a promising cancer biomarker for response to therapy. This issue should be further explored in future studies.

Functional changes in children, adolescents, and young adults with cerebral palsy.

Children with multiple handicaps, including cerebral palsy (CP), often lose or regress in their functional ability through adolescence and adulthood. The purpose of this study was to examine functional and psychological changes in children, adolescents and young adults with CP. A retrospective chart review and a prospective telephone interview of 30 patients (11-29 years, M = 16.8, S.D. = 4.9) was conducted. Seventy-three percent of the patients were male (n = 22) and 83% (n = 25) had spastic CP. According to the McNemar's test, four significant functional losses were found including crawling (p = 0.03), standing independently (p = 0.05), walking with or without assistance (p = 0.014), and eating by mouth (p = 0.01). Standing function loss was significantly related to walking function loss (p = 0.02). Sixty-three percent (n = 19) of the patients experienced anxiety and 10% (n = 3) reported depression. Results of this study indicate that a validated yearly assessment tool is needed to measure functional and emotional changes in children with CP rather than relying on parent recall. This data may also lead to a review of the current physical therapy national standards.

The experience of urban aboriginals with health care services in Canada: implications for social work practice.

This exploratory study investigates the experience of Canadian Urban Aboriginal persons as consumers of health care services. Results highlight significant gaps in the training, skills, and knowledge of health care providers to optimally serve their Aboriginal patients. Also, several programs which are potentially most problematic for Aboriginal patients are identified. The discussion outlines important roles for hospital social workers in improving the care provided to urban Aboriginal patients.