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We studied the genetic pattern of inheritance of the ratio between circulating CD4+ and CD8+ T lymphocytes in a population of healthy donors. The distribution of the CD4/CD8 ratio in males and females was significantly different and was significantly affected by age. In 46 randomly selected families, the parental CD4/CD8 ratio significantly influenced the ratio in offspring. Complex segregation analysis of the data rejected the non-genetic hypothesis; among the genetic models tested, a major recessive gene with a polygenic component and random environmental effects was the most parsimonious model. These findings indicate that the ratio of CD4+ and CD8+ T cells is genetically controlled in humans.

The clinical use of circulating tumor cells (CTCs) enumeration for staging of metastatic breast The clinical use of circulating tumor cells (CTCs) enumeration for staging of metastatic breast cancer (MBC): International expert consensus paper.

Purpose: This study aimed to detect the M30 neoepitope on circulating tumor cells (CTC) as a tool for quantifying apoptotic CTC throughout disease course and treatment.Experimental Design: An automated sample preparation and analysis platform for computing CTC (CellSearch) was integrated with a monoclonal antibody (M30) targeting a neoepitope disclosed by caspase cleavage at cytokeratin 18 (CK18) in early apoptosis. The assay was validated using cell lines and blood samples from healthy volunteers and patients with epithelial cancer.Results: M30-positive CTC could be detected in >70% of CTC-positive carcinoma patients, which were free for both chemotherapy and radiologic treatments. The fraction of M30-positive CTC varied from 50% to 80%, depending on the histotype. To investigate the potential application of the M30 CTC assay for the evaluation of response in early phase trials, CTC and M30-positive CTC were enumerated in a small case series of breast cancer patients during treatment. Results indicate that changes in the balance of M30-negative/positive CTC may be used as a dynamic parameter indicating an active disease, as documented by consistent radiologic findings.Conclusions: M30 expression on CTC is detectable by immunofluorescence. The M30-integrated test has potential for monitoring dynamic changes in the quote of apoptotic CTC (in addition to CTC count) to evaluate response in clinical trials of molecularly targeted anticancer therapeutics as well as for translational research, in which there is a pressing need for informative circulating biomarkers.Clin Cancer Res; 16(21); 5233-43. ©2010 AACR.The finding of tumor cells in peripheral blood raises questions as to their metastatic potential. In fact, notwithstanding that a single tumor cell was proved to sustain metastasis in vivo (1), in humans the half-life of circulating tumor cells (CTC) in peripheral blood is estimated at between 1 and 2.4 hours, depending on the mathematical model of the extrapolated curve (2) and on the fact that apoptotic cells significantly contribute to the CTC fraction in breast (3) and prostate cancer (4) patients. On the other hand, a strict correlation was established between CTC count and prognosis (5), and elevated numbers of CTC at any time during therapy was reported to be an accurate indication of subsequent rapid progression and mortality (6). Nevertheless, the phenotypic and biological properties of the CTC that are necessary for the metastatic process are far from clear. Theoretically, CTC should be adapted to shed into peripheral blood and at least some of the CTC should be live cells. Moreover, although the metastatic phenotype may be later acquired as a result of selective pressure exerted at secondary sites, at least some of the CTC should be able to self-renew (7).Addressing the role and mechanism of CTC in the development of metastasis, we investigated whether or not CTC are live cells, considering mainly when and how often the percentage of apoptotic CTC changes throughout disease course and treatment...