Circulating tumor cells (CTCs) are shed from cancerous tumors, enter the circulatory system, and migrate to distant organs to form metastases that ultimately lead to the death of most patients with cancer. Identification and characterization of CTCs provides a means to study, monitor, and potentially interfere with the metastatic process. Isolation of CTCs from blood is challenging because CTCs are rare and possess characteristics that reflect the heterogeneity of cancers. Various methods have been developed to enrich CTCs from many millions of normal blood cells. Microfluidics offers an opportunity to create a next generation of superior CTC enrichment devices. This review focuses on various microfluidic approaches that have been applied to date to capture CTCs from the blood of patients with cancer.

Background:The HER-2/neu oncogene and its p185 receptor protein are indicators of a more aggressive form of breast cancer. HER-2/neu status guides Herceptin therapy, specifically directed to the extracellular domain (ECD) of the HER-2/neu oncoprotein. The HER-2/neu ECD is shed from cancer cells into the circulation and is measurable by immunoassay. Methods: We performed a systematic review of the peer-reviewed literature on circulating ECD with respect to prevalence, prognosis, prediction of response to therapy, and monitoring of breast cancer. Results: The prevalence of increased ECD in patients with primary breast cancer varied between 0% and 38% (mean, 18.5%), whereas in metastatic disease the range was from 23% to 80% (mean, 43%). Some women with HER-2/neu-negative tumors by tissue testing develop increased ECD concentrations in metastatic disease. Increased ECD has been correlated with indicators of poor prognosis, e.g., overall survival and disease-free survival. Increased ECD predicts a poor response to hormone therapy and some chemotherapy regimens but can predict improved response to combinations of Her-

Patients with ER(+) and serum HER-2/neu-positive metastatic breast cancer are less likely to respond to hormone treatment and have a shorter duration of response than ER(+) and serum HER-2/neu-negative patients. Their survival duration is also shorter.

Pretreatment circulating NRP levels predict a low likelihood of benefit from HT, specifically DRO, in patients with estrogen receptor (ER)-positive and/or progesterone receptor (PgR)-positive or receptor-unknown metastatic breast cancer, even when adjusted for other known predictive factors, such as ER and/or PgR levels, site of disease, disease-free interval from primary treatment to recurrence, and prior adjuvant chemotherapy. These data suggest that pretreatment NRP levels may be useful in deciding whether to treat a patient who otherwise appears to be likely to respond to HT.

Patients with normal serum HER-2/neu receiving letrozole demonstrated a significantly greater ORR and CB and longer TTP and TTF than patients receiving tamoxifen. Although in patients with elevated serum HER-2/neu there was no significant difference between letrozole and tamoxifen in ORR or CB, there was a strong trend favoring longer TTP and significantly longer TTF with letrozole.

We report on two patients with advanced Parkinson's disease who were exhibiting a peculiar and stereotyped behavior characterized by an irrepressible need to sing compulsively when under high‐dose dopamine replacement therapy. Sharing many features with punding, this singing behavior is proposed as a distinct manifestation of the dopamine dysregulation syndrome in Parkinson's disease. Ann Neurol 2007

During acute cytomegaloviral (CMV) mononucleosis, mononuclear leukocytes displayed diminished responsiveness to certain mitogens. Responses to phytohemagglutinin were normal in patients with community-acquired CMV illness but were reduced in patients with transfusion-associated infection. Both groups were hyporesponsive to pokeweek mitogen and concanavalin A. Cells from convalescent CMV mononucleosis patients responded as well as cells from normal donors to the three mitogens. Preculture of cells from patients with acute CMV mononucleosis for up to seven days before addition of concanavalin A greatly enhanced the blastogenic response to that mitogen. The effect was increased further by depletion of adherent cells after preculture for seven days and could be markedly reduced by the addition of fresh, autologous adherent cells to the precultured nonadherent cells. Suppressor activity was not observed in the serum of patients with acute CMV mononucleosis. These studies suggest that mitogen hyporesponsiveness in CMV mononucleosis may be mediated by suppressor cells included among the plastic-adherent mononuclear leukocyte population.

Virus-monocyte interactions were evaluated in patients with mononucleosis due to cytomegalovirus (CMV). Group 1 patients studied about two weeks after the onset of symptoms had lymphocyte responses to concanavalin A (con A) that were maximally suppressed and unaffected by in vitro culture or reconstitution with monocytes. Lymphocytes from group 2 patients studied about three weeks after the onset of symptoms had less markedly suppressed responses, which were reversed by in vitro culture or by reconstitution with monocytes. Monocyte depletion resulted in a marked diminution of fresh lymphocyte responses of group 2 patients but not of group 1 patients. CMV was isolated from blood monocytes of four patients with mononucleosis; intact, infected monocytes were capable of suppressing responses of cultured autologous lymphocytes to con A. Monocytes from uninfected control donors were infected in vitro with CMV and evaluated for the induction of suppressor activity. CMV-infected monocytes were significantly more suppressive for autologous lymphocyte responses to con A than were uninfected monocytes.