Circulating tumor cell counts are prognostic of overall survival in SWOG S0421: a phase III trial of docetaxel with or without atrasentan for metastatic castration-resistant prostate cancer.

Purpose: Circulating tumor cell (CTC) enumeration has not been prospectively validated in standard first-line docetaxel treatment for metastatic castration-resistant prostate cancer. We assessed the prognostic value of CTCs for overall survival (OS) and disease response in S0421, a phase III trial of docetaxel plus prednisone with or without atrasentan.

Patients And Methods: CTCs were enumerated at baseline (day 0) and before cycle two (day 21) using CellSearch.

Could hypoxia increase the prevalence of thrombotic complications in polycythemia vera?

Thromboses represent a major cause of morbidity and mortality in polycythemia vera but the contributing mechanisms are not fully described. To evaluate whether environmental conditions such as altitude/hypoxia could impact thrombosis history, we retrospectively analyzed thrombosis history in 71 polycythemia vera patients living at an elevation of 5000 feet or more in the Salt Lake City (SLC) area and 166 polycythemia vera patients living near sea level in the Baltimore (BLM) area. The SLC cohort was older with a longer disease duration.

Mechanisms of thrombosis in paraproteinemias: the effects of immunomodulatory drugs.

The introduction of immunomodulatory drugs (IMiDs) has improved clinical outcome in patients with multiple myeloma (MM). However, their use has been associated with a higher risk of cardiovascular complications. The use of IMiDs with dexamethasone, chemotherapy, or in combination with erythropoietic agents enhances the risk of venous thromboembolism (VTE) up to 25%.

Pharmacological targeting of the thrombomodulin-activated protein C pathway mitigates radiation toxicity.

Tissue damage induced by ionizing radiation in the hematopoietic and gastrointestinal systems is the major cause of lethality in radiological emergency scenarios and underlies some deleterious side effects in patients undergoing radiation therapy. The identification of target-specific interventions that confer radiomitigating activity is an unmet challenge. Here we identify the thrombomodulin (Thbd)-activated protein C (aPC) pathway as a new mechanism for the mitigation of total body irradiation (TBI)-induced mortality.

Inhibition of protease-activated receptor 1 ameliorates intestinal radiation mucositis in a preclinical rat model.

Purpose: To determine, using a specific small-molecule inhibitor of protease-activated receptor 1 (PAR1) signaling, whether the beneficial effect of thrombin inhibition on radiation enteropathy development is due to inhibition of blood clotting or to cellular (PAR1-mediated) thrombin effects.

Methods And Materials: Rats underwent fractionated X-irradiation (5 Gy×9) of a 4-cm small-bowel segment. Early radiation toxicity was evaluated in rats receiving PAR1 inhibitor (SCH602539, 0, 10, or 15 mg/kg/d) from 1 day before to 2 weeks after the end of irradiation.

Procalcitonin as a predictive biomarker for total body irradiation-induced bacterial load and lethality in mice.

Sepsis is the leading cause of mortality in intensive care units. Early detection and intervention are critical to prevent death. The acute radiation syndrome is characterized by damage of the gastrointestinal and hematopoietic systems.

Isolation, characterization, and in vitro propagation of infantile hemangioma stem cells and an in vivo mouse model.

Background: Infantile hemangiomas (IH) are the most common benign tumors of infancy. The typical clinical course consists of rapid growth during the first year of life, followed by natural and gradual involution over a multi-year time span through unknown cellular mechanisms. Some tumors respond to medical treatment with corticosteroids or beta-blockers, however, when this therapy fails or is incomplete, surgical extirpation may be necessary.

Enhanced self-renewal of hematopoietic stem/progenitor cells mediated by the stem cell gene Sall4.

Background: Sall4 is a key factor for the maintenance of pluripotency and self-renewal of embryonic stem cells (ESCs). Our previous studies have shown that Sall4 is a robust stimulator for human hematopoietic stem and progenitor cell (HSC/HPC) expansion. The purpose of the current study is to further evaluate how Sall4 may affect HSC/HPC activities in a murine system.

Comparison of circulating MicroRNA 141 to circulating tumor cells, lactate dehydrogenase, and prostate-specific antigen for determining treatment response in patients with metastatic prostate cancer.

Our aim was to determine the utility of circulating micro RNA miR-141 as a potential biomarker of therapeutic response in prostate cancer (CaP) patients. We compared the values of miR-141 in plasma of 21 CaP patients to the levels of prostate specific antigen (PSA), circulating tumor cells (CTC) and lactate dehydrogenase (LDH). Data suggest a strong correlation of miR-141 values and clinical course.

Circulating tumor cells as a predictive biomarker in patients with hormone-sensitive prostate cancer.

Unlabelled: Little information exists regarding the utility circulating tumor cell (CTC) enumeration in hormone sensitive prostate cancer. We enumerated CTC in 33 consecutive patients undergoing androgren deprivation therapy (ADT) at our institution. Multivariate analysis revealed baseline CTC as the only independent predictor of progression to CRPC.

Epithelial to mesenchymal transition (EMT) induced by bleomycin or TFG(b1)/EGF in murine induced pluripotent stem cell-derived alveolar Type II-like cells.

Induced pluripotent stem (iPS) cells are derived from reprogrammed somatic cells and are similar to embryonic stem (ES) cells in morphology, gene/protein expression, and pluripotency. In this study, we explored the potential of iPS cells to differentiate into alveolar Type II (ATII)-like epithelial cells. Analysis using quantitative real time polymerase chain reaction and immunofluorescence staining showed that pulmonary surfactant proteins commonly expressed by ATII cells such as surfactant protein A (SPA), surfactant protein B (SPB), and surfactant protein C (SPC) were upregulated in the differentiated cells.

Low venous thromboembolic risk with bortezomib in multiple myeloma and potential protective effect with thalidomide/lenalidomide-based therapy: review of data from phase 3 trials and studies of novel combination regimens.

Patients with multiple myeloma (MM) are at elevated risk of venous thromboembolism (VTE), specifically deep vein thrombosis (DVT) and pulmonary embolism (PE). VTE risk in MM is increased by various patient- and disease-related factors. The type of anti-MM therapy represents a key factor, with a substantially elevated VTE risk in patients treated with the immunomodulatory drugs (IMiDs) thalidomide or lenalidomide in combination with dexamethasone and/or chemotherapy; VTE risk with lenalidomide-dexamethasone is further increased with concomitant erythropoietin.

Activated protein C resistance as measured by residual factor V after Russell's viper venom and activated protein C treatment analyzed as a continuous variable in multiple myeloma and normal controls.

Increased risk of venous thromboembolism (VTE) has been described in multiple myeloma patients, particularly when exposed to immunomodulatory drugs. Epidemiological studies have shown that monoclonal gammopathy of undetermined significance (MGUS) patients also have an increased risk of VTE compared with normal individuals. Acquired activated protein C resistance (APC-R) is an independent risk factor for VTE in hematologic malignancies.

Increases in quantitative D-dimer levels correlate with progressive disease better than circulating tumor cell counts in patients with refractory prostate cancer.

Changes in quantitative D-dimer levels, circulating tumor cell (CTC) counts, and prostate-specific antigen (PSA) levels were measured in 28 patients with refractory castration-resistant prostate cancer to assess their concordance during the course of therapy and their relationship with risk of progressive disease. A significant correlation was identified between changes in PSA and both CTC counts and D-dimer levels (r = 0.67 and 0.

Reversal of hyperglycemia in diabetic mouse models using induced-pluripotent stem (iPS)-derived pancreatic beta-like cells.

Diabetes mellitus is characterized by either the inability to produce insulin (type 1 diabetes) or as insensitivity to insulin secreted by the body (type 2 diabetes). In either case, the body is unable to move blood glucose efficiently across cell membranes to be used. This leads to a variety of local and systemic detrimental effects.

Racial disparities in prescriptions for cardioprotective drugs and cardiac outcomes in Veterans Affairs Hospitals.

Previous reports have suggested that blacks receive life-saving cardioprotective therapies less often than whites, probably because of a lower socioeconomic status, which leads to poor access to physicians. We questioned whether racial disparity existed in the Veterans Affairs Healthcare System. We examined the Veterans' Integrated Service Network (VISN 16) database with regard to the prescription rates for 4 cardiovascular agents-aspirin, beta blockers, statins, and angiotensin-converting enzyme inhibitors.

Generation of murine hepatic lineage cells from induced pluripotent stem cells.

Induced pluripotent stem (iPS) cells can be generated from somatic cells of individuals by retrodifferentiation using defined transcription factors. Similar to embryonic stem (ES) cells, iPS cells can be differentiated into a variety of specific cell types. However, to date, no detailed hepatic differentiation of mouse iPS cells has been reported.

Dramatically elevated circulating tumor cell numbers in a patient with small cell neuroendocrine carcinoma of the prostate.

Detection of circulating tumor cells in whole blood is a useful prognostic tool for patients with castration-resistant prostate cancer, as well as for patients with metastatic breast cancer and colorectal carcinoma. In this report, we present the case of a patient with neuroendocrine small cell prostate cancer with normal prostate-specific antigen levels throughout the course of disease but who had markedly elevated circulating tumor cells, as detected with the CellSearch (Veridex) system.

Survival effect of venous thromboembolism in patients with multiple myeloma treated with lenalidomide and high-dose dexamethasone.

PURPOSE We conducted a retrospective analysis of the survival effect of venous thromboembolism (VTE) development in patients with multiple myeloma (MM). METHODS Two identically designed, multicenter, double-blind, phase III clinical trials (MM-009 and MM-010) were conducted in Europe and the United States to assess the effect of lenalidomide in combination with dexamethasone versus dexamethasone plus placebo in patients with relapsed or refractory MM, after failing at least one prior line of treatment. In this retrospective analysis, we evaluated incidence and survival effect of thromboembolism in 353 patients randomly assigned to receive 25 mg of lenalidomide on days 1 through 21 of a 28-day cycle, plus 40 mg of oral dexamethasone on days 1 through 4, 9 through 12, and 17 through 20 for the first four cycles; after the fourth cycle, 40 mg of dexamethasone was administered on days 1 through 4 only.

Generation and characterization of functional cardiomyocytes using induced pluripotent stem cells derived from human fibroblasts.

We have successfully developed both spontaneous and inductive cardiomyocyte differentiation of iPS cells reprogrammed from human foreskin fibroblasts. The reprogrammed iPS cells morphologically resemble human cardiomyocytes which can beat. RT-PCR and immunostaining show that cardiac markers are expressed that are comparable to the differentiation pattern of authentic human embryonic stem cells, indicating the existence of both immature and mature differentiated cardiomyocytes.

Thrombotic events in patients with cancer receiving antiangiogenesis agents.

Tumor-associated neoangiogenesis has recently become a suitable target for antineoplastic drug development. In this overview, we discuss specific drug-associated hemostatic complications, the already known pathogenetic mechanisms involved, and the effect of varying antithrombotic strategies. Multiple agents with angiogenic inhibitory capacity (thalidomide, lenalidomide, bevacizumab, sunitinib, sorafenib, and sirolimus) have obtained US Food and Drug Administration approval, and many others have entered clinical trials.

Circulating tumor cells in patients with castration-resistant prostate cancer baseline values and correlation with prognostic factors.

Purpose: Circulating tumor cells (CTC) have been recently accepted by the Food and Drug Administration of the United States as a prognostic tool in advanced prostate cancer. However, a number of questions remain about the use of the test. The optimal clinical cut-off has never been determined.

Hypercoagulable states in patients with multiple myeloma can affect the thalidomide-associated venous thromboembolism.

The therapeutic use of thalidomide in patients with multiple myeloma is often complicated by the development of venous thromboembolism. The objective of the present study was to identify hypercoagulable states associated with development of venous thromboembolism in thalidomide-treated multiple myeloma patients. We screened 49 consecutive multiple myeloma patients treated with thalidomide at baseline for hypercoagulability.