Teaming Up for Trouble: Cancer Cells, Transforming Growth Factor-β1 Signaling and the Epigenetic Corruption of Stromal Naïve Fibroblasts.

It is well recognized that cancer cells subvert the phenotype of stromal naïve fibroblasts and instruct the neighboring cells to sustain their growth agenda. The mechanisms underpinning the switch of fibroblasts to cancer-associated fibroblasts (CAFs) are the focus of intense investigation. One of the most significant hallmarks of the biological identity of CAFs is that their tumor-promoting phenotype is stably maintained during in vitro and ex vivo propagation without the continual interaction with the adjacent cancer cells.

Vitamin D and Myofibroblasts in Fibrosis and Cancer: At Cross-purposes with TGF-β/SMAD Signaling.

The multifaceted involvement of the active vitamin D metabolite 1,25-dihydroxyvitamin D (henceforth referred to by the synonyms 1,25(OH)D, calcitriol or vitamin D) in blunting the growth of cancer cells is amply recognized. In this review we focused our attention on the cross-talk between 1,25 (OH)D and the tumor microenvironment (TME), signaling out stromal cancer-associated fibroblasts (CAFs), the most abundant TME population, as a target for calcitriol anticancer action. In view of the commonality of the phenotypic signature in myofibroblasts, resident in the cancer stroma and in non-neoplastic fibrotic loci, we examined modes of action of vitamin D in non-neoplastic chronic diseases and in cancer to assess mechanistic similarities and divergences.

Sodium valproate, a histone deacetylase inhibitor, enhances the efficacy of vinorelbine-cisplatin-based chemoradiation in non-small cell lung cancer cells.

Aim: To enhance the anticancer activity of vinorelbine, cisplatin and ionizing radiation (IR) combination against non-small cell lung cancer (NSCLC) cells by co-administration of sodium valproate (VPA), a histone deacetylase inhibitor, and to elucidate molecular events underpinning treatment efficacy.

Materials And Methods: The NSCLC A549 cell line was treated with cisplatin (0.2 μg/ml), vinorelbine (2 nM), VPA (1 mM) and IR (2.

Association between bone mineral density and incidence of breast cancer.

Introduction: Previous studies have suggested an inverse relationship between bone mineral density (BMD) and breast cancer incidence. The primary objective of this study was to assess whether BMD is associated with risk of subsequent breast cancer occurrence in the female population of southern Israel.

Methods: The electronic medical charts of women who underwent BMD at the Soroka Medical Center (SMC) between February 2003 and March 2011 were screened for subsequent breast cancer diagnoses.

Increased vitamin D serum levels correlate with clinical improvement of rheumatic diseases after Dead Sea climatotherapy.

Background: Ultraviolet B (UVB) rays are required by the skin for the production of vitamin D. The intensity of UVB at the Dead Sea area is the lowest in the world. Low vitamin D levels are often associated with musculoskeletal symptoms.

A combined pretreatment of 1,25-dihydroxyvitamin D3 and sodium valproate enhances the damaging effect of ionizing radiation on prostate cancer cells.

Radiotherapy is one of the curative treatment options for prostate cancer (PCa). However, effective doses of ionizing radiation (IR) have a high risk of side effects. To increase sensitivity of PCa to IR we pretreated human androgen-refractory DU145 PCa cells with a combination of sodium valproate (VPA), a well-tolerated drug with histone deacetylases inhibiting activity, and 1,25-dihydroxyvitamin D3, 1,25(OH)2D3, the active metabolite of vitamin D, a well known anticancer agent.

Serum 25-OH vitamin D levels in patients with fibromyalgia.

Background: The association between low levels of 25-hydroxyvitamin D and non-specific musculoskeletal pain, including fibromyalgia syndrome, is controversial. Several studies have reported a "positive association" and two others found "no association."

Objectives: To test levels of 25OHD in patients with fibromyalgia syndrome and in matched controls.

Nutritional status in relation to balance and falls in the elderly: a preliminary look at serum folate.

Background/aim: In elderly persons, fall-related injury is a serious public health problem. We investigated the impact of essential nutritional elements on falls in the elderly.

Methods: Clinical function, balance, gait and disability tests and health and nutritional status assessments were performed.

Efficient dual treatment of the hormone-refractory prostate cancer cell line DU145 with cetuximab and 1,25-dihydroxyvitamin D3.

Background: Targeting of the epidermal growth factor receptor (EGFR) pathway is a promising treatment strategy for aggressive androgen-refractory prostate cancer (PCa). The effect of treating the androgen-resistant PCa cell line DU145 with a combination of the anti-EGFR drug cetuximab and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) was evaluated.

Materials And Methods: DU145 cells were treated with 5 nM cetuximab, 100 nM 1,25(OH)2D3 or a combination of both.

The anti-inflammatory activity of 1,25-dihydroxyvitamin D3 in macrophages.

In a previous study we demonstrated a down-regulatory effect of vitamin D active metabolite (1,25(OH)(2)D(3)) and its vitamin D(2) analog (1,24(OH)(2)D(2)) on TNFalpha expression in macrophages. We also found an inhibitory effect in the physiological concentration (10(-10)M) of 1,25(OH)(2)D(3) which was dose-dependent. This down-regulation, caused by the decrease in NFkappaB activity by 1,25(OH)(2)D(3) and 1,24(OH)(2)D(2), was demonstrated in P388D1 cells transfected with NFkappaB reporter gene (p NFkappaB-Luc) and by EMSA.

Vitamin D decreases NFkappaB activity by increasing IkappaBalpha levels.

Background: In a previous study we demonstrated the inhibitory effect of 1,25-dihydroxyvitamin D (1,25(OH)(2)D(3)) and its less calcaemic analog 1,24(OH)(2)D(2) on the production of tumour necrosis factor alpha (TNFalpha) by human peritoneal macrophages. The aim of the present study is to examine whether this vitamin D inhibition of TNFalpha is mediated by its major transcription factor, nuclear factor-kappaB (NFkappaB).

Methods: Murine macrophage cells (P388D1) were incubated with 10(-7) M 1,25(OH)(2)D(3) or 1,24(OH)(2)D(2) and then stimulated with lipopolysaccharide.

The combined treatment of 1,25-dihydroxyvitamin D3 and a non-steroid anti-inflammatory drug is highly effective in suppressing prostate cancer cell line (LNCaP) growth.

Background: The active metabolite of vitamin D3, 1,25(OH)2D3, is known to possess anti-proliferative and pro-differentiative activities in prostate cancer (PCa) cells. However, its clinical use is limited because of the risk of hypercalcemia. Concurrent administration of lower doses of 1,25(OH)2D3 together with other anticancer drugs may help to overcome this obstacle and lead to an effective and tolerable therapy.

Novel role of 1,25(OH)(2)D(3) in induction of erythroid progenitor cell proliferation.

Objective: Burst-forming unit erythroid and colony-forming unit erythroid growth in vitro is lower in studies of continuous ambulatory peritoneal dialysis patients than healthy controls. Burst-forming unit erythroid growth was potentiated by addition of 1alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] and normalized by erythropoietin (Epo) therapy, suggesting an interaction between Epo and 1,25(OH)(2)D(3) at the stem cell level. The objective of this study was to determine the mechanism by which 1,25(OH)(2)D(3) enhances the stimulatory effect of Epo on the growth of erythroid precursor cells.

Usefulness of lipoprotein changes during acute coronary syndromes for predicting postdischarge lipoprotein levels.

The aim of our study was to evaluate the lipoprotein changes that occur during acute coronary events, and to determine the lipoprotein threshold levels that identify patients who require future statin therapy. Lipoprotein levels were measured at admission, at 6 hours, the morning after admission, before discharge, and 3 months after discharge in patients with myocardial infarction and unstable angina. Patients with myocardial infarction on thrombolytic therapy (n = 63) and patients with unstable angina (n = 33) had a decrease in low-density lipoprotein (LDL) cholesterol levels < or = 24 hours after admission (-12 +/- 20% and -6 +/- 23%, respectively), but these levels returned to baseline before discharge.