Bleomycin Electrochemotherapy of Dermal Cylindroma as an Alternative Treatment in a Rare Adnexal Neoplasm: A Case Report and Literature Review.

Background: Brooke-Spiegler syndrome is a rare autosomal dominant disorder characterized by the continuous development of multiple benign skin appendage tumors. It is treated usually by repeated standard surgery. Here, we present a case study where electrochemotherapy (ECT) with bleomycin was used as an effective alternative approach in treating advanced dermal cylindromatosis of the head and neck in a patient with Brooke-Spiegler syndrome.

Bleomycin electrosclerotherapy (BEST) for the treatment of vascular malformations. An International Network for Sharing Practices on Electrochemotherapy (InspECT) study group report.

Background: Biomedical applications of electroporation are expanding out of the field of oncology into vaccination, treatment of arrhythmias and now in the treatment of vascular malformations. Bleomycin is a widely used sclerosing agent in the treatment of various vascular malformations. The application of electric pulses in addition to bleomycin enhances the effectiveness of the drug, as demonstrated by electrochemotherapy, which utilizes bleomycin in the treatment of tumors.

Electrochemotherapy for the management of cutaneous and subcutaneous metastasis: a series of 39 patients treated with palliative intent.

Background And Objectives: Electrochemotherapy (ECT) is technique for local control of skin metastasis. This study is primarily aimed at assessing the clinical activity of ECT in a prospective cohort of patients, and evaluating the association between primary tumor histology, number of metastatic lesions and size of tumor deposits and objective response rate.

Methods And Results: Thirty-nine patients with skin metastases from melanoma and other tumors underwent intravenous bleomycin ECT with palliative intent.

Norepinephrine reuptake inhibition promotes mobilization in mice: potential impact to rescue low stem cell yields.

The mechanisms mediating hematopoietic stem and progenitor cell (HSPC) mobilization by G-CSF are complex. We have found previously that G-CSF-enforced mobilization is controlled by peripheral sympathetic nerves via norepinephrine (NE) signaling. In the present study, we show that G-CSF likely alters sympathetic tone directly and that methods to increase adrenergic activity in the BM microenvironment enhance progenitor mobilization.

Rapid mobilization of hematopoietic progenitors by AMD3100 and catecholamines is mediated by CXCR4-dependent SDF-1 release from bone marrow stromal cells.

Steady-state egress of hematopoietic progenitor cells can be rapidly amplified by mobilizing agents such as AMD3100, the mechanism, however, is poorly understood. We report that AMD3100 increased the homeostatic release of the chemokine stromal cell derived factor-1 (SDF-1) to the circulation in mice and non-human primates. Neutralizing antibodies against CXCR4 or SDF-1 inhibited both steady state and AMD3100-induced SDF-1 release and reduced egress of murine progenitor cells over mature leukocytes.

Bone marrow CD169+ macrophages promote the retention of hematopoietic stem and progenitor cells in the mesenchymal stem cell niche.

Hematopoietic stem cells (HSCs) reside in specialized bone marrow (BM) niches regulated by the sympathetic nervous system (SNS). Here, we have examined whether mononuclear phagocytes modulate the HSC niche. We defined three populations of BM mononuclear phagocytes that include Gr-1(hi) monocytes (MOs), Gr-1(lo) MOs, and macrophages (MΦ) based on differential expression of Gr-1, CD115, F4/80, and CD169.

Cooperation of beta(2)- and beta(3)-adrenergic receptors in hematopoietic progenitor cell mobilization.

CXCL12/SDF-1 dynamically regulates hematopoietic stem cell (HSC) attraction in the bone marrow (BM). Circadian regulation of bone formation and HSC traffic is relayed in bone and BM by beta-adrenergic receptors (beta-AR) expressed on HSCs, osteoblasts, and mesenchymal stem/progenitor cells. Circadian HSC release from the BM follows rhythmic secretion of norepinephrine from nerve terminals, beta(3)-AR activation, and Cxcl12 downregulation, possibly from reduced Sp1 nuclear content.

Mobilized hematopoietic stem cell yield depends on species-specific circadian timing.

Endogenous rhythmicity likely evolved as a mechanism allowing organisms to anticipate predictable daily changes in the environment (Rutter et al., 2002). Under homeostasis, murine hematopoietic stem cell (HSC) egress is orchestrated by rhythmic beta 3 adrenergic signals delivered by the sympathetic nervous system (SNS) that regulate Cxcl12 expression in stromal cells (Mendez-Ferrer et al.

Haematopoietic stem cell release is regulated by circadian oscillations.

Haematopoietic stem cells (HSCs) circulate in the bloodstream under steady-state conditions, but the mechanisms controlling their physiological trafficking are unknown. Here we show that circulating HSCs and their progenitors exhibit robust circadian fluctuations, peaking 5 h after the initiation of light and reaching a nadir 5 h after darkness. Circadian oscillations are markedly altered when mice are subjected to continuous light or to a 'jet lag' (defined as a shift of 12 h).

Signals from the sympathetic nervous system regulate hematopoietic stem cell egress from bone marrow.

Hematopoietic stem and progenitor cells (HSPC), attracted by the chemokine CXCL12, reside in specific niches in the bone marrow (BM). HSPC migration out of the BM is a critical process that underlies modern clinical stem cell transplantation. Here we demonstrate that enforced HSPC egress from BM niches depends critically on the nervous system.

Muscle-specific interaction of caveolin isoforms: differential complex formation between caveolins in fibroblastic vs. muscle cells.

It is generally well accepted that caveolin-3 expression is muscle specific, whereas caveolin-1 and -2 are coexpressed in a variety of cell types, including adipocytes, endothelial cells, epithelial cells, and fibroblasts. Caveolin-1 and -2 are known to form functional hetero-oligomeric complexes in cells where they are coexpressed, whereas caveolin-3 forms homo-oligomeric high molecular mass complexes. Although caveolin-2 might be expected to interact in a similar manner with caveolin-3, most studies indicate that this is not the case.

Intracellular retention of glycosylphosphatidyl inositol-linked proteins in caveolin-deficient cells.

The relationship between glycosylphosphatidyl inositol (GPI)-linked proteins and caveolins remains controversial. Here, we derived fibroblasts from Cav-1 null mouse embryos to study the behavior of GPI-linked proteins in the absence of caveolins. These cells lack morphological caveolae, do not express caveolin-1, and show a approximately 95% down-regulation in caveolin-2 expression; these cells also do not express caveolin-3, a muscle-specific caveolin family member.

Caveolin-2-deficient mice show evidence of severe pulmonary dysfunction without disruption of caveolae.

Caveolin-2 is a member of the caveolin gene family with no known function. Although caveolin-2 is coexpressed and heterooligomerizes with caveolin-1 in many cell types (most notably adipocytes and endothelial cells), caveolin-2 has traditionally been considered the dispensable structural partner of the widely studied caveolin-1. We now directly address the functional significance of caveolin-2 by genetically targeting the caveolin-2 locus (Cav-2) in mice.