Culture and isolation of melanoma-initiating cells.

Melanoma is the most aggressive skin cancer. This unit illustrates protocols for culture and isolation of human melanoma cancer stem cells/tumor-initiating cells (CSC/TIC). We describe two complementary methods to enrich for melanoma CSC/TIC.

Hedgehog-GLI signaling drives self-renewal and tumorigenicity of human melanoma-initiating cells.

The question of whether cancer stem/tumor-initiating cells (CSC/TIC) exist in human melanomas has arisen in the last few years. Here, we have used nonadherent spheres and the aldehyde dehydrogenase (ALDH) enzymatic activity to enrich for CSC/TIC in a collection of human melanomas obtained from a broad spectrum of sites and stages. We find that melanomaspheres display extensive in vitro self-renewal ability and sustain tumor growth in vivo, generating human melanoma xenografts that recapitulate the phenotypic composition of the parental tumor.

Targeting EGFR/HER2 pathways enhances the antiproliferative effect of gemcitabine in biliary tract and gallbladder carcinomas.

Background: Advanced biliary tract carcinomas (BTCs) have poor prognosis and limited therapeutic options. Therefore, it is crucial to combine standard therapies with molecular targeting. In this study EGFR, HER2, and their molecular transducers were analysed in terms of mutations, amplifications and over-expression in a BTC case series.

Sema4C-Plexin B2 signalling modulates ureteric branching in developing kidney.

Semaphorins, originally identified as axon guidance molecules, have also been implicated in angiogenesis, function of the immune system and cancerous growth. Here we show that deletion of Plexin B2 (Plxnb2), a semaphorin receptor that is expressed both in the pretubular aggregates and the ureteric epithelium in the developing kidney, results in renal hypoplasia and occasional double ureters. The rate of cell proliferation in the ureteric epithelium and consequently the number of ureteric tips are reduced in the kidneys lacking Plexin B2 (Plxnb2-/-).

Structure and function of the intracellular region of the plexin-b1 transmembrane receptor.

Members of the plexin family are unique transmembrane receptors in that they interact directly with Rho family small GTPases; moreover, they contain a GTPase-activating protein (GAP) domain for R-Ras, which is crucial for plexin-mediated regulation of cell motility. However, the functional role and structural basis of the interactions between the different intracellular domains of plexins remained unclear. Here we present the 2.

Novel mutations in CYP11B1 gene leading to 11 beta-hydroxylase deficiency in Brazilian patients.

Background: Deficiency of 11 beta-hydroxylase results in the impairment of the last step of cortisol synthesis. In females, the phenotype of this disorder includes different degrees of genital ambiguity and arterial hypertension. Mutations in the CYP11B1 gene are responsible for this disease.

Molecular profiling of the "plexinome" in melanoma and pancreatic cancer.

Plexins are transmembrane high-affinity receptors for semaphorins, regulating cell guidance, motility, and invasion. Functional evidences implicate semaphorin signals in cancer progression and metastasis. Yet, it is largely unknown whether plexin genes are genetically altered in human tumors.

Semaphorin 4D regulates gonadotropin hormone-releasing hormone-1 neuronal migration through PlexinB1-Met complex.

In mammals, reproduction is dependent on specific neurons secreting the neuropeptide gonadotropin hormone-releasing hormone-1 (GnRH-1). These cells originate during embryonic development in the olfactory placode and migrate into the forebrain, where they become integral members of the hypothalamic-pituitary-gonadal axis. This migratory process is regulated by a wide range of guidance cues, which allow GnRH-1 cells to travel over long distances to reach their appropriate destinations.

Plexin-B2, but not Plexin-B1, critically modulates neuronal migration and patterning of the developing nervous system in vivo.

Semaphorins and their receptors, plexins, have emerged as important cellular cues regulating key developmental processes. B-type plexins directly regulate the actin cytoskeleton in a variety of cell types. Recently, B-type plexins have been shown to be expressed in striking patterns in the nervous system over critical developmental windows.

Plexin-B1 plays a redundant role during mouse development and in tumour angiogenesis.

Background: Plexins are a large family of transmembrane receptors for the Semaphorins, known for their role in the assembly of neural circuitry. More recently, Plexins have been implicated in diverse biological functions, including vascular growth, epithelial tissue morphogenesis and tumour development. In particular, PlexinB1, the receptor for Sema4D, has been suggested to play a role in neural development and in tumour angiogenesis, based on in vitro studies.

[11beta-hydroxylase deficiency].

Congenital adrenal hyperplasia due to 11beta-hydroxylase enzyme deficiency is a result of the impairment of 11-deoxycortisol to cortisol conversion. In general, it is responsible for less than 5% of the congenital adrenal hyperplasia cases. The clinical expression of androgen excess in females includes several degrees of genital ambiguity, varying from clitoromegaly to complete virilization.