BMP receptor 2 inhibition regulates mitochondrial bioenergetics to induce synergistic cell death with BCL-2 inhibitors in leukemia and NSLC cells.

Background: Bone morphogenetic protein (BMP) signaling cascade is a phylogenetically conserved stem cell regulator that is aberrantly expressed in non-small cell lung cancer (NSLC) and leukemias. BMP signaling negatively regulates mitochondrial bioenergetics in lung cancer cells. The impact of inhibiting BMP signaling on mitochondrial bioenergetics and the effect this has on the survival of NSLC and leukemia cells are not known.

Advances in epidermal growth factor receptor specific immunotherapy: lessons to be learned from armed antibodies.

The epidermal growth factor receptor (EGFR) has been recognized as an important therapeutic target in oncology. It is commonly overexpressed in a variety of solid tumors and is critically involved in cell survival, proliferation, metastasis, and angiogenesis. This multi-dimensional role of EGFR in the progression and aggressiveness of cancer, has evolved from conventional to more targeted therapeutic approaches.

Antibody-Based Immunotherapy: Alternative Approaches for the Treatment of Metastatic Melanoma.

Melanoma is the least common form of skin cancer and is associated with the highest mortality. Where melanoma is mostly unresponsive to conventional therapies (e.g.

Desensitization of metastatic melanoma cells to therapeutic treatment through repeated exposure to dacarbazine.

Aberrant anti-cancer drug efflux mediated by membrane protein ABC transporters (ABCB5 and ABCG2) is thought to characterize melanoma heterogeneous chemoresistant populations, presumed to have unlimited proliferative and self-renewal abilities. Therefore, this study primarily aimed to investigate whether continuous exposure of melanoma cells to dacarbazine (DTIC) chemotherapeutic drug enriches cultures with therapy resistant cells. Thereafter, we sought to determine whether combining the genotoxic activity of DTIC with the oxidative insults of hypericin activated photodynamic therapy (HYP-PDT) could synergized to kill heterogenous chemoresistant melanoma populations.

Effect of aqueous extracts of Ficus vogeliana Miq and Tieghemella africana Pierre in 7,12-Dimethylbenz(a)anthracene -induced skin cancer in rats.

Ethnopharmacological Relevance: Skin cancer is the most common form of cancer responsible for considerable morbidity and mortality. Tieghemella africana and Ficus vogeliana are used in traditional medicine to treat cancers.

Aim Of The Study: Therefore, the aim of this study was to investigate the antioxidant, antiangiogenic and anti-tumor activities of these plant extracts.

Antibody-Based Targeted Interventions for the Diagnosis and Treatment of Skin Cancers.

Background: Cutaneous malignancies most commonly arise from skin epidermal cells. These cancers may rapidly progress from benign to a metastatic phase. Surgical resection represents the gold standard therapeutic treatment of non-metastatic skin cancer while chemo- and/or radiotherapy are often used against metastatic tumors.

Progranulin deficiency exacerbates spinal cord injury by promoting neuroinflammation and cell apoptosis in mice.

Purpose: Spinal cord injury (SCI) often results in significant and catastrophic dysfunction and disability and imposes a huge economic burden on society. This study aimed to determine whether progranulin (PGRN) plays a role in the progressive damage following SCI and evaluate the potential for development of a PGRN derivative as a new therapeutic target in SCI.

Methods: PGRN-deficient (Gr) and wild-type (WT) littermate mice were subjected to SCI using a weight-drop technique.

Controlled JAGGED1 delivery induces human embryonic palate mesenchymal cells to form osteoblasts.

Osteoblast commitment and differentiation are controlled by multiple growth factors including members of the Notch signaling pathway. JAGGED1 is a cell surface ligand of the Notch pathway that is necessary for murine bone formation. The delivery of JAGGED1 to induce bone formation is complicated by its need to be presented in a bound form to allow for proper Notch receptor signaling.

Combined MEK inhibition and BMP2 treatment promotes osteoblast differentiation and bone healing in Nf1Osx -/- mice.

Neurofibromatosis type I (NF1) is an autosomal dominant disease with an incidence of 1/3000, caused by mutations in the NF1 gene, which encodes the RAS/GTPase-activating protein neurofibromin. Non-bone union after fracture (pseudarthrosis) in children with NF1 remains a challenging orthopedic condition to treat. Recent progress in understanding the biology of neurofibromin suggested that NF1 pseudarthrosis stems primarily from defects in the bone mesenchymal lineage and hypersensitivity of hematopoietic cells to TGFβ.

Asfotase-α improves bone growth, mineralization and strength in mouse models of neurofibromatosis type-1.

Individuals with neurofibromatosis type-1 (NF1) can manifest focal skeletal dysplasias that remain extremely difficult to treat. NF1 is caused by mutations in the NF1 gene, which encodes the RAS GTPase-activating protein neurofibromin. We report here that ablation of Nf1 in bone-forming cells leads to supraphysiologic accumulation of pyrophosphate (PPi), a strong inhibitor of hydroxyapatite formation, and that a chronic extracellular signal-regulated kinase (ERK)-dependent increase in expression of genes promoting PPi synthesis and extracellular transport, namely Enpp1 and Ank, causes this phenotype.

The ras-GTPase activity of neurofibromin restrains ERK-dependent FGFR signaling during endochondral bone formation.

The severe defects in growth plate development caused by chondrocyte extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) gain or loss-of-function suggest that tight spatial and temporal regulation of mitogen-activated protein kinase signaling is necessary to achieve harmonious growth plate elongation and structure. We provide here evidence that neurofibromin, via its Ras guanosine triphosphatase -activating activity, controls ERK1/2-dependent fibroblast growth factor receptor (FGFR) signaling in chondrocytes. We show first that neurofibromin is expressed in FGFR-positive prehypertrophic and hypertrophic chondrocytes during growth plate endochondral ossification.

Down-regulation of the expression of RB18A/MED1, a cofactor of transcription, triggers strong tumorigenic phenotype of human melanoma cells.

The RB18A/MED1 human gene, also named TRAP220, DRIP205 and PBP, encodes for a single 205 kDa component, which interacts with nuclear receptors and transcription factors. RB18A/MED1 chromosome localization on locus 17q12-q21.1 suggests its involvement in human cancers.