Predictive value of VEGF gene polymorphisms for metastatic colorectal cancer patients receiving first-line treatment including fluorouracil, irinotecan, and bevacizumab

The aim of this study is to evaluate the influence of germline vascular endothelial growth factor (VEGF) gene polymorphisms (VGPs) on the efficacy of the anti-VEGF antibody bevacizumab (Bev) in metastatic colorectal cancer (MCRC) patients

Universus terrarum orbis scriptorum calamo delineatus hoc est auctorum fere omnium...

Texto a 3 col.Port. a dos tintas con grab. xil.Las h. de grab. calc. : "In Padova q Matrio Cadorin", mapas, monumentos.Las il. calc. y xil., mapas, fortalezas y trajes

PTHrP produced by myeloma plasma cells regulates their survival and pro-osteoclast activity for bone disease progression.

To promote their survival and progression in the skeleton, osteotropic malignancies of breast, lung, and prostate produce parathyroid hormone–related protein (PTHrP), which induces hypercalcemia. PTHrP serum elevations have also been described in multiple myeloma (MM), although their role is not well defined. When we investigated MM cells from patients and cell lines, we found that PTHrP and its receptor (PTH‐R1) are highly expressed, and that PTHrP is secreted both as a full‐length molecule and as small subunits. Among these subunits, the mid‐region, including the nuclear localization sequence (NLS), exerted a proliferative effect because it was accumulated in nuclei of MM cells surviving in starvation conditions. This was confirmed by increased transcription of several genes enrolled in proliferation and apoptosis control. PTHrP was also found to stimulate PTH‐R1 inMMcells. PTH‐R1’s selective activation by the full‐length PTHrP molecule or the NH2‐terminal fragment resulted in a significant increase of intracellular Ca2þ influx, cyclic adenosine monophosphate (cAMP) content, and expression of receptor activator of NF‐kB ligand (RANKL) and monocyte chemoattractant protein‐1 (MCP‐1). Our data definitely clarify the role of PTHrP in MM. The PTHrP peptide is functionally secreted by malignant plasma cells and contributes to MM tumor biology and progression, both by intracrine maintenance of cell proliferation in stress conditions and by autocrine or paracrine stimulation of PTH‐R1, which in turn reinforces the production of osteoclastogenic factors

A novel K-ras mutation in colorectal cancer. A case report and literature review

Activating mutations in the K-ras oncogene mainly occur in codons 12 and 13 and may be predictive of response to drugs directly linked to the K-ras signaling pathway, such as panitumumab and cetuximab