Neuropilin-2 contributes to tumor progression in preclinical models of small intestinal neuroendocrine tumors.

The identification of novel regulators of tumor progression is a key challenge to gain knowledge on the biology of small intestinal neuroendocrine tumors (SI-NETs). We recently identified the loss of the axon guidance protein semaphorin 3F as a protumoral event in SI-NETs. Interestingly the expression of its receptor neuropilin-2 (NRP-2) was still maintained.

Combinatorial Treatment with mTOR Inhibitors and Streptozotocin Leads to Synergistic and Antitumor Effects in Insulinoma Cells.

Streptozotocin-based chemotherapy is the first-line chemotherapy recommended for advanced pancreatic neuroendocrine tumors (pNETs), whereas targeted therapies, including mTOR inhibitors, are available in second-line treatment. Unfortunately, objective response rates to both treatments are limited. Because mTOR pathway activation, commonly observed in pNETs, has been reported as one of the major mechanisms accounting for chemoresistance, we investigated the potential benefit of mTOR inhibition combined with streptozotocin treatment in a subset of pNETs, namely insulinomas.

mTOR inhibitors activate PERK signaling and favor viability of gastrointestinal neuroendocrine cell lines.

mTOR and Unfolded Protein Response (UPR) are two signaling pathways frequently activated in cancer cells. The mTOR pathway has been shown to be up-regulated in most gastroenteropancreatic neuroendocrine tumors. In contrast, little is known about the UPR status in neoplastic neuroendocrine cells.

Prediction of response to everolimus in neuroendocrine tumors: evaluation of clinical, biological and histological factors.

Objectives Several targeted therapies are available for metastatic neuroendocrine tumours (NETs) but no predictive factor of response to these treatments has been identified yet. Our aim was to identify and evaluate clinical, biological, histological and functional markers of response to everolimus. Methods We retrospectively reviewed 53 patients with NETs treated with everolimus (68 % in clinical trials).

The axon guidance molecule semaphorin 3F is a negative regulator of tumor progression and proliferation in ileal neuroendocrine tumors.

Gastro-intestinal neuroendocrine tumors (GI-NETs) are rare neoplasms, frequently metastatic, raising difficult clinical and therapeutic challenges due to a poor knowledge of their biology. As neuroendocrine cells express both epithelial and neural cell markers, we studied the possible involvement in GI-NETs of axon guidance molecules, which have been shown to decrease tumor cell proliferation and metastatic dissemination in several tumor types. We focused on the role of Semaphorin 3F (SEMA3F) in ileal NETs, one of the most frequent subtypes of GI-NETs.

CRMP5 Controls Glioblastoma Cell Proliferation and Survival through Notch-Dependent Signaling.

Collapsin response mediator protein 5 (CRMP5) belongs to a family of five cytosolic proteins that play a major role in nervous system development. This protein was first described in cancer-induced autoimmune processes, causing neurodegenerative disorders (paraneoplastic neurologic syndromes). CRMP5 expression has been reported to serve as a biomarker for high-grade lung neuroendocrine carcinomas; however, its functional roles have not been examined in any setting of cancer pathophysiology.

The workflow from post-mortem human brain sampling to cell microdissection: a Brain Net Europe study.

Brain banks manage and store fully clinically and pathologically characterised brains. The diversity of techniques used in research projects increases. These biological resource centres are made to adapt brain tissue processing.

Mechanisms of local invasion in enteroendocrine tumors: identification of novel candidate cytoskeleton-associated proteins in an experimental mouse model by a proteomic approach and validation in human tumors.

Small-intestinal neuroendocrine tumors (SI-NETs) are defined as locally invasive only after extension to the muscularis propria. To gain further insight into the molecular mechanisms, we applied a proteomic approach to an orthotopic xenograft model to identify candidate proteins evaluable in human SI-NETs. After grafting STC-1 neuroendocrine tumor cells on the caecum of nude mice, comparative proteomic studies were performed between the pre-invasive and the invasive stages, respectively 2 and 8 weeks after grafting.

Extensive expression of collapsin response mediator protein 5 (CRMP5) is a specific marker of high-grade lung neuroendocrine carcinoma.

The diagnosis of high-grade neuroendocrine tumors has strong clinical relevance because it identifies patients at higher risk of an unfavorable outcome who should receive multimodal treatment. However, these tumors can be mistaken for poorly differentiated nonsmall cell carcinoma or carcinoid lung tumors. In fact, no immunohistochemical marker can currently distinguish between histologic lung subtypes.