Receptor Tyrosine Kinase Expression Predicts Response to Sunitinib in Breast Cancer.

Background: Preliminary data indicate that tyrosine kinase inhibitors (TKIs) function through rearranged during transfection (RET) in breast cancer. However, TKIs are not specific and can block several receptor tyrosine kinases (RTKs). This study used cell lines and primary breast cancer specimens to determine factors associated with TKI response.

Gene expression accurately distinguishes liver metastases of small bowel and pancreas neuroendocrine tumors.

Small bowel (SBNETs) and pancreatic neuroendocrine tumors (PNETs) often present with liver metastases. Although liver biopsy establishes a neuroendocrine diagnosis, the primary tumor site is frequently unknown without exploratory surgery. Gene expression differences in metastases may distinguish primary SBNETs and PNETs.

GIPR expression in gastric and duodenal neuroendocrine tumors.

Background: Compounds targeting somatostatin-receptor-type-2 (SSTR2) are useful for small bowel neuroendocrine tumor (SBNET) and pancreatic neuroendocrine tumor (PNET) imaging and treatment. We recently characterized expression of 13 cell surface receptor genes in SBNETs and PNETs, identifying three drug targets (GIPR, OXTR, and OPRK1). This study set out to characterize expression of this gene panel in the less common neuroendocrine tumors of the stomach and duodenum (gastric and duodenal neuroendocrine tumors [GDNETs]).

Gastric inhibitory polypeptide receptor (GIPR) is a promising target for imaging and therapy in neuroendocrine tumors.

Background: Ligands binding the somatostatin receptor type 2 (SSTR2) are useful for imaging and treatment of neuroendocrine tumors (NETs), but not all tumors express high levels of these receptors. The aim of this study was to evaluate gene expression of new therapeutic targets in NETs relative to SSTR2.

Methods: RNA was extracted from 103 primary small bowel and pancreatic NETs, matched normal tissue, and 123 metastases.

Overexpression of membrane proteins in primary and metastatic gastrointestinal neuroendocrine tumors.

Background: Small bowel and pancreatic neuroendocrine tumors (SBNETs and PNETs) are rare tumors whose incidence is increasing. Drugs targeting the somatostatin receptor are beneficial in these tumors. To identify additional cell-surface targets, we recently found receptors and membrane proteins with gene expression significantly different from adjacent normal tissues in a small number of primary SBNETs and PNETs.

Discriminating pheochromocytomas from other adrenal lesions: the dilemma of elevated catecholamines.

Background: Screening tests for pheochromocytoma involve measuring levels of catecholamines in the urine or plasma, which have significant false-positive rates. We reviewed patients with adrenal masses and elevated levels of catecholamines to determine the value of different preoperative tests in diagnosing pheochromocytomas.

Methods: A retrospective chart review identified patients who underwent adrenalectomy between 1997 and 2011 with elevation of urine or serum catecholamines.

BMPR1A mutations in juvenile polyposis affect cellular localization.

Background: Juvenile polyposis (JP) is characterized by the development of hamartomatous polyps of the gastrointestinal tract that collectively carry a significant risk of malignant transformation. Mutations in the bone morphogenetic protein receptor type 1A (BMPR1A) are known to predispose to JP. We set out to study the effect of such missense mutations on BMPR1A cellular localization.

The response to neoadjuvant chemotherapy predicts clinical outcome and increases breast conservation in advanced breast cancer.

Background: The aim of this study was to determine outcomes in patients with breast cancer treated with neoadjuvant chemotherapy.

Methods: Seventy-two consecutive patients receiving neoadjuvant chemotherapy for breast cancer were enrolled.

Results: Mastectomy was avoided in 46% of patients, and 42% converted to negative nodes after neoadjuvant chemotherapy.

The value of preoperative imaging in small bowel neuroendocrine tumors.

Background: Neuroendocrine tumors of the small bowel (SBNETs) are a rare but important subgroup of malignancies. Since 30 % of SBNETs present with metastatic disease, often with an occult primary, preoperative imaging is critical for determining who will benefit most from abdominal exploration. We set out to evaluate the usefulness of the two most commonly performed imaging modalities in predicting the extent of disease found at exploration in patients with SBNETs.

Differentiation of small bowel and pancreatic neuroendocrine tumors by gene-expression profiling.

Background: Between 10% and 20% of patients with neuroendocrine tumors (NETs) present with metastases of unknown primary site. Because knowledge of the primary site has important implications for treatment, we set out to define gene-expression profiles to differentiate between small-bowel NETs (SBNETs) and pancreatic NETs (PNETs).

Methods: RNA was extracted from tumor and normal tissues in 11 patients with SBNETs and 15 patients with PNETs, and qPCR was performed for 367 GPCR genes.

Germline mutations in SMAD4 disrupt bone morphogenetic protein signaling.

Introduction: Juvenile polyposis (JP) is an autosomal dominant disease that predisposes to GI malignancies. Germline mutations in the tumor suppressor gene SMAD4 account for approximately 20% of JP cases. SMAD4 is the common intracellular mediator of the TGF-β and bone morphogenetic protein (BMP) pathways.

SP1 regulates the transcription of BMPR1A.

Background: BMPR1A is a cell surface receptor in the bone morphogenetic protein (BMP) pathway. Mutations in BMPR1A predispose to juvenile polyposis (JP). Sp1 and related proteins are widely expressed regulators of gene transcription, including members of the BMP pathway.

Comparison of clinicopathologic factors in 122 patients with resected pancreatic and ileal neuroendocrine tumors from a single institution.

Background: Recent population-based studies have demonstrated significant differences in outcome between patients with pancreatic and ileal neuroendocrine tumors. The objective of this study was to examine the clinicopathologic differences between ileal and pancreatic neuroendocrine tumors following resection.

Methods: A retrospective chart review was performed and data on clinicopathologic variables, biochemical markers, and follow-up of patients with resected ileal (INETs) and pancreatic (PNETs) neuroendocrine tumors were collected.

Discovery of SMAD4 promoters, transcription factor binding sites and deletions in juvenile polyposis patients.

Inactivation of SMAD4 has been linked to several cancers and germline mutations cause juvenile polyposis (JP). We set out to identify the promoter(s) of SMAD4, evaluate their activity in cell lines and define possible transcription factor binding sites (TFBS). 5'-rapid amplification of cDNA ends (5'-RACE) and computational analyses were used to identify candidate promoters and corresponding TFBS and the activity of each was assessed by luciferase vectors in different cell lines.