Advancements in pancreatic neuroendocrine tumors.

Pancreatic neuroendocrine tumors (PanNETs) have increased in incidence in the USA over the last 20 years. Although PanNETs are often misconceived as being indolent tumors as they have a far more favorable prognosis over pancreatic adenocarcinoma, roughly 60-70% of patients have metastatic disease at the time of diagnosis due to presentation late in the disease process. While improvements in imaging modalities allow for early detection and better tumor localization, recent advancements in basic science, as well as surgical and medical management of PanNETs have further improved the prognosis.

Secretory phospholipase A2 mediates human esophageal adenocarcinoma cell growth and proliferation via ERK 1/2 pathway.

Background/aim: Secretory phospholipase-A2 (sPLA2) mediates growth and proliferation of human esophageal adenocarcinoma cells (HEAC). Two major molecular pathways of cancer growth regulation include extracellular signal-regulated kinase 1/2 (ERK 1/2) and protein kinase-B (AKT). Phospholipase enzymes have been demonstrated to significantly influence these two growth regulating pathways in other tumor cells.

Group IIa sPLA2 inhibition attenuates NF-κB activity and promotes apoptosis of lung cancer cells.

Background/aim: Group IIa secretory phospholipase A2 (sPLA2 IIa) has been implicated in the regulation of metastasis of non-small cell lung cancer (NSCLC) and the present study investigates its contribution to lung cancer growth and progression. PLA2s initiate signaling in several pathways that mediate cell survival including phosphatidylinositol 3-kinase-AKT (PI3K-AKT), p38 mitogen-activated protein kinase (p38 MAPK), extracellular-signal-regulated kinase (ERK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB).

Materials And Methods: Human NSCLC cell lines (A549 and NCI-H358) were treated with a specific sPLA2 IIa inhibitor.

Lung cancer cell invasion and expression of intercellular adhesion molecule-1 (ICAM-1) are attenuated by secretory phospholipase A₂ inhibition.

Objective: Invasive lung tumors are associated with intercellular adhesion molecule-1 (ICAM-1) expression. Secretory phospholipase A(2) (sPLA(2)) enzymes produce inflammatory mediators that stimulate ICAM-1 expression, and upregulation of PLA(2) activity can enhance metastasis. We hypothesize a link between sPLA(2) activity, ICAM-1 expression, and tumor cell invasion.

Statin therapy attenuates growth and malignant potential of human esophageal adenocarcinoma cells.

Objectives: Esophageal adenocarcinoma is an aggressive malignancy generally diagnosed after metastatic spread and currently lacks effective medical therapy. Expression of intracellular adhesion molecule-1 (ICAM-1) is an adverse prognostic indicator in various human tumor cells and contributes significantly to their metastatic potential. Statin therapy reduces circulating ICAM-1 levels in patients with coronary heart disease and is associated with reduction in progression from Barrett esophagus to esophageal adenocarcinoma.

Cytokine expression profile in human lungs undergoing normothermic ex-vivo lung perfusion.

Background: A donor lung shortage prevents patients from receiving life-saving transplants. Ex-vivo lung perfusion (EVLP) is a viable means of expanding the donor pool by evaluating and potentially improving donor lung function. The metabolic and inflammatory effects of EVLP on human lung tissue are currently unknown.

DITPA, a thyroid hormone analog, reduces infarct size and attenuates the inflammatory response following myocardial ischemia.

Background: Thyroid hormone can have positive effects on the cardiovascular system but its therapeutic potential is limited secondary to its adverse effects. DITPA (3,5-diiodothyroproprionic acid) is a synthetic thyroid hormone analog with positive inotropic effects similar to thyroid hormone but with minimal systemic effects. DITPA has previously been shown to reduce pathologic remodeling and improve cardiac output following myocardial infarction; however, few studies have examined the role of DITPA in determining infarct size or the early inflammatory response following myocardial ischemia.

Secretory phospholipase A2 inhibition attenuates intercellular adhesion molecule-1 expression in human esophageal adenocarcinoma cells.

Background: Esophageal adenocarcinoma is an aggressive malignancy, with most patients succumbing to metastatic disease. The presence of intercellular adhesion molecule-1 (ICAM-1) in these cancer cells contributes to their metastatic potential. The ICAM-1 production in other cell types is stimulated by the actions of phospholipase enzymes.

Hemolysis, elevated liver enzymes, and low platelets syndrome: when is surgical help needed?

Background: Life-threatening hemorrhage is a rare event in hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. Epidemiologic data are lacking to predict patients at risk for hemorrhage requiring surgical consultation. We sought to identify early clinical predictors of hemorrhagic complications in patients at risk for HELLP syndrome.

Negative regulation of MHC class II gene expression by CXCR4.

Objective: CXCR4 is overexpressed in 23 types of cancers of both hematopoietic and nonhematopoietic origin. Based on the known role of CXCR4 and its ligand CXCL12 in homing of hematopoietic cells, CXCR4 is likely to play a role in metastasis. We have initiated a study aimed at dissecting additional functions of CXCR4 in cancer cells, particularly in relation to the immune system.

Differential effect of anti-apoptotic genes Bcl-xL and c-FLIP on sensitivity of MCF-7 breast cancer cells to paclitaxel and docetaxel.

Background: Intrinsic or acquired resistance to chemotherapy is a major clinical problem leading to the fatality of patients with advanced and metastatic breast cancer. The overexpression of anti-apoptotic genes is believed to play a role in the resistance to chemotherapy. In the present study, we tested the sensitivity of MCF-7 breast cancer cells overexpressing anti-apoptotic genes TRAF-1, c-FLIP, Bcl-xL, clAP-2 or Mn-SOD to paclitaxel and docetaxel.

The sesquiterpene lactone parthenolide in combination with docetaxel reduces metastasis and improves survival in a xenograft model of breast cancer.

Parthenolide, a sesquiterpene lactone, shows antitumor activity in vitro, which correlates with its ability to inhibit the DNA binding of the antiapoptotic transcription factor nuclear factor kappaB (NF-kappaB) and activation of the c-Jun NH(2)-terminal kinase. In this study, we investigated the chemosensitizing activity of parthenolide in vitro as well as in MDA-MB-231 cell-derived xenograft metastasis model of breast cancer. HBL-100 and MDA-MB-231 cells were used to measure the antitumor and chemosensitizing activity of parthenolide in vitro.