Lyn, a Src family kinase, regulates activation of epidermal growth factor receptors in lung adenocarcinoma cells.

Background: Activation of receptors for growth factors on lung epithelial cells is essential for transformation into tumor cells, supporting their viability and proliferation. In most lung cancer patients, EGFR is constitutively activated without evidence of mutation. Defining mechanisms for constitutive activation of EGFR could elucidate additional targets for therapy of lung cancers.

Effect of pemetrexed on innate immune killer cells and adaptive immune T cells in subjects with adenocarcinoma of the pancreas.

Baseline levels of innate and adaptive immune cell functions were studied in patients with pancreatic cancer. The effects of pemetrexed were measured at 7 and 14 days after initial therapy then 14 days after combination therapy with gemcitabine. Pretherapy levels of absolute numbers of natural killer (NK) cells positively correlated with survival.

Advances in therapeutic vaccines for pancreatic cancer.

Pancreatic cancer is one of the most difficult-to-treat cancers. Despite surgical resection, radiation and/or chemotherapy, greater than 94% of people with pancreatic cancer do not survive beyond 5 years. In fact, median survival after diagnosis of metastatic pancreatic cancer is 4.

Clinical trials of vaccines for immunotherapy in pancreatic cancer.

A greater understanding of the molecular events that trigger oncogenesis and events that negatively regulate immune responses has allowed for the development of targeted therapies with specific vaccines to match tumor antigens coupled with immunotherapy specifically directed against that tumor's immunosuppressive microenvironment. In order to be effective, vaccine therapies need to both expand the immune response to tumors and overcome immunosuppressive microenvironments therein. Specifically, targeted therapy must be personalized for each cancer patient.

Major histocompatibility complex class I-related chain A/B (MICA/B) expression in tumor tissue and serum of pancreatic cancer: role of uric acid accumulation in gemcitabine-induced MICA/B expression.

Background: Major histocompatibility complex class I-related chain A and B (MICA/B) are two stress-inducible ligands that bind the immunoreceptor NKG2D and play an important role in mediating the cyotoxicity of NK and T cells. In this study, we sought to study MICA/B expression in pancreatic cancer and to determine whether and how genotoxic drugs such as gemcitabine can affect MICA/B expression and natural killer cytotoxity.

Methods: Seven pancreatic cancer cell lines were analyzed for MICA/B expression by flow cytometry and for their sensitivity to NK-92 cell killing by a 51Cr release assay.

Countering tumor-induced immunosuppression during immunotherapy for pancreatic cancer.

Background: Vaccines for pancreatic cancer have been challenged by a number of factors, especially the immunosuppressive microenvironment within the tumor that allows for escape from immune surveillance.

Objective/methods: We sought to identify results that define mechanisms of pancreatic-cancer-associated immunosuppression and strategies that might be useful to overcome them thereby resulting in effective immune responses to cancer vaccines capable of deleting pancreatic cancer cells.

Results/conclusion: Immunosuppressive tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSC), and regulatory T cells (Treg) reside in tumors, and their products along with tumor derived products (such as VEGF, TGFbeta and IL-10), create a microenvironment that counters immune activation and attack.

Current immunotherapeutic strategies in pancreatic cancer.

The immune systems of patients with newly diagnosed pancreatic cancers are functional, with T-cell responses capable of responding to tumor antigen presentation. Pancreatic tumors have been demonstrated to express tumor antigens as mutated, altered, underglycosylated and/or inappropriately overexpressed proteins. Considering these two facts, it should be possible for patients' bodies to recognize their tumors as foreign and to reject them.

Clinicopathological significance of major histocompatibility complex class I-related chain a and B expression in thyroid cancer.

Context: Major histocompatibility complex class I-related chains A and B (MICA/B) are two stress-inducible ligands for the immunoreceptor NKG2D that is expressed on cytotoxic T cells and natural killer (NK) cells. It is not known whether MICA/B expression is up-regulated in thyroid cancer as a result of oncogene activation.

Objective: The objective of the investigation was to study MICA/B expression and regulation in thyroid cancer and its role in mediating the cytotoxicity of NK cells.

Elevated serum heparanase-1 levels in patients with pancreatic carcinoma are associated with poor survival.

Background: It has previously been shown that heparanase-1 (HPR1), an endoglycosidase, is up-regulated in pancreatic carcinoma. The purpose of this study was to test whether serum HPR1 levels in pancreatic carcinoma patients are elevated, and whether higher serum HPR1 levels are associated with a shortened survival.

Methods: Serum HPR1 levels in 40 healthy donors, 31 pancreatic carcinoma patients, and 11 patients treated with gemcitabine were measured by a novel enzyme-linked immunoadsorbent assay.

Effect of gemcitabine on immune cells in subjects with adenocarcinoma of the pancreas.

Effects of gemcitabine (Gemzar) on immune cells were examined in pancreas cancer patients to determine whether it was immunosuppressive, or potentially could be combined with vaccines or other immunotherapy to enhance patient's responses to their tumors. Blood was obtained at five time-points, before therapy, 3-4 days after initial gemcitabine infusion and immediately preceding three additional weekly infusions. Effects on T-cell subsets, B-cells, myeloid dendritic cell precursors, antigen presenting cells (APC), activated/memory, and naive cells were examined.

Immunobiotherapy directed against mutated and aberrantly expressed gene products in pancreas cancer.

Genetic alterations are responsible for the development of cancer in ductal cells of the pancreas. These genetic changes result in abnormal molecular expression of proteins that are involved in cell proliferation, cell cycle control and adhesion. Some of the genetic mutations result in aberrant proteins that can be recognized as novel or foreign by cells of innate and adaptive immune systems.

PI3-kinase regulates survival of chronic lymphocytic leukemia B-cells by preventing caspase 8 activation.

Studies to investigate signal transduction pathways that support viability and prevent apoptosis of chronic lymphocytic leukemia cells (CLL) were initiated as a result of microarray cDNA analyses which revealed expression of genes whose products regulate cell cycle progression. Immunoblots revealed translation of several genes including caspases, cyclin D1, and the PI3-kinase dependent, survival kinase, Akt. Akt was found to be activated.