Constructs of biotin mimetic peptide with CC49 single-chain Fv designed for tumor pretargeting.

Single-chain Fv constructs comprising a biotin mimetic peptide (BMP) and scFv of CC49 monoclonal antibody were produced to improve pretargeted radioimmunotherapy. BMP units that bind streptavidin were added to the carboxyl terminus of the CC49 V(H) region. An engineered scFvBMP monomer and a sc(Fv)(2)BMP dimer showed an excellent antigen recognition in vitro with a specific binding of 72+/-5 and 81+/-4%, respectively.

Neural invasion in the staging of pancreatic cancer.

The natural history of pancreatic ductal adenocarcinoma makes it one of the most malignant human diseases. Unknown etiology, lack of early symptoms, explosive outcome, short survival, and resistance to therapy are hallmarks of this cancer. Although surgery has been shown to be an effective therapeutic approach, the inevitable tendency for recurrence, even after apparently curative operation, has remained a mystery.

Aberrant expression of MUC3 and MUC4 membrane-associated mucins and sialyl Le(x) antigen in pancreatic intraepithelial neoplasia.

Introduction: Ductal adenocarcinoma of the pancreas has recently been suggested to arise from histologically identifiable ductal lesions known as pancreatic intraepithelial neoplasia (PanINs). Altered levels and patterns of mucin gene expression have been reported to occur in epithelial cancers.

Aim: To examine the pattern of expression of membrane-associated mucins, MUC3 and MUC4, and a mucin-associated carbohydrate tumor antigen, sialyl Le(x), in these precursor lesions and ductal adenocarcinoma of the pancreas.

What is the origin of pancreatic adenocarcinoma?

The concept of pancreatic cancer origin is controversial. Acinar, ductal or islet cells have been hypothesized as the cell of origin. The pros and cons of each of these hypotheses are discussed.

Pharmacokinetics and biodistribution of genetically engineered antibodies.

The engineering of monoclonal antibodies has created a new generation of pharmaceuticals with the desired pharmacokinetics and biodistribution properties. For radioimmunotherapy and radioscintigraphy, optimum tumor targeting can be achieved using engineered constructs that provide high antigen affinity and specificity, effective tumor penetration, circulation properties that allow high tumor uptake with acceptable doses to the normal tissues, and fast clearance allowing low background. Recent advances have made possible the development of antibodies with these properties.

Current status of the molecular genetics of human prostatic adenocarcinomas.

Molecular genetic mechanisms involved in the progression of prostate cancer are not well understood due to extensive tumor heterogeneity and lack of suitable models. New methods such as fluorescence in-situ hybridization (FISH), comparative genomic hybridization (CGH) and microsatellite analysis have documented losses or gains on various chromosomes. Altered chromosomal regions have been associated with the activation of oncogenes and the inactivation of tumor suppressor genes or defects in mismatch repair (MMR) genes.

The pattern of xenobiotic-metabolizing enzymes in the human pancreas.

Our previous study on phase II detoxifying enzymes, showing a significant reduction of glutathione S-transferase-pi in chronic pancreatitis compared to the normal pancreas, indicated that xenobiotic-metabolizing enzymes are involved in the pathogenesis of pancreatic diseases. This study presents an overall look at the distribution of the phase I xenobiotic-metabolizing enzymes, which are responsible for the metabolism of many common environmental toxins and carcinogens, in the normal pancreas. Twenty-four normal pancreases from 7 donors and 17 early autopsy cases, as well as cultured human islet cells, were analyzed by immunohistochemistry, Western blot analysis, and/or reverse-transcription polymerase chain reaction (RT-PCR) for the expression of nine cytochrome P-450 mono-oxygenases (CYP) and the NADPH cytochrome P-450 oxidoreductase.

Are islet cells the gatekeepers of the pancreas?

The pancreas is one of the body's most complex tissues composed of a mixture of endocrine and exocrine cell components. Although, islets comprise 1-2% of the pancreatic volume, there is some evidence that they control the function and the integrity of the pancreas and play the role of a gatekeeper. This review intends to highlight the importance of islet cells, not only for glucose metabolism, but also for their significant role in drug metabolism and diseases, especially in pancreatic cancer.

Genomic organization of MUC4 mucin gene. Towards the characterization of splice variants.

The human MUC4 gene encodes a large membrane-associated mucin, characterized by a mucin tandem repeat domain and a growth factor-like transmembrane domain. In addition to the originally published sequence (sv0-MUC4), several MUC4 cDNA sequences (called sv1-MUC4 to sv21-MUC4, MUC4/X, MUC4/Y) from various tissues and cell lines have been recently described. They differ from sv0-MUC4 by deletions and/or insertions located in the 3' region or, for two of them, by deletion of the central repetitive domain.

MUC4 expression increases progressively in pancreatic intraepithelial neoplasia.

Pancreatic adenocarcinoma is believed to develop from histologically identifiable intraductal lesions known as pancreatic intraepithelial neoplasias (PanINs) that undergo a series of architectural, cytologic, and genetic changes, a progression model similar to the adenoma-carcinoma sequence in the colon. The apomucin MUC4 has been implicated in invasive pancreatic adenocarcinoma. MUC4 expression is not detectable at the RNA level in normal pancreas but is detectable at high levels in invasive pancreatic adenocarcinoma.

Expression profile of differentially-regulated genes during progression of androgen-independent growth in human prostate cancer cells.

Because of the heterogeneous nature of prostate cancer, identifying the molecular mechanisms involved during the transition from an androgen-sensitive to an androgen-independent phenotype is very complex. An LNCaP cell model that recapitulates prostate cancer progression, comprising early passage androgen-sensitive (LNCaP-C33) and late passage androgen-independent (LNCaP-C81) phenotypes, would help to provide a better understanding of such molecular events. In this study, we examined the genes expressed by LNCaP-C33 and LNCaP-C81 cells using cDNA microarrays containing 1176 known genes.

Establishment and characterization of androgen-independent human prostate cancer LNCaP cell model.

Background: The acquisition of an androgen-independent phenotype is the most serious issue of prostate cancer treatment. Although several experimental cell models have been reported for studying androgen independence, they have limited applications related to hormone-refractory prostate cancer. To investigate the molecular mechanism of androgen-independent growth of prostate cancer, we established a useful LNCaP cell model that resembles the clinical scenario of hormone-refractory prostate cancer.

Purification and characterization of a human pancreatic adenocarcinoma mucin.

Pancreatic mucins consist of core proteins that are decorated with carbohydrate structures. Previous studies have identified at least two physically distinct populations of mucins produced by a pancreatic adenocarcinoma cell line (HPAF); one is the MUC1 core protein, which includes an oligosaccharide structure identified by a monoclonal antibody (MAb) recognizing the DU-PAN-2 epitope. In this study, we purified and characterized a second mucin fraction, which also shows reactivity with the DU-PAN-2 antibody, but which has an amino acid composition that is not consistent with the MUC1 core protein.