Identification of a novel germline missense mutation of the androgen receptor in African American men with familial prostate cancer

Race, family history and age are the unequivocally accepted risk factors for prostate cancer （PCa）. Androgen receptor （AR）-dependent signaling is an important element in prostate carcinogenesis and its progression to metastatic disease. We examined the possibility of genomic changes in the AR in association with familial PCa in African Americans who have a higher incidence and mortality rate and a clinically more aggressive disease presentation than Caucasians. Genomic DNAs of 60 patients from 30 high-risk African American and Caucasian families participating in the Louisiana State University Health Sciences Center genetic linkage study of PCa were studied. Exon-specific polymerase-chain reaction, bi-directional automated sequencing and restriction enzyme genotyping were used to analyze for mutations in the coding region of the AR gene. We identified a germline AR （A1675T） （T559S） substitution mutation in the DNA-binding domain in three PCa-affected members of an African- American family with a history of early-onset disease. The present study describes the first AR germline mutation in an African-American family with a history of familial PCa. The AR （T559S） mutation may contribute to the disease by altering AR DNA-binding affinity and/or its response to androgens, non-androgenic steroids or anti-androgens. Additional studies will be required to define the frequency and contribution of the AR （A 1675T） allele to early-onset and/or familial PCa in African Americans.

Human benign prostatic hyperplasia heterotransplants as an experimental model

Benign prostatic hyperplasia is a nonmalignant adenomatous enlargement of the pefiurethral prostate gland. It is a common disease in older men. In addition to man,spontaneous benign prostatic hyperplasia occurs in chimpanzee and the dog. Alternatives to these spontaneous models are induced benign prostatic hyperplasia,xenografts and in vitro models. Xenografts may be induced by cells cultured in vitro or by the heterotransplantation of primary surgical specimens into immunosuppressed mice. The purpose of this review is to integrate data from more than 30 years of heterotransplantation research in the study of benign hyperplasia of the prostate. Heterotransplantation has provided data regarding the histopathology,morphology,tissue markers,androgen receptor expression,tissue kinetics,take rate and tissue vasculature for this prostate disease.There are advantages,as well as limitations,that have been identified for human prostate disease heterotransplants versus xenotransplantation of cultured cells.Overall,heterotransplanted tissue is better at retaining tissue morphology,pathology,secretory activity,expression of tissue markers and human vasculature of the patient＇s original specimen. Furthermore,heterotransplanted tissue preserves the three-dimensional tissular architecture of the prostate to maintain critical stromal-epithelial cell interactions.

Pancreatic cancer: genetics, disease progression, therapeutic resistance and treatment strategies

Pancreatic cancer is a deadly disease and the third-highest cause of cancer-related deaths in the United States.It has a very low five-year survival rate(<5%)in the United States as well as in the world(about 9%).The current gemcitabine-based therapy soon becomes ineffective because treatment resistance and surgical resection also provides only selective benefit.Signature mutations in pancreatic cancer confer chemoresistance by deregulating the cell cycle and promoting anti-apoptotic mechanisms.The stroma-rich tumor microenvironment impairs drug delivery and promotes tumor-specific immune escape.All these factors render the current treatment incompetent and prompt an urgent need for new,improved therapy.In this review,we have discussed the genetics of pancreatic cancer and its role in tumor evolution and treatment resistance.We have also evaluated new treatment strategies for pancreatic cancer,like targeted therapy and immunotherapy.

Introduction to Volume 1 Issue 2 of Journal of Cancer Metastasis and Treatment

It is my privilege to introduce the second issue of the Journal of Cancer Metastasis and Treatment.In keeping with the format we have chosen for our journal,this issue contains two reviews focusing on fields of great translational and clinical interest,five original articles,and three case reports.The first review discusses the rapidly evolving field of circulating tumor cells(CTC)as cancer biomarkers.Since the introduction of the first Food and Drug Administration approved CTC test to assess the progression of metastatic breast,colorectal and prostate cancer,CTC have generated tremendous interest among clinicians seeking sensitive progression biomarkers and basic scientists interested in isolating and studying these cells.