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Harry T Papaconstantinou

Publications and source records attributed to Harry T Papaconstantinou.

5 recordsLinked to original sources
PubMed2006

Identification of apoptotic genes mediating TGF-beta/Smad3-induced cell death in intestinal epithelial cells using a genomic approach.

Transforming growth factor (TGF)-beta-dependent apoptosis is important in the elimination of damaged or abnormal cells from normal tissues in vivo. Previously, we have shown that TGF-beta inhibits the growth of rat intestinal epithelial (RIE)-1 cells. However, RIE-1 cells are relatively resistant to TGF-beta-induced apoptosis due to a low endogenous Smad3-to-Akt ratio. Overexpression of Smad3 sensitizes RIE-1 cells (RIE-1/Smad3) to TGF-beta-induced apoptosis by altering the Smad3-to-Akt ratio in favor of apoptosis. In this study, we utilized a genomic approach to identify potential downstream target genes that are regulated by TGF-beta/Smad3. Total RNA samples were analyzed using Affymetrix oligonucleotide microarrays. We found that TGF-beta regulated 518 probe sets corresponding to its target genes. Interestingly, among the known apoptotic genes included in the microarray analyses, only caspase-3 was induced, which was confirmed by real-time RT-PCR. Furthermore, TGF-beta activated caspase-3 through protein cleavage. Upstream of caspase-3, TGF-beta induced mitochondrial depolarization, cytochrome c release, and cleavage of caspase-9, which suggests that the intrinsic apoptotic pathway mediates TGF-beta-induced apoptosis in RIE-1/Smad3 cells.

Animals↗
PubMed2005

Screening methods for high-grade dysplasia in patients with anal condyloma.

UNLABELLED: Human papilloma virus (HPV) is one of the most common sexually transmitted diseases in the United States. HPV infection can cause anal condylomas and is a risk factor for dysplasia. High-grade dysplasia may progress to squamous cell carcinoma. Currently, biopsy and histological examination are required to grade dysplasia. The purpose of this study is to determine whether anal cytology, morphological characteristics, and/or the presence of high-risk oncogenic HPV-types are effective noninvasive methods to detect high-risk anal condylomas. PATIENTS AND METHODS: From November 2003 to June 2004, all patients with anal condyloma were prospectively evaluated for anal cytology, high-risk oncogenic HPV-types, and tissue biopsies. The Bethesda classification system was used to classify cytologic findings and histological examination, which were grouped as high-risk (HRL) and low-risk (LRL) lesions. Histology results served as true disease for all comparisons. RESULTS: Forty-seven patients with anal condyloma were studied; 43 (91.5%) were men, and the mean age was 39 +/- 11 years. Histology showed 19 (40.5%) patients with HRL, and 28 (59.5%) patients with LRL. Cytology correctly identified 8 patients with HRL and 27 patients with LRL (sensitivity 42% and specificity 96%). High-risk oncogenic HPV-types were found in 84.2% of HRL and 39.3% of LRL (P = 0.0029). Combining cytology with oncogenic HPV-testing, the sensitivity of detecting HRL increased to 89%, and specificity decreased to 42%. CONCLUSION: Anal cytology alone is not accurate for detecting HRL in patients with anal condylomas. Combining oncogenic HPV-testing with cytology is more sensitive in detecting HRL in patients with anal condyloma, and therefore, a more effective screening tool.

Adult↗
PubMed2004

Characteristics and survival patterns of solid organ transplant patients developing de novo colon and rectal cancer.

PURPOSE: Immunosuppression used in transplantation is associated with an increased incidence of various cancers. Although the incidence of colorectal cancer in transplant patients seems to be equal to nontransplant population, the effects of immunosuppression on patients who develop colorectal cancer are not well defined. The purpose of this study was to define the characteristics and survival patterns of transplant patients developing de novo colorectal cancer. METHODS: The Israel Penn International Transplant Tumor Registry was queried for patients with colorectal cancer. Analysis included patient demographics, age at transplantation and colorectal cancer diagnosis, tumor stage, and survival. Age and survival rates were compared to United States population-based colorectal cancer statistics using the National Cancer Institute Surveillance Epidemiology and End Results database. RESULTS: A total of 150 transplant patients with de novo colorectal cancer were identified: 93 kidney, 29 heart, 27 liver, and 1 lung. Mean age at transplantation was 53 years. Age at transplantation and colorectal cancer diagnosis was not significant for gender, race, or stage of disease. Compared to National Cancer Institute Surveillance Epidemiology and End Results database, transplantation patients had a younger mean age at colorectal cancer diagnosis (58 vs. 70 years; P < 0.001), and a worse five-year survival (overall, 44 vs. 62 percent, P < 0.001; Dukes A and B, 74 vs. 90 percent, P < 0.001; Dukes C, 20 vs. 66 percent, P < 0.001; and Dukes D, 0 vs. 9 percent, P = 0.08). CONCLUSIONS: Transplant patients develop colorectal cancer at a younger age and exhibit worse five-year survival rates than the general population. These data suggest that chronic immunosuppression results in a more aggressive tumor biology. Frequent posttransplantation colorectal cancer screening program may be warranted.

Aged↗