DPC4 Expression in the Small Intestinal Adenocarcinomas

BACKGROUND: Small intestinal adenocarcinomas (SACs) are rare malignancies of the alimentary tract with uncertain carcinogenesis. METHODS: We investigated the expression of deleted in pancreatic cancer 4 (DPC4) in 188 cases of surgically resected SACs, using tissue microarray technology. RESULTS: Twenty-four of the 188 tumors showed complete loss of Smad4/DPC4 expression in cytoplasm (score, 0; 12.8%). Eighty-four and 31 cases were moderately and strongly positive, respectively (score, 2 and 3; 44.7% and 16.5%, respectively) and 49 cases were focally or weakly stained (score, 1; 29.1%). Immunohistochemistry analysis showed that the expression of Smad4/DPC4 was related to an increased risk of lymphatic invasion but not to other clinicopathological features of the tumors (tumor location, differentiation, growth pattern, T stage, direct invasion, vascular invasion, and nodal metastasis). There was no significant association between Smad4/DPC4 expression and patient survival. CONCLUSIONS: The present research is the first study to evaluate Smad4/DPC4 expression in a large sample of SACs with clinicopathologic correlation. Future studies should focus on the immunohistochemical and molecular characteristics of SACs to clarify their tumorigenesis.

Effect of DPC4 gene transfection on chemotherapy sensitivity of pancreatic carcinoma cells / 中华肝胆外科杂志

Objective To observe the effect of DPC4 gene transfection on the chemotherapy sensitivity of pancreatic carcinoma cells. Methods The human DPC4 complementary DNA was subcloned to the retroviral vector pLXSN to obtain recombinant pLXSN/DPC4 with direct inserting potential. The daughter cell BxPC-3/DPC4 which had DPC4 stable expression was acquired after the pancreatic carcinoma BxPC-3 cells had been transfected with pLXSN/DPC4. The sensitivity of the carcinoma cells for 5-Fu and gemcitabine was observed. Meanwhile, the mRNA level of Mdr-1 and Chk1was detected by semi-quantity PCR assay. Results The 50% inhibiting concentrations (IC50)of 5-Fuand gemcitabin4e for BxPC-3 (culturing for 72 h) were rather lower than those of BxPC-3/pLXSN and BxPC-3/-cells. Moreover, the semi-quantity PCR assay revealed that the mRNA level of Mdr-1 and Chk1 was down-regulated. These findings indicated that pLXSN/DPC4 vector, 5-Fu and gemcitabine could inhibit the growth of pancreatic cancer cells. The combined therapy with pLXSN/DPC4 vector and chemotherapeutic drugs could further inhibit the growth of cancer cells. Conclusion The DPC4 gene transfection could enhance the sensitivity of pancreatic cells to chemotherapy, which may be realized through the down-regulation of Mdr-1 and Chk1 gene expression.

Expression of Her-2/neu,DPC4 and P16 in pancreatic carcinoma and its implication / 基础医学与临床

Objective To detect the expression of genes Her-2/neu,DPC4 and P16 in pancreatic carcinomas and to investigate the role of their alterations in tumorigenesis and progression of pancreatic carcinomas.Methods We studied the immunohistochemical markers Her-2/neu,DPC4 and P16 in 34 adenocarcinomas and 12 nonmalignant specimens of the pancreas,and the relationship between DPC4 alterations and various clinicopathological parameters was evaluated.Results There was a significant difference between normal pancreatic tissues and benign pancreatic lesions and primary pancreatic carcinomas for frequency of Her-2/neu expression and loss of P16 expression(P

Advances of the Relationship Between Tumor Suppressor Gene DPC4 and Pancreatic Carcinoma / 中国普外基础与临床杂志

Objective To investigate the relationship between tumor suppressor gene DPC4 and the development and prognosis of pancreatic carcinoma. Methods Relevant literatures of recent years were reviewed. Results DPC4 was located on chromosome 18. Its product was Smad 4 protein. Smad 4 protein was the central component of the transforming growth factor-beta signaling pathway, and all the biological effect was the results of interaction of Smad 4 and different Smads. The gene was deleted or inactive in about 50% of pancreatic carcinomas. The deletion of DPC4 had a great relation to the development and prognosis of pancreatic carcinoma. Conclusion The alteration of tumor suppressor gene DPC4 is connected with the development and prognosis of pancreatic carcinoma. However, this research should be further studied.

Mutations of DPC4/Smad4 Gene in Gallbladder Carcinoma

PURPOSE: The DPC4/Smad4 gene is known to perform a key role in the TGF-beta group protein signaling pathway, which regulates cell proliferation, differentiation and death. DPC4/ Smad4 gene mutation has been studied in cancers of the breast, ovary, esophagus, colo-rectum, bile duct, as well as the pancreas. The mutation rates depend on the kind of carcinoma sites, and range from 10% to around 50%, but no study has been performed on gallbladder carcinomas. This study was performed to search for mutation of the DPC4/Smad4 gene in the gallbladder carcinomas. METHODS: Eighteen surgically resected gallbladder cancers were screened for mutation of the exons; 8, 9, 10 and 11 of the DPC4/Smad4 gene using dideoxyfingerprinting (ddF), and single strand conformational polymorphism (SSCP). The results were confirmed using automatic DNA sequencing, and the expressions examined by immunohistochemical staining with the monoclonal anti-DPC4/Smad4 protein antibody, B8. RESULTS: DdF revealed 3 mutations in two of the exons, which were confirmed by direct sequencing. In one case, a single-base substitution mutation existed in exon 11 with codon change (missense mutation), whereas in two cases such mutations were detected in exon 9 without codon change (silent mutation). Immunohistochemical staining showed negative to weakly positive expression for all three mutated cases, but had high false-positive rates (7/11). CONCLUSION: DPC4/Smad4 gene mutation exists in a certain proportion of gallbladder carcinomas, but the mutation rate seems to be low compared to organogenetically related pancreas or bile duct carcinomas. This suggests somewhat different mechanisms may operate on the carcinogenesis of these organs.

The Expression and Their Clinical Significance of DPC_4/ Smad_4 and nm23-H1/NDPK in Pancreatic Carcinoma / 中国医师杂志

Objective To explore the expression and significance of DPC 4/Smad 4 and nm23-H1/NDPK in human pancreatic carcinoma. Methods The expressions of DPC 4/Smad 4 and nm23/NDPK were detected by immunohistochemical method in 34 pancreatic carcinoma tissues and 34 chronic pancreatitis tissues. Results The positive rate of DPC 4/Smad 4 expression was significantly higher in the chronic pancreatitis than in the pancreatic carcinoma(P

The inhibitory effect of DPC4 gene expression on growth of pancreatic cancer cells in vitro / 中国普通外科杂志

Objective To observe the inhibitory effect of DPC4 gene on growth of pancreatic carcinoma in vitro. Methods The human DPC4 cDNA was subcloned to the retroviral vector pLXSN and then packaged with GP+E86 and PA317 packaging cells respectively. AntiG418 clones were acquired and named as PA317/ pLXSN DPC4+ cells. The DPC4 gene was restored to the human pancreatic cancer cell line BxPC-3 by the infection of the pLXSN/DPC4 and then had a stable expression after antiG418 selection, which was demonstrated by RT-PCR and Western blot. The inhibitory action of DPC4 gene expression on growth of these daughter cells was observed.Results DPC4/Smad4 gene integration in GP+E86、PA317/ pLXSN DPC4+ cells was detected by polymerase chain reaction. The BxPC-3 cells, which were null for DPC4, had stable expression of DPC4 after the infection of the pLXSN/DPC4. The expression of DPC4 gene was able to inhibit the growth of these cancer cells in vitro and downregulate the VEGF mRNA level.Conclusions This study suggested that there can be marked inhibition of growth and angiogenetic ability of pancreatic cancer cells after infection by retrovirus vector containing DPC4.

The expression of DPC4 during carcinogenesis of golden hamaster check pouch / 实用口腔医学杂志

Objective:To elucidate the role of dpc4 gene in the development of squamous cell carcinoma. Methods:DMBA at 5 g/L was locally applied in check pouch 3 times a week for 6,9 and 12 weeks respectively in three groups of golden hamasters to induce carcinoma.The animals were sacrificed after DMBA application.Normal controls were the check pouch samples of golden hamasters without any treatment and negative controls were established by local application of acetone for 12 weeks.DPC4 4 expression was examined by immunohistochemical staining.Results:DPC4 expression was observed in all(22) cases of the normal epithelium samples(100%),20 of the 21 cases of simple hyperplasia(95.2%),20 of the 27 cases of abnormal hyperplasia(74.1%) and 12 of the 25 cases of squomous cell carcinoma(48%).Conclusion:dpc4 may play an important role in the development of oral squomous cell carcinoma.

Alterations of the DPC4 Gene in Human Stomach Cancers / 대한암학회지

PURPOSE: Allelic loss on chromosome 18q is a hallmark of presence of a tummor represser gene. Recently, DPC4 (deleted in pancreatic carcinoma, locus 4), a candidate tumor suppressor gene, has been localized at 18q21. Inactivation of DPC4 gene was reported in pancreatic carcinomas, coloretal carcinomas, and prostatic carcinomas. The aim of the present study was to determine if it might be altered in stomach cancer. MATERIALS AND METHODS: We tested for DPC4 gene mutations and allelic status at 18q21 using a modified 'cold SSCP' method in 48 primary gastric carcinoma and correlated the findings with various clinicopathologic characteristics of the patients. RESULTS: The frequency of mutations in primary gastric cancer was 27.1% (13/48). Mutations of exon 1, 8, 10 were found in 2 (4.1%), 4 (8.2%) and 7 cases (14.6%), respectively. DNA sequencing of 13 cases with DPC4 mutations identified six cases (46.1%) with substitution, four cases with deletion (30.7%), and two cases (23.1%) with insertion. No significant difference was observed in the frequency of DPC4 mutations in terms of other various clinicopathologic characteristics. CONCLUSION: These findings suggest that DPC4 mutations may play a significant role in the establishment and progression of the primary gastric cancer.

Investigation of expression of c-erbB-2 and DPC4 in tissues of colonic schistosomiasis and colorectal carcinoma / 中国普通外科杂志

Objective To determine the relationship between chronic colonic schistosomiasis and colorectal carcinoma.Methods Expression levels of c-erbB-2 and DPC4 were detected by two-step and SP immunohistochemical method respectively in normal colonic mucosa of 15 cases,in colonic mucosa of 15 cases with simple schistosomiasis,20 cases of colorectal carcinoma with schistosomiasis and 20 cases of colorectal carcinoma without schistosomiasis.Results c-erbB-2 was expressed in each group with different levels,but the level in colonic mucosa with schistosomiasis was the highest compared to other groups,which had statistical significance(P