The effects of genistein on transforming growth factor-β1-induced invasion and metastasis in human pancreatic cancer cell line Panc-1 in vitro / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Pancreatic cancer is a devastating disease with the worst mortality rate. Therefore, a rational strategy for future drug development is critical. Genistein is a small, biologically active flavonoid that is found in high amounts in soy. This important compound supports a wide variety of biological activities, but is best known for its ability to inhibit cancer progression.</p><p><b>METHODS</b>Transwell chamber assay was performed to determine the effect of genistein on the invasion of the human pancreatic cancer cell line Panc-1 induced by transforming growth factor-β1 (TGF-b1) in the different condition (5 ng/ml 24 hours and 10 ng/ml 48 hours); Reverse transcription-polymerase chain reaction (RT-PCR) was used to estimate the mRNA levels of urinary plasminogen activator (uPA), matrix metallopeptidase 2/9 (MMP-2/9), Smad4, E-Cadherin and Vimentin; Western blotting was used to detect the protein levels of uPA, E-Cadherin, ERK1/2, P38 and P-P38, and the activity of MMP-2/9 protein were detected by gelatin zymography assay method. Cells structure was observed and analyzed by microscopy.</p><p><b>RESULTS</b>Genistein can inhibit effectively TGF-b1-induced invasion and metastasis in Panc-1 by Transwell assay, which is through regulating the mRNA and protein expression of uPA and MMP2, but not MMP9 by RT-PCR/Western blotting, and is positively correlated with the concentration of genistein. At the same time, genistein also could improve the progress of epithelial-mesenchymal transition (EMT) via morphology observation using light microscopy/transmission electron microscopy (TEM), which is mediated by the down-regulation of E-cadherin and the up-regulation of vimentin.</p><p><b>CONCLUSIONS</b>TGF-b1 mediates EMT process via numerous intracellular signal transduction pathways. The potential molecular mechanisms are all or partly through Smad4-dependent and -independent pathways (p38 MAPK) to regulate the antitumor effect of genistein.</p>

Indications, technique and efficacy of organ preserving pancreatectomy / 中华外科杂志

<p><b>OBJECTIVE</b>To discuss the proper surgical management of pancreatic benign and low-grade malignant potential neoplasm.</p><p><b>METHODS</b>The experience of 72 cases who accepted organ preserving pancreatectomy from January 1990 to May 2010 was analyzed retrospectively. There were 24 male and 48 female, aged from 15 to 68 years with mean age of 46 years. There were 9 cases underwent duodenum-preserving resection of the head of the pancreas, 29 cases underwent spleen-preserving distal pancreatectomy, 11 cases underwent middle segmental pancreatectomy, 23 cases underwent tumor extirpation of huge pancreatic cancer in pancreatic head and body.</p><p><b>RESULTS</b>Pancreatic fistula and biliary fistula in 1 case respectively were cured among who accepted duodenum-preserving resection of the head of the pancreas. Pancreatic fistula was found in 3 cases who accepted spleen-preserving distal pancreatectomy. Pancreaticobiliary anastomotic bleeding in 1 case was cured among who accepted middle segmental pancreatectomy. Pancreatic fistula was found in 5 cases among who accepted tumor extirpation of huge pancreatic cancer in pancreatic head and body, and liver metastasis was found in 3 cases at 6, 12, 16 months after surgery respectively.</p><p><b>CONCLUSIONS</b>Organ preserving pancreatectomy can obviously reduce operative injury to patients, its therapeutic effect is similar to that of classical operation, it is the first option of benign and low-grade malignant potential neoplasm.</p>

Macrocystic serous adenoma of the pancreas: a report of 5 cases / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the diagnosis and treatment of macrocystic serous adenoma of the pancreas (MSAP).</p><p><b>METHODS</b>The clinical data of 5 patients with MSAP treated from October 1999 to October 2009 were retrospectively analyzed. There were 5 female and 1 male.</p><p><b>RESULTS</b>Of the 5 patients, 3 patients presented with abdominal pain and fullness, 1 patient with jaundice, 1 patient with asymptomatic. Ultrasonography and CT could manifest macrocystic lesion of the pancreas; all the lesion showed a well-defined border, internal septations, enhanced cyst walls, with no intramural (mural) nodule and papillary projections; the wall was smooth and thin in 4 cases; irregular lobulation could be observed in 3 cases, round or oval in 2 cases; 2 cases had pancreatic duct dilatation, 1 case had biliary duct dilatation. The tumors located in the pancreatic body and tail in 3 cases, the tumors located the pancreatic head in 2 cases. The sizes of the tumors ranged from 6.5 cm to 13.0 cm (mean, 8.8 cm). Five patients all accepted surgical intervention. The main postoperative complication was pancreatic fistula (2 cases); all the fistula was cured. Recurrence or metastasis were not found in 5 patient followed up postoperatively from 8 to 35 months.</p><p><b>CONCLUSIONS</b>MSAP has no specific symptoms. The imaging appearance of MSAP is similar to mucinous cystic neoplasm of the pancreas. The tumor can gradually grow up and produce compression symptoms. MSAP can be cured by complete resection.</p>

Diagnosis and surgical treatment of 98 cases with adult primary retroperitoneal malignant tumor / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the diagnosis and surgical treatment of adult primary retroperitoneal malignant tumor (APRMT).</p><p><b>METHODS</b>The clinical data of 98 cases with APRMT underwent resection from January 1990 to April 2003 were analyzed retrospectively.</p><p><b>RESULTS</b>Among the 98 cases, complete excision were performed in 79 cases (80.6%), palliative excision in 16 cases (16.3%), tumor biopsy only in 3 cases (3.1%). Resection of involved adjacent organs were carried out in 25 cases (25.5%) and the re-operation rate for recurrence was 28.6% (28 cases). The 1, 3, 5 year survival rates for 79 cases with complete resection were 93.7%, 73.4% and 34.2%, respectively. The 1, 3, 5 year survival rate for 16 cases with palliative resection were 75.0%, 6.3% and 6.3%, respectively.</p><p><b>CONCLUSIONS</b>Certain imaging examinations are crucial to the diagnosis and preoperative evaluation of APRMT. Resection of the involved organs could improve resection rate and prognosis. For the recurrent cases, earlier reoperation is strongly recommended.</p>

Expression of programmed cell death 4 and its clinicopathological significance in human pancreatic cancer / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the expression of programmed cell death 4 (PDCD4) protein and its clinicopathological significance in human pancreatic cancer.</p><p><b>METHODS</b>Immunohistochemistry was used to examine the expression of PDCD4 protein in 69 specimens of pancreatic cancer and Western blot in 8 fresh specimens.</p><p><b>RESULTS</b>The expression of PDCD4 protein was significantly lower in all 8 fresh pancreatic cancer tissues than that in non-cancerous tissues detected by Western blot. Compared with non-cancerous pancreatic tissue (> 80% of positive cells), low PDCD4 expression was shown in 69 pancreatic cancer tissues (< 30% of positive cells in 36 cases and 30%-80% of positive expression cells in 33 cases). In the 33 cases with 30% and 80% of positive expression cells, the expression rates of PDCD4 protein were 57.6%, 24.2%, and 18.2% in well, moderately, and poorly differentiated cancers, respectively. In the 36 cases less than 30% of positive expression cells, however, the expression rate of PDCD4 protein in well, moderately, and poorly differentiated cases were 19.4%, 41.7%, and 38.9%, respectively. 67.4% (15/23) of the moderately differentiated cases and 70% (14/20) of the poorly differentiated cases showed < 30% of positive expression cells. Only 26.9% (7/26) of the well differentiated cases, however, showed < 30% of positive expression cells, indicating that low PDCD4 expression was associated with histological grade (P < 0.01). There was no relationship between PDCD4 expression and other clinicopathological parameters including patients' sex, age, and TNM stage.</p><p><b>CONCLUSIONS</b>Expression of PDCD4 protein is low in human pancreatic cancer and is correlated with the differentiation levels of human pancreatic cancer. PDCD4 may play an important role in the occurrence and development of pancreatic carcinomas.</p>

Comparison of pBcl-2 and pBax expression in primary invasive ductal pancreatic cancer between Chinese and Japanese patients / 中国医学科学院学报

<p><b>OBJECTIVE</b>To clarify the clinicopathologic significance of the expression of the Bcl-2 protein (pBcl-2) and the Bax protein (pBax), and their clinical implications in Chinese and Japanese patients with human invasive ductal carcinomas (IDCs) of the pancreas.</p><p><b>METHODS</b>The study included 59 Chinese and 65 Japanese patients with IDCs of the pancreas. pBcl-2 and pBax expression were immuno-stained with streptavidin-biotin (SAB) method.</p><p><b>RESULTS</b>pBcl-2 (+) was seen in 35.6% of Chinese and in 23.1% of Japanese patients. pBax (+) was seen in 49.2% of Chinese and 64.7% of Japanese patients. A comparison between them showed that there were significant differences in the male patients, in the patients with the moderately differentiated cancer, and in the elderly patients (chi squared = 4.447, P = 0.035; chi squared = 4.114, P = 0.043; chi squared = 6.657, P = 0.010 respective). In both Chinese and Japanese patients, those with pBcl-2 positive expression had a significantly higher survival rate than those with negative one (chi squared = 9.99, P = 0.0016; chi squared = 7.63, P = 0.0058). The group with pBax positive expression had a significantly higher survival rate in Japanese patients (chi squared = 9.37, P = 0.0022). Japanese patients whose tumors exhibited pBcl-2 and pBax positive immunostaining survived significantly longer than Chinese patients did (chi squared = 4.48, P = 0.0342; chi squared = 5.23, P = 0.023).</p><p><b>CONCLUSIONS</b>The expressions of both pBcl-2 and pBax are high found in Chinese and Japanese patients. The pBcl-2 positive expression implies a better prognosis in both Chinese and Japanese patients with IDCs of the pancreas. The effect of pBax expression on prognosis is different between Chinese and Japanese patients.</p>

Expressions of p53 and Gadd45a proteins in human pancreatic cancer and their clinicopathological significance / 中国医学科学院学报

<p><b>OBJECTIVE</b>To study the expressions of p53 and Gadd45a proteins and their clinicopathological significance in human pancreatic cancer.</p><p><b>METHODS</b>The expression of p53 and Gadd45a proteins was detected with immunohistochemistry in a series of 59 pancreatic cancers. Their relationships with the clinicopathological parameters including gender, tumor site, TNM stage, histological differentiation, and the prognosis of pancreatic cancer patients were analyzed.</p><p><b>RESULTS</b>The positive expression rate of p53 protein was 67.8% (40/59) and that of Gadd45a protein was 42.4% (25/59). The positive expression rate of p53 protein is significantly higher in patients < 65 years than in patients > or = 65 years (chi squared = 4.711, P = 0.030). Gadd45a expression was not correlated to the age of the patients. No significant difference was found between the expression of p53 proteins and histological differentiation and TNM stage of the tumors. Gadd45a expression was correlated with histological differentiation of pancreatic cancer (chi squared = 10.052, P = 0.007), but not with TNM stage of the tumors. No significant differences in the prognosis were found between the groups with and without p53 expression (chi squared = 0.09, P = 0.764) and the groups with and without Gadd45a expression (chi squared = 0.14, P = 0.704).</p><p><b>CONCLUSIONS</b>Both p53 and Gadd45a are highly expressed in human pancreatic cancer and may be associated with biological features of pancreatic cancer. Their expression alone or co-expression may be not helpful to evaluate the prognosis of patients with pancreatic cancer.</p>

Role of Epidermal Growth Factor in Invasion and Metastasis of Pancreatic Cancer Cells / 中国普外基础与临床杂志

Objective Overexpressions of epidermal growth factor(EGF)and EGF receptor have been associ- ated with progression and invasive phenotype of pancreatic cancer.However,the underlying molecular mechanism by which EGF worked in pancreatic cancer cells has not been completely understood.In this study,effect of EGF on the invasion and metastasis of pancreatic cancer cells and its regulatory mechanism were investigated.Methods The effects of EGF on the proliferation,adhesion and invasion of pancreatic cancer cells were detected by WST-1 prolif- eration assay,adhesion assay and invasive assay,respectively.The activity and expression of MMP-2 and MMP-9 were examined by zymography,Western blot and RT-PCR,respectively.The activity of NF-?B was examined by EMSA.Results EGF could significantly promote the invasiveness of pancreatic cancer cells but did not affect cell proliferation or adhesion.The expressions of NF-?B and MMP-9 were significantly increased by EGF,but EGF did not affect the activity and expression of MMP-2.Furthermore,EGF stimulated the NF-?B binding activity.Pre- treatment with NF-?B inhibitors,pyrrolidine dithiocarbamate(PDTC),could significantly inhibit the activity of NF-?B induced by EGF.Meanwhile,the EGF-induced expression and activity of MMP-9,as well as cell invasiveness were also inhibited by NF-?B inhibitor.Conclusion EGF could increase the expression and promote the invasiveness of MMP-9 via the activation of NF-?B in pancreatic cancer cells,which implies that NF-?B inhibitant,such as PDTC,may diminish the invasiveness of pancreatic cancer cells.