[Show abstract][Hide abstract] ABSTRACT: Since telomerase expression is highly prevalent in human cancers, the quantitation of serum/plasma hTERT (human telomerase reverse transcriptase) mRNA levels may be useful for early detection of PCa (pancreatic cancer). To analyse the correspondence between exhTERT (extracellular hTERT) mRNA levels and hTERT expression, we designed a cell culture system to investigate factors modulating the extracellular levels of hTERT mRNA in media conditioned by eight PCa cell lines. We found that the level of exhTERT mRNA was dependent on cell growth rate. MIAPaCa-2, PANC-1, KLM-1 and PK-9 cells expressed high levels of exhTERT mRNA, independent of cell density, whereas proliferating PK-59, BxPC-3 and PK-45H cells released low levels of exhTERT mRNA. The augmented release of mRNA by spontaneous dead MIAPaCa-2 cells was further increased at postconfluence. In Capan-1 cells, low correspondence of marker was also due to RNase secretion. Upon reaching confluence, some PCa cell lines showed down-regulation of hTERT expression. Following cell-cell adhesion, as shown by E-cadherin engagement, PK-59 cells showed levels of extracellular message below the limits of detection, a loss not due to an increase in message degradation. These results suggest that the levels of exhTERT mRNA in the medium of PCa cell lines are altered not only in response to cell growth rate and cell destruction, but are responsive to extracellular cues such as RNases and cell density. A cell-free assay for exhTERT mRNA may therefore not be useful for early detection of PCa.
Preview · Article · Nov 2010 · Cell Biology International
[Show abstract][Hide abstract] ABSTRACT: We report a 48-year-old man with hepatocellular carcinoma (HCC) treated with hepatic arterial infusion (HAI) chemotherapy followed by proton beam therapy. The HCC lesion in this patient was 88 mm in diameter, with portal vein tumor thrombosis in the right lobe of the liver. He was first treated with 5-fluorouracil, cisplatin, and isovorin, administered by HAI, combined with interferon-alpha, and he was subsequently treated with epirubicin and mitomycin-C administered by HAI. However, no definite efficacy of either of these treatments was observed. Then, after 3 weeks' continuous administration of irinotecan by HAI, the tumor size decreased to 68 mm in diameter. However, 3 months after reduction of the tumor, the tumor had become enlarged to 100 mm in diameter and intrahepatic metastases were prominent. Angiographic findings indicated that the HCC was fed not only from the right hepatic artery but also from the left gastric and right and left subphrenic arteries. After rearrangement of the arteries, and 3 months' continuous HAI chemotherapy with irinotecan, plus hyperthermia, the tumor size had decreased to 50 mm in diameter. The reduction rate of the main tumor according to the Response Evaluation Criteria in Solid Tumors was 43%; therefore, the efficacy of this treatment was judged as a partial response. Two months after reduction of the tumor, the patient's serum alpha-fetoprotein (AFP) level was elevated, and so docetaxel was administered by HAI instead of irinotecan. The liver tumors showed gradual enlargement during the administration of docetaxel, although the AFP level was suppressed. Proton beam therapy was instituted and the liver tumors showed necrosis after this therapy. The patient died of hepatic failure and distant metastases 6 years after the onset of HCC. As far as we know, this is the first case report of HCC treated effectively with irinotecan administered by HAI followed by proton beam therapy in which tumor suppression and the long-term survival of the patient were observed.
Full-text · Article · Oct 2009 · Journal of Infection and Chemotherapy
[Show abstract][Hide abstract] ABSTRACT: In view of carcinoembryonic properties with respect to -GTP, we investigated whether or not hepatoma specific -GTP isoenzyme was found in the sera of patients with hepatoma. Fractionations of serum -GTP were carried out in sera from 229 patients with various hepatobiliary diseases including 68 with hepatoma by polyacrylamide gradient gel electrophoresis. The band II which was seen in the region near to ceruloplasmin could be detected in 25 out of the 68 patients with hepatoma (37%), but not in the patients with other diseases. In addition to the II band, an extra band (II) was found in 15 of these 25 patients. The band II and II′ could not be found in any groups of patients studied except hepatoma patients. It was presumed that band II and II′ could be specific for hepatoma.
No preview · Article · Feb 2009 · Scandinavian Journal of Immunology
[Show abstract][Hide abstract] ABSTRACT: We report usefulness of endoscopic ultrasonography (EUS) for the diagnoses of chronic pancreatitis (CP). We evaluated EUS features of hyperechoic foci, hyperechoic strand, lobular out gland margin, lobularity, cyst, stone, ductal dilatation, side branch dilatation, duct irregularity, hyperechoic duct margins, atrophy, localized swelling in cases with CP (30 definite and 6 probable) diagnosed by computed tomography (CT) or endoscopic retrograde cholangiopancreatography (ERCP). Hyperechoic foci, hyperechoic strand, lobularity, hyperechoic duct margins in definite or probable CP were recognized in more than 80 % cases. Lobular out gland margin was observed in 14 (47 %) of 30 cases with definite CP, although none with probable CP (P = 0.06). In conclusions, hyperechoic foci, hyperechoic strand, lobularity, hyperechoic duct margins are useful for screening of CP, and lobular out gland margin would be reliable finding in definite CP.
No preview · Article · Apr 2008 · Gastroenterological Endoscopy
[Show abstract][Hide abstract] ABSTRACT: Because autoimmune pancreatitis (AIP) responds well to corticosteroids, many AIP patients are given this treatment. However, there is no consensus on the indications, dose, or duration of steroid treatment. The aim of this study was to establish the most appropriate steroid therapy regimen.
We retrospectively reviewed morphological and serological improvement after steroid therapy and long-term outcome including relapse in 41 AIP patients who were given steroid therapy and were prospectively followed-up for more than 1 year.
All patients responded to steroid therapy, which was given because of bile duct stenosis secondary to sclerosing cholangitis in 34 AIP patients. Pancreatic enlargement normalized within one month; however, 13 patients had incomplete resolution of pancreatic duct narrowing, and 14 patients had incomplete resolution of bile duct stenosis. There was no correlation between the degree of morphological improvement and the initial prednisolone dose (30 mg and 40 mg/day). In 58% of 19 patients, serum IgG4 elevation failed to normalize. Glucose intolerance improved in 38% of the 21 patients with diabetes mellitus. Nine patients who had complete morphological and serological resolution, stopped their medication, and none have relapsed. Thirty-two patients continued maintenance therapy, and 4 of these patients suffered relapse.
The indications for steroid therapy in AIP patients include bile duct stenosis caused by sclerosing cholangitis and other systemic diseases, such as retroperitoneal fibrosis and diabetes mellitus. We recommend that oral prednisolone be used at an initial dose of 30 mg/day; maintenance therapy is required in cases without complete morphological and serological resolution.
No preview · Article · Feb 2008 · Scandinavian Journal of Gastroenterology
[Show abstract][Hide abstract] ABSTRACT: Mass-forming pancreatitis can be divided into two distinct types: alcoholic and autoimmune. There have been some cases of an ambiguous diagnosis although care was taken to differentiate between alcoholic mass-forming pancreatitis, focal type autoimmune pancreatitis and pancreatic cancer.
We report a case of pancreatic cancer mimicking alcoholic or autoimmune pancreatitis with the formation of a mass in a 32-year-old man with a history of heavy drinking. Although both serum immunoglobulin G and immunoglobulin G4 levels were normal, many serum auto-antibodies, including the antinuclear antibody, were detected. After he stopped drinking, abdominal computed tomography showed a pancreatic head mass 28 mm in diameter with little and weak enhancement in the early and delayed phases, respectively. Endoscopic retrograde cholangiopancreatography showed an obstruction of the main pancreatic duct in the pancreatic head and marked stenosis of the lower common bile duct. Although a percutaneous ultrasound-guided pancreatic biopsy demonstrated no evidence of autoimmune pancreatitis, he was treated with prednisolone to test the efficacy of steroid therapy. However, the pancreatic mass became enlarged after steroid therapy, and he underwent surgery during which the mass was found to be pancreatic cancer. Although the patient was treated with gemcitabine, he died 5 months after surgery. We retrospectively assessed DNA hypermethylation in the patient's pure pancreatic juice obtained on admission. We observed hypermethylation of the cancer-specific gene tissue factor pathway inhibitor 2 (TFPI2).
This finding suggests that if the DNA hypermethylation of pure pancreatic juice had been assayed before steroid therapy, it would have supported the diagnosis of pancreatic cancer, and steroid therapy could have been avoided.
Full-text · Article · Feb 2008 · JOP: Journal of the pancreas
[Show abstract][Hide abstract] ABSTRACT: This study was undertaken to elucidate the diagnostic significance of the measurement of a cancer-associated carbohydrate antigen, NCC-ST-439 (ST-439), in pure pancreatic juice collected by endoscopic cannulation, chiefly from patients with pancreatic diseases.
The mean concentrations of ST-439 in each of the 4 fractions collected were significantly higher in patients with pancreatic cancer than in controls, but patients with chronic pancreatitis or cholecystolithiasis did not have higher levels. Similarly, a significant increase in the mean output of ST-439 was observed only in patients with pancreatic cancer. When the cut-of value was set at the mean concentration+ 2 X the standard deviations of the controls, significant concentrations of ST-439 were found, in the first fraction (washout phase) in 56% of the pancreatic cancer cases, 31% of the chronic pancreatitis cases and 0% of the cholecystolithiasis cases; in the third fraction (secretory phase) results were 50%, 7% and 0%, respectively. Furthermore, when the cut-of value was set at the highest concentration found among patients with chronic pancreatitis (to enhance the specificity for pancreatic cancer), the prevalence of significant ST-339 levels among Pancreatic cancer patients was 50% in the first fraction and 44% in the third fraction.
These results indicate that the measurement of ST-439 in pancreatic juice is useful as a specific marker for pancreatic cancer, although its sensitivity is less than was initially hoped
No preview · Article · Aug 2007 · Digestive Endoscopy
[Show abstract][Hide abstract] ABSTRACT: Endoscopic ultrasonography has become an important diagnostic procedure complementary to endoscopy and histopathological study in the preoperative evaluation of gastric carcinoma. Despite allowing visualization of tumoral infiltration with quite high accuracy, certain factors have limited the accuracy of this modality or even led to misinterpretation. We designed a prospective study to evaluate the accuracy of gastric carcinoma diagnosis with special reference to factors resulting in misdiagnosis. During a 22 month period, 86 patients with early and advanced gastric carcinoma underwent surgical or endoscopic resection on the basis of endosonographic findings. In all patients, endosonographic findings, location and macroscopic type of the tumor and histopathological characteristics including depth of invasion, malignant cell type and/or differentiation, and the presence/absence of ulceration in the tumor focus were recorded. The endosonographic and histopathological results were compared at the end of the study. Overall accuracy was 85% using the TNM staging system. There were no significant differences in accuracy in the location of the tumor, histological grading or macroscopic type of tumor, although the accuracy rate was lower for tumors located in the antrum. Ulceration in the tumor focus was a major factor leading to misinterpretation of the findings of early gastric cancer (p<0.02). The diagnosis of microinvasion is an issue which remains to be resolved.
No preview · Article · Aug 2007 · Digestive Endoscopy
[Show abstract][Hide abstract] ABSTRACT: Autoimmune pancreatitis is characterized by diffuse enlargement of the pancreas, diffuse irregular narrowing of the main pancreatic duct, severe lymphoplasmacytic infiltration and fibrosis of the pancreas. Retroperitoneal fibrosis may occasionally be associated with autoimmune pancreatitis.
We report a 77-year-old man with autoimmune pancreatitis associated with retroperitoneal fibrosis. Abdominal ultrasonography and computed tomography demonstrated diffuse enlargement of the pancreas and a capsule-like rim. Furthermore, a retroperitoneal mass was recognized anterior to the abdominal aorta. Antinuclear antibody, IgG and IgG4 values were elevated. Therefore, this patient was diagnosed as having autoimmune pancreatitis associated with retroperitoneal fibrosis. We performed steroid therapy using prednisolone. After 4 weeks, both IgG and IgG4 values decreased and both the swelling of the pancreas and also the retroperitoneal mass were obviously diminished.
This is a rare case of autoimmune pancreatitis associated with retroperitoneal fibrosis.
Full-text · Article · Feb 2007 · JOP: Journal of the pancreas
[Show abstract][Hide abstract] ABSTRACT: Chronic pancreatitis is characterized by acinar destruction and fibrosis. We previously reported that apoptosis is involved in acinar destruction in chronic pancreatitis in the WBN/Kob rat. This study aimed to elucidate the antiapoptotic effect of Saikokeishito (TJ-10).
Four-week-old male WBN/Kob rats were fed a special pellet diet (MB-3) with or without TJ-10 (80 mg/100 g body weight) for 20 weeks. Pancreas was histopathologically examined every 4 weeks, and the expression of apoptosis-related factors such as Fas and Fas ligand (FasL) mRNA and protein was analyzed with RT-PCR, in situ hybridization and immunohistochemistry. Apoptosis was detected with a TUNEL method.
In untreated WBN/Kob rats, chronic pancreatitis developed at 12 weeks and progressed with marked acinar cell destruction at 16 weeks. The expression of Fas and FasL peaked at 12 and 20 weeks. An apoptotic index in acinar cells correlated to the expression of Fas and FasL mRNA. However, in the TJ-10-treated rats, the rate of pancreatic acinar cell destruction, the apoptotic index at 12-20 weeks, and the expression of Fas and FasL at 12 and 20 weeks decreased significantly compared to those in untreated rats.
These results suggest that TJ-10 has a therapeutic effect on chronic pancreatitis by the suppression of acinar cell apoptosis via the Fas/FasL system.
[Show abstract][Hide abstract] ABSTRACT: The tissue factor pathway inhibitor 2 (TFPI-2) is a Kunitz-type serine proteinase inhibitor. Recently, the aberrant methylation of TFPI-2 was detected frequently in pancreatic carcinoma (PCa) tissues but not in normal pancreatic tissues. We analyzed the aberrant methylation of TFPI-2 in the pure pancreatic juice (PPJ) aspirated endoscopically from patients with various pancreatic diseases. Using the highly sensitive methylation-specific polymerase chain reaction (MSP) and quantitative MSP (Q-MSP) assay, we investigated the aberrant methylation of TFPI-2 in nine human PCa cell lines and in the PPJ from patients with PCa, intraductal papillary mucinous neoplasms (IPMN) and chronic pancreatitis (CP). The incidence of aberrant TFPI-2 methylation was seven (77.8%) of nine PCa cell lines by Q-MSP. In cell lines, the expression of TFPI-2 mRNA by quantitative reverse transcription-polymerase chain reaction showed an inverse correlation to the aberrant methylation of TFPI-2. The incidence of aberrant TFPI-2 methylation in the PPJ was 21 (58.3%) of 36 PCa patients, three (17.6%) of 17 IPMN and one (4.8%) of 21 CP by MSP assay. Using a suitable cut-off value of 2.5 according to the receiver operating characteristic curve, the incidence of aberrant TFPI-2 methylation in the PPJ by real-time MSP was 18 (62.1%) of 29 PCa patients, one (5.1%) of 17 IPMN and three (14.3%) of 21 CP, respectively. The incidence of quantitative TFPI-2 hypermethylation in the PPJ with PCa was significantly higher than that with IPMN (P < 0.001) or CP (P < 0.001). Moreover, the aberrant methylation rate of TFPI-2 in the PPJ was 100%, as observed (6/6) in the PCa patients with liver metastasis, and 86.7% (26/30) in stages IVa + IVb of PCa by Q-MSP assay. These results suggest that promoter methylation of TFPI-2 in the PPJ may be a useful marker in the diagnosis and progression of PCa using an endoscopically feasible approach.
[Show abstract][Hide abstract] ABSTRACT: To examine whether there is a difference in the autoimmune pancreatitis (AIP) seen in young and elderly patients.
AIP has a preponderance for elderly males, although the reason is unknown.
A total of 64 patients with AIP were divided into a young (<40 y old) group and a middle-aged or elderly group (> or =40 y old) according to the age at diagnosis. The clinical findings of each group were compared.
The young group consisted of 6 patients (3 men, 3 women) with a mean age of 33.0 (range, 28 to 37) years. In the middle-aged or elderly group, there were 58 patients with a mean age of 66.4 (range, 46 to 83) years; males predominated (79%). Abdominal pain as the presenting symptom was significantly more frequent in the young group than in the middle-aged or elderly group (100% vs. 43%, P<0.05). Obstructive jaundice was detected in only 17% (1/6) of patients in the young group compared with 59% (34/58) of patients in the middle-aged or elderly group. Serum amylase elevations were detected more frequently in the young group than in the middle-aged or elderly group (83% vs. 40%, P<0.05). One young patient also had ulcerative colitis.
Although rare in Japan, young patients with AIP show different clinical features from middle-aged or elderly patients with AIP; young patients are more likely to have abdominal pain and serum amylase elevations.
No preview · Article · Oct 2006 · Journal of Clinical Gastroenterology
[Show abstract][Hide abstract] ABSTRACT: Aberrant methylation of CpG islands is a common mechanism for the dysregulation of tumor suppressor genes in a variety of human malignancies. Preproenkephalin ppENK) hypermethylation is recognized in 90% of pancreatic carcinoma (PCa) tissues, but not in normal pancreas. We analyzed ppENK hypermethylation in pure pancreatic juice (PPJ) in patients with PCa, intraductal papillary mucinous neoplasms (IPMN), and chronic pancreatitis (CP), and elucidated its usefulness as a marker in the diagnosis of PCa compared with p53 mutation.
PPJ was collected endoscopically from 28 patients with PCa, 15 patients with IPMN, and 20 patients with CP. DNA was extracted from the supernatant and the sediment of PPJ. Methylation-specific polymerase chain reaction was performed for hypermethylation analysis of ppENK. In addition, single-strand conformation polymorphism and direct sequencing were performed simultaneously to identify p53 mutations.
The incidence of ppENK hypermethylation in the supernatant and/or the sediment of PPJ was 50% (14 of 28) in patients with PCa. In contrast, the incidence of ppENK hypermethylation was 26.7% (4 of 15) in patients with IPMN, and 5% (1 of 20) in patients with CP (P < 0.002). The incidence of p53 mutations in the PPJ was 42.9% (12 of 28) in patients with PCa and 0% (0 of 20) in patients with CP. Furthermore, the incidence of ppENK hypermethylation and/or p53 mutations in the PPJ was enhanced to 67.9% (19 of 28) in patients with PCa in the combination assay.
These results suggest that ppENK hypermethylation in PPJ is specific for cancer, and the combination assay with p53 enhances the genetic diagnosis of PCa.
No preview · Article · Aug 2006 · Journal of Gastroenterology
[Show abstract][Hide abstract] ABSTRACT: The incidence of acute pancreatitis in Japan is increasing and ranges from 187 to 347 cases per million populations. Case fatality was 0.2% for mild to moderate, and 9.0% for severe acute pancreatitis in Japan in 2003. Experts in pancreatitis in Japan made this document focusing on the practical aspects in the early management of patients with acute pancreatitis. The correct diagnosis of acute pancreatitis and severity stratification should be made in all patients using the criteria for the diagnosis of acute pancreatitis and the multifactor scoring system proposed by the Research Committee of Intractable Diseases of the Pancreas as early as possible. All patients diagnosed with acute pancreatitis should be managed in the hospital. Monitoring of blood pressure, pulse and respiratory rate, body temperature, hourly urinary volume, and blood oxygen saturation level is essential in the management of such patients. Early vigorous intravenous hydration is of foremost importance to stabilize circulatory dynamics. Adequate pain relief with opiates is also important. In severe acute pancreatitis, prophylactic intravenous administration of antibiotics at an early stage is recommended. Administration of protease inhibitors should be initiated as soon as the diagnosis of acute pancreatitis is confirmed. A combination of enteral feeding with parenteral nutrition from early stage is recommended if there are no clear signs and symptoms of ileus and gastrointestinal bleeding. Patients with severe acute pancreatitis should be transferred to ICU as early as possible to perform special measures such as continuous regional arterial infusion of protease inhibitors and antibiotics, and continuous hemodiafiltration. The Japanese Government covers medical care expense for severe acute pancreatitis as one of the projects of Research on Measures for Intractable Diseases.
Full-text · Article · Jul 2006 · World Journal of Gastroenterology
[Show abstract][Hide abstract] ABSTRACT: Secreted apoptosis-related protein (SARP) families are considered to counteract the oncogenic Wnt signaling pathway, and inactivation of this gene may aid cancer development and progression. Recently, the aberrant methylation of SARP2 was detected frequently in pancreatic carcinoma (PCa) tissue, but not in normal pancreatic tissue. We evaluated the hypermethylation of SARP2 in pure pancreatic juices (PPJ) aspirated endoscopically from patients with PCa, intraductal papillary mucinous neoplasm of the pancreas (IPMN), chronic pancreatitis (CP), and a control group who were consequently free of pancreatic diseases according to the differential diagnosis of PCa.
We investigated the aberrant methylation of SARP2 in 9 human PCa cell lines and in the PPJ samples from 33 patients with PCa, 20 with IPMN, 19 with CP, and 10 control patients. DNAs extracted from not only sediment, but also the supernatant of the PPJ and PCa cell lines were treated with sodium bisulfite and analyzed by methylation-specific polymerase chain reaction (PCR) (MSP). Moreover, real-time MSP was also performed for the melting curve analysis and the quantitative analysis of SARP2 in the PPJ.
The incidence of the aberrant methylation of SARP2 using MSP was 8/9 (89%) in PCa cell lines, 26/33 (79%) in the PPJ with PCa, and 17/20 (85%) with IPMN. However, it was only 1/19 (5%) in the PPJ with CP, and 0/10 (0%) in the PPJ of the control patients, respectively. The incidences of aberrant methylation of SARP2 in the PPJ with PCa and IPMN were significantly higher than that in the PPJ with CP (P < 0.001, P < 0.001). Melting curve analysis by real-time MSP revealed that the incidences of aberrant methylation of SARP2 in PPJ was 28/33 (85%) with PCa, 9/11 (82%) with the malignant group of IPMN, 5/9 (56%) with the benign group of IPMN and 5/19 (26%) with CP. In this analysis, there were significant differences between PCa and CP (P < 0.001), and between the malignant group of IPMN and CP (P < 0.005). In the quantitative analysis by real-time MSP with a suitable cut-off value, the incidences of aberrant methylation of SARP2 in the PPJ with PCa, the malignant group of IPMN, the benign group of IPMN, and CP were 19/33 (58%), 6/11 (55%), 3/9 (33%), and 2/19 (11%), respectively. The incidence of the aberrant methylation of SARP2 in the PPJ was significantly different between PCa and CP and between the malignant group of IPMN and CP (P < 0.005 and P < 0.05, respectively).
Hypermethylation of SARP2 in the PPJ may be a highly sensitive and useful marker for the detection of pancreatic neoplasms, including PCa and the malignant group of IPMN.
[Show abstract][Hide abstract] ABSTRACT: To investigate the expression of genes involved in the gemcitabine-induced cytotoxicity in human pancreatic cancer cells.
A human pancreatic cancer cell line, PANC-1, was cultured. 1x10(4) PANC-1 cells were plated in 96-well microtiter plates. After being incubated for 24 h, gemcitabine was added to the medium at concentrations ranging 2.5-1000 mg/L. The AlamarBlue dye method was used for cell growth analysis. DNA fragmentation was quantitatively assayed using a DNA fragmentation enzyme-linked immunosorbent assay (ELISA) kit. PAP and TP53INP1 mRNA expression was determined using the reverse transcription-polymerase chain reaction with semi-quantitative analysis. The expression of GSK-3beta and phospho-GSK-3beta proteins was examined with Western blot analysis.
The IC50 for the drug after a 48-h exposure to gemcitabine was 16 mg/L. The growth of PANC-1 cells was inhibited by gemcitabine in a concentration-dependent manner (P<0.0001) and the cell growth was also inhibited throughout the time course (P<0.0001). The DNA fragmentation rate in the gemcitabine-treated group at 48 h was 44.7%, whereas it was 25.3% in the untreated group. The PAP mRNA expression was decreased after being treated with gemcitabine, whereas the TP53INP1 mRNA was increased by the gemcitabine treatment. Western blot analysis showed that phospho- GSK-3beta (ser9) was induced by the gemcitabine treatment.
Gemcitabine suppresses PANC-1 cell proliferation and induces apoptosis. Apoptosis is considered to be associated with the inhibition of PAP and GSK-3beta, and the activation of TP53INP1 and pospho-GSK-3beta (ser9).
Preview · Article · Apr 2006 · World Journal of Gastroenterology
[Show abstract][Hide abstract] ABSTRACT: Overexpression of tumor protein p53-induced nuclear protein 1 (TP53INP1) induces G1 cell cycle arrest and increases p53-mediated apoptosis. To clarify the clinical importance of TP53INP1, we analyzed TP53INP1 and p53 expression in gastric cancer.
TP53INP1 and p53 expression were examined using immunohistochemistry in 142 cases of gastric cancer. The apoptosis of gastric cancer cells was analyzed using the TUNEL method. The relationship between the expression of TP53INP1 and clinicopathological factors was statistically analyzed.
TP53INP1 was expressed in 98% (139/142 cases) of non-cancerous gastric tissues and was down-expressed in 64% (91/142 cases) of gastric cancer lesions from the same patients. TP53INP1 expression was significantly decreased (43.9%) in poorly differentiated adenocarcinoma compared with well or moderately differentiated adenocarcinoma (81.6%). Cancers invading the submucosa or deeper showed lower positively (59.1%) compared with mucosal cancers (85.2%). Decrease or loss of TP53INP1 expression was significantly correlated with lymphatic invasion (54.3% vs 82.0% without lymphatic invasion) and node-positive patients (31.3% vs 68.3% in node-negative patients). P53 was expressed in 68 (47.9%) patients of gastric cancer, whereas it was absent in normal gastric tissues. A significant association was also observed between TP53INP1 status and the level of apoptosis in tumor cells: the apoptotic index in TP53INP1-positive tissues was significantly higher than that in TP53INP1-negative portions. Finally, when survival data were analyzed, loss of TP53INP1 expression had a significant effect in predicting a poor prognosis (P=0.0006).
TP53INP1-positive rate decreases with the progression of gastric cancer. TP53INP1 protein negativity is significantly associated with aggressive pathological phenotypes of gastric cancer. TP53INP1 is related to the apoptosis of gastric cancer cells. The decreased expression of the TP53INP1 protein may reflect the malignant grade of gastric cancer and is regarded as an adverse prognostic factor.
Preview · Article · Mar 2006 · World Journal of Gastroenterology
[Show abstract][Hide abstract] ABSTRACT: A 72-year-old man was admitted to our hospital for investigation of jaundice. We made a preoperative diagnosis of macrocystic serous cystadenoma (SCA) of the pancreas, but did not perform palliative choledochojejunostomy because aspiration of the pancreatic cystic fluid caused the cysts to shrink and relieved the compressive stenosis of the common bile duct (CBD) during the operation. Frozen sections of the cyst wall taken by incision biopsy showed no signs of malignancy. Therefore, we performed fenestration of the cystic wall after fixing the inner epithelium of the cyst with 100% ethanol and aspirating the cystic fluid. Cholangiography after the cystic fenestration showed resolution of the CBD stenosis and abdominal computed tomography (CT) confirmed the disappearance of the pancreatic cysts. No recurrence of cystic swelling or obstructive jaundice has been detected by abdominal CT or laboratory data for more than 2 years since the cystic fenestration. Thus, cystic fenestration may be a better palliative option for treating benign compressive tumors such as macrocystic SCA of the pancreas causing obstructive jaundice.