Biomedical subjects

T Aikou

Publications and source records attributed to T Aikou.

At least 91 records · Page 5Linked to original sources

PubMed1999

Postoperative prediction of and strategy for metastatic recurrent hepatocellular carcinoma according to histologic activity of hepatitis.

BACKGROUND: The hepatitis activity index (HAI) score describes the histologic status of accompanying chronic hepatitis and was established by pathologists. The aim of this study was twofold: 1) to investigate the correlation between intrahepatic metastatic recurrence (IM) and the HAI score of the noncancerous region of the liver and 2) to estimate the usefulness of postoperative preventive chemotherapy in patients with hepatocellular carcinoma (HCC). METHODS: The study included 158 consecutive patients who underwent curative resection for HCC and had been observed for > 1 year. Based on the HAI scores of the noncancerous region the patients were classified into 3 groups: those with mild hepatitis (n = 33) (i.e., with HAI scores of 0-5), those with moderate hepatitis (n = 77) (with HAI scores of 6-9), and those with severe hepatitis (n = 48) (those with HAI scores of > or = 10). In addition, a prospective randomized trial of postoperative adjuvant chemotherapy was performed for 21 patients with moderate hepatitis. RESULTS: The patients in the moderate hepatitis group were found to be at higher risk for IM recurrence within 2 years after HCC resection compared with those patients in the mild (P = 0.05) and severe (P < 0.01) hepatitis groups. The incidences of more than two tumors and portal vein involvement in patients with moderate hepatitis were much higher than in those patients with mild or severe hepatitis. Multivariate analysis showed that intraoperative bleeding volume, the number of nodules, portal vein involvement, and moderate hepatitis were independent predictive factors for IM recurrence free survival. Ten patients with moderate hepatitis had received postoperative intrahepatic arterial chemotherapy (2-3 courses with a maximum dose of 80 mg of cisplatin and 10 mg of mitomycin C at 1-month intervals) for the last 3 years. Although the number of patients was small, the therapy improved the disease free survival rate significantly compared with 11 patients who received no therapy. CONCLUSIONS: The patients with moderate hepatitis (HAI score of 6-9) had the highest rate of IM recurrence among the three HAI groups. Postoperative hepatic arterial chemotherapy may be useful in improving the rate of disease free survival after surgery among these patients.

Aged↗

PubMed1999

Expression of mucin 1 (MUC1) in esophageal squamous-cell carcinoma: its relationship with prognosis.

Using 2 anti-mucin 1 (MUC1) monoclonal antibodies (MAbs), DF3 and BCP8, we examined MUC1 expression immunohistochemically in 192 esophageal squamous-cell carcinomas (SCCs). In normal squamous epithelium of the esophagus, DF3 was not expressed, but BCP8 was expressed on the cell membrane, mainly in the surface layer. In esophageal SCCs, DF3 and BCP8 were expressed mainly on the cell membrane of SCC cells, but also in the cytoplasm in several cases. To analyze the correlation of MUC1 expression and the prognosis of the patients, the 192 cases were divided into 2 groups: high-expression group (HEG, > 50% of the neoplastic cells stained) and low-expression group (LEG, < 50% of neoplastic cells stained). DF3-HEG (24 patients) showed a significantly poorer survival rate than DF3-LEG (168 patients), whereas there was no significant difference in survival between BCP8-HEG (43 patients) and BCP8-LEG (149 patients). Also, in the analysis of 162 patients with advanced stage (submucosal or deeper invasion) to exclude the influence of low expression of DF3 and BCP8 in 30 patients with early stage (up to the level of muscularis mucosae), DF3-HEG (24 patients) showed significantly poorer survival than DF3-LEG (138 patients), whereas there was no significant difference in survival between BCP8-HEG (42 patients) and BCP8-LEG (120 patients). The results of our study on esophageal SCC suggest that the expression of sialyl oligosaccharides detected by DF3 is related to poor prognosis.

Carcinoma, Squamous Cell↗

PubMed1999

Thymidine phosphorylase in human esophageal squamous cell carcinoma.

BACKGROUND: Experimental evidence has shown that thymidine phosphorylase (dThdPase) is identical to platelet-derived endothelial cell growth factor (PD-ECGF) and has angiogenic activity. The enzymatic activity of dThdPase was needed for the angiogenesis by the enzyme. These observations were catalysts for the current study. METHODS: The authors examined retrospectively the expression of the angiogenic factor dThdPase in 163 primary esophageal squamous cell carcinomas and its association with angiogenesis and clinicopathologic findings. To determine whether dThdPase expression was a prognostic factor after adjustment for the established prognostic factors and microvessel count, the authors conducted a survival analysis using the Cox proportional hazards model. RESULTS: dThdPase was expressed significantly more frequently (P < 0.001) in esophageal carcinomas (83 of 163, 50.9%) than in adjacent nonneoplastic esophageal tissue samples (20 of 163, 12.3%). Microvessel counts were significantly higher (P < 0.001) in dThdPase positive carcinomas (18.3+/-6.2) than in dThdPase negative carcinomas (8.2+/-7.5). Significant correlations were observed between dThdPase expression and numerous clinicopathologic findings, including pT, pN, pM categories; lymphatic invasion; venous invasion; and residual tumors. Prognostic variables studied using a Cox hazard regression model confirmed that dThdPase expression was an independent prognostic factor in esophageal squamous cell carcinoma, although pN category was the best predictor of patient survival. CONCLUSIONS: This study indicated that in esophageal squamous cell carcinoma, dThdPase expression is associated with angiogenesis and is an unfavorable prognostic factor. These findings implied that the inhibition of dThdPase would improve the prognoses of some patients with dThdPase positive esophageal tumors.

Aged↗

PubMed1999

Treatment for accidental occlusion of the hepatic artery after hepatic resection: report of two cases.

Two patients in whom accidental hepatic artery occlusion (HAO) occurred after hepatic resection (Hx) were reported. A 59-year-old female who underwent Hx for hepatocellular carcinoma with underlying liver cirrhosis developed HAO on postoperative day (POD) 14 and died of hepatic failure on POD 23. The autopsy findings showed multiple necrosis in the remnant liver and an extraluminal hematoma of the hepatic artery, suggesting an injury caused by Pringle's maneuver. The second case was a 53-year-old male who underwent Hx for cholangiocarcinoma without any underlying liver disease. He developed HAO on POD 6, and radiological studies indicated a pseudoaneurysma formation and severe stenosis of the hepatic artery. It was speculated that the cause of the HAO was intraluminal injury of the hepatic artery during an angiographic study conducted prior to Hx. Partial arterialization of the portal vein was performed, following which his liver function test results improved. In both cases, measuring the serum hepatocyte growth factor level and the hepatic vein oxygen saturation proved useful, not only for determining the degree of liver injury, but also for predicting the outcome after treatments for HAO. Furthermore, the partial arterialization of the portal vein for HAO after Hx may rescue the normal remnant liver.

Aneurysm, False↗

PubMed1999

Does preoperative chemotherapy cause adverse effects on the perioperative course of patients undergoing esophagectomy for carcinoma?

The aim of this study was to clarify whether preoperative chemotherapy caused adverse effects on the perioperative course of patients undergoing esophagectomy. A total of 42 esophageal cancer patients were entered into a randomized trial and were analyzed. Twenty-one patients were assigned to immediate surgery (Surgery Group). The other 21 received two 5-day courses of chemotherapy comprising cisplatin (70 mg/m2) on day 1, and fluorouracil (700 mg/m2) and leucovorin (20 mg/m2) on each of days 1 to 5 (chemotherapy group). Hospital mortality comprised of one patient (2.3%) who had undergone an operation in the beginning of this series at 21 days after chemotherapy. Thereafter, the interval between the chemotherapy and operation was prolonged, with the average being 35 +/- 7 days. Preoperatively, both the lymphocyte counts and serum albumin levels were not increased in the chemotherapy group of patients even though their body weights increased. In the chemotherapy group, the operation time and the blood loss were increased and, on the 1st postoperative day, the development of systemic inflammatory response syndrome was high but the level of C-reactive protein was low. The incidence of positive microbial cultures of sputum and/or wound discharge within 8 postoperative days was higher in the chemotherapy group (42.9%) than in the surgery group (4.8%). The host defense damage caused by chemotherapy may be prolonged and may show adverse effects in patients undergoing esophagectomy in the early postoperative period. Minimally, a 4-week interval between the completion of chemotherapy and operation is recommended for preventing surgical mortality related to the preoperative chemotherapy.

Aged↗

PubMed1999

Molecular detection of circulating cancer cells during surgery in patients with biliary-pancreatic cancer.

BACKGROUND: It remains unclear whether surgical treatment for biliary-pancreatic cancers provokes the hematogenous dissemination of cancer cells. The aim of this study was to detect circulating cancer cells in the blood stream before and during tumor resection for biliary-pancreatic cancer. METHODS: We analyzed blood samples obtained perioperatively from the portal vein, peripheral artery, and superior vena cava, using a carcinoembryonic antigen (CEA)-specific nested reverse transcriptase-polymerase chain reaction. RESULTS: CEA-mRNA expression was detected in the blood of 21 (52.5%) of 40 patients with biliary-pancreatic cancer. The patients with detectable CEA-mRNA expression included 8 (42.1%) of 19 with bile duct cancers and 13 (61.9%) of 21 with pancreatic cancers. CEA-mRNA expression was not detected in blood obtained from 15 healthy volunteers and 15 patients with benign disease. The positive rate of CEA-mRNA of advanced clinical stage (TNM pStage III and IV) showed higher than that of early stage (pStage I and II; P <0.05). Tumor resection increased significantly the positive rates of CEA-mRNA in the blood stream of three kinds of vessel. CONCLUSIONS: Surgical procedures provoke the hematogenous dissemination of cancer cells perioperatively. Therefore, new strategies during operations to prevent liver metastases are needed to improve the survival of patients with biliary-pancreatic cancer.

Bile Duct Neoplasms↗

PubMed1999

Fat emulsion administration in the early postoperative period in patients undergoing esophagectomy for carcinoma depresses arachidonic acid metabolism in neutrophils.

The aim of this study was to evaluate the effect of fat emulsion administration on neutrophil arachidonic acid and leukotriene B4 (LTB4) generation in surgically stressed patients. Total parenteral nutrition was administered to 17 patients for 2 wk after esophagectomy for carcinoma. Eight patients received fat with glucose (fat group, 30% of total calories) and 9 patients received glucose (glucose group) as a non-protein calorie source from the day of the operation to the seventh postoperative day (POD), and they gradually were converted to enteral nutrition during the second postoperative week. The arachidonic acid in the fat group decreased in the serum from POD 4 to 14. and in neutrophils from 12 h after the beginning of surgery to POD 14, compared to preoperative levels. LTB4 production by A23187-stimulated neutrophils was highest 6 h after the beginning of surgery, when neutrophil arachidonic acid concentration was decreasing, and then fell below the preoperative value from POD 4 to 14 in both groups. LTB4 production on POD 14 was lower in the fat group than in the glucose group. Biosynthesis of arachidonic acid from linoleic acid is inhibited in surgically stressed patients receiving fat emulsion, resulting in the diminished synthesis of LTB4 by neutrophils. The decrease in LTB4 may diminish chemotactic and chemokinetic signals to other leukocytes.

Aged↗

PubMed1999

Does hoarseness of voice from recurrent nerve paralysis after esophagectomy for carcinoma influence patient quality of life?

BACKGROUND: Recurrent laryngeal nerve injury caused by esophageal cancer surgery is worrisome but often temporary; it is unclear when and how the paralysis is resolved. Hoarseness of voice from vocal cord paralysis (VCP) can have detrimental effects on postoperative patients. The aims of this study were to clarify the progress of nerve paralysis related to difficulty in talking after surgery and to assess whether hoarseness influences patient quality of life. STUDY DESIGN: Between 1985 and 1996, 141 esophageal cancer patients undergoing a resection by the Akiyama procedure were cancer free 1 year after surgery. Among them, 51 patients with VCP on discharge from the hospital were retrospectively reviewed. Their VCPs, body weights, and pulmonary functions were examined yearly. They were given a questionnaire relating to the difficulty in talking 1 year after surgery. RESULTS: VCP on discharge spontaneously healed within 1 year of surgery in 21 patients (41.2%), with the mean duration of difficulty in talking 5.7 months. The remaining 30 patients had persistent VCP 1 year after surgery; 4 VCPs spontaneously healed approximately 2 years after surgery. Eleven of the 30 patients with persistent VCP, who complained of severe hoarseness at 1 year postoperatively from inability to close the glottis during exertion, showed debilitation in performance status, abilities to go up stairs, and swallowing. In the group of patients with severe hoarseness, the percentage of ideal body weight (90.6%+/-11.0%) preoperatively and pulmonary functions at 3 years postoperatively were deteriorated, resulting in 3 patients with repeated aspiration pneumonia. CONCLUSIONS: The inability to compensate for aspiration, presenting as severe hoarseness, may be dependent on the preoperative nutritional state of patients along with degree of vocal cord atrophy and a decrease in pulmonary support. Persistent nerve paralysis deteriorates quality of life until it is adequately treated.

Airway Obstruction↗

PubMed1999

Liver metastases after curative resection in patients with distal bile duct cancer.

BACKGROUND: Curative resection cannot ensure long-term survival for patients with distal bile duct cancer. The aim of this study was to determine the most frequent mode of recurrence after curative resection and to analyse its risk factors. METHODS: Clinical details for 64 consecutive patients with distal bile duct cancer who underwent surgical resection between 1980 and 1997 were reviewed. Modes of recurrence and clinicopathological findings were analysed based on the residual tumour (R) classification. RESULTS: The overall actuarial 5-year survival rate was 32 per cent. Of 42 patients undergoing R0 resection 10 were alive at 5 years, of 17 having R1 resection one was alive at 5 years, and none of the five patients having R2 resection survived for 5 years (R0 versus R1, P = 0.02). In the R0 group, the incidence of liver recurrence (14 of 42 patients) was similar to that in the R1 resection group (six of 17), although there were fewer lymph node and peritoneal recurrences than in patients who had R1 resection (P < 0.05). The high-risk factor for liver metastasis was microscopic vascular involvement. Important factors for survival were lymph node metastasis, microscopic vascular involvement and age. In addition, microscopic vascular involvement was the only independent factor for survival in the R0 group. CONCLUSION: R0 resection provided significant survival benefit but had no effect on liver recurrence. Therefore, new agents or strategies to prevent liver metastasis are necessary for improvement of survival.

Adult↗

PubMed1999

Gene expression of gastric type mucin (MUC5AC) in pancreatic tumors: its relationship with the biological behavior of the tumor.

Previously it has been found that the MUC2 gene for intestinal type secretory mucin is highly expressed in intraductal papillary mucinous tumors (IPMT), which are characterized by non-invasive growth and a favorable outcome. In contrast, MUC2 mRNA is rarely expressed in invasive ductal carcinomas (IDC), which have poor outcomes. The gastric type secretory mucin, MUC5AC, is strongly expressed in the surface mucous cells of gastric mucosa. As both MUC2 and MUC5AC mucins share the characteristics of forming highly viscous gels, it is expected that not only MUC2 mucin expression but also MUC5AC mucin expression may be associated with a favorable prognosis in patients with pancreatic tumors. MUC5AC mucin gene expression was examined in 24 cases of IPMT and 38 cases of IDC by in situ hybridization using a digoxigenin-labeled oligonucleotide. The results were compared with MUC2 mucin gene expression. Neither MUC5AC mRNA nor MUC2 mRNA was detected in normal pancreatic tissues. MUC5AC mRNA was expressed in 20 of 24 cases of IPMT (83%) and in five of 38 cases of IDC (13%). In contrast, MUC2 mRNA was expressed in 14 of 24 cases of IPMT (58%) and in none of the 38 cases of IDC (0%). The expression rates of MUC5AC mRNA and MUC2 mRNA in IPMT were significantly higher than those in IDC (P< 0.001, respectively). Intraductal papillary mucinous tumors are characterized by three histological types: (i) villous dark cell type; (ii) papillary clear cell type; and (iii) compact cell type. The villous dark cell type generally expressed both MUC5AC+ and MUC2+ genes. Alternatively, the papillary clear cell type and the compact cell type usually showed MUC5AC+ and MUC2- expression. Patients with MUC5AC mRNA expression had a significantly better survival prognosis than those with no MUC5AC mRNA expression (P< 0.005). In conclusion, MUC5AC gene expression occurs in a majority of IPMT cases, even in those with no MUC2 production. MUC5AC expression can be

Adenocarcinoma, Mucinous↗

PubMed1999

Endorectal ultrasonography for the assessment of rectal wall invasion in intrapelvic tumor: a preliminary report.

BACKGROUND: The purpose of the present study was to determine the usefulness of endorectal ultrasonography (ERUS) in assessing rectal wall involvement in intrapelvic tumors. METHODS: Rectal wall invasion was assessed in 16 patients; 14 with deeply invasive bladder tumors, one with prostatic leiomyosarcoma, and one with prostatic leiomyoma. Computed tomography (CT), magnetic resonance (MR) imaging and ERUS with a flexible-type radial scanner (7.5 MHz) were used and the results were compared with the histopathologic findings in surgical specimens. RESULTS: The normal rectum was shown by ERUS to be a five- or seven-layer structure. Characteristic abnormal ERUS findings included disappearance of the perirectal fat tissue layer with or without disruption of the propria muscle layer. Endorectal ultrasonography accurately assessed rectal wall involvement in all four patients who had two bladder tumors, plus the one patient with prostatic leiomyoma and the one with prostatic leiomyosarcoma. However, ERUS overstaged one of 12 bladder tumors with no rectal wall involvement, which was strongly adhesive to the rectum because of an inflammatory change but had no tumor invasion. There were no cases of understaging by ERUS. In comparison, CT accurately assessed rectal wall involvement in two patients, but overstaged in three and understaged in two. Magnetic resonance imaging, which was performed in 14 patients, accurately assessed rectal wall involvement in two patients, but overstaged in three and understaged in one. CONCLUSION: This preliminary study suggests that ERUS more accurately assesses rectal wall involvement in intrapelvic tumor than CT or MRI.

Adult↗

PubMed1999

How the lymph node metastases toward cervico-upper mediastinal region affect the outcome of patients with carcinoma of the thoracic esophagus.

BACKGROUND: The aim of this study was to establish whether the site of lymph node metastasis influences the survival of patients with carcinoma of the thoracic esophagus. METHODS: A series of 159 patients with lymph node metastasis who underwent right transthoracic R0 esophagectomy was analyzed retrospectively. Sites of the nodal metastasis were divided into two regions; the neck and/or upper mediastinum above (upward metastasis) and the abdomen and/or lower mediastinum below (downward metastasis) the tracheal carina. RESULTS: Univariate analysis of prognostic factors revealed the tumor location, distant lymphatic metastasis, number of metastatic nodes and upward metastasis influenced survival, but downward metastasis did not. Multivariate analysis showed that the number of metastatic nodes and upward metastasis were also significant prognostic factors. Thirty-one (33.3%) of the 93 patients with, but only 6 (9.1%) without, upward metastasis had recurrences in the neck and/or upper mediastinum (P = 0.0002). Eighteen (60.0%) of the 30 patients with extranodal invasion in the neck and/or upper mediastinum had recurrence in these regions. CONCLUSIONS: Nodal metastasis in the neck and/or upper mediastinum was a significant risk factor for prognosis, the same as the number of metastatic nodes.

Esophageal Neoplasms↗

PubMed1999

Assessment of cervical lymph node metastasis in esophageal carcinoma using ultrasonography.

OBJECTIVE: To evaluate the efficacy of ultrasonography for the diagnosis of cervical lymph node metastasis in esophageal carcinoma. SUMMARY BACKGROUND DATA: Ultrasound (US) examination is useful for diagnosing lymph node metastasis. However, few reports have examined its role in the decision to perform cervical lymph node dissection in esophageal carcinoma. METHODS: Ultrasound examination was performed to evaluate cervical lymph node metastasis in 519 patients with esophageal carcinoma. The patients were divided into 5 groups according to treatment received: group 1, 153 patients who underwent curative resection of primary tumor by right thoracotomy and complete bilateral cervical lymphadenectomy; group 2, 112 patients who underwent curative resection of primary tumor by right thoracotomy but without cervical lymphadenectomy; group 3, 78 patients who underwent esophagectomy by left thoracotomy or blunt dissection with or without removal of cervical lymph nodes; group 4, 76 patients with palliative resection without cervical lymphadenectomy; and group 5, 100 patients without any surgical treatment. US diagnosis was compared with histologic findings or cervical lymph node recurrence. RESULTS: Lymph node metastasis was detected in 30.8% of patients (160/519). The sensitivity, specificity, and accuracy of US diagnosis in group 1 were 74.5%, 94.1%, and 87.6%, respectively. Cervical lymph node recurrence was seen in 7 patients (4.6%) in group 1, in 4 patients (3.6%) in group 2, and 3 patients (3.8%) in group 3. Although the incidence of cervical lymph node metastasis as determined by US examination was high in groups 4 and 5, almost none of the patients died of cervical lymph node metastasis. CONCLUSIONS: Ultrasound examination plays a useful role in the decision to perform cervical lymph node dissection in patients with esophageal carcinoma, particularly in those with potentially curative dissection.

Esophageal Neoplasms↗

PubMed1999

So-called carcinosarcoma of the esophagus: A clinicopathologic, immunohistochemical and DNA flow-cytometric analysis of 6 cases.

Six cases of carcinosarcoma of the esophagus were studied clinicopathologically, immunohistochemically and with DNA flow cytometry. Transitional areas with morphology intermediate between carcinoma and sarcoma were found microscopically in all cases. Immunohistochemically, the carcinomatous areas contained keratin-positive cell components in all cases while vimentin-positive cells were found in sarcomatous areas in 5 cases. By DNA flow analysis of microdissection, the sarcomatous components of the tumors showed an aneuploid pattern with one exception, in contrast the carcinomatous components were diploid in all cases. In these few cases, PCNA, S-phase fraction and the mitotic rate were extremely high, apparently indicating a correlation with malignant behavior. Accordingly, examination by immunohistochemistry and DNA ploidy is useful for the analysis of biological properties in the so-called carcinosarcoma of the esophagus.

Aged↗

PubMed1999

Cooccurrence of reduced expression of alpha-catenin and overexpression of p53 is a predictor of lymph node metastasis in early gastric cancer.

BACKGROUND AND OBJECTIVES: Even though the pathological background contributes to lymph node metastasis, the biological characteristics of tumors have also gained wide attention. In this study, the expression of the cadherin-catenin complex and p53 was studied in early gastric cancer. Their correlation with lymph node metastasis and the predictability of lymph node metastases, by combining these factors, were also discussed. METHODS: One hundred and one specimens obtained from surgery were studied by immunohistochemistry using monoclonal anti-E-cadherin, anti-alpha-catenin and anti-p53 antibodies. RESULTS: Expression of E-cadherin and alpha-catenin was reduced in 50.5 and 64.4%, respectively. p53 protein staining was positive in 29.7%. There was a significant correlation between E-cadherin and alpha-catenin expression, but no correlation was found between p53 expression and E-cadherin or alpha-catenin expression. A reduction in alpha-catenin expression and p53 overexpression correlated to lymph node metastases, respectively. Multivariate analysis showed that cooccurrence of reduced expression of alpha-catenin and overexpression of p53 was an independent factor indicating lymph node metastases. CONCLUSION: A study of both alpha-catenin and p53 expression may be helpful to predict lymph node metastases in early gastric cancer.

Adult↗

PubMed1999

Hepatic metastasis of gastroenterological cancer: its tumor biology and oncological surgery.

Tumor angiogenesis and ability of basement membrane invasion for invasion of cancer cells into the tumor vessels and for circulating in the blood stream for hepatic metastasis are required. The molecular detection of cancer cells in the circulatory system strongly indicates the possibility of hepatic metastasis of a gastroenterological cancer. As an effect of the general anesthesia or the surgical procedure, a large amount of cancer cells in the tumor vessels may easily enter into the circulatory system at once from the primary tumor beds. Oncological surgeons should understand that the operation is not only the best treatment for gastroenterological cancer but also the crucial event of hepatic metastasis for cancer cells. Although further investigations are required to determine the relationship between circulating cancer cells and hepatic metastasis, at present, the most important issue to be addressed is the development of new strategies for the prevention of hepatic metastasis following the tumor resection in gastroenterological cancer.

Basement Membrane↗

PubMed1999

Expression of p21WAF1/Cip1 in the p53-dependent pathway is related to prognosis in patients with advanced esophageal carcinoma.

The proteins p53 and p21 are important components that regulate G1-S transition through the cell cycle. We immunohistochemically investigated p53 and p21 expression in 111 patients with esophageal squamous cell carcinoma. We also evaluated whether the expression of either of these proteins is a prognostic factor according to the p53-dependent and -independent pathways. The positive rates of p53 and p21 expression were 42.8 and 43.2%, respectively. Clinicopathological findings according to p53 and p21 expression did not differ significantly. The 5-year-survival rates between p21 positive and negative expression did not differ significantly in the p53-positive group. In the p53-negative group, the 5-year-survival rate of patients with p21-positive expression was 22.9%, which was significantly better than that of patients with p21-negative expression (12.7%; P<0.05). Multivariate analysis revealed that p21 expression in the p53-dependent pathway was an independent prognostic factor. Accordingly, the prognostic values of p21 expression between the p53-dependent and -independent pathways differed. Examination of p21-positive expression in the p53-dependent pathway will help to estimate the favorable prognosis of patients with advanced esophageal carcinoma.

Adult↗

PubMed1999

[Mechanisms for resistance to anticancer agents and the reversal of the resistance].

MDR results from overexpression of P-glycoprotein (Pgp) and multidrug resistance protein (MRP or MRP1) that function as ATP-dependent efflux pumps. Lung resistance related protein (LRP) is also supposed to be involved in MDR. The human canalicular multispecific organic anion transporter (cMOAT) gene that is responsible for the defects in Dubin-Johnson syndrome was isolated. cMOAT is homologous to MRP1 and supposed to be involved in drug resistance. Human cMOAT cDNA transfected LLC-PK1 cells, LLC/cMOAT-1, have increased resistance to vincristine (VCR), 7-ethyl-10-hydroxycamptothecin (SN-38), and cisplatin. The multidrug resistance (MDR)-reversing agents, cyclosporin A (CsA) and PAK-104P, almost completely reversed the resistance to VCR, SN-38 and cisplatin of LLC/cMOAT-1 cells by interacting with the substrate binding site of cMOAT. Treatment of human colorectal carcinoma SW-620 cells with sodium butyrate(NaB) induced LRP in the cells and conferred resistance to Adrianycin(ADM), VCR, VP-16, gramicidin D and taxol. Two LRP-specific ribozymes inhibited the NaB-induced expression of LRP in SW-620 cells and almost completely abolished their acquisition of the MDR phenotype. The accumulation of ADM, VCR and taxol was not decreased in NaB-treated cells, suggesting that ATP-binding cassette transporters are not involved in the MDR of NaB-treated cells. ADM was mainly located in the nuclei of untreated and the cytoplasm of NaB-treated cells. The accumulation level of ADM in the nuclei isolated from untreated cells or those from treated cells in the presence of anti-LRP polyclonal antibody was higher than that from treated cells in the absence of the antibody. Efflux of ADM from nuclei isolated from NaB-treated cells was enhanced compared with those from untreated cells and NaB-treated cells transfected with a LRP-specific ribozyme. The polyclonal antibody against LRP inhibited the enhanced efflux of ADM from nuclei isolated from NaB-treated cells. These findings indicate that LRP is involved in resistance to ADM, VCR, VP-16, taxol and gramicidin D, and has an important role in the transport of ADM from the nucleus to the cytoplasm.

ATP Binding Cassette Transporter, Subfamily B, Mem↗