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T Itoi

Publications and source records attributed to T Itoi.

At least 19 recordsLinked to original sources
PubMed2006

Absence of Bcl-2 and Fas/CD95/APO-1 predicts the response to immunotherapy in metastatic renal cell carcinoma.

Immunotherapy is the only available treatment for metastatic renal cell cancer (RCC), but the response rate is only about 20% and the treatment is occasionally associated with severe adverse effects. Thus, the selection of patients with a high susceptibility to immunotherapy is needed; however, there is no promising molecular marker that can predict the response to immunotherapy for RCC. This study was carried out to elucidate the potential role of apoptosis-related molecules Bcl-2 and Fas, as well as apoptotic and proliferating indexes (AI, PI) as predictors of the susceptibility of metastatic RCC to immunotherapy. Immunohistochemical examination of tumour tissues from 40 patients with metastatic RCC undergoing postoperative immunotherapy after radical nephrectomy was performed. Patients with progressive disease (PD) after immunotherapy presented with decreased survival (P=0.006). Progressive disease correlated with higher PI in the primary lesion (P=0.0087). All primary tumours of CR or PR patients were negative for Bcl-2, whereas among NC+PD patients, 40.6% were positive for Bcl-2 (P=0.0373). Patients in whom the primary tumours were both Bcl-2- and Fas-negative showed significantly better responses to immunotherapy in comparison with the remaining group (P=0.0022). The Bcl-2 and Fas status of the primary lesion may become useful criteria for the selection of patients with metastatic RCC for immunotherapy.

Adult↗
PubMed2005

Prognostic impact of FAS/CD95/APO-1 in urothelial cancers: decreased expression of Fas is associated with disease progression.

The death receptor Fas (Apo1/CD95) and Fas ligand (FasL) system is recognised as a major pathway for the induction of apoptosis in vivo, and antiapoptosis via its blockade plays a critical role in carcinogenesis and progression in several malignancies. However, the function of Fas-FasL system in urothelial cancer (UC) has not been elucidated. We therefore investigated the expression of Fas, FasL and Decoy receptor 3 for FasL (DcR3) in UC specimens and cell lines, and examined the cytotoxic effect of an anti-Fas-activating monoclonal antibody (mAb) in vitro. Immunohistochemical examinations of Fas-related molecules were performed on 123 UC and 30 normal urothelium surgical specimens. Normal urothelium showed Fas staining in the cell membrane and cytoplasm. In UC, less frequent Fas expression was significantly associated with a higher pathological grade (P < 0.0001), a more advanced stage (P = 0.023) and poorer prognosis (P = 0.010). Fas and the absence thereof were suggested to be crucial factors with which to select patients requiring more aggressive treatment. Moreover, low-dose anti-Fas-activating mAb sensitised resistant cells to adriamycin, and this synergistic effect could be applied in the development of new treatment strategy for UC patients with multidrug-resistant tumours.

Adult↗
PubMed2005

Puncture of solid pancreatic tumors guided by endoscopic ultrasonography: a pilot study series comparing Trucut and 19-gauge and 22-gauge aspiration needles.

BACKGROUND AND STUDY AIMS: The aim of this prospective study was to compare endoscopic ultrasonography-guided Trucut needle biopsy (EUS-TNB) with EUS-guided fine-needle aspiration biopsy (EUS-FNAB) using 19- and 22-gauge needles for biopsy from different sites in patients with solid pancreatic cancers. PATIENTS AND METHODS: Sixteen consecutive patients with masses in the uncinate process (n = 3), the head (n = 5), or the body and tail (n = 8) of the pancreas underwent both EUS-TNB and EUS-FNAB. The specimens obtained were evaluated by histopathological analysis alone RESULTS: Tissue specimens were obtained by Trucut needle, and by 19-gauge and 22-gauge aspiration needles in 69 %, 69 %, and 100 % of patients respectively. Sensitivity for malignancy was 69 % for all needles. Tissue sampling by Trucut and by 19-gauge aspiration needle from masses in the uncinate process was impossible. The sensitivity of the Trucut and 19-gauge aspiration needles was 100 % in the 11 patients with successful procedures. If Trucut or 19-gauge aspiration needles had been used for body and tail masses, and the 22-gauge aspiration needle for masses in the uncinate process and head, the sensitivity for malignancy would have been 81 %. CONCLUSIONS: EUS-TNB allows reliable tissue sampling for the diagnosis of pancreatic masses, but its use is limited to lesions in the body and tail of the pancreas. EUS-FNAB using a 22-gauge needle may be useful for accurate diagnosis in some patients with masses in the uncinate process or the head of the pancreas.

Aged↗
PubMed2004

Impact of frequent Bcl-2 expression on better prognosis in renal cell carcinoma patients.

Previously, we reported that Bcl-2 was frequently expressed in renal cell carcinoma (RCC) specimens, but p53 mutation was a rare event. However, it was unclear whether Bcl-2 positivity was associated with the clinicopathological characteristics and prognosis in RCC. Therefore, we investigated the expression of Bcl-2 protein and its roles in 101 RCC specimens. In addition, the proliferation index (PI), apoptotic index (AI), caspase-3 and p53 expression were examined. The immunohistochemical method was applied for Bcl-2, caspase-3 and p53 protein expression. To investigate the proliferation activity and apoptosis of tumour cells, PI and AI were calculated based on Ki-67 and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling (TUNEL)-positive cells, respectively. Bcl-2 expression was detected in 72 out of 101 (71.3%) specimens. Bcl-2 positivity was inversely correlated with PI (P<0.0001) and AI (P=0.0074). Furthermore, Bcl-2 positivity was significantly correlated with better survival (P=0.0014), and was associated with lower stage (P=0.0301) and grade (P=0.0020). In RCC, frequent Bcl-2 expression was correlated with favourable character without higher PI and AI. Thus, Bcl-2 expression might be applied as a novel predictor of better prognosis in RCC patients.

Adult↗
PubMed2002

Intention myoclonus in paediatric patients following severe cardiopulmonary failure: a report of three cases.

We describe the development of intention myoclonus following severe cardiopulmonary failure in three paediatric patients. Symptoms occurred during the withdrawal of midazolam and fentanyl, which were used for prolonged sedation, and resolved spontaneously. Because the three patients had concomitant brain injury secondary to cardiopulmonary failure.related hypoxia, we propose that the combination of hypoxic brain injury and sedative withdrawal may predispose to intention myoclonus.

Journal Article↗
PubMed2001

Detection of telomerase reverse transcriptase mRNA in biopsy specimens and bile for diagnosis of biliary tract cancers.

Human telomerase reverse transcriptase (hTERT), which codes for the catalytic subunit of telomerase, is essential for telomerase activity. Recent studies revealed that levels of hTERT mRNA as well as telomerase activity are high in neoplasm. The purpose of this study was to correlate the expression of hTERT mRNA with telomerase activity in biopsy specimens and bile from biliary tract cancers and to evaluate the potential diagnostic value of hTERT mRNA analysis for biliary malignancy. We analyzed hTERT mRNA and telomerase activity in biopsy specimens and exfoliated bile cells from patients with cholangiocarcinoma, gallbladder carcinoma and bile duct stones. hTERT was detected by either nested reverse transcriptase-polymerase chain reaction (PCR) or real-time PCR. Telomerase activity was examined by a fluorescence-based telomeric repeat amplification protocol assay. Six of 10 malignant biopsy specimens had detectable hTERT and 7 of 10 had telomerase activity. All cases with hTERT expression had telomerase activity. In bile, 7 of 10 malignant patients had detectable hTERT and 3 of 10 had telomerase activity. Importantly, there were no false positive results in tissue specimens or bile examined in 6 non-cancerous cases. In conclusion, the detection of hTERT mRNA in biopsy specimens and bile cells, in combination with routine histologic and cytologic examination may improve the diagnosis of biliary tract cancers.

Aged↗
PubMed2000

Nuclear cyclin D1 overexpression is a critical event associated with cell proliferation and invasive growth in gallbladder carcinogenesis.

Cyclin D1 overexpression is remarkably frequent in several human carcinomas and is believed to be a critical event in oncogenesis. We examined cyclin D1 expression, p53 expression, and the Ki-67 labeling index by immunostaining in human gallbladder mucosa in conditions varying from normal to malignant tissue. We also examined K-ras codon 12 mutations in these tissues with a two-step polymerase chain reaction. Nuclear cyclin D1 overexpression was observed in 48% of carcinomas occurring independently of adenoma, but not in adenomas, carcinomas arising in adenomas, or nonneoplastic lesions. Cytoplasmic cyclin D1 overexpression was observed in about 15% of abnormal specimens, irrespective of the type of epithelial abnormality. Carcinomas showing nuclear cyclin D1 overexpression had significantly higher Ki-67 labeling indexes than those with no overexpression. Moderately to poorly differentiated adenocarcinomas showed a higher incidence of nuclear cyclin D1 overexpression than papillary to well differentiated carcinomas. Specimens with cyclin D1 overexpression showed a high incidence of lymph permeation, venous permeation, and lymph node metastasis. We conclude that nuclear cyclin D1 overexpression is a critical event importantly associated with cell proliferation and invasive growth in gallbladder carcinogenesis, and that cyclin D1 immunostaining may become a useful marker for evaluating gallbladder carcinomas.

Adenocarcinoma↗
PubMed2000

Detection of telomerase activity in biopsy specimens for diagnosis of biliary tract cancers.

BACKGROUND: Telomerase activity is detectable in more than 85% of primary cancers. We determined telomerase activity in biopsy specimens obtained from biliary tract cancers to evaluate the clinical application of telomerase activity detection in combination with p53 immunostaining and routine histologic examination. METHODS: Biopsy specimens obtained during percutaneous transhepatic cholangioscopy from 13 patients with cholangiocarcinoma, 3 patients with gallbladder carcinoma, and 4 patients with intrahepatic bile duct stones were evaluated by routine histologic examination, p53 immunostaining, and telomerase activity. Semiquantitative determination of telomerase activity was performed using a fluorescence-based telomeric repeat amplification protocol. RESULTS: Thirteen of 16 specimens of malignant tissue had detectable telomerase activity, whereas no specimen of nonmalignant tissue had detectable telomerase activity. A p53 overexpression was recognized by immunostaining in 9 of 16 samples with cancers. Combining both telomerase activity and p53 overexpression resulted in the detection of all cancer with a sensitivity of 100%. There were no false-positive results by either modality (specificity 100%). CONCLUSIONS: The detection of telomerase activity in biopsy specimens and p53 overexpression in combination with routine histologic examination may improve the diagnosis of biliary tract cancers. (Gastrointest Endosc 2000;52:380-6).

Aged↗
PubMed1999

K-ras codon 12 and p53 mutations in biopsy specimens and bile from biliary tract cancers.

To evaluate whether it is useful for diagnosis to detect K-ras and p53 mutations in biopsy specimens and bile of biliary tract lesions, 12 cholangiocarcinomas (CC), eight cases of cholangitis, seven gallbladder carcinomas (GBC), seven gallbladder cholesterol polyps, four cases of adenomyomatosis of the gallbladder and five cases of cholecystitis were examined. K-ras and p53 mutations in bile were detected by a two-step polymerase chain reaction (PCR) and nested PCR-single-strand conformation polymorphism (SSCP) analysis. In addition, p53 protein expression in biopsy specimens from CC were examined by immunostaining. K-ras mutations at codon 12 were detected in 50% of CC and 57.1% of GBC in both biopsy specimens and bile. The incidence of p53 mutations was 33.3% in CC and 42.9% in GBC. p53 protein overexpression was observed in 60% CC biopsy specimens. In contrast, K-ras and p53 abnormalities were not detected in any non-neoplastic biliary tract lesion. K-ras and p53 mutations in biliary tract cancers showed the same mutation patterns in spite of differences in the collection methods used between bile and biopsy specimens or surgically resected tissue. Genetic analysis of K-ras and p53 mutations in biopsy specimens and bile may be useful for the diagnosis of biliary tract cancers, although it may be effectively limited to patients with advanced disease.

Base Sequence↗
PubMed1999

Detection of telomerase activity in exfoliated cancer cells obtained from bile.

Telomerase is detected by the telomeric repeat amplification protocol (TRAP) assay in more than 85% of primary cancers. In the present study, we determined telomerase activity using exfoliated bile cells obtained from biliary tract neoplasia specimens. The aim of this study was to provide additional information regarding minimally invasive approaches to the detection of biliary tract cancer in combination with routine cytologic examination. We analyzed for telomerase activity bile juice from patients with gallbladder carcinoma, cholangiocarcinoma, cholecystitis and cholangitis. Semiquantitative determination of telomerase activity was performed using both a fluorescence-based TRAP assay on cell extracts and at the cellular level by an in situ TRAP assay. The fluorescence-based TRAP assay detected bile telomerase activity in samples from 4 of 10 patients with biliary tract cancer. In contrast, the in situ TRAP assay detected telomerase positive cells in samples from 6 of 10 patients with biliary tract cancer. However, only one of these samples showed class V cytology. A combination of semiquantitative analysis and an in situ TRAP assay to detect telomerase positive cells may improve the diagnosis of biliary tract cancers with the combination of routine cytologic examination.

Adult↗
PubMed1999

Histological and genetic changes in malignant transformation of gallbladder adenoma.

DESIGN: Elucidate the histological and genetic changes in malignant transformation of adenoma of the gallbladder. MATERIALS AND METHODS: Forty-three adenomas and 20 intramucosal tumors of carcinoma-in-adenomas were studied for histological and genetic changes (particularly K-ras mutation and p53 protein overexpression by immunohistochemistry) in malignant transformation. The genetic changes were compared with those of 164 carcinomas without anomalous union and 17 carcinomas with anomalous union of pancreatico-biliary duct. RESULTS: Atypical cell foci, i.e. spindle cell foci, were observed only in the adenoma area, with a frequency of 23% in 39 adenomas, and of 45% in 20 tumors of carcinoma-in-adenoma. 129 of 130 spindle cell foci examined were negative for Ki-67 staining and all the spindle cell foci were negative for p53 stain. K-ras mutation and p53 overexpression were not found in all adenomas, pure and with carcinoma i.s., and only one carcinoma (1/16, 6%) with adenoma showed p53 overexpression. K-ras mutation was low (10%, 4/40) in carcinomas without adenoma, but high in carcinomas with anomalous union of pancreatico-biliary duct. While, p53 overexpression was high and similar in carcinomas with and without anomalous union. CONCLUSIONS: These results suggest that there are three distinct pathways in gallbladder carcinogenesis; that is, de novo carcinoma develops from a predominant p53 alteration with low K-ras mutation, de novo carcinoma with anomalous union from K-ras mutation and p53 mutation, and carcinoma-in-adenoma from K-ras-, p53-, and probably APC-gene-related, as yet unknown, alteration.

Adenoma↗
PubMed1997

Correlation of p53 protein expression with gene mutation in gall-bladder carcinomas.

The correlation of p53 protein expression and p53 mutation of 33 gall-bladder carcinomas was studied according to the depth of invasion and grade of cytological atypia. Overexpression of p53 protein was detected by immunostaining in seven (70.0%) of 10 intramucosal and in 16 (69.6%) of 23 invasive carcinomas. p53 mutation was detected in five (71.4%) of the seven intramucosal carcinomas with overexpression and in eight (50.0%) of the 16 invasive cancers with overexpression and in one (10%) of the 10 non-overexpressing carcinomas at exons 5-8 by nested polymerase chain reaction-single-strand conformation polymorphism. The overexpression of p53 protein was present in nine (56.3%) of 16 low-grade carcinomas and in 14 (82.3%) of 17 high-grade carcinomas. In cases of overexpression, p53 mutation was detectable in four (44.4%) of nine low-grade and in nine (64.3%) of 14 high-grade carcinomas. In total, p53 mutation was verified in 56.5% (13/23) of cases involving protein overexpression and in 10% (1/10) of cases of non-overexpression. The sensitivity of p53 mutation was 56.5% (13/23), the specificity was 90.0% (9/10) and the validity was 1.47. In conclusion, our study indicates that p53 protein overexpression correlates well with gene mutation and that p53 alteration may be related to increasing grade of cytologic atypia of carcinomas.

Adenocarcinoma↗
PubMed1996

Calcium improves mechanical function and carbohydrate metabolism following ischemia in isolated Bi-ventricular working hearts from immature rabbits.

In the adult heart an increase in extracellular [Ca2+] can contribute to the severity of ischemic injury. While experimental studies have suggested that the immature heart is more resistant to ischemia than the mature heart, the reasons for this are unclear. In this study, we determined the effects of increasing perfusate [Ca2+] from 1.25 to 2.5 mM on reperfusion recovery of mechanical function and energy substrate metabolism following ischemia. Isolated bi-ventricular working hearts from 2-week-old rabbits were subjected to a 55-min period of global ischemia followed by 40 min of aerobic reperfusion. Perfusate contained 11 mM glucose, 0.5 mM lactate, and 1.2 mM palmitate, containing either: (i) 1.25 mM Ca2+ throughout the perfusion period (n = 22), (ii) 1.25 mM Ca2+ prior to and during ischemia and 2.5 mM Ca2+ following ischemia (n = 19), or (iii) 2.5 mM Ca2+ throughout the perfusion period (n = 18). In hearts perfused with 1.25 mM Ca2+ throughout, a 57% recovery of preischemic function was seen following ischemia. If [Ca2+] was increased to 2.5 mM during reperfusion a significant improvement of function was seen (hearts recovered 127% of preischemic function). A concentration of 2.5 mM Ca2+ throughout the perfusion resulted in an increase in both pre- and post-ischemic function compared to hearts perfused with 1.25 mM Ca2+ throughout. In both experimental groups reperfused with 2.5 mM Ca2+ a greater than 200% increase in both glucose and lactate oxidation was seen during reperfusion. Fatty acid oxidation rates also returned to pre-ischemic levels in both groups reperfused with 2.5 mM Ca2+, while rates returned to only 53% in hearts reperfused with 1.25 mM Ca2+. As a result, increasing [Ca2+] from 1.25 to 2.5 mM resulted in a 100% increase in ATP production rates during reperfusion. In conclusion, this study demonstrates that increasing [Ca2+] significantly improves post-ischemic recovery of function in isolated bi-ventricular working immature rabbit hearts subjected to a 55-min period of ischemia. The beneficial effects of Ca2+ in these immature hearts may be due to both a direct inotropic effect and a marked increase in carbohydrate oxidation and ATP production during reperfusion.

Adenosine Triphosphate↗
PubMed1996

p53 and Ki-67 immunoreactivity and nuclear morphometry of 'carcinoma-in-adenoma' and adenoma of the gall-bladder.

Twenty intramucosal tumors of "carcinoma-in-adenoma' and 43 adenomas (39 pyloric gland type, 4 intestinal type) of the gall-bladder were studied to establish more precise histological criteria of carcinoma or adenoma in cases of "carcinoma in pyloric gland type adenoma', to compare carcinoma in adenoma with pure, that is, without adenomatous components, carcinoma, and to confirm the benign nature of spindle cell foci in the adenomas. Ki-67 and p53 immunostaining and nuclear morphometry were used. Eight pure intramucosal cancers were used as controls. The formalin-fixed, paraffin-embedded sections were stained with p53 and Ki-67 antibodies. Spindle cell foci were observed only in the adenoma area of the pyloric gland type, with a frequency of 23% in 39 adenomas, and of 45% in 20 tumors of carcinoma-in-adenoma. Ki-67 staining was negative in 129 of 130 spindle cell foci examined, regardless of their size, and positive in only one focus (550 microns in size, Ki-67 index 0.2%). All of the spindle cell foci were negative for p53 stain. The Ki-67 positive index was 36.6 +/- 5.6% in the 8 pure carcinomas, and 12.5 +/- 1.9% in the cancer areas of 16 tumors with carcinoma-in-adenoma, while it was 7.9 +/- 1.7% in the adenoma areas of 16 tumors with carcinoma-in-adenoma and 4.9 +/- 0.5% in the 32 pure pyloric gland adenomas. The p53-protein over-expression was found in seven of eight pure intramucosal cancers, and in one of 16 cancer components of carcinoma-in-adenoma. However, it was not found in any of 16 adenoma components of carcinoma-in-adenoma, and 35 adenomas. Cells of the cancer tissue of carcinoma-in-adenoma showed a significantly larger nuclear area and a larger nuclear minor axis than those of the pyloric gland type adenomas, as well as other architectural and cytologic abnormalities differing from the features of adenomas. These results suggest that clustered spindle cells do not indicate a malignant transformation of adenoma cells and that carcinomas in carcinoma-in-adenoma are different from pyloric gland type adenomas in terms of morphology and proliferative activity. Moreover, the results of the present study indicate that carcinomas in carcinoma-in-adenoma are lower in malignancy than pure carcinomas, and that their genetic abnormality may differ from that of pure carcinomas.

Adenocarcinoma↗
PubMed1996

APC, K-ras codon 12 mutations and p53 gene expression in carcinoma and adenoma of the gall-bladder suggest two genetic pathways in gall-bladder carcinogenesis.

Current histopathological evidence suggests that gall-bladder cancer has two main morphological pathways for its development: de novo (ab initio) origin and adenoma-carcinoma sequence. In order to investigate the genetic difference between them, APC mutations were examined by RNase protection analysis, K-ras mutations by nested polymerase chain reaction-restriction fragment length polymorphism analysis, and p53 gene overexpression by immunohisto-chemical analysis in both tumors and benign lesions of the gall-bladder. Overexpression of the p53 gene was detected in 105 of 164 (64%) de novo carcinomas regardless of size and depth of invasion, but not in 16 tumors of carcinoma-in-pyloric-gland-type adenoma, or in 51 adenomas (47 pyloric gland-type and 4 intestinal-type). K-ras codon 12 mutation was detected in 4 of 40 (10%) de novo carcinomas, all four being associated with p53 gene overexpression, but not in 12 tumors of carcinoma in adenoma or 16 adenomas (14 pyloric gland-type and 2 intestinal-type). APC mutation was not found in 16 de novo carcinomas or the one pyloric gland-type adenoma examined. These results suggest that there are two distinct genetic pathways in gall-bladder carcinogenesis; that is, de novo carcinoma develops from a predominant p53 alteration with low K-ras mutation, and carcinoma-in-pyloric-gland-type adenoma develops from p53-, K-ras-, and APC-gene-unrelated, as yet unknown, alteration.

Adenoma↗