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H Yamana

Publications and source records attributed to H Yamana.

At least 19 recordsLinked to original sources
PubMed2002

Detection of peptide-specific CTL-precursors in peripheral blood lymphocytes of cancer patients.

Development of therapeutic vaccines is one of the major areas of tumour immunotherapy today. However, clinical trials of peptide-based cancer vaccines have rarely resulted in tumour regression. This failure might be due to an insufficient induction of cytotoxic T lymphocytes in the current regimes, in which cytotoxic T lymphocytes-precursors in pre-vaccination peripheral blood mononuclear cells are not measured. Initiation of immune-boosting through vaccination could be better than that of immune-priming with regard to induction of prompt and strong immunity. If this is also the case for therapeutic vaccines, pre-vaccination measurement of peptide-specific cytotoxic T lymphocytes-precursors will be important. In the present study, we investigated whether cytotoxic T lymphocytes-precursors reacting to 28 kinds of peptides of vaccine candidates (13 and 15 peptides for HLA-A24(+) and HLA-A2(+) patients, respectively) were detectable in pre-vaccination peripheral blood mononuclear cells of 80 cancer patients. Peptide-specific cytotoxic T lymphocytes-precursors were found to be detectable in peripheral blood mononuclear cells of the majority of cancer patients (57 out of 80 cases, 71%). The mean numbers of positive peptides were 2.0 peptides per positive case. Peripheral blood mononuclear cells incubated with positive peptides, not with negative peptides, showed significant levels of HLA-class-I-restricted cytotoxicity to cancer cells. The profiles of positive peptides entirely varied among patients, and were not influenced by the cancer origin. These results may provide a scientific basis for the development of a new approach to cancer immunotherapy, e.g.) cytotoxic T lymphocytes-precursor-oriented peptide vaccine.

Antigens, Neoplasm↗
PubMed2001

Prediction of sensitivity of esophageal tumors to adjuvant chemotherapy by cDNA microarray analysis of gene-expression profiles.

We applied cDNA microarray analyses of 9216 genes to establish a genetic method for predicting the outcome of adjuvant chemotherapy to esophageal cancers. We analyzed expression profiles of 20 esophageal cancer tissues from patients who were treated with the same adjuvant chemotherapy after removal of tumor by operation, and we attempted to find genes associated with the duration of survival after surgery. By comparing expression profiles of those cancer tissues, we identified by statistical analysis 52 genes that were likely to be correlated with prognosis and possibly with sensitivity/resistance to the anticancer drugs. We also developed a drug response score based on the differential expression of these genes, and we found a significant correlation between the drug response score and individual patients' prognoses. Our results indicated that this scoring system, based on microarray analysis of selected genes, is likely to have great potential for predicting the prognosis of individual cancer patients with the adjuvant chemotherapy.

Aged↗
PubMed2001

Recognition of the Lck tyrosine kinase as a tumor antigen by cytotoxic T lymphocytes of cancer patients with distant metastases.

The Lck protein (p56(lck)), a src family tyrosine kinase that is essential for T cell development and function, is aberrantly expressed in metastatic colon cancers. p56(lck) seems to facilitate the malignant transformation of epithelial cells through initiation of anchorage-independent proliferation. We demonstrate that the lck gene encodes antigenic epitopes recognized by the HLA class I-restricted and tumor-specific CTL of metastatic cancer patients. Lck peptides augmented CTL activity in peripheral blood mononuclear cells (PBMC) of colon and other epithelial cancer patients with distant metastases, but not those without distant metastases. CTL precursors recognizing the Lck peptide were identified in freshly prepared PBMC of patients with distant metastases, and their frequency was significantly augmented by stimulation with the peptide. Thus, Lck peptides could be useful in developing a specific immunotherapy for cancer patients with distant metastases.

Antigens, Neoplasm↗
PubMed2001

Optimum treatment strategy for superficial esophageal cancer: endoscopic mucosal resection versus radical esophagectomy.

This study was designed to determine the optimum treatment for a superficial esophageal cancer involving the mucosal or submucosal layer of the esophagus. The subjects were 150 patients with a superficial esophageal cancer who underwent endoscopic mucosal resection (EMR) or esophagectomy in Kurume University Hospital from 1981 to 1997. The mortality and morbidity rates, survival rate, and recurrence rate were retrospectively compared for (1) 35 patients who underwent EMR and 37 patients who underwent esophagectomy for a mucosal esophageal cancer and (2) 45 patients who underwent extended radical esophagectomy and 33 patients who underwent less radical esophagectomy for a submucosal esophageal cancer. Among the 72 patients with a mucosal cancer, lymph node metastasis/recurrence was observed in only one (1%); whereas of 78 patients with a submucosal cancer it was observed in 30 (38%). Among patients with a mucosal cancer the mortality and morbidity rates after EMR were lower than for those after esophagectomy. The survival rate after EMR was the same as that after esophagectomy. No recurrence was observed after either treatment modality. Among the patients with a submucosal cancer, the survival rate was higher and the recurrence rate lower after extended radical esophagectomy; than after less radical esophagectomy; the mortality and morbidity rates after extended radical esophagectomy were the same as those after less radical esophagectomy. Multivariate analysis demonstrated that the treatment modality (EMR versus esophagectomy) did not influence the survival of patients with a mucosal esophageal cancer, whereas it strongly influenced the survival of patients with a submucosal esophageal cancer. We concluded that EMR was the mainstay of treatment for a mucosal esophageal cancer, and extended radical esophagectomy was the mainstay of treatment for a submucosal esophageal cancer.

Aged↗
PubMed2001

Preoperative evaluation of cardiopulmonary reserve with the use of expired gas analysis during exercise testing in patients with squamous cell carcinoma of the thoracic esophagus.

OBJECTIVE: We evaluated the usefulness of analyzing expired gas during exercise testing for the prediction of postoperative cardiopulmonary complications in patients with esophageal carcinoma. BACKGROUND DATA: Radical esophagectomy with 3-field lymphadenectomy is performed in patients with thoracic esophageal carcinoma but has a high risk of postoperative complications. To reduce the surgical risk, we performed preoperative risk analysis using 8 factors. Although hospital mortality was decreased when this risk analysis was used, severe cardiopulmonary complications still occurred. METHODS: The study group consisted of 91 patients who had undergone curative esophagectomy with 3-field lymphadenectomy. The maximum oxygen uptake, anaerobic threshold, vital capacity, percent vital capacity, forced expiratory volume in 1 second, percent forced expiratory volume, V.(25)/HT, forced expired flow at 75% of forced vital capacity to height ratio (FEF(75%)/HT), forced expired flow at 50% to 75% of forced vital capacity ratio (FEF(50%)/FEF(75%)), percent diffusion capacity for carbon monoxide, and arterial oxygen tension were measured. Patients were divided into 2 groups on the basis of the presence or absence of postoperative cardiopulmonary complications. RESULTS: Only the maximum oxygen uptake was significantly different between the 2 groups. All patients were grouped according to the value of the maximum oxygen uptake, and the occurrence of postoperative cardiopulmonary complications was calculated for each group. A cardiopulmonary complication rate of 86% was found for patients with a maximum oxygen uptake of less than 699 mL. min(-1). m(-2); for those with a value of 700 to 799 mL. min(-1). m(-2), the complication rate was 44%. CONCLUSIONS: The maximum oxygen uptake obtained by expired gas analysis during exercise testing correlates with the postoperative cardiopulmonary complication rate. On the basis of these results, esophagectomy with 3-field lymphadenectomy can be safely performed in patients with a maximum oxygen uptake of at least 800 mL. min(-1). m(-2).

Adult↗
PubMed2001

Phase II evaluation of protracted infusion of cisplatin and 5-fluorouracil in advanced squamous cell carcinoma of the esophagus: a Japan Esophageal Oncology Group (JEOG) Trial (JCOG9407).

BACKGROUND: Surgery for advanced esophageal carcinoma has its limits as regards aggressiveness and therapeutic effect, therefore effective multimodality treatment is required to obtain better survival. The objective of this study was to evaluate whether daily continuous infusion of CDDP could achieve a higher clinical response rate with less toxicity than its drip infusion in the previous phase II study that we had conducted. METHODS: Patients with primary extensive or relapsed esophageal carcinoma after esophagectomy, which had distant organ metastasis and histologically proven SCC, were eligible for this study. A dose of 20 mg/m(2) of cisplatin and 800 mg/m(2) of 5-fluorouracil was given by continuous infusion for 24 h on days 1-5. This treatment was repeated every 4 weeks for up to four cycles. A total of 36 men and six women with a median age of 64 (range 39-75) years were registered and 36 patients were eligible. RESULTS: The overall response rate of the registered patients was 33.3% (12/36) and the median response duration was 175 days. Median survival time was 201.5 days and the 1-year survival rate was 27.8%. Change from bolus to continuous infusion of cisplatin affected neither the type nor the degree of toxicity. CONCLUSION: Daily continuous infusion of cisplatin was not associated with higher response or lower toxicity than those seen with the high-dose bolus or multibolus treatment regimens. We conclude that this regimen in this setting is not worthy of further phase III trials. JEOG is now evaluating other drug combination regimens.

Adult↗
PubMed2001

Expression of G1 cell cycle markers and the effect of adenovirus-mediated overexpression of p21Waf-1 in squamous cell carcinoma of the esophagus.

To determine the crucial abnormality in the cell cycle regulatory proteins in human squamous cell carcinoma of the esophagus, we examined the cell growth ratio (CGR) and basal expression levels of G1 cyclins (cyclin D1, cyclin E), cyclin-dependent kinase (cdk) 2, cdk4, proliferating cell nuclear antigen (PCNA), and p21Waf-1 using 9 cell lines (KE3, KE4, TE8, TE9, TE10, TE11, YES1, YES2, and YES6). Western blotting revealed an inverse linear correlation between the basal levels of p21Waf-1 expression and CGR. The protein levels of G1 cyclins, cdks, and PCNA did not coordinately reflect the CGR. There was no relationship between p21Waf-1 expression levels and mutation of the p53 gene. Next, when the cells were stimulated with serum 48 h after the starvation, stimulated levels of the above G1 cell cycle markers were variously observed among cell lines irrespective of CGR. Serum stimulation markedly induced phosphorylated Rb in TE9 (a high CGR cell line, CGR>2.0), but not in KE4 (a low CGR cell line, CGR<1.5). Furthermore, adenovirus-mediated expression of exogenous p21Waf-1 effectively reduced cell growth in KE3 and TE9 (high CGR cell lines), but not in KE4 and TE11 (low CGR cell lines). p21Waf-1-mediated growth suppression was associated with the induction of involucrin, a marker of squamous cell differentiation. Our data suggested that the basal level, but not the stimulated level, of p21Waf-1 expression play a pivotal role in abnormal growth in human squamous cell carcinoma of the esophagus.

Adenoviridae↗
PubMed2001

[Experimental gene therapy using p21/WAF1 gene in esophageal squamous cell carcinoma--adenovirus infection and gene gun technology].

p21/WAF1 (p21) inhibits the activity of the cyclin/cdk complex and controls the G1 to S cell phase transition. In the present study, we used a recombinant adenoviral approach and gene gun technology to introduce p21 into esophageal cancer cells in order to assess the effect of p21 on cell growth. Infection with the p21 adenovirus (AdV) using gene gun technology resulted in inhibition of TE9 and KE3 cell growth. The levels of involucrin, which is a marker of squamous epithelium differentiation, markedly increased at 48 h and 72 h after p21 AdV infection in TE9 cells. These results indicate that p21 plays an important role in esophageal cancer cell proliferation. Overexpression of the p21 gene can inhibit cell growth and induce differentiation in esophageal cancer cells. p21 gene therapy may prove beneficial in the treatment of esophageal cancer.

Adenoviridae↗
PubMed2001

[Cellular immunotherapy for local recurrence of rectal cancer after surgery by activated lymphocyte administration--a case report].

UNLABELLED: Intrapelvic recurrence of the rectal cancer after surgery is a challenging status. We report here a case of intrapelvic tumor due to the recurrence of rectal cancer postoperatively treated by adoptive cellular immunotherapy. CASE REPORT: A 57-year-old Japanese man with an intrapelvic tumor showing bone destruction due to the recurrence of rectal cancer after abdomino-peritoneal resection was diagnosed by CT scan. He consented to simultaneous adaptive cellular immunotherapy for local recurrent lesions by administration of the activated lymphocytes. The tumor sample used for the activation of PBMC was obtained by operation. Tumor cells were prepared by mincing and enzymatic digestion of the tumor sample, and they were irradiated with a dosage of 50 Gy. Peripheral blood samples were collected from the same patient. PBMC for about 2 weeks to prepare cells for treatment were obtained from the blood sample. One million PBMC were incubated in 2 ml of the culture medium containing 10(5) irradiated autologous tumor cells and 100 IU/ml recombinant IL-2. The activated PBMCs, as autologous cancer specific killer T cells, were administered by direct regional injection (from 2 million to 8 x 10(7) cells). These injections were given repeatedly about once a week at 2-week intervals for three months. The surface phenotypes of activated PBMC or PBMC were tested by two color immunostaining technique with anti-CD3, -CD4, -CD8 and also anti-CD16, -CD25 or -CD56. Natural killer cell activity was also investigated. The clinical outcome was evaluated by CT scan and serum CEA levels. In the cultured activated PBMCs, NK cell activity was 40%, both CD3 and CD4 positive cells was 30%, and both CD3 and CD8 positive cells was 48%. There were far more CD8 cells than CD4 cells. In the PBMC, NK cell activity had increased, both CD3 and CD4 positive cells had decreased and both CD3 and CD8 positive cells had increased. There were then predominantly more CD8 cells than CD4 cells by repeated administration of the cultured activated PBMCs. The only adverse effect was grade 2 fever. Serum CEA levels fell from 293.7 ng/ml to 160 ng/ml, but the tumor size on the CT scan was slightly increased except for the directly administered region. We have been observing him as an outpatient.

Humans↗
PubMed2001

Induction of cellular immune responses to tumor cells and peptides in colorectal cancer patients by vaccination with SART3 peptides.

The tumor-rejection antigen SART3 possesses two antigenic epitopes (SART3(109-118) and SART3(315-323)) capable of inducing HLA-A24-restricted and tumor-specific CTLs. To determine its safety and ability to generate antitumor immune responses, 12 patients with advanced colorectal cancer were administered s.c. vaccinations of these peptides. No severe adverse events were associated with the vaccinations. Significant levels of increased cellular immune responses to both HLA-A24+ colon cancer cells and the vaccinated peptide were observed in the postvaccination peripheral blood mononuclear cells in 7 of 11 and 7 of 10 patients tested, respectively, and the higher responses were observed in those patients vaccinated with the highest dose (3 mg/injection) of the peptides. These results encourage further development of SART3 peptide vaccine for colorectal cancer patients.

Adult↗
PubMed2000

Identification of a gene coding for a new squamous cell carcinoma antigen recognized by the CTL.

Peptide-based specific immunotherapy has resulted in tumor regression in some melanoma patients. However, tumor Ags and peptides for specific immunotherapy, except for treatment of melanomas, have not yet been well identified. In this study, we report a gene encoding a new squamous cell carcinoma (SCC) Ag recognized by cells of the HLA-A24-restricted and tumor-specific CTL line. This gene with 3958-bp length was transcribed from the chromosome 6q22 with six exons, and its mRNA was ubiquitously expressed in both SCCs and normal tissues, and partly expressed in adenocarcinomas. The deduced 958-aa sequence encoded by this gene showed no similarity to any known amino acid sequences. This gene product had a characteristic of an endoplasmic reticulum-resident protein. A 100-kDa protein was detected in the vast majority of SCCs from various tissues, in majority of renal cell carcinomas and brain tumors, and in about one-third of melanomas and adenocarcinomas from various organs other than the breast. In contrast, it was not expressed at all in any of the normal cells or tissues tested, including the testis and fetal liver. Three different peptides at positions 93-101, 161-169, and 899-907 of this Ag were recognized by this CTL line, and all of them induced HLA-A24-restricted and tumor-specific CTLs from PBMCs of SCC patients. Therefore, these peptides may be useful for peptide-based specific immunotherapy of HLA-A24+ patients with SCC in various organs, as well as for treatment of other cancer.

Amino Acid Sequence↗
PubMed2000

Differential role of the JNK and p38 MAPK pathway in c-Myc- and s-Myc-mediated apoptosis.

The s-Myc is similar to c-Myc in its ability to induce apoptosis requiring caspase activation. However, s-Myc is distinct from c-Myc in that it has activity to suppress tumor growth and does not require wild-type p53 to induce apoptosis. These facts suggest differential regulation between s-Myc and c-Myc. Here we showed that s-Myc-mediated apoptosis triggered by UV was not inhibited by the inactive form mutant JNK (APF), though c-Myc-mediated apoptosis was. Moreover, we found that JNK did not affect the transactivation activity of s-Myc, but stimulated that of c-Myc. In contrast, both Myc-mediated apoptosis and caspase-3-like protease activation were suppressed by kinase-negative MKK6 and an inactive form mutant p38(AGF). Our results indicate that s-Myc does not require the JNK signaling unlike c-Myc during UV-triggered apoptosis, but the MKK6/p38MAPK pathway might regulate common apoptotic machinery for both s-Myc and c-Myc upstream of caspase.

Animals↗
PubMed2000

Expression of the SART1 tumor-rejection antigens in colorectal cancers.

PURPOSE: Colorectal cancer is one of the major causes of cancer death in the world, including in the United States and Japan. We recently identified the tumor-rejection antigen gene SART1, which encodes both the SART1(259) antigen expressed in the cytosol of epithelial cancers and the SART1(800) antigen expressed in the nucleus of the majority of proliferating cells. This study investigated the expression of these tumor antigens to explore a potential molecule for specific immunotherapy of colorectal cancer patients. METHODS: SART1 antigens were investigated by Western blotting in six colorectal cancer cell lines and in 33 colorectal cancer tissues. The cancer cell lines were tested for their ability to stimulate interferon-gamma production by the human-leukocyte-antigen-A24-restricted and SART1-specific cytotoxic T lymphocytes and were also tested for their susceptibility to the lysis by the cytotoxic T lymphocytes. RESULTS: The SART1(259) antigen was detected in the cytosol of four of six cancer cell lines, 13 of 33 (39 percent) cancer tissues, and 0 of 20 nontumorous colorectal tissues. The SART1(800) antigen was expressed in the nucleus of all the colorectal cancer cell lines, 18 of 33 (55 percent) cancer tissues, and 0 of 20 nontumorous tissues. The human-lymphocyte-antigen-A24-restricted and SART1-specific cytotoxic T lymphocytes killed the human-lymphocyte-antigen-A24+ SART1(259+) cancer cells. CONCLUSIONS: The SART1(259) antigen could be an appropriate target molecule for specific immunotherapy of approximately 40 percent of the human-lymphocyte-antigen-A24+ patients with colorectal cancer.

Adenocarcinoma↗
PubMed2000

Relationship between cancer cell proliferation and thallium-201 uptake in lung cancer.

UNLABELLED: Although thallium-201 (201Tl) uptake is related to perfusion in many normal tissues, the biologic rationale for 201Tl uptake in tumors is uncertain. To determine if tumor uptake is related to cell proliferation, we correlated the relative retention of 201Tl in lung tumors with expression of Ki-67, an indicator of cell proliferation. METHODS: Sixty patients with lung tumors, included small cell carcinoma (n = 8) and non-small cell carcinoma (n = 52), underwent 201Tl single photon emission computed tomography (SPECT) imaging. The 201Tl lesion uptake was determined on early and delayed images and the radiotracer retention index (RI) was calculated. Tumor specimens were obtained at surgery or bronchoscopy. The cell proliferation ratio was estimated with MIB-1, a monoclonal antibody that recognized the nuclear antigen Ki-67. RESULTS: The average 201Tl index was 2.13+/-0.61 (early) and 2.46+/-0.83 (delayed). The average RI was 17.44+/-35.01. Overall, the 201Tl index (delayed) and the cancer cell proliferation were correlated (r = 0.70, p < 0.0001). Of interest, there was a significant correlation (r = 0.872, p < 0.0005) between the 201Tl index on delayed images and the cell proliferation ratio in patients with small cell but not non-small cell lung carcinoma. The 201Tl index (delayed) was significantly higher (p < 0.0001) in patients with small cell lung carcinoma than in patients with non-small cell lung carcinoma. CONCLUSION: 201Tl imaging appears to be useful for evaluating patients with small cell lung carcinoma but not non-small lung carcinoma, and is correlated with the monoclonal antibody MIB-1, a marker of cell proliferation.

Adult↗
PubMed2000

Radical esophagectomy and secondary anastomosis for high-risk patients with intrathoracic esophageal carcinoma.

OBJECTIVE: We have often conducted esophageal reconstruction via a thoracic subcutaneous route in high-risk patients to avoid major complications following anastomotic leakage. This type of reconstruction is nonphysiological, however, and presents a poor cosmetic appearance. In better risk patients, therefore, we usually conduct gastric-tube replacement via a posterior mediastinal route. We have recently begun gastric-tube replacement via the posterior mediastinal route with secondary anastomosis for high-risk patients to avoid anastomotic leakage. RESULTS: From 1996 to 1999, secondary anastomosis was conducted in 25 patients with different degrees of risk--10 with diabetes mellitus, 7 with liver dysfunction, 3 with simultaneous laryngeal and/or pharyngeal cancer, 2 each with induction chemoradiotherapy, cardiac failure, renal dysfunction, respiratory failure, and cardiorespiratory dysfunction, and 1 with cerebral infarction. 6 patients had with multiple combined diseases. Secondary anastomosis was conducted 3-12 weeks (mean: 5.5 weeks) after esophagectomy. Stomach-tube necrosis was not seen in any of the 25 patients undergoing this 2-step procedure. Anastomosis leakage was seen in 5 of the 25 patients (20%), but was slight, in all but 1. CONCLUSION: Our 2-step procedure has the following advantages: low risk of anastomotic leakage, radical surgery for esophageal cancer, the potential for early adjuvant therapy after esophagectomy, easy and early training in swallowing, and no cosmetic problem. Its disadvantages are prolonged hospitalization, multiple surgery, and esophageal stoma formation. Secondary anastomosis thus appears helpful in treating high-risk patients with advanced esophageal cancer.

Aged↗
PubMed2000

CDw108 expression during T-cell development.

We recently reported a gene encoding the human CDw108, a glycosylphosphatidylinositol (GPI)-anchored membrane glycoprotein that is preferentially expressed on activated T lymphocytes and erythrocytes. The present study investigated the expression of CDw108 on various tissues and cells, particularly on T cells during development. The murine CDw108 cDNA was cloned initially, and it was highly homologous to the human CDw108 (88.0% or 89.3% similarity at the nucleotide or amino acid level, respectively) or identical to the murine semaphorin K1/Sema7A. The CDw108 mRNA was demonstrated in a few tissues including thymus and brain with the highest expression coming on day 7 in whole embryo followed by relatively consistent expression during development. Cell-surface expression of the CDw108 during T-cell development was further examined by flow cytometry in the human umbilical cord blood and thymus. It was preferentially expressed on a CD34+ stem cell population of umbilical cord blood, and CD3dull CD34+/- CD117 (c-kit)+ CD4bright CDbright cells in the thymus that are involved in the stage of positive selection. These results suggest the contribution of CDw108 in T-cell development, especially in the stage of positive selection in the thymus.

Age Factors↗
PubMed2000

Mutations in zinc-binding domains of p53 as a prognostic marker of esophageal-cancer patients.

Some investigators have suggested that mutations of the p53 gene may be molecular markers for poor prognosis of cancer patients, although others have reported conflicting results. We examined esophageal cancers from 138 patients to investigate whether mutational status of p53 could be correlated either with prognosis or with response to chemotherapy or radiation. We detected p53 mutations in the tumors of 78 (56.5%) patients. Kaplan-Meier analysis showed that these 78 patients tended to have shorter survival times and greater resistance to either form of therapy than patients whose tumors carried two wild-type p53 alleles. The difference became more evident when we focused on mutations in zinc-binding domains of p53 (L2 and L3); the prognosis was significantly poorer among the 29 patients with tumors in this category than among patients whose tumors had no p53 mutations, or p53 mutations outside L2 or L3 (P=0.0060). Moreover, those tumors as a group were more resistant to chemotherapy or radiation than the others (P=0.0105). Our results underscore the importance of the zinc-binding domains of p53 with respect to clinical prognosis for patients with esophageal carcinomas.

Adult↗