Search PubMed⌕ Search

Biomedical subjects

Kazuo Shirouzu

Publications and source records attributed to Kazuo Shirouzu.

At least 91 records · Page 5Linked to original sources
PubMed2003

Immunological evaluation of CTL precursor-oriented vaccines for advanced lung cancer patients.

Recent clinical trials of peptide vaccine for cancer patients have rarely resulted in tumor regression. One of the reasons for this failure could be an insufficient induction of anti-tumor responses in these regimens, in which peptide-specific memory cytotoxic T lymphocytes (CTLs) were not measured prior to vaccination. We investigated in this study whether pre-vaccination measurement of peptide-specific CTLs can provide any advantages in lung cancer patients receiving peptide vaccination with regard to safety and immunological responses. Ten patients with advanced lung cancer received vaccination with peptides under a regimen of CTL precursor-oriented vaccination, in which pre-vaccination peripheral blood mononuclear cells (PBMCs) were at first screened for reactivity in vitro to each of 14 peptides, followed by in vivo administration of only the reactive peptides. Profiles of the vaccinated peptides varied markedly among the 10 patients. This regimen was generally well-tolerated, although local skin reactions, diarrhea, and colitis were observed in 8, 2, and 1 patient, respectively. Increased CTL responses against the immunized peptides and tumor cells were observed in the post-vaccination PBMCs from 4 of 8 and 3 of 10 patients tested, respectively. Peptide-specific IgG became detectable in post-vaccination sera in 4 of 10 patients tested, and these 4 patients had a long progression-free survival. Furthermore, the median survival time of 9 patients with non-small cell lung cancer was 668.0 +/- 164.2 days. These results encourage further development of CTL precursor-oriented peptide vaccination for lung cancer patients.

Adenocarcinoma↗
PubMed2003

Adjuvant chemotherapy after radical resection of squamous cell carcinoma in the thoracic esophagus: who benefits? A retrospective study.

BACKGROUND: A definitive combined modality therapy superior to surgery alone has not yet been found for esophageal cancer. This retrospective study investigated the impact of postoperative adjuvant chemotherapy in patients who underwent curative (R0) esophagectomy with radical lymphadenectomy. STUDY DESIGN: Two hundred and eleven patients with a squamous cell carcinoma in the thoracic esophagus who underwent transthoracic curative (R0) esophagectomy with radical lymphadenectomy, such as 3-field lymphadenectomy or total 2-field lymphadenectomy, between 1988 and 2000, were retrospectively reviewed. Ninety-four patients received postoperative chemotherapy - 2 courses of cisplatin (CDDP) plus fluorouracil (5-FU) or vindesine (VDS) - while the other 117 patients received surgery alone. The overall survival rate was compared between the two groups after being stratified by the numbers of the metastasis- positive lymph nodes. RESULTS: Only in the subgroup of patients with 8 or more lymph nodes metastasis- positive, the surgery-with-postoperative-chemotherapy group had a significantly better survival than the surgery-alone group. No significant difference was found in survival between the two groups in any other stratified subgroup. CONCLUSIONS: Postoperative adjuvant chemotherapy following curative (R0) esophagectomy with radical lymphadenectomy such as 3-field lymphadenectomy or total 2-field lymphadenectomy provided a benefit only in patients having metastasis in a large number - 8 or more - lymph nodes.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

The expression of p53, p21 and TGF beta 1 in gastric carcinoma.

The aim of the present study was to examine the significance of the p21 expression in gastric cancer. We examined the expression of p53, p21, TGF beta 1 and PCNA in 75 cases of gastric cancer using immunohistochemical examinations and the expression of p21 RNA by in situ hybridization (ISH). The combination of p53 and p21 expression was related to depth of invasion, lymph node metastasis, and stage grouping. The survival curves of the p53 negative-Group and the p21-positive Group were significantly higher than those of the p53-positive and the p21-negative Group, the p53-and-p21-both-positive Group, and the p53-and-p21-both-negative Group (each p < 0.01). The average PCNA Labelling Index (LI) of the p53-negative-and-p21-positive Group was significantly lower than that of either the p53-positive-and-p21-negative Group or the p53-and-p21-both-positive Group or the p53-and-p21-both-negative Group (p < 0.01, p < 0.05, p < 0.05, respectively). All of the p53-and-p21-both-positive cases were TGF beta 1 positive, and the rate of the TGF beta 1 positive cases in the p53-and-p21-both-positive Group was significantly higher than that of the p53-positive-and-p21-negative Group, and than the rate in the p53-and-p21-both-negative Group (each p < 0.01). The survival curves of the cases with expression of p21 RNA were higher than that of cases without p21 RNA (p < 0.05). Many of the p53-positive-and-p21-negative cases were advanced cancer with very poor prognosis, but many of the p53-negative-and-p21-positive cases were early cancer with good prognosis. These results suggest that p21 suppressed synthesis of DNA via PCNA, and TGF beta 1 is a regulation factor for the expression of p21, and that the combination of p53 and p21 expression is concluded to be a useful prognostic marker of gastric carcinoma.

Humans↗
PubMed2003

Resection of synchronous lung and Vater's papilla cancer.

We present a case of a 78-year-old man with a synchronous double cancer of the lung and Vater's papilla. A pancreaticoduodenectomy was performed for Vater's papilla cancer and a partial lung resection for lung cancer. The pathological diagnosis of the tumors was a well differentiated tubular adenocarcinoma and well differentiated bronchioloalveolar carcinoma, respectively. Although most cases of synchronous double cancers involve lung and gastric cancers, a combination of lung and Vater's papilla is extremely rare. This patient is still alive with no recurrence for 5 years after the last operation.

Adenocarcinoma↗
PubMed2003

Rapid-growth lung cancer associated with a pulmonary giant bulla: a case report.

A giant bulla of the lung is suggested as a risk factor for lung cancer. Here we report a case with lung cancer in a giant bulla, which showed rapid progression. A 57-year-old man, who had a history of heavy smoking, was admitted to our hospital due to hemoptysis. A chest X-ray revealed a giant bulla with a ground glass shadow and a high fluid level in the right upper lung. Sputum cytology was negative for malignant cells. A chest X-ray a month later showed increases of the size of the radio-opaque shadow and of the air-fluid retention, suggesting pulmonary hemorrhage from the giant bulla. Limited resection or lobectomy was indicated, but pneumonectomy was performed due to the severe air-leak. Macroscopically, a multiple nodular tumor arose from the bulla wall, which might be related to blood flow and necrotic tissue. The postoperative pathological diagnosis was papillary adenocarcinoma. Unfortunately, the patient developed a recurrence of carcinoma in the pleuroperitoneal cavity and died at 2.5 months after the operation. Based on this report and review of other cases in the literature, we should keep in mind the rapid progression of lung cancer in association with an emphysematous bulla.

Adenocarcinoma, Papillary↗
PubMed2003

Evaluation of resection of the papilla of Vater for the treatment of cancer in the papilla of Vater.

We evaluated the resection of the papilla of Vater performed in patients with cancer in the papilla of Vater. The subjects were 6 patients who underwent resection of the papilla of Vater between January 1969 and December 2001. The patients aged 57-87 years consisted of 3 males and 3 females. The maximal diameter of the tumors was 0.5 cm in 1 patient, 1.5 cm in 3 patients, and 2.0 cm in 2 patients. Macroscopically, the tumors were of the protruded type (exposed) in 3 patients, of the mixed type (predominant protruded type) in 2 patients, and of the ulcerative type in 1 patient. The histological depth of the tumors was up to the mucosa in 1 patient, up to the oddi in 1 patient, up to the panc0, du1 in 1 patient, up to the panc1, du2 in 1 patient, and unknown in 2 patients. Histologically, the tumors were papillotubular adenocarcinoma (pap-tub) in 4 patients and tubular adenocarcinoma of the well-differentiated type (tub1) in 2 patients. Resection of the papilla of Vater was chosen because of high risk factors such as advanced age in 2 patients, complicated severe cirrhosis and confinement to bed due to poor systemic conditions after intracerebral hemorrhage in 3 patients, and hepatic metastasis observed during surgery in 1 patient. Residual cancer cells around the excised region were positive in 4 patients and unknown in the remaining 2 patients. Of the 6 patients, 5 died within 2 years after surgery, but 1 is alive without symptoms of recurrence 7 years after surgery. The death causes were the primary disease in 3 of the 5 patients. From the viewpoint of radical treatment, resection of the papilla of Vater cannot be chosen as a reduced surgery for cancer in the papilla of Vater. However, resection of the papilla of Vater can be applied to very elderly patients and patients under poor systemic conditions, for whom pancreatoduodenectomy (PD) is considered excessively invasive due to a small diameter of tumor.

Aged↗
PubMed2003

A case of small mucosal gastric carcinoma with lymph node metastasis: a case report.

We have experienced a case of small early mucosal gastric cancer with lymph node metastasis. The patient was a 75-year-old woman diagnosed as having early gastric cancer type 0 IIa on the greater curvature of the antrum. We performed distal gastrectomy, with Billroth I method reconstruction. The tumor lesion was on the greater curvature of the antrum. Metastasis was discovered in the number 4d lymph node, histologically. The tumor was type 0 IIa confined to the mucosa, 1.0 cm in diameter and differentiated histological type, and no ulcer scar could be seen in tumor lesion. However, the tumor was massively invading to the mucosal membrane, with positive lymph vessel invasion, and was of mixed histological type. This was a rare case of small early mucosal cancer 1.0 cm in diameter with lymph node metastasis.

Aged↗
PubMed2003

Two cases of early gastric carcinoma with synchronous liver metastasis.

We have experienced two cases of early gastric cancer with synchronous liver metastasis. One patient was a 64-year-old man diagnosed as having early gastric cancer type 0 IIa at 15 x 10 mm on the lesser curvature of the cardia. The other patient was a 58-year-old man diagnosed as having early gastric cancer type 0 IIa + IIc at 24 x 18 mm on the posterior wall of the antrum. The histological findings showed that proliferation of moderately differentiated tubular adenocarcinoma with hepatoid pattern was massively invading to the deep layer of the submucosa, with positive lymph vessel, vein invasion and lymph node metastasis, in both cases. These results suggested that elevated or mixed macroscopic type, differentiated adenocarcinoma massively invading to the deep layer of submucosa, positive lymph vessel and vein invasion, lymph node metastasis, and hepatoid adenocarcinoma were risk factors for liver metastasis from early gastric cancer.

Combined Modality Therapy↗
PubMed2003

Alpha-fetoprotein-producing early gastric cancer: report of two cases.

We have experienced two cases of alpha-fetoprotein (AFP)-producing early gastric cancer. One patient was a 73-year-old man diagnosed as having an early gastric cancer type 0 I + IIa at 40 x 40 mm on the greater curvature of the lower body of the stomach. The histological findings showed that proliferation of a well-differentiated tubular adenocarcinoma with hepatoid pattern was massively invading to the middle layer of the submucosa, with positive lymph vessel, and lymph node metastasis. The other patient was a 76-year-old man diagnosed as having an early gastric cancer type 0 IIa + IIc at 25 x 25 mm on the anterior wall on the greater curvature of the antrum. The histological findings showed that proliferation of a small cell carcinoma was massively invading to the deep layer of the submucosa, with positive lymph vessel, and lymph node metastasis. AFP was immunohistochemically found in the tumor cells of these two cases. Both patients died from liver metastasis. AFP-producing early gastric cancer was concluded to be at high risk of liver metastasis.

Aged↗
PubMed2003

[Chemoradiotherapy for esophageal cancer].

Since mucosal (T1a) esophageal cancer is well controlled by endoscopic treatment, chemoradiotherapy (CRTx) is not indicated. However, for a submucosal (T1b, N0) esophageal cancer, CRTx may be the first line of treatment, since it can provide a good response rate, with an excellent survival rate comparable to that after esophagectomy. Definitive CRTx is also in the first line of treatment for a T4 esophageal cancer, because there was no difference in the survival rate between CRTx with surgery and CRTx without surgery in our trial. Esophagectomy is indicated only for non-responders or recurrence-salvage surgery. For patients with a potentially-resectable (T2-T3) esophageal cancer, esophagectomy offered a longer survival rate than CRTx did, in our series. However, there remains controversy over the efficacy of CRTx for a T2-T3 esophageal cancer. It has been reported by the National Cancer Center Hospital East Group that definitive CRTx provided the same survival rate as esophagectomy. A prospective trial comparing the survival rate after esophagectomy and that after CRTx for a T2-T3 esophageal cancer is needed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Bystander effect in suicide gene therapy is directly proportional to the degree of gap junctional intercellular communication in esophageal cancer.

Gap junctional intercellular communication (GJIC) has been shown to be involved in the bystander effect through herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV) gene therapy. In this study, we examined the expression of connexins, the components of gap junction, and the degree of GJIC in esophageal cancer cell lines and compared the bystander effect in cells with different capacities of GJIC. We found loss in connexin 26 expression and reduced connexin 43 in esophageal cancer. GJIC capacity varied among cell lines and was dependent on the connexin 43 expression in the cell-cell contact areas. In mixing assay, the extent of the bystander effect was tightly correlated with the degree of GJIC capacity. The effects of retinoic acid and cAMP on the bystander effect were also investigated. Treatment with retinoic acid, but not with cAMP, was associated with augmented bystander killing by increase in GJIC in some esophageal cancer cell lines. Our results indicated that the degree of GJIC was predictive to identify a tumor as suitable for gene therapy with the HSV-tk/GCV system. Also GJIC chemically-enhanced with retinoic acid might be useful to improve response in suicide gene therapy.

Blotting, Western↗
PubMed2003

[Autologous tumor specific immunotherapy of refractory cancers with ex vivo-generated T cells stimulated by autologous tumor cell].

OBJECTIVES: Autologous tumor-cell stimulated cytotoxic T lymphocytes (AuTLs) were prepared from peripheral blood T cells and the T cells were activated ex vivo over a 2-week culturing process in the presence of IL-2 and autologous biopsied tumor-cells from advanced cancer patients. These AuTLs may have potential for efficacy as a locoregional therapy in patients with refractory cancer. METHODS: Twenty-nine of 35 cancer patients (13 esophagus, 5 lung, 3 stomach, 4 breast, 1 melanoma) were enrolled in an early Phase II clinical trial. The patients received direct locoregional intratumoral injection of AuTLs biweekly through medical endoscope or intraarterial infusion reservoir system. Mean 0.25 x 10(9) AuTLs were injected 1 x /2 weeks for 6 weeks. RESULTS: Adverse events related to AuTL were minimal. AuTLs specific for autologous tumor cells were observed in 12 of 29 patients. Seven of these 12 patients (58.3%) had partial response (PR) or stable disease (SD). In contrast, 8 of 23 (34.8%) remaining patients treated by non-specific AuTLs had SD. Infiltration of T effector cells was significantly increased on the biopsied tumor specimens in the immunohistological studies. Furthermore, 11 patients receiving systemic infusion of non-specific LAK/NK T cells without autologous tumor-cell stimulation only had 2 SDs (18.2%). CONCLUSIONS: Our results demonstrated the clinical potential of intra-peritumoral administration of AuTLs. Thus, locoregional immunotherapy with autologous tumor specific AuTLs may be more effective than systemic adoptive immunotherapy using intravenous infusion of autologous tumor non-specific LAK/NK T cells for the treatment of solid cancers.

Breast Neoplasms↗
PubMed2003

[Chemoradiation therapy for stage IV pancreatic cancer].

BACKGROUND: Pancreatic cancer is a malignant tumor with a poor prognosis. It frequently presents with locally advanced and distant metastasis at the time of diagnosis. Favorable results were obtained by performing intraoperative radiation therapy (IORT) and chemotherapy (administration of GEM) for the treatment of inoperable pancreatic cancer. A study was conducted on its efficacy as an adjuvant therapy for inoperable and advanced pancreatic cancer. SUBJECTS AND METHODS: Between May 1998 and December 2002, 40 patients with stage IV pancreatic cancer were treated at our institution. The study comprised background factors, adjuvant therapy and survival rate. RESULTS: According to the treatment modality, the study population was classified into four groups: group A, consisting of 3 patients with localized unresectable tumors who had been treated with IORT: group B, 5 patients who underwent curative resection of primary tumor combined with IORT: group C, 6 patients who were administered GEM combined with IORT: group D, 26 patients not falling into groups A, B or C. The mean survival for group A, B, C and D was 10.3 months, 6.7 months, 16.8 months and 9.4 months, respectively. The 1-year survival rates were 0%, 0%, 80.0% and 19.3%, respectively. The mean survival and the 1-year survival rate were significantly better in group C than in the other groups. In group C, the tumor decreased in size, invasion of large vessels and pancreatic posterior evolution was suppressed, and 4 patients survived for 17 months or more. CONCLUSIONS: Prolongation of the survival period was shown by concomitant IORT and administration of GEM for inoperable advanced pancreatic cancer. Thus, attempting to combine chemotherapy with IORT and giving additional consideration to the administration method was shown to provide adjuvant therapy that can be expected to be effective against stage IV inoperable pancreatic cancer.

Adult↗
PubMed2003

[Preliminary evaluation of chemotherapy with docetaxel, 5-FU, CDDP for recurrent esophageal cancer--a pilot study].

A pilot study has been conducted since January 2002 to investigate whether chemotherapy with docetaxel, 5-FU, CDDP could be an effective regimen for recurrent esophageal cancer. Ten patients with recurrent esophageal cancer were treated with the combination of docetaxel 60 mg/m2 (day 1), CDDP 10 mg/body (days 1-5) and 5-FU 500 mg/body (days 1-5) at intervals of 2-3 weeks. All patients had undergone surgery, had a recurrent tumor and had already been treated with chemo-radiotherapy or chemotherapy with CDDP + 5-FU. Response evaluation in 10 patients with measurable disease: partial response 4 patients, stable disease 2 patients and progressive disease 4 patients. The main NCI-CT grade 3/4 toxicity was leukopenia (8/10). Mild to moderate nausea (> or = grade 2) occurred in 3/10 patients.

Aged↗
PubMed2002

Expression of tumor rejection antigens in colorectal carcinomas.

BACKGROUND: The authors recently reported that the SART2 and SART3 antigens encode tumor epitopes recognized by HLA-A24-restricted and tumor-specific cytotoxic T lymphocytes (CTLs) established from esophageal carcinoma patients. The current study investigated these antigens to explore a potential molecule for specific immunotherapy for colorectal carcinoma patients. METHODS: The SART2 and SART3 antigens were investigated by Western blotting in colorectal carcinoma cell lines and in cancer tissues. For induction of CTLs, peripheral blood mononuclear cells (PBMCs) of HLA A-24-positive cancer patients were stimulated in vitro with peptides. RESULTS: The 140 kD SART3 antigen was expressed in both the cytosol and nuclear fractions of all six colon carcinoma cell lines, 27 of 41 (65.9%) cytosol fractions, 30 of 41 (73.2%) nuclear fractions of colorectal carcinoma tissue samples, and in 0 of 7 non-tumorous tissues. The 100 kD SART2 antigen was expressed in the cytosol fractions of 2 of 6 colon carcinoma cell lines, 5 of 20 (25%) cytosol fractions of colorectal carcinoma tissue samples, and in 0 of 7 non tumorous tissues. HLA-A24-restricted CTLs cytotoxic to colon carcinoma cells were induced from PBMCs of colon carcinoma patients by stimulation with the two immunogenic peptides of SART3. CONCLUSIONS: The SART3 antigen could be an appropriate target molecule for specific immunotherapy for colorectal carcinoma patients.

Aged↗
PubMed2002

Effect of prophylactic intracerebroventricular injection of methylprednisolone on nitrogen and catecholamine excretion in the urine after laparotomy in rats.

BACKGROUND: This study was carried out to determine whether the prophylactic injection of glucocorticoid into the intracerebroventricular (i.c.v.) space reduced TNF-alpha and IL-1beta mRNA synthesis in the brain after laparotomy, resulting in a reduction of nitrogen excretion in the urine. PATIENTS AND METHODS: Male SD rats (body wt., 225-250 g, n = 114) were catheterized into the i.c.v. space on day 0. On day 4, the rats were assigned to four groups: (1) Control, (2) laparotomy (Trauma), (3) intraperitoneal (i.p.) injection of methylprednisolone (MP) plus laparotomy (IPMP), and (4) i.c.v. injection of MP plus laparotomy (ICVMP). Either 3 or 24 h after surgery, the animals were sacrificed. TNF-alpha and IL-1beta mRNA levels in tissues, including the brain cortex and hypothalamus, were measured by RT-PCR. The amounts of nitrogen and catecholamine excretion in the 24-h urine were determined. RESULTS: The i.p. injection of MP reduced TNF-alpha and IL-1beta mRNA levels in all the tissues 3 h after laparotomy compared with those of the Trauma group. The icv injection of MP prevented elevation of the TNF-alpha and IL-1beta mRNA levels in the brain (cortex, TNF-alpha, ICVMP 0.43 +/- 0.06, P < 0.05, vs Trauma; cortex, IL-1beta, ICVMP 0.25 +/- 0.09, P < 0.05, vs. Trauma; hypothalamus, TNF-alpha, ICVMP 0.31 +/- 0.04, P < 0.05, vs. Trauma; hypothalamus, IL-1beta, ICVMP 0.25 +/- 0.14, P < 0.05, vs. Trauma), but did not inhibit an increase in TNF-alpha and IL-1beta mRNA levels in the liver and skeletal muscle. Both nitrogen and catecholamine excretions in the urine were decreased by ip and by i.c.v. injection of MP compared to those of the Trauma group (nitrogen, ICVMP 559.3 +/- 52.0 mg/day, P < 0.05, vs. Trauma; catecholamine, ICVMP 13.8 +/- 1.8 microg/day, P < 0.05, vs. Trauma). CONCLUSION: A reduction in TNF-alpha and IL-1beta mRNA synthesis in the brain due to prophylactic injection of MP into the icv space reduced the catabolic response after laparotomy.

Animals↗
PubMed2002

Outcome for malignant tracheobronchial stenoses in esophageal cancer.

OBJECTIVE: Optimal tracheobronchial stenosis treatment in esophageal cancer remains a clinical challenge. METHODS: Subjects were 26 patients with tracheobronchial stenosis due to esophageal cancer treated by modalities such as expandable metallic stent emplacement, laser therapy, radiotherapy, and/or chemotherapy. We assessed patient outcome and modality efficacy, and determined prognostic factors for survival using multivariate analysis. RESULTS: Of the 26, 16 (61%) had improved respiration after treatment. Average posttreatment survival was 140 days (10-1550 days). Multivariate analysis indicated that a Karnofsky performance score of > or = 70% was the most significant prognostic factor, with chemotherapy and laser therapy also significant factors. CONCLUSIONS: Although individual modalities were effective in ameliorating respiratory symptoms, patients with good performance status survived the longest. After a tracheobronchial stenosis diagnosis in esophageal cancer patients, chemotherapy and laser therapy are recommended if the patient is in good general condition.

Aged↗