PubMed Health⌕ Search

Biomedical subjects

Y Naomoto

Publications and source records attributed to Y Naomoto.

At least 37 records · Page 2Linked to original sources
PubMed2000

Evaluation of endoscopic mucosal resection for superficial esophageal carcinoma.

Esophageal superficial carcinoma safely can be resected surgically or endoscopically. We evaluated indications for endoscopic mucosal resection (EMR) and optimal treatment modality for superficial carcinoma of the esophagus based on clinical and pathologic analyses. Between January 1, 1984, and September 30, 1999, 113 patients with superficial cancer of the esophagus underwent surgical or endoscopic resection (n = 33 patients, 36 lesions). The two-channel method, esophageal EMR-tube method or EMR cap-fitted panendoscope was used. Mucosal and submucosal cancers were classified to be epithelial layer (m1), proper mucosal layer (m2), muscularis mucosae (m3), upper third of the submucosal level (sm1), middle third of the submucosal layer (sm2), or the lower third of the submucosal level (sm3) cancers, according to criteria of the Japanese Society for Esophageal Disease. Absolute indication for EMR was restricted to m1 or m2 cancers, and relative indications for EMR included m3 or sm1 lesions. In our department, indications for EMR were not related to size or circumference of lesions. Lymph vessel invasion and lymph node metastasis markedly increased in lesions that infiltrated the lamina muscularis mucosa (m3). All lesions resected with use of EMR were 0-II (flat), and the depth of invasion in 10 0-IIa or 0-IIb lesions was m1 or m2. Twenty-one 0-IIc lesions were distributed widely from m1 to sm1. All 0-IIa+IIc lesions were m3 or sm1. Preoperative diagnosis accurately was established preoperatively in 61% of patients. Complications related to EMR were detected in 21% of patients and included perforation, stenosis, and hemorrhage. Ten patients also received radiotherapy, chemotherapy, or esophagectomy with lymph node dissection after use of EMR. No such combination therapy was administered in six patients with m3 lesions, but without lymph vessel invasion. All patients treated with use of EMR, including patients with m3 cancer who did not receive additional treatment, are living without recurrence. Local resection with use of EMR could be regarded to be the preferred treatment of superficial esophageal cancers limited to the lamina propria mucosae. Endoscopic mucosal resection also could be regarded to be the preferred treatment of m3 cancer without lymph vessel invasion. Use of additional therapy, such as radiotherapy, allows the use of EMR for m3 cancer with lymph vessel invasion or sm1 cancers.

Aged↗
PubMed1999

Multiple primary cancers of the esophagus and thyroid gland.

The occurrence of multiple primary cancers in the aerodigestive tract is a well known phenomenon that has been explained by the concept of 'field carcinogenesis'. Metachronous or synchronous esophageal cancer has usually been identified in patients with head and neck cancer, gastric cancer or colon cancer. The incidence of multiple primary cancers of the esophagus and thyroid gland is very low. We treated four patients with synchronous cancers of the cervical esophagus and the thyroid gland. Histologically, all of the esophageal cancers were squamous cell carcinomas. Thyroid cancers were evaluated as papillary carcinoma or follicular carcinoma. Both the esophageal cancer and the thyroid cancer frequently metastasized to lymph nodes. All patients had multiple lymph nodes metastasis from the esophageal or the thyroid cancer. In one patient, both the esophageal and the thyroid cancers were detected in the same lymph node. Three of four patients died from recurrence of esophageal cancer. The prognosis of these patients was poor. In the treatment of esophageal carcinoma, cancers of other organs including the thyroid gland should be carefully investigated.

Aged↗
PubMed1999

Multiple liver metastases of breast cancer: report of a case successfully treated with hormone-cytokine-chemotherapy.

The prognosis of patients with hepatic metastasis from breast cancer is usually extremely poor. We present the case of a 39-year-old Japanese woman diagnosed with multiple liver metastasis from breast cancer. A novel approach consisting of hormone-cytokine-chemotherapy with an arterial infusion therapy was carried out. Computed tomography and ultrasonography revealed that the multiple liver metastases were reduced with remaining calcification. Tumor markers decreased rapidly. Complete regression was achieved after these treatments. To date, there has been no relapse during the 8-year follow-up period. These results suggest that the hormone-cytokine-chemotherapy might be a rational modality of treatment against multiple metastatic breast cancer.

Adult↗
PubMed1999

Effect of 5-fluorouracil on cell cycle regulatory proteins in human colon cancer cell line.

We investigated the effects of 5-fluorouracil (5-FU) on cell cycle-regulating proteins in RPMI 4788 cells. 5-FU inhibited cell growth dose-dependently and this growth inhibition was accompanied with cell cycle accumulation in early S phase and increased expression of cyclin A. When cells were released from short-term treatment (3 or 24 h) with 5-FU, the cell cycle started to progress again and cyclin A protein levels decreased. Cyclin A-associated kinase activity assay showed that cyclin A-cyclin-dependent kinase (Cdk) 2 kinase activity was altered by 5-FU treatment concomitantly with the changes in cell cycle state seen in flow cytometric analysis. Furthermore, the elevation of cyclin A protein level by 5-FU treatment was observed in three other human cancer cell lines, DLD-1, H226Br and T.Tn. These results suggest that cyclin A protein levels in cancer cells are increased by 5-FU, and the cyclin A function and degradation mechanism remain normal.

Antimetabolites, Antineoplastic↗
PubMed1998

In vivo influence of p53 status on proliferation and chemoradiosensitivity in non-small-cell lung cancer.

Alteration of the p53 gene product is a frequent event in the progression of lung cancer. However, its importance to proliferation and response to chemoradiotherapy remains unclear. Thus, to assess its influence directly in vivo, we implanted into nude mice two kinds of human non-small-cell lung cancer (NSCLC) cells: H226br having a homozygous gene mutation in p53 (mt-p53) and H226b with intact p53 (wt-p53). We found that mt-p53 tumors grew substantially faster than wt-p53 tumors. Furthermore, treatment with cisplatin and radiation did not reduce the size of mt-p53 tumors, while wt-p53 tumors regressed by approximately 60%. Terminal-deoxytransferase-mediated dUTP-biotin nick-end labeling assay revealed apoptosis to be the mechanism responsible for the regression. Interestingly, apoptosis occurred in mt-p53 tumors although only at high doses of cisplatin and not at the magnitude detected in wt-p53 tumors. Cell labeling by staining with bromodeoxiuridine indicated that p53 is an important factor in modulating growth in NSCLC tumors. Our results are consistent with the notion that correction of a single genetic lesion enhances the therapeutic effect of chemotherapy.

Animals↗
PubMed1998

Primary malignant melanoma of the esophagus: report of a case successfully treated with pre- and post-operative adjuvant hormone-chemotherapy.

Primary malignant melanoma of the esophagus is a very rare and deadly disease, with a survival of 2.2% at 5 years and a median survival of about 10 months. The aggressive biological behavior of this disease and advanced stage at the time of diagnosis together with the lack of effective treatment have contributed to its poor prognosis. We present the case of a 45-year-old Japanese man diagnosed as having a primary melanoma of the esophagus by clinical evaluation and a histological examination of endoscopic biopsy specimens. A novel approach consisting of pre- and post-operative chemo-hormone therapy with dacarbazine, nimustine, cisplatin and tamoxifen in conjunction with radical esophagectomy accompanied by lymph node dissection was carried out. The tumor size was decreased to 70% by the pre-operative chemo-hormone therapy. During the post-operative 32 months of follow-up, no evidence of recurrence or metastatic disease has been found. Although this is only one case, the outcome observed suggests that the combination of pre- and post-operative chemo-hormone therapy and radical esophagectomy with lymph node dissection is a modality that can increase the possibility of curability or at least improve the survival of patients with primary melanoma of the esophagus.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Tuberculosis of the esophagus.

We report a case of a patient with esophageal tuberculosis, a very uncommon form of extrapulmonar tuberculosis. Initially, because of constitutional symptomatology and radiological findings of mediastinal lymph node enlargement, lymphoma was considered. However, the endoscopic findings of ulcerative masses and a sinus tract revealed by esophagram were suspicious of tuberculous origin. Diagnosis was achieved after bacterial examination of smear samples from esophageal ulcers that revealed bacillus tuberculous and histological demonstration of caseating granulomas in cervical lymph nodes. Tuberculous mediastinal lymphadenitis was thought to be source of the spread to esophagus. The patient was successfully treated with a three antituberculous drugs regimen. In spite of its rarity, even in patients without risk factors, the diagnosis would be considered in the differential diagnosis of uncertain esophageal lesions.

Adult↗
PubMed1997

Apoptosis in cultured human colon cancer cells induced by combined treatments with 5-fluorouracil, tumor necrosis factor-alpha and interferon-alpha.

Biochemical analysis using nick end-labeling was performed to investigate the effect of various combinations of 5-fluorouracil, natural human tumor necrosis factor-alpha and natural human interferon-alpha on the induction of apoptosis in RPMI 4788 human colon cancer cells. After treatment with 5-fluorouracil (1 mM) for 48 h, the number of nick end-positive cells was significantly increased in comparison to the situation without treatment. When tumor cells were treated with 1 mM 5-fluorouracil, 2.86 Japan Reference Units (JRU)/ml natural human tumor necrosis factor-alpha and 1 x 10(3) IU/ml natural human interferon-alpha in combination for 48 h, the number of nick end-positive cells was significantly higher than that after treatment with 5-fluorouracil alone. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay revealed a significant decrease of relative viability, as compared to treatment with 5-fluorouracil (1 mM), 5-fluorouracil + natural human tumor necrosis factor-alpha, or 5-fluorouracil + natural human interferon-alpha for 48 h. Pretreatment with 5-fluorouracil (1 mM) for 24 h prior to treatment with natural human tumor necrosis factor-alpha (2.86 JRU/ml) and natural human interferon-alpha (10(3) IU/ml) for 24 h resulted in a significant increase of nick end-positive cells compared to pretreatment with natural human tumor necrosis factor-alpha and natural human interferon-alpha prior to treatment with 5-fluorouracil for 24 h (p < 0.05). These results suggest that 5-fluorouracil alone can induce apoptosis in RPMI 4788 tumor cells and that this effect can be enhanced by combination with natural human tumor necrosis factor-alpha and natural human interferon-alpha.

Antimetabolites, Antineoplastic↗
PubMed1997

Effect of suramin on human esophageal cancer cells in vitro and in vivo.

BACKGROUND: Suramin disrupts several kinds of growth factor receptors. Since human esophageal squamous cell carcinoma expresses abundant epidermal growth factor receptors (EGFR) and proliferates in an autocrine and paracrine manner, it was expected that suramin inhibits tumor growth by disrupting EGFR. METHODS: We studied the effect of suramin on the human esophageal squamous cell carcinoma cell line KEsC-II in vitro and in an animal model. RESULTS: Cell proliferation was stimulated at a low concentration and inhibited at a high concentration of suramin in vitro. Since autophosphorylation of EGFR was stronger at the low concentration and weaker at the high concentration of suramin compared with the control, the effect of suramin was thought to be via phosphorylation of receptors. In the animal model tumor growth was significantly stimulated in the suramin-treated group compared with the control group, and the BrdU labeling index was also higher in the suramin-treated group. CONCLUSIONS: As it was impossible to increase the dose of suramin intravenously because of side effects, administration of suramin by another method, such as subcutaneous injection around the tumor, may increase the concentration of suramin in the tumor tissue and promote the anti-tumor effect of suramin.

Animals↗
PubMed1996

The p53 gene is a potent determinant of chemosensitivity and radiosensitivity in gastric and colorectal cancers.

We previously reported that introduction of the wild-type p53 gene into human cancer cells with deleted p53 enhanced apoptosis induced by chemotherapy [Fujiwara et al. (1994) Cancer Res 54:2287]. This suggests that p53 status could be a potent determinant of the therapeutic efficacy of DNA-damaging cancer therapy. We analyzed 24 patients with gastric or colorectal cancer for p53 mutations and apoptotic changes in surgical specimens. Out of 11 patients with gastric cancer, 3 were treated with chemotherapeutic drugs before resection; 5 of 13 patients with colorectal cancer had 30 Gy radiation prior to surgery. p53 mutations were detected in 4 cases of gastric cancer (36.4%) and in 6 cases of colorectal cancer (46.2%) by immunohistochemical staining. The preoperative DNA-damaging therapies increased the number of apoptotic cells in wild-type-p53-expressing tumors; tumors with mutant p53, however, significantly showed fewer apoptotic cells compared with those expressing wild-type p53. The p53-inducible WAF1/CIP1 protein was immunohistochemically observed in wild-type-p53-containing tumors, whereas mutant-p53-expressing tumors expressed no detectable WAF1/CIP1. Taken together, we conclude that p53 mutations are associated with the poor response of chemotherapy and radiotherapy.

Adult↗
PubMed1996

Suppressed apoptotic induction in esophageal squamous cell carcinomas expressing extensive p53 protein.

p53 protein accumulation, thought to be caused by p53 gene mutation, is closely related to poor prognosis of patients with certain types of carcinomas. The progression of esophageal squamous cell carcinoma (SCC) is also strongly suspected to depend on the p53 tumor suppressor gene. Formalin-fixed, paraffin-embedded sections were taken from 25 patients who underwent esophagectomy for SCC. Fourteen patients had no preoperative therapy (control group), while the other 11 patients received preoperative radiotherapy (radiation group). There was no difference in pathological TNM classification between the two groups. These sections were examined by immunostaining with monoclonal antibody PAb 1801 to determine the accumulation of p53 protein, and apoptotic frequency was determined by TdT mediated dUTP-biotin nick end-labeling (TUNEL). In the control group, well to moderately differentiated cases showed a significantly higher AI (apoptotic index which is the number of apoptotic cells among 1000 cancer cells. %0) (51.7+/-83.4) than poorly differentiated cases (AI=1.3+/-1.0) (P<0.05). Similar results were obtained in the radiation group. The former group included 4 cases of p53 grade 4 (p53 protein detected in over 70% of the tumor cells), and the latter included 2. Few apoptotic cells were observed in any of 6 tumor tissues. In each patient, tumor cells with accumulated p53 protein were very rare to be apoptotic. On the other hand, apoptosis was observed in tumor cells without p53 protein accumulation. Spontaneous apoptosis in esophageal SCC can be induced more easily in differentiated than in poorly differentiated cases. This tendency may be enhanced by preoperative radiotherapy. Extensive p53 protein may suppress apoptotic induction in esophageal squamous cell carcinomas.

Adult↗
PubMed1996

Postoperative gastric motility, secretory function, and pre- and postoperative carbohydrate metabolic states in esophageal cancer patients.

This study was undertaken to assess postoperative gastric motility and gastric acid secretion, and pre- and postoperative carbohydrate metabolism in patients with esophageal cancer. The gastric motility was compared among 3 different reconstruction routes in 26 patients who were divided into 2 groups according to the duration of postoperative follow-up; group A, 3 months or less; and group B, 18 months or more. The routes used for subtotal resection of the stomach were the posterior mediastinal, retrosternal, and subcutaneous routes. All patients showed positive resting pressure in the esophagus, but peristaltic waves did not reach the gastric tube at dry swallowing in any patients and peristaltic waves appeared after eating pudding only in 1 patient in group B. The resting pressure and gastric emptying time were similar among reconstruction routes, but the incidence and amplitude of metoclopramide (MCP)-induced peristaltic waves were significantly higher in group B than in group A. Furthermore, 24-h intragastric pH monitoring of gastric secretion in a group of 9 patients revealed individual variation in gastric secretion. Some patients showed high acidity soon after operation, suggesting the need for prophylactic treatment for preventing gastric ulcer. Postoperatively, postprandial serum gastrin levels were significantly higher than preoperative levels. In the other group of 11 patients tested, preoperative and postoperative carbohydrate metabolism were not significantly different. Postoperatively, carbohydrate metabolism recovered to preoperative levels after a transient decrease. These results demonstrated that postoperative motility improved over time although no difference was found among the 3 reconstruction routes used.

Adult↗
PubMed1996

Cytokine production-suppressive effect by macrophage colony-stimulating factor (M-CSF).

Macrophage colony-stimulating factor (M-CSF) is a protein which is necessary for proliferation and differentiation of monocyte-macrophage precursor cells. We examined the effect of M-CSF on the cytokine production using BCG sensitized mice in vivo. On Day 0, BCG 1 mg/mouse was injected via the tail vein. Starting from Day 2, M-CSF 30 mu g/mouse (1 X 10(8) U/mg) was injected every 2 days for a total of six times (Day 2, 4, 6, 8, 10 and 12). On Day 14. LPS 25 mu g/mouse was injected via the tail vein, and Interferon (IFN)/Tumor necrosis factor-alpha (TNF-alpha) in serum were determined. The productions of IFN and TNF-alpha were suppressed significantly. These cytokine production-suppressive effects of M-CSF were found also in the in vitro experimental system using spleen cells collected. On Day 14, spleen cells were collected and adjusted to 5 X 10(6) cells/ml. 20 micro-grams of LPS was added to 2ml of spleen cells and they were incubated in a C02 incubator for 24 hours. IFN and TNF-alpha in the supernatant were determined. In the experiment using nude mice, the cytokine suppressive effect of M-CSF was not observed. MLR test was performed with spleen cells of C57BL/6 treated with M-CSF as the responder cells, and spleen cells of C3H were treated with mitomycin C as the stimulator cells. MLR was suppressed significantly by administration of M-CSF. These results might possibly reflect the actual effect of M-CSF in the living body, and the T-cell and cellular immunity might be concerned with the mechanism of the cytokine production-suppressive effect of M-CSF.

Animals↗
PubMed1995

Cyclin A and Cdk2 kinase activity are suppressed by combined treatment with tumor necrosis factor-alpha and interferon-alpha.

We previously reported that combined treatment with tumor necrosis factor-alpha (TNF-alpha) and interferon-alpha (IFN-alpha) showed a synergistic antitumor effect via regulation of cell cycle progression in the S phase. Here, we investigated the effect of the combined treatment with TNF-alpha and IFN-alpha on cell cycle regulating protein in RPMI 4788 cells. Treatment with TNF-alpha or IFN-alpha alone showed no effect on these proteins, however, the combined treatment showed suppression of cyclin A protein and its associated kinase activity. Furthermore, although the combined treatment inhibited Cdk2 kinase activity, the amount of Cdk2 protein was not affected. These results suggested that TNF-alpha and IFN-alpha work together to suppress cyclin A and Cdk2 kinase activity and to inhibit cell cycle progression in the S phase.

CDC2 Protein Kinase↗
PubMed1995

Endoscopic mucosal resection for superficial carcinoma and high-grade dysplasia of the esophagus.

Endoscopic mucosal resection (EMR) is a recently introduced therapeutic method based on the principles of the strip biopsy for resection of flat lesions of the gastrointestinal tract. Eleven asymptomatic patients (nine men, two women) with superficial carcinoma or high-grade dysplasia of the intrathoracic esophagus were treated by EMR during a 6-month period. The patients' mean age was 64 years (range, 49-78). The site of the lesions was the middle third of the esophagus in eight, upper third in two, and lower third in one patient. All patients in this series had a flat (II) type of superficial cancer. The procedure was carried out in all 11 patients without complication. Histopathological examination of the specimens revealed squamous cell carcinoma in nine patients. The remaining two patients were confirmed to have dysplasia only. Free margins measured greater than 5 mm in all cases. No recurrence was detected in a mean follow-up of 8 (5-10) months. For superficial flat lesions, EMR proved to be a safe and curative procedure that provided good quality of life following resection. However, larger trials are needed to confirm these results. Applying EMR to esophageal dysplasia could decrease the incidence of esophageal cancer.

Aged↗
PubMed1995

Suppressive effect of TNF-alpha on increased production of FdUMP by IFN-alpha.

Interferon-alpha (IFN-alpha) exhibits synergistic antitumor activity when combined with tumor necrosis factor-alpha (TNF-alpha) in vitro and in vivo and increases the cytotoxicity of 5-fluorouracil (5-FU) in vitro. Using a colon cancer cell line transplanted into nude mice, we examined the effects of pretreatment for 3 days with IFN-alpha (10(6) IU) and/or TNF-alpha (2.9 x 10(3) JRU) on 5-FU metabolism. 5-FU 30 mg/kg was administered after the pretreatment. IFN-alpha increased the tumor level of 5-fluorodeoxuridine monophosphate (FdUMP), and decreased the free level of thymidylate synthetase. Pretreatment with TNT-alpha alone decreased HUMP whereas TNF-alpha plus IFN-alpha abolished the enhancement of FdUMP production by IFN-alpha. TNF-alpha also suppressed thymidine kinase activity. Neither IFN-alpha nor TNF-alpha altered the incorporation of 5-FU into RNA.

Animals↗