Search PubMed⌕ Search

Biomedical subjects

N Boku

Publications and source records attributed to N Boku.

49 records · Page 3Linked to original sources

Fluorescent diagnosis of experimental gastric cancer using a tumor-localizing photosensitizer.

To clarify the usefulness of fluorescent diagnosis for gastric cancer, we assessed the sensitivity and specificity of the tumor-localizing photochlorine photosensitizer ATX-S10 in combination with a new fluorescence diagnostic system. Into the submucosa of the stomachs of five rabbits, VX-2 tumor cells originating from squamous cell carcinoma were injected. After 3 weeks, three rabbits (Group I) were sacrificed 3 h after intravenous injection of ATX-S10 at a dose of 20 mg/kg, and their stomachs were observed by the Hg-lamp-induced fluorescence diagnostic system. The other two rabbits (Group II) were also sacrificed without injection of ATX-S10 and observed by the same method. In all cases in Groups I and II, gastric cancers that were invaded from the submucosa to the serosa were recognized histologically. The concentration of ATX-S10 examined by high-performance liquid chromatography (HPLC) in the gastric cancer was significantly higher than in the normal stomach. Fluorescent spectroscopy could detect 630 nm fluorescence selectively, consistent with the cancerous tissue of Group I. Moreover, fluorescent images were detected in only the exposed area of cancerous tissue and were undetected in the surrounding normal mucosa. Conversely, no fluorescent images could be detected in the stomachs of Group II. It is suggested that a fluorescence diagnostic system using ATX-S10 may become useful for the diagnosis of the existence or extension of carcinoma of the gastrointestinal tract.

Animals↗

Clinicopathological studies on coexisting gastric malignant lymphoma and gastric adenocarcinoma: report of four cases and review of the Japanese literature.

Among 121 cases of primary gastric malignant lymphoma from 1962 to 1994 at the National Cancer Center Hospital, Tokyo, we found four cases (three males and one female) of adenocarcinoma coexisting in the stomach. The incidence of gastric malignant lymphoma together with gastric adenocarcinoma was 3.3%, suggesting that patients with lymphoma may have an increased incidence of gastric adenocarcinoma. A review of the Japanese literature revealed an additional 62 patients who developed coexisting gastric malignant lymphoma and adenocarcinoma. In the total series of 66 patients whose age and sex were recorded, there were 48 males with a mean age of 63.8 years and 18 females with a mean age of 58.6 years. Most adenocarcinomas were macroscopically early (76%) and of histologically differentiated type (75%). Conversely, 71% of lymphomas were of the advanced type macroscopically. The correct preoperative diagnoses were made in only 27% (16/59) of cases, when both tumors were located independently.

Adenocarcinoma↗

Phase I-II study of irinotecan hydrochloride combined with cisplatin in patients with advanced gastric cancer.

PURPOSE: A dose-escalation study of irinotecan hydrochloride (CPT-11) combined with fixed-dose cisplatin was conducted to determine the maximum-tolerated dose (MTD), dose-limiting toxicities, and objective response rate in patients with advanced gastric cancer. PATIENTS AND METHODS: Twenty-four patients with or without prior chemotherapy were enrolled. All patients were assessable for toxicities and response. On day 1, CPT-11 was administered as a 90-minute intravenous (I.V.) infusion, which was followed 2 hours later by a 120-minute I.V. infusion of cisplatin 80 mg/m2. CPT-11 alone at the same dose was administered again on day 15. The treatment was repeated every 4 weeks until disease progression was observed. The initial dose of CPT-11 was 60 mg/m2, and was escalated in increments of 10 mg/m2 until severe or life-threatening toxicity was observed. RESULTS: The MTD of this combination was CPT-11 80 mg/m2. At this dose level, 16.7% of patients (two of 12) had leukopenia of less than 1,000/microL, 66.7% (eight of 12) had neutropenia of less than 500/microL, and 16.7% (two of 12) had severe diarrhea of grade 4 during the first course. The dose-limiting toxicity was neutropenia. Ten patients achieved a partial response (PR), and the overall response rate was 41.7% among 24 patients (95% confidence interval, 21.9% to 61.4%). CONCLUSION: The recommended dose and schedule is CPT-11 70 mg/m2 on days 1 and 15 and cisplatin 80 mg/m2 on day 1 every 4 weeks. This combination of CPT-11 and cisplatin, considered to be active against advanced gastric cancer with acceptable toxicity, should be further assessed in a phase II study.

Adult↗

Diagnostic utility of endoscopic ultrasonography for preoperative rectal cancer staging estimation.

The preoperative staging accuracy of endoscopic ultrasonography (EUS) was assessed in 38 rectal cancer patients who underwent rectal EUS and curative surgery from July 1992 to September 1994. We used a GF-UM20 instrument with both 12- and 7.5-MHz transducers. Compared with the histological findings, the diagnostic accuracy rate for EUS was 76% (29/38) for the invasion depth and 85% (sensitivity) and 72% (specificity) for level one lymph node metastasis, resulting in an overall preoperative staging accuracy of 74% (28/38). The diagnostic accuracy of invasion depth was poor (only 45%: 5/11) in cases shown histologically to be a1 (tumor invasion through muscularis propria into parietal fat), but ranged from 90 to 100% when the a1 cases were excluded. The diagnostic accuracy for level one lymph node metastasis was proportional to the nodal size. The size of lymph nodes that had been diagnosed as metastatic and non-metastatic (P < 0.05) differed significantly. Eighteen (86%) of the 21 metastatic nodes with histologically massive invasion were detected preoperatively by EUS. Eight of the 11 undetected metastatic nodes were either less than 4 mm in diameter or showed only slight invasion. Most (81%) of the level one metastatic nodes larger than 5 mm were found. The worst preoperative staging diagnostic accuracy was for stage II cases (63%: 5/8), and in four of the 10 misdiagnosed cases, the stage was underestimated due to slight nodal invasion or skip metastasis (2 cases each). Although it was difficult to diagnose nodal metastasis correctly in these cases, preoperative staging using EUS was considered useful for diagnosing almost 80% of our rectal cancer cases.

Humans↗

Association of p53 protein expression with responses and survival of patients with locally advanced esophageal carcinoma treated with chemoradiotherapy.

Immunohistochemical analysis was performed to determine the clinical role of p53 mutations in patients with locally advanced esophageal carcinomas treated with concurrent chemoradiotherapy. The subjects of this study were 20 patients with previously untreated esophageal carcinomas with evidence of T4 disease and/or distant node metastases. Treatment comprised protracted 5-fluorouracil and 2-h cisplatinum infusions along with radiation treatment with a total radiation dose of 60 Gy. Tumor specimens from 18 of the 20 patients were analyzed immunohistochemically. Mutant p53 protein expression in the biopsy materials from the primary tumors was analyzed by immunohistochemical staining using a polyclonal antibody, RSP53. Expression of p53 was detected immunohistochemically in 10 (56%) of the 18 esophageal tumors, the cancer cell nuclei of which were diffusely stained. There were no significant differences between the patient backgrounds of the p53-"positive" and "negative" groups. Four (40%) of the 10 patients with p53 expression achieved overall complete remissions (CRSs) and 7 (70%) of these 10 achieved CRs of their primary tumors. In contrast, none of the 8 p53-negative patients achieved overall CRs and two (25%) achieved CRs of their primary tumors. The CR rates overall and of primary tumors tended to be higher in the p53-positive than negative group, but the differences were not significant. The survival rate for the 10 patients with p53 expression was better than that for the 8 negative ones (P>0.01): their median survival times were 12 and 4.5 months, respectively. Expression of p53 protein may be an indicator of a favorable prognosis in patients with locally advanced esophageal carcinomas treated with concurrent chemoradiotherapy.

Aged↗

A case of advanced gastric cancer complicated by severe toxicity induced by a combination of tegafur, uracil and mitomycin C, and associated with abnormal pharmacokinetics.

A 60-year-old female patient with gastric cancer and lymph node and liver metastases was treated with a combination of tegafur and uracil (UFT) (375 mg/m2/day) and mitomycin C (MMC) (5 mg/m2 once weekly). On day 15, when diarrhea appeared, chemotherapy was stopped immediately. On day 21, the WBC decreased to 900/microl and high fever developed. Despite treatment with granulocyte colony-stimulating factor and antibiotics, leukopenia persisted and the patient went into septic shock on day 26. On day 34, WBC increased to 5,400/microl and she recovered, with reduction in the size of the lymph node and liver metastases. Pharmacokinetic examination after intravenous injection of low-dose MMC (0.5 mg/m2) showed a markedly high peak plasma concentration (PPC), a large area under the time-versus-concentration curve (AUC) and reduced clearance. Similarly, oral administration of UFT (tegafur 300 mg/body) produced a relatively higher PPC and a larger AUC of 5-fluorouracil (FU). The activity of dihydropyrimidine dehydrogenase, the rate-limiting enzyme in the metabolism of FU, in peripheral mononuclear cells was within the normal range (0.265 nmol/min/mg). MMC is believed to have played a large part in inducing the severe toxicity observed in this patient. Physicians should be aware of the possibility of severe toxicity during treatment with UFT and MMC, although details of its incidence and mechanism are unclear.

Adenocarcinoma↗

Expression of integrin alpha 3 in gastric and colorectal cancers: its relation to wall contraction and mode of invasion.

We macroscopically classified 25 gastric and 23 colorectal advanced cancers into "contracted" and "uncontracted" types, and found immunohistochemically that integrin subunit alpha 3 was more frequently expressed in the extracellular matrix (ECM) in the former than in the latter (75%:9/12 vs. 38%: 5/13 in gastric and 86%:6/7 vs. 25%:4/16 in colorectal cancers, respectively). Integrin subunit alpha 3 was also expressed more frequently in cancers producing transforming growth factor-beta (TGF-beta), which is related to ECM deposition, integrin expression and cell mobility, than in those which did not produce TGF-beta (67%:10/15 vs. 40%:4/10 in gastric and 57%:4/7 vs. 38%:6/16 in colorectal cancers, respectively). In addition, integrin subunit alpha 3 was not expressed in 2 benign gastric ulcers combined with gastric cancer elsewhere in the stomach. On the other hand, a retrospective analysis of 107 cases of rectal cancer which recurred after a curative operation revealed that local recurrence was more frequent in "contracted" than "uncontracted" types (44%:11/25 vs. 26%:21/82). These results may suggest that the abundant interstitial fibrosis which leads to remarkable gastric or colorectal wall contraction is a result of the interaction between cancer cells and ECM, along with the expression of integrin and/or the production of TGF-beta. This fibrosis may also be closely related to the mode of gastric and colorectal cancer invasion.

Antigens, CD↗

Concurrent chemotherapy and radiation therapy for locally advanced carcinoma of the esophagus.

A pilot study was undertaken to clarify the efficacy of concurrent chemoradiotherapy against locally advanced esophageal carcinoma. The 20 patients in this study had previously untreated esophageal carcinoma with evidence of T4 disease and/or distant node metastases. Chemotherapy consisted of protracted infusion of 5-fluorouracil at a dose of 400 mg/m2/day on days 1-5 and 8-12, combined with a 2-h infusion of cisplatinum at 40 mg/m2 on days 1 and 8. Radiation treatment for the mediastinum was administered 5 days per week for 3 wk at 2 Gy/day, along with chemotherapy. These schedules were repeated twice to give a total radiation dose of 60 Gy. For patients who responded, two additional courses of chemotherapy were administered. Five of the 20 patients had UICC stage III disease and 15 had stage IV. Seventeen (85%) of the 20 patients exhibited an objective response, including 6 (30%) complete responses. Local control was excellent with 10 (50%) complete responses. Toxic effects were severe. Major toxicities were leukocytopenia of grade 3 or more in 45% of the patients and esophagitis, including four perforations. There were two treatment-related deaths. The median survival time was 9 mo (range: 2 to 34+). Concurrent chemotherapy and radiotherapy was effective even for locally advanced esophageal carcinoma, but was associated with significant toxicity.

Aged↗

Suppression of T-lymphoma cell apoptosis by monoclonal antibodies raised against cell surface adhesion molecules.

We have previously established a mouse malignant T-lymphoma CS-21 cell line that preferentially metastasizes to lymph nodes after s.c. inoculation into BALB/c mice. The CS-21 lymphoma cells were grown in vitro in the presence of CA-12 stromal cells isolated from lymph nodes. When CS-21 cells were cultured alone, they underwent apoptotic cell death with DNA fragmentation. In contrast, the culture of CS-21 cells attached to a monolayer of CA-12 stromal cells prevented CS-21 cell apoptosis and enhanced cell proliferation. To identify the cell adhesion molecules, we developed monoclonal antibodies (mAbs) directed against CS-21 cell surface proteins. Fourteen mAbs partially inhibited the binding of CS-21 cells to a CA-12 stromal cell monolayer. MCS-5 (mAb against CS-21 No. 5) directed against a M(r) 168,000 cell membrane protein and MCS-19 against a M(r) 23,000 protein were found to suppress apoptosis and to stimulate CS-21 cell growth. Soluble factors secreted from CA-12 stromal cells enhanced CS-21 cell growth but were not sufficient to prevent apoptosis. In the presence of both stromal cell-secreted factors and mAbs MCS-5 or MCS-19, CS-21 lymphoma cells evaded apoptosis and grew as fast as in the coculture with CA-12 stromal cells. Because of these results, we conclude that CA-12 lymph node stromal cells support CS-21 lymphoma cell growth by secreting paracrine growth factors and by presenting receptors for the M(r) 168,000 and M(r) 23,000 cell surface adhesion molecules of CS-21 cells that transmit signals to prevent CS-21 cell apoptosis.

Animals↗

Small cell carcinoma of the esophagus with an esophago-mediastinal fistula successfully treated by chemoradiation therapy and intubation: a case report.

A case of esophageal small cell carcinoma with cervical node metastases and an esophago-mediastinal fistula was treated successfully by chemoradiotherapy. The fistula, after irradiation, was handled successfully by esophageal intubation, followed by infusional 5-fluorouracil and cisplatinum chemotherapy, resulting in the closure of the fistula. Two courses of concurrent chemoradiotherapy, followed by additional cisplatinum and etoposide chemotherapy, were administered. The tumor, including the cervical lymph node metastases, disappeared completely after the treatment.

Antineoplastic Combined Chemotherapy Protocols↗

Streptococcus milleri infection and pericardial abscess associated with esophageal carcinoma: report of two cases.

We report 2 cases of esophageal carcinoma with esophago-mediastinal fistula that developed pericardial abscess due to Streptococcus intermedius infection. Streptococcus intermedius, a generally harmless commensals in healthy humans, is not usually associated with infections of the oral cavity but may account for non-oral purulent infections. This report, however, highlights that Streptococcus intermedius infection can be life-threatening for some patients such as those with esophageal carcinoma with fistula.

Abscess↗

Primary squamous cell carcinoma of the stomach: a case report with a review of Japanese and Western literature.

A case of a 75 year-old male with primary squamous cell carcinoma of the stomach is reported. It is extremely rare to see squamous cell carcinoma developing in the stomach, without being accompanied by a component of adenocarcinoma. Up to the present, 18 Japanese and 62 Western cases of this type of carcinoma have been reported in the literature. The origin of this malignancy has not been well elucidated yet and thus, several plausible hypotheses have been proposed. In this presented case, the tumor consisted of only squamous cell carcinoma and the focus of squamous metaplasia was not found histologically in the adjacent mucosa. Therefore, it may be considered that the carcinoma arises from misplaced squamous cell nests of the stomach.

Aged↗