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Biomedical subjects

K Kubota

Publications and source records attributed to K Kubota.

At least 163 records · Page 9Linked to original sources

[Evidence for Taxotere treatment with solid tumors].

Evidence based medicine is essential to further develop the state of the art for cancer treatments. We introduce the levels of evidence for Taxotere treatment against various solid tumors. Most evidence for Taxotere therapy was produced in other countries. However, in Japan we have some data from phase II clinical trials for the approval of Taxotere. We review these domestic results, which reveal its usefulness and toxicity in Japanese patients. In addition, we analyze the evidence from the data of clinical trials of Taxotere conducted by investigators in the USA/Europe. Japanese physicians or academies must build a consensus for the application of Taxotere to Japanese patients with solid tumors.

Antineoplastic Agents, Phytogenic↗

[Vinorelbine in the treatment of non-small-cell lung cancer and breast cancer].

Vinorelbine is a new semisynthetic vinca alkaloid with significantly less neurotoxicity than other vinca alkaloids. It was recently approved by the Ministry of Health and Welfare in Japan for the treatment of non-small-cell lung cancer. Vinorelbine is active in metastatic breast cancer with a first time response rate of 40% to 52%. High response rates were observed with combination chemotherapies of vinorelbine and other active agents for breast cancer. In non-small-cell lung cancer, four randomized phase III trials of vinorelbine demonstrated that vinorelbine alone, or combination chemotherapy of vinorelbine with cisplatin, improved survival more than best supportive care or cisplatin plus vindesine, respectively. There is a high level of evidence that vinorelbine is an effective agent for the treatment of non-small-cell lung cancer.

Antineoplastic Agents↗

[Obstructive sleep apnea syndrome in a patient with superior vena cava syndrome caused by lung cancer].

A 48-year-old man was treated with chemotherapy and irradiation therapy for superior vena cava syndrome (SVCS) caused by adenocarcinoma of the lung, and his symptoms subsided temporarily. However, the same symptoms recurred, and severe snoring during sleep and daytime hypersomnolence developed. Obstructive sleep apnea syndrome (OSAS) was diagnosed by respiratory inductive plethysmography. After chemotherapy, the symptoms of edema of the face and arms, snoring, and daytime somnolence tendency were alleviated, and the patient's apnea hypopnea index decreased remarkably. In addition, lateral cephalograms disclosed improved patency of the upper respiratory tract and dilation of the soft palate. These findings suggested a relationship between SVCS and OSAS. OSAS may cause a deterioration of circulatory dynamics and the quality of life when it develops secondary to SVCS. Therefore, it is necessary to determine whether OSAS is present and accordingly provide suitable treatment in patients with SVCS.

Adenocarcinoma↗

Comparison of intratumoral distribution of 99mTc-MIBI and deoxyglucose in mouse breast cancer models.

UNLABELLED: The aims of this study were to evaluate the distribution of 99mTc-methoxyisobutylisonitrile (MIBI) in 3 animal models of breast cancer, the effect of radiotherapy on 99mTc-MIBI uptake, and the relationship between uptake and microvessel density. METHODS: We used syngeneic, subcutaneously transplanted FM3A, MM48, and Ehrlich mouse breast cancer. 99mTc-MIBI and FDG were injected intravenously, and tumor uptake was measured 30 min later. Double-tracer macroautoradiography (ARG) images were prepared with 99mTc-MIBI and 2-deoxy-D-[1-14C]-glucose (14C-DG), analyzed quantitatively, and compared with histology. The radiotherapeutic effects of 20 Gy x-ray irradiation were monitored by measuring tumor volume, tumor uptake, and ARG findings using 99mTc-MIBI and FDG in FM3A tumors. Microvessel density was quantified by immunohistochemical staining for CD34 and compared with ARG using 99mTc-MIBI in FM3A tumors. RESULTS: FM3A, MM48, and Ehrlich tumors showed different growth rates and radiosensitivities. Uptake of FDG, but not of 99mTc-MIBI, correlated significantly with growth rates. Compared with 14C-DG, 99mTc-MIBI accumulated more in cancer cells and less in infiltrating fibroblasts and macrophages in all tumor models. Irradiation significantly decreased 99mTc-MIBI uptake, but a rapid increase was noted at recurrence on day 7. Changes in FDG uptake were not significant at recurrence. Microvessel density in tumor tissue correlated significantly with 99mTc-MIBI uptake on ARG. CONCLUSION: Accumulation of 99mTC-MIBI in cancer cells is preferential and can be used as a sensitive marker to examine the response to radiotherapy. Angiogenesis seems to enhance accumulation of 99mTc-MIBI in tumors. These characteristics may be favorable for tumor imaging using 99mTC-MIBI.

Animals↗

[Use of passing intestine pump (EN) from home ingredient nutrition passing pipe nutrition method (HEN) in home medical treatment support].

Introducing the passing intestine pump (EN) into home medical treatment from October 1999 for passing intestine nutrition management, and to the passing intestine nutrition management to the management is thought to increase the quality of life (QOL) of the patient and the family. The life style of the patient broadens and this seems to be an effective piece of home support equipment. We here in report the actual general management of the passing intestine pump in home medical treatment.

Aged↗

Rheological evidence of the gelation behavior of hyaluronan-gellan mixtures.

It was found that solutions of calcium hyaluronate (CaHA) (0.1 to approximately 0.5 wt%) could form a gel by mixing with solutions of sodium type gellan (0.1 to approximately 0.5 wt%), although neither polymer by itself forms a gel at low concentrations (0.1 to approximately 0.5 wt% in this experiment). The rheological properties of CaHA-gellan mixtures were investigated by dynamic and steady shear measurements. Both storage shear modulus G' and loss shear modulus G'' for CaHA-gellan mixtures increased with increasing time, and tended to an equilibrium value after 1 h. After reaching steady values of G' and G", the frequency dependence of G' and G'' was observed. G' was always larger than G'' in the accessible frequency range from 10(-2) to 10(2) rad/s. The effects of pH and calcium ions were examined. Gel formation of the mixtures was promoted by decreasing pH and adding from 0.01 to 0.1 M calcium ions, but excessive calcium ions weakened the gel.

Calcium↗

Over-expression and lack of retinoblastoma protein are associated with tumor progression and metastasis in hepatocellular carcinoma.

To determine the role of retinoblastoma (Rb) gene alteration in hepatocarcinogenesis, we examined Rb protein expression immuno-histochemically in a series of surgically resected specimens including non-cancerous liver tissues with cirrhosis or chronic hepatitis, large regenerative nodules, pre-cancerous adenomatous hyperplasias as well as primary and metastatic lesions of hepatocellular carcinoma (HCC). All of the non-cancerous liver tissues, large regenerative nodules and adenomatous hyperplasias showed normal Rb protein expression. Altered Rb protein expression was observed in 31 (lack of Rb protein in 16 and over-expression in 15) of the 81 primary HCCs (38%) and was significantly associated with tumor differentiation grade: altered Rb protein expression occurred in 1 of 23 (4%), 16 of 43 (37%) and 14 of 15 (93%) well-, moderately and poorly differentiated tumors (moderately vs. well-differentiated p < 0.01; poorly vs. moderately differentiated p < 0.001). Incidences of both Rb protein absence and over-expression were higher for moderately differentiated than for well-differentiated tumors and even higher for poorly differentiated tumors. Rb protein absence and over-expression were observed in 9 (39%) and 10 (44%) of the 23 metastatic lesions of HCC, respectively, and the incidence of altered Rb protein expression (absence or over-expression) was significantly higher than in primary lesions (83% vs. 38%, p < 0.001). Our observations suggest that elevated and absent Rb protein are closely associated with tumor progression and developing metastatic disease rather than tumor initiation in cases of HCC. Int. J. Cancer (Pred. Oncol.) 84:604-608, 1999.

Adolescent↗

Direct binding of three tight junction-associated MAGUKs, ZO-1, ZO-2, and ZO-3, with the COOH termini of claudins.

ZO-1, ZO-2, and ZO-3, which contain three PDZ domains (PDZ1 to -3), are concentrated at tight junctions (TJs) in epithelial cells. TJ strands are mainly composed of two distinct types of four-transmembrane proteins, occludin, and claudins, between which occludin was reported to directly bind to ZO-1/ZO-2/ZO-3. However, in occludin-deficient intestinal epithelial cells, ZO-1/ZO-2/ZO-3 were still recruited to TJs. We then examined the possible interactions between ZO-1/ZO-2/ZO-3 and claudins. ZO-1, ZO-2, and ZO-3 bound to the COOH-terminal YV sequence of claudin-1 to -8 through their PDZ1 domains in vitro. Then, claudin-1 or -2 was transfected into L fibroblasts, which express ZO-1 but not ZO-2 or ZO-3. Claudin-1 and -2 were concentrated at cell-cell borders in an elaborate network pattern, to which endogenous ZO-1 was recruited. When ZO-2 or ZO-3 were further transfected, both were recruited to the claudin-based networks together with endogenous ZO-1. Detailed analyses showed that ZO-2 and ZO-3 are recruited to the claudin-based networks through PDZ2 (ZO-2 or ZO-3)/PDZ2 (endogenous ZO-1) and PDZ1 (ZO-2 or ZO-3)/COOH-terminal YV (claudins) interactions. In good agreement, PDZ1 and PDZ2 domains of ZO-1/ZO-2/ZO-3 were also recruited to claudin-based TJs, when introduced into cultured epithelial cells. The possible molecular architecture of TJ plaque structures is discussed.

Amino Acid Motifs↗

Portal venoplasty for recipients in living-related liver transplantation.

BACKGROUND: In living-related liver transplantation (LRLT) in small children, standard end-to-end portal vein (PV) anastomosis is usually difficult because of a inadequate total PV length, or because of a size mismatch between the graft and the recipient PV. In this report, we present our new portal venoplasty technique for the recipient PV. METHODS: After dissection of the recipient PV, the wall between the right and left branches of the PV is severed longitudinally as in the branch patch technique. The anterior and posterior edges of both branches are joined using running sutures, to form a longer and wider PV for anastomosis. RESULTS: This new portal venoplasty technique was used in 7 of 28 child cases, and gave good results without thrombosis or other complications. CONCLUSIONS: Our new portal venoplasty technique is useful in LRLT in small children when the recipient or graft PV is not long enough.

Adult↗

Histologic types of lung carcinoma and related family history of anatomic sites and histologic types of cancers.

BACKGROUND: Familial factors are suggested to play roles in lung carcinogenesis, but may well be different for each histologic cell type. METHODS: Information regarding smoking, past medical history, and family history of malignant diseases among first-degree relatives was collected from a total of 1188 patients with primary lung carcinoma (participants) who were treated in the thoracic oncology ward at the National Cancer Center Hospital, Tokyo, Japan. These data were analyzed for associations with the histologic type of the lung carcinoma. The main outcome measures were the relative risk of developing a malignancy, at any site or at certain specific sites, in first-degree relatives of participants who had a specific histologic type of lung carcinoma compared with the relative risk in those first-degree relatives of participants with other cell types. RESULTS: Participants with multiple malignant lesions reported significantly more first-degree relatives with a malignancy than those without multiple tumors (P = 0.008 by the Wilcoxon rank sum test). There was no statistically significant correlation between age, gender, smoking history, or histologic tumor type in the participant and the overall family history of malignancy. Site specific analyses revealed that participants with adenocarcinoma reported a family history of colorectal carcinoma, and those with squamous cell carcinoma reported a family history of head and neck carcinoma, more frequently than other participants (P = 0.041 and 0. 001, respectively, by chi-square analysis). CONCLUSIONS: The data from the current study suggest an association between familial factors and histologic type of lung carcinoma. Genetic factors to determine individual susceptibility to lung carcinogenesis should be investigated according to each histologic type.

Adenocarcinoma↗

Ca(2+)-independent cell-adhesion activity of claudins, a family of integral membrane proteins localized at tight junctions.

In multicellular organisms, various compositionally distinct fluid compartments are established by epithelial and endothelial cellular sheets. For these cells to function as barriers, tight junctions (TJs) are considered to create a primary barrier for the diffusion of solutes through the paracellular pathway [1] [2] [3]. In ultrathin sections viewed under electron microscopy, TJs appear as a series of apparent fusions, involving the outer leaflets of plasma membranes of adjacent cells, to form the so-called kissing points of TJs, where the intercellular space is completely obliterated [4]. Claudins are a family of 16 proteins whose members have been identified as major integral membrane proteins localized exclusively at TJs [5] [6] [7] [8]. It remains unclear, however, whether claudins have the cell-adhesion activity that would explain the unusual intercellular adhesion at TJs. Using mouse L-fibroblast transfectants expressing various amounts of claudin-1, -2 or -3, we found that these claudins possess Ca(2+)-independent cell-adhesion activity. Using ultrathin-section electron microscopy, we observed many kissing points of TJs between adjacent transfectants. Furthermore, the cell-adhesion activity of occludin, another integral membrane protein localized at TJs [9] [10] [11], was negligible when compared with that of claudins. Thus, claudins are responsible for TJ-specific obliteration of the intercellular space.

Animals↗

No-mortality liver resection for hepatocellular carcinoma in cirrhotic and noncirrhotic patients: is there a way? A prospective analysis of our approach.

BACKGROUND: Low resectability rates and significant morbidity and mortality rates often make surgery for hepatocellular carcinomas (HCCs) unfeasible. HYPOTHESIS: Our policy for surgical treatment of cirrhotic and noncirrhotic patients with HCC is adequate and safe. DESIGN: Prospective validation cohort study. SETTING: University hospital. PATIENTS: One hundred seven consecutive patients with HCCs. Associated cirrhosis was present in 64 (59.8%), and only 7 (6.5%) had normal livers. INTERVENTIONS: The presence of ascites, serum bilirubin level, and indocyanine green retention rate at 15 minutes were considered when selecting patients for surgery. Preoperative recovery of liver function was achieved with portal venous branch embolization, liver volumetry, bed rest, and control of serum aminotransferase levels. The surgical techniques mainly involved bloodless dissection using intraoperative ultrasonography and intermittent warm ischemia. The main perioperative care regimen was fresh frozen plasma infusion and strict limitation of blood transfusion. MAIN OUTCOME MEASURES: The 30-day postoperative mortality and morbidity rates. RESULTS: All the patients underwent surgery (37 major resections, 45 segmentectomies, and 25 limited resections), with no 30-day postoperative mortality, overall morbidity of 26.2%, and no major complications. Multiple logistic regression analysis revealed that only the type of operation was associated with a significantly higher morbidity risk (P = .05). CONCLUSION: With high resectability, low morbidity, and no mortality, our policy represents a solution to the drawbacks of surgical resection for treatment of HCCs, especially in patients with associated liver cirrhosis.

Adolescent↗

A design for prescription-event monitoring in Japan (J-PEM).

OBJECTIVES: To present a design for Prescription-Event Monitoring in Japan (J-PEM). METHODS: In J-PEM, pharmacists are asked to register patients who are prescribed the 'test drug' or a 'control drug' for the first time ever, the drug, and prescribing physician. Although J-PEM does not identify all users of a drug, this method provides concurrent controls. In J-PEM, a questionnaire for the pharmacist and one for the prescribing physician are mailed 6 months after the drug to be monitored is first prescribed to a patient. Doctors and pharmacists are asked to report events that occurred in the patient after the drug was prescribed. The questionnaire for the physician includes questions that are specific to the class of drug that was prescribed, to obtain information on possible confounding variables. Pharmacists are requested to give information on all concomitant drugs used by the patient during or for a part of the period that the patient was taking the drug to be monitored. RESULTS AND CONCLUSIONS: Compared with the UK PEM, the weakness of J-PEM is its inability to identify all users of a drug, and its strengths are the availability of concurrent controls and a relatively large amount of information per patient.

Journal Article↗

Accurate preoperative evaluation of liver mass lesions without fine-needle biopsy.

Fine-needle biopsy (FNB) is associated with problems, such as tumor seeding, which are probably underestimated. The aim of this study was to validate prospectively the accuracy of our diagnostic work-up without FNB, for defining indications for surgery in a cohort of patients with focal liver lesions (FLLs). Between January 1997 and December 1998, 160 consecutive patients carrying 225 FLLs admitted to our department were evaluated prospectively. Preoperative diagnoses were established by means of clinical histories, serum tumor marker levels, ultrasonography, and spiral computed tomography (CT). Angiography, magnetic resonance imaging (MRI), and Lipiodol-CT were performed when it was considered necessary to plan the surgical strategy. All the patients underwent surgery and results of pathological examinations were obtained for all of them. The preoperative diagnoses of 221 of the 225 lesions (98.2%) were confirmed, and the indications for liver resection in 156 of the 160 patients (97.5%) were correct. The respective accuracy, sensitivity, specificity, and positive and negative predictive values were 99.6%, 100%, 98.9%, 99.3%, and 100% for diagnosis of hepatocellular carcinoma (HCC); 99.1%, 100%, 98.8%, 96.9%, and 100% for metastases; 99.6%, 100%, 99.5%, 91%, and 100% for cholangiocellular carcinomas (CCCs); all 100% for mixed HCC-CCCs; and 98.7%, 57.1%, 100%, 100%, and 98.6% for benign tumors. In view of these results, the fact that the real risks of FNB have yet to be established and the possibility that tumor seeding has a major impact on patient prognosis, the use of FNB should be drastically limited.

Angiography↗

Advanced primary Hodgkin's disease of the spleen cured by surgical resection: report of a case.

We describe herein the case of a 61-year-old man who underwent successful resection of advanced primary Hodgkin's disease of the spleen. On admission, computed tomography and ultrasonography showed a fist-sized, slightly enhanced mass, and angiography demonstrated a typical neoplastic tumor stain in the spleen. Exploratory laparotomy revealed a hard mass invading the splenic hilar lymph nodes, gastric upper body, transverse colon, pancreatic tail, and left lateral segment of the liver. The patient underwent splenectomy with combined resection of the surrounding organs invaded by the tumor, followed by postoperative chemotherapy. Histological examination showed many Reed-Sternberg cells, and the tumor was subsequently diagnosed as Hodgkin's disease of the spleen. The patient is currently well without any signs of recurrence 4 years after surgery.

Hodgkin Disease↗

Comparison of the distribution of fluorine-18 fluoromisonidazole, deoxyglucose and methionine in tumour tissue.

To evaluate the tumour imaging potential of fluorine-18 fluoromisonidazole (FMISO), we studied FMISO uptake in an experimental tumour model and examined the correlation between intratumoral distributions of FMISO, 14C-2-deoxyglucose (2DG) and 14C-methionine (Met). The study was performed using control rats with the AH109A tumour and rats with the same tumour under local hypoxia. Tumour uptake of FMISO was constant between 30 min and 2 h after injection, and the tumour to muscle ratio was 2 from 2 to 4 h. A tumour study with FMISO was scheduled at 2 h. Double-tracer autoradiography of the tumour demonstrated that in the areas of high FMISO uptake, there was low uptake of Met, while areas of low FMISO uptake showed high Met uptake. FMISO showed high grain density in the rim of the tumour surrounding the necrotic area. 2DG showed a more uniform distribution over the entire section of viable cells. The mean uptake of FMISO by hypoxic, radioresistant tumours was significantly higher than that by the control tumours (P<0.05), while both 2DG and Met uptake by the control tumours was higher than uptake by hypoxic tumours. When individual tumours were examined, the uptake of FMISO was inversely correlated with that of Met (r = -0.507, P<0.02), while 2DG showed almost uniform uptake with no significant correlation to FMISO. In conclusion, hypoxic and radioresistant tumours could be identified by increased FMISO uptake in our model, consistent with findings reported by others. We found a large overlap in the distribution of FMISO and 2DG within the tumour, but only a small overlap in the distribution of FMISO and Met. A combination of FMISO and other tracers in positron emission tomography or single-photon emission tomography studies might be more helpful than single-tracer studies in predicting the response of tumour tissues to radiotherapy.

Animals↗

Retrocaval ureter and preaortic iliac venous confluence in a patient with an abdominal aortic aneurysm.

Anomalous anatomic location of a large venous system poses a potential hazard in aortic operations. We encountered a patient with an infrarenal abdominal aortic aneurysm who was also found at preoperative contrast-enhanced computed tomography to have a retrocaval right ureter and a preaortic iliac vein confluence. This combined anomaly has not previously been reported except for one postmortem case. As abdominal aortic surgery is currently performed routinely, care must be taken to avoid injury to surrounding organs due to rare anatomic anomalies.

Abnormalities, Multiple↗