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BACKGROUND: The presence of depressive symptoms in patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD) is an important research topic; however, the prevalence of depressive symptoms and the factors that influence their development are unclear.OBJECTIVE: To analyse the association between CES-D (Center for Epidemiological Studies Depression Scale) scores and clinical parameters such as age, disease duration, pulmonary function, imaging findings, blood data, physical functions, sleep disturbances, respiratory symptoms and health-related quality of life (HRQOL).METHODS: We conducted a cross-sectional retrospective study of 114 patients with NTM-PD at a single centre from March 2016 to January 2021 to evaluate the relationship between CES-D scores and clinical parameters.RESULTS: Participants had a median age of 64 years; 32.5% of them had depressive symptoms. Disease duration, albumin, C-reactive protein, pulmonary function, dyspnoea, exercise capacity, respiratory symptoms, cough-related HRQOL and sleep disturbances were associated with depressive symptoms. Binomial logistic regression analyses indicated that the CES-D score was significantly associated with cough-related HRQOL and sleep disturbances.CONCLUSION: A high percentage of NTM-PD patients in this study experienced depressive symptoms, and these patients had abnormalities of various clinical parameters. Cough-related HRQOL and sleep disturbance had a strong influence on the development of depressive symptoms.

Although substantial progress has been made in the treatment of B-cell acute lymphoblastic leukemia (B-ALL), the prognosis of patients with either refractory or relapsed B-ALL remains dismal. Novel therapeutic strategies are needed to improve the outcome of these patients. KPT-9274 is a novel dual inhibitor of p21-activated kinase 4 (PAK4) and nicotinamide phosphoribosyltransferase (NAMPT). PAK4 is a serine/threonine kinase that regulates a variety of fundamental cellular processes. NAMPT is a rate-limiting enzyme in the salvage biosynthesis pathway of nicotinamide adenine dinucleotide (NAD) that plays a vital role in energy metabolism. Here, we show that KPT-9274 strongly inhibits B-ALL cell growth regardless of cytogenetic abnormalities. We also demonstrate the potent in vivo efficacy and tolerability of KPT-9274 in a patient-derived xenograft murine model of B-ALL. Interestingly, although KPT-9274 is a dual PAK4/NAMPT inhibitor, B-ALL cell growth inhibition by KPT-9274 was largely abolished with nicotinic acid supplementation, indicating that the inhibitory effects on B-ALL cells are mainly exerted by NAD

第7回極域科学シンポジウム/特別セッション：[S] 「南極地域観測第Ⅷ期から第Ⅸ期6か年計画に向けて」12月1日（木）国立極地研究所 1階交流アトリウム

This study was carried out to examine the effect of postactivation treatment with latrunculin A (LatA), an actin polymerisation inhibitor, on in vitro and in vivo development of somatic cell nuclear transfer (SCNT) embryos derived from gene-modified Clawn miniature pig cells. After the fusion and activation, SCNT embryos were treated with or without a cytoskeletal inhibitor [LatA or 10.4 microM cytochalasin B (CB) for 2 h]. The cleavage rate was significantly higher (p0.05) in embryos exposed to 0.5 microM LatA than those in embryos exposed to CB and without a cytoskeletal inhibitor. Moreover, the blastocyst formation rate was significantly higher (p0.05) in embryos exposed to 0.5 or 1 microM LatA than those in embryos exposed to CB and without a cytoskeletal inhibitor. In addition, five fetuses were obtained from recipient uteri after transfer of embryos treated with 0.5 muM LatA. The results of this study show for the first time that postactivation treatment with LatA is effective to improve in vitro developmental capacity of gene-modified cloned miniature pig embryos and embryos treated with LatA have the ability to develop into fetuses.

Midkine (MK) is a heparin-binding growth factor and a product of a retinoic acid-responsive gene. Midkine is overexpressed in many carcinomas and thought to play an important role in carcinogenesis. However, no studies have been focussed on the role of MK in pancreatic carcinoma. This study sought to evaluate the clinical significance of MK expression in pancreatic head carcinoma, including the relationship between immunohistochemical expression and clinicopathologic factors such as prognosis. Immunohistochemical expression of MK and CD34 was evaluated in pancreatic head carcinoma specimens from 75 patients who underwent surgical resection. Midkine was expressed in 53.3% of patients. Midkine expression was significantly correlated with venous invasion, microvessel density, and liver metastasis (P=0.0063, 0.0025, and 0.0153, respectively). The 5-year survival rate was significantly lower for patients positive for MK vs patients negative for MK (P=0.0073). Multivariate analysis revealed that MK expression was an independent prognostic factor (P=0.0033). This is the first report of an association between MK expression and pancreatic head carcinoma. Midkine may play an important role in the progression of pancreatic head carcinoma, and evaluation of MK expression is useful for predicting malignant properties of pancreatic head carcinoma.

In this phase-I trial, we evaluated the safety of S-1, a novel oral fluoropyrimidine anticancer agent, combined with external-beam radiotherapy (EBRT) to determine the maximum-tolerated dose and dose-limiting toxicity (DLT) in unresectable pancreatic cancer patients. Patients had histologically proven unresectable locally advanced or metastatic pancreatic cancer. S-1 was administered orally twice daily. External-beam radiotherapy was delivered in fractions of 1.25 Gy x 2 per day, totalling 50 Gy per 40 fractions for 4 weeks. S-1 was given at five dose levels: 60 mg m(-2) day(-1) on days 1-7 and 15-21 (level 1), 1-14 (level 2), and 1-21 (level 3a) and 80 mg m(-2) day(-1) on days 1-21 (level 3b) and 1-28 (level 4). We studied 17 patients: dose levels 1 (four patients), 2 (four patients), 3a (three patients), 3b (three patients), and 4 (three patients). One patient in level 1 (grade 3 vomiting) and two patients in level 4 (grade 4 neutropenia and grade 3 anorexia) showed DLT. No DLT was seen for levels 2, 3a, and 3b. Clinical effects by computed tomography included 5 partial responses (35%), 11 cases of stable disease, and one case of progressive disease. CA19-9 levels of less than half the starting values were observed in 8 of 16 (50%) patients. S-1 at a dose of 80 mg m(-2) day(-1) given on days 1-21 is safe and recommended for phase-II study in patients with locally advanced and unresectable pancreatic cancer when given with EBRT.

During the period from January to July 2004, a total of 131 influenza C viruses were detected by cell culture or reverse transcription-PCR (RT-PCR) from specimens that were obtained from children with acute respiratory symptoms in 10 prefectures across Japan. Influenza C virus was identified most frequently in the Miyagi (1.4%, 45 of 3,226 specimens) and Yamagata (2.5%, 31 of 1,263 specimens) prefectures, and the frequency in this year was the highest since 1990. Phylogenetic analysis of the hemagglutinin esterase gene of the 13 strains isolated in nine prefectures revealed that genetically similar strains belonging to the Kanagawa/1/76-related lineage dominantly spread throughout Japan. During the 2004 influenza season, influenza C virus coexisted with epidemics of influenza A virus (H3 strain), and 12 cases were identified from patients who had been diagnosed with influenza-like illness (7 were detected by RT-PCR, and 5 were detected by culture). A comparison of specimens that were found positive by culture with those found positive only by RT-PCR shows that the amount of virus in PCR-positive specimens tended to be lower than in isolation-positive specimens. Although the mean peak temperature in patients in the PCR-positive group was slightly lower, there were no significant differences in characteristics between specimens (i.e., kind of specimen, period from onset to specimen collection, age distribution of patients, and severity of illness). These results suggest that an epidemic of influenza C virus occurred on a national scale during this period and that RT-PCR can be an effective supplemental tool for the evaluation of clinical and epidemiological information.

The p53 family regulates cell-cycle arrest, triggers apoptosis or is involved in repair of DNA damage. In the present study, we analysed the expression of some p53 family proteins and their responses to chemoradiation therapy (CRT) in cases of oesophageal squamous cell carcinoma (ESCC). We immunohistochemically investigated the relationship between p53, p53R2, and p21 expression in biopsy specimens of untreated primary tumours and their clinical and histological responses to CRT in 62 patients with ESCC. Chemoradiation therapy consisted of 5-fluorouracil plus cisplatin and 40 Gy of radiation. The rates of clinical and histological responses (complete or partial) to CRT were 71.0% (clinical) and 52.8% (histological). The rate of positive expression was 43.5% for p53, 37.1% for p53R2, and 54.8% for p21 expression. Statistically significant correlations were found between p53 or p53R2 expression and favourable response to CRT (P=0.0001 or 0.041 clinical, P=0.016 or 0.0018 histological, respectively). Furthermore, in p53-negative tumours, CRT was more effective in tumours with p53R2 negative expression than those with p53R2 positive expression (P=0.0014). We demonstrated that the negative expression of p53 and p53R2 expression was closely related to the effect of CRT and should predict the CRT outcome in patients with ESCC.

Purpose: To develop a method for treating shallow and moving tumors (e.g., lung tumors) with respiratory-gated spot-scanning proton therapy using real-time image guidance (RTPT). Methods: An applicator was developed which can be installed by hand on the treatment nozzle. The mechanical design was considered such that the Bragg peaks are placed at the patient surface while a sufficient field of view (FOV) of fluoroscopic X-rays was maintained during the proton beam delivery. To reduce the treatment time maintaining the robustness of the dose distribution with respect to motion, a mini-ridge filter (MRF) was sandwiched between two energy absorbers. The measurements were performed to obtain a data for beam modeling and to verify the spot position-invariance of a pencil beam dose distribution. For three lung cancer patients, treatment plans were made with and without the MRF and the effects of the MRF were evaluated. Next, the effect of respiratory motion on the dose distribution was investigated. Results: To scan the proton beam over a 14 x 14 cm area while maintaining the φ16 cm of fluoroscopic FOV, the lower face of the applicator was set 22 cm upstream of the isocenter. With an additional range variance of 2.2 mm and peak-to-peakmore » distance of 4 mm of the MRF, the pencil beam dose distribution was unchanged with the displacement of the spot position. The quality of the treatment plans was not worsened by the MRF. With the MRF, the number of energy layers was reduced to less than half and the treatment time by 26–37%. The simulation study showed that the interplay effect was successfully suppressed by respiratory-gating both with and without MRF. Conclusions: The spot-scanning proton beam was successfully delivered to shallow and moving tumors within a sufficiently short time by installing the developed applicator at the RTPT nozzle.« less

Background This study was designed to assess the impact of oxygen transport variables on outcome in 115 patients undergoing elective surgery for oesophageal carcinoma. Methods Haemodynamic parameters were determined using a Swan-Ganz catheter in all patients on the day before operation, 6 h after operation, and daily for the first 4 days after operation. Results Oxygen delivery and consumption at 6 h were significantly higher in survivors than in non-survivors. However, oxygen delivery and consumption in both groups did not differ significantly after postoperative day 1. Of 17 patients with oxygen delivery levels lower than 445 ml min -1 m -2 at 6 h, eight died in hospital. Oxygen delivery in patients who developed either an anastomotic leak or severe pneumonia was significantly lower 6 h after surgery. Lower levels of oxygen delivery preceded postoperative complications. Conclusion Oxygen delivery 6 h after oesophagectomy correlates with postoperative complications and may be a determinant of hospital mortality.

To evaluate more precisely the incidence of lymph node metastasis in patients with submucosally invaded (sm) gastric cancer, three additional sections were made from the remaining half of 1,794 lymph nodes taken from 57 patients, for a detailed reexamination. Lymph node metastasis was demonstrated in 19 nodes from 11 patients by the initial routine examination; however, the detailed reexamination showed cancer involvement in a further nine lymph nodes from eight patients. Of these eight patients, metastasis had not been detected in any lymph nodes by routine examination in six. Macroscopically, the lesion was of the depressed or mixed type in six of the eight patients. From the intranodal location and growth pattern of the cancer foci, lymph nodes with occult metastasis were divided into the marginal sinus type, the medullary sinus type, and the mixed type, with the marginal type being found most frequently. The overall incidence of lymph node metastasis in patients with sm gastric cancer was as high as 29.8% (17/57) in this series. Moreover, a follow-up study revealed that two patients with occult metastasis died of cancer recurrence postoperatively. Accordingly, systematic regional lymph node dissection should be carried out at the time of surgery for sm gastric cancer.

A case of an inflammatory pseudotumor arising in the spleen of a 60-year-old Japanese male is described herein. This benign lesion is extremely rare, with only 12 cases, including our own, having been reported in the world literature. We preoperatively diagnosed the splenic tumor as a metastasis, due to the coexistance of advanced stage carcinoma in the sigmoid colon. However, after splenectomy, histopathological examination of the mass revealed an inflammatory process. Inflammatory pseudotumors often pose diagnostic difficulties because the clinical and radiologic findings are suggestive of malignancy. The clinical and pathological features of cases previously reported are reviewed following the presentation of this case.

Advances in interventional radiology have made possible magnetic compression anastomosis between the bile duct and the small intestine as a novel treatment. A 70-year-old man who had undergone subtotal gastrectomy for gastric cancer 2 years previously experienced recurring cholangitis with high fever and jaundice. Diagnostic evaluation subsequently demonstrated complete obstruction of the common bile duct which was attributed to recurrent cholangitis. A parent magnet was placed endoscopically into the afferent loop of the duodenum through the gastrojejunostomy with Billroth II reconstruction. The daughter magnet attached to a guide wire was placed in the obstructed common bile duct through a percutaneous transhepatic cholangiographic drainage tube. Two magnets were immediately attracted towards each other transmurally, and anastomosis was established on day 32 after the procedure. This novel method of magnetic compression anastomosis has the advantages of noninvasiveness and simplicity, as well as being a well-tolerated procedure for indications such as biliary obstruction.

Secondary ion mass spectrometry (SIMS) was applied for the analysis of asbestos fibers. It was possible to identify the asbestos fibers by the pattern of the positive secondary ion mass spectrum. The image of the asbestos fibers was measurable by use of any major positive secondary ions. The smallest size of detectable asbestos fiber was about 5 and 1 μm in length and diameter, respectively. Using a fast atom bombardment (FAB) source instead of primary ion beam, asbestos fibers collected on a membrane filter were easily detected without any pretreatment.

Purpose: To demonstrate the feasibility of x-ray fluorescence computed tomography induced with proton beams (pXFCT) for imaging of gold contrast agent by means of experiments and Monte Carlo (MC) simulations. Methods: A 7-cm diameter water phantom containing 2.2-cm diameter vials filled with gold solutions of 3–5% Au (percent weight concentration) was imaged with pXFCT using a 7-mm FWHM 220-MeV proton beam and a 3×3mm2 CdTe photon-counting detector. The phantom was imaged in 1st generation CT scanner geometry using a programmable rotation/translation stage and 21 translation steps separated by 3.3 mm and 36 rotation steps in 10° intervals. Each of the 756 x-ray spectra was acquired for 20 s using 5×101⁰ incident protons with the CdTe detector placed at 45 cm from the isocenter and at 90° with respect to the proton beam. The 220 MeV proton beam was stopped in a solid water beam dump and the total imaging time was 4.2 hours. The experimental pXFCT data acquisition geometry was modeled based on the actual and a simplified geometry with the TOPAS MC code. pXFCT images were reconstructed based on experimental and MC-simulated x-ray spectra with filtered back-projection using Kα peaks of gold. Results: All gold vials were visible in both the experimental and simulated pXFCT images. Contrast-to-noise ratio (CNR) of the 3% Au vial was 5.8 and 11.5 in the experimental and simulated pXFCT image, respectively. pXFCT detection limit of the experimental setup was determined to be 1.8% Au, which was twice as high as the MC-simulated detection limit. Further MC simulations revealed that x-ray scatter from the beam dump was the main contribution to x-ray fluorescence signal contamination. Conclusion: We have demonstrated the feasibility of proton-induced XFCT imaging of gold. We anticipate that pXFCT imaging sensitivity will be improved in an optimized pXFCT imaging system utilizing beam collimation.

We have studied the prevalence of the subgenus F adenoviruses and the molecular characteristics of adenovirus type 41 in Hiroshima Prefecture, Japan, as a limited area during the period of 1997–2004. Subgenus F adenoviruses were detected in 30 (3.4%) of 892 fecal specimens by enzyme immunoassay (EIA), and 80.0% (24 of 30) of positive patients were

The present study was undertaken to examine the effects of microinjection of sodium nitroprusside (SNP), which releases nitric oxide (NO) spontaneously, into the nucleus tractus solitarii (NTS) on cerebral circulation. Cerebral blood flow (CBF) was measured in urethane-anesthetized (1.5 g·kg−1, i.p.), paralysed and artificially ventilated rats using labeled microspheres or laser Doppler flowmetry. The CBF was significantly decreased by microinjection of SNP (5 nmol, n=10, microsphere technique; 0.5 nmol, n=6, laser Doppler flowmetry) into the unilateral NTS. Microinjection of N G-monomethyl-L-arginine (L-NMMA), an inhibitor of the formation of NO, prevented cerebral vasoconstrictor responses induced by microinjection of l-glutamate into the NTS (n=10). Microinjection of N G-monomethyl-d-arginine (D-NMMA) had no effect on the cerebral vasoconstrictor responses induced by l-glutamate (n=11). Unilateral microinjections of L-NMMA into the NTS (n=9), of SNP into the area adjacent to the NTS (n=9), of vehicle solution into the NTS (n=10), and of light-inactivated SNP into the NTS (n=6) had no effect on cerebral circulation. Cerebral autoregulation was well maintained in our protocols (n=9). These results indicate that microinjection of SNP, an NO donor, into the NTS decreases CBF.

Between October 1999 and May 2000, a total of 28 strains of influenza C virus were isolated in four Japanese prefectures: Yamagata, Miyagi, Saitama and Hiroshima. Antigenic analysis showed that the 28 isolates were divided into three distinct antigenic groups, and viruses belonging to different antigenic groups were co-circulating in each of the four prefectures. Phylogenetic analysis of the seven protein genes demonstrated that the viruses having a similar genome composition spread in various areas of Japan during the same period. Furthermore, phylogenetic analysis showed that most of the influenza C viruses isolated in various areas of the world between the 1970s and 1980s were closely related to the contemporary Japanese viruses in all gene segments. These observations suggest that the influenza C viruses cause epidemics in some communities during the same season and that antigenically and genetically similar influenza C viruses spread throughout Japan and may be circulating worldwide.

In this paper, we focus on a problem of how to confirm a feasible condition of applied force to a multi-legged robot on rough terrain. The problem often appeals as a subject of walking stability criterion for a legged robot. ZMP (zero moment point) is one of the well-known criteria. It shows the condition as footprints of a legged robot, but it cannot be defined on the rough terrain. Therefore, we suggest a new criterion FSW (feasible solution of wrench), which gives the feasible condition even on the rough terrain from the viewpoint of "wrench"-a special representation of force screw. And we present two short examples of FSW for a biped robot, how to analyse the validity of ZMP on stairs and how to design a force trajectory on rough terrain.

In this research work, we will develop a 3D biped which simulates walking and running motion of human. First, we will explain the the equation of motion of our 3D biped (Runbot 2). Next, we will derive a control strategy of the walking biped which realizes these differential equations as motion pattern. Experimental results suggest that a biped having smooth walking gait will be realized.

Thymidine phosphorylase (TP) has chemotactic and angiogenic activity in vitro, and it promotes tumor growth and inhibits apoptosis in vivo. It plays a key role in the invasiveness and metastasis of TP-expressing solid tumors. KB/TP cells transfected with a TP cDNA have been shown to be resistant to hypoxia-induced apoptosis, suggesting that TP has effects on tumor growth and cell death independent of its effects on angiogenesis. However, the mechanisms of cell death inhibition by TP are unknown. In the present study, we demonstrate that caspase-8 is cleaved in control transfectant KB cells early on during Fas-induced apoptosis. Caspase-8 activation leads to the loss of mitochondrial membrane potential, followed by the release of cytochrome c, the activation of caspase-3, and apoptosis. In contrast, Fas-induced caspase-8 cleavage is inhibited in KB/TP cells, which lead to inhibition of the downstream apoptotic cascade and inhibition of apoptosis. These findings indicate that TP plays an important role in intracellular apoptotic signal transduction in the Fas-induced apoptotic pathway. Therefore, inhibition of TP may suppress the progression of TP-overexpressing solid tumors by inducing apoptosis.

Few studies have investigated the presence of lymph node micrometastases (MM) in the cervical region of patients with esophageal squamous cell cancer. The present study examines the presence of cervical MM and attempts to determine a way to predict the occurrence and site of such micrometastases. A total of 2203 cervical lymph nodes and 118 mediastinal recurrent nerve nodes obtained from 86 patients with esophageal carcinoma were examined immunohistochemically using cytokeratins. Cervical lymph nodes and mediastinal recurrent nerve nodes metastases were detected histologically in 33 and 41 of the 86 patients respectively. Cervical lymph node and mediastinal recurrent nerve node MM were immunohistochemically detected in 16 (18.6%) and 6 (7.0%) patients respectively. Of these 16 patients with cervical MM, seven were found to have lymph node metastases in different cervical regions, whereas cervical MM only were detected in nine patients. Among the former group of patients, five were diagnosed by ultrasound examination as having cervical lymph node metastases. Mediastinal recurrent nerve node metastases and MM correlated with the presence of cervical MM in all but one patient. Cervical lymph node metastasis, including micrometastasis, can be predicted by preoperative ultrasonography and the routine histologic examination of mediastinal recurrent nerve nodes.

Seroprevalence of antibodies to human T-lymphotropic virus type-1 (HTLV-1) was surveyed among the Thai population by the particle agglutination test and Western blotting test. None of a total of 727 individuals from seven ethnic groups were positive for the specific antibody to HTLV-1. Among hospital based 3,427 subjects in Southern Thailand, one patient with a brain tumor showed positivity in the Western blotting test, however, HTLV-1 proviral genome was not identified by PCR. The present data suggest that HTLV-1 is not endemic in the Thai population and that HTLV-1 is not a major public health problem in Thailand because HTLV-1 rarely causes its associated diseases.

An optical system for lensless Fourier transformed holographic interferometry is constructed to enable the measurement of minute displacement from nm to micrometers scale and corresponding strain distribution using a CCD camera. In this technique, Fourier spectrum of the object beam is recorded on a hologram then the hologram image is easily reconstructed by a single pass of 2D FFT. In this paper, phase difference distribution is wrapped from -(pi) to (pi) , unwrapping process is required. The maximum spanning tree method is adopted here, which seeks a spanning tree that maximizes overall edge weights given by the cross amplitude. Displacement is calculated from the phase difference distribution. Even if there is no problem in the precision of loading device, displacement distribution of the object can be measured easily with high precision.© (2001) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

The antioxidant N-acetyl cysteine (NAC) is a precursor of intracellular glutathione (GSH) and is also a well known as one of the chemopreventive agents which act through a variety of cellular mechanisms. We examined the effects of NAC on cell cycle progression in the pancreatic carcinoma cell lines, SW1990 and JHP1. Cells were incubated with or without NAC. Cell cycle distribution was analyzed by flow cytometry and immunoblotting. NAC suppressed cell proliferation in a concentration-dependent manner, whereas NAC increased intracellular glutathione content significantly in a dose-dependent manner. The percentage of cells in the G1 phase after treatment with NAC was significantly higher than the percentage seen for control cells. Cyclin D1 expression of carcinoma cells treated with NAC decreased remarkably compared with cells without NAC treatment. Thus, the antiproliferative effect of NAC by prolongation of the G1 phase in human pancreatic carcinoma cells shows its possible utility as an antitumor agent.

Surgical treatment of pancreatic adenocarcinoma has failed to produce many cures secondary to high rates of intraperitoneal relapses and liver metastases. The aim of this ex vivo study was to evaluate the inherent chemosensitivity, radiosensitivity and hyperthermic sensitivity of pancreatic adenocarcinoma and to investigate the usefulness of a 3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay utilized in each sensitivity test.Nine human pancreatic adenocarcinomas were tested ex vivo after growth in nude mice. After 72 hr of chemotherapy, radiotherapy and hyperthermia, efficacy was assessed using MTT assay to determine the ratio of surviving fraction of treated cells-to-that of untreated control cells (TIC ratio).Tumor sensitivities as measured by the IC50 (drug concentration producing 50% growth inhibition) varied largely between drugs, ranging larger than 3 x 10(5) ng/mL for 5-FU, larger than 1.5 x 10(2) ng/mL for MMC, 20 ng/mL to 1.4 x 10(3) ng/mL for ADM, and 80 ng/mL to 2.4 x 10(3) ng/mL for CDDP. D0 (dose of radiation reducing the surviving fraction to 37%) ranged from 3.2 to 8.3 Gy (mean +/- standard deviation; 5.8 +/- 1.6 Gy). For hyperthermia, the mean T50 (duration of hyperthermia reducing the surviving fraction to 50%) at 43 degrees C was 9.4 +/- 3.3 min 4.8 to 14.2 min). The T/C ratio at 43 degrees C for 12 min was less than that at 41 degrees C for 30 min (p = .01; the Wilcoxon signed-ranks test). No clear relationship among chemosensitivity, radiosensitivity, hyperthermic sensitivity and pathologic features could be established.Nine human pancreatic adenocarcinomas varied widely in their sensitivity to chemotherapies, especially for 5-FU. These results suggested that MTT assay may be useful in excluding some less sensitive cases of pancreatic cancer. For hyperthermia, sufficient therapeutic time and temperature may realize enough effect against pancreatic adenocarcinoma.

To investigate the correlation between angiogenesis and tumor growth pattern as well as the lymph node metastasis to reveal the significance of vascularity in the early stage of gastric cancer.97 specimens from patients with early gastric cancer were studied by immunohistochemical method using anti-factor VIII related antigen antibody.Microvessel count was related to tumor growth pattern. The mean vessel count was higher in superficially spreading and penetrating types of tumors. Lymph node metastasis was correlated to microvessel count. Tumors with lymph node metastasis had higher microvessel counts than those without lymph node metastasis.In the early stage of gastric carcinoma, angiogenesis is correlated with tumor growth pattern and lymph node metastasis. Identification of tumors with high density of vascularization is beneficial for closer follow-up and adjuvant therapy.

The signals of the transforming growth factor beta (TGF-beta) superfamily are conveyed through cell surface serine/threonine kinase receptors to the intracellular mediators known as Smads. Activation of Smads causes their translocation from the cytoplasm to the nucleus, where they function to control gene expression. The present study analyzed the expression of Smad4 and TGF-beta1 to determine their prognostic significance in advanced gastric cancer. Of 249 cases of advanced gastric cancer, 41 had invaded the muscular layer, 114 had invaded the subserosal layer, and 94 had invaded the serosa. Anti-Smad4 and TGF-beta1 antibodies were used for immunohistochemical staining. Reduced expression of Smad4 was 75.1%, whereas positive expression of TGF-beta1 was 39.6% in gastric cancer. Smad4 expression was related to the depth of tumor invasion (P0.05), and TGF-beta1 expression correlated with tumor gross type (P0.05). Postoperative survival analysis indicated that patients who had a tumor with reduced Smad4 expression had a poorer clinical outcome than those with preserved expression (P0.05). Furthermore, in patients with TGF-beta1-positive tumors, survival rate was significantly better in patients with preserved Smad4 expression than in those with reduced Smad4 expression (P0.05). According to multivariate analysis, Smad4 expression acted as an independent prognostic factor. Smad4 expression, particularly in the TGF-beta pathway, is an effective predictor of outcome for patients with advanced gastric cancer.

A 66-year-old male underwent partial gastrectomy (resection of the pyloric side of the stomach) at another hospital on the basis of a diagnosis of gastric cancer (Fig. 1). Five months later, his CEA level began to rise. At that time, multiple liver metastases were detected by ultrasonography and CT scans. The patient received oral UFT therapy (400 mg/day) at our hospital. A reduction in CEA was observed 63 days after the start of this therapy. A judgment of CR (complete response) was made after 4 months of the therapy. At present, 2 years and 4 months after UFT was first administered, the patient shows no signs of tumor recurrence. This case is noteworthy since there has been no previous report of a case where UFT showed a high efficacy in treating liver metastasis after surgical resection of gastric cancer.

We developed a novel inhibitor of thymidine phosphorylase (TP), 5-chloro-6-[1-(2-iminopyrrolidinyl) methyl] uracil hydrochloride (TPI), that is about 1000-fold more active than 6-amino-5-chlorouracil, one of the most potent TP inhibitors. TPI inhibited the high chemotactic motility and basement membrane invasion of KB/TP cells, a TP-positive clone transfected with Rous sarcoma virus (RSV)/TP, to the levels seen in KB/CV cells, a control clone transfected with RSV. In nude mice, oral administration of TPI suppressed not only macroscopic liver metastases of highly metastatic KB/TP cells but also the level of human beta-globin as a molecular marker of micrometastases in the livers of the mice. These findings demonstrate that TP plays a key role in the invasiveness and metastasis of TP-expressing solid tumors and suggest that TPI might be a novel antimetastatic agent for blood-borne metastasis.

Pancreatic carcinoma shows a marked invasiveness around tissues lymph node and/or hematogenous metastases resulting in poor prognoses of the patients. We examined on whether E-cadherin is associated with these malignant behaviors of pancreatic carcinoma cells using a human pancreatic adenocarcinoma cell line, JHP-1. Immunohistochemically, E-cadherin expression of JHP-1 cells was remarkably inhibited by treatment with E-cadherin antisense oligonucleotide. By invasion-MTT assay, JHP-1 cells treated with E-cadherin antisense oligonucleotide showed a significant increase of invasiveness compared to those treated with the control oligonucleotide (P0.001), whereas the proliferation of JHP-1 cells was not affected by the presence of either E-cadherin antisense or control oligonucleotide. Thus, down-regulation of E-cadherin of pancreatic carcinoma cells induced the invasiveness into the basement membrane. These results suggest that the reduction in E-cadherin expression plays a key role not only in detachment of cell-cell adhesion but also in invasion and metastasis of pancreatic carcinoma cells.

According to current TNM classification, paraaortic nodes involvement in gastric cancer is now distant metastasis. Anatomically, however, proximal gastric cancer may drain preferentially to the left-paraaortic area which represents a regional lymph-node basin.Seventy-five patients who underwent an extended gastrectomy with paraaortic lymphadenectomy for advanced carcinoma of the upper-third of the stomach were retrospectively studied.Of the 75 patients, 55 (73.3%) were positive for nodal metastasis and 21 (28.0%) had paraaortic nodes involvement. Paraaortic nodes involvement tended to be left-sided (the left side of the aorta around the left renal vein) and its incidence did not increase as the overall number of infiltrated nodes increased. Five (23.8%) of the 21 patients with paraaortic nodes involvement did not have nodal metastases in the paraceliac area. Overall survival was not different whether or not paraaortic nodes involvement was present, but was dependent on the overall number of infiltrated nodes (viz. 10 vs.10). Eight (22.2%) of 36 patients with 1-10 infiltrated nodes had PNI, with a 5-year survival rate of 46.9%.Removal of lymph nodes around the left renal vein should be included during extended gastrectomy in patients with advanced carcinoma of the upper-third of the stomach. Left-paraaortic lymphadenectomy may benefit such patients if the overall number of infiltrated nodes is low (viz. 10).

We observed the morphological changes in microspheres containing cisplatin (CDDP) embedded in poly-d,l,-lactic acid (PLA) and polyethylene glycol acid (CDDP-PPMS). The in vitro release of CDDP from CDDP-PPMS continued for more than four weeks. Scanning electron microscopy revealed that though the particles of CDDP-PPMS were spherical and superficially smooth, small pores with a superficial irregularity appeared six months later. CDDP-PPMS particles were found in the stomata of the omentum after intraperitoneal administration. When CDDP-PPMS was administered after Yoshida sarcoma cells were intraperitoneally transplanted, CDDP-PPMS was observed histologically in the necrotic tissues of the omentum. These experimental results confirmed the release of CDDP from CDDP-PPMS and the histological efficacy of CDDP-PPMS in the omentum against peritoneal metastasis.

During 1997 to 1998, a nationwide epidemic of aseptic meningitis occurred in Japan. More than 4,500 isolates from patients with aseptic meningitis were identified as echovirus type 30. To investigate the character of these isolates, we examined the nucleotide sequences of thirty-seven geographical representatives and compared them with 50 strains isolated during the past 20 years. The phylogenic analysis used partial sequences from either the VP1 or VP4-VP2 region of the viral capsid. This analysis revealed that the isolates were divided into six genomic groups. All isolates identified during 1997-1998 belonged to only two genomic groups; these two groups are thought to be the causative viral agents involved in the recent epidemic.

The purpose of the present study was to investigate the relationship between macroscopic appearance of superficial esophageal carcinoma, with particular attention to the horizontal and vertical extent of tumor growth, clinicopathologic findings and p53 expression.Eighty-seven patients with superficial esophageal carcinoma were divided into three groups: 1) group A, patients with protruding or distinct depressed lesions (n = 28); 2) group B, patients with superficial and flat lesionsor = 5 cm in length (n = 45); and, group C, patients with superficial and flat lesions (5 cm in length (n = 14). Tumors were examined immunohistochemically for p53 expression.The incidence of submucosal invasion, lymph node metastasis and lymphatic invasion was significantly higher in group A than in groups B and C. The rate of p53 expression was significantly lower in group B than in the other two groups. The prognosis in groups B and C was better than that in group A.Vertical extent was more strongly associated with tumor depth, lymph node metastasis and prognosis than was horizontal extent, although p53 overexpression was related to both the vertical and horizontal extent of tumors. Analysis of the macroscopic appearance of superficial esophageal carcinoma is useful in choosing treatment strategies.