Biomedical subjects

N Mitsuhashi

Publications and source records attributed to N Mitsuhashi.

At least 19 recordsLinked to original sources

PubMed2001

Analysis of recurrence of squamous cell carcinoma of the uterine cervix after definitive radiation therapy alone: patterns of recurrence, latent periods, and prognosis.

PURPOSE: A retrospective analysis was performed with emphasis on the patterns of recurrence, latent period, and prognosis in patients with cervical squamous cell carcinoma of the uterus treated with definitive radiation therapy alone. Late recurrence, which was observed more than 5 years after the initial radiation therapy, was finally focused on and discussed. MATERIALS AND METHODS: Between 1976 and 1994, 256 patients with squamous cell carcinoma of the uterine cervix without hematogenous metastasis were treated with definitive radiation therapy alone. The patients were staged as follows according to the FIGO classification: 26 in Stage I, 56 in Stage II, 124 in Stage III, 28 in Stage IVa, and 22 in Stage IVb. All the patients were treated with external beam irradiation and low-dose-rate intracavitary brachytherapy. RESULTS: A total of 74 patients had recurrence. The recurrence appeared in 67 cases (90.5%) within 5 years. Metastasis to para-aortic and/or supraclavicular nodes developed later than other types of recurrence. Among patients with lymphogenous metastasis, there were more 5-year survivors after recurrence than with other types of recurrence. Patients with early recurrence, within 2 years of the initial therapy, had a worse prognosis than those with recurrence more than 2 years after treatment. Seven patients (2.7%) in all developed late recurrence more than 5 years after the treatment. The first site of recurrence was an abdominal para-aortic or supraclavicular node in all patients, excluding one patient who developed intrapelvic lymph node metastasis. Six patients had pelvic node metastasis detected with lymphangiography at the initial treatment. Median survival after late recurrence was 16.0 months. Two of 7 patients survived more than 3 years after secondary radiation therapy, and the remainder died of recurrent disease. CONCLUSION: Patients with para-aortic and/or supraclavicular node metastasis that developed late after the initial treatment are more likely to survive due to secondary radiation therapy. Careful follow-up is emphasized for long-term survivors.

Aged↗

PubMed2001

Genistein, a tyrosine kinase inhibitor, enhanced radiosensitivity in human esophageal cancer cell lines in vitro: possible involvement of inhibition of survival signal transduction pathways.

PURPOSE: The effect of genistein, a tyrosine kinase inhibitor, on radiosensitivity was examined, especially focusing on "survival signal transduction pathways." METHODS AND MATERIALS: Two human esophageal squamous cell cancer cell lines, TE-1 (p53, mutant) and TE-2 (p53, wild), were used. Radiosensitivity was determined by clonogenic assay, and activation of survival signals was examined by Western blot. RESULTS: Genistein (30 microM) greatly enhanced radiosensitivity in these cell lines by suppressing radiation-induced activation of survival signals, p42/p44 extracellular signal-regulated kinase and AKT/PKB. Significant increase in the percentage of apoptotic cells and increased poly[ADP-ribose] polymerase cleavage were observed in TE-2, but not in TE-1 even after combination of genistein with irradiation. In terms of changes in expression of p53-related proteins, increase in expression of Bax and decrease in that of Bcl-2 were observed in TE-2 but not in TE-1, suggesting that the main mode of cell death induced by genistein in a cell line with wild type p53 differed from that with mutant p53. CONCLUSIONS: This study suggested that survival signals, including p42/p44 ERK and AKT/PKB, may be involved in determining radiosensitivity, and genistein would be a potent therapeutic agent that has an enhancing effect on radiation.

Apoptosis↗

PubMed2001

The effects of p53 status and human papillomavirus infection on the clinical outcome of patients with stage IIIB cervical carcinoma treated with radiation therapy alone.

BACKGROUND: It has been suggested that the p53 tumor suppressor gene regulates the radiosensitivity in human malignancies after irradiation; however, in cervical carcinoma, the role of the p53 gene is still unclear because of inactivation of functional p53 by infection with human papillomavirus (HPV). The objective of this study was to clarify the effects of p53 status and HPV infection on the clinical outcome of patients with cervical carcinoma after undergoing radiation therapy. METHODS: Fifty-two patients with International Federation of Gynecology and Obstetrics Stage IIIB squamous cell carcinoma of the cervix who received radiation therapy alone were reviewed. The combination of external beam irradiation therapy and three sessions of intracavity brachytherapy irradiation was performed for all patients. Genomic DNA extracted from paraffin embedded tissues was examined for HPV types 16, 18 and 33 by the polymerase chain reaction (PCR) method and for p53 status by PCR-single-strand conformation polymorphism (PCR-SSCP) technique. The effects of HPV infection, p53 status, and other parameters on clinical outcome were investigated by univariate analysis. RESULTS: HPV-DNA was detected in 40 patients (76.9%), and 14 patients (26.9%) had mutations of the p53 gene in the study. There was a significant correlation between the existence of HPV and p53 status (P < 0.001). Mutations of the p53 gene were detected in 6 of 12 patients (50%) who had local recurrent tumors, whereas p53 were wild type in 32 of 40 patients (80%) who achieved local control. The p53 mutation had a significant correlations with local tumor recurrence. Furthermore, p53 status caused statistical significant differences in the curves of the recurrence free survival rate and local control rate as determined by the log rank test (P = 0.02 and P = 0.03, respectively). Conversely, no obvious correlation with any clinical outcome for patients with cervical carcinoma was found concerning HPV infection. CONCLUSIONS: It is possible that the p53 gene may be used as a predictive factor in radiation therapy for patients with Stage IIIB squamous cell carcinoma of the cervix.

Adult↗

PubMed2001

Accumulation of 67Ga citrate in early pregnancy.

A 26-year-old pregnant woman complained of chest pain and dyspnea and was diagnosed with malignant lymphoma of the mediastinum. To determine the stage of malignant lymphoma, tumor scintigraphy with 67Ga citrate was performed. 67Ga scintigraphy revealed an abnormal accumulation in the center of the pelvic cavity. An artificial abortion was performed, and the early pregnancy obtained from the abortion showed a prominent uptake of 67Ga citrate ex vivo. 67Ga citrate re-examination, which was performed immediately after the abortion, showed no abnormal accumulation in the pelvic cavity. To our knowledge, this is the first medical report on an aborted tissue investigated ex vivo to determine whether it demonstrated increased uptake of 67Ga citrate.

Abortion, Induced↗

PubMed2001

Vascular endothelial growth factor secreted by replicating hepatocytes induces sinusoidal endothelial cell proliferation during regeneration after partial hepatectomy in rats.

BACKGROUND: The aim of this study was to investigate regulatory mechanisms of sinusoidal endothelial cell (SEC) proliferation after hepatectomy in rats. METHODS: We investigated expressions of vascular endothelial cell growth factor (VEGF) and its receptors, flt-1 and KDR/flk-1, in regenerating liver after 70% hepatectomy. Proliferation of both hepatocytes and SECs was also monitored by evaluating the proliferating cell nuclear antigen (PCNA) labeling index. Furthermore, VEGF production by cultured hepatocytes isolated at different times after hepatectomy was measured in vitro. RESULTS: The expression of VEGF mRNA was increased markedly between 48 and 72 h after hepatectomy, and thereafter decreasing gradually. The immunohistochemical staining revealed that expression of VEGF started to increase 24 h after hepatectomy, with a peak at 72 h, and the majority of the VEGF-positive cells were hepatocytes located in periportal areas. Meanwhile, expression of flt-1 and KDR/flk-1 was observed along the sinusoids even before hepatectomy, but was increased between 72 and 120 h. Furthermore, VEGF production by cultured hepatocytes isolated 72 h after hepatectomy was significantly increased. The PCNA labeling index of the SECs exhibited a delayed and slower regenerative response in comparison to the hepatocytes, reaching a peak at 72 h. CONCLUSIONS: These data strongly suggest that VEGF secreted by proliferating hepatocytes may represent an important stimulator of SEC proliferation.

Animals↗

PubMed2001

High-dose radiation therapy for elderly patients with inoperable or unresectable non-small cell lung cancer.

PURPOSE: To evaluate definitive radiation therapy delivering doses in excess of 60 Gy for elderly patients aged 75 years or over with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: The treatment results for 97 patients aged 75 years or older (mean age 78 years; elderly group) with inoperable or unresectable NSCLC were retrospectively analyzed and compared with those for 206 patients younger than 75 year old (mean age 64 years; younger group). The elderly patients were classified into two groups; 67 patients aged 75-79 years (the elderly A) and 30 patients aged 80 years or older (the elderly B). Most of all patients were treated with a total dose of 60 Gy or more in 2 Gy daily standard fractionation. RESULTS: The overall 2 and 5 year survival rates were 32 and 13% for the elderly A group, and 28 and 4% for the elderly B group, respectively, compared with 36 and 12% for the younger group. There was not a statistically significant difference in survival rates among three groups. In stage I-II NSCLC patients there was also no significant difference in survival curves among the three groups. In patients with stage III disease, however, the survival curve of the elderly B was inferior to those of the younger group and the elderly A group, although the difference was not statistically significant. After the treatment the deterioration rate of the performance status was only 5% in the younger group and 8% in the elderly group. Only three younger and two elderly patients died of late pulmonary insufficiency associated with high-dose irradiation to the proximal bronchus. No other treatment-related event was observed except for mild acceptable acute complications in the elderly groups. CONCLUSIONS: Definitive radiation therapy is recommended to the elderly aged 75 years or older with inoperable or unresectable NSCLC, especially early stage disease, as an acceptable choice of treatment.

Aged↗

PubMed2001

Small cell lung cancer with a brain metastasis controlled for 5 years: a case report.

We report a case of small cell lung cancer whose initial presentation was a solitary brain metastasis. On chest radiography the primary tumor was unclear and only detected by bronchofiberscopy. A small single pulmonary metastasis was noted in the right lower lobe. Subtotal resection and external irradiation were applied to the brain tumor and external irradiation was applied to the lung. Concurrently one course of systemic chemotherapy was administered. The tumors in the brain and lung had disappeared by the end of the treatment. The patient has been alive and well for 5 years without recurrence.

Brain Neoplasms↗

PubMed2001

The future demand for and structural problems of Japanese radiotherapy.

BACKGROUND: Recently, as the number of elderly people in Japan is growing, so is the number of new cancer cases. The number of patients treated with radiotherapy is therefore also on the increase, so that it is important to estimate the future demand for radiotherapy and to make preparations for it. METHODS: All the surveys were conducted for 106 facilities selected randomly out of 556 radiotherapy facilities in Japan. To obtain trends in the number of new cancer patients treated with radiotherapy in Japan, we conducted a survey with a self-administered mail questionnaire designed to obtain the number of new patients treated with radiotherapy for each year of the past decade (1990-99). The future number of new patients treated with radiotherapy was estimated from the data thus obtained. To investigate structural problems of Japanese radiotherapy, surveys about the number of treatment machines and full-time equivalent (FTE) radiation oncologists were conducted according to data from the Japanese Society for Therapeutic Radiology and Oncology (JASTRO) structure survey and the Patterns of Care Study (PCS). We also compared the structure of Japanese radiotherapy with that in the USA. RESULTS: The number of patients treated with radiotherapy has increased for every institutional stratum, with an overall increase of 1.4-fold over the past 10 years in Japan. It is estimated that the number of cancer patients treated with radiotherapy will reach 190 000 in 2015. In Japanese non-academic institutions, less than one FTE radiation oncologist has been managing many of these patients. In both equipment and manpower, academic institutions exceed nonacademic institutions. CONCLUSION: The future demand for Japanese radiotherapy will grow substantially, so that it is of vital importance to prepare for it. Specifically, the number of FTE radiation oncologists must be increased.

Cancer Care Facilities↗

PubMed2001

Characterization of an Arabidopsis cDNA encoding a subunit of serine palmitoyltransferase, the initial enzyme in sphingolipid biosynthesis.

Serine palmitoyltransferase (SPT; EC 2.3.1.50) catalyzes the condensation of serine with palmitoyl-CoA to form 3-ketosphinganine in the first step of de novo sphingolipid biosynthesis. In this study, we describe the cloning and functional characterization of a cDNA from Arabidopsis thaliana encoding the LCB2 subunit of SPT. The Arabidopsis LCB2 (AtLCB2) cDNA contains an open reading frame of 1,467 nucleotides, encoding 489 amino acids. The predicted polypeptide contains three transmembrane helices and a highly conserved motif involved in pyridoxal phosphate binding. Expression of this open reading frame in the Saccharomyces cerevisiae mutant strains defective in SPT activity resulted in the expression of a significant level of sphinganine, suggesting that AtLCB2 cDNA encodes SPT. Southern blot analysis and inspection of the complete Arabidopsis genome sequence database suggest that there is a second LCB2-like gene in Arabidopsis. Expression of a green fluorescent protein (GFP) fusion product in suspension-cultured tobacco BY-2 cells showed that AtLCB2 is localized to the endoplasmic reticulum. AtLCB2 cDNA may be used to study how sphingolipid synthesis is regulated in higher plants.

Acyltransferases↗

PubMed2001

A novel membrane protein that is transported to protein storage vacuoles via precursor-accumulating vesicles.

A novel protein, MP73, was specifically found on the membrane of protein storage vacuoles of pumpkin seed. MP73 appeared during seed maturation and disappeared rapidly after seed germination, in association with the morphological changes of the protein storage vacuoles. The MP73 precursor deduced from the isolated cDNA was composed of a signal peptide, a 24-kD domain (P24), and the MP73 domain with a putative long alpha-helix of 13 repeats that are rich in glutamic acid and arginine residues. Immunocytochemistry and immunoblot analysis showed that the precursor-accumulating (PAC) vesicles (endoplasmic reticulum-derived vesicles responsible for the transport of storage proteins) accumulated proMP73, but not MP73, on the membranes. Subcellular fractionation of the pulse-labeled maturing seed demonstrated that the proMP73 form with N-linked oligosaccharides was synthesized on the endoplasmic reticulum and then transported to the protein storage vacuoles via PAC vesicles. Tunicamycin treatment of the seed resulted in the efficient deposition of proMP73 lacking the oligosaccharides (proMP73 Delta Psi) into the PAC vesicles but no accumulation of MP73 in vacuoles. Tunicamycin might impede the transport of proMP73 Delta Psi from the PAC vesicles to the vacuoles or might make the unglycosylated protein unstable in the vacuoles. After arrival at protein storage vacuoles, proMP73 was cleaved by the action of a vacuolar enzyme to form a 100-kD complex on the vacuolar membranes. These results suggest that PAC vesicles might mediate the delivery of not only storage proteins but also membrane proteins of the vacuoles.

Amino Acid Sequence↗

PubMed2001

Biological cell survival mapping for radiofrequency intracavitary hyperthermia combined with simultaneous high dose-rate intracavitary irradiation.

We examined the best way to combine recently developed radiofrequency intracavitary hyperthermia with simultaneous high dose-rate intracavitary brachytherapy in an original experimental model. Temperature distribution was measured with an experimental phantom which was immersed in a water bath with the temperature controlled at 37 degrees C. Radiation dose distribution was calculated with a treatment-planning computer. Cell survival was measured by colony assay with HeLa-TG cells in vitro. Radiation dose response at 1 - 7 Gy and time response with hyperthermia in the range of 40 - 46 degrees C were estimated. Radiation dose-response curves in simultaneous treatment with hyperthermia for 30 min at 37 to 46 degrees C were estimated and the surviving fractions in combined treatment were plotted against temperature. For intracavitary radiation alone, cell survival rates increased with increasing distance from the source. For intracavitary hyperthermia alone, the maximum temperature was observed at a depth of 13 mm from the surface of the applicator under suitable treatment conditions. Homogeneous cell killing from the surface of the applicator to a tumor depth of 13 mm was observed under a specific treatment condition. Our experimental model is useful for evaluating the best simultaneous combined treatment.

Brachytherapy↗

PubMed2001

[Radiation therapy for head and neck cancer].

Radiation therapy is the first choice of treatment for most of the early squamous cell carcinoma of the head and neck. Conventional radiotherapy however, contributes to the high local control rates only for carcinoma of the glottic larynx and the nasopharynx. Squamous cell carcinoma of the other sites cannot be sterilized easily only by external beam radiation therapy alone. Chemoradiotherapy, conformal three-dimensional radiotherapy and multi-daily fractionation are introduced clinically to improve local control and/or survival for radioresistant tumor. In this review, consensus report of radiation therapy for carcinoma of the larynx and pharynx, which was reached an agreement in JASTRO meeting in 1998, is introduced. The role of radiation therapy in the management of head and neck cancer in present and near future is also discussed.

Carcinoma, Squamous Cell↗

PubMed2000

MTABC3, a novel mitochondrial ATP-binding cassette protein involved in iron homeostasis.

Atm1p, a mitochondrial half-type ATP-binding cassette (ABC) protein in Saccharomyces cerevisiae, transports a precursor of the iron-sulfur (Fe/S) cluster from mitochondria to the cytosol. We have identified a novel half-type human ABC protein, designating it MTABC3 (mammalian mitochondrial ABC protein 3). MTABC3 mRNA is ubiquitously expressed in all of the rat and human tissues examined. MTABC3 protein is shown to be present in the mitochondria, as assessed by immunoblot analysis and confocal microscopic analysis of subcellular fractions of Chinese hamster ovary cells stably expressing MTABC3. Accumulation of iron in the mitochondria, mitochondrial DNA damage, and respiratory dysfunction in the yeast ATM1 mutant strain (atm1-1 mutant cells) were almost fully reversed by expressing MTABC3 in these mutant cells. These results indicate that MTABC3 is a novel ortholog of the yeast and suggest an important role in mitochondrial function. Interestingly, the human MTABC3 gene has been mapped to chromosome 2q36, a region within the candidate locus for lethal neonatal metabolic syndrome, a disorder of the mitochondrial function associated with iron metabolism, indicating that MTABC3 is a candidate gene for this disorder.

ATP-Binding Cassette Transporters↗

PubMed2000

Caffeine enhanced radiosensitivity of rat tumor cells with a mutant-type p53 by inducing apoptosis in a p53-independent manner.

The radiosensitizing effects of caffeine on two rat yolk sac tumor cell lines with a different p53 status were investigated. A reduction of radiation-induced G(2) arrest was caused by caffeine at a concentration of 2 mM in both cell lines. The reduction of survival was observed in a combination of radiation and 2 mM caffeine only in a lower radiation dose range, but not in a higher dose range in NMT-1 with a wild type p53. Radiosensitization of caffeine was recognized even in a higher dose range for cells with a mutant-type p53. Apoptosis, which was not prominent after irradiation alone or caffeine treatment alone, was induced by irradiation in combination with caffeine in cells with a mutant-type p53 through a p53-independent pathway.

Animals↗

PubMed2000

Structure and expression pattern of a human MTG8/ETO family gene, MTGR1.

AML1-MTG8 fusion protein, which is produced from the rearranged gene formed between AML1 and MTG8 in myeloid leukemia with t(8;21) chromosomal translocation, plays an important role in the pathogenesis of leukemia. We previously showed that ectopically expressed AML1-MTG8 fusion protein is associated with an MTG8-like protein in the mouse myeloid precursor cell line L-G, and this association seemed to be required for AML1-MTG8 to stimulate proliferation. As a candidate cDNA for this MTG8-like protein, a 6.4 kb MTGR1 cDNA encoding human MTGR1b protein of 604 amino acids was isolated. Since this cDNA was shorter than the main mRNA (about 7.5 kb), the 5'-end of the MTGR1 cDNA was extended using Marathon Ready cDNA. When the newly obtained 5'-sequence was combined with the previous cDNA, the resultant MTGR1 cDNA (6995 bp), including exon 3 that the previous cDNA lacked, could encode MTGR1a protein of 575 amino acids. Transcripts of the MTGR1 gene were expressed ubiquitously in the human tissues and cell lines examined. PCR analyses of the cDNAs from human tissues showed the presence of various splicing variants with regard to the 5'-region including exons 1, 2 and 3. The MTGR1 gene consists of 14 exons and spans about 68 kb. The genomic structure of MTGR1 is highly similar to those of other MTG 8-family genes, MTG8 and MTG16. MTG16 was recently cloned from the translocation breakpoint of myeloid malignancies with t(16;21) chromosomal translocation.

Alternative Splicing↗

PubMed2000

Radiation therapy for elderly patient with squamous cell carcinoma of the uterine cervix.

OBJECTIVE: The purpose of this study was to profile cervical squamous cell carcinoma in elderly patients undergoing radiation therapy and to study the treatment outcome and side effects of therapy. MATERIALS AND METHODS: A retrospective analysis was carried out from the records of 380 patients with squamous cell carcinoma of the uterine cervix who had been given radiation therapy between 1970 and 1994. The patients were divided into three age groups: under 70 years (youngest group; n = 215), 70 to 79 years (intermediate group; n = 124), and 80 years or older (oldest group; n = 41). Radiation therapy was performed by a combination of external beam therapy and three brachytherapy fractions using low-dose-rate sources. RESULTS: The 5-year overall survival rates in the youngest, intermediate, and oldest groups were 58, 50, and 33%, respectively, while cause-specific survival rates were 68, 70, and 65%, respectively. For the patients with stage III, the 5-year overall survival rates in the youngest, intermediate, and oldest groups were 59, 48, and 36%, respectively, while cause-specific survival rates were 72, 70, and 70%, respectively. There was no statistical significance in the 5-year intrapelvic recurrence rates among the three groups. Grade 3 or 4 complications occurred in 6.5% of the youngest, 11.3% of the intermediate, and 7.3% of the oldest groups. CONCLUSION: Radiation therapy with external beam combined with three fractions of low-dose-rate brachytherapy proved both highly effective and safe for senior patients with cervical squamous cell carcinoma.

Adult↗

PubMed2000

Magnetic resonance images of primary malignant lymphoma of the uterine body: a case report.

Primary malignant lymphoma of the uterine body is extremely rare. There are few reports concerning magnetic resonance images (MR) of uterine body lymphoma although there are several reports concerning uterine cervical lymphoma. The MR images of a 66-year-old woman with primary malignant lymphoma of the uterine body showed that the myometrium was diffusely involved, exhibiting an almost homogeneous character, and the normal zonal anatomy of the uterine cervix was preserved, with the endometrium being partly recognized near the center of the tumor. We report suggestive findings on MR images of primary malignant lymphoma of the uterine body.

Aged↗

PubMed2000

Characterization of organelles in the vacuolar-sorting pathway by visualization with GFP in tobacco BY-2 cells.

We have shown the localization and mobilization of modified green fluorescent proteins (GFPs) with various signals in different compartments in a vacuolar-sorting system of tobacco BY-2 cells. In contrast to the efficient secretion of GFP from the transformed cells expressing SP-GFP composed of a signal peptide and GFP, accumulation of GFP in the vacuoles was observed in the cells expressing SP-GFP fused with the C-terminal peptide of pumpkin 2S albumin. This indicated that this peptide is sufficient for vacuolar targeting. Interestingly, the fluorescence in the vacuoles disappeared sharply at 7 d after inoculation of the cells, but it appeared again after re-inoculation into a new culture medium. When SP-GFP was fused with the region, termed PV72C, including a transmembrane domain and a cytosolic tail of a vacuolar-sorting receptor PV72, GFP-PV72C was detected in the Golgi-complex-like small particles. Prolonged culture showed that GFP-PV72C that reached the prevacuolar compartments was cleaved off the PV72C region to produce GFP, that arrived at the vacuoles to be diffused. These findings suggested that the vacuolar-sorting receptor might be recycled between the Golgi complex and prevacuolar compartments.

Base Sequence↗