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Biomedical subjects

M Hareyama

Publications and source records attributed to M Hareyama.

At least 19 recordsLinked to original sources

Chemotherapy as an adjunct to radiotherapy in locally advanced nasopharyngeal carcinoma.

BACKGROUND: A previous meta-analysis investigated the role of chemotherapy in head and neck locally advanced carcinoma. This work had not been performed on nasopharyngeal carcinoma. OBJECTIVES: The aim of the project was to study the effect of adding chemotherapy to radiotherapy on overall survival (OS) and event-free survival (EFS) in patients with nasopharyngeal carcinoma. SEARCH STRATEGY: We searched MEDLINE (1966 to October 2003), EMBASE (1980 to October 2003) and the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 3, 2003) and trial registers. Handsearches of meeting abstracts, references in review articles and of the Chinese medical literature were carried out. Experts and pharmaceutical companies were asked to identify trials. SELECTION CRITERIA: Randomised trials comparing chemotherapy plus radiotherapy to radiotherapy alone in locally advanced nasopharyngeal carcinoma were included. DATA COLLECTION AND ANALYSIS: The meta-analysis was based on updated individual patient data. The log rank test, stratified by trial, was used for comparisons and the hazard ratios (HR) of death and failure (loco-regional/distant failure or death) were calculated. MAIN RESULTS: Eight trials with 1753 patients were included. One trial with a 2 x 2 design was counted twice in the analysis. The analysis was performed including 11 comparisons based on 1975 patients. The median follow up was six years. The pooled hazard ratio of death was 0.82 (95% confidence interval (CI) 0.71 to 0.95; P = 0.006) corresponding to an absolute survival benefit of 6% at five years from chemotherapy (from 56% to 62%). The pooled hazard ratio of tumour failure or death was 0.76 (95% CI 0.67 to 0.86; P < 0.00001) corresponding to an absolute event-free survival benefit of 10% at five years from chemotherapy (from 42% to 52%). A significant interaction was observed between chemotherapy timings and overall survival (P = 0.005), explaining the heterogeneity observed in the treatment effect (P = 0.03) with the highest benefit from concomitant chemotherapy. AUTHORS' CONCLUSIONS: Chemotherapy led to a small but significant benefit for overall survival and event-free survival. This benefit was essentially observed when chemotherapy was administered concomitantly with radiotherapy.

Chemotherapy, Adjuvant↗

MEK/ERK pathway protects ionizing radiation-induced loss of mitochondrial membrane potential and cell death in lymphocytic leukemia cells.

MEK/ERK-mediated signals have recently been found to inhibit Fas-mediated cell death through inhibition of caspase-8 activity. It remains unknown whether MEK/ERK-mediated signals affect ionizing radiation (IR)-induced cell death. Here we demonstrate that MEK/ERK-mediated signals selectively inhibit IR-induced loss of mitochondrial membrane potential (DeltaPsi(m)) and subsequent cell death. In Jurkat cells, TPA strongly activated ERK and inhibited the IR-induced caspase-8/Bid cleavage and the loss of DeltaPsi(m). The inhibitory effect of TPA was mostly abrogated by pretreatment of a specific MEK inhibitor PD98059, indicating that the effect depends upon MEK/ERK-mediated signals. Moreover, BAF-B03 transfectants expressing IL-2 receptor (IL-2R) beta(c) chain lacking the acidic region, which is responsible for MEK/ERK-mediated signals, revealed higher sensitivity to IR than the transfectants expressing wild-type IL-2R. Interestingly, the signals could neither protect the DeltaPsi(m) loss nor cell death in UV-irradiated cells. These data imply that the anti-apoptotic effect of MEK/ERK-mediated signals appears to selectively inhibit the IR-induced cell death through protection of the DeltaPsi(m) loss. Our data enlighten an anti-apoptotic function of MEK/ERK pathway against IR-induced apoptosis, thereby implying its contribution to radioresistance.

BH3 Interacting Domain Death Agonist Protein↗

Radiation therapy for superficial esophageal cancer: a comparison of radiotherapy methods.

PURPOSE: A comparison of treatment outcomes in response to various methods of radiotherapy for superficial esophageal cancer (SEC) was carried out for a large series of patients. METHODS AND MATERIALS: During the period from March 1987 to November 1998, 147 patients with superficial esophageal cancer received definitive radiation therapy at nine radiotherapy institutions in Japan. Fifty-five patients were treated with external radiation therapy alone, 69 with high-dose-rate intracavitary radiation therapy with or without external radiation therapy, and 23 with low-dose-rate intracavitary radiation therapy and external radiation therapy. RESULTS: The 5-year survival rates for mucosal and submucosal cancer patients were 62% and 42%, respectively. The 5-year cause-specific survival rates for mucosal and submucosal cancer patients were 81% and 64%, respectively (p = 0.013). There was no statistically significant difference in the survival rates for either mucosal or submucosal cancer patients between treatment groups. Metastasis was observed only in submucosal cancer patients. Esophageal ulcers developed only in patients who received intracavitary radiation therapy, and were especially common in patients treated with a fraction size of 5 Gy or more. CONCLUSIONS: The use of intracavitary radiation therapy does not influence the survival or local control rate of SEC. Optimal radiotherapy methods for SEC should be determined by a randomized clinical trial.

Adult↗

Nuclear BAG-1 localization and the risk of recurrence after radiation therapy in laryngeal carcinomas.

BAG-1 is a multifunctional chaperone modulator may contribute to p53-mediated cell cycle arrest. We attempted to investigate whether BAG-1 expression is correlated with prognosis of laryngeal carcinoma patients after radiotherapy. Immunohistochemical analyses revealed BAG-1 expression was present in all laryngeal carcinomas examined, and its expression pattern varied, i.e. cytoplasmic, nuclear and both these staining types. Patients whose tumors predominantly express nuclear BAG-1 have a significantly poor failure-free survival rate after radiotherapy. We thus propose that nuclear BAG-1 localization is a prediction of unfavorable outcome should radiation therapy be undertaken for laryngeal carcinoma patients.

Biomarkers, Tumor↗

Expression of genes involved in repair of DNA double-strand breaks in normal and tumor tissues.

BACKGROUND: DNA double-strand breaks (DSB) are the major lethal lesions induced by ionizing radiation. The capability for DNA DSB repair is crucial for inherent radiosensitivity of tumor and normal cells. DNA-PKcs, Ku 70, Ku 85, Xrcc4, and Nbs1 play a critical role in DNA DSB repair. METHODS: We immunohistochemically investigated the expression of DNA-PKcs, Ku 70, Ku85, Xrcc4, and Nbs1 in 134 specimens from various normal and tumor tissues with different radiosensitivity. RESULTS AND CONCLUSION: Immunopositivity to Ku70, Ku85, DNA-PKcs, Xrcc4, and Nbs1 was found in all tumor tissues examined. The staining for Ku70, Ku85, and DNA-PKcs was nuclear; but, for Xrcc4 and Nbs1, it was nuclear and cytoplasmic. There were no apparent differences in the expression of these five proteins among cancerous tissues and the corresponding normal tissues. No apparent differences in nuclear staining intensity were detected in the expression of these five proteins among tumor tissues with different radiosensitivity, although non-Hodgkins' lymphoma (B or T cell) tended to show a lower expression than the others. The stromal cells generally expressed these five proteins at much lower frequency than either tumor or epithelial cells in both tumor and normal tissues.

Antigens, Nuclear↗

Pancreas: imaging diagnosis with color/power Doppler ultrasonography, endoscopic ultrasonography, and intraductal ultrasonography.

Recent advances of ultrasound imaging have made possible to depict various diseases and conditions of the pancreas. Color/power Doppler ultrasonography, endoscopic ultrasonography, and intraductal ultrasonography are feasible to show vascular abnormalities, differentiate the solid and cystic tumors, decide tumor extent, and help to perform interventional treatments of the pancreatic diseases. Those techniques will contribute to the more precise and easier diagnosis and to prompt decision of the treatments of the pancreatic disorders. Radiologists should recognize the diagnostic feasibility and limitations of those techniques in order to avoid unnecessary examinations on the patients, and obtain precise diagnostic images.

Endoscopy, Gastrointestinal↗

Virtual CT cholangioscopy: comparison with fiberoptic cholangioscopy.

BACKGROUND AND STUDY AIMS: No studies comparing virtual computed tomography (CT) cholangioscopy of the common bile duct compared with fiberoptic cholangioscopy are available. The aim of our study was to evaluate the feasibility of virtual CT cholangioscopy of the common bile duct. PATIENTS AND METHODS: The study population comprised 52 patients (25 women, 27 men; mean age 56.5, range 32 - 81) with biliopancreatic disorders. Endoscopic images were produced by a volume-rendering method and a perspective projection. The ability to detect the endoluminal view and abnormalities of the common bile duct by virtual CT cholangioscopy and fiberoptic cholangioscopy was evaluated. RESULTS: Except for two cases (4 %), virtual CT cholangioscopy revealed excellent and moderate endoluminal visualization. There was no significant difference between the techniques (virtual CT cholangioscopy vs. fiberoptic cholangioscopy: excellent, 73 % vs. 85 %, P = 0.149; moderate 23 % vs. 15 % (P = 0.319); poor, 4 % vs. 0 %, P = 0.153). Virtual CT cholangioscopy revealed no significantly different ability to detect stenosis and obstruction of the common bile duct, compared with fiberoptic cholangioscopy. However, the ability of virtual CT cholangioscopy to detect minute papillary tumors (virtual CT cholangioscopy 30 % vs. fiberoptic cholangioscopy 100 %, P = 0.001) and stones smaller than 5 mm (virtual CT cholangioscopy 25 % vs. fiberoptic cholangioscopy 100 %; P = 0.002 was significantly less than that of fiberoptic cholangioscopy. CONCLUSIONS: Virtual CT cholangioscopy cannot replace fiberoptic cholangioscopy completely. However, the use of this technique, instead of fiberoptic cholangioscopy, may be feasible for following up patients after biliary intervention.

Adult↗

Usefulness of magnetic resonance imaging for surgical management of extravasation of an antitumor agent: a case report.

We report a case of extravasation of an antitumor agent by preoperative magnetic resonance (MR) imaging. MR studies demonstrated a decreased signal intensity on T1- and T2-weighted images and a strong enhancement of contrast media in injured tissue, including subcutaneous adipose tissue and deep fascia, which was cicatrical macroscopically. The MR findings were in good agreement with the macroscopic findings. We believe that MR imaging is useful for estimating deep tissue damage due to extravasation of an antitumor agent.

Adipose Tissue↗

Supratentorial astrocytomas and oligodendrogliomas treated in the MRI era.

BACKGROUND: There is at present no consensus on the policy for the treatment of patients with low-grade gliomas (LGGs). METHODS: This report is a retrospective multi-institutional study of 100 patients (ages 16-65 years) with astrocytoma (grade II), oligodendroglioma, anaplastic oligodendroglioma and anaplastic oligoastrocytoma of the supratentorial areas which were treated with surgery and postoperative radiotherapy at five university hospitals in northern Japan between 1990 and 1997 when MRI was routinely used to determine the target volume. Most patients were irradiated with 50-60 Gy. The target volume usually covered the areas with T2 prolongation of MRI with a margin of 2 cm. RESULTS: The disease-specific 5-year survival rate was 87.4% for patients with oligodendroglioma and 75.3% for patients with astrocytoma. Survival for patients with astrocytoma in the MRI era appears to be improved compared with historical controls in the literature. Patients with astrocytoma aged 40 years and under had a significantly better disease-specific survival rate than those over 40 years (P < 0.05) and patients with oligodendroglioma and oligoastrocytoma showed a similar tendency. Patients with astrocytoma who had over 50% of their tumor removed had a significantly better survival rate than those who had less than 50% removed (P < 0.05). Chemotherapy appeared to improve the disease-specific survival rate of patients with oligodendroglioma but not that of patients with astrocytoma. CONCLUSION: Oligodendroglioma has a more protracted course of disease progression than astrocytoma. This particular feature and the sensitivity of LGGs to chemotherapy as well as their relevant prognostic factors, such as age, histopathology and amount of tumor removal, should be taken into account before any decision on treatment methods for LGGs is made.

Adult↗

Four cases of meningeal hemangiopericytoma treated with surgery and radiotherapy.

We report our experiences of four cases with meningeal hemangiopericytoma treated with surgery and postoperative radiotherapy and survey the literature to elucidate the efficacy of radiotherapy. Patients were treated with surgical resection and 46-52 Gy postoperative radiotherapy. Three patients had local control for 30, 54 and 138 months, respectively and one patient had local recurrence after 49 months. Distant metastases were observed in two patients; one had multiple bone, liver and lung metastases and the other multiple bone and brain metastases. For bone and brain metastases, better tumor control was obtained with palliative radiotherapy and stereotactic radiotherapy. Literature analyses demonstrated that surgery and postoperative radiotherapy of 50 Gy or more resulted in significantly better local control than surgery alone (p = 0.02). Stereotactic radiosurgery was effective for intracranial recurrence or metastasis, especially when the tumor volume was <8 cm(3) and >15 Gy at the 50% isodose line was used. Radiotherapy for bone metastases was also effective for palliation.

Adult↗

Congenital arteriovenous malformation of the pancreas: its diagnostic features on images.

To analyze diagnostic features on images of congenital arteriovenous malformation (AVM) of the pancreas, we analyzed the diagnostic findings in six patients with the disease, using gray-scale ultrasonography (US), color Doppler US, computed tomography, and angiography and analyzed previously reported cases. AVM characteristic findings on images were multiple, small hypoechoic nodules on US, mosaic appearance of the lesion and pulsatile wave form in the portal vein on color Doppler US, conglomerated small nodular enhancement of the lesion and early appearance of the portal vein on CT, and a racemose network and early appearance of the portal vein on angiography. Five of the six patients underwent surgery, and all resected specimens were histologically found to be AVMs of the pancreas; however, one with developed portal hypertension at surgery died of repeated bleeding from esophageal varices. From analysis of total of 35 cases including our six cases, a mosaic appearance of the lesion was found in 100% and a pulsatile wave form in the portal vein in 77.8% on color Doppler US. Color Doppler US is noninvasive and useful for detecting congenital AVM of the pancreas at an early stage, preventing the portal hypertension causing esophageal varices and their rupture.

Adult↗

Spiral CT venography of the lower extremities by injection via an arm vein in patients with leg swelling.

The purpose of this prospective study was to assess the role of spiral CT venography (CTV) via an arm vein injection in the detection of causes of leg swelling. 42 consecutive patients with leg swelling were studied with indirect spiral CTV and ultrasound (US). CT parameters were as follows: 5 mm beam collimation; 7-10 mm s(-1) table speed; and 2-3 mm reconstruction. Two consecutive spiral scans with a 40 s exposure time were performed from the pelvis to the knee. One bolus of 150 ml non-ionic contrast medium was injected at a rate of 3 ml s(-1) by a power injector via an arm vein. The delay times to the first and second scans were 120 s and 180 s, respectively. Spiral CTV demonstrated not only deep vein thrombosis (DVT) (n=12) but also other abnormalities (n=25). US showed DVT (n=10) and some other abnormalities (n=5). The sensitivity and specificity of spiral CTV for femoropopliteal DVT, as compared with US, were both 100%. Two cases of DVT in the left common-external iliac vein (iliac vein compression syndrome) detected by spiral CTV were not confirmed by US. We were able to evaluate DVT above the knee with this method. Indirect spiral CTV showed promise for the diagnosis of DVT and other soft tissue diseases in patients with leg swelling.

Adult↗

[Model of biological equivalent dose distribution modified by volume effect in radiotherapy].

This paper demonstrates that a biologically equivalent dose distribution including volume effect can be generated. Since the time-dose-fractionation (TDF) concept is convenient for comparing various radiation treatment schedules, TDF distribution maps are made on the basis of the physical dose distribution. On the other hand, the dose volume histogram is useful to evaluate volume effect, but is not necessarily an easy approach owing to the absence of spatial linkage. If distribution maps also representing the volume effect could actually be made, it would become easier to simultaneously predict both tumor control probability and the normal tissue complication rate. Because such tools should be very useful for planning radiotherapy, we proposed an experimental volume effect model. In this, one pixel is affected by all its surrounding pixels and the effect depends on the distance between pixels, volume, and the irradiated dose of another pixel. When the model was adapted to the conventional power law model, we could acquire a new equation with mathematical analysis. This permitted us to calculate the volume effect on each voxel within the treatment volume. Using a personal computer and treatment planning system, we calculated the "TDF-volume" distribution and drew maps based on this equation and the TDF values of each voxel for radiotherapy of a pelvic tumor.

Humans↗

Accelerated radiotherapy for T1, 2 glottic carcinoma: analysis of results with KI-67 index.

PURPOSE: Hyperfractionated and accelerated radiotherapy without a split was performed to improve the local control probability of early glottic carcinomas. We analyzed the results of this regimen by using the Ki-67 index. METHODS AND MATERIALS: Over a 12-year period, 85 T1N0M0 glottic cancers and 50 T2N0M0 glottic cancers were treated with conventional fractionation (CF) from 1984 to 1989 and with accelerated fractionation (AF) since 1990. The CF program consisted of five daily fractions of 2 Gy per week, for a total of 64 Gy. The AF program consisted of 1.72 Gy per fraction, two fractions per day, 5 days a week, for a total of 55 or 58 Gy. The specimens, taken before radiotherapy, were immunohistochemically stained with anti-Ki-67 antibody. RESULTS: The 5-year local control probability for T1 tumors was 79.6 +/- 6.9% with CF treatment, whereas with AF it was 86.9 +/- 5.6%. For T2 tumors it was 62.7 +/- 12.2% with CF, whereas it was 74.7 +/- 7.8% with AF. The difference between CF and AF did not reach the point of statistical significance. However, when T1 tumors had a Ki-67 index lower than 50%, the local control rate achieved with AF was significantly better than that with CF (p = 0.018). When the tumors had a Ki-67 index that was 50% or more, there was no difference in the local control rate between CF and AF, whether they were T1 or T2. The peak mucosal reactions at the larynx and/or hypopharynx were much more severe and appeared at smaller doses and earlier in AF than in CF. The patients with AF showed no severe late complications. CONCLUSIONS: AF could not obtain statistically significant improvement in local control probability of T1 or T2 glottic carcinomas.

Adult↗

Identification of genes highly expressed in G2-arrested Chinese hamster ovary cells by differential display analysis.

Abnormal cell cycle regulation is believed to be an important step in tumorigenesis. In mammalian cells, DNA damage commonly leads to cell cycle arrest in G2; however, little is known about the detailed biochemical mechanisms underlying the DNA damage-induced G2 arrest. In order to identify genes differentially expressed in association with G2 arrest, differential display analysis was performed between exponentially growing Chinese hamster ovary (CHO) cells and G2-arrested CHO cells induced by etoposide, SN-38, or X-radiation. We identified five cDNA clones whose expression was up-regulated in G2-arrested CHO cells. Sequence analysis revealed that three clones were homologous to known genes: isogene I of translation initiation factor eIF-4A, ribosomal protein L13, and translation repressor NAT1. The remaining two clones showed no homology to known genes. These results indicate that DNA damage can alter the expression of multiple genes, including translational regulators.

Animals↗

Simultaneous development of a pineal tumor and an intradural spinal mass during remission of acute lymphocytic leukemia.

A small percentage of children with acute lymphocytic leukemia experience relapse in the central nervous system in spite of prophylaxis. Diffuse leptomeningeal infiltration is common but an intracranial leukemic mass or spinal cord involvement is a rare manifestation. We report a child with acute lymphocytic leukemia who simultaneously developed a pineal tumor and an intradural spinal cord mass as her first relapse. She was successfully managed by comprehensive combined treatment including peripheral blood stem cell transplantation. She remains in continuous complete remission for more than 5 years without further evidence of neurological sequelae.

Child, Preschool↗