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Biomedical subjects

H Niibe

Publications and source records attributed to H Niibe.

At least 37 records · Page 2Linked to original sources

Cancer in patients aged 90 years or older: radiation therapy.

PURPOSE: To investigate the clinical efficacy of radiation therapy for cancer in patients aged 90 years or older. MATERIALS AND METHODS: Cancer cases in 32 patients (11 men, 21 women) aged 90 years or older who underwent radiation therapy in 1970-1997 were retrospectively analyzed. The mean patient age was 92.2 years, with a range of 90-98 years. Head and neck cancer (n = 14 [44%]) and skin cancer (n = 6 [19%]) were the most common. RESULTS: Eleven (79%) of the 14 patients with head and neck cancer were treated with curative intent. Radiation response without any severe complication was observed in nine (90%) of the 10 patients with head and neck cancer treated with curative intent who finished treatment. The median survival time was 8 months (range, 3-55 months) in the 10 patients with head and neck cancer who completed treatment with curative intent. Complete response was achieved in all of the patients with skin cancer without any major sequelae. Complete response was also observed in all three of the patients with non-Hodgkin lymphoma, but two patients treated with adjuvant chemotherapy died of drug-induced pneumonitis. Palliation was achieved in all nine of the patients treated with palliative intent. CONCLUSION: Age of 90 years or older is not a limiting factor for radiation therapy.

Age Factors↗

Apoptosis and appearance of Trp53-positive micronuclei in murine tumors with different radioresponses in vivo.

The purpose of this paper is to determine the relationship between the response to radiation and the appearance of apoptosis and micronuclei with Trp53 protein in murine tumors after irradiation. Two murine tumors, EL4, which was derived from a mouse lymphoma, and FM3A, which was derived from a mouse mammary carcinoma, were locally irradiated with 15 Gy and sections were stained with H&E and an anti-Trp53 antibody. The response to radiation was greater in EL4 tumors than in FM3A tumors. The frequency of apoptotic cells in EL4 tumors was 6.1 +/- 1.2% at time zero, reached a peak of 36.3 +/- 3. 8% at 6 h, and then decreased with time through 72 h to 2.5 +/- 1.5% after 15 Gy irradiation. In FM3A tumors, no apoptotic cells were detected at 0, 1, 3, 6 or 24 h after exposure. At 48 and 72 h, the frequency was only 3.0 +/- 0.6% and 1.3 +/- 0.3%. Apoptotic cells increased significantly at 3, 6 and 24 h after irradiation in EL4 tumors (P < 0.008) and at 48 and 72 h in FM3A tumors (P < 0.006). The frequency of Trp53-positive cells was 17.9 +/- 2.2 and 15.2 +/- 2.3% at time zero in EL4 and FM3A tumors, respectively, increased to 74.5 +/- 4.5% in EL4 cells (P = 0.001), and increased to 33.9 +/- 1. 1% in FM3A cells (P = 0.005) 1 h after irradiation. Trp53-positive micronuclei appeared in cells in both tumors from 24 to 72 h after irradiation. The frequency of Trp53-positive micronuclei was 3.8 +/- 0.5 and 13.5 +/- 1.3% at 24 h in EL4 and FM3A tumors, respectively, and gradually decreased by 72 h. After exposure to 15 Gy, Trp53-positive micronuclei increased significantly in FM3A tumors compared to EL4 tumors at both 24 and 48 h (P < 0.02). The frequency of these micronuclei increased with increasing dose in FM3A tumors, and the difference between these percentages after 3 Gy and after 5, 10 and 15 Gy was significant (P < 0.02). Many apoptotic cells were observed in the radiosensitive EL4 tumor after irradiation. Death by apoptosis may be related to an early response to radiation in these tumors. The appearance of micronuclei may be an important mechanism of cell death in FM3A tumors in which no apoptosis was induced.

Animals↗

Giant cell tumor of the thoracic spine simulating mediastinal neoplasm.

A case of giant cell tumor of the thoracic spine simulating mediastinal neoplasm was identified on plain films, CT scans, MR images, and with scintigraphy. CT showed a hypervascular soft-tissue mass with shell-like calcification in the right upper mediastinum. MR imaging showed a collapse of the T1 vertebral body and a mass extending to the mediastinum. The mass had a low signal on T1-weighted MR images and a predominantly high signal on T2-weighted images with heterogeneity. Technetium-99m methylene diphosphonate bone scintigraphy showed intense uptake in both the T1 and marginal parts of the mediastinal mass. There was no accumulation of gallium-67 citrate, but 18-fluorine fluorodeoxyglucose positron emission tomography showed marked uptake. The variation in these imaging findings played an important role in the differential diagnosis of this uncommon mediastinal mass.

Adult↗

Early radiation effects in highly apoptotic murine lymphoma xenografts monitored by 31P magnetic resonance spectroscopy.

PURPOSE: Phosphorus-31 magnetic resonance spectra (31P-MRS) were obtained from highly apoptotic murine lymphoma xenografts before and up to 24 hr following graded doses of radiation ranging from 2 to 30 Gy. Radiation-induced apoptosis was also estimated up to 24 hr by scoring apoptotic cells in tumor tissue. METHODS AND MATERIALS: Highly apoptotic murine lymphoma cells, EL4, were subcutaneously transplanted into C57/BL mice. At 7 days after transplantation, radiation was given to the tumor with a single dose at 3, 10, and 30 Gy. The beta-ATP/Pi, PME/Pi, and beta-ATP/PME values were calculated from the peak area of each spectrum. Radiation-induced apoptosis was scored with counting apoptotic cells on hematoxylin and eosin stained specimens (% apoptosis). RESULTS: The values of % apoptosis 4, 8, and 24 hr after radiation were 21.8, 19.6, and 4.6% at 3 Gy, 35.1, 25.6, and 14.8% at 10 Gy, 38.4, 38.0, and 30.6% at 30 Gy, respectively (cf. 4.4% in control). There was no correlation between early change in beta-ATP/Pi and % apoptosis at 4 hr after radiation when most of the apoptosis occurred. An early decrease in PME/Pi was observed at 4 hr after radiation dose at 30 Gy. For each dose, the values of beta-ATP/Pi 24 hr after radiation were inversely related to radiation dose. CONCLUSION: The increase in beta-ATP/Pi observed by 31P-MRS was linked to the degree of histological recovery from radiation-induced apoptosis.

Adenosine Triphosphate↗

Effect of radiation on the expression of E-cadherin and alpha-catenin and invasive capacity in human lung cancer cell line in vitro.

PURPOSE: To investigate the effect of radiation on E-cadherin and alpha-catenin expression in a human lung cancer cell line, and also evaluate invasive capacity in the membrane invasion culture system using the Boyden Chamber. MATERIALS AND METHODS: The immunoblot and immunofluorescence analyses were performed using the human lung cancer cell line A549 to examine altered expression of E-cadherin and alpha-catenin after irradiation. We also compared invasive capacity of untreated cells with that of irradiated cells. RESULTS: Immunoblot analysis revealed that the expression of E-cadherin increased after irradiation. In a time-course analysis, the expression was increased 6 h after irradiation with 10 Gy and reached its peak level at 24 h, being 2.3 times the control value, whereas expression at 1 and 3 h after irradiation was almost equivalent to that of the control. A slight increase in expression was observed after irradiation of 2 Gy and the expression reached peak levels after 5 Gy. After fractionated irradiation, the increase in expression of both E-cadherin and alpha-catenin was observed, and the alteration of alpha-catenin was more prominent than that after a single irradiation of the same total dose. In the immunofluorescence study for E-cadherin antibody analyzed by confocal laser scanning microscopy, increased intensity in irradiated cells produced as a nondisrupted and continuous line at cell-cell contact sites. In an invasive assay, the number of migrated cells in irradiated cells after a dose of 5 and 10 Gy was reduced significantly compared to untreated cells. CONCLUSION: The results indicate that irradiation of A549 increased the expression of E-cadherin, possibly preserving their functional property.

Cadherins↗

Change in E-cadherin expression after X-ray irradiation of a human cancer cell line in vitro and in vivo.

PURPOSE: To investigate changes in E-cadherin expression after X-ray irradiation of a human cancer cell line in vitro and in vivo. METHODS AND MATERIALS: E-cadherin expression on a human squamous cell carcinoma of the thyroid gland (T-SCC cell), which was established in our laboratory, at 24 h after graded single doses of irradiation and at 7 successive times after 10-Gy irradiation were investigated in vitro by immunoblot analysis with the monoclonal antibody to human E-cadherin. The changes in E-cadherin expression caused by irradiation of T-SCC tumors that were transplanted into athymic nude mice were also determined in vivo by immunohistochemical staining and immunoblot analysis in a similar fashion to that in vitro. RESULTS: In vitro studies revealed that E-cadherin expression had increased significantly on T-SCC cells at 24 h after irradiation with doses of 2 to 10 Gy and that, in a time-course analysis, the expression had increased significantly at 3 to 72 h after irradiation compared with an unirradiated control cell, although it was not observed at 1 h after irradiation. In in vivo studies, a significant increase in E-cadherin expression was observed at 24 h after irradiation with 5 and 10 Gy by immunohistochemical staining and time-course studies demonstrated that E-cadherin increased temporarily at 12 to 24 h after 10-Gy irradiation; however, immunoblot analysis did not show alteration of E-cadherin expression by irradiation. CONCLUSION: X-ray irradiation upregulated E-cadherin expression on T-SCC cells in vitro and in vivo.

Animals↗

Radiotherapeutic Management of Brain Metastases from Breast Cancer.

We have reviewed the medical records of 28 breast cancer patients with brainmetastases who were treated with radiotherapy at our clinic from 1980 through 1994(4 patients, postoperatively; 24 patients, radiotherapy alone). Radiotherapy was delivered as whole brain irradiation using lateral opposed 10 MV X-rays. Tenpatients received an additional boost to a reduced field. One patient was treated with localized stereotactic irradiation alone. The radiation dose for tumorsranged from 32 Gy to 60 Gy(mean, 49 Gy)in 2 or 3 Gy daily fractionated doses. The brain was the first site of metastatic involvement in only two patients. In the 26 evaluable patients, neurologic functional improvement was achieved in 24 patients(92%)with complete response(CR)in 12 patients(46%)and partial response(PR)in 12 patients(46%). The survival rates from the initial treatment were 39% at 5 years and 16% at 10 years(median survival time, 50 months), and those after treatment of brain metastases were 29% at one year and 18% at 2 years(median survival time, 6 months). Performance status tended to be associated with survival(p=0.10), and the presence of liver metastasis was the most important risk factor concerning survival(p=0.056). Two patients suffered severe chronic complications.One patient developed severe dementia after whole brain irradiation with a total dose of 45 Gy in 3 Gy daily fractionated dose, and another patient developed widespread brain necrosis after combined radiotherapy with intrathecal local infusion of methotrexate. Radiotherapeutic management is useful for breast cancer patients with brain metastasis, and long-term survival may also be possible even if patients have preexisting extracranial metastases, except for hepatic involvement. Radiation-related complications should therefore be avoided in these patients.

Journal Article↗

Malignant neuroendocrine tumor presenting a huge mediastinal mass controlled with radiation therapy.

A case of malignant neuroendocrine tumor presenting a huge mediastinal mass controlled with radiation therapy is reported. A thoracotomy was performed on a 57-year-old male and a mass was found to invade the trachea, main bronchus, and left atrium. The tumor was unresectable. Subsequently, cisplatin was administered, but the tumor grew in size and radiation therapy was recommended. The tumor responded well to thoracic irradiation (56 Gy) and disappeared. Three months later, lymph nodes metastases were noted in the retrocrural and upper abdominal paraaortic regions, but these were controlled again with palliative irradiation. Without further treatment, he survived free of disease for over 5 years. Specimens obtained during the thoracotomy showed that the tumor consisted mainly of small round cells with a rosette formation. Immunohistochemically the tumor was positive to NSE and slightly positive to keratin, but negative to LCA, L26, UCLH-1, EMA, Leu7, and chromogranin, suggesting a malignant tumor derived from neuroendocrine tissue.

Diagnosis, Differential↗

Cytotoxic effect of paclitaxel (taxol) either alone or in combination with irradiation in two rat yolk sac tumour cell lines with different radiosensitivities in vitro.

PURPOSE: To investigate the differences between two rat yolk sac tumour cell lines with different radiosensitivities in paclitaxel sensitivity and in the sensitizing effects of paclitaxel in combination with irradiation. MATERIALS AND METHODS: NMT-1 is a parent radiosensitive cell line and NMT-1R is a variant radioresistant cell line. RESULTS: Clonogenic assay demonstrated almost the same paclitaxel sensitivity with Do of 5.15 nM in NMT-1 and 5.02 nM in NMT-1R. Many apoptotic cells and DNA ladder formations were observed at 24 h after exposure to paclitaxel in both cell lines. The incidence of DNA fragmentation after 24 h exposure to 20 nM paclitaxel was 12.4 +/- 3.3% for NMT-1, and 13.0 +/- 1.9% for NMT-1R. Paclitaxel showed a supra-additive effect in combination with irradiation in both cell lines at 12 h after paclitaxel treatment only when the accumulation of cells in the G2/M phase reached its peak. CONCLUSIONS: Paclitaxel had the same cytotoxic effect in two cell lines with different radiosensitivity due to the induction of apoptosis. A supra-additive effect to radiation was observed with 12 h pretreatment in both cell lines. Paclitaxel may be effective for tumours with a component of different radiosensitivity in combination with irradiation.

Animals↗

Nasopharyngeal cancer with neck recurrence at 8 years and a lung metastasis at 15 years after the first definitive radiotherapy: a case report.

We report a patient with nasopharyngeal cancer with long-term follow-up of more than 16 years after the first course of radiotherapy in 1981. He developed a lung metastasis in 1996 after having a second course of radiotherapy for neck recurrence in 1989. The patient was a 42-year-old man with a nasopharyngeal tumor and a fixed upper neck metastasis (T1N1M0), which was treated with definitive radiotherapy. He manifested regional recurrence, at the margin of the radiation portal, with an 8 year disease-free interval, which was treated successfully by definitive re-irradiation. He developed a solitary lung metastasis, which was treated by video-assisted thoracoscopic lung resection, 7 years disease-free after the second course of radiotherapy. For 20 months after the removal of the lung metastasis he has been generally well without any signs of recurrence of sequelae. This case indicates the efficacy of definitive re-irradiation for regional recurrence and the necessity for long-term observation after radiation therapy for nasopharyngeal cancer.

Adult↗

Clinical features of esophageal cancer in the octogenarian treated by definitive radiotherapy: a multi-institutional retrospective survey.

BACKGROUND: As age-related infirmity often influences treatment options and outcome of esophageal cancer, the optimization of treatment for the elderly, especially in octogenarians, has been the subject of considerable debate. METHODS: We performed a retrospective, multi-institutional survey to assess the effect of age on the outcome of definitive radiotherapy for esophageal cancer by a questionnaire sent to eight institutions in Japan. RESULTS: There were 362 evaluable replies. The patients included 317 males and 45 females, with a median age of 72 years (range 35-93 years), and 96% had squamous cell carcinoma. There were 30 clinical stage 1, 71 stage IIA, 17 stage IIB, 113 stage III and 116 stage IV cases. The stage was not specified in 16 cases. Multiple co-morbidities existed in 40% of the patients who were 70 years of age or older. There was no statistically significant age-related difference in the incidence of adverse reactions to radiotherapy (P > 0.05). Overall survival was more significantly affected by Karnofsky Performance Status than by the patient's age. The influence of performance status on cumulative survival for stage I and II disease was more pronounced in patients in their 80s. CONCLUSION: The safety of radiotherapy for esophageal carcinoma is not influenced by the patient's age. Because the performance status strongly influenced survival, the multi-disciplinary assessment of functional status is mandatory for optimizing the choice of treatment for patients in their 80s with esophageal cancer.

Adult↗

Patterns of care study of radiation therapy for esophageal cancer in Japan: influence of the stratification of institution on the process.

BACKGROUND: To improve the quality of radiation therapy in Japan, Patterns of Care Study (PCS), a widely known QA program in the USA, was introduced in Japan. The feasibility was tested by collecting nationwide data by extramural audit for esophageal cancer. METHODS: From July 1996 through February 1997, PCS audits were performed for 29 institutions. Based on the facility survey by Tsunemoto, 13 institutes were classified as A1 (university hospital/cancer center treating > 300 patients/year), 10 as B1 (other institutes > 120 patients/year) and six as B2 (other institutes < 120 patients/year). Medical charts for 455 patients with thoracic esophageal cancer between 1992 and 1994 were reviewed based on the data format of PCS in the USA. RESULTS: Concerning external beam equipment, linear accelerators of > or = 10 MV were used for 73% of patients in A1, whereas in B1-2, 60Co machines were still used for 13% of patients (P < 0.0001). The median number of full-time equivalent (FTE) radiation oncologists was 2.7 in A1, 0.65 in B1 and 0.2 in B2. Forty-five percent of patients had received surgery in A1 and 34% in B1-2 (P = 0.0068). In the non-surgery group, a higher radiation dose of > 60 Gy was delivered in A1 than in B1-2 (P = 0.0008). Chemotherapy was administered to 51% of the patients in A1 and to 30% in B1-2 (P < 0.0001). Brachytherapy was utilized for 17% in A1 and only for 5% in B1-2 (P = 0.0001). CONCLUSION: Institutional stratification, including equipment and personnel, significantly affected the patterns of care for esophageal cancer. Therefore, to improve the quality of radiation therapy nationwide, improvement of equipment and supply of FTE personnel is extremely important. PCS was found to have great potential for the practical evaluation of how much will be required in Japan.

Adult↗

Placental metastasis from maternal primitive neuroectodermal tumor.

The occurrence of placental metastasis from maternal primitive neuroectodermal tumor (PNET) is extremely rare. A 33-year-old woman at 33 weeks' gestation was admitted to the hospital. She died of the disease on hospital day 28 because the unresectable tumor was located over a wide area of the retroperitoneum. A neonate was delivered by a caesarean section without evidence of disease and has survived to 1 year of age. Pathologically, the tumor consisted of monotonous small round cells with a high nuclear cytoplasmic ratio, including several pseudorosettes and Homer-Wright-type rosettes. On immunohistochemical examination, the tumor cells were positively stained for neuron-specific enolase. Microscopically, the placenta showed intervillous metastasis from the maternal PNET. This case may be the first one of placental metastasis from PNET ever reported in the literature.

Adult↗

Transrectal ultrasonography in evaluation of chronic rectal complications after radiation therapy for carcinoma of the uterine cervix.

RATIONALE AND OBJECTIVES: The authors studied the ability of transrectal ultrasonography (TRUS) to assess chronic rectal complications after radiation therapy for carcinoma of the uterine cervix. METHODS: One hundred twenty-five TRUSs were performed for 67 consecutive patients with carcinoma of the uterine cervix. Transrectal ultrasonography images of the rectal anterior wall and perirectal connective tissue adjacent to the uterine cervix were recorded with real-time scanner with 7.5 MHz transducer. The severity of TRUS abnormalities was graded on a scale developed by the authors. The relationships of the TRUS grade with the clinical grade of chronic rectal complications and with rectal radiation doses were analyzed retrospectively. RESULTS: Thickening of the perirectal connective tissue associated with obscuration of the submucosal echogenic layer in rectal anterior wall was observed between 6 months to 2 years after radiation therapy in all 19 patients who developed chronic rectal complications. The TRUS grade correlated with the clinical grade of chronic rectal complications, but did not correlate with rectal radiation doses. CONCLUSIONS: Transrectal ultrasonography can monitor the chronic rectal complications after radiation therapy for the patients with carcinoma of the uterine cervix.

Adult↗

Resistance of differentiating spermatogonia to radiation-induced apoptosis and loss in p53-deficient mice.

The effect of the p53 gene on the survival of mouse testicular cells was evaluated by analysis of degenerating and terminal transferase-mediated end labeling (TUNEL)-positive cells and the subsequent production of further differentiated progeny. In p53 null mice, in contrast to wild-type mice, radiation induced negligible levels of degenerating or TUNEL-positive differentiating spermatogonia within 24 h. This was correlated with higher production of differentiated progeny of the differentiating spermatogonia in p53 null mice. Contrary to the differentiating spermatogonia, the stem spermatogonia of p53 null mice produced fewer differentiated progeny after irradiation than did the stem cells of wild-type mice. We conclude that, because the degeneration and TUNEL positivity of the differentiating spermatogonia in mice of different genotypes were correlated with each other and were dependent on p53, this process is indeed apoptosis. In the differentiating spermatogonia, p53-dependent apoptosis accounted for the bulk of the loss of their progeny after irradiation. Furthermore, whereas the differentiating spermatogonia died by apoptosis that was dependent on p53, the stem spermatogonia, which are more radioresistant, did not.

Animals↗

A Case Report of Long-term Survival after Radiotherapy for a Solitary Brain Metastasis from Breast Cancer.

This is the report of a patient with a solitary brain metastasis from breast cancer who survived more than 8 years after the first brain metastasis. The brain metastasis was treated with partial removal followed by 30 Gy/15 fructions of whole brain irradiation plus 20 Gy/10 fructions of local boost irradiation for 5weeks. Brain metastases from breast cancer are usually a sign of rapid systemic tumor progression and long-term survivors are extremely rare. However, this case demonstrated the possibility of long-term survival in rare cases of brain metastases from breast cancer. This suggests a need for aggressive therapy in patients with a solitary brain metastasis.

Journal Article↗

Outcome of radiation therapy for patients with Kasabach-Merritt syndrome.

PURPOSE: The efficacy of radiation therapy for Kasabach-Merritt syndrome, which is characterized by a huge hemangioma with consumption coagulopathy, remains controversial. In this study, we retrospectively investigated the treatment outcome of radiation therapy for seven neonates with Kasabach-Merritt syndrome. METHODS AND MATERIALS: During the past 25 years we have seen seven children with Kasabach-Merritt syndrome who were treated with radiation therapy. Their ages ranged from 1 day to 5 months, with a median age of 1 month. The hemangioma was located in the extremities in four of seven children. Tumor sizes ranged from 70 cm to more than 150 cm in greatest diameter. Initial platelet counts were all less than 40,000/mm3 except for one patient. In principle, the total dose applied to the hemangioma was 8-10 Gy, with a daily dose of 1 Gy five times a week. RESULTS: Four of seven hemangiomas responded dramatically, with a concomitant rise of the platelet count to radiation therapy. Although the remaining three hemangiomas, all of which were ill circumscribed by widespread overlying shiny, dusky purple skin, became less tense during radiation therapy. Disseminated intravascular coagulopathy was not improved, but they have responded favorably to two or three courses of radiation therapy with an extended radiation field by 1.5 years of age. As a result, all seven patients are now surviving with no evidence of hemangioma or hematological abnormalities. Shortening of the extremity was observed in three patients who received multiple courses of radiation therapy. CONCLUSIONS: Radiation therapy appears to be one of the effective treatment options for Kasabach-Merritt syndrome despite the risk of growth delay and malignancy.

Disseminated Intravascular Coagulation↗