Koh-ichi Sakata

High-dose-rate versus low-dose-rate intracavitary therapy for carcinoma of the uterine cervix: a randomized trial.

This was a prospective randomized clinical trial undertaken at our institution to compare low‐dose‐rate (LDR) intracavitary radiation therapy versus high‐dose‐rate (HDR) intracavitary radiation therapy for the treatment of cervical carcinoma.

Prognostic factors of nasopharynx tumors investigated by MR imaging and the value of MR imaging in the newly published TNM staging

PURPOSE To examine the usefulness of MR imaging for predicting local control of nasopharyngeal carcinoma (NPC) and the value of MR imaging in the newly published fifth edition of the TNM classification. METHODS AND MATERIALS We studied 29 patients with NPC with MR imaging and CT before and after treatment. Staging was done according to the fourth and newly published fifth editions of the International Union Against Cancer (UICC) staging system. The radiotherapy protocol was designed to deliver 66 to 68 Gy to the primary tumor and clinically involved nodes. RESULTS MR proved better than CT at identifying obliteration of the pharyngobasilar fascia, invasion of the sinus of Morgagni, through which the cartilaginous portion of the eustachian tube and the levator veli palatini muscle pass, invasion of the skull base, and metastases to lymph nodes in the carotid and retropharyngeal spaces. All seven patients without invasion of the pharyngobasilar fascia had local control. The local control rates of patients with invasion of the skull base were not good (60 to 73%). There was no apparent relationship between tumor volume determined by T1-weighted MR images and local control when the tumor volume was more than 20 cc. The newly published N staging system appears to successfully identify the high-risk group for distant metastasis as N3. In our series, four of five patients with N3 disease developed distant metastases. CONCLUSION Deep infiltration of the tumor is a more important prognostic factor in NPC than tumor volume. Since the newly published T staging system requires a search for tumor invasion into soft tissue such as parapharyngeal space and bony structures, MR imaging may be indispensable for the newly published NPC staging system.

Treatment of Lethal Midline Granuloma Type Nasal T-Cell Lymphoma

Nasal T-cell lymphoma of the LMG type (LMG-NTL) is characterized by progressive, unrelenting ulceration, and necrosis of the nasal cavity and midline facial tissues. The clinical behavior of this tumor in 16 patients is compared with that of a nasal lymphoma of non-LMG-NTL type (non-LMG-NTL) in 8 patients and a paranasal sinus lymphoma (PSL) in 6 patients. All patients had stage I or II disease. Fourteen of the 16 patients with LMG-NTL received chemotherapy before and/or after radiotherapy. Cause-specific 5-year survival rates for patients with LMG-NTL, non-LMG-NTL, and PSL were 22%, 75%, and 67% respectively. Seven patients with LMG-NTL, had complete response, although 3 recurred, whereas it was incomplete in 9 patients. The data indicates that it is desirable to deliver 50 Gy or more to achieve in-field control of LMG-NTL.

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 (ΔΨm) and subsequent cell death. In Jurkat cells, TPA strongly activated ERK and inhibited the IR-induced caspase-8/Bid cleavage and the loss of ΔΨm. 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) βc 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 ΔΨm 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 ΔΨm loss. Our data enlighten an anti-apoptotic function of MEK/ERK pathway against IR-induced apoptosis, thereby implying its contribution to radioresistance.

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.

Renal Artery Aneurysm: Evaluation with Color Doppler Ultrasonography Before and After Percutaneous Transarterial Embolization

Renal artery aneurysms account for 22% of all visceral aneurysms.1 The prevalence of renal artery aneurysms in the general population is reported to vary between 0.01% and 1.0%2; however, this prevalence has recently increased because of the greater detection of these aneurysms made possible by advances in ultrasonography, CT, and MR imaging. The most serious complication of renal artery aneurysms is their rupture, which is followed by sudden death.3 The likelihood of rupture seems to increase as the diameter of the aneurysm exceeds 1 cm.2,3 Although surgical treatment had been common for these aneurysms (i.e., total renal resection), a percutaneous embolization technique has also recently been performed with success.4 This technique is less invasive than surgical resection for patients with renal artery aneurysms and sometimes preserves renal function. We report a case of a renal artery aneurysm 4 cm in diameter treated with percutaneous transcatheter embolization whose therapeutic effect was better evaluated by color Doppler ultrasonography than CT and MR imaging.

Radiotherapy of Vertebral Hemangiomas

Between 1975 and 1996, 14 patients (11 females, 3 males) with vertebral hemangioma received treatment with radiotherapy. Thirteen patients had a history of back pain or lumbago and 2 patients had neurological symptoms such as sensory impairment or paraplegia. The standard dose administered was 36 Gy in 18 fractions (five treatments per week). In the 13 patients with pain, this was completely or partially relieved. The condition of a man with hypesthesia of the legs deteriorated and a woman with paraplegia who was treated with decompressive laminectomy followed by radiotherapy recovered completely after irradiation. CT scan before irradiation showed thickened trabeculae as small punctate areas of sclerosis in all patients. At MR imaging before irradiation, T2-weighted MR images showed areas of high intensity in all patients and MR images demonstrated lesion enhancement. However, none of the patients who were treated successfully with radiation demonstrated any changes of the affected vertebra in the conventional radiographic films. CT scan or MR imaging, even 5 years after irradiation. Radiological imaging is indispensable for the diagnosis of vertebral hemangiomas but does not appear to be useful for evaluating the effects of radiotherapy.

HIGH-DOSE-RATE INTRACAVITARY BRACHYTHERAPY: RESULTS OF ANALYSES OF LATE RECTAL COMPLICATIONS

PURPOSE To examine the incidence of radiation-induced late rectal complications by analyzing the data of measured rectal doses in patients with cancer of the uterine cervix treated with high-dose-rate intracavitary brachytherapy. METHODS AND MATERIALS We measured doses to the rectum in 105 patients with cancer of the cervix during high-dose-rate intracavitary brachytherapy with a semiconductor dosimeter that can measure five points in the rectum simultaneously. On the basis of these measurements, equivalent doses, to which the biologically equivalent doses were converted as if given as fractionated irradiation at 2 Gy/fraction, were calculated as components of the cumulative dose at five rectal points in intracavitary brachytherapy combined with the external whole pelvic dose. RESULTS The calculated values of equivalent doses for late effects at the rectum ranged from 15 to 100 Gy (median 60 Gy for patients who did not develop complications and 76 Gy for patients who subsequently developed Grade II or III complications). When converted to a graph of absolute rectal complication probability, the data could be fitted to a sigmoid curve. The data showed a very definite dose-response relationship, with a threshold for complications at approximately 50 Gy and the curve starting to rise more steeply at approximately 60 Gy. The steepest part of the curve had a slope equivalent to approximately 4% incidence/1 Gy increase in equivalent doses. CONCLUSION The radiation tolerance dose, 5% and 50% complication probability, was about 64 and 79 Gy, respectively. Our data almost agree with the prescribed dose for the rectum for the radiation tolerance doses on the basis of the recorded human and animal data. The probability of rectal complications increased drastically after the maximal rectal dose was >60 Gy.

The effect of radiation on the expression of intercellular adhesion molecule-1 of human adenocarcinoma cells

PURPOSE To investigate the changes in antigenic expression of intercellular adhesion molecule-1 (ICAM-1) caused by ionizing radiation of cultured human adenocarcinoma cells. METHODS AND MATERIALS Human colonic BM314 and gastric MKN45 adenocarcinoma cells were irradiated to investigate the expression of ICAM-1 on the cell membrane and in the supernatant. In addition, the ICAM-1 gene expression (mRNA) was analyzed using a ICAM-1 cDNA as a probe. RESULTS The expression of ICAM-1 on the membrane was found to increase by irradiation. This effect was also observed in the supernatant. In addition, the irradiated cell population showed slight, but clear increases in ICAM-1 mRNA expression. CONCLUSIONS These results show that the enhancement of expression of ICAM-1 by radiation takes place at the ICAM-1 gene expression (mRNA) level. The results suggest that the low dose radiation may be useful for accumulating LFA-1 positive cytotoxic T lymphocytes (CTL) at the local tumor tissue, by which tumor cells may be attacked.

Gimeracil sensitizes cells to radiation via inhibition of homologous recombination

BACKGROUND AND PURPOSE 5-Chloro-2,4-dihydroxypyridine (Gimeracil) is a component of an oral fluoropyrimidine derivative S-1. Gimeracil is originally added to S-1 to yield prolonged 5-FU concentrations in tumor tissues by inhibiting dihydropyrimidine dehydrogenase, which degrades 5-FU. We found that Gimeracil by itself had the radiosensitizing effect. METHODS AND MATERIALS We used various cell lines deficient in non-homologous end-joining (NHEJ) or homologous recombination (HR) as well as DLD-1 and HeLa in clonogenic assay. gamma-H2AX focus formation and SCneo assay was performed to examine the effects of Gimeracil on DNA double strand break (DSB) repair mechanisms. RESULTS Results of gamma-H2AX focus assay indicated that Gimeracil inhibited DNA DSB repair. It did not sensitize cells deficient in HR but sensitized those deficient in NHEJ. In SCneo assay, Gimeracil reduced the frequency of neo-positive clones. Additionally, it sensitized the cells in S-phase more than in G0/G1. CONCLUSIONS Gimeracil inhibits HR. Because HR plays key roles in the repair of DSBH caused by radiotherapy, Gimeracil may enhance the efficacy of radiotherapy through the suppression of HR-mediated DNA repair pathways.