Biomedical subjects

Kaori Seki

Publications and source records attributed to Kaori Seki.

8 recordsLinked to original sources

PubMed2006

Enhancement of radiosensitivity by dual inhibition of the HER family with ZD1839 ("Iressa") and trastuzumab ("Herceptin").

PURPOSE: The aims of this study were twofold: (1) to examine the effects of dual inhibition of 2 members of the HER family, the epidermoid growth factor receptor (EGFR) and HER2/neu, by gefitinib (ZD1839) and trastuzumab on radiosensitivity; and (2) to explore the molecular mechanism of radiosensitization especially focusing on the survival signal transduction pathways by using A431 human vulvar squamous carcinoma cells expressing EGFR and HER2/neu. METHODS AND MATERIALS: The effects of inhibitors on the radiation-induced activation of EGFR and/or HER2/neu, and the intracellular proteins that are involved in their downstream signaling, were quantified by the Western blot. Radiosensitizing effects by the blockage of EGFR and/or HER2/neu were determined by a clonogenic assay. RESULTS: Radiation-induced activation of the EGFR and HER2/neu was inhibited with ZD1839 and/or trastuzumab. ZD1839 also inhibited the radiation-induced phosphorylation of HER2/neu. Radiation in combination with the HER family inhibitors inhibited the activation of Akt and MEK1/2, the downstream survival signaling of the HER family. ZD1839 enhanced radiosensitivity with a dose-modifying factor (DMF) (SF3) of 1.45 and trastuzumab did so with a DMF (SF3) of 1.11. Simultaneous blockade of EGFR and HER2/neu induced a synergistic radiosensitizing effect with a DMF (SF3) of 2.29. CONCLUSIONS: The present data suggest that a dual EGFR and HER2/neu targeting may have potential for radiosensitization in tumors in which both of these pathways are active.

Antibodies, Monoclonal↗

PubMed2006

[Intensity Modulated Radiation Therapy (IMRT)].

Radiotherapy plays an important role in the management of cancer patients, and half of the patients with malignant tumors are treated with radiotherapy in the United States. In Japan, the necessity of radiation therapy has come to be widely acknowledged in cancer treatment, and more and more cancer patients are being treated with radiation. External beam radiation is the most-used radiotherapy at the present time. The advantage is that this treatment modality can be used in a short time, although the problem is that not only the cancer lesion but also the surrounding normal tissue is irradiated,causing an adverse effect on normal tissue. In order to solve this problem,treatments such as 3D-Conformal Radiation Therapy (3D-CRT), Intensity Modulated Radiation Therapy (IMRT), Stereotactic Radiation Surgery (SRS) and Stereotactic Radiation Therapy (SRT) are clinically used as an extremely precise radiotherapy, thanks to the advances in computer technology in recent years. Therefore, the purpose of these extremely precise radiation therapies is to administer a high dose to the tumor intensively, and to suppress quantities of magnetism to normal tissues. IMRT treatment results for prostate cancer patients and head and neck cancer patients are reportedly better than with other irradiation methods. In this chapter,we explain the external irradiation method with the focus on IMRT and the extremely precise radiotherapy preformed in the Tokyo Women's Medical University Hospital.

Head and Neck Neoplasms↗

PubMed2005

Assessment of psychological responses in patients about to receive radiotherapy.

PURPOSE: Radiotherapy is considered to be associated with psychological distress. We assessed the mental status, anxiety, and the factors associated with these in cancer patients about to receive radiotherapy. MATERIALS AND METHODS: Hospitalized patients about to receive radiotherapy participated. Psychological status was assessed by a psychiatrist, based on interview about the type of anxiety related to cancer or radiotherapy as well as self-rating questionnaires. RESULTS: Eligible data were collected from 94 patients. The incidence of mental disorders was 20%. The total mood disturbance scores were significantly higher in patients with poor performance status. The most common type of anxiety regarding radiotherapy was acute adverse effect, and the predictors were palliative treatment and living alone. CONCLUSION: Mental disorders, mood disturbance, and anxiety in patients cannot be neglected in radiation oncology practice. Especially careful attention should be paid to patients with these predictive factors.

Anxiety Disorders↗

PubMed2004

Primary central nervous system lymphoma in Japan 1995-1999: changes from the preceding 10 years.

PURPOSE: Previously, we conducted a nationwide survey of primary central nervous system lymphoma (PCNSL) treated between 1985 and 1994 in Japan. In the present study, we conducted further investigations of PCNSL patients treated between 1995 and 1999 to clarify possible changes with time in the clinical features, treatment, and outcome of this disease. METHODS: Thirteen Japanese institutions were surveyed, and data on 101 patients with histologically-confirmed PCNSL were collected. These data were compared with those of 167 patients treated at the same institutions between 1985 and 1994. RESULTS: Regarding patient and tumor characteristics, the proportion of patients with good performance status (PS) was significantly higher in the group treated during 1995-1999 than in that treated during 1985-1994, but other characteristics were not significantly different. Regarding treatment, more patients in the more recent period (66%) received systemic chemotherapy than those in the preceding period (53%, P = 0.049). For all patients, including those who did not complete radiotherapy, the median survival time was 17 months and 30 months in patients treated between 1985 and 1994 and those treated between 1995 and 1999, respectively, and the 5-year survival rate was 15% versus 31% (P = 0.0003). In both patient groups, higher age and tumor multiplicity were associated with poor prognosis in multivariate analysis. In patients treated between 1995 and 1999, those who received systemic chemotherapy showed significantly better prognosis than those who did not (P = 0.0049), but the difference was not significant in multivariate analysis (P = 0.23). CONCLUSIONS: The high survival rates observed in the present survey are comparable with those of recent prospective studies employing intensive chemoradiotherapy. The improvement in prognosis appeared to result, at least in part, from the increase in the proportion of patients with better PS. Since the clinical feature and treatment outcome of patients with PCNSL can thus change with the era, historical control data should not be used in comparing different treatment modalities.

Adolescent↗

PubMed2004

A patient with classic severe primary hyperparathyroidism in whom both Tc-99m MIBI scintigraphy and FDG-PET failed to detect the parathyroid tumor.

A 24-year-old woman was admitted to our department for further examination of hypercalcemia, a high level of intact parathyroid hormone (PTH) and a right parathyroid tumor. She complained of bone pain throughout her body and was unable to walk due to systemic cystic osteofibrosis, including a brown tumor of the left lower extremities. Neck ultrasonography (US) and magnetic resonance imaging (MRI) revealed a tumor 2 cm in diameter in the upper side of the right thyroid lobe. 99mTc sestamibi (99mTc-MIBI) imaging and F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) were performed to diagnose primary hyperparathyroidism and examination of other parathyroid glands. However, neither imaging modality detected the parathyroid tumor. To confirm the diagnosis, we performed selective venous sampling around the parathyroid and the patient was diagnosed with primary hyperparathyroidism due to a right parathyroid tumor. Resection of the right parathyroid tumor was performed and the pathological diagnosis was parathyroid adenoma. To date, both 99mTc-MIBI and FDG-PET are useful to localize parathyroid tumors. In this case, however, neither modality detected the tumor. Although recent studies state that expression of P-glycoprotein (P-gp) in parathyroid tumors plays an important role in the false-negative results of both 99mTc-MIBI scans and FDG-PET, immunohistological study detected no P-gp expression in the parathyroid tumor in the current case.

Adenoma↗

PubMed2003

Radiotherapy with concurrent docetaxel for advanced and recurrent breast cancer.

BACKGROUND: Docetaxel has shown remarkable radiosensitizing properties in vitro. In this study we investigated whether the addition of docetaxel to radiotherapy enhanced tumor response in patients with advanced or recurrent breast cancer. METHODS: A total of 35 patients were enrolled in this study. Docetaxel was administered concurrently during radiotherapy. Radiation doses were 54 to 69 Gy (median 60 Gy). In those enrolled through January 2000, docetaxel 40 mg/m2 was administered biweekly (once every two weeks), with subsequent dose adjustments based on tolerance and bone marrow and liver function. Beginning in February 2000, a weekly docetaxel schedule was used instead. This new regimen was based on data suggesting reduced myelosuppression with this regimen. The weekly dose rate was 20 mg/m2, with dose reductions for impaired organ function. RESULTS: All patients were evaluated for toxicity and response and a total of 40 irradiated sites were evaluated for local response. The overall response rate of irradiated sites was 95% and the CR rate was 68%. CR and PR were achieved in 40%, 37% of patients, respectively. Acute toxicities were tolerated by most patients: 17% had Grade 3-4 neutropenia, 6% had Grade 3-4 radiation dermatitis, and 3% had Grade 3-4 pneumonitis. CONCLUSION: The combination of docetaxel with radiotherapy is an active and safe regimen in patients with inoperable advanced or recurrent breast cancer. We determined the recommended dose of docetaxel with concomitant radiotherapy to be 20 mg/m2 weekly for a Phase II study. Further study is necessary to assess the impact of this treatment on long-term outcome.

Adult↗

PubMed2002

[A case of recurrent breast cancer with chronic renal failure treated on an outpatient basis].

We report a case of recurrent breast cancer with chronic renal failure in a 58-year-old female. She could be treated on an outpatient basis under good general condition for most of her remaining life by chemoradiotherapy in combination with hemodialysis. Modification of the chemoradiotherapy procedures and collaboration of medical staff including the doctor in charge of home medical care and her family was indispensable in keeping her hospital stay as short as possible.

Ambulatory Care↗

PubMedDate not supplied

Induction chemotherapy followed by hyperfractionated radiotherapy with concurrent chemotherapy for locally advanced head and neck cancer.

BACKGROUND: The aim of this study was to improve tumor control, the survival rate and organ preservation for locally advanced head and neck cancer by using induction chemotherapy followed by hyperfractionated radiotherapy and concurrent chemotherapy. MATERIALS AND METHODS: Thirty-five patients with stage III-IVB head and neck cancer were treated with this protocol. Induction chemotherapy consisted of cisplatin and fluorouracil and concurrent chemotherapy consisted of carboplatin and doxifluridin. Radiotherapy was administered twice a day until a dose of 72 Gy was reached. RESULTS: Twenty-two (63%) and 13 patients (37%) achieved complete responses and partial responses, respectively. In terms of non-hematological toxicities, grade 3 mucositis was observed in 49% of the patients. The overall 5-year survival was 53.5% and the progression-free survival was 40.6%. CONCLUSION: Response to induction chemotherapy was useful as a predictive factor for ultimate outcome and organ conservation. More intensive regimen or other combination chemotherapy is needed to improve treatment outcome with hyperfractionated radiotherapy.

Adult↗