Biomedical subjects

Tsuneo Imai

Publications and source records attributed to Tsuneo Imai.

23 records · Page 2Linked to original sources

PubMed2002

Inhibition of NF-kappaB activity decreases the VEGF mRNA expression in MDA-MB-231 breast cancer cells.

VEGF (vascular endothelial growth factor) secreted from tumor cells including breast cancer serves as a potent angiogenic factor which favors tumor growth and metastasis. Indeed, a higher concentration of serum VEGF has been shown to associate with a poorer prognosis in patients with breast cancer. On the other hand, constitutive expression of a transcription factor, NF-kappaB was correlated with progression and metastasis in a number of human breast cancers, suggesting a possible regulation of VEGF expression by NF-kappaB. We thus investigated the relationship between the expression of VEGF and constitutive NF-kappaB activity in three breast cancer cell lines, MCF-7, T47D, and MDA-MB-231. The basal levels of VEGF mRNA expression correlated with those of nuclear NF-kappaB activity in these cell lines. The highest NF-KB activity in MDA-MB-231 cells was associated with the highest expression of VEGF mRNA, while the activity and the mRNA levels were moderate in MCF cells and the lowest in T47D cells. In MDA-MB-231 cells, inhibition of NF-KB by adenovirus-mediated expression of a dominant negative NF-kappaB or by a proteasome inhibitor, MG132, decreased the VEGF mRNA. These results suggest that NF-kappaB is involved in the upregulation of VEGF mRNA and inhibition of the activity could be a new approach for the treatment of breast cancer by preventing angiogenesis.

Breast Neoplasms↗

PubMed2001

Cases with fewer than four parathyroid glands in patients with renal hyperparathyroidism at initial parathyroidectomy.

In the surgical treatment of secondary hyperparathyroidism (2HPT) due to uremia, it is considered necessary to remove all parathyroid glands from the neck to prevent persistent and recurrent parathyroid hyperfunction. However, in some cases fewer than four parathyroid glands can be recognized at initial operation; in the present study, we evaluated the long-term prognosis and estimated surgical strategy in such cases. Between March 1981 and January 1999, 822 patients underwent total parathyroidectomy (PTx) with forearm autograft for advanced 2HPT at the Department of Transplant Surgery of Nagoya Second Red Cross Hospital. In 21 cases (2.6%) fewer than four parathyroid glands were macroscopically found at the initial operation. These cases were followed up and their parathyroid function was evaluated by measurement of intact parathyroid hormone (PTH). In 20 of the 21 cases three glands were found, in 1 patient only two glands. In 5 of these cases the fourth gland was identified first after postoperative histopathologic evaluation. In all these cases the intact PTH level was normalized. In 8 of the remaining 16 cases high PTH levels persisted after the initial operation, including 3 patients who underwent neck reexploration. However, in the other 7 patients PTH levels dropped within normal range immediately after PTx and a fourth gland has never been recognized. One patient was lost to follow-up. Thus, using our operative strategy, 12 of 822 cases (0.85%) did not develop persistent or recurrent HPT even though only three glands were identified at the operation. To avoid postoperative hypoparathyroidism, autotransplantation should be performed when fewer than four parathyroid glands are found at the initial operation.

Adult↗

PubMedDate not supplied

Paclitaxel administered weekly in patients with docetaxel-resistant metastatic breast cancer: a single-center study.

AIMS AND BACKGROUND: We evaluated retrospectively the efficacy and toxicity of paclitaxel in patients with docetaxel-resistant metastatic breast cancer. STUDY DESIGN: Paclitaxel (80 mg/m2) was administered weekly to 44 patients who had previously received chemotherapy regimens for metastatic breast cancer. All patients had progressive disease in spite of having received docetaxel therapy. RESULTS: Treatment was repeated until there was evidence of disease progression. Objective responses were obtained in 14 of 44 assessable patients (31.8%; 95% confidence interval, 17.5-46.1). Fourteen patients had partial responses; none responded completely. Seven of 14 responders had primary resistance to docetaxel therapy. The median duration of response was 6.1 months (range, 2.1-12.7). The median time to progression was 5.0 months. Clinically severe adverse events (grade 3 or 4) included neutropenia (27.2%), leukopenia (25.0%), neuropathy-sensory (13.6%), febrile neutropenia (6.8%), anemia (2.2%), constipation (2.2%), and edema (2.2%). Treatment was generally well tolerated and could be continued on an out-patient basis. CONCLUSIONS: Weekly paclitaxel is effective in patients with docetaxel-resistant metastatic breast cancer. This observation suggests partial cross-resistance between paclitaxel and docetaxel. There was no evidence for additive cumulative toxic effects of the two taxanes.

Adult↗

PubMedDate not supplied

Efficacy and safety of trastuzumab as a single agent in heavily pretreated patients with HER-2/neu-overexpressing metastatic breast cancer.

AIMS AND BACKGROUND: The human epidermal growth factor receptor 2 (HER2) protein is a unique and useful target for antibody therapy against breast cancers that overexpress the HER-2/neu gene. The recombinant humanized anti-HER2 monoclonal antibody, trastuzumab, was approved for clinical use in the United States in 1998. It became available in Japan in June 2001. This study focuses on the efficacy and safety of trastuzumab as a single agent in second-third line treatment of HER2/neu-overexpressing metastatic breast cancer. STUDY DESIGN: Between June 2001 and May 2002, we treated 62 patients with trastuzumab, as a single agent or in combination chemotherapy, for second-third line treatment of HER2-overexpressing metastatic breast cancer. Twenty-seven of 62 patients were treated with trastuzumab as a single agent. We reviewed retrospectively the efficacy and safety of the drug given as a single agent. The expression of HER2 was determined by immunohistochemical staining. All patients received a standard loading dose of 4 mg/kg followed by 2 mg/kg weekly. RESULTS: Patients received a median of 16.7 weekly infusions (range, 1-66 infusions). Trastuzumab therapy was generally well tolerated. Clinically severe adverse events (grade 3 or 4) included hypotension (7.4%), and hypoxia (3.7%). Grade 1 to 2 toxicity included fever (11.1%) and diarrhea (3.7%). Infusion-related reactions were infrequent, as were serious hematologic complications. Cardiotoxicity did not occur in the study. Three patients had a complete and 3 a partial response, 3 had no change, 17 had progressive disease, and one was not evaluated. The overall response rate in the 26 patients with available data was 23.1% (95% confidence interval, 5.7-40.4). The median duration of response was 6.4 months (range, 2.5-14.0). The median time to progression was 3.1 months (range, 0.2-16.7). Response rates differed by metastatic site as follows: lung 0% (0/12), bone 10.0% (1/10), liver 0% (0/8), skin 50.0% (4/8), lymph nodes 42.9% (3/7), brain 0% (0/2). CONCLUSIONS: Molecular target therapy with trastuzumab appears safe and is generally well tolerated. For treatment of metastatic breast cancer, single agent therapy produces a durable response in some patients but lacks sufficient efficacy. Single agent use of trastuzumab is a viable option for treatment in cases with non-life-threatening disease without visceral metastasis.

Adult↗

PubMedDate not supplied

Multi-slice CT of thyroid nodules: comparison with ultrasonography.

PURPOSE: To evaluate the usefulness of multi-slice computed tomography (MSCT) in comparison with ultrasonography (US) for the differentiation of benign from malignant thyroid nodules and the evaluation of tumor extension. MATERIALS AND METHODS: Thirty patients with thyroid nodules (14 malignant, 16 benign) who underwent both MSCT and US participated in the present study. MSCT with contrast enhancement was performed, and 3D shaded volume rendering (SVR) and multiplanar reconstruction (MPR) were employed to differentiate benign from malignant nodules and to evaluate tumor extension. US images were obtained using a 7.5 MHz annular array probe. A three-point rating scale was used for image interpretation, and the kappa statistic was employed to evaluate agreement between MSCT and US. RESULTS: Sensitivity in differentiating benign from malignant nodules was found to be 85.7% for US and 78.6% for MSCT. Disagreement between MSCT and US occurred in assessing the homogeneity of the solid component and the presence of fibrous capsule. In two of seven T4 cases, MPR provided a more accurate diagnosis than US examination in detecting extracapsular invasion. CONCLUSION: For differential diagnosis of thyroid nodules, US was found to be better than MSCT. However, MSCT could be useful for the evaluation of advanced cases with suspicion of extracapsular extension.

Diagnosis, Differential↗