Human T-cell leukemia virus type 1 (HTLV-1) and HTLV-2 are retroviruses with similar biological properties. Whereas HTLV-1 is the causative agent of an aggressive T-cell leukemia, HTLV-2 has been associated with only a few cases of lymphoproliferative disorders. Tax1 and Tax2 are the transcriptional activators of HTLV-1 and HTLV-2, respectively. Here we show that Tax2 transformed a Rat-1 fibroblast cell line to form colonies in soft agar, but the size and number of the colonies were lower than those of Tax1. Use of a chimeric Tax protein showed that the C-terminal amino acids 300 to 353 were responsible for the high transforming activity of Tax1. Activation of cellular genes by Tax1 through transcription factor NF-B is reportedly essential for the transformation of Rat-1 cells. Tax2 also activated the transcription through NF-B in Rat-1 cells, and such activity was equivalent to that induced by Tax1. Thus, the high transforming activity of Tax1 is mediated by mechanisms other than NF-B activation. Our results showed that Tax2 has a lower transforming activity than Tax1 and suggest that the high transforming activity of Tax1 is involved in the leukemogenic property of HTLV-1.
Medroxyprogesterone acetate (MAP) in the treatment of advanced breast cancer has been regarded as a minor agent according to the previous reports when used at low doses (less than 500 mg/day). High doses of more than 500 mg which have come into use since 1973 give a response rate of over 40%, but sometimes cause gluteal abscess or induration because of daily intramuscular injections. In order to administer easily and to avoid the side effect, we have attempted to use oral administration in a daily dose of 1200 mg (400 mg X 3). Of those 20 patients treated with oral high-dose MAP, 1 showed complete response, 6 showed partial response, 7 no change, and 6 progressive disease. As for site of lesion, 4 out of 6 (67%) in skin and 4 out of 16 (25%) in bone responded. Neither severe side effects nor abnormal laboratory data were seen. Then, we examined the blood levels of MAP in vivo by RIA in 9 patients. The blood level of MAP reached 39-250 ng/ml in 3 days and was maintained at least over 50 ng/ml for 1 or 2 months of continuous administration. Subsequently, we examined the effects of MAP on binding to ER in vitro. The inhibition of binding of estradiol-17 beta to ER was about 60% at 10(-5) M MAP. The blood level of 50 ng/ml in vivo corresponds to about 1.3 X 10(-5) M.
Elevated preoperative serum-soluble IL-2R concentrations in patients with operable NSCLC reflect the occurrence of intrapulmonary metastasis. Preoperative examination of serum-soluble IL-2R concentrations may be valuable in the detection of the intrapulmonary metastasis preoperatively.
A rare case of bilateral pneumothorax in a 54-year-old woman with advanced breast cancer associated with lung and pleural metastases is presented. The patient was admitted to our hospital complaining of unexpected severe dyspnea. A chest X-ray showed bilateral pneumothorax associated with multiple lung metastases and pleural effusions, followed by immediate pleural drainage. Although air leak and effusions of the right lung were well controlled by the conservative management, massive air leaks of the left lung had continued for 40 days. Because of patient's poor general status a surgical closure of the leaking site was selected using video-assisted thoracoscopic surgery techniques. Thoracoscopy revealed a ruptured bulla in the lower lobe ($6), thus, followed by a successful bullectomy with a stapling device. We speculate that multiple pleural metastasis may disturb the normal repair mechanism of the lung tissue and cause prolonged persistent air leaks.
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