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Biomedical subjects

S Sakai

Publications and source records attributed to S Sakai.

At least 307 records · Page 17Linked to original sources

Cause of failure of lactation in mouse mammary tumor virus/human transforming growth factor alpha transgenic mice.

Transgenic female mice bearing human transforming growth factor-alpha (TGF alpha) cDNA under the control of the mouse mammary tumor virus enhancer/promoter became pregnant but failed lactation. TGF alpha mRNA was detected in the mammary glands of these mice by the reverse transcriptase-polymerase chain reaction. By the use of collagenase-dissociated mammary epithelial cells, the binding of prolactin to its receptor was determined before and after parturition. At the end of pregnancy, the binding in TGF alpha transgenic (TGF alpha [+]) mice was small and its amount was comparable to that in the TGF alpha negative (TGF alpha [-]) mice. On the day of parturition, prolactin binding in TGF alpha (+) mice increased approximately 1.9-fold (insignificant), while that in TGF alpha (-) mice elevated over 5.3-fold (P < 0.01). The binding sites per cell were also higher in TGF alpha (-)mice. Radioimmunoassay of prolactin suggested that in TGF alpha (+) mice the low level of prolactin binding after parturition was not due to masking effect of serum prolactin. Among six TGF alpha (+) mice assayed, one mother with the highest prolactin binding activity (3.7-fold increase) initiated lactation, but the others did not. As there was little difference between groups in the growth and synthesis in the mammary glands, it was concluded that the failure of lactation in TGF alpha (+) mice is principally due to the lack of elevation of mammary prolactin receptor after parturition. At present, the role of TGF alpha in this process is obscure; however, TGF alpha was revealed not to interfere with the binding of prolactin to the receptor.

Animals↗

[A correlation between metastasis and histopathological differentiation in patients with carcinoma of the nasal cavity and paranasal sinuses].

The aim of this retrospective study was to investigate a correlation between histopathological differentiation and metastasis in patients with carcinoma of the nasal cavity and paranasal sinuses to improve the survival. Between 1984 and 1992, 52 cases of sino-nasal malignant tumors were treated at Kagawa Medical School Hospital. Squamous cell carcinoma was evaluated in 29 patients and undifferentiated carcinoma in five patients. Treatment in most cases consisted of radiotherapy, 50 Gy/25 fr/5 weeks, continuous intra-arterial infusion of 5-FU 2000 mg/4 weeks, and an extensive Denker's operation 2-3 weeks after the completion of radiotherapy. The 5-year survival rate was 53%, and the local control rate was 82%. Patients died of local failure (six), distant metastases (six), lymph node metastases (one) and other causes (three). Twenty-eight patients with local control were classified into G1-2 (well- and moderately-differentiated) and G3-4 (poorly-differentiated and undifferentiated) groups. Lymph node metastasis was unrelated to the degree of differentiation, but distant metastasis was significantly correlated to the degree of differentiation (P = 0.014). The 5-year survival rates in lymph node metastasis (n = 7), non-lymph node metastasis (n = 21), distant metastasis (n = 7), non-distant metastasis (n = 21), and the G1-2 (n = 17) group and the G3-4 group (n = 11) with local control were 57%, 63%, 14%, 78% (P = 0.002), 72% and 44% (P = 0.0384), respectively. The results of combination therapy were poor in patients with poorly-differentiated or undifferentiated carcinoma because of distant metastasis, and adjuvant chemotherapy may be necessary in such patients to prevent distant metastasis.

Aged↗

[Evaluation of the method of treating non-Hodgkin's lymphoma].

Forty-two patients with non-Hodgkin's lymphoma were treated between October 1983 and December 1992 in the department of Otolaryngology, Kagawa Medical School Hospital. The twenty-six of these patients whose tumor originated in Waldeyer's ring and who were diagnosed as Stage I or II have been reviewed. In principle, method of treatment was a combination of chemotherapy and radiotherapy. Between 1983 to 1987, COP was primarily used (9 cases) as combination chemotherapy, and after 1988 CHOP was used (17 cases). VAMA was used to treat the poor response and recurring cases. The five-year estimated overall survival rates calculated by the Kaplan-Meier method were 33.3% and 94.1% in the COP and CHOP groups, respectively. We investigated age, stage, cell type and grade, as factors related to recovery, but except for cell type, there were no significant differences in overall survival. The most serious side effect was decreased leucocyte count, but we prescribed G-CSF and were able to continue treatment.

Adult↗

[Immunohistological study of dendritic cells and macrophages in sino-nasal lesions--distributions in metaplastic squamous epithelium and squamous cell carcinoma].

Dendritic cells, macrophages and lymphocytes infiltrating the epithelia of sino-nasal lesions were investigated immunohistochemically using antibody S-100 protein for dendritic cells, Ki-M1P for macrophages, MT1 for T-cells and L26 for B-cells, respectively. Seventy-five specimens of sino-nasal mucosae involving 51 cases of metaplastic squamous epithelium (MSE), 12 of inverted papilloma, 1 of atypical hyperplasia and 11 of squamous cell carcinoma (SCC) were studied. Dendritic cells were observed in 12 cases of MSE (23.5%), in 4 of inverted papilloma (33.3%), and in 6 of SCC (54.5%). More dendritic cells were found infiltrating MSE of the infective and fibrotic types than of the mild and edematous types, histopathologically. Furthermore, infiltration correlated with the degree of squamous differentiation in MSE, but not in SCC. The number of macrophages was significantly smaller in MSE than in columnar ciliated epithelium, while that in SCC was significantly greater than that in MSE. With dendritic cell infiltration macrophages in MSE as well as SCC and T-cells in and around the carcinoma were often increased. These findings suggest that dendritic cells may be attracted to maturative squamous epithelium, and may play an important role in the immunologic defence mechanisms of MSE. Dendritic cells, in contrast, may play a role in the cellular immune response of T-cells against the carcinoma.

Adolescent↗

Effect of newly synthesized indole derivatives on multidrug resistance in human cancer cells.

Twenty indole derivatives were investigated for their ability to reverse multidrug resistance (MDR), for their ability to compete with [3H]azidopine in binding to P-glycoprotein (P-gp) and for their hydrophobicity. Six derivatives almost completely reversed the resistance to vincristine (VCR) in multidrug-resistant KB-C2 cells, and other derivatives partially overcame the resistance. The ability of the derivatives to enhance vincristine cytotoxicity did not significantly correlate with the inhibition of [3H]azidopine binding to P-gp or with their hydrophobicity. However, all the derivatives that inhibited > 50% of the photolabeling completely reversed VCR resistance. The 2-pyridyl group with a basic nitrogen atom attached at position 3 of indole in an appropriate spatial orientation seems to be an important feature for the interaction of the indole derivatives with P-gp. One of the derivatives, 1, which has low cytotoxicity and hydrophobicity, completely reversed the resistance of KB-C2 cells to Adriamycin, actinomycin D and VCR. Our data indicate that MDR-reversing indole derivatives with low cytotoxicity and hydrophobicity exist. These characteristics will surely be profitable for clinical use.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[A case of fistula-cancer response to arterial chemoembolization].

Arterial chemoembolization was performed three times preoperatively for cancer associated with fistula-in-ano for diminishing the postoperative surgical tissue defect of the perineum. Partial response of the tumor to this treatment was confirmed by computed tomography. A sixty-two-year-old male patient recognized a mass in the perineum one and a half years ago. He had suffered from fistula-in-ano for thirty years. The mass increased its size and formed a tumor in the bilateral buttocks (12 x 9 cm and 9 x 9 cm in diameter). Biopsy specimen showed a moderately differentiated adenocarcinoma. Angiography showed a hypervascular tumor stain. The main feeders to the tumor were the superior rectal artery and bilateral internal iliac artery. Arterial chemoembolization was performed three times through the right and left internal iliac artery with Gelfoam particle. Arterial infusion chemotherapy was added through inferior mesenteric artery and bilateral internal iliac artery with a total 120 mg of adriamycin and 1,500 mg of 5-FU simultaneously. The tumor decreased in size to 44% of the preoperative size by the treatment. A radical operation was performed following the preoperative treatment. Preoperative arterial chemoembolization for cancer associated fistula-in-ano was considered to be helpful for local control.

Adenocarcinoma↗

A case report of recurrent cervical cancer which responded to a combination of biological therapies.

Adoptive immunotherapy with tumor-infiltrating lymphocytes (TIL) has been challenged to human cancer patients during these years. However, as the efficacy of the therapy alone is still limited, another approach, a combination with other therapies may be required to obtain more favorable antitumor effects. Tumor necrosis factor alpha (TNF) is worth considering for combination, because at least its various potential roles in immune response suggest that it might increase the killing activity of T cells against autologous tumor cells. We attempted to treat the cancer patients with TIL combined with TNF therapy. A patient with recurrent cervical cancer was treated with multiple biological therapies including TIL and TNF therapy, and irradiation. Biological therapies consisted of endogenous and exogenous TNF (EET) therapy, TIL, administration of rTNF-SAM2 combined with hyperthermia and several biological response modifiers such as schizophyllan and lentinan. After 50 days of therapy, the recurrent tumor had remarkably decreased in size, and cystic change of the tumor was observed by CT scanning. By further continuation of these therapies, the disease condition was much improved. As these antitumor effects cannot well be explained by irradiation therapy alone, multiple biological therapies are considered to be potentially effective against the highly malignant advanced tumors.

Adult↗

[Post-pregnancy osteoporosis].

The onset of idiopathic osteoporosis after delivery is called "Post-Pregnancy Osteoporosis", which was suggested for the syndrome by Nordin in 1955. Back pain and vertebral collapse are the most frequent feature. This disease usually occurs in the first pregnancy and dose not recur, but the mechanisms remains to be elucidated. It is suggested that in patients with post-pregnancy osteoporosis there may have been a transient failure of the usual changes in calciotropic hormones such as 1,25-(OH)2D, calcitonin and parathyroid hormone (PTH) to prepare the maternal skeleton due to the stress of childbirth. The clinical course of these patients accords well with previous reports.

25-Hydroxyvitamin D 2↗

[Improvement of clinical symptoms by UFT and TAM and a case of bone metastasis from breast carcinoma during pregnancy].

At age 35, the patient was diagnosed with left breast carcinoma (T4bN0M0, Stage IIIb) during her first pregnancy, and underwent mastectomy of the left breast and bilateral oophorectomy. Although CPA was administered as adjuvant chemotherapy after the operation, left pelvic pain developed about a year after the operation, and bone metastasis was detected from the imaging diagnosis. Then, the therapy was switched to UFT (600 mg/day) and tamoxifen (20 mg/day), which markedly relieved the pain along with bone scintiscan (NC) and simple X-P (NC). Five years have passed since the operation, and the progress is excellent. There is neither increase of pain nor adverse reactions to drugs. Furthermore, the patient received breast reconstruction operation at her strong insistence in the third year after operation, and has achieved a high quality of life (QOL).

Adult↗

[Breast reconstruction after mastectomy].

A variety of procedures can be used in breast reconstruction following mastectomy depending on the condition of the residual tissue. A silicone implant or tissue expander is used when the skin and subcutaneous fatty tissue are preserved, although silicone implants are no longer used in the United States. Alternatively, a lateral abdominal flap, lateral thoracic flap, latissimus dorsi flap, or rectus abdominus myocutaneous flap may be used. We have performed breast reconstruction using the latissimus dorsi myocutaneous flap without a silicone implant, and the vertical axis of the rectus abdominus myocutaneous flap was also used. Nipple-areola reconstruction was also investigated.

Abdominal Muscles↗

[A comparative clinical study on the treatment of head and neck tumors by adjuvant chemotherapy with HCFU--Second Study by Kinki Head and Neck Tumor Study Group].

In the first study by the "Kinki Head and Neck Tumor Study Group," we performed a comparative study to investigate intergroup difference between a control group consisting of patients given radical treatment only, and a HCFU group consisting of patients receiving long-term administration of HCFU after radical treatment. We earlier reported that subsequent observations by stratification revealed a favorable tendency in the cumulative disease-free rate in Stage II and Stage III patients in the HCFU group. In the second study, the same methods of treatment as in the first study were compared in a prospective control study. No differences were found between the two groups in Stage II patients. In Stage III patients, however, the disease-free rate tended to increase significantly in the HCFU group as in the first study.

Adult↗

Possible involvement of endothelin-1 in cardiac hypertrophy.

In an attempt to ascertain a possible involvement of endothelin-1 (ET-1) in the development of cardiac hypertrophy induced by hemodynamic overloads in vivo, the expression of prepro ET-1 mRNA in the cardiac tissue and the plasma level of ET-1 were determined in rats undergoing various treatments for inducing cardiac hypertrophy. One week after aortic banding (AB), the rat exhibited left ventricular hypertrophy characterized by ventricular wall thickening, i.e. concentric hypertrophy. In contrast, the aortic regurgitation (AR) produced left ventricular enlargement without wall thickening 1 week after the operation, i.e. eccentric hypertrophy. Monocrotaline treatment (s.c.) also caused marked hypertrophy in the right ventricle (concentric hypertrophy) 3 weeks later, which was accompanied by a severe pulmonary hypertension (MCT-PH). A Northern blot analysis revealed that AB and MCT-PH markedly increased the expression of prepro ET-1 mRNA in the left and right ventricles, respectively. The rats with MCT-PH but not with AB displayed a significant higher level in their plasma ET-1 levels compared with control animals. In contrast, the rats undergoing AR surgery exhibited no significant elevation in either prepro ET-1 mRNA in the heart or the plasma ET-1 concentration. The results of the present study suggest that ET-1 is involved at least in part in the development of concentric but probably not eccentric cardiac hypertrophy induced by hemodynamic overloads.

Animals↗

Increased production of endothelin-1 in the hypertrophied rat heart due to pressure overload.

Endothelin-1 (ET-1) has been demonstrated to induce hypertrophy in cultured cardiac myocytes. We investigated the production of ET-1 in the heart of aorta-banded rats in vivo. Seven days after the banding of the abdominal aorta, rats developed a significant left ventricular hypertrophy. The tissue content of mature ET-1 and the level of expression of prepro ET-1 mRNA were higher in the left ventricle of aorta-banded rats than in those of sham-operated rats. The expression of prepro ET-1 mRNA in the right ventricle was not different between the two groups. These findings indicate that the production of ET-1 increased in the hypertrophied left ventricle, thereby suggesting the possible involvement of endogenous ET-1 in the development of cardiac hypertrophy due to pressure overload.

Animals↗