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61.
Keiji Inoue Takashi Karashima Satoshi Fukata Asuka Nomura Chiaki Kawada Atsushi Kurabayashi Mutsuo Furihata Yuji Ohtsuki Taro Shuin 《Clinical cancer research》2005,11(18):6669-6677
PURPOSE: Transitional cell carcinoma (TCC) of the urinary tract is a chemosensitive tumor. Most deaths from TCC of the urinary tract are caused by metastasis, which is resistant to conventional chemotherapy. Frequent sites of metastases from TCC of the urinary tract are regional lymph nodes, liver, lung, and bone. Of these distant metastases, bone metastasis is consistently resistant to cisplatin-based conventional chemotherapy. Therefore, in this study, we investigated whether or not a newly developed minodronate, YM529, could prevent osteolytic bone metastasis of human TCC and also enhance the effect of docetaxel in a bone tumor model of athymic nude mice. EXPERIMENTAL DESIGN: In the present study, we evaluated the effect of in vitro treatment with minodronate and/or docetaxel on the proliferation by cell count, the induction of apoptosis by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay, and the biological activity of osteoclast by pit formation assay in human bladder cancer cell line, UMUC-14, and mouse osteoclast cells. In vivo, we examined the effect of minodronate in a bone tumor model of athymic nude mice, in which the percutaneous intraosseal injection in the tibia of UMUC-14, leads to osteolytic bone tumor, as a bone metastasis model. To examine whether or not minodronate could inhibit tumorigenicity and enhance the effect of the chemotherapeutic agent, docetaxel, we gave minodronate i.p. and/or docetaxel i.p. to nude mice 3 days after an intraosseal tumor implantation. Moreover, proliferation and the induction of apoptosis of cancer cells and osteoclasts in bone tumors were determined by immunohistochemistry and the TUNEL assay. RESULTS: In vitro: In vitro treatment with docetaxel inhibited proliferation and resorption pit-forming activity and induced apoptosis of mouse osteoclast cells and UMUC-14 cells. In vitro treatment with minodronate inhibited proliferation and activity and induced apoptosis of mouse osteoclast cells but not UMUC-14 cells. The treatment with minodronate enhanced the inhibition of proliferation and activity by docetaxel in osteoclasts. In vivo: In vivo combination therapy with docetaxel and minodronate significantly reduced the tumor incidence compared with the control (P < 0.05) and also growth of intraossal TCC in athymic nude mice compared with the control (P < 0.001), single therapy with docetaxel (P < 0.01), and minodronate (P < 0.05). Drug-induced body weight loss was not significantly different in any treatment group. Therapy with minodronate significantly enhanced inhibition of proliferation by docetaxel in osteoclasts of bone tumors compared with the control (P < 0.01), single therapy with docetaxel (P < 0.01), and minodronate (P < 0.05). CONCLUSIONS: These studies indicate that combination therapy with minodronate and docetaxel may be beneficial in patients with bone metastasis of human TCC in the urinary tract. 相似文献
62.
土槿皮乙酸体外诱导A375-S2细胞凋亡 总被引:6,自引:1,他引:6
目的 :研究土槿皮乙酸 (pseudolaricacidB)诱导A375 S2细胞凋亡的作用 ,探讨其抗癌作用机制。方法 :采用噻唑蓝 (MTT)法、形态学观察、DNA凝胶电泳及Westernblot检测法。结果 :土槿皮乙酸可剂量 时间依赖性的诱导A375 S2细胞凋亡 ,5 μmol·L-1土槿皮乙酸处理 36h的细胞 ,Hoechst 332 5 8荧光染色后有明显的凋亡小体出现 ;凝胶电泳法显示有明显的DNAladder出现。细胞内抑制凋亡蛋白Bcl 2 ,Bcl xL和caspase激活的DNA酶抑制物(ICAD)表达量时间依赖性地减少 ,而促凋亡蛋白Bax表达量增加。结论 :土槿皮乙酸对A375 S2细胞的杀伤作用主要通过诱导细胞凋亡 ,降低Bcl 2 ,Bcl xL和ICAD蛋白的表达 ,增加Bax蛋白表达为其诱发A375 S2细胞凋亡的机制之一。 相似文献
63.
Qiong Wang Miao Liu Wei-Wei Liu Wen-Bo Hao Shin-ichi Tashiro Satoshi Onodera 《Journal of Asian natural products research》2013,15(5):413-423
Improper adjustments of autophagy and silent information regulator 1 (Sirt-1) expression were reported to be closely associated with metabolic disorders. In this study, we examined the roles of Sirt-1 and autophagy in streptozotocin-induced diabetes mellitus, assessed the relationship between autophagy and Sirt-1, and investigated the protective mechanism of silibinin. Diabetes was induced in 6-week-old mice by intravenous injection of streptozotocin (150 mg/kg/day, for 2 weeks). In the treatment groups, silibinin (50 mg/kg/day, intramuscular injection, for 8 weeks) or inhibitors (50 mg/kg/day, subcutaneous injection, for 8 weeks) were given. Diabetic control animals received vehicle for the same time. Compared with diabetic controls, silibinin or autophagy inhibitor, 3-methyladenine, treated mice showed decreased levels of glycosylated hemoglobin A1C (P < 0.01), serum triglyceride (P < 0.01), cholesterol (P < 0.01), blood glucose (P < 0.05), autophagy (P < 0.05), and apoptosis ratio (P < 0.05) of pancreatic β-cells. Systemic administration of silibinin reversed streptozotocin-induced downregulation of Sirt-1 expression. Sirt-1 may play a role in regulating the physiological level of autophagy and is associated with loss of pancreatic β-cells and metabolic biochemical disorders. Through promoting Sirt-1 expression and recovering autophagy physiologically, silibinin may reverse hyperglycemia and repair damaged pancreatic β-cells. 相似文献
64.
目的水飞蓟素和CH11共同作用诱导人黑色素瘤细胞A375-S2凋亡的分子机制。方法结晶紫法测定细胞生长抑制率;细胞凋亡的形态学观察,LDH法测定凋亡与坏死的比率;用免疫印迹法检测凋亡抑制性的去乙酰化酶SIRT1、Bc l-2家族成员(抗凋亡蛋白Bc l-2,Bc l-xL和促凋亡蛋白Bax)、细胞色素C和Caspase-3的表达。结果水飞蓟素和CH11共同作用能诱导A375-S2细胞发生凋亡;形态学观察可见凋亡小体的形成;免疫印迹法检测发现水飞蓟素和CH11共同作用的A375-S2细胞中Bax蛋白的表达增加,Bc l-2蛋白和Bc l-xL蛋白的表达降低,细胞色素C释放增加,pro-caspase-3表达量明显降低。结论水飞蓟素协同CH11能明显促进A375-S2细胞的凋亡。 相似文献
65.
A 60-year-old man, who suffered from advanced rectal cancer accompanied with liver metastasis, underwent an abdominoperineal
resection and a partial hepatectomy. He remained well until 4 months after surgery when he developed a biopsy-proven recurrent
intrapelvic mass and multiple liver tumors. At 6 months after surgery, the metastatic liver tumors grew larger and almost
completely occupied both lobes of the liver. However, 9 months after surgery, the liver tumors regressed remarkably and his
clinical condition improved without any specific treatment for cancer. Although he died of cancerous peritonitis 18 months
after surgery, the autopsy findings did not indicate any apparent regrowth of the liver tumors. To date, only one case report
of a spontaneous regression of a metastatic liver tumor from colorectal cancer has been published in the English literature.
We herein describe this rare case and discuss some of the reasons potentially responsible for the regression.
Received: July 16, 2001 / Accepted: March 5, 2002 相似文献
66.
Eiji Wada Mitsuru Fukui Kazuhisa Takahashi Daisaku Takeuchi Hiroshi Hashizume Masahiko Kanamori Noboru Hosono Tsukasa Kanchiku Yuichi Kasai Miho Sekiguchi Shin-ichi Konno Mamoru Kawakami Kazuo Yonenobu 《Journal of orthopaedic science》2019,24(1):57-61
Background
In 1999, the Japanese Orthopaedic Association decided to develop a new Cervical Myelopathy Evaluation Questionnaire (JOACMEQ). The final version of the JOACMEQ, comprising 24 questions and five domains (cervical spine function (CF); upper extremity function (UF); lower extremity function (LF); bladder function (BF); and quality of life (QOL)), was established after three nationwide investigations. The fourth investigation, reported in this paper, was performed to confirm the responsiveness of the questionnaire.Methods
A total of 137 patients with cervical myelopathy were included in the study. Each patient was interviewed twice using the JOACMEQ before and after treatment. At the second interview, the patients self-rated their condition in five domains for “worse,” “somewhat worse,” “no change,” “somewhat better,” or “better,” and these scores were defined as the external assessment rating. The difference of the points in five domains between the first and the second interview was calculated against each external assessment. Based on the results, substantial clinical benefit (SCB) thresholds for the JOACMEQ were determined.Results
The statistically significant median values of the acquired points were 17.5 for CF, 16.0 and 21.0 for UF, 27.0 and 20.5 for LF, 13.0 for BF, and 29.0 for QOL. After consideration of the results, the committee decided that an acquired point ≥20 could be interpreted as representing an SCB threshold for the JOACMEQ.Conclusion
We have concluded that a treatment can be judged to be effective for a patient if 1) The patient give all answers for the questions necessary to calculate the functional score of a domain and an increase of ≥20 points is obtained for that score, or 2) The functional score after treatment is > 90 points even if the answer for the unanswered questions was supposed to be the worst possible choice. 相似文献67.
Yasushi Rino Munetaka Masuda Norio Yukawa Hitoshi Murakami Ken Takata Tsutomu Hayashi Shin-ichi Suzuki Kei-ichiro Kasama Toshio Imada 《Esophagus》2010,7(1):71-74
In this report, we describe our traction suture technique of the pericardium for suspension of the heart without hemodynamic
instability to obtain excellent exposure in the abdominal-transhiatal approach (TH). Our technique is an application of deep
pericardium stitches for off-pump coronary artery bypass surgery. In detail, the left hepatic lobe is detached at its triangular
ligament from the diaphragm and is deflected to the right. Then, the tendinous portion of the diaphragm arching over the esophagus
is incised upward in the midline until the pericardium is exposed. Pericardial fatty tissue was dissected. Three U-shaped
sutures reinforced with a felt pledget are placed on the posterior aspect of the pericardium and diaphragm. A 15 Fr. flexible
catheter is placed over both ends of the suture to avoid damage of the adjacent organs. Finally, the sutures are fixed to
the drape of anterior wall of the patient to maintain good exposure. 相似文献
68.
Osamu Kitamura Toshiaki Takeichi Elaine Lu Wang Itsuo Tokunaga Akiko Ishigami Shin-ichi Kubo 《Legal medicine (Tokyo, Japan)》2010,12(2):57-62
Little is known about the role of glial cells in the striatum of chronic methamphetamine (METH) users. In this study, we immunohistochemically examined glial reactions in the striatum of chronic METH users who did not abstain from METH use and died of drug intoxication. Human glucose transporter 5 (hGLUT), a useful marker of microglia, and CR3.43, a major histocompatibility complex class II antigen specific for reactive microglia, were immunostained. Glial fibrillary acidic protein (GFAP) and S100Β were used for astrocyte immunohistochemistry. We analyzed 12 chronic METH users and 13 control subjects, and detected a 200–240% increase in the number of hGLUT5-positive cells in chronic METH users (p < 0.01). However, we did not detect any proliferation of CR3.43-positive cells. The number of GFAP-positive astrocytes increased, but this increase was not significant (p > 0.05). Moreover, S100B-positive cell density between the two groups was not significant (p > 0.05). This study demonstrates the absence of reactive gliosis in the striatum of chronic METH users who did not abstain for prolonged periods from METH use. The results suggest that chronic METH use by itself did not activate glial cells in humans and reactive gliosis may not be involved in the mechanism underlying the loss of control in drug intake, which is a characteristic feature of drug addiction. 相似文献
69.
Shin-ichi Ando Keita Odashiro Toshiaki Ashihara Hiroshi Ando Wataru Mitsuoka Hirofumi Tagawa Takaya Fukuyama 《Heart and vessels》1994,9(2):104-107
Summary We angiographically documented coronary vasospasm which resulted in myocardial infarction during the acute phase of aortic dissection (Stanford A). Coronary and aortic angiography performed at admission of the patient revealed complete occlusion of the right coronary artery and dissection of the aorta. Intracoronary injection of isosorbide dinitrate and intravenous administration of verapamil opened the occluded right coronary artery and blood flow was fully restored. We conclude that, in this case of aortic dissection, the severe stimulation by the aortic dissection brought about vasospasm of the right coronary artery which was the major cause of myocardial infarction. This is the first case report showing clear evidence that myocardial infarction is brought about by vasospasm associated with aortic dissection. 相似文献