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61.
Yano A Tsutsumi S Soga S Lee MJ Trepel J Osada H Neckers L 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(40):15541-15546
Hsp90 inhibitors are being evaluated extensively in patients with advanced cancers. However, the impact of Hsp90 inhibition on signaling pathways in normal tissues and the effect that this may have on the antitumor activity of these molecularly targeted drugs have not been rigorously examined. Breast and prostate carcinomas are among those cancers that respond to Hsp90 inhibitors in animal xenograft models and in early studies in patients. Because these cancers frequently metastasize to bone, it is important to determine the impact of Hsp90 inhibitors in the bone environment. In the current study, we show that, in contrast to its activity against prostate cancer cells in vitro and its inhibition of s.c. prostate cancer xenografts, the Hsp90 inhibitor 17-AAG stimulates the intraosseous growth of PC-3M prostate carcinoma cells. This activity is mediated not by a direct effect on the tumor but by Hsp90-dependent stimulation of osteoclast maturation. Hsp90 inhibition transiently activates osteoclast Src kinase and promotes Src-dependent Akt activation. Both kinases are key drivers of osteoclast maturation, and three agents that block osteoclastogenesis, the Src inhibitor dasatinib, the bisphosphonate alendronate, and the osteoclast-specific apoptosis-inducer reveromycin A, markedly reduced 17-AAG-stimulated tumor growth in bone. These data emphasize the importance of understanding the complex role played by Hsp90 in regulating signal transduction pathways in normal tissues as well as in cancer cells, and they demonstrate that drug-dependent modulation of the local tumor environment may profoundly affect the antitumor efficacy of Hsp90-directed therapy. 相似文献
62.
Anil Rana Jimi Marin Alex Monika Chauhan Gaurav Joshi Raj Kumar 《Medicinal chemistry research》2015,24(3):903-920
Past few decades have witnessed the dawn of new diseases in which cancer is a major problem and the race ensued to eradicate cancer by charting out various effective therapeutic regimens. Circumventing resistance issues and combating the toxicity and selectivity problems are matter-of-concern in cancer treatment. Persistent failure to ensure complete remission and eradication of cancer instigated the researchers to exploit the strategies of combining pharmacophores as targeted therapeutic agents. Momentous improvement in the pharmacokinetic as well as pharmacodynamic profile resulting in the enhancement of bioavailability was seen with the introduction of these pharmacophores. The scope of molecular hybridization can be clearly exemplified through the US-FDA approved estramustine and others such as CUDC-101, CBLC-137, PLX3397, E-3810, and CUDC-907 that are currently in different phases of clinical trials. This review seeks to highlight and discuss anti-proliferative activity of some important hybrid, dual, and multi-targeted pharmacophores reported to date along with their designs, structure activity relationships, scope, and limitations. Further, an emphasis has been made to summarize US-FDA approved as well as drugs currently undergoing clinical trials of anticancer drug development. 相似文献
63.
Kihara Mari Sugihara Takahiko Asano Junichi Sato Midori Kaneko Hiroshi Muraoka Sei Ohshima Shiro Nanki Toshihiro 《Clinical rheumatology》2022,41(12):3661-3673
Clinical Rheumatology - To describe clinical characteristics of patients in Japan with coronavirus disease 19 (COVID-19) and pre-existing rheumatic disease and examine the possible risk factors... 相似文献
64.
Maki Akasu M.D. Keijiro Saku M.D. Masanori Okabe M.D. Koichi Handa M.D. Kunihiro Matsuo M.D. Shiro Jimi Ph.D. Kikuo Arakawa M.D. 《The International journal of angiology》1995,4(3):169-171
Typical angioid streaks were found on routine ophthalmologic examination in a 42-year-old female with yellowish, coalescing papules on her neck without any symptoms. Biopsy of the cutaneous lesion showed degeneration and fragmentation of the elastic fibers and many basophilic-stained calcifications in mid-dermis, which are consistent with pseudoxanthoma elasticum. Twenty-four-hour Holter electrocardiography (ECG) showed sinus arrest for 2.5 seconds, and an electrophysiological study revealed sinus nodal dysfunction (sick sinus syndrome), whereas all of the coronary arteries were intact, despite a treadmill stress ECG test showing significant ST depressions. The association of pseudoxanthoma elasticum and sick sinus syndrome is very rare. One possible explanation for this association here is that the degeneration of elastic fiber in endomysium of the sino-atrial node may have affected heart conduction systems, resulting in sick sinus syndrome.Part of this work was presented at the 76th Japanese Circulation Society Kyushu Meeting, Japan, June 18, 1994 相似文献
65.
Shingen Nakamura Momoyo Azuma Tomoko Maruhashi Kimiko Sogabe Ryohei Sumitani Munenori Uemura Masami Iwasa Shiro Fujii Hirokazu Miki Kumiko Kagawa Takashi Hiraga Noriyasu Kondo Hiromi Fujita Fumihiko Mahara Masahiro Abe 《Journal of infection and chemotherapy》2018,24(5):389-392
Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infectious disease caused by the SFTS virus (SFTSV). Clinical symptoms of SFTS often involve encephalopathy and other central neurological symptoms, particularly in seriously ill patients; however, pathogenesis of encephalopathy by SFTSV is largely unknown. Herein, we present case reports of three patients with SFTS, complicated by encephalopathy, admitted to Tokushima University hospital: one patient was a 63-year-old man, while the other two were 83- and 86-year-old women. All of them developed disturbance of consciousness around the 7th day post onset of fever. After methylprednisolone pulse therapy of 500 mg/day, all of them recovered without any neurological sequelae. SFTSV genome was not detected in the cerebrospinal fluid of 2 out of the 3 patients that were available for examination. In these patients, disturbance of consciousness seemed to be an indirect effect of the cytokine storm triggered by SFTSV infection. We propose that short-term glucocorticoid therapy might be beneficial in the treatment of encephalopathy during early phase of SFTSV infection. 相似文献
66.
Mutsumi Matsuu-Matsuyama Kazuko Shichijo Kumio Okaichi Tomomi Kurashige Hisayoshi Kondo Shiro Miura Masahiro Nakashima 《Journal of radiation research》2015,56(3):493-501
Exposure to ionizing radiation during childhood is a well-known risk factor for thyroid cancer. Our study evaluated the effect of age on the radiosensitivity of rat thyroid glands. Four-week-old (4W), 7 -week-old (7W), and 8-month-old (8M) male Wistar rats were exposed to 8 Gy of whole-body X-ray irradiation. Thyroids were removed 3–72 h after irradiation, and non-irradiated thyroids served as controls. Ki67-positivity and p53 binding protein 1 (53BP1) focus formation (a DNA damage response) were evaluated via immunohistochemistry. Amounts of proteins involved in DNA damage response (p53, p53 phosphorylated at serine 15, p21), apoptosis (cleaved caspase-3), and autophagy (LC3, p62) were determined via western blotting. mRNA levels of 84 key autophagy-related genes were quantified using polymerase chain reaction arrays. Ki67-positive cells in 4W (with high proliferative activity) and 7W thyroids significantly decreased in number post-irradiation. The number of 53BP1 foci and amount of p53 phosphorylated at serine 15 increased 3 h after irradiation, regardless of age. No increase in apoptosis or in the levels of p53, p21 or cleaved caspase-3 was detected for any ages. Levels of LC3-II and p62 increased in irradiated 4W but not 8M thyroids, whereas expression of several autophagy-related genes was higher in 4W than 8M irradiated thyroids. Irradiation increased the expression of genes encoding pro-apoptotic proteins in both 4W and 8M thyroids. In summary, no apoptosis or p53 accumulation was noted, despite the expression of some pro-apoptotic genes in immature and adult thyroids. Irradiation induced autophagy in immature, but not in adult, rat thyroids. 相似文献
67.
Shiro Ono Kiyomi Yoshimoto Nobushiro Nishimura Ryo Yoneima Hiromasa Kawashima Tadanao Kobayashi Yoshiaki Tai Makiko Miyamoto Emiko Tsushima Noritaka Yada Kenji Nishio 《Internal medicine (Tokyo, Japan)》2021,60(8):1303
TAFRO syndrome is a systemic inflammatory, lymphoproliferative disorder, but the pathophysiology of the disease is unknown. It is typically characterized by thrombocytopenia, anasarca, a fever, reticulin fibrosis, renal dysfunction, and organomegaly. However, other manifestations have been also reported. We encountered a 43-year-old man with TAFRO syndrome who showed mediastinal panniculitis, liver damage, and adrenal lesions in addition to the core signs. He achieved complete remission with combination therapy of corticosteroids, tocilizumab, and cyclosporin, and remission was maintained even after drug discontinuation at 15 months. Atypical manifestations and complete remission of TAFRO syndrome were remarkable features of our case. 相似文献
68.
Ryohei Sumitani Taiki Hori Jumpei Murai Shiyori Kawata Masahiro Oura Kimiko Sogabe Mamiko Takahashi Takeshi Harada Shiro Fujii Hirokazu Miki Kumiko Kagawa Masahiro Abe Shingen Nakamura 《Internal medicine (Tokyo, Japan)》2021,60(11):1753
A 33-year-old man was admitted to our hospital for fever and abdominal pain. A blood analysis revealed pancytopenia and increased serum pancreatic enzymes with disseminated intravascular coagulation. A detailed examination revealed acute pancreatitis, with diffuse swelling of the pancreas and diffuse beaded dilatation of the main pancreatic duct, which mimicked autoimmune pancreatitis complicated by acute myeloid leukemia. Systemic cytotoxic chemotherapy led to the remission of leukemia and pancreatitis. We hypothesized that the etiology of acute pancreatitis was invasion of leukemia cells. Acute pancreatitis is rare as a symptom of leukemia; however, we should consider the possibility of leukemia during the differential diagnosis of acute pancreatitis. 相似文献
69.
Shinzaki Shinichiro Matsuoka Katsuyoshi Tanaka Hiroki Takeshima Fuminao Kato Shingo Torisu Takehiro Ohta Yuki Watanabe Kenji Nakamura Shiro Yoshimura Naoki Kobayashi Taku Shiotani Akiko Hirai Fumihito Hiraoka Sakiko Watanabe Mamoru Matsuura Minoru Nishimoto Shohei Mizuno Shinta Iijima Hideki Takehara Tetsuo Naka Tetsuji Kanai Takanori Matsumoto Takayuki 《Journal of gastroenterology》2021,56(6):560-569
Journal of Gastroenterology - This multicenter prospective study (UMIN000019958) aimed to evaluate the usefulness of serum leucin-rich alpha-2 glycoprotein (LRG) levels in monitoring disease... 相似文献
70.
Hitoshi Mori MD PhD Daisuke Kawano MD Naokata Sumitomo MD PhD FHRS Shota Muraji MD Taisuke Nabeshima MD Kenta Tsutsui MD PhD Yoshifumi Ikeda MD PhD Shiro Iwanaga MD PhD Shintaro Nakano MD PhD Toshihiro Muramatsu MD PhD Toshiki Kobayashi MD PhD Ritsushi Kato MD PhD Kazuo Matsumoto MD PhD 《Journal of cardiovascular electrophysiology》2021,32(7):1877-1883