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101.
Tobacco carcinogen induces both lung cancer and non‐alcoholic steatohepatitis and hepatocellular carcinomas in ferrets which can be attenuated by lycopene supplementation 下载免费PDF全文
Koichi Aizawa Chun Liu Sanyuan Tang Sudipta Veeramachaneni Kang‐Quan Hu Donald E. Smith Xiang‐Dong Wang 《International journal of cancer. Journal international du cancer》2016,139(5):1171-1181
Early epidemiologic studies have reported that tobacco smoking, which is causally associated with liver cancer, is an independent risk factor for non‐alcoholic fatty liver diseases (NAFLD). Lycopene from tomatoes has been shown to be a potential preventive agent against NAFLD and hepatocellular carcinoma (HCC). In the present study, we investigated whether the tobacco carcinogen 4‐(N‐methyl‐N‐nitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (NNK) induces lesions in both lungs and livers of ferrets with or without lycopene intervention. Male ferrets (6 groups, n = 8–10) were treated either with NNK (50 mg/kg BW, i.p., once a month for four consecutive months) or saline with or without dietary lycopene supplementation (2.2 and 6.6 mg/kg BW/day, respectively) for 26 weeks. Results demonstrate that NNK exposure results in higher incidences of lung tumors, HCC and steatohepatitis (which is characterized by severe inflammatory cell infiltration with concurrent fat accumulation in liver, hepatocellular ballooning degeneration and increased NF‐κB expression), as well as elevations in bilirubin and AST levels in ferrets. Lycopene supplementation at two doses prevented NNK‐induced expressions of α7 nicotinic acetylcholine receptor in the lung and NF‐κB and CYP2E1 in the liver and attenuated the NNK‐induced mortality and pathological lesions in both the lungs and livers of ferrets. The present study provided strong experimental evidence that the tobacco carcinogen NNK can induce both HCC and steatohepatitis in the ferrets and can be a useful model for studying tobacco carcinogen‐associated NAFLD and liver cancer. Furthermore, lycopene could provide potential benefits against smoke carcinogen‐induced pulmonary and hepatic injury. 相似文献
102.
Takatoshi Aoki Toshihiro Miyamoto Yasuo Mori Goichi Yoshimoto Takuji Yamauchi Kenjiro Kamezaki Katsuto Takenaka Hiromi Iwasaki Naoki Harada Koji Nagafuji Nobuyuki Shimono Takanori Teshima Koichi Akashi 《Mycoses》2011,54(4):e255-e259
Invasive aspergillosis (IA) is an important cause of infectious morbidity and mortality in patients who undergo haematopoietic stem cell transplantation (HSCT). History of IA before allogeneic HSCT is still challenging because of the high risk of recurrence after HSCT. Recent advances in early‐stage diagnosis and new, more effective classes of antifungal agents have improved the management of IA in the HSCT recipients. We report two cases with acute myelogenous leukaemia after primary failure of induction chemotherapy with the patients developing pulmonary IA. They responded well to a combination of voriconazole (VCZ) and micafungin, resulting in a remarkable reduction of pulmonary IA lesions at short intervals. Thereafter, antifungal therapy was switched to liposomal amphotericin B (L‐AmB), followed by conditioning regimen for allogeneic HSCT, because of the possibility of VCZ altering the metabolism of chemotherapeutic agents and calcineurin inhibitors. Successful engraftment was achieved without severe adverse side‐effects or aggravation of IA after HSCT. Combining VCZ with micafungin followed by L‐AmB throughout HSCT could be advantageous in stabilising IA in HSCT patients. 相似文献
103.
Ichiki M Kawasaki M Takayama K Ninomiya K Kuba M Iwami F Miyazaki N Oishi K Takeo S Aizawa H Nakanishi Y 《Cancer chemotherapy and pharmacology》2006,58(3):368-373
Purpose: This multicenter phase II study was conducted to investigate the efficacy and safety of carboplatin in combination with paclitaxel administered according to a biweekly schedule as a first-line chemotherapy for advanced non-small-cell lung cancer (NSCLC). Patients and methods: Eligibility criteria included histologically or cytologically confirmed NSCLC (stage IIIb or IV), no prior treatment, and measurable or evaluable disease. Paclitaxel (140 mg/m2) was administered intravenously on day 1, in combination with carboplatin at an area under the concentration time curve (AUC) of 3, every 2 weeks. Results: Seventy-four patients (45 men) with a median age of 62 years (range 40–74) and a median ECOG performance status of 1 (range 0–2) were enrolled. The response rate was 35.1% [95% confidence interval (CI): 24.4–47.1%], with 26 partial responses. The median survival was 357 days, and the median time to progression was 218 days. Toxicity was generally mild; National Cancer Institute-Common Toxicity Criteria (NCI-CTC) grades 3 and 4 neutropenia was observeded in 50.0% of the patients, and grades 3 and 4 nausea/vomiting in 4.1%. Conclusions: Biweekly carboplatin combined with paclitaxel demonstrated anti-tumor activity in advanced NSCLC, with response and survival rates similar to those of carboplatin combined with paclitaxel administered every 3 weeks but with a more favorable toxicity profile, and the present data indicate that the regimen is suitable for use on an outpatient basis. 相似文献
104.
Shibuya H Hamamura K Hotta H Matsumoto Y Nishida Y Hattori H Furukawa K Ueda M Furukawa K 《Cancer science》2012,103(9):1656-1664
The expression and implications of gangliosides in human osteosarcomas have not been systematically analyzed. In this study, we showed that gangliosides GD3 and GD2 are highly expressed in the majority of human osteosarcoma cell lines derived from oral cavity regions. Introduction of GD3 synthase cDNA into a GD3/GD2-negative (GD3/GD2-) human osteosarcoma subline resulted in the establishment of GD3/GD2+ transfectant cells. They showed increased cell migration and invasion activities in wound healing and Boyden chamber invasion assays, respectively, compared to the control cells. When treated with serum, GD3/GD2+ cells showed stronger tyrosine phosphorylation of p130Cas, focal adhesion kinase, and paxillin than GD3/GD2- cells. In particular, paxillin underwent much stronger phosphorylation, suggesting its role in cell motility. Furthermore, we tried to dissect the roles of GD3 and GD2 in the malignant properties of the transfectant cells by establishing single ganglioside-expressing cells, that is, either GD3 or GD2. Although GD3/GD2+ cells showed the most malignant properties, GD2+ cells showed almost equivalent levels to GD3/GD2+ cells in invasion and migration activities, and in the intensities of tyrosine phosphorylation of paxillin. Among Src family kinases, Lyn was expressed predominantly, and was involved in the invasion and motility of GD3- and/or GD2-expressing transfectants. Furthermore, it was elucidated by gene silencing that Lyn was located in a different pathway from that of FAK to eventually lead paxillin activation. These results suggested that GD2/GD3 are responsible for the enhancement of the malignant features of osteosarcomas, and might be candidate targets in molecular-targeted therapy. 相似文献
105.
Kanto S Sugawara J Masuda H Sasano H Arai Y Kyono K 《Fertility and sterility》2008,90(5):2010.e5-2010.e7
106.
107.
Tsung-Che Chang Yoshiyuki Manabe Keita Ito Ryuku Yamamoto Kazuya Kabayama Shino Ohshima Yoshie Kametani Yukari Fujimoto Chun-Cheng Lin Koichi Fukase 《RSC advances》2022,12(29):18985
Sialyl-Tn (STn), overexpressed on various tumors, has been investigated for its application in anti-cancer vaccine therapy. However, Theratope, an STn-based vaccine, failed in the phase III clinical trial due to poor immunogenicity and epitope suppression by the foreign carrier protein. We therefore developed a self-adjuvanting STn based-vaccine, a conjugate of clustered STn (triSTn) antigen, TLR1/2 ligand (Pam3CSK4), and T-helper (Th) cell epitope, and found that this three-component self-adjuvanting vaccine effectively resulted in the production of anti-triSTn IgG antibodies. We herein analyzed immune responses induced by this self-adjuvanting vaccine in detail. We newly synthesized two-component vaccines, i.e., Pam3CSK4- or Th epitope-conjugated triSTn, as references to evaluate the immune-stimulating functions of Pam3CSK4 and Th epitope. Immunological evaluation of the synthesized vaccine candidates revealed that Pam3CSK4 was essential for antibody production, indicating that the uptake of triSTn antigen by antigen-presenting cells (APCs) was promoted by the recognition of Pam3CSK4 by TLR1/2. The function of the Th epitope was also confirmed. Th cell activation was important for boosting antibody production and IgG subclass switching. Furthermore, flow cytometric analyses of immune cells, including T cells, B cells, dendritic cells, and other monocytes, were first employed in the evaluation of self-adjuvanting vaccines and revealed that the three-component vaccine was able to induce antigen-specific immune responses for efficient antibody production without excessive inflammatory responses. Importantly, the co-administration of Freund''s adjuvants was suggested to cause excessive myeloid cell accumulation and decreased plasma cell differentiation. These results demonstrate that vaccines can be designed to achieve the desired immune responses via the bottom-up construction of each immune element.Detailed analysis of a three-component self-adjuvanting vaccine revealed that conjugate vaccines can be designed to achieve the desired immune responses via bottom-up construction of the necessary immune elements. 相似文献
108.
Masaki Uchihara Jun Ehara Keiichi Iwanami Koichi Kitamura Toshihiko Suzuki Noriyoshi Ishizuka Toru Yamada Eiji Hiraoka 《Internal medicine (Tokyo, Japan)》2022,61(13):1995
Chylous ascites (CA) is the accumulation of fluid with a high triglyceride content in the peritoneal cavity. Only two cases in the literature have reported CA with hyperthyroidism. A 28-year-old previously healthy woman presented with gradual-onset abdominal swelling, exertional dyspnea, and diarrhea. Hyperthyroidism and heart failure were diagnosed using laboratory investigation and echocardiography. Ultrasonography revealed a large amount of ascites. The ascitic fluid was milky with elevated triglyceride levels. Treatment with anti-thyroid therapy and diuretics improved all symptoms, and the free triiodothyronine (T3) level normalized after five days. Hyperthyroidism and heart failure should be considered as reversible causes of CA. 相似文献
109.
Yuta Yamamura Kengo Furuichi Tadashi Toyama Megumi Oshima Hisayuki Ogura Koichi Sato Shiori Nakagawa Taro Miyagawa Shinji Kitajima Akinori Hara Yasunori Iwata Norihiko Sakai Miho Shimizu Hiroko Ikeda Tomoko Toma Kazuya Takasawa Akihiro Yachie Takashi Wada 《Internal medicine (Tokyo, Japan)》2022,61(7):1105
We herein report a 36-year-old man with repeated necrotizing lymphadenitis due to MEFV gene mutations. The patient''s chief complaints were a fever and painful cervical lymphadenopathy. We diagnosed him with necrotizing lymphadenitis based on the pathological findings of the lymph nodes and the exclusion of other differential diseases. The same episode recurred four times. We speculated the involvement of autoinflammatory backgrounds and detected MEFV gene mutations of E148Q (homo), P369S, and R408Q. Considering the elevation of interleukin-18, these mutations probably played roles in the repeated necrotizing lymphadenitis. 相似文献
110.
Kenji Nakahama Hiroyasu Kaneda Koichi Ogawa Yoshiya Matsumoto Yoko Tani Tomohiro Suzumura Shigeki Mitsuoka Tetsuya Watanabe Kazuhisa Asai Tomoya Kawaguchi 《Internal medicine (Tokyo, Japan)》2022,61(7):1039
A 68-year-old Japanese man was diagnosed with lung adenocarcinoma stage IVB. We introduced a first-line chemotherapy of four cycles of carboplatin and pemetrexed and pembrolizumab, followed by pemetrexed and pembrolizumab maintenance therapy. Approximately four months after anticancer therapy, a small nodule appeared in the right peripheral S3 lesion. After five months, the nodule was confirmed as a Mycobacterium tuberculosis (TB) nodule. We initiated anti-TB therapy without stopping pembrolizumab, and the right S3 nodule shrank immediately. This report supports the concurrent use of anti-TB treatment with an immune checkpoint inhibitor when the TB infection area is limited. 相似文献