Carbonic anhydrases (CAs) play an important role in maintaining pH homeostasis. We previously demonstrated that overexpression of CA2 was associated with invasion and progression of urothelial carcinoma (UC) in humans. The purpose of the present study was to evaluate the effects of the CA inhibitor acetazolamide (Ace) on N ‐butyl‐ N ‐(4‐hydroxybutyl)nitrosamine (BBN)‐induced bladder carcinogenesis in mice and explore the function of CA2 in muscle invasion by UC. Male mice were treated with 0.025% (experiment 1) or 0.05% BBN (experiment 2) in their drinking water for 10 weeks, then treated with cisplatin (Cis), Ace, or Cis plus Ace for 12 weeks. In experiment 1, the overall incidence of BBN‐induced UCs was significantly decreased in the BBN→Ace and BBN→Cis+Ace groups. In experiment 2, the overall incidence of BBN‐induced UCs was significantly decreased in the BBN→Cis+Ace group, and the incidence of muscle invasive UC was significantly decreased in both the BBN→Ace and the BBN→Cis+Ace groups. We also show that overexpression of CA2 by human UC cells T24 and UMUC3 significantly increased their migration and invasion capabilities, and that Ace significantly inhibited migration and invasion by CA2‐overexpressing T24 and UMUC3 cells. These data demonstrate a functional association of CA2 with UC development and progression, confirming the association of CA2 with UC that we had shown previously by immunohistochemical analysis of human UC specimens and proteome analysis of BBN‐induced UC in rats. Our finding that inhibition of CA2 inhibits UC development and muscle invasion also directly confirms that CA2 is a potential therapeutic target for bladder cancers.
Cigarette smoking is known to increase the risk of cancer and chronic obstructive pulmonary disease (COPD). In this study, we evaluated the effects of short-term nose-only inhalation exposure to cigarette smoke in mice. Male 10-week-old C57BL mice were exposed to clean air (control) or mainstream cigarette smoke for 1 h/day, 5 days/week, for 2 or 4 weeks. Exposure to cigarette smoke increased the number of inflammatory cells, especially neutrophils, in the bronchoalveolar lavage fluid, increased inflammatory cell infiltration foci, and caused an increase in the thickness of the peripheral bronchial epithelium. Microarray gene expression analysis indicated that smoke exposure induced inflammatory responses, including leukocyte migration and activation of phagocytes and myeloid cells, as early as two weeks after the initiation of exposure. Importantly, chemokine (C-C motif) ligand 17, resistin-like alpha, and lipocalin 2 were upregulated and may serve as useful markers of the toxic effects of exposure to cigarette smoke before pulmonary histological changes become evident.
Background: Acute upper limb ischemia (AULI) is a potential complication associated with massages of occluded vascular accesses in patients undergoing hemodialysis. Pharmacological thrombolysis, endovascular intervention and surgical intervention are possible treatment options. Deciding the appropriate treatment strategy is still a controversial issue. Case Presentation: The patient was a 43-year-old woman with renal failure who underwent hemodialysis and peritoneal dialysis. She was found to have an arteriovenous graft (AVG) thrombosis at the start of a hemodialysis session. She underwent massage of the vascular access, and immediately after the massage, she reported pain and cyanosis in her right-hand fingers and was referred to our hospital. Duplex ultrasonography revealed a large number of thrombi in the brachial, radial and ulnar arteries. AULI due to brachial artery thrombosis was diagnosed and surgical intervention was performed on the same day. The vascular wall of the forearm artery was incised vertically against the running vessel and thrombi around the bifurcation of the radial and ulnar arteries were removed. Angiography guided-surgical intervention was performed and improvement in blood flow was achieved. The patient was discharged on the second day after the operation. Conclusion: Surgical intervention has been reported as an effective treatment of AULI due to brachial artery thrombosis after massage of an occluded vascular access.
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