We previously reported that the platelet-derived growth factor B-chain (PDGF-B)/PDGF receptor (PDGFR) axis is involved in tubular regeneration after ischemia/reperfusion injury of the kidney. In the present study, we examined the activation of Src tyrosine kinase, a crucially important signaling molecule for PDGFR, and assessed the role of Src in PDGF-B-dependent renal tubular regeneration afterischemia/reperfusion injury. Immunoblot using clone 28, a monoclonal antibody specific for the active form of Src kinases, demonstrated increased active Src expression in the injured rat kidney 6 hours after reperfusion with peak activation at 12 hours. In vitro kinase assay confirmed increased Src activity that concurred with PDGFR-beta activation as detected by the increment of receptor-phosphorylated tyrosine. Immunohistochemistry using clone 28 demonstrated that active Src was preferentially expressed in the S3 segment of the proximal tubule in reperfused kidney, where it is not normally expressed. This enhanced expression of active Src was co-localized with the increased PDGFR expression in the tubular cells that were undergoing cell proliferation cycle. Trapidil administration suppressed Src and PDGFR-beta activation in the reperfused kidney and resulted in deteriorated renal function. These findings suggest that active Src participates in PDGF-B-dependent regeneration of tubular cells from acute ischemic injury.

p62/SQSTM1 (sequestosome1) has never been evaluated in oral epithelium. In order to clarify the role of p62/SQSTM1 in carcinogenesis in oral epithelium, both p62/SQSTM1 and Nrf2 were immunohistochemically evaluated in 54 carcinomas and 14 low grade dysplasias. p62/SQSTM1 knockdowns were also designed in oral cancer cells, and we analyzed the Nrf2 pathway, GSH contents and ROS accumulation. The association between p62/SQSTM1 excess and prognosis was addressed in a clinical cohort of oral carcinoma cases. p62/SQSTM1 excess was more obvious in carcinomas, but Nrf2 was abundant in almost all samples of the oral epithelium. In oral carcinoma cells, p62/SQSTM1 knockdown did not affect the Nrf2-Keap1 pathway but did significantly reduce GSH content with subsequent ROS accumulation, and caused cell growth inhibition in the irradiated condition. Finally, p62/SQSTM1 excess was associated with poor prognosis in a clinical cohort. In oral epithelial carcinogenesis, p62/SQSTM1 excess played a role in GSH induction rather than Nrf2 accumulation, and may cause resistance to cytotoxic stresses such as radiation or chemotherapy. Immunohistochemical evaluation of p62/SQSTM1 may be a potential significant marker to identify early carcinogenesis, chemo-radiotherapeutic resistance or poor prognosis of oral squamous cell carcinomas.

Granulomatous mycosis fungoides (GMF) represents an uncommon variant of mycosis fungoides (MF) characterized by the presence of an associated granulomatous reaction. Most cases of GMF are CD4 positive, and CD8 positive cases are extremely rare. Herein, we report a case of CD8-positive GMF. A 75-year-old Japanese woman presented with brownish maculae on the trunk and upper and lower extremities. She had been diagnosed with MF, and most of the eruption improved by psoralen ultraviolet A therapy. However, the eruption relapsed and gradually expanded 5 months prior to her visit to our hospital. Histopathology showed an atypical lymphocytic infiltrate in the dermis accompanied by granulomatous reaction with multinucleated giant cells. Epidermotropism was evident and elastophagocytosis was also found. Immunohistochemically, the atypical lymphocytes expressed betaF1, CD3 and CD8, and some of the atypical lymphocytes were also T cell intracellular antigen-1 positive. These findings were consistent with CD8-positive GMF. The dermatopathological diagnosis of GMF is challenging in some cases because of the prominent secondary granulomatous reaction. Therefore, when dermatopathologists diagnose granulomatous skin lesions, GMF should also be considered. In addition, the prognosis of GMF, especially CD8-positive GMF, is still controversial. Additional studies are required to clarify the clinicopathological features of CD8-positive GMF.

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We report a case of hepatocellular carcinoma (HCC) occurring in a patient with Crohn's disease (CD) without chronic hepatitis or liver cirrhosis, and review the clinicopathological features of HCC in CD patients. A 37-year-old Japanese man with an 8-year history of CD and a medication history of azathioprine underwent resection of a liver tumor. The histopathology of the liver tumor was pseudoglandular type HCC. In the non-neoplastic liver, focal hepatocyte glycogenosis (FHG) was observed, however, there was no evidence of liver cirrhosis or primary sclerosing cholangitis. Only nine cases of HCC in CD patients have been reported previously in the English-language literature. Eight of 10 cases (including the present case) had received azathioprine treatment, and four of these cases also showed FHG, which is considered a preneoplastic liver lesion, within the non-neoplastic liver. Although the precise mechanism of the development of HCC in CD patients is controversial, these results suggest that azathioprine therapy and FHG in the non-neoplastic liver contribute to the development of HCC. These findings also indicate that it is important to survey CD patients treated with prolonged azathioprine therapy for potential liver tumors.