Context:Oral lichen planus (OLP) is a potentially malignant disease with a prevalence rate of 0.5–2.2%. It is a T-cell-mediated autoimmune disease, in which cytotoxic CD8+ T-cells trigger apoptosis of the basal cells of oral epithelium. The reported progression of OLP to oral squamous cell carcinoma (OSCC) ranges from 0.4% to 6.5%. Apoptosis plays a major role in the maintenance of tissue homeostasis. The evasion of apoptosis in the form of dysregulation of inhibitors of apoptosis proteins (IAPs) may lead to malignant transformation. Survivin belongs to the second gene family of IAPs, which is overexpressed in many tumors such as OSCC and gastric carcinomas, and its expression is widely involved in apoptosis as well as in tumor metastasis.Materials and Methods:Sections were obtained from the paraffin-embedded archival blocks of patients diagnosed histologically as OLP, and cases with normal epithelium were used for comparison whereas cases with OSCC were used as positive control.Results:We analyzed the expression of survivin in OLP and normal epithelium. Survivin expression with moderate intensity was seen in the cells of basal layer with nuclear positivity in cases of OLP, whereas mild to nil expression was seen in normal epithelium with nuclear and cytoplasmic positivity in different layers.Conclusions:Survivin positivity was seen predominantly in the basal cells of OLP suggesting increased longevity of these cells which in turn might acquire dysplastic changes leading to increased risk of malignant transformation of this premalignant condition. Although the conversion rate may be low, the potential exists in the indolent course of the disease.
Ectodermal dysplasia is a hereditary disorder characterized by developmental dystrophies of ectodermal derivatives. It is characterized by triad of signs comprising sparse hair, abnormal or missing teeth and inability to sweat. This case of 12-year-old boy with hypohidrotic ectodermal dysplasia and complete anodontia of both primary and permanent dentition is presented. Owing to the need for treatment at an early age for anodontia and due to the ill-formed maxillary and mandibular residual ridges, the prosthetic management can be difficult. Complete dentures with soft liners and hollow maxillary denture were provided to encourage normal psychological development and to improve the function of the stomatognathic system.
Odontogenic myxoma (OM) is a rare and locally benign neoplasm of high aggressive behavior found exclusively in the jaws. OM commonly occurs in the second and third decade, its quite rare to find in maxilla that to invading the maxillary sinus completely. The lesion often grows without symptoms and presents as a painless swelling. The radiographic features are variable, and the diagnosis is therefore not easy. This article presents a case of OM of maxilla in a 13-year-old boy, which was previously diagnosed as fibrosseous lesion with the help of CT.
Objective: The development of anticancer drugs that selectively kills cancer cells while sparing the surrounding healthy tissues is of paramount importance for safe and effective anti-cancer therapy. We have developed a novel class of compounds that are fluoro-substituted analogs of curcumin, called diarylidenylpiperiden-4-ones (DAPs). We hypothesize that the structural backbone of DAP compounds would have cytotoxic activity, and the -NOH moiety would function as a tissue-specific modulator of this cytotoxicity via its anti-oxidant properties. The goal of this study was to analyze the differential cytotoxic effects of one of these compounds, HO-3867, on both ovarian cancer and normal cells. Methods: Protein expression in pro-apoptotic and survival signaling pathways were analyzed via western blotting, and immunofluorescence assays using human ovarian cancer (SKOV-3) and normal ovarian surface epithelial (hOSE) cell lines treated with 10 μM HO-3867. Flow cytometry was used to quantify apoptosis and immunohistochemistry was performed to analyze cellular localization of proteins. The selective cytotoxic effect of HO-3867 was verified using STAT3 cDNA and Akt siRNA transfection. In vivo analysis was performed on mice administered oral HO-3867 using histopathological analysis and TUNEL assays. Efficacy of HO-3867 proved in STAT3 knockdown SKOV3 ovarian cancer cell line. Results: HO-3867 did not affect the proliferation rate of hOSE cells while showing potent cytotoxic activity against SKOV-3 cells. In vivo histopathological evaluation of internal organs collected from treated adult mice revealed no evidence of toxicity. TUNEL staining of collected tissues suggested that selective apoptotic induction was limited to neoplastic cells in tumor xenografts. HO-3867 protected the normal cells by up-regulating the pro-survival protein pAkt. Tumor cells were targeted through downregulation of pAkt, pStat3, pErk1/2 and Bcl2 and upregulation of p21 and p53. Furthermore, HO-3867 was selectively regulates kinase activity in ovarian cancer cells and compared with hOSE cells. In addition, HO-3867 treated into STAT3 knockdown SKOV3 cells, resulted in the decreased apoptosis. These data indicated that HO-3867 induced apoptosis through the targeting STAT3. Conclusion: Our results showed that HO-3867 protects normal cells while retaining antiproliferative activity against ovarian cancer cells. Increased levels of pAkt and the free radical-scavenging effects of the pro-nitroxide N-hydroxypyrroline group mediate this selective protection. The results suggest that the antioxidant-conjugated DAPs may be useful as safe and effective anticancer agents for treatment of ovarian cancer Citation Format: Georgia A. McCann, Kellie S. Rath, Shan Naidu, Pushpa Lata, Bid Hemant, Meryl Sudhakar, Kálmán Hideg, Peter Houghton, Periannan Kuppusamy, David E. Cohn, Karuppaiyah Selvendiran. HO-3867, is selectively cytotoxic to ovarian cancer cells through a dual mechanism of action involving the STAT3 and AKT pathways . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1039. doi:10.1158/1538-7445.AM2013-1039
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