Tropical protozoal infections are
a significant cause of morbidity
and mortality worldwide; four in particular (human African trypanosomiasis
(HAT), Chagas disease, cutaneous leishmaniasis, and malaria) have
an estimated combined burden of over 87 million disability-adjusted
life years. New drugs are needed for each of these diseases. Building
on the previous identification of NEU-617 (1) as a potent
and nontoxic inhibitor of proliferation for the HAT pathogen (Trypanosoma brucei), we have now tested this class of analogs
against other protozoal species: T. cruzi (Chagas
disease), Leishmania major (cutaneous leishmaniasis),
and Plasmodium falciparum (malaria). Based on hits
identified in this screening campaign, we describe the preparation
of several replacements for the quinazoline scaffold and report these
inhibitors’ biological activities against these parasites.
In doing this, we have identified several potent proliferation inhibitors
for each pathogen, such as 4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)-6-(4-((4-methyl-1,4-diazepan-1-yl)sulfonyl)phenyl)quinoline-3-carbonitrile
(NEU-924, 83) for T. cruzi and N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-7-(4-((4-methyl-1,4-diazepan-1-yl)sulfonyl)phenyl)cinnolin-4-amine
(NEU-1017, 68) for L. major and P. falciparum.
β catenin belongs to the armadillo family of proteins. It plays a crucial role in developmental and homeostatic processes. Wnts are a family of 19 secreted glycoproteins that transduce multiple signaling cascades, including the canonical Wnt/β catenin pathway, Wnt/Ca2+ pathway and the Wnt/polarity pathway. This is a review on β catenin, Wnt proteins and their secretion, the signaling pathway, the associated factors and the crucial role of β catenin in odontogenesis.
Aim:To assess p53 and Cyclin D1 expression using Immunohistochemistry in normal mucosa and oral squamous cell carcinoma.Materials and Methods:Twenty cases of Oral squamous cell carcinoma (OSCC) and 10 normal mucosa were used and the primary antibodies used were p53 (DAKO-DO7) and Cyclin D1 Mouse Anti human Cyclin D1 (DCS-6) 1: 100 dilution. Statistical analysis: Labelling index was calculated and mean LI and SD were calculated, using Descriptive Statistics and t-test was used to compare mean LI between antibodies used in OSCC. Percentage positivity was done by Chi-Square test. Comparison of LI between p53 and Cyclin D1 was studied using t test.Results:p53 was positive in 30% and Cyclin D1 in40% of normal cases and 65% and 95% of OSCC were positive for p53 and Cyclin D1 respectively. Mean LI of p53 and Cyclin D1 were found to be statistically significant between the normal mucosa and OSCC. The correlation of mean LI of p53 and Cyclin D1 in OSCC was found to be statistically significant. LI of p53 was found to be higher than Cyclin D1 in OSCC.Conclusion:In the present study, increased p53 and Cyclin D1 expression were seen in OSCC when compared to the normal mucosa and a positive correlation was seen between increased p53 and Cyclin D1 expression in OSCC.
Background and Objectives:The behavior of odontogenic lesions varies with some tumors behaving like a cyst and some cysts behaving like tumors. p63, a member of the p53 family of tumor suppressor genes has recently come into light in view of its role as an oncogene. The aim of the present study was to investigate the expression of p63 protein in OKC, Solid ameloblastoma, Unicystic Ameloblastoma and Follicular tissue.Materials and Methods:p63 expression was compared in 12 cases of OKC, 12 Solid Ameloblastoma, 14 cases of Unicystic ameloblastoma and 10 cases of Follicular tissue using immunohistochemical technique. All 48 cases were subjected to heat-induced antigen retrieval method using citrate buffer in a pressure cooker. Then the sections were stained with anti-p63 polyclonal antibody and visualized using super sensitive polymer HRP detection system. In each case, number of cells showing p63 positivity were assessed in two compartments - basal and suprabasal and compared.Results:Statistical analysis showed that p63 expression in the suprabasal compartment in Odontogenic keratocysts was equivalent to that of central neoplastic cells of Solid Ameloblastoma and Unicystic Ameloblastoma type 3. Statistically significant difference in the expression of p63 was observed between OKC and Unicystic Ameloblastoma Type 1 and Solid Ameloblastoma and Unicystic Ameloblastoma Type 1.Conclusion:We conclude that the higher expression of p63 in these odontogenic lesions correlates well with their aggressive behavior and thereby suggesting alterations in treatment modalities.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.