BACKGROUND: Oral lichen planus (OLP) is an immune-mediated potentially malignant disorder of the oral cavity. Dysplastic OLP has an altered cytogenic profile and can progress into oral squamous cell carcinoma. The epidemiology of OLP is well-described in several relatively large series from various geographic locations, whereas such series from southern India is rare. The aim of the present study was to determine the epidemiology of OLP in a cohort of South Indian population. METHODS: All the case data records of 29,606 patients who visited Mar Baselios Dental College and Hospital, Kerala, India from 2014 to 2015 were retrospectively reviewed. For data review, 122 patients of OLP were selected Estimated were type, number, and location of lesions, clinical manifestation, age of the patient, gender, onset and duration of lesion, stressful life style, habits, skin involvement and associated systemic illness, and presence/absence of dysplasia. RESULTS: When the distribution of OLP among the gender was considered, we found more prevalence in females than males. Fifty-seven percent of patients were associated with stressful lifestyle. Reticular lichen planus was the most common clinical subtype found. Bilateral buccal mucosal was the common site, when the distribution of sites of OLP were compared (P < 0.05). Hypersensitivity reaction was frequently associated with systemic illness with OLP (P < 0.05). Anaplasia was found among 5% of lichen planus lesions. CONCLUSIONS: OLP patients had high incidence of hypersensitivity reactions and 5% of OLP lesions showed anaplasia. Long term follow-up is necessary to monitor the recurrence, prognosis, and malignant transformation of OLP.
Anaplasia ; Carcinoma, Squamous Cell ; Cohort Studies* ; Epidemiology* ; Female ; Follow-Up Studies ; Geographic Locations ; Humans ; Hypersensitivity ; Immune System Diseases ; Incidence ; India ; Lichen Planus ; Lichen Planus, Oral* ; Life Style ; Male ; Mouth ; Prevalence ; Prognosis ; Recurrence ; Retrospective Studies* ; Skin

OBJECTIVEIn the present study, we systemically evaluated the ability of two bioactive compounds from traditional Chinese medicine, celastrol and pristimerin, to enhance recombinant adeno-associated virus (rAAV) serotype vector-mediated transgene expression both in human cell lines in vitro, and in murine hepatocytes in vivo.

METHODSHuman cell lines were infected with rAAV vectors with either mock treatment or treatment with celastrol or pristimerin. The transgene expression, percentage of nuclear translocated viral genomes and the ubiquitination of intracellular proteins were investigated post-treatment. In addition, nonobese diabetic/severe combined immunodeficient gamma (NSG) mice were tail vain-injected with rAAV vectors and co-administered with either dimethyl sulfoxide, celastrol, pristimerin or a positive control, bortezomib. The transgene expression in liver was detected and compared over time.

RESULTSWe observed that treatment with pristimerin, at as low as 1 μmol/L concentration, significantly enhanced rAAV2 vector-mediated transgene expression in vitro, and intraperitoneal co-administration with pristimerin at 4 mg/(kg·d) for 3 d dramatically facilitated viral transduction in murine hepatocytes in vivo. The transduction efficiency of the tyrosine-mutant rAAV2 vectors as well as that of rAAV8 vectors carrying oversized transgene cassette was also augmented significantly by pristimerin. The underlying molecular mechanisms by which pristimerin mediated the observed increase in the transduction efficiency of rAAV vectors include both inhibition of proteasomal degradation of the intracellular proteins and enhanced nuclear translocation of the vector genomes.

CONCLUSIONThese studies suggest the potential beneficial use of pristimerin and pristimerin-containing herb extract in future liver-targeted gene therapy with rAAV vectors.

Animals ; Cell Line ; Dependovirus ; genetics ; physiology ; Gene Expression ; drug effects ; Genetic Therapy ; Genetic Vectors ; genetics ; physiology ; Hepatocytes ; metabolism ; virology ; Humans ; Liver ; cytology ; metabolism ; virology ; Mice ; Transgenes ; drug effects ; Triterpenes ; pharmacology

OBJECTIVELittle effort has been made to study the protein-encoding genes isolated from traditional Chinese medicine (TCM) drugs, and the delivery of these genes into malignant cells through recombinant adeno-associated virus (rAAV) vectors has not been attempted.

METHODSWe synthesized the cDNAs of five known cytotoxic proteins isolated from TCM drugs and the FLAG epitope-tagged cDNAs were subcloned into a rAAV plasmid vector. The protein expression was confirmed by Western blot assay. Various cancer cell lines were transfected with the above plasmids and cell growth was monitored both in vitro and in vivo. The best cytotoxic gene was further packaged into rAAV vectors, under the control of a liver cancer-specific promoter. The liver tumor growth was then monitored following intratumor administration of the rAAV vectors.

RESULTSThe expression plasmids, encoding individual potential cytotoxic genes tagged with FLAG epitope, were successfully generated and sequenced. Among these genes, trichosanthin (TCS) gene yielded the most promising results for the inhibition of cancer cell growth in vitro. The over-expressed TCS functioned as a type I ribosome-inactivating protein, followed by inducing apoptosis that is associated with the Bcl-PARP signaling pathway. Furthermore, intratumor injection of rAAV vectors containing the TCS gene significantly inhibited the growth of human hepatocellular carcinoma tumors in a murine xenograft model.

CONCLUSIONOur studies suggest that the use of TCM cytotoxic genes is a useful therapeutic strategy for treating human cancers in general, and liver tumors in particular.

Animals ; Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; physiology ; Cell Line, Tumor ; DNA, Complementary ; Dependovirus ; Genetic Vectors ; Humans ; Liver Neoplasms ; physiopathology ; Medicine, Chinese Traditional ; methods ; Mice ; Neoplasms ; physiopathology ; Trichosanthin ; genetics ; pharmacology