Costunosides A-C: cytotoxic sesquiterpene lactones from the rhizomes of Aucklandia costus Falc.

Three new eudesmane type rare sesquiterpene lactone galactosides, costunosides A-C (1-3) were isolated from the rhizomes of Aucklandia costus along with ten known compounds (4-13). Costunosides A-C (1-3) are the first example of naturally eudesmane glycosides containing a ß-galactopyranoside moiety. The structure and relative configurations of these compounds were established by comprehensive analysis of MS and, in particular 1D/2D NMR spectroscopic data. The isolated compounds were tested against a panel of human cancer cell lines, where compounds 3, 6 and 7 have shown promising cytotoxic activity against PC-3, HCT-116 and A549 cell lines with IC50 values in the range of 3.4 µM to 9.3 µM, respectively. Costunosides A-C (1-3) were also screened for inhibition assay of acetyl-cholinesterase (AChE), and butyrylcholinesterase (BChE) and found inactive at a concentration of 10 µM.

Preparation, characterization and toxicological investigation of copper loaded chitosan nanoparticles in human embryonic kidney HEK-293 cells.

Metallic nanoparticles often attribute severe adverse effects to the various organs or tissues at the molecular level despite of their applications in medical, laboratory and industrial sectors. The present study highlights the preparation of copper adsorbed chitosan nanoparticles (CuCSNPs), its characterization and validation of cytotoxicity in human embryonic kidney HEK-293 cells. Particle size of the CuCSNPs was determined by using Zetasizer and the copper loading was quantified with the help of ICP/MS. Further characterization of CuCSNPs was carried out by FT-IR analysis to determine the formation of nanoparticles and SEM was conducted for the morphological analysis of the CuCSNPs. The CuCSNPs exhibited pronounced cytotoxic effects towards HEK-293 cells as analyzed by MTT assay. Moreover, the CuCSNPs inhibited the colony formation and induced nuclear damage at the dose of 100 µg/mL, much more effectively than the in built control copper sulfate (CuSO4). At the molecular level, the CuCSNPs were found to be triggering reactive oxygen species (ROS), activating effector caspases and subsequent PARP cleavage to induce cell death in HEK-293 cells.

Dual targeted polymeric nanoparticles based on tumor endothelium and tumor cells for enhanced antitumor drug delivery.

Some specific types of tumor cells and tumor endothelial cells represented CD13 proteins and act as receptors for Asn-Gly-Arg (NGR) motifs containing peptide. These CD13 receptors can be specifically recognized and bind through the specific sequence of cyclic NGR (cNGR) peptide and presented more affinity and specificity toward them. The cNGR peptide was conjugated to the poly(ethylene glycol) (PEG) terminal end in the poly(lactic-co-glycolic) acid PLGA-PEG block copolymer. Then, the ligand conjugated nanoparticles (cNGR-DNB-NPs) encapsulating docetaxel (DTX) were synthesized from preformed block copolymer by the emulsion/solvent evaporation method and characterized for different parameters. The various studies such as in vitro cytotoxicity, cell apoptosis, and cell cycle analysis presented the enhanced therapeutic potential of cNGR-DNB-NPs. The higher cellular uptake was also found in cNGR peptide anchored NPs into HUVEC and HT-1080 cells. However, free cNGR could inhibit receptor mediated intracellular uptake of NPs into both types of cells at 37 and 4 °C temperatures, revealing the involvement of receptor-mediated endocytosis. The in vivo biodistribution and antitumor efficacy studies indicated that targeted NPs have a higher therapeutic efficacy through targeting the tumor-specific site. Therefore, the study exhibited that cNGR-functionalized PEG-PLGA-NPs could be a promising approach for therapeutic applications to efficient antitumor drug delivery.

Overexpression of COX-2 in oral squamous cell carcinoma patients undergoing chemoradiotherapy.

AIMS AND OBJECTIVES: To evaluate the prognostic significance of cyclooxygenase-2 (COX-2) overexpression in oral squamous cell carcinoma (OSCC) patients undergoing chemoradiation therapy. Purpose of the study was to determine whether COX-2 could be used as a diagnostic and prognostic index in OSCC. MATERIALS AND METHODS: Forty-four patients of SCC were included in the present study and immunohistochemical examination was done for COX-2 expression. Negative and <5% COX-2 positivity were taken as negative expression and ≥5% COX-2 positivity as positive expression group. ≥30% COX-2 positivity was taken as overexpressed group and <30% COX-2 positivity was taken as underexpressed group. All the data were analyzed statistically. RESULTS: COX-2 overexpression in OSCC was found in 15.90% cases. The proportion of COX-2 overexpression was higher in patients with large tumor size than in those with small tumor size. The proportions of COX-2 positive expression cases were higher with cervical lymph node metastasis. Negative COX-2 expression was higher in well-differentiated OSCC and positive expression was higher in moderately differentiated tumors. COX-2 underexpressed cases had better response to chemoradiation therapy as compared to cases with overexpressed COX-2. CONCLUSION: COX-2 expression in OSCC can be used as a prognostic marker. Studies with large sample size and long-term follow-up are required to find out the exact role and prognostic significance of COX-2 expression in OSCC.

Metastatic malignant melanoma of palate: A review of literature and report of an unusual case.

Oral malignant melanoma is a rare tumor, accounting 0.8to 1.8 % of all oral malignancies. It occurs most commonly in Japanese and Negros. Radical surgery is mainstay of the treatment. Prognosis is very poor with 5 years survival rate. We present a case of malignant melanoma in a 55 years female, metastatizing to liver spleen and vertebrae.

Ameloblastic carcinoma.

Ameloblastic carcinoma (AC) is a rare aggressive malignant epithelial odontogenic tumor of the maxillofacial skeleton with a distinct predilection in the mandible. It may appear de novo or originate from a pre-existing ameloblastoma or odontogenic cyst. It exhibits cytological features of ameloblastoma and carcinoma. It may present as a cystic lesion with benign clinical features or as a large tissue mass with ulceration, significant bone resorption and tooth mobility. The clinical course of ameloblastic carcinoma is typically aggressive, with extensive local destruction. Direct extension of the tumour, lymph node involvement and metastasis to various sites has been reported. Wide local excision is the treatment of choice. Regional lymph node dissection should be considered and performed selectively. Radiotherapy and chemotherapy have limited role in the treatment of ameloblastic carcinomas. Close periodic reassessment of the patient is mandatory.