Gold nanoparticles (AuNPs) of ultrafine size have drawn attention for their use in drug delivery systems. Tissue toxicity may be an issue when AuNPs are used for such applications. We investigated the long-term biokinetics (90 d), redistribution, and urinary excretion of three different-sized (2 ± 0.5 nm, 5 ± 1 nm, and 10 ± 2 nm) AuNPs after a single intravenous (i.v.) administration of 1250 µg/kg dose in mice. ICP-AES analysis of lungs, liver, spleen, heart, kidney, brain, blood, and urine revealed highest accumulation of gold in spleen around 15 d after injection. A low concentration was detected in brain after 1 d without any residual AuNPs after 30 d. Ultrastructural study of brain tissue also showed few AuNPs in lysosome with no changes in cellular architecture. Renal retention of AuNPs was limited indicating low nephrotoxic potential. AuNPs were detectable in urine till 30 d after single injection indicating slow excretion from the body. No evidence of significant toxicity was observed in hemogram, serum biochemistry, and tissue histology. No mortality, changes in behavior, hair color, weight, and food intake was observed as compared to control mice. Therefore, we conclude that the ultrafine AuNPs are predominantly excreted in urine without any systemic toxicity following i.v. administration and are hence safe for use in drug delivery systems.
Background:The Indian subcontinent has the highest incidence of oral cavity squamous cell carcinoma in the world. The high incidence of tobacco chewing habit with or without smoking has been found to be the chief culprit. However in a minor subset of patients Human Papilloma Virus may play a role. Materials and Methods: A total of 800 cases of Oral squamous cell carcinoma were included in the study. The patients were given a questionnaire comprising of questions about demographic details and habits. The biopsy samples were routinely processed for immunohistochemistry for p16 (E6H4 clone, CINtec histology, Roche diagnostics). Cases with 2+/3+ positive nuclear staining with more than 75% cells immunopositive were taken as p16 immunopositive as per the AJCC criteria and were further subjected to HPV DNA PCR for which DNA was extracted from the formalin fixed paraffin embedded tissue. Results: Out of 800 OSCC cases 139 (17.37%) showed p16 immunopositivity by AJCC criteria. Out of these, 104 (104/139, 74.8%) cases were positive by HPV DNA PCR for HPV-16/18. Following patient characteristics were associated with a higher proportion of p16 and HPV DNA positivity-urban residence, vegetarian diet, illiteracy, graduate or higher education. No correlation was noted with gender, tobacco smoking or chewing habits, religion, occupation or site of tumor. The p16 immunopositivity was higher in the younger age group with no tobacco habits. Conclusion: A significant proportion of OSCC cases in India are associated with HPV infection. A higher percentage of p16 immunopositivity amongst younger patients with no tobacco habits points towards a distinct subset of patients in whom HPV may be the chief culprit and not just playing a supporting role.
Human breast cancer cell proliferation involves a complex interaction between growth factors, steroid hormones and peptide hormones. The interaction of growth factors, such as epidermal growth factor (EGF), with their receptors on breast cancer cells can lead to the hydrolysis of phospholipids and release of fatty acid such as arachidonic acid, which can be further metabolized by cyclooxygenase (COX) and lipoxygenase (LOX) pathways to produce prostaglandins. The high concentration of prostaglandins has been associated with chronic inflammatory diseases and several types of human cancers. This is due to the over expression COX, LOX and other inflammatory enzymes. Ten peptides were designed and synthesized by solid phase peptide synthesis and analyzed
in vitro
for enzyme inhibition. Out of these peptides, YWCS had shown significant inhibitory effects. The dissociation constant (K
D
) was determined by surface plasmon resonance (SPR) analysis and was found to be 3.39×10
−8
M and 8.6×10
−8
M for YWCS and baicalein (positive control), respectively. The kinetic constant Ki was 72.45×10
−7
M as determined by kinetic assay. The peptide significantly reduced the cell viability of estrogen positive MCF-7 and estrogen negative MDA-MB-231 cell line with the half maximal concentration (IC
50
) of 75 µM and 400 µM, respectively. The peptide also induced 49.8% and 20.8% apoptosis in breast cancer cells MCF-7 and MDA-MB-231, respectively. The YWCS was also found to be least hemolytic at a concentration of 358 µM.
In vivo
studies had shown that the peptide significantly inhibits tumor growth in mice (p<0.017). This peptide can be used as a lead compound and complement for ongoing efforts to develop differentiation therapies for breast cancer.
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