A novel curcumin-based vaginal cream Vacurin selectively eliminates apposed human cervical cancer cells

Objective. Human papillomavirus (HPV) infections remain a leading cause of mortality worldwide. In the U.S. strategies via screening and vaccination prevent HPV-associated cervical neoplasms, but consume im- mense healthcare costs. The spice component curcumin has potent anticancer and antiviral properties, which have been difficult to harness as a treatment, due to its poor systemic bioavailability. This project tests the possibility of developing a curcumin-based therapy for cervical cancer. Methods. Using four HPV(+) cervical cancer cell lines and normal fibroblasts we first tested the selectivity and potency of curcumin in eliminating HPV(+) cells. Subsequently, we developed a curcumin-based cervical cream and tested its efficacy in eliminating apposed HPV(+) cells and also its possible side effects on the vaginal epithelium of healthy mice. Results. Curcumin selectively eliminates a variety of HPV(+) cervical cancer cells (HeLa, ME-180, SiHa, and SW756), suppresses the transforming antigen E6, dramatically inhibits the expression of the pro-cancer protein epidermal growth factor receptor (EGFR), and concomitantly induces p53. Additionally, Vacurin, a uniform colloidal solution of curcumin in a clinically used amphipathic vaginal cream, eliminates apposed HeLa cells while suppressing the expression of EGFR. In mice, daily intravaginal application of Vacurin for three weeks produced no change in body weight and when the mice were sacrificed, the vaginal tract epithelium showed no Vacurin-evoked adverse effects. Conclusion. We have developed a curcumin-based vaginal cream, which effectively eradicates HPV(+) cancer cells and does not affect non-cancerous tissue. Our preclinical data support a novel approach for the treatment of cervical HPV infection

Corrosion behaviour of sintered ferrous alloys and Ferro-TiC in H₂SO₄and NaCl solutions

153-160The room temperature corrosion behaviour of plain carbon steel Fe-0.5C, low alloy steel Fe-5Cu-0.5C, tool steels ASP 23 and ASP 30, and ferro-TiC cermet was investigated in H2SO4 (0.1-5N) and 0.6 N NaCl solutions by potentiodynamic polarization technique. The study also includes X-ray diffraction, optical microscopy and scanning electron microscopy of the as-received as well as corroded surfaces. Porosities present in Fe-0.5C and Fe-5Cu-0.5C steels were found to be responsible for their poor corrosion resistance. ASP 30 steels were found to exhibit good corrosion resistance as compared to ASP 23 in both the media

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Escherichia vulneris: an unusual cause of complicated diarrhoea and sepsis in an infant. A case report and review of literature

Escherichia vulneris is an opportunistic human pathogen. It has been primarily reported in adult patients and invasive infections have been observed in immune-suppressed individuals. This is the first report of E. vulneris causing complicated diarrhoea and sepsis in an infant. Two month old sick infant, born full-term, was admitted to the paediatrics department with loose motions and refusal to feed for four days. E. vulneris was isolated from blood in pure culture. The isolate was characterized for diarrhoeal virulence markers: heat labile and heat stable toxins (LT, ST) and hemolysin (hlyA) by PCR. The presence of LT enterotoxin and hemolysin provides strong evidence of the diarrhoeagenic potential of E. vulneris, further leading to the invasive infection triggering sepsis. As E. vulneris can lead to serious complications, an attempt should be made in clinical laboratories to identify and further characterize this new Escherichia species

Coupling to a glioblastoma-directed antibody potentiates antitumor activity of curcumin

Current therapies for glioblastoma are largely palliative, involving surgical resection followed by chemotherapy and radiation therapy, which yield serious side effects and very rarely produce complete recovery. Curcumin, a food component, blocked brain tumor formation but failed to eliminate established brain tumors in vivo, probably because of its poor bioavailability. In the glioblastoma GL261 cells, it suppressed the tumor-promoting proteins NF-kappa B, P-Akt1, vascular endothelial growth factor, cyclin D1 and BClXL and triggered cell death. Expression of exogenous p50 and p65 subunits of NF-kappa B conferred partial protection on transfected GL261 cells against curcumin insult, indicating that NF-kappa B played a key role in protecting glioblastoma cells. To enhance delivery, we coupled curcumin to the glioblastoma-specific CD68 antibody in a releasable form. This resulted in a 120-fold increase in its efficacy to eliminate GL261 cells. A very similar dose response was also obtained with human glioblastoma lines T98G and U87MG. GL261-implanted mice receiving intratumor infusions of the curcumin-CD68 adduct followed by tail-vein injections of solubilized curcumin displayed a fourfold to fivefold reduction in brain tumor load, survived longer, and about 10% of them lived beyond 100 days. Hematoxylin-eosin staining of brain sections revealed a small scar tissue mass in the rescued mice, indicating adduct-mediated elimination of glioblastoma tumor. The tumor cells were strongly CD68+ and some cells in the tumor periphery were strongly positive for microglial Iba1, but weakly positive for CD68. This strategy of antibody targeting of curcumin to tumor comes with the promise of yielding a highly effective therapy for glioblastoma brain tumors