Effect of Doxorubicin on Squamous Cell Carcinoma of Skin: Assessment by MRI Relaxometry at 4.7T.

Squamous cell carcinoma (SCC) of skin has no standard treatment regimen, resulting in recurrences/metastasis. Although, doxorubicin (Dox), an anthracycline antibiotic has demonstrated some degree of efficacy. Molecular imaging can help in assessment of treatment response and prognosis of SCCs. MRI data showed that spin-spin relaxation (T2) time was longer (138 ± 2 msec) in Dox treated Test-II and there is no significant difference in spin-lattice relaxation (T1) time with respective controls. These findings further corroborated with the histology, proliferation index, apoptotic index, and HMGA1 protein expression. Thus, MRI may be a useful tool for monitoring treatment response noninvasively for skin tumor prognosis.

A study of interleukin 1ß levels in peri-miniscrew crevicular fluid (PMCF).

BACKGROUND: This study provides a vital insight in assessing the clinical and biochemical changes in interleukin (IL)-1ß levels in peri-miniscrew crevicular fluid (PMCF) during the course of orthodontic tooth movement. METHODS: The study comprised the analysis of IL-1ß in peri-miniscrew crevicular fluid obtained from crevices around the miniscrews inserted in 11 patients (eight females and three males, mean age 17.3 ± 4.64 years) with all first premolar extraction and maximum anchorage requirement using miniscrew-supported anchorage. Miniscrews were loaded at 3 weeks after placement by 200-g nitinol closed coil springs of 9-mm length for en masse retraction. Peri-miniscrew crevicular fluid was collected at miniscrew placement (T1), at 3 weeks (T2/baseline) and on loading at 0 (T3) and 1 day (T4), 21 (T5), 72 (T6), 120 (T7), 180 (T8) and 300 (T9) days. IL-1ß levels were estimated by enzyme-linked immunosorbent assay (ELISA). Peri-miniscrew tissue was examined for signs of inflammation, and also, miniscrew mobility was assessed with Periotest and handles of two mouth mirrors. RESULTS: IL-1ß levels in all miniscrews were significantly higher at T1 and peaked again at T4 showing a bimodal peak. However, there was a gradual and statistically significant decrease in IL-1ß till T5, while further changes till the end of the study were statistically not significant. CONCLUSIONS: The changing levels of IL-1ß levels in PMCF over a duration of 300 days are suggestive of the underlying inflammatory process. IL-1ß levels in PMCF show a significant rise during miniscrew insertion and on immediate loading. The trend of gradually reducing IL-1ß levels around the miniscrew over the period after loading towards baseline is suggestive of adaptive bone response to stimulus.

Interaction of adriamycin with a promoter region of hmga1 and its inhibitory effect on HMGA1 expression in A431 human squamous carcinoma cell line.

The high mobility group A1 (HMGA1) are non-histone chromosomal proteins consisting of HMGA1a and HMGA1b which act as architectural transcription factors. Elevated levels of HMGA1 are reported in a number of human cancers and suggested as tumor markers. Due to their role in neoplastic transformation and tumor progression, we considered HMGA1 as a potential target for downregulation at the transcriptional level. The present paper deals with the binding of a widely used chemotherapeutic agent, adriamycin (ADM), to hmg a1 gene promoter (-304 to -284), 21RY, and its effect on the expression of hmga1 at the mRNA and protein levels and further its cytotoxic efficacy in A431 cells. A strong complex (21RY-ADM) formation caused hypochromic and bathochromic changes in UV-absorption, considerable spectral changes in circular dichroism of adriamycin and DNA and significant quenching of fluorescence emission of ADM. Thermodynamics of 21RY-ADM interaction was studied by isothermal titration and differential scanning calorimetric techniques that revealed the binding to be exothermic and favored by both negative enthalpy and positive entropy changes. Further, even low concentrations (10.3 nM) of ADM showed cytotoxicity on human squamous carcinoma cells (A431) and caused downregulation (by ∼ 70%) of hmga1 at mRNA and protein levels. Present findings clearly support the inhibitory effect of ADM on hmg a1 which quite probably is the consequence of its binding to the targeted region of hmg a1. Therefore, it appears that hmg a1 is a novel potential chemotherapeutic target in treating carcinomas of epithelial origin like prostate, breast, thyroid etc.