Activation of the CREB Coactivator CRTC2 by Aberrant Mitogen Signaling promotes oncogenic functions in HPV16 positive head and neck cancer.

Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide and incidence rates are continuing to rise globally. Patients often present with locally advanced disease and a staggering 50% chance of relapse following treatment. Aberrant activation of adaptive response signaling pathways, such as the cAMP/PKA pathway, induce an array of genes associated with known cancer pathways that promote tumorigenesis and drug resistance. We identified the cAMP Regulated Transcription Coactivator 2 (CRTC2) to be overexpressed and constitutively activated in HNSCCs and this confers poor prognosis. CRTCs are regulated through their subcellular localization and we show that CRTC2 is exclusively nuclear in HPV(+) HNSCC, thus constitutively active, due to non-canonical Mitogen-Activated Kinase Kinase 1 (MEKK1)-mediated activation via a MEKK1-p38 signaling axis. Loss-of-function and pharmacologic inhibition experiments decreased CRTC2/CREB transcriptional activity by reducing nuclear CRTC2 via nuclear import inhibition and/or by eviction of CRTC2 from the nucleus. This shift in localization was associated with decreased proliferation, migration, and invasion. Our results suggest that small molecules that inhibit nuclear CRTC2 and p38 activity may provide therapeutic benefit to patients with HPV(+) HNSCC.

A Split Face Comparative Study of Safety and Efficacy of Microneedling with Tranexamic Acid versus Microneedling with Vitamin C in the Treatment of Melasma.

INTRODUCTION: Melasma is a common pigmentary disorder affecting the face. Although a few risk factors have been identified, the exact pathogenesis remains elusive. Many treatment modalities have been tried, but none have been completely successful. AIM: To compare safety and efficacy of microneedling with Tranexamic acid versus microneedling with Vitamin C in the treatment of melasma. MATERIALS AND METHODS: It was a split face, comparative study conducted on 30 female melasma patients. After obtaining informed consent, microneedling with Tranexamic acid was done on left side and microneedling with Vitamin C was done on right side of face. The improvement was evaluated on the basis of clinical photographs, MASI, Physician Global Assessment (PGA) and Patient Global Assessment (PtGA) at each visit (0, 4 and 8 weeks). Z test was used to test the significant difference in the means of the 2 groups at 4 weeks and at 8 weeks. RESULTS: At the end of 8 weeks, MASI, PGA and PtGA showed improvement with both tranexamic acid and vitamin C. However the improvement was more with tranexamic acid than with vitamin C, although not statistically significant. CONCLUSION: Both TXA and Vitamin C are effective and safe treatments for melasma. But, TXA was found to be more effective.

Dermoscopic pre- and posttreatment evaluation in patients with androgenetic alopecia on platelet-rich plasma-A prospective study.

BACKGROUND: Platelet-rich plasma is rich in growth factors that promote differentiation and growth of dermal papilla cells by various signaling pathways. Dermoscopy is handy, bedside tool that helps to improve diagnostic accuracy in various hair disorders. OBJECTIVES: To evaluate and study the role of dermoscopy in patients with androgenetic alopecia (AGA) pre- and posttreatment with platelet-rich plasma (PRP). METHODS: It is a prospective comparative study. Twenty male patients with AGA, aged 18-45 years with modified Norwood-Hamilton classification grade II-VI were included in this study. Patients were given platelet-rich plasma injections every 3 week for a period of 3 months. Dermoscopy was performed with 10 x magnifications in polarized mode at baseline and at 3 months from the baseline and photographs were taken. Patients were evaluated based on following dermoscopic findings (a) hair count, (b) hair density, (c) hair diameter diversity, perifollicular pigmentation, yellow dots, multi-hair follicular units, honeycomb pigment pattern and white dots, (d) patient's hair growth assessment score. RESULTS: Posttherapy, patients showed significant improvement in hair count (27.4%), hair diversity (84.2%), increase in number of thick, terminals hairs, reduction in yellow dots (60%), perifollicular pigmentation (92.3%) was appreciated. Hair pull test negative after treatment in 10 patients (50%). Patient's hair growth assessment score showed 50%-75% improvement in 7 (35%) patients. CONCLUSION: Dermoscopy helps to easily evaluate and compare the therapeutic response pre- and posttreatment which can be easily documented and visualized at every visit.