Profile of vismodegib and its potential in the treatment of advanced basal cell carcinoma.

Basal cell carcinoma (BCC) is the most common human malignancy. Recent advances in our understanding of the critical biologic pathways implicated in the development and progression of BCC have led to the development of the first molecular targeted therapy for this disease. The hedgehog pathway is mutated in virtually all patients with BCC and recent trials with vismodegib, an inhibitor of this pathway, have shown significant responses. This review will discuss the importance of the hedgehog pathway in the pathogenesis of BCC and describe in detail the pharmacology of vismodegib in relation to its activity in advanced BCC

Sweet syndrome: a sweet disease with a bitter diagnosis

Sweet syndrome is an acute febrile neutrophilic dermatosis first described by Robert Douglas Sweet in 1964. Sweet syndrome presents in three clinical settings: classical (or idiopathic), malignancy-associated, and drug-induced. It has been associated with hematopoietic malignancies and myelodysplastic disorders. A-28-years married woman presented to us with chief complaints of Fever and Multiple swellings over the body since 2 months. At presentation she has Pallor; venous hum present. Multiple, tender, erythematous subcutaneous swellings, firm in consistency noted in both forearms. Skin over the swellings is pinchable; superficial skin is normal. Sweet syndrome can occasionally cause an intense systemic response involving the lungs, liver and musculoskeletal system. The skin lesions in Sweet syndrome typically start as erythematous papules, plaques, and nodules. The lesions can take on pseudovesicular or pseudopustular appearance, and sometimes fully formed vesicles or pustules develop. The lesions can be subcutaneous mimicking erythema nodosum which can’t be differentiated unless a biopsy is taken. Because the diagnosis of Sweet syndrome can be challenging, particularly when associated with other connective tissue disorders such as SLE, a set of diagnostic criteria were proposed initially by Su and Liu and then revised by Von den Driesch. The diagnosis is based upon the presence of two major and two of the four minor criteria. Concurrent Sweet syndrome and SLE are exceedingly rare. Twelve patients with both Sweet syndrome and systemic lupus erythematosus (SLE) have been previously reported. We report a case of sweet syndrome associated with SLE diagnosed in our hospital. In our patient, diagnostic criteria are satisfied for Sweet syndrome as well as for SLE (ACR criteria-patient had polyarthralgia, anemia, thrombocytopenia, ANA and Ds DNA positive. Four out of 11 are fulfilled for SLE). Patient responded to corticosteroids

Anti-Inflammatory Activity of Calotropis gigantea and Tridax procumbens on Carrageenin-Induced Paw Edema in Rats

The anti-inflammatory activities of extract of Calotropis gigantea R.Br. and Tridax procumbens Linn., were assessed on carrageenin-induced paw edema along with standard drug, Ibuprofen. The Ibuprofen significantly reduced paw edema at the dose of 200mg/Kg bw orally. The oral administration equi-effective dose (ED50) of C. gigantea (600mg/Kg bw) and T. procumbens (400 mg/Kg bw) individually revealed about 20-35% more activity than the one rendered by administration of 50mg/Kg bw of Ibuprofen. The effect of C. gigantea and T. procumbens along with various dose regimen of Ibuprofen showed greater anti-inflammatory activities than the Ibuprofen alone

Novel role of pancreatic differentiation 2 in facilitating self-renewal and drug resistance of pancreatic cancer stem cells.

BACKGROUND: Cancer stem cells (CSCs) contribute towards disease aggressiveness and drug resistance. Specific identification of CSC maintenance genes and targeting can improve the efficiency of currently available treatment modalities. Pancreatic differentiation 2 (PD2) has a major role in the self-renewal of mouse embryonic stem cells. In the present study, we investigated the role of PD2 in pancreatic CSCs. METHODS: Characterisation of CSCs and non-CSCs from mouse models, pancreatic cancer cells and human tissues by CSC and self-renewal marker analysis using confocal assay. Effect of PD2 knockdown in CSCs (after gemcitabine treatment) was studied by immunoblot and apoptosis assays. RESULTS: A subpopulation of cells displayed PD2 overexpression in mouse (Kras(G12D); Pdx1-Cre and Kras(G12D); Trp53(R172H/+); Pdx1-Cre) and human pancreatic tumours, which co-express CSC markers. Cancer stem cells exhibited elevated expression of PD2 and self-renewal markers, such as Oct3/4, Shh and β-catenin. Gemcitabine treatment maintained the CSC population with simultaneous maintenance of PD2 and CSC marker expression. Knockdown of PD2 in CSCs resulted in reduced viability of cells and enhanced apoptosis along with abrogated expression of CD133 and MDR2. CONCLUSIONS: Our results suggest that PD2 is a novel CSC maintenance protein, loss of which renders the CSCs more susceptible to drug-induced cell death

SenseWorld: Towards Cyber-Physical Social Networks

Web-based social networks such as LinkedIn, FaceBook and MySpace have gained wide popularity in recent years. With the advent of ubiquitous sensing, future social net-works will be cyber-physical, combining measured ele

A Secure Data Transmission Using Efficient Aggregate Signature Scheme to Verify Data in Wireless Sensor N/W

We stretch an ID-based aggregate signature (IBAS) scheme for WSNs in cluster-based method . The opponent in our refuge model has the competence to presentation any alliance attacks. If an opponent can use some solitary signatures counting invalid ones to make a valid aggregate signature approximately that the attack is successful. In detail, our ID-based aggregate signature scheme not only can defend data integrity, but also can lessen bandwidth and storage cost for WSNs. we largely attention on data integrity shield, give an identity-based aggregate signature scheme with a selected verifier for wireless sensor networks. Outline not only can keep data integrity, but also can cut bandwidth and storage cost for wireless sensor networks

Targeting EGF-receptor(s) - STAT1 axis attenuates tumor growth and metastasis through downregulation of MUC4 mucin in human pancreatic cancer.

Transmembrane proteins MUC4, EGFR and HER2 are shown to be critical in invasion and metastasis of pancreatic cancer. Besides, we and others have demonstrated de novo expression of MUC4 in ~70-90% of pancreatic cancer patients and its stabilizing effects on HER2 downstream signaling in pancreatic cancer. Here, we found that use of canertinib or afatinib resulted in reduction of MUC4 and abrogation of in vitro and in vivo oncogenic functions of MUC4 in pancreatic cancer cells. Notably, silencing of EGFR family member in pancreatic cancer cells decreased MUC4 expression through reduced phospho-STAT1. Furthermore, canertinib and afatinib treatment also inhibited proliferation, migration and survival of pancreatic cancer cells by attenuation of signaling events including pERK1/2 (T202/Y204), cyclin D1, cyclin A, pFAK (Y925) and pAKT (Ser473). Using in vivo bioluminescent imaging, we demonstrated that canertinib treatment significantly reduced tumor burden (P=0.0164) and metastasis to various organs. Further, reduced expression of MUC4 and EGFR family members were confirmed in xenografts. Our results for the first time demonstrated the targeting of EGFR family members along with MUC4 by using pan-EGFR inhibitors. In conclusion, our studies will enhance the translational acquaintance of pan-EGFR inhibitors for combinational therapies to combat against lethal pancreatic cancer