Critical role of miR-10b in B-RafV600E dependent anchorage independent growth and invasion of melanoma cells.

Recent high-throughput-sequencing of cancer genomes has identified oncogenic mutations in the B-Raf genetic locus as one of the critical events in melanomagenesis. B-Raf encodes a serine/threonine kinase that regulates the MAPK/ERK kinase (MEK) and extracellular signal-regulated kinase (ERK) protein kinase cascade. In normal cells, the activity of B-Raf is tightly regulated and is required for cell growth and survival. B-Raf gain-of-function mutations in melanoma frequently lead to unrestrained growth, enhanced cell invasion and increased viability of cancer cells. Although it is clear that the invasive phenotypes of B-Raf mutated melanoma cells are stringently dependent on B-Raf-MEK-ERK activation, the downstream effector targets that are required for oncogenic B-Raf-mediated melanomagenesis are not well defined. miRNAs have regulatory functions towards the expression of genes that are important in carcinogenesis. We observed that miR-10b expression correlates with the presence of the oncogenic B-Raf (B-RafV600E) mutation in melanoma cells. While expression of miR-10b enhances anchorage-independent growth of B-Raf wild-type melanoma cells, miR-10b silencing decreases B-RafV600E cancer cell invasion in vitro. Importantly, the expression of miR-10b is required for B-RafV600E-mediated anchorage independent growth and invasion of melanoma cells in vitro. Taken together our results suggest that miR-10b is an important mediator of oncogenic B-RafV600E activity in melanoma.

Nuclear and cytoplasmic features in the diagnosis of banal nevi, Spitz nevi, and melanoma.

BACKGROUND: Many authors have described cytologic features in a variety of melanocytic lesions but, to our knowledge, a statistical analysis of sensitivity, specificity, and overall accuracy of these features alone or in combination has not been performed. OBJECTIVE: We sought to determine the diagnostic value of nuclear and cytoplasmic characteristics in the diagnosis of melanocytic lesions via multivariate statistical analysis. METHODS: This is a retrospective observational study conducted on 300 melanocytic lesions. We evaluated a series of distinctive features; subsequently a multivariate model was used to determine sensitivity and specificity. RESULTS: Major features that favor a diagnosis of melanoma include: pleomorphism with enlarged nuclei, mitotic figures, notching/corrugation of the nuclear envelope, and peppered moth nucleus. Features with intermediate value include: solid hyperchromasia, vesicular nucleus with single round nucleolus, and nuclear/cytoplasmic ratio greater than 4:1. LIMITATIONS: Limitations of this study include its retrospective nature, and the reliance on the original diagnostic classification of each neoplasm. CONCLUSION: Our data suggest that some nuclear alterations have greater value in the diagnosis of benign and malignant melanocytic lesions.

Diffuse Autoimmune Enteropathy and Colopathy in an Adult Patient Successfully Treated With Adalimumab and a Review of the Literature.

Autoimmune enteropathy (AIE) is a rare disease that causes intractable diarrhea not responsive to a gluten free diet and must be distinguished from refractory sprue. It is associated with circulating autoantibodies against goblet cells and enterocytes. AIE mainly involves the small intestines, with very few cases reported in adults. Because of the paucity of cases, the epidemiology of the disease remains unclear, and treatment is based on the cases found in the literature. Of the 35 adult cases reported, only 4 involved the colon. Because of the low number of cases, there have been no clear recommendations on treatment modalities with most reports heavily emphasizing steroids as the mainstay of treatment. We present the case of adult female patient who developed postpartum AIE and colopathy with profuse diarrhea successfully treated with adalimumab and a review of the literature. To the best of our knowledge, this case is only the fourth case of a tumor necrosis factor alpha antagonist being used in the treatment of AIE and the first case of adalimumab being used.

The Jarisch-Herxheimer reaction: revisited.

The Jarisch-Herxheimer reaction (JHR) is a transient immunological phenomenon seen commonly in patients during treatment for syphilis, and it manifests clinically with short-term constitutional symptoms such as fever, chills, headache and myalgias, besides exacerbation of existing cutaneous lesions. The complex interplay of its underlying patho-physiological mechanisms continues to elude modern medicine, ever since it was described over a century ago. An increase in the incidence of JHR may be expected among patients co-infected with HIV and other infectious diseases including syphilis. Since this subject has not received much attention in recent literature except for brief mentions in standard textbooks, we felt it important to provide an overview of its various attributes including the current concepts in pathophysiology and management.

Clopidogrel resistance.

Clopidogrel resistance is an emerging clinical scenario, as antiplatelet therapy has become the cornerstone of modern cardiovascular treatment. This leads to an increase in stent thromboses and recurrent ischemic events which add to the health care costs, and increased periprocedural morbidity and mortality. Management of clopidogrel resistance is challenging as there are no standardized guidelines. The arrival of newer antiplatelet drugs and the detection of genetic polymorphisms in susceptible populations may have an impact on the management. Further trials are needed regarding the target population who should be screened for clopidogrel resistance, a standardized diagnostic test to detect clopidogrel resistance, the role of pharmacogenetics, and the need for tailored therapeutic options for a patient with clopidogrel resistance.

Giant sporadic renal angiomyolipoma treated with nephron-sparing surgery.

Angiomyolipoma is a benign renal tumor that tends to grow with time and can be associated with complications, such as hemorrhage and pain, requiring active intervention. Nephron-sparing surgery for sporadic renal angiomyolipomas offers preservation of renal function and is associated with acceptable complication and recurrence rates. Preoperative embolization of the large tumors is recommended to avoid excess blood loss during surgery. We report a case of giant renal angiomyolipoma treated with preoperative embolization, followed by partial nephrectomy without complications.