Dysregulated mitogen-activated protein kinase pathway mediated cell cycle disruption in sporadic parathyroid tumors.

OBJECTIVES: The study was designed to evaluate expression profiling of mitogen-activated protein kinase (MAPK) signalling pathway genes in sporadic parathyroid adenoma. METHODS: Expression of MAPK signalling pathway genes including activated transcription factors and cell cycle regulatory genes was analysed by real-time PCR- based array in parathyroid adenoma (N = 20) and normal parathyroid tissue (N = 4). RESULTS: MAPK signalling pathway as studied by PCR array revealed that a total of 22 genes were differentially expressed (≥ twofold change, p ≤ 0.05) in parathyroid adenoma. Up-regulated genes were ARAF, MAPK12, CREBBP, MYC, HSPB1, HRAS, CDK4, CCND1, and E2F1, and down-regulated genes were MAP4K1, DLK1, MAP3K4, MAPK10, MAPK8, ATF2, SMAD4, MEF2C, LAMTOR3, FOS, CDKN2A CDKN2B, and RB1. The present study revealed that ERK1/2 signalling pathway with up-regulation of HRAS, ARAF, and MEK1 genes and up-regulation of positive regulators of cell cycle (CCND1, CDK4, and E2F1) and down-regulation negative regulators of cell cycle (CDKN2A, CDKN2B, and RB1) made highly dysregulated MAPK signalling pathway in parathyroid adenoma. Expression of CDK4 was positively associated with plasma PTH level (r = 0.60, p = 0.04) and tumor weight (r = 0.80, p = 0.02) of the adenoma patients, respectively. Expression of CDKN2A was correlated negatively with PTH level (r = - 0.52, p = 0.04) of the adenoma patients. CONCLUSION: The current study revealed that ERK pathway and associated cell cycle regulator genes are dysregulated in sporadic parathyroid adenoma.

Quantitative proteomics analysis of sporadic parathyroid adenoma tissue samples.

OBJECTIVE: Molecular pathogenesis of parathyroid tumors is incompletely understood. Identification of novel molecules and understanding their role in parathyroid tumorigenesis by proteomics approach would be informative with potential clinical implications. METHOD: Adenomatous (n = 5) and normal (n = 2) parathyroid tissue lysates were analyzed for protein profile by LC-MS/MS method and the proteins were classified using bioinformatics tools such as PANTHER and toppfun functional enrichment tool. Identified proteins were further validated by western blotting and qRT-PCR (n = 20). RESULT: Comparative proteomics analysis revealed that a total of 206 proteins (74 upregulated and 132 downregulated) were differentially expressed (≥ twofold change) in adenomas. Bioinformatics analysis revealed that 48 proteins were associated with plasma membrane, 49 with macromolecular complex, 39 were cytoplasm, 38 were organelle related, 21 were cell junction and 10 were extracellular proteins. These proteins belonged to a diverse protein family such as enzymes, transcription factors, cell signalling, cell adhesion, cytoskeleton proteins, receptors, and calcium-binding proteins. The major biological processes predicted for the proteins were a cellular, metabolic and developmental process, cellular localization, and biological regulation. The differentially expressed proteins were found to be associated with MAPK, phospholipase C (PLC) and phosphatidylinositol (PI) signalling pathways, and with chromatin organization. Western blot and qRT-PCR analysis of three proteins (DNAJC2, ACO2, and PRDX2) validated the LC-MS/MS findings. CONCLUSION: This exploratory study demonstrates the feasibility of proteomics approach in finding the dysregulated proteins in benign parathyroid adenomas, and our preliminary results suggest that MAPK, PLC and PI signalling pathways and chromatin organization are involved in parathyroid tumorigenesis.

Primary hyperparathyroidism: review and recommendations on evaluation, diagnosis, and management. A Canadian and international consensus.

The purpose of this review is to assess the most recent evidence in the management of primary hyperparathyroidism (PHPT) and provide updated recommendations for its evaluation, diagnosis and treatment. A Medline search of "Hyperparathyroidism. Primary" was conducted and the literature with the highest levels of evidence were reviewed and used to formulate recommendations. PHPT is a common endocrine disorder usually discovered by routine biochemical screening. PHPT is defined as hypercalcemia with increased or inappropriately normal plasma parathyroid hormone (PTH). It is most commonly seen after the age of 50 years, with women predominating by three to fourfold. In countries with routine multichannel screening, PHPT is identified earlier and may be asymptomatic. Where biochemical testing is not routine, PHPT is more likely to present with skeletal complications, or nephrolithiasis. Parathyroidectomy (PTx) is indicated for those with symptomatic disease. For asymptomatic patients, recent guidelines have recommended criteria for surgery, however PTx can also be considered in those who do not meet criteria, and prefer surgery. Non-surgical therapies are available when surgery is not appropriate. This review presents the current state of the art in the diagnosis and management of PHPT and updates the Canadian Position paper on PHPT. An overview of the impact of PHPT on the skeleton and other target organs is presented with international consensus. Differences in the international presentation of this condition are also summarized.

Multiple nodules on the face and trunk in metastatic adenocarcinoma of unknown primary origin.

Metastatic cancer of unknown primary (CUP) may unexpectedly manifest on the skin and subcutaneous tissue, prompting the patient to first visit a dermatologist. We describe an interesting case of cutaneous metastases from poorly differentiated adenocarcinoma of an unknown primary site in a 57-year-old man. The CUP had an unusually long period of indolence between presentation as a solitary axillary lymph node metastasis and rapid cutaneous dissemination. The possible causes of such a presentation are reviewed, and the management is briefly discussed. Diagnosis of unusual cutaneous manifestations of occult systemic malignancies could pose a diagnostic challenge to dermatologists.

Fanconi's anemia in monozygotic twins.

Fanconi's anemia is one of the inherited causes of bone marrow failure. It is inherited in autosomal recessive fashion. It presents as aplastic anemia usually at the age of 7-8 yr. Leukemias and solid tumours are complications in those who manage to survive beyond two decades. Though it has been seen in siblings, reports in monozygotic twins have been very few.

Efficacy of kshara sutra mad from papaya and snuhi latex in the treatment of fistula in ano.

Fistula in ano is treated conventionally, by using the surgical techniques like fistulectomy or fistulotomy. In this practice of surgery there are many complications like delayed healing and stenosis or incontinence. The period of convalescence is also long. But after the advent of 'Kshara Sutra' for the treatment of fistula in ano, the complications he reduced to negligible level. It has become a boon to the patients of fistula in ano. But still the quest is continuing to improve the efficacy of Kshara sutra , to make it more acceptable, of late Kshara sutra  is being prepared in different ways of changing materials used for preparation, One such modification of Kshara sutra  is preparing it by the use of latex expressed form the tender fruit of papaya. The advantages of this thread are low corrosiveness, less pain and speed cutting besides easy availability.

Dhatwagni vyapara in carcinogenesis.

Dosha Dhatu Sammurchana is the basis of all pathogenisis. The state of Agni also should be considered in the pathogenisis. This will explain the disease at the cellular level in the parlances of Ayurveda. In cancer, enormous research is going on to understand the molecular and cellular level of Carcinogenisis, to formulate a cure for this disease. In Ayurveda with the help of various explanations can be made in the context of cancer. An effort is made in this paper in this regard which will definitely carve new ways in the field of cancer research.

Hyperparathyroidism following head and neck irradiation.

A history of head and neck irradiation in childhood or adolescence was found in 22 of 130 patients with primary hyperparathyroidism compared with only 12 of 400 control patients, a significant difference (P less than .025). Among 200 patients with a known history of childhood irradiation, biochemical or surgical evidence of hyperparathyroidism was found in ten, a prevalence of 5%. This is at least 30 times the prevalence of hyperparathyroidism in the general population (P less than .025). The data indicate that head and neck irradiation should be regarded as an important risk factor in the subsequent development of hyperparathyroidism.