DNMT Inhibitors Increase Methylation in the Cancer Genome

In conclusion, we showed hypermethylation of CpGs as a novel mechanism of action for DNMTi agents and identified 638 hypermethylated molecular targets (CpGs) common to decitabine and azacytidine therapy. These novel results suggest that hypermethylation of CpGs should be considered when predicting the DNMTi responses and side effects in cancer patients. Introduction DNA methyltransferase inhibitors (DNMTi) are widely used as chemical tools for hypomethylating the genome, with an aim to understand the role of DNA methylation in multiple processes (e.g., X-chromosome inactivation and DNA imprinting) and as an anti-cancer therapy (Minkovsky et al., 2015; Ramos M.P. et al., 2015; Bohl et al., 2018). At present, two DNMTi drugs, decitabine and azacytidine, have been approved for treating patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) (Döhner et al., 2017; Bohl et al., 2018), and are also being tested as therapeutic options in multiple solid cancers (Fu et al., 2011; Singal et al., 2015; Lee et al., 2018). However, treatment response rates have remained very low in both solid and hematological cancers patients (Derissen et al., 2013; Nervi et al., 2015; Koch et al., 2018). At the same time, DNMTi treatment incurs considerable side effects (e.g., bleeding, anemia, and joint pain). Attempts are being made to improve treatment efficacy (e.g., by testing combinations of DNMTis with other anticancer agents) and safety (e.g., by stratifying can...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research

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We report a rare case of 74-year-old female of primary hyperparathyroidism caused by parathyroid carcinoma (PC) and coexisting multiple parathyroid adenomas. She was referred to our hospital for primary hyperparathyroidism and a suspected thyroid tumor. She had no family history of malignant tumor. Computed tomography (CT) and ultrasonography of the neck revealed some masses posterior to both thyroid lobes. Those masses were believed to be parathyroid lesions. However, another mass located posterior to the right upper thyroid lobe seemed to be heterogeneous, which indicated a malignant thyroid tumor as well as parathyroid ...
Source: Endocrine Journal - Category: Endocrinology Tags: Endocr J Source Type: research
We describe a unique, complex case of a man resulted affected by both APS-2 and MEN-2a. The patient developed Hashimoto's thyroiditis, diabetes mellitus type 1 and AAD, despite testing negative for adrenal cortex autoantibodies (ACA) and steroid 21-hydroxylase autoantibodies (21-OHAb). Moreover, he had also a family history for MEN-2a and he first developed medullay thyroid cancer, then bilateral pheochromocytoma on the adrenal substrate of an AAD. On adrenal histology we found complete bilateral cortical atrophy in the presence of a lymphocytic infiltration and fibrosis, confirming an ACA and 21-OHAb-negative AAD. This da...
Source: Endocrine Journal - Category: Endocrinology Tags: Endocr J Source Type: research
CONCLUSIONS: The ATA risk stratification system is a reliable predictor of short-term outcomes in patients with DTC in real-world clinical settings characterized by center heterogeneity in terms of size, location, level of care, local management strategies, and resource availability. PMID: 32475305 [PubMed - as supplied by publisher]
Source: Thyroid : official journal of the American Thyroid Association - Category: Endocrinology Tags: Thyroid Source Type: research
In conclusion, we suggest that in the presence of intolerance or resistance to colchicine, interleukin (IL)-1 inhibition could suppress peritoneal inflammation and prevent MSTs. PMID: 32477360 [PubMed - in process]
Source: Pain Physician - Category: Anesthesiology Authors: Tags: Front Immunol Source Type: research
CONCLUSION: Inpatient consultations is very useful to the patient and managing physician. Although a better knowledge in the identification of common ophthalmic conditions can help to reduce the number of inpatient consults from other medical specialties. PMID: 32476114 [PubMed - in process]
Source: Pain Physician - Category: Anesthesiology Authors: Tags: West Afr J Med Source Type: research
Authors: Chuling F, Qian Z, Na W, Xiaoyan J, Zuojun X Abstract Background: Pulmonary sarcoidosis patients who get disease progression despite corticosteroid treatment or can't tolerate corticosteroid required second-line drug. Methotrexate (MTX) is the most widely used in our clinical practice. Data on its safety and efficacy at different doses are still limited, especially for those without folic acid supplements. Objective: To report effectiveness of different MTX dosages and tolerability of MTX in pulmonary sarcoidosis without folic acid supplements. Methods: A retrospective study on pulmonary sarcoidosi...
Source: Sarcoidosis Vasculitis and Diffuse Lung Diseases - Category: Respiratory Medicine Tags: Sarcoidosis Vasc Diffuse Lung Dis Source Type: research
Source: World Journal of Surgery - Category: Surgery Source Type: research
Source: World Journal of Surgery - Category: Surgery Source Type: research
Source: World Journal of Surgery - Category: Surgery Source Type: research
Source: World Journal of Surgery - Category: Surgery Source Type: research
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