Prominent role for T cell-derived Tumour Necrosis Factor for sustained control of Mycobacterium tuberculosis infection

Tumour Necrosis Factor (TNF) is critical for host control of M. tuberculosis, but the relative contribution of TNF from innate and adaptive immune responses during tuberculosis infection is unclear. Myeloid versus T-cell-derived TNF function in tuberculosis was investigated using cell type-specific TNF deletion. Mice deficient for TNF expression in macrophages/neutrophils displayed early, transient susceptibility to M. tuberculosis but recruited activated, TNF-producing CD4+ and CD8+ T-cells and controlled chronic infection. Strikingly, deficient TNF expression in T-cells resulted in early control but susceptibility and eventual mortality during chronic infection with increased pulmonary pathology. TNF inactivation in both myeloid and T-cells rendered mice critically susceptible to infection with a phenotype resembling complete TNF deficient mice, indicating that myeloid and T-cells are the primary TNF sources collaborating for host control of tuberculosis. Thus, while TNF from myeloid cells mediates early immune function, T-cell derived TNF is essential to sustain protection during chronic tuberculosis infection

DETECTION OF AUTOANTIBODIES RECOGNIZING CANCERRETINA ANTIGEN RECOVERIN IN BLOOD OF PATIENTS WITH NON-INVASIVE FOLLICULAR THYROID NEOPLASMS WITH PAPILLARY-LIKE NUCLEAR FEATURES (NIFTP)

Autoantibodies recognizing the cancer-retina autoantigen called recoverin (RCVRN-AutoAb) may serve as a highly specific biomarker of cancer-associated retinopathy. However, they may also be found in some cancer patients without clinical evidence of retinopathy. In the present study, dot-ELISA and Western blot assays were used to demonstrate the presence of circulating RCVRN-AutoAb in 4/7 (57%) of patients with recently recognized pathological entity, non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP); other thyroid tumors represented by follicular adenomas, and classical and follicular variants of papillary thyroid carcinomas, demonstrated low frequencies of RCVRN-AutoAb (0/15, 1/20 (5%) and 1/15 (7%), respectively), with no significant differences from healthy individuals (0/15). Our data implicate the circulating RCVRN-AutoAb as a potential biomarker of NIFTP capable of discrimination of this novel pathological entity from other thyroid tumors

Histone deacetylases as new therapy targets for platinum-resistant epithelial ovarian cancer

Introduction: In developed countries, ovarian cancer is the fourth most common cancer in women. Due to the nonspecific symptomatology associated with the disease many patients with ovarian cancer are diagnosed late, which leads to significantly poorer prognosis. Apart from surgery and radiotherapy, a substantial number of ovarian cancer patients will undergo chemotherapy and platinum based agents are the mainstream first-line therapy for this disease. Despite the initial efficacy of these therapies, many women relapse; therefore, strategies for second-line therapies are required. Regulation of DNA transcription is crucial for tumour progression, metastasis and chemoresistance which offers potential for novel drug targets. Methods: We have reviewed the existing literature on the role of histone deacetylases, nuclear enzymes regulating gene transcription. Results and conclusion: Analysis of available data suggests that a signifant proportion of drug resistance stems from abberant gene expression, therefore HDAC inhibitors are amongst the most promising therapeutic targets for cancer treatment. Together with genetic testing, they may have a potential to serve as base for patient-adapted therapies