The Mechanisms of Action of Tumor Treating Fields.

Tumor treating fields (TTFields), a new modality of cancer treatment, are electric fields transmitted transdermally to tumors. The FDA has approved TTFields for the treatment of glioblastoma multiforme and mesothelioma, and they are currently under study in many other cancer types. While antimitotic effects were the first recognized biological anticancer activity of TTFields, data have shown that tumor treating fields achieve their anticancer effects through multiple mechanisms of action.

An overview of potential novel mechanisms of action underlying Tumor Treating Fields-induced cancer cell death and their clinical implications.

Traditional cancer therapy choices for clinicians are surgery, chemotherapy, radiation and immune therapy which are used either standalone therapies or in various combinations. Other physical modalities beyond ionizing radiation include photodynamic therapy and heating and the more recent approach referred to as Tumor Treating Fields (TTFields). TTFields are intermediate frequency, low-intensity, alternating electric fields that are applied to tumor regions and cells using noninvasive arrays.

Tumor treating fields cause replication stress and interfere with DNA replication fork maintenance: Implications for cancer therapy.

Tumor treating fields (TTFields) is a noninvasive physical modality of cancer therapy that applies low-intensity, intermediate frequency, and alternating electric fields to a tumor. Interference with mitosis was the first mechanism describing the effects of TTFields on cancer cells; however, TTFields was shown to not only reduce the rejoining of radiation-induced DNA double-strand breaks (DSBs), but to also induce DNA DSBs. The mechanism(s) by which TTFields generates DNA DSBs is related to the generation of replication stress including reduced expression of the DNA replication complex genes MCM6 and MCM10 and the Fanconi's Anemia pathway genes.

miR-125a-5p Functions as Tumor Suppressor microRNA And Is a Marker of Locoregional Recurrence And Poor prognosis in Head And Neck Cancer.

MicroRNAs (miRNAs) are short single-stranded RNAs, measuring 21 to 23 nucleotides in length and regulate gene expression at the post-transcriptional level through mRNA destabilization or repressing protein synthesis. Dysregulation of miRNAs can lead to tumorigenesis through changes in regulation of key cellular processes such as cell proliferation, cell survival, and apoptosis. miR-125a-5p has been implicated as a tumor suppressor miRNA in malignancies such as non-small cell lung cancer and colon cancer.

Tumor-treating fields elicit a conditional vulnerability to ionizing radiation via the downregulation of BRCA1 signaling and reduced DNA double-strand break repair capacity in non-small cell lung cancer cell lines.

The use of tumor-treating fields (TTFields) has revolutionized the treatment of recurrent and newly diagnosed glioblastoma (GBM). TTFields are low-intensity, intermediate frequency, alternating electric fields that are applied to tumor regions and cells using non-invasive arrays. The predominant mechanism by which TTFields are thought to kill tumor cells is the disruption of mitosis.

Kidney protein profiling of Wilms' tumor patients by analysis of formalin-fixed paraffin-embedded tissue samples.

Unlabelled: Wilms' tumor (nephroblastoma, WT) is the most frequent renal cancer in children. However, molecular details leading to WT have not been characterized sufficiently yet. Proteomic studies might provide new insights but are hampered by limited availability of fresh frozen tissue specimen.

Metastasis-associated protein 1/histone deacetylase 4-nucleosome remodeling and deacetylase complex regulates phosphatase and tensin homolog gene expression and function.

Metastasis-associated protein 1 (MTA1) is widely overexpressed in human cancers and is associated with malignant phenotypic changes contributing to morbidity in the associated diseases. Here we discovered for the first time that MTA1, a master chromatin modifier, transcriptionally represses the expression of phosphatase and tensin homolog (PTEN), a tumor suppressor gene, by recruiting class II histone deacetylase 4 (HDAC4) along with the transcription factor Yin-Yang 1 (YY1) onto the PTEN promoter. We also found evidence of an inverse correlation between the expression levels of MTA1 and PTEN in physiologically relevant breast cancer microarray datasets.

Proteome analysis reveals new mechanisms of Bcl11b-loss driven apoptosis.

The Bcl11b protein was shown to be important for a variety of functions such as T cell differentiation, normal development of central nervous system, and DNA damage response. Malignant T cells undergo apoptotic cell death upon BCL11B down-regulation, however, the detailed mechanism of cell death is not fully understood yet. Here we employed two-dimensional difference in-gel electrophoresis (2D-DIGE), mass spectrometry and cell biological experiments to investigate the role of Bcl11b in malignant T cell lines such as Jurkat and huT78.

Complete primary structure of a newly characterized galactose-specific lectin from the seeds of Dolichos lablab.

A new unique lectin (galactose-specific) purified from the seeds of Dolichos lablab, designated as DLL-II is a heterodimer composed of closely related subunits alpha and beta. These were separated by SDS-PAGE and isolated by electroelution. By ESI-MS analysis their molecular masses were found to be 30.