TFAM as a sensor of UVC-induced mitochondrial DNA damage.

Mitochondria lack nucleotide excision DNA repair; however, mitochondrial DNA (mtDNA) is resistant to mutation accumulation following DNA damage. These observations suggest additional damage sensing or protection mechanisms. Transcription Factor A, Mitochondrial (TFAM) compacts mtDNA into nucleoids.

Androgen receptor monomers and dimers regulate opposing biological processes in prostate cancer cells.

Most prostate cancers express the androgen receptor (AR), and tumor growth and progression are facilitated by exceptionally low levels of systemic or intratumorally produced androgens. Thus, absolute inhibition of the androgen signaling axis remains the goal of current therapeutic approaches to treat prostate cancer (PCa). Paradoxically, high dose androgens also exhibit considerable efficacy as a treatment modality in patients with late-stage metastatic PCa.

The use of race terms in epigenetics research: considerations moving forward.

The field of environmental epigenetics is uniquely suited to investigate biologic mechanisms that have the potential to link stressors to health disparities. However, it is common practice in basic epigenetic research to treat race as a covariable in large data analyses in a way that can perpetuate harmful biases without providing any biologic insight. In this article, we i) propose that epigenetic researchers open a dialogue about how and why race is employed in study designs and think critically about how this might perpetuate harmful biases; ii) call for interdisciplinary conversation and collaboration between epigeneticists and social scientists to promote the collection of more detailed social metrics, particularly institutional and structural metrics such as levels of discrimination that could improve our understanding of individual health outcomes; iii) encourage the development of standards and practices that promote full transparency about data collection methods, particularly with regard to race; and iv) encourage the field of epigenetics to continue to investigate how social structures contribute to biological health disparities, with a particular focus on the influence that structural racism may have in driving these health disparities.

Acetazolamide: Old drug, new evidence?

Acetazolamide is an old drug used as an antiepileptic agent, amongst other indications. The drug is seldom used, primarily due to perceived poor efficacy and adverse events. Acetazolamide acts as a noncompetitive inhibitor of carbonic anhydrase, of which there are several subtypes in humans.

Is repeat fine needle aspiration required in thyroid nodules with initial benign cytology? Results from a large Irish series.

Unlabelled: BACKGROUND : Fine needle aspiration (FNA) cytology is the preferred method for assessing thyroid nodules for malignancy. Concern remains about the rate of false negative results. The primary aim of this study is to investigate the malignancy rate of thyroid nodules initially classified as benign (Thy 2).

Aging and CNS Myeloid Cell Depletion Attenuate Breast Cancer Brain Metastasis.

Purpose: Breast cancer diagnosed in young patients is often aggressive. Because primary breast tumors from young and older patients have similar mutational patterns, we hypothesized that the young host microenvironment promotes more aggressive metastatic disease.

Experimental Design: Triple-negative or luminal B breast cancer cell lines were injected into young and older mice side-by-side to quantify lung, liver, and brain metastases.

Targeting Dormant Ovarian Cancer Cells and in an Mouse Model of Platinum Resistance.

Spheroids exhibit drug resistance and slow proliferation, suggesting involvement in cancer recurrence. The protein kinase C inhibitor UCN-01 (7-hydroxystaurosporine) has shown higher efficacy against slow proliferating and/or quiescent ovarian cancer cells. In this study, tumorigenic potential was assessed using anchorage-independent growth assays and spheroid-forming capacity, which was determined with ovarian cancer cell lines as well as primary ovarian cancers.

Reactive astrocytic S1P3 signaling modulates the blood-tumor barrier in brain metastases.

Brain metastases are devastating complications of cancer. The blood-brain barrier (BBB), which protects the normal brain, morphs into an inadequately characterized blood-tumor barrier (BTB) when brain metastases form, and is surrounded by a neuroinflammatory response. These structures contribute to poor therapeutic efficacy by limiting drug uptake.

Liposomal Irinotecan Accumulates in Metastatic Lesions, Crosses the Blood-Tumor Barrier (BTB), and Prolongs Survival in an Experimental Model of Brain Metastases of Triple Negative Breast Cancer.

Purpose: The blood-tumor barrier (BTB) limits irinotecan distribution in tumors of the central nervous system. However, given that the BTB has increased passive permeability we hypothesize that liposomal irinotecan would improve local exposure of irinotecan and its active metabolite SN-38 in brain metastases relative to conventional irinotecan due to enhanced-permeation and retention (EPR) effect.

Methods: Female nude mice were intracardially or intracranially implanted with human brain seeking breast cancer cells (brain metastases of breast cancer model).

Semi-automated rapid quantification of brain vessel density utilizing fluorescent microscopy.

Background: Measurement of vascular density has significant value in characterizing healthy and diseased tissue, particularly in brain where vascular density varies among regions. Further, an understanding of brain vessel size helps distinguish between capillaries and larger vessels like arterioles and venules. Unfortunately, few cutting edge methodologies are available to laboratories to rapidly quantify vessel density.

Characterization of passive permeability at the blood-tumor barrier in five preclinical models of brain metastases of breast cancer.

The blood-brain barrier (BBB) is compromised in brain metastases, allowing for enhanced drug permeation into brain. The extent and heterogeneity of BBB permeability in metastatic lesions is important when considering the administration of chemotherapeutics. Since permeability characteristics have been described in limited experimental models of brain metastases, we sought to define these changes in five brain-tropic breast cancer cell lines: MDA-MB-231BR (triple negative), MDA-MB-231BR-HER2, JIMT-1-BR3, 4T1-BR5 (murine), and SUM190 (inflammatory HER2 expressing).