The past decade has highlighted the central role of epigenetic processes in cancer causation, progression and treatment. Next-generation sequencing is providing a window for visualizing the human epigenome and how it is altered in cancer. This view provides many surprises, including linking epigenetic abnormalities to mutations in genes that control DNA methylation, the packaging and the function of DNA in chromatin, and metabolism. Epigenetic alterations are leading candidates for the development of specific markers for cancer detection, diagnosis and prognosis. The enzymatic processes that control the epigenome present new opportunities for deriving therapeutic strategies designed to reverse transcriptional abnormalities that are inherent to the cancer epigenome.

http://sdjohnston.faculty.noctrl.edu/360/Cancer%20Epigenome.pdf

A decade of exploring the cancer epigenome — biological and translational implications

The IL-6/JAK/STAT3 pathway is aberrantly hyperactivated in many types of cancer, and such hyperactivation is generally associated with a poor clinical prognosis In the tumour microenvironment, IL-6/JAK/STAT3 signalling acts to drive the proliferation, survival, invasiveness, and metastasis of tumour cells, while strongly suppressing the antitumour immune response Thus, treatments that target the IL-6/JAK/STAT3 pathway in patients with cancer are poised to provide therapeutic benefit by directly inhibiting tumour cell growth and by stimulating antitumour immunity Agents targeting IL-6, the IL-6 receptor, or JAKs have already received FDA approval for the treatment of inflammatory conditions or myeloproliferative neoplasms and for the management of certain adverse effects of chimeric antigen receptor T cells, and are being further evaluated in patients with haematopoietic malignancies and in those with solid tumours Novel inhibitors of the IL-6/JAK/STAT3 pathway, including STAT3-selective inhibitors, are currently in development Herein, we review the role of IL-6/JAK/STAT3 signalling in the tumour microenvironment and the status of preclinical and clinical investigations of agents targeting this pathway We also discuss the potential of combining IL-6/JAK/STAT3 inhibitors with currently approved therapeutic agents directed against immune-checkpoint inhibitors

Targeting the IL-6/JAK/STAT3 signalling axis in cancer.

MicroRNAs (miRNAs) are endogenous ∼23 nt RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. This review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.

MicroRNAs: Target Recognition and Regulatory Functions

With the WHO in China

Extracellular matrix hydrogels from decellularized tissues: Structure and function.

Automated diagnosis of breast ultrasonography images using deep neural networks.

Background 
Aberrant DNA methylation patterns might be used as a biomarker for diagnosis and management of cancer patients.


Methods and Findings 
To achieve a gene panel for developing a breast cancer blood-based test we quantitatively assessed the DNA methylation proportion of 248 CpG sites per sample (total of 31,248 sites in all analyzed samples) on 10 candidate genes (APC, BIN1, BMP6, BRCA1, CST6, ESR-b, GSTP1, P16, P21 and TIMP3). The number of 126 samples consisting of two different cohorts was used (first cohort: plasma samples from breast cancer patients and normal controls; second cohort: triple matched samples including cancerous tissue, matched normal tissue and serum samples). In the first cohort, circulating cell free methylated DNA of the 8 tumor suppressor genes (TSGs) was significantly higher in patients with breast cancer compared to normal controls (P<0.01). In the second cohort containing triple matched samples, seven genes showed concordant hypermethylated profile in tumor tissue and serum samples compared to normal tissue (P<0.05). Using eight genes as a panel to develop a blood-based test for breast cancer, a sensitivity and specificity of more than 90% could be achieved in distinguishing between tumor and normal samples.


Conclusions 
Our study suggests that the selected TSG panel combined with the high-throughput technology might be a useful tool to develop epigenetic based predictive and prognostic biomarker for breast cancer relying on pathologic methylation changes in tumor tissue, as well as in circulation.

/pdf/hypermethylation-of-tumor-suppressor-genes-involved-in-4n9xcumhro.pdf

Hypermethylation of tumor suppressor genes involved in critical regulatory pathways for developing a blood-based test in breast cancer.

Background: Breast cancer stem cells (BCSCs) can be enriched by culturing of cells in non-adherent nondifferentiating conditions. However, culturing mammospheres from primary breast tumors are costly and difficult to control. In order to overcome problems associated with using primary human tissues, continuous breast cancer cell lines have been developed from various sources. Methods: In this study, a luminal subtype breast cancer cell line MCF-7 and a basal subtype cell line MDAMB- 231 were chosen. We explored the optimal culturing system for BCSCs from the two cell lines and primary breast tumors. Then, mammosphere formation efficiency (MFE), CD44 + /CD24 –/low ESA + Lin – cell proportion in mammospheres, and tumorigenecity of mammospheres generated from the two breast cancer cell lines and primary breast tumors were compared. Results: Enzymatic digestion of 60 mins and the addition of B27 to the culture medium were optimal for mammosphere culturing. Mammospheres could be formed in all the three cells, in which MCF-7 had the highest MFE. After 3 weeks culture, CD44 + /CD24 –/low ESA + Lin – cell proportion in mammospheres from MCF-7, MDA-MB-231 cells and primary breast tumors was 95.0%±2.5%, 82%±22% and 21.5%±1.0%, respectively. A total of 1,000 cells from MCF-7, MDA-MB-231 mammospheres but not primary mammospheres were tumorigenic. Conclusions: This study validates the use of breast cancer cell lines as models to elucidate the nature of BCSCs.

/pdf/comparison-of-mammosphere-formation-from-breast-cancer-cell-220oa9tpg0.pdf

Comparison of mammosphere formation from breast cancer cell lines and primary breast tumors

Gastrointestinal microbiome plays as a symbiont which provides protection effect against invading pathogens, aids in the immune system development, nutrient reclamation and absorption as well as molecule breakdown. And it may avert carcinogenesis through these biological activities. By now, studies have been carried out to elaborate the association between gastrointestinal microbiome and breast cancer. It has been implicated that breast cancer was substantially associated with estrogen-dependent and estrogen-independent functions of gastrointestinal microbiome. Evidence from animal experiments also confirmed mammary tumor-related changes in microbial community. The possible mechanisms involve estrogen metabolism, immune regulation, obese status and so forth. Based on the current evidence, cues on future management strategies of breast cancer such as antibiotics and dietary interventions are proposed. In conclusion, large-scale clinical studies and bench-based researches are needed to validate the associations and elaborate the mechanisms, so as to reduce the risk of breast cancer and improve the outcomes of those already diagnosed.

Gastrointestinal microbiome and breast cancer: correlations, mechanisms and potential clinical implications.

were significantly higher than those in adjacent nontumor tissues, respectively. With survival analysis, only number of lymph node metastasis (N stage) was identified as the independent predic tors of the OS of breast cancer patients. Besides, we demonstrated there was the most prominent correlation between STAT3 expression and lymph node metastasis in breast cancer tissues by using the multinominal regression method. Conclusion: STAT3, a poor survival biomarker potential association with lymph node metastasis, was suitable for predication the OS of breast cancer patients after curative resection.

/pdf/stat3-a-poor-survival-predicator-is-associated-with-lymph-3zsbpbragf.pdf

Qing Lv

Papers

Automated diagnosis of breast ultrasonography images using deep neural networks.

Hypermethylation of tumor suppressor genes involved in critical regulatory pathways for developing a blood-based test in breast cancer.

Comparison of mammosphere formation from breast cancer cell lines and primary breast tumors

Gastrointestinal microbiome and breast cancer: correlations, mechanisms and potential clinical implications.

STAT3, a Poor Survival Predicator, Is Associated with Lymph Node Metastasis from Breast Cancer