3D Cell Culture for the Study of Microenvironment-Mediated Mechanostimuli to the Cell Nucleus: An Important Step for Cancer Research.

The discovery that the stiffness of the tumor microenvironment (TME) changes during cancer progression motivated the development of cell culture involving extracellular mechanostimuli, with the intent of identifying mechanotransduction mechanisms that influence cell phenotypes. Collagen I is a main extracellular matrix (ECM) component used to study mechanotransduction in three-dimensional (3D) cell culture. There are also models with interstitial fluid stress that have been mostly focusing on the migration of invasive cells. We argue that a major step for the culture of tumors is to integrate increased ECM stiffness and fluid movement characteristic of the TME. Mechanotransduction is based on the principles of tensegrity and dynamic reciprocity, which requires measuring not only biochemical changes, but also physical changes in cytoplasmic and nuclear compartments. Most techniques available for cellular rheology were developed for a 2D, flat cell culture world, hence hampering studies requiring proper cellular architecture that, itself, depends on 3D tissue organization. New and adapted measuring techniques for 3D cell culture will be worthwhile to study the apparent increase in physical plasticity of cancer cells with disease progression. Finally, evidence of the physical heterogeneity of the TME, in terms of ECM composition and stiffness and of fluid flow, calls for the investigation of its impact on the cellular heterogeneity proposed to control tumor phenotypes. Reproducing, measuring and controlling TME heterogeneity should stimulate collaborative efforts between biologists and engineers. Studying cancers in well-tuned 3D cell culture platforms is paramount to bring mechanomedicine into the realm of oncology.

Current and Emerging Magnetic Resonance-Based Techniques for Breast Cancer.

Breast cancer is the most commonly diagnosed cancer among women worldwide, and early detection remains a principal factor for improved patient outcomes and reduced mortality. Clinically, magnetic resonance imaging (MRI) techniques are routinely used in determining benign and malignant tumor phenotypes and for monitoring treatment outcomes. Static MRI techniques enable superior structural contrast between adipose and fibroglandular tissues, while dynamic MRI techniques can elucidate functional characteristics of malignant tumors. The preferred clinical procedure-dynamic contrast-enhanced MRI-illuminates the hypervascularity of breast tumors through a gadolinium-based contrast agent; however, accumulation of the potentially toxic contrast agent remains a major limitation of the technique, propelling MRI research toward finding an alternative, noninvasive method. Three such techniques are magnetic resonance spectroscopy, chemical exchange saturation transfer, and non-contrast diffusion weighted imaging. These methods shed light on underlying chemical composition, provide snapshots of tissue metabolism, and more pronouncedly characterize microstructural heterogeneity. This review article outlines the present state of clinical MRI for breast cancer and examines several research techniques that demonstrate capacity for clinical translation. Ultimately, multi-parametric MRI-incorporating one or more of these emerging methods-presently holds the best potential to afford improved specificity and deliver excellent accuracy to clinics for the prediction, detection, and monitoring of breast cancer.

Evaluation of α-amylase, lipase inhibition and in-vivo pharmacological activities of Eucalyptus camaladulensis Dehnh leaf extract.

In this present study, phytochemical screening, anti-ulcer assay, anti-diarrhea assay, anti-inflammatory assay, analgesic assay, lipase activity assay, amylase activity assay and the anti-bacterial activity of Eucalyptus camaladulensis Dehnh leaf extracted with methanol and 50% ethanol was analyzed for biological significance. Physical characterization of the non-volatile component revealed the higher yield of 16.92% in 50% ethanol expediting the use of 50% ethanol as a better alternative. Further use of crude extract revealed 33.89% (IC50 = 1.44 mg/ml) of α-amylase inhibition by methanol extract and 33.87% (IC50 = 3.21 mg/ml) lipase inhibition by 50% ethanol extract. Furthermore, 44.44% protective ratio towards ulcer was observed with the methanol extract, whereas 54.58% anti-inflammatory activity was shown by the 50% ethanol extract. The effectiveness of the extract was further enhanced by the presence of 62.54% motility and best analgesic property at 180 min of the exposure of the extract orally. The antioxidant activity of crude methanol extract revealed an IC50 value 601.8 µg/ml whereas, ethanol extract showed 1279.58 µg/ml in DPPH assay. Result revealed several health benefits of E. camaldulensis Dehnh leaf.

Cell Culture and Coculture for Oncological Research in Appropriate Microenvironments.

With the increase in knowledge on the importance of the tumor microenvironment, cell culture models of cancers can be adapted to better recapitulate physiologically relevant situations. Three main microenvironmental factors influence tumor phenotype: the biochemical components that stimulate cells, the fibrous molecules that influence the stiffness of the extracellular matrix, and noncancerous cells like epithelial cells, fibroblasts, endothelial cells, and immune cells. Here we present methods for the culture of carcinomas in the presence of a matrix of specific stiffness, and for the coculture of tumors and fibroblasts as well as epithelial cells in the presence of matrix. Information is provided to help with choice and assessment of the matrix support and in working with serum-free medium. Using the example of a tissue chip recapitulating the environmental geometry of carcinomas, we also highlight the development of engineered platforms that provide exquisite control of cell culture parameters necessary in research and development. © 2019 by John Wiley & Sons, Inc.