A systematic understanding of the evolution and growth dynamics of invasive solid tumors in response to different chemotherapy strategies is crucial for the development of individually optimized oncotherapy. Here, we develop a hybrid three-dimensional (3D) computational model that integrates pharmacokinetic model, continuum diffusion-reaction model and discrete cell automaton model to investigate 3D invasive solid tumor growth in heterogeneous microenvironment under chemotherapy. Specifically, we consider the effects of heterogeneous environment on drug diffusion, tumor growth, invasion and the drug-tumor interaction on individual cell level. We employ the hybrid model to investigate the evolution and growth dynamics of avascular invasive solid tumors under different chemotherapy strategies. Our simulations indicate that constant dosing is generally more effective in suppressing primary tumor growth than periodic dosing, due to the resulting continuous high drug concentration. In highly heterogeneous microenvironment, the malignancy of the tumor is significantly enhanced, leading to inefficiency of chemotherapies. The effects of geometrically-confined microenvironment and non-uniform drug dosing are also investigated. Our computational model, when supplemented with sufficient clinical data, could eventually lead to the development of efficient in silico tools for prognosis and treatment strategy optimization.

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Objective: To explore the association of famine exposure in early life with the risk of metabolic syndrome (MS) in the Chinese adults. Methods: Data were obtained from the wave 2009 of the China Health and Nutrition Survey. MS was identified when 3 or more of the following components happened: (1) waist circumference > 90 cm in males or > 85 cm in females; (2) fasting glucose ≥6.1 mmol/L; (3) systolic blood pressure ≥130 mm Hg/diabolic blood pressure ≥85 mm Hg; (4) fasting triglyceride ≥1.70 mmol/L; and (5) high-density lipids cholesterol < 1.04 mmol/L. All participants were divided into 5 groups: no exposure, born after 1961; fetal life exposure, between 1959 and 1961; early childhood exposure, between 1956 and 1958; mid-childhood exposure, between 1953 and 1955; and late childhood exposure, between 1949 and 1952. A total of 2,080 subjects were included in this study. Results: In rural, famine exposure in fetal life and early childhood was associated with the lower risk of MS (p = 0.0491 and 0.0245; OR 0.583 and 0.703; and OR, 95% CI 0.341-0.998 and 0.517-0.956, respectively). But famine exposure in late childhood was associated with the higher risk of MS (p = 0.0140; OR 3.096; and OR, 95% CI 1.257-7.625). Famine exposure in early childhood was associated with the lower risk of MS (p = 0.0120; OR 0.633; and OR, 95% CI 0.443-0.904) in males. Conclusions: Famine exposure in mid-and late-childhood was associated with the higher risk of MS, especially in rural, males, and severe famine areas.

Development of an in vitro three-dimensional (3D) model that closely mimics actual environment of tissue has become extraordinarily important for anti-cancer study. In recent years, various 3D cell culture systems have been developed, with multicellular tumor spheroids being the most popular and effective model. In this work, we present a microfluidic device used as a robust platform for generating core-shell hydrogel microspheres with precisely controlled sizes and varied components of hydrogel matrix. To gain a better understanding of the governing mechanism of microsphere formation, computational models based on multiphase flow were developed to numerically model the droplet generation and velocity field evolution process with COMSOL Multiphysics software. Our modeling results show good agreement with experiments in size dependence on flow rate as well as effect of vortex flow on microsphere formation. With real-time tuning of the flow rates of aqueous phase and oil phase, tumor cells were encapsulated into the microspheres with controllable coreshell structure and different volume ratios of core (comprised of alginate, Matrigel, and/or Collagen) and shell (comprised of alginate). Viability of cells in four different hydrogel matrices were evaluated by standard acridine orange (AO) and propidium iodide (PI) staining. The proposed microfluidic system can play an important role in engineering the in vitro micro-environment of tumor spheroids to better mimic the actual in vivo 3D spatial structure of a tumor and perfect the 3D tumor models for more effective clinical therapies.

The process of in situ tumors developing into malignant tumors and exhibiting invasive behavior is extremely complicated . From a biophysical point of view, it is a phase change process affected by many factors, including cell-to-cell, cell-to-chemical material, cell-to-environment interaction, etc. In this study, we constructed spheroids based on green fluorescence metastatic breast cancer cells MDA-MB-231 to simulate malignant tumors in vitro, while constructed a three-dimensional (3D) biochip to simulate a micro-environment for the growth and invasion of spheroids. In the experiment, the 3D spheroid was implanted into the chip, and the oriented collagen fibers controlled by collagen concentration and injection rate could guide the MDA-MB-231 cells in the spheroid to undergo directional invasion. The experiment showed that the oriented fibers greatly accelerated the invasion speed of MDA-MB-231 cells compared with the traditional uniform tumor micro-environment, namely obvious invasive branches appeared on the spheroids within 24 hours. In order to analyze this interesting phenomenon, we have developed a quantitative analyzing approach to explore strong angle correlation between the orientation of collagen fibers and invasive direction of cancer cell. The results showed that the oriented collagen fibers produced by the chip can greatly stimulate the invasion potential of cancer cells. This biochip is not only conducive to modeling cancer cell metastasis and studying cell invasion mechanisms, but also has the potential to build a quantitative evaluation platform that can be used in future chemical drug treatments.