Rapid 3D Bioprinting of Glioblastoma Model Mimicking Native Biophysical Heterogeneity.

Glioblastoma multiforme (GBM) is the most lethal primary brain tumor characterized by high cellular and molecular heterogeneity, hypervascularization, and innate drug resistance. Cellular components and extracellular matrix (ECM) are the two primary sources of heterogeneity in GBM. Here, biomimetic tri-regional GBM models with tumor regions, acellular ECM regions, and an endothelial region with regional stiffnesses patterned corresponding to the GBM stroma, pathological or normal brain parenchyma, and brain capillaries, are developed. Patient-derived GBM cells, human endothelial cells, and hyaluronic acid derivatives are used to generate a species-matched and biochemically relevant microenvironment. This in vitro study demonstrates that biophysical cues are involved in various tumor cell behaviors and angiogenic potentials and promote different molecular subtypes of GBM. The stiff models are enriched in the mesenchymal subtype, exhibit diffuse invasion of tumor cells, and induce protruding angiogenesis and higher drug resistance to temozolomide. Meanwhile, the soft models demonstrate enrichment in the classical subtype and support expansive cell growth. The three-dimensional bioprinting technology utilized in this study enables rapid, flexible, and reproducible patient-specific GBM modeling with biophysical heterogeneity that can be employed by future studies as a tunable system to interrogate GBM disease mechanisms and screen drug compounds

Rapid 3D Bioprinting of Glioblastoma Model Mimicking Native Biophysical Heterogeneity

Glioblastoma multiforme (GBM) is the most lethal primary brain tumor characterized by high cellular and molecular heterogeneity, hyper-vascularization, and innate drug resistance. Current treatment options include a combination of surgical resection, radiotherapy, and chemotherapy primarily with temozolomide, but the prognosis is poor with an average life expectancy of 15 months. Despite significant research and drug development efforts, therapeutic advances to treat glioblastoma remain stagnant. Cellular components and extracellular matrix (ECM) are the two primary sources of heterogeneity in GBM. One of the major roadblocks in understanding the genetic basis of the cancer and developing new therapies is the lack of physiologically relevant and patient-specific GBM tumor models. Here, we develop biomimetic tri-regional GBM models with a tumor region, an acellular ECM region, and an endothelial region – with regional stiffnesses patterned corresponding to the GBM stroma, pathological or normal brain parenchyma, and brain capillaries. Patient-derived GBM cells, human endothelial cells, and hyaluronic acid derivatives are used to generate a species-matched and biochemically relevant microenvironment. This in vitro study demonstrates that biophysical cues are involved in various tumor cell behaviors and angiogenic potentials and promote different molecular subtypes of GBM. The stiff models are enriched in the mesenchymal subtype, exhibit diffuse invasion of tumor cells, and induce protruding angiogenesis and higher drug resistance to temozolomide. Meanwhile, the soft models demonstrate enrichment in the classical subtype and support expansive cell growth. The 3D bioprinting technology utilized in our study enables rapid, flexible, and reproducible GBM modeling with biophysical heterogeneity that can be employed by future studies as a tunable system to interrogate GBM disease mechanisms and screen drug compounds

A comparison of the clinical characteristics of Chinese patients with recurrent major depressive disorder with and without dysthymia☆

BACKGROUND: The relationship between major depressive disorder (MDD) and dysthymia, a form of chronic depression, is complex. The two conditions are highly comorbid and it is unclear whether they are two separate disease entities. We investigated the extent to which patients with dysthymia superimposed on major depression can be distinguished from those with recurrent MDD. METHODS: We examined the clinical features in 1970 Han Chinese women with MDD (DSM-IV) between 30 and 60 years of age across China. Logistic regression was used to determine the association between clinical features of MDD and dysthymia and between dysthymia and disorders comorbid with major depression. RESULTS: The 354 cases with dysthymia had more severe MDD than those without, with more episodes of MDD and greater co-morbidity for anxiety disorders. Patients with dysthymia had higher neuroticism scores and were more likely to have a family history of MDD. They were also more likely to have suffered serious life events. LIMITATIONS: Results were obtained in a clinically ascertained sample of Chinese women and may not generalize to community-acquired samples or to other populations. It is not possible to determine whether the associations represent causal relationships. CONCLUSIONS: The additional diagnosis of dysthymia in Chinese women with recurrent MDD defines a meaningful and potentially important subtype. We conclude that in some circumstances it is possible to distinguish double depression from recurrent MDD

Protocol for a gallbladder cancer registry study in China: the Chinese Research Group of Gallbladder Cancer (CRGGC) study

Introduction Gallbladder cancer (GBC), the sixth most common gastrointestinal tract cancer, poses a significant disease burden in China. However, no national representative data are available on the clinical characteristics, treatment and prognosis of GBC in the Chinese population.Methods and analysis The Chinese Research Group of Gallbladder Cancer (CRGGC) study is a multicentre retrospective registry cohort study. Clinically diagnosed patient with GBC will be identified from 1 January 2008 to December, 2019, by reviewing the electronic medical records from 76 tertiary and secondary hospitals across 28 provinces in China. Patients with pathological and radiological diagnoses of malignancy, including cancer in situ, from the gallbladder and cystic duct are eligible, according to the National Comprehensive Cancer Network 2019 guidelines. Patients will be excluded if GBC is the secondary diagnosis in the discharge summary. The demographic characteristics, medical history, physical examination results, surgery information, pathological data, laboratory examination results and radiology reports will be collected in a standardised case report form. By May 2021, approximately 6000 patient with GBC will be included. The clinical follow-up data will be updated until 5 years after the last admission for GBC of each patient. The study aimed (1) to depict the clinical characteristics, including demographics, pathology, treatment and prognosis of patient with GBC in China; (2) to evaluate the adherence to clinical guidelines of GBC and (3) to improve clinical practice for diagnosing and treating GBC and provide references for policy-makers.Ethics and dissemination The protocol of the CRGGC has been approved by the Committee for Ethics of Xinhua Hospital, Shanghai Jiao Tong University School of Medicine (SHEC-C-2019–085). All results of this study will be published in peer-reviewed journals and presented at relevant conferences.Trial registration number NCT04140552, Pre-results