Panigrahi, M. | Search bioRxiv

bioRxiv2020

In Vitro Patients Derived Glioma Culture Model: Identification of Aggressive, Drug Resistant Phenotype Among Low-Grade Gliomas

BackgroundClinical management of glioma is crucial irrespective of tumor grade. Despite newer treatment modalities, the prognosis of glioma is abysmal and, survival statistics are not remarkable. In vitro glioma culture is emerging as a standard model to get insight into phenotypic transformation, drug response, and tumor relapse. In this viewpoint, this study established comprehensive patient-specific short-term cultures comprising low-grade, and high-grade glioma, and evaluated their pertinence in the potential disease management. Methods50 patients with MRI diagnosed glioma were recruited for this study. Primary glioma cultures established from fresh surgical tumor tissues, which were then evaluated for their intrinsic growth kinetics, response to temozolomide, and expression profile of Glial-Mesenchymal Transition (GMT) markers along with an oncogenic marker, cMyc. ResultsShort-term glioma culture was successfully established in 40 clinical samples. Glioma culture, irrespective of tumor grade, displayed two distinct patterns of growth kinetics - one with shorter doubling time (high-proliferating) and another group with longer doubling time (low-proliferating). Significant distinctive features were noticed between these two groups in terms of response to temozolomide, the expression pattern of GMT markers and their association with 1p/19q co-deletion and p53 expression. ConclusionOur findings effectively demonstrated the practicality of the development of short-term glioma culture toward a functional approach for personalized medicine. Our study revealed the presence of a highly proliferative, drug-resistant phenotype irrespective of tumor grade. Hence, short-term culture could be an important prognostic tool for predicting patient clinical responses and cue about imminent tumor relapse.

cancer biology↗

bioRxiv2020

Prediction analysis of SARS-COV-2 entry in Livestock and Wild animals

BackgroundSARS-CoV-2 is a viral pathogen causing life-threatening disease in human. Interaction between spike protein of SARS-CoV-2 and ACE2 receptor on the cells is a potential factor in the infectivity of a host. The interaction of SARS-CoV-2 spike receptor-binding domain with its receptor - ACE2, in different hosts was evaluated to understand and predict viral entry. The protein and nucleotide sequences of ACE2 were initially compared across different species to identify key differences among them. The ACE2 receptor of various species was homology modeled (6LZG, 6M0J, and 6VW1 as a reference), and its binding ability to the spike ACE2 binding domain of SARS-CoV-2 was assessed. Initially, the spike binding parameters of ACE2 of known infected and uninfected species were compared with each Order (of animals) as a group. Finally, a logistic regression model vis-a-vis the spike binding parameters of ACE2 (considering data against 6LZG and 6M0J) was constructed to predict the probability of viral entry in different hosts. ResultsPhylogeny and alignment comparison did not lead to any meaningful conclusion on viral entry in different hosts. Out of several spike binding parameters of ACE2, a significant difference between the known infected and uninfected species was observed for six parameters. However, these parameters did not specifically categorize the Orders (of animals) into infected or uninfected. The logistic regression model constructed revealed that in the mammalian class, most of the species of Carnivores, Artiodactyls, Perissodactyls, Pholidota, and Primates had high probability of viral entry. However, among the primates, African Elephant had low probability of viral entry. Among rodents, hamsters were highly probable for viral entry with rats and mice having a medium to low probability. Rabbits have a high probability of viral entry. In Birds, ducks have a very low probability, while chickens seemed to have medium probability and turkey showed the highest probability of viral entry. ConclusionsMost of the species considered in this study showed high probability of viral entry. This study would prompt us to closely follow certain species of animals for determining pathogenic insult by SARS-CoV-2 and for determining their ability to act as a carrier and/or disseminator.

microbiology↗