Microarray analysis of ductal carcinoma in situ samples obtained by puncture from surgical resection specimens

Objective The incidence of ductal carcinoma in situ (DCIS) is increasing due to more widespread mammographic screening. DCIS, the earliest form of breast cancer, is non-invasive at the time of detection. If DCIS tissues are left undetected or untreated, it can spread to the surrounding breast tissue. Thus, surgical resection is the standard treatment. Understanding the mechanism underlying the non-invasive property of DCIS could lead to more appropriate medical treatments, including nonsurgical options. Data description We conducted a microarray-based genome-wide transcriptome analysis using DCIS specimens obtained by puncture from surgical specimens immediately after surgery.

Neurological Manifestations of COVID-19

The year 2020 started with the news of a novel coronavirus, severe acute respiratory syndrome corona virus 2(SARS-CoV2), induced disease in China which was termed as coronavirus disease 2019 (COVID-19). This viralinfection soon became pandemic and affected millions of people all over the world. The virus preferentiallyaffects respiratory system causing dry cough and fever, but has the tendency to spread to different organs in the body leading to multiple organ failure. Recent evidences show that corona virus can invade nervous system and damage it. This review is based on different articles and case reports that provide an evidence of neuro-virulent nature of COVID-19 and its consequences. The neuro-invasive property of the virus is divided into threecategories i) Central Nervous System (CNS) manifestations, ii) Peripheral Nervous System (PNS) manifestationsand iii) Skeletal Muscle damage. Headache and dizziness were observed to be common symptoms for CNS,whereas loss of smell and taste for PNS damage due to COVID-19. The aim of this review is, to develop anunderstanding of the devastating effects of COVID-19 on nervous system for the early recognition of virusinduced damage. This information can be used for the development of better therapeutic strategies.

Investigation of the Therapeutic Potential of Momelotinib on Hepatitis Virus-Associated Liver Cancer Is Through Suppressing Oncogenic/Stemnes IFNGR-JAK-STAT Pathway

Background: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, accounting for more than 700,000 deaths annually. In this study, we hypothesized that momelotinib could regulate the progression of HCC by targeting Jak family related protein. The proteins of IFN gamma-related pathways are obviously activated after hepatitis virus infection. This result suggests the difference in signal transmission between viral liver cancer and general liver cancer. Based on this observation, we are linked to the relevant targets of the JAK family and the potential applications of targeted therapy inhibitors.Methods: We analyzed possible synergism between Momelotinib and Sorafenib in hepatitis virus-associated liver cancer. Immunostaining, colony formation Assay, cell invasion, migration, and tumorsphere-formation assay was used drug cytotoxicity, cell viability and possible molecular mechanism. Result: We found that Jak2 downstream gene STAT1 expression was correlated with poor prognosis and poor overall survival of patients with HCC. Treatment of momelotinib significantly inhibits Jak2, resultant in the reduction of the migratory, invasive property of vHCC cells. Interestingly, cell cycle arrest and inhibition of the stem cell-like phenotype of vHCC cells were also observed after the momelotinib treatment. Furthermore, the combined effect of momelotinib and sorafenib both at in-vitro and in-vivo synergistically suppresses the proliferation of vHCC cells and effectively reduces the tumor burden.Conclusion: Our results showed that momelotinib effectively suppressed the expression of Jak2, which results in the downregulation of cancer stem cell genes and enhances the antitumor efficacy of sorafenib by initiating the expression of apoptosis-related genes in vHCC cells, thus maximizing its therapeutic potential for patients with HCC.

The role of macrophages in the formation of hypertrophic scars and keloids

Numerous studies have shown that macrophages can orchestrate the microenvironment from the early stage of wound healing to the later stages of scar formation. However, few reviews have highlighted the significance of macrophages during the formation of abnormal scars. The purpose of this review was to outline the polarization of macrophages from early to late stage of pathological scar formation, focusing on spatiotemporal diversity of M1 and M2 macrophages. In this review, the role of macrophages in the formation of hypertrophic scars and keloids is summarized in detail. First, an increased number of M2 cells observed before injuries are significantly associated with susceptibility to abnormal scar pathogenesis. Second, decreased expression of M1 at the early stage and delayed expression of M2 at the late stage results in pathological scar formation. Third, M2 cells are highly expressed at both the margin and the superficial region, which is consistent with the invasive property of keloids. Finally, this review helps to characterize strategies for the prediction and prevention of pathological scar formation.

The interplay of immune components and ECM in oral cancer

We report that in Oral Squamous Cell Carcinoma (OSCC), extracellular matrix (ECM) plays a vitally important role in defining the characteristics of cancer vs. normal, as it is a compartment with significant enrichment of known OSCC biomarkers, and the number of genes constituting ECM are more prominently upregulated in OSCC than almost all the rest of the cancer types. This is probably due to the constant exposure of oral cavity to external stimuli, resulting in the ECM remodeling, which further is a key player in tumor invasion. While we showed ECM molecules alone could well distinguish oral cancer from normal tissue samples, a significant portion of these predictive ECM molecules, share the same transcriptional regulator, NFKB1, a master regulator of immune response. We further studied the level of involvement of the immune system in OSCC, and found that the immune composition in OSCC is distinctly different from the other cancer types. OSCC has a higher level of infiltration of adaptive immune cells, including B cell, T cell and neutrophil, compared with other cancer types, while a lower level of infiltration of innate immune, including macrophage and monocyte. Previous studies have revealed the roles of ECM and immune system in OSCC development, and our study showed that ECM plays a very prominent role in OSCC, subject to the complex microenvironment in oral cavity, particularly the immune system profile, and our association analysis revealed it is likely the interactions between ECM and immune cells that define the highly invasive property of OSCC.

Extent of EMT promotes invasive, contact-induced sliding on progressively narrower fiber-like tracks

Epithelial-mesenchymal transition (EMT) is a complex process by which cells acquire invasive properties that enable escape from the primary tumor. Complete EMT, however, is not required for metastasis: circulating tumor cells exhibit hybrid epithelial-mesenchymal states, and genetic perturbations promoting partial EMT induce metastasis in vivo. An open question is whether and to what extent intermediate stages of EMT promote invasiveness. Here, we investigate this question, building on recent observation of a new invasive property. Migrating cancer cell lines and cells transduced with prometastatic genes slide around other cells on spatially-confined, fiber-like micropatterns. We show here that low-dosage/short-duration exposure to TGFβ induces partial EMT and enables sliding on narrower (26 μm) micropatterns than untreated counterparts (41 μm). High-dosage/long-duration exposure induces more complete EMT, including disrupted cell-cell contacts and reduced E-cadherin expression, and promotes sliding on the narrowest (15 μm) micropatterns. These results demonstrate that EMT is a potent inducer of cell sliding, even under significant spatial constraints, and EMT-mediated invasive sliding is progressive, with partial EMT promoting intermediate sliding behavior. Our findings suggest a model in which fiber maturation and partial EMT work synergistically to promote invasiveness during cancer progression.

CAS/Crk Coupling Serves as a “Molecular Switch” for Induction of Cell Migration

Carcinoma cells selected for their ability to migrate in vitro showed enhanced invasive properties in vivo. Associated with this induction of migration was the anchorage-dependent phosphorylation of p130CAS (Crk-associated substrate), leading to its coupling to the adaptor protein c-CrkII (Crk). In fact, expression of CAS or its adaptor protein partner Crk was sufficient to promote cell migration, and this depended on CAS tyrosine phosphorylation facilitating an SH2-mediated complex with Crk. Cytokine-stimulated cell migration was blocked by CAS lacking the Crk binding site or Crk containing a mutant SH2 domain. This migration response was characterized by CAS/Crk localization to membrane ruffles and blocked by the dominant-negative GTPase, Rac, but not Ras. Thus, CAS/Crk assembly serves as a “molecular switch” for the induction of cell migration and appears to contribute to the invasive property of tumors.