scholarly journals Comprehensive Analysis of Spatial Architecture in Primary Liver Cancer

2021 ◽  
Author(s):  
Rui Wu ◽  
Wenbo Guo ◽  
Xinyao Qiu ◽  
Shicheng Wang ◽  
Chengjun Sui ◽  
...  
Keyword(s):  
Immune Cell ◽  
Primary Liver Cancer ◽  
Leading Edge ◽  
Liver Cancers ◽  
Receptor Interactions ◽  
Potential Benefits ◽  
Cancer Intervention ◽  
Spatial Architecture ◽  
Sequential Comparison ◽  
Transcriptome Diversity

Heterogeneity is the major challenge for cancer prevention and therapy. Here, we firstly constructed high-resolution spatial transcriptomes of primary liver cancers (PLCs) containing 84,823 spots within 21 tissues from 7 patients. The sequential comparison of spatial tumor microenvironment (TME) characteristics from non-tumor to leading-edge to tumor regions revealed that the tumor capsule potentially affects intratumor spatial cluster continuity, transcriptome diversity and immune cell infiltration. Locally, we found that the bidirectional ligand-receptor interactions at the 100 μm wide cluster-cluster boundary contribute to maintaining intratumor architecture. Our study provides novel insights for diverse tumor ecosystem of PLCs and has potential benefits for cancer intervention.

scholarly journals Subcellular optogenetic activation of Cdc42 controls local and distal signaling to drive immune cell migration

2016 ◽  
Vol 27 (9) ◽  
pp. 1442-1450 ◽  
Author(s):  
Patrick R. O’Neill ◽  
Vani Kalyanaraman ◽  
N. Gautam
Keyword(s):  
Cell Migration ◽  
Intracellular Signaling ◽  
Immune Cell ◽  
Leading Edge ◽  
Signaling Networks ◽  
Membrane Protrusions ◽  
A Cell ◽  
Immune Cell Migration ◽  
Directional Cell Migration ◽  
Rhoa Signaling

Migratory immune cells use intracellular signaling networks to generate and orient spatially polarized responses to extracellular cues. The monomeric G protein Cdc42 is believed to play an important role in controlling the polarized responses, but it has been difficult to determine directly the consequences of localized Cdc42 activation within an immune cell. Here we used subcellular optogenetics to determine how Cdc42 activation at one side of a cell affects both cell behavior and dynamic molecular responses throughout the cell. We found that localized Cdc42 activation is sufficient to generate polarized signaling and directional cell migration. The optically activated region becomes the leading edge of the cell, with Cdc42 activating Rac and generating membrane protrusions driven by the actin cytoskeleton. Cdc42 also exerts long-range effects that cause myosin accumulation at the opposite side of the cell and actomyosin-mediated retraction of the cell rear. This process requires the RhoA-activated kinase ROCK, suggesting that Cdc42 activation at one side of a cell triggers increased RhoA signaling at the opposite side. Our results demonstrate how dynamic, subcellular perturbation of an individual signaling protein can help to determine its role in controlling polarized cellular responses.

scholarly journals Induced pluripotent stem cells are Japanese brand sources for therapeutic cells to pretrial clinical research

2020 ◽  
Vol 7 (1) ◽  
pp. 296-303
Author(s):  
Rupendra Shrestha
Keyword(s):  
Pluripotent Stem Cells ◽  
Clinical Studies ◽  
Immune Cell ◽  
Government Support ◽  
Cardiac Cell ◽  
Pluripotent Cells ◽  
Cell Lineages ◽  
Research Institution ◽  
Potential Benefits ◽  
Induced Pluripotent

iPSCs are promising and have potential benefits for medical use, understanding human organogenesis, and cell therapy for advanced diseases. iPSCs are derived pluripotent cells which can further differentiate into functional human cell-lineages, such as neuronal, epithelial cells, cardiac cell, immune cell, and blood cells, etc. Thirteen years on, the discovery of iPSC has revolutionized the field of regenerative medicine, and also the number of clinical studies using iPSC has been growing rapidly worldwide. However, Japan is leading the race of iPSC-based studies and clinical trials due to government support. The Japanese government implemented the world’s fastest approval system and set to host first pretrial clinical studies using iPSC derived therapeutic products. Also, multinational companies of Japan are investing enormously in iPSC-based research for mobilization of iPSC-derived regenerative products to the research institution globally. This review presents an overview of iPSCs, potential benefits, commercialization of iPSC, iPSC-based pretrial clinical studies, and iPSC biobanking in Japan.

Vitamin D and Omega-3 Polyunsaturated Fatty Acids in Type 1 Diabetes modulation

2022 ◽  
Vol 22 ◽  
Author(s):  
Thais Sibioni Berti Bastos ◽  
Tárcio Teodoro Braga ◽  
Mariana Rodrigues Davanso
Keyword(s):  
Fatty Acids ◽  
Vitamin D ◽  
Type 1 Diabetes ◽  
Polyunsaturated Fatty Acids ◽  
Immune Cell ◽  
Omega 3 ◽  
Β Cells ◽  
Potential Benefits ◽  
Chronic Autoimmune Disease

Background: Type 1 diabetes (T1D) is a chronic autoimmune disease that affects people globally. Usually developed during childhood, T1D is characterized by the destruction of pancreatic β-cells due to immune cell attack and the establishment of an inflammatory process. Objective: The study aimed to investigate the effects of vitamin D through its nuclear receptor and the ω-3 polyunsaturated fatty acids (PUFAs) through their lipid derivatives in T1D modulation. Both components exert anti-inflammatory activity and act directly on cells of the immune system, attenuating the destruction of insulin-producing cells. Furthermore, they lead to a better glycemic level, reducing the need for insulin and a normal immune state, such as C-peptide maintenance. Method: Presently, our review highlights the significant studies that evaluated the supplementation of vitamin D and ω-3 PUFAs in humans and animal models in the modulation of T1D. Conclusion: The data collected suggests that supplementation can provide potential benefits, mainly when done early in the diagnosis, since it reduces the need for insulin and the risk of complications generated by the disease.

Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma

2020 ◽  
Vol 04 (02) ◽  
pp. 187-194
Author(s):  
Shauna R. Campbell ◽  
Timothy D. Smile ◽  
Sarah M.C. Sittenfeld ◽  
Kevin L. Stephans
Keyword(s):  
Hepatocellular Carcinoma ◽  
Radiation Therapy ◽  
Stereotactic Body Radiation Therapy ◽  
Primary Liver Cancer ◽  
Effective Treatment Option ◽  
Stereotactic Body Radiation ◽  
Common Cancer ◽  
Clinical Presentations ◽  
Liver Cancers ◽  
Bridging To Transplant

AbstractPrimary liver cancer is the seventh most common cancer worldwide and is the second leading cause of cancer-related death. Hepatocellular carcinoma (HCC) accounts for three-quarters of primary liver cancers and less than a third of patients present with curable disease. Liver-directed therapy is essential for the treatment of patients with unresectable HCC and the advancement of stereotactic body radiation therapy (SBRT) has made radiation a safe and effective treatment option in a range of clinical presentations. In this review, we discuss the technical aspects of SBRT and the general approach to treatment of HCC. We explore the use of SBRT for bridging to transplant, downstaging, and the treatment of large tumors and portal vein tumor thrombus. Although there is limited high-quality randomized data, we review the evidence comparing SBRT with other liver-directed therapies and explore areas for future investigation.

Affinity chromatography used in distinguishing alpha-fetoprotein in serum from patients with tumors of hepatic parenchyma and of germ cells.

1984 ◽  
Vol 30 (7) ◽  
pp. 1257-1258 ◽  
Author(s):  
P K Buamah ◽  
C Cornell ◽  
A W Skillen
Keyword(s):  
Germ Cell ◽  
Affinity Chromatography ◽  
Germ Cells ◽  
Concanavalin A ◽  
Primary Liver Cancer ◽  
Germ Cell Tumors ◽  
Alpha Fetoprotein ◽  
Hepatic Parenchyma ◽  
Liver Cancers ◽  
Serum Alpha Fetoprotein

Abstract We used affinity chromatography on concanavalin A Sepharose to study the serum alpha-fetoprotein of 10 patients with histologically proven germ-cell tumors and 12 patients with primary liver cancer. Less than 50% of the fetoprotein from germ-cell tumors bound to concanavalin A, as compared with more than 80% of the alpha-fetoprotein from primary liver cancers.

scholarly journals Roles of Lysyl Oxidase Family Members in the Tumor Microenvironment and Progression of Liver Cancer

2020 ◽  
Vol 21 (24) ◽  
pp. 9751
Author(s):  
Hung-Yu Lin ◽  
Chia-Jung Li ◽  
Ya-Ling Yang ◽  
Ying-Hsien Huang ◽  
Ya-Tze Hsiau ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Liver Cancer ◽  
Lysyl Oxidase ◽  
Primary Liver Cancer ◽  
Target Therapy ◽  
Family Members ◽  
Clinical Value ◽  
Ecm Remodeling ◽  
Liver Cancers ◽  
Advanced Stages

The lysyl oxidase (LOX) family members are secreted copper-dependent amine oxidases, comprised of five paralogues: LOX and LOX-like l-4 (LOXL1-4), which are characterized by catalytic activity contributing to the remodeling of the cross-linking of the structural extracellular matrix (ECM). ECM remodeling plays a key role in the angiogenesis surrounding tumors, whereby a corrupt tumor microenvironment (TME) takes shape. Primary liver cancer includes hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), ranked as the seventh most common cancer globally, with limited therapeutic options for advanced stages. In recent years, a growing body of evidence has revealed the key roles of LOX family members in the pathogenesis of liver cancer and the shaping of TME, indicating their notable potential as therapeutic targets. We herein review the clinical value and novel biological roles of LOX family members in tumor progression and the TME of liver cancers. In addition, we highlight recent insights into their mechanisms and their potential involvement in the development of target therapy for liver cancer.

scholarly journals Clinical characterization, genetic profiling, and immune infiltration of TOX in diffuse gliomas

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Hao Zhang ◽  
Fan Fan ◽  
Yuanqiang Yu ◽  
Zeyu Wang ◽  
Fangkun Liu ◽  
...  
Keyword(s):  
Immune Cell ◽  
Malignant Gliomas ◽  
Leading Edge ◽  
Cell Types ◽  
Tumour Microenvironment ◽  
The Cancer Genome Atlas ◽  
Low Grade ◽  
Lymphocyte Migration ◽  
Who Grade ◽  
Genome Atlas

Abstract Background Immunotherapies targeting glioblastoma (GBM) have led to significant improvements in patient outcomes. TOX is closely associated with the immune environment surrounding tumors, but its role in gliomas is not fully understood. Methods Using data from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA), we analyzed the transcriptomes of 1691 WHO grade I-IV human glioma samples. The R language was used to perform most of the statistical analyses. Somatic mutations and somatic copy number variation (CNV) were analyzed using GISTIC 2.0. Results TOX was down-regulated in malignant gliomas compared to low grade gliomas, and upregulated in the proneural and IDH mutant subtypes of GBM. TOXlow tumours are associated with the loss of PTEN and amplification of EGFR, while TOXhigh tumours harbor frequent mutations in IDH1 (91%). TOX was highly expressed in leading edge regions of tumours. Gene ontology and pathway analyses demonstrated that TOX was enriched in multiple immune related processes including lymphocyte migration in GBM. Finally, TOX had a negative association with the infiltration of several immune cell types in the tumour microenvironment. Conclusion TOX has the potential to be a new prognostic marker for GBM.

scholarly journals Immune Checkpoint Inhibitor Associated Hepatotoxicity in Primary Liver Cancer Versus Other Cancers: A Systematic Review and Meta‐Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Jianyang Fu ◽  
Wang-Zhong Li ◽  
Nicole A. McGrath ◽  
Chunwei Walter Lai ◽  
Gagandeep Brar ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Primary Liver Cancer ◽  
Meta Analysis ◽  
High Grade ◽  
Liver Cancers ◽  
Grade 3

BackgroundOverall risks of hepatotoxicity with immune checkpoint inhibitors (ICIs) have yet to be compared in primary liver cancers to other solid tumors.MethodsWe reviewed data from the PubMed, Embase, and Scopus databases, and assessed the risk of hepatotoxicity associated with ICIs.ResultsA total of 117 trials were eligible for the meta‐analysis, including 7 trials with primary liver cancers. The most common hepatotoxicity was ALT elevation (incidence of all grade 5.29%, 95% CI 4.52-6.20) and AST elevation (incidence of all grade 5.88%, 95% CI 4.96-6.97). The incidence of all grade ALT and AST elevation was 6.01% and 6.84% for anti-PD‐1 (95% CI 5.04-7.18/5.69-8.25) and 3.60% and 3.72% for anti-PD-L1 (95% CI 2.72-4.76/2.82-4.94; p< 0.001/p<0.001). The incidence of ≥ grade 3 ALT and AST elevation was 1.54% and 1.48% for anti-PD‐1 (95% CI 1.19-1.58/1.07-2.04) and 1.03% and 1.08% for anti-PD-L1 (95% CI 0.71-1.51/0.80-1.45; p= 0.002/p<0.001). The incidence of all grade ALT and AST elevation was 13.3% and 14.2% in primary liver cancers (95% CI 11.1-16.0 and 9.93-20.36) vs. 4.92% and 5.38% in other solid tumors (95% CI 4.21-5.76 and 4.52-5.76 in other solid tumors; p <0.001/p<0.001).ConclusionOur study indicates that anti-PD-1 is associated with a higher risk of all‐ and high‐grade hepatotoxicity compared to anti-PD-L1, and primary liver cancers are associated with a higher risk of all‐ and high‐grade hepatotoxicity compared to other solid tumors.

scholarly journals Association of GSTM1 and GSTT1 Null Deletions and GSTP1 rs1695 Polymorphism with the Risk of Hepatocellular Carcinoma: A Systematic Review and Meta-analysis

2021 ◽  
Vol 20 (11) ◽  
Author(s):  
Mohammad Hossein Khosravi ◽  
Heidar Sharafi ◽  
Seyed Moayed Alavian
Keyword(s):  
Hepatocellular Carcinoma ◽  
Random Effects ◽  
Primary Liver Cancer ◽  
Meta Analysis ◽  
Inclusion Criteria ◽  
Random Effects Models ◽  
Asian Populations ◽  
Liver Cancers ◽  
Glutathione S Transferases ◽  
Common Malignancy

Context: Hepatocellular carcinoma (HCC), as the most common type of primary liver cancer (accounting for 70% - 90% of all liver cancers), is the seventh most common malignancy worldwide. Glutathione S-transferases (GSTs) are a specific group of enzymes that are responsible for the detoxification of carcinogens. According to the available literature, genetic variations in this group of enzymes may be associated with the risk of HCC. In this study, we aimed to assess the association of GSTM1 and GSTT1 null deletions and GSTP1 rs1695 polymorphism with the risk of HCC. Methods: We systematically searched electronic databases, including PubMed, Scopus, and Web of Science, using appropriate keywords to gather relevant data until March 2019. Studies that met the inclusion criteria were included in the meta-analysis, using either fixed- or random-effects models based on the presence of heterogeneity. Results: This meta-analysis pooled 19 studies for GSTM1 null deletions, 14 studies for GSTT1 null deletions, and five studies for GSTP1 rs1695 polymorphism. In terms of heterogeneity, the pooled odds ratio (OR) was calculated in a random-effects model for both Asian and non-Asian populations. HCC was found to be associated with GSTM1 null deletions (OR = 1.26, 95% CI: 1.00 - 1.58, P = 0.05) and GSTT1 null deletions (OR = 1.39, 95% CI: 1.10 - 1.74, P = 0.005); however, no significant association was found between HCC and GSTP1 rs1695 polymorphism (OR = 1.14, 95% CI: 0.86 - 1.50, P = 0.36). Conclusions: We found that GSTM1 and GSTT1 null deletions increased the risk of HCC; however, the GSTP1 rs1695 polymorphism did not have a similar effect.

scholarly journals Clinical characterization, genetic profiling, and immune infiltration of TOX in diffuse gliomas

2020 ◽  
Author(s):  
Zhang Hao ◽  
Fan Fan ◽  
Yu Yuanqiang ◽  
Wang Zeyu ◽  
Liu Fangkun ◽  
...  
Keyword(s):  
Immune Cell ◽  
Malignant Gliomas ◽  
Leading Edge ◽  
Cell Types ◽  
Tumour Microenvironment ◽  
The Cancer Genome Atlas ◽  
Low Grade ◽  
Lymphocyte Migration ◽  
Who Grade ◽  
Genome Atlas

Abstract Background: Immunotherapies targeting glioblastoma (GBM) have led to significant improvements in patient outcomes. TOX is closely associated with the immune environment surrounding tumors, but its role in gliomas is not fully understood. Methods: Using data from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA), we analyzed the transcriptomes of 1691 WHO grade I-IV human glioma samples. The R language was used to perform most of the statistical analyses. Somatic mutations and somatic copy number variation (CNV) were analyzed using GISTIC 2.0. Results: TOX was down-regulated in malignant gliomas compared to low grade gliomas, and upregulated in the proneural and IDH mutant subtypes of GBM. TOXlow tumours are associated with the loss of PTEN and amplification of EGFR, while TOXhigh tumours harbor frequent mutations in IDH1 (91%). TOX was highly expressed in leading edge regions of tumours. Gene ontology and pathway analyses demonstrated that TOX was enriched in multiple immune related processes including lymphocyte migration in GBM. Finally, TOX had a negative association with the infiltration of several immune cell types in the tumour microenvironment. Conclusion: TOX has the potential to be a new prognostic marker for GBM.

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