scholarly journals 924 The spatial hierarchy of primary and recurrent medulloblastoma tumor ecosystems

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A969-A969
Author(s):  
Laura Donovan ◽  
Bei Hopkins ◽  
Ben Draper ◽  
Rivani Shah ◽  
Kristin Roman ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Immune Cell ◽  
Spectral Unmixing ◽  
Cell Interactions ◽  
Treatment Modalities ◽  
Cell Of Origin ◽  
Human Brain Tissue ◽  
Cell Counts ◽  
Pediatric Medulloblastoma ◽  
Average Signal Intensity

BackgroundMedulloblastoma recurrence occurs in approximately 30% of patients and is universally fatal, presenting one of the most significant unmet clinical challenges in pediatric oncology. It is now clear that medulloblastomas are complex ecosystems, evolving under selective pressure from their microenvironment and cell of origin. Different tumor-immune cell interactions, including, but not limited to, tumor-infiltrating lymphocytes and various tumor suppressive myeloid cell populations, significantly hamper effective treatment strategies for primary, metastatic, and recurrent tumors. Recurrent medulloblastomas are rarely biopsied making biological material for interrogation scarce. Research has assumed that recurrent and primary medulloblastoma tumors have similar biological composition and therefore will respond to the same therapeutic regimens, however, therapies designed using primary biopsies, but tested in Phase I/II trials on children with recurrent disease, have been largely unsuccessful. We hypothesize that there are select immunosuppressive population differences within primary vs. recurrent tumor microenvironments (TME) that need to be elucidated in order to improve treatment modalities and outcomes in pediatric patients.MethodsUsing Akoya’s MOTiFTM PD-1/PD-L1 Panel: Auto Melanoma Kit, the staining protocol was adapted for optimal staining performance on human brain tissue. Following this, 24-formalin-fixed, paraffin embedded pediatric medulloblastoma samples (primary and recurrent biopsies from 12 patients) were stained for the following markers on the Leica BOND RX. Multispectral images were acquired using the Vectra Polaris, and five regions of interest selected on each image. An analysis algorithm was developed using inForm tissue analysis software, and samples were batch processed and data exported. Cell counts, densities, and spatial parameters were generated using the R-script package phenoptrReports to produce outputs of the image analysis data.ResultsFollowing spectral unmixing and autofluorescence isolation, no signal crosstalk was observed. The average signal intensity counts for all markers was found to be within the recommended ranges of 10–30, with a coefficient of variation of ≤15%, indicating successful and consistent staining of the medulloblastoma samples. Comparison between primary vs. recurrent tissues revealed distinctive spatial differences between immune-tumor cell interactions.ConclusionsWe have demonstrated successful adaptation of the MOTiF PD-1/PD-L1 Melanoma panel kit in conjunction with the Phenoptics workflow to support examination of the TME in patient-matched primary and recurrent pediatric medulloblastoma tumor biopsies. Our study provides the first insight into distinctive spatial interactions between primary vs. recurrent tissues, which may improve strategies to comprehend cancer progression, immune surveillance, and ultimately the development of rational, targeted therapeutics based on the differences between the tumor compartments and their immune-microenvironment.Ethics ApprovalEthical approval obtained by Brain UK, ref: 20/008. All participants gave consent to use of their material.

IS tRNA DRIVING BREAST CANCER PROGRESSION?

2019 ◽  
Author(s):  
Zil-e- Rubab
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Developing Countries ◽  
Molecular Mechanism ◽  
Cancer Progression ◽  
Critical Review ◽  
Driving Forces ◽  
Treatment Modalities ◽  
Critical Research ◽  
Research Article

This critical research periodical is mainly based on critical review of research article titled ‘Modulated Expression of Specific tRNAs Drives Gene Expression and Cancer Progression published in Cell by Goodarzi et al1. According to Globocan, 2008 report2, breast is among the leading site of new cancer cases and deaths (691,300/268,900) in females of developing countries and second leading site in USA (Globocan, 2012)3. The extensive research is in progress on different aspects of molecular mechanism of driving forces and different treatment modalities to ease this burden. The above mentioned research article is also part of this effort.

Recent Advances of Small Molecular Regulators Targeting G Protein- Coupled Receptors Family for Oncology Immunotherapy

2019 ◽  
Vol 19 (16) ◽  
pp. 1464-1483 ◽  
Author(s):  
Peng He ◽  
Wenbo Zhou ◽  
Mingyao Liu ◽  
Yihua Chen
Keyword(s):  
G Protein ◽  
Cell Biology ◽  
Immune Cell ◽  
G Protein Coupled Receptors ◽  
Treatment Modalities ◽  
Immune Checkpoints ◽  
Considerable Proportion ◽  
Prostaglandin E ◽  
Recent Advances ◽  
G Protein Coupled

The great clinical success of chimeric antigen receptor T cell (CAR-T) and PD-1/PDL-1 inhibitor therapies suggests the drawing of a cancer immunotherapy age. However, a considerable proportion of cancer patients currently receive little benefit from these treatment modalities, indicating that multiple immunosuppressive mechanisms exist in the tumor microenvironment. In this review, we mainly discuss recent advances in small molecular regulators targeting G Protein-Coupled Receptors (GPCRs) that are associated with oncology immunomodulation, including chemokine receptors, purinergic receptors, prostaglandin E receptor EP4 and opioid receptors. Moreover, we outline how they affect tumor immunity and neoplasia by regulating immune cell recruitment and modulating tumor stromal cell biology. We also summarize the data from recent clinical advances in small molecular regulators targeting these GPCRs, in combination with immune checkpoints blockers, such as PD-1/PDL-1 and CTLA4 inhibitors, for cancer treatments.

scholarly journals Immune-Related Circulating miR-125b-5p and miR-99a-5p Reveal a High Recurrence Risk Group of Pancreatic Cancer Patients after Tumor Resection

2019 ◽  
Vol 9 (22) ◽  
pp. 4784
Author(s):  
Vietsch ◽  
Peran ◽  
Suker ◽  
van den Bosch ◽  
Sijde ◽  
...  
Keyword(s):  
Cancer Progression ◽  
B Lymphocyte ◽  
Immune Cell ◽  
Tumor Resection ◽  
Progression Free Survival ◽  
Tumor Stroma ◽  
Recurrence Risk ◽  
High Serum ◽  
Ductal Adenocarcinoma ◽  
Before And After

Clinical follow-up aided by changes in the expression of circulating microRNAs (miRs) may improve prognostication of pancreatic ductal adenocarcinoma (PDAC) patients. Changes in 179 circulating miRs due to cancer progression in the transgenic KrasG12D/+; Trp53R172H/+; P48-Cre (KPC) animal model of PDAC were analyzed for serum miRs that are altered in metastatic disease. In addition, expression levels of 250 miRs were profiled before and after pancreaticoduodenectomy in the serum of two patients with resectable PDAC with different progression free survival (PFS) and analyzed for changes indicative of PDAC recurrence after resection. Three miRs that were upregulated ≥3-fold in progressive PDAC in both mice and patients were selected for validation in 26 additional PDAC patients before and after resection. We found that high serum miR-125b-5p and miR-99a-5p levels after resection are significantly associated with shorter PFS (HR 1.34 and HR 1.73 respectively). In situ hybridization for miR detection in the paired resected human PDAC tissues showed that miR-125b-5p and miR-99a-5p are highly expressed in inflammatory cells in the tumor stroma, located in clusters of CD79A expressing cells of the B-lymphocyte lineage. In conclusion, we found that circulating miR-125b-5p and miR-99a-5p are potential immune-cell related prognostic biomarkers in PDAC patients after surgery.

scholarly journals Wound Infections of Snakebites from the Venomous Protobothrops mucrosquamatus and Viridovipera stejnegeri in Taiwan: Bacteriology, Antibiotic Susceptibility, and Predicting the Need for Antibiotics—A BITE Study

Toxins ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 575 ◽  
Author(s):  
Chih-Chuan Lin ◽  
Yen-Chia Chen ◽  
Zhong Ning Leonard Goh ◽  
Chen-Ken Seak ◽  
Joanna Chen-Yeen Seak ◽  
...  
Keyword(s):  
Wound Infection ◽  
Roc Curve ◽  
Predictive Performance ◽  
Antibiotic Usage ◽  
Emergency Department Visits ◽  
Treatment Modalities ◽  
Wound Infections ◽  
Neutrophil Lymphocyte Ratio ◽  
Cell Counts ◽  
Freeze Dried

Snakebites from Taiwan habus (Protobothrops mucrosquamatus) and green bamboo vipers (Viridovipera stejnegeri) account for two-thirds of all venomous snakebites in Taiwan. While there has been ongoing optimization of antivenin therapy, the proper management of superimposed bacterial wound infections is not well studied. In this Bacteriology of Infections in Taiwanese snake Envenomation (BITE) study, we investigated the prevalence of wound infection, bacteriology, and corresponding antibiotic usage in patients presenting with snakebites from these two snakes. We further developed a BITE score to evaluate the probability of wound infections and guide antibiotic usage in this patient population. All snakebite victims who presented to the emergency departments of seven training and research hospitals and received at least one vial of freeze-dried hemorrhagic antivenin between January 2001 and January 2017 were identified. Patient biodata, laboratory investigation results, and treatment modalities were retrieved. We developed our BITE score via univariate and multiple logistic regression analyses. The receiver operating characteristic (ROC) curve was plotted to evaluate the predictive performance of the BITE score. Out of 8,295,497 emergency department visits, 726 patients presented with snakebites from a Taiwan habu or a green bamboo viper. The wound infection rate was 22.45%, with seven positive wound cultures, including six polymicrobial infections. Morganella morganii, Enterococcus spp., Bacteroides fragilis, and Aeromonas hydrophila were most frequently cultured. There were no positive blood cultures. A total of 33.0% (n = 106) of snakebite patients who received prophylactic antibiotics nevertheless developed wound infections, while 44.8% (n = 73) of wound infection patients were satisfactorily treated with one of the following antibiotics: amoxicillin/clavulanic acid, oxacillin, cefazolin, and ampicillin/sulbactam. With the addition of gentamicin, the success of antibiotic therapy increased by up to 66.54%. The prognostic factors for the secondary bacterial infection of snakebites were white blood cell counts, the neutrophil lymphocyte ratio, and the need for hospital admission. The area under the ROC curve for the BITE score was 0.839. At the optimal cut-off point of 5, the BITE score had a 79.58% accuracy, 82.31% sensitivity, and 79.71% specificity when predicting infection in snakebite patients. Our BITE score may help with antibiotic stewardship by guiding appropriate antibiotic use in patients presenting with snakebites. It may also be employed in further studies into antibiotic prophylaxis in snakebite patients for the prevention of superimposed bacterial wound infections.

scholarly journals The Role of Cancer-Associated Fibroblasts in Tumor Progression

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1399
Author(s):  
Rushikesh S. Joshi ◽  
Samanvi S. Kanugula ◽  
Sweta Sudhir ◽  
Matheus P. Pereira ◽  
Saket Jain ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Tumor Progression ◽  
Cancer Progression ◽  
Immune Cell ◽  
Systemic Disease ◽  
Genomic Medicine ◽  
Therapeutic Targets ◽  
Therapy Resistance ◽  
Cancer Associated Fibroblasts ◽  
Breast Cancers

In the era of genomic medicine, cancer treatment has become more personalized as novel therapeutic targets and pathways are identified. Research over the past decade has shown the increasing importance of how the tumor microenvironment (TME) and the extracellular matrix (ECM), which is a major structural component of the TME, regulate oncogenic functions including tumor progression, metastasis, angiogenesis, therapy resistance, and immune cell modulation, amongst others. Within the TME, cancer-associated fibroblasts (CAFs) have been identified in several systemic cancers as critical regulators of the malignant cancer phenotype. This review of the literature comprehensively profiles the roles of CAFs implicated in gastrointestinal, endocrine, head and neck, skin, genitourinary, lung, and breast cancers. The ubiquitous presence of CAFs highlights their significance as modulators of cancer progression and has led to the subsequent characterization of potential therapeutic targets, which may help advance the cancer treatment paradigm to determine the next generation of cancer therapy. The aim of this review is to provide a detailed overview of the key roles that CAFs play in the scope of systemic disease, the mechanisms by which they enhance protumoral effects, and the primary CAF-related markers that may offer potential targets for novel therapeutics.

scholarly journals Human amniotic mesenchymal stem cells to promote/suppress cancer: two sides of the same coin

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ameneh Jafari ◽  
Mostafa Rezaei-Tavirani ◽  
Behrouz Farhadihosseinabadi ◽  
Hakimeh Zali ◽  
Hassan Niknejad
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cancer Treatment ◽  
Cancer Progression ◽  
Adult Stem Cells ◽  
Treatment Modalities ◽  
Human Amniotic Membrane ◽  
Amniotic Mesenchymal Stem Cells ◽  
Growth And Aging

AbstractCancer is a leading cause of death in both developed and developing countries, and because of population growth and aging, it is a growing medical burden worldwide. With robust development in medicine, the use of stem cells has opened new treatment modalities in cancer therapy. In adult stem cells, mesenchymal stem cells (MSCs) are showing rising promise in cancer treatment due to their unique properties. Among different sources of MSCs, human amniotic fluid/membrane is an attractive and suitable reservoir. There are conflicting opinions about the role of human amniotic membrane/fluid mesenchymal stem cells (hAMSCS/hAFMSCs) in cancer, as some studies demonstrating the anticancer effects of these cells and others suggesting their progressive effects on cancer. This review focuses on recent findings about the role of hAMSCs/hAFMSCs in cancer treatment and summarizes the suppressing as well as promoting effects of these cells on cancer progression and underling mechanisms.

scholarly journals Predicting Host Immune Cell Dynamics and Key Disease-Associated Genes Using Tissue Transcriptional Profiles

Processes ◽  
2019 ◽  
Vol 7 (5) ◽  
pp. 301
Author(s):  
Muying Wang ◽  
Satoshi Fukuyama ◽  
Yoshihiro Kawaoka ◽  
Jason E. Shoemaker
Keyword(s):  
Gene Expression ◽  
Gene Expression Data ◽  
Immune Cell ◽  
Mean Squared Error ◽  
Expression Profiles ◽  
Statistical Tests ◽  
Critical Factor ◽  
Expression Data ◽  
Cell Dynamics ◽  
Cell Counts

Motivation: Immune cell dynamics is a critical factor of disease-associated pathology (immunopathology) that also impacts the levels of mRNAs in diseased tissue. Deconvolution algorithms attempt to infer cell quantities in a tissue/organ sample based on gene expression profiles and are often evaluated using artificial, non-complex samples. Their accuracy on estimating cell counts given temporal tissue gene expression data remains not well characterized and has never been characterized when using diseased lung. Further, how to remove the effects of cell migration on transcript counts to improve discovery of disease factors is an open question. Results: Four cell count inference (i.e., deconvolution) tools are evaluated using microarray data from influenza-infected lung sampled at several time points post-infection. The analysis finds that inferred cell quantities are accurate only for select cell types and there is a tendency for algorithms to have a good relative fit (R 2 ) but a poor absolute fit (normalized mean squared error; NMSE), which suggests systemic biases exist. Nonetheless, using cell fraction estimates to adjust gene expression data, we show that genes associated with influenza virus replication and increased infection pathology are more likely to be identified as significant than when applying traditional statistical tests.

scholarly journals Immunometabolic Status of COVID-19 Cancer Patients

2020 ◽  
Vol 100 (4) ◽  
pp. 1839-1850
Author(s):  
A. Sica ◽  
M. P. Colombo ◽  
A. Trama ◽  
L. Horn ◽  
M. C. Garassino ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Cancer Progression ◽  
Macrophage Activation ◽  
Viral Infections ◽  
Immune Cell ◽  
Case Series ◽  
The United States ◽  
Alternative Activation ◽  
Nad Metabolism ◽  
Increased Risk

Cancer patients appear to be more likely to be diagnosed with coronavirus disease 2019 (COVID-19). This is supported by the understanding of immunometabolic pathways that intersect patients with infection and cancer. However, data derived by case series and retrospective studies do not offer a coherent interpretation, since data from China suggest an increased risk of COVID-19, while data from the United States and Italy show a prevalence of COVID-19 in cancer patients comparable with the general population. Noteworthy, cancer and COVID-19 exploit distinct patterns of macrophage activation that promote disease progression in the most severe forms. In particular, the alternative activation of M2-polarized macrophages plays a crucial role in cancer progression. In contrast, the macrophage-activation syndrome appears as the source of M1-related cytokine storm in severe COVID-19 disease, thus indicating macrophages as a source of distinct inflammatory states in the two diseases, nonetheless as a common therapeutic target. New evidence indicates that NAMPT/NAD metabolism can direct both innate immune cell effector functions and the homeostatic robustness, in both cancer and infection. Moreover, a bidirectional relationship exists between the metabolism of NAD and the protective role that angiotensin converting enzyme 2, the COVID-19 receptor, can play against hyperinflammation. Within this immunometabolic framework, the review considers possible interference mechanisms that viral infections and tumors elicit on therapies and provides an overview for the management of patients with cancer affected by COVID-19, particularly for the balance of risk and benefit when planning normally routine cancer treatments and follow-up appointments.

scholarly journals Impact of Weight on Immune Cell Counts among HIV-Infected Persons

2011 ◽  
Vol 18 (6) ◽  
pp. 940-946 ◽  
Author(s):  
Nancy F. Crum-Cianflone ◽  
Mollie Roediger ◽  
Lynn E. Eberly ◽  
Anuradha Ganesan ◽  
Amy Weintrob ◽  
...  
Keyword(s):  
Highly Active Antiretroviral Therapy ◽  
Immune Cell ◽  
White Cell Count ◽  
Normal Weight ◽  
Longitudinal Models ◽  
Hiv Diagnosis ◽  
Highly Active ◽  
Cell Counts ◽  
Few Data ◽  
Cd4 Percentage

ABSTRACTPrior studies have shown that weight may impact immune cell counts. However, few data exist about the relationship of weight and immune cell counts among HIV-infected patients. We examined documented HIV seroconverters (mean window, 15.7 months) in a prospective U.S. Military HIV Natural History Study (1 January 1986 to 20 January 2010). We estimated the association of the time-updated body mass index (BMI) category with changes in immune cell counts from HIV diagnosis across time (mean follow-up of 5.1 years) using multiply adjusted longitudinal linear mixed-effects models. Of 1,097 HIV seroconverters, 448 (41%) were overweight and 93 (8%) were obese at HIV diagnosis. Immune cell counts at HIV diagnosis did not significantly differ by BMI category. In the longitudinal models for those diagnosed before the advent of the highly active antiretroviral therapy (HAART) era, mean postdiagnosis decreases in the white cell count, total lymphocyte count, CD4 count, CD4 percentage, and CD4/CD8 ratio were less as the BMI category increased (all withPvalues of <0.05). Among HIV seroconverters diagnosed in the HAART era, obese compared to normal-weight patients had significantly smaller increases in CD4 counts, CD4 percentages, and the CD4/CD8 ratio (all withPvalues of <0.05). Similar findings were also noted among underweight versus normal-weight patients. In conclusion, although BMI was not associated with immune cell levels at the time of HIV diagnosis, weight appears to affect immune cells counts over the course of infection. In the HAART era, being either underweight or obese was associated with smaller increases in several important immune cell levels, including the CD4/CD8 ratio.

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