scholarly journals The Gastrointestinal Tumor Microenvironment: An Updated Biological and Clinical Perspective

2019 ◽  
Vol 2019 ◽  
pp. 1-22 ◽  
Author(s):  
Silvia Batista ◽  
Ana C. Gregório ◽  
Andreia Hanada Otake ◽  
Nuno Couto ◽  
Bruno Costa-Silva
Keyword(s):  
Extracellular Matrix ◽  
Immune Modulation ◽  
Tumor Biology ◽  
Tumor Development ◽  
Therapeutic Strategies ◽  
Clinical Perspective ◽  
Gastrointestinal Cancers ◽  
Gastrointestinal Tumor ◽  
Resistance To Therapy ◽  
Potential Benefits

Gastrointestinal cancers are still responsible for high numbers of cancer-related deaths despite advances in therapy. Tumor-associated cells play a key role in tumor biology, by supporting or halting tumor development through the production of extracellular matrix, growth factors, cytokines, and extracellular vesicles. Here, we review the roles of these tumor-associated cells in the initiation, angiogenesis, immune modulation, and resistance to therapy of gastrointestinal cancers. We also discuss novel diagnostic and therapeutic strategies directed at tumor-associated cells and their potential benefits for the survival of these patients.

DENDRITIC CELL VACCINATION IN PATIENTS WITH MALIGNANT GLIOMAS

Neurosurgery ◽  
2006 ◽  
Vol 59 (5) ◽  
pp. 988-1000 ◽  
Author(s):  
Steven de Vleeschouwer ◽  
Marion Rapp ◽  
Rüdiger V. Sorg ◽  
Hans-Jakob Steiger ◽  
Walter Stummer ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Immune Modulation ◽  
Malignant Gliomas ◽  
Tumor Biology ◽  
Active Immunotherapy ◽  
Dendritic Cell Vaccination ◽  
Dismal Prognosis ◽  
Clinical Responses ◽  
Potential Benefits ◽  
Small Clinical Trials

Abstract OBJECTIVE Despite recent advances in neurosurgical resection techniques, radiation therapy, and chemotherapy, malignant gliomas continue to have a dismal prognosis because relapses are unavoidable. METHODS Dendritic cell vaccination has recently emerged as a promising type of active immunotherapy that aims to induce rather than transfer specific antitumor immune responses in patients. Active immunotherapy is the only type of immunotherapy able to induce immunological memory. RESULTS Although an increasing number of small clinical trials show safety, feasibility, and immunological and clinical responses, this technology requires further clarification of some critical basic and clinical issues before its presumed place in the treatment of malignant gliomas can be specified. This article addresses the basic and clinical pitfalls that, more than with conventional therapies, may interfere with the potential benefits of this approach. CONCLUSION Considering the particular mechanisms involved in the immune modulation of tumor biology using dendritic cell-based vaccinations, the authors summarize the arguments in favor of a further, appropriate assessment of this technology.

scholarly journals The PDAC Extracellular Matrix: A Review of the ECM Protein Composition, Tumor Cell Interaction, and Therapeutic Strategies

2021 ◽  
Vol 11 ◽  
Author(s):  
Vincent M. Perez ◽  
Joseph F. Kearney ◽  
Jen Jen Yeh
Keyword(s):  
Extracellular Matrix ◽  
Tumor Biology ◽  
Fluid Pressure ◽  
Protein Composition ◽  
Cell Interaction ◽  
Biochemical Properties ◽  
Therapeutic Strategies ◽  
Cell Junctions ◽  
Host Responses ◽  
Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is notorious for a dense fibrotic stroma that is interlaced with a collagen-based extracellular matrix (ECM) that plays an important role in tumor biology. Traditionally thought to only provide a physical barrier from host responses and systemic chemotherapy, new studies have demonstrated that the ECM maintains biomechanical and biochemical properties of the tumor microenvironment (TME) and restrains tumor growth. Recent studies have shown that the ECM augments tumor stiffness, interstitial fluid pressure, cell-to-cell junctions, and microvascularity using a mix of biomechanical and biochemical signals to influence tumor fate for better or worse. In addition, PDAC tumors have been shown to use ECM-derived peptide fragments as a nutrient source in nutrient-poor conditions. While collagens are the most abundant proteins found in the ECM, several studies have identified growth factors, integrins, glycoproteins, and proteoglycans in the ECM. This review focuses on the dichotomous nature of the PDAC ECM, the types of collagens and other proteins found in the ECM, and therapeutic strategies targeting the PDAC ECM.

Diabetic Cardiomyopathy: From Mechanism to Management in a Nutshell

2020 ◽  
Vol 20 ◽  
Author(s):  
Shahzad Khan ◽  
Syed S. Ahmad ◽  
Mohammad A. Kamal
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Immune Modulation ◽  
Cell Injury ◽  
Interstitial Fibrosis ◽  
Systolic Dysfunction ◽  
Therapeutic Strategies ◽  
Cardiac Cell ◽  
Clinical Heart Failure ◽  
Artery Disease ◽  
Apoptosis And Necrosis

: Diabetic cardiomyopathy (DCM) is a significant complication of diabetes mellitus characterized by gradual failing heart with detrimental cardiac remodellings such as fibrosis and diastolic and systolic dysfunction, which is not directly attributable to coronary artery disease. Insulin resistance and resulting hyperglycemia is the main trigger involved in the initiation of diabetic cardiomyopathy. There is a constellation of many pathophysiological events such as lipotoxicity, oxidative stress, inflammation, inappropriate activation of the renin-angiotensin-aldosterone system, dysfunctional immune modulation promoting increased rate of cardiac cell injury, apoptosis, and necrosis which ultimately culminates into interstitial fibrosis, cardiac stiffness, diastolic dysfunction initially and later systolic dysfunction too. These events finally lead to clinical heart failure of DCM. Herein, we have briefly discussed the pathophysiology of DCM. We have also briefly mentioned potential therapeutic strategies currently used for DCM.

scholarly journals Consumption of Select Dietary Emulsifiers Exacerbates the Development of Spontaneous Intestinal Adenoma

2021 ◽  
Vol 22 (5) ◽  
pp. 2602
Author(s):  
Emilie Viennois ◽  
Benoit Chassaing
Keyword(s):  
Intestinal Inflammation ◽  
Tumor Development ◽  
Low Grade ◽  
Gastrointestinal Cancers ◽  
Cancer Initiation ◽  
And Function ◽  
The Impact ◽  
Chronic Intestinal Inflammation ◽  
Low Grade Inflammation ◽  
Intestinal Adenoma

Inflammation is a well-characterized critical driver of gastrointestinal cancers. Previous findings have shown that intestinal low-grade inflammation can be promoted by the consumption of select dietary emulsifiers, ubiquitous component of processed foods which alter the composition and function of the gut microbiota. Using a model of colitis-associated cancer, we previously reported that consumption of the dietary emulsifiers carboxymethylcellulose or polysorbate-80 exacerbated colonic tumor development. Here, we investigate the impact of dietary emulsifiers consumption on cancer initiation and progression in a genetical model of intestinal adenomas. In APCmin mice, we observed that dietary emulsifiers consumption enhanced small-intestine tumor development in a way that appeared to be independent of chronic intestinal inflammation but rather associated with emulsifiers’ impact on the proliferative status of the intestinal epithelium as well as on intestinal microbiota composition in both male and female mice. Overall, our findings further support the hypothesis that emulsifier consumption may be a new modifiable risk factor for colorectal cancer (CRC) and that alterations in host–microbiota interactions can favor gastrointestinal carcinogenesis in individuals with a genetical predisposition to such disorders.

Epigenetics in Clinical Management of Children and Adolescents with Brain Tumors

2017 ◽  
Vol 18 (1) ◽  
pp. 57-64 ◽  
Author(s):  
Andres Morales La Madrid ◽  
Mark W. Kieran
Keyword(s):  
Nervous System ◽  
Brain Tumors ◽  
Children And Adolescents ◽  
Tumor Biology ◽  
Tumor Development ◽  
Integrated Approach ◽  
Cell Types ◽  
Pediatric Brain Tumors ◽  
Tumor Formation ◽  
Molecular Profile

Central nervous system (CNS) tumors represent the second most prevalent group of cancers in children and adolescents, yet account for the majority of childhood cancer-related deaths and considerable morbidity among survivors, due to high-intensity non-selective standard therapies delivered to immature nervous system structures undergoing development. These tumors arise at different ages –not infrequently very early in life-, in different locations and cellular contexts, have varied cell types of origin, and have heterogeneous responses to the “classic” current therapeutic approaches. Demographic, radiologic and morphological characterization have several limitations, putting into the “classic boxes” heterogeneous tumors that are diverse in their genetic and epigenetic background and that will likely behave biologically different. Given that, epigenetic disruption (i.e. DNA methylation, histone modification and chromatin remodeling) is a common feature identified more and more frequently in pediatric cancer, it is logical to speculate that interrogating epigenetic marks may help to further define the molecular profile, and therefore tumor biology, evolution and treatment of these tumors. An integrated approach that incorporates traditional features complemented with genetic and epigenenetic specific markers offers tremendous promise to “risk-group” stratification and better prognostication. Also, it will help unveil the key driver pathways for tumor formation and for the discovery of targeted therapy for neoplasms that appear in the developing brain, facilitating early identification of therapy responders and track accurately disease progression. In this paper, we reviewed the most representative pediatric brain tumors where epigenetic alterations have been identified as initiating or driving events in tumor development, maintenance or progression.

The extracellular matrix in skin tumor development – a morphological study

1999 ◽  
Vol 26 (7) ◽  
pp. 327-338 ◽  
Author(s):  
Frej Stenback ◽  
Markus J. Makinen ◽  
Tommi Jussila ◽  
Saila Kauppila ◽  
Juha Risteli ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Morphological Study ◽  
Tumor Development ◽  
Skin Tumor

scholarly journals Therapeutic Strategies for Diabetes: Immune Modulation in Pancreatic β Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Sugyeong Jo ◽  
Sungsoon Fang
Keyword(s):  
Clinical Trials ◽  
T Cells ◽  
Type Ii Diabetes ◽  
Immune Modulation ◽  
Therapeutic Strategies ◽  
Immune Homeostasis ◽  
Type I ◽  
Type Ii ◽  
Pancreatic Β Cell ◽  
Β Cell

Increased incidence of type I and type II diabetes has been prevailed worldwide. Though the pathogenesis of molecular mechanisms remains still unclear, there are solid evidence that disturbed immune homeostasis leads to pancreatic β cell failure. Currently, autoimmunity and uncontrolled inflammatory signaling pathways have been considered the major factors in the pathogenesis of diabetes. Many components of immune system have been reported to implicate pancreatic β cell failure, including helper T cells, cytotoxic T cells, regulatory T cells and gut microbiota. Immune modulation of those components using small molecules and antibodies, and fecal microbiota transplantation are undergoing in many clinical trials for the treatment of type I and type II diabetes. In this review we will discuss the basis of molecular pathogenesis focusing on the disturbed immune homeostasis in type I and type II diabetes, leading to pancreatic β cell destruction. Finally, we will introduce current therapeutic strategies and clinical trials by modulation of immune system for the treatment of type I and type II diabetes patients.

scholarly journals Roles of tumor-associated macrophages in tumor progression: implications on therapeutic strategies

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Shangli Zhu ◽  
Ming Yi ◽  
Yuze Wu ◽  
Bing Dong ◽  
Kongming Wu
Keyword(s):  
Tumor Progression ◽  
Tumor Development ◽  
Treatment Strategies ◽  
Therapeutic Strategies ◽  
Tumor Associated Macrophages ◽  
Promising Target ◽  
Multiple Processes ◽  
Enhance Tumor Cell ◽  
Patient Prognosis ◽  
Anti Tumor Activity

AbstractMacrophages are heterogeneous cells that present as different functional phenotypes due to their plasticity. They can be classified into two categories, namely M1- and M2-like macrophages, which are involved in processes as diverse as anti-tumor activity and immunosuppressive tumor promotion. Tumor-associated macrophages (TAMs) are defined as being of an M2-type and are considered as the active component in tumor microenvironment. TAMs are involved in multiple processes of tumor progression through the expression of cytokines, chemokines, growth factors, protein hydrolases and more, which lead to enhance tumor cell proliferation, angiogenesis, and immunosuppression, which in turn supports invasion and metastasis. It is assumed that the abundance of TAMs in major solid tumors is correlated to a negative patient prognosis. Because of the currently available data of the TAMs’ role in tumor development, these cells have emerged as a promising target for novel cancer treatment strategies. In this paper, we will briefly describe the origins and types of TAMs and will try to comprehensively show how TAMs contribute to tumorigenesis and disease progression. Finally, we will present the main TAM-based therapeutic strategies currently available.

scholarly journals Expression of Extracellular Matrix—Laminin in Oral Squamous Cell Carcinoma: An Immunohistochemical Study

2012 ◽  
Vol 13 (2) ◽  
pp. 194-200
Author(s):  
Sonam C Kapse ◽  
Ajit V Koshy ◽  
Nirmala N Rao ◽  
Sushant S Kamat ◽  
Kamal Kiswani ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Immunohistochemical Study ◽  
Tumor Development ◽  
Treatment Strategies ◽  
Prognostic Indicators ◽  
Chi Square

ABSTRACT Aim To evaluate the expression of laminin in various grades of oral squamous cell carcinoma (OSCC) in order to determine whether this protein can be used as a marker for early detection and elucidation of oral cancer. Materials and methods Immunohistochemical staining for laminin was done on 60 selected archival blocks of histopathologically diagnosed cases of primary OSCC and the laminin expression was compared between the different histopathological grades of primary OSCC. The statistical analysis was performed by using Chi-square (÷ square) test and Gaussiantest with a probability of p < 0.05 was considered as significant. Results It was observed that laminin expression decreased with tumor progression which may be correlated to the tumor aggressiveness. Conclusion There was a gradual decrease of laminin staining with decreasing cellular differentiation, with differentiated lesions showing a more conspicuous staining of basement membrane glycoprotein than less differentiated lesions. Clinical significance An understanding of how the extracellular matrix influences tumor development and invasion is fundamental in the development of new prognostic indicators and treatment strategies for oral squamous cell carcinoma. How to cite this article Koshy AV, Rao NN, Kamat SS, Kiswani K, Kapse SC, Shaikh NA. Expression of Extracellular Matrix— Laminin in Oral Squamous Cell Carcinoma: An Immunohistochemical Study. J Contemp Dent Pract 2012;13(2):194-200.

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