scholarly journals The Inflammatory Milieu of Adamantinomatous Craniopharyngioma and Its Implications for Treatment

2020 ◽  
Vol 9 (2) ◽  
pp. 519 ◽  
Author(s):  
Ros Whelan ◽  
Eric Prince ◽  
Ahmed Gilani ◽  
Todd Hankinson
Keyword(s):  
Checkpoint Inhibitors ◽  
Critical Role ◽  
Current Treatment ◽  
Safe Alternative ◽  
Close Proximity ◽  
Inflammatory Processes ◽  
Adamantinomatous Craniopharyngioma ◽  
Aggressive Clinical Course ◽  
Inflammatory Milieu ◽  
Solid Tumor Tissue

Pediatric Adamantinomatous Craniopharyngiomas (ACPs) are histologically benign brain tumors that often follow an aggressive clinical course. Their suprasellar location leaves them in close proximity to critical neurological and vascular structures and often results in significant neuroendocrine morbidity. Current treatment paradigms, involving surgical resection and radiotherapy, confer significant morbidity to patients and there is an obvious need to discover effective and safe alternative treatments. Recent years have witnessed significant efforts to fully detail the genomic, transcriptomic and proteomic make-up of these tumors, in an attempt to identify potential therapeutic targets. These studies have resulted in ever mounting evidence that inflammatory processes and the immune response play a critical role in the pathogenesis of both the solid and cystic portion of ACPs. Several inflammatory and immune markers have been identified in both the cyst fluid and solid tumor tissue of ACP. Due to the existence of effective agents that target them, IL-6 and immune checkpoint inhibitors seem to present the most likely immediate candidates for clinical trials of targeted immune-related therapy in ACP. If effective, such agents may result in a paradigm shift in treatment that ultimately reduces morbidity and results in better outcomes for our patients.

scholarly journals Novel Self-Healing Metallocopolymers with Pendent 4-Phenyl-2,2′:6′,2″-terpyridine Ligand: Kinetic Studies and Mechanical Properties

Polymers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1760
Author(s):  
Rose K. Baimuratova ◽  
Gulzhian I. Dzhardimalieva ◽  
Evgeniy V. Vaganov ◽  
Valentina A. Lesnichaya ◽  
Gulsara D. Kugabaeva ◽  
...  
Keyword(s):  
Critical Role ◽  
Specific Effect ◽  
Kinetic Studies ◽  
Radical Copolymerization ◽  
Self Healing ◽  
Free Radical Copolymerization ◽  
Polymer Hydrogels ◽  
Close Proximity ◽  
Metal Group ◽  
Metal Polymer

We report here our successful attempt to obtain self-healing supramolecular hydrogels with new metal-containing monomers (MCMs) with pendent 4-phenyl-2,2′:6′,2″-terpyridine metal complexes as reversible moieties by free radical copolymerization of MCMs with vinyl monomers, such as acrylic acid and acrylamide. The resulting metal-polymer hydrogels demonstrate a developed system of hydrogen, coordination and electron-complementary π–π stacking interactions, which play a critical role in achieving self-healing. Kinetic data show that the addition of a third metal-containing comonomer to the system decreases the initial polymerization rate, which is due to the specific effect of the metal group located in close proximity of the active center on the growth of radicals.

scholarly journals Dendritic Cell Tumor Vaccination via Fc Gamma Receptor Targeting: Lessons Learned from Pre-Clinical and Translational Studies

Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 409
Author(s):  
Enrique Gómez Alcaide ◽  
Sinduya Krishnarajah ◽  
Fabian Junker
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Tumor Antigens ◽  
Checkpoint Inhibitors ◽  
Critical Role ◽  
Lessons Learned ◽  
Antigen Delivery ◽  
Tumor Vaccination ◽  
Translational Studies

Despite significant recent improvements in the field of immunotherapy, cancer remains a heavy burden on patients and healthcare systems. In recent years, immunotherapies have led to remarkable strides in treating certain cancers. However, despite the success of checkpoint inhibitors and the advent of cellular therapies, novel strategies need to be explored to (1) improve treatment in patients where these approaches fail and (2) make such treatments widely and financially accessible. Vaccines based on tumor antigens (Ag) have emerged as an innovative strategy with the potential to address these areas. Here, we review the fundamental aspects relevant for the development of cancer vaccines and the critical role of dendritic cells (DCs) in this process. We first offer a general overview of DC biology and routes of Ag presentation eliciting effective T cell-mediated immune responses. We then present new therapeutic avenues specifically targeting Fc gamma receptors (FcγR) as a means to deliver antigen selectively to DCs and its effects on T-cell activation. We present an overview of the mechanistic aspects of FcγR-mediated DC targeting, as well as potential tumor vaccination strategies based on preclinical and translational studies. In particular, we highlight recent developments in the field of recombinant immune complex-like large molecules and their potential for DC-mediated tumor vaccination in the clinic. These findings go beyond cancer research and may be of relevance for other disease areas that could benefit from FcγR-targeted antigen delivery, such as autoimmunity and infectious diseases.

scholarly journals Immune System Efficiency in Cancer and the Microbiota Influence

Pathobiology ◽  
2021 ◽  
pp. 1-17
Author(s):  
Ana Margarida Barbosa ◽  
Alexandra Gomes-Gonçalves ◽  
António G. Castro ◽  
Egídio Torrado
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Immune Checkpoint Inhibitors ◽  
Therapeutic Response ◽  
Checkpoint Inhibitors ◽  
Critical Role ◽  
Antitumor Immune Response ◽  
System Efficiency ◽  
Novel Targets ◽  
Cancer Immunosurveillance

The immune system plays a critical role in preventing cancer development and progression. However, the complex network of cells and soluble factor that form the tumor microenvironment (TME) can dictate the differentiation of tumor-infiltrating leukocytes and shift the antitumor immune response into promoting tumor growth. With the advent of cancer immunotherapy, there has been a reinvigorated interest in defining how the TME shapes the antitumor immune response. This interest brought to light the microbiome as a novel player in shaping cancer immunosurveillance. Indeed, accumulating evidence now suggests that the microbiome may confer susceptibility or resistance to certain cancers and may influence response to therapeutics, particularly immune checkpoint inhibitors. As we move forward into the age of precision medicine, it is vital that we define the factors that influence the interplay between the triad immune system-microbiota-cancer. This knowledge will contribute to improve the therapeutic response to current approaches and will unravel novel targets for immunotherapy.

scholarly journals The Evolutionary Landscape of Treatment for BRAFV600E Mutant Metastatic Colorectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 137
Author(s):  
Gianluca Mauri ◽  
Erica Bonazzina ◽  
Alessio Amatu ◽  
Federica Tosi ◽  
Katia Bencardino ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Checkpoint Inhibitors ◽  
Mapk Pathway ◽  
Treatment Options ◽  
Braf Inhibitor ◽  
Current Treatment ◽  
Cytotoxic Chemotherapy ◽  
Cytotoxic Agents ◽  
Poor Prognostic Factor

The BRAFV600E mutation is found in 8–10% of metastatic colorectal cancer (mCRC) patients and it is recognized as a poor prognostic factor with a median overall survival inferior to 20 months. At present, besides immune checkpoint inhibitors (CPIs) for those tumors with concomitant MSI-H status, recommended treatment options include cytotoxic chemotherapy + anti-VEGF in the first line setting, and a combination of EGFR and a BRAF inhibitor (cetuximab plus encorafenib) in second line. However, even with the latter targeted approach, acquired resistance limits the possibility of more than an incremental benefit and survival is still dismal. In this review, we discuss current treatment options for this subset of patients and perform a systematic review of ongoing clinical trials. Overall, we identified six emerging strategies: targeting MAPK pathway (monotherapy or combinations), targeting MAPK pathway combined with cytotoxic agents, intensive cytotoxic regimen combinations, targeted agents combined with CPIs, oxidative stress induction, and cytotoxic agents combined with antiangiogenic drugs and CPIs. In the future, the integration of new therapeutic strategies targeting key players in the BRAFV600E oncogenic pathways with current treatment approach based on cytotoxic chemotherapy and surgery is likely to redefine the treatment landscape of these CRC patients.

scholarly journals Pharmacological Interventions for Pulmonary Involvement in Rheumatic Diseases

2021 ◽  
Vol 14 (3) ◽  
pp. 251 ◽  
Author(s):  
Eun Ha Kang ◽  
Yeong Wook Song
Keyword(s):  
Rheumatic Diseases ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Pulmonary Involvement ◽  
Current Treatment ◽  
Targeted Agents ◽  
Pharmacological Interventions ◽  
Inflammatory Processes ◽  
Pulmonary Arterial ◽  
Epidemiologic Features

Among the diverse forms of lung involvement, interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) are two important conditions in patients with rheumatic diseases that are associated with significant morbidity and mortality. The management of ILD and PAH is challenging because the current treatment often provides only limited patient survival benefits. Such challenges derive from their common pathogenic mechanisms, where not only the inflammatory processes of immune cells but also the fibrotic and proliferative processes of nonimmune cells play critical roles in disease progression, making immunosuppressive therapy less effective. Recently, updated treatment strategies adopting targeted agents have been introduced with promising results in clinical trials for ILD ad PAH. This review discusses the epidemiologic features of ILD and PAH among patients with rheumatic diseases (rheumatoid arthritis, myositis, and systemic sclerosis) and the state-of-the-art treatment options, focusing on targeted agents including biologics, antifibrotic agents, and vasodilatory drugs.

scholarly journals Duodenal imaging on the spotlight: from A to Z

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Carolina Terra ◽  
Daniel Ramos-Andrade ◽  
Ivo Sá-Marques ◽  
Jorge Brito ◽  
Filipe Caseiro-Alves ◽  
...  
Keyword(s):  
Imaging Features ◽  
Upper Gastrointestinal Series ◽  
Alphabetical Order ◽  
Gastrointestinal Series ◽  
Local Extension ◽  
General Radiologist ◽  
Gastrointestinal Radiology ◽  
Close Proximity ◽  
Inflammatory Processes ◽  
Upper Gastrointestinal

AbstractAbdominal computed tomography (CT) is frequently performed to evaluate gastrointestinal pathologic conditions. The majority of the gastrointestinal radiology literature has concentrated on the colon, stomach, and distal small bowel. The duodenum is often overlooked on imaging, namely on CT, but its anatomy (intra and retroperitoneal) and location in such close proximity to other viscera results in involvement by a multitude of primary and secondary processes, some of them exclusive to this bowel segment. While some conditions, like duplications, lipomas, and diverticula, are usually asymptomatic and are incidentalomas that have no pathologic significance, others are symptomatic and very relevant and should be recognized by every general radiologist: development conditions such as annular pancreas and gut malrotation; inflammatory processes such as ulcers and secondary involvement from pancreatitis; neoplastic conditions such as adenocarcinoma, lymphoma, or local extension from adjacent malignancies. They all can be reliably diagnosed with CT. In this article, we demonstrate the typical imaging features of various diseases involving the duodenum, such as developmental, traumatic, inflammatory, infectious, neoplastic, and postsurgical pathologic conditions in alphabetical order, focusing mainly on upper gastrointestinal series (UGIS) and CT but also some radiography, ultrasound, and magnetic resonance (MR) imaging.

scholarly journals Clinical Presentation, Pathogenesis, Diagnosis, and Treatment of Epidermolysis Bullosa Acquisita

2013 ◽  
Vol 2013 ◽  
pp. 1-25 ◽  
Author(s):  
Ralf J. Ludwig
Keyword(s):  
Epidermolysis Bullosa ◽  
Clinical Presentation ◽  
Tissue Injury ◽  
Critical Role ◽  
Current Treatment ◽  
Epidermolysis Bullosa Acquisita ◽  
Target Antigen ◽  
In Vivo Models ◽  
Type Vii Collagen ◽  
Novel Therapeutic

Epidermolysis bullosa acquisita (EBA) is a chronic mucocutaneous autoimmune skin blistering disease. The pathogenic relevance of autoantibodies targeting type VII collagen (COL7) has been well-documented. Therefore, EBA is a prototypical autoimmune disease with a well-characterized pathogenic relevance of autoantibody binding to the target antigen. EBA is a rare disease with an incidence of 0.2 new cases per million and per year. The current treatment of EBA relies on general immunosuppressive therapy, which does not lead to remission in all cases. Therefore, there is a high, so far unmet medical need for the development of novel therapeutic options. During the last 10 years, several novel in vitro and in vivo models of EBA have been established. These models demonstrated a critical role of the genetic background, T cells, and cytokines for mediating the loss of tolerance towards COL7. Neutrophils, complement activation, Fc gamma receptor engagement, cytokines, several molecules involved in cell signaling, release of reactive oxygen species, and matrix metalloproteinases are crucial for autoantibody-induced tissue injury in EBA. Based on this growing understanding of the diseases’ pathogenesis, several potential novel therapeutic targets have emerged. In this review, the clinical presentation, pathogenesis, diagnosis, and current treatment options for EBA are discussed in detail.

scholarly journals Embryological Remnants of the Thyroid Gland and their Significance in Thyroidectomy

2014 ◽  
Vol 6 (3) ◽  
pp. 110-112 ◽  
Author(s):  
R Fernando ◽  
Anuradha Rajapaksha ◽  
Narada Ranasinghe ◽  
Duminda Gunawardana
Keyword(s):  
Thyroid Gland ◽  
Current Knowledge ◽  
Critical Role ◽  
Close Proximity ◽  
Pyramidal Lobe

ABSTRACT Thyroid gland has three main embryological remnants: pyramidal lobe, tubercle of Zuckerkandl and thyrothymic remnants. They are commonly missed or misidentified during dissection. Each of these remnants plays a critical role in thyroidectomy as they help to identify the relevant anatomy and therefore help prevent accidental damage to other structures in close proximity during dissection. In this article, we describe the current knowledge of each of these remnants and their significance in thyroidectomy. Conclusion It is important that all these remnants are objectively looked for and removed during surgery in order to prevent recurrences. How to cite this article Fernando R, Rajapaksha A, Ranasinghe N, Gunawardana D. Embryological Remnants of the Thyroid Gland and their Significance in Thyroidectomy. World J Endoc Surg 2014;6(3):110-112.

scholarly journals What Makes a Great Resident Teacher? A Multicenter Survey of Medical Students Attending an Internal Medicine Conference

2014 ◽  
Vol 6 (4) ◽  
pp. 694-697 ◽  
Author(s):  
Lindsay Melvin ◽  
Zain Kassam ◽  
Andrew Burke ◽  
Parveen Wasi ◽  
John Neary
Keyword(s):  
Internal Medicine ◽  
Medical Students ◽  
Effective Teachers ◽  
Critical Role ◽  
High Expectations ◽  
Multicenter Survey ◽  
Close Proximity ◽  
Core Concepts ◽  
Giving Feedback ◽  
Teacher Traits

Abstract Background Residents have a critical role in the education of medical students and have a unique teaching relationship because of their close proximity in professional development and opportunities for direct supervision. Although there is emerging literature on ways to prepare residents to be effective teachers, there is a paucity of data on what medical students believe are the attributes of successful resident teachers. Objective We sought to define the qualities and teaching techniques that learners interested in internal medicine value in resident teachers. Methods We created and administered a resident-as-teacher traits survey to senior medical students from 6 medical schools attending a resident-facilitated clinical conference at McMaster University. The survey collected data on student preferences of techniques employed by resident teachers and qualities of a successful resident teacher. Results Of 90 student participants, 80 (89%) responded. Respondents found the use of clinical examples (78%, 62 of 80) and repetition of core concepts (71%, 58 of 80) highly useful. In contrast, most respondents did not perceive giving feedback to residents, or receiving feedback from residents, was useful to their learning. With respect to resident qualities, respondents felt that a strong knowledge base (80%, 64 of 80) and tailoring teaching to the learner's level (83%, 66 of 80) was highly important. In contrast, high expectations on the part of resident supervisors were not valued. Conclusions This multicenter survey provides insight into the perceptions of medical students interested in internal medicine on the techniques and qualities that characterize successful resident teachers. The findings may be useful in the future development of resident-as-teacher curricula.

scholarly journals Epigenetic Reprogramming for Targeting IDH-Mutant Malignant Gliomas

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1616 ◽  
Author(s):  
Jong-Whi Park ◽  
Şevin Turcan
Keyword(s):  
Treatment Effectiveness ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Malignant Gliomas ◽  
Current Treatment ◽  
Epigenetic Therapy ◽  
Lower Grade ◽  
Recurrent Mutations ◽  
Tumor Immunogenicity ◽  
Dna Methylation Inhibitors

Targeting the epigenome has been considered a compelling treatment modality for several cancers, including gliomas. Nearly 80% of the lower-grade gliomas and secondary glioblastomas harbor recurrent mutations in isocitrate dehydrogenase (IDH). Mutant IDH generates high levels of 2-hydroxyglutarate (2-HG) that inhibit various components of the epigenetic machinery, including histone and DNA demethylases. The encouraging results from current epigenetic therapies in hematological malignancies have reinvigorated the interest in solid tumors and gliomas, both preclinically and clinically. Here, we summarize the recent advancements in epigenetic therapy for lower-grade gliomas and discuss the challenges associated with current treatment options. A particular focus is placed on therapeutic mechanisms underlying favorable outcome with epigenetic-based drugs in basic and translational research of gliomas. This review also highlights emerging bridges to combination treatment with respect to epigenetic drugs. Given that epigenetic therapies, particularly DNA methylation inhibitors, increase tumor immunogenicity and antitumor immune responses, appropriate drug combinations with immune checkpoint inhibitors may lead to improvement of treatment effectiveness of immunotherapy, ultimately leading to tumor cell eradication.

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