scholarly journals Immune Sensing and Potential Immunotherapeutic Approaches to Control Chromoblastomycosis

2020 ◽  
Vol 7 (1) ◽  
pp. 3
Author(s):  
Leandro C. D. Breda ◽  
Isabela G. Menezes ◽  
Larissa N. M. Paulo ◽  
Sandro Rogério de Almeida
Keyword(s):  
Social Stigma ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Treatment Interruption ◽  
Lower Limbs ◽  
Disease Treatment ◽  
Immune Sensing ◽  
Skin Immunology ◽  
Anti Fungal ◽  
Made In

Chromoblastomycosis (CBM) is a neglected, chronic, and progressive subcutaneous mycosis caused by different species of fungi from the Herpotrichiellaceae family. CBM disease is usually associated with agricultural activities, and its infection is characterized by verrucous, erythematous papules, and atrophic lesions on the upper and lower limbs, leading to social stigma and impacts on patients’ welfare. The economic aspect of disease treatment is another relevant issue. There is no specific treatment for CBM, and different anti-fungal drug associations are used to treat the patients. However, the long period of the disease and the high cost of the treatment lead to treatment interruption and, consequently, relapse of the disease. In previous years, great progress had been made in the comprehension of the CBM pathophysiology. In this review, we discuss the differences in the cell wall composition of conidia, hyphae, and muriform cells, with a particular focus on the activation of the host immune response. We also highlight the importance of studies about the host skin immunology in CBM. Finally, we explore different immunotherapeutic studies, highlighting the importance of these approaches for future treatment strategies for CBM.

scholarly journals Molecular Subtypes and Precision Oncology in Intrahepatic Cholangiocarcinoma

2021 ◽  
Vol 10 (13) ◽  
pp. 2803
Author(s):  
Carolin Czauderna ◽  
Martha M. Kirstein ◽  
Hauke C. Tews ◽  
Arndt Vogel ◽  
Jens U. Marquardt
Keyword(s):  
Clinical Care ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Growth Factor Receptor ◽  
Treatment Modalities ◽  
Precision Oncology ◽  
Recurrence Rates ◽  
Isocitrate Dehydrogenase 1 ◽  
Liver Cancers

Cholangiocarcinomas (CCAs) are the second-most common primary liver cancers. CCAs represent a group of highly heterogeneous tumors classified based on anatomical localization into intra- (iCCA) and extrahepatic CCA (eCCA). In contrast to eCCA, the incidence of iCCA is increasing worldwide. Curative treatment strategies for all CCAs involve oncological resection followed by adjuvant chemotherapy in early stages, whereas chemotherapy is administered at advanced stages of disease. Due to late diagnosis, high recurrence rates, and limited treatment options, the prognosis of patients remains poor. Comprehensive molecular characterization has further revealed considerable heterogeneity and distinct prognostic and therapeutic traits for iCCA and eCCA, indicating that specific treatment modalities are required for different subclasses. Several druggable alterations and oncogenic drivers such as fibroblast growth factor receptor 2 gene fusions and hotspot mutations in isocitrate dehydrogenase 1 and 2 mutations have been identified. Specific inhibitors have demonstrated striking antitumor activity in affected subgroups of patients in phase II and III clinical trials. Thus, improved understanding of the molecular complexity has paved the way for precision oncological approaches. Here, we outline current advances in targeted treatments and immunotherapeutic approaches. In addition, we delineate future perspectives for different molecular subclasses that will improve the clinical care of iCCA patients.

scholarly journals When to Substitute a Missing Upper Lateral With a Canine: A Simplified Approach

2021 ◽  
pp. 030157422098054
Author(s):  
Renu Datta
Keyword(s):  
Anterior Segment ◽  
Specific Treatment ◽  
Simplified Approach ◽  
Special Cases ◽  
Randomized Control ◽  
The One ◽  
Individual Presentation ◽  
Available Information ◽  
Missing Tooth ◽  
Made In

Introduction: The upper lateral incisor is the most commonly missing tooth in the anterior segment. It leads to esthetic and functional imbalance for the patients. The ideal solution is the one that is most conservative and which fulfills the functional and esthetic needs of the concerned individual. Canine substitution is evolving to be the treatment of choice in most of the cases, because of its various advantages. These are special cases that need more time and effort from the clinicians due to space discrepancy in the upper and lower arches, along with the presentation of individual malocclusion. Aims and Objectives: Malocclusion occurring due to missing laterals is more complex, needing more time and effort from the clinicians because of space discrepancy, esthetic compromise, and individual presentation of the malocclusion. An attempt has been made in this article to review, evaluate, and tabulate the important factors for the convenience of clinicians. Method: All articles related to canine substitution were searched in the electronic database PubMed, and the important factors influencing the decision were reviewed. After careful evaluation, the checklist was evolved. Result: The malocclusions in which canine substitution is the treatment of choice are indicated in the tabular form for the convenience of clinicians. Specific treatment-planning considerations and biomechanics that can lead to an efficient and long-lasting result are also discussed. Conclusion: The need of the hour is an evidence-based approach, along with a well-designed prospective randomized control trial to understand the importance of each factor influencing these cases. Until that time, giving the available information in a simplified way can be a quality approach to these cases.

scholarly journals Molecular subtype-specific efficacy of anti-EGFR therapy in colorectal cancer is dependent on the chemotherapy backbone

2021 ◽  
Author(s):  
Sanne ten Hoorn ◽  
Dirkje W. Sommeijer ◽  
Faye Elliott ◽  
David Fisher ◽  
Tim R. de Back ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Subtype ◽  
Primary Tumour ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
Tumour Location ◽  
Selection For

Abstract Background Patient selection for addition of anti-EGFR therapy to chemotherapy for patients with RAS and BRAF wildtype metastatic colorectal cancer can still be optimised. Here we investigate the effect of anti-EGFR therapy on survival in different consensus molecular subtypes (CMSs) and stratified by primary tumour location. Methods Retrospective analyses, using the immunohistochemistry-based CMS classifier, were performed in the COIN (first-line oxaliplatin backbone with or without cetuximab) and PICCOLO trial (second-line irinotecan with or without panitumumab). Tumour tissue was available for 323 patients (20%) and 349 (41%), respectively. Results When using an irinotecan backbone, anti-EGFR therapy is effective in both CMS2/3 and CMS4 in left-sided primary tumours (progression-free survival (PFS): HR 0.44, 95% CI 0.26–0.75, P = 0.003 and HR 0.12, 95% CI 0.04–0.36, P < 0.001, respectively) and in CMS4 right-sided tumours (PFS HR 0.17, 95% CI 0.04–0.71, P = 0.02). Efficacy using an oxaliplatin backbone was restricted to left-sided CMS2/3 tumours (HR 0.57, 95% CI 0.36–0.96, P = 0.034). Conclusions The subtype-specific efficacy of anti-EGFR therapy is dependent on the chemotherapy backbone. This may provide the possibility of subtype-specific treatment strategies for a more optimal use of anti-EGFR therapy.

scholarly journals Single cell-derived clonal analysis of human glioblastoma links functional and genomic heterogeneity

2015 ◽  
Vol 112 (3) ◽  
pp. 851-856 ◽  
Author(s):  
Mona Meyer ◽  
Jüri Reimand ◽  
Xiaoyang Lan ◽  
Renee Head ◽  
Xueming Zhu ◽  
...  
Keyword(s):  
Functional Significance ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Clonal Analysis ◽  
Specific Drug ◽  
Drug Resistant ◽  
Naive Patient ◽  
Functional Behavior ◽  
Proliferation And Differentiation ◽  
Genomic Analyses

Glioblastoma (GBM) is a cancer comprised of morphologically, genetically, and phenotypically diverse cells. However, an understanding of the functional significance of intratumoral heterogeneity is lacking. We devised a method to isolate and functionally profile tumorigenic clones from patient glioblastoma samples. Individual clones demonstrated unique proliferation and differentiation abilities. Importantly, naïve patient tumors included clones that were temozolomide resistant, indicating that resistance to conventional GBM therapy can preexist in untreated tumors at a clonal level. Further, candidate therapies for resistant clones were detected with clone-specific drug screening. Genomic analyses revealed genes and pathways that associate with specific functional behavior of single clones. Our results suggest that functional clonal profiling used to identify tumorigenic and drug-resistant tumor clones will lead to the discovery of new GBM clone-specific treatment strategies.

scholarly journals Cancer-Associated Fibroblasts in Breast Cancer Treatment Response and Metastasis

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3146
Author(s):  
Patricia Fernández-Nogueira ◽  
Gemma Fuster ◽  
Álvaro Gutierrez-Uzquiza ◽  
Pere Gascón ◽  
Neus Carbó ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hormone Receptors ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Growth Factor Receptor ◽  
Cancer Associated Fibroblasts ◽  
Luminal A ◽  
Luminal B ◽  
Number Of Patients ◽  
Current Therapies

Breast cancer (BrCa) is the leading cause of death among women worldwide, with about one million new cases diagnosed each year. In spite of the improvements in diagnosis, early detection and treatment, there is still a high incidence of mortality and failure to respond to current therapies. With the use of several well-established biomarkers, such as hormone receptors and human epidermal growth factor receptor-2 (HER2), as well as genetic analysis, BrCa patients can be categorized into multiple subgroups: Luminal A, Luminal B, HER2-enriched, and Basal-like, with specific treatment strategies. Although chemotherapy and targeted therapies have greatly improved the survival of patients with BrCa, there is still a large number of patients who relapse or who fail to respond. The role of the tumor microenvironment in BrCa progression is becoming increasingly understood. Cancer-associated fibroblasts (CAFs) are the principal population of stromal cells in breast tumors. In this review, we discuss the current understanding of CAFs’ role in altering the tumor response to therapeutic agents as well as in fostering metastasis in BrCa. In addition, we also review the available CAFs-directed molecular therapies and their potential implications for BrCa management.

Ranscriptome Analysis Reveals the Molecular Mechanism of Yiqi Rougan Decoction in Reducing CCl4-induced Liver Fibrosis in Rats

2021 ◽  
Author(s):  
Yu Xiong ◽  
Jinyuan Hu ◽  
Chen Xuan ◽  
Jiayu Tian ◽  
Kaiyue Tan ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Liver Fibrosis ◽  
Liver Injury ◽  
Molecular Mechanism ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Mitogen Activated Protein Kinase ◽  
Signalling Pathways ◽  
High Dose ◽  
Peroxisome Proliferator

Abstract BackgroundLiver fibrosis develops from various chronic liver diseases, and there is currently a lack of specific treatment strategies. Yiqi Rougan decoction (YQRG) is a traditional Chinese medicine that has shown durative effects in the treatment of liver fibrosis; however, the mechanism associated with YQRG-related improvements in liver fibrosis remains to be experimentally determined. This study evaluated the therapeutic effect of YQRG on carbon tetrachloride (CCl4)-induced liver fibrosis in rats and its molecular mechanism. MethodsWe used low-, medium-, and high-dose YQRG to treat CCl4-induced liver fibrosis in rats, followed by assessment of liver injury and fibrosis according to liver appearance, body weight, liver mass index, histopathologic examination, and serum testing. Additionally, we performed transcriptome analysis using RNA-sequencing (RNA-seq) technology, including cluster, Gene Ontology (GO), and pathway analyses, to identify differentially expressed genes (DEGs), and protein and gene expression were detected by immunofluorescence (IFC), western blot, and real-time quantitative PCR. ResultsThe results showed that YQRG effectively alleviated CCl4-induced liver injury and fibrosis in rats, including observations of improved liver function, decreased activity of hepatic stellate cells (HSCs), and decreased extracellular matrix (ECM) deposition. Moreover, we identified downregulated and upregulated DEGs in the model group relative to the control and YQRG-treated groups, with GO analysis revealing their enrichment in biological processes, such as endoplasmic reticulum stress (ERS), apoptosis, and autophagy. Furthermore, pathway analysis showed that YQRG treatment downregulated the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase/Akt (PI3K/AKT) signalling pathways and upregulated other signalling pathways, including those related to peroxisome proliferator-activated receptors(PPAR) and AMP-activated protein kinase(AMPK), with these finding subsequently verified experimentally. ConclusionThese findings showed that YQRG improved CCl4-induced liver fibrosis through multiple mechanisms and pathways, offering critical insight into the YQRG-related therapeutic mechanism and promoting further research into its potential application.

Stratifying Sepsis in Uganda Using Rapid Pathogen Diagnostics and Clinical Data: A Prospective Cohort Study

2021 ◽  
Author(s):  
Matthew J. Cummings ◽  
Barnabas Bakamutumaho ◽  
Nicholas Owor ◽  
John Kayiwa ◽  
Joyce Namulondo ◽  
...  
Keyword(s):  
Prospective Cohort ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Sub Saharan Africa ◽  
Rapid Diagnostics ◽  
Suspected Sepsis ◽  
Laboratory Capacity ◽  
Antimicrobial Management ◽  
Sub Saharan ◽  
Tb 32

The global burden of sepsis is concentrated in sub-Saharan Africa, where extensive pathogen diversity and limited laboratory capacity challenge targeted antimicrobial management of life-threatening infections. In this context, established and emerging rapid pathogen diagnostics may stratify sepsis patients into subgroups with prognostic and therapeutic relevance. In a prospective cohort of adults (age ≥18 years) hospitalized with suspected sepsis in Uganda, we stratified patients using rapid diagnostics for HIV, tuberculosis (TB), malaria, and influenza, and compared clinical characteristics and 30-day outcomes across these pathogen-driven subgroups. From April 2017 to August 2019, 301 adults were enrolled (median age, 32 years [interquartile range, 26–42 years]; female, n = 178 [59%]). A total of 157 patients (53%) were HIV infected. Sixty-one patients (20%) tested positive for malaria, 52 (17%), for TB (including 49 of 157 [31%] HIV-infected patients), and 17 (6%), for influenza. Co-infection was identified in 33 (11%) patients. The frequency of multi-organ failure, including shock and acute respiratory failure, was greatest among patients with HIV-associated TB. Mortality at 30 days was 19% among patients with malaria, 40% among patients with HIV-associated TB, 32% among HIV-infected patients without microbiological evidence of TB, 6% among patients with influenza, and 11% among patients without a pathogen identified. Despite improvements in anti-retroviral delivery, the burden of sepsis in Uganda remains concentrated among young, HIV-infected adults, with a high incidence of severe HIV-associated TB. In parallel with improvements in acute-care capacity, use of rapid pathogen diagnostics may enhance triage and antimicrobial management during emergency care for sepsis in sub-Saharan Africa, and could be used to enrich study populations when trialing pathogen-specific treatment strategies in the region.

scholarly journals Zika Virus: A Clinical Review

KYAMC Journal ◽  
2017 ◽  
Vol 7 (1) ◽  
pp. 719-725
Author(s):  
Md Daharul Islam ◽  
SM Tajdit Rahman ◽  
Khaleda Akhter ◽  
Md Azizul Hoque ◽  
Anannya Roy ◽  
...  
Keyword(s):  
Yellow Fever ◽  
Zika Virus ◽  
Yellow Fever Virus ◽  
Virus Disease ◽  
Specific Treatment ◽  
Abrupt Onset ◽  
Fever Virus ◽  
Control Measures ◽  
Disease Treatment ◽  
Antibodies Detection

Zika virus is a flavivirus related to Dengue virus, yellow fever virus and West Nile virus. It is considered an emerging arbovirus transmitted by mosquito of the genus Aedes. Its first description took place in 1947 in the Zika Forest in Uganda, isolated on Rhesus monkey used as bait to study the yellow fever virus. Clinical picture is characterized as a 'dengue-like' syndrome, with abrupt onset of fever; and an early onset of evanescent rash, often pruritic. Occasionally the disease has been associated with Guillain-Barré syndrome. The diagnosis can be performed by PCR or by IgG and IgM antibodies detection. No specific treatment or vaccine is available for Zika virus disease. Treatment is generally supportive. Control measures are same for dengue and chikungunya based mostly on health education and vector control.KYAMC Journal Vol. 7, No.-1, Jul 2016, Page 719-725

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