scholarly journals STAT3 and STAT5 Targeting for Simultaneous Management of Melanoma and Autoimmune Diseases

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1448 ◽  
Author(s):  
Stella Logotheti ◽  
Brigitte M. Pützer
Keyword(s):  
Immune Responses ◽  
Autoimmune Diseases ◽  
Disease Burden ◽  
Patient Management ◽  
Immune Dysregulation ◽  
Systemic Delivery ◽  
Simultaneous Management ◽  
Melanoma Patients ◽  
Targeting Strategy

Melanoma is a skin cancer which can become metastatic, drug-refractory, and lethal if managed late or inappropriately. An increasing number of melanoma patients exhibits autoimmune diseases, either as pre-existing conditions or as sequelae of immune-based anti-melanoma therapies, which complicate patient management and raise the need for more personalized treatments. STAT3 and/or STAT5 cascades are commonly activated during melanoma progression and mediate the metastatic effects of key oncogenic factors. Deactivation of these cascades enhances antitumor-immune responses, is efficient against metastatic melanoma in the preclinical setting and emerges as a promising targeting strategy, especially for patients resistant to immunotherapies. In the light of the recent realization that cancer and autoimmune diseases share common mechanisms of immune dysregulation, we suggest that the systemic delivery of STAT3 or STAT5 inhibitors could simultaneously target both, melanoma and associated autoimmune diseases, thereby decreasing the overall disease burden and improving quality of life of this patient subpopulation. Herein, we review the recent advances of STAT3 and STAT5 targeting in melanoma, explore which autoimmune diseases are causatively linked to STAT3 and/or STAT5 signaling, and propose that these patients may particularly benefit from treatment with STAT3/STAT5 inhibitors.

Late Boosting of the RV144 Regimen Improves the Magnitude and Quality of Immune Responses

2019 ◽  
Author(s):  
Punnee Pitisuttithum ◽  
Sorachai Nitayapha ◽  
Suwat Chariyalertsak ◽  
Jaranit Kaewkungwal ◽  
Peter Dawson ◽  
...  
Keyword(s):  
Immune Responses

scholarly journals Autoimmunity and Genetic Syndromes: A Focus on Down Syndrome

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 268
Author(s):  
Marta Ferrari ◽  
Stefano Stagi
Keyword(s):  
Down Syndrome ◽  
Autoimmune Diseases ◽  
Normal Population ◽  
Underlying Mechanism ◽  
Short Review ◽  
Immune Dysregulation ◽  
Infectious Complications ◽  
Genetic Syndromes ◽  
Genetic Syndrome

Within immune system-related diseases, autoimmunity has always represented a field of great interest, although many aspects remain poorly understood even today. Genetic syndromes associated with immunity disorders are common and represent an interesting model for a better understanding of the underlying mechanism of autoimmunity predisposition. Among these conditions, Down syndrome (DS) certainly deserves special attention as it represents the most common genetic syndrome associated with immune dysregulation, involving both innate and adaptive immunity. Autoimmunity represents a well-known complication of DS: it is estimated that people affected by this disease present a risk four to six times higher than the normal population to develop autoimmune diseases such as celiac disease, type 1 diabetes mellitus, and hypo- or hyperthyroidism. Several factors have been considered as possible etiology, including genetic and epigenetic modifications and immune dysregulation. In times in which the life expectancy of people with DS has been extremely prolonged, thanks to improvements in the diagnosis and treatment of congenital heart disease and infectious complications, knowledge of the mechanisms and proper management of autoimmune diseases within this syndrome has become essential. In this short review, we aim to report the current literature regarding the genetic, immune, and environmental factors that have been proposed as the possible underlying mechanism of autoimmunity in individuals with DS, with the intent to provide insight for a comprehensive understanding of these diseases in genetic syndromes.

scholarly journals Assessment and management of disease burden and quality of life in patients with hereditary angioedema: a consensus report

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Konrad Bork ◽  
John T. Anderson ◽  
Teresa Caballero ◽  
Timothy Craig ◽  
Douglas T. Johnston ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Hereditary Angioedema ◽  
Clinical Management ◽  
Disease Burden ◽  
The United States ◽  
Consensus Meeting ◽  
Consensus Statements ◽  
Consensus Report

Abstract Background Hereditary angioedema (HAE) is a rare disease characterized by unpredictable, potentially life-threatening attacks, resulting in significant physical and emotional burdens for patients and families. To optimize care for patients with HAE, an individualized management plan should be considered in partnership with the physician, requiring comprehensive assessment of the patient’s frequency and severity of attacks, disease burden, and therapeutic control. Although several guidelines and consensus papers have been published concerning the diagnosis and treatment of HAE, there has been limited specific clinical guidance on the assessment of disease burden and quality of life (QoL) in this patient population. Practical guidance is critical in supporting effective long-term clinical management of HAE and improving patient outcomes. The objective of this review is to provide evidence-based guidelines for an individualized assessment of disease burden and QoL in patients with HAE. Methods A consensus meeting was held on February 29, 2020, consisting of 9 HAE experts from the United States and Europe with extensive clinical experience in the treatment of HAE. Consensus statements were developed based on a preliminary literature review and discussions from the consensus meeting. Results Final statements reflect the consensus of the expert panel and include the assessment of attack severity, evaluation of disease burden, and long-term clinical management of HAE caused by C1-esterase inhibitor deficiency. Patient-reported outcome measures for assessing HAE attack severity and frequency are available and valuable tools; however, attack frequency and severity are insufficient markers of disease severity unless they are evaluated in the broader context of the effect on an individual patient’s QoL. QoL assessments should be individualized for each patient and minimally, they should address the interference of HAE with work, school, social, family, and physical activity, along with access to and burden of HAE treatment. Advances in HAE therapies offer the opportunity for comprehensive, individualized treatment plans, allowing patients to achieve minimal attack burden with reduced disease and treatment burden. Conclusion This consensus report builds on existing guidelines by expanding the assessment of disease burden and QoL measures for patients with HAE.

scholarly journals The impact of multimorbidity patterns on health-related quality of life in the general population: results of the Belgian Health Interview Survey

2021 ◽  
Author(s):  
Lisa Van Wilder ◽  
Brecht Devleesschauwer ◽  
Els Clays ◽  
Stefanie De Buyser ◽  
Johan Van der Heyden ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Chronic Diseases ◽  
Disease Burden ◽  
Health Related Quality ◽  
Health Interview Survey ◽  
Related Quality ◽  
Health Related ◽  
Interview Survey ◽  
The Impact

Abstract Background Chronic diseases and multimorbidity are a major cause of disease burden—for patients, caregivers, and society. Little is known however about potential interaction effects between specific disease combinations. Besides an additive effect, the presence of multiple conditions could also act synergistically or antagonistically regarding the impact on patients’ health-related quality of life (HRQoL). The aim was to estimate the impact of coexisting chronic diseases on HRQoL of the adult general Belgian population. Methods The Belgian Health Interview Survey 2018 provided data on self-reported chronic conditions and HRQoL (EQ-5D-5L) for a nationally representative sample. Linear mixed models were used to analyze two-way and three-way interactions of disease combinations on HRQoL. Results Multimorbidity had a prevalence of 46.7% (≥ 2 conditions) and 29.7% (≥ 3 conditions). HRQoL decreased considerably with the presence of multiple chronic diseases. 14 out of 41 dyad combinations and 5 out of 13 triad combinations showed significant interactions, with a dominant presence of negative/synergistic effects. Positive/antagonistic effects were found in more subjective chronic diseases such as depression and chronic fatigue. Conditions appearing the most frequently in significant disease pair interactions were dorsopathies, respiratory diseases, and arthropathies. Conclusions Diverse multimorbidity patterns, both dyads and triads, were synergistically or antagonistically associated with lower HRQoL. Tackling the burden of multimorbidity is needed, especially because most disease combinations affect each other synergistically, resulting in a greater reduction in HRQoL. Further knowledge about those multimorbidity patterns with a greater impact on HRQoL is needed to better understand disease burden beyond mortality and morbidity data.

Clinical Traits Characterizing an Exacerbation-Prone Phenotype in Chronic Rhinosinusitis

2019 ◽  
Vol 161 (5) ◽  
pp. 890-896 ◽  
Author(s):  
Katie M. Phillips ◽  
Eric Barbarite ◽  
Lloyd P. Hoehle ◽  
David S. Caradonna ◽  
Stacey T. Gray ◽  
...  
Keyword(s):  
Chronic Rhinosinusitis ◽  
Disease Burden ◽  
Tertiary Care ◽  
Symptom Burden ◽  
Cross Sectional ◽  
Patient Reported ◽  
Oral Corticosteroids ◽  
Sinonasal Outcome Test ◽  
Snot 22

Objective Acute exacerbation of chronic rhinosinusitis (AECRS) is associated with significant quality-of-life decreases. We sought to determine characteristics associated with an exacerbation-prone phenotype in chronic rhinosinusitis (CRS). Study Design Cross-sectional. Setting Tertiary care rhinology clinic. Subjects Patients with CRS (N = 209). Methods Patient-reported number of sinus infections, CRS-related antibiotics, and CRS-related oral corticosteroids taken in the last 12 months were used as metrics for AECRS frequency. Sinonasal symptom burden was assessed with the 22-item Sinonasal Outcome Test (SNOT-22). Ninety patients reporting 0 for all AECRS metrics were considered to have had no AECRS in the prior 12 months. A total of 119 patients reported >3 on at least 1 AECRS metric and were considered as having an exacerbation-prone phenotype. Characteristics associated with patients with an exacerbation-prone phenotype were identified with exploratory regression analysis. Results An exacerbation-prone phenotype was positively associated with comorbid asthma (adjusted odds ratio [ORadj] = 3.68, 95% CI: 1.42-9.50, P = .007) and SNOT-22 (ORadj = 1.06, 95% CI: 1.04-1.09, P < .001). Polyps were negatively associated (ORadj = 0.27, 95% CI: 0.11-0.68, P = .005) with an exacerbation-prone phenotype. SNOT-22 score ≥24 identified patients with an exacerbation-prone phenotype with a sensitivity of 93.3% and a specificity of 57.8%. Having either a SNOT-22 score ≥24 with a nasal subdomain score ≥12 or a SNOT-22 score ≥24 with an ear/facial discomfort subdomain score ≥3 provided >80% sensitivity and specificity for detecting patients prone to exacerbation. Conclusions In total, these results point to a CRS exacerbation-prone phenotype characterized by high sinonasal disease burden with comorbid asthma but interestingly without polyps.

scholarly journals Therapy for myeloproliferative neoplasms: when, which agent, and how?

Hematology ◽  
2014 ◽  
Vol 2014 (1) ◽  
pp. 277-286 ◽  
Author(s):  
Holly L. Geyer ◽  
Ruben A. Mesa
Keyword(s):  
Quality Of Life ◽  
Disease Burden ◽  
Myeloproliferative Neoplasms ◽  
Jak Inhibitors ◽  
Symptom Profiles ◽  
Risk Of Progression ◽  
Life Threatening ◽  
Jak2 Inhibition

Abstract Myeloproliferative neoplasms, including polycythemia vera (PV), essential thrombocythemia, and myelofibrosis (MF) (both primary and secondary), are recognized for their burdensome symptom profiles, life-threatening complications, and risk of progression to acute leukemia. Recent advancements in our ability to diagnose and prognosticate these clonal malignancies have paralleled the development of MPN-targeted therapies that have had a significant impact on disease burden and quality of life. Ruxolitinib has shown success in alleviating the symptomatic burden, reducing splenomegaly and improving quality of life in patients with MF. The role and clinical expectations of JAK2 inhibition continues to expand to a variety of investigational arenas. Clinical trials for patients with MF focus on new JAK inhibitors with potentially less myelosuppression (pacritinib) or even activity for anemia (momelotinib). Further efforts focus on combination trials (including a JAK inhibitor base) or targeting new pathways (ie, telomerase). Similarly, therapy for PV continues to evolve with phase 3 trials investigating optimal frontline therapy (hydroxyurea or IFN) and second-line therapy for hydroxyurea-refractory or intolerant PV with JAK inhibitors. In this chapter, we review the evolving data and role of JAK inhibition (alone or in combination) in the management of patients with MPNs.

Successful induction of immune responses against mutant ras in melanoma patients using intradermal injection of peptides and GM-CSF as adjuvant

2001 ◽  
Vol 10 (3) ◽  
pp. 161-167 ◽  
Author(s):  
R. E. Hunger ◽  
C. U. Brand ◽  
M. Streit ◽  
J. A. Eriksen ◽  
M. K. Gjertsen ◽  
...  
Keyword(s):  
Immune Responses ◽  
Intradermal Injection ◽  
Gm Csf ◽  
Successful Induction ◽  
Melanoma Patients

scholarly journals Gender Specific Differences in Disease Susceptibility: The Role of Epigenetics

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 652
Author(s):  
Lucia Migliore ◽  
Vanessa Nicolì ◽  
Andrea Stoccoro
Keyword(s):  
Immune Responses ◽  
Autoimmune Diseases ◽  
X Chromosome ◽  
Complex Traits ◽  
Differential Susceptibility ◽  
X Chromosome Inactivation ◽  
Adverse Outcomes ◽  
Chromosome Inactivation ◽  
Gender Specific Differences ◽  
Gender Specific

Many complex traits or diseases, such as infectious and autoimmune diseases, cancer, xenobiotics exposure, neurodevelopmental and neurodegenerative diseases, as well as the outcome of vaccination, show a differential susceptibility between males and females. In general, the female immune system responds more efficiently to pathogens. However, this can lead to over-reactive immune responses, which may explain the higher presence of autoimmune diseases in women, but also potentially the more adverse effects of vaccination in females compared with in males. Many clinical and epidemiological studies reported, for the SARS-CoV-2 infection, a gender-biased differential response; however, the majority of reports dealt with a comparable morbidity, with males, however, showing higher COVID-19 adverse outcomes. Although gender differences in immune responses have been studied predominantly within the context of sex hormone effects, some other mechanisms have been invoked: cellular mosaicism, skewed X chromosome inactivation, genes escaping X chromosome inactivation, and miRNAs encoded on the X chromosome. The hormonal hypothesis as well as other mechanisms will be examined and discussed in the light of the most recent epigenetic findings in the field, as the concept that epigenetics is the unifying mechanism in explaining gender-specific differences is increasingly emerging.

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