Hupeterson3262

The primary cilium, a sensory organelle that protrudes from the surface of most eukaryotic cells, receives and transduces various critical signals that are essential for normal development and homeostasis. Structural or functional disruption of primary cilia causes a number of human diseases, including cancer. Primary cilia has cross talks with cell cycle and it may act as a cell cycle checkpoint to suppress cancer development. Moreover, primary cilia has cross-regulation with autophagy, which may affect tumor progression. We then discuss the association of the primary cilia with several oncogenic signaling pathways, including Shh, Wnt, Notch and platelet-derived growth factor receptor (PDGFR). Since these signaling pathways are often over-activated in many types of human cancers, primary cilia are likely to play a role in the tumorigenesis by modulating these pathways. Finally, we summarize current progress on the role of cilia during tumorigenesis and the challenges that the cilia-cancer field faces.Oral lichen planus (OLP) is a chronic inflammatory oral mucosal disease with unclear etiology. Autoimmune thyroid diseases (AITD) is a type of autoimmune disease characterized by increased thyroid-specific antibodies. In recent years, more and more studies have found that the incidence of AITD is increased in OLP patients. The occurrence and development of OLP and AITD may be related to the expression of thyroid autoantigen in oral keratinocytes, the imbalance of thyroid hormone （Th）1/Th2 and Th17/Treg cell subsets, the abnormal quantity and function of follicular helper T cells and chemokines and the specific killing ability of CD8 T cells to target cells. In this article, the possible immune mechanisms involved in the coexistence of OLP and AITD are reviewed to provide insights for the diagnosis, treatment and prevention of these two diseases from the perspective of immunology.

Recent advances in targeted therapy and immunotherapy have improved the prognosis of melanoma patients but brain metastasis remains a major challenge. Currently, it is unclear how existing therapies can be best used to prevent or treat brain metastasis in melanoma patients.

We aimed to assess brain metastasis free survival (BMFS), overall survival (OS), incidence of brain metastases, and sequencing strategies of immunotherapy and targeted therapy in patients with BRAF-mutated advanced melanoma.

We retrospectively analyzed 683 patients with BRAF-mutated advanced melanoma treated with first line (1L) immunotherapy (N= 266) or targeted therapy (N= 417). The primary outcome was BMFS. Secondary outcomes included OS of all patients and incidence of brain metastases in patients without documented brain metastases prior to 1L therapy. The median BMFS was 13.7 months [95% confidence interval (CI) 12.4-16.0] among all patients. The median BMFS for patients receiving 1L immunotherapy was 41.9 months [95% CI 22.8-netastases are warranted.

Patients with advanced BRAF mutant melanoma treated with 1L immunotherapy have significantly longer BMFS and OS, and reduced incidence of brain metastases, compared with those treated with 1L targeted therapy. Further studies evaluating the ability of immunotherapy and targeted therapy to improve OS and prevent brain metastases are warranted.Osteoarthritis (OA) is a disabling joint disease associated with chronic inflammation. The polarization of macrophages plays the key role in inflammatory microenvironment of joint which is a therapeutic target for OA treatment. Herein, a boronate-stabilized polyphenol-poloxamer assembled dexamethasone nanodrug with reactive oxygen species (ROS)-responsive drug release behavior and ROS scavenging ability is prepared. Thanks to that, the nanodrug can efficiently inhibit the ROS and nitric oxide production in lipopolysaccharide-activated RAW264.7 macrophages and modulate macrophages M2 polarization at a much lower concentration than free drug dexamethasone. Furthermore, the monosodium iodoacetate-induced OA mice treated with this nanodrug is very similar with the normal mice with the evaluation of body weight and scores including clinical arthritis scores, claw circumference, and kinematics score. The inflammation associated angiogenesis is also reduced which revealed by 68 Ga-labeled arginine-glycine-aspartic acid peptide micro-positron emission tomography imaging. Cartilage degradation and bone erosion in the joints are also inhibited by the nanodrug, along with the inhibition of proinflammatory cytokines. In addition, the biosafety of this nanodrug is also verified. This nanodrug with excellent immunomodulation properties can be used not only for OA therapy but also for other inflammatory diseases associated with excess oxidative stress and macrophage polarization.Iron is an essential co-factor for cellular processes. In the immune system, it can activate macrophages and represents a potential therapeutic for various diseases. To specifically deliver iron to macrophages, iron oxide nanoparticles are embedded in polymeric micelles of reactive polysarcosine-block-poly(S-ethylsulfonyl-l-cysteine). Upon surface functionalization via dihydrolipoic acid, iron oxide cores act as crosslinker themselves and undergo chemoselective disulfide bond formation with the surrounding poly(S-ethylsulfonyl-l-cysteine) block, yielding glutathione-responsive core cross-linked polymeric micelles (CCPMs). When applied to primary murine and human macrophages, these nanoparticles display preferential uptake, sustained intracellular iron release, and induce a strong inflammatory response. ISA2011B This response is also demonstrated in vivo when nanoparticles are intratracheally administered to wild-type C57Bl/6N mice. Most importantly, the controlled release concept to deliver iron oxide in redox-responsive CCPMs induces significantly stronger macrophage activation than any other iron source at identical iron levels (e.g., Feraheme), directing to a new class of immune therapeutics.

This study quantifies how changes in healthcare utilization and delivery during the first months of the COVID-19 pandemic have altered the presentation, treatment, and management of patients with gastrointestinal (GI) malignancies within an academic health system.

Patients diagnosed with a GI malignancy (ICD10 C15-C26) who received medical care within the health system during the observation period (first 44 weeks of 2019 and 2020) were identified for a retrospective cohort study. Deidentified patient encounter parameters were collected for this observation period and separated into pre-pandemic (weeks 1-10) and early pandemic (weeks 11-20) study periods. Difference-in-difference analyses adjusted for week-specific and year-specific effects quantified the impact of the COVID-19 pandemic on care delivery between pre-pandemic and early pandemic study periods in 2020. Across all GI malignancies, the COVID-19 pandemic has been associated with a significant decline in the number of patients with new patient visits (NPVs) (p=1.