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Immunogenomics studies of colon cancer have lagged behind other cancer types, such as melanoma and lung cancer, potentially limiting immunotherapy approaches to colon cancer, also less common than in the cases of melanoma and lung cancer. Here we applied an extensively benchmarked algorithm for retrieving immune receptor recombination sequencing reads from colon cancer exomes available via the cancer genome atlas. Assessment of the complementarity determining region-3 chemical features represented by the reads revealed associations of distinct chemical features with better or worse survival rates, for both T-cell and B-cell receptor, recombination reads. A follow up assessment of immune gene expression correlations with the recovery of the recombination reads revealed a consistent association of high level expression of BTN gene family members and better survival rates. Overall, these approaches provide several striking consistencies connecting immunogenomics features with colon cancer survival rates, potentially providing a basis for guiding immuno-therapy applications.
To determine the tumor genomic, immunologic expression, and risk factors of treatment outcomes for patients with double head and neck squamous cell carcinoma (HNSCC) and esophageal squamous cell carcinoma (ESCC).
We reviewed patients with double HNSCC and ESCC between 1995 and 2014. The TP53 genomic mutation, CD8+ tumor infiltrating lymphocytes (TIL) and tumor programmed cell death ligand 1 (PD-L1) expression of paired HNSCC and ESCC were analyzed.
A total of 116 patients (57 metachronous and 59 synchronous) were included. There were 88 (75.86%) patients with HNSCC and 80 (68.97%) with ESCC harboured TP53 disruptive mutation. Nearly 106 (91.38%) patients had different clonality of TP53 mutation in paired HNSCC and ESCC. Dihydroartemisinin chemical structure The immunologic expression of synchronous and metachronous patients was significantly different. Compared to the metachronous patients, the synchronous patients had significantly higher HNSCC CD8+ TIL (p=0.03), ESCC CD8+ TIL (p<0.001), HNSCC PD-L1+ tumor proportion score (TPS, p=0.04), and ESCC PD-L1+ TPS (p=0.04). Furthermore, among the synchronous patients, the immunologic expression between HNSCC and ESCC was significantly correlated. The CD8+ TIL and PD-L1 TPS had strongly (r=0.63, p<0.0001) and moderately (r=0.42, p=0.001) positive correlations, respectively. link2 Finally, advanced stage (III/IV) HNSCC was a significant factor for disease-free (p=0.03) and overall survival (p=0.005).
In patients with double HNSCC and ESCC, nearly all HNSCC and ESCC were of multicentric origin. For the synchronous patients, there was more adaptive immune resistance in HNSCC and ESCC. The immunologic expression between paired HNSCC and ESCC was also significantly correlated.
In patients with double HNSCC and ESCC, nearly all HNSCC and ESCC were of multicentric origin. For the synchronous patients, there was more adaptive immune resistance in HNSCC and ESCC. The immunologic expression between paired HNSCC and ESCC was also significantly correlated.
Depth of invasion (DOI) is the most important predictor for lymph node metastasis (LNM) in early stage (T1-T2) oral cancer. The aim of this study is to validate the cut-off value of 4mm on which the decision to perform an Elective Neck Dissection (END) is made.
We performed a retrospective study in patients with pathologically proven early stage oral cavity squamous cell carcinoma (OCSCC) without clinical or radiological signs of LNM, who were treated between 2013 and 2018. An END was performed when DOI was≥4mm and a watchful waiting protocol was applied in patients with DOI<4mm.
Three hundred patients were included. END was performed in 77% of patients with DOI≥4mm, of which 36% had occult LNM (pN+). Patients in the watchful waiting group (48%) developed a regional recurrence in 5.2% for DOI<4mm and 24.1% for DOI≥4mm. For DOI≥4mm, regional recurrence free survival was higher for patients who were treated with END compared to watchful waiting (p=0.002). A Receiver-Operator-Curve -analysis showed that a DOI cut-off value of 4.0mm was the optimal threshold for the prediction of occult LNM (95.1% sensitivity, 52.9% specificity).
A DOI of≥4mm is an accurate cut-off value for performing an END in early stage OCSCC. END results in higher survival rates and lower regional recurrence rates in patients with DOI≥4mm.
A DOI of ≥ 4 mm is an accurate cut-off value for performing an END in early stage OCSCC. END results in higher survival rates and lower regional recurrence rates in patients with DOI ≥ 4 mm.Rasmussen encephalitis (RE) is a unilateral hemispheric encephalitis whose main clinical features include refractory focal epilepsy or epilepsia partialis continua, hemiparesis, and progressive cognitive decline. Despite the autoimmune pathogenesis of RE, the only definitive therapeutic option is currently represented by surgery. We review the clinical features, the immune pathogenesis, and the available therapeutic options for RE, with special focus on immunosuppressive agents. The research includes systematic reviews, meta-analyses, observational studies, clinical trials, cases series and reports, until 2020. The use of immunosuppressive agents in RE is supported by the evidence of an autoimmune involvement of the central nervous system in this condition. Although often insufficient to modify the disease course and to achieve symptomatic control, immune therapy can be effective in patients with slow disease progression or in patients in which surgery is not applicable. Moreover, the documentation of T-cell involvement in the pathogenesis of RE, with a specific cytokine pattern, opens a window of opportunity for the use of T-targeted therapies and biologic drugs (i.e. anti-TNFα agents) in the treatment of this disease.
Persistence hyperglycemia results in the formation of advanced glycation end products (AGEs) by non-enzymatic glycation. AGEs and their receptor RAGE play an important role in generation of inflammatory molecules and oxidative stress. Metformin regulates insulin responsive gene and helps to achieve glycemic control however, no extensive study reported about its role against glycation induced oxidative stress and vascular inflammation. Therefore, present work focused on clinical relevance of three months metformin therapy in type 2 diabetes mellitus patients against glycation induced oxidative stress and vascular inflammation.
Among recruited 40 medicated-naive type 2 diabetes mellitus patients, 31 patients were continued with metformin therapy. Biomarkers of plasma protein glycation (fructosamine, protein carbonyls, β-amyloid) antioxidants and oxidative stress markers (GSH, catalase, NO, PON-1, AOPP, LPO; RAGE isoforms (sRAGE, esRAGE); inflammatory markers (IL-6, TNF-α) were determined at baseline and after 3-months of treatment. The expression profile of membrane RAGE, NF-κB, CML was studied in PBMNCs and GLUT-1 in erythrocyte ghost by western blotting.
Metformin showed maximum percent declined from baseline to three months therapy in levels of fructosamine, β-amyloid, sRAGE, inflammatory cytokines (IL-6, TNF-α) and percent increment in esRAGE and antioxidants levels. link3 It showed reduced levels of IL-6 and TNF-α by declining expression of CML, membrane RAGE and NF-κB in type 2 diabetes mellitus patients after three months therapy.
First report in Indian diabetes mellitus patients, where metformin showed effective inhibition against glycation and receptor mediated cellular inflammation. However, these findings need to be tested in a randomized trial.
First report in Indian diabetes mellitus patients, where metformin showed effective inhibition against glycation and receptor mediated cellular inflammation. However, these findings need to be tested in a randomized trial.Sleep disorders are progressively common and sometimes are associated with aberrant regulation of the adaptive and innate immune responses. Sleep interruption can increase the inflammatory burden by enhancing the pro-inflammatory cytokines particularly in patients with chronic diseases such as inflammatory bowel disease (IBD). IBD is a chronic inflammatory disease characterized by immune dysregulation, dysbiosis of gut microbiome, and poor-quality life. Therefore, this review highlights the crosstalk between sleep and immune responses during the progression of IBD.
Mandibular advancement devices (MADs) are one of the treatment options used for the obstructive sleep apnea syndrome (OSAS). At present, MADs are designed with standard titration systems, without considering each patient's anatomical characteristics of the temporomandibular joint and mandible shape. The main objective of this study is to evaluate if a variability in mandibular morphology will influence the displacement of the jaw with a MAD. Such knowledge will be of help to find optimal mandibular positions with MAD even when opening the mouth.
By using a mandibular movement model, the movement patterns of different points on the chin have been analyzed. The influence of different skeletal mandibular shapes on these movements have also been studied. The results show differences in the movement patterns of the lower front teeth depending on its distance to the center of the condyle, with a more horizontal direction in those in which there is a greater distance.
Variations in mandibular morphology imply differences in movement patterns of the analyzed points of the mandible. Consequently, MADs should be designed according to each patient's anatomy to avoid mandibular retrusion in those areas that may narrow the upper airways.
This study may help to understand why not all patients move their lower jaws forwards equally with the same degree of mandibular protrusion measured in relation to the teeth. These results might also partially explain why airway obstruction is more severe in certain untreated sleep apnea subjects than in others when opening their mouth during sleep.
This study may help to understand why not all patients move their lower jaws forwards equally with the same degree of mandibular protrusion measured in relation to the teeth. These results might also partially explain why airway obstruction is more severe in certain untreated sleep apnea subjects than in others when opening their mouth during sleep.
Autonomic instability during sleep can influence the risk of cerebrovascular diseases. In this study, we performed a polygraphy to evaluate, heart rate variability (HRV) in a group of patients with lacunar stroke that is a condition at high risk of recurrence.
Twenty-one lacunar stroke patients were enrolled one month after stroke occurrence. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). The presence of common sleep disorders and autonomic changes during the night was investigated by a polygraphy monitoring. Results were compared with those obtained in a group of 21 healthy subjects.
Patients and controls were similar for age, sex distribution and main cardiovascular risk factors with the exception of the body mass index. Significant differences were detected for all polysomnographic (PSG) parameters and for the PSQI score. By considering HRV values, patients with pathologic values (12 patients, HRV>2) showed significantly higher values in BMI (31±2.9 vs. 26.6±3.6, p=0.006) and PSQI scores (7.
Website: https://www.selleckchem.com/products/Dihydroartemisinin(DHA).html
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