This article presented a case of a human leukocyte antigen (HLA)-A2-positive patient with advanced cancer/testis antigen New York esophageal squamous cell carcinoma-1 (NY-ESO-1) expressing lung adenocarcinoma (LADC) who received adoptive cell therapy of T cell receptor engineered-T cells (TCR-T cells) targeting the cancer-testis antigen NY-ESO-1. The appropriate clinical and laboratory assessments were conducted to investigate the safety and efficacy of this therapy for this lung cancer patient. The patient had a clinical response to and was well-tolerated with this therapy in the clinical trial. In addition, a preliminary evaluation of the safety of NY-ESO-1 TCR-T cell therapy was performed in four patients with non-small cell lung cancer (NSCLC) enrolled in a clinical trial. It was well-tolerated and did not observe any serious adverse events post-infusion. Fever, anemia, and a decrease in white blood cell count were common adverse events, which were likely due to the TCR-T cell therapy. Two patients had clinical responses to NY-ESO-1 TCR-T cell therapy, including the 44-year-old female patient with LADC, who achieved a short-term partial response for 4 months, improved in Karnofsky performance status, and had a recovery of drug sensitivity. This suggests that TCR-T cell therapy targeting NY-ESO-1 antigen may be beneficial for HLA-A2-positive late-stage patients with NY-ESO-1-expressing NSCLC.
Acitretin has been a valuable option for the treatment of psoriasis, however, the molecular events of acitretin leading to the normalization of keratinocytes differentiation on psoriasis patients have not been fully explored. To investigate whether there were certain relationship between keratinocytes proliferation and JAK/STAT signaling pathways in psoriasis, and how acitretin modulated the signaling pathways. HaCaT cells, an in vitro immortal human keratinocyte cell line, was chosen as a in vitro model of psoriasis. The small interfering RNA targeting STAT1 (siRNA-STAT1) and STAT3 (siRNA-STAT3) were subsequently transfected into the HaCaT cells which were treated with or without acitretin. We found that HaCaT cells proliferation and the expression of STAT1 or STAT3 were inhibited by acitretin, siRNA-STAT1 and siRNA-STAT3. Our experimental data shows that acitretin might inhibit HaCaT cells proliferation in psoriasis by decreasing the expression of STAT- and STAT3-dependent mechanism.
Precise isolation and analysis of circulating tumor cells (CTCs) from blood samples offer considerable potential for cancer research and personalized treatment. Currently, available CTCs isolation approaches remain challenging in the...
Psoriasis is an autoimmune disease, which is characterized by aberrantly high levels of inflammation, but the underlying pathogenic mechanisms are still not fully understood. Signal transducer and activator of transcription 1 (STAT1) and STAT3, and the downstream proteins suppressor of cytokine signaling 1 (SOCS1) and SOCS3, have been implicated in psoriasis disease progression. Calcipotriol, a synthetic derivative of vitamin D, has been used clinically to treat psoriasis, but the mechanism of action that underlies the beneficial effects of calcipotriol is still being explored. The objective of this study was to determine whether STAT1 and STAT3 signaling is involved in calcipotriol treatment. Using an in vitro immortal human keratinocyte cell line, HaCaT cells, as a psoriasis model, we examined the molecular signaling induced by calcipotriol treatment. We found that calcipotriol treatment or silencing of either STAT1 or STAT3 inhibited proliferation of HaCaT cells. Calcipotriol downregulated the expression of STAT1 and STAT3 at the messenger RNA (mRNA) and protein levels. The levels of phosphorylated STAT1 and STAT3 were also decreased, suggesting calcipotriol treatment inhibited STAT1 and STAT3 activation. Calcipotriol-mediated STAT inhibition was further substantiated by the downregulation of SOCS1 and SOCS3 at the mRNA and protein expression levels. Taken together, our results suggest a novel molecular mechanism for calcipotriol-mediated treatment effects in psoriasis.
G roup B Streptococcus (GBS) is a common commensal bacteria of vaginal fl ora with reported carriage rates of 4%-40% (1-3). Vertical transmission of (GBS) through fetal aspiration of infected amniotic fl uid or during birth canal passage has been considered one of the most important causes of neonatal illness and death (3,4). GBS colonization during pregnancy has been a leading cause of severe neonatal infectious diseases, including sepsis, pneumonia, and meningitis (5,6). Early onset neonatal infections can be prevented in most cases by providing intrapartum antibiotic prophylaxis to the colonized mother (7). However, GBS carriages are often intermittent, and the rate of GBS colonization varies during pregnancy (1,8). On the other hand, use of antibiotic prophylaxis solely relying on risk assessment leads to unnecessary treatment in many women. Therefore, determination of colonization at the time of delivery is crucial for the prevention of neonatal infection (9).Culture-based methods remain the most commonly used screening practice and the standard for GBS detection; however, because of technical limitations, including turnaround time, pregnant women are usually screened for GBS at 35-37 weeks of gestation (6). As many studies have pointed out, the predictive value of GBS decreases as the interval time increases between screening and delivery (10,11). These studies underlie the needs for a more rapid and sensitive diagnostic for intrapartum GBS screening.CRISPR/Cas has been widely used as a programmable tool for gene editing and other in vivo applications since 2013 (12-14). However, recently, the collateral, promiscuous cleavage activities of a unique group of Cas enzymes were discovered and harnessed for in vitro nucleic acid detection (15)(16)(17).To address the unmet clinical needs for GBS screening, we developed CRISPR-GBS, a novel CRIS-PR/Cas13-based in vitro diagnostic assay, and conducted a prospective cohort study and a validation study in >400 clinical cases to evaluate its diagnostic performance among different technology platforms, including culture and PCR-based methods. Our fi ndings demonstrate that CRISPR-GBS is rapid and easy-
In this study, construction of conductive and biocompatible three-dimensional nickel scaffolds (NiF) with electrodeposited chitosan (CS) for tissue engineering. The scaffolds were characterized by scanning electron microscopy (SEM), mechanical testing, water absorption, retention capacity and conductive sensitivity. Three-dimensional nickel scaffolds with electrodeposited chitosan (NiFC-n) exhibited uniformly filling structure on their surfaces and the inner structure and good mechanical property. When the versatile NiFC-n sensors were attached to different deformation, they could detect a variety of motion signals. MTT assay, Cells were stained with carboxyfluoresceinsuccinimidyl ester (CFSE) assay, apoptosis experiment and cell culture experiment results showed that NiFCn had good biocompatibility. The results indicated that the NiFC2 had a low immunogenicity, and can promote cell proliferation and support cell adhesion. This work provides a safe and feasible electrodeposition method to construct conductive and biocompatible three-dimensional nickel scaffolds with electrodeposited chitosan for tissue engineering. Therefore, NiFCn had potential application as biomaterials that may contact with real time measurement of rehabilitation for tissue engineering.
BackgroundStatin may confer anticancer efficacy, while the studies evaluating the influence of statin on survival of patients with renal cell cancer (RCC) yielded inconsistent results. A systematic review and meta-analysis was performed to investigate the association between statin use and survival of patients with RCC.Materials and MethodsCohort studies were identified by search of PubMed, Embase, and Web of Science databases according to the objective of the meta-analysis. A random-effect model incorporating the possible between-study heterogeneity was used for meta-analysis. Subgroup analyses according to study characteristics were also performed.ResultsSeventeen cohort studies involving 42528 patients with RCC were available for the meta-analysis. Results showed that statin use was associated with a better overall survival (OS, hazard ratio [HR]: 0.73, 95% confidence interval [CI]: 0.65 to 0.84, p < 0.001; I2 = 40%), progression progression-free survival (PFS, HR: 0.82, 95% CI: 0.68 to 0.98, p = 0.03; I2 = 52%), and cancer-specific survival (CSS, HR: 0.76, 95% CI: 0.59 to 0.99, p = 0.04; I2 = 38%). Besides, for the outcome of OS and PFS, subgroup analyses showed similar results in patients with surgical and non-surgical anticancer treatments, and in patients with stage I-III and stage IV RCC (p values for subgroup difference all > 0.05).ConclusionsStatin use may be associated with improved survival outcomes in patients with RCC. Although prospective clinical studies should be considered to validate these results, these findings suggest that statins may be potential adjuvant therapy for patients with RCC.
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