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Circulating tumor DNA (ctDNA) is a type of cell-free DNA released by tumor cells after necrosis and apoptosis, and it can be actively secreted by tumor cells. Since ctDNA is derived from various tumor sites, it can provide far more comprehensive genomic and epigenomic information than a single-site biopsy. Therefore, ctDNA can overcome tumor heterogeneity, which is the major limitation of a traditional tissue biopsy approach. Noninvasive ctDNA assays allow continuous real-time monitoring of the molecular status of cancers. Recently, ctDNA assays have been widely used in clinical practice, including cancer diagnosis, evaluation of therapeutic efficacy and prognosis, and monitoring of relapse and metastasis. Although ctDNA shows a high diagnostic performance in advanced esophageal cancer, it is far from satisfactory for early diagnosis of esophageal cancer. Monitoring the dynamic changes of ctDNA is beneficial for the evaluation of therapeutic efficacy and prediction of early recurrence in esophageal cancer. It is necessary to establish standards for individualized ctDNA detection in the evaluation of treatment response and surveillance of esophageal cancer and to develop clinical practice guideline for the systemic treatment of patients with "ctDNA recurrence." This review aims to provide an update on the role of ctDNA in the diagnosis and monitoring of esophageal cancer.

NOTCH signaling is significantly upregulated in the lens capsules of eyes with pseudoexfoliation syndrome (PXF) but not in those with pseudoexfoliation glaucoma (PXG) when compared with healthy controls.

NOTCH signaling has neuroprotective functions and altered NOTCH signaling is associated with neurodegenerative diseases with protein aggregation such as Alzheimer disease. As PXG is also a protein aggregate disease associated with neural degeneration, NOTCH molecular expression was explored in the lens capsules of patients with PXF, PXG, primary open-angle glaucoma (POAG), and healthy controls.

Anterior lens capsules were collected from 106 patients (27 PXF, 24 PXG, 22 POAG, and 33 controls) undergoing cataract surgery. Gene expression profiling for NOTCH pathway molecules (ligands, receptors, and downstream target genes) was performed on the tissue using a quantitative reverse transcription-polymerase chain reaction. The results were confirmed by protein analysis using dot-blot or immunostaining techniques.

There was no difference in the demographic characteristics between the groups. There was an increase in NOTCH4 receptor expression (>14-fold) in the PXF group as compared with the controls. Similarly, the Delta-like 3 and Delta-like 4 ligands were significantly elevated in the PXF group compared with controls (P<0.05). Downstream targets HES3, HES5, and HEY1 expression were significantly elevated (P<0.005) in PXF lens capsules, confirming a higher activity of NOTCH signaling in this cohort. Immunostaining also corroborated the gene expression profile.

The finding that NOTCH signaling is significantly upregulated in the lens capsule of eyes with PXF and not in PXG or POAG patients suggests a possible protective role in the development of glaucoma.

The finding that NOTCH signaling is significantly upregulated in the lens capsule of eyes with PXF and not in PXG or POAG patients suggests a possible protective role in the development of glaucoma.

We used anterior segment optical coherence tomography to investigate anterior chamber angle in primary angle-closure glaucoma (PACG) eyes following phacoemulsification and phacotrabeculectomy. Angle widening was significantly greater after phacoemulsification up to 6 months after the surgery.

To compare anterior chamber angle following 2 common surgeries for PACG.

One hundred ten glaucoma patients were evaluated in this single center, prospective, randomized clinical trial. Those with concomitant PACG and senile cataract and without a history of ocular surgery, trauma, or chronic miotic use were recruited. Monocular patients were also excluded. Finally, 52 eligible subjects were randomly assigned to phacoemulsification ("Phaco" group, 25 eyes) or phacotrabeculectomy ("Combined" group, 27 eyes) surgeries. A swept-source, anterior segment optical coherence tomography device (CASIA SS-1000 OCT) was used to image the anterior segment. Mask graders used the images to measure the following parameters before alowing surgery and was significantly greater after phacoemulsification compared with combined phacotrabeculectomy at all time points. Similar IOP and medication burden were noted for up to 6 months as secondary outcomes. The contribution of angle changes to the IOP-lowering effect of phacoemulsification in PACG eyes needs further study.

Anterior chamber angle widening by anterior segment optical coherence tomography was observed in PACG patients following surgery and was significantly greater after phacoemulsification compared with combined phacotrabeculectomy at all time points. Similar IOP and medication burden were noted for up to 6 months as secondary outcomes. The contribution of angle changes to the IOP-lowering effect of phacoemulsification in PACG eyes needs further study.Glioblastoma (GBM) is the most common and deadly malignant primary brain tumor. Chromobox (CBX) family proteins are essential components of the epigenetic regulatory complex and are involved in the occurrence and development of various cancers. However, the roles of CBX members in GBM is little known. In this analysis, we synthesized several mainstream bioinformatics databases to comprehensively explore the expression profiles, prognostic implications, genetic alterations, immune infiltration, and potential biological functions of the CBXs in GBM, and cell experiments were also conducted to investigate the role of CBX8 in GBM. We found that the elevated mRNA expression of CBX2/3/5/8 and reduced mRNA expression of CBX6/7 were found in GBM. The protein levels of CBX2/3/5/8 were elevated in GBM tissues, whereas the protein levels of CBX6/7 showed no significant difference. The upregulated expression of CBX2/3/8 was found to be both correlated with the tumor grade and recurrent status. The overexpression of CBX3/8 and underexpression of CBX6 mRNA were associated with the poor prognosis. These findings suggested that CBX3 and CBX8 might be useful diagnostic and prognostic biomarkers in GBM. Further cell experiment results supported that CBX8 promoted the proliferation of glioma cells. Moreover, a high genetic alteration rate of CBXs (37%) was found in GBM and to varying degrees. The expression of CBXs was significantly related to the immune cells infiltration. CBX7 methylation level was significantly increased in GBM tissues. Our results may provide novel ideas to find potential prognostic markers and new therapeutic targets among CBX family members in glioblastoma.Hexavalent chromium [Cr(VI)] pollution is a serious environmental problem, due to not only its toxicity but also carcinogenesis. Although studies reveal several features of Cr(VI)-induced carcinogenesis, the underlying mechanisms of how Cr(VI) orchestrates multiple mitogenic pathways to promote tumor initiation and progression remain not fully understood. Src/Ras and other growth-related pathways are shown to be key players in Cr(VI)-initiated tumor prone actions. The role of protein kinase C (PKC, an important signal transducer) in Cr(VI)-mediated carcinogenesis has not been thoroughly investigated. In this study, using human bronchial/lung epithelial cells and keratinocytes, we demonstrate that PKC activity is increased by transient or chronic Cr(VI) exposure, which plays no role in the activation of Src/Ras signaling and ROS upregulation by this metal toxin. PKC in chronic Cr(VI)-treated cells stabilizes Bcl-2 to mitigate doxorubicin (an anti-cancer drug)-mediated apoptosis. After the suppression of this kinase by GO6976 (a PKC inhibitor), the cells chronically exposed to Cr(VI) partially regain the sensitivity to doxorubicin. However, when co-suppressed PKC and Ras, the chronic Cr(VI)-treated cells become fully responsive to doxorubicin and are unable to be transformed. Taken together, our study provides a new insight into the mechanisms, in which PKC is an indispensable player and cooperates with other mitogenic pathways to achieve Cr(VI)-induced carcinogenesis as well as to establish drug resistance. The data also suggest that active PKC can serve as a potential biomarker for early detection of health damages by Cr(VI) and therapeutic target for developing new treatments for diseases caused by Cr(VI).Mounting evidence suggests that nematode infection can protect against disorders of immune dysregulation. Administration of live parasites or their excretory/secretory (ES) products has shown therapeutic effects across a wide range of animal models for immune disorders, including asthma. Human clinical trials of live parasite ingestion for the treatment of immune disorders have produced promising results, yet concerns persist regarding the ingestion of pathogenic organisms and the immunogenicity of protein components. Despite extensive efforts to define the active components of ES products, no small molecules with immune regulatory activity have been identified from nematodes. Here we show that an evolutionarily conserved family of nematode pheromones called ascarosides strongly modulates the pulmonary immune response and reduces asthma severity in mice. AZD4547 Screening the inhibitory effects of ascarosides produced by animal-parasitic nematodes on the development of asthma in an ovalbumin (OVA) murine model, we found that administration of nanogram quantities of ascr#7 prevented the development of lung eosinophilia, goblet cell metaplasia, and airway hyperreactivity. Ascr#7 suppressed the production of IL-33 from lung epithelial cells and reduced the number of memory-type pathogenic Th2 cells and ILC2s in the lung, both key drivers of the pathology of asthma. Our findings suggest that the mammalian immune system recognizes ascarosides as an evolutionarily conserved molecular signature of parasitic nematodes. The identification of a nematode-produced small molecule underlying the well-documented immunomodulatory effects of ES products may enable the development of treatment strategies for allergic diseases.The antigen specificity and long serum half-life of monoclonal antibodies have made them a critical part of modern therapeutics. These properties have been coopted in a number of synthetic formats, such as antibody-drug conjugates, bispecific antibodies, or Fc-fusion proteins to generate novel biologic drug modalities. Historically, these new therapies have been generated by covalently linking multiple molecular moieties through chemical or genetic methods. This irreversible fusion of different components means that the function of the molecule is static, as determined by the structure. Here, we report the development of a technology for switchable assembly of functional antibody complexes using chemically induced dimerization domains. This approach enables control of the antibody's intended function in vivo by modulating the dose of a small molecule. We demonstrate this switchable assembly across three therapeutically relevant functionalities in vivo, including localization of a radionuclide-conjugated antibody to an antigen-positive tumor, extension of a cytokine's half-life, and activation of bispecific, T cell-engaging antibodies.