Epigenetic reader ZMYND11 noncanonical function restricts HNRNPA1-mediated stress granule formation and oncogenic activity.

Epigenetic readers frequently affect gene regulation, correlate with disease prognosis, and hold significant potential as therapeutic targets for cancer. Zinc finger MYND-type containing 11 (ZMYND11) is notably recognized for reading the epigenetic marker H3.3K36me3; however, its broader functions and mechanisms of action in cancer remain underexplored. Here, we report that ZMYND11 downregulation is prevalent across various cancers and profoundly correlates with poorer outcomes in prostate cancer patients. Depletion of ZMYND11 promotes tumor cell growth, migration, and invasion in vitro, as well as tumor formation and metastasis in vivo. Mechanistically, we discover that ZMYND11 exhibits tumor suppressive roles by recognizing arginine-194-methylated HNRNPA1 dependent on its MYND domain, thereby retaining HNRNPA1 in the nucleus and preventing the formation of stress granules in the cytoplasm. Furthermore, ZMYND11 counteracts the HNRNPA1-driven increase in the PKM2/PKM1 ratio, thus mitigating the aggressive tumor phenotype promoted by PKM2. Remarkably, ZMYND11 recognition of HNRNPA1 can be disrupted by pharmaceutical inhibition of the arginine methyltransferase PRMT5. Tumors with low ZMYND11 expression show sensitivity to PRMT5 inhibitors. Taken together, our findings uncover a previously unexplored noncanonical role of ZMYND11 as a nonhistone methylation reader and underscore the critical importance of arginine methylation in the ZMYND11-HNRNPA1 interaction for restraining tumor progression, thereby proposing novel therapeutic targets and potential biomarkers for cancer treatment.

A rare case report of endobronchial neurofibroma treated with transbronchial endoscopic resection and literature review.

RATIONALE: Endobronchial neurofibroma is an extremely rare neoplastic disease. The majority of endobronchial neurofibroma are symptomatic, but nonspecific. The treatment of endobronchial neurofibroma is controversial that surgery is previously considered to be the main option. With the development of bronchoscopic intervention, most endobronchial neurofibroma can be treated with transbronchial endoscopic resection with few complications. Here we reported a case of diagnosed endobronchial neurofibroma that was successfully resected with transbronchial electrical snaring and laser coagulation. Moreover, the relevant literature was reviewed to raise awareness of this disease. PATIENT CONCERNS: A 57-year-old man presented to our hospital with cough, sputum, and shortness of breath for 2 days. Physical examination was normal. Laboratory tests revealed moderately increased C-reactive protein. Chest computed tomography showed a 10 × 8 mm round, polypoid-shaped nodule located in the left main bronchus, which was heterogeneous after contrast enhancement. It demonstrated a smooth, round, hypervascularized neoplasma obstructing most of the lumen of the upper left main bronchus under bronchoscopy. INTERVENTIONS AND OUTCOMES: The tumor was removed with electrical snaring and laser coagulation completely instead of surgical resection, without any complications. Pathologically, it was confirmed of endobronchial neurofibroma. Repeated bronchoscopy showed no recurrence of the tumor, and the procedure site healed with a little of fibrotic scar formation. LESSONS: Endobronchial neurofibroma is rare. Although the standard treatment for endobronchial neurofibroma is surgery, transbronchial endoscopic resection (electrical snaring and laser coagulation) is an applicable option, especially for those lesions strictly in the lumen.

Combined Use of Endoscopic Techniques and Virtual Surgical Planning for Intraoral Approach for Hemi-mandibular Resection and Reconstruction.

Background: The study aimed to describe our experience in using endoscopic procedures to aid hemi-mandibular reconstruction with bone flaps through transoral approach. Methods: Five patients with huge benign mandibular tumors underwent transoral mandibulectomy and hemi-mandibular reconstruction, using endoscopy. Facial symmetry, occlusion, bone healing, and mandibular similarity were all evaluated postoperatively. The paired-samples t test was used to compare quantitative data, and a P value less than 0.05 was considered a significant difference. Results: All five patients who received transoral mandibular surgery recovered in terms of TMJ functionality, facial symmetry, and aesthetic results. Endoscopy monitored and ensured that bone flaps were correctly connected and fixed. The accuracy of endoscopy-guided mandibular reconstruction was confirmed by quantitative examination for four cases, which revealed no statistically significant variations between postoperative CT analysis and preoperative virtual surgical planning data. Conclusions: Endoscopy-assisted virtual surgery may resolve concerns with transoral hemi-mandibular reconstruction and broaden indications for mini-invasive mandibular reconstruction. However, only patients with benign mandibular tumors were included in our study, so surgeons should be very cautious if applying this technique to malignant lesions or bony tumors invading soft tissues.

FGL1 in plasma extracellular vesicles is correlated with clinical stage of lung adenocarcinoma and anti-PD-L1 response.

Fibrinogen-like protein-1 (FGL1) is confirmed a major ligand of lymphocyte activation gene-3 which could inhibit antigen-mediated T-cell response and evade immune supervision. Although hepatocytes secrete large amounts of FGL1, its high expression also be detected in solid tumors such as lung cancer, leading to a poor efficacy of immune checkpoint inhibitors therapy. Here we reported that FGL1 was overexpressed in lung adenocarcinoma (LUAD) but not in lung squamous cell carcinoma. However, FGL1 in tissue and plasma can only distinguish LUAD patients from healthy donors and cannot correlate with clinical Tumor Node Metastasis (TNM) stage. Using lung cancer cell lines, we confirmed that FGL1 can be detected on extracellular vesicles (EVs) and we established a method using flow cytometry to detect FGL1 on the surface of EVs, which revealed that FGL1 could be secreted via EVs. Both animal model and clinical samples proved that plasma FGL1 in EVs would increase when the tumor was loaded. The level of FGL1 in plasma EVs was correlated with clinical TNM stage and tumor size, and a higher level indicated non-responsiveness to anti-programmed cell death ligand 1 (anti-PD-L1) immunotherapy. Its effect on tumor progression and immune evasion may be achieved by impairing the killing and proliferating capacities of CD8+ T cells. Our result demonstrates that FGL1 levels in plasma EVs, but not total plasma FGL1, could be a promising biomarker that plays an important role in predicting anti-PD-L1 immune therapy in LUAD and suggests a new strategy in LUAD immunotherapy.

Clinical features of anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis with macrophage activation syndrome.

OBJECTIVES: This study aimed to describe the clinical features of patients with anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive dermatomyositis (DM) who had macrophage activation syndrome (MAS). METHODS: We retrospectively examined 44 patients with anti-MDA5-positive DM and compared the clinical features between patients with MAS (n = 11) and those without (n=33). Patients without MAS were selected randomly in the same year as those with MAS at a ratio of 3:1. Among patients with MAS, we compared the features between non-survivors and survivors. We used Fisher's exact test, Student's t test, the Mann-Whitney U test and the log-rank test for statistical analysis. RESULTS: Patients complicated with MAS had a significantly higher incidence of infection, heliotrope sign, Gottron's papule, V-neck sign, and higher serum levels of ferritin, aspartate aminotransferase (AST), lactic dehydrogenase (LDH), and creatine kinase (CK) than those without MAS (p<0.05). Among the 11 patients with MAS, 4 (36.4%) died after intensive treatment. Deceased patients were older, given more combination therapy with tofacitinib (TOF) and had a higher incidence of rapid progressive interstitial lung disease, infection, heart failure and renal impairment than those who survived (p<0.05). CONCLUSIONS: Among anti-MDA5-positive DM, Infection, DM typical rashes, and higher serum levels of ferritin, AST, LDH, and CK were more common in patients complicated with MAS. The mortality of patients with MAS was high, particularly among patients who were older, given more combination therapy with TOF, and had RP-ILD, infection, heart failure and renal impairment.

Omega-3 polyunsaturated fatty acids ameliorate PM2.5 exposure induced lung injury in mice through remodeling the gut microbiota and modulating the lung metabolism.

Short-term or long-term exposure to fine particulate matter (PM2.5) is related to increased incidences of respiratory diseases. This study aimed to investigate the influences of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) supplementation on oxidative stress, inflammation, lung metabolic profile, and gut microbiota in PM2.5-induced lung injury mice. Mice were divided into four groups (n = 15, per group): two unsupplemented groups, control group and PM2.5 group, and two supplemented groups with ω-3 PUFAs, ω-3 PUFAs group, and ω-3 PUFAs + PM2.5 group. Mice in the supplemented groups were placed on an ω-3 PUFAs-enriched diet (ω-3 PUFAs, 21 g/kg). During the 5th to 6th week of dietary supplementation, mice were exposed to PM2.5 by intra-tracheal instillation. ω-3 PUFAs ameliorate lung histopathological injury, reduce inflammatory responses and oxidative stress, affect lung metabolite profile, and modulate gut microbiota in PM2.5-induced lung injury mice. Thus, supplementary ω-3 PUFAs showed effectiveness in attenuation of PM2.5-induced lung injury, indicating that the interventions exhibited preventive and therapeutic potential.

Diabetes associated with HPV infection in women aged over 50 years: A cross-sectional study from China's largest academic woman's hospital.

Background: Metabolic disturbances and immune alterations caused by diabetes are not just bystanders of HPV infection, but the conclusion that diabetes increases the risk of HPV infection requires more clinical epidemiological evidence to confirm. Our aim was to evaluate the association of diabetes with HPV infection risk in female patients aged over 50 years in the cervical clinic. Methods: We conducted a cross-sectional study of 6402 women aged over 50 years in the cervical clinic between May 2019 and March 2022 from China's largest academic woman's hospital. The quantitative-effect relationship between diabetes and HPV infection was observed by dose-response graph. Segmented multivariate logistic regression analysis was conducted to estimate the relative risk of HPV infection in diabetes patients. Multivariable predicted marginal proportions from logistic regression models were used to compute adjusted risk ratios. Results: There is a nonlinear relationship between HbA1c and the risk of HPV infection. When the HbA1c exceeds 5.7%, there is a saturation effect. After adjustment for confounders, the risk ratio for HPV infection in women with prediabetes was 1.09 (95% CI: 1.00-1.18) compared with women with HbA1c <5.7%, and the risk ratio for HPV infection in women with diabetes was 1.18 (95%). CI: 1.04-1.33). Sensitivity analysis showed that the risk ratio for HPV infection was 1.47 (95% CL: 1.07-1.91) when diabetes was associated with vaginitis. E-value analysis suggested robustness to unmeasured confounding. Conclusions: Diabetes and prediabetes are at increased risk of coinfection with HPV in female patients aged over 50 years in the cervical clinic.

Diabetes associated with cervical carcinoma among high-risk HPV-infected patients with cytologically diagnosed high grade squamous intraepithelial lesion.

Background: Diabetes causes metabolic disorders and immune changes that may be potential triggers of cervical cancer. Therefore, diabetes is not a "bystander" to cervical cancer. However, the conclusion that diabetes promotes cervical cancer lacks clinical epidemiological evidence, and the reported potential association between diabetes and cervical cancer is controversial. Methods: We conducted an explorative cross-sectional study of 791 women with cytological HGSIL and HR-HPV, who attended the cervical clinic of the largest academic women's hospital in China from May 2019 to March 2022. After cervical screening, patients who were requiring colposcopy were tested for HbA1c. HbA1c level of 6.5% or higher defines diabetes and HbA1c level of 5.7%-6.4% was defined as prediabetes. The relationship between diabetes and cervical cancer was observed by a dose-response graph. Subgroup analysis and multivariate logistic regression analysis were conducted to estimate the associations between diabetes and cervical cancer. Results: Among HGSIL patients with high-risk HPV infection, compared with women with HbA1c <5.7%, the odds ratio for women with prediabetes was 1.72 (95% CI: 0.87-3.41) and the odds ratio for women with diabetes was 3.29 (95% CI: 1.10-9.80) for cervical cancer. Sensitivity analysis showed that diabetes was significantly associated with cervical cancer in different age groups and different HPV variant. E-value analysis showed robustness to unmeasured confounding. Conclusions: In patients with HR-HPV combined with HGSIL, diabetes and prediabetes are associated with cervical cancer.

Metabolic network changes during skotomorphogenesis in Arabidopsis thaliana mutant (atdfb-3).

The metabolic networks underlying skotomorphogenesis in seedlings remain relatively unknown. On the basis of our previous study on the folate metabolism in seedlings grown in darkness, the plastidial folylpolyglutamate synthetase gene (AtDFB) T-DNA insertion Arabidopsis thaliana mutant (atdfb-3) was examined. Under the nitrate-sufficient condition, the mutant exhibited deficient folate metabolism and hypocotyl elongation, which affected skotomorphogenesis. Further analyses revealed changes to multiple intermediate metabolites related to carbon and nitrogen metabolism in the etiolated atdfb-3 seedlings. Specifically, the sugar, polyol, and fatty acid contents decreased in the atdfb-3 mutant under the nitrate-sufficient condition, whereas the abundance of various organic acids and amino acids increased. In response to nitrate-limited stress, multiple metabolites, including sugars, polyols, fatty acids, organic acids, and amino acids, accumulated more in the mutant than in the wild-type control. The differences in the contents of multiple metabolites between the atdfb-3 and wild-type seedlings decreased following the addition of exogenous 5-F-THF under both nitrogen conditions. Additionally, the mutant accumulated high levels of one-carbon metabolites, such as Cys, S-adenosylmethionine, and S-adenosylhomocysteine, under both nitrogen conditions. Thus, our data demonstrated that the perturbed folate metabolism in the atdfb-3 seedlings, which was caused by the loss-of-function mutation to AtDFB, probably altered carbon and nitrogen metabolism, thereby modulating skotomorphogenesis. Furthermore, the study findings provide new evidence of the links among folate metabolism, metabolic networks, and skotomorphogenesis.

Evaluation of Clinical Outcomes of Icotinib in Patients With Clinically Diagnosed Advanced Lung Cancer With EGFR-Sensitizing Variants Assessed by Circulating Tumor DNA Testing: A Phase 2 Nonrandomized Clinical Trial.

Importance: The inability to obtain a pathological diagnosis in a certain proportion of patients with clinically diagnosed advanced lung cancer impedes precision treatment in clinical practice. Objective: To evaluate the clinical outcome of first-line icotinib in patients with clinically diagnosed advanced lung cancer with unknown pathological status and positive epidermal growth factor receptor (EGFR)-sensitizing variants assessed by circulating tumor DNA (ctDNA). Design, Setting, and Participants: The Efficiency of Icotinib in Plasma ctDNA EGFR Mutation-Positive Patients Diagnosed With Lung Cancer (CHALLENGE) trial is a prospective, multicentered, open-label, single-arm phase 2 nonrandomized clinical trial conducted between July 1, 2017, and July 31, 2019. Patients with systemic treatment-naive, clinically diagnosed advanced peripheral lung cancer, unknown pathological status, and positive pretreatment plasma EGFR-sensitizing variants were eligible. A total of 391 potentially eligible Chinese patients from 19 centers in China were screened for ctDNA EGFR variants by 3 independent detection platforms (Super amplification refractory mutation system [SuperARMS] polymerase chain reaction, droplet digital polymerase chain reaction, and next-generation sequencing), and those with EGFR variants tested by any platform were included. Analyses were conducted from September 9 to December 31, 2021. Interventions: Enrolled patients were treated with oral icotinib tablets (125 mg 3 times daily) until disease progression, death, or treatment discontinuation due to various reasons, such as toxic effects and withdrawing consent. Main Outcomes and Measures: The primary end point was objective response rate (ORR). The secondary end points included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and the concordance among the 3 detection platforms. Results: Of 116 included patients, 76 (65.5%) were female, and the median (range) age was 64 (37-85) years. The median (IQR) follow-up duration was 36.3 (30.2-40.7) months. The ORR was 52.6% (95% CI, 43.1%-61.9%). The median PFS and OS were 10.3 months (95% CI, 8.3-12.2) and 23.2 months (95% CI, 17.7-28.0), respectively, and the DCR was 84.5% (95% CI, 76.6%-90.5%). The concordance rate among the 3 detection platforms was 80.1% (313 of 391), and the clinical outcomes in patients identified as positive by any platform were comparable. Conclusions and Relevance: This prospective phase 2 nonrandomized clinical trial suggests that for patients with clinically diagnosed advanced lung cancer with unknown pathological status, ctDNA-based EGFR genotyping could help decision-making in particular clinical situations, while still warranting future larger-scaled real-world exploration. Trial Registration: ClinicalTrials.gov Identifier: NCT03346811.

Design of Uracil-Modified DNA Nanotubes for Targeted Drug Release via DNA-Modifying Enzyme Reactions.

DNA nanostructure-based responsive drug delivery has become an increasingly potent method in cancer therapy. However, a variety of important cancer biomarkers have not been explored in searching of new and efficient targeted delivery systems. Uracil degradation glycosylase and human apurinic/apyrimidinic endonuclease are significantly more active in cancer cells. Here, we developed uracil-modified DNA nanotubes that can deliver drugs to tumor cells through an enzyme-induced disassembly process. Although the reaction of these enzymes on their natural DNA substrates has been established, their reactivity on self-assembled nanostructures of nucleic acids is not well understood. We leveraged molecular dynamic simulation based on coarse-grained model to forecast the enzyme reactivity on different DNA designs. The experimental data are highly consistent with the simulation results. It is the first example of molecule simulation being used to guide the design of enzyme-responsive DNA nano-delivery systems. Importantly, we found that the efficiency of drug release from the nanotubes can be regulated by tuning the positions of uracil modification. The DNA nanotubes equipped with cancer-specific aptamer AS1411 are used to deliver doxorubicin to tumor-bearing mice not only effectively inhibiting tumor growth but also protecting major organs from drug-caused damage. We believe that this work provides new knowledge on and insights into future design of enzyme-responsive DNA-based nanocarriers for drug delivery.

DNA Logic Circuits for Cancer Theranostics.

Cancer diagnosis and therapeutics (theranostics) based on the tumor microenvironment (TME) and biomarkers has been an emerging approach for precision medicine. DNA nanotechnology dynamically controls the self-assembly of DNA molecules at the nanometer scale to construct intelligent DNA chemical reaction systems. The DNA logic circuit is a particularly emerging approach for computing within the DNA chemical systems. DNA logic circuits can sensitively respond to tumor-specific markers and the TME through logic operations and signal amplification, to generate detectable signals or to release anti-cancer agents. In this review, the fundamental concepts of DNA logic circuits are clarified, the basic modules in the circuit are summarized, and how this advanced nano-assembly circuit responds to tumor-related molecules, how to perform logic operations, to realize signal amplification, and selectively release drugs through discussing over 30 application examples, are demonstrated. This review shows that DNA logic circuits have powerful logic judgment and signal amplification functions in improving the specificity and sensitivity of cancer diagnosis and making cancer treatment controllable. In the future, researchers are expected to overcome the existing shortcomings of DNA logic circuits and design smarter DNA devices with better biocompatibility and stability, which will further promote the development of cancer theranostics.

Tumor markers are associated with rapidly progressive interstitial lung disease in adult-dermatomyositis.

OBJECTIVES: DM-associated rapidly progressive interstitial lung disease (DM-RP-ILD) has been the clinical conundrum. We assess the serum levels of tumor markers (TMs) in different types of ILD, and explore the diagnostic utility of TMs for DM/ADM-RP-ILD. METHODS: This was a retrospective cohort study, data including clinical and laboratory records were collected from the first affiliated hospital of Zhengzhou University from December 2015, to June 2020. Tumor markers (TMs) include CEA, CA153, CA724, CA125, and CA199. Spearman analysis, ROC, and Kaplan-Meier curve were used for data analysis. RESULTS: Total 272 patients (149 DM and 123 ADM) were enrolled, 152 (55.88%) with ILD (116 with chronic ILD, 36 with RP-ILD) and 120 (44.12%) without ILD among them. The serum levels of CEA and ferritin were significantly higher in patients with RP-ILD than in the other two groups. Serum CA125, CA199, and CA153 levels in patients with RP-ILD were higher than those without ILD. CEA levels were associated with the ferritin, KL-6 and anti-MDA5 levels, and CEA concentration was significantly negatively correlated with DLco (P = 0.016, R2 = - 0.281). CEA [AUC = 0.7, 95% CI = (0.594, 0.806)] and ferritin [AUC = 0.737, 95% CI = (0.614, 0.860)] had diagnosed value for patients developing RP-ILD. Patients with high serum CEA levels had higher mortality rate within the DM-ILD population. CONCLUSIONS: TMs and ferritin were increased in DM/ADM-RP-ILD, and serum CEA and CA153 levels can evaluate disease severity of DM. And CEA and ferritin can be used as noninvasive diagnostic biomarkers for patients with DM-RP-ILD. Key Points • Interstitial lung disease (ILD) is a serious complication of DM, and is a leading cause of mortality, especially rapidly progressive ILD. • Tumor markers as a kind of noninvasive detection can reflect the disease severity of DM, and CEA and ferritin can be used to identify patients with RP-ILD.

Olaparib Maintenance Monotherapy in Asian Patients with Platinum-Sensitive Relapsed Ovarian Cancer: Phase III Trial (L-MOCA).

PURPOSE: In patients with platinum-sensitive relapsed (PSR) ovarian cancer, olaparib maintenance monotherapy significantly improves progression-free survival (PFS) versus placebo. However, evidence in the Asian population is lacking. This is the first study to evaluate olaparib efficacy and tolerability exclusively in Asian patients with PSR ovarian cancer. PATIENTS AND METHODS: Considering the limited placebo effect and significant clinical benefit of olaparib in previous trials, and the rapid approval of olaparib in China, this phase III study was designed as an open-label, single-arm trial. Patients with high-grade epithelial PSR ovarian cancer were enrolled from country-wide clinical centers across China and Malaysia. Patients received oral olaparib (300 mg) twice daily until disease progression or unacceptable toxicity. Primary endpoint was median PFS (mPFS). Primary analysis of PFS using the Kaplan-Meier method was performed when data reached 60% maturity (clinicaltrials.gov NCT03534453). RESULTS: Between 2018 and 2020, 225 patients were enrolled, and 224 received olaparib; 35.7% had received ≥3 lines of chemotherapy, 35.3% had achieved complete response to their last line of platinum-based chemotherapy, and 41.1% had a platinum-free interval ≤12 months. At primary data cut-off (December 25, 2020), overall mPFS was 16.1 months; mPFS was 21.2 and 11.0 months in BRCA-mutated and wild-type BRCA subgroups, respectively. Adverse events (AE) occurred in 99.1% of patients (grade ≥3, 48.7%); 9.4% discontinued therapy due to treatment-related AEs. CONCLUSIONS: Olaparib maintenance therapy was highly effective and well tolerated in Asian patients with PSR ovarian cancer, regardless of BRCA status. This study highlights the promising efficacy of olaparib in this Asian population. See related commentary by Nicum and Blagden, p. 2201.

Prognostic significance of tumor-infiltrating lymphocytes and macrophages in nasopharyngeal carcinoma: a systematic review and meta-analysis.

PURPOSE: Many studies have investigated the prognostic value of tumor-infiltrating lymphocytes (TILs) and tumor-infiltrating macrophages (TIMs) in patients with nasopharyngeal carcinoma (NPC), but the results remain controversial. Here, we performed a meta-analysis to evaluate the prognostic significance of TILs/TIMs in patients with NPC METHODS: The study was registered with PROSPERO (CRD42021234078). PubMed, Embase, and Web of Science databases were searched up to Dec 30, 2020. We reviewed studies that evaluated the relationship between TILs/TIMs and overall survival (OS), disease-free survival (DFS), or progression-free survival (PFS) in NPC. For TILs, CD3, CD4, CD8, and FOXP3 were searched as T-cell markers, CD19 and CD20 as B-cell markers, and CD56 as a natural killer cell marker. For TIMs, CD68 and CD163 were searched as total and M2 macrophage markers, respectively. RESULTS: In total, 19 studies with 3708 NPC were included in this meta-analysis. We found that high total numbers of TILs were significantly associated with favorable OS [hazard ratio (HR) 0.46, 95% confidence interval (CI) 0.38-0.57 and PFS (HR 0.48, 95% CI 0.38-0.62)]. In contrast, tumor infiltration by CD3+ T cells (HR 0.55, 95% CI 0.39-0.76), CD4+ T cells (HR 0.40, 95% CI 0.18-0.85), and CD8+ T cells (HR 0.56, 95% CI 0.34-0.93) correlated positively with OS. No significant relationship was found between survival and tumor infiltration by FOXP3+ T cells, CD68+ macrophages, or CD163+ macrophages. CONCLUSION: Our findings revealed that tumor infiltration by CD3+ , CD4+ , and CD8+ T cells could be prognostic biomarkers in NPC.

The PITX gene family as potential biomarkers and therapeutic targets in lung adenocarcinoma.

ABSTRACT: The PITX gene family of transcription factors have been reported to regulate the development of multiple organs. This study was designed to investigate the role of PITXs in lung adenocarcinoma (LUAD).In this study, the transcriptional levels of the 3 identified PITXs in patients with LUAD were examined using the gene expression profiling interactive analysis interactive web server. Meanwhile, the immunohistochemical data of the 3 PITXs were obtained in the Human Protein Atlas website, and western blotting was additionally conducted for further verification. Moreover, the association between the levels of PITXs and the stage plot as well as overall survival of patients with LUAD was analyzed.We found that the mRNA and protein levels of PITX1 and PITX2 were higher in LUAD tissues than those in normal lung tissues, while those of PITX3 displayed no significant differences. Additionally, PITX1 and PITX3 were found to be significantly associated with the stage of LUAD. The Kaplan-Meier Plot showed that the high level of PITX1 conferred a better overall survival of patients with LUAD while the high level of PITX3 was associated with poor prognosis.Our study implied that PITX1 and PITX3 are potential targets of precision therapy for patients with LUAD while PITX1 and PITX2 are regarded as novel biomarkers for the diagnosis of LUAD.

Plasma Heat Shock Protein 90 Alpha: A Valuable Predictor of Early Chemotherapy Effectiveness in Advanced Non-Small-Cell Lung Cancer.

BACKGROUND Heat shock protein-90 alpha (HSP90a) is more abundant in non-small-cell lung cancer (NSCLC) patients than in control individuals. However, whether it can reflect chemotherapy efficacy remains unknown. This study aimed to investigate the association of HSP90a with chemotherapy in advanced NSCLC. MATERIAL AND METHODS We retrospectively evaluated data from patients admitted to the Department of Respiratory Medicine, Shaoxing People's Hospital, from September 2016 to September 2018 with stage IIIB or IV NSCLC and administered 4 cycles of third-generation platinum-based combination chemotherapy (2 drugs simultaneously). Based on the RECIST1.1 criteria, complete remission (CR), partial response (PR), and stable disease (SD) in 60 cases were determined before and after chemotherapy. Before chemotherapy and after 1, 2, and 4 cycles of chemotherapy, plasma HSP90alpha levels were quantitated by ELISA. Chest CT was performed before and after 2 and 4 cycles of chemotherapy. RESULTS After 1-4 cycles of chemotherapy, plasma HSP90alpha levels were significantly lower than pre-chemotherapy levels (P<0.05). The sums of the longest tumor diameters after 2 and 4 cycles of chemotherapy were decreased compared with pre-chemotherapy values (P<0.05). Plasma HSP90alpha levels and tumor size showed no significant correlation before and after chemotherapy (r=0.244, P=0.06). CONCLUSIONS Plasma HSP90alpha can be considered a valuable predictor of early chemotherapy effectiveness in advanced NSCLC, and is positively correlated with tumor remission after chemotherapy. However, plasma HSP90alpha level is not correlated with tumor diameter and pathological type.

Behcet's disease with peripheral nervous system involvement successfully treated with golimumab: a case report and review of the literature.

Nervous system involvement is a rare and serious complication of Behcet's disease (BD), and the peripheral type is rarer. This article aimed to describe a case of BD with the peripheral nervous system (PNS) involvement and present a comprehensive literature review. One case of BD with PNS involvement was reported and related literature was retrospectively reviewed via PubMed/MEDLINE and Scopus database. The patient was resistant to traditional treatments, such as glucocorticoids and immunosuppressants, but had rapid quiescence after using golimumab. Our literature review suggests that the involved peripheral nerves in BD were diverse, the most common were the tibial nerves and peroneal nerves, vasculitis might be the main cause, and prednisone was still the cornerstone of treatment. TNF-α inhibitors have been increasingly used for refractory BD in recent years. This well-illustrated case demonstrates the potential benefit of golimumab to the patient with PNS involvement. Given the diversity and complexity of PNS involvement, we recommend golimumab as a new trial treatment in clinical practice.