An increase in SNHG5 expression is associated with poor cancer prognosis, according to a meta-analysis.

BACKGROUND: He long noncoding RNA small nucleolar host RNA 5 (SNHG5) is highly expressed in many cancers, and there is a notable correlation between the elevated expression of SNHG5 and survival outcome in cancer patients. The objective of this study was to conduct a meta-analysis to evaluate the correlation between SNHG5 expression and the clinical outcome of cancer patients. METHODS: Six relevant electronic databases were exhaustively searched, and, depending on the inclusion and exclusion criteria, appropriate literature was obtained. The Newcastle-Ottawa Scale (NOS) score was utilized to evaluate the quality of the research for every article included, and pertinent data from each study were carefully extracted. Hazard ratios (HRs), odds ratios (ORs) and 95% confidence intervals (CIs) were combined to explore the association of SNHG5 expression levels with cancer prognosis, and sensitivity analyses and assessments of publication bias were also conducted to investigate any possibility in the publication of the studies. RESULTS: Eleven studies encompassing 721 patients were ultimately collected. When combined, the hazard ratios (HRs) revealed a substantial direct correlation between elevated SNHG5 expression and an unfavourable prognosis for cancer patients (HR = 1.90, 95% CI 0.87-4.15); however, the correlation did not reach statistical significance. Furthermore, high SNHG5 expression was predictive of advanced TNM stage (OR: 1.988, 95% CI 1.205-3.278) and larger tumour size (OR: 1.571, 95% CI 1.090-2.264); moreover, there were nonsignificant relationships between SNHG5 expression and DM (OR: 0.449, 95% CI 0.077-2.630), lymph node metastasis (OR: 1.443, 95% CI 0.709-2.939), histological grade (OR: 2.098, 95% CI 0.910-4.838), depth of invasion (OR: 1.106, 95% CI 0.376-3.248), age (OR: 0.946, 95% CI 0.718-1.247) and sex (OR: 0.762, 95% CI 0.521-1.115). CONCLUSION: SNHG5 expression is typically increased in the majority of tumour tissues. Elevated SNHG5 expression may indicate poor prognosis in cancer patients. Therefore, SNHG5 is a promising potential therapeutic target for tumours and a reliable prognostic biomarker.

Case Report: A novel intergenic MIR4299/MIR8070-RET fusion with RET amplification and clinical response to pralsetinib in a lung adenocarcinoma patient.

The identification of receptor-tyrosine kinase gene (RET) fusions in lung cancer has become crucial owing to actionable events that predict responsiveness to tyrosine kinase inhibitors (TKIs). However, RET fusions with distinct partner genes respond differently to TKIs. In this case, a 60-year-old man was diagnosed with advanced lung adenocarcinoma. A novel RET-MIR4299/MIR8070 fusion and RET amplification were identified using next-generation sequencing (NGS). The patient was then administered with pralsetinib. After 3 weeks of therapy, the patient had a partial response. At the time of reporting, the patient was on continuous pralsetinib. These findings broaden the range of RET fusion types and provide the basis for the hypothesis that RET intergenic fusion and amplification respond to pralsetinib treatment in lung adenocarcinoma.

Corrigendum: Case report: A novel intergenic MIR4299/MIR8070-RET fusion with RET amplification and clinical response to pralsetinib in a lung adenocarcinoma patient.

[This corrects the article DOI: 10.3389/fonc.2022.929763.].

Anti-VEGF reduces inflammatory features in macular edema secondary to retinal vein occlusion.

AIM: To investigate the anti-inflammatory effect of intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) in patients with macular edema secondary to retinal vein occlusion (RVO-ME). METHODS: Twenty-eight eyes from twenty-eight treatment-naïve patients (14 males and 14 females) with RVO-ME were included in this retrospective study. The retinal vein occlusion (RVO) was comprised of both central retinal vein occlusion (CRVO, n=14) and branch retinal vein occlusion (BRVO, n=14). Intravitreal injection of anti-VEGF reagents were administered monthly for three consecutive months, in which 18 patients were injected with ranibizumab and 10 patients were injected with conbercept. All eyes were imaged with optical coherence tomography angiography (OCTA) at baseline and 1wk after monthly intravitreal anti-VEGF injection. The visual acuity (VA), central macular thickness (CMT), the number of hyperreflective foci (HRF) recognized as an inflammatory sign in OCT images, and non-perfusion area (NPA), were compared before and after anti-VEGF treatments. RESULTS: The mean interval between baseline and follow-up was 29.4±0.79 (range, 27-48)d. Compared with the baseline, the VA improved (logMAR 1.5±0.1 vs 0.8±0.1, P<0.05) and CMT decreased (460±34.0 µm vs 268.8±12.0 µm, P<0.05), significantly, after anti-VEGF treatment. The number of HRF was decreased significantly (76.5±4.8 vs 47.8±4.3, P<0.05) after anti-VEGF treatment. CONCLUSION: Anti-VEGF therapy is effective in treating RVO-ME. The mechanisms for the decreased HRF and the reduction of NPA by anti-VEGF therapy merits further exploration.

Is Iba-1 protein expression a sensitive marker for microglia activation in experimental diabetic retinopathy?

AIM: To investigate the changes of Iba-1 and other potential markers for microglia activation in experimental diabetic retinopathy (DR). METHODS: Male Sprague-Dawley rats were rendered diabetes via intraperitoneal injection of streptozotocin. The retinas were harvested at 1 to 24wk after diabetes onset. Hypoxia-treated mouse microglial cell line (BV2 cells) was employed as the in vitro model to mimic diabetic condition. The expressions of Iba-1, CD11b, ICAM-1 as well as the inflammatory factors were examined with real-time polymerase chain reaction, Western blot and immunofluorescence both in vivo and in vitro. RESULTS: Compared with age-matched normal control, the number of microglia (Iba-1 positive immunostaining) in diabetic rat retinas was increased from 1 to 24wk of diabetes, which was most obvious at 12wk of diabetes. Iba-1 protein expression detected by Western blot was increased slightly in diabetic rat retinas compared with that in age-matched normal control; however, there was statistically significant between two groups only at 2wk after diabetes onset. The mRNA expression of Iba-1 was decreased significantly at 2 and 4wk of diabetic rat retinas, and remained unchanged at 8 and 12wk of diabetes. In BV2 cells, there was no significant change for the Iba-1 protein expression between normoxia and hypoxia groups; however, its mRNA level was decreased significantly under hypoxia. To further characterize microglial activation, F4/80, CD11b and inflammatory factors were detected both in vivo and in vitro. Compared with normal control, the expressions of F4/80 and CD11b as well as the inflammatory factors, such as ICAM-1, iNOS, COX2, IL-1ß and IL-6, were increased significantly both in vivo and in vitro. CONCLUSION: Iba-1 protein expression might not be a sensitive marker to evaluate the activation of microglia in experimental DR. However, Iba-1 immunostaining, in combination with other markers like CD11b and ICAM-1, could be well reflect the activation of microglia. Thus, it is of great importance to explore other potential marker to evaluate the activation of microglia.

Severe immune-related hyperthermia followed by immune-related pneumonitis with PD-1 inhibitor (sintilimab) in small cell lung cancer: A case report.

Immune checkpoint inhibitors (ICIs) have achieved prominent efficacy in the treatment of numerous cancers, which is the most significant breakthrough in cancer therapy in recent years. However, ICIs are associated with a series of immune-related adverse events (irAEs). Pneumonitis is an uncommon but potentially fatal irAE. In the case reported here, a patient with advanced small cell lung cancer (SCLC) had rapid progression of disease following chemotherapy and received ICIs. The patient experienced severe immune-related hyperthermia followed by immune-related pneumonitis. Fortunately, a good clinical response was achieved after the patient received corticosteroids and tocilizumab.

A highly-sensitive "turn on" probe based on coumarin ß-diketone for hydrazine detection in PBS and living cells.

Herein, a new "turn on" fluorescent probe C-1 is developed to specifically detect hydrazine using coumarin nucleus as the fluorophore and ß-diketone as the recognition group. The probe shows high selectivity towards hydrazine over other common ions and amine-containing species, as well as good water solubility and quantitative detectability of hydrazine in concentration range of 1-200 µM. The detection limit is as low as 1.89 ppb, which is lower than the threshold set by EPA (10 ppb). Probe-coated filter papers are confirmed to detect gaseous hydrazine successfully through obvious fluorescence color changes. In addition, the probe has been verified to detect hydrazine in actual water environment and living cells.

ALK-rearrangement in non-small-cell lung cancer (NSCLC).

The ALK gene encodes a transmembrane tyrosine kinase receptor. ALK is physiologically expressed in the nervous system during embryogenesis, but its expression decreases postnatally. ALK first emerged in the field of oncology in 1994 when it was identified to fuse to NPM1 in anaplastic large-cell lymphoma. Since then, ALK has been associated with other types of cancers, including non-small-cell lung cancer (NSCLC). More than 19 different ALK fusion partners have been discovered in NSCLC, including EML4, KIF5B, KLC1, and TPR. Most of these ALK fusions in NSCLC patients respond well to the ALK inhibitor, crizotinib. In this paper, we reviewed fusion partner genes with ALK, detection methods for ALK-rearrangement (ALK-R), and the ALK-tyrosine kinase inhibitor, crizotinib, used in NSCLC patients.

Circulating microRNAs as novel biomarkers of ALK-positive nonsmall cell lung cancer and predictors of response to crizotinib therapy.

Circulating microRNAs are potential diagnostic and predictive biomarkers, but have not been investigated for patients with anaplastic lymphoma kinase (ALK)-positive lung cancer. In this exploratory study, we sought to identify potential plasma biomarkers for ALK-positive non-small cell lung cancer (NSCLC). A microRNA microarray was used to select ALK-related microRNAs in ALK-positive NSCLC (n = 3), ALK-negative NSCLC (n = 3), and healthy subjects (n = 3). Plasma levels of 21 microRNAs were differentially expressed for ALK-positive and ALK-negative NSCLC, including 14 down-regulated and 7 up-regulated microRNAs. We also identified 5s rRNA as the most stable endogenous control gene using geNorm and NormFinder algorithms. Candidate microRNAs in plasma from ALK-positive (n = 41) and ALK-negative NSCLC patients (n = 32) were quantified using real-time reverse transcriptase quantitative polymerase chain reaction. The expression levels of miR-28-5p, miR-362-5p, and miR-660-5p were all down-regulated in ALK-positive NSCLC, compared with ALK-negative NSCLC. The areas under the receiver operating characteristic curves of miR-28-5p, miR-362-5p, miR-660-5p, and 3-microRNAs panel were 0.873, 0.673, 0.760, and 0.876, respectively. The positive predictive values of miR-28-5p, miR-362-5p, and miR-660-5p were 96.43%, 80.77%, and 83.87%, respectively. Increased plasma levels of miR-660-5p after crizotinib treatment predicted good tumor response (p = 0.012). The pre-crizotinib levels of miR-362-5p were significantly associated with progression-free survival (p = 0.015). Thus, in this preliminary investigation, we identified a potential panel of 3 microRNAs for distinguishing between patients with ALK-positive and ALK-negative NSCLC. We also identified miR-660-5p and miR-362-5p as potential predictors for response to crizotinib treatment.

Research on mouse model of grade II corneal alkali burn.

AIM: To choose appropriate concentration of sodium hydroxide (NaOH) solution to establish a stable and consistent corneal alkali burn mouse model in grade II. METHODS: The mice (n=60) were randomly divided into four groups and 15 mice each group. Corneal alkali burns were induced by placing circle filter paper soaked with NaOH solutions on the right central cornea for 30s. The concentrations of NaOH solutions of groups A, B, C, and D were 0.1 mol/L, 0.15 mol/L, 0.2 mol/L, and 1.0 mol/L respectively. Then these corneas were irrigated with 20 mL physiological saline (0.9% NaCl). On day 7 postburn, slit lamp microscope was used to observe corneal opacity, corneal epithelial sodium fluorescein staining positive rate, incidence of corneal ulcer and corneal neovascularization, meanwhile pictures of the anterior eyes were taken. Cirrus spectral domain optical coherence tomography was used to scan cornea to observe corneal epithelial defect and corneal ulcer. RESULTS: Corneal opacity scores (x±s) were not significantly different between the group A and group B (P=0.097). Incidence of corneal ulcer in group B was significantly higher than that in group A (P=0.035). Incidence of corneal ulcer and perforation rate in group B was lower than that in group C. Group C and D had corneal neovascularization, and incidence of corneal neovascularization in group D was significantly higher than that in group C (P=0.000). CONCLUSION: Using 0.15 mol/L NaOH can establish grade II mouse model of corneal alkali burns.

[Application of partial costectomy and costophrenic angle closure to supplement high intensity focused ultrasound treatment for liver tumor].

OBJECTIVE: To investigate the application of partial costectomy and costophrenic angle closure (PCCAC) and perioperative management in the treatment of liver tumor by high intensity focused ultrasound (HIFU). METHODS: The clinical data of 69 patients with liver tumor underwent HIFU within the recent four years were retrospectively reviewed. RESULTS: 92.8% of these 69 liver tumor patients had had concomitant diseases and 13.0% of them developed postoperative complications without anyone died. There was no significant postoperative dysfunctions of kidney or lung as compared with the preoperative ones (P > 0.05). CONCLUSION: In the treatment of liver tumor by HIFU, PCCAC, as an auxillary means, giving few complications and little harmful effects on respiratory physiology, is highly safe.

Annexin A2 silencing enhances apoptosis of human umbilical vein endothelial cells in vitro.

OBJECTIVE: To study the effects of inhibited Annexin A2 (ANXA2) on human umbilical vein endothelial cells (HUVECs) in vitro. METHODS: Short hairpin RNA (shRNA) targeting ANXA2 was designed and cloned into double marked lentivirial vector GV248 for RNAi to generate the recombinant expression plasmids, which were stably transfected into HUVECs. The protein and mRNA expression levels of ANXA2 were analyzed by western blotting and real-time polymerase chain reaction, respectively. Cell proliferation (cell counting kit-8 assay), apoptosis (flow cytometry analysis), the expression (western blotting) and the activity of caspases (enzyme-linked immunosorbent assay) were used to assess the effects of silencing ANXA2 on HUVECs in vitro. RESULTS: The plasmids to express ANXA2-specific shRNA were constructed and were infected into HUVEC resulting in the stably transfected experimental (ANXA2-shRNA), control (control-shRNA) and mock (no plasmid) cell lines, which were verified with western blot and real-time PCR. HUVEC/ANXA2-shRNA showed an inhibition rate 91.89% of ANXA2 expression compared to the mock HUVEC. ANXA2 silencing cell strain obviously presented a lower cell proliferation activity compared to the control and mock HUVECs, with an inhibition rate 82.35% on day 7 in vitro. FACS analysis indicated that the HUVEC/ANXA2-shRNA cells undergoing apoptosis increased by 102.61% compared to the mock HUVECs (P < 0.01). Moreover, the activity levels of caspase-3, caspase-8 and caspase-9 in HUVEC/ANXA2-shRNA cells were increased and the activated cleaved caspase-3, cleaved caspase-8 and cleaved caspase-9 were upregulated evidently compared with that of the control and mock HUVECs by 56.29%, 89.59% and 144.58% (P < 0.01). CONCLUSIONS: shRNA-mediated silencing of ANXA2 could not only be able to suppress HUVECs proliferation but to upregulate the enzyme activity of caspases, which bring to an increase of cell apoptosis. This work suggested that ANXA2 may represent a useful target of future molecular therapies.

Combination of icotinib, surgery, and internal-radiotherapy of a patient with lung cancer severely metastasized to the vertebrae bones with EGFR mutation: a case report.

A 48-year-old Chinese female was referred to us regarding EGFR-mutated advanced non-small cell lung cancer, and metastasis to left scapula and vertebrae bones which caused pathological fracture at T8 and T10 thoracic vertebrae. An aggressive combined therapy with icotinib, vertebrae operation, and radioactive particle implantation and immunotherapy was proposed to prevent paraplegia, relieve pain, and control the overall and local tumor lesions. No postoperative symptoms were seen after surgery, and the pain was significantly relieved. Icotinib merited a 31-month partial response with grade 1 diarrhea as its drug-related adverse event. High dose of icotinib was administered after pelvis lesion progression for 3 months with good tolerance. Combination therapy of icotinib, surgery, and internal radiation for metastases of the vertebrae bones from non-small cell lung cancer seems to be a very promising technique both for sufficient pain relief and for local control of the tumor, vertebrae operation can be an encouraging option for patients with EFGR positive mutation and good prognosis indicator.

Serum CEA level change and its significance before and after Gefitinib therapy on patients with advanced non-small cell lung cancer.

OBJECTIVE: The aim of this study was to explore change and significance of serum carcino-embryonic antigen (CEA) before and after gefitinib therapy in patients with advanced non-small-cell lung cancer (NSCLC). METHODS: Forty patients with advanced NSCLCs in III~IV stages were selected as study objects given gefitinib therapy combined with routine local radiotherapy until tumor progression or intolerable toxicity. After treatment, all patients were divided into control and non-control groups according to the results of evaluation based on RECIST 1.1 (Response Evaluation Criteria in Solid Tumors in 2009). Peripheral fasting blood from all patients was collected in the early morning and serum CEA was assessed by electro-chemiluminescence immunoassay (ECLIA) before and after treatment. Before treatment, patients were divided into high CEA group (CEA level > 50 ng/mL) and low CEA group (CEA level ≤ 50 ng/mL). Adverse reactions were noted and progression-free survival (PFS) in both groups was recorded after long-term follow-up that ended in December, 2012. RESULTS: There was no difference between control and non-control groups in CEA level before treatment (P>0.05), whereas serum CEA decreased more markedly lower in the control group after treatment (P<0.01). All patients were divided into high CEA group (26) and low CEA group (14) according to serum CEA level. There was no statistically significant difference between two groups in adverse reactions (P>0.05) but the rate in former group was lower. Additionally, survival rates at 9 and 12 months in high CEA group were clearly higher than in the low CEA group (P<0.01). CONCLUSIONS: Serum CEA level can serve as a biochemical index to evaluate the prognosis with gefitinib treatment for NSCLC.

Whole brain radiotherapy plus chemotherapy in the treatment of brain metastases from lung cancer: a meta-analysis of 19 randomized controlled trails.

OBJECTIVE: To evaluate the efficacy and safety of whole brain radiotherapy (WBRT) plus chemotherapy versus WBRT alone for treating brain metastases (BM) from lung cancer by performing a meta-analysis based on randomized controlled trials (RCTs). METHODS: The PubMed, Embase, CENTRAL, ASCO, ESMO, CBM, CNKI, and VIP databases were searched for relevant RCTs performed between January 2000 and March 2012. After quality assessment and data extraction, the meta-analysis was performed using the RevMan 5.1 software, with funnel plot evaluation of publication bias. RESULTS: 19 RCTs involving 1,343 patients were included. The meta-analyses demonstrated that compared to WBRT alone, WBRT plus chemotherapy was more effective with regard to the objective response rate (OR = 2.30, 95% CI = 1.79-2.98; P < 0.001); however, the incidences of gastrointestinal reactions (RR = 3.82, 95% CI = 2.33-6.28, P <0.001), bone marrow suppression (RR = 5.49, 95% CI = 3.65-8.25, P < 0.001), thrombocytopenia (RR = 5.83, 95% CI = 0.39-86.59; P = 0.20), leukopenia (RR = 3.13, 95% CI = 1.77-5.51; P < 0.001), and neutropenia (RR = 2.75, 95% CI = 1.61-4.68; P < 0.001) in patients treated with WBRT plus chemotherapy were higher than with WBRT alone. There was no obvious publication bias detected. CONCLUSION: WBRT plus chemotherapy can obviously improve total efficacy rate, but also increases the incidence of adverse reactions compared to WBRT alone. From the limitations of this study, more large-scale, high-quality RCTs are suggested for further verification.

A comparison of ARMS and direct sequencing for EGFR mutation analysis and tyrosine kinase inhibitors treatment prediction in body fluid samples of non-small-cell lung cancer patients.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutation is strongly associated with the therapeutic effect of tyrosine kinase inhibitors (TKIs) in patients with non-small-cell lung cancer (NSCLC). Nevertheless, tumor tissue that needed for mutation analysis is frequently unavailable. Body fluid was considered to be a feasible substitute for the analysis, but arising problems in clinical practice such as relatively lower mutation rate and poor clinical correlation are not yet fully resolved. METHOD: In this study, 50 patients (32 pleural fluids and 18 plasmas) with TKIs therapy experience and with direct sequencing results were selected from 220 patients for further analysis. The EGFR mutation status was re-evaluated by Amplification Refractory Mutation System (ARMS), and the clinical outcomes of TKIs were analyzed retrospectively. RESULTS: As compared with direct sequencing, 16 positive and 23 negative patients were confirmed by ARMS, and the other 11 former negative patients (6 pleural fluids and 5 plasmas) were redefined as positive, with a fairly well clinical outcome (7 PR, 3 SD, and 1 PD). The objective response rate (ORR) of positive patients was significant, 81.3% (direct sequencing) and 72.7% (ARMS) for pleural fluids, and 80% (ARMS) for plasma. Notably, even reclassified by ARMS, the ORR for negative patients was still relatively high, 60% for pleural fluids and 46.2% for plasma. CONCLUSIONS: When using body fluids for EGFR mutation analysis, positive result is consistently a good indicator for TKIs therapy, and the predictive effect was no less than that of tumor tissue, no matter what method was employed. However, even reclassified by ARMS, the correlation between negative results and clinical outcome of TKIs was still unsatisfied. The results indicated that false negative mutation still existed, which may be settled by using method with sensitivity to single DNA molecule or by optimizing the extraction procedure with RNA or CTC to ensure adequate amount of tumor-derived nucleic acid for the test.