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Kinesin family member 2A (KIF2A) represents an oncogene in several cancers, however, its involvement in non-small cell lung cancer (NSCLC) is limitedly investigated. Therefore, the present study aimed to explore potential molecular mechanism of KIF2A knockdown in repressing NSCLC malignant behaviors. The effect of KIF2A knockdown on cell proliferation, apoptosis, invasion, epithelial-mesenchymal transition (EMT) markers, stemness, chemosensitivity was detected after transfecting KIF2A short hairpin RNA (ShRNA) plasmids into A549 and NCI-H1975 cells. Moreover, KIF2A knockdown mediated signaling pathways were analyzed by RNA sequencing (RNA-seq), and then validated by western blot assay. Both KIF2A mRNA and protein expressions were increased in A549, NCI-H650, NCI-H358, NCI-H2106, NCI-H1299, NCI-H1650 and NCI-H1975 cells compared with BEAS-2B cells. KIF2A knockdown inhibited proliferation, invasion, EMT, stemness, but enhanced chemosensitivity to cisplatin and paclitaxel in both A549 and NCI-H1975 cells. Meanwhile, it only promoted apoptosis in NCI-H1975 cells but not in A549 cells. Moreover, after KIF2A knocking down, RNA-seq data indicated that 356 accordant differentially expressed genes (DEGs) in both A549 and NCI-H1975 cells, and these DEGs were enriched in PI3K-Akt, Wnt and Notch signaling pathways. Further western blot disclosed that KIF2A knockdown indeed inactivated PI3K-Akt, Wnt and Notch signaling pathways in both A549 and NCI-H1975 cells. In conclusion, KIF2A knockdown suppresses NSCLC cell malignant behaviors, EMT and stemness, but enhances chemosensitivity via inactivating PI3K-Akt, Wnt, and Notch signaling pathways, which proposes it as a potential therapeutic target for NSCLC treatment., Competing Interests: None., (AJTR Copyright © 2022.)

Objective: To carry out prenatal diagnosis for a fetus with absent nasal bone by using cytogenetic and molecular techniques., Methods: Chromosomal karyotyping, single nucleotide polymorphism array (SNP-array) and fluorescence in situ hybridization (FISH) assays were applied for the diagnoses. Peripheral blood samples were also taken from the parents for chromosomal karyotyping and FISH analysis., Results: The fetus was found to have a 46,XX,add(21)(p11.2) karyotype, and SNP-array has revealed a 11.3 Mb duplication at 21q22.12q22.3 (hg19: 36 762 648-48 093 361), which was confirmed by FISH. Both parents were found to be normal by chromosomal karyotyping and FISH analysis. The fetus was ultimately found to have a karyotype of 46,XX,der(21)t(21;21)(p11.2;q22.1), resulting a de novo partial trisomy of 21q22.1., Conclusion: Combined use of various techniques has enabled accurate prenatal diagnosis and genetic counseling for the fetus.

Purpose: To determine the optimal threshold of examined lymph node (ELN) number from cervical lymph node dissection for head and neck squamous cell carcinoma (HNSCC). Further to compare the prognostic value of multiple lymph node classification systems and to determine the most suitable scheme to predict survival., Methods: A total of 20991 HNSCC patients were included. Odds ratios (ORs) for negative-to-positive node stage migration and hazard ratios (HRs) for survival were fitted using the LOWESS smoother. Structural breakpoints were determined by the Chow test. The R square, C-index, likelihood ratio, and Akaike information criterion (AIC) were used to compare the prognostic abilities among AJCC N stage, number of positive lymph nodes (pN), positive lymph node ratio (LNR) and log odds of positive lymph nodes (LODDS) stages., Results: A minimal threshold ELN number of fifteen had the discriminatory capacities for both stage migration and survival. LODDS stages had the highest R square value (0.208), C-index (0.736) and likelihood ratio (2467) and the smallest AIC value (65874). LODDS stages also showed prognostic value in estimating patients with AJCC N0 stage. A novel staging system was proposed and showed good prognostic performance when stratified by different primary sites., Conclusion: Fifteen lymph nodes should be examined for HNSCC patients. LODDS stage allows better prognostic stratification, especially in N0 stage. The proposed staging system may serve as precise evaluation tools to estimate postoperative prognoses., Competing Interests: Declaration of competing interest The authors have no potential conflicts of interest., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objective: To carry out prenatal diagnosis for a fetus with increased nuchal translucency (NT) and another fetus with non-invasive prenatal testing (NIPT) suggested reduced sex chromosomes by cytogenetic and molecular techniques., Methods: Chromosomal karyotyping, single nucleotide polymorphism array (SNP-array) and fluorescence in situ hybridization (FISH) were applied for the diagnoses. Peripheral blood samples were also taken from their parents for chromosomal karyotyping and SNP-array analysis., Results: Both fetuses showed a 46,X,+mar/45,X karyotype. SNP-array has detected a 22.0 Mb duplication at Yp11.31q11.223 and a 3.9 Mb microdeletion at Yq11.223q11.23 in fetus 1, and a 16.9 Mb duplication at Yp11.31q11.221 and a 8.1 Mb deletion at Yq11.222q11.23 in fetus 2. The results were confirmed by FISH. The parents of both fetuses were normal by chromosomal karyotyping and SNP-array., Conclusion: Combined use of various techniques can enable accurate prenatal diagnosis and genetic counseling.

Background: The purpose of the study was to investigate the potential of a radiomic signature developed in a general non-small-cell lung cancer (NSCLC) cohort for predicting the overall survival of anaplastic lymphoma kinase (ALK)-positive (ALK + ) patients with different treatment types., Materials and Methods: After test-retest in the Reference Image Database to Evaluate Therapy Response data set, 132 features (intraclass correlation coefficient > 0.9) were selected in the least absolute shrinkage and selection operator Cox regression model with a leave-one-out cross-validation. The NSCLC radiomics collection from The Cancer Imaging Archive was randomly divided into a training set (n = 254) and a validation set (n = 63) to develop a general radiomic signature for NSCLC. In our ALK + set, 35 patients received targeted therapy and 19 patients received nontargeted therapy. The developed signature was tested later in this ALK + set. Performance of the signature was evaluated with the concordance index (C-index) and stratification analysis., Results: The general signature had good performance (C-index > 0.6; log rank P < .05) in the NSCLC radiomics collection. It includes 5 features: Geom&#95;va&#95;ratio, W&#95;GLCM&#95;Std, W&#95;GLCM&#95;DV, W&#95;GLCM&#95;IM2, and W&#95;his&#95;mean. Its accuracy of predicting overall survival in the ALK + set achieved 0.649 (95% confidence interval [CI], 0.640-0.658). Nonetheless, impaired performance was observed in the targeted therapy group (C-index = 0.573; 95% CI, 0.556-0.589) whereas significantly improved performance was observed in the nontargeted therapy group (C-index = 0.832; 95% CI, 0.832-0.852). Stratification analysis also showed that the general signature could only identify high- and low-risk patients in the nontargeted therapy group (log rank P = .00028)., Conclusion: This preliminary study suggests that the applicability of a general signature to ALK + patients is limited. The general radiomic signature seems to be only applicable to ALK + patients who had received nontargeted therapy, which indicates that developing special radiomics signatures for patients treated with tyrosine kinase inhibitors might be necessary., (Copyright © 2019. Published by Elsevier Inc.)

Objective: To diagnose chromosomal abnormalities in amniotic fluid cells by combining karyotyping and single nucleotide polymorphism array (SNP-array) analysis, and to explore the application of SNP-array in routine clinical practice., Methods: Conventional G banding was used to karyotype a fetal amniotic fluid sample and the corresponding peripheral blood samples from the parents, followed by SNP-array analysis of the fetal genomic DNA from the amniotic fluid., Results: The karyotype of the amniocytes was 47, XX, +mar. The marker chromosome was further identified as psu idic (22) (q11.2) by SNP-array analysis, revealing tetraploidy of a 1.7 Mb fragment in 22q11.1-q11.2 interval that involves the critical region for Cat eye syndrome., Conclusion: A rare chromosomal abnormality was identified by combining conventional G banding and SNP-array. The high resolution SNP-array could provide more detailed information for determining the origin of chromosomal abnormalities.

Objective: Statins are widely used lipid-lowering drugs, which have pleiotropic effects, such as anti-inflammation, and vascular protection. In our study, we investigated the radioprotective potential of simvastatin (SIM) in a murine model of radiation-induced salivary gland dysfunction., Design: Ninety-six Institute of Cancer Research mice were randomly divided into four groups: solvent + sham irradiation (IR) (Group I), SIM + sham IR (Group II), IR + solvent (Group III), and IR + SIM (Group IV). SIM (10 mg/kg body weight, three times per week) was administered intraperitoneally 1 week prior to IR through to the end of the experiment. Saliva and submandibular gland tissues were obtained for biochemical, morphological (hematoxylin and eosin staining and Masson's trichrome), and Western blot analysis at 8 hours, 24 hours, and 4 weeks after head and neck IR., Results: IR caused a significant reduction of salivary secretion and amylase activity but elevation of malondialdehyde. SIM remitted the reduction of saliva secretion and restored salivary amylase activity. The protective benefits of SIM may be attributed to scavenging malondialdehyde, remitting collagen deposition, and reducing and delaying the elevation of transforming growth factor β1 expression induced by radiation., Conclusion: SIM may be clinically useful to alleviate side effects of radiotherapy on salivary gland.

Background: Radiofrequency ablation (RFA) is a minimally invasive thermal ablation technique. We conducted a meta-analysis based on eligible studies to assess the efficacy and safety of RFA for treating patients with breast cancer., Methods: A literature search was conducted in PubMed, Embase, and Web of Science databases. Eligible studies were clinical trials that assessed RFA in patients with breast cancer. The outcomes included complete ablation rate, recurrence rate, excellent or good cosmetic rates, and complication rate. A random-effects or fixed-effects model was used to pool the estimate, according to the heterogeneity among the included studies., Results: Fifteen studies, with a total of 404 patients, were included in this meta-analysis. Pooled results showed that 89% (95% confidence interval: 85%-93%) of patients achieved a complete ablation after RFA treatment and 96% of patients reported a good-to-excellent cosmetic result. Although the pooled result for recurrence rate was 0, several cases of relapse were observed at different follow-up times. No RFA-related complications were recorded, except for skin burn with an incidence of 4% (95% confidence interval: 1%-6%)., Conclusion: This meta-analysis showed that RFA can be a promising alternative option for treating breast cancer since it produces a higher complete ablation rate with a low complication rate. Further well-designed randomized controlled trials are needed to confirm the efficacy and safety of RFA for breast cancer.

Tumour self-seeding by circulating tumour cells (CTCs) enhances tumour progression and recurrence. Previously, we demonstrated that tumour self-seeding by CTCs occurs in osteosarcoma and revealed that interleukin-6 (IL-6) may promote CTC attraction. Here, we investigated the underlying mechanisms of IL-6 in tumour self-seeding by CTCs. IL-6 suppression inhibited in vitro cell proliferation, migration, and invasion. In addition, rhIL-6 activated the Janus-activated kinase/signal transducers and activators of transcription 3 (JAK/STAT3) and mitogen-activated protein kinase/extracellular-signal regulated kinase1/2 (MAPK/ERK1/2) pathways in vitro. Both pathways increased cell proliferation, but only the JAK/STAT3 pathway promoted migration. Suppressing IL-6 inhibited in vivo tumour growth and metastasis. IL-6 suppression or JAK/STAT3 pathway inhibition reduced CTC seeding in primary tumours. Collectively, IL-6 promotes tumour self-seeding by CTCs in a nude mouse model. This finding may provide a novel strategy for future therapeutic interventions to prevent osteosarcoma progression and recurrence.