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BACKGROUND: Non-small cell lung cancer (NSCLC) is a malignant tumor with the highest mortality rate in our country. It has been found in many studies that microRNA-4521 (miR-4521) is abnormally expressed and plays a role in clear cell renal cell carcinoma and other cancers. OBJECTIVE: The purpose of this study was to explore the relationship between miR-4521 expression and clinical prognosis, as well as its influence on cell biological behavior. METHODS: The expression differences of miR-4521 in NSCLC tissues and cells were examined by qRT-PCR technology. Kaplan-Meier survival analysis and Cox regression analysis were used to analyze the clinical information and survival status of patients to explore the relationship. Using the vitro cell MTT assay, Transwell assay, and western-blot analysis, the effects of miR-4521 on cell proliferation, migration, and invasion were analyzed. RESULTS: The expression of miR-4521 in NSCLC tissues and cells was significantly downregulated. miR-4521 can be used as an independent prognostic factor. The survival rate of the miR-4521 low expression group was lower, which was significantly related to poor prognosis. In addition, the low expression of miR-4521 significantly promoted cell proliferation, migration, and invasion with highly expressed related protein levels. FOXM1 might be a direct target of miR-4521. CONCLUSION: The results of this study showed that the low expression of miR-4521 indicated the poor prognosis of NSCLC and promoted cell proliferation, migration, and invasion by targeting FOXM1.

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MicroRNAs exert crucial effects in the drug resistance. The purpose of this research was to investigate the miR-25-3p effects on DDP resistance in NSCLC. We used RT-qPCR to evaluate the expression of miR-25-3p. Cell growth was determined using MTS assay. Cellular bio-activity was analyzed via Colony formation, Annexin V/PI, and Transwell assay. Luciferase reporter assay was used to determine miR-25-3p and PTEN binding. Western blot was used to determine PTEN, PI3K, p-AKT/AKT expression. In-vivo study was used to determine the effects of miR-25-3p on the tumor growth. Expression of miR-25-3p is increased in NSCLC cisplatin resistant A549 and H1299 cells. Furthermore, miR-25-3p mimic enhanced drug resistance, and accelerated cell invasion and metastasis. Moreover, miR-25-3p mimic resulted in the activation of PTEN/PI3K/AKT pathway. However, miR-25-3p inhibitors exhibited the opposite trend. We further identified PTEN as a potential target of miR-25-3p. PTEN knockout promoted cisplatin resistance, while PTEN mimic displayed opposite effects. Interestingly, miR-25-3p further boosted cisplatin resistance cells in vivo, and miR-25-3p inhibitors reduced the in-vivo tumor volume. MiR-25-3p/PTEN/PI3K/AKT axis might accelerate DDP tolerance in NSCLC, which may serve as a potential target for chemotherapy resistance in NSCLC.

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BACKGROUND: Immune checkpoint inhibitors (ICIs) have good efficacy on most advanced tumors, which brings new hope to patients with advanced tumors. However, the immune system activated by ICIs may attack human normal tissues and organs, resulting in corresponding immunotoxicity, such as checkpoint inhibitor pneumonitis. This article carried out a meta-analysis on the incidence and risk of programmed cell death protein 1 (PD-1) and programmed cell death protein ligand 1 (PD-L1) inhibitor-associated pneumonia in advanced tumors patients. METHODS: The computer retrieval of PubMed, Cochrane Library, EMbase and CNKI was performed, and the studies on the occurrence rate of PD-1/PD-L1 inhibitor-associated pneumonia in terminal cancer patients were collected, with the retrieval time limit of January 2000 to January 2020. Statistical analysis was conducted by using Revman 5.3 and R 3.6.2 software to compare the occurrence rate of pneumonia under different circumstances. RESULTS: 15 studies were included, involving 8,642 patients, of which those with PD-1/PD-L1 inhibitor were treatment group, and those with chemotherapy were control group. The odds radio of all grades of immune pneumonia was 6.63, and that of high grade was 4.87. The occurrence rate of all grades of pneumonia in the ICI group with non-small cell lung cancer (NSCLC) was 1.658 times than other tumors, and that of high grade was 2.299 times. The occurrence rate of all grades of pneumonia in second-line or more treatment with ICI was 0.489 times than that in first-line, and that of high grade was 0.449 times than that in first-line or more treatment with ICI. CONCLUSIONS: Compared with chemotherapy, the risk of immune-associated pneumonia is higher in PD-1 and PD-L1 inhibitors, and its occurrence risk is high in the ICI group with NSCLC and the first-line treatment with ICI. This paper provides guidance for clinic treatment of terminal cancers and prevention of complications.

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Gold nanoparticles (AuNPs) as the most excellent anticancer theranostic nanoparticles were synthesized through efficient, simple, and green synthesis method using Marsdenia tenacissima plant extracts and they are widely characterized by several techniques including ultraviolet-visible (UV) spectroscopy, atomic force microscopy (AFM), energy-dispersive X-ray spectrometers (EDS), transmission electron microscopy (TEM), and Fourier transform infrared (FT-IR) spectroscopy. From the AuNPs synthesized by M. tenacissima extracts, it was discovered that particle size around 50 nm, which is admirable nano dimension, was achieved by plant-mediated synthesis. After characterization of these nanoparticles, they performed as in vitro anticancer activity against lung cancer cell lines (A549). MTT assay revealed that AuNPs produce toxicity based on the dose-dependent A549 cells growth inhibition. AuNPs treatment activates caspase expression and down-regulates the anti-apoptotic protein expression in A549 cells. Our results point out that the AuNPs from M. tenacissima extract are apposite stabilizing agents, which serve as an effective anticancer agent against lung cancer cell lines (A549).

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Nonsmall cell lung cancer (NSCLC) is one of the leading causes of cancer-related death worldwide. Kinesin family member 2C (KIF2C), a modulator in microtubule depolymerization, bipolar spindle formation, and chromosome segregation, has been reported to take roles in cancer biology, but its role in NSCLC remains unclear. This study was intended to investigate the expression and function of KIF2C in NSCLC. Our results demonstrated that KIF2C was up-regulated in NSCLC tissues and cell lines. The high expression of KIF2C in NSCLC tissues was significantly correlated with higher T stage (0.0078), worse differentiation status (0.0049), and lymph node metastasis (P < .0001). We also proved that the high expression level of KIF2C predicted worse prognosis of the patients. After knockdown of KIF2C, the proliferation and metastasis of NSCLC cells were inhibited. Luciferase reporter assay suggested that KIF2C was a target gene of miR-325-3p, which was reported to be a tumour suppressor in NSCLC. In conclusion, this study proved an oncogenic role of KIF2C in NSCLC and partly clarified the mechanism of its high expression. Our findings provided a useful insight into the mechanism of NSCLC progression and offered clues to novel therapy strategies.

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BACKGROUND: Aspirin, an anti-inflammatory drug, has been widely investigated in the treatment of many cancer types, including colorectal, ovarian, breast, and prostate cancers. MicroRNAs (miRNAs) are the most well studied noncoding RNAs in cancers. In the current study, we were interested in defining the function of aspirin in lung cancer treatment and the related noncoding RNAs involved in this process. METHODS: The function of aspirin in lung cancer growth was evaluated by cell viability and colony formation assays. Screening of miRNAs affected by aspirin was performed through quantitative real-time PCR. Prediction of miR-98 targeting WNT1 was performed using online bioinformatics software and was further confirmed by luciferase reporter gene analysis. The levels of miR-98 and WNT1 were tested through immunoblotting and quantitative real-time PCR analysis in lung cancer cells under aspirin treatment. RESULTS: Cell viability was sharply suppressed in lung cancer cells with an increasing dose of aspirin. Aspirin markedly weakened the malignant colony formation ability of lung cancer cells. One out of six tumor suppressor miRNAs could be obviously regulated by aspirin in lung cancer cells. The inhibition of miR-98 on the luciferase activities of wild-type 3' untranslated region vectors of WNT1 was clearly revealed in lung cancer cells. Meanwhile, the inhibitor of miR-98 increased the luciferase activities of wild-type 3' untranslated region vectors of WNT1. After treatment with aspirin the expression of miR-98 was induced and then its target gene, WNT1, was depressed in the cells. CONCLUSION: Aspirin targets the miR-98/WNT1 axis to ameliorate lung cancer development.

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Langerhans cell histiocytosis (LCH) is a proliferative disease of histiocyte-like cells, with a wide range of clinical presentations that vary from a solitary lesion to more severe multifocal or disseminated lesions. The disease can affect any age group; however, the peak incidence rate is in infants aged between 1 and 3 years-old. Diagnosis of LCH should be based on the synthetical analysis of clinical presentations, in addition to features of imaging and histopathology. Although certain cases regress spontaneously, other patients require systemic chemotherapy together with the administration of steroids. The present study reports the case of an infant with LDH with multisystem involvement, including that of the bone, skin, orbit, spleen and lungs. The patient received chemotherapy and obtained rapid improvement in the involved systems. A total of 2.5 years after completion of the therapy, the patient still remains in follow-up and no evidence of active disease has been noted.

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PURPOSE: This study aimed to explore the diagnostic performance of single photon emission computed tomography / computerized tomography (SPECT/CT) using a new radiotracer 99mTc-RGD-BBN for breast malignant tumor compared with 99mTc-3P4-RGD2. METHODS: 6 female patients with breast malignant tumors diagnosed by fine needle aspiration cytology biopsy (FNAB) who were scheduled to undergo surgery were included in the study. 99mTc-3P4-RGD2 and 99mTc-RGD-BBN were performed with single photon emission computed tomography (SPECT) at 1 hour after intravenous injection of 299 ± 30 MBq and 293 ± 32 MBq of radiotracers respectively at separate day. The results were evaluated by the Tumor to non-Tumor ratios (T/NT). 99mTc-RGD-BBN and 99mTc-3P4-RGD2 SPECT/CT images were interpreted independently by 3 experienced nuclear medicine physicians using a 3-point scale system. All of the samples were analyzed immunohistochemically to evaluate the integrin αvß3 and gastrin-releasing peptide receptor (GRPR) expression. The safety, biodistribution and radiation dosimetry of 99mTc-RGD-BBN were also evaluated in the healthy volunteers. RESULTS: No serious adverse events were reported in any of the patients during the study. The effective radiation dose entirely conformed to the relevant standards. A total of 6 palpable malignant lesions were detected using 99mTc-RGD-BBN SPECT/CT with clear uptake. All malignant lesions were also detected using 99mTc-3P4-RGD2 SPECT/CT. The results showed that five malignant lesions were with clear uptake and the other one with barely an uptake. 4 malignant cases were found with both αvß3 and GRPR expression, 1 case with only GRPR positive expression (integrin αvß3 negative) and 1 case with only integrin αvß3 positive expression (GRPR negative). CONCLUSION: 99mTc-RGD-BBN is a safe agent for detecting breast cancer. 99mTc-RGD-BBN may have the potential to make up for the deficiency of 99mTc-3P4-RGD2 in the detection of breast cancer with only GRPR positive expression (integrin αvß3 negative). The preliminary application of 99mTc-RGD-BBN has demonstrated its powerful potential in breast cancer diagnosis and therapy.

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PURPOSE: The aim of this study was to evaluate the diagnostic value of FNA-Tg for detecting lymph node metastases in patients with a history of differentiated thyroid cancer (DTC). MATERIALS AND METHODS: A total of 58 patients with DTC diagnosis and evidence of single or multiple suspicious cervical lymph nodes were assessed. All underwent total or near-total thyroidectomy with (35 cases) or without (23 cases) radioiodine (RAI) ablation, followed by thyroid stimulating hormone (TSH) suppression therapy. A total of 68 lymph nodes were examined by ultrasound-guided fine needle aspiration (US-FNA) for both cytological examination and FNA-Tg measurement. Serum Tg and anti-thyroglobulin antibody (TgAb) levels were also measured. Diagnostic performance including sensitivity, specificity, accuracy, positive (PPV) and negative predictive value (NPV) of FNAC and FNA-Tg were calculated and compared. The Spearman's rank correlation coefficient was used to estimate the relationship between FNA-Tg and serum TgAb. RESULTS: The FNA-Tg levels were significantly higher with DTC metastatic lymph nodes (median 927.7 ng/mL, interquartile range 602.9 ng/mL) than non-metastatic lymph nodes (median 0.1 ng/mL, interquartile range 0.4 ng/mL) (p<0.01). Considering 1.0 ng/mL as a threshold value for FNA-Tg, the sensitivity, specificity, accuracy, PPV and NPV of FNA-Tg were 95.7%, 95.5%, 95.6%, 97.8% and 91.3%, respectively. The sensitivity and accuracy of the combination of FNAC and FNA-Tg were significantly higher than that of FNAC alone (p<0.05). The diagnostic performance of FNA-Tg was not significantly different between cases with or without RAI ablation, and the serum TgAb levels did not interfere with FNA-Tg measurements. CONCLUSIONS: Measurement of FNA-Tg is useful. The combination of FNAC and FNA-Tg is more sensitive and accurate for detecting lymph node metastases in patients with a history of DTC than FNAC alone. Serum TgAbs appear to be irrelevant for measurement of FNA-Tg.

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VSV-G-pseudotyped lentiviral vectors expressing p16(INK4a) or p14(ARF) were used to infect at high-efficiency Philadelphia chromosome (Ph)-positive leukemia cell lines lacking endogenous transcripts. Restoration of p16(INK4a) accumulated cells in the G0/G1 phase of cell cycle and restoration of p14(ARF) induced their apoptosis, followed by significant growth inhibition. Transduction of primary blast cells from chronic myeloid leukemia in blast crisis (CML-BC) and Ph-positive acute lymphoblastic leukemia (ALL) with p16(INK4a) or p14(ARF) virus also resulted in cell growth inhibition and/or apoptosis with a patient-to-patient variation, whereas clonal growth and differentiation of cord blood progenitor cells were not affected by enforced expression of INK4a/ARF. Furthermore, upon viral transduction at low multiplicity of infection, INK4a/ARF potentiated the effect of imatinib mesylate on Ph-positive leukemia cell lines in an additive but not synergistic manner. These results suggest that INK4a/ARF protein-mimetic agents may be promising options for Ph-positive leukemias in combination with imatinib mesylate.

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OBJECTIVE: To investigate the effect of up-regulated expression of tumor suppressor gene p14(ARF) on apoptosis of chronic myeloid leukemia (CML) cells and its interaction with imatinib. METHODS: Tumor suppressor gene p14(ARF) was transduced into K562 (K562-p14(ARF)) and 4 blast crisis primary CML cells (CML-BC 1-4) using vesicular stomatitis virus glycoprotein (VSV-G) pseudotyped lentiviral vector with cells transduced by empty vector as control. Fluorescence microscopy and flow cytometry were applied to measure transduction efficiency, and Western blotting assay was used to detect p14(ARF) protein of K562 cells. WST-8 method was used to determine cell growth inhibition rate of K562 cells transduced by the target gene under different concentrations of imatinib (0, 0.015, 0.062, 0.125, 0.25, 0.5, 1.0, 2.0 µmol/L). Cell apoptosis and leukemic cellular colony-forming ability were detected by Annexin V-FITC/PI dyeing using flow cytometry (FCM) and semi-solid culture method respectively. RESULTS: Fluorescence microscopy and FCM showed that transduction efficiency (GFP positive cells) of K562-p14(ARF), K562-VSV and CML-BC1 cells were close to 100%, and CML-BC 2-4 cells were 80% to 90% on average. Results of Western blotting showed that the levels of ARF protein expression of K562 cells transduced by p14(ARF) were significantly higher than of untransduced cells; the apoptosis rate of K562-p14(ARF) was 20%; the mean apoptosis rate of 4 primary leukemic cells transduced by the p14(ARF) [(71.1±22.4)%] was significantly higher than of control group [(12.4±6.2)%] (P<0.05). Imatinib significantly inhibited the proliferation of K562-p14(ARF) cells in a dose-dependent manner. The mean leukemic cellular colony-forming unit of 4 primary leukemic cells transduced by the p14(ARF) (41.5±13.2) was significantly lower than of the control group (88.5±7.9) (P<0.05). CONCLUSION: Increased p14(ARF) gene expression could induce apoptosis of CML cells; Moreover, it could enhance inhibitory effect on cell proliferation when combined with imatinib.

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Dihydropyrimidine dehydrogenase (DPD) activity could be affected by single nucleotide polymorphisms (SNPs), resulting in either no effect, partial or complete loss of DPD activity. To evaluate if SNPs of DPD can be used to predict 5-FU toxicity, we evaluated five SNPs of DPD (14G1A, G1156T, G2194A, T85C and T464A) by TaqMan real time PCR in 60 colorectal cancer patients. Clinical data demonstrated that there was higher correlation between DPD activity and toxic effects of 5-FU (p<0.05). Six patients were positive for G2194A detection, which were all heterozygous. Two patients had lower DPD activities (< 3) with higher toxic effects (≥ stage III) while one patient was also positive for T85C detection. Ten patients were positive for T85C detection. Two patients were homozygous with lower DPD activities and higher toxic effects. Two patients were positive for the T464A detection, which were heterozygous with lower DPD activity and higher toxic effects and also positive for T85C detection. These data clearly indicated that the T464A and homozygous of the T85C are stronger biomarkers to predict the 5-FU toxicity. Our study significantly indicated that the detection for G2194A, T85C and T464A could predict ~13% of 5-FU severe toxic side effects.

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