2020 Vol. 47 No. 9
To investigate the effect of HK2 on the proliferation and migration of cervical cancer cell lines HeLa and related mechanism.
HeLa cells with stable HK2 expression were screened. Cell proliferation, viability and cell cycle were detected by cell growth curves, MTT assay and flow cytometry, respectively. Wound-healing assay and Transwell cell invasion assay were used to detect the effect of HK2 on the migration and invasion potential of HeLa cells. The expression of β-catenin, Cyclin D1, MMP7 and Slug were detected by Western blot and immunocytochemistry. The activity of Wnt/β-catenin signalling pathway was detected by TOP/FOP assay. Cell growth, migration and invasion were detected in HeLa-HK2 cells treated with Wnt/β-catenin inhibitor (XAV-939).
HeLa cells lines that stably expressing HK2 were successfully constructed. HK2 overexpression promoted the proliferation, migration, invasion and viability of HeLa cells, accelerated the transition of cell cycle from G0/G1 phase to S phase, enhanced the activity of Wnt/β-catenin signalling pathway and up-regulated the protein expression of downstream factors, such as Cyclin D1, MMP7 and Slug. The promoted growth, migration and invasion of HeLa-HK2 cells were inhibited by Wnt/β-catenin inhibitor XAV-939.
HK2 could promote the proliferation, migration and invasion of HeLa cells by up-regulating the expression of Cyclin D1, MMP7 and Slug via Wnt/β-catenin signaling pathway.
To investigate the effects of DCLK1 on the proliferation, migration and invasion of glioma cells and their mechanisms.
The mRNA and protein expression of DCLK1 in glioma tissues and glioma cell lines U87 and A172 were detected by RT-qPCR, immunohistochemical staining and Western blot. sh-DCLK1 and the corresponding negative control (sh-Con) were transfected into glioma cell lines U87 and A172 by Lipofectamine 2000 to silence DCLK1 expression. The effects of DCLK1 knockdown on the proliferation, migration and invasion of glioma cells were analyzed by MTT assay and Transwell assay. The effects of DCLK1 knockdown on the expression of TGF-β/Smads signaling pathway-related proteins TGF-β1, p-Smad2 and p-Smad7 in glioma cells were detected by Western blot. U87 cells transfected with sh-DCLK1 or sh-Con were injected into the subcutaneous neck of BALB/c nude mice, the tumor volume and weight were measured.
Compared with normal adjacent tissues and normal glial cells, the mRNA and protein expression levels of DCLK1 were significantly increased in glioma tissues and cells (P < 0.001). Compared with sh-Con group, the proliferation, migration and invasion abilities, and the expressions of TGF-β1, p-Smad2 and p-Smad7 proteins of glioma cells in sh-DCLK1 group were significantly decreased (P < 0.01; P < 0.001); in addition, tumor volume and weight of sh-DCLK1 group were significantly reduced in vivo (P < 0.001).
DCLK1 knockdown could inhibit the proliferation, migration and invasion of glioma cells, which may be related to the inhibition of TGF-β/Smads signal activity.
To investigate the differential expression levels of Pim1 and Notch1 in breast tissues and their clinical and prognostic significance.
qRT-PCR, immunohistochemistry and databases were used to detect the mRNA and protein levels of Pim1 and Notch1 genes in adjacent normal breast tissues (ANBT), usual ductal hyperplasia (UDH), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). The relation between Pim1/Notch1 expression and the clinicopathological parameters of breast cancer patients was analyzed. The prognostic value of Pim1 and Notch1 protein in breast cancer was evaluated by Kaplan-Meier Plotter databases.
The expression of Pim1 mRNA in breast cancer tissues was increased. The expression of Pim1 protein in the breast cancer tissues was significantly decreased. The expression of Pim1 mRNA was markedly associated with lymph node metastasis and advanced TNM stage. The expression of Pim1 protein was significantly decreased in the patients with lymph node metastasis or histological grade 3. The patients with low expression of Pim1 had a shorter relapse-free survival (P=0.000). The expression of Notch1 mRNA and protein in breast cancer were higher than those in normal breast tissues. Notch1 mRNA was closely related to the lymph node metastasis, high grade and advanced stage. Notch1 protein expression in lymph node metastasis group had markedly increased. The overall survival time of patients with high level of Notch1 was shorter (P=0.025). The protein levels of Pim1 and Notch1 were negatively correlated in breast cancer tissues (r=-0.385, P=0.001).
Low Pim1 expression and high Notch1 expression may promote the carcinogenesis and progression of breast cancer and may be risk factors for poor prognosis. Pim1 and Notch1 may be used as potential biomarkers for clinical evaluation of breast cancer patients.
To establish a simple and convenient early warning scoring system by retrospectively analyzing the high risk factors of early intracranial hemorrhage (ICH) in acute non-promyelocytic leukemia (ANPL) patients.
We enrolled 1281 adult patients with ANPL (model group) and 378 adult patients (validation group), all patients were followed up for 12 months respectively. We used the data of model group to summarize the relevant factors of ICH occurrence and established risk scoring system. The risk scoring system was validated by the data of the validation group (each patient in the validation group was scored by the scoring system and divided into high, medium and low risks groups). The prediction efficiency of the scoring system was evaluated by ROC curves.
Univariate and multivariate analyses showed that the independent risk factors of early ICH in ANPL were WBC≥30.00×109/L, Fibrinogen(FIB) < 2.92 g/L and PT≥12.91 s. A new early warning scoring system was established based on the weights of the above three factors. The area under ROC curve of the scoring system was 0.774 (95%CI: 0.688-0.859). The area under the ROC curve of the scoring system was 0.715 (95%CI: 0.559-0.872) confirmed by the validation group.
The new early warning scoring system could predict the occurrence of early ICH in ANPL and guide the medical staff to identify potential critical patients as early as possible.
To investigate the early and accurate prediction of recurrence and metastasis of stage ⅢB gastric cancer by CEA, PAK5 combined with CTC.
ELISA and multiple RNA/DNA in situ analysis were used to detect CEA, PAK5, CTC and imaging CT at the same time in 150 patients with stage ⅢB gastric cancer. Patients were divided into CEA progressive increase group (group A, n=50), CEA irregular increase group (group B, n=50) and control group (n=50).
CEA: the median time of biological progress (T2) in the group A was 13(3-24) months, and that of the group B was 22(4-32) months; 39(78%) cases in group A had image progression and the median occurrence time of image progression (T3) was 6.2(5-8) months, and those were 12(24%) cases and 10.6(4-15) months in group B. The medium expression range of PAK5 at T2 was 13.6%-83% and the high expression range of PAK5 at T3 was 37.8%-100% in 51 patients with image progression. CTC test showed that the ratio of mixed type + interstitial type/total cell number > 30% could predict the biological progress time, and the ratio of mixed type + interstitial type/total single cell number > 50% and (or) interstitial-type cell number ≥1 could predict the imaging CT progression. In 39 patients with image progression in group A, the consistency of positive expression of CEA, PAK5 and CTC was 82% at biological progression time and 94% at image CT progression time.
Combined detection of CEA, PAK5 and CTC could early predict the recurrence and metastasis of stage Ⅲ B gastric cancer.
To analyze the expression of CEA, CA199 and CA724 in patients with urachal carcinoma, and to explore their correlation with disease diagnosis, staging, progression and treatment response.
Twelve urachal carcinoma patients with related tumor markers were selected as the research object and further divided into distant metastasis group (n=4) and non-metastasis group (n=8). We selected 40 patients with urothelial carcinoma of the bladder and 40 healthy people as the control groups. SPSS 23.0 and MedCalc 19 were used for data analysis.
Twelve patients with urachal carcinoma were all adenocarcinomas. The expression of CEA in the urachal carcinoma group was significantly higher than that in urothelial carcinoma group and healthy control group (P=0.01). The positive rate of CA724 in the distant metastasis group was significantly higher than that in the non-metastasis group (75% vs. 0, P=0.018). In single test, CEA diagnosed urachal carcinoma with the highest AUC of 0.750 and 95%CI of 0.584 to 0.916. The AUC detected by the combination of both CEA and CA724 or three tumor markers were all larger than the AUC detected by single test, but without statistical significance (0.817 vs. 0.805, P=0.8509).
The expression of CEA in patients with urachal carcinoma is significantly increased. CA724 can be used as a predictor of distant metastasis of urachal carcinoma, and the combination detection of CA724 and CEA can provide an effective reference for the clinical diagnosis of urachal cancer.
To compare the diagnostic accuracy, sensitivity, specificity and complications between ultrasound-guided fine needle aspiration cytology and core needle biopsy histology in thyroid nodules.
A total of 98 thyroid nodules of 95 patients suspected as malignancy by ultrasonography were collected and examined by ultrasonic-guided fine needle aspiration cytology and core needle biopsy histology, which were confirmed by surgical treatment and postoperative routine pathological examination. The diagnostic accuracy, sensitivity, specificity and complications of the two methods were compared. The correlation of nodules diameter with the adequacy and diagnostic accuracy was analyzed.
The adequacy of fine needle aspiration and core needle biopsy were 89.8% and 96.9%. The accuracy, sensitivity, specificity of fine needle aspiration cytology and core needle biopsy histology in diagnosing thyroid nodules were 86.4%, 82.6%, 90.5% and 90.5%, 93.2%, 86.1%, respectively. The complication rate of core needle biopsy was higher than that of fine needle aspiration (14.3% vs. 2.0%, P < 0.05). When the diameter of the thyroid nodules was ≥1.0 cm, the diagnostic accuracy of the core needle biopsy was higher than that of the fine needle aspiration (P < 0.05).
Fine needle aspiration cytology and core needle biopsy histology are complementary in the diagnosis of thyroid nodules.
The spread of COVID-19 has affected the routine medical care of cancer patients. Due to the low immunity, tumor patients are vulnerable to infection and the prognosis is poor. Especially the patients undergoing radiotherapy need to travel between the ward and the radiotherapy room every day, which increases the chance of infection and they should be the focus of epidemic prevention object. As an oncology hospital, our hospital achieved prevention, control and admission during the outbreak. Under the guidance of infection and control office of the hospital, hospital-level and department-level prevention and control teams were established to adopt a series of prevention and control management measures, including the combination of online training and offline assessment, the establishment of a unified and standardized space division for the seven wards of the radiotherapy center, standardization of patient admission, semi-enclosed management of wards, optimization of radiotherapy process and closed-loop management. In Wuhan, where the epidemic outbreak was the most severe in China, the radiotherapy center of our hospital achieved zero infection of patients and staff within two months of clinical reception, effectively prevented new coronary pneumonia, and ensured the safety and normal treatment of the patients undergoing radiotherapy.
To analyze the screening results of colorectal cancer in urban area of Hebei Province from 2018 to 2019.
According to the screening process of early diagnosis and treatment of colorectal cancer in urban area of Hebei Province, we enrolled local residents aged 40-74 years from the selected communities in Shijiazhuang and Tangshan City. The high-risk populations were evaluated by national unified evaluation model after the questionnaires. The early colorectal lesions were detected by colonoscopy, and further confirmed pathologically if necessary.
From 2018 to 2019, a total of 37849 urban residents were involved in the risk assessment of colorectal cancer, and 6938 (18.33%) cases were evaluated as the high risk population of colorectal cancer, among which 1230 cases received colonoscopy examination and 37.8%(465/1230) received pathological examination. The age of the residents who received pathological diagnosis was mainly distributed in the age group of 50-64 years. A total of 6 (0.49%) patients with colorectal cancer were diagnosed, including 4 (0.33%) cases of colon cancer and 2 (0.16%) cases of rectum cancer. The detection rates of colorectal precancerous lesion, non-advanced adenoma/polyp and inflammatory intestinal disease were 15.45%, 20.22% and 13.66%, respectively.
Colonoscopy screening could effectively detect colorectal cancer and precancerous lesions, and achieve early detection, early diagnosis and early intervention of colorectal cancer.
To understand the current prevalence of cervical and breast cancers and their influencing factors in women aged 30-64 years in Xiangyang city.
A questionnaire survey was conducted to collect information of demographic characteristics, past medical history, family tumor history, menstrual and reproductive history and the prevalence of common gynecological diseases among married women aged 30-64 years in Xiangyang. Cervical cancer screening was performed primarily by high-risk HPV typing detection, followed by Thinprep cytologic test, colposcopy and pathological examination. Breast cancer screening was performed through visual inspection, palpation and color Doppler ultrasonography, followed by X-ray mammography and pathological examination.
A total of 318067 women participated in the screening in 2017, among which 91143(28.66%) cases had non-HPV genital tract infection and 91143(28.66%) cases had benign uterine disease; 826(259.69/105) cases had cervical precancerous lesions, including 385 cases of CINⅡ, 425 cases of CINⅢ and 16 cases of adenocarcinoma in situ; 79(24.84/105) cases were cervical cancer, including 18 cases of microinvasive carcinoma and 61 cases of invasive cancer; 44097(13.86%) cases had benign breast disease and 80(25.27/105) cases were breast cancer. Multivariate regression analysis indicated that age, family history of cervical cancer, multiple pregnancies, delayed menopause and reproductive tract infection may be risk factors for cervical cancer, while age, high level of education and family history may be risk factors for breast cancer.
The incidence of cervical and breast cancers in Xiangyang city is at a moderate level. Regular screening and active control of high-risk factors are of great significance to the prevention and treatment of cervical and breast cancers.
With the rapid development of high-throughput sequencing technology represented by the second generation sequencing technology, whole-genome detection technology has been able to detect data from multiple levels, such as genome, transcriptome and epigenome. Biomass is a complicated regulatory system, involving many levels of complicated regulatory mechanism. Considering the limitation of single omics data analysis in exploring pathogenic factors, integrative multi-omics analysis with linear or nonlinear relationship can provide a new method for the study of the disease. Integrative analysis of multiple omics has widely used in various diseases, including lung cancer, and DNA or gene molecular level is particularly important as a basis for intermolecular correlations and complex networks. Hence, this paper briefly describes integrative analysis of genome, transcriptome and epigenome in lung cancer.
For lacking of HR and HER-2, triple-negative breast cancer (TNBC) is one type of breast cancers with the worst prognosis. The current treatments are mainly chemotherapy, radiotherapy and surgery, but the results are still not satisfactory, which leads us to explore the new molecular markers or new therapeutic targets.. LncRNA and its related epigenetic modifications may provide new targets for the treatment of TNBC. This paper reviews the existing studies on LncRNA and other epigenetic changes as TNBC biomarkers and their potential use as TNBC therapeutic targets.
N6-methyladenosine (m6A) modification is the most common, abundant and conservative posttranscriptional modification. More and more evidence suggest that via various mechanisms, it has a certain impact on tumors, such as liver cancer, gastric cancer, lung cancer, bladder cancer and melanoma. It has been found that YTHDF1, as a kind of m6A-modification binding protein, plays an important role in tumor transcription, translation, protein synthesis, immune escape, EMT, chemotherapy resistance and so on. It is expected to find new methods for the diagnosis and treatment of cancer by revealing the mechanism of YTHDF1. This article reviews the research progress in this field.
Immunity checkpoint inhibitors (ICI) can enhance the original anti-tumor immune response by restoring the identification and killing of T cells to tumor cells. ICI have been approved for melanoma, NSCLC and renal cells carcinoma, etc. However, many patients do not respond to immunotherapy due to immunosuppression, which is mediated partly by myeloid-derived suppressor cells (MDSCs). This heterogeneous population of immature bone marrow cells strongly inhibit the anti-tumor activity of T cells and NK cells and stimulate regulatory T cells (Treg), leading to tumor progression. MDSCs can promote the patient's resistance to immune checkpoint inhibition. Increasing evidence show that the proportion of MDSCs in cancer patients and immunosuppressive function can be used as the predictors of therapeutic response. This review highlights the role of MDSCs in the suppression of immune checkpoints and analyzes the combined strategy of MDSCs and ICI, to improve the therapeutic efficacy of cancer patients.
