2019 Vol. 46 No. 11
Early detection and accurate diagnosis for lung cancer is crucial to reduce disease-related mortality. Low-dose CT image is the main method of early lung cancer screening. This review introduces the importance of lung cancer screening and the feasibility of small biopsies of lung nodule in clinical practice, and focuses on how to obtain the sample from lung nodule efficiently with low cost and less side effect, and manage the specimen appropriately in order to achieve accurate diagnosis and following ancillary tests to guide clinical practice. We summarize the common pathological diagnosis and differential diagnosis in small biopsies, and the application of small lung biopsy in the pathological staging and molecular tests.
To investigate the role of oncolytic adenovirus RCA-TERT-Ad35 carrying human telomerase reverse transcriptase promoter in targeting breast cancer stem cells.
Breast cancer cell line MCF-7 propagated as spheroid bodies in growth factors-defined serum-free medium. At the same time, we constructed oncolytic adenovirus RCA-TERT-Ad35 carrying TERT promoter, and observed its killing effect on stem like-cancer cells by oncolytic assay, MTT assay and in vivo antitumor assay.
MCF-7 sphere cells displayed CSC properties, including chemo-resistance to paclitaxel and TERT gene overexpression, compared with parental cells. Oncolytic adenovirus RCA-TERT-Ad35 replicated in TERT positive cells and inhibited cell growth. In the xenograft models, RCA-TERT-Ad35 significantly inhibited tumour growth and improved survival status of mice, compared with RCA-Ad35.
Oncolytic adenovirus RCA-TERT-Ad35 could kill breast cancer stem cells with TERT overexpressing preferentially.
To investigate the influence and partial underlying mechanism of HOXB7 on the proliferation, migration and invasion abilities of hepatoma cells.
SMMC-7721 and HepG2 cell lines with high expression of HOXB7 mRNA were detected by real-time fluorescence quantitative PCR. To assess the silence efficiency of shRNA, the expression of HOXB7 at mRNA and protein levels were detected by real-time PCR and Western blot in the hepatoma cells transfected with shRNA. The cell proliferation, invasion and migration abilities of hepatoma cells were measured by CCK8 assay, Transwell assay and cell scratch test. The expression of Smad3 and p-Smad3 in SMMC-7721 cells were measured by Western blot.
The expression of HOXB7 at mRNA and protein levels were reduced significantly after shRNA transfection, and the proliferation, invasion and migration abilities of SMMC-7721 cells were reduced at the same time. And the expression of p-Smad3 protein in TGF-β pathway was decreased.
HOXB7 could enhance the proliferation, invasion and migration abilities of hepatoma cells, which may be related to promoting the phosphorylation of Smad3 in TGF-β pathway.
To investigate the influence of Glutathione S-transferase P-1 (GSTP-1) genetic variation on the prognosis of postoperative glioblastoma patients received temozolomide combined with radiotherapy regimens.
We included 175 glioblastoma patients received temozolomide combined with radiotherapy after surgical resection. Peripheral blood of the glioblastoma patients was collected for the genotyping of GSTP-1 genetic variation. Additionally, RNA was extracted from peripheral blood mononuclear cell specimens of patients prior to chemotherapy for GSTP-1 mRNA expression analysis. The correlation analysis was performed between the genetic variation and other characteristics.
The prevalence of Ile105Val among the study population were as follows: 119 cases (68.00%) of G/G genotype, 51 cases (29.14%) of G/A genotype, 5 cases (2.86%) of A/A genotype, minimum allele frequency of Ile105Val was 0.17; the distribution of three genotypes were in accordance with Hardy-Weinberg Equilibrium (P=0.868). The median progression-free survival (mPFS) of patients with G/A+A/A genotypes and GG genotype were 4.4 and 6.9 months, respectively (P=0.005); the median overall survival (mOS) of the two genotypes was 11.0 and 15.3 months, respectively (P < 0.001). G/A+A/A genotype was an independent factor for OS (OR=1.68, P=0.011). Additionally, the GSTP-1 mRNA expression in the patients with G/A+A/A genotypes were significantly higher than those in the G/G genotype patients (P < 0.001).
The prognosis of postoperative glioblastoma patients received temozolomide combined with radiotherapy regimens may be influenced by GSTP-1 Ile105Val genetic variation through mediating the mRNA expression of GSTP-1.
To investigate CircHIPK3 expression in esophageal squamous cell carcinoma (ESCC) tissues, so as to find a new way of diagnosis and targeted therapy.
qRT-PCR, CCK-8, Transwell and flow cytometry were performed to detect the difference of CircHIPK3 expression in tumor tissues and adjacent normal tissues, and its effect on cell proliferation, invasion, migration and apoptosis, respectively. Bioinformatics analysis was used to determine the possible pathway of CircHIPK3, and Western blot was used to verify its pathway-related functional proteins.
qRT-PCR results showed the abnormal expression of CircHIPK3 in 11 cases of cancer tissues and 7 cases of paracancerous tissues (P=0.027). The high expression of CircHIPK3 increased cell proliferation (P < 0.001), migration (P < 0.001) and invasion (P < 0.001) abilities. CircHIPK3 overexpression inhibited the apoptosis of EC9706 cells and tumor suppressor gene p53, activated intracellular Akt-Mdm2 signaling pathway, and increased the expression of p53-Akt-Mdm2 pathway protein accordingly. Ultimately, cancer cell proliferation, migration, invasion and cancer protein expression were enhanced.
CircHIPK3 promotes the proliferation, migration and invasion of human esophageal cancer cells, and inhibits the apoptosis by regulating the p53-Akt-Mdm2 signaling pathway. CircHIPK3 may be a potential target for the diagnosis and treatment of esophageal cancer.
To evaluate the relation between the expression of programmed cell death protein receptor-1 (PD-L1) and 18F-deoxyglucose (18F-FDG) uptake in lung adenocarcinoma.
We retrospectively analyzed the clinical data of 102 patients with pathologically-confirmed lung adenocarcinoma who underwent 18F-FDG PET/CT examinations before treatment and immunohistochemical examination after treatment to detect the expression of PD-L1. The relation between the maximum standard uptake of 18F-FDG(SUVmax) and the expression of PD-L1 was analyzed.
PD-L1 positive were detected in 50 patients (49%), the SUVmax was significantly higher in PD-L1 positive patients than that in the negative patients (6.59±5.03 vs. 2.89±4.65, P=0.0001). For the prediction of PD-L1 expression by SUVmax, the area under the ROC curve was 0.801, P=0.0001; when the cut off value was 1.70, the maximum value of Jordan index was 0.522.
18F-FDG uptake is associated with PD-L1 expression in primary lung adenocarcinoma, and the patients with high SUVmax are more likely to harbor PD-L1 expression.
To analyze the clinicopathological characteristics and prognosis of de novo metastatic breast cancer(DnMBC) patients, so as to provide some guidance for clinical diagnosis and treatment.
We retrospectively analyzed the clinicopathologic characteristics of 124 DnMBC patients treated in the Tianjin Medical University Cancer Hospital from January 2011 to December 2016. Univariate and multivariate analysis were carried out for the survival and prognosis. Subgroup analysis was performed to analyze the effect of surgical treatment on the prognosis of patients.
The median age at diagnosis of 124 patients was 53(26-77) years old. The median follow-up time was 29 months, the median progression-free survival PFS) and overall survival(OS) were 14(10.6-17.4) and 35(29.1-40.9) months, respectively. ER status and primary tumor stage were independent influence factors of PFS and OS(P < 0.05).
The clinicopathological characteristics of DnMBC patients are more invasive, with a higher risk of progression. Palliative surgical treatment may improve the prognosis of HR+/HER2- patients with large primary tumor. Therefore, individualized treatment as needed is particularly important.
To investigate the relation between 18F-FDG PET/CT metabolic parameters and the clinicopathological characteristics of colorectal cancer (CRC) patients.
We included 358 CRC patients who met the admission criteria. 18F-FDG PET/CT scans were performed before any treatment. Maximum standard uptake, average standard uptake, tumor metabolic volume (MTV) and total glycolysis (TLG) of the primary lesion of CRC were measured and calculated. The correlation of metabolic parameters with lesion location, pathological profile and TNM staging were investigated through Mann-Whitney U test and Kruskal-Wallis test.
The MTV and TLG values in the primary foci of colon cancer were the highest, followed by sigmoid cancer and the lowest in rectal cancer, with statistically significant differences between the groups (P < 0.001). SUVmax values of poorly/poorly-moderately differentiated colorectal cancer were higher than those of moderately/well differentiated colorectal cancer (P=0.028). MTV values of primary mucinous adenocarcinoma were higher than those of primary adenocarcinoma (P=0.023). MTV and TLG values were higher in T4 lesions than those in T2-3 lesions (P=0.0001, P=0.007); SUVmax and SUVmean values of sigmoid carcinoma with distant metastasis were lower than those without distant metastasis(P=0.015, P=0.011).
The metabolic parameters of CRC are correlated with the lesion location, pathological features and TNM staging, which could partly reflect the pathological characteristics and heterogeneity of CRC.
To systematically evaluate the prognostic and clinicopathological significance of PD-L1 expression in colorectal cancer(CRC) tissues by meta-analysis.
PubMed, Embase, Web of Science, Cochrane Library, CNKI and Wanfang database were used to search for the studies related to PD-L1 expression and the prognosis of CRC. The search time was until June 2018. The data of survival and clinicopathological features were extracted from eligible studies and analyzed by Stata SE12.0 software.
Eighteen studies with 5724 CRC patients were enrolled. PD-L1 expression in CRC tissues was associated with shorter overall survival (OS) (HR:1.40, 95%CI:1.02-1.93, P=0.039) and relapse-free survival (RFS) (HR:1.67, 95%CI:1.27-2.20, P=0.000), but not with disease-free survival (DFS)(P=0.933). And PD-L1 expression was significantly associated with tumor differentiation(P=0.016) and lymph node metastasis(P=0.028), but not with gender, tumor location, TNM staging, invasion depth, venous invasion, chemotherapy, MSI status or KRAS mutation. In addition, subgroup analysis showed that PD-L1 expression in tumor cells, not in tumor infiltrating immune cells (OS: P=0.991; RFS: P=0.210), was significantly associated with shorter OS(P=0.033) and RFS(P=0.001).
PD-L1 expression in CRC tissues is associated with poor prognosis. In addition, the prognostic significance of PD-L1 expression in tumor cells might be inconsistent with that in tumor-infiltrating immune cells.
Prostate specific membrane antigen(PSMA) is a glutamate carboxypeptidase Ⅱ secreted by the epithelial cells of prostate gland. PSMA is over-expressed in the cells of prostate cancer and metastases, and also positively expressed in the tumor-related neovascular endothelial cells. Therefore, more than twenty PSMA-targeted probes had been used for the diagnosis and therapy of prostate cancer. This article reviews the expression of PSMA in non-prostate cancer and the clinical application of PSMA-PET/CT specific probes in detecting non-prostate cancer, to expand the clinical application of novel PSMA-targeted PET probes in the diagnosis of tumors.
Intestinal microbiota are able to influence tumor initiation, progression, as well as therapy through local or systemic inflammation. Currently, the role of intestinal microbiota in cancer treatment is becoming increasingly significant, and investigators have found that intestinal microbiota affect the responsiveness of solid tumor to immune checkpoint inhibitor treatment, but the mechanisms responsible for inter-individual differences in immune responses are unclear. Some scholars believe that gut microbiota may play a potential regulatory role in it, such as Akkermansia muciniphila, lactobacillus and bifidobacterium can regulate the function of tumor cells and immune cells, and promote the production of a variety of cytokines, thereby improving the therapeutic effect of immune checkpoint inhibitors. Therefore, in this paper, the effects of gut microbiota on tumor cells and immune cells, as well as the current status of research on gut microbiota and immune checkpoint inhibitors are described.
Thyroid cancer is the most common malignant tumor in the endocrine system, accounting for about 1% of all malignant tumors. At present, it has become a hot research topic to study the pathogenesis of thyroid cancer at the level of gene DNA. However, the role of different RNA molecules such as RNA, microRNA, lncRNA and circRNA in the pathogenesis of thyroid cancer remains unclear yet. In addition, studies have shown that RNA molecules such as RNA, lncRNA and circRNA constitute a dynamic molecular network. At present, there are mainly two regulatory networks, including lncRNA-microRNA-RNA and circRNA-microNA-RNA, which regulate gene expression, participate in the proliferation, invasion, migration and apoptosis of tumor cells, and regulate the occurrence and progression of thyroid cancer. However, the specific mechanism of different types of RNA molecules in thyroid cancer remains unclear. In this review, we will focus on the relation between RNA molecules such as RNA, microRNAs, lncRNA, circRNA, ceRNA and thyroid cancer, in order to elucidate the molecular mechanism of RNA related to thyroid cancer, and provide new ideas for the diagnosis and treatment of thyroid cancer.
Cyclooxygenase 2 (COX2) can promote the synthesis of prostaglandins through metabolism, and is highly expressed in various tumor tissues including ovarian cancer. It can affect the occurrence and development of tumors in different ways by regulating downstream metabolites. It stimulates tumor cell proliferation and migration, promotes angiogenesis, inhibits apoptosis, plays an important role in tumor progression and may provide new ideas for tumor therapy.
The nuclear protein of the testis (NUT) midline carcinoma is a highly aggressive malignant epithelial neoplasm. The tumor is characterized by chromosome rearrangement of the NUT gene on 15q14, which results in the expression of NUT protein outside the testis. Pathologically, the tumor is an undifferentiated carcinoma with focal squamous differentiation. The NUT midline carcinoma can occur in multiple parts of the body, most of which happen in the midline structure of the head and neck and the mediastinum. Pulmonary cases are unusual and rarely recorded. However, the clinical course of primary lung NUT midline carcinoma is abnormally rapid and dangerous, and the diagnostic characteristics are still unclear. Therefore, this paper mainly discusses the clinical diagnosis and treatment of primary lung NUT midline carcinoma.