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2019  Vol. 46  No. 12

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Expert Forum
Hot Issues in Internal Medicine Treatment for HER2 Positive Early Breast Cancer Reflected in the 2019 St. Gallen International Breast Cancer Conference
Abstract:

The 16th St. Gallen International Breast Cancer Conference was held in Vienna, Austria from March 20, 2019 to March 23, 2019. The biennial St. Gallen International Breast Cancer Conference and Expert Consensus present an inventory and summary of the progress of breast cancer treatment over the past two years. The theme of this conference is "assessing the clinical benefits of early breast cancer (EBC) treatment". The meeting mainly focused on the hot topics of surgical treatment, medical treatment and radiotherapy for early breast cancer, as well as controversial topics, and finally formed an expert consensus. The paper presents an overview of the hot issues (HER2 positive early breast cancer) reflected in this conference.

Basic Research
Effects of Sanguinarine on Invasion, Migration and Wnt/β-catenin Signaling Pathway of Lung Adenocarcinoma Cells
Abstract:
Objective 

To investigate the effect of sanguinarine on the invasion and migration of lung adenocarcinoma cells and its preliminary molecular mechanism.

Methods 

MTT assay was used to observe the proliferative capacity of A549 and H1975 cells. Wound healing and Transwell assays were performed to determine the invasion and migration abilities of A549 and H1975 cells, respectively. RT-qPCR and Western blot were used to detect the mRNA and protein expression of core genes in Wnt/β-catenin signaling pathway.

Results 

Compared with the control group, sanguinarine(1-10μmol/L) could inhibit the activity of human lung adenocarcinoma cells in a concentration- and time- dependent manner (P < 0.05); the migration and invasion abilities of A549 and H1975 cells were significantly weakened by 1μmol/L sanguinarine after 48 h (P < 0.01); sanguinarine (1, 2.5, 5μmol/L) could significantly down-regulate the protein expression of β-catenin, phosphorylated GSK3β and DVL2 in Wnt/β-catenin pathway, thereby inhibiting the mRNA levels of TCF/LEF and CyclinD1, in a concentration-dependent manner (P < 0.05).

Conclusion 

Sanguinarine may inhibit the migration and invasion of human lung adenocarcinoma cells by down-regulating the Wnt/β-catenin signaling pathway.

Expression and Functional of LncRNA XIST in MCF-7 Breast Cancer Cells
Abstract:
Objective 

To investigate the expression and function of lncRNA XIST in MCF-7 breast cancer cells.

Methods 

The expression of XIST in MCF 10A human normal breast epithelial cells and MCF-7 human breast cancer cells were detected by qRT-PCR. Transient transfection technique was used to overexpress XIST in MCF-7 cells. MTT assay and Transwell assay were used to detect the changes of proliferation, migration and invasion of MCF-7 cells after XIST overexpression in MCF-7 cells. Bioinformatics and qRT-PCR were used to predict and detect the changes of miRNA expression which have potential binding sites of XIST. qRT-PCR was used to detect the expression of XIST in MCF-7 cells which was transfected instantaneously by miR-130b-3p inhibitor.

Results 

XIST expression was decreased in MCF-7 cells, while miR-130b-3p expression was increased, compared with those in MCF-10A cells (both P < 0.001). Overexpression of XIST significantly inhibited the proliferation of MCF-7 cells (P < 0.001), promoted cell migration and invasion. And the expression level of miR-130b-3p in MCF-7 cells was reduced significantly after overexpression of XIST (P < 0.01), while the expression level of XIST in MCF-7 cells was increased significantly after down-expression of miR-130b-3p (P < 0.001).

Conclusion 

The expression levels of XIST and miR-130b-3p in breast cancer MCF-7 cells are negatively correlated, and the overexpression of XIST could significantly inhibit the proliferation, and promote the migration and invasion of MCF-7 cells.

Autophagy Related Protein 5 Regulates Colon Cancer Cell Senescence Through p53/p21 Pathway
Abstract:
Objective 

To investigate the effect of ATG5 on the senescence and proliferation of colon cancer HT29 cell line.

Methods 

The senescence of colon cancer HT29 cell line was induced by doxorubicin. ATG5 expression was detected by Western blot. Low expression of ATG5 was detected by transient transfection of small interfering RNA, and the proportion of cell senescence and proliferation ability were detected by beta-galactosidase staining and CCK assay, respectively. At the same time, we added Rapa to induce autophagy and detected the proportion of cell senescence and proliferation ability. The effect of ATG5 on cell senescence related pathway proteins P53 and P21 was detected by Western blot.

Results 

The protein expression of ATG5 was down-regulated by doxorubicin-induced cell senescence. The mean number of senescent cells in the SiNC control group was 3±1, while that in the SiATG5 group was 12±2, and that in the low-expression ATG5 plus Rapa group was 12±1. Low expression of ATG5 could up-regulate the expression of senescence-related proteins P53 and P21.

Conclusion 

Down-regulation of ATG5 promotes the senescence of colon cancer cells by up-regulating p53/p21.

Clinical Research
Mechanism of miRNA-451 Regulating Resistance of Gastric Cancer Cells to 5-Fu Through MRP
Abstract:
Objective 

To investigate the mechanism of miR-451 regulating the resistance of gastric cancer to 5-Fu by down-regulating the expression of MRP.

Methods 

Real-time quantitative PCR was used to detect the relative expression of miR-451 in 20 pairs of human gastric cancer tissues and adjacent tissues and gastric cancer cell lines. The expression of miR-451 in the resistance group and non-resistant group were detected. We constructed gastric cancer cell line with stable plent-miR-451 overexpression, and the overexpression efficiency of miR-451 in gastric cancer cell line was detected by real-time quantitative PCR. The proliferation activity of the cells was detected by CCK8. The miR-451 target gene was analyzed by bioinformatics method and verified by luciferase assay. The effect of miR-451 on the mRNA and protein of targeted gene MRP were detected by real-time quantitative PCR and Western blot.

Results 

The expression of miR-451 in normal tissues was higher than that in cancer tissues, and miR-451 expression in the non-resistant gastric cancer tissues was higher than that in the drug-resistant gastric cancer tissues. The overexpression of miR-451 reduced the resistance of gastric cancer cells to 5-Fu treatment (P=0.0006). Bioinformatics analysis showed that MRP was the target gene of miR-451. Luciferase assay also confirmed that MRP was a potential target gene of miR-451. miR-451 overexpression decreased the mRNA and protein of the drug resistance gene MRP (P=0.00069).

Conclusion 

Overexpression of miR451 could down-regulate MRP expression, which reduces the resistance of tumor cells to 5-Fu.

Global Status and Trends of Tumor Hypoxia: A Scientometric Analysis
Abstract:
Objective 

This study aimed to explore the status quo, hot topics, and future prospects in the field of tumor hypoxia by scientometric analysis.

Methods 

The literatures about tumor hypoxia were downloaded from the Web of Science Core Collection from inceptions to Dec.31st. 2018. We used CiteSpace 5.4.R1, VOSviewer 1.6.10 and Excel 2016 to analyze literature information, such as country, institution, author, keywords and references.

Results 

A total of 4399 papers about tumor hypoxia were identified, involving 20157 authors from 3604 institutions in 84 countries. Vaupel P, Harris AL and Dewhirst MW published the most literatures. United States, China and United Kingdom contributed the most publications. The three most contributed institutions are the University of Toronto, Stanford University and Oxford University. International Journal of Radiation Oncology Biology Physics (n=175, IF2017=5.554), Cancer Research (n=144, IF2017=9.13) and Radiotherapy Oncology (n=114, IF2017=4.942) are the most productive journals. The main hot topics in tumor hypoxia field are tumor hypoxic cells and cytokines, tumor hypoxia therapy, tumor hypoxia diagnosis, tumor hypoxia prognosis.

Conclusion 

Developed countries in Europe and America are dominant in the field of tumor hypoxia research. The diagnosis and treatment of tumor hypoxic is still a difficult problem, especially how to overcome the drug resistance caused by tumor hypoxic.

Effect of Da Vinci Robot Radical Gastrectomy on Gastrointestinal Motility and Gastrointestinal Hormones of Gastric Cancer Patients
Abstract:
Objective 

To investigate the effect of Da Vinci robot radical gastrectomy on gastrointestinal motility and hormones of gastric cancer patients.

Methods 

We selected 217 patients who underwent radical gastrectomy. According to different surgical methods, the patients were divided into Da Vinci operation group and open operation group.The recovery time of bowel sounds and the time of first anal exhaust after operation were recorded. The levels of gastrointestinal hormones, surgical-related factors and inflammatory factors were measured before and after operation.

Results 

The recovery time of bowel sounds and the first time of anal exhaust in the Da Vinci operation group were shorter than those in the open operation group(both P < 0.05). The motilin, gastrin, somatostatin levels at 24h after operation were significantly lower than those at 12h before operation in both groups(all P < 0.05), the vasoactive intestinal peptide levels were significantly increased(P < 0.05). At 24h after operation, the motilin and gastrin levels in the Da Vinci operation group were higher than those in the open operation group(both P < 0.05); the levels of vasoactive intestinal peptide in the Da Vinci operation group were lower than those in the open operation group(P < 0.05). In all patients, the recovery time of bowel sounds and the time of first anal exhaust were negatively correlated with the motilin and gastrin levels(P < 0.05), while they were positively correlated with the levels of vasoactive intestinal peptide at 24h after operation(all P < 0.05). There were significant differences in operative time, operative blood loss, drainage tube removal time, VAS pain grade and inflammatory factors between the two groups(all P < 0.05).

Conclusion 

The recovery of gastrointestinal motility of gastric cancer patients treated with Da Vinci surgery is significantly faster than that with traditional laparotomy. The inflammation and stress reaction caused by trauma may be the important factors affecting gastrointestinal hormone secretion.

Dosimetric Comparison Between VMAT with Different Arc and dIMRT for Early-stage Peripheral Lung Adenocarcinoma
Abstract:
Objective 

To compare the dosimetric characteristics of single-arc volumetric modulated arc therapy(VMAT) and 5-field dynamic intensity-modulated radiotherapy(dIMRT) for early-stage peripheral lung adenocarcinoma patients with spherical or spheroidal tumor lesions, and explore the appropriate curvature of single-arc VMAT.

Methods 

We collected 32 early-stage peripheral lung adenocarcinoma patients with spherical or spheroidal tumor lesions and designed three treatment plans for selected cases: single-arc 180° and single-arc 360° VMAT and 5-field dIMRT. The volume of each parameter was compared.

Results 

The three types of plans could meet all the dosimetric requirements of the clinical target area. There was no significant statistical difference in maximum dose(Dmax), minimum dose(Dmin), mean dose(Dmean), homogeneity index(HI) and conformity index(CI) of PTV among three groups (P > 0.05). The mean lung dose (MLD), V5, V10 and V20 of the bilateral-lungs and affected-lung in the dIMRT plan group were lower than those of the other two single-arc VMAT plans, and those of single-arc 360° VMAT plan were slightly higher than those of the single-arc 180° VMAT plan (P < 0.05). Dmean of spinal cord was the lowest in dIMRT group and the highest in single-arc 360° VMAT group (P < 0.05). Dmean of esophagus in dIMRT group was less than those in the single-arc VMAT groups (P < 0.05). MUs was the lowest in dIMRT group and the highest in single-arc 360° VMAT group (P < 0.05).

Conclusion 

For early-stage peripheral lung adenocarcinoma patients with spherical or spheroidal tumor lesions, 5-field dIMRT is preferred; for single-arc VMAT, 180° single-arc is better.

Detection of WNT7A Methylation in Peripheral Blood of NSCLC Patients and Its Diagnostic Value
Abstract:
Objective 

To explore the relation between WNT7A methylation and clinical factors of NSCLC patients.

Methods 

We selected 120 NSCLC patients as NSCLC group and 120 healthy people as control group. The detection rate of WNT7A methylation in two groups was compared by methylation specific polymerase chain reaction, and the relation between WNT7A methylation and clinical factors of NSCLC patients was compared.

Results 

The methylation rate of WNT7A in peripheral blood of NSCLC group was significantly higher than that in control group (P < 0.05). In peripheral blood of NSCLC group, there was no significant correlation between WNT7A gene methylation and gender, pathological type, age, smoking history(P > 0.05). The methylation rate of WNT7A gene was significantly correlated with tumor size, distant metastasis, TNM stage and pleural effusion(P < 0.05). The detection rate of WNT7A gene methylation in peripheral blood of NSCLC patients with pleural effusion, tumor size > 5cm and TNM stage Ⅲ-Ⅳ was significantly higher than that of patients without pleural effusion, tumor size ≤5cm and stage Ⅰ-Ⅱ (P < 0.05).

Conclusion 

The detection rate of WNT7A gene methylation is high in NSCLC patients, which can be used as an effective diagnostic basis for NSCLC.

PKM2 Expression and Elevated CD163 in Macrophage Synergistically Promote Osteosarcoma Progression
Abstract:
Objective 

To investigate the relation between PKM2 and related pathological features of osteosarcoma, to further explore the markers for predicting the prognosis of osteosarcoma patients.

Methods 

We collected 88 cases of paraffin-embedded primary osteosarcoma specimens, and the specimens were constructed by tissue microarray. Serial sections were used to detect the expression of PKM2 in the above tissues by immunohistochemistry. Kaplan-Meier analysis was used to demonstrate the prognostic value. Correlation analysis between parameters and patient's prognosis was performed using Cox regression model.

Results 

M2 macrophage-specific marker CD163 was elevated in osteosarcoma matrix, suggesting that M2 macrophages were densely infiltrated in osteosarcoma. PKM2 overexpression is positively correlated with M2 macrophage infiltration in osteosarcoma.

Conclusion 

PKM2 overexpression and M2 macrophage infiltration were influence factors for patients' poor prognosis.

Clinical Diagnosis
Characteristics of Laboratory Biomarkers Associated with Hypercoagulability in Lung Cancer Patients During Perioperative Period and Its Diagnostic Value for Deep Venous Thrombosis
Abstract:
Objective 

To analyze the characteristics of laboratory biomarkers associated with hypercoagulability in patients undergoing lung cancer surgery during the perioperative period and its diagnostic value for deep venous thrombosis (DVT).

Methods 

We enrolled 143 patients treated with lung cancer surgery based on eligibility criteria. The lower extremity deep vein was examined perioperatively by compressed ultrasonic (CUS) to determine the DVT. The laboratory biomarkers associated with hypercoagulability were measured. We analyzed the area under curve (AUC) of ROC and cutoff in DVT (+) and DVT (-) groups with significant different biomarkers.

Results 

Thirty-three patients with DVT were first diagnosed from the postoperative 3rd day (POD3) to 7th day (POD7). The fibrinogen degradation product (FDP), D-Dimer, brain natriuretic peptide and C reactive protein were significantly increased in the postoperative POD1-POD7 (P < 0.05). There were significant differences in the change levels of FDP and D-D during the perioperative period between the DVT (+) and DVT (-) groups (P < 0.05). The AUC and diagnostic cutoff values of POD1-FDP, POD3-FDP, POD3-D-D were 0.726 and 4.65μg/ml, 0.811 and 4.85 μg/ml, 0.772 and 1.55 μg/ml, respectively. The sensitivity and specificity of serial test were 46.5% and 94.9% for the combined diagnosis.

Conclusion 

The value of increased levels of POD1-FDP, POD3-FDP and POD3-D-Dimer for DVT diagnosis is moderate. The combined diagnosis with serial test could improve the specificity of diagnosis.

Clinical Application
Efficacy of Definitive External-beam Radiotherapy Versus Radical Prostatectomy on Clinically Localized High-risk Prostate Cancer Patients: A Retrospective Study
Abstract:
Objective 

To retrospectively compare the efficacy between definitive external-beam radiotherapy (ExRT) and radical prostatectomy(RP) on patients with localized high-risk prostate cancer (PCa).

Methods 

We retrospectively studied 150 patients with high-risk PCa(T2b-T4N0M0) who underwent definitive ExRT or RP. The inclusion criteria for high-risk PCa were PSA≥20 ng/ml or above cT3 or GS≥8. The primary end point was biochemical failure free survival(BFFS), and the secondary end point was distant metastasis free survival(DMFS), cancer-specific survival(CSS) and overall survival(OS).

Results 

A total of 88 patients underwent definitive ExRT and androgen deprivation therapy(ADT), and the remaining 62 patients underwent RP and pelvic lymphadenectomy(PLND). The median age and follow-up time were statistically significant between ExRT and RP groups(P < 0.05). The biochemical failure(BF) rate in ExRT group was significantly lower than that in RP group(P < 0.001), while BFFS was significantly increased(P < 0.001). The DMFS, CSS and OS were not significantly different between the two groups.

Conclusion 

BF rate after definitive ExRT in patients with localized high-risk PCa are significantly lower than those undergoing RP, while BFFS is significantly increased.

Therapeutic Effect of Elemene Combined with Chemoradiotherapy and Its Influence on Immune Function in Nasopharyngeal Carcinoma Patients
Abstract:
Objective 

To observe the therapeutic effect of elemene emulsion injection combined with chemoradiotherapy and its effect on immune function in nasopharyngeal carcinoma (NPC) patients.

Methods 

Random number method was used to divide the patients into control group (IMRT+fluorouracil+cisplatin) and observation group (IMRT+fluorouracil+cisplatin+elemene injection 500 mg/d). We evaluated the short-term efficacy, the changes of T lymphocyte subsets in peripheral blood and adverse reactions.

Results 

All patients successfully completed the treatment. There was statistically significant difference between control group and observation group in the total effective rate (71.74% vs. 82.61%, P < 0.05), CD8+ level in peripheral blood lymphocyte subsets (31.35±2.39 vs. 34.37±1.97, P < 0.05), the ratio of CD4+/CD8+ (1.37±0.03 vs. 0.98±0.18, P < 0.05), and the quality of life (57.2±7.4 vs. 60.3±5.3, P < 0.05). Compared with control group, the observation group had lower hematological toxicity and grade Ⅲ-Ⅳ skin reactions, and the incidence of grade Ⅲ-Ⅳ gastrointestinal reactions (nausea, vomiting) was significantly lower (P < 0.05).

Conclusion 

Elemene combined with chemoradiotherapy could improve the quality of life of nasopharyngeal carcinoma patients, reduce the incidence of adverse reactions and obtain a better prognosis.

Comparison of Efficacy Between S-1 and Capecitabine/Fluorouracil on Advanced Colorectal Cancer: A Meta-analysis
Abstract:
Objective 

To conduct a meta-analysis on the data of S-1 and capecitabine or fluorouracil in the treatment of advanced colorectal cancer, to demonstrate the feasibility of S-1 replacing capecitabine or fluorouracil.

Methods 

We searched published literature in the PubMed, Cochrane Library, Embase and CNKI databases, and searched for controlled trials at the Clinical Trials Center (https://www.clinicaltrials.gov/). The data extraction and quality evaluation were conducted according to Cochrane Handbook 5.1.0, and RevMan 5.3 software was used for the meta-analysis of relevant case-control studies.

Results 

The data of 3462 patients from 11 randomized controlled trials were included. Compared with the capecitabine/fluorouracil regimen, OS was improved in the S-1 treatment group, but there was no statistically significant difference in PFS, DCR or ORR. The incidence of diarrhea, renal insufficiency and hand-foot syndrome in the S-1 group was lower than that in the control group. But the incidence of platelet reduction in the S-1 group was higher than that in the control group at a reasonable contrast dose.

Conclusion 

S-1 has a certain therapeutic advantage after replacing capecitabine or fluorouracil in conventional chemotherapy on advanced colorectal cancer.

Adverse Reaction of HIPEC Combined with Intravenous Chemotherapy on Ovarian Cancer Patients
Abstract:
Objective 

To evaluate adverse reactions of the hyperthermic intraperitoneal chemotherapy (HIPEC) combined with intravenous chemotherapy in the treatment of ovarian cancer(OC) after the cytoreductive surgery (CRS), and to analyse the effect of adverse reactions on the survival time of patients.

Methods 

We selected 163 patients with ovarian cancer. All patients got CRS for OC, and then were divided into two groups according to the different treatment modes: observation group (n=47, HIPEC in combination of intravenous chemotherapy) and control group (n=116, intravenous chemotherapy). The adverse reactions of the two groups were observed. All patients were followed up after operation.

Results 

The incidence of hypoproteinemia in the observation group was higher than that in the control group, while the incidence of leukopenia, thrombocytopenia, abdominal distention and abdominal pain were lower than those in the control group (P < 0.05), and the other adverse reactions were not statistically different. The incidence of D-Dimer increase, hypocalcemia, hyperglycemia as well as nausea and vomiting in patients with > 2 cycles of HIPEC were increased (P < 0.05). There was no significant difference in overall survival rate between the two groups. The survival of patients without anemia or mild anemia in the observation group was better than that of patients with severe anemia (P < 0.05). The occurrence of other adverse reactions had no significant effect on the overall survival rate of the patients.

Conclusion 

HIPEC combined with intravenous chemotherapy after CRS would not increase adverse reactions, especially severe adverse reactions in OC patients, but there is a high incidence of hypoproteinemia.

Reviews
Progress of Intestinal Flora Disorder and Hepatocellular Carcinoma
Abstract:

Hepatocellular carcinoma (HCC) is a common therioma of digestive system. The occurrence of HCC involves many aspects, such as environment, metabolism and genetic factors. In recent years, it has been found that intestinal flora imbalance is also an important factor in the occurrence of HCC. When intestinal flora disorders occur, the intestinal mucosal barrier can be destroyed, bacterial translocation and endotoxemia can cause chronic inflammatory response of hepatocytes. Long-term and chronic changes of intestinal flora metabolites such as short-chain fatty acids and bile acids also play a role in promoting HCC. At present, a variety of methods to improve intestinal flora disorders have shown a bright future in the treatment of HCC. This article reviews the mechanisms of intestinal flora-induced HCC and the preventive and therapeutic measures against intestinal flora imbalance.

Case Report
A Case Report of Four Primary Malignant Tumors
Tumor Information
Novel Luminescent Nanomaterials Synthesized by Chinese Scientists are Exected to Be Used for Photodynamic Therapy of Tumor, etc