Chinese Experts Consensus on Immune Checkpoint Inhibitors for Non-small Cell Lung Cancer (2020 Version) / 中国肺癌杂志

Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. The systemic antitumor therapy of advanced NSCLC has undergone renovations of chemotherapy, targeted therapy and immunotherapy, which results in greatly improved survival for patients with advanced NSCLC. Immune checkpoint inhibitors (ICIs), especially targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1), has changed the treatment paradigm of NSCLC. ICIs have become the standard treatment for advanced NSCLC without epidermal growth factor receptor(EGFR) mutation or anaplastic lymphomakinase(ALK) translocation in the first- or second-line setting, and for locally advanced NSCLC following concurrent radiotherapy and chemotherapy. ICIs are also promising in adjuvant/neoadjuvant therapy. More and more ICIs have been approved domestically for the treatment of NSCLC. Led by the NSCLC expert committee of Chinese Society of Clinical Oncology (CSCO), this consensus was developed and updated based on thoroughly reviewing domestic and foreign literatures, clinical trial data, systematic reviews, experts' discussion and the consensus(2019 version). This consensus will aid domestic clinicians in the treatment of NSCLC with ICIs.
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Chinese Experts Consensus on Immune Checkpoint Inhibitors for Non-small Cell Lung Cancer (2019 version) / 中国肺癌杂志

Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer, most NSCLC patients are at advanced stage at the time of diagnosis. For patients without sensitive driven-oncogene mutations, chemotherapy is still the main treatment at present, the overall prognosis is poor. Improving outcomes and obtaining long-term survival are the most urgent needs of patients with advanced NSCLC. In recent years, immunotherapy has developed rapidly. Immune checkpoint inhibitors (ICIs), especially targeting programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1), have made a breakthrough in the treatment of NSCLC, beneficial to patients' survival and changed the treatment pattern for NSCLC. It shows more and more important role in the treatment of NSCLC. Led by NSCLC expert committee of Chinese society of clinical oncology (CSCO), relevant experts in this field were organized. On the basis of referring to domestic and foreign literature, systematically evaluating the results of Chinese and foreign clinical trials, and combining the experiences of the experts, the experts group reached an agreement to develop this consensus. It will guide domestic counterparts for better application of ICIs to treat NSCLC.

The expressions of c-Met, VEGF, EGFR and HER-2 in the AFP-producing gastric cancer / 中国癌症杂志

Background and purpose:Alpha fetoprotein (AFP)-producing gastric cancer (AFPGC) is considered to be a special type of gastric cancer. Currently, the effect on AFPGC is not as good as the common AFP- negative gastric cancer. Therefore, it is very important to explore clinicopathological features of AFPGC cancer, to improve diagnosis and individualized treatment. This study is to investigate the expressions of hepatocyte growth factor receptor c (c-Met), vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER-2) in the AFPGC.Methods:A total number of 44 cases of AFPGC (serum AFP≥10 μg/L) tissues were selected as a test group. There were 30 cases of serum AFP≥200 μg/L. This study collected 30 cases of gastric cancer with normal AFP and 30 cases of hepatocellular carcinoma with increased AFP (serum AFP≥200 μg/L) as 2 control groups. The cases of the 3 groups had the same clinical stage basically. The expressions of c-Met, VEGF, EGFR and HER-2, CD34 were detected by immunohistochemistry (EnVision staining method). Tumor microvessel density (MVD) was calculated by marking CD34, and the results were analyzed. The clinicopathologic parameters were recorded accurately: gender, age, highest level of serum AFP, tumor differentiation, tumor stage, tumor location, lymph node metastasis, liver metastasis, Lauren classiifcation, etc. These patients were followed up regularly. The clinical pathological features of AFPGC patients were investigated.Results:AFPGC clinical characteristics showed that, among 44 cases of AFPGC group, 86.36% (38/44) had lymph node metastasis, 54.55% (24/44) had hepatic metastasis, intestinal type was 36.36% (16/44), diffuse type was 56.82% (25/44), mixed type was 6.82% (3/44). The positive expression rates of c-Met protein in AFPGC, gastric cancer with normal AFP, hepatocellular carcinoma with increased AFP were 73.33% (22/30), 70.00% (21/30) and 53.33% (16/30), respectively. The positive expression rates of VEGF protein were 76.67% (23/30), 56.67% (17/30) and 66.67% (20/30), respectively. The positive expression rates of EGFR protein were 53.33% (16/30), 40.00% (12/30) and 73.33% (22/30), respectively. The “++ and +++” expression rates of HER-2 in AFPGC, gastric cancer with normal AFP and hepatocellular carcinoma with increased AFP were 38.64% (17/44), 23.33% (7/30) and 26.67% (7/30), respectively. The MVD values in AFPGC, gastric cancer with normal AFP and hepatocellular carcinoma with increased AFP were 23.03±10.24, 21.92±11.45 and 19.43±7.83, respectively. Compared with gastric cancer with normal AFP, expression of VEGF protein was signiifcantly higher in the AFPGC (P<0.05). Compared with hepatocellular carcinoma with increased AFP, the expression of c-Met protein was significantly higher in AFPGC (P<0.05).Conclusion:AFPGC is prone to lymph node metastasis and hepatic metastasis. The major part is the diffuse type in Lauren classiifcation. The positive expression rates of VEGF protein in AFPGC were signiifcantly higher than the gastric cancer with normal AFP. The positive expression rates of c-Met protein in AFPGC were signiifcantly higher than the hepatocellular carcinoma with AFP increased.

A Preliminary Study on Risk and Benefit Assessment in Ethical Review of Clinical Trials / 中国医学伦理学

The risk and benefit assessment is an important part of ethical review in clinical trials, of which the significance is to minimize the risk and maximize the benefit, thus to protect the rights of the subject. Begin with introducing the nature of the risk and benefit of clinical trial, this paper analyzed the way of ethical review based on risk consideration and discussed some key points of risk and benefit assessment including the minimum risk, the risk and benefit of vulnerable groups, risk informing, benefit of clinical trials, the fairness of recruitment and the importance of strengthening follow-up review. Ethical review should play a role as the balance, which neither-hinder the development of clinical trial to protect the rights of the subjects nor damage the rights and interests of subject to develop clinical trials.

Mechanisms of bevacizumab inducing proteinuria in mice models / 医学研究生学报

Objective Bevacizumab ( BM ) is an angiogenesis inhibitor widely used in cancer therapy, but its off-target effect of proteinuria may lead to discontinuation of treatment.This study was to explore the mechanisms of BM inducing proteinuria in mice. Methods Twenty-four healthy mice were randomly divided into four groups, saline control, low-dose BM, medium-dose BM, and high-dose BM, treated by injection of normal saline and BM at 10, 35, and 60 mg per kg of the body weight, respectively, though the tail vein.At 4 weeks after injection, 24-hour urine was collected to determine the total urine protein and blood obtained from the eyeballs for biochemical analysis.Then all the mice were sacrificed and the kidneys harvested for observation of pathologic changes in the glomeruli as well as for immunohistochemistry, Western blotting, and real-time PCR analysis. Results Compared with normal saline,BM obviously elevated the level of 24-hour urine protein, with statistically significant differences between the control and the medium-and high-dose BM groups (0.23 ±0.02 vs 1.14 ±0.13 and 1.43 ±0.10, P0.05).No significant differences were observed among the four groups in the levels of Cr, BUN, AST and ALT (P>0.05).Under the optical microscope, the kidneys showed normal structures in the control group, no signifi-cant pathologic changes in the low-dose BM, and vacuolus-like alteration with atrophic glomerular endothelial cells in the medium-and high-dose BM groups.Immunohistochemical analysis demonstrated the expressions of VEGF and podocin were moderately or strongly positive in the control and low-dose BM groups, by weakly positive or negative in the medium-and high-dose BM groups.Compared with the control group, the expression of the VEGF protein in the renal tissue was significantly decreased in the high-dose BM group (0.76 ±0.09 vs 0.39 ±0.05, P0.05), and the expression of the podocin protein was significantly reduced in the medium-dose BM (0.67 ±0.07 vs 0.43 ±0.10, P0.05).The mRNA expressions of VEGF and podocin were not significantly changed in the low-dose BM group as compared with the control (1.07 ±0.61 and 1.12 ±0.09 vs 1.23 ±0.25 and 1.17 ±0.19, P>0.05) but remarkably de-creased in the medium-dose (0.82 ±0.38 and 0.71 ±0.18) and high-dose BM groups and (0.47 ±0.64 and 0.42 ±0.09) groups (P<0.01). Conclusion Bevacizumab damages glomerular filtration membrane and induce proteinuria partially by down-regulating the protein and mRNA expressions of VEGF and podocin.

Immunotherapy of biliary tract cancer / 国际肿瘤学杂志

Biliary tract cancer (BTC)is one of the most aggressive malignancies with only 1 0% early-stage diagnosis rate.For advanced BTC,regimen of gemcitabine and cisplatin has been regarded as the first line standard combination,but the curative effect is still unsatisfied.Infiltration of immune cells and immune-related microenvironment can inhibit various types of cancers.In BTC,higher frequencies of tumor-infiltrating CD8 + cytotoxic T cells and CD4 + T cells are closely associated with favorable prognosis.These findings have provided the rationale for further development of immunotherapies as a novel treatment modality against BTC.

Efficacy analysis of crizotinib for brain metastases in ALK-rearrangement-positive non-small cell ;lung cancer / 中国癌症杂志

Background and purpose: Although crizotinib could manifest marked antitumor activity in anaplastic lymphoma kinase (ALK)-rearrangement-positive non-small cell lung cancer (NSCLC) patients, but brain metastases is always occured in such patients. This study aimed to explore the efifcacy and treatment mode of crizotinib for brain metastases in ALK-rearrangement-positive NSCLC. Methods: The clinical data of 6 patients with brain metastases in ALK-rearrangement-positive NSCLC treated in 81 Hospital of PLA from Jan. 2011 to Aug. 2014 were analyzed retrospectively. Results: Three patients had brain metastases before crizotinib administration, 1 obtained partial response (PR) and 2 obtained stable disease (SD) in intracraninal tumors. The median progression free survival (PFS)for the ifrst period of crizotinib administration were 5.7 months, and the sites of ifrst disease progression were brains. All the 6 patients continued to receive crizotinib after radiotherapy with the median PFS of 4 months. One patient even experienced a median PFS of 23.3 months for the second period of crizotinib administration, and her brain tumors obtained complete response (CR). Conclusion:The data of this study suggest that crizotinib is effective for brain metastases in ALK-rearrangement-positive NSCLC, and continued administration of crizotinib after radiotherapy for isolated intracraninal tumor progression is a elective treatment option for such patients.

Effect of combined application of recombinant human endostatin and paclitaxel on the proliferation and invasion of gastric cancer cell / 医学研究生学报

Objective Antiangiogenesis therapy has been shown to prolong survival for patients with malignant tumor .However the present study has not been observed the clinical benefit of antiangiogenesis therapy combination with chemotherapy treated with gastric canc-er.Human recombinant vascular endothelial inhibition (endostar) as a multi-targeted anti-angiogenesis drug, the mechanism is different from other Antiangiogenesis drugs.It can block different pathways of signal transduction to inhibit angiogenesis .This study aimed to observe the effect of combined application of endostar and paclitaxel on biological behavior of gastric cancer cell lines . Methods MMT assay and Tr-answell invasion assay were respectively used to examine the inhibition rate of cell growth and invasion ability when cells were treated with va-rious concentrations of endostar and paclitaxel alone or in combination.The protein expressions of VEGF,MMP-2 and MMP-9 were examined by Western blot. Results Endostar or paclitaxel effectively inhibited the growth of MGC803 cells and the in vitro invasion of MGC803 cells in a concentration-dependent manner.The proliferation and invasion ability of combined treatment with endostar and paclitaxel was significantly lower than that of endostar or paclitaxel alone (P<0.05).Compared with con-trol group, the VEGF,MMP-2 and MMP-9 protein expressions were de-creased in experimental groups ( P <0.05).Compared with paclitaxel group, the VEGF, MMP-2 and MMP-9 protein expressions were relatively reduced in combination groups (P<0.05). Conclusion Endostar combined with paclitaxel can suppress the growth and invasion of MGC803 cells, and the decreasing VEGF , MMP-2 and MMP-9 expressions may be involved in the mechanism .

Experience of doctor-patient communication skills training for residents in oncology department / 中华医学教育探索杂志

With the increasing of doctor-patient conflicts,the communication between them gradually becomes a critical element in medical service activities.How to improve the doctor-patient communication is an important content in resident communication skill training.Oncology is a developing discipline with fast development and high risk and residents in oncology department need more communications with patients in the era which individualized treatment is emphasized.Systematization and institutionalization of the training system of doctor-patient communication is beneficial to popularizing doctor-patient communication experiences,protecting the rights and interests of them and ensuring the smooth process of medical treatment.

The occurrence and evolution of portal vein tumor thrombus in primary liver cancer / 肿瘤研究与临床

Primary liver cancer is a high incidence and common malignant tumor in China. Portal vein tumor thrombus is one of the biologic marks of advanced liver cancer and difficult to be cured, and the prognosis is extremely poor. This paper systematically describes the formation mechanism, diagnosis,classification and prognosis of portal vein tumor thrombus. It would provide a theoretical basis for this clinical problem in order to reasonably understand and actively treat it.

Mutation of k-ras mutation and evaluation of anti-EGFR monoclonal antibody combined with chemotherapy in Chinese colorectal cancer patients / 肿瘤研究与临床

Objective To observe the k-ras mutation rate of colorectal cancer in China, and assess the effect and toxicity in advanced colorectal cancer (CRC) patients (pts) receiving chemotherapy combined with monoclonal antibody against Epidermal Growth Factor Receptor (EGFR). Methods The k-ras mutation of 139 samples collected from our hospital were tested by pyrophosphoric acid sequencing. Twenty-three advanced colorectal cancer patients were treated with chemotherapy combined with anti-EGFR monoclonal antibody, including 3 initial treated and 20 retreated. In the total 23 patients, 18 were treated with cetuximab and chemotherapy, and S were treated with nimotuzumab and chemotherapy. Cetuximab was taken with 400 mg/m2 first time, and then 250 mg/m2 every week. Nimotuzumab was taken with 400 mg first time, and then 200 mg every week. Eight patients of the total 23 received anti-EGFR monoclonal antibody combined with irinotecan, 12 with FOLFIRI, 3 with FOLFOX4. Results k-ras mutation type (mt) was detected in 39.6 % (55/139) of pts, k-ras wild type (wt) was 60.4 % (94/139). In 22 effect evaluable patients, 5 received PR and 9 SD, and RR and DCR were 22.7 % and 63.6 %, respectively. TTP was 124 days. Thirteen of the 22 patients tested k-ras mutation, of the 11 k-ras mt pts, 4 received PR, 4 SD and 3 PD. Two patients of k-ras mt received PD after 2 cycles treatment. Acneform eruptions were observed in 15 patients of 18 pts who received cetuximab and paronychia in 3 pts. Eruption or paronychia was not observed in all patients who received nimotuzumab. Grade 3 hypersensitivity were occured in 2 patients with cetuximab, and one of them alternated nimotuzumab in next cycle didn't get hypersensitivity any more. Conclusion The mutation rate of k-ras in Chinese colorectal cancer patients was similar with westerners. The effect of cetuximab combined with chemotherapy on advanced colorectal cancer was reliable. Nimotuzumab combined with chemotherapy worth to be studied further because of the promising effect and mild toxicity.

Treatment strategies of primary hepatocellular carcinoma with portal vein tumor thrombus / 肿瘤研究与临床

Portal vein tumor thrombus is a common complication of primary liver cancer,in the event,and often indicates that his condition has office in the late irreversible,the prognosis is extremely poor.This article describes the treatment of portal vein tumor thrombus of existing methods,to promote muhidisciplinary treatment,improve survival in patients with advanced liver cancer.

Progress on antitumor effects of Marsdenia tenacissima / 中国中药杂志

The article reviewed the progress in the research of antitumor activities and mechanisms of Marsdenia tenacissima. Its origin producing area and antitumor constituents were analyzed. The herb possessed extensive antitumor effects in experimental and clinical applications. It provides theoretical evidences for study on constituents in this traditional Chinese medicine. Futher studies on the species in M. tenacissima are needed for better medicinal utilization.

The mechanism and management for acneform eruption which related to inhibitors of epidermal growth factor / 肿瘤研究与临床

Inhibitors of epidermal growth factor have played an important role in the treatment of oncology.One of the most common adverse effects is aeneform eruption.This article reviews the incidence,clinical manifestation, mechanism and management for acneform eruption which related to inhibitors of epidermal growth factor.

Experimental Research of Cross Resistance About Paclitaxel Resistant Human Lung Adenocarcinoma Cell / 医学研究杂志

Objective To investigate paclitaxel cross resistance and provide information for clinical therapy by establishing a paclitaxel resistant human lung adenocarcinoma cell line.Method A paclitaxel resistant human lung adenocarcinoma cell line named with SPC-A1/Taxol was developed by intermittent exposure to gradually increasing concentration of taxol.Resistant index was calculated from median inhibitory concentration(IC50)which was evaluated by MTT assay.Results SPC-A1/Taxol cell line displayed high resistance to taxotere,vinorelbine,vincristine and doxorubicin.It also displayed median or low resistance to camptothecins and podophyllotoxins.No cross resistance was observed to antitumor platinum and antimetabolite drugs and elemene emusion.Conclusion SPC-A1/Taxol cell line is a typical multidrug-resistant cell line in vitro.It could be useful for studing the cross resistance and direct clinical medication.

Inhibitory effect of arsenic trioxide on angiogenesis of chick embryo chrioallantoic membrane / 中国癌症杂志

Background and purpose:Arsenic trioxide(As_(2)O_(3)) injection actually has an effect on solid tumors such as hepatoma in the clinic.In order to find out its mechanism of action,we studied the action of arsenic trioxide injection on angiogenesis of chick embryo chrioallantoic membrane(CAM).Methods:The effect of arsenic trioxide injection on angiogenesis was investigated by CAM model and computer image analysis.Results:Administered at three different concentrations of arsenic trioxide injection at 10,20 and 40,3 days later,the vessel area were 25.66%?4.17%,24.74%?2.54% and 21.51%?6.70%,respectively.Compared to the NS control group(vessel area was 30.68%?(4.64%)),there was an obvious difference(P0.05 among the three different concentration groups).Conclusions:arsenic trioxide injection has a strong inhibitory effect on angiogenesis,which may be used in suppressing cancer angiogenesis.

Present state and future of gastrointestinal stromal tumors / 肿瘤研究与临床

Gastrointestinal stromal tumors (GIST) have been considered as an excellent example in solid tumors transferring rapidly from experimental study to clinical therapy. This paper highly sums up and reviews its new diagnosis and treatment as well as future development, especially the advancement of the related understands.

Cloning of human preferentially expressed antigen of melanoma gene and its expression in E.coli / 医学研究生学报

Objective: To clone and express the preferentially expressed antigen of melanoma (PRAME) gene in E.coli. Methods: The cDNA encoding human PRAME gene was extracted from human AML cell line HL-60 and amplified by RT-PCR, then the PRAME gene was inserted into plasmid PGEM-T-easy. After sequenced, it was cloned into the prokaryotic expression vector pGEX-4T-2 to construct a clone with high level expression and the recombinant plasmid was cloned in E.coli. Results:The protein product reached the highest level at 5 h after IPTG induction. Conclusion: Since PRAME is only expressed at low levels in a few normal tissues and encodes an antigen recognized by autologous cytotoxic T lymphocytes, while expressed at high levels in patients with leukemia, it might be a new targeting candidate for tumor immunotherapy.

Clinical observation of paraplatin used within the cavity for malignant serous cavity effusion / 肿瘤研究与临床

Objective To evaluate the efficacy and toxicity of paraplatin used within the cavity for the treatment of malignant serous cavity effusion. Methods Puncturing with catheter of centre vein and permanent catheter, withdrawing proper volume of malignant effusion, 150 ～ 450 mg paraplatin was infused into the serous cavity each time for once or twice a week till the effusion was disappeared or there was no change. Results 76 cases were evaluable for response and toxicity. There were 21 patients with CR, 33 patients with PR and 22 patients with NR. The ORR was 71 %. Among them, the RR in malignant pleural effusion group was 79 %(27/34), 50 %(13/26) in the peritoneal effusion and 87 %(14/16) in the pericardial effusion. Only I ~ II degree bone marrow suppression was observed. Conclusions Paraplatin used within the cavity is more effective and safe for treating malignant serous cavity effusion.

Anti-invasion and anti-metastasis effects of ginsenoside Rg3 on the hepatocellUlar carcinoma cell line / 中国癌症杂志

Purpose:To explore the effects and mechanisms o f anti-invasion and anti-metastasis of ginsenoside Rg3 on human hepatocellular carcinoma cells. Methods:To select human hepatocellular carcinoma cell line SMMC -7721 and the human allantoic veins endothelial cell line ECV304 as the study objects. We observed the effet of ginsenoside Rg3’s effect on the growth of SM MC-7721 and ECV304 by MTT methods,the adhesion of SMMC-7721 and Fibronectin by cell adhesion experiment, the expression of gene protein of nm23,CD44 and VEGF by immunohisto-chemical method. Results:Ginsenoside Rg3 could inhibit not only the growth of SM MC-7721 and ECV304 significantly, but also the adhesion of SMMC-7721 and FN. I t might also down-regulate the expression of CD44, VEGF and up-regulate the nm 23 gene expression. Conclusions:Ginsenoside Rg3 can inhibit invasion and metastasis of the hepatic carcinoma cell. The mechanisms are probably that Ginsenoside Rg3 can inhibit the hepatic carcinoma cells’ invasion activity,regulate the expres sion of the gene proteins which are closely related with invasion and metastasis ,inhibit neovasularization.