[Advances in Treatment of Human Epidermal Growth Factor Receptor 2-Positve Gastric Cancer].

Gastric cancer ranks as the fifth most common malignant tumor worldwide and the fourth leading cause of cancer-related deaths.Human epidermal growth factor receptor 2 (HER2)-positive gastric cancer is a special type of gastric adenocarcinoma,the prognosis of which can be improved by trastuzumab plus cytotoxic chemotherapy such as cisplatin and fluorouracil.Pembrolizumab on the basis of Tmabplus chemotherapy can further improve the overall response rate,which has become the first-line standardized therapy against HER2-positive gastric cancer.However,there are still some obstacles such as the innate resistance to Tmab in specific populations.The research on HER2-targeted therapy provides clues for clinical decision-making.This review documents the current neoadjuvant and adjuvant therapies against late-stage HER2-positive gastric cancer,as well as the progress in novel HER2 pathway-targeted drugs.

[A method of screening highly common neoantigens with immunogenicity in colorectal cancer based on public somatic mutation library].

Colorectal cancer (CRC) is a malignant cancer with high incidence and mortality in the world. Immunotherapy targeting neoantigens can induce durable tumor regression in cancer patients, but is almost limited to personalized precision therapy, due to the individual differences of unique neoantigens. With the discovery of many common oncogenic mutations, and such mutation-associated neoantigens could cover more patients, and hence are valuable in clinical field. However, whether the common neoantigens can be identified in CRC is unknown. Combining the somatic mutations data from 321 CRC patients with a filter standard and 7 predicted algorithms, we screened and obtained 25 HLA-A*1101-restricted common neoantigens with a high binding affinity (IC50<50 nmol/L) and presentation score (>0.90). Besides the positive epitope KRAS_G12V8-16, 11 out of 25 common neoantigens specifically induced in vitro pre- stimulated cytotoxic lymphocyte (CTL) to secrete interferon gamma (IFN-γ). Moreover, combining cell-sorting technology and single-cell RNA sequencing, the immune repertoire profiles of C1orf170_S418G413-421 and KRAS_G12V8-16-specific CTL were analyzed and validated. Their related T-cell receptor engineered T cell (TCR-T) cells could also recognize the neoantigens and secrete IFN-γ. Hence, we have established a method to screen for common neoantigens with immunogenicity in CRC based on the public somatic mutation library. It can provide essential peptide and TCR information for immunotherapies, such as peptides, dendritic cells (DC) vaccines, TCR-like antibodies, TCR-T, etc., for the CRC and other cancers, which has practical application value in the clinics.

[Gut Microbiome Differences between Gastrointestinal Cancer Patients and Healthy People].

Objective To compare the differences in fecal flora among patients with esophageal cancer,gastric cancer,or colorectal cancer and between patients with gastrointestinal tumors and healthy people.Methods The 16S rRNA method was used to analyze the differences in fecal flora among 13 patients with esophageal squamous cell carcinoma,23 patients with gastric cancer,6 patients with colorectal cancer,and 49 healthy persons.Results Bifidobacterium,Faecalibacterium prausnitzii,and Ruminococcus callidus were less abundant in the fecal flora of cancer patients than in those of healthy controls(all P<0.05).Some species of Firmicutes and Actinobacteria were significantly reduced in the feces of patients with esophageal cancer or gastric cancer than in healthy people(P<0.05),whereas others showed consistency with the intestinal cancer group.Anti-tumor treatment,antibiotics,and lactic acid could affect the fecal flora of cancer patients.Conclusion The gut microbiota compositions(mainly Firmicutes and Actinobacteria)and some specific bacteria species in the feces of patients with esophageal cancer and gastric cancer are similar to those in the feces of patients with intestinal cancer,suggesting these bacteria may be involved in the development of upper gastrointestinal tumors.

[Clinical Analysis of 25 Cases of Malignant Peritoneal Mesothelioma].

Objective To investigate the clinicopathological features,treatment,and prognosis of patients with malignant peritoneal mesothelioma(MPM). Methods Clinical data of 25 MPM patients admitted to Peking Union Medical College Hospital from 1993 to 2017 were retrospectively analyzed.Results The mean age of these 25 patients with pathologically confirmed MPM(epithelioid subtype) was 50 years.The tumors were diffuse in 24 patients(96%) and localized in 1 patient(4%).Cytoreductive surgery was performed in 6 patients(24%),intraperitoneal chemotherapy in 12 patients(48%),and systemic chemotherapy in 24 patients(96%).The median overall survival was 26 months,with 1-year survival rate of 74.2% and 5-year survival rate of 16.7%.Cytoreductive surgery or intraperitoneal chemotherapy combined with systemic chemotherapy showed a significant survival advantage over intraperitoneal or intravenous chemotherapy alone(P=0.046,P=0.005).Cytoreductive surgery(P=0.018) showed statistical significance by multivariate analysis as a predictive factor in survival(hazard rate=6.889;95%CI=1.386-34.247).Conclusions MPM has its diverse clinical manifestations.Patients after cytoreductive surgery have longer survival time.Chemotherapy drugs(except for pemetrexed) and targeted therapy may be promising treatments.Cytoreductive surgery is an independent prognostic factor.

Characteristics and treatment strategy of hepatic angiomyolipoma: a series of 94 patients collected from four institutions.

AIM: To report on a Chinese multicenter series of hepatic angiomyolipoma (HAML) patients and to study the characteristics and the treatment strategy of the disease. METHOD: Data of 94 patients diagnosed with HAML from four institutions of China between December 1997 and January 2008 were reviewed retrospectively. Immunohistochemical assays were performed on the surgical specimens and follow up studies were done in all the patients. RESULTS: 52 of 94 patients (55.3%) showed no significant clinical symptoms. There were no specific findings on laboratory examinations. The correct preoperative diagnostic rate of ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI) was 0% (0/94), 15.7% (11/70) and 22.7% (10/44), respectively. Regarding the treatment, 93 patients had a hepatectomy and 1 patient was treated by radiofrequency ablation. The postoperative pathology showed HAML in all the patients: 69 patients were studied with HMB-45 staining by immunohistochemistry and the positive rate was 100% . The postoperative follow-up rate was 91.5% (86/94), no sign of recurrence or metastasis was observed during the follow-up period. CONCLUSION: This is the largest HAML series reported in the literature. There are no specific signs and symptoms in HAML patients; the preoperative imaging diagnosis (including CT, MRI) is insensitive. The common pathological features include the basic histological components and expression of HMB-45. Conservative treatment is not suggested; surgical resection should be considered as a treatment choice for HAML.