Review on the adjuvant effects of renin-angiotensin system regulators on antitumor drugs / 中国药房

The re gulators of renin-angiotensin system （RAS） include renin inhibitors ，angiotensin converting enzyme inhibitors，angiotensin Ⅱ receptor blockers ，angiotensin Ⅱ receptor agonists and angiotensin 1-7. This paper summarizes and analyzes the adjuvant effects of RAS regulators on antitumor drugs by searching the literature published from January 1992 to June 2021. The regulators of RAS can reduce the cardiotoxicity ，hematological toxicity and peripheral neurotoxicity of antitumor drugs ， and has renal protective effect ；the regulators of RAS combined with other chemotherapy drugs show favorable effects on promoting chemotherapeutic drugs delivery ，improving anti-angiogenesis and bypass activation of targeted drugs ，enhancing tumor immune response of immune checkpoint inhibitors ，so as to improve therapeutic efficacy of antitumor drugs. The combination of RAS regulators with antitumor drugs is expected to reduce the side effects of antitumor drugs ，enhance its efficacy and improve the prognosis of patients.

Advances in Treatment of Non-small Cell Lung Cancer Harboring EGFR Exon 20 Insertion Mutations / 中国肺癌杂志

Epidermal growth factor receptor (EGFR) exon 20 insertion mutations are the third most prevalent activating EGFR mutation in non-small cell lung cancer (NSCLC), accounting for 5%-12% of all EGFR mutations in NSCLC cases. Patients harboring EGFR exon 20 insertion mutations exhibit similar clinical characteristics except for worse prognosis as compared to those with 'classic' EGFR mutations. EGFR exon 20 insertion mutations are considered as a heterogeneous class of alterations that cause different conformational changes in EGFR. The majority of mutations (almost 90% of cases) is positioned in the loop that immediately follows the C-terminal of the C-helix, and the most widely reported subtype of insertion mutations is D770_N771>ASVDN(A767_V769dupASV) with frequency of 21%-28%. NSCLC patients with EGFR exon 20 insertion mutations show primary drug resistance to previously approved EGFR tyrosine kinase inhibitors and are generally insensitive to conventional chemotherapy and immunotherapy. The recently approved targeted drugs Amivantamab and Mobocertinib shift the treatment paradigm for NSCLC patients harboring EGFR exon 20 insertion mutations. There are also several new compounds targeting NSCLC EGFR exon 20 insertion mutations are in development. In this article, we provide a through overview on the treatment development in EGFR exon 20 insertion mutant NSCLC.
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A Real-world Study on the Assessment of Pathological Characteristics and Targeted Therapeutic Effect of Non-small Cell Lung Cancer Patients with Positive Driving Genes and High PD-L1 Expression / 中国肺癌杂志

BACKGROUND@#Targeted therapy for patients with driver genes positive and immunotherapy for patients with driver gene-negative but high programmed death ligand 1 (PD-L1) expression are the standards of first-line treatment for patients with advanced non-small cell lung cancer (NSCLC). The treatment options for patients with driver gene positive and high PD-L1 expression are still worth exploring.@*METHODS@#The characteristics of 315 patients with NSCLC were identified to analyze the clinicopathological characteristics of patients with driver gene positive and high PD-L1 expression, and the efficacy of targeted therapy.@*RESULTS@#Among the 315 patients, the total positive rate of driver genes was 62.2%, and the high PD-L1 expression rate (≥50.0%) was 11.2%. The proportion of patients with driver gene positive and high PD-L1 expression was 10.7%. PD-L1 was highly expressed in patients with epidermal growth factor receptor (EGFR) mutation, KRAS mutation, ALK fusion, BRAF mutation, and MET 14 exon skip mutation, the proportions were 7.8% (11/141), 18.2% (4/22), and 23.1%, (3/13), 50.0% (2/4) and 100.0% (1/1) respectively. EGFR mutation positive with PD-L1 high expression was mainly in patients with stage IV lung adenocarcinoma. KRAS mutation positive with PD-L1 high expression was mainly in patients with a history of smoking. Among them, two patients were followed in detail for targeted therapy, who with ALK fusion-positive and PD-L1 high expression (90.0%), EGFR L858R mutation and PD-L1 high expression (70.0%) respectively. The total OS of the patients was 5 months, 2 months.@*CONCLUSIONS@#The high PD-L1 expression rate in NSCLC patients with different driver gene mutations was variable, which maybe correlated with distinct clinicopathological characteristics. Patients with sensitive mutations and high PD-L1 expression may be less benefit from targeted therapy and have poor prognosis.

Transferrin-functionalized co-delivery microemulsion of β-elemene and celastrol for synergistic anti-colorectal cancer treatment / 中草药

Objective To verify the synergistic effect of transferrin modified β-elemene and celastrol co-loaded microemulsion (Tf-EC-MEs) on anti-colorectal cancer treatment. Methods The optimal mass ratio of β-elemene and celastrol to growth inhibition of Lovo and HT-29 colorectal cancer cells was optimized by MTT staining method in vitro. Tf-EC-MEs was prepared by “mixing-dripping” method, and the preparation and physicochemical properties of the particles were characterized by high performance liquid chromatography (HPLC), laser particle analyzer, and transmission electron microscope. The MTT staining, HPLC-BCA combined method, and Annexin V-PE/7-Aminoactinomycin D (Annexin V-PE/7-AAD) kit were used to investigate the antitumor activity of Tf-EC-MEs in vitro, and its effect on cell uptake, and apoptosis of tumor cells. The tumor-bearing nude mice model was established by subcutaneous injection of Lovo cells, and the tumor growth, weight, and survival time were observed after intravenous injection of β-elemene + celastrol, β-elemene-celastrol co-loaded microemulsion (EC-MEs), and Tf-EC-MEs. Results The combined administration of β-elemene and celastrol (40:1) had significant synergistic effect on the anti-colorectal cancer of Lovo and HT-29 cells. IC50 of β-elemene + celastrol in Lovo and HT-29 cells were (17.5 ± 2.9) and (36.4 ± 3.6) μg/mL, with the CI as 0.89 and 0.96, respectively. IC50 of Tf-EC-MEs in Lovo and HT-29 cells were (11.7 ± 0.6) and (27.4 ± 1.2) μg/mL, with the CI as 0.61 and 0.72 respectively. The 4 h of Lovo uptake of Tf-EC-MEs was 7.2 μg/mg, which was 3.3 times higher than that of β-elemene + celastrol. Tf-EC-MEs induced apoptosis in 59.2% of Lovo cells, which was significantly higher than that in beta-elemene + celastrol and EC-MEs groups. Tf-EC-MEs showed the overwhelming inhibition of growth of Lovo tumor-bearing tumors. The survival rate of Tf-EC-MEs-treated mice was 37.5% at day 60. In Tf-EC-MEs treated group, HE staining sections of tumor tissues showed substantial cell necrosis and the Ki-67 immunohistochemical sections displayed the significant inhibition of proliferation of tumor cells. Conclusion Compared with the combination group (beta-elemene and celastrol) and EC-MEs groups, Tf-EC-MEs has a promising potential in the synergistic anti-colorectal cancer treatment.

Research progress of regulation mechanism of innate immunity in malaria / 中国药理学通报

Malaria is a kind of disease detrimental to human health and plasmodium is a critical pathogen in it. The immunity against foreign antigens including plasmodium could be divided into two categories, namely, adaptive immunity and innate im-munity. Innate immunity induces non-specific immune response, and is composed of monocyte,macrophage,γδT cell,DC,NK, and cytokines etc. Innate immunity cooperates with adaptive im-munity efficiently to protect against malaria. Meanwhile,autoph-agy is not only the cellular degrading process, but also gets in-volved in regulating immune system and defending against plas-modium infection. Therefore, elucidation of corresponding mechanism could provide proof for efficiently controlling and cu-ring malaria,developing related medicine and vaccine,and clin-ical treatment as well. This article reviews the constitution of in-nate immunity in malaria,related regulation mechanism and rel-evant therapeutic targets for it.

Expression and function of c-Myc in tumor / 国际肿瘤学杂志

The proto oncogene c-Myc is expressed in many kinds of organs, and its dysfunction is closely related to the occurrence and prognosis of lymphoma, prostatic cancer, breast cancer and pancreatic cancer.With a large number of studies focus on the expression and function of c-Myc in tumor, the treatment of tumor by targeting c-Myc has made a wealth of progress.

Current status of targeted treatment for advanced renal carcinoma in China / 中国肿瘤临床

Targeted treatment for tumors is based on the molecular biological aspects of a tumor. Identifying tumor-associated mole-cules as targets and then creating molecular preparations based on these targets is the goal of drug treatment and targeted therapy. Treatment for advanced renal carcinoma has evolved since the era of targeted therapy began eleven years ago when sorafenib was ap-proved in China in September, 2006. This article reviews the development of molecular targeted treatment for tumors, discuss the effi-cacy of vascular endothelial growth factor (VEGF) inhibitors for the treatment of advanced renal carcinoma, evaluate the problems aris-ing from clinical experiences, and put forward some suggestions for targeted treatment of advanced renal carcinoma.

Treatment advances in myeloproliferative neoplasms: reports from the 56th American Society of Hematology annual meeting / 白血病·淋巴瘤

Great advances have been made in understanding the pathogenesis,diagnosis,risk stratification and treatment of classic bcr-abl-negative myeloproliferative neoplasms (MPN).This article reviews current situation in the treatment of these MPNs presented in the 56th American Society of Hematology (ASH) annual meeting.

Overview of molecular diagnosis and targeted treatment of tumor / 国际肿瘤学杂志

The occurrence and outcome of cancer is related to the involved gene;Detecting the expres-sion of gene in body by the real-time PCR technology can diagnose and evaluate the prognosis of patients early. Through analyzing the abnormal genes and molecular,designing and studying the targeted drugs can achieve the therapeutic effect of steady,accurate,relentless,at the same time to reduce side effects and to improve the quality of life.

Epstein-Barr Virus in Human Malignancy: A Special Reference to Epstein-Barr Virus associated Gastric Carcinoma / Journal of the Korean Cancer Association, 대한암학회지

Epstein-Bar virus (EBV), a human herpesvirus, establishes a life-long persistent infection in 90~95% of human adult population worldwide. EBV is the etiologic agent of infectious mononucleosis, and EBV is associated with a variety of human malignancy including lymphoma and gastric carcinoma. Recently, EBV has been classified as group 1 carcinogen by the WHO International Agency for Research on Cancer. Evidence is presented which suggests that failures of the EBV-specific immunity may play a role in the pathogenesis of EBV-associated malignancy. At present, the precise mechanisms by which EBV transforms B lymphocytes have been disclosed. Encouragingly, they have had enough success so far to keep them enthusiastic about novel therapeutic trial in the field of EBV-associated lymphoma. However, information on EBV-associated gastric carcinoma is still at dawn. This article reviews EBV biology, immunological response of EBV infection, unique oncogenic property of EBV, peculiarity of EBV-associated gastric carcinoma, and lastly, EBV-targeted therapy and vaccination.

Research advances in sorafenib:a multiple targeted anti-tumor agent / 中国药理学通报

Sorafenib,a novel oral multikinase inhibitor,targts on serine/threonine kinase and tyrosine kinases receptor of the tumor cells and vasculature.So Sorafenib can inhibit the tumor cell proliferation and revascularization.400 mg sorafenib administered twice a day is chosen as the recommended dosage for several phase Ⅰ studies,and it shows broad-spectrum antitumor activity in renal cancer,hepatocellular carcinoma,melanoma and non-small-cell lung cancer(NSCLC)in phase Ⅱ and Ⅲ clinical trials.Now FDA has approved the usage of sorafenib in renal cancer therapy.

Preparation of anti-gastric cancer monoclonal antibody with daunorubicin methotrexate conjugate and its cytotoxiciy to gastric cancer cells / 中国免疫学杂志

It is first time to use dextren T-40 oxidative method to conjugate anti-gastric cancer mono-colonal antibody(McAb)with anti-tumor medicines of daunorubicin(DNR)and methotrexate(MTX)together.Cytotoxicity of conjugates was measured by MTT method and ~3H-TdR incor-poration method respectively.Both sensitivity is similar.The results have showed that this conju-gate exhibited selective cytotoxicity on human gastric cancer cells in vitro.