ABSTRACT
Immune checkpoint consists of inhibitory and stimulatory molecules. Drugs blocking inhibitory checkpoint programmed cell death receptor-1 (PD-1) and cytotoxic T lymphocyte-associated molecule-4 (CTLA-4) are currently utilized for wide variety of human cancers. Agonists of stimulatory checkpoints such as GITR, OX40, 4-1BB, ICOS, CD40 and STING are undergoing critical clinical trials. Immune checkpoint agonists that affect stimulatory checkpoint molecules develop rapidly, and immune agonist antibodies thus represent an important approach for solid tumor treatments.
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Objective To investigate the expression of m6A methylatransferase ZC3H13 in tissues and peripheral blood of patients with gastric cancer and its application value in gastric cancer. Methods UALCAN and GEPIA databases were used to analyze the expression difference of ZC3H13 in gastric cancer and adjacent normal tissues at transcription level; GEPIA and Kaplan-Meier Plotter databases were used to analyze the correlation between ZC3H13 expression level and OS of gastric cancer patients.ELISA was used to determine the concentration of ZC3H13 in 80 newly-diagnosed gastric cancer patients and 50 healthy controls, and to analyze its relation with clinicopathological data; IHC method was used to detect the expression level of ZC3H13 in 74 cases of cancer tissues and 40 cases of unpaired paracancerous tissues, and to analyze its relation with clinicopathological data. Results The expression of ZC3H13 in gastric cancer tissues was significantly higher than that in adjacent gastric tissues (P < 0.05).The positive rate of ZC3H13 protein in gastric cancer tissues was significantly higher than that in adjacent normal tissues (74.3%vs.52.5%, P < 0.05).Serum ZC3H13 concentration in gastric cancer group was significantly higher than that in healthy control group (P < 0.05).The expression level of ZC3H13 in gastric cancer tissues and peripheral blood was related to gender, differentiation degree, clinical stage and infiltration depth of gastric cancer (P < 0.05).Multivariate analysis showed that ZC3H13 expression was not an independent risk factor for poor prognosis of gastric cancer patients (P > 0.05).The AUC was 0.826(P < 0.05), indicating good diagnostic value.The critical value of serum ZC3H13 protein concentration was 4.87 ng/ml, and the sensitivity and specificity of ZC3H13 in the diagnosis of gastric cancer were 98.8% and 50.0%. Conclusion ZC3H13 is highly-expressed in gastric cancer tissues, and the concentration of ZC3H13 protein in peripheral blood is also significantly increased.ZC3H13 may play an important role in the occurrence and development of gastric cancer, and has certain clinical diagnostic value for gastric cancer.
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Conventional clinical trials of antitumor drugs are conducted at clinical sites. In contrast, without clinical sites or site-less, digital clinical trials can be performed online. Virtual clinical trials analyze the therapeutic response of virtual patients to digital drugs using artificial intelligence and may reduce the costs of trials. Precision oncology trials based on biomarkers can invite more people to join clinical trials and guide the optimal choice of therapeutics for cancer patients. Oncology clinical trials will enter the era of digital, virtual and precision medicine.
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Human nerves promote the initiation of a variety of solid tumor via regulating the stem cells, inducing angiogenesis, interacting immune system and modulating microbiota, and axonogenesis further drives the growth of early cancer. Nerves have emerged as an important component of the tumor microenvironment, and the control of nerves and neural signaling will be used as the novel treatment of human cancers. The article reviews the mechanisms of nerves promoting tumorigenesis.
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Microrobots (from several millimetres down to a few micrometres in all dimensions) are constructed of nanoscale or molecular components and include various types of magneto-aerotactic bacteria microrobots, nanomotors, biohybrid magnetite microrobots, DNA nanorobots, soft-bodied robots and soft matter. Microrobots may enable applications in cargo delivery, targeting cancer, cellular manipulation and killing cancer. Microrobots swarms exhibit a variety of intriguing collective behaviors, and will serve as a functional bio-microrobot system for cancer " subtle therapy" .
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Cancer develops as result of evolution and targeting cancer evolution may be a promising cancer therapeutics. Cancer adaptive therapy is defined as targeting cancer evolution through selective adaption and co-evolution. Adaptive therapy of human cancers provides new insight into the strategies for adaption and integration through reprogramming the functions of vessel, immune, metabolism, microbiota and circadian clock, and facilitating hosts and their cancers evolution as a unit.
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Cyclin-dependent kinase (CDK) inhibitors have been approved for the treatment of ER +/HER2-advanced breast cancer,and preclinical study and clinical trials are under way for multiple solid cancers.CDK4/6 inhibitors have shown good efficacy for human solid cancers,and it's future development direction are biomarkers,drug resistance and combined therapy in the future.
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Immune checkpoint blockades can induce long lasting responses but only in a fraction of patients owing to deficient of antibody as well as the neglect of immune suppressive cells.Next-generation immune checkpoint blockades,including FcγR-binding anti-programmed cell death-1 (PD-1)/PD ligand 1 (PD-L1) antibodies,co-inhibitors of immune checkpoint,small-molecule modulators and antibody-drugs conjugated with PD-1/PD-L1,will overcome the deficiencies of current anti-PD-1/PD-L1 antibodies and will become the direction of immunotherapy in the future.
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The similar mechanism of human cancer and aging means that cancer is the natural result of aging.Mitochondrial replacement, genome editing, telomere synthesis and immune editing can induce cancer cell senescence and resist human aging, which may breach a limit to human lifespan.
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Therapeutic cancer vaccines offer a novel avenue for the development of cancer immunothe rapy.Tumor antigens can induce T cell antitumor immune responses,but lack of tumor-specific antigens has hampered clinical efficacy.Vaccine types include peptide vaccines,dendritic cell vaccines and oncolytic virus vaccines.Personalizing tumor vaccines may provide a new immunotherapeutic strategy to treat cancer.
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Numerous studies support the importance of gut microbiota as environment factors in the development of cancer.The mechanisms that gut microbiota drive certain cancers include impacting immunity,modulating inflammation,inducing DNA damage,producing cancer promoting metabolites and regulating signaling pathway.Microbiome-based therapies provide potential prospects for cancer treatment.
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Objective To determine the relationship between Methylenetetrahydrofolate reductase (MTHFR)(C677T, A1298C and G1793A)polymorphisms and stillbirth.Methods 33 unexplained stillbirth and 582 normal livebirth were col-lected for case-control study from August 2014 to August 2016.The genotyping of C677T,A1298C and G1793A polymor-phisms of the MTHFR gene was tested by using restriction fragment length polymorphism polymerase chain reaction.The relationship between MTHFR polymorphisms and stillbirth susceltibility was analyzed by logistic regression.Results There was no significant difference in the genetype frequencies of A1298C and G1793A of MTHFR polymorphisms between case and control.But there was significant difference in the genetype frequencies of C677T between case and control (CT:P=0.02,χ2=3.67;TT:P=0.02,χ2=3.65).Heterozygous CT and homozygous TT would be high risk factors of stillbirth. C677T was found in one (14.3%)of the cases with early stillbirth and in three (11.5%)of the cases with late stillbirth, having no significant difference.Twin pregnancy and MTHFR C677T increased the risk 8-fold (P<0.001,χ2=13.28)and 3.4(P=0.02,χ2=3.65)for stillbirth,respectively.Conclusion MTHFR C677T polymorphism is high risk factors associ-ated with the susceptibility of stillbirth.MTHFR C677T may be used as a prognostic marker of pregnancy cases predisposed to preterm delivery.
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Precision chemotherapy is the prospective direction of cancer chemotherapy,which involves the selection of the effective chemotherapy regimens based on the chemotherapy-related genes.Chemotherapyrelated genes include DNA repair genes,drug metabolism enzymes,drug transporters,apoptosis-related genes and cancer-related genes.These genes can predict the response and toxicity of chemotherapy,and determine the clinical outcome.
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Holistic therapy of cancer is helping to design more effective cancer therapies by combination individual properties (such as performance status,histological types and molecular types) and novel clinical results.Holistic therapy in oncology reflects individual,precision,whole course and real-time treatment strategy,and includes sequential,synchronizational,interval and metronomic therapy models.Holistic therapy in oncology would be help in selecting appropriate choices for patients and clinic doctors.
ABSTRACT
Holistic therapy of cancer is helping to design more effective cancer therapies by combination individual properties (such as performance status,histological types and molecular types) and novel clinical results.Holistic therapy in oncology reflects individual,precision,whole course and real-time treatment strategy,and includes sequential,synchronizational,interval and metronomic therapy models.Holistic therapy in oncology would be help in selecting appropriate choices for patients and clinic doctors.
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Cancers evolution is a process of clonal selection,cell competition and clonal expansion. Cancers evolution includes cancer memory,heterogeneity,resistance,transformation and adaption et al.This evolution enables cancer cells to adapt to any hostile environment and to survive.An understanding of cancers evolution will provide a theoretical guidance for the implementation of the precision therapy.
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Metronomic chemotherapy involves antiangiogenic processes that help host to fight against cancer by using continuous low dose drugs.Metronomic chemotherapy can be an effective treatment option for patients with head and neck carcinoma,breast cancer,gastrointestinal cancer,ovarian and prostate cancer. Metronomic chemotherapy also involves multiple mechanisms that include antiangiogenesis,immune stimulation and direct tumor cell targeting effects.We need to carefully evaluate the clinical effects of combination chemo-therapies that incorporate the other treatment schedules.
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With the coming era of targeted therapy,novel criteria such as the modified response evalu-ation criteria in solid tumors (RECIST),positron emission tomography response criteria in solid tumors (PETRCIST),Choi criteria and immune-related response criteria have been proposed as standardized methods to assess therapeutic response.Biomarkers and circulating tumor cells may be considered suitable for the evalu-ation of response.These criteria may be useful for the evaluation of therapeutic response to tumors.
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Cancer is like a planet , which consists of a heterogeneous mixture of distinct cancer cells . Cancer planet includes four varying levels:niche,surface,middle and core .Cancer architecture based system ther-apies are starting to be exploited for the development of novel strategies to war for cancer .
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Cancer precision therapeutics is defined as a therapy strategy based on molecular profiles and classifiers generated from high-throughput molecular assays.Precision therapeutics in oncology is becoming reality thanks to the next-generation sequencing and cancer targeted agents.Selecting optimal targets,identif-ying appropriate combinations of therapies and real-time monitoring of tumor evolution may be critical for practi-cing precision therapeutics.