ABSTRACT
A 54-year-old male was diagnosed with extensive liver metastasis and small nodule metastasis in the lungs from gastric adenocarcinoma [Her-2 (-)]. The patient achieved significant partial response (PR) after chemotherapy combined with anti-angiogenesis therapy but developed progressive disease (PD) after 5 months. Then, the chemotherapeutic and anti-angiogenic drugs were replaced. Meanwhile, the delivery route of some chemotherapeutic drugs was changed, and some chemotherapeutic drugs were given via transcatheter arterial chemoembolization (TACE) to achieve PR, and PD developed after 3 months of remission maintenance. During chemotherapy combined with anti-angiogenesis, the application of programmed cell death-1 (PD-1) inhibitor achieved PR again and maintained for 5 months before disease progression. The progression of the lesions in the left lobe of the liver and the hepatic hilar lymph nodes was significant. Hence, chemotherapy was terminated and gamma stereotactic body radiation therapy (SBRT) was performed on left lobe lesions and hilar lymph nodes. The lesions both inside and outside the radiation field regressed significantly, reaching PR and abscopal effects. The immune-related adverse events (irAEs) occurred, including erythema and black and luster hair. The abscopal effects of lesion reduction in the radiation field and the enhancement of the immune function stimulated by radiation are a highlight of the combination of radiation and immunotherapy. In the end, the patient died of gastrointestinal failure, with overall survival of 18 months.
ABSTRACT
The clinical efficacy, serum tumor markers, and miR-34 expression levels of bronchial artery embolization (BAE) in patients with lung cancer with hemoptysis are investigated. 92 patients with lung cancer hemoptysis treated in our hospital from January 2019 to December 2021 are randomly selected, and 92 patients are randomly divided into the conservative group and the BAE group according to the number table method, with 46 patients in each group. The efficacy, overall survival (OS) rate, coagulation function, hemoptysis volume, serum tumor markers, and miR-34 expression are compared among all groups at different time points. The experimental results show that the BAE treatment can promote the expression of miR-34 and inhibit the expression of tumor markers, so it can improve the efficacy of patients with lung cancer hemoptysis, improve the symptoms of hemoptysis and coagulation function, and prolong the life cycle of patients.
Subject(s)
Lung Neoplasms , MicroRNAs , Biomarkers, Tumor , Bronchial Arteries , Hemoptysis/therapy , Humans , Lung Neoplasms/complications , Lung Neoplasms/therapy , MicroRNAs/genetics , Retrospective StudiesABSTRACT
Deregulated microRNAs (miRNAs) are small noncoding RNAs that are involved in the carcinogenesis of various cancers, including lung cancer. HIF1a has been suggested to be a master regulator of hypoxia-induced cell proliferation. The relationship between HIF1a expression and the progression of non-small cell lung cancer (NSCLC) is not fully understood, and whether HIF1a expression is regulated by miRNAs in this process remains unclear. In this study, we found that the upregulation of HIF1a expression and the reduction in miR-199a levels were highly associated with NSCLC progression. NSCLC cells derived from cancer tissues with low miR-199a levels showed high HIF1a expression and high proliferation capacity. Moreover, HIF1a and glycolysis inhibitors suppress the proliferation of NSCLC cells. MiR-199a overexpression suppressed the hypoxia-induced proliferation of NSCLC cells through targeting elevated HIF1a and blocking the downstream upregulation of PDK1 without affecting AKT activation. Together, these results indicate that downregulation of miR-199a is essential for hypoxia-induced proliferation through derepressing the expression of HIF1a expression and affecting HIF1a mediated glycolytic pathway in NSCLC progression.
Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Cell Hypoxia/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Lung Neoplasms/genetics , MicroRNAs/genetics , Cell Line, Tumor , Cell Proliferation , Glycolysis/genetics , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , MicroRNAs/metabolism , Protein Serine-Threonine Kinases/biosynthesis , Proto-Oncogene Proteins c-akt/metabolism , Pyruvate Dehydrogenase Acetyl-Transferring Kinase , Up-RegulationABSTRACT
The ATR-ATRIP protein kinase complex plays a crucial role in the cellular response to replication stress and DNA damage. Recent studies found that ATR could be activated in response to hypoxia and be involved in hypoxia-induced genetic instability in cancer cells. However, the underlying mechanisms for ATR activation in response to hypoxic stress are still not fully understood. We reported that ATRIP is a direct target of HIF-1. Silencing the expression of HIF-1α in cancer cells by RNA interference abolished hypoxia-induced ATRIP expression. Silencing the expression of ATRIP by RNA interference abolished hypoxia induced ATR activation and CHK1 phosphorylation in cancer cells. Taken together, these data shed novel insights on the mechanism of hypoxia-induced activation of the ATR pathway.
Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Cell Cycle Proteins/genetics , DNA-Binding Proteins/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Protein Serine-Threonine Kinases/genetics , Adaptor Proteins, Signal Transducing/metabolism , Ataxia Telangiectasia Mutated Proteins , Binding Sites/genetics , Blotting, Western , Cell Cycle Proteins/metabolism , Cell Hypoxia , Cell Line , Checkpoint Kinase 1 , Chromatin Immunoprecipitation , DNA-Binding Proteins/metabolism , Gene Expression Regulation, Neoplastic , HEK293 Cells , HeLa Cells , Hep G2 Cells , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , MCF-7 Cells , Neoplasms/genetics , Neoplasms/metabolism , Neoplasms/pathology , Phosphorylation , Promoter Regions, Genetic/genetics , Protein Binding , Protein Kinases/metabolism , Protein Serine-Threonine Kinases/metabolism , RNA Interference , Response Elements/genetics , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
Cytochrome P450 1A1 (CYP1A1), an important phase I xenobiotic metabolizing enzyme, is responsible for metabolizing numerous carcinogens, particularly polycyclic aromatic hydrocarbons. The genetic polymorphism of CYP1A1 at the site of MspI (CYP1A1 MspI) has been implicated in prostate cancer risk, but the results of individual studies remain conflicting and inconclusive. The aim of this meta-analysis was to investigate the association of CYP1A1 MspI polymorphism with prostate cancer risk more precisely. We performed a comprehensive search of the PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases from their inception up to September 20, 2012 for relevant publications. The pooled odds ratios with the corresponding 95% confidence intervals (95% CIs) were calculated to assess the association of CYP1A1 MspI polymorphism with prostate cancer risk. In addition, stratified analyses by ethnicity and sensitivity analyses were conducted for further estimation. Sixteen eligible publications with 6,411 subjects were finally included into the meta-analysis after checking the retrieved papers. Overall, meta-analysis of total studies suggested that individuals carrying the TC genotype and a combined C genotype (CC + TC) were more susceptible to prostate cancer (OR(TC vs. TT) = 1.33, 95% CI 1.10-1.61, P(OR) = 0.004; OR(CC+TC vs. TT) = 1.27, 95% CI 1.05-1.55, P(OR) = 0.016). Stratified analysis of high quality studies also confirmed the significant association (OR(TC vs. TT) = 1.32, 95% CI 1.04-1.67, P(OR) = 0.024; OR(CC+TC vs. TT) = 1.30, 95% CI 1.02-1.66, P(OR) = 0.035). In subgroup analyses by ethnicity, a significant association between the CYP1A1 MspI polymorphism and risk of prostate cancer was found among Asians (OR(TC vs. TT) = 1.44, 95% CI 1.20-1.72, P(OR) < 0.001; OR(CC+TC vs. TT) = 1.33, 95% CI 1.12-1.58, P(OR) = 0.001), but not in Caucasians or mixed populations. The meta-analysis suggests an important role of the CYP1A1 MspI polymorphism in the risk of developing prostate cancer, especially in Asians.
Subject(s)
Cytochrome P-450 CYP1A1/genetics , Genetic Predisposition to Disease , Polymorphism, Genetic , Prostatic Neoplasms/genetics , Alleles , Case-Control Studies , Genotype , Humans , Male , Odds Ratio , Publication BiasABSTRACT
Hepatocellular carcinoma (HCC) is the most common type of liver cancer. HDAC6 is a transcriptional regulator of the histone deacetylase family, subfamily 2. Previous studies have shown that HDAC6 plays critical roles in transcription regulation, cell cycle progression and developmental events. However, its biological roles in the development of HCC remain largely unexplored. In the present study, we found that mRNA and protein levels of HDAC6 were up-regulated in HCC tissues and cell lines. The proinflammatory cytokines, which were up-regulated in the human HCC microenvironment, increased HDAC6 expression through a proximal NF-kappaB binding site on the HDAC6 gene promoter. Furthermore, overexpression of HDAC6 could promote cell proliferation in HCC cell lines. In contrast, HDAC6 knockdown using small interfering RNA inhibited cell proliferation. At the molecular level, we demonstrated that HDAC6 could interact with p53 and attenuate its transcriptional activity through promotion of its degradation. Therefore, our results suggest a previously unknown HDAC6-p53 molecular network controlling HCC development.