Mortality Of Malignant Tumors Research Articles

Chinese expert consensus on diagnosis and treatment of pulmonary nodules(2024)

Lung cancer is the leading cause of the incidence and mortality of malignant tumors in China. The 5-year survival rate released for China in 2018 was 19.7%. The 5-year survival rate for stage Ⅰ patients is 77%-92%. Early diagnosis and treatment of lung cancer are key to improving the 5-year overall survival rate and prognosis of lung cancer patients. Therefore, experts from the Academic Group of Lung Cancer in Chinese Thoracic Society and Chinese Alliance Against Lung Cancer Expert Group formulated the Chinese Expert Consensus on the Diagnosis and Treatment of Lung Nodules in 2015 to standardize the diagnosis and treatment of lung nodules. In 2018, this consensus was updated to formulate the Chinese Expert Consensus on Diagnosis and Treatment of Lung Nodules (2018 edition), and widely applied in multiple branch centers of Chinese Alliance Against Lung Cancer, proposing the Intelligent Treatment of Million Early Lung Cancer Project. Based on applied experience of the expert consensus in recent years, with reference to the latest evidence has been updated, Chinese Expert Consensus on Diagnosis and Treatment of Lung Nodules (2024 edition) was formulated. The updated content of this consensus mainly includes the following aspects: (1) Define the screening age of high-risk lung cancer populations in China based on the national conditions; (2) Propose definition of "difficult-to-determine pulmonary nodules" to avoid delaying the diagnosis and treatment; (3) Evaluate pulmonary nodules assisted by artificial intelligence (AI) imaging-assisted diagnostic system and propose human-machine MDT to avoid the limitations of AI; (4) Evaluate pulmonary nodules by routine and individualized evaluations for different populations, and make recommendations based on evidence-based management guidelines for different types and sizes of pulmonary nodules. In the updated consensus, 18 consensus points were recommended as a reference for clinical management of pulmonary nodules to improve the 5-year overall survival rate and the prognosis of lung cancer in China.

Comparison of the latest cancer statistics, cancer epidemic trends and determinants between China and the United States

Objective: To provide supports for the cancer prevention and control strategies in China by comparing the disease burden, epidemic trends, 5-year relative survival rate and major determinants of common cancers between China and the United States. Methods: A descriptive secondary analysis was conducted using data extracted from the GLOBOCAN database, the Surveillance, Epidemiology, and End Results database, Global Burden of disease 2019 database, and previous studies. The main indicators included the cases of malignant tumors in different sites, the cases of deaths, the age-standardized incidence (world standard incidence) and mortality (world standard mortality), the 5-year relative survival rate, and population attributable fraction (PAF). Results: In 2022, an estimated 4.825 million new cases and 2.574 million deaths of malignant neoplasms in China. The world standard incidence rate (201.6/100 000) in China was lower than that in the United States (367.0/100 000), and the world standard mortality rate (96.5/100 000) was higher than that in the United States (82.3/100 000). Lung cancer ranked first in the disease burden of malignant tumors in China, the new cases and deaths accounted for 22.0% and 28.5% of all malignant tumors, respectively. The top three malignant tumors in China were breast cancer (11.5%), prostate cancer (9.7%) and lung cancer (9.5%), which were also among the top five causes of death. However, the second to fifth leading causes of death from malignant tumors in China were digestive system tumors (liver cancer 12.3%, stomach cancer 10.1%, colorectal cancer 9.3%, and esophageal cancer 7.3%). From 2000 to 2018, the world standard incidence of malignant tumors showed an increasing trend and the world standard mortality of malignant tumors showed a decreasing trend in China, while the world standard incidence and mortality of malignant tumors in the United States showed a significant decreasing trend after 2000. The incidence of breast cancer, colorectal cancer and thyroid cancer increased rapidly in China, while the incidence and mortality of stomach cancer, liver cancer and esophageal cancer decreased, but they still had a heavy disease burden. From 2003 to 2015, the overall 5-year relative survival rate of malignant tumors increased from 30.9% to 40.5% in China. However, with the exception of esophageal cancer, the 5-year relative survival rates of other major malignant tumors were lower than those in the United States. In 2019, the PAF of malignant tumors death attributable to potential modifiable risk factors was 48.3% in China, which was similar to the United States (49.8%). Of these, smoking was the most important attributable risk factor, and the PAF was more than 30% both in China and the United States. In addition, about 18.8% of malignant tumors were caused by preventable chronic infections, such as hepatitis B virus and Helicobacter pylori, while less than 4% of malignant tumors in the United States were caused by infection. Conclusions: China has made great progress in the prevention and treatment of malignant tumors, but it still faces a serious disease burden. The cancer spectrum is changing from developing countries to developed countries. We should pay attention to modifiable factors, take comprehensive measures, and prevent cancer scientifically.

The influence of meteorological factors and total malignant tumor health risk in Wuhu city in the context of climate change

With the increasing severity of the malignant tumors situation worldwide, the impacts of climate on them are receiving increasing attention. In this study, for the first time, all-malignant tumors were used as the dependent variable and absolute humidity (AH) was innovatively introduced into the independent variable to investigate the relationship between all-malignant tumors and meteorological factors. A total of 42,188 cases of malignant tumor deaths and meteorological factors in Wuhu City were collected over a 7-year (2014–2020) period. The analysis method combines distributed lagged nonlinear modeling (DLNM) as well as generalized additive modeling (GAM), with prior pre-analysis using structural equation modeling (SEM). The results showed that AH, temperature mean (T mean) and diurnal temperature range (DTR) all increased the malignant tumors mortality risk. Exposure to low and exceedingly low AH increases the malignant tumors mortality risk with maximum RR values of 1.008 (95% CI: 1.001, 1.015, lag 3) and 1.016 (95% CI: 1.001, 1.032, lag 1), respectively. In addition, low and exceedingly low T mean exposures also increased the risk of malignant tumors mortality, the maximum RR was 1.020 (95% CI: 1.006, 1.034) for low T mean and 1.035 (95% CI: 1.014, 1.058) for exceedingly low T mean. As for DTR, all four levels (exceedingly low, low, high, exceedingly high, from low to high) of exposure increased the risk of death from malignant tumors, from exceedingly low to exceedingly high maximum RR values of 1.018 (95% CI: 1.004, 1.032), 1.011 (95% CI: 1.005, 1.017), 1.006 (95% CI: 1.001, 1.012) and 1.019 (95% CI: 1.007, 1.031), respectively. The results of the stratified analysis suggested that female appear to be more sensitive to humidity, while male require additional attention to reduce exposure to high level of DTR.

Low-dimensional nanomaterials as an emerging platform for cancer diagnosis and therapy.

The burden of cancer is increasing, being widely recognized as one of the main reasons for deaths among humans. Despite the tremendous efforts that have been made worldwide to stem the progression and metastasis of cancer, morbidity and mortality in malignant tumors have been clearly rising and threatening human health. In recent years, nanomedicine has come to occupy an increasingly important position in precision oncotherapy, which improves the diagnosis, treatment, and long-term prognosis of cancer. In particular, LDNs with distinctive physicochemical capabilities have provided great potential for advanced biomedical applications, attributed to their large surface area, abundant surface binding sites, and good cellular permeation properties. In addition, LDNs can integrate CT/MR/US/PAI and PTT/PDT/CDT/NDDS into a multimodal theranostic nanoplatform, enabling targeted therapy and efficacy assessments for cancer. This review attempts to concisely summarize the classification and major properties of LDNs. Simultaneously, we particularly emphasize their applications in the imaging, diagnosis, and treatment of cancerous diseases.

Chinese expert consensus on diagnosis of early lung cancer (2023 Edition)

Lung cancer is the leading cause of the incidence and mortality of malignant tumors in our country, seriously endangering people's lives and health. The treatment of lung cancer has made great progress in the past 10 years, and the 5-year survival rate of lung cancer in China has also increased from 16.1% to 19.7%, but about 75% of patients are still in advanced stages of lung cancer at the time of diagnosis, missing the best time for radical surgery. Early diagnosis can significantly improve the prognosis and survival of lung cancer patients. From the 5-year survival rate of lung cancer patients, it can be seen that the 5-year survival rate of stage Ⅰ patients was 77%-92%, while that of stage ⅢA-ⅣA patients was only 10%-36%, and there was a significant difference in the 5-year survival rate. Studies have shown that early-diagnosed and completely resected lung adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) have 5-year disease-specific survival rates of 100% and 100%, respectively. Early diagnosis is the key to improving the prognosis of lung cancer. In order to further improve the level of early lung cancer diagnosis in China, especially the standardization in the diagnosis and evaluation of pulmonary nodules and early lung cancer, experts from the Lung Cancer Group of Chinese Thoracic Society formulated the "Chinese Expert Consensus on Diagnosis of Early Lung Cancer (2023 Edition)", on the basis of the actual situation in the field of diagnosis and treatment, with reference to the latest research data and relevant guidelines at home and abroad. Consensus on the application of artificial intelligence, big data and robotics, the Internet of Things and multidisciplinary cooperation in the diagnosis of early lung cancer, the management of pulmonary nodules and follow-up strategies for suspected early lung cancer, etc., were respectively recommended to provide references for clinicians in the diagnosis of early lung cancer, in order to further promote the early diagnosis of lung cancer in China.

Mechanism of PDZK1 in Hepatocellular Carcinoma Complicated with Hyperuricemia.

Hepatocellular carcinoma (HCC) is a kind of primary liver cancer that accounts for more than 90% of primary hepatocellular carcinomas. Hyperuricemia is closely related to the development, recurrence, metastasis, and prognosis of cancer. Previous studies have proved that the serum uric acid level can increase the incidence rate and mortality of malignant tumors. However, the specific pathogenesis remains unstudied. RT-qPCR analysis showed that the mRNA expression of PDZK1 and ABCG2 increased significantly after HCC cells were exposed to different concentrations of soluble uric acid (2.5, 5, 10, 20 mg/dl) for 24 hours. Then, in HCC shRNAs, PDZK1, or over expression PDZK1 were used. CCK8, wound healing, and Transwell assay showed that PDZK1 regulates cell proliferation, invasion, and migration. Flow cytometry results revealed that PDZK1 affects cell apoptosis. Western blot results show that PDZK1 affects the STAT3/C-myc pathway. Then, in vivo tumorigenesis, allopurinol maybe an effective drug to advance: the prognosis of HCC. In our study, RT-qPCR analysis showed that the mRNA expression of PDZK1 and ABCG2 increased significantly after different concentrations of soluble uric acid in HCC. Then, PDZK1 affects the proliferation, migration, and apoptosis of HCC through the STAT3/C-myc pathway. Hyperuricemia response affects the expression of PDZK1; PDZK1 affects the proliferation, migration, and apoptosis through the STAT3/C-myc pathway in hepatocellular carcinoma. It is suggested that PDZK1 maybe closely related to the occurrence, development, and prognosis of HCC and allopurinol maybe have potential anticancer effects.

Nanomedicine-Enabled/Augmented Cell Pyroptosis for Efficient Tumor Nanotherapy.

The terrible morbidity and mortality of malignant tumors urgently require innovative therapeutics, especially for apoptosis-resistant tumors. Pyroptosis, a pro-inflammatory form of programmed cell death (PCD), is featured with pore formation in plasma membrane, cell swelling with giant bubbles, and leakage of cytoplasmic pro-inflammatory cytokines, which can remodel the tumor immune microenvironment by stimulating a "cold" tumor microenvironment to be an immunogenic "hot" tumor microenvironment, and consequently augment the therapeutic efficiency of malignant tumors. Benefiting from current advances in nanotechnology, nanomedicine is extensively applied to potentiate, enable, and augment pyroptosis for enhancing cancer-therapeutic efficacy and specificity. This review provides a concentrated summary and discussion of the most recent progress achieved in this emerging field, highlighting the nanomedicine-enabled/augmented specific pyroptosis strategy for favoring the construction of next-generation nanomedicines to efficiently induce PCD. It is highly expected that the further clinical translation of nanomedicine can be accelerated by inducing pyroptotic cell death based on bioactive nanomedicines.

Targeting TMEM88 as an Attractive Therapeutic Strategy in Malignant Tumors.

According to authoritative surveys, the overall morbidity and mortality of malignant tumors show an upward trend, and it is predicted that this trend will not be well contained in the upcoming new period. Since the influencing factors, pathogenesis, and progression characteristics of malignant tumors have not been fully elucidated, the existing treatment strategies, mainly including surgical resection, ablation therapy and chemotherapy, cannot achieve satisfactory results. Therefore, exploring potential therapeutic targets and clarifying their functions and mechanisms in continuous research and practice will provide new ideas and possibilities for the treatment of malignant tumors. Recently, a double-transmembrane protein named transmembrane protein 88 (TMEM88) was reported to regulate changes in downstream effectors by mediating different signaling pathways and was confirmed to be widely involved in cell proliferation, differentiation, apoptosis and tumor progression. At present, abnormal changes in TMEM88 have been found in breast cancer, ovarian cancer, lung cancer, thyroid cancer and other malignant tumors, which has also attracted the attention of tumor research and attempted to clarify its function and mechanism. However, due to the lack of systematic generalization, comprehensive and detailed research results have not been comprehensively summarized. In view of this, this article will describe in detail the changes in TMEM88 in the occurrence and development of malignant tumors, comprehensively summarize the corresponding molecular mechanisms, and explore the potential of targeting TMEM88 in the treatment of malignant tumors to provide valuable candidate targets and promising intervention strategies for the diagnosis and cure of malignant tumors.

Trends of cancer mortality in Xi'an City, China: 2005-2020.

Describe and predict the malignant tumor deaths in Xi'an so as to provide evidence for the government to formulate the prevention and treatment plans. Overall malignant tumor death in Xi'an in the past 16years was described. The multi-decrease life table was used to calculate cumulative mortality risk by cause and life expectancy reduction years by cause of malignant tumors in 2020. The join point regression models were used to analyze the change trend of standard mortality of malignant tumors in Xi'an from 2005 to 2020. The appropriate gray models were selected to predict the death of malignant tumors in Xi'an in the next decade. The mortality of total malignant tumors in Xi'an showed that men are higher than women and the elderly are higher than other groups. As for 2020, lung cancer had the highest risk of death for both men and women, while leukemia had the highest life expectancy reduction years by cause. From 2005 to 2020, standardized mortality of majority malignant tumors showed downward trends, which were particularly obvious in recent years. The prediction results of several major malignant tumors showed that in the next decade, the mortality of most malignant tumors had downward trends, but combined with the increase of population in the future, the number of malignant tumor deaths in Xi'an will continue to increase. Malignant tumors in Xi'an have decreasing mortality trends in recent years, and effective measures to prevent and treat tumors should be strengthened in the future.

Synthesis and characterization of berberine-loaded chitosan nanoparticles for the protection of urethane-induced lung cancer

Lung cancer is one of the most common types of malignant tumors of the respiratory system and has the highest rates of incidence and mortality of malignant tumors. This study aimed to synthesize and characterize berberine-loaded chitosan nanoparticles (BBR-COSNPs) and to evaluate their protective effects against urethane-induced lung cancer. Forty male albino mice were divided into four groups, with the first serving as a negative control and the other three groups were injected intraperitoneally with urethane (1 mg/kg b.w) each other day for 1 week then group 2 was served as a positive control, however, groups 3 and 4 were treated orally with a daily dose of BBR or BBR-COSNPs (75 mg/kg b.w) for 10 consecutive weeks. Blood and lung tissue samples are collected for laboratory assay. The BBR-COSNPs were spherical, with an average particle size of 45.56 nm and zeta potential of 39.82 1.82 mV. The in vivo data demonstrated that mice given urethane alone had a significant increase in MDA, NO, NF-κB level, HIF1-α, and COX-2-positive expression in the lung tissue and serum VEGFR2, ALT, AST, urea, and creatinine accompanied with a significant decrease in GSH, SOD, caspase 9 in the lung tissue and serum BAX. Co-treatment with BBR-COSNPs suppressed lung cancer growth and promoted apoptosis by modulating serum BAX and lung caspase 9 gene expressions. In addition, BBR-COSNPs inhibited tumor angiogenesis by reduction in levels of serum VEGFR2 and lung HIF 1 gene expression. It is possible to conclude that BBR-COSNPs can be used in oral administration formulations for lunganticancer therapy.

Spatial and temporal distribution and influencing factor analysis of the malignant tumor mortality rate around the mining area.

Mining activities can threaten residents' health even lives. Integrating spatial empirical Bayesian smoothing, joinpoint regression and spatiotemporal scanning methods, we analyzed aggregations and possible factors of four tumor mortality rates at township and village scales from 2012 to 2016 in Suxian district of Hunan Province, China. Results indicate: (1) Mortality rates were ranked: lung cancer > liver cancer > gastric cancer > colorectal cancer. (2) Lung cancer had a higher five-year mortality rate in the middle; relative risk (RR) of death from lung cancer from 2012 to 2015 in Xujiadong Village was 7.48. Liver cancer had a higher five-year mortality rate in the Middle West; RR in areas centered on Nanta Street with a radius of 9.87km from 2015 to 2016, was 1.83. Gastric cancer had a higher five-year mortality rate in the east; RR in Xujiadong Village from 2012 to 2014 was 6.9. Five-year mortality rate of colorectal cancer was higher in the northwest; RR in regions centered on Huangcao Village with a radius of 12.11km in 2016, was 2.88. (3) Pollution from ore mining and smelting, heavy metal and non-metallic, and mine transportation were the main possible factors. This research provides a method reference for studying spatiotemporal patterns of disease in China even the world.

Circular RNA-UBE2D2 accelerates the proliferation and metastasis of non-small cell lung cancer cells via modulating microRNA-376a-3p/Eukaryotic Translation Initiation Factor 4γ2 axis

ABSTRACT Non-small cell lung cancer (NSCLC) ranks first in the morbidity and mortality of malignant tumors in China. As reported, circular RNAs (circRNAs) are emerged in the progress of NSCLC. The study was to figure out the potential mechanism of circ-UBE2D2 in the progression of NSCLC. First, plasmid vectors intervening circ-UBE2D2, microRNA (miR)-376a-3p or Eukaryotic Translation Initiation Factor 4γ2 (EIF4G2) expression were transfected into NSCLC cells, and the expression of circ-UBE2D2, miR-376a-3p and EIF4G2 was detected by reverse transcription quantitative polymerase chain reaction or Western blot. Then, cell proliferation was detected by Cell counting kit-8 assay and plate cloning. Cell apoptosis was tested by flow cytometry. Plate scratches and Transwell were used to detect cell migration and invasion. Finally, the binding sites of circRNA UBE2D2, EIF4G2 and miR-376a-3p were verified by bioinformatics website starBase analysis and dual luciferase reporter gene assay. The results manifested the up-regulation of circ-UBE2D2 expression in NSCLC tissues and cells. Circ-UBE2D2 promoted the proliferation, migration and invasion, but repressed apoptosis of NSCLC cells. Interestingly, circ-UBE2D2 directly targeted miR-376a-3p and up-regulated miR-376a-3p restrained proliferation, migration and invasion, but accelerated apoptosis of NSCLC cells. More importantly, EIF4G2 was the target of miR-376a-3p, and overexpression of EIF4G2 reversed the effects of circ-UBE2D2 downregulation on proliferation, migration, invasion and apoptosis of NSCLC cells. These results suggest that circ-UBE2D2 promotes the proliferation, migration and invasion but restrains apoptosis of lung cancer cells by regulating miR-376a-3p/EIF4G2 axis.

Deduction of CDC42EP3 suppress development and progression of osteosarcoma

BackgroundOsteosarcoma is a disease with high mortality of malignant tumors in children and adolescents. CDC42 effector protein 3 (CDC42EP3) has been reported to be associated with human cancer cell progression. This study aimed to investigate the biological function and preliminary molecular mechanism of CDC42EP3 in osteosarcoma. MethodsCDC42EP3 expression in osteosarcoma was analyzed by immunohistochemical (IHC) staining. Secondly, the biological effects of CDC42EP3 in osteosarcoma cells was determined by loss/gain-of-function assays in vitro and in vivo. ResultsCDC42EP3 expression was higher in osteosarcoma tissue than in noncancerous tissue. The expression of CDC42EP3 was positively correlated with age, pathological stage and grade of patients with osteosarcoma. Furthermore, downregulation of CDC42EP3 suppressed tumor progression by inhibiting proliferation, migration and inducing apoptosis in vivo. Importantly, knockdown of CDC42EP3 reduced the expression of interstitial markers (N-cadherin, Vimentin and Snail) and increased the expression of epithelial markers (E-cadherin). In addition, CDC42EP3 knockdown downregulated PI3K and reduced the phosphorylation levels of AKT and mTOR. The mice xenograft model further confirmed that CDC42EP3 knockdown inhibited osteosarcoma growth in vitro. ConclusionsIn summary, these findings highlighted the significance of CDC42EP3 in tumor progression, which implicated CDC42EP3 as a promising candidate molecular target for osteosarcoma therapy.

Retracted] Meta‐Analysis of the Main Components of Nanophotodynamics Combined with Traditional Chinese Medicine in the Treatment of Tumors

At present, cancer has become one of the main reasons that affect people’s life and health. With the development of nanomaterials and nanotechnology, tumor phototherapy such as photodynamic therapy, photothermal therapy, and combination therapy has been developed rapidly. Based on this, this paper proposes to take gastric cancer, esophageal cancer, liver cancer, intestinal cancer, and pancreatic cancer as the starting point and apply the methods of network meta‐analysis to comprehensively carry out the horizontal comprehensive evaluation of the efficacy and safety of traditional Chinese medicine injections. It is hoped that this article can provide high‐quality evidence‐based medicine for clinical decision‐making and promote clinical rational drug use. The purpose of this paper is to study the meta‐analysis of the main components of tumor treatment with nanophotodynamics combined with traditional Chinese medicine. The experimental results in this paper show that non‐small‐cell lung cancer has the largest number of evaluations, with 77 evaluations, accounting for 38.5% of the total frequency of tumor types. This may be related to the fact that lung cancer ranks first in the morbidity and mortality of malignant tumors. It is followed by the evaluation times of liver cancer and gastric cancer, which were 29 times and 25 times, respectively, accounting for 14.5% and 12.5% of the total frequency of tumor types. The therapeutic effect of SM‐NP light therapy group on tumor was significantly higher than that of free Ce6 light therapy group, and its destruction and killing effect on tumor tissue was greater.

County-based demographics, patterns of treatment seeking, and disease burden for malignant tumor patients in China.

The mortality of malignant tumors in rural areas of China in 2015 was significantly higher than that in city areas (213.6 per 100,000 vs. 191.5 per 100,000), bringing huge economic pressure to individuals and the local community. The comprehensive reform of county-level public hospitals in Yun County has helped patients with critical disease receive appropriate treatment. Therefore, an analysis focused on the epidemiology and disease burden of malignant tumors in Yun County could provide guidance for administrators and health practitioners in other counties. This retrospective database study extracted data from the Yun County medical community (including two higher level hospitals: Yun County People's Hospital and Yun County Chinese Medicine Hospital, and 13 township central hospitals) from 1st Jul 2017 to 30th Aug 2020. Patients diagnosed as having a malignant tumor were enrolled and those with abnormal key baseline information were excluded. The epidemiology and disease burden for malignant tumor patients were assessed. A total of 3,792 patients were enrolled, and the most prevalent cancer in 2018 was thyroid (35.4 patients/100,000) and in 2019 this was lung cancer (30.6 patients/100,000). The mean outpatient visits per person for all-cause and tumor-specific visits were 9.99 and 3.94 visits across 2018 and 2019, respectively, and the mean inpatient visits per person in both years were the same at 2.56 visits. Total costs were 14.471 and 20.29 million in 2018 and 2019, respectively, and 71.7% and 73.0% of the total cost were covered by medical insurance over the 2 years. The medical environment has improved since medical system reform commenced in 2019 in Yun County, and medical insurance has decreased the disease burden for patients and their families significantly.

Сlinical and morphological case of cervical cancer due to HIV-associated infection

Cervical cancer ranks second in the structure of mortality of malignant tumors of the female reproductive system. Of particular interest is cervical cancer in patients with HIV infection, which develops more rapidly than in HIV-negative women. In this regard, the purpose of our study was to analyze the clinical and morphological case of the development of cervical cancer with HIV infection and to describe the features of metastasis in a young patient.Materials and methods. A postmortem examination was carried out, the material of the accompanying documentation (case history, outpatient card) was studied, a histological examination of the material was carried out (staining with hematoxylin and eosin, immunohistochemical examination for CK5/14, p16, p63).Research results. In a young patient (41 years old), HIV-infected, the cervix is revealed with destructive changes, ulceration, with signs of infiltrative growth, with the growth of the tumor structure into the surrounding tissues. Squamous cell non-keratinizing cancer of the cervix of a moderate degree of differentiation was histologically exposed. In the analyzes — CD4+ lymphocytes 18 cells/ml. The peculiarity and rarity of the presented clinical and morphological case is that against the background of the aggressive course of cervical cancer, there is an absence of characteristic metastases, there is a pronounced infiltrating growth and germination of atypical cells into the surrounding tissues, with the development of severe complications.

The landscape of germline mutations and the relationship with tumor mutation burden in Chinese patients with lung cancer.

10522 Background: Lung cancer is one of the most common types of cancer, ranking the first in the incidence and mortality of malignant tumors in the world and China. Although studies have been reported that genetic susceptibility to lung cancer is associated with certain germline mutations, the relationship between lung cancer risk and inherited genetic factors remains relatively elusive. However, the effect of germline mutation on TMB in lung cancer has not been explored. Herein, DNA genomic profiling was performed through NGS with a 539-gene panel to explore the germline mutations and the relationship with TMB in Chinese patients with lung cancer. Methods: We retrospectively analyzed the germline mutations through a comprehensive 539-gene profiling of 3541 Chinese patients with lung cancer. 539-gene panel contained germline mutations in 90 hereditary tumor-associated genes. We screened out the pathogenic and likely pathogenic germline mutations according to the standards and guidelines for the interpretation of sequence variants of The American College of Medical Genetics and Genomics (ACMG), and picked out there is no records in Clinvar database and no literature report. TMB of tissue or blood ctDNA in 3541 patients were further analyzed in with pathogenic mutations (P group), with likely pathogenic mutations (LP group), and no germline mutations group (Non-P group). The difference in TMB was analyzed via the Wilcoxon sign test. Results: In 3541 patients with lung cancer, 177 (4.999%) patients were identified harboring pathogenic or likely pathogenic germline mutations, in which 78 P group and 99 LP group, the rest 3364 were Non-P group. The highest prevalence of germline mutation was found in BRCA2 (0.565%), ATM (0.339%), MUTYH (0.282%), and BRCA1 (0.254%). In 177 patients with pathogenic or likely pathogenic germline mutations, 67 mutations were recorded as UNK (unknow) in Clinvar database and no literature report. The media TMB of tissue in P group, LP group and Non-P group were 5.149, 5.535 and 5.547 respectively. The media TMB of blood ctDNA in P group, LP group and Non-P group were 4.257, 3.945 and 4.483 respectively. There was no statistical difference in TMB between P and Non-P groups (tissue p = 0.98; ctDNA p = 0.5). Conclusions: In our study, we firstly identified 67 novel germline mutations and studied on the relationship between germline mutations and TMB in lung cancer, which expanded the understanding of germline mutations.

Teaching new tricks to old dogs: A review of drug repositioning of disulfiram for cancer nanomedicine

AbstractThe increasing incidence and mortality of malignant tumors have required the development of diversified innovative therapies. Compared with the new therapeutic molecule invention, it is a more economical and efficient way to reposition old drugs that have been marketed or in clinical trials for tumor treatment. Studies have been carried out for repositioning the old approval drugs that are widely applied clinically with reliable biosafety and effectiveness evidence, including aspirin, artemisinin (and its derivatives, eg, dihydroartemisinin), metformin, and disulfiram (DSF). In addition to the approved pharmacological activity, these old drugs exhibited broad tumor‐suppressive effects. This review summarizes the drug repositioning strategy of DSF through nanotechnology and outlines the DSF nano‐formulations for cancer targeting delivery and therapy.

Unravelling the Role of LncRNA WT1-AS/miR-206/NAMPT Axis as Prognostic Biomarkers in Lung Adenocarcinoma.

Lung cancer is the world’s highest morbidity and mortality of malignant tumors, with lung adenocarcinoma (LUAD) as a major subtype. The competitive endogenous RNA (ceRNA) regulative network provides opportunities to understand the relationships among different molecules, as well as the regulative mechanisms among them in order to investigate the whole transcriptome landscape in cancer pathology. We designed this work to explore the role of a key oncogene, MYC, in the pathogenesis of LUAD, and this study aims to identify important long noncoding RNA (lncRNA)-microRNA (miRNA)- transcription factor (TF) interactions in non-small cell lung cancer (NSCLC) using a bioinformatics analysis. The Cancer Genome Atlas (TCGA) database, containing mRNA expression data of NSCLC, was used to determine the deferentially expressed genes (DEGs), and the ceRNA network was composed of WT1-AS, miR-206, and nicotinamide phosphoribosyltransferase (NAMPT) bashing on the MYC expression level. The Kaplan–Meier univariate survival analysis showed that these components may be closely related prognostic biomarkers and will become new ideas for NSCLC treatment. Moreover, the high expression of WT1-AS and NAMPT and low expression of miR-206 were associated with a shortened survival in NSCLC patients, which provided a survival advantage. In summary, the current study constructing a ceRNA-based WT1-AS/miR-206/NAMPT axis might be a novel important prognostic factor associated with the diagnosis and prognosis of LUAD.

Estimation of Dose-Rate Effectiveness Factor for Malignant Tumor Mortality: Joint Analysis of Mouse Data Exposed to Chronic and Acute Radiation

Uncertainties due to confounding factors in epidemiological studies have limited our knowledge of the effects of low-dose-rate chronic exposure on human health. Animal experiments, wherein each subject is considered to be nearly identical, can complement the limitations of epidemiological studies. Therefore, we conducted a joint analysis of previously published cancer mortality data in B6C3F1 female mice chronically and acutely irradiated with 137Cs γ rays to estimate the dose-rate effectiveness factor. In the chronically irradiated animal experiment conducted by the Institute for Environmental Sciences, mice received irradiation at dose rates of 0.05, 1.1 or 21 mGy per day for 400 days from 8 weeks of age. For the acutely irradiated animal experiment conducted by the National Institute of Radiological Sciences, mice received irradiation at 35, 105, 240 or 365 days of age with 1.9, 3.8 or 5.9 Gy at a dose rate of 0.98 Gy per min. Because the preliminary analyses suggested that the risk was dependent on the age at exposure, a model was applied that considered risk differences depending on this factor. The model analysis revealed a three-fold, significantly decreased risk per Gy in mice exposed to 21 mGy per day compared to that in acutely irradiated mice. This resulted in a dose-rate effectiveness factor larger than that reported previously.