Occurrence Of Cancer Research Articles

Pirfenidone and risk of lung cancer development in IPF: a nationwide population-based study.

Idiopathic pulmonary fibrosis (IPF) carries a high risk of lung cancer, but the effect of pirfenidone on lung cancer development remains uncertain. We investigated the association between pirfenidone use and lung cancer development in patients with IPF. We included 10 084 patients with IPF from the national claims database. Propensity score analysis with inverse probability of treatment weighting (IPTW) and landmark analyses were employed to evaluate lung cancer occurrence according to pirfenidone use. The association was evaluated using Cox regression models adjusted for clinical and socioeconomic variables. A single-center IPF clinical cohort (n=941) was used for validating the findings. The mean patient age was 69.4 years, 73.8% were men, and 31.6% received pirfenidone. Lung cancer developed in 766 patients with IPF (7.6%; 21.9 cases per 1000 person-years) during a median follow-up of 3.0 years. After IPTW, the pirfenidone group showed lower incidence (10.4 versus 27.9 cases per 1000 person-years) than the no-pirfenidone group. Landmark analysis at 6 months after IPF diagnosis also showed lower incidence of lung cancer in the pirfenidone group than in the no-pirfenidone group. Pirfenidone use was independently associated with a reduced lung cancer risk (weighted adjusted hazard ratio [HR]: 0.347; 95% confidence interval [CI]: 0.258-0.466). A clinical cohort showed similar association (weighted adjusted HR: 0.716; 95% CI: 0.517-0.991). The association persisted across subgroups defined by age or sex. Pirfenidone use may be associated with a reduced lung cancer risk in patients with IPF.

Colonoscopy is associated with lower colorectal cancer occurrence and mortality in the older population: A population-based cohort study.

We aimed to evaluate the association between colonoscopy (CS) and colorectal cancer (CRC) occurrence and related mortality in an older population. This retrospective, nationwide, population-based cohort study used data of adults aged ≥40 years from the Health Insurance Review and Assessment Service database. After excluding CS within 6 months of CRC diagnosis during enrollment, CRC occurrence and related mortality were compared between CS and non-CS groups using a time-dependent Cox proportional hazard model. Sub-group analysis was conducted among four age groups: young, middle age, old, and very old. Results Among 748,989 individuals followed for 9.64±0.99 years, the CS group had a 65% lower CRC occurrence (adjusted hazard ratio [HRa]: 0.35, 95% confidence interval [95%CI]: 0.32-0.38) and 76% lower CRC-related mortality (HRa: 0.24, 95%CI: 0.18-0.31) after 5 years than the non-CS group. CS was associated with the most significant reduction in CRC occurrence in the middle age group (HRa: 0.32, 95%CI: 0.29-0.35) and CRC-related mortality in the young age group (HRa: 0.04, 95%CI: 0.01-0.33); the very old age group had the least reduction in both CRC occurrence and CRC-related mortality (HRa: 0.44, 95%CI: 0.33-0.59 and HRa: 0.28, 95%CI: 0.15-0.53, respectively). Conclusion We found a significant association between colonoscopy and reduction in CRC occurrence and CRC-related mortality in adults aged ≥ 40 years after 5 years of follow-up; however, these associations were weaker in the very old group. Research is needed on the association between colonoscopy and older age.

Label-free differential chemiluminescent immunosensor based on magnetic nanoparticles CuFe2O4@ABEI-GNPs with dual catalytic sites

BackgroundCancer has become one of the main causes of death globally. The level of tumor markers in serum is correlated with the occurrence of cancer. Carcinoembryonic antigen (CEA) is the most commonly utilized tumor marker for cancer detection. Recently, various analytical technologies have been reported to detect biomarkers. However, developing a simple, sensitive, and noninvasive approach for CEA detection remains challenging in cancer diagnosis. Consequently, there is an urgent need for researchers to carry out innovative approaches for CEA detection. ResultIn this work, copper ferrite nanoparticles (CuFe2O4 NPs) with excellent dispersity and fascinating magnetism have been successfully synthesized. To get CuFe2O4@ABEI-GNPs, ABEI-gold NPs (ABEI-GNPs) were generated on the surface of CuFe2O4 NPs by using N-(4-Aminobutyl)-N-ethylisoluminol (ABEI) as a mild reduction reagent to reduce chloroauric acid tetrahydrate (HAuCl4·4H2O). The CuFe2O4@ABEI-GNPs exhibited a superior chemiluminescence (CL) performance compared with CuFe2O4@ABEI NPs, which was attributed to the synergistic catalysis effects of CuFe2O4 NPs and GNPs. Interestingly, two unique CL emission peaks were observed in the kinetic curve of CuFe2O4@ABEI-GNPs. Furthermore, it was found that the kinetic curve could be regulated by the pH of hydrogen peroxide (H2O2) and a possible CL mechanism was proposed. Owing to the favorable CL properties of CuFe2O4@ABEI-GNPs, a label-free differential immunosensor was fabricated for CEA monitoring using the intensity difference between CL-1 and CL-2. The developed immunosensor exhibited a wide linear range from 0.1 to 5000 pg/mL, and a low detection limit of 0.05 pg/mL. Significance and noveltyThe immunosensor was capable of determining CEA in real samples with simple operation, high accuracy, and good sensitivity. This study introduces a novel approach for developing CL functionalized materials, which have broad application potential in bioassays. The proposed differential method could serve as a novel tool for determining CEA in the diagnosis of clinical cancer.

SGSM2 in Uveal Melanoma: Implications for Survival, Immune Infiltration, and Drug Sensitivity.

The abnormal expression of small G protein signaling modulator 2 (SGSM2) is related to the occurrence of thyroid cancer and breast cancer. However, the role of SGSM2 in uveal melanoma (UVM) is unclear. To elucidate this ambiguity, our study utilized bioinformatics analysis and experimental validation. The expression of SGSM2 was detected in UVM cell lines through quantitative real-- time PCR (qRT-PCR). We utilized the Cancer Genome Atlas (TCGA) database to assess the relationship between SGSM2 expression and clinical characteristics, as well as its prognostic significance in UVM. Furthermore, the study examined potential regulatory networks involving SGSM2 in relation to immune infiltration, immune checkpoint genes, microsatellite instability (MSI), and drug sensitivity in UVM. The study also examined SGSM2 expression in UVM single-cell sequencing data. SGSM2 was highly expressed in UVM cell lines. Moreover, elevated levels of SGSM2 in UVM patients were significantly linked to poorer overall survival (OS) (p < 0.001), progress- free survival (PFS) (p < 0.001), and disease-specific survival (DSS) (p < 0.001). Additionally, SGSM2 expression was identified as an independent prognostic factor in UVM patients (p < 0.001). SGSM2 was associated with several pathways, including the calcium signaling pathway, natural killer cell-mediated cytotoxicity, cell adhesion molecules (CAMs), and others. The study revealed that SGSM2 expression in UVM is linked to immune infiltration, immune checkpoint genes, and MSI. Additionally, a significant inverse correlation was observed between SGSM2 expression and the compounds GSK690693, TL-2-105, PHA-793887, Tubastatin A, and SB52334 in UVM patients. SGSM2 may not only serve as an important indicator for prognostic assessment. Still, it may also be a key target for the development of new therapeutic approaches, providing new perspectives on the treatment of UVM patients.

In Situ Transformable Fibrillar Clusters Disrupt Intracellular Copper Metabolic Homeostasis by Comprehensive Blockage of Cuprous Ions Efflux.

Dysregulation of copper metabolism is intricately associated with the occurrence and therapeutic management of colorectal cancer. Previous studies have attempted to induce cuproptosis by delivering lethal doses of copper ions into tumor cells, often with systemic safety risks. In vivo, transformable peptide is modular and designed for various tumor-related proteins, which can affect protein function and distribution. Here, a fibrillar transformation peptidic (FTP) nanoparticle is synthesized, which can bind ATP7B membrane proteins (cuprous ions transporter) and transform into nanofibrils/ATP7B clusters, inducing "copper-free cuproptosis" in vivo. Without adding exogenous copper ions, the spherical FTP nanoparticles bound the high distribution regions of ATP7B membrane proteins, transforming into fibrillar networks in situ with prolonged retention. The cage-like fibrillar network would further capture unbound or newly generated free ATP7B membrane proteins, thereby significantly and consistently preventing cuprous ions efflux. The FTP nanoparticles would not undergo in situ fibrillar transformation on the low expression region of ATP7B membrane proteins but enter the cell for safe degradation, which exhibited high specificity and safety in vivo. By disrupting intracellular copper homeostasis, the transformable fibrillar clusters displayed a long-term anti-tumor effect on subcutaneous transplantation and liver metastatic CRC models.

The causal relationship between anti-CD20 antibodies and endometrial cancer: a Mendelian randomization study

PurposeTo determine the effects of anti-B cell surface marker CD20 antibody on the occurrence and progression of endometrial cancer to provide insights into clinical treatment in the future.MethodsWe performed a two-sample Mendelian randomization analysis (MR) to analyze the causal relationship between EC and immune cell markers. The genome-wide association study (GWAS) data of MS4A1 single nucleotide polymorphism encoding gene of CD20 were collected, and a drug target MR analysis was performed to detect the causal relationship between anti-CD20 antibody and the risk of EC. The risk of follicular lymphoma was used as a positive control, and EC was used as the outcome.ResultsEC exerted an effect on 28 immunophenotypes, predominantly on CD20. CD20 in immunoglobulin D+ CD38− B cells, memory B cells, and unsw memory B cells increased after EC onset. In addition, we detected one immunophenotype that exerted a dangerous effect on EC, i.e., CD3/TD CD4+ (mature stage of the T cell group). Simultaneously, CD20 could be used as both a risk factor and a protective factor for EC (P > 0.05). Anti-CD20 antibodies significantly reduced the risk of follicular lymphoma, including two GWAS pooled datasets. In addition, anti-CD20 antibodies exerted a protective effect on EC in two GWAS pooled datasets (P > 0.05).ConclusionOur study confirms the close relationship between CD20 and EC. Anti-CD20 antibodies may exert a protective effect on EC and reduce the risk of EC morbidity, providing a reference for future clinical diagnosis and treatment. However, further clinical verification of our results is warranted.

GdX inhibits the occurrence and progression of breast cancer by negatively modulating the activity of STAT3

ABSTRACT Aim To elucidate the biological functionality and regulatory mechanisms of GdX in breast cancer (BC). Methods The examination of GdX expression in human BC tissues and cell lines was conducted through immunohistochemical (IHC) and Western blot. Cell proliferation capacity was assessed via the CCK-8 and colony formation assay, while cell migration was determined through the wound healing assay. The expression levels of BCL-XL, Cyclin D1, and C-myc gene were quantified using RT-qPCR and Western blot. In vivo tumor growth was evaluated in nude mice xenografted with MDA-MB-231 cells overexpressing GdX, and a mouse model with GdX-deficient BC was established to observe the impact of GdX on BC formation and metastasis. Dual-luciferase reporter assay and immunofluorescence were employed to confirm the interaction between GdX and STAT3. Western blot was employed to validate the influence of GdX overexpression on the phosphorylation process of STAT3. Results GdX exhibited low expression in the cancer tissues of BC patients and cell lines. MDA-MB-231 and MCF-7 cells overexpressing GdX displayed a notable reduction in proliferation and diminished migratory capabilities, accompanied by downregulated mRNA and protein expression of BCL-XL, Cyclin D1, and C-myc. In the xenograft mouse model, heightened GdX expression correlated with a decelerated in vivo tumor growth. Furthermore, in mice deteleing GdX, both the quantity and weight of tumors increased, along with evident pulmonary metastasis. Mechanistically, STAT3 emerged as a downstream target gene of GdX. Conclusions GdX exerts its inhibitory effects on the initiation and progression of BC by negatively modulating the phosphorylation of STAT3.

Risk of Incident Cancer in Patients with Inflammatory Bowel Disease with Prior Breast Cancer: A Multicenter Cohort Study

Background and AimsBreast cancer is the most common malignancy observed in patients with inflammatory bowel diseases (IBD). The aim of our study was to evaluate incident cancer rate (recurrence or new-onset cancer) in a cohort of IBD patients with a history of breast cancer according to the subsequent IBD treatment provided. MethodsA multicenter retrospective study included consecutive IBD patients with prior breast cancer. The inclusion date corresponded to the diagnosis of index malignancy. Follow-up lasted from cancer diagnosis until the occurrence of incident cancer. ResultsAmong 207 patients included (median disease duration: 13 years [IQR 6 - 21]), first line treatment (median interval of 28 months [IQR 7 - 64]) was a conventional immunosuppressant in 19.3 % of patients, anti-TNF in 19.8 %, vedolizumab in 7.2 % and ustekinumab in 1.9 %.After a median follow-up of 71 months [IQR, 34 - 148], 42 (20%) incident cancers were observed (34 breast cancer recurrences). Adjusted incidence rates per 1000 person-years were 10.2 (95%CI 6.0- 16.4) for the untreated arm and 28.9 (95%CI 11.6-59.6) for exposed patients (p= 0.0519). There was no significant difference between treated patients and controls regarding incident-cancer free survival rates (p=0.4796). In multivariable analysis, factors associated with incident cancer were stage T4d (p=0.036), triple negative tumor (p=0.016) and follow-up of less than 71 months (p=0.005). ConclusionWe did not find a statistically significant increase in incident breast cancer related to IBD treatment beyond the already known poor prognostic factors of breast cancer.

STIM1 promotes cervical cancer progression through autophagy activation via TFEB nuclear translocation

BackgroundAutophagy plays an important role in maintaining the stability of intracellular environment, abnormal autophagy is associated with the occurrence and progression of cancer, the role of STIM1 in regulating cancer autophagy remains controversial, and its clinical relevance is unclear. Our study aimed to investigate the effect and mechanism of STIM1 on cervical cancer, thus to provide new molecular therapeutic targets for cervical cancer in clinic. MethodsWe collected CIN III, FIGO IB and IIA fresh Specimens without chemotherapy from patients in Renmin Hospital of Hubei University of Medicine (n = 10). STIM1, TFEB and autophagy related proteins of different stage tissues were detected. In vitro, SKF96365 and AncoA4 were used to inhibit STIM1-administrated Ca2+ entry of SiHa cells, Cyclosporine A (calcineurin inhibitors) were used to inhibit CaN/TFEB pathway, Ad-mCherry-GFPLC3B was used to detect autophagy flux, shSTIM1 was used to knockdown STIM1 expression. ResultsThe expression levels of STIM1, TFEB and autophagy related proteins were positively correlated with the progression of cervical cancer. Inhibition of STIM1-mediated SOCE can decrease proliferation and migration, and promoted the apoptosis of cervical cancer cells. Knockdown STIM1 can inhibit autophagy and TFEB nuclear translocation. ConclusionSTIM1 can promote autophagy and accelerate cervical cancer progression by increasing TFEB nuclear translocation of cervical cancer cells.

(-)-Epicatechin regulates endoplasmic reticulum stress and promotes ferroptosis in lung cancer cells via the PERK/eIF2α/ATF4 signaling pathway.

(-)-Epicatechin (EC) is an active ingredient of Fagopyrum dibtrys (D. Don) Hara and can regulate lung cancer progression. However, the specific regulatory mechanism is poorly understood. This study explored the specific mechanism of EC in the treatment of lung cancer. H460 cells were injected subcutaneously into the left dorsal sides of nude mice to establish an animal model of lung cancer. H460 and H1299 cells and nude mice were treated with different concentrations of EC. The expression levels of related proteins were detected by Western blotting. Cell proliferation, migration, and invasion were detected by CCK-8, colony formation, and Transwell assays. Flow cytometry was used to detect the Ca2+ level in lung cancer cells. Immunohistochemistry was used to detect the expression of Ki-67 in tumor tissues. This study revealed that ferroptosis in lung cancer cells was inhibited during lung cancer development. EC treatment promotes ferroptosis, inhibits the proliferation, migration and invasion of lung cancer cells, and inhibits the formation of tumors in vivo. Ferroptosis inhibitors (Fer-1) weaken the effects of EC on lung cancer cells, whereas a ferroptosis inducer (erastin) further promotes the effects of EC. In addition, endoplasmic reticulum (ER) stress is involved in the EC-induced ferroptosis of lung cancer cells, and treatment with GSK, an inhibitor of the ER stress protein PERK, can reverse the effect of EC. EC therapy activates the PERK-eIF2α-ATF4 signaling pathway to increase ER stress, thereby promoting ferroptosis in lung cancer cells and inhibiting the occurrence and development of lung cancer. Our research suggests that EC may become a drug candidate for treating lung cancer.

The Correlation Between Age of Marriage with Cervical Cancer Incidence in X Hospital Manado

Cervical cancer is one of the most common cancers affecting women. Marriage at a very young age is suspected to be one of the risk factors for the occurrence of cervical cancer. This study aims to analyze the relationship between the age of marriage and the incidence of cervical cancer. Method: This study uses a case control design with 120 sample respondent using total sampling method. Data were collected through medical records and interviews. Data analysis using the chi-square test. Results: Of the 27 respondents 54 % of women who married at age &lt; 20 years suffered from cervical cancer, while in the age group 20 years, only 23 respondent 46 % cancer cervix. The statistical test results indicate a significant relationship between the age of marriage and the incidence of cervical cancer (p=0.026), with a correlation value of 0.222, which is considered weak as it falls within the range of (0.20-0.399). There is a significant relationship between the age of marriage and the incidence of cervical cancer. Women who marry at age &lt; 20 years have a higher risk of suffering from cervical cancer compared to those who marry at age 20 years. Recommendation future researchers should conduct further studies to identify other factors that play a role in the relationship between marriage age and cervical cancer, and evaluate cervical cancer prevention interventions among women who marry at a young age.

Glycolysis regulated exosomal LINC01214 inhibited CD8+ T cell function and induced anti-PD1 resistance in melanoma via modulating miR-4492/PPP1R11 axis

BackgroundLong non-coding RNAs (lncRNAs) can be incorporated into exosomes to mediate the intercellular communication, regulating the occurrence, development, and immunosuppression of cancers. T cell dysfunction has been a hallmark of many cancers, including melanoma, which enables cancer cells escape from host immune surveillance. However, the molecular mechanism of exosome-transmitted lncRNAs in CD8+ T cell dysfunction in melanoma remains largely unclear. MethodThe expression of circulating LINC01214 (cirLINC01214) was detected by quantitative real-time polymerase chain reaction (RT-qPCR). Exosomes were isolation from the culture medium and plasma of melanoma patients via ultracentrifugation and characterized by transmission electronic microscopy. The regulation of exosomal LINC01214 on CD8+ T cell function was determined by ELISA. The molecular mechanism of exosomal LINC01214 in CD8+ T cells were assessed by the RNA immunoprecipitation and pull-down assay. A mouse model with reconstituted human immune system was used to explore the role of exosomal LINC01214 in the resistance to anti-PD1 therapy. ResultsLINC01214 was highly expressed in melanoma tissues compared with matched adjacent normal tissues. Increased levels of circulating LINC01214 (cirLINC01214) was observed in melanoma patient plasma and correlated with poor PD-1 immunotherapy response. The cirLINC01214 was predominantly released by melanoma cells in an exosome manner. Melanoma cell-derived exosomal LINC01214 inhibits the production of IFN-γ, TNF-α, Granzyme-B and Perforin by CD8+ T cells. Further mechanism study found that cirLINC01214 delivered by exosomes suppressed CD8+ T cell function by up-regulating the expression of Protein Phosphatase 1 Regulatory Inhibitor Subunit 11 (PPP1R11) through sponging miR-4492. CirLINC01214 conferred resistance to PD-1 immunotherapy in melanoma xenograft mouse model. Melanoma patients with poor prognosis after PD-1 treatment carried high levels of exosomal LINC01214. Additionally, the secretion of exosomal cirLINC01214 was enhanced by the Warburg effect, which was consistent with the reprogrammed glucose metabolism of melanoma. ConclusionsOur results demonstrated that exosomal LINC01214 released by melanoma cells promoted immunotherapy resistance by inducing CD8+ T cell dysfunction via the miR-4492/PPP1R11 regulatory loop. Targeting cirLINC01214 might be a potential therapeutic strategy to enhance the outcome of immunotherapy in melanoma.

The relationship between TMCO1 and CALR in the pathological characteristics of prostate cancer and its effect on the metastasis of prostate cancer cells.

Calcium homeostasis is correlated closely with the occurrence and development of various cancers. The role of calcium homeostasis in prostate cancer has remained unclear. The present study aimed to investigate the relationship between transmembrane and crimp-crimp domain 1 (TMCO1) and calreticulin (CALR) in the pathological characteristics of prostate cancer and the mechanism of action on prostate cancer metastasis. Effects of CALR recombinant protein and TMCO1 knockdown on prostate cancer cells were investigated using following methods: cell cloning, Transwell, wound scratch assay, JC-1 assay, Fluo-4 Assay, endoplasmic reticulum (ER) fluorescent probe, mitochondrial fluorescence probe, Western blot and Immunofluorescence. TMCO1 and CALR are overexpressed in prostate cancer and knockdown of TMCO1 significantly inhibited the invasion, migration and cell proliferation. Furthermore, knocking down TMCO1 modulated the intensity of ER probes and mitochondrial fluorescence probes, and affected the levels of intracellular calcium ion and mitochondrial membrane potential. In addition, CALR recombinant protein upregulated the expression of epithelial-mesenchymal transition marker, Vimentin, Conversely, knockout of TMCO1 significantly reduced the expression of CALR and Vimentin. Knockout of TMCO1 can reverse the effect of CALR recombinant protein, elucidating the pivotal roles of TMCO1 and CALR in the regulation of prostate cancer metastasis through modulation of calcium homeostasis.

Association of hypertension and the risk of cancer: a study based on the UK Biobank

Abstract Introduction With the increasing incidence rate of hypertension and carcinoma, there is a growing interest in investigating the potential link between these two diseases. The subdiscipline of hypertension, Onco-hypertension, has been proposed and attracted much attention. However, there are still few researches on this subdiscipline. Purpose This study aims to investigate the relationship between hypertension and the occurrence of cancer. Additionally, we explore whether anti-hypertensive treatment has any impact on the incidence of cancer. Methods This study involved 244,496 participants recruited between 2006-2010 from the UK Biobank, with 21,765 participants were diagnosed with the hypertension according to the ICD10 coding. The Cox regression was used to analyse the the risk of cancer associated with hypertension. The effect of anti-hypertensive treatment on the occur of cancer was also verified according to the Cox regression and the Drug target Mendelian randomization. Results Compared to those participants without hypertension, those people with hypertension have higher risk of the occur of cancer(adjusted hazard ratio(aHR) 1.35, 95% confidence interval(CI)1.3-1.4), especially in breast cancer(aHR 1.43, 95% CI 1.27-1.61), prostate cancer(aHR 1.85, 95% CI 1.7-2.02), lung cancer(aHR 2.15, 95% CI 1.86-2.48), renal cancer(aHR 1.91, 95% CI 1.46-2.49), pancreas cancer(aHR 1.55, 95% CI 1.2-2). Compared to those people with hypertension but without anti-hypertensive treatment, the anti-hypertensive treatment increase the cancer risk(aHR 1.19, 95% CI 1.06-1.33). However, thiazide diuretic have protect effect for hypertension patients on occur of the prostate cancer (aHR 0.74, 95% CI 0.61-0.89) and beta-receptor blocker have protect effect for hypertension patients on occur of the lung cancer (aHR 0.71, 95% CI 0.54-0.93). The result of Drug target Mendelian randomization shows the anti-hypertensive treatment have no significant effect on the risk of cancer. Conclusion The onset of high blood pressure is linked to an elevated risk of several cancers. However, it cannot be conclusively determined whether the use of medications for high blood pressure increases or decreases the overall risk of cancer. This study provides instructive evidences for the further study of Onco-hypertension.The result of main analyseThe analyse of the antihypertensive drug

Mechanisms of Bone Morphogenetic Protein 2 in Respiratory Diseases.

Bone morphogenetic protein 2 (BMP2) belongs to the transforming growth factor-β (TGF-β) superfamily and plays an important role in regulating embryonic development, angiogenesis, osteogenic differentiation, tissue homeostasis, and cancer invasion. Increasing studies suggest BMP2 is involved in several respiratory diseases. This study aimed to review the role and mechanisms of BMP2 in respiratory diseases. BMP2 signaling pathway includes the canonical and non-canonical signaling pathway. The canonical signaling pathway is the BMP2-SMAD pathway, and the non-canonical signaling pathway includes mitogen-activated protein kinase (MAPK) pathway and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway. The BMP2 is related to pulmonary hypertension (PH), lung cancer, pulmonary fibrosis (PF), asthma, and chronic obstructive pulmonary disease (COPD). BMP2 inhibits the proliferation of pulmonary artery smooth muscle cells (PASMCs), promotes the apoptosis of PASMCs to reduce pulmonary vascular remodeling in PH, which is closely related to the canonical and non-canonical pathway. In addition, BMP2 stimulates the proliferation and migration of cells to promote the occurrence, colonization, and metastasis of lung cancer through the canonical and the non-canonical pathway. Meanwhile, BMP2 exert anti-fibrotic function in PF through canonical signaling pathway. Moreover, BMP2 inhibits airway inflammation to maintain airway homeostasis in asthma. However, the signaling pathways involved in asthma are poorly understood. BMP2 inhibits the expression of ciliary protein and promotes squamous metaplasia of airway epithelial cells to accelerate the development of COPD. In conclusion, BMP2 may be a therapeutic target for several respiratory diseases.

Cancer screening and surveillance bias

Abstract We will discuss the issue of surveillance bias, which arises when differences in the frequency of cancer are due to changes in screening and detection strategies rather than to differences in the true occurrence of cancer (2). This bias hampers the surveillance of scrutiny-dependent cancers, such as thyroid and prostate cancers and melanoma, leading to misinterpretations of cancer trends. Moreover, it can lead to the misinterpretation of potential risk factors for cancer occurrence, such as socioeconomic status.

ZNF775 inhibits MCF-7 breast cancer cell migration by downregulating Wnt5a

C2H2 zinc finger protein is widely involved in the occurrence and development of cancer. However, the function and mechanism of most C2H2 zinc finger proteins in breast caner (BC) remains unclear. Here, we reported the expression prognosis of C2H2 type zinc finger protein ZNF775 in BC patients and its possible biological mechanism. First, multiple public databases showed that ZNF775 was significantly overexpressed in BC tissues. Interestingly, high expression of ZNF775 was significantly associated with a better prognosis. Immunohistochemistry were used for verification, and the expression of ZNF775 was consistent with the databases. Considering the large heterogeneity of different breast cancer cells, we temporarily selected MCF-7 cell line for verification. In vitro overexpression experiments showed that overexpression of ZNF775 significantly inhibited the proliferation and migration of MCF-7 BC cell. We further combined RNA-sequencing (RNA-seq) and CUT & Tag, and found that overexpression of ZNF775 can down-regulate the expression of most genes in the Wnt signaling pathway. The cBioportal database showed that ZNF775 was negatively correlated with the expression of Wnt5a, suggesting that its downstream target was likely Wnt5a. Finally, we discovered that Wnt5a could partially reverse the inhibitory effect of ZNF775 on MCF-7 BC cell migration through transwell migration experiments. In conclusion, our findings will provide new ideas for the diagnosis, treatment and prognosis assessment of BC in the future.

Effect of Natural Ionizing Radiation on Health Indicators in Region with Monazite Sand in Brazil

Abstract Objective This article compares the occurrence of cancer and germinal damage in the city of Guarapari-Espírito Santo (ES), an area with high natural ionizing radiation, with other coastal cities. Material and Methods The evaluated cities were: Guarapari (ES), Campos (Rio de Janeiro), Rio Grande (Rio Grande do Sul), and Ilhéus (Bahia); the following factors were considered: mortality rate % from tumors (2007–2017), mortality rate % from tumors up to 15 years of age (2007–2017), hospital morbidity rate % from tumors up to 15 years of age (2008–2018), and hospital morbidity rate % from congenital malformation and chromosomal anomalies (2008–2018). Radiometric surveys were conducted by the Applied Physics Group at Universidade Federal do Espírito Santo. Results The natural radiation levels recorded in Guarapari resulted in accumulated dose between 3.65 and 10.95 mSv/year, and 1 mSv in the other cities. The highest average cancer mortality rates were: Rio Grande = 22.4%; Guarapari = 17.6%; Campos = 16.7%; and Ilhéus = 11.8%. The proportional hospital mortality and morbidity rates for cancer up to 15 years of age are as follows: Ilhéus = 3.36 and 5.87%; Rio Grande = 0.79 and 7.38%; Guarapari = 0.64 and 7.25%; and Campos = 0.39 and 9.13%. The hospital morbidity rate due to congenital malformations and chromosomal anomalies was 0.72% for Campos, 0.63% for Rio Grande, 0.62% for Guarapari, and 0.43% for Ilhéus. Conclusion There was no increase in cases of cancer or germ damage in Guarapari. These results indicated a dose threshold in the induction of these damages, contradicting the current linear no-threshold theory.

The oncogenic axis YAP/MYC/EZH2 impairs PTEN tumor suppression activity enhancing lung tumorigenicity

The tumor suppressor PTEN (phosphatase and tensin homolog deleted in chromosome 10) is genetically deleted or downregulated in many cancer types. Loss of PTEN protein expression is frequently found in lung cancer while genetic alterations are less abundant. PTEN expression is regulated at multiple genetic and epigenetic levels and even partial reduction of its expression increases cancer occurrence. We show that YAP and TAZ cooperate with EZH2, and MYC to transcriptionally repress onco-suppressor genes, including PTEN, in non-small cell lung cancer (NSCLC) cells. YAP/TAZ-EZH2-MYC transcriptional regulators form a nuclear complex that represses PTEN transcription, while their combinatorial targeting restores PTEN expression, attenuates NSCLC cell growth, and prevents compensatory responses induced by single treatments. Datasets analysis of NSCLC patients revealed that PTEN expression is negatively correlated to YAP/TAZ, EZH2 and MYC and that low expression of PTEN is predictive of poor prognosis, especially at earlier stages of the disease. These findings highlight the repressive role of the YAP/TAZ-EZH2-MYC axis on tumor-suppressor genes and offer a potential therapeutic strategy for lung cancer patients with low PTEN levels.

CRISPR-based molecule-regulatory expression platform for specific immunotherapy of cancer.

Cancer is still a major challenge of human health. The abnormality of intracellular cancer-related signal pathways is an important mechanism for the occurrence of cancer. We used a molecular-senor to act on the endogenous signal molecules within the cell to redirect the abnormal signal flows in the cell to treat cancer. Based on CRISPR-dCas12f procedures, we combined aptamers and ribozymes to construct riboswitches, which served as molecular switches to reprogram sgRNAs, so that CRISPR-dCas12f redirected the intracellular anti-cancer signal flows after sensing specific input signal molecules. In addition, the activated molecular sensors and the inhibitory molecular sensors were constructed by combining transcription factors (VP64) and transcription inhibitors (KRAB) to specifically activate and inhibit target genes of interest. Our experimental results showed that the molecular sensors that we designed and constructed specifically sensed the endogenous signal molecules and then redirect the cancer related signal networks of cancer cells. In addition, corresponding logic gates were constructed to distinguish cancer cells from normal cells and redirect anticancer signal flows to trigger specific cancer immunotherapy. The constructed molecular sensors constructed specifically recognized the signal molecules within the cell and redirected the endogenous signal pathway to reprogram the fate of cancer cells.