• IHC
• cancer
• histopathology
• mIHC
• multiplex immunohistochemistry
• tumour biomarkers

• Humans
• Immunohistochemistry/methods
• Image Processing, Computer-Assisted/methods
• Neoplasms/pathology
• Neoplasms/metabolism
• Biomarkers, Tumor/analysis
• Biomarkers, Tumor/metabolism
• Tumor Microenvironment

• cyst size
• extra-pancreatic malignancy
• intraductal papillary mucinous neoplasm

• Prediction model
• magnetic resonance imaging
• ovarian neoplasm or metastasis close to the rectum of serous ovarian carcinoma
• residual disease

• Humans
• Female
• Ovarian Neoplasms/diagnostic imaging
• Ovarian Neoplasms/pathology
• Ovarian Neoplasms/surgery
• Middle Aged
• Retrospective Studies
• Magnetic Resonance Imaging/methods
• Neoplasm, Residual/diagnostic imaging
• Aged
• Adult
• Cystadenocarcinoma, Serous/diagnostic imaging
• Cystadenocarcinoma, Serous/surgery
• Cystadenocarcinoma, Serous/pathology
• Predictive Value of Tests
• Rectum/diagnostic imaging
• Rectum/pathology
• Rectum/surgery
• CA-125 Antigen/blood
• Rectal Neoplasms/diagnostic imaging
• Rectal Neoplasms/pathology
• Rectal Neoplasms/surgery
• Risk Factors
• Cytoreduction Surgical Procedures/methods
• Ovary/diagnostic imaging
• Ovary/pathology
• Ovary/surgery

• Anlotinib
• DCR
• ORR
• Recurrent epithelial ovarian cancer
• Survival

• cancer
• cytotoxicity
• kisspeptin
• kisspeptin receptor
• signal transduction

• Kisspeptins/metabolism
• Kisspeptins/genetics
• Kisspeptins/pharmacology
• Humans
• Uterine Cervical Neoplasms/metabolism
• Uterine Cervical Neoplasms/pathology
• Uterine Cervical Neoplasms/drug therapy
• Uterine Cervical Neoplasms/genetics
• Female
• Signal Transduction/drug effects
• Cell Movement/drug effects
• Cell Line, Tumor
• Cell Proliferation/drug effects
• Receptors, Kisspeptin-1/metabolism
• Receptors, Kisspeptin-1/genetics

• 808-2017. Ministerio de Ciencia Tecnología e Innovación, Gobierno de Colombia.

• CXCL12
• HMGB1
• breast cancer
• heterocomplex
• prostate cancer
• thioredoxin

• Humans
• HMGB1 Protein/metabolism
• HMGB1 Protein/genetics
• Receptors, CXCR4/metabolism
• Receptors, CXCR4/genetics
• Cell Movement
• Chemokine CXCL12/metabolism
• Protein Isoforms
• Cell Line, Tumor
• Female
• Tumor Microenvironment
• Male
• Neoplasms/metabolism
• Neoplasms/pathology

• Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung

• biophysics
• cold tumors
• imaging
• immuno-suppressive tumors
• tumor acidity

• P20 GM103430 NIGMS NIH HHS
• R01 GM073857 NIGMS NIH HHS
• T34 GM131948 NIGMS NIH HHS
• National Institute of General Medical Sciences

• CIBERSORT
• GEO database
• biomarker
• immune infiltration
• ovarian cancer

• Humans
• Female
• Genetic Markers
• Ovarian Neoplasms/diagnosis
• Ovarian Neoplasms/genetics
• Databases, Factual
• Macrophages
• Biomarkers

• cancer
• drug discovery

• Animals
• Lung Neoplasms/drug therapy
• Lung Neoplasms/genetics
• Lung Neoplasms/metabolism
• Carcinoma, Non-Small-Cell Lung/drug therapy
• Carcinoma, Non-Small-Cell Lung/genetics
• Carcinoma, Non-Small-Cell Lung/metabolism
• Salvia miltiorrhiza/genetics
• Tight Junction Proteins
• Occludin
• MicroRNAs/genetics
• Cell Proliferation

• 82074405 National Natural Science Foundation of China
• 82004179 National Natural Science Foundation of China
• 82104656 National Natural Science Foundation of China
• ZZ15-YQ-024 Program of the Fundamental Research Funds for the Central Public Welfare Research Institutes
• 7214294 Beijing Municipal Natural Science Foundation

• A549
• Carvotanacetone
• GC–MS
• MTT
• Pulicaria arabica

• Honokiol
• lung cancer
• treatment mechanism

• Lung Neoplasms/drug therapy
• Lignans/pharmacology
• Biphenyl Compounds/pharmacology
• Signal Transduction
• Apoptosis
• Cell Line, Tumor

• Hepatocellular carcinoma
• Molecular typing
• Prognostic genes
• Tumor microenvironment
• m6A/m5C/m1A/m7G regulatory genes

• antioxidant
• antiproliferative
• apoptosis
• quinoline
• triazole

• Humans
• Antioxidants/pharmacology
• ErbB Receptors
• Lung Neoplasms
• Mutation
• Protein Kinase Inhibitors

• CD73
• Disease-free survival
• Nomogram
• Pancreatic ductal adenocarcinoma
• Prognostic

• Humans
• Prognosis
• Disease-Free Survival
• Pancreatic Neoplasms/pathology
• Carcinoma, Pancreatic Ductal/genetics

• Nos. 81972299 the National Natural Science Funds
• No. 2017YFC0910002 National Key Research and Development Plan

• apoptosis
• carbon nanotubes
• hyaluronic acid
• nasopharyngeal carcinoma
• photothermal therapy

• anti-cancer mechanisms
• anti-inflammatory
• anti-oxidative
• bioactive compounds
• chemotherapy
• haematological cancers

• 00000000 Covenant University Centre for Research Innovation and Discovery (CUCRID)

• Cervical cancer
• Internally validation
• Multiplex immunofluorescence
• Nomogram
• Preoperative individualized prediction

• Female
• Humans
• Fluorescent Antibody Technique
• Lymph Nodes/surgery
• Lymph Nodes/pathology
• Lymphatic Metastasis/pathology
• Nomograms
• Retrospective Studies
• Uterine Cervical Neoplasms/surgery
• Uterine Cervical Neoplasms/pathology

• T Cell related gene
• T-cell score
• gastric cancer
• immune microenvironment infiltration
• immune therapy

• SLC4A7
• breast cancer
• heterogeneity
• mutant allele
• polymorphism
• risk
• rs4973768

• NPS
• locally advanced NSCLC
• neoadjuvant treatment
• prognosis
• surgery

• cellular senescence
• glioma
• immune microenvironment
• long non-coding RNA
• overall survival
• prognostic signature

• cutaneous melanoma
• fatty acid metabolism
• immune checkpoint
• immune infiltration
• prognosis
• tumor metabolism
• tumor microenvironment

• Humans
• Melanoma/genetics
• Skin Neoplasms/genetics
• Programmed Cell Death 1 Receptor
• Biomarkers
• Fatty Acids
• Tumor Microenvironment/genetics
• L-Amino Acid Oxidase

• immuno-oncology
• proteome
• spatial profiling technologies
• transcriptome
• tumor heterogeneity

• Humans
• Tumor Microenvironment/genetics
• Proteomics
• Medical Oncology
• Neoplasms
• High-Throughput Nucleotide Sequencing

• National Key Research and Development Program of China
• National Natural Science Foundation of China
• Natural Science Foundation of Anhui Province

Despite significant progress in the development of novel STING agonists (STINGa), applications appear to be challenged by the low efficiency and poor selectivity of these agents. A pH Low Insertion Peptide (pHLIP) extends the lifetime of a STINGa in the blood and targets it to acidic cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), myeloid derived suppressor cells (mMDSCs) and dendritic cells (DCs). CAFs constitute 25% of all live cells within CT26 tumors, and M2-type TAMs and mMDSCs are the most abundant among the immune cells. The resulting activation of cytokines within the tumor microenvironment (TME) triggers the eradication of small (100 mm³) and large (400-700 mm³) CT26 tumors in mice after a single dose of pHLIP-STINGa. The tumor stroma was destroyed (the number of CAFs was reduced by 98%), intratumoral hemorrhage developed, and the level of acidity within the TME was reduced. Further, no tumors developed in 20 out of 25 tumor-free mice re-challenged by an additional injection of cancer cells. The therapeutic effect on CT26 tumors was insignificant in nude mice, lacking T-cells. Thus, targeted delivery of STINGa to tumor stroma and TAMs induces activation of signaling, potentially resulting in the recruitment and infiltration of T-cells, which gain access to the tumor core. The cytotoxic activity of T-cells is not impaired by an acidic environment and immune memory is developed.

• R01 GM073857 NIGMS NIH HHS
• National Institutes of Health

Metastasis is a major obstacle in the treatment of cervical cancer (CC), and SPOP-mediated regulatory effects are involved in metastasis. However, the mechanisms have not been fully elucidated.

Proteomic sequencing and SPOP immunohistochemistry (IHC) were performed for the pelvic lymph node (pLN)-positive and non-pLN groups of CC patients. The corresponding patients were stratified by SPOP expression level for overall survival (OS) and relapse-free survival (RFS) analysis. In vitro and in vivo tests were conducted to verify the causal relationship between SPOP expression and CC metastasis. Multiplex immunofluorescence (m-IF) and the HALO system were used to analyse the mechanism, which was further verified by in vitro experiments.

SPOP is upregulated in CC with pLN metastasis and negatively associated with patient outcome. In vitro and in vivo, SPOP promotes CC proliferation and metastasis. According to m-IF and HALO analysis, SPOP may promote CC metastasis by promoting the separation of PD-1 from PD-L1. Finally, it was further verified that SPOP can achieve immune tolerance by promoting the movement of PD-1 away from PD-L1 in spatial location and function.

This study shows that SPOP can inhibit the immune microenvironment by promoting the movement of PD-1 away from PD-L1, thereby promoting pLN metastasis of CC and resulting in worse OS and RFS.

The SPOP is associated with pelvic lymph node (pLN) metastasis and prognosis in cervical cancer (CC) patients.

• CXCL16/CXCR6 axis
• Cervical cancer
• Multiplex immunofluorescence
• PD-1/PD-L1 axis
• SPOP

Perioperative fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT) improves prognosis in locally advanced gastric cancer (LAGC). Neutrophil-to-lymphocyte (NLR), lymphocyte-to-monocyte (LMR), and platelet-to-lymphocyte (PLR) ratios are prognostic biomarkers but not predictive factors.

To assess blood ratios’ (NLR, LMR and PLR) potential predictive response to FLOT and survival outcomes in resectable LAGC patients.

This was a multicentric retrospective study investigating the clinical potential of NLR, LMR, and PLR in resectable LAGC patients, treated with at least one preoperative FLOT cycle, from 12 Portuguese hospitals. Means were compared through non-parametric Mann-Whitney tests. Receiver operating characteristic curve analysis defined the cut-off values as: High PLR > 141 for progression and > 144 for mortality; high LMR > 3.56 for T stage regression (TSR). Poisson and Cox regression models the calculated relative risks/hazard ratios, using NLR, pathologic complete response, TSR, and tumor regression grade (TRG) as independent variables, and overall survival (OS) as the dependent variable.

This study included 295 patients (mean age, 63.7 years; 59.7% males). NLR was correlated with survival time (r = 0.143, P = 0.014). PLR was associated with systemic progression during FLOT (P = 0.022) and mortality (P = 0.013), with high PLR patients having a 2.2-times higher risk of progression [95% confidence interval (CI): 0.89-5.26] and 1.5-times higher risk of mortality (95%CI: 0.92-2.55). LMR was associated with TSR, and high LMR patients had a 1.4-times higher risk of achieving TSR (95%CI: 1.01-1.99). OS benefit was found with TSR (P = 0.015) and partial/complete TRG (P < 0.001). Patients without TSR and with no evidence of pathological response had 2.1-times (95%CI: 1.14-3.96) and 2.8-times (95%CI: 1.6-5) higher risk of death.

Higher NLR is correlated with longer survival time. High LMR patients have a higher risk of decreasing T stage, whereas high PLR patients have higher odds of progressing under FLOT and dying. Patients with TSR and a pathological response have better OS and lower risk of dying.

• Gastric cancer
• Perioperative fluorouracil plus leucovorin, oxaliplatin, and docetaxel
• Neutrophil-to-lymphocyte
• Lymphocyte-to-monocyte
• Platelet-to-lymphocyte
• Tumor regression grade

•

FAM83D is upregulated in the glioma cells and tissues.

To explore the mechanism by which the family with sequence similarity 83, member D (FAM83D)-mediated AKT/mTOR signaling pathway activation affects the proliferation and metastasis of glioma cells.

FAM83D protein expression in glioma cells and tissues was detected by western blotting. Glioma U87 and U251 cells were selected and divided into the Mock, siNC, siFAM83D, FAM83D, MK2206 and FAM83D + MK2206 groups. Cell proliferation was assessed by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) and clone formation assays, while invasion and migration were evaluated by Transwell assays and wound healing tests. The protein expression of members of the AKT/mTOR pathway was determined via western blotting. Xenograft models were also established in nude mice to observe the in vivo effect of FAM83D on the growth of glioma.

FAM83D was upregulated in glioma patients, especially in those with Stage III-IV. In addition, cells treated with siFAM83D had significant downregulation of p-AKT/AKT and p-mTOR/mTOR, with decreased proliferation and colony numbers, as well as decreased invasion and migration compared to the Mock group. However, FAM83D overexpression could activate the Akt/mTOR pathway and promote the proliferation, invasion and migration of glioma cells. Moreover, treatment with MK2206, an inhibitor of AKT, reversed the promoting effect of FAM83D on the growth of glioma cells. The in vivo experiments demonstrated that silencing FAM83D could inhibit the in vivo growth of glioma cells

FAM83D was upregulated in glioma and silencing FAM83D suppressed the proliferation, invasion and migration of glioma cells via inhibition of the AKT/mTOR pathway.

• AKT/mTOR
• FAM83D
• Glioma
• Invasion
• Migration
• Proliferation

• DDR1a
• Warburg effect
• colorectal cancer
• lactic acid
• proliferation

RNA-binding proteins (RBPs) have been related to cancer development. Their functions in cervical cancer, however, are virtually unknown. One of these proteins, Mex-3 RNA-binding family member D (MEX3D), has been recently found to exhibit oncogenic properties in a variety of cancer types. In this present study, the functional roles and the regulatory mechanisms underlying MEX3D were examined in cervical cancer. The detection of MEX3D mRNA expression levels in cervical tissues was performed using reverse transcription-quantitative PCR. For functional analysis, for detecting apoptosis and cell proliferation in cervical cancer cells, the Cell Counting Kit-8, colony formation, and flow cytometry were utilized (SiHa and CaSki). The potential mechanisms of MEX3D were assessed and elucidated utilizing western blot analysis, RNA pull-down, RNA immunoprecipitation, and mRNA stability assays. For verification of MEX3D role in vivo, mouse xenograft models were established. When compared to normal cervical tissues, MEX3D expression was observed to be higher in cervical cancer tissues. MEX3D expression was increased in human papillomavirus (HPV) 16 positive cervical cancer tissues and positively regulated by HPV16 E7. When MEX3D expression was knocked down in cervical cancer cells, cell proliferation was decreased, colony formation was inhibited, and apoptosis was promoted. Furthermore, in a mouse xenograft model, knocking down MEX3D expression reduced cervical cancer tumor growth. In addition, MEX3D acted as an RBP to reduce TSC22 domain family protein 1 (TSC22D1) mRNA stability by directly binding to TSC22D1 mRNA. The findings revealed that MEX3D is upregulated by HPV16 E7 and has a crucial oncogenic in cervical cancer development via sponging TSC22D1 for destabilizing its mRNA levels. According to the findings of this study, MEX3D may be a potential therapeutic target for treating cervical cancer patients.

Early diagnosis of ovarian cancer and the discovery of prognostic markers can significantly improve survival and reduce mortality. OPA3 protein exists in a structure called mitochondria, which is the energy production center of cells, but its molecular and biological functions in ovarian cancer are still unclear. Here, the expression of OPA3 mRNA in ovarian cancer was estimated using TCGA, Oncomine, TIMER databases. We found that functional OPA3 activation caused by mutations and profound deletions predicted poor prognosis in OV patients. OPA3 was highly expressed in both OV tissues and cells compared to normal ovarian tissues/cells. High OPA3 expression is associated with poorer overall survival (OS). The association between OPA3 and immune infiltration of ovarian cancer was assessed by TIMER and CIBERSORT algorithms. OPA3 showed a strong correlation with various immune marker sets. Most importantly, pharmacogenetic analysis of OV cell lines revealed that OPA3 inactivation was associated with increased sensitivity to PFI-1, and WZ4003. Therefore, we investigated the clinical application of OPA3 to provide a basis for sensitive diagnosis, prognosis and targeted treatment of ovarian cancer.

• OPA3
• immune infiltration
• multi-omics
• ovarian cancer

• Neoplasms
• Nucleosides/metabolism
• RNA/metabolism

• P30 CA062203 NCI NIH HHS

Ovarian endometriosis may increase the risk of malignancy. Several studies have suggested atypical endometriosis as the direct precursor of endometriosis-associated ovarian cancer. We performed an advanced, systematic search of the online medical databases PubMed and Medline. The search revealed n = 40 studies eligible for inclusion in this systematic review. Of these, n = 39 were finally included. The results from included studies are characterized by high heterogeneity, but some consistency has been found for altered expression in phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway, ARID1a, estrogen and progesterone receptors, transcriptional, nuclear, and growth factors in atypical endometriosis. Although many targets have been proposed as biomarkers for the presence of atypical endometriosis, none of them has such strong evidence to justify their systematic use in clinical practice, and they all need expensive molecular analyses. Further well-designed studies are needed to validate the evidence on available biomarkers and to investigate novel serum markers for atypical endometriosis.

• atypia
• atypical
• atypical endometriosis
• biomarker
• endometriosis
• marker

• cachexia
• chronic inflammation
• obesity

New predictors of the efficacy of hepatocellular carcinoma (HCC) immunotherapy are needed. The ability of a single gene mutation to predict the therapeutic effect of immune checkpoint inhibitors (ICI) in HCC remains unknown.

The most frequently mutated genes in HCC were analyzed using the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets. Mutant genes that correlated with the tumor mutational burden (TMB) and prognosis were obtained. The mutation pattern and immunological function of one of the most frequently mutated genes, LRP1B, were determined. A pan-tumor analysis of LRP1B expression, association with cancer prognosis, and immunological role was also explored. A retrospective clinical study was conducted using 102 HCC patients who received ICI treatment to further verify whether gene mutations can predict the effectiveness of immunotherapy and prognosis of HCC.

LRP1B is among the most frequently mutated genes in HCC cohorts in TCGA and ICGC datasets. TCGA data showed that the LRP1B mutation activated immune signaling pathways and promoted mast cell activation. Patients with LRP1B mutations had significantly higher TMB than those with wild-type LRP1B. LRP1B expression correlated with the cancer-immunity cycle and immune cell infiltration. High LRP1B expression was also associated with poor survival among HCC patients. Results from the clinical study showed that HCC patients in the LRP1B mutation group had a poor response to ICI and worse prognosis than the wild-type group. The LRP1B mutation group had significantly higher TMB and mast cell infiltration in tumor tissues.

This study is the first to report that a single gene LRP1B mutation is associated with a poor clinical response to ICI treatment and negative outcomes in HCC patients. HighLRP1B expression correlated with tumor immunity and HCC prognosis.

• National Natural Science Foundation of China
• Guangzhou Science and Technology plan project

Cancer is a heterogeneous and multifactorial disease that causes high mortality throughout the world; therefore, finding the most effective therapies is a major research challenge. Currently, most anticancer drugs present a limited number of well‐established targets, such as cell proliferation or death; however, it is important to consider that the worse progression of cancer toward pathological stages implies invasion and metastasis processes. Medicinal Inorganic Chemistry (MIC) is a young area that deals with the design, synthesis, characterization, preclinical evaluation, and mechanism of action of new inorganic compounds, called metallodrugs. The properties of metallic ions allow enriching of strategies for the design of new drugs, enabling the adjustment of physicochemical and stereochemical properties. Metallodrugs can adopt geometries, such as tetrahedral, octahedral, square planar, and square planar pyramid, which adjusts their arrangement and facilitates binding with a wide variety of targets. The redox properties of some metal ions can be modulated by the presence of the bound ligands to adjust their interaction, thereby opening a range of mechanisms of action. In this regard, the mechanisms of action that trigger the biological activity of metallodrugs have been generally identified by: (a) coordination of the metal to biomolecules (for instance, cisplatin binds to the N7 in DNA guanine, as Pt‐N via coordination of the inhibition of enzymes); (b) redox‐active; and (c) ROS production. For this reason, a series of metallodrugs can interact with several specific targets in the anti‐invasive processes of cancer and can prevent metastasis. The structural base of several metal compounds shows great anticancer potential by inhibiting the signaling pathways related to cancer progression. In this minireview, we present the advances in the field of antimetastatic effects of metallodrugs.

• Cancer
• Invasion
• Metallodrugs
• Metastasis
• Transition metals

Ovarian cancer (OV) is a highly lethal disease, and the fifth leading cause of all cancer-related deaths in women. The study aimed to identify potential key genes associated with the proliferation and prognosis of OV.

Differentially expressed genes (DEGs) between ovarian cancer and normal tissues were screened by the robust rank aggregation (RRA) method. The expression of CENPA and MYBL2 were examined in SKOV3 and A2780 ovarian cancer cell lines and tumor tissues by qRT-PCR and western blot. Small RNA interference assays, plasmid overexpression assays and EdU assays were used to validate the proliferative effect of the MYBL2-CENPA axis in ovarian cancer cell lines. The ChIP assay was used to verify the direct regulation of MYBL2 on CENPA.

133 up-regulated genes and 158 down-regulated genes were identified, and the up-regulated genes mainly enrichment in cell cycle. The three up-regulated gene with DNA separation (CENPA, CENPF and CEP55) might be tightly correlated with proliferation and prognosis of OV. Knockdown CENPA expression inhibited the proliferation of A2780 and SKOV3 cells After the knockout of MYBL2, the expression of CENPA significantly decreased. MYBL2 directly binds to the promoter region of CENPA.

The MYBL2-CENPA pathway plays an important role in the proliferation of ovarian cancer cells, suggesting that this pathway may be a potential target for the treatment of ovarian cancer.

• CENPA
• MYBL2
• ovarian cancer
• proliferation
• robust rank aggregation (RRA)

Natural products are a major source of biologically active compounds that make promising lead molecules for developing efficacious drug-like molecules. Natural withanolides are found in many flora and fauna, including plants, algae, and corals, that traditionally have shown multiple health benefits and are known for their anti-cancer, anti-inflammatory, anti-bacterial, anti-leishmaniasis, and many other medicinal properties. Structures of these withanolides possess a few reactive sites that can be exploited to design and synthesize more potent and safe analogs. In this review, we discuss the literature evidence related to the medicinal implications, particularly anticancer properties of natural withanolides and their synthetic analogs, and provide perspectives on the translational potential of these promising compounds.

• anti-bacterial
• anti-inflammatory
• anti-leishmaniasis
• anticancer
• withaferin A
• withanolides

• gsrc
• neutrophil–lymphocyte ratio
• prognosis

• Carcinoma, Signet Ring Cell/surgery
• Female
• Humans
• Lymphocyte Count
• Lymphocytes/immunology
• Male
• Middle Aged
• Neoplasm Recurrence, Local
• Neutrophils/immunology
• Predictive Value of Tests
• Prognosis
• ROC Curve
• Retrospective Studies
• Stomach Neoplasms/surgery
• Survival Analysis

To investigate the characteristics of the tumor immune microenvironment in patients with gastrointestinal stromal tumor (GIST) and identify cancer stem-like properties of GIST to screen potential druggable molecular targets.

The gene expression data of 60 patients with GIST was retrieved from the Array Express database. CIBERSORT was applied to calculate the level of immune infiltration. ssGSEA and ESTIMATE were used to calculate the cancer stemness index and tissue purity. The Connectivity Map (CMAP) database was implemented to screen targeted drugs based on cancer stem-like properties of GIST.

There was a difference in the level of immune infiltration between the metastasis and non-metastasis GIST groups. The low level of T-cell infiltration was correlated with high tumor purity and tumor stemness index, and the correlation coefficients were -0.87 and -0.61 (p < 0.001), respectively. Furthermore, there was a positive correlation between cancer stemness index and cell purity (p < 0.001). The cancer stemness index in the metastasis group was higher than that in the non-metastasis group (p = 0.0017). After adjusting for tumor purity, there was no significant correlation between T-cell infiltration and cancer stemness index (p = 0.086). Through the pharmacological mechanism of topoisomerase inhibitors, six molecular complexes may be the targets of GIST treatment.

Immune infiltration in GIST patients is related to cancer stem-like properties, and the correlation relies on tumor purity. Cancer stemness index can be used as a new predictive biomarker of tumor metastasis and targets of drug therapy for GIST patients.

• cancer stem cells
• gastrointestinal stromal tumor
• immune infiltration
• targeted therapy
• tumor immune microenvironment

• Biomimetic camouflage
• biomimetic enzyme
• cell membrane
• photodynamic therapy
• photothermal therapy

Although spread through air spaces (STAS) is a robust biomarker in surgically resected lung cancer, its application to biopsies is challenging. Moreover, limited resection is not an effective treatment for STAS-positive lung adenocarcinoma. This study aimed to identify histologic features from preoperative percutaneous transthoracic needle biopsies (PTNBs) to predict STAS status in the subsequently resected specimens, and thus help in selecting the surgical extent.

Between January 2014 and December 2015, 111 PTNB specimens and subsequent resection specimens from consecutive lung adenocarcinoma patients were retrospectively examined. Histopathologic features of PTNB specimens and presence of STAS in subsequent resection specimens were evaluated and correlations between them were analyzed statistically.

The study participants had a mean age of 59 years (range, 35–81) and included 50 men and 61 women. Thirty-six patients were positive for STAS whereas 75 were negative. The micropapillary/solid histologic subtypes of lung adenocarcinoma (26 of 39; 66.7%; P <  0.001), necrotic/tumor debris (31 of 42; 73.8%; P <  0.001), intratumoral budding (ITB) (20 of 33; 60.6%; P <  0.001), desmoplasia (35 of 41; 85.4%; P <  0.001), and grade 3 nuclei (12 of 14; 85.7%; P <  0.001) were more common in STAS-positive tumors. Micropapillary/solid histologic subtype (OR, 1.35; 95% CI: 1.06, 1.67), ITB (OR, 1.64; 95% CI: 1.09, 2.83), desmoplasia (OR, 1.83; 95% CI: 1.36, 3.12), and N stage (N1 stage: OR, 1.37; 95% CI: 1.19, 1.87) (N2 stage: OR, 1.29; 95% CI: 1.07, 1.73) were independent predictors of STAS.

Micropapillary/solid histologic subtype, ITB, and desmoplasia in preoperative PTNB specimens were independently associated with STAS in the subsequent resection specimens. Therefore, these can predict STAS and may help to optimize therapeutic planning.

• Histopathologic features
• Lung adenocarcinoma
• PTNB
• Risk stratification
• Spread through air spaces

• Apoptosis
• Bezafibrate
• Hypolipidemic drug
• Oxidative stress
• Pt(IV) prodrugs
• ROS-AMPK pathway

• biomarker
• cin
• nlr

• Adult
• Aged
• Biomarkers, Tumor
• Female
• Humans
• Lymphocytes/metabolism
• Middle Aged
• Neutrophils/metabolism
• Papillomaviridae
• Papillomavirus Infections/epidemiology
• Retrospective Studies
• Uterine Cervical Neoplasms/blood
• Uterine Cervical Neoplasms/epidemiology
• Uterine Cervical Neoplasms/virology
• Young Adult
• Uterine Cervical Dysplasia/blood
• Uterine Cervical Dysplasia/epidemiology
• Uterine Cervical Dysplasia/virology

Cancer and neurodegenerative diseases are caused by genetic and environmental factors. Expression of tumour suppressor genes is suppressed by mutations or epigenetic silencing, whereas for neurodegenerative disease-related genes, nucleic acid-based effects may be presented through loss of protein function due to erroneous protein sequences or gain of toxic function from extended repeat transcripts or toxic peptide production. These diseases are triggered by damaged genes and proteins due to lifestyle and exposure to radiation. Recent studies have indicated that transient, non-canonical structural changes in nucleic acids in response to the environment can regulate the expression of disease-related genes. Non-canonical structures are involved in many cellular functions, such as regulation of gene expression through transcription and translation, epigenetic regulation of chromatin, and DNA recombination. Transcripts generated from repeat sequences of neurodegenerative disease-related genes form non-canonical structures that are involved in protein transport and toxic aggregate formation. Intracellular phase separation promotes transcription and protein assembly, which are controlled by the nucleic acid structure and can influence cancer and neurodegenerative disease progression. These findings may aid in elucidating the underlying disease mechanisms. Here, we review the influence of non-canonical nucleic acid structures in disease-related genes on disease onset and progression.