Cancer Development Research Articles

Jaranol Loaded in Ferroferric Oxide Nanoparticles Inhibits the Activities of Liver Cancer Cell Through Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Signaling Pathway

Liver cancer is highly aggressive and the MEK/ERK signaling regulates tumor cell proliferation and metastasis. Jaranol is a natural product with anti-proliferative and anti-metastatic effects in several tumors. However, its interaction with the MEK/ERK pathway in liver cancer is unclear. This study explores whether ferroferric oxide nanoparticles-loaded Jaranol inhibits proliferation and metastasis in liver cancer cell Hep3B by regulating MEK/ERK signaling, and its underlying mechanism. Fe3O4-Jaranol nanoparticles were prepared and used in Hep3B experiments to observe the biological efficacy of Fe3O4-Jaranol, and further explore its effect and mechanism on the MEK/ERK pathway using PCR, WB, etc. Fe3O4-Jaranol were successfully prepared with a certain tumor suppressor effect in liver cancer. The expression of MEK/ERK was increased in liver cancer. Inhibiting its pathway activity suppressed the development of liver cancer. Trametinib and C16-PAF were used to inhibit Hep3B respectively. MEK expression in cells treated with Trametinib was reduced accompanied by a low expression of ERK, while the expression of MEK and ERK levels in the C16-PAF group showed an opposite trend, indicating that Trametinib, C16-PAF successfully intervened on MEK and ERK. Further analysis of the activity of Hep3B cells found that the proliferation ability of the Trametinib group was significantly inhibited. Fe3O4-Jaranol significantly inhibited liver cancer cell Hep3B and this effect was accomplished by inhibiting MEK/ERK signaling, causing tumor cell proliferation to be restricted and reducing the ability to metastasize. This research result provides strong evidence for a deep understanding of the mechanism of Jaranol in treating liver cancer, so as to better guide clinical practice.

Radiation-Induced Childhood Thyroid Cancer after the Fukushima Daiichi Nuclear Power Plant Accident

After the Fukushima Nuclear Power Plant accident in March 2011, a large-scale ultrasound examination of childhood thyroid cancer for all Fukushima residents aged 18 years old or younger was initiated. Fukushima was divided into four areas according to the external radioactivity released by the accident: the highest (A), high-intermediate (B), low-intermediate (C), and the lowest (D). Five rounds of surveys were carried out from October 2011 to March 2023. The annual incidence rates of the “Common Case” not affected by the accident were able to be estimated. The difference between the incidence rate of whole patients and the “Common Case” is that of the “Radiation-induced Case”. The annual incidence rate of the “Radiation-induced Case” began to increase immediately after the accident, where the highest level was seen in A area, and the order was A > B > C > D. It showed that the development of childhood thyroid cancer was affected by the radiation released by the accident. The effect of the radiation consisted of two phases: the first phase may have been due to the damage to the immune system, and the second phase may have been due to the genetic mutation in the children who were youngest at the time of the accident.

ENAH transcriptionally activated by YY1 promotes growth and invasion of laryngocarcinoma cells through PI3K/AKT signaling

BackgroundLaryngocarcinoma is a common malignancy in the upper respiratory tract. Enabled homolog (ENAH) is an actin-binding protein that is associated with the development of various cancers. However, its role and mechanism in laryngocarcinoma remain unknown. MethodsThe ENAH level in laryngocarcinoma was examined in silico, in vitro and in vivo. The prognostic analysis of the ENAH level was assessed on laryngocarcinoma patients. Gain- and loss-of-function assays were conducted in AMC-HN-8 and TU686 cells. Sh-ENAH-containing AMC-HN-8 cells were implanted into naked mice. The role and mechanism of ENAH in laryngocarcinoma were investigated by CCK-8, transwell, immunofluorescence, dual luciferase, RT-qPCR, immunohistochemistry, and western blotting experiments. ResultsThe ENAH level was upregulated in laryngocarcinoma, which predicted a poor prognosis in laryngocarcinoma patients. Gain- and loss-of-function results showed that ENAH promoted proliferation, invasion and EMT of laryngocarcinoma cells. Moreover, ENAH was transcriptionally activated by YY1, and YY1/ENAH axis enhanced these malignant progresses of laryngocarcinoma cells. Besides, ENAH activated the PI3K/AKT pathway, and 740Y-P abolished the accelerative role of ENAH in proliferation, invasion and EMT of laryngocarcinoma cells. Furthermore, knockdown of ENAH reduced tumor size and weight, and the expression level of vimentin and PI3K/AKT pathway in tumor-bearing mice. ConclusionENAH transcriptionally activated by YY1 promotes cell growth, invasion and EMT of laryngocarcinoma through the activation of PI3K/AKT signaling.

Extrachromosomal circular DNA-related SPOCK1 contributes to development and enzalutamide resistance of prostate cancer by regulating epithelial mesenchymal transition

Prostate cancer is a significant contributor to cancer-related mortality, and the tumor typically develops into castration-resistant prostate cancer (CRPC). Hence, few effective clinical strategies are available to patients with advanced disease. Extrachromosomal circular DNA (eccDNA) is a type of circular DNA originating from the chromosomes but is likely independent of them. Because of its unique structural characteristics, eccDNA has extensive applications as a new biomarker for cancer prevention and treatment. Circle-seq obtains a comprehensive picture of the overall landscape of eccDNA sizes and content in cell populations. In this study, we used Circle-seq and studied the distribution pattern and expression level of eccDNA in prostate cancer. We confirmed that eccDNA is derived from every human chromosome and has sequences from all known types of genomic structures, revealing it is a common mutational element in prostate cancer. We also identified an eccDNA-related gene SPOCK1 that promotes drug resistance, proliferation, and metastasis of many cancers through the epithelial-mesenchymal transition (EMT) mechanism. The SPOCK1-associated eccDNA was highly upregulated in various groups of sequencing results, and SPOCK1 was highly expressed in prostate cancer tissues and cells. Therefore, SPOCK1 exists as eccDNA in prostate cancer and encourages its development and drug resistance via the EMT mechanism. Our results suggest that upregulated genes in the form of eccDNA are oncogenes in prostate cancer and play a pivotal role in carcinogenesis.

Puerarin Decreases the Expression of FUS-Dependent MAPK4 to Inhibit the Development of Triple-Negative Breast Cancer.

Puerarin has been reported to have anticancer properties; however, its mechanism in regulating triple-negative breast cancer (TNBC) remains unclear. Cell function was assessed using a cell counting kit-8 assay, 5-ethynyl-2'-deoxyuridine assay, flow cytometry, and transwell assay. Additionally, the glucose assay kit, lactate assay kit, and ADP/ATP ratio assay kit were used to analyze glucose metabolism. mRNA and protein expression levels were analyzed using qRT-PCR and western blotting assays, respectively. The relationship between FUS RNA binding protein (FUS) and mitogen-activated protein kinase 4 (MAPK4) was determined using an RNA immunoprecipitation assay. TNBC cell malignancy invitro was validated using a xenograft mouse model assay. Puerarin treatment or MAPK4 knockdown effectively inhibited TNBC cell proliferation, invasion, and glucose metabolism, and induced cell apoptosis. Additionally, puerarin treatment downregulated MAPK4 and FUS expression. Conversely, MAPK4 overexpression attenuated the effects of puerarin in TNBC cells. FUS stabilized MAPK4 mRNA expression in TNBC cells. Furthermore, puerarin decreased MAPK4 expression by downregulating FUS in TNBC cells. Finally, puerarin inhibited tumor formation invivo. Puerarin inhibited TNBC development by decreasing the expression of FUS-dependent MAPK4, indicating that puerarin may serve as a promising therapeutic agent to hind TNBC.

Knockdown of LncRNA-HAGLR restrains the viability and motility of pancreatic cancer via miR-625-5p/TAF15 axis in vitro and invivo

Dysregulation of long non-coding RNAs (lncRNAs) has been strongly involved to the development of pancreatic cancer (PC). However, the potential mechanisms by which lncRNA regulate PC development still need to be further explored. We attempted to elucidate the functional role and regulatory mechanism of lncRNA HAGLR on PC progression in vitro and vivo. RT-qPCR, Western blot, RNA pull-down, luciferase reporter assay, RNA immunoprecipitation assay, CCK-8 assay, EdU assay, flow cytometry, transwell assay and xenograft tumor experiment were performed in this study. We found that the expressions of HAGLR and TAF15 were increased in PC tissues and cells. HAGLR silencing restrained the PC cell growth and invasion, but induced cell apoptosis. Moreover, HAGLR targeted miR-625-5p to modulate the expression of TAF15. HAGLR overexpression partially eliminated the suppressive effect of TAF15 depletion on PC cell growth and the stimulative effect on apoptosis. In vivo assays showed that HAGLR knockdown inhibited PC cell growth by regulating the TAF15 expression. These findings suggest HAGLR could facilitate PC cell malignant behaviors through regulating the TAF15 expression, demonstrating that HAGLR might be a valuable target for the PC treatment.

Kinesin Family Member C1: Function in liver hepatocellular carcinoma and potential target for chemotherapeutic

MiR-105 exerts inhibitory effects on the development and progression of various cancers, including breast cancer, lung cancer, and gastric cancer. Through GEO data analysis, we observed decreased expression of miR-105 in liver cancer tissues compared to adjacent tissues. Furthermore, miR-105 downregulates KIFC1 expression levels by targeting its 3' UTR. KIFC1 (Kinesin Family Member C1), a Protein Coding gene, may play a role in mitotic metaphase plate polymerization and mitotic spindle assembly. However, our findings suggest that this gene could serve as a potential chemotherapeutic target for Liver hepatocellular carcinoma (LIHC). We obtained the LIHC dataset from the TCGA database and genotype Tissue Expression Project (GTEx) normal tissue data for differential analysis. Additionally, we utilized the cBioPortal database, tumor immune single-cell center (TISCH) database, gene set enrichment analysis (GSEA), and R software to investigate the possible functions and mechanisms of KIFC1. These findings were further validated through experiments such as immunohistochemistry and wound healing assays. Our results indicate that KIFC1 might be involved in DNA repair and cell cycle regulation in LIHC cells which subsequently impacts tumor cell proliferation; moreover, miR-105 influences hepatoma cell line proliferation via its interaction with KIFC1. Collectively, these results highlight the potential therapeutic significance of targeting KIFC1 for chemotherapy treatment in LIHC patients.

The Effects of Perfluorooctanoic Acid on Breast Cancer Metastasis Depend on the Phenotypes of the Cancer Cells: An in vivo Study with Zebrafish Xenograft Model

Per- and polyfluorinated substances (PFAS) have been associated with numerous human diseases. Recent in vitro studies have implicated the association of PFAS with an increased risk of breast cancer in humans. This study aimed to assess the toxic effects of PFAS during the development of human breast cancer using a zebrafish xenograft model. Perfluorooctanoic acid (PFOA) was used as a PFAS chemical of interest for this study. Two common breast cancer cell lines, MCF-7 and MDA-MB-231, were used to represent the diversity of breast cancer phenotypes. Human preadipocytes were co-implanted with the breast cancer cells into the zebrafish embryos to optimize the microenvironment for tumor cells in vivo. With this modified model, we evaluated the potential effects of the PFOA on the metastatic potential of the two types of breast cancer cells. The presence of human preadipocytes resulted in an enhancement to the metastasis progress of the two types of cells, including the promotion of cell in vivo migration and proliferation, and the increased expression levels of metastatic biomarkers. The enhancement of MCF-7 proliferation by preadipocytes was observed after 2 days post injection (dpi) while the increase of MDA-MB-231 proliferation was seen after 6 dpi. The breast cancer metastatic biomarkers, cadherin 1 (cdh1), and small breast epithelial mucin (sbem) genes demonstrated significant down- and upregulations respectively, by the co-injection of preadipocytes. In the optimized xenograft model, the PFOA consistently promoted cell proliferation and migration and altered the metastatic biomarker expression in MCF-7, which suggested a metastatic effect of PFOA on MCF-7. However, those effects were not consistently observed in MDA-MB-231. The presence of the preadipocytes in the xenograft model may provide a necessary microenvironment for the progress of tumor cells in zebrafish embryos. The finding suggested that the impacts of PFOA exposure on different phenotypes of breast cancers may differ.

Risk stratification models incorporating oxidative stress factors to predict survival and recurrence in patients with gastric cancer after radical gastrectomy: a real-world multicenter study

BackgroundOxidative stress significantly influences the development and progression of gastric cancer (GC). It remains unreported whether incorporating oxidative stress factors into nomograms can improve the predictive accuracy for survival and recurrence risk in GC patients. Methods3498 GC patients who underwent radical gastrectomy between 2009 and 2017 were enrolled and randomly divided into training cohort (TC) and internal validation cohort (IVC). Cox regression analysis model was used to evaluate six preoperative oxidative stress indicators to formulate the Systemic oxidative stress Score (SOSS). Two nomograms based on SOSS was constructed by multivariate Cox regression and validated using 322 patients from another two hospitals. ResultsA total of 3820 patients were included. The SOSS, composed of three preoperative indicators—fibrinogen, albumin, and cholesterol—was an independent prognostic factor for both overall survival (OS) and disease-free survival (DFS). The two nomograms based on SOSS showed a significantly higher AUC than the pTNM stage (OS: 0.830 vs. 0.778, DFS: 0.824 vs. 0.775, all P < 0.001) and were validated in the IVC and EVC (all P<0.001). The local recurrence rate, peritoneal recurrence rate, distant recurrence rate and multiple recurrence rate in high-risk group were significantly higher than those in low-risk group (P < 0.05). ConclusionsThe two novel nomograms based on SOSS which was a combination score of three preoperative blood indicators, demonstrated outstanding predictive abilities for both survival and recurrence in GC patients with different risk groups, which may potentially improve survival through perioperatively active intervention strategies and individualized postoperatively close surveillance.

Gambogic acid impairs the maintenance and therapeutic resistance of glioma stem cells by targeting B-cell-specific Moloney leukemia virus insert site 1

BackgroundGlioblastoma (GBM) is the most common and lethal primary brain tumor with low effectiveness of available treatments. The tumor heterogeneity and therapeutic resistance are largely due to the presence of glioma stem cells (GSCs). Therefore, eliminating GSCs can overcome the progression, relapse, and resistance of GBM. Previous studies have shown that gambogic acid (GA), a natural active ingredient, has anti-glioma properties. Nonetheless, it is still unclear whether it has an inhibitory effect on GSCs and what its target might be. This study aimed to investigate the anti-tumor effects of GA on GSCs. In addition, this study found the target of GA in GSCs and elucidated the potential specific mechanisms by conducting both in vitro and in vivo experiments.B-cell-specific Moloney leukemia virus insert site 1 (BMI1) is a key stem cell factor of the polycomb group (PcG) family with important effects on the development, recurrence, and chemoresistance of several cancers. In both normal and cancer stem cells, BMI1 maintains stem cell self-renewal by regulating the cell cycle, cellular immortalization, and senescence. Its high expression in a variety of cancers correlates with poor clinical prognosis and chemoresistance. These mechanisms of BMI1 make it a potential therapeutic target for cancer therapy, and future studies may further reveal the specific roles of BMI1 mechanism and provide a basis for the development of new cancer therapeutic strategies. PurposeThis study investigated the in vitro and in vivo effects of GA in inducing apoptosis in GSCs and inhibiting GSCs self-renewal, as well as its underlying mechanisms. MethodsThis study synthesized biotinylated gambogic acid for the first time and angled for the target of gambogic acid using LC-MS/MS analysis, which has not been reported previously. Human-derived glioma stem cells GSC123 and GSC111 were used for in vitro studies, analyzing functions and mechanisms via microscale thermophoresis (MST), Annexin V/PI staining, Western blotting, immunofluorescence, and co-immunoprecipitation. The orthotopic glioma mouse model was used to assess the anti-tumor effects of GA in vivo. ResultsThis study demonstrated that GA is a specific inhibitor of BMI1, a key regulator controlling stem cell growth and self-renewal. GA binds to BMI1′s RING domain, accelerating K51-dependent degradation and suppressing H2A ubiquitination. Importantly, GA induces apoptosis, and inhibits GSC self-renewal, but minimally impacts neural progenitor cells (NPCs). GA can also be combined effectively with temozolomide and radiotherapy to increase their sensitivities in resistant cells. Furthermore, exogenous induction of BMI1 expression significantly hinders the disruption of GSCs by GA. In vivo, GA inhibits tumorigenicity, enhances the effect of temozolomide, and reduces BMI1 expression. ConclusionThese findings suggest that GA is a potential candidate for targeting GSCs and therefore be used to treat GBM.

Poor Prognosis among Radiation-Associated Bladder Cancer Is Defined by Clinicogenomic Features.

Clinicogenomic analysis of radiation-associated bladder cancer uncovered mutational signatures that, in addition to a short tumor latency, smoking, and CDKN2A loss, are associated with a poor outcome. These clinical and genomic features provide a potential method to identify patients with prostate cancer who are at an increased risk for the development of aggressive bladder cancer following prostate RT.

Increased skin cancer development in a previously stable elderly female.

Increased skin cancer development in a previously stable elderly female.

Unlocking the potential of exosomes: A new frontier in liver cancer liquid biopsy

Liquid biopsy has emerged as one of the non-invasive diagnostic strategies for cancer, offering significant advantages over traditional tissue biopsies. Exosomes the nanoscale extracellular vesicles, have significantly been in the spotlight of research and investigation as highly informative biomarkers in liquid biopsy. These vesicles, which are secreted by a variety of cells, including tumor cells, contain useful information on the molecular characteristics of the parent cell and could be used as a mirror into the processes underlying cancer biology. The analysis of the biomolecular exosomal cargo, including proteins, nucleic acids, and lipids, has shown great promise for the development of sensitive and specific liquid biopsy-based biomarkers for cancer detection, monitoring, and prognosis. This review discusses the role of exosomes in the liver cancer development and metastatic process, including their ability to transfer oncogenic material and facilitate tumor progression. It also explores the application of exosomes as a tool for early cancer detection, monitoring disease status, and predicting prognosis, with a specific focus on liver cancer. Exosomes hold great promise as a minimally invasive liquid biopsy approach that could revolutionize the way we diagnose and manage this deadly disease.

Dissection of intratumor microbiome-host interactions at single-cell level in lung cancer

The intratumor microbiome, one of the hallmarks of cancer, plays a crucial role in cancer progression through interaction with the host. However, the underlying mechanisms remain poorly understood. Here we investigated the heterogeneity of host-microbiome interactions at the single-cell level by integrating six single-cell transcriptomic lung cancer datasets using single-cell analysis of host-microbiome interactions (SAHMI). Our findings indicate that primary tumor tissues display a high proportion of fungi-associated cells, whereas metastatic brain tissues predominantly feature bacteria-associated cells. A distinct distribution of fungal and bacterial taxa across various cell types was observed. Notably, the presence of specific bacteria significantly influences the transcriptome of resident host cells, including T cells and macrophages, by modulating pathways related to rRNA processing, cellular responses to stress and stimuli, and the metabolism of RNA and proteins. Finally, specific cell-associated bacteria are significantly correlated with clinical features, such as lung cancer stages and smoking frequency. These single-cell insights into microbiome-host interactions facilitate our understanding of lung cancer development and progression, offering potential microecological and diagnostic insights.

Does each Component of Reactive Oxygen Species have a Dual Role in the Tumor Microenvironment?

Reactive oxygen species (ROS) are a class of highly reactive oxidizing molecules, including superoxide anion (O2•-) and hydrogen peroxide (H2O2), among others. Moderate levels of ROS play a crucial role in regulating cellular signaling and maintaining cellular functions. However, abnormal ROS levels or persistent oxidative stress can lead to changes in the tumor microenvironment (TME) that favor cancer development. This review provides an overview of ROS generation, structure, and properties, as well as their effects on various components of the TME. Contrary to previous studies, our findings reveal a dual effect of ROS on different components of the TME, whereby ROS can either enhance or inhibit certain factors, ultimately leading to the promotion or suppression of the TME. For example, H2O2 has dual effects on immune cells and non-cellular components within the TME, while O2•- has dual effects on T cells and fibroblasts. Furthermore, each component demonstrates distinct mechanisms of action and ranges of influence. In the final section of the article, we summarize the current clinical applications of ROS in cancer treatment and identify certain limitations associated with existing therapeutic approaches. Therefore, this review aims to provide a comprehensive understanding of ROS, highlighting their dual effects on different components of the TME, and exploring the potential clinical applications that may pave the way for future treatment and prevention strategies.

Let-7 reduces the proliferation and migration of oral cancer cells via PI3K/AKT signaling pathway.

The involvement of let-7 in the occurrence and progression of various cancers has been well-documented. However, the precise molecular mechanisms underlying its impact on oral cancer development remain unclear. In this study, we aimed to elucidate the role of let-7 in oral cancer progression and investigate its underlying molecular mechanisms. The expression of let-7 and high mobility group A2 (HMGA2) mRNA was assessed using the quantitative reverse transcription polymerase chain reaction. Western blot analysis was employed to detect the expression of key proteins in the PI3K/AKT signaling pathway as well as HMGA2 protein levels. The targeting relationship between let-7 and HMGA2 was predicted through bioinformatics methods and confirmed via luciferase reporter gene assay. The effects of let-7 and HMGA2 on the functionality of oral cancer cells were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, colony formation assay, Transwell assay, wound healing assay, and Annexin V/PI apoptosis assay. Additionally, the impact of let-7 on the growth of oral cancer cells in vivo was investigated by inducing subcutaneous tumor formation in nude mice. Let-7 effectively suppresses the proliferation, migration, and invasion of oral cancer cells by inhibiting the activation of the PI3K/AKT signaling pathway. HMGA2, a downstream target gene of let-7, exhibits high expression in oral cancer. However, overexpression of HMGA2 diminishes the inhibitory effects induced by let-7 overexpression on the proliferation, migration, and invasion of oral cancer cells. The occurrence and progression of oral cancer cells are inhibited by Let-7 through the downregulation of HMGA2, potentially mediated by the inhibition of PI3K/AKT signaling pathway activation.

Regulation of KIF23 by miR-107 controls replicative tumor cell fitness in mouse and human hepatocellular carcinoma

Background & AimsIn hepatocellular carcinoma (HCC), there is a lack of successful translation of experimental targets identified in mouse models to human patients. In this study, we used a comprehensive transcriptomic approach in mice to identify novel potential targets for therapeutic intervention in humans. MethodsWe analyzed combined genome-wide miRNA and mRNA expression data in three pathogenically distinct mouse models of liver cancer. Effects of target genes on hepatoma cell fitness were evaluated by proliferation, survival and motility assays. TCGA and GEO databases, in combination with tissue microarrays (TMA), were used to validate the mouse targets and their impact on human HCC prognosis. Finally, the functional effects of the identified targets on tumorigenesis and tumor therapy were tested in hydrodynamic tail vein injection (HDTVi)-based preclinical HCC models in vivo. ResultsThe expression of miR-107 was found to be significantly reduced in mouse models of liver tumors of various etiologies and in cohorts of human HCC patients. Overexpression of miR-107 or inhibition of its novel target Kinesin family member 23 (Kif23) significantly reduced proliferation by interfering with cytokinesis, thereby controlling survival and motility of mouse and human hepatoma cells. In humans, KIF23 expression was found to be a prognostic marker in liver cancer, with high expression associated with poor prognosis. HDTVi of vectors carrying either pre-miR-107 or anti-Kif23 shRNA inhibited the development of highly aggressive c-Myc-NRAS-induced liver cancers in mice. ConclusionsDisruption of the miR-107/Kif23 axis inhibited hepatoma cell proliferation in vitro and prevented oncogene-induced liver cancer development in vivo, offering a novel potential avenue for the treatment of HCC in humans. Impact and implicationsOur study revealed the central role of the miR-107/KIF23 axis in controlling tumor cell fitness and HCC progression. The results demonstrate that the overexpression of miR-107 or silencing of its target, KIF23, markedly suppresses the proliferation, survival, and motility of human and mouse hepatoma cells. In this work, we demonstrate that the disruption of miR-107/Kif23 signaling effectively protects mice from an aggressive form of oncogene-induced liver cancer in vivo, implying that targeting miR-107/KIF23 might be a novel therapeutic approach for HCC in humans.

786. ANATOMICAL DISTRIBUTION OF HUMAN PAPILLOMAVIRUS INFECTION IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Abstract Background Human Papillomavirus (HPV) infection is a high-risk factor for many types of cancer development. The reported infectious rate in esophageal squamous cell carcinoma (ESCC) varies widely, ranging from 0% to 88.9%. It may be caused due to geographical location, sample size, and detection methods. In general, p16 expression is considered as a biomarker for HPV infection. However, the correlation between the p16 expression and HPV infectious status has been controversial. Methods Patients with ESCC underwent esophagectomy without neoadjuvant chemotherapy (NAC) from 2007 to 2021 were included. Three formalin-fixed paraffin-embedded blocks (oral side, tumor, and esophagogastric junction (EGJ)) from each surgical resected specimen were collected. p16 expression was examined by immunohistochemistry (labeling index ≥ 10% is defined as positive expression). The presence of HPV DNA was investigated by polymerase chain reaction. In addition, the anatomical distribution of HPV infection was investigated. Results A total of 158 patients with 417 samples were included. The positive expression rate of p16 was 3.6% (5/137), 19.2% (30/156) and 2.1% (3/146) in oral side, tumor, and EGJ, respectively. The HPV infectious rate was 7% (11/158), and six cases were detected in tumor site and the other 5 cases were detected in oral side or EGJ. In tumor tissue, HPV positive cases showed p16 positive, and the sensitivity and specificity for detecting HPV DNA by IHC of p16 were 100% and 84%, respectively. The HPV infection in ESCC specimens appears to be irregular. Conclusion This study is the largest sample size in Japan, demonstrating the p16 positive rate of 19.2% and HPV infectious rate of 7% in ESCC patients without NAC. IHC of p16 can be used as a screening examination for predicting HPV infection in ESCC because the false negative rate was 0%. In addition, we firstly reported the HPV infectious mapping in ESCC specimens, and it appears irregular and random.

The Cutting-edge of CRISPR for Cancer Treatment and its Future Prospects.

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a versatile technology that allows precise modification of genes. One of its most promising applications is in cancer treatment. By targeting and editing specific genes involved in cancer development and progression, CRISPR has the potential to become a powerful tool in the fight against cancer. This review aims to assess the recent progress in CRISPR technology for cancer research and to examine the obstacles and potential strategies to address them. The two most commonly used CRISPR systems for gene editing are CRISPR/Cas9 and CRISPR/Cas12a. CRISPR/Cas9 employs different repairing systems, including homologous recombination (HR) and nonhomologous end joining (NHEJ), to introduce precise modifications to the target genes. However, off-target effects and low editing efficiency are some of the main challenges associated with this technology. To overcome these issues, researchers are exploring new delivery methods and developing CRISPR/Cas systems with improved specificity. Moreover, there are ethical concerns surrounding using CRISPR in gene editing, including the potential for unintended consequences and the creation of genetically modified organisms. It is important to address these issues through rigorous testing and strict regulations. Despite these challenges, the potential benefits of CRISPR in cancer therapy cannot be overlooked. By introducing precise modifications to cancer cells, CRISPR could offer a targeted and effective treatment option for patients with different types of cancer. Further investigation and development of CRISPR technology are necessary to overcome the existing challenges and harness its full potential in cancer therapy.

Staphylococcus aureus lipid factors modulate melanoma cell clustering and invasion.

The microbiome can influence cancer development and progression. However, less is known about the role of the skin microbiota in melanoma. Here, we took advantage of a zebrafish melanoma model to probe the effects of Staphylococcus aureus on melanoma invasion. We found that S. aureus produces factors that enhance melanoma invasion and dissemination in zebrafish larvae. We used a published in vitro 3D cluster formation assay that correlates increased clustering with tumor invasion. S. aureus supernatant increased clustering of melanoma cells and was abrogated by a Rho-Kinase inhibitor, implicating a role for Rho-GTPases. The melanoma clustering response was specific to S. aureus but not to other staphylococcal species, including S. epidermidis. Our findings suggest that S. aureus promotes melanoma clustering and invasion via lipids generated by the lipase Sal2 (officially known as GehB). Taken together, these findings suggest that specific bacterial products mediate melanoma invasive migration in zebrafish.