Tumor Invasion Research Articles

CaCO3-encircled hollow CuS nanovehicles to suppress cervical cancer through enhanced calcium overload-triggered mitochondria damage

Cervical cancer stands is a formidable malignancy that poses a significant threat to women's health. Calcium overload, a minimally invasive tumor treatment, aims to accumulate an excessive concentration of Ca2+ within mitochondria, triggering apoptosis. Copper sulfide (CuS) represents a photothermal mediator for tumor hyperthermia. However, relying solely on thermotherapy often proves insufficient in controlling tumor growth. Curcumin (CUR), an herbal compound with anti-cancer properties, inhibits the efflux of exogenous Ca2+ while promoting its excretion from the endoplasmic reticulum into the cytoplasm. To harness these therapeutic modalities, we have developed a nanoplatform that incorporates hollow CuS nanoparticles (NPs) adorned with multiple CaCO3 particles and internally loaded with CUR. This nanocomposite exhibits high uptake and easy escape from lysosomes, along with the degradation of surrounding CaCO3, provoking the generation of abundant exogenous Ca2+in situ, ultimately damaging the mitochondria of diseased cells. Impressively, under laser excitation, the CuS NPs demonstrate a photothermal effect that accelerates the degradation of CaCO3, synergistically enhancing the antitumor effect through photothermal therapy. Additionally, fluorescence imaging reveals the distribution of these nanovehicles in vivo, indicating their effective accumulation at the tumor site. This nanoplatform shows promising outcomes for tumor-targeting and the effective treatment in a murine model of cervical cancer, achieved through cascade enhancement of calcium overload-based dual therapy.

Machine learning models reveal ARHGAP11A's impact on lymph node metastasis and stemness in NSCLC.

Most patients with non-small cell lung cancer (NSCLC) are diagnosed at an advanced stage of the disease, which complicates treatment due to a heightened risk of metastasis. Consequently, the timely identification of biomarkers associated with lymph node metastasis is essential for improving the clinical management of NSCLC patients. In this research, the WGCNA algorithm was utilized to pinpoint genes linked to lymph node metastasis in NSCLC. A cluster analysis was carried out to investigate how these genes correlate with the prognosis and the outcomes of immunotherapy for NSCLC patients. Following this, diagnostic and prognostic models were created and validated through various machine learning methodologies. The random forest technique highlighted the importance of ARHGAP11A, leading to an in-depth examination of its role in NSCLC. By analyzing 78 tissue chip samples from NSCLC patients, the study confirmed the association between ARHGAP11A expression, patient prognosis, and lymph node metastasis. Finally, the influence of ARHGAP11A on NSCLC cells was assessed through cell function experiments. This research utilized the WGCNA technique to identify 25 genes that are related to lymph node metastasis, clarifying their connections with tumor invasion, growth, and the activation of stemness pathways. Cluster analysis revealed significant associations between these genes and lymph node metastasis in NSCLC, especially concerning immunotherapy and targeted treatments. A diagnostic system that combines various machine learning approaches demonstrated strong efficacy in forecasting both the diagnosis and prognosis of NSCLC. Importantly, ARHGAP11A was identified as a key prognostic gene associated with lymph node metastasis in NSCLC. Molecular docking analyses suggested that ARHGAP11A has a strong affinity for targeted therapies within NSCLC. Additionally, immunohistochemical assessments confirmed that higher levels of ARHGAP11A expression correlate with unfavorable outcomes for NSCLC patients. Experiments on cells showed that reducing ARHGAP11A expression can hinder the proliferation, metastasis, and stemness traits of NSCLC cells. This investigation reveals the novel insight that ARHGAP11A may function as a potential biomarker connected to lymph node metastasis in NSCLC. Moreover, reducing the expression of ARHGAP11A has demonstrated the ability to diminish tumor stemness characteristics, presenting a promising opportunity for improving treatment strategies for this condition.

Exosomal Delivery of miR-155 Inhibitor can Suppress Migration, Invasion, and Angiogenesis Via PTEN and DUSP14 in Triple-negative Breast Cancer.

Triple-Negative Breast Cancer (TNBC) is the most common type of breast cancer (BC). In order to develop effective treatments for TNBC, it is vital to identify potential therapeutic targets. Angiogenesis stimulates tumor growth and metastasis in TNBC, and miR-155 plays a crucial role in this process. The exosome is a nano-sized vesicle that carries many cargoes, including miRNAs. The present study investigated the effect of exosomal delivery of miR-155 antagomir on tumor migration, invasion, and angiogenesis in TNBC. From MDA-MB-231 cells, exosomes were extracted, characterized, and loaded with miR-155 antagomir using electroporation. The expression of miR-155 and its target genes, including PTEN and DUSP14, was analyzed using RTqPCR. The wound-healing and transwell assays were used to measure cell migration and invasion. Furthermore, angiogenesis was evaluated by tube formation and chorioallantoic membrane (CAM) assays. The results indicated that exosomal delivery of miR-155 antagomir to HUVEC cells significantly suppressed miR-155 expression while upregulating PTEN and DUSP14. The tube formation properties of HUVEC cells were also significantly reduced following treatment with exosomes containing miR-155 antagomirs, and these results were confirmed using CAM assay. The migration and invasion of MDA-MB-231 cells were significantly reduced after treatment with miR-155 antagomir-loaded exosomes. It was found that miR-155 antagomir delivery using exosomes can inhibit migration, invasion, and angiogenesis viaPTEN and DUSP14 in TNBC.

Progress in the study of anti-tumor effects and mechanisms of vitexin.

Vitexin (apigenin-8-C-beta-D-glucopyranoside) is a natural flavonoid derivative with anti-cancer, antioxidant, anti-inflammatory, antihypertensive, anti-asthma, anti-epilepsy, and other therapeutic effects. It is extracted from pearl millet, hawthorn, pigeon bean, mung bean, and other medicinal plants. Vitexin has received widespread attention because of its significant anti-tumor effect. It induces apoptosis and anti-tumor angiogenesis, inhibits tumor cell migration and invasion, regulates tumor cell autophagy and immunity, and increases patient sensitivity to radiotherapy and chemotherapy. It has a significant anti-tumor effect on breast, prostate, liver, cervical, and colon cancers, gliomas, and other malignant tumors. This review demonstrates the latest research progress on the anti-tumor effects and potential mechanisms of vitexin. It summarizes its anti-tumor mechanism to provide new theoretical support and reference for cancer treatment.

Modified salpingopharyngeus myomucosal flap: a novel technique for skull base reconstruction.

Advancements in endoscopic skull base surgery have enabled complex tumor resections, necessitating a variety of reliable reconstructive techniques to repair resultant defects. Vascularized flaps represent optimal options, but frequently used local pedicled intranasal flaps may be unavailable due to tumor invasion or prior surgery. This study applies a modification to the previously described salpingopharyngeus myomucosal flap (Dicle flap) with potential for its use in extensive endoscopic skull base surgery defect's repair. Cadaveric dissections (n = 5) were performed utilizing endoscopic visualization to access the skull base via endonasal and transoral routes. A superiorly based posterior pharyngeal myomucosal flap along the salpingopharyngeus muscle was elevated off the superior pharyngeal constrictors, preserving their vascular pedicles. This combined flap could be 180 degrees transposed to reconstruct clival defects up to the sella turcica. The modified salpingopharyngeus myomucosal flap (Modified Dicle flap) provided approximately 40 cm2 of robust vascularized tissue based on the ascending pharyngeal artery and random posterior pharyngeal vessels. It was sufficiently mobilized to cover extensive skull base defects in the craniocervical junction, sella turcica, and protecting the exposed internal carotid artery segments. The modified Dicle flap offers a viable reconstructive option for extensive endoscopic endonasal skull base defects when commonly utilized vascularized flaps are unavailable. Further research on clinical cases is warranted to investigate postoperative function and refine techniques to minimize donor site morbidity. Not applicable.

Analysis of the therapeutic effect and influencing factors on unresectable gastric cancer treated with conversion therapy.

Gastric cancer (GC) is one of the leading causes of cancer-related death in China, and with the extensive development of conversion therapy, the treatment of advanced unresectable gastric cancer (AUGC) patients has ushered in a new dawn. This study aimed to analyze the efficacy of conversion therapy in AUGC patients and explored the relevant factors affecting the efficacy. We collected information from GC patients who received conversion therapy from this center and designed a retrospective study. We collected relevant clinical data from 160 patients with AUGC. A total of 120 patients who underwent routine R0 resection were identified as conversion cases. A total of 25 patients (15.6%) achieved pCR, 92 patients (57.5%) achieved objective response rate (ORR), 140 patients (87.5%) achieved disease control rate (DCR), and 20 cases (12.5%) observed tumor progression. There were 86 patients who achieved pathological downgrading, with a total downgrading rate of 53.8%. Among the 160 patients, 37 patients (23.1%) had postoperative complications of varying degrees. A total of 72 patients (45.0%) had tumor recurrence/progression at the end of follow-up. The last chemotherapy and surgery (CST) (OR = 1.046, 95% CI 1.013-1.081, p = 0.006), tumor invasion (OR = 32.096, 95% CI 5.091-202.349, p < 0.001), and distant metastasis (OR = 7.050, 95% CI 1.888-26.323, p = 0.004) were independent factors influencing the efficacy of conversion therapy. Conversion therapy may have a good therapeutic efficacy for AUGC, and some clinical factors affect the efficacy response.

Histopathological Profile of Cholecystectomy Specimens at a Tertiary Care Center: A Retrospective Study

Abstract Introduction: Gallbladder is one of the most frequently received specimens in any histopathology laboratory. Its diseases may present with a varied spectrum ranging from congenital anomalies, cholelithiasis, and inflammatory or noninflammatory lesions to noninvasive and invasive neoplasms. Cholelithiasis (gallstones) is the most common lesion and accounts for more than 95% of gallbladder diseases and affects 10%–20% of the adult population. The incidence is 2–4 times higher in females than in males. Aims and Objectives: This study was designed to study the histopathological spectrum of gall bladder diseases in the population, study the most common gall bladder diseases in cholecystectomy specimens, and study the frequency of gall bladder carcinoma. Methodology: This retrospective observational study was done in the Pathology department at a tertiary care hospital and research center, from September 2016 to September 2023. Tissue was fixed in 10% buffered formalin and then processed by the routine paraffin embedding techniques. Sections were cut at 4–5 μ thickness and stained with hematoxylin and eosin stains. Special stains were done if required for confirmation. All the slides were analyzed and reported by a trained histopathologist. Results: Females were affected more as compared to males. The commonest age group affected was 41-50 years. Gallstones were observed in 33.58% of patients. Gallbladder neoplasm was rare and incidental findings. Conclusion: Gallbladder disease demonstrated a diverse spectrum of histopathological changes in the cholecystectomy specimens and showed female preponderance. Gallbladder carcinoma was observed as a rare occurrence and was an incidental finding mainly. Hence, a microscopic (histopathological) examination is required for every cholecystectomy specimen.

Diagnostic significance of peritumoral enhancement in distinguishing between muscle-invasive and non-muscle-invasive bladder cancer.

The aim of this study was to assess the prevalence of peritumoral enhancement (PTE) in patients with muscle-invasive bladder cancer (MIBC) and non-MIBC (NMIBC) and to propose a modified diagnostic criterion for Vesical Imaging Reporting and Data System (VI-RADS) that incorporates PTE. This retrospective study included 95 patients with bladder cancer (age, 72 ± 11; 77 men; 36 MIBCs and 59 Non-MIBCs) who underwent multiparametric MRI in our referral center between 2011 and 2023. The images were interpreted by four radiologists. The readers classified the possibility of muscle layer invasion into categories 1-5, based on the VI-RADS categorical diagnostic criterion. PTE was defined as a linear contrast enhancement observed at the edge of tumor invasion which is convex outward from the normal bladder wall and contrasts more than the normal muscle layer and tumor. A modified VI-RADS that upgrades the final VI-RADS category to 4 if PTE is present when the original VI-RADS category is 3 or less was proposed. The frequency of PTE in the MIBC and NMIBC groups was compared using the Fisher's exact test. Sensitivity and specificity for the diagnosis of MIBC were compared with the original VI-RADS using McNemar test. Pathologic diagnosis was used as the reference standard. PTE was present in 70-81% (25/36-29/36) of MIBC and absent in 92-98% (54/59-58/59) of non-MIBC. For all readers, the PTE was significantly more frequent (p < 0.001) in the MIBC group than the NMIBC group. The sensitivities of modified VI-RADS (75.0-86.1%) were significantly higher than those of original VI-RADS (41.7-55.6%) (p = 0.002-0.008). The specificity of modified VI-RADS (91.5-98.3%) were not statistically different from original VI-RADS (98.3-100%). In conclusion, PTE is a highly specific finding for MIBC. modified VI-RADS incorporating PTE increases sensitivity for MIBC.

Perivascular epithelioid cell tumor of the uterus and pelvic cavity.

Primary perivascular epithelioid cell tumors (PEComas) of the female reproductive tract have been primarily reported as case reports owing to their clinical rarity. Limited incidence rates and clinical case data hinder a comprehensive understanding of the risks and invasiveness of this disease. We discuss herein the diagnosis, treatment, and prognosis of this disease to enhance comprehension and therapeutic strategies. We conducted a clinical analysis of patients with PEComa treated at the Gynecology Department of The West China Second University Hospital of Sichuan University between May 2018 and January 2024. Diagnosis and treatment were evaluated based on pertinent literature. Overall, eight patients (seven patients with tumors in the uterus and one patient with tumors in the pelvic cavity) were evaluated. One patient with PEComa of unknown malignant potential and two patients with malignant PEComa underwent hysterectomy and bilateral adnexectomy with or without adjuvant therapy and did not develop recurrence. Meanwhile, three patients who underwent lesion resection only exhibited radiological evidence of new lesions. Furthermore, postoperative imaging identified new pulmonary nodules in three patients. Although the current criteria are generally effective in assessing the tumor invasiveness of PEComa, emphasizing the significance of complete lesion resection remains crucial. Inadequate treatment significantly increases the risks of recurrence and metastasis. Additionally, the prevalence of pulmonary metastases may have been underestimated. Refining risk stratification to prevent overtreatment of low-grade malignancies or overlooking highly aggressive tumors is an important area for further study.

Assembly of glioblastoma tumoroids and cerebral organoids: a 3D in vitro model for tumor cell invasion.

Glioblastoma (GBM) has a fatal prognosis because of its aggressive and invasive characteristics. Understanding the mechanism of invasion necessitates an elucidation of the relationship between tumor cells and the tumor microenvironment. However, there has been a scarcity of suitable models to investigate this. In this study, we established a glioblastoma-cerebral organoid assembloid (GCOA) model by co-culturing patient-derived GBM tumoroids and human cerebral organoids. Tumor cells from the tumoroids infiltrated the cerebral organoids, mimicking the invasive nature of the parental tumors. Using time-lapse imaging, various invasion patterns of cancer cells within cerebral organoids resembling a normal tissue milieu were monitored. Both single- and collective-cell invasion was captured in real-time. We also confirmed the formation of an intercellular tumor network and tumor-normal-cell interactions. Furthermore, the transcriptomic characterization of GCOAs revealed distinct features of invasive tumor cells. Overall, this study established the GCOA as a three-dimensional (3D) in vitro assembloid model to investigate invasion mechanisms and interactions between tumor cells and their microenvironment.

A Comparison Between Immunohistochemistry and mRNA Expression to Identify Human Epidermal Growth Factor Receptor 2–Low Breast Cancer

Context.— Breast cancers (BCs) with low levels of human epidermal growth factor receptor 2 (HER2) expression (HER2-low) have become a targetable subset because of novel antibody-drug conjugates. HER2 immunohistochemistry (IHC) is the recommended assay for HER2 classification but is associated with limited interobserver agreement concerning HER2-low identification. Objective.— To investigate whether mRNA expression quantified via quantitative reverse transcription–polymerase chain reaction (RT-qPCR) could serve as a valuable complementary and more objective method to identify HER2-low BCs. Design.— We selected all cases from a previously published interobserver study, which included 105 needle biopsies from HER2 nonamplified BC cases. HER2 IHC was evaluated by 16 pathologists. For the current study, mRNA was extracted from microdissected invasive tumor cells. RT-qPCR was performed for quantitative evaluation of HER2, using the cutoff values of the MammaTyper assay. We compared the mRNA expression levels with the IHC scores of the majority agreement (IHC 0, IHC &amp;gt;0, &amp;lt;1+ [ultralow], 1+, 2+) and the following HER2 subcategories: HER2 0/ultralow and HER2-low (IHC 1+ and 2+/fluorescence in situ hybridization negative). Results.— In total, 88 nonamplified HER2 cases could be analyzed. Based on IHC, 17 cases were HER2 0/ultralow and 71 were HER2-low. The mean rank HER2 mRNA level was significantly higher in HER2-low cases than in the HER2 0/ultralow group (P &amp;lt; .001). However, 10 of 17 HER2 0/ultralow cases by IHC (58.8%) were classified as HER2-low by MammaTyper, 2 of 71 cases (2.8%) were HER2-low by IHC and HER2 0/ultralow by MammaTyper, and 2 (2.8%) were HER2-low by IHC and HER2-positive by RP-qPCR. Conclusions.— Our findings indicate a strong agreement between mRNA expression quantified by RT-qPCR and HER2 IHC scores, although there was a substantial proportion of discordant HER2 results between both methods owing to overestimation of HER2 expression by MammaTyper compared to IHC. Future large-scale trials should determine which technique is best associated with clinical outcome.

Impact of CA9 expression in the diagnosis of lymph-node metastases in non-small cell lung cancer based on [18F]FDG PET/CT.

Lung cancer is the leading cause of the global cancer incidence and mortality. It is important to obtain an accurate diagnosis of lymph-node metastasis before surgery to select the therapeutic strategy for non-small cell lung cancer (NSCLC) patients. Carbonic anhydrase 9 (CA9) is considered a marker of hypoxia and it has reported that CA9 is associated with tumor invasion and metastasis. In this study, the correlation between the CA9 expression for lymph-node metastases in NSCLC and [18F]FDG PET/CT results was investigated in order to clarify the efficacy of [18F]FDG PET/CT for detecting lymph-node metastases of NSCLC patients. Among the 564 patients who underwent surgical treatment for NSCLC between 2010 and 2016 at our hospital, a total of 338 patients who underwent preoperative [18F]FDG PET/CT were included in this study. CA9 expression was evaluated by immunochemistry. A lymph node with maximum standardized uptake value (SUVmax) ≥2.5 on [18F]FDG PET/CT was preoperatively defined as a metastatic lymph node. CA9 positivity was detected in 122 patients; the other 216 patients were CA9-negative. The CA9-positive NSCLC cases significantly associated with pleural invasion (p = 0.0063), pT-factor (p = 0.0080), pN-factor (p = 0.036) and pStage (p = 0.043). CA9-positive patients presented significantly poorer survival rate for OS than that of the CA9-negative patients (p = 0.0024). In the multivariable analysis, histological SCC and CA9 positivity were independent poor-prognosis factors for OS. For the total patient population, the sensitivity and specificity of [18F]FDG PET/CT for lymph-node metastases were 54% and 89%, respectively. In contrast, the sensitivity and specificity were particularly low in the CA9-positive SCC cases (36% and 69%, respectively). [18F]FDG PET/CT might not be useful for diagnosing lymph-node metastases of CA9-positive SCC cases of NSCLC.

Patterns of expression of VEGFR2, PDGFRs and c-Kit in pediatric patients with high grade non-rhabdomyosarcoma soft tissue sarcoma.

Activated vascular endothelial growth factor receptors (VEGFRs), platelet-derived growth factor receptors (PDGFRs) and c-Kit have been shown to be involved in the growth, invasion and metastasis of non-rhabdomyosarcoma soft tissue sarcoma tumor (NRSTS) with promising results for targeted therapy. Our aim was to assess the expression of these markers among different histological types and correlate with outcomes. This retrospective study included pediatric patients aged ≤ 18 years diagnosed with high-grade NRSTS who were treated at Children Cancer Hospital Egypt 57357 as per the COG NRSTS protocol (ARST0332). Expression of VEGFR2, PDGFRs (α and β) and c-Kit in tumor tissue was assessed by immunohistochemistry and correlated with clinical outcome. Of 113 patients, 96 were eligible for the analysis with a median age of 11 years. Overall, 32.3% demonstrated high expression of PDGFRα, 17.7% for PDGFRβ, 19.8% for VEGFR2 and 8.3% exhibited positive expression for c-kit on the tumor cells. Most cases of synovial sarcoma (45.8%) and 43.7% of patients with undifferentiated sarcoma exhibited high expression of PDGFRα while 41.6% of MPNST showed high expression to PDGFRβ. The 5-year overall survival (OS), event free survival and relapse free survival (RFS) for the whole cohort were 59%, 54% and 60% respectively. In univariate analyses, only PDGFRα had a negative prognostic impact on relapse free survival (RFS) (p=0.03). In multivariate analyses, VEGFR2 was found to have a negative prognostic impact for OS (p = 0.02). Our findings indicated that tyrosine kinase receptors are upregulated in NRSTS and exhibited a distinct expression pattern within various subgroups. High expression of VEGFR2 and PDGFRα significantly correlated with reduced survival and may guide targeted therapy approaches for this poor prognosis group of patients.

Clinical significance of Talin-1 and HER-2 status in different types of gastric carcinoma

Background Talin-1 (TLN1) is crucial in cell migration, metastasis, and cancer development. This study evaluated Talin-1 expression and its clinical significance in gastric cancer (GC), along with human epidermal growth factor receptor-2 (HER-2) expression and its correlation with Talin-1. Methods Bioinformatics analysis assessed the potential prognostic value of Talin-1 and HER-2 in GC patients. The study included 223 GC patients (Signet Ring Cells and Intestinal subtypes) and 29 non-malignant tissue samples. Immunohistochemistry (IHC) on tissue microarray slides evaluated Talin-1 and HER-2 expression and clinical significance. Receiver operating characteristic (ROC) curves assessed their diagnostic value. Results Bioinformatics identified Talin-1 as a potential prognostic factor and HER-2 as an oncogene in GC. Talin-1 and HER-2 expression increased in SRC-type GC samples compared to non-malignant tissues. High cytoplasmic Talin-1 expression inversely correlated with tumor expansion and invasion in SRC-type GC. Increased HER-2 expression positively correlated with metastasis. ROC curves showed significant diagnostic values for both proteins. Conclusions Higher cytoplasmic Talin-1 expression is associated with less invasive tumor behavior, while increased membranous HER-2 expression is associated with metastasis in SRC-type GC. These findings suggest potential use in assessing diagnosis and screening high-risk cancer patients, particularly those with SRC-type GC.

ZNF671 Silencing Affects Signaling Pathways in Head and Neck Cancer via Activation of Oncogenic Non-Coding RNAs

Background: Novel ZNF genes, such as ZNF671, that are located on chromosome 19q13 are known to be hypermethylated at a high frequency in HNSCC as well as in other epithelial solid tumors. Their function is largely unknown. Results: Here, we show that ZNF671 is epigenetically silenced in HNSCC primary tumors compared to matched adjacent normal tissue. Moreover, low expression of ZNF671 is significantly associated with decreased survival in HNSCC patients. Over-expression of ZNF671 in UM-SCC-1 oral cancer cells resulted in a significant reduction in tumor cell mobility and invasion compared to the empty-vector control cells. Transcriptomic analysis showed that ZNF671 re-expression resulted in a significant decrease in the expression of a major oncogenic long non-coding RNA LINC00665. Conclusions: Together, these results suggest that epigenetic silencing of ZNF671 may activate multiple oncogenic signaling pathways via the resulting up-regulation of LINC00665.

COLONOSCOPIC TREATMENT FOR EARLY STAGE RECTUM ADENOCARCINOMA

Colorectal cancer is a malignant neoplasm that arises in the colon or rectum, characterized by the uncontrolled growth of epithelial cells, forming invasive tumors that can metastasize. It is the third most common neoplasm globally, with approximately 1.9 million new cases per year. In Brazil, in 2022, 5,573 deaths from rectal cancer were recorded, with a high incidence among women and a growing concern in younger age groups. Risk factors include type II Diabetes Mellitus, use of anti-inflammatory drugs, smoking and obesity, which is related to chronic inflammation and hormonal changes that favor cancer. Approximately 20% of patients with non-metastatic tumors can develop metastases, often affecting the gastrointestinal tract and organs such as the liver and lungs. The main treatment involves surgery and, in some cases, radiotherapy. Recommended screening for people aged 50 and over includes colonoscopy, with recent suggestions to start screening five years earlier, due to the global increase in the incidence of these conditions.

Tumor Receptor-Mediated Morphological Transformation and In Situ Polymerization of Diacetylene-Containing Lipidated Peptide Amphiphile on Cell Membranes for Tumor Suppression.

In situ polymerization on cell membranes can decrease cell mobility, which may inhibit tumor growth and invasion. However, the initiation of radical polymerization traditionally requires exogenous catalysts or free radical initiators, which might cause side effects in normal tissues. Herein, we synthesized a Y-type diacetylene-containing lipidated peptide amphiphile (TCDA-KFFFFK(GRGDS)-YIGSR, Y-DLPA) targeting integrins and laminin receptors on murine mammary carcinoma 4T1 cells, which underwent nanoparticle-to-nanofiber morphological transformation and in situ polymerization on cell membranes. Specifically, the polymerized Y-DLPA induced 4T1 cell apoptosis and disturbed the substance exchange and metabolism. In vitro assays demonstrated that the polymerized Y-DLPA nanofibers decreased the migration capacity of 4T1 cells, potentially suppressing tumor invasion and metastasis. When administered locally to 4T1 tumor-bearing mice, the Y-DLPA nanoparticles formed a biomimetic extracellular matrix that effectively suppressed tumor growth. This study provides an in situ polymerization strategy that can serve as an effective drug-free biomaterial with low side effects for antitumor therapy.

What if we could eradicate cervical cancer?

Abstract Introduction WHO wants to achieve the elimination of Cervical Cancer: all countries must achieve and maintain an incidence rate of less than 4 per 100,000 women. Three key pillars: 90% of girls fully vaccinated against HPV by 15 years of age; 70% of women aged 35-45 years screened; 90% of women with pre-tumour lesion and invasive tumour treated. Our study assessed the position of the Tuscany South East Local Health Authority(LHA TSE) with respect to these three pillars and how to improve it. Methods A retrospective observational study was conducted. The following were used: ISTAT data of incidence of cervical cancer standardised by age from 2013 to 2017;data from ISPRO on screening(PAP and HPV test)from 2013 to 2022;data of vaccination coverage taken from the Health Information System of Collective Prevention(SISPC) from 2012 to 2023 for children&amp;lt;12 years, Results The incidence rate of cervical cancer in LHA TSE is 9.4 per 100 thousand. About HPV vaccine coverage by age 12, for girls it has been rising from 80.5% in 2012 to a peak of 84.8% in 2019 and then progressively decreasing to 76.3% in 2023.Coverage for boys has also been progressively increasing from 0.8% in 2012 to a peak in 2019 of 74.9% and then decreasing to 69.8% in 2023. A total of 52 thousand children are vaccinated. As for the adjusted adherence to screening, we started from an average adherence of 51.8% in 2013 (75 thousand women invited with 102% coverage) to 53.2% in 2022 (54 thousand women invited with 107% coverage). In 2013, ASC-US+ lesions were found in 6.4 % of women by PAP Test and in 2022 in 6.3 % of women. In the examined period, more than 90% of women with pre-tumour lesion and more than 90% with invasive tumour were treated. Conclusions LHA TSE will have to implement actions to increase vaccination coverage and screening adherence rates through awareness campaigns and open days, also considering whether a change in the age range for starting screening is necessary as vaccination coverage increases. Key messages • Cervical cancer is one of the most preventable cancers, but too few young women are vaccinated against HPV infection, the main causative factor. • Prevention through adherence to screening enables early identification of lesions caused by HPV virus.

N6‐methyladenosine reader YTHDF3‐mediated zinc finger protein 41 inhibits hepatocellular carcinoma progression by transcriptional repression of Snail

AbstractAdvanced metastasis of hepatocellular carcinoma (HCC) significantly contributes to high death rates among patients. The efficiency of targeted therapies and chemotherapeutic agents shows individual variability. Therefore, there is no effective treatment for advanced HCC. Zinc finger proteins (ZFPs) are known to be crucial in various tumors, especially on HCC. In our study, we verified that ZFP41 could suppress the progression and metastasis of HCC through in vitro and in vivo experiments. During the past years, N6‐methyladenine (m6A) regulation has also been increasingly reported in HCC. To investigate whether ZFP41 could be regulated via m6A methylation, our results showed that YTHDF3 bound to the mRNA of ZFP41 and degrade it. Subsequently, to further elucidate the function of ZFP41, we identified Snail, a well‐known oncogenic molecule, through RNA‐seq. As a canonical component in the epithelial‐to‐mesenchymal transition (EMT) pathway, Snail plays a pivotal role and is a critical marker for tumor invasion and metastasis. Our results showed ZFP41 could inhibit Snail and the EMT pathway through its transcriptional repression. In conclusion, our study revealed that ZFP41 is a potential prognostic element for patients with HCC, and targeting ZFP41 might be used for translational clinical applications as a promising therapeutic target.

Probing the Depths of Molecular Complexity: STAT3 as a Key Architect in Colorectal Cancer Pathogenesis.

Colorectal cancer (CRC) has become a significant threat in recent decades, and its incidence is predicted to continue rising. Despite notable advancements in therapeutic strategies, managing CRC poses complex challenges, primarily due to the lack of clinically feasible therapeutic targets. Among the myriad molecules implicated in CRC, the signal transducer and activator of transcription 3 (STAT3) stands out as a promising target tightly regulated by various genes. This intracellular transcription factor, spanning 750-795 amino acids and weighing approximately 92 kDa, is crucial in key cellular activities such as growth, migration, invasion, inflammation, and angiogenesis. Aberrant activation of STAT3 signaling has been linked to various cancers, including CRC. Therefore, targeting this signaling pathway holds significance for potential CRC treatment strategies.STAT3, as a central intracellular transcription factor, is implicated in colorectal cancer development by activating aberrant signaling pathways. Numerous studies have demonstrated that the abnormal hyperactivation of STAT3 in CRC tissues enhances cell proliferation, suppresses apoptosis, promotes angiogenesis, and facilitates tumor invasion and metastasis. As a focal point in colorectal cancer research, STAT3 emerges as a promising candidate for detecting and treating CRC. This review aims to present recent data on STAT3, emphasizing the activation and functions of STAT3 inhibitors in CRC. Indeed, STAT3 inhibitors have been identified to have therapeutic potential in CRC, especially inhibitors targeting the DNA-binding domain (DBD). Indeed, STAT3 inhibitors have been identified to have a therapeutic potential in CRC, especially the inhibitors targeting the DNA binding domain (DBD). For example, imatinib acts by targeting cell surface receptors, and these inhibitors have shown potential for the control and treatment of tumor growth, angiogenesis, and metastasis. Imatinib, for example acts by targeting cell surface receptors, and these inhibitors have shown the future direction toward the control and treatment of tumor growth, angiogenesis, and metastasis.