Tumor Invasion Research Articles

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<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.

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.

The Biological Roles of ZKSCAN3 (ZNF306) in the Hallmarks of Cancer: From Mechanisms to Therapeutics

ZKSCAN3 (also known as ZNF306) plays a pivotal role in the regulation of various cellular processes that are fundamental to the development of cancer. It has been widely acknowledged as a key contributor to cancer progression, with its overexpression consistently reported in a broad spectrum of malignancies. Importantly, clinical studies have demonstrated a significant association between elevated ZKSCAN3 levels and adverse prognosis, as well as resistance to therapeutic drugs. Specifically, ZKSCAN3 promotes tumor progression by enhancing multiple hallmark features of cancer and promoting the acquisition of cancer-specific phenotypes. These effects manifest as increased tumor cell proliferation, invasion, and metastasis, accompanied by inhibiting tumor cell apoptosis and modulating autophagy. Consequently, ZKSCAN3 emerges as a promising prognostic marker, and targeting its inhibition represents a potential strategy for anti-tumor therapy. In this review, we provide an updated perspective on the role of ZKSCAN3 in governing tumor characteristics and the underlying molecular mechanisms. Furthermore, we underscore the clinical relevance of ZKSCAN3 and its potential implications for tumor prognosis and therapeutic strategies.

Morphodynamics of interface between dissimilar cell aggregations

Tissue interfaces are essential for development and their disruption often leads to diseases such as tumor invasion. Here, we combine experiments, theoretical modeling, and numerical simulations to quantify the morphodynamics of interface in a biphasic system composed of Madin Darby canine kidney (MDCK) and mouse myoblast (C2C12) cells. We show that cellular activity regulates the interface morphodynamics and drives wave propagation along the interface. Based on the dispersion relationship, we identify that the wave dynamics results from the activity-mediated instability of the interface and coherent flow. It is found that the topological defects accumulate around and destabilize the interface and +1/2 topological defects are more likely to aggregate in MDCK cell clusters. A biphasic active nematic theory is employed to reproduce our experimental observations and decipher the underlying mechanisms. These findings provide physical insights into the interfacial evolution that could be implicated in tissue morphogenesis and tumor invasion.

Anti-tumor mechanism of artesunate

Artesunate (ART) is a classic antimalarial drug with high efficiency, low toxicity and tolerance. It has been shown to be safe and has good anti-tumor effect. Existing clinical studies have shown that the anti-tumor mechanisms of ART mainly include inducing apoptosis and autophagy of tumor cells, affecting tumor microenvironment, regulating immune response, overcoming drug resistance, as well as inhibiting tumor cell proliferation, migration, invasion, and angiogenesis. ART has been proven to fight against lung cancer, hepatocarcinoma, lymphoma, multiple myeloma, leukemia, colorectal cancer, ovarian cancer, cervical cancer, malignant melanoma, oral squamous cell carcinoma, bladder cancer, prostate cancer and other neoplasms. In this review, we highlight the effects of ART on various tumors with an emphasis on its anti-tumor mechanism, which is helpful to propose the potential research directions of ART and expand its clinical application.

Prognostic value of isolated tumor cells and micrometastasis of lymph nodes in invasive urinary bladder cancer.

The prognostic significance of nodal micrometastasis and isolated tumor cells (ITC) in urinary bladder cancer (UBC) is unknown. We aimed to evaluate the prevalence, clinical impact, and clinicopathological characteristics of nodal micrometastasis and ITC in UBC. A total of 124 patients with UBC undergoing surgery were investigated. Detection of micrometastasis and ITC was performed using pancytokeratin immunohistochemistry (IHC). Histopathologic and clinical findings were correlated with patients' outcome. IHC detected nodal micrometastasis and ITC (pNmi group) in 12.9% (13/101) of originally node-negative patients and in 26.1% (6/23) of originally node-positive patients (pN+ group). The remaining 88 were truly node-negative patients (pN0 group). After IHC, all 13 patients in the pNmi group were upstaged from pN0 to pN1-2 and one patient in the pN+ group was changed from pN1 to pN2. Nodal micrometastasis and ITC were significantly associated with mixed urothelial carcinoma (UC) (p = 0.002), UC with discohesive pattern (p = 0.006), glandular differentiation (p = 0.043), lymphovascular invasion (p = 0.009), and budding-like tumor cell clusters (p = 0.002). The pNmi group had significantly worse cancer-specific survival than the pN0 group in univariate (p = 0.004) and multivariate (p = 0.040) analysis. IHC frequently identified nodal micrometastasis and ITC in originally node-negative UBC patients on routine pathological examination. Nodal micrometastasis and ITC were independently associated with cancer-related mortality in UBC. IHC might be selectively used to detect micrometastasis and ITC in UBC having specific pathological features.

OSSN in South India: Clinical presentation, treatment outcomes, and histopathologic correlations.

This study aimed to analyze the clinical presentation, treatment outcomes, and histopathology features of ocular surface squamous neoplasia (OSSN) in a South Indian population and correlate the area of lesions to the histopathological grade/severity of carcinoma in situ (CIN) and squamous cell carcinoma (SqCC) invasive and noninvasive tumors. The study was a retrospective cross-sectional study. The study reviewed electronic medical records (EMRs) of 99 eyes of 99 South Indian patients who underwent en bloc excision and biopsy for tumors in the corneal and conjunctival epithelium with suspicion of OSSN over 1 year from January 2019 to December 2019. Postoperatively, patients were treated with three cycles of topical 0.04% mitomycin C eye drops. Sixty-three had requisite EMR data with a follow-up period of 1 year. Patients had equal gender distribution with an age range of 28-83 years. The most common clinical variant was leukoplakic lesion, and the area of the lesion was the only predicting factor for SqCC and CIN. Bigger (T2) lesions should be strongly suspected for OSSN and promptly excised. Histopathologic analysis should be performed, and post-op topical mitomycin C or interferon alpha 2b is administered to avoid recurrence. In this study, by correlating the area of the lesion, we introduce a new variable that may aid in clinical prognostication alongside the AJCC classification.

SEMA7A-mediated juxtacrine stimulation of IGFBP-3 upregulates IL-17RB at pancreatic cancer invasive front.

Tumor invasion is the hallmark of tumor malignancy. The invasive infiltration pattern of tumor cells located at the leading edge is highly correlated with metastasis and unfavorable patient outcomes. However, the regulatory mechanisms governing tumor malignancy at the invasive margin remain unclear. The IL-17B/IL-17RB pathway is known to promote pancreatic cancer invasion and metastasis, yet the specific mechanisms underlying IL-17RB upregulation during invasion are poorly understood. In this study, we unveiled a multistep process for IL-17RB upregulation at the invasive margin, which occurs through direct communication between tumor cells and fibroblasts. Tumor ATP1A1 facilitates plasma membrane expression of SEMA7A, which binds to and induces IGFBP-3 secretion from fibroblasts. The resulting gradient of IGFBP-3 influences the direction and enhances IL-17RB expression to regulate SNAI2 in invasion. These findings highlight the importance of local tumor-fibroblast interactions in promoting cancer cell invasiveness, potentially leading to the development of new therapeutic strategies targeting this communication.

Splicing dysregulation in glioblastoma alters the function of cell migration-related genes.

Glioblastoma (GBM) has a poor prognosis with a high recurrence and low survival rate. Previous RNA-seq analyses have revealed that alternative splicing (AS) plays a role in GBM progression. Here, we present a novel AS analysis method (Semi-Q) and describe its use to identify GBM-specific AS events. We analyzed RNA-seq data from normal brain (NB), normal human astrocytes (NHAs) and GBM samples, and found that comparison between NHA and GBM was especially informative. Importantly, this analysis revealed that genes encoding cell migration-related proteins, including filamins (FLNs) and actinins (ACTNs), were among those most affected by differential AS. Functional assays revealed that dysregulated AS of FLNA, B and C transcripts produced protein isoforms that not only altered transcription of cell proliferation-related genes but also led to enhanced cell migration, resistance to cell death and/or mitochondrial respiratory function, while a dysregulated AS isoform of ACTN4 enhanced cell migration. Together, our results indicate that cell migration and actin cytoskeleton-related genes are differentially regulated by AS in GBM, supporting a role for AS in facilitating tumor growth and invasiveness.

RCAN1.4 regulates tumor cell engraftment and invasion in a thyroid cancer to lung metastasis-on-a-chip microphysiological system

Progressive metastasis is the primary cause of cancer-related deaths. It has been recognized that many cancers are characterized by long periods of stability followed by subsequent progression. Genes termed metastasis progression suppressors (MPS) are functional gatekeepers of this process, and their loss leads to late-stage progression. Previously, we identified regulator of calcineurin 1, isoform 4 (RCAN1.4) as a functional MPS for several cancers, including thyroid cancer, a tumor type prone to metastatic dormancy. RCAN1.4 knockdown increases expression of the cancer-promoting transcription factor NFE2-like bZIP transcription factor (NFE2L3), and through this mechanism increases cancer cell proliferation and invasion inin vitroandin vivoand promotes metastatic potential to lungs in tail vein models. However, the mechanisms by which RCAN 1.4 regulates specific metastatic steps is incompletely characterized. Studies of the metastatic cascade are limited in mouse systems due to high cost and long duration. Here, we have shown the creation of a thyroid-to-lung metastasis-on-a-chip (MOC) model to address these limitations, allowing invasion analysis and quantification on a single cell level. We then deployed the platform to investigate RCAN1.4 knockdown in fluorescently tagged hTh74 and FTC236 thyroid cancer cell lines. Cells were circulated through microfluidic channels, running parallel to lung hydrogel constructs allowing tumor cell-lung tissue interactions. Similar to studies in mouse models, RCAN1.4 knockdown increased NFE2L3 expression, globally increased invasion distance into lung constructs and had cell line and clonally dependent variations on bulk metastatic burden. In line with previousin vivoobservations, RCAN1.4 knockdown had a greater impact on hTh74 metastatic propensity than FTC236. In summary, we have developed and validated a novel MOC system evaluate and quantify RCAN1.4-regulated thyroid cancer cell lung adherence and invasion. This system creates opportunities for more detailed and rapid mechanistic studies the metastatic cascade and creates opportunities for translational assay development.

TRAF4 promotes lung cancer development by activating tyrosine kinase of EGFR

Objective: To explore the role of tumor necrosis factor receptor-associated factor 4 (TRAF4) in promoting the abnormal activation of epidermal growth factor receptor (EGFR) and its effect on lung cancer cell proliferation, migration and invasion. Methods: Tumor tissues from patients who underwent lung adenocarcinoma resection at The First Affiliated Hospital of Second Military Medical University, from January 2015 to May 2017 were collected, and the expressions of TRAF4 and Ki-67 in lung cancer tissues were detected by immunohistochemistry, the mRNA levels of Cyclin D and Vimentin were detected by real-time fluorescence quantitative PCR (qRT-PCR). The effect of TRAF4 on the tumor growth ability of lung cancer A549 cells was investigated by the xenograft model, the effect of TRAF4 or EGFR on the tumor proliferation ability was detected by using cell counting kit 8 (CCK8) and BrdU assay, and the migration and invasion abilities of tumor cells were detected by Transwell assay. Different structural domain deletion expression vectors of TRAF4 and EGFR were constructed to transfect cells, and the interaction mode of TRAF4 and EGFR was investigated by immunoprecipitation assay. Results: The expression of TRAF4 in non-small cell lung cancer (NSCLC) tissues was positively correlated with the expressions of Ki-67, cyclin D, and vimentin (r2: 0.438, 0.695, and 0.736, respectively, all P＜0.01). Immunohistochemical assay of tumor tissues from NSCLC patients showed that tissues with high expression of TRAF4 were also high in Ki-67. Patients with high TRAF4 expression (TRAF4 positivity >30%) had a shorter progression-free survival (PFS) time than that of patients with low TRAF4 expression (TRAF4 positivity ≤30%) (median PFS of 12 and 19 months, respectively; P=0.034). Traf4-/- cells had a weakened proliferative capacity than traf4+/+ cells and formed tumors with smaller size (P＜0.05). The expression level of Ki-67 in the tumor tissues formed by traf4-/- cells [(45.6±8.7)%] was lower than that in the tumor tissues formed by traf4+/+ cells [(62.3±10.3)%, P=0.015], the mRNA levels of cyclin D (1.01±0.15) and vimentin (1.01±0.12) in the traf4-/- cells were lower than those of the traf4+/+ cells (3.41±0.32 and 3.12±0.18, respectively, both P＜0.05).The western blot results showed that, with the elevated intracellular expression level of TRAF4, phosphorylation level of EGFR was significantly increased in both wild-type EGFR and activation mutant EGFR-expression cells. The capacities of proliferation, migration and invasion of A549 cells was weakened after EGFR knockdown (all P＜0.01). Immunoprecipitation experiments showed that TRAF4 binds to the peptide segment of the near-membrane region of EGFR through the TRAF structural domain, and the mutual binding between EGFR molecules was enhanced under TRAF4 overexpression conditions. Increasing TRAF4 expression promoted EGFR molecular phosphorylation and activation of downstream signaling. Conclusions: TRAF4 expression is elevated in NSCLC tissues and tumor cells, which promotes tumor proliferation, migration and invasion. TRAF4 directly binds to EGFR molecules, enhances its own phosphorylation and activates the downstream signaling pathway by promoting the interaction between EGFR molecules.

Risk stratification of thymic epithelial tumors based on peritumor CT radiomics and semantic features.

To develop and validate nomograms combining radiomics and semantic features to identify the invasiveness and histopathological risk stratification of thymic epithelial tumors (TET) using contrast-enhanced CT. This retrospective multi-center study included 224 consecutive cases. For each case, 6764 intratumor and peritumor radiomics features and 31 semantic features were collected. Multi-feature selections and decision tree models were performed on radiomics features and semantic features separately to select the most important features for Masaoka-Koga staging and WHO classification. The selected features were then combined to create nomograms for the two systems. The performance of the radiomics model, semantic model, and combined model was evaluated using the area under the receiver operating characteristic curves (AUCs). One hundred eighty-seven cases (56.5 years ± 12.3, 101 men) were included, with 62 cases as the external test set. For Masaoka-Koga staging, the combined model, which incorporated five peritumor radiomics features and four semantic features, showed an AUC of 0.958 (95% CI: 0.912-1.000) in distinguishing between early-stage (stage I/II) and advanced-stage (III/IV) TET in the external test set. For WHO classification, the combined model incorporating five peritumor radiomics features and two semantic features showed an AUC of 0.857 (0.760-0.955) in differentiating low-risk (type A/AB/B1) and high-risk (B2/B3/C) TET. The combined models showed the most effective predictive performance, while the semantic models exhibited comparable performance to the radiomics models in both systems (p > 0.05). The nomograms combining peritumor radiomics features and semantic features could help in increasing the accuracy of grading invasiveness and risk stratification of TET. Peripheral invasion and histopathological type are major determinants of treatment and prognosis of TET. The integration of peritumoral radiomics features and semantic features into nomograms may enhance the accuracy of grading invasiveness and risk stratification of TET. Peritumor region of TET may suggest histopathological and invasive risk. Peritumor radiomic and semantic features allow classification by Masaoka-Koga staging (AUC: 0.958). Peritumor radiomic and semantic features enable the classification of histopathological risk (AUC: 0.857).

Tumor Microenvironment and Dermatological Conditions in Prostate Cancer

Tumor initiation, progression, and invasion are closely related to the tumor microenvironment. Inflammation can modulate the activity of the cells in the TME and contribute to all stages of tumor development. The etiopathogenesis of cutaneous manifestations associated with prostate cancer is unclear. The cutaneous phenotype associated with prostate cancer could be supported by intratumoral heterogeneity, the remodeling of interactions in the tumor microenvironment, and the dynamics of the epithelial–mesenchymal transition. Among the urinary system cancers, prostate cancer presents few cutaneous signs and symptoms, most being diagnosed in the advanced stages of the disease. In this review, we analyze the cutaneous events associated with prostate cancer, represented by direct or indirect manifestations of the primary malignancy and the skin toxicities caused by oncological medications.

Young Black Women's Breast Cancer Knowledge and Beliefs: A Sequential Explanatory Mixed MethodsStudy.

Black women under the age of 50 have a 111% higher breast cancer mortality rate than their White counterparts. The breast cancer mortality disparities among young Black women may be due in part to the fact that they are more likely to be diagnosed with late-stage, invasive breast cancer tumors. Psychosocial factors, such as lack of perceived risk for breast cancer, lack of awareness of breast cancer risk factors, and ambiguity about breast cancer screening guidelines are areas that are under investigated among young Black women. The purpose of this study was to identify young Black women's cancer beliefs and level of breast cancer risk knowledge. A sequential explanatory mixed methods study was conducted using quantitative data from the Health Information Trends Survey 6 (HINTS 6) (n = 25) and qualitative data from interviews with young Black female college students (n = 13). The results of the quantitative data analysis were used to guide the development of the qualitative interview guide. Data regarding participants' cancer beliefs, cancer risk factor knowledge, perceived cancer risk, and ambiguity about cancer screening behaviors were analyzed. The findings indicated young Black women have low perceived risk of developing cancer. Most participants were not aware of cancer recommendations that were targeted towards women under the age of 40. In addition, knowledge about lifestyle behavior risk factors for breast cancer was relatively low. Our findings underscore the importance of developing, disseminating, and implementing breast cancer education interventions that are targeted towards young Black women.

Suppression of dystroglycan function accompanies pancreatic acinar-to-ductal metaplasia and favours dysplasia development.

The basement membrane (BM) is among the predominant microenvironmental factors of normal epithelia and of precancerous epithelial lesions. Evidence suggests that the BM functions not only as a barrier to tumour invasion but also as an active tumour-suppressing signalling substrate during premalignancy. However, the molecular foundations of such mechanisms have not been elucidated. Here we explore potential tumour-suppressing functions of the BM during precancer evolution, focusing on the expression and function of the extracellular matrix receptor dystroglycan in the pancreas and pancreatic disease. We show that the dystroglycan protein is highly expressed in the acinar compartment of the normal pancreas but lower in the ductal compartment. Moreover, there is a strong suppression of dystroglycan protein expression with acinar-to-ductal metaplasia in chronic pancreatitis and in all stages of pancreatic precancer and cancer evolution, from acinar-to-ductal metaplasia to dysplasia to adenocarcinoma. The conditional knockout of dystroglycan in the murine pancreas produced little evidence of developmental or functional deficiency. However, conditional deletion of dystroglycan expression in the context of oncogenic Kras expression led to a clear acceleration of pancreatic disease evolution, including accelerated dysplasia development and decreased survival. These data establish dystroglycan as a suppressor of pancreatic dysplasia development and one that is muted in chronic pancreatitis and at the earliest stages of oncogene-induced transformation. We conclude that dystroglycan is an important mediator of the tumour-suppressing functions of the BM during precancer evolution and that reduced dystroglycan function increases cancer risk, highlighting the dynamics of cell-BM interactions as important determinants of early cancer progression. © 2024 The Pathological Society of Great Britain and Ireland.

Locally Advanced Splenic Flexure Tumor With Invasion And Formation Of Splenic Abscess

Introduction: Splenic abscesses are rare, with an incidence of 0.14-0.70% in autopsies, affecting mainly men and immunosuppressed patients. Symptoms include fever, abdominal pain, nausea, and vomiting. Splenic invasion by colon cancer at the splenic flexure is uncommon. We report a case of cancer at the splenic flexure resulting in a splenocolic fistula and splenic abscess. Case Description: A 43-year-old man, with a history of injectable drug use, presented with diffuse abdominal pain. Tests revealed leukocytosis, thrombocytopenia, and elevated bilirubins and liver enzymes. A CT scan identified thickening in the colon and a splenic abscess. Total splenectomy and left colectomy with colon-colonic anastomosis were performed. Discussion: Splenic abscesses are rare and, when associated with colonic neoplasms, present a diagnostic and therapeutic challenge. This case highlights the importance of aggressive surgical intervention to treat tumor invasions and associated complications.

The Intersection of the Oral Microbiome and Salivary Metabolites in Head and Neck Cancer: From Diagnosis to Treatment

Head and neck cancers (HNCs) are the seventh most common cancer worldwide, accounting for 4–5% of all malignancies. Salivary metabolites, which serve as key metabolic intermediates and cell-signalling molecules, are emerging as potential diagnostic biomarkers for HNC. While current research has largely concentrated on these metabolites as biomarkers, a critical gap remains in understanding their fluctuations before and after treatment, as well as their involvement in oral side effects. Recent studies emphasise the role of the oral microbiome and its metabolic activity in cancer progression and treatment efficacy by bacterial metabolites and virulence factors. Oral bacteria, such as P. gingivalis and F. nucleatum, contribute to a pro-inflammatory environment that promotes tumour growth. Additionally, F. nucleatum enhances its virulence through flagellar assembly and iron transport mechanisms, facilitating tumour invasion and survival. Moreover, alterations in the oral microbiome can influence chemotherapy efficacy and toxicity through the microbiota–host irinotecan axis, highlighting the complex interplay between microbial communities and therapeutic outcomes. Salivary metabolite profiles are influenced by factors such as gender, methods, and patient habits like smoking—a major risk factor for HNC. Radiotherapy (RT), a key treatment for HNC, often causes side effects such as xerostomia, oral mucositis, and swallowing difficulties which impact survivors’ quality of life. Intensity-modulated radiotherapy (IMRT) aims to improve treatment outcomes and minimise side effects but can still lead to significant salivary gland dysfunction and associated complications. This review underscores the microbial and host interactions affecting salivary metabolites and their implications for cancer treatment and patient outcomes.

Enhancing glioma treatment with 3D scaffolds laden with upconversion nanoparticles and temozolomide in orthotopic mouse model

Targeted drug delivery for primary brain tumors, particularly gliomas, is currently a promising approach to reduce patient relapse rates. The use of substitutable scaffolds, which enable the sustained release of clinically relevant doses of anticancer medications, offers the potential to decrease the toxic burden on the patient’s organism while also enhancing their quality of life and overall survival. Upconversion nanoparticles (UCNPs) are being actively explored as promising agents for detection and monitoring of tumor growth, and as therapeutic agents that can provide isolated therapeutic effects and enhance standard chemotherapy. Our study is focused on the feasibility of constructing scaffolds using methacrylated hyaluronic acid with additional impregnation of UCNPs and the chemotherapeutic drug temozolomide (TMZ) for glioma treatment. The designed scaffolds have been demonstrated their efficacy as a drug and UCNPs delivery system for gliomas. Using the aggressive orthotopic glioma model in vivo, it was found that the scaffolds possess the capacity to ameliorate neurological disorders in mice. Moreover, upon intracranial co-implantation of the scaffolds and glioma cells, the constructs disintegrate into distinct segments, augmenting the release of UCNPs into the surrounding tissue and concurrently reducing postoperative damage to brain tissue. The use of TMZ in the scaffold composition contributed to restraining glioma development and the reduction of tumor invasiveness. Our findings unveil promising prospects for the application of photopolymerizable biocompatible scaffolds in the realm of neuro-oncology.

A case report on renal metastasis as an unusual presentation of choriocarcinoma

BackgroundChoriocarcinoma is an aggressively invasive neoplasm, characterized by its rapid proliferation and propensity for metastasis to distant organs via hematogenous dissemination. Lungs (80%), vagina (30%), pelvis (20%), liver (10%), and brain (10%) are the most frequently metastasized organs. Renal metastases are very rare. The clinical manifestations of choriocarcinoma varies depending on the site of disease, making diagnosis challenging. In this report, we provide a clinical case of choriocarcinoma with metastases to the renal and pulmonary systems, displaying symptoms akin to those observed in ectopic pregnancy.Case presentationA 27-year-old female, G2P1, with a previous history of full-term pregnancy in 2018, presented to the hospital with the onset of vaginal bleeding and accompanying abdominal aches. Investigations uncovered a left adnexal mass with a human chorionic gonadotropin (hCG) level of 77,4 mIU/mL and a left pulmonary nodule measuring 31 mm x 21 mm. Laparoscopy was performed due to the high suspicion of an ectopic pregnancy. However, no visible villi were identified during the surgery, and postoperative blood hCG levels continued to rise. A diagnostic curettage also failed to reveal any villi, maintaining the suspicion of a persistent ectopic pregnancy. Following two ineffective courses of methotrexate therapy, the patient was referred to our facility. Prior to her referral, an ultrasound had indicated a mass in the right kidney. However, upon arrival at our hospital, subsequent ultrasonography failed to detect any renal masses. Despite two months of outpatient monitoring, there was a sudden and significant increase in her serum hCG levels. An emergency laparoscopy was performed, revealing no pregnancy-related lesion. After surgery, the patient’s hCG levels dropped dramatically to less than one-tenth of the original amount. Multisite enhanced computed tomography(CT)revealed suspicious lesions in both the renal and pulmonary regions. Upon thorough multidisciplinary consultation, a diagnosis of choriocarcinoma was entertained. Consequently, the patient successfully underwent eight cycles of chemotherapy and has remained recurrence-free for the past year.ConclusionsThis case underscores the potential for choriocarcinoma in women of reproductive age who exhibit radiological signs of renal masses. Early and accurate diagnosis, followed by prompt intervention, is essential to prevent needless surgery procedures.