Tumor Markers Research Articles

Molecular Interactions of the Plant Steroid Hormone Epibrassinolide on Human Drug-Sensitive and Drug-Resistant Small-Cell Lung Carcinoma Cells

Background: Small-cell lung cancer (SCLC) has a poor prognosis because it is often diagnosed after it has spread and develops multi-drug resistance. Epibrassinolide (EB) is a plant steroid hormone with widespread distribution and physiological effects. In plants, EB-activated gene expression occurs via a GSK-mediated signaling pathway, similar to Wnt-β-catenin signaling in animal cells that is elevated in cancer cells. Methods: This mechanistic parallel prompted investigations of the molecular interactions of EB on drug-sensitive (H69) and multi-drug-resistant (VPA) SCLC cells. Cellular and molecular investigations were performed. Results: Pharmacologic interactions between EB and the Wnt signaling inhibitors IGC-011 and PRI-724 were determined by the combination index method and showed antagonism, indicating that EB acts on the same pathway as these inhibitors. Following incubation of drug-sensitive and drug-resistant SCLC cells with EB, there was a reduction in β-catenin (e.g., 3.8 to 0.7 pg/µg protein), accompanied by a reduction in β-catenin promoter activity, measured by firefly luciferase-coupled promoter element transfection. Cellular β-catenin concentration is regulated by the active form of GSK3β. In Wnt signaling, active GSK3β is converted to inactive pGSK3β, thereby increasing the concentration of β-catenin. After incubation of SCLC cells with EB, there was a reduction in the inactive form (pGSK3β) and a relative increase in the active form (GSK3β). In vitro enzyme assays showed that EB did not inhibit purified GSK3β, but there was non-competitive inhibition when SCLC cell extracts were used as the source of enzyme. This indirect inhibition by EB indicates that it may act on the Wnt pathway by blocking the phosphorylation of GSK3β. The protein levels of three SCLC tumor markers, namely, NSE, CAV1, and MYCL1, were elevated in drug-resistant SCLC cells. EB incubation led to a significant reduction in the levels of the three markers. Two major effects of EB on SCLC cells are the promotion of apoptosis and the reversal of drug resistance. Transcriptional analyses showed that after exposure of SCLC cells to EB, there were increases in the expression of genes encoding apoptotic inducers (e.g., BAX and FAS) and effectors (e.g., CASP3) and reductions in the expression of genes encoding apoptosis inhibitors (e.g., survivin). PGP1 and MRP1, two membrane efflux pumps expressed in SCLC cells, were elevated in drug-resistant cells, but EB incubation did not affect these protein levels. Cellular assays of drug efflux by PGP1 showed an increase in drug-resistant cells, but EB did not alter efflux activity. Following exposure to human liver microsomes, EB was metabolized by NADPH-dependent oxidation and UDPG-dependent glucuronidation, as evidenced by the elimination of EB cytotoxicity against SCLC cells. Conclusions: Taken together, these data indicate that EB, a steroid hormone in plants consumed in the human diet, is pharmacologically active in drug-sensitive and drug-resistant SCLC cells in the Wnt signaling pathway, alters apoptotic gene expression, and is a substrate for microsomal modifications.

Spectral CT-based nomogram for preoperative prediction of Lauren classification in locally advanced gastric cancer: a prospective study.

To develop a nomogram based on clinical features and spectral quantitative parameters to preoperatively predict the Lauren classification for locally advanced gastric cancer (LAGC). Patients diagnosed with LAGC by postoperative pathology who underwent abdominal triple-phase enhanced spectral computed tomography (CT) were prospectively enrolled in this study between June 2023 and December 2023. All the patients were categorized into intestinal- and diffuse-type groups according to the Lauren classification. Traditional characteristics, including demographic information, serum tumor markers, gastroscopic pathology, and image semantic features, were collected. Spectral quantitative parameters, including iodine concentration (IC), effective atomic number (Zeff), and slope of the energy spectrum curve from 40 keV to 70 keV (λ), were measured three times for each patient by two blinded radiologists in arterial/venous/delayed phases (AP/VP/DP). Differences in traditional features and spectral quantitative parameters between the two groups were compared using univariable analysis. Independent predictors of the Lauren classification of LAGC were screened using multivariable logistic regression analysis. Receiver operating characteristic (ROC) curve analysis was used to assess the discriminating capability. Ultimately, the nomogram, including clinical features and spectral CT quantitative parameters, was developed. Gender, nIC in AP (APnIC), and λ in DP (λd) were independent predictors for Lauren classification. The nomogram based on these indicators produced the best performance with an area under the curve of 0.841 (95% confidence interval: 0.749-0.932), specificity of 85.3%, accuracy of 76.4%, and sensitivity of 68.4%. The nomogram based on clinical features and spectral CT quantitative parameters exhibits great potential in the preoperative and non-invasive assessment of Lauren classification for LAGC. Question Can the proposed nomogram, integrating clinical features and spectral quantitative parameters, preoperatively predict the Lauren classification in locally advanced gastric cancer (LAGC)? Findings The nomogram, based on gender, arterial phase normalized iodine concentration, and slope of the energy spectrum curve in the delayed phase showed satisfactory predictive ability. Clinical relevance The established nomogram could contribute to guiding individualized treatment strategies and risk stratification in patients by predicting the Lauren classification for LAGC before surgery.

Multi-center study on the application potential of Siaα-2,6Gal in early and differential diagnosis of lung cancer.

This study aimed to investigate the application potential of the abnormal glycan structure Siaα-2,6Gal in the early and differential diagnosis of lung cancer. Clinical data and serum samples from 730 patients and 120 healthy individuals participating in clinical trials on Siaα-2,6Gal were collected at three medical centers between January 2022 and June 2023. The levels of Siaα-2,6Gal, carcinoembryonic antigen (CEA), cytokeratin 19 fragment antigen (CYFRA21-1), squamous cell carcinoma antigen (SCC), neuron-specific enolase (NSE), and pro-gastrin-releasing peptide (ProGRP) in serum were measured. The application potentials of these markers in the early and differential diagnosis, classification, and staging of lung cancer were explored. (1) Serum Siaα-2,6Gal levels in the lung cancer group were 2,606 (1,970-3,458) U/mL, significantly higher than those in the benign lung disease, miscellaneous malignant tumor, miscellaneous benign disease, and healthy individual groups at 1,359 (950-1,528), 1,252 (903-1,532), 1,196 (850-1,490), and 1,210 (1,100-1,287) U/mL (P < 0.0001). (2) Serum Siaα-2,6Gal levels in the early-stage lung cancer (stages 0-II) group were 2,576 (1,929-3,338) U/mL, significantly higher than those in the benign pulmonary nodule group at 1,419 (1,105-1,820) U/mL (P < 0.0001). (3) Receiver operating characteristic curves showed that Siaα-2,6Gal had a high diagnostic efficiency for lung cancer (area under the curve (AUC) = 0.9217), significantly superior to CEA, CYFRA21-1, SCC, NSE, and ProGRP (AUCs of 0.6618, 0.6605, 0.5783, 0.5985, and 0.6381). Siaα-2,6Gal is a promising biomarker for lung cancer diagnosis and may offer superior differential diagnosis of early-stage lung cancer from benign pulmonary nodules compared to traditional tumor markers.

Quantitative proteogenomic characterization in MUC1 and MUC4 in oral squamous cell carcinoma, oral potentially malignant disorders, and normal oral mucosa in carcinogenesis.

Mucins are glycoproteins with a significant molecular weight that have a diverse range of biological functions. MUC1 & MUC4 are transmembrane mucin family members that are expressed in airway epithelial cells and body fluids. It is expressed excessively in numerous carcinomas in addition to their alteredexpression. A thorough review of the literature reveals very limited research about MUC1 & 4 expressionsin oral malignancies and oralpremalignant disorders. The aim of the research is to assess the pattern and quantity of gene expression in MUC1 & MUC4 individually in various grades of oral squamous cell carcinoma (OSCC), oral premalignant disorders (OPMDs)- oral epithelial dysplasia (OED), oral submucous fibrosis (OSF), oral lichen planus (OLP), and compared with normal oral mucosa (NOM). Immunohistochemistry and qRTPCR evaluation of MUC1 & 4 on sixty-three cases of OSCC, OPMD, and NOM was accomplished. The one-way ANOVA test and Chi-square test were done for statistical analysis. The overall immunoexpression of MUC1 & 4 increased significantly from NOM to OPMDs to OSCC. In the subgrades of OSCC and OPMDs, the staining intensity varied. For MUC4, the intensity was strongest in well-differentiated grades and MUC1, exhibiting a higher expression in poorly differentiated grades of OSCC and OPMDs. The study's results indicate that MUC1 & 4 individually are crucial formonitoringOSCC and OPMD pathogenesis as the former gives an idea of highly undifferentiated grades while the latter indicated more differentiated tumors and perhaps a better prognosis. Therefore, the two can be useful tumor markers for determining the severity and eliminating it in its early phases.

Abstract A061: A cost-effective two-step approach for multi-cancer early detection in general population

Abstract In population-wide cancer screening, three key issues need to be focused on: number of cancer cases identified, the issue of false positives, and cost. A high false positive rate can result in a significant waste of healthcare resources. Large-scale screening inevitably leads to significant financial burdens on the healthcare system which is a key factor constraining nationwide screening. OncoSeek is a multi-cancer early detection (MCED) test using a panel of seven plasma protein tumor markers (PTMs) and artificial intelligence (AI). SeekInCare is a MCED test that integrates the seven PTMs and four cancer genomic features (aneuploidy, fragment size, end motifs, and oncogenic viruses) from cell-free DNA (cfDNA) by shallow whole-genome sequencing (sWGS). In a two-step approach, the initial screening is conducted using OncoSeek and SeekInCare is then used as the secondary test for those individuals who tested positive by OncoSeek. In a case-control study (n = 1197) including both OncoSeek and SeekInCare testing results, OncoSeek showed 49.9% sensitivity at 91.0% specificity, while SeekInCare demonstrated 60.0% sensitivity at 98.3% specificity. In the two-step process, specificity significantly increased from 91.0% to 99.3%, while sensitivity decreased from 49.9% to 39.9%. We modeled a screening in five million adults aged ≥ 50 years with a cancer incidence rate of 1.9%. The simulated real-world sensitivities of OncoSeek and two-step were adjusted downward proportionally to 28.0% and 22.4% based on the sensitivity differences observed between GRAIL’s CCGA study (case-control, 51.5%) and PATHFINDER study (prospective, 28.9%). While at 91.0% specificity OncoSeek had 441,450 cases of false positives, using the two-step approach significantly reduced false positives to 34,335 (0.7%). Although Galleri ($949 per test) identified more cancer cases than the two-step MCED, with 27,455 and 21,280 cases respectively, its total cost for the former reached $4,745 million. As the positive predictive value (PPV) of two-step (38.3%) was the same as Galleri (38.3%), it reduced cost 6.6-fold, amounting to a total cost of $713.6 million and a cost of $143 per individual screened. The cost of per cancer case detected using Galleri is $172,828 compared to $33,534 using the two-step MCED, which represents a 5.2-fold difference. In conclusion, the two-step approach not only significantly reduces false positives, but also cuts the screening cost down substantially, making it a cost-effective strategy for population-wide cancer screening. Citation Format: Mao Mao, Geng shuai peng, Li shi yong, Wu Wei, Chang Yin Yin. A cost-effective two-step approach for multi-cancer early detection in general population [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A061.

Primary dedifferentiated liposarcoma of the gallbladder: a case report and literature review

BackgroundLiposarcoma (LPS) is a kind of malignancy of soft tissue usually found in the retroperitoneal, limb, or neck region, and some may be detected with delayed symptoms (pain or palpable mass), and less frequently occurs in organs of the digestive system. In contrast, Dedifferentiated liposarcoma (DDLPS) is a common histological subtype of LPS. The present study reported a case of dedifferentiated liposarcoma originating in the gallbladder. Differentiated liposarcoma originating from the gallbladder is rarely reported.Case descriptionA 64-year-old female patient presented to our hospital with a painless abdominal mass. Abdominal computed tomography (CT) showed that the gallbladder had lost its normal shape, and a 9.1 cm × 7.1 cm × 12.1 cm mass was seen in the area of the gallbladder fossa and the right upper abdomen below it, which had an irregular morphology, inhomogeneous density, and nodular calcification, with marked inhomogeneous enhancement on enhancement scan. Preoperative tumor markers and liver function indicators were not abnormal. With suspicion of a giant malignant tumor of the gallbladder, she underwent a cholecystectomy combined with abdominal mass resection. After surgery, the tumor and gallbladder, were completely resected, and postoperative pathological results confirmed the diagnosis of dedifferentiated liposarcoma deriving from gallbladder. After surgery, the patient and his family refused to continue treatment. After 15 months follow-up, the patient remains asymptomatic and does not show any signs of recurrence. And she is now under continued follow - up.ConclusionsTreatment of dedifferentiated liposarcoma is still at exploratory stage, and a lack of clinical evidence for this condition might hinder access to clinical trials and studies. Currently, the treatment of choice for dedifferentiated liposarcoma remains radical resection. In the available clinical studies, there are no robust data to support clinical use of neoadjuvant and adjuvant radiochemotherapy. As with other diseases, the use of radiotherapy and chemotherapy before and after surgery may be a potential future treatment.

The Advancement Stage of Gastric Cancer and the Levels of CEA and Ca19-9 in Serum and Peritoneal Lavage

Background: This study aimed to analyze the relationship between the levels of tumor markers—specifically, carcinoembryonic antigen (CEA) and Ca19-9 antigen—determined in both serum (sCEA and sCa19-9) and intraoperative peritoneal washings (pCEA and pCa19-9) and the advanced stage of gastric cancer (including the occurrence of cancer cells in cytology from abdominal fluid). Methods: This study included 47 patients with histopathologically confirmed gastric cancer or gastroesophageal junction cancer who underwent surgical treatment. The material for the cytological examination and assessment of CEA and Ca19-9 concentrations in peritoneal fluid was collected intraoperatively. Later, blood was drawn to assess the CEA and Ca19-9 concentrations in blood serum. Results: There was a statistical correlation between a positive cytology result or the presence of peritoneal carcinomatosis and a positive result for the tumor markers obtained from abdominal washings. This correlation was not observed with marker levels obtained from blood serum. The pCEA marker was highly sensitive (93.3%) and specific (93.8%) for detecting cancer cells. The pCa19-9 marker was less effective in detecting cancer but matched pCEA in identifying the absence of cancer. No differences were observed in sCEA and sCA19-9 levels between patients who underwent neoadjuvant chemotherapy and those who did not receive this treatment. However, statistical analysis showed that this relationship did not apply to pCEA and pCa19-9 levels. Conclusions: Intraoperative determinations of tumor marker levels in peritoneal washings may be a predictive factor for a poor prognosis in patients with gastric cancer.

Abundance of Tumor-Infiltrating B Cells in Human Epithelial Malignancies

Cancer is a major global health problem. The type of malignant neoplasm and the potency of the immune response against tumors are two of the key factors influencing the outcome of the disease. The degree of tumor infiltration by lymphocytes plays an important role in antitumor response development, generally correlating with a favorable prognosis of treatment for certain cancers. We analyzed the abundance of tumor-infiltrating B cells (TIBs) in solid tumors of different cancers. TIBs were shown to be more abundant in colon and sigmoid colon cancer samples compared with cecal, rectal, and kidney cancer samples. The median and interquartile range of the TIB fraction were 11.5% and 4–20% in colon cancer, 6% and 3–11% in sigmoid colon cancer, 2.7% and 0.7–3.7% in cecal cancer, 2.5% and 0.9–3.6% in rectal cancer, 1.4% and 1.0–2.3% in kidney cancer, and 3.0% and 1.8–12% in lung cancer, respectively. However, there were no significant differences in the abundance of TIBs among samples at different stages of the cancer. Hence, investigation of the B cell response in colon cancer is of particular interest, since increased quantities of TIBs may indicate the existence of immunogenic tumor markers or the cell-cell interactions involved in disease progression. We believe that studying the diversity of TIBs in colon cancer will increaseour understanding of the mechanisms of the disease, contributing to the identification of new molecular targets for targeted oncotherapy.

TMOD-28. MODELING MICROENVIRONMENTAL DYNAMICS: A NOVEL 3D GLIOMA-NEURON FUSION MODEL

Abstract Gliomas engage in bidirectional interactions with their microenvironment, wherein neuronal activity influences glioma proliferation and gliomas induce neuronal hyperexcitability. Although various models elucidate this complex interplay, a preference for a three-dimensional (3D) cell culture model has emerged to mimic intra-tumoral heterogeneity and microenvironmental interactions influencing glioma invasion, resistance, and recurrence. This study introduces an in vitro, self-assembled, scaffold-free, neuron-glioma spheroid fusion model to investigate the electrophysiological and functional interplay between glioma and its microenvironment. Primary mouse cortical neurons (MCN) were isolated from prenatal brain tissues and were cultured at 500,000 cells/spheroid on ultra-low attachment plates. Glioma organoids (WHO Grade 2-4) were developed from primary patient-derived tissue samples and were allowed to self-assemble for at least two weeks. After spontaneous spiking activity was detected in MCN spheroids, they were combined with glioma organoids in culture and allowed to fuse. A multielectrode array (MEA) was used to characterize the electrophysiological properties of the fusion model. Structural and functional characterizations were performed using immunofluorescence staining of proliferation, microglial, astrocytic, synaptic, and tumor markers. Additionally, the electrophysiological effects of the dual-IDH-mutant inhibitor, Vorasidenib, were assessed in WHO grade 2-4 IDH-mutant gliomas. Electrophysiological analysis of glioma-neuron co-cultures using MEA demonstrated a significantly increased network synchrony and firing rate in the fusion model when compared with the neuron-only condition, consistent with 2D models in the past. In correlation, the fusion model also demonstrated a significant increase in the Ki67 proliferation index across WHO grade 2-4 gliomas when compared to the glioma organoid-only condition. Vorasidenib treatment decreased neuronal firing rate and synchrony. Together, these results offer a high-throughput 3D model for recapitulating the tumor-brain microenvironment for both low and high-grade gliomas. Future studies will focus on the use of this model for drug screening and the exploration of malignant transformation in gliomas.

NIMG-02. DEVELOPING A RADIOMIC HIERARCHICAL GAUSSIAN PROCESS BOOSTING MODEL TO PREDICT PRIMARY TUMOR ORIGIN FROM MULTICENTRIC LONGITUDINAL MRI DATA OF BRAIN METASTASES

Abstract Focal neurologic deficits due to brain metastases might be the initial presentation in patients with cancer. Common approaches to investigate the occult primary malignancy include a whole-body PET-CT, whole-body MRI, studying tumor markers, or histopathological examination. Most of these modalities are expensive, time-consuming, invasive, and delay treatment. The field of radiomics leverages quantitative features extracted from images to improve the decision-making process in clinical practices. Although not easily understandable, these features are proxies for the tumor’s shape, contour, texture, and intensity patterns. They can help understand tumor heterogeneity, predict tumor behavior, and assess treatment response. We propose a robust radiomic workflow using longitudinal MRI data from 914 high-resolution imaging studies from 12 different centers (Ocaña-Tienda et al. (2023), Ramakrishnan et al. (2023), Wang et al. (2023)) to predict the origin of brain metastases from brain MRI scans. After using ensemble feature selection methods, we trained three fixed-effects and one mixed-effects multiclass classification model to account for longitudinal data. Fixed-effects logistic regression and support vector kernel models performed the worst (AUC 0.74 and 0.75, respectively), while the random forest performed better (AUC 0.97). The mixed-effects hierarchical Gaussian process boosting (GPBoost) model performed the best with an accuracy of 85.8%, precision of 85.4%, sensitivity of 85.8%, specificity of 95.7%, and an AUC of 0.98. In one-versus-rest classification, the GPBoost model identified the primary tumor as melanoma with the highest accuracy (96.1%) and non-small cell lung cancer with the lowest accuracy (89.0%). Developing such models holds great promise in reducing patient and institutional costs, improving time to effective treatment, and enhancing overall survival rates through personalized therapy approaches. In the future, we hope that incorporating newer patient data and refining the model to improve external validity would enable more accurate and generalizable predictions, leading to better clinical outcomes across diverse populations.

Left-sided portal hypertension caused by a solid pseudopapillary neoplasm of pancreas tail: a pediatric case report

BackgroundSolid pseudopapillary neoplasm (SPN) is a low-grade malignant tumor that occurs in 60% of all pediatric pancreas tumors. Radical tumor resection is essential; however, spleen preservation is also crucial to prevent overwhelming post-splenectomy infection. In contrast, spleen preservation is not always possible, because left-sided portal hypertension (LSPH) can cause splenic vein stenosis or occlusion induced by pancreatic tumor. We herein report on a pediatric patient of LSPH due to SPN in the pancreatic tail.Case presentationA 12-year-old girl was admitted to our hospital with left upper quadrant abdominal pain. A solid mass was palpated in the left costal region. The patient showed slight anemia (Hb: 11.8 g/dL) and elevation of inflammatory reaction (CRP: 5.98 mg/dL) without positive tumor markers. A radiological examination revealed that a 9 cm-sized mass with hemorrhagic necrosis in the pancreatic tail. Splenic venous flow was not detected and collateral draining into the left gastric vein and left renal veins were developed with splenomegaly. LSPH was involved at the time of diagnosis. The tumor was diagnosed with SPN, hence tumor resection with spleen preservation was performed. Six months after surgery, the patient developed a left quadrant abdominal pain that worsened during exercise. There was no improvement of splenic venous flow and splenomegaly. LSPH remained with splenomegaly, which possibly triggered the patient’s abdominal pain. The patient underwent splenectomy 9 months after the tumor resection. After the splenectomy, the patient’s abdominal pain disappeared without any recurrence 8-year post-surgery.ConclusionsLSPH has not been a major focus in previous SPN pediatric patients, although most symptomatic LSPH patients required splenectomy. Careful post-operative observation for LSPH is important for pediatric SPN patients.

Optimization of upper respiratory tract cancer diagnosis method based on exhaled breath gas analysis

Introduction. Head and neck tumors comprise about 7 % of all malignant neoplasms. In the head and neck area, tumors are usually located on the tongue (25–40 %) and floor of mouth (15–20 %). In the majority of cases, diagnosis, especially at early disease stages, is based on clinical and histopathological evaluation of tumor process. However, recently development and implementation of non-invasive techniques of early diagnosis of upper respiratory tract tumors through detection of pathognomonic volatile tumor markers in the exhaled air has become topical.Aim. To evaluate diagnostic accuracy of sensory gas analysis device and artificial neural network for examination of exhaled gas samples from patients with oropharyngeal, laryngeal, laryngopharyngeal cancer and to establish the optimal conditions for sampling.Materials and methods. The study included 28 patients with oropharyngeal, laryngeal, laryngopharyngeal cancers and 25 healthy volunteers. The proposed technique is based on analysis of samples of exhaled gas from the studied individuals using a diagnostic device developed by the authors. The device detects volatile compounds in the exhaled air using a set of semiconductor sensors with subsequent analysis by a neural network. The exhaled air was sampled using two methods: in the morning in the fasted state before daily hygienic procedures and physical activity (prepared samples) and in the context of everyday life, nutrition and hygiene without restrictions before sampling (non-prepared samples).Results. Based on the signals from the sensors, the neural network classified and detected patients with malignant tumors. Accuracy of the prepared samples from healthy volunteers and patients with oropharyngeal, laryngeal, laryngopharyngeal cancers was 79.17 %, of non-prepared – 84.09 %.Conclusion. High diagnostic accuracy of the developed technique of non-invasive diagnosis of malignant tumors of the oropharyngeal, laryngeal, laryngopharyngeal areas using exhaled air samples which does not require special preparation of the studied samples was demonstrated.

The comparison of clinicopathological characteristics of two distinct manifestations of gastric signet ring cell carcinoma under EUS

ABSTRACT Background and Objectives There are two different endoscopic ultrasonographic manifestations of gastric signet ring cell carcinoma (GSRCC). No studies have been reported on the differences in the clinical profiles of patients based on EUS examination. We aim to study the variations in clinicopathological characteristics between two distinct endoscopic ultrasonographic manifestations of GSRCC. Methods A total of 302 patients with GSRCC confirmed by pathological examination who underwent EUS were enrolled in the study. Based on the endoscopic ultrasonographic features, patients were categorized into two groups: type 1, where the entire layer structure disappeared, and type 2, where the layer structure was still present and appeared lymphomatoid. Clinicopathologic features were collected retrospectively and analyzed. Results Compared with type 2 patients, type 1 patients tended to develop GSRCC at an older age (P = 0.033) and had higher serum levels of tumor markers and were more likely to experience anemia (P &lt; 0.001) and weight loss (P &lt; 0.001) during the disease progression. Significant increases in the tumor size (P &lt; 0.001), thickness of the affected gastric wall (P &lt; 0.001), and depth of tumor invasion (P &lt; 0.001) were observed in type 1 patients. Furthermore, type 1 patients had higher prevalence of affected blood vessels (P &lt; 0.001), nerves (P &lt; 0.001), lymph nodes (P &lt; 0.001), and peritoneal metastasis (P &lt; 0.001). However, no difference was found in the duration of disease between the two groups, and all deficient mismatch repairs were observed in type 1 patients. Conclusions The two distinct endoscopic ultrasonographic manifestations of GSRCC exhibited different clinicopathological characteristics, suggesting that they may represent different subtypes of the disease that require special attention in management strategies.

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

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

Iodinated PSMA Ligands as XFI Tracers for Targeted Cell Imaging and Characterization of Nanoparticles

Prostate cancer is the second most commonly diagnosed cancer in men worldwide. Despite this, current diagnostic tools are still not satisfactory, lacking sensitivity for early-stage or single-cell diagnosis. This study describes the development of small-molecule tracers for the well-known tumor marker prostate-specific membrane antigen (PSMA). These tracers contain a urea motif for PSMA-targeting and iodinated aromatic moieties to allow detection via X-ray fluorescence imaging (XFI). Tracers with a triiodobenzoyl moiety allowed the specific targeting and successful imaging of PSMA+ cell lines with XFI. The XFI-measured uptake of 7.88 × 10−18 mol iodine (I) per cell is consistent with the uptake of known PSMA tracers measured by other techniques such as inductively coupled plasma mass spectrometry (ICP-MS). This is the first successful application of XFI to tumor cell targeting with a small-molecule tracer. In addition, iodinated tracers were used for the characterization of quantum dots (QDs) conjugated to PSMA-targeting urea motifs. The resulting targeted QD conjugates were shown to selectively bind PSMA+ cell lines via confocal microscopy. The immobilized iodinated targeting vectors allowed the determination of the tracer/QD ratio via XFI and ICP-MS. This ratio is a key property of targeted particles and difficult to measure by other techniques.

Construction of electrochemical immunosensors based on Au@MXene and Au@CuS nanocomposites for sensitive detection of carcinoembryonic antigen

Cancer is currently one of the major causes of human mortality and has received widespread attention. In this paper, Au@CuS composite nanomaterial as a sandwich immunosensor tag for carcinoembryonic antigen (CEA) detection strategy was studied. Herein, Au@CuS composite nanomaterials were obtained by Au nanoparticles modified with CuS, which were combined with secondary antibody (Ab2) to construct an immunosensor that interacted with H2O2 to produce a current response. The anti-CEA primary antibody (Ab1) was fixed on the glassy carbon electrode (GCE) modified by Au@MXene. The completed electrochemical immunosensor was constructed with rapid detection and high sensitivity for CEA. Under optimal conditions, the linearity ranged from 0.01 pg/mL to 0.5 ng/mL, and the detection limit was 3.8 fg/mL. This tactic possesses good reproducibility, constancy and selectivity. At the same time, this strategy has latent practical value for the test of other tumor markers.

Short-term Outcomes of Robot-assisted Colectomy Using the Overlap Method for Right-sided Colon Cancer.

The recent development of minimally invasive surgery has led to transition from laparoscopic right colectomy (LC) to robot-assisted right colectomy (RC) in Japan. However, it is unclear whether the introduction of RC in municipal hospitals could be as safe as that in high-volume centers in Japan. Therefore, this retrospective study aimed to compare the short-term operative outcomes of RC and LC for right colon cancer at a local municipal hospital in Japan. Patients with stage I-IV right colon cancer who underwent elective RC or LC between January 2021 and July 2023 were retrospectively analyzed. Patients with double cancer and those who underwent delta anastomosis were excluded. Postoperative surveillance included patient interviews, physical examinations, tumor marker examinations, and whole-body computed tomography every six months. Forty patients were analyzed, and 24 (60%) and 16 (40%) patients assigned in the LC and RC groups, respectively, were compared. The operative time, bleeding, postoperative complications, and pathological examinations did not differ significantly between the LC and RC groups. RC using overlapping anastomoses was comparable to LC in terms of short-term operative outcomes. The introduction of RC with overlapping anastomosis is a feasible surgical technique.

Clinical and Genetic Mechanisms in Patients with MC2R Deficiency Presenting with Early Puberty.

Melanocortin receptor 2 (MC2R) in the adrenal cortex controls the hypothalamic-pituitary-adrenal axis. The melanocortin system, influenced by leptin, regulates GnRH neurons, crucial for puberty onset and fertility. This study evaluates early puberty in primary adrenal insufficiency (PAI) patients due to MC2R gene alterations. Seven patients with PAI (P1-P7) from five unrelated families, all presenting with early or precocious puberty, were included. MC2R deficiency diagnosis ranged from 1 day to 11 months. MKRN3, DLK1, KISS1, and KISS1R genes were analyzed using Sanger sequencing in four cases (P2,P4,P6 and P7). All clinical data were obtained retrospectively. Puberty onset mean age was 8.6 years (7.4-9.5) in boys (P1, P2, P3, P7) and 8.5 years (7.4-9.5) in girls (P4, P5, P6). Tumor markers were negative; no adrenal rest or tumors were found. GnRH analogs were used for rapid puberty in P2, P3, P6. Final height in P1 and P2 was below target (-2.6 SDS, -0.7 SDS). Menarche occurred at 11 and 11.3 years in P4 and P5. No pathogenic variants were found. Genetic causes of early puberty were not identified. Elevated ACTH may stimulate kisspeptin neurons, triggering puberty. Close monitoring of these patients for pubertal development is recommended.

Detection of carcinoembryonic antigen specificity using microwave biosensor with machine learning

Early diagnosis and screening of tumor markers are essential for effective cancer treatment and improve the treatment efficiency and prognosis of tumor recurrence and metastasis. In this study, a split-ring resonator circuit based on an interdigital electrode structure was developed and applied to microwave biosensors along with machine learning to detect extremely low concentrations of Carcinoembryonic Antigen (CEA). CEA was detected using a microwave sensor operating at a resonance frequency of 4.33 GHz. When the microwave sensor is exposed to CEA analytes, it generates a new frequency in the range of 1–2 GHz. The position and intensity of the newly generated frequency can be used to characterize and predict the concentration of the CEA solution. The proposed sensor exhibits excellent resonance linearity for various concentrations of CEA (R2 = 0.999), as well as a very low detection limit (39 pg/mL) and high sensitivity (27.5 MHz/(ng/mL)). A machine learning approach was implemented to predict the CEA concentration in blood samples. The results showed close concurrence with the CEA concentration detected by the sensor. Western Blot (WB) was used to compare the CEA contents of four different cell types, and a biosensor was used for validation; the results of the two experiments showed good agreement. This is the first demonstration of the validation of biosensor reliability at the cellular level. The proposed concept exhibits outstanding detection performance with convenient and rapid tumor marker detection. Hence, it has important implications as an auxiliary diagnosis method for cancer.

LINC00365 as a potential biomarker for total nephrectomy in advanced-stage renal cell carcinoma patients

BackgroundRenal cell carcinoma (RCC) is one of the most frequent urological cancers globally that has a good prognosis in the early tumor stages. However, there is a poor prognosis in metastatic RCC patients. Therefore, it is needed to evaluate the molecular biology of RCC progression to introduce the efficient diagnostic and therapeutic markers in these patients. Long non-coding RNAs (lncRNAs) have key roles in regulation of molecular mechanisms during RCC progression. In the present study, we assessed the levels of LINC00365 expressions in RCC patients to suggest that as a tumor marker in these patients. MethodsFifty fresh RCC tumor tissues and their normal margins were collected to assess the levels of LINC00365 expressions and probable correlations with clinicopathological features of RCC patients. ResultsThere was significant LINC00365 up regulation in females compared with males (p=0.050). Among the RCC patients with total nephrectomy, there was a significant LINC00365 up regulation in advanced stage compared with primary stage tumors (p=0.035). RCC patients older than 60 years old who were undergone the total nephrectomy had also significant LINC00365 up regulation compared with RCC patients younger than 60 years old (p=0.039). Conclusionsgiven the significant increase in LINC00365 expression in advanced stage RCC tumors and patients over 60 years old who had total nephrectomy; it could serve as a useful diagnostic marker in screening programs for old high-risk individuals. It was also noticed that female RCC patients had elevated levels of LINC00365 expressions in their tumor samples, suggesting its potential use as a gender-specific diagnostic marker for high-risk females. Nevertheless, evaluating the levels of LINC00365 in serum samples of RCC patients is necessary to suggest that as a reliable diagnostic marker in clinical settings.