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A novel impedimetric immunosensor was fabricated for the determination of carcino-embryonic antigen (CEA) using conductive and adhesive gold/polypyrrole-polydopamine nanocomposite as an immobilization matrix. A polypyrrole-polydopamine complex (PPy-PDA) was first prepared by the polymerization of pyrrole and dopamine, which was then blended with chloroauric acid solution (HAuCl4). The in situ reduction of AuCl4− ions to gold nanoparticles (Au NPs) by polydopamine leads to the successful preparation of gold/polypyrrole-polydopamine nanocomposites (Au/PPy-PDA). The obtained Au/PPy-PDA nanocomposite not only provides a highly biocompatible and stable matrix for loading antibody, but also accelerate the electron transfer process owing to the conductive PPy as well as encapsulated Au NPs, which is quite suitable to be applied as high-efficiency immunoassay platform. CEA antibody (CEA-Ab) was efficiently loaded on Au/PPy-PDA film, and a label-free impedimetric immunosensor was successfully constructed. Under optimal conditions, a wide linear range (0.001–500 ng mL−1) and low detection limit (0.2 pg mL−1) was demonstrated for the detection of CEA. Furthermore, the proposed CEA immunosensor exhibited high specificity, excellent reproducibility, and stability, providing an experimental evidence for early diagnosis of cancer. Accurate detection of CEA in human serum samples was also exhibited. [ABSTRACT FROM AUTHOR]

An ultrasensitive enzyme-linked immunosorbent assay (ELISA) is reported for the determination of carcinoma embryonic antigen (CEA) in human serum. It was realized using a microplate reader using a 384-well plate. Monoclonal antibody (Ab) against CEA (1° Ab) acting as the capture probe was immobilized on zinc oxide nanoparticles (ZnO-NPs) in the form of self-assembled monolayers (SAMs). CEA captured by 1° Ab was quantified using a sandwich ELISA wherein a polyclonal second antibody against CEA (2° Ab) was used for detection and quantified using an HRP-labeled secondary antibody (3° Ab). The ZnO-NPs-CEA capture probe was deposited on the bottom of the wells in order to enhance capture of CEA. A 3-fold enhancement in the chemiluminescence (CL) signal of luminol is found (compared to a conventional ELISA). CEA can be quantified by this method in concentrations as low as 1 pg · mL. The upper limit of detection is 20 ng · mL. The use of ZnO-NPs also imparts improved thermal stability. When stored at 4 °C in phosphate-buffered saline of pH 7.4, the probe displays stability of up to 30 days. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

ESA-10 is an embryonic antigen expressed by tumor cells. A method to detect the antigen in the blood based on alterations in the erythrocyte sedimentation rate that occur when antiserum to ESA-10 is bound to the antigen in blood was devised and used here to determine the sensitivity and predictive value of the test in patients with biopsy proven non-hematologic malignancies, and in normal control subjects. The test was positive in 22 of 24 cancer patients tested, and negative in 30 of 35 control subjects. Of the five positive control subjects, one female had recently given birth and was lactating. Another control subject was recently diagnosed with prostate cancer, just months after having participated in this study. Therefore, this tumor marker test (Turtest) had a sensitivity of 91.7% and a positive predictive value of 81.5% in patients with biopsy proven cancer, and a specificity and negative predictive value in control subjects of 88.2 and 93.8%, respectively, if the control subject who subsequently developed prostate cancer is removed from the control group. Therefore, this simple test has potential as a clinically useful tumor marker with sensitivity and specificity equal to or greater than other commercially available tumor markers and should be explored further in larger studies. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine whether lysyl oxidase (LOX) is a useful marker of metastasis in gastric cancer (GC) patients in combination with tumor markers carcino-embryonic antigen (CEA), carbohydrate antigen 724 (CA724), carbohydrate antigen 19-9 (CA19-9), and carbohydrate antigen 125 (CA125). There were 215 GC patients (67 without metastasis, 102 with lymph node metastasis, and 46 with peritoneal metastasis) who presented to the Affiliated Cancer Hospital of Guangxi Medical University between May 2009 and November 2012 that were enrolled in this study. The LOX expression level and the serum concentration of the four tumor markers were evaluated preoperatively. All patients underwent computed tomography (CT) and ultrasonography (US) before surgery. Statistical analysis, including receiver operating characteristic (ROC) curve analysis, area under the curve (AUC) analysis, and logistic regression analysis, was performed to evaluate the diagnostic value of these markers in predicting metastasis in GC. For predicting lymph node metastasis in GC, the sensitivity of LOX, CEA, CA724, CA199, and CA125 was 44.12, 12.75, 21.57, 23.53, and 15.69 %, respectively, and increased to 79.41 % in combination. For predicting peritoneal metastasis in GC, the sensitivity of these markers was 56.52, 23.91, 34.78, 36.96, and 34.78 %, respectively, and increased to 91.30 % in combination. Combining LOX with CEA, CA724, CA199, and CA125 could increase the sensitivity of predicting lymph nodes metastasis and peritoneal metastasis in GC. Surgeons can use these markers to determine the best treatment options for patients. Additional large-scale, prospective, multicenter studies are urgently needed to further confirm the results of this study. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: The carcino-embryonic antigen-related cell adhesion molecule (CEACAM)2 is produced in many feeding control centres in the brain, but not in peripheral insulin-targeted tissues. Global Ceacam2 null mutation causes insulin resistance and obesity resulting from hyperphagia and hypometabolism in female Ceacam2 homozygous null mutant mice ( Cc2 [also known as Ceacam2]) mice. Because male mice are not obese, the current study examined their metabolic phenotype. Methods: The phenotype of male Cc2 mice was characterised by body fat composition, indirect calorimetry, hyperinsulinaemic-euglycaemic clamp analysis and direct recording of sympathetic nerve activity. Results: Despite hyperphagia, total fat mass was reduced, owing to the hypermetabolic state in male Cc2 mice. In contrast to females, male mice also exhibited insulin sensitivity with elevated β-oxidation in skeletal muscle, which is likely to offset the effects of increased food intake. Males and females had increased brown adipogenesis. However, only males had increased activation of sympathetic tone regulation of adipose tissue and increased spontaneous activity. The mechanisms underlying sexual dimorphism in energy balance with the loss of Ceacam2 remain unknown. Conclusions/interpretation: These studies identified a novel role for CEACAM2 in the regulation of metabolic rate and insulin sensitivity via effects on brown adipogenesis, sympathetic nervous outflow to brown adipose tissue, spontaneous activity and energy expenditure in skeletal muscle. [ABSTRACT FROM AUTHOR]

Carcino Embryonic Antigen (CEA) and Cancer Antigen 15.3 (CA15.3) are the most common tumor markers in breast cancer patients. Measurement of circulating tumor markers is a non-invasive quantitative method. Serum levels of CEA and CA 15.3 were studied in female breast cancer patients prior to treatment. To evaluate the utility of these markers, 207 Breast carcinoma patients belonging to all the stages were considered. Healthy age matched 75 female individuals formed the control group. The serum levels of CEA and CA 15.3 were analyzed by Enzyme Linked Immunosorbent Assay (ELISA). Results were taken and compared with stages, tumor size, node and grade. The serum CA 15.3 levels were significant in all the study parameters whereas serum CEA levels showed no significant changes with any of the parameters. Measurement of serum CA 15.3 levels showed significant correlation (24.8%) with advanced stages and larger tumor sizes, whereas serum CEA levels did not show any significant correlation in breast cancer patients prior to treatment. [ABSTRACT FROM AUTHOR]

This prospective study of radioimmunoscintigraphy using In-labelled, C46, a monoclonal antibody against carcino embryonic antigen, CEA, was undertaken in 23 patients with colorectal cancer, 18 with primary carcinomas, 3 with recurrences and 2 with metastases. A sensitivity of 95% and an accuracy of 91% was found. New observations through the use of two administered doses of antibody and the analysis of surgical specimens showed that for the low dose of antibody (average 0.76 mg) tumour uptake was 1.14×10% of the injected dose per gram, whereas on the higher dose (average 4.67 mg) the average tumour uptake was 6.77% (same units) p<0.01. Thus a six-fold increase of antibody caused a sixfold increase in tumour uptake, but no change was seen in the tumour to mucosa ratio 4.8±0.5 (low dose) and 4.0±1.0 (high dose). A further observation was that well and moderately differentiated tumours took up about four times more than poorly differentiated tumours ( p<0.05). It was also found that tumour free lymph nodes had a six-fold greater uptake than tumour involved nodes ( p<0.05) confirming other work with anti-CEA monoclonal antibody. In conclusion, although biological factors influence its efficacy,In labelled C46 anti-CEA is a suitable radiopharmaceutical for the radioimmunoscintigraphy of colorectal cancer. [ABSTRACT FROM AUTHOR]

This study concerns the immunohistologic distribution of carcino-embryonic antigen (CEA) in tissues and organs from 86 legal abortions, stillborn fetuses and perinatal deaths and from 5 adults without inflammatory disease or cancer. Monospecific antibodies to CEA of both polyclonal and monoclonal origin were applied to serial sections obtained from formalin-fixed, paraffin-embedded tissue blocks. Starting from the 9th week of gesta-tional age, a positive staining reaction for CEA was found in the surface epithelium of the tongue, the tracheal mucosa and the following locations of the gastro-intestinal tract: the gastro-oesophageal junction, the pyloric antrum, the upper duodenum, throughout the colon and appendix. In the adult, CEA was also found at these sites. All other organs such as the central nervous system, lung, thyroid, thymus, liver, pancreas, gastric corpus, spleen, adrenals, kidney, ureter, bladder, gonads and breast were negative for CEA. Therefore, CEA appears to be a normal antigen in the gastro-intestinal tract at any age from fetal life onwards. Copyright © 1988 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

A high-level secretion system for the production of mouse-human chimeric antibody 21B2 (MHC 21B2) Fab fragment specific for human carcino embryonic antigen (hCEA) in Escherichia coli has been constructed. The genes encoding a light chain and an Fd fragment (a variable region and the CH domain of a heavy chain) of a mouse-human chimeric antibody were directly fused to the signal peptide of the E. coli ompF gene sequence. E. coli cells containing expression vectors in which each of the two genes are located downstream of a separate tac promoter were able to secrete the light chain and Fd fragment as two of their major cellular proteins. The signal peptides were efficiently removed from the primary products by post-translational processing, although they formed insoluble aggregates, possibly in the periplasm. In high-cell-density culture experiments using a jar fermentor, the amount of light chain and Fd fragment produced was at levels of up to 2.88 g/l and 1.28 g/l culture, respectively. By optimizing the conditions that encourage correct folding, formation of disulphide bonds, and association of the light chain with the Fd fragment, we have established a procedure that can purify, refold, and combine aggregated products to electrophoretically homogeneous Fab fragment with a yield of approximately 47%. Fab fragment produced in this manner shows essentially the same antigen-binding activity and specificity to hCEA as the parental mouse antibody 21B2 (MoAb 21B2). [ABSTRACT FROM AUTHOR]

Serum carcinoembryonic antigen (CEA) levels were studied in 128 patients with histologically proven breast cancer. When measured at diagnosis in patients with non-metastatic disease (all stages except Stage IV) 27% of patients had levels greater than 10 ng/ ml. Measurement of the CEA at initial diagnosis gave little guide to which patients subsequently relapsed. Patients with Stage IV disease at diagnosis had levels in excess of 10 ng/ml in 75% of cases. Furthermore, changes in serum CEA levels were found to reflect changes in tumour bulk, in individual patients, in 75.8% of cases. It is concluded that while serial measurements of serum CEA levels can be of value, particularly in the management of advanced breast cancer patients, it is of less value in the earlier stages as a predicator of recurrence. [ABSTRACT FROM AUTHOR]

A mammalian embryonic cell surface glycoprotein (ESGp), whose expression and biochemical structure seem to be developmentally regulated, has been isolated and characterized. The molecule expressed in two cell through morula stage mouse embryos has a molecular weight, by electrophoretic analyses, of 90 kDa. At the blastocyst stage, however, the molecule migrates as a broad, heterogeneous band ranging from 90 to 110 kDa. Evidence obtained from studies of embryonal carcinoma (EC) cells indicates that this band is actually a composite of three distinct molecules (molecular weight 90, 95, and 105 to 110 kDa), each of which is synthesized uniquely by one of the different cell types of the blastocyst: the embryonic ectoderm and visceral and parietal endoderms, respectively. A survey of various mouse tissues and cell lines has revealed that undifferentiated cells express the low molecular weight form (90 kDa) characteristic of embryonic ectoderm, whereas differentiated cells and adult tissues express the high molecular weight form (110 kDa) characteristic of parietal endoderm. Only the EC visceral endoderm cell analogues have been shown to express the intermediate molecule (95 kDa). In embryos, the antigen is uniformly distributed over the cell surface during early cleavage stages (two to eight cell); just before compaction, however, it seems to redistribute and becomes polarized at the outside exposed edges of blastomeres. In cultured EC cells, ESGp is found only in areas of cell-to-cell contact; free-standing surfaces of cells are negative for expression. It is possible, therefore, that ESGp may be involved in the intercellular adhesion of both EC cells and compacting embryos. [ABSTRACT FROM AUTHOR]

Copyright of Virchows Archiv A Pathological Anatomy & Histology is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Lactoperoxidase (LPO) and lactoferrin (LF) are promising bovine proteins that can be nano-formulated with chitosan nanoparticles giving a potent pharmaceutical product. This study aimed to evaluate the therapeutic potential of a prepared nano-combination composed of LPO and LF loaded on chitosan nanoparticles (LPO + LF/CNPs) against oxidative damage in the liver of rats exposed to 7,12-dimethylbenz[a]anthracene (DMBA). Twenty-four male Wistar albino rats (4 months old) were divided into three equal groups and treated orally as follow: (1) rats were given saline and served as control, (2) rats received a single dose (20 mg/kg) of DMBA dissolved in soy oil, and (3) rats intoxicated with a single dose (20 mg/kg) of DMBA, 56 days prior to their oral treatment with the nano-combination (50 mg /kg/day) for consecutive 30 days. Then, blood and liver samples were collected for biochemical determinations. Histological and immunohistochemistry examinations of liver tissue were also performed. TEM image of LPO + LF/CNPs showed semi-rounded shape particles with an average size of 336.8 nm and 47.30 mV zeta potential. DMBA intoxication increased serum aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), and gamma-glutamyl transferase (GGT) activities. DMBA increased also the values of hepatic malondialdehyde (MDA) and nitric oxide (NO), serum nuclear factor κB (NF-κB), caspase-3, interleukin-1beta (IL-1β), and tumor necrosis factor-alpha (TNF- α), and the tumor markers alpha fetoprotein (AFP) and carcino embryonic antigen (CEA), whereas hepatic glutathione (GSH) content and the activities of hepatic glutathione peroxidase (GPx), catalase (CAT), and glutathione–S-transferase (GST) were significantly decreased. In addition, serum triglycerides, total, and low-density lipoprotein cholesterol (LDL-C) levels were significantly elevated with a significant decrease in high-density lipoprotein cholesterol (HDL-C) and albumin levels. Moreover, DMBA induced severe histological alterations in the liver tissue and the immunohistochemistry investigation revealed that DMBA exposure upregulated the hepatic protein expression of caspase 3. The post-treatment with LPO + LF/CNPs ameliorated most of the above parameters and improved the histological picture of the liver. The present study indicated that LPO + LF/CNPs have a potent therapeutic potential against DMBA hepatotoxicity through the suppression of oxidative stress and inflammation which leads to liver damage. [ABSTRACT FROM AUTHOR]

Multiple linear stapler firings is a risk factor for anastomotic leakage (AL) in laparoscopic low anterior resection (LAR) using double stapling technique (DST) anastomosis. In this study, our objective was to establish the risk factors for ≥ 3 linear stapler firings, and to create and validate a predictive model for ≥ 3 linear stapler firings in laparoscopic LAR using DST anastomosis. We retrospectively enrolled 328 mid–low rectal cancer patients undergoing laparoscopic LAR using DST anastomosis. With a split ratio of 4:1, patients were randomly divided into 2 sets: the training set (n = 260) and the testing set (n = 68). A clinical predictive model of ≥ 3 linear stapler firings was constructed by binary logistic regression. Based on three-dimensional convolutional networks, we built an image model using only magnetic resonance (MR) images segmented by Mask region-based convolutional neural network, and an integrated model based on both MR images and clinical variables. Area under the curve (AUC), sensitivity, specificity, accuracy, positive predictive value (PPV), and Youden index were calculated for each model. And the three models were validated by an independent cohort of 128 patients. There were 17.7% (58/328) patients received ≥ 3 linear stapler firings. Tumor size ≥ 5 cm (odds ratio (OR) = 2.54, 95% confidence interval (CI) = 1.15–5.60, p = 0.021) and preoperative carcinoma embryonic antigen (CEA) level > 5 ng/mL [OR = 2.20, 95% CI = 1.20–4.04, p = 0.011] were independent risk factors associated with ≥ 3 linear stapler firings. The integrated model (AUC = 0.88, accuracy = 94.1%) performed better on predicting ≥ 3 linear stapler firings than the clinical model (AUC = 0.72, accuracy = 86.7%) and the image model (AUC = 0.81, accuracy = 91.2%). Similarly, in the validation set, the integrated model (AUC = 0.84, accuracy = 93.8%) performed better than the clinical model (AUC = 0.65, accuracy = 65.6%) and the image model (AUC = 0.75, accuracy = 92.1%). Our deep-learning model based on pelvic MR can help predict the high-risk population with ≥ 3 linear stapler firings in laparoscopic LAR using DST anastomosis. This model might assist in determining preoperatively the anastomotic technique for mid–low rectal cancer patients. [ABSTRACT FROM AUTHOR]

We studied the expression of CD66b (a protein of the cancer-embryonic antigen family, expressed mainly in neutrophils) in tumor and stromal cells of non-small cell lung cancer (93 samples). The number of CD66b+ neutrophils is not associated with clinical and morphological parameters of the tumors and the disease prognosis. However, CD66b is expressed in the tumor cells of most studied samples. CD66b expression is also associated with the histological type of tumor and its localization. Increased expression of CD66b in tumor cells indicated a more favorable prognosis, which allows using this protein as a prognostic marker and as a potential target for the immunotherapy. [ABSTRACT FROM AUTHOR]

Background and objective: No effective preoperative tool is available for predicting the prognosis of advanced gastric cancer (AGC) treated by neoadjuvant chemotherapy (NAC). We aimed to explore the association between change values ("delta") in the radiomic signatures of computed tomography (CT) (delCT-RS) before and after NAC for AGC and overall survival(OS). Methods and design: A total of 132 AGC patients with AGC were studied as a training cohort in our center, and 45 patients from another center were used as an external validation set. A radiomic signatures-clinical-nomogram(RS-CN) was established using delCT-RS and preoperative clinical variables. The prediction performance of RS-CN was evaluated using the area under the receiver operating characteristic (ROC)curve (AUC values), time-dependent ROC, decision curve analysis(DCA) and C-index. Results: Multivariable Cox regression analyses showed that delCT-RS, cT-stage, cN-stage, Lauren-type and the value of variation of carcinoma embryonic antigen (CEA) between NAC were independent risk factors for 3-year OS of AGC. In the training cohort, RS-CN had a good prediction performance for OS (C-Index 0.73) and AUC values were significantly better than those of delCT-RS, ypTNM-stage and tumor regression grade(TRG) (0.827 vs 0.704 vs 0.749 vs 0.571, p < 0.001). DCA and time-dependent ROC of RS-CN were better than those of ypTNM stage, TRG grade and delCT-RS. The prediction performance of the validation set was equivalent to that of the training set. The cut-off (177.2) of RS-CN score was obtained from X-Tile software, a score of > 177.2 was defined as high-risk group(HRG), and scores of ≤ 177.2 were defined as the low-risk group(LRG). The 3-year OS and disease free survival(DFS) of patients in the LRG were significantly better than those in the HRG. Adjuvant chemotherapy(AC) can only significantly improve the 3-year OS and DFS of the LRG. (p < 0.05). Conclusions: Our nomogram based on delCT-RS has good prediction of prognosis before surgery and helps identify patients that are most likely to benefit from AC. It works well in precise and individualised NAC in AGC. [ABSTRACT FROM AUTHOR]

Aim: To cross-sectionally and longitudinally investigate the association between tumor markers (Cancer embryonic antigen (CEA) Carbohydrate antigen 19–9 (CA19-9)) and malignancies in type 2 diabetes patients without evidence of malignancy. Materials and Methods: The study included 707 patients admitted for the treatment of diabetes from 1 August 2010 to 1 September 2018. Serum CEA and CA19-9 levels were measured for screening of malignancies at admission. Abdominal ultrasonography, computed tomography, and endoscopy were performed for close examination. The percentage of patients diagnosed with malignancy was calculated, and among those without malignancy, the incidence of malignancies was examined after discharge. Results: A total of 26 patients (3.7%) were newly diagnosed with malignancy during hospitalization. The optimal cut-off value of CEA and CA19-9 by receiver operating characteristic analysis was 5.0 ng/mL and 75 U/mL, and their positive predictive values (PPV) were 8.7% and 22.5%, respectively. The addition of CA19-9 to age, smoking status, body mass index, and glycated hemoglobin significantly improved classification performance for malignancy using net reclassification improvement (0.682, 95% CI 0.256–1.107) and integrated discrimination improvement (0.150, 95% CI 0.007–0.294). Among 681 patients without malignancies during hospitalization, 30 patients (4.4%) developed malignancies during an average follow-up of 3.9 years. CA19-9 (hazard ratio: 1.005, 95% CI: 1.003–1.008) was associated with the development of malignancies. Conclusions: PPV of serum CEA and CA19-9 for detecting malignancy was high in type 2 diabetes patients with poor glycemic control. Measuring CA19-9 was found to be valuable to cross-sectionally and longitudinally detect malignancies. [ABSTRACT FROM AUTHOR]

Presents a case study of an epidermoid cyst in the spleen of a 12-year-old girl. Medical equipment and antigens used in diagnosing the disease; Potential severe complications; Factors which raise the level of carcinoembryonic antigen in patients with an epidermoid cyst.

Expression profiles of glycosphingolipids (GSLs) in human embryonic stem cell (hESC) lines and their differentiated embryoid body (EB) outgrowth cells, consisting of three germ layers, were surveyed systematically. Several globo- and lacto-series GSLs were identified in undifferentiated hESCs and during differentiation of hESCs to EB outgrowth cells, and core structure switching of these GSLs to gangliosides was observed. Such switching was attributable to altered expression of key glycosyltransferases (GTs) in GSL biosynthetic pathways, reflecting the unique stage-specific transitions and mechanisms characteristic of the differentiation process. Lineage-specific differentiation of hESCs was associated with further GSL alterations. During differentiation of undifferentiated hESCs to neural progenitor cells, core structure switching from globo- and lacto-series to primarily gangliosides (particularly GD3) was again observed. During differentiation to endodermal cells, alterations of GSL profiles were distinct from those in differentiation to EB outgrowth or neural progenitor cells, with high expression of Gb4Cer and low expression of stage-specific embryonic antigen (SSEA)-3, -4, or GD3 in endodermal cells. Again, such profile changes resulted from alterations of key GTs in GSL biosynthetic pathways. Novel glycan structures identified on hESCs and their differentiated counterparts presumably play functional roles in hESCs and related cancer or cancer stem cells, and will be useful as surface biomarkers. We also examined GSL expression profiles in breast cancer stem cells (CSCs), using a model of epithelial-mesenchymal transition (EMT)-induced human breast CSCs. We found that GD2 and GD3, together with their common upstream GTs, GD3 synthase (GD3S) and GD2/GM2 synthase, maintained stem cell phenotype in breast CSCs. Subsequent studies showed that GD3 was associated with epidermal growth factor receptor (EGFR), and activated EGFR signaling in breast CSCs and breast cancer cell lines. GD3S knockdown enhanced cytotoxicity of gefitinib (an EGFR kinase inhibitor) in resistant MDA-MB468 cells, both in vitro and in vivo. Our findings indicate that GD3S contributes to gefitinib resistance in EGFR-positive breast cancer cells, and is a potentially useful therapeutic target in drug-resistant breast cancers. [ABSTRACT FROM AUTHOR]

This study was to explore the application value of back propagation (BP) neural network (BPNN) and genetic algorithm (GA) in the combined detection and prognosis of tumor markers in patients with gallbladder cancer. 446 patients with gallbladder cancer were included in the experimental group, 279 patients with benign gallbladder disease were included in the control group, and 188 healthy people were selected and included in the blank group. Serum tumor markers (CA242, CA199, CEA, and CA125) of the three groups were detected by electrochemical luminescent immune analyzer, and follow-up data for 5 years after surgery were collected. Based on BPNN and GA, an optimization algorithm for multi-tumor markers was constructed and applied to the combined detection of tumor markers in patients. The artificial neural network (ANN), dynamic network biomarker (DNB), auxiliary diagnosis algorithm of the support vector machine (SVM) based on the particle swarm optimization (PSO) (PSO-SVM), matched-pairs feature selection (MPFS) based on the machine learning, and the BPNN were introduced to compare with the algorithm constructed. The diagnostic performances of the algorithms were evaluated with the fivefold cross-validation method. The results showed that the levels of CanAg (CA) 242, carcinoma embryonic antigen (CEA), CA199, and CA125 and positive rates in the experimental group were significantly higher than those in the control group and the blank group (P < 0.05); but the differences between control group and blank group were not visible (P > 0.05). The sensitivity (91.72%) and specificity (87.49%) in detecting CA242 and CA199 based on the proposed algorithm were the highest; the sensitivity (0.9186), specificity (0.8622), and accuracy (94.94%) of the proposed algorithm were higher than those of the conventional algorithms. The postoperative follow-up survival rate of patients in the experimental group was reduced from 41.72% in the first year to 4.28% in the fifth year; tumor node metastasis (TNM) stage IV, neck gallbladder cancer, and CA199 were significantly correlated with the survival rate of patients in the experimental group (P < 0.05). In summary, the combined detection technology of multiple tumor markers based on deep learning algorithms showed excellent diagnostic and prognostic performance for gallbladder cancer. The occurrence of gallbladder cancer was related to the tumor markers CA242, CA199, CEA, and CA125, showing better detection effects by combination of CA242 and CA199. The TNM stage IV, neck gallbladder cancer, and CA199 were independent risk factors for the decrease in survival rate of patients with gallbladder cancer. [ABSTRACT FROM AUTHOR]

A photochromic immunoassay was built for tumor marker detection based on ZnO/AgI nanophotocatalyst. Frist, ZnO/AgI nanoparticles were synthesized and characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray powder diffraction (XRD), and Fourier transform infrared spectrometry (FTIR). The color development is caused by tetramethyl benzidine (TMB) solution oxidated by ZnO/AgI nanomaterials. The electron transitions in ZnO/AgI nanomaterials are driven by visible light irradiation, generating photogenerated hole and oxidizing TMB to blue solution. Appropriate band width between ZnO and AgI promotes separation of photogenerated electrons and holes and enhances oxidation efficiency. A sandwich-type immunoassay was constructed based on ZnO/AgI nanomaterial as labels. The absorbance at 650 nm of reaction solution is positively correlated with antigen concentration. The developed immunoassay showed good performance for carcinoma embryonic antigen (CEA) detection in the range 0.1–7.0 ng/mL with a detection limit of 65 pg/mL. The photochromic immunoassay also exhibited preferable selectivity, repeatability, and stability. A novel colorimetric immunoassay was constructed based on ZnO/AgI photocatalyst. ZnO/AgI nanomaterials occur electron transitions under visible light irradiation and generate photogenerated hole, which can oxidize TMB to blue solution. Carcinoembryonic antigen in sample was detected sensitively due to the high catalytic efficiency of ZnO/AgI nanomaterials. [ABSTRACT FROM AUTHOR]

The purpose of this study is to describe the clinical efficacy and safety of the combined use of systemic chemotherapy and CT-guided radiofrequency ablation (RFA) in treatment of lung cancer. A panel of 256 patients with lung cancer who were admitted to our hospital from June 2017 to October 2019 were recruited. According to the treatment plan, the patients were divided into test group (n = 128) and control group (n = 128). Patients in the test group were treated by systemic chemotherapy combined with CT-guided RFA, while patients in the control group were given systemic chemotherapy only. After treatment, a comparative analysis was conducted in terms of clinical efficacy, level of tumor markers, and adverse reactions. Meanwhile, patients in the two groups were followed up for analysis of progression-free survival (PFS) and overall survival (OS). After treatment, the tumor objective response rate and disease control rate of patients in the test group were significantly higher than those in the control group. Besides, in patients of the test group, tumor markers, such as serum carcino-embryonic antigen, neuro-specific enolase, cytokeratin-19, and carbohydrate antigen-199, presented a remarkably lower level relative to those in the control group (p < 0.05). However, there was no significant difference observed with regard to the incidence of complications (p > 0.05). Additionally, patients in the test group were more likely to have better PFS and OS. Notably, we monitored that in the test group, superior clinical efficacy was achieved in patients with non-small cell lung cancer and lung adenocarcinoma relative to that in patients with small cell lung cancer and lung squamous cell carcinoma, respectively. The combined use of systemic chemotherapy and CT-guided RFA can produce good clinical efficacy in treatment of lung cancer. It is relatively safe and deserves promotion and application in clinic. [ABSTRACT FROM AUTHOR]

Purpose: Signet Ring Rectal Cancer (SRRC) of rectum is rare high-grade subtype with poor prognosis and characteristic histopathology. We evaluated its imaging appearance and correlated its outcomes. Materials and methods: We conducted a retrospective review of the rectal MRIs of 97 patients with rectal SRRC, evaluating tumor morphology, T2 signal, length, location, pattern of tumor growth, nodal status and location, EMVI (extramural vascular invasion), site of metastases, and response to chemotherapy. The tumor signal on T2W images was categorized into intermediate, T2 hyperintense, and fluid/mucin bright. Imaging findings were correlated with risk of metastatic/ recurrent disease, disease-free survival, and overall survival. Results: The median age of patients of SRRC in our study was 35 years and more frequently found in male patients. The common imaging features of SRRC were T2-hyperintense signal (63%), infiltrative growth pattern (76%), positive MR CRM (Circumferential Resection Margin on MRI) (84%), presence of EMVI (51%), and advanced T and N stage (97% and 84%, respectively). Peritoneum and nodes were the most common sites of metastases. Raised serum CEA (Carcino-embryonic Antigen) levels, positive MR CRM status, extramesorectal adenopathy, and advanced N stage had statistically significant predictive value for recurrence or metastases. Elevated serum CEA levels (p = 0.019) and intermediate T2 signal (p = 0.012) demonstrated significant independent association with poor overall survival, while advanced N stage (p = 0.033) demonstrated significant independent association with worse disease-free survival in multivariate analysis. Conclusion: SRRC affected young patients and demonstrated T2-hyperintense signal and subepithelial spread in an infiltrative pattern. Elevated CEA levels and T2-intermediate signal intensity are independent predictors for worse overall survival and advanced nodal stage is independent prognostic factor of poor disease-free survival. MRI rectum can pinpoint the pathology given the distinct MRI morphology and age of presentation. [ABSTRACT FROM AUTHOR]

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Background: Lung cancer is a disease that severely endangers human health. Non-small cell lung cancer (NSCLC) accounts for approximately 4/5 of lung cancers. Aims: To investigate the efficacy of early combination of local radiotherapy and granulocyte macrophage colony-stimulating factor (GM-CSF) for advanced NSCLC treated with icotinib. Methods: Forty-two patients with stage IV NSCLC complicated with EGFR gene mutation were selected and randomly divided into two groups, with 21 patients in each group. Patients in control group were treated with icotinib, and patients in experimental group were treated with icotinib combined with local radiotherapy and subcutaneous injection of GM-CSF. One-year progression free survival between two groups was compared. Results: Three months after treatment, the efficacy in experimental group was significantly better than that in control group, and objective response rate was 95.24% in experimental group, which was higher than the 71.43% in control group. Patients in experimental group had no differences in white blood cell and neutrophil, but had significantly lower carcino-embryonic antigen and neuron-specific enolase levels and higher CD3+, CD4+, and CD4+/CD8+ than those in control group and before treatment. There were no differences in the proportion of patients with adverse reactions between two groups. One-year progression free survival was significantly better in experimental group than in control group. Conclusions: Early combination of local radiotherapy and GM-CSF has a significant efficacy for advanced NSCLC accounts for approximately 4/5 of lung cancers treated with icotinib, and it can improve patients' autoimmunity and lengthen progression free survival. [ABSTRACT FROM AUTHOR]

MFECP1 is a glycosylated recombinant fusion protein composed of MFE-23, a high-affinity anti-carcinoembryonic antigen (CEA) single chain Fv (scFv), fused to the enzyme carboxypeptidase G2 (CPG2), and has been constructed for use in antibody-directed enzyme pro-drug therapy (ADEPT). Radiolabelling of glycosylated MFECP1 with technetium-99m was developed for the purpose of determining tumour localisation of MFECP1 in a phase I ADEPT clinical study. The method used was 99mTc-carbonyl [99mTc(H2O)3(CO)3]+ (abbreviated to TcCO) mediated labelling of 99mTc to the hexahistidine (His) tag of MFECP1. MFECP1 fusion protein was labelled with TcCO under a variety of conditions, and this was shown to be a relatively simple and robust method. Tissue biodistribution was assessed in a CEA-expressing LS174T (human colon carcinoma) nude mouse xenograft model. Tissues were taken at 1, 4 and 6 h for assessment of distribution of radioactivity and for measurement of CPG2 enzyme levels. The amount of radioactivity retained by the tumour proved to be an accurate estimation of actual measured enzyme activity, indicating that this radiolabelling method does not appear to damage the antibody–antigen binding or the enzyme activity of MFECP1. However, correlation between CPG2 enzyme activity and measured radioactivity in liver, spleen and kidney was poor, indicating retention of radioactivity in non-tumour sites but loss of enzyme activity. The high retention of technetium radioisotope in normal tissues may limit the clinical applicability of this radiolabelling method for MFECP1; however, these results suggest that this technique does have applicability for measuring the biodistribution of His-tagged recombinant proteins. [ABSTRACT FROM AUTHOR]

Alterations in protein glycosylation are observed in many solid tumor types leading to formation of tumor-associated carbohydrate antigens (TACAs). The most common TACA is the Tn antigen (CD175), which is a mucin-type O-GalNAc-Ser/Thr/Tyr glycan in membrane and secreted glycoproteins. In addition, two other TACAs are CA19-9 (sialyl-Lewis a), which is used as a prognostic serum marker for pancreatic cancer, and its isomer sialyl-Lewis x (SLex, CD15s), which is overexpressed in many cancer types and associated with metastasis. While CD175 and other TACAs may be expressed by many human carcinomas, little is known about their differential expression patterns in tumors, thus limiting their use as tissue biomarkers or therapeutic targets. Here we address the clinicopathological relevance of the expression of CA19-9, CD15s, and CD175 in pancreatic ductal adenocarcinoma (PDAC) tissues. Semi-quantitative IHC staining with well-defined monoclonal antibodies demonstrates that CD175 is expressed in all PDAC specimens analyzed. Unexpectedly, however, these TACAs are differentially expressed within PDAC specimens and their glycoproteins, but not significantly expressed in adjacent normal tissues. These data provide avenues for novel therapeutic approaches that could combine CD175- and CA19-9-targeting therapies for PDAC patients. [ABSTRACT FROM AUTHOR]

This review paper explores the realm of non-invasive methods for early cancer detection. Early identification is crucial for effective therapeutic intervention, and non-invasive techniques have emerged as promising tools to enhance diagnostic accuracy and improve patient outcomes. The paper thoroughly examines the advantages, limitations, and prospects of various non-invasive approaches, including blood tests, non-blood-based tests, and diverse imaging modalities. It discusses the biomarkers found in blood for early-stage cancer detection, specifying the types of cancer associated with each biomarker. The non-blood-based tests focus on components in saliva, urine, and breath for cancer detection, alongside current studies and future perspectives on various cancers. Optical imaging methods covered in this review include fluorescence imaging in the near-infrared (NIR) region, bioluminescence imaging, and Raman spectroscopy for early-stage cancer detection. The review also highlights the pros and cons of ultrasound imaging in early-stage cancer detection. Additionally, the clinical implications of using AI for cancer detection, both present and future, are explored. This paper provides valuable insights for researchers and clinicians working in the field of non-invasive early-stage cancer detection. [ABSTRACT FROM AUTHOR]

Background: Surgical site infection (SSI) represents a significant postoperative complication in colorectal cancer (CRC). Identifying associated factors is therefore critical. We evaluated the predictive value of clinicopathological features and inflammation-based prognostic scores (IBPSs) for SSI occurrence in CRC patients. Methods: We retrospectively analyzed data from 1445 CRC patients who underwent resection surgery at Wuhan Union Hospital between January 2015 and December 2018. We applied two algorithms, least absolute shrinkage and selector operation (LASSO) and support vector machine-recursive feature elimination (SVM-RFE), to identify key predictors. Participants were randomly divided into training (n = 1043) and validation (n = 402) cohorts. A nomogram was constructed to estimate SSI risk, and its performance was assessed by calibration, discrimination, and clinical utility. Results: Combining the 30 clinicopathological features identified by LASSO and SVM-RFE, we pinpointed seven variables as optimal predictors for a pathology-based nomogram: obstruction, dNLR, ALB, HGB, ALT, CA199, and CA125. The model demonstrated strong calibration and discrimination, with an area under the curve (AUC) of 0.838 (95% CI 0.799–0.876) in the training cohort and 0.793 (95% CI 0.732–0.865) in the validation cohort. Decision curve analysis (DCA) showed that our models provided greater predictive benefit than individual clinical markers. Conclusion: The model based on simplified clinicopathological features in combination with IBPSs is useful in predicting SSI for CRC patients. [ABSTRACT FROM AUTHOR]

Ultrasonic biochemical detection is important for biomarker detection, drug monitoring, and medical diagnosis, as it can predict disease progression and enable effective measures to be taken in a timely manner. However, the ultrasonic technology currently used for biochemical marker detection is directly modified on the surface of the device. The associated test methods are costly and unreliable while having poor repeatability; therefore, they cannot achieve low-cost rapid testing. In this study, a detection mechanism based on the Rayleigh scattering of acoustic waves caused by nanoparticles, which causes changes in the received sound pressure, was developed for the first time. The modification of antibodies on an insertable substrate decouples the functionalization step from the sensor surface and facilitates the application of capacitive micromachined ultrasonic transducers (CMUTs) in conjunction with Au nanoparticles (AuNPs) for CA19-9 cancer antigen detection. A corresponding detection theory was established, and the relevant parameters of the theoretical formula were verified using different nanoparticles. Using our fabricated CMUT chip with a resonant frequency of 1 MHz, the concentrations and substances of the CA19-9 antigen markers were successfully measured. In the concentration range of 0.1–1000 U/mL, the receiving voltage decreased with increasing concentration. Further investigations revealed that the influence of other interfering markers in the human body can be ignored, demonstrating the feasibility and robustness of biochemical detection based on CMUTs combined with nanoparticles. [ABSTRACT FROM AUTHOR]

Conventional treatment strategies suffer from a lack of solubility, low bioavailability at the target site, a lack of target specificity, and indiscriminate drug distribution, all of which lead to drug resistance. Therefore, the present study aimed to deliver capsaicin into breast cancer cells through folic acid-conjugated capsaicin-loaded carboxylic acid-functionalised multiwalled carbon nanotubes (FA-CAP-COOHMWCNTs). FA-CAP-COOHMWCNTs was formulated and characterized by FTIR (Fourier transform infrared spectroscopy), SEM (Scanning electron microscopy), HR-TEM (High-resolution transmission electron microscopy), and XRD (X-ray diffraction) analysis. In silico studies demonstrated that the active molecule, capsaicin can strongly bind onto C-SRC kinase receptor to suppress cancer progression. The in vitro cellular viability of MCF-7 breast cancer cells after 24h treatment with 100 µg × mL− 1 of FA-CAP-COOHMWCNTs was found to be 29.27 ± 2.59% and IC50 value was observed to be 22.71 µg × mL− 1. Subsequently, in vivo anticancer activity of FA-CAP-COOHMWCNTs was performed against 7,12-dimethylbenz(a) anthracene (DMBA)-induced breast cancer in female Wistar rats. After 21 days of treatment with FA-CAP-COOHMWCNTs, breast cancer-induced rats showed a significant reduction in mammary tumor size, and elevated levels of antioxidant enzymes in serum/breast tissue. The most powerful antioxidant effects were seen in the medium dose (5 mg × kg− 1) of FA-CAP-COOHMWCNTs, which also caused tumors to shrink significantly, almost as much as the standard drug (doxorubicin). Histopathological studies also showed near-normal architecture of breast tissue. Altogether, it can be interpreted that FA-CAP-COOHMWCNTs have antiproliferative efficacy against breast tumor progression in breast cancer-induced rats. [ABSTRACT FROM AUTHOR]

The author outlines his philosophy and practice of management of gall bladder cancer based on his more than three-decade experience at a large tertiary level super-specialty referral hospital attached to a university-status teaching institution at Lucknow in northern India where GBC is very common. [ABSTRACT FROM AUTHOR]

Background: Patients with advanced pancreatic ductal adenocarcinoma (PDAC) need timely medical assistance since the emergence of complications due to the disease and antitumor treatment. Studies have confirmed that instant messaging can improve the quality of life and compliance of cancer patients. However, the prognostic role of instant doctor–patient communication based on instant messaging applications in PDAC has not been studied. Methods: Patients with PDAC who received first-line chemotherapy at Peking Union Medical College Hospital between January 2015 and October 2022 were reviewed. We categorized patients into two groups according to whether they received WeChat-based instant doctor–patient communication, and the prognosis and toxicity data between the two groups were compared. Results: A total of 431 PDAC patients were enrolled, of whom 163 had long-term instant communication with their doctors based on WeChat, and 268 did not receive WeChat-based instant communication. There was no significant correlation between WeChat-based communication and first-line chemotherapy overall response rate (14.1% vs. 8.6%, p = 0.074), incidence of grade ≥ 3 adverse events (66.9% vs. 65.7%, p = 0.814) or overall survival (14.7 vs. 13.9 months, p = 0.170) in all enrolled patients. However, patients who received WeChat-based instant communication had a higher completion rate of first-line chemotherapy (42.0% vs. 30.7%, p = 0.023). Consistently, in the patients who developed grade ≥ 3 adverse events (n = 231), those who received WeChat-based instant communication had significantly longer overall survival (17.3 vs. 15.3 months, p = 0.018), even after adjustment for biases. Conclusions: WeChat-based instant doctor–patient communication demonstrated no superiority in improving the efficacy of chemotherapy or preventing chemotherapy toxicity in PDAC patients, but it may contribute to improving the completion rate of chemotherapy and the prognosis in patients who experienced severe adverse events. Implications for Cancer Survivors: Instant doctor‒patient communication may help to timely and appropriately deal with adverse events and prolong the survival time of patients with PDAC, supporting the promotion of mobile technology in clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: We evaluated the diagnostic and prognostic value of three tumor markers: carcino-embryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and carbohydrate antigen 125 (CA125), in the pretreatment serum of patients with unresectable advanced or recurrent gastric cancer.Methods: The subjects of this retrospective analysis were 245 patients with unresectable advanced or recurrent gastric cancer diagnosed at Kochi Medical School between 2007 and 2015. We ascertained the sensitivity of CEA, CA19-9, and CA125 to identify a certain survival time and then evaluated the relative prognosis of the patients.Results: The overall positive rates for each tumor marker in the study group were as follows: 57.6% (141/245) for CEA, 38.4% (94/245) for CA19-9, and 34.3% (84/245) for CA125; the sensitivity of these three biomarkers in combination was 73.1% (179/245). The median survival time of the CA125-positive patients was 4.5 months, which was significantly shorter than that of a normal range group (18.3 months, P < 0.001). Multivariate survival analysis identified that high CA125 was independently associated with a worse prognosis (HR 3.941; 95% CI 2.544-6.106; P < 0.001).Conclusions: Pretreatment serum CA125 is a useful prognostic biomarker in patients with unresectable advanced or recurrent gastric cancer. Evaluating a panel of serum tumor biomarkers is a useful diagnostic tool as elevated values might be associated with poor survival. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is the second most common malignancy affecting men globally. Recent advances in metabolomics have highlighted significant alterations in specific amino acid (AA) metabolism linked to PCa, indicating their potential utility in diagnosis and therapy. However, no direct causal association between serum AA levels and PCa risk has been established. A total of 35 patients with PCa and 30 individuals with benign prostatic hyperplasia (BPH) were recruited for this study. Targeted metabolomic analysis was performed using ultra-high-performance liquid chromatography-tandem mass spectrometry on serum samples. Two-sample Mendelian randomization (MR) was applied to explore potential causal links between serum AA levels and PCa risk, including mediator effects using dual-phase MR and assessing reverse causality through reverse MR. Results Targeted metabolomic profiling identified six amino acids—glutamate (Glu), Ser, histidine (His), arginine (Arg), aspartic acid (Asp), and glycine (Gly)—that showed significant area under the ROC curve in differentiating between BPH and PCa cases. Notably, Glu demonstrated an inverse association with PCa risk, distinct from the other AAs identified. However, definitive evidence supporting a causal relationship between low Glu levels and increased PCa risk was not observed. Our results suggest a protective role of Glu against PCa development, which may have implications for disease prognosis. Increasing dietary Glu intake may present a potential preventive or therapeutic approach for PCa. [ABSTRACT FROM AUTHOR]

Mutant KRAS promotes the proliferation, metastasis, and aggressiveness of various cancers including pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC), and colorectal adenocarcinoma (CRC) respectively. Mutant KRAS therapeutics are limited, while Sotorasib and Adagrasib were the only FDA-approved drugs for the treatment of KRASG12C mutated NSCLC. Chimeric antigen receptor (CAR) T-cell therapy has been emerged as an effective strategy against hematological malignancies and being extended towards solid cancers including PDAC. mesothelin (MSLN) and Carcinoembryonic Antigen (CEA) were reported to be highly overexpressed in KRAS-mutated PDAC. Meanwhile, in clinical trials, several CAR T-cell therapy studies are mainly focused towards these two cancer antigens in PDAC, however, the dual targeting of these two neoantigens is not reported. In the present study, we have designed and developed a novel dual-targeting CAR protein by employing various bioinformatics approaches such as functional analysis (antigenicity, allergenicity, antigen binding sites & signalling cascades), qualitative analysis (physicochemical, prediction, refinement & validation of 2D and 3D structures), molecular docking, and in silico cloning. Our results revealed that the designed CAR protein specifically binds with both MSLN & CEA with significant binding affinities, and was predicted to be stable & non-allergenic. Additionally, the protein–protein interaction network reveals the T-cell mediated antitumor responses of each domain in the designed CAR. Conclusively, we have designed and developed a dual targeting (MSLN & CEA) CAR protein towards KRAS-mutated PDAC using computational approaches. Alongside, we further recommend to engineer this designed CAR in T-cells and evaluating their therapeutic efficiency in in vitro and in vivo studies in the near future. [ABSTRACT FROM AUTHOR]

Background: Metabolomics is an emerging field that quantifies numerous metabolites systematically aiming to determine the metabolites corresponding to each biological phenotype and then provide an analysis of the mechanisms involved. Bile acids (as an organic metabolites) are synthesized in the liver from cholesterol and could be used as indicator of hepatobiliary impairment. However, the role of these bile acids in the pathogenesis of cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC) is still unclear. Therefore, the current study aimed to use serum bile acid profiles potential diagnostic biomarkers for early detection of cholangiocarcinoma and differentiating it from hepatocellular carcinoma. Subjects and methods: Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC/MS/ MS) analytical method was used for the measurement of bile acids in the serum of patients with hepatocellular carcinoma (n = 35), cholangiocarcinoma (n = 35), and control group (n = 35) to determine role as markers for differentiation between hepatocellular carcinoma and cholangiocarcinoma. Results: This study revealed that there was a significant increase in all 14 bile acids in both HCC and CCA compared to control. Also, there was significant increase in LCA, TCA, GDCA, and GCA in cholangiocarcinoma (CCA) compared to HCC with AUC 0.775, 0.825, 0.797, and 0.831 respectively with highest sensitivity and specificity for GCA (82% and 74%, respectively) for differentiation between the two types of cancers. Conclusion: Determination of the serum bile acids pattern using UPLC/MS/MS may help to differentiate between hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) especially GCA which may be a good biomarker for differentiation between two types of liver cancers. [ABSTRACT FROM AUTHOR]

Immune evasion represents a crucial milestone in the progression of cancer and serves as the theoretical foundation for tumor immunotherapy. In this study, we reveal a negative association between Human Papillomavirus (HPV)-encoded circular RNA, circE7, and the infiltration of CD8+ T cells in head and neck squamous cell carcinoma (HNSCC). Both in vitro and in vivo experiments demonstrate that circE7 suppresses the function and activity of T cells by downregulating the transcription of LGALS9, which encodes the galectin-9 protein. The molecular mechanism involves circE7 binding to acetyl-CoA carboxylase 1 (ACC1), promoting its dephosphorylation and thereby activating ACC1. Activated ACC1 reduces H3K27 acetylation at the LGALS9 gene promoter, leading to decreased galectin-9 expression. Notably, galectin-9 interacts with immune checkpoint molecules TIM-3 and PD-1, inhibiting the secretion of cytotoxic cytokines by T cells and promoting T cell apoptosis. Here, we demonstrate a mechanism by which HPV promotes immune evasion in HNSCC through a circE7-driven epigenetic modification and propose a potential immunotherapy strategy for HNSCC that involves the combined use of anti-PD-1 and anti-TIM-3 inhibitors. Immune evasion is a feature of HPV-positive head and neck squamous cell carcinoma (HNSCC). Here the authors report that a circular RNA, circE7, encoded by HPV promotes immune evasion in HNSCC by promoting downregulation of galectin-9. [ABSTRACT FROM AUTHOR]

Introduction: The role of neoadjuvant therapy (NAT) in the treatment of locally advanced rectal cancer (LARC) has been well proven, but its impact on patients who relapse remains unknown. This study aims to elucidate the influence of initial treatment and MRI-defined risk factors on postrecurrent survival in patients with LARC recurrence. Patients and methods: LARC patients who underwent radical surgery and subsequently developed recurrence were retrospectively identified. Patients were stratified on the basis of MRI-defined local risk assessment and the initial treatment modality for the primary tumor (NAT or primary surgery). The patients were classified into four groups: high-risk LARC with NAT (HiN), high-risk LARC with primary surgery (HiS), low-risk LARC with NAT (LoN), and low-risk LARC with primary surgery (LoS). The primary endpoint was survival after recurrence. Results: A total of 381 patients who experienced relapse were identified from among 2329 LARC patients. Salvage surgery was performed on 33.1% of these patients. Patients who experienced single-site recurrence or who underwent salvage surgery exhibited significantly prolonged survival times after recurrence (P < 0.001). Patients in the HiS group had poorer survival after recurrence than those in the other three groups (P = 0.034). This subset of patients, characterized by receiving less adjuvant treatment after primary surgery, had a shorter recurrence interval than those in the other groups (P = 0.001). Conclusions: Our findings reaffirm the prognostic significance of salvage surgery in patients from a LARC cohort who experienced relapse. Moreover, MRI-defined high-risk LARC patients who received upfront surgery without NAT had shorter intervals of recurrence and poorer survival outcomes after recurrence. Our results highlight the critical role of NAT in improving patient survival after recurrence. Trial registration: Supplementary registration was carried out at clinicaltrials.gov (Registration number: NCT06314737) on March 14, 2024. The study was retrospectively registered. [ABSTRACT FROM AUTHOR]

Glycan-mediated interactions play a crucial role in biology and medicine, influencing signalling, immune responses, and disease pathogenesis. However, the use of glycans in biosensing and diagnostics is limited by cross-reactivity, as certain glycan motifs can be recognised by multiple biologically distinct protein receptors. To address this specificity challenge, we report the enzymatic synthesis of a 150-member library of site-specifically fluorinated Lewisx analogues ('glycofluoroforms') using naturally occurring enzymes and fluorinated monosaccharides. Subsequent incorporation of a subset of these glycans into nanoparticles or a microarray revealed a striking spectrum of distinct binding intensities across different proteins that recognise Lewisx. Notably, we show that for two proteins with unique binding sites for Lewisx, glycofluoroforms exhibited enhanced binding to one protein, whilst reduced binding to the other, with selectivity governed by fluorination patterns. We finally showcase the potential diagnostic utility of this approach in glycofluoroform-mediated bacterial toxin detection by lateral flow. Distinguishing between different proteins that each bind to the same type of glycan is challenging. Here, the authors demonstrate that an enzymatically synthesised library of Lewisx 'glycofluoroforms' that feature site-specific fluorination can discriminate closely related proteins. [ABSTRACT FROM AUTHOR]

Diffusion layer dispersed electrodes were presented for application in electrochemical immunoassays. The diffusion layer refers to the region on the electrode surface where concentration gradients occur during the redox reactions of the target analytes. To control the diffusion layer, electrodes of the same area and size were fabricated, and the shape of the diffusion layer was controlled by adjusting each electrode distance. To estimate the properties of the electrodes, cyclic voltammetry (CV) analysis was performed using ferricyanide ([Fe(CN)6–3]) and 3,3′5,5′-tetramethylbenzidine (TMB) as a model redox couple. Changes in the diffusion layer shape according to electrode distance were compared through simulation. The redox currents for the target analytes increased as electrode distance increased. These results indicate that even if the electrode shape and area are the same, dispersing the diffusion layer by adjusting the distance between the electrodes can affect the microelectrode characteristics. Finally, the diffusion layer dispersed electrode was applied for the medical diagnosis of the human hepatitis B virus (hHBV) antigen, and the human hepatitis C virus (hHCV) antibody was compared with conventional assay methods, such as TMB-based chromogenic detection. [ABSTRACT FROM AUTHOR]