Carbohydrate Antigen Research Articles

Extended survival of 9- and 10-gene-edited pig heart xenografts with ischemia minimization and CD154 costimulation blockade-based immunosuppression

BackgroundXenotransplantation has made significant advances recently using pigs genetically engineered to remove carbohydrate antigens, either alone or with addition of various human complement, coagulation, and anti-inflammatory ‘transgenes’. Here we evaluated results associated with gene-edited (GE) pig hearts transplanted in baboons using an established costimulation-based immunosuppressive regimen and a cold-perfused graft preservation technique. MethodsEight baboons received heterotopic abdominal heart transplants from 3-GE (GalKO.β4GalNT2KO.hCD55, n=3), 9-GE (GalKO.β4GalNT2KO.GHRKO.hCD46.hCD55. TBM.EPCR.hCD47.HO-1, n=3) or 10-G (9-GE+CMAHKO, n=2) pigs using Steen’s cold continuous perfusion for ischemia minimization. Immunosuppression (IS) included induction with anti-thymocyte globulin and αCD20, ongoing αCD154, MMF, and tapered corticosteroid. ResultsAll three 3-GE grafts functioned well initially, but failed within 5 days. One 9-GE graft was lost intraoperatively due to a technical issue and another was lost at POD 13 due to antibody mediated rejection (AMR) in a baboon with a strongly positive pre-operative cross-match. One 10-GE heart failed at POD113 with combined cellular and antibody mediated rejection. One 9-GE and one 10-GE hearts had preserved graft function with normal myocardium on protocol biopsies, but exhibited slowly progressive graft hypertrophy until elective necropsy at POD393 and 243 respectively. Elevated levels of IL-6, MCP-1, C-reactive protein, and human thrombomodulin were variably associated with conditioning, the transplant procedure, and clinically significant postoperative events. ConclusionRelative to reference genetics without thrombo-regulatory and anti-inflammatory gene expression, 9- or 10-GE pig hearts exhibit promising performance in the context of a clinically applicable regimen including ischemia minimization and αCD154-based IS, justifying further evaluation in an orthotopic model.

Predicting lymph node metastasis using preoperative parameters in patients with T1 ampulla of vater cancer

BackgroundLymph node (LN) metastasis is an established prognostic factor for patients with surgically resected ampulla of Vater (AoV) cancer. The standard procedure for radical resection, including removal of regional LNs, is pancreaticoduodenectomy (PD); however, local excision has been considered as an alternative option for patients in the early stage cancer with significant comorbidities. In the present study, we elucidated the preoperative factors associated with LN metastasis to determine the appropriate surgical extent for T1 AoV cancer.MethodsWe included patients who underwent surgery for T1 AoV cancer at Samsung Medical Center and Severance Hospital between 2000 and 2019. Risk factors were analyzed to identify the preoperative parameters associated with LN metastasis or regional LN recurrence during follow-up. Finally, using the identified risk factors, a prediction model was constructed.ResultsAmong 342 patients, 311 patients underwent PD, whereas 31 patients underwent transduodenal ampullectomy. Fourty-eight patients had LN metastasis according to pathology report, and two patients presented with regional LN recurrence. Age, carbohydrate antigen 19 − 9 (CA 19 − 9), and tumor differentiation were identified as factors associated with the increased risk of LN metastasis or regional LN recurrence. The area under the curve of the prediction model with these three factors was 0.728.ConclusionOur newly developed prediction model using age, CA 19 − 9, and tumor differentiation can help select patients who require PD over local excision. Nevertheless, additional in-depth analysis is warranted to select appropriate surgical extent for patients with presumed T1 AoV cancer.

Ultrasensitive aptamer-based electrochemical nanobiosensor in diagnosis of prostate cancer using 2D:2D reduced graphene oxide/graphitic carbon nitride decorated with Au nanoparticles

Prostate-specific antigen (PSA) remains the cornerstone for prostate cancer diagnosis. This study presents a highly sensitive aptamer-based electrochemical biosensor for PSA detection utilizing a novel two-dimensional (2D):2D reduced graphene oxide (rGO)/graphitic carbon nitride (g-C3N4) composite decorated with gold nanoparticles (Au NPs). The aptamer chains were immobilized on a glassy carbon electrode (GCE) modified with the rGO/g-C3N4/Au NPs composite. The successful synthesis of the nanomaterial and electrode modification were confirmed using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and transmission electron microscopy (TEM). The electrochemical properties and selectivity of the modified GCE were characterized by cyclic voltammetry (CV), square wave voltammetry (SQW), and electrochemical impedance spectroscopy (EIS). The biosensor exhibited high selectivity towards PSA compared to potential interferents like carbohydrate antigen 15-3 (CA 15-3), bovine serum albumin (BSA), fetal bovine serum (FBS), and glucose (C6H12O6). Under optimized conditions, the biosensor achieved a rapid detection time of 30 min for PSA and a remarkable limit of detection (LOD) of 0.44 fM (femtomolar) using methylene blue (MB) as the redox mediator. The limit of quantification (LOQ) was also exceptionally low at 2.5 fM. The applicability of the developed biosensor was further validated by analyzing real serum samples, demonstrating its potential for clinical use.

Phosphoglyceride crystal deposition with suspected malignant ovarian tumor: a case report and literature review.

Phosphoglyceride crystal deposition disease is a rare condition occurring in soft tissues, resulting in scarring and affecting the bones, making preoperative differentiation from malignant tumors challenging. Here, we describe a case of phosphoglyceride crystal deposition disease initially suspected to be a malignant ovarian tumor before surgery. A 50-year-old woman with a history of three cesarean sections presented with lower abdominal pain. Transvaginal ultrasonography revealed a 54 × 58mm tumor in the lower right abdomen. Pelvic contrast-enhanced magnetic resonance imaging showed a thickened cystic wall with diffusion restriction, a low signal intensity region on T1-weighted images, and a slightly high signal intensity region on T2-weighted images. The tumor markers, cancer antigen 125 and carbohydrate antigen 19-9 levels, were within normal ranges; however, positron emitting tomography-computed tomography revealed fluorodeoxyglucose accumulation (SUVmax 31.28) in the tumor wall. Suspecting a malignant ovarian tumor, a laparoscopy was performed to observe the abdominal cavity. A 10cm white solid tumor was identified in the midline of the lower abdominal wall, leading to an open surgery recommendation. The tumor, adhering to the pubic bone, was excised. The tumor measured 9 × 7cm, with the cut surface showing a yellow brownish solid periphery and central region with liquefied degeneration. Histologically, radial basophilic deposits, dense infiltration of macrophages, multinucleated giant cells, and foam-like tissue spheres were observed. The central region exhibited cholesterol clefts, fibrin exudation, and necrosis, leading to a diagnosis of phosphoglyceride crystal deposition disease. This disease is rare, occurring in patients with atypical fluorodeoxyglucose accumulation on positron emission tomography-computed tomography or with a history of tissue damage, such as abdominal surgery.

Conversion surgery for BRCA-mutated pancreatic ductal adenocarcinoma with liver metastasis treated with platinum-based chemotherapy followed by olaparib

BackgroundWith recent dramatic developments in chemotherapy, attempts to incorporate surgery into the multidisciplinary treatment of unresectable pancreatic ductal adenocarcinoma with metastasis (UR-M PDAC) have emerged. Maintenance therapy with olaparib after chemotherapy including a platinum-based regimen, which inhibits the poly ADP-ribose polymerase (PARP) involved in DNA repair, was approved for UR-M PDAC with positive BRCA mutations.Case presentationA 47-year-old male patient with a high carbohydrate antigen 19-9 (CA19-9) level was diagnosed with PDAC in the pancreatic tail. Staging laparoscopy revealed occult liver metastasis. Because BRCA2 mutation was confirmed, triple combination chemotherapy with SOXIRI (S-1/oxaliplatin/irinotecan) was introduced and continued for 16 weeks, followed by 14 weeks of olaparib. After that, CA19-9 was normalized, and no obvious liver metastases of any size could be seen on imaging studies during chemotherapy. Since staging laparoscopy after chemotherapy proved that the liver metastasis had disappeared, laparoscopic distal pancreatectomy was performed, and curative resection was completed. After adjuvant chemotherapy with olaparib for 12 months, the patient is alive 36 months from his initial diagnosis and 27 months postoperatively without recurrence.ConclusionWe report a case of PDAC with liver metastasis and BRCA mutation-positivity who underwent conversion surgery and achieved long-term survival after irinotecan-based chemotherapy followed by maintenance therapy with olaparib.

Synthesis and Thermodynamic Evaluation of Sialyl-Tn MUC1 Glycopeptides Binding to Macrophage Galactose-Type Lectin.

Interactions between the tumor-associated carbohydrate antigens of Mucin 1 (MUC1) and the carbohydrate-binding proteins, lectins, often lead to the creation of a pro-tumor microenvironment favoring tumor initiation, progression, metastasis, and immune evasion. Macrophage galactose binding lectin (MGL) is a C-type lectin receptor found on antigen-presenting cells that facilitates the uptake of carbohydrate antigens for antigen presentation, modulating the immune response homeostasis, autoimmunity, and cancer. Considering the crucial role of tumor-associated forms of MUC1 and MGL in tumor immunology, a thorough understanding of their binding interaction is essential for it to be exploited for cancer vaccine strategies. The synthesis of MUC1 glycopeptide models carrying a single or multiple Tn and/or sialyl-Tn antigen(s) is described. A novel approach for the sialyl-Tn threonine building block suitable for the solid phase peptide synthesis was developed. The thermodynamic profile of the binding interaction between the human MGL and MUC1 glycopeptide models was analyzed using isothermal titration calorimetry. The measured dissociation constants for the sialyl-Tn-bearing peptide epitopes were consistently lower compared to the Tn antigen and ranged from 10 μM for mono- to 1 μM for triglycosylated MUC1 peptide, respectively. All studied interactions, regardless of the glycan's site of attachment or density, exhibited enthalpy-driven thermodynamics.

A striking elevation of CA19-9 after preoperative therapy negates prognostic benefit from radical surgery in resectable and borderline resectable pancreatic cancer

Identifying patients who can be spared nonbeneficial surgery is crucial, as pancreatic cancer surgery is highly invasive, with substantial negative effects on quality of life. The study objective was to investigate a useful indicator of patients who do not gain prognostic benefit from radical surgery after neoadjuvant therapy for resectable and borderline resectable pancreatic cancer. We compared factors among 609 patients with resectable or borderline resectable pancreatic cancer receiving neoadjuvant therapy during 2005-2019. Patients were divided into a poor-prognosis group (no surgery or postresection recurrence within a year) and a good-prognosis group (no recurrence or recurrence >1year after resection). Patients who experience a recurrence within a year of resection (poor-prognosis group) did no better than patients who received neoadjuvant therapy and progressed but never made it to surgery. The value of carbohydrate antigen 19-9 after neoadjuvant therapy was the most significant indicator to predict the poor prognosis group and the elevation of carbohydrate antigen 19-9 (>200 U/mL) identified only poor prognosis group with high specificity of 96.6%. The overall survival of patients with more than 200 of carbohydrate antigen 19-9 after neoadjuvant therapy was significantly very poor and their 2-year survival rate was only 41.4%. A striking elevation of carbohydrate antigen 19-9 after neoadjuvant therapy for resectable or borderline resectable pancreatic cancer is a good indicator of poor prognosis. Patients with carbohydrate antigen 19-9 >200 U/mL after neoadjuvant therapy should not undergo radical surgery.

MicroRNA-193a-3p as a Valuable Biomarker for Discriminating between Colorectal Cancer and Colorectal Adenoma Patients.

Specific markers for colorectal cancer (CRC), preceded by colorectal adenoma (pre-CRC), are lacking. This study aimed to investigate whether microRNAs (miR-19a-3p, miR-92a-3p, miR-193a-3p, and miR-210-3p) from tissues and exosomes are potential CRC biomarkers and compare them to existing biomarkers, namely carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9. MiRNA was isolated in the samples of 52 CRC and 76 pre-CRC patients. Expression levels were analyzed by RT-qPCR. When comparing pre-CRC and CRC tissue expression levels, only miR-193a-3p showed statistically significant result (p < 0.0001). When comparing the tissues and exosomes of CRC samples, a statistically significant difference was found for miR-193a-3p (p < 0.0001), miR-19a-3p (p < 0.0001), miR-92a-3p (p = 0.0212), and miR-210-3p (p < 0.0001). A receiver-operating characteristic (ROC) curve and area under the ROC curve (AUC) were used to evaluate the diagnostic value of CEA, CA 19-9, and miRNAs. CEA and CA 19-9 had good diagnostic values (AUCs of 0.798 and 0.668). The diagnostic value only of miR-193a-3p was highlighted (AUC = 0.725). The final logistic regression model, in which we put a combination of CEA concentration and the miR-193a-3p expression level in tissues, showed that using these two markers can distinguish CRC and pre-CRC in 71.3% of cases (AUC = 0.823). MiR-193a-3p from tissues could be a potential CRC biomarker.

Clinical curative effect of enteroscopic stent implantation combined with laparoscopy in patients with colorectal cancer and intestinal obstruction

To explore the clinical curative effect of enteroscopic stent implantation combined with laparoscopy in patients with colorectal cancer and intestinal obstruction. A retrospective analysis was performed on the data of patients with colorectal cancer and intestinal obstruction in Gastrointestinal Surgery of Henan Provincial People's Hospital between November 2019 and October 2020. Among patients, there were 46 cases in traditional group (laparotomy+intraoperative intestinal irrigation), 42 cases in stent-laparotomy group (enteroscopic stent implantation+laparotomy), and 41 cases in stent-laparoscopy group (enteroscopic stent implantation+laparoscopy). The perioperative situation, levels of biochemical indexes, peripheral serum carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA199), and prognosis were compared among the three groups. The results showed that among the three groups, operation time [(203.6±30.5) min] was longer, postoperative exhaust time [(1.2±0.3) d] and length of hospital stay [(10.5±2.1) d] were shorter, and intraoperative blood loss [(102.5±22.3) ml] was less in stent-laparoscopy group (all P values<0.05). The incidence of postoperative complications in stent-laparoscopy group was lower than that in traditional group (4.8% vs 21.7%, P<0.05). At 1 day after surgery, EOS was decreased, while PLT and CRP were increased in all three groups. Compared with traditional group and stent-laparotomy group after surgery, EOS was increased, while PLT and CRP were decreased in stent-laparoscopy group [EOS: (4.2±0.2) % vs (3.6±0.3) % vs (3.9±0.2) %; PLT: (259.6±11.4)×109/L vs (294.4±11.5)×109/L vs (271.7±10.7)×109/L; CRP: (8.8±2.0) vs (16.4±2.2) vs (14.9±2.3) ng/L; P<0.05]. At 3 months after surgery, levels of serum CEA and CA199 were decreased in the three groups. There was no significant statistical difference in serum CEA or CA199 among the three groups. During 3 years of follow-up, there was no significant statistical difference in postoperative recurrence rate or incidence of postoperative metastasis among the three groups. The study indicated that enteroscopic stent implantation combined with laparoscopy was more advantageous in terms of reducing intraoperative blood loss, accelerating recovery of postoperative exhaust function, relieving surgical stress and reducing the incidence of postoperative complications, which could decrease levels of serum CEA and CA199.

Prediction of postoperative residual primary ovarian neoplasm or metastatic lesion close to rectum of serous ovarian carcinoma based on clinical and MR T1-DEI features.

The optimal primary debulking surgery outcome of serous ovarian carcinoma (SOC) is greatly affected by primary ovarian neoplasm or metastatic lesion close to the rectum. To study the risk factors affecting postoperative residual primary ovarian neoplasm or metastatic lesion close to the rectum of SOC. The clinical and MRI data of 164 patients with SOC eligible from institution A (training and test groups) and 36 patients with SOC eligible from institution B (external validation group) were collected and retrospectively analyzed. The clinical data included age, serum carbohydrate antigen 125 (CA-125), human epididymis protein 4, and neutrophil-to-lymphocyte ratio (NLR). Magnetic resonance imaging (MRI) data included ovarian mass distribution, maximum diameter of ovarian mass, ovarian mass features, degree of rectal invasion of the primary ovarian neoplasm or metastatic lesion, and amount of ascites. A model was established using multivariate logistic regression. By univariate and multivariate logistic regressions, CA-125 (P = 0.024, odds ratio [OR] = 3.798, 95% confidence interval [CI] = 1.24-13.32), NLR (P = 0.037, OR = 3.543, 95% CI = 1.13-12.72), and degree of rectal invasion of the primary ovarian neoplasm or metastatic lesion (P < 0.001, OR = 37.723, 95% CI = 7.46-266.88) were screened as independent predictors. The area under the curve values of the model in the training, test, and external validation groups were 0.860, 0.764, and 0.778, respectively. The clinical-radiological model based on T1-weighted dual-echo MRI can be used non-invasively to predict postoperative residual ovarian neoplasm or metastasis close to SOC in the rectum.

A Versatile One-Step Enzymatic Strategy for Efficient Imaging and Mapping of Tumor-Associated Tn Antigen.

Tn antigen (CD175), recognized as the precursor monosaccharide (α-GalNAc) of mucin O-glycan, is a well-known tumor-associated carbohydrate antigen (TACA). It has emerged as a potential biomarker for cancer diagnosis and prognosis. However, the role it plays in cancer biology remains elusive due to the absence of a sensitive and selective detection method. In this study, we synthesized two new probes based on a unique uridine-5'-diphospho-α-d-galactose (UDP-Gal) derivative, each functionalized with either a fluorescence or a cleavable biotin tag, to develop an innovative one-step enzymatic labeling strategy, enabling the visualization, enrichment, and site-specific mapping of the Tn antigen with unparalleled sensitivity and specificity. Our versatile strategy has been successfully applied to detect and image Tn antigen across various samples, including the complex cell lysates, live cells, serum, and tissue samples. Compared to the traditional lectin method, this one-step enzymatic method is simpler and more efficient (>10/100-fold in sensitivity). Furthermore, it allowed us to map 454 Tn-glycoproteins and 624 Tn-glycosylation sites from HEK293FTn+ and Jurkat cells. Therefore, our strategy provides an exceptionally promising tool for revealing the biological functions of the Tn antigen and advancing cancer diagnostics.

Investigating the Effect of Thalassemia on Serum Creatinine, Uric Acid, and Cholesterol Levels

A thalassemia is a group of inherited blood disorders characterized by decreased or absent production of hemoglobin. Symptoms of thalassemia vary greatly from patient to patient but may include anemia, fatigue, and susceptibility to infections that can plague their quality of life. Therefore, a detailed evaluation of the serum biomarker profile in thalassemia patients is necessary to elucidate its effects on the body. This study was performed to define the serum biomarker profile. This study aimed to evaluate the serum marker levels among 100 thalassemic patients and compare them with their physiological ranges. Blood urea (B.UREA), serum creatinine (S.CREAT), aspartate aminotransferase (AST), alanine aminotransferase (Alt), alkaline phosphatase (ALP), total serum bilirubin (TSB), serum uric acid (S.U.A), triglycerides (TG), cholesterol (CHOL), albumin (Alb), serum calcium (S.CA) and Carbohydrate Antigen 15-3 (CA15.3) were analyzed comprehensively as key indicators in this study. The test showed that B. UREA's mean number was 24.33±0.8805, which was safe within normal limits. So, no abnormal results were found for this indicator in our tests despite the fact that others showed irregularity. The means of the values measured by S.CREAT, AST, AlT, AlP, TSB, S.U.A, TG, CHOL, AlB, S.CA, and CA15.3 were respectively, 0.8109±0.2007, 28.93±3.325, 26.1±2.698, 101±13.64, 3.261±1.978, 12.78±8.951, 146.8±87.2, 147.5±22.89, 67.94±44.7. This study makes valuable contributions to the field by elucidating the serum biomarkers of individuals with thalassemia and presenting changes in some markers compared to normal levels. However, further research is required in order to investigate the clinical significance of such alterations.2, 9.392±0.4079, and 42.08±7.275.

Different roles of the heterodimer architecture of galectin-4 in selective recognition of oligosaccharides and lipopolysaccharides having ABH antigens

The dimeric architecture of tandem-repeat type galectins, such as galectin-4 (Gal-4), modulates their biological activities, although the underlying molecular mechanisms have remained elusive. Emerging evidence show that tandem-repeat galectins play an important role in innate immunity by recognizing carbohydrate antigens present on the surface of certain pathogens, which very often mimic the structures of the human self-glycan antigens. Herein, we have analyzed the binding preferences of the C-domain of Gal-4 (Gal-4C) toward the ABH-carbohydrate histo-blood antigens with different core presentations and their recognition features have been rationalized by using a combined experimental approach including NMR, solid-phase and hemagglutination assays, and molecular modeling. The data show that Gal-4C prefers A over B antigens (two-fold in affinity), contrary to the N-domain (Gal-4N), although both domains share the same preference for the type-6 presentations. The behavior of the full-length Gal-4 (Gal-4FL) tandem-repeat form has been additionally scrutinized. Isothermal titration calorimetry and NMR data demonstrate that both domains within full-length Gal-4 bind to the histo-blood antigens independently of each other, with no communication between them. In this context, the heterodimeric architecture does not play any major role, apart from the complementary A and B antigen binding preferences. However, upon binding to a bacterial lipopolysaccharide containing a multivalent version of an H-antigen mimetic as O-antigen, the significance of the galectin architecture was revealed. Indeed, our data point to the linker peptide domain and the F-face of the C-domain as key elements that provide Gal-4 with the ability to cross-link multivalent ligands, beyond the glycan binding capacity of the dimer.

Radiomics combined with clinical and MRI features may provide preoperative evaluation of suboptimal debulking surgery for serous ovarian carcinoma.

To develop and validate a model for predicting suboptimal debulking surgery (SDS) of serous ovarian carcinoma (SOC) using radiomics method, clinical and MRI features. 228 patients eligible from institution A (randomly divided into the training and internal validation cohorts) and 45 patients from institution B (external validation cohort) were collected and retrospectively analyzed. All patients underwent abdominal pelvic enhanced MRI scan, including T2-weighted imaging fat-suppressed fast spin-echo (T2FSE), T1-weighteddual-echomagnetic resonanceimaging (T1DEI), diffusion weighted imaging (DWI), and T1 with contrast enhancement (T1CE). We extracted, selected and eliminated highly correlated radiomic features for each sequence. Then, Radiomic models were made by each single sequence, dual-sequence (T1CE + T2FSE), and all-sequence, respectively. Univariate and multivariate analyses were performed to screen the clinical and MRI independent predictors. The radiomic model with the highest area under the curve (AUC) was used to combine the independent predictors as a combined model. The optimal radiomic model was based on dual sequences (T2FSE + T1CE) among the five radiomic models (AUC = 0.720, P < 0.05). Serum carbohydrate antigen 125, the relationship between sigmoid colon/rectum and ovarian mass or mass implanted in Douglas' pouch, diaphragm nodules, and peritoneum/mesentery nodules were considered independent predictors. The AUC of the radiomic-clinical-radiological model was higher than either the optimal radiomic model or the clinical-radiological model in the training cohort (AUC = 0.908 vs. 0.720/0.854). The radiomic-clinical-radiological model has an overall algorithm reproducibility and may help create individualized treatment programs and improve the prognosis of patients with SOC.

EHSP90α in front-line therapy in EGFR exon 19 deletion and 21 Leu858Arg mutations in advanced lung adenocarcinoma

PurposeExtracellular heat shock protein 90 AA1(eHSP90α) is intricately linked to tumor progression and prognosis. This study aimed to investigate the difference in the value of eHSP90α in post-treatment response assessment and prognosis prediction between exon 19 deletion(19DEL) and exon 21 Leu858Arg(L858R) mutation types in lung adenocarcinoma(LUAD).MethodsWe analyzed the relationship between the expression of eHSP90α and clinicopathological features in 89 patients with L858R mutation and 196 patients with 19DEL mutation in LUAD. The Kaplan-Meier survival curve was used to determine their respective cut-off values and analyze the relationship between eHSP90α expression and the survival time of the two mutation types. The area under the curve (AUC) was used to evaluate the diagnostic performance of biomarkers. Then, the prognostic model was developed using the univariate-Cox multivariate-Cox and LASSO-multivariate logistic methods.ResultsIn LUAD patients, eHSP90α was positively correlated with carcinoembryonic antigen(CEA), carbohydrate antigen 125(CA125), and carbohydrate antigen 153(CA153). The truncated values of eHSP90α in L858R and 19DEL patients were 44.5 ng/mL and 40.8 ng/mL, respectively. Among L858R patients, eHSP90α had the best diagnostic performance (AUC = 0.765), and higher eHSP90α and T helper cells(Th cells) expression were significantly related to shorter overall survival(OS) and worse treatment response. Also, high eHSP90a expression and short progression-free survival(PFS) were significantly correlated. Among 19DEL patients, CEA had the best diagnostic efficacy (AUC = 0.734), and CEA and Th cells were independent prognostic factors that predicted shorter OS. Furthermore, high CA125 was significantly associated with short PFS and poor curative effect.ConclusionseHSP90α has a better prognostic value in LUAD L858R patients than 19DEL, which provides a new idea for clinical diagnosis and treatment.

Thiol/Disulfide Homeostasis: A New Oxidative Marker in Heart Failure Patients with Preserved Ejection Fraction.

It is suggested that myocardial dysfunction in heart failure patients may result from increased oxidative stress-related membrane changes. Thiol/disulfide homeostasis is a new oxidative stress indicator. The aim of this study was to evaluate serum thiol levels and thiol/disulfide homeostasis in patients with heart failure with preserved ejection fraction (HFpEF). Eighty-four overweight patients who applied to our clinic between November 2016 and February 2018 and diagnosed with hypertension and left ventricule concentric hypertrophy with normal systolic function are included in the study. Forty-two patients who were asymptomatic and had normal N terminal pro-B type natriuretic peptide (NT-proBNP) levels (≤125) were in the control group. Forty-two patients who have cardiac failure symptoms and have high NT-roBNP levels (>125) were in the patient group. Native thiol, total thiol, and disulfide values of the patient group are found to be significantly lower than the control group (P =.001; P <.001; P =.041 respectively). There is a statictically significant negative correlation between native thiol, total thiol values, and NT-proBNP. There is a statictically significant negative correlation between native thiol, total thiol values, and carbohydrate antigen 125 (CA-125) values. As far as we know from literature, this is the first study on HFpEF and thiol/disulfide homeostasis. It is found that native, total thiol, and disulfide values are low in HFpEF patients and that there is a negative correlation between native, total thiol values and NT-proBNP, CA-125 values. It can be said that oxidant/antioxidant balance is impaired in patients with HFpEF and that larger, randomized studies are needed in order to use oxidant/antioxidant balance in diagnosis and treatment of HFpEF.

Establishment of a multi-line immunochromatography based on magnetic nanoparticles for simultaneous screening of multiple biomarkers.

Biomarkers screening is a benefit approach for early diagnosis of major diseases. In this study, magnetic nanoparticles (MNPs) have been utilized as labels to establish a multi-line immunochromatography (MNP-MLIC) for simultaneous detection of carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA 19-9), and alpha-fetoprotein (AFP) in a single serum sample. Under the optimal parameters, the three biomarkers can be rapidly and simultaneously qualitative screening within 15 min by naked eye. As for quantitative detection, the MNP-MLIC test strips were precisely positioned and captured by a smartphone, and signals on the test and control lines were extracted by ImageJ software. The signal ratio of test and control lines has been calculated and used to plot quantitative standard curves with the logarithmic concentration, of which the correlation coefficients are more than 0.99, and the limit of detection for CEA, CA 19-9, and AFP were 0.60 ng/mL, 1.21 U/mL, and 0.93 ng/mL, respectively. The recoveries of blank serum were 75.0 ~ 112.5% with the relative standard deviation ranging from 2.5 to 15.3%, and the specificity investigation demonstrated that the MNP-MLIC is highly specific to the three biomarkers. In conclusion, the developed MNP-MLIC offers a rapid, simple, accurate, and highly specific method for simultaneously detecting multiple biomarkers in serum samples, which provides an efficient and accurate approach for the early diagnosis of diseases.

Misdiagnosis Based on Neoplastic Markers-Extremely High Alpha-Fetoprotein in Patients with Intrahepatic Cholangiocarcinoma with Literature Review of the Published Cases.

Background: Alpha-fetoprotein (AFP) and carbohydrate antigen 19-9 (CA 19-9) are two tumor markers that are widely used in the differential diagnosis in patients with primary liver tumors. Very high levels of AFP are sporadically observed in patients with intrahepatic cholangiocarcinoma (ICC) and may cause an incorrect initial diagnosis of hepatocellular carcinoma (HCC). Methods: Two cases of tumors in cirrhotic livers were described, in which the initial diagnosis, based on very high AFP levels (Patient I: 10,464 ng/mL, Patient II: 2212 ng/mL, reference range: ≤8.04 ng/mL) was HCC. In addition, the PubMed database was searched for cases of ICC with elevated AFP. Discussion: In both individuals, liver cirrhosis was diagnosed, but there was no typical rapid "washout" in the contrast-enhanced computed tomography. Based on the histological assessment of samples obtained in the core biopsies, the initially assumed diagnosis of HCC was changed to ICC in both cases. Only nine cases of patients with ICC and high AFP levels were found in the PubMed database. The AFP levels ranged from slightly elevated to over 16,000 ng/mL. Conclusions: A very high AFP level does not necessarily correlate with the presence of HCC. Therefore, the diagnosis has to be verified histologically, when the radiological imaging is uncertain in patients with liver cirrhosis.

Risk of hepatic steatosis with the preoperative treatment of pancreatic cancer and the short-term postoperative outcomes.

We investigated whether the preoperative treatment of patients with pancreatic cancer is a risk factor for hepatic steatosis (HS), and whether preoperative HS affects the short-term postoperative outcomes. Patients who underwent radical surgery for pancreatic cancer between 2010 and 2023 were enrolled. The patients' medical records were reviewed. Albumin and carbohydrate antigen 19-9 were measured before and after chemotherapy in the patients who received preoperative chemotherapy. A logistic regression univariate analysis was performed to analyze the factors associated with new-onset HS. A total of 230 patients who underwent surgery were included. HS was observed on the date of surgery in 11 (10%) and two (2%) patients with and without preoperative chemotherapy, respectively. Female sex, initially borderline resectable or unresectable disease, history of cholangitis, presence of PEI, long-term (≥ 3months) biliary drainage, preoperative chemotherapy, and serum albumin ≥ 3.9mg/dl before chemotherapy were identified as risk factors for HS. The incidence of postoperative morbidity did not differ between the patients with and without preoperative steatosis. Preoperative chemotherapy, a history of cholangitis, the presence of PEI, and ≥ 3months' duration of biliary drainage were risk factors for the development of HS before surgery for pancreatic cancer. However, preoperative HS did not affect the short-term postoperative outcomes.

Prognostic model for resected borderline and locally advanced pancreatic cancer after neoadjuvant chemotherapy.

The current AJCC 8th has been reported to have a poor ability to predict the prognosis in patients with resected borderline resectable pancreatic cancer and locally advanced pancreatic cancer following neoadjuvant chemotherapy. This study was aimed to develop an improved prognostic model by incorporating pathology and parameters of biologic response (BR). A retrospective cohort study was conducted including patients who underwent curative-intent surgery following chemotherapy. We developed a modified ypT staging system and incorporated the BR, involving normalization of carbohydrate antigen 19-9 and reduction in the maximum standardized uptake value simultaneously after chemotherapy. The prognostic performance of the current pathologic system, modified pathologic system, and newly developed system incorporating pathology and BR were compared. In this study, 171 patients underwent surgery following chemotherapy. The modified T stage, which unified ypT2 and ypT3, demonstrated improved prognostic performance than the current staging system (area under the curve: 0.706 vs. 0.661). Biologic unresponsiveness was an independent prognostic factor for worse survival (hazard ratio 2.31, 95% confidence interval 1.50-3.55, P<0.001). The modified pathology with BR system demonstrated the highest discriminative ability in predicting 5-year overall survival than the current pathologic system (area under the curve: 0.785 vs. 0.661, P=0.010) and modified pathologic staging system (area under the curve: 0.785 vs. 0.706, P=0.002). The prognostic model, incorporating modified ypT staging and elevated carbohydrate antigen 19-9 levels and maximum standardized uptake value simultaneously, demonstrated improved results in predicting oncologic outcomes for patients who underwent surgery following neoadjuvant chemotherapy.