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Midkine is a heparin-binding growth factor that is believed to have functional antagonism, although it helps in tissue repair, it can also enhance inflammatory reactions resulting in more tissue injury. This study aimed to determine serum and synovial fluid (SF) levels of midkine in patients with primary knee osteoarthritis (KOA) and to correlate these levels with patients' clinical and functional parameters as well as radiological progression of KOA. Midkine was measured in the serum and 23 SF samples from 52KOA patients as well as in the serum from 20 healthy controls. In the patients, The Western Ontario McMaster scale (WOMAC) was recorded to assess functional status. Graded plain radiographs using Thomas score, and musculoskeletal ultrasound examination (MSUS) of both knees were performed at baseline and after 2 years to assess radiological progression. The patients mean age was 51.5 ± 10.6 years and disease duration was 5.4 ± 4.7 years. Serum levels were significantly increased in KOA patients (80.8 ± 31.8 pg/mL) compared to the controls (65.6 ± 14.8 pg/mL). Patients with elevated serum and SF midkine had twofold increased risk of radiological progression with MSUS (RR2.4 and 2.6 respectively). However, there was no increased risk of radiological progression detected with plain radiography. Osteoarthritis patients have significantly elevated serum and synovial levels of midkine that were correlated with functional status assessed with WOMAC index and obviously associated with radiological progression on MSUS suggesting that it could be a useful marker to reflect OA severity and implies a possible role in the disease pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Studies investigating serum midkine (s-MK) concentrations have employed a polyclonal antibody enzyme-linked immunosorbent assay system (ELISA), because the targeted polyclonal antibody has low specificity. We used a newly developed monoclonal antibody ELISA to investigate the prognostic and diagnostic capabilities of s-MK in patients with esophageal squamous cell carcinoma. Methods: Serum samples from 102 patients with esophageal squamous cell carcinoma were analyzed using a newly developed monoclonal antibody ELISA specifically developed to detect s-MK. s-MK cutoff value was set at 421 pg/mL (mean + 2 SD) based on data from healthy controls. Clinicopathological characteristics, including tumor stage and positivity rates for two conventional tumor markers, serum p53 (s-p53-Abs) antibodies and SCC-antigen, were evaluated to assess a possible correlation with s-MK. The prognostic capability of a high s-MK level was evaluated using univariate and multivariate methods. Results: Overall positive rate for s-MK concentrations: 21%. Large tumors (> 50 mm) showed significantly higher concentrations than smaller specimens, but other clinicopathological factors were not associated with s-MK. A combination assay using SCC-antigen together with s-p53-Abs and s-MK clearly increased our capability to detect esophageal squamous cell carcinoma. Although the difference was not statistically significant (P = 0.310), the high s-MK group experienced worse overall survival than our low s-MK group. Conclusions: s-MK and conventional tumor marker combination increased our capability to detect esophageal squamous cell carcinoma. Although s-MK might be associated with esophageal squamous cell carcinoma progression, it was not an independent risk factor reducing patient survival. This study was registered as UMIN000014530. [ABSTRACT FROM AUTHOR]

Midkine (MDK) and Pleiotrophin (PTN) belong to a group of heparin-binding growth factors that has been shown to have pleiotropic functions in various biological processes during development and disease. Development of the vertebrate eye is a multistep process that involves coordinated interactions between neuronal and non-neuronal cells, but very little is known about the potential function of MDK and PTN in these processes. In this study, we demonstrate by section in situ hybridization, the spatiotemporal expression of MDK and PTN during ocular development in chick and mouse. We show that MDK and PTN are expressed in dynamic patterns that overlap in a few non-neuronal tissues in the anterior eye and in neuronal cell layers of the posterior eye. We show that the expression patterns of MDK and PTN are only conserved in a few tissues in chick and mouse but they overlap with the expression of some of their receptors LRP1, RPTPZ , ALK, NOTCH2, ITGβ1, SDC1, and SDC3. The dynamic expression patterns of MDK , PTN and their receptors suggest that they function together during the multistep process of ocular development and they may play important roles in cell proliferation, adhesion, and migration of neuronal and non-neuronal cells. • MDK and PTN show unique expression patterns in neuronal and non-neuronal tissues during ocular development. • Expression patterns of MDK and PTN are dynamic and only conserved between chick and mouse in a few ocular tissues. • The receptors RPTPZ , ALK, NOTCH2, ITGβ1, LRP1, SDC1, and SDC3 are expressed various patterns that overlap with MDK and PTN. • Expression is consistent with potential functions in cell proliferation, adhesion, migration, and neurite outgrowth. [ABSTRACT FROM AUTHOR]

Abstract Midkine antisense oligonucleotide (MK-ASODN) nanoliposomes have previously been shown to have inhibitory activity against hepatocellular carcinoma growth. Herein we report the 4-week sub-chronic toxicity of MK-ASODN nanoliposomes in SD rats. The adverse effects included loss of body weight gain and food consumption, peri-rhinal bleeding, piloerection, peri-anal filth, and kidney, liver, spleen, thymus, lung, and injection site lesions at high doses. Macroscopic changes were observed in the kidneys of the high-dose group, accompanied by a variation in urine protein and white blood cells, blood urea nitrogen, and serum creatinine. The increased spleen and liver coefficient, and the variation in circulating white blood cells, lymphocytes, and eosinophils in the high-dose group demonstrated that inflammation was caused by MK-ASODN nanoliposomes and was consistent with the macroscopic changes in the spleen and liver. The main necropsy findings of the animals that died were macroscopic changes in the lung. No severe toxic effects or mortalities occurred in the low- and medium-dose groups. However, a No Adverse Effect Level (NOAEL) was not identified since there were changes in organs deemed to be adverse at all dose levels. Thus, the maximum tolerated dose of MK-ASODN nanoliposomes for rats was considered to be 6 mg/kg/day. Highlights • The sub-chronic (4-weeks) toxicity of MK-ASODN nanoliposomes in rats was assessed. • Lesions were observed on kidney, liver, spleen, thymus, lungs and injection site. • Toxic effects mainly occurred in dose of 18 mg/kg/day. • The MTD of MK-ASODN nanoliposomes for rats was considered to be 6 mg/kg/day. [ABSTRACT FROM AUTHOR]

Aim: We evaluated the diagnostic impact of serum midkine (s‐MK) levels in patients with gastric cancer using a monoclonal antibody enzyme‐linked immunosorbent assay system (ELISA) to detect s‐MK levels. Methods: Serum samples were obtained from 131 patients with gastric cancer including stage I (n = 71), stage II (n = 28), stage III (n = 16), and stage IV (n = 16) before surgery. Serum samples were analyzed using ELISA to detect soluble midkine. A cut‐off value was fixed at 421 pg/mL, and the sample divided into two groups: a high s‐MK group and a low s‐MK group. Clinicopathological factors and prognosis were compared between these two groups using univariate and multivariate analyses. Comparison of two groups was analyzed by Fisher's exact probability test. Statistical significance was considered at P < 0.05. Results: High s‐MK was significantly associated with high carcinoembryonic antigen (CEA) (P < 0.01). Positive rate of s‐MK was higher than the positive rates of CEA in patients with stage I/II gastric cancer. Combination with CEA + CA19‐9 + s‐MK increased the positive rates of patients with stage I/II gastric cancer. No other clinicopathological factors were associated with s‐MK. Although the high s‐MK group showed worse overall survival than the low s‐MK group, the difference was not statistically significant. Conclusion: s‐MK level is increased even during early‐stage gastric cancer. Combined with s‐MK, the positive rate of CEA + CA19‐9 was increased in patients with stage I/II gastric cancer. s‐MK level is increased even during early‐stage gastric cancer. Combined with s‐MK, the positive rate of CEA + CA19‐9 was increased in patients with stage I/II gastric cancer. [ABSTRACT FROM AUTHOR]

Abstract Midkine (MK) and pleiotrophin (PTN) are the only two members of heparin-binding growth factor family. MK/PTN homologues found from Drosophila to humans are shown to have antibacterial activities and their antibacterial domains are conserved during evolution. However, little is known about MK/PTN homologue in the basal chordate amphioxus, and overall, information regarding MK/PTN homologues is rather limited in invertebrates. In this study, we identified a single MK/PTN homologue in Branchiostoma japonicum , termed BjMiple , which has a novel domain structure of PTN-PTNr1-PTNr2, and represents the ancestral form of vertebrate MK/PTN family proteins. BjMiple was expressed mainly in the ovary in a tissue-dependent fashion, and its expression was remarkably up-regulated following challenge with bacteria or their signature molecules LPS and LTA, suggesting its involvement in antibacterial responses. Functional assays revealed that BjMiple had strong antimicrobial activity, capable of killing a panel of Gram-negative and Gram-positive bacteria via a membranolytic mechanism, including interaction with bacterial membrane via LPS and LTA, membrane depolarization and high intracellular levels of ROS. Importantly, strong antibacterial activity was localized in PTN 42-61 and PTNr1 42-66. Additionally, BjMiple and its derived peptides PTN 42-61 and PTNr1 42-66 were not cytotoxic to human RBCs and mammalian cells. Taken together, our study suggests that amphioxus Miple is the ancestral type of vertebrate MK/PTN family homologues, and can play important roles as innate peptide antibiotics, which renders it a promising template for the design of novel peptide antibiotics against multi-drug resistant bacteria. Highlights • A single MK/PTN homologue termed BjMiple with new domain structure was identified from amphioxus. • BjMiple killed both Gram-negative and -positive bacteria via a membranolytic mechanism. • Its antibacterial activity was mapped to PTN 42-61 and PTNr1 42-66. • Neither BjMiple nor PTN 42-61 nor PTNr1 42-66 displayed toxicity to RAW264.7 cells and human RBCs. [ABSTRACT FROM AUTHOR]

Abstract Midkine (Mdk) is a cytokine involved in controlling tissue repair and new tissue development, and regulating inflammation involved in several signaling pathway, such as the mitogen-activated protein kinase (MAPK) and phosphatidyl inositol 3-kinase (PI3K)/AKT pathways. But the role of Mdk in the development of Cynoglossus semilaevis is poorly understood. In this study, the Midkine of C. semilaevis (CsMdk) was cloned, and its spatiotemporal expression pattern and structural characteristics were analyzed. Furthermore, the essential genes related to nervous system development and germ layer formation marker gene were identified by qRT-PCR and in situ hybridization after overexpression the CsMdk via zebrafish model. The result showed CsMdk was mainly expressed in the brain of embryo, especially in the diencephalon, mid-hindbrain boundary (MHB) and hindbrain. In adult fish, it could only be detected in brain. Overexpression of CsMdk mRNA in zebrafish embryos suppressed the development of forebrain, midbrain, hindbrain and the notochord in zebrafish and influence the development of the mesoderm. All results showed CsMdk played a significant role on the germ layer and nervous development. [ABSTRACT FROM AUTHOR]

Background: Celiac disease (CeD) is a chronic inflammatory small intestine disorder caused by an abnormal immune response to an array of the epitopes of the wheat gluten and related proteins of rye and barley in genetically susceptible individuals. Midkine (MK) is an angiogenic cytokine, chemotactic in the direction of polymorphonuclear neutrophils and macrophages, and a T-regulatory cell suppressor. So far, a possible relationship with CeD has not yet been explored. Diagnosis of CeD is based on serologic test in a clinical setting suggestive of CeD and confirmatory histologic examination of the duodenal biopsy. Sometimes, genetic testing of human leukocyte antigen (HLA)-DQ2 and HLA-DQ8 may be needed. The objective of this study was to measure and compare the circulating MK in the celiac patients and healthy individuals. Materials and Methods: Twenty newly untreated CeD cases and 20 normal controls were enrolled in this study. The enzyme-linked immunosorbent assay was used to measure the circulating MK in the celiac patients and controls. Results: There was insignificant difference in the circulating MK between the patients and controls (P > 0.05). Conclusions: The study results suggest that the MK marker does not have any diagnostic value in CeD activity to be used at the time of diagnosis or during follow-ups.

Midkine (MK) is a heparin-binding growth factor, whose role as a biomarker of coronary artery disease, myocardial ischaemia and necrosis has not been well measured. This study quantified serial MK levels in patients undergoing coronary angiography (CA) and identified factors associated with MK. In this single-centre, parallel cohort study, forty patients undergoing CA had arterial samples collected prior, 10 and 20 min after heparin administration. Four groups were examined: 1—stable coronary artery disease (CAD) without percutaneous coronary intervention (PCI); 2—stable CAD for elective PCI; 3—non-ST elevation myocardial infarction (NSTEMI) with or without PCI; 4—ST elevation myocardial infarction (STEMI) with primary PCI. Groups 1, 2 and 4 were heparin naïve, allowing assessment of the effects of myocardial necrosis between baseline levels; group 3 had received low-molecular-weight heparin. MK levels were analysed by ELISA. Median MK at baseline did not differ between groups, demonstrating that myocardial ischaemia or necrosis does not affect MK levels. Heparin administration had an immediate effect on median MK at 10 min, showing an average 500-fold increase that is dose-dependent (R2 = 0.35, p = 0.001). Median MK levels remained elevated at 20 min following heparin administration. Multivariate analysis showed that the estimated glomerular filtration rate (eGFR) was the only predictor of elevated baseline MK (p = 0.02). Baseline MK did not correlate with high-sensitivity troponin-I (HsTnI) taken just before CA (p = 0.97), or peak HsTnI during admission (p = 0.74). MK is not a reliable marker of myocardial ischaemia or necrosis. MK increased significantly in all patients following heparin administration in a dose-dependent manner. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease that poses a significant challenge to medical professionals due to its increasing incidence and prevalence coupled with the limited understanding of its underlying molecular mechanisms. In this study, we employed a novel approach by integrating five expression datasets from bulk tissue with single-cell datasets; they underwent pseudotime trajectory analysis, switch gene selection, and cell communication analysis. Utilizing the prognostic information derived from the GSE47460 dataset, we identified 22 differentially expressed switch genes that were correlated with clinical indicators as important genes. Among these genes, we found that the midkine (MDK) gene has the potential to serve as a marker of Idiopathic pulmonary fibrosis because its cellular communicating genes are differentially expressed in the epithelial cells. We then utilized midkine and its cellular communication-related genes to calculate the midkine score. Machine learning models were further constructed through midkine and related genes to predict Idiopathic pulmonary fibrosis disease through the bulk gene expression datasets. The midkine score demonstrated a correlation with clinical indexes, and the machine learning model achieved an AUC of 0.94 and 0.86 in the Idiopathic pulmonary fibrosis classification task based on lung tissue samples and peripheral blood mononuclear cell samples, respectively. Our findings offer valuable insights into the pathogenesis of Idiopathic pulmonary fibrosis, providing new therapeutic directions and target genes for further investigation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Zhang, Wang, Wang, Wu, Cai, Mo and Yang.)

Midkine (MK) and pleiotrophin (PTN) belong to the same family of cytokines. They have similar sequences and functions. Both have important roles in cellular proliferation, tumors, and diseases. They regulate and are expressed by some immune cells. We have recently demonstrated MK production by some human innate antigen-presenting cells (iAPCs), i.e., monocyte-derived dendritic cells (MDDCs) and macrophages stimulated through Toll-like receptor (TLR)-4, and plasmacytoid dendritic cells (pDCs) stimulated through TLR 7. While PTN production was only documented in tissue macrophages. TLRs 3, 7, 8, and 9 are nucleic acid sensing (NAS) TLRs that detect nucleic acids from cell damage and infection and induce iAPC responses. We investigated whether NAS TLRs can induce MK and PTN production by human iAPCs, namely monocytes, macrophages, MDDCs, myeloid dendritic cells (mDCs), and pDCs. Our results demonstrated for the first time that PTN is produced by all iAPCs upon TLR triggering ( p < 0.01). IAPCs produced more PTN than MK ( p < 0.01). NAS TLRs and iAPCs had differential abilities to induce the production of MK, which was induced in monocytes and pDCs by all NAS TLRs ( p < 0.05) and in MDDCs by TLRs 7/8 ( p < 0.05). TLR4 induced a stronger MK production than NAS TLRs ( p ≤ 0.05). Monocytes produced higher levels of PTN after differentiation to macrophages and MDDCs ( p < 0.05). The production of MK and PTN differs among iAPCs, with a higher production of PTN and a selective induction of MK production by NAS TLR. This highlights the potentially important role of iAPCs in angiogenesis, tumors, infections, and autoimmunity through the differential production of MK and PTN upon TLR triggering., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Elias A. Said et al.)

Graphical abstract Abstract Aims To examine the functions of growth factor midkine (MK) and a flavonoid quercetin on survival, apoptosis and migration of prostate cancer (PCa) stem cells (CSCs). Main methods CD44+/CD133+ and CD44+ stem cells were isolated from PC3 and LNCaP cells, respectively by magnetic-activated cell sorting system. 3D cell culture was used to evaluate the ability of quercetin, MK siRNA, and the combination of both to inhibit spheroid formation, apoptosis and cell cycle arrest. Image-based cytometer, RT-qPCR, Western blotting and transwell migration assays were performed. Key findings Quercetin treatment for 24–72 h inhibited PC3 and CD44+/CD133+ stem cell proliferation in a time- and dose-dependent manner. Knockdown of endogenous MK expression significantly suppressed proliferation of CD44+/CD133+ and CD44+ cells as well as their parent cells. Co-administration of MK siRNA and quercetin reduced the cell survival, induced apoptosis and caused G1 phase cell cycle arrest more effectively than the individual therapy. Knockdown of MK significantly enhanced the inhibitory effect of quercetin on CD44+/CD133+ migration and spheroid formation. In addition, the combined therapy inhibited the phosphorylation of PI3K, AKT and ERK1/2, and reduced the protein expression of p38, ABCG2 and NF-κB. Significance Quercetin alone exhibited significant cytotoxic effects on CD44+/CD133+. MK plays an important role in the proliferation of CD44+/CD133+ and CD44+ cells in particular, and quercetin and MK-silencing therapy may be an important strategy in targeting CSCs that play a role in relapse, migration and drug resistance. [ABSTRACT FROM AUTHOR]

Objectives: To detect the presence of Midkine in serum and gingival crevicular fluid (GCF) of healthy non-smokers, chronic gingivitis smokers, and non-smoker individuals and to evaluate the role of Midkine in the progression of gingival inflammation. Materials and Methods: Periodontal clinical parameters examination including gingival index, pocket probing depth, clinical attachment level, and collection of GCF and serum was performed on 60 subjects, categorized into three groups with 20 subjects in each group: Group I (healthy non-smokers); Group II (chronic gingivitis non-smokers), and Group III (chronic gingivitis smokers). GCF and serum were collected from 20 patients of each group. Midkine levels were estimated using the enzyme-linked immunosorbent assay. Results: Midkine was detected in all samples. The results of this study suggest that mean GCF and serum Midkine levels were the highest in Group III and varied significantly from those of Groups I and II. Furthermore, GCF and serum Midkine levels increased proportionally with the progression of inflammation. Conclusion: As the gingival disease progresses, there is a substantial increase of Midkine concentrations in serum and GCF. Since, Midkine levels in the GCF and serum correlated positively with clinical parameters, Midkine may be considered as a "novel biomarker" in disease progression. However, controlled longitudinal studies are required to confirm this possibility. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the effects of electroacupuncture (EA) intervention administered at rats of middle cerebral artery occlusion (MCAO)/reperfusion. Fifty-four male Sprague-Dawley rats were divided into three groups, consisting of sham group, MCAO/R group, and EA group. EA treatment at Quchi and Zusanli acupoints was applied in rats of EA group at 24 h after MCAO once per day for 3 days. Our results indicated that EA treatment reduced infarct volumes and neurological deficits, as well alleviated the apoptotic cells in peri-infarct cortex, indicating that EA exerted neuroprotective effect in cerebral ischemic rats. Moreover, EA treatment may effectively reverse the upregulation of caspase-3 and Bim and alleviate the inhibition of Bcl-2 following 72-h ischemic stroke. EA may significantly reverse the promoted relative density level of p-ERK1/2, p-JNK, and p-p38 in the EA group compared with the MCAO/R group. In addition, the growth factor midkine (MK) was upregulated at 72 h after MCAO/R, and EA treatment may significantly prompt expression of MK. Our study demonstrated that EA exerted neuroprotective effect against neuronal apoptosis and the mechanism might involve in upregulation of MK and mediation of ERK/JNK/p38 signal pathway. [ABSTRACT FROM AUTHOR]

Pleiotrophin (PTN) and Midkine (MK) are neurotrophic factors that are upregulated in the prefrontal cortex after alcohol administration and have been shown to reduce ethanol drinking and reward. PTN and MK are the endogenous inhibitors of Receptor Protein Tyrosine Phosphatase (RPTP) β/ζ (a.k.a. PTPRZ1, RPTPβ, PTPζ), suggesting a potential role for this phosphatase in the regulation of alcohol effects. To determine if RPTPβ/ζ regulates ethanol consumption, we treated mice with recently developed small-molecule inhibitors of RPTPβ/ζ (MY10, MY33-3) before testing them for binge-like drinking using the drinking in the dark protocol. Mice treated with RPTPβ/ζ inhibitors, particularly with MY10, drank less ethanol than controls. MY10 treatment blocked ethanol conditioned place preference, showed limited effects on ethanol-induced ataxia, and potentiated the sedative effects of ethanol. We also tested whether RPTPβ/ζ is involved in ethanol signaling pathways. We found that ethanol treatment of neuroblastoma cells increased phosphorylation of anaplastic lymphoma kinase (ALK) and TrkA, known substrates of RPTPβ/ζ. Treatment of neuroblastoma cells with MY10 or MY33-3 also increased levels of phosphorylated ALK and TrkA. However, concomitant treatment of neuroblastoma cells with ethanol and MY10 or MY33-3 prevented the increase in pTrkA and pALK. These results demonstrate for the first time that ethanol engages TrkA signaling and that RPTPβ/ζ modulates signaling pathways activated by alcohol and behavioral responses to this drug. The data support the hypothesis that RPTPβ/ζ might be a novel target of pharmacotherapy for reducing excessive alcohol consumption. [ABSTRACT FROM AUTHOR]

Background: Midkine (MK) is a heparin binding growth factor and is involved in neurogenesis, neural development and neuroprotection. Additionally, MK may contribute to cancer development and pathogenesis of neurodegenerative disorders and schizophrenia. Considering these effects of MK, this study researched whether MK is involved in autism spectrum disorders (ASD) pathogenesis. Methods: We evaluated serum MK levels of 38 patients with ASD and 32 healthy control group. MK levels were measured with ELISA, while ASD severity was assessed with Childhood Autism Rating Scale. Results: Our data showed that the serum MK concentration in ASD patients (mean ± SD, 11.51 ± 8.53 pg/ml) is significantly higher than healthy controls (mean ± SD, 6.19 ± 3.94 pg/ml) (p = 0.007). Conclusions: According to these results, MK may play a role in ASD pathogenesis. [ABSTRACT FROM AUTHOR]

Midkine (Mdk) is a heparin-binding growth factor that is involved in regulating cell growth, differentiation and migration. Here, we report the isolation and characterization of duplicated mdk genes in blunt snout bream ( Megalobrama amblycephala ). The mdka and - b genes encode 146 aa and 147 aa peptides, respectively, sharing a sequence identity of 64%. During embryogenesis, mdka mRNA is detectable after 12 h post-fertilization (hpf) and mdkb mRNA can be detected after 8 hpf, about 4 h prior to mdka mRNA. Whole-mount in situ hybridization demonstrated that two paralogs of mdk mRNA were detected in the brain and dorsal neural tube at 16 hpf. At 22 hpf, mdka mRNA was abundant in the brain and dorsal neural tube, whereas mdkb mRNA were transcribed in the brain and tailbud. Later, at 55 hpf, both paralogs were mainly expressed in the brain. Furthermore, both the mdk genes were highly expressed in multiple adult tissues except in the skin and a low expression of mdka in the muscle. In addition, they were differentially inhibited in the liver and intestine with exogenous recombinant human growth hormone, while their mRNA levels were up-regulated in the brain. During starvation, both the mdk genes were significantly up-regulated in the intestine, brain and liver and returned to the control levels following 6 days of refeeding. Our results suggest that duplicated mdk genes may play conserved and divergent roles in embryonic development and tissue growth regulation in blunt snout bream. [ABSTRACT FROM AUTHOR]

Background: hepatocellular carcinoma (HCC) represents a global health problem. It is the fifth most common cancer but the second leading cause of cancer-related death in men worldwide. In Middle Eastern countries, liver cancer is a major concern among men, especially in Egypt and Saudi Arabia. The incidence of HCC has increased sharply in the last 5–10 years, with an especially high incidence in Egypt. So, early detection and diagnosis of these cases are required for successful treatments and improved outcomes. Aim of the Work: this study aimed to detect the efficacy of serum level of Midkine as an early marker for HCC diagnosis compared to AFP serum level. Patients and Methods: this prospective study was conducted on a total of 50 subjects, 30 of them with HCC and 20 apparently healthy subjects matched for age and sex with patients. It was carried out at the Clinical Pathology Department, Tanta University Hospital. Results: a significant increase (p < 0.001) in serum midkine level was detected in HCC group compared with control group from a mean of 391.45 ± 96.09, in control group to a mean of 1074.53 ± 106.27, in HCC. Conclusion: serum midkine may serve as a novel diagnostic tumor marker for the detection of hepatocellular carcinomas. Recommendations: it was recommended to do further studies on early cases with larger population including AFP-negative patients, to justify its implementation in clinical practice. [ABSTRACT FROM AUTHOR]

Development and progression of malignant tumors is in part characterized by the ability of a tumor cell to overcome cell-cell and cell-matrix adhesion and to disseminate in organs distinct from that in which they originated. This study was undertaken to analyze the clinical significance of the expression of the following cell-cell and cell-matrix adhesion molecules in pancreatic ductal adenocarcinomas (PDACs) and synchronous liver metastases: intercellular adhesion molecule 1 (ICAM-1), E-cadherin, periostin, and midkine (MK). ICAM-1, E-cadherin, periostin and MK expression was analyzed by immunohistochemistry on a tissue microarray containing 34 PDACs and 12 liver metastasis specimens. ICAM-1 expression was predominantly localized in the membranes of the cells and was found in weak to moderate intensities in PDACs and liver metastases. E-cadherin expression was absent in the majority of PDACs and corresponding liver metastases. The secreted proteins periostin and MK were expressed in various intensities in primary cancers and liver metastases. Statistical analysis demonstrated that the expression levels of the analyzed markers were neither significantly associated with metastasis in PDACs nor with clinical outcome of patients. Our study shows that the expression of the cell-cell and cell-matrix adhesion molecules ICAM-1, E-cadherin, periostin and MK was not significantly linked to metastatic disease in PDACs. Moreover, our study excludes the analyzed markers as prognostic markers in PDACs. [ABSTRACT FROM AUTHOR]

Background: Angiogenesis is associated with tumor progression in a range of malignancies. Herein, we develop custom immunobead assays for several mechanistically important targets and evaluated these against sera from cohorts of non-small cell lung cancer (NSCLC) patients. Methods: Antigen “capture” antibodies for midkine, syndecan-1, and ANGPTL4 were independently conjugated to MagPlex® Microspheres using standard carbodiimide/NHS-based chemistry. These reagents served as the basis for quantitative sandwich assay assembly using biotinylated detection antibodies and R-phycoerythrin-conjugated streptavidin reporter system. Standard curves were created using dilution series of recombinant target proteins with assay performance characteristics calculated, accordingly. Finally, we evaluated a range of serum samples from NSCLC patients (n = 32) to verify assay performance. Results: Multiplexed assays for midkine, syndecan-1, and ANGPTL4 were developed with three orders of magnitude in dynamic range, excellent intra- and inter-assay precision, and accuracy parameters (<10%, and <15% variability, respectively). Detection and quantifications limits were suitable for the three assays to efficiently evaluate sera across a range of disease stages with a four-fold dilution factor. Conclusion: We successfully developed and analytically validated a 3-plex immunobead assay for quantifying midkine, syndecan-1, and ANGPTL4 in patient sera. This multiplexed assay will provide an important tool for future studies delineating the role of angiogenesis in lung cancer progression. [ABSTRACT FROM AUTHOR]