Serum anti­KIAA0513 antibody as a common biomarker for mortal atherosclerotic and cancerous diseases.

Numerous antibody biomarkers have been reported for cancer and atherosclerosis-related diseases. The major complications of atherosclerosis and diabetes mellitus (DM) are acute ischemic stroke (AIS), cardiovascular disease (CVD) and chronic kidney disease (CKD). Cancer development is accompanied by arterial disorders, such as angiogenesis and atherosclerosis, and DM is a risk factor for the development of certain types of cancer. Atherosclerosis-related diseases and cancers are therefore interrelated and could be detected using a common biomarker. In the present study, the initial screening using the protein array method identified KIAA0513 as an antigen recognized by serum IgG antibodies in patients with atherosclerosis. The amplified luminescent proximity homogeneous assay-linked immunosorbent assay revealed significantly higher serum antibody levels against recombinant KIAA0513 protein in patients with AIS, transient ischemic attack (TIA), DM, CVD, obstructive sleep apnea syndrome (OSAS), CKD and solid cancers, such as esophageal, gastric, colon, lung and breast cancers, compared with healthy donors. A receiver operating characteristic (ROC) analysis revealed that the highest areas under the ROC curves of anti-KIAA0513 antibodies were obtained for esophageal cancer, nephrosclerosis-type CKD and DM. Spearman's correlation analysis revealed that serum anti-KIAA0513 antibody levels were associated with maximum intima-media thickness and plaque score, which are indices of atherosclerosis and stenosis. Serum anti-KIAA0513 antibody markers appear to be useful for diagnosing AIS, TIA, DM, CVD, OSAS, CKD and solid cancers, and may reflect common arterial alterations leading to atherosclerotic and cancerous diseases.

JMJD6 Autoantibodies as a Potential Biomarker for Inflammation-Related Diseases.

Inflammation is closely associated with cerebrovascular diseases, cardiovascular diseases, diabetes, and cancers, and it is accompanied by the development of autoantibodies in the early stage of inflammation-related diseases. Hence, it is meaningful to discover novel antibody biomarkers targeting inflammation-related diseases. In this study, Jumonji C-domain-containing 6 (JMJD6) was identified by the serological identification of antigens through recombinant cDNA expression cloning. In particular, JMJD6 is an antigen recognized in serum IgG from patients with unstable angina pectoris (a cardiovascular disease). Then, the serum antibody levels were examined using an amplified luminescent proximity homogeneous assay-linked immunosorbent assay and a purified recombinant JMJD6 protein as an antigen. We observed elevated levels of serum anti-JMJD6 antibodies (s-JMJD6-Abs) in patients with inflammation-related diseases such as ischemic stroke, acute myocardial infarction (AMI), diabetes mellitus (DM), and cancers (including esophageal cancer, EC; gastric cancer; lung cancer; and mammary cancer), compared with the levels in healthy donors. The s-JMJD6-Ab levels were closely associated with some inflammation indicators, such as C-reactive protein and intima-media thickness (an atherosclerosis index). A better postoperative survival status of patients with EC was observed in the JMJD6-Ab-positive group than in the negative group. An immunohistochemical analysis showed that JMJD6 was highly expressed in the inflamed mucosa of esophageal tissues, esophageal carcinoma tissues, and atherosclerotic plaques. Hence, JMJD6 autoantibodies may reflect inflammation, thereby serving as a potential biomarker for diagnosing specific inflammation-related diseases, including stroke, AMI, DM, and cancers, and for prediction of the prognosis in patients with EC.

Transarterial embolization of radicular arteriovenous fistula at the craniocervical junction.

Craniocervical junction arteriovenous fistula (CCJ AVF) is a rare vascular disorder. Direct surgery for CCJ AVF is generally reported to have better outcome compared to endovascular treatment. However, no certain consensus has been obtained so far. We report a case of radicular CCJ AVF treated by transarterial embolization that resulted in a good outcome. A 69-year-old man presented with subarachnoid hemorrhage primarily in the posterior cranial fossa. Based on digital subtraction angiography showed radicular CCJ AVF with varix. Transarterial embolization was performed with n-butyl-2-cyanoacrylate on day 17 after onset and successfully cured. The neurovascular anatomy of CCJ AVF is complicated, but endovascular treatment may be a treatment option with detailed understanding of angioarchitecture and selective endovascular procedure.

Serum anti-PCK1 antibody levels are a prognostic factor for patients with diabetes mellitus.

BACKGROUND: Autoantibodies develop in autoimmune diseases, cancer, diabetes mellitus (DM), and atherosclerosis-related diseases. However, autoantibody biomarkers have not been successfully examined for diagnosis and therapy. METHODS: Serological identification of antigens through recombinant cDNA expression cloning (SEREX) was used for primary screening of antigens. The cDNA product was expressed in bacteria and purified. Amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) was used to evaluate antibody levels in serum samples. RESULTS: Phosphoenolpyruvate carboxykinase 1 (PCK1) was recognized as an antigen by serum IgG antibodies in the sera of patients with atherosclerosis. AlphaLISA showed significantly higher serum antibody levels against recombinant PCK1 protein in patients with DM and cardiovascular disease than in healthy donors, but not in those with acute ischemic stroke, transient ischemic attack, or obstructive sleep apnea syndrome. The area under the receiver operating characteristic curve for anti-PCK1 antibodies was 0.7024 for DM. The serum anti-PCK1 antibody levels were associated with age, platelet count, and blood pressure. Anti-PCK1-antibody-positive patients showed significantly lower overall survival than the negative patients. CONCLUSIONS: Serum anti-PCK1 antibody levels were found to be associated with DM. The anti-PCK1 antibody marker is useful for predicting the overall survival of patients with DM.

Utility of atherosclerosis-associated serum antibodies against colony-stimulating factor 2 in predicting the onset of acute ischemic stroke and prognosis of colorectal cancer.

Introduction: Autoantibodies against inflammatory cytokines may be used for the prevention of atherosclerosis. Preclinical studies consider colony-stimulating factor 2 (CSF2) as an essential cytokine with a causal relationship to atherosclerosis and cancer. We examined the serum anti-CSF2 antibody levels in patients with atherosclerosis or solid cancer. Methods: We measured the serum anti-CSF2 antibody levels via amplified luminescent proximity homogeneous assay-linked immunosorbent assay based on the recognition of recombinant glutathione S-transferase-fused CSF2 protein or a CSF2-derived peptide as the antigen. Results: The serum anti-CSF2 antibody (s-CSF2-Ab) levels were significantly higher in patients with acute ischemic stroke (AIS), acute myocardial infarction (AMI), diabetes mellitus (DM), and chronic kidney disease (CKD) compared with healthy donors (HDs). In addition, the s-CSF2-Ab levels were associated with intima-media thickness and hypertension. The analyzes of samples obtained from a Japan Public Health Center-based prospective study suggested the utility of s-CSF2-Ab as a risk factor for AIS. Furthermore, the s-CSF2-Ab levels were higher in patients with esophageal, colorectal, gastric, and lung cancer than in HDs but not in those with mammary cancer. In addition, the s-CSF2-Ab levels were associated with unfavorable postoperative prognosis in colorectal cancer (CRC). In CRC, the s-CSF2-Ab levels were more closely associated with poor prognosis in patients with p53-Ab-negative CRC despite the lack of significant association of the anti-p53 antibody (p53-Ab) levels with the overall survival. Conclusion: S-CSF2-Ab was useful for the diagnosis of atherosclerosis-related AIS, AMI, DM, and CKD and could discriminate poor prognosis, especially in p53-Ab-negative CRC.

Carotid Artery Stenting for Patients with Radiation-Induced Carotid Artery Stenosis.

Objective: In radiation-induced carotid artery stenosis (RIS), morphological characteristics, such as bilateral and long lesion distances and in-stent stenosis, have been reported as common after carotid artery stenting (CAS). Here, we present 25 cases at our hospital wherein CAS was performed for RIS and compare the morphological characteristics and the safety of the treatment with cases of atherosclerotic carotid artery stenosis (AS). Methods: Twenty-five lesions from 21 patients underwent CAS for RIS at our hospital between March 2002 and July 2020. The procedure was performed at a mean of 10.0 ± 5.2 years after radiation therapy with 60-72 Gy, with a median follow-up of 45 months. We retrospectively selected consecutive patients with AS with comparable follow-up times from the beginning of the study as controls. We compared the patients' background, stenosis findings including plaque MRI, perioperative period, and postoperative course. Results: All patients in both groups completed the procedure, and the median follow-up time for the RIS and AS groups was 45 and 40 months, respectively (p = 0.1479). Patients in the RIS group had a lower mean age (69.9 ± 6.9 vs. 75.3 ± 7.04, p = 0.0075), a higher stenosis rate (79.1 ± 8.7% vs. 68.6 ± 11.7%, p = 0.0032), and longer stenosis greater than one vertebra (long lesions) (10 vs. 1, p = 0.0046) compared with the patients in the AS group. Although there was no significant difference in outcomes between the two groups, restenosis tended to be more common in the RIS group. Plaque MRI was characterized by a significantly higher T2WI signal (p = 0.0381) in the RIS group, which was attributable to the fact that a necrotic core has been reported commonly in the plaque tissue of RIS. Conclusion: RIS has a high likelihood of restenosis both morphologically and in terms of plaque characteristics. Thus, close follow-up is crucial.

Serum anti-AP3D1 antibodies are risk factors for acute ischemic stroke related with atherosclerosis.

Atherosclerosis has been considered as the main cause of morbidity, mortality, and disability worldwide. The first screening for antigen markers was conducted using the serological identification of antigens by recombinant cDNA expression cloning, which has identified adaptor-related protein complex 3 subunit delta 1 (AP3D1) as an antigen recognized by serum IgG antibodies of patients with atherosclerosis. Serum antibody levels were examined using the amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) using a recombinant protein as an antigen. It was determined that the serum antibody levels against AP3D1 were higher in patients with acute ischemic stroke (AIS), transient ischemic attack, diabetes mellitus (DM), cardiovascular disease, chronic kidney disease (CKD), esophageal squamous cell carcinoma (ESCC), and colorectal carcinoma than those in the healthy donors. The area under the curve values of DM, nephrosclerosis type of CKD, and ESCC calculated using receiver operating characteristic curve analysis were higher than those of other diseases. Correlation analysis showed that the anti-AP3D1 antibody levels were highly associated with maximum intima-media thickness, which indicates that this marker reflected the development of atherosclerosis. The results of the Japan Public Health Center-based Prospective Study indicated that this antibody marker is deemed useful as risk factors for AIS.

Metastasis of Renal Cell Carcinoma to Spinal Hemangioblastoma in a Patient with von Hippel-Lindau Disease: A Case Report.

von Hippel-Lindau (VHL) disease is characterized by neoplastic and cystic lesions, such as central nervous system (CNS) hemangioblastoma and clear cell renal cell carcinoma (RCC), arising in multiple organs. Here, we report a case of an RCC that metastasized to a spinal hemangioblastoma in a patient diagnosed with VHL disease. This is a unique case study because visceral neoplasms rarely metastasize to the CNS. The patient had undergone posterior fossa surgery for the removal of hemangioblastomas in the right cerebellar hemisphere as a child. He was diagnosed with RCC at the age of 20 years, and he underwent partial nephrectomy at the age of 35 years. The patient underwent surgical removal of a spinal tumor from Th8, which was also diagnosed as a hemangioblastoma at the age of 40. However, the residual spinal tumor rapidly regrew within 1.5 years. A second surgery was performed due to progressive leg motor weakness. The resected tumor from the second surgery had two distinct components between the tumor center and the margin. Immunohistochemistry of CD10, PAX 8, and inhibin A demonstrated the predominant region of the tumor was RCC. Pathological findings confirmed tumor-to-tumor metastasis of the RCC migrating into residual spinal hemangioblastoma. It can be challenging to distinguish hemangioblastoma from RCC in neuroimaging. We suggest that tumor-to-tumor metastasis should be considered as a differential diagnosis if benign tumors grow rapidly, even if the pathological diagnosis does not initially confirm malignancy. The biological mechanisms of RCC migrating into residual hemangioblastoma are discussed.

De Novo Vestibular Schwannoma: A Report of Three Cases.

The reported growth rate of vestibular schwannoma varied widely in the literature. However, emergence of vestibular schwannoma remains unsolved. We presented three patients who had undergone previous magnetic resonance imaging (MRI) confirming the absence of tumor and were diagnosed with a unilateral vestibular schwannoma with a diameter of 18-30 mm, 6-9 years after the initial MRI. One patient had solid tumor and experienced stereotactic radiosurgery. Following stereotactic radiosurgery, continuous tumor growth led to hydrocephalus and trigeminal dysfunction, resolved by surgical removal. Other two patients had the tumor with cystic component and experienced surgical removal as first treatment. All tumors were pathologically diagnosed as schwannomas without evidence of high potential of proliferation. This is the first report of three patients with de novo vestibular schwannoma, showing tumor emergence and rapid growth in a short period. Considering a de novo aspect, the "wait and scan" policy may not be appropriate for the subset of VS such as de novo VS.