Tubular Endogenous Erythropoietin Protects Renal Function against Ischemic Reperfusion Injury.

Many large-scale studies show that exogenous erythropoietin, erythropoiesis-stimulating agents, lack any renoprotective effects. We investigated the effects of endogenous erythropoietin on renal function in kidney ischemic reperfusion injury (IRI) using the prolyl hydroxylase domain (PHD) inhibitor, Roxadustat (ROX). Four h of hypoxia (7% O) and 4 h treatment by ROX prior to IRI did not improve renal function.

Ten-Gram-Scale Total Synthesis of the Anticancer Drug Candidate E7130 to Supply Clinical Trials.

E7130 is a novel drug candidate with an exceedingly complex chemical structure of the halichondrin class, discovered by a total synthesis approach through joint research between the Kishi group at Harvard University and Eisai. Only 18 months after completion of the initial milligram-scale synthesis, ten-gram-scale synthesis of E7130 was achieved, providing the first good manufacturing practice (GMP) batch to supply clinical trials. This paper highlights the challenges in developing ten-gram-scale synthesis from the milligram-scale synthesis.

Immune profile analysis of peripheral blood and tumors of lung cancer patients treated with immune checkpoint inhibitors.

Background: Immune checkpoint inhibitors (ICIs) have become central to lung cancer drug therapy, and establishing biomarkers that can predict effects and adverse events (AEs) is awaited. We prospectively analyzed the association between the immune-related molecular expression in peripheral blood mononuclear cells (PBMCs) and lung cancer tissues, and the effects of ICI monotherapy.

Methods: Twenty-one patients with advanced non-small cell lung cancer (NSCLC) who received ICI monotherapy were included.

Detection of Kita-Kyushu Lung Cancer Antigen-1, a Cancer/Testis Antigen, in the Stomach Close to a Cancerous Condition.

Kita-Kyushu lung cancer antigen-1 (KK-LC-1), encoded by , is a cancer/testis antigen (CTA) and an attractive target for immunotherapy. Our previous study demonstrated frequent expression in gastric cancers (GCs) and non-tumor sites of the stomach with tumors. Additionally, there was a correlation with () infection.

Effects of Roxadustat on Erythropoietin Production in the Rat Body.

Anemia is a major complication of chronic renal failure. To treat this anemia, prolylhydroxylase domain enzyme (PHD) inhibitors as well as erythropoiesis-stimulating agents (ESAs) have been used. Although PHD inhibitors rapidly stimulate erythropoietin (Epo) production, the precise sites of Epo production following the administration of these drugs have not been identified.

Relationship between Kita-Kyushu Lung Cancer antigen-1 expression and prognosis of cases with lung squamous cell carcinoma.

Background: Previously, we identified the highly immunogenic cancer testicular antigen named Kita-Kyushu Lung Cancer antigen-1 (KK-LC-1). In this study, we analyzed the effect of KK-LC-1 expression on the prognosis of patients with resected squamous cell lung cancer.

Methods: Fifty squamous cell lung cancer patients, who received complete resection, were enrolled in this study.

An analysis of the immunological tumor microenvironment of primary tumors and regional lymph nodes in squamous cell lung cancer.

Background: Various immune cells that play a central role in antitumor immunity accumulate in primary tumors and regional lymph nodes. Such cellular accumulation and the molecular expression were analyzed to elucidate the immunological tumor microenvironment.

Methods: Fifty squamous cell lung cancer patients with complete resection were included.

Effects of Angiotensin II on Erythropoietin Production in the Kidney and Liver.

The kidney is a main site of erythropoietin production in the body. We developed a new method for the detection of Epo protein by deglycosylation-coupled Western blotting. Detection of deglycosylated Epo enables the examination of small changes in Epo production.

Differentiation of endogenous erythropoietin and exogenous ESAs by Western blotting.

Doping tests for the illegal use of erythropoiesis-stimulating agents (ESAs) have been developed. We developed a new Western blotting method to detect and distinguish endogenous erythropoietin (Epo, 35-38 kDa) and exogenous ESAs (epoetin α and β, 38-42 kDa; darbepoetin α, 47-50 kDa; epoetin β pegol, 93-110 kDa). Epo and ESAs are glycoproteins and deglycosylation using peptide-N-glycosidase F shifted all Epo and ESA bands except epoetin β pegol to 22 kDa.

Development of adoptive immunotherapy with KK-LC-1-specific TCR-transduced γδT cells against lung cancer cells.

The present study analyzed the antitumor effect of γδT cells transduced with the TCR of cancer-specific CTLs to establish forceful cancer-specific adoptive immunotherapy. We cloned the TCRαβ genes from CTLs showing HLA-B15 restricted recognition of Kita-Kyushu lung cancer antigen-1 (KK-LC-1), a cancer/germline gene antigen, identified in a lung adenocarcinoma case (F1121). The TCRαβ and CD8 genes were transduced into γδT cells induced from PBLs of healthy volunteers stimulated with zoledronate and IL-2.

Should Lung-Sparing Surgery Be the Standard Procedure for Malignant Pleural Mesothelioma?

Background: Surgical procedures for malignant pleural mesothelioma (MPM) include extrapleural pneumonectomy (EPP), extended pleurectomy/decortication (P/D) and P/D. EPP has been applied to MPM for a long time, but the postoperative status is extremely poor due to the loss of one whole lung. We compared the mortality, morbidity and median survival time (MST) of lung-sparing surgery (extended P/D or P/D) and lung-sacrificing surgery (EPP) for MPM by performing a systematic review.

Erythropoietin production by the kidney and the liver in response to severe hypoxia evaluated by Western blotting with deglycosylation.

The detection of erythropoietin (Epo) protein by Western blotting has required pre-purification of the sample. We developed a new Western blot method to detect plasma and urinary Epo using deglycosylation. Epo in urine and tissue, and erythropoiesis-stimulating agents (ESAs) in urine were directly detected by our Western blotting.

Cancer/testis antigen, Kita-Kyushu lung cancer antigen-1 and ABCD stratification for diagnosing gastric cancers.

Background: The ABCD stratification [(combination of serum pepsinogen (PG) levels and titers of antibody (immunoglobulin G, IgG) against ()] is effective for the classification of individuals at risk of developing gastric cancer (GC). The Kita-Kyushu lung cancer antigen-1 (KK-LC-1) is a Cancer/Testis antigen frequently expressed in GC.

Aim: To evaluate the effectiveness of KK-LC-1 and ABCD stratification in the diagnosis of GC.

Expression of Kita-Kyushu Lung Cancer Antigen-1 as Detected by a Novel Monoclonal Antibody in Gastric Cancer.

Background/aim: Kita-Kyushu lung cancer antigen-1 (KK-LC-1) is a known cancer/testis antigen. Our group has previously shown KK-LC-1 gene expression in gastric cancer. However, could not be detected the KK-LC-1 protein due to the lack of an appropriate antibody.

A landmark in drug discovery based on complex natural product synthesis.

Despite their outstanding antitumour activity in mice, the limited supply from the natural sources has prevented drug discovery/development based on intact halichondrins. We achieved a total synthesis of C52-halichondrin-B amine (E7130) on a >10 g scale with >99.8% purity under GMP conditions.

Detection of KK-LC-1 Protein, a Cancer/Testis Antigen, in Patients with Breast Cancer.

Background: Kita-Kyushu lung cancer antigen-1 (KK-LC-1) is a cancer/testis antigen and predominant target for cancer immunotherapy. Its detection is only established based on gene expression. In this study, we established a monoclonal antibody against KK-LC-1 to detect its protein expression in formalin-fixed samples.

Fludrocortisone stimulates erythropoietin production in the intercalated cells of the collecting ducts.

Erythropoietin has been thought to be secreted to plasma soon after the production because of the difficulty of Western blot analysis and immunohistochemistry. We established the new methods of Western blot analysis and immunohistochemistry. Using the new methods, we investigated the effects of aldosterone and fludrocortisone, an analogue of aldosterone on erythropoietin mRNA and protein production by the kidneys.

Expression of KK-LC-1, a cancer/testis antigen, at non-tumour sites of the stomach carrying a tumour.

Kita-Kyushu lung cancer antigen-1 (KK-LC-1) is a cancer/testis antigen (CTA) and predominant target for cancer immunotherapy. Our previous study indicated that KK-LC-1 was expressed in 82% of gastric cancers, and also in 79% of early stage of gastric cancers, with a correlation to Helicobacter pylori (H. pylori) infection.

Early gastric cancer frequently has high expression of KK-LC-1, a cancer-testis antigen.

Aim: To assess cancer-testis antigens (CTAs) expression in gastric cancer patients and examined their associations with clinicopathological factors.

Methods: Eighty-three gastric cancer patients were evaluated in this study. Gastric cancer specimens were evaluated for the gene expression of CTAs, Kitakyushu lung cancer antigen-1 (KK-LC-1), melanoma antigen (MAGE)-A1, MAGE-A3 and New York esophageal cancer-1 (NY-ESO-1), by reverse transcription PCR.

Targeted DNA methylation in pericentromeres with genome editing-based artificial DNA methyltransferase.

To study the impact of epigenetic changes on biological functions, the ability to manipulate the epigenetic status of certain genomic regions artificially could be an indispensable technology. "Epigenome editing" techniques have gradually emerged that apply TALE or CRISPR/Cas9 technologies with various effector domains isolated from epigenetic code writers or erasers such as DNA methyltransferase, 5-methylcytosine oxidase, and histone modification enzymes. Here we demonstrate that a TALE recognizing a major satellite, consisting of a repeated sequence in pericentromeres, could be fused with the bacterial CpG methyltransferase, SssI.

Correlation Between Expression of the Cancer/Testis Antigen KK-LC-1 and Infection in Gastric Cancer.

Background/aim: Our previous study indicated that Kita-kyushu lung cancer antigen-1 (KK-LC-1) is a cancer/testis antigen (CTA) expressed in 82% of gastric cancer cases. Here, we investigated the relationship between KK-LC-1 expression and Helicobacter pylori infection in Japanese patients with gastric cancer.

Patients And Methods: We examined CTA expression in 25 surgical gastric cancer specimens and anti-H.

Self-Propelled Vesicles Induced by the Mixing of Two Polymeric Aqueous Solutions through a Vesicle Membrane Far from Equilibrium.

This study describes the development of self-propelled vesicles using transient interfacial energy in an aqueous two-phase system composed of polyethylene glycol (PEG), dextran (DEX), and water. The transient interfacial energy was generated at the mixing boundary between the PEG and DEX solutions when the two miscible liquids were in contact with each other far from equilibrium. Vesicles encapsulating 20 wt % DEX solution traveled spontaneously when the PEG concentration in the environmental media was >15 wt %.