Carcinoma-containing CEA in colon cancers in primary and metastatic tumors

Carcinoma-containing CEA was measured as compared with normal tissues and metastases in the lymph nodes and the liver. The high CEA production was remarkable in the potent malignant tumors and metastases in the liver and the lymph nodes as compared with those in normal colon tissues as well as in non metastatic lymph nodes. It is reasonable to consider that high plasma CEA may well indicate advancing or highly potent malignant diseases or recurrence of colon cancers due to destruction of vascular structure by cancer invasion

Surgery for postoperative recurrence of gastric cancer

The six patients who underwent reoperation for recurrence of gastric cancer following surgery were clinically analysed, of whom one had lung metastasis and the other five local recurrences. The conditions of resectability are that carcinoma infiltration should be limited, the disease-free interval-after the first operation should be long and there are no blood-borne metastases into the lung and the liver. The surgical outcome for lung metastasis was pessimistic. It is emphasized that multidisciplinary therapy and early detection are indispensable for improving the surgical outcome in the treatment of recurrence of gastric cancer

Primary malignant tumors of the small intestine

From 1967 through 1987, 43 of primary malignant tumors of the small intestine were experienced at the First Department of Surgery, Nagasaki University Hospital and affiliated hospital, and clinically analysed. 1) Carcinoma, leiomyosarcoma and malignant lymphoma occupied one third in number. The preferable location of carcinomas and malignant lymphomas was lower part of the small bowel although that of leiomyosarcoma was upper part. 2) Diagnosis was mainly made by means of laparotomy which was carried out by clinical signs of obstruction or peritonitis. poor prognosis attributed to extension of a disease to nodes and liver. An early and accurate diagnosis of small bowel tumors is necessary for improving the survival rate

Tumor-containing CEA in Colon Cancers

Carcinoembryonic antigen (CEA) in serum and fresh cancer tissue taken at surgery was measured and analyzed in terms of the disease stage. The CEA level in serum (s-CEA ) has become higher with advance in the disease stage. However, in stage V it was lowered as well as CEA level in cancer mass (ca-CEA). It is suggested that S-CEA is influenced by cancer invasion into the vessel wall, tumor necrosis and/or degeneration which ca-CEA may well be migrated from the tumor cells

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target