Background
Accumulating evidence shows an overabundance of
Fusobacterium nucleatum
in colorectal tumor tissues. However, the correlation between the absolute copy number of
F. nucleatum
in colorectal ...cancer tissues and colorectal cancer progression is unclear from previous reports. Therefore, we performed a study to compare the abundance of
F. nucleatum
in colorectal tissues with clinicopathologic and molecular features of colorectal cancer.
Methods
We collected 100 colorectal cancer tissues and 72 matched normal-appearing mucosal tissues. Absolute copy numbers of
F. nucleatum
were measured by droplet digital PCR.
Results
The detection rates of
F. nucleatum
were 63.9% (46/72) in normal-appearing mucosal tissues and 75.0% (75/100) in CRC tissue samples. The median copy number of
F. nucleatum
was 0.4/ng DNA in the normal-appearing colorectal mucosa in patients with colorectal cancer and 1.9/ng DNA in the colorectal cancer tissues (
P
= 0.0031).
F. nucleatum
copy numbers in stage IV colorectal cancer tissues were significantly higher than those in the normal-appearing mucosa in patients with colorectal cancer (
P
= 0.0016). The abundance of
F. nucleatum
in colorectal cancer tissues correlated with tumor size and KRAS mutation and was significantly associated with shorter overall survival times; this trend was notable in the patients with stage IV colorectal cancer. Focusing on normal-appearing mucosa in the patients with colorectal cancer, the
F. nucleatum
copy number was significantly higher in the patients with stage IV rather than stages I–III.
Conclusion
These results suggest that determining
F. nucleatum
levels may help predict clinical outcomes in colorectal cancer patients. Further confirmatory studies using independent datasets are required to confirm our findings.
Background and study aims
The diagnostic ability of endoscopists to determine invasion depth of early gastric cancer is not favorable. We designed an artificial intelligence (AI) classifier for ...differentiating intramucosal and submucosal gastric cancers and examined it to establish a diagnostic method based on cooperation between AI and endoscopists.
Patients and methods
We prepared 500 training images using cases of mainly depressed-type early gastric cancer from 250 intramucosal cancers and 250 submucosal cancers. We also prepared 200 test images each of 100 cancers from another institution. We designed an AI classifier to differentiate between intramucosal and submucosal cancers by deep learning. We examined the performance of the AI classifier and the majority vote of the endoscopists as high confidence and low confidence diagnostic probability, respectively, and cooperatively combined them to establish a diagnostic method providing high accuracy.
Results
Internal evaluation of the training images showed that accuracy, sensitivity, specificity, and F1 measure by the AI classifier were 77%, 76%, 78%, and 0.768, and those of the majority vote of the endoscopists were 72.6%, 53.6%, 91.6%, and 0.662, respectively. A diagnostic method based on cooperation between AI and the endoscopists showed that the respective values were 78.0%, 76.0%, 80.0%, and 0.776 for the test images. The value of F1 measure was especially higher than those by AI or the endoscopists alone.
Conclusions
Cooperation between AI and endoscopists improved the diagnostic ability to determine invasion depth of early gastric cancer.
Crystal-Storing Histiocytosis of the Stomach Goto, Atsushi; Hamabe, Koichi; Seto, Keisuke ...
The American journal of gastroenterology,
09/2023, Letnik:
118, Številka:
9
Journal Article
From a mouse triple‐negative breast cancer cell line, 4T1, we previously established 4T1.3 clone with a high capacity to metastasize to bone after its orthotopic injection into mammary fat pad of ...immunocompetent mice. Subsequent analysis demonstrated that the interaction between cancer cells and fibroblasts in a bone cavity was crucial for bone metastasis focus formation arising from orthotopic injection of 4T1.3 cells. Here, we demonstrated that a member of the adhesion G‐protein–coupled receptor (ADGR) family, G‐protein–coupled receptor 56 (GPR56)/adhesion G‐protein–coupled receptor G1 (ADGRG1), was expressed selectively in 4T1.3 grown in a bone cavity but not under in vitro conditions. Moreover, fibroblasts present in bone metastasis sites expressed type III collagen, a ligand for GPR56/ADGRG1. Consistently, GPR56/ADGRG1 proteins were detected in tumor cells in bone metastasis foci of human breast cancer patients. Deletion of GPR56/ADGRG1 from 4T1.3 cells reduced markedly intraosseous tumor formation upon their intraosseous injection. Conversely, intraosseous injection of GPR56/ADGRG1‐transduced 4T1, TS/A (mouse breast cancer cell line), or MDA‐MB‐231 (human breast cancer cell line) exhibited enhanced intraosseous tumor formation. Furthermore, we proved that the cleavage at the extracellular region was indispensable for GPR56/ADGRG1‐induced increase in breast cancer cell growth upon its intraosseous injection. Finally, inducible suppression of Gpr56/Adgrg1 gene expression in 4T1.3 cells attenuated bone metastasis formation with few effects on primary tumor formation in the spontaneous breast cancer bone metastasis model. Altogether, GPR56/ADGRG1 can be a novel target molecule to develop a strategy to prevent and/or treat breast cancer metastasis to bone.
GPR56/ADGRG1 expression conferred growth advantage on breast cancer cells in the bone cavity, thereby promoting bone metastasis formation.GPR56/ADGRG1 can be a novel target molecule to develop a strategy to treat breast cancer metastasis to bone.
Abstract
Senescent cells are predicted to occur and increase in animal tissues with aging. However, senescent cells in the tissues of aged animals remain to be identified. We refer to the marker ...genes to identify senescent cells in tissues as “age-associated genes”. In this study, we searched for age-associated genes to identify senescent cells in the livers of aged animals. We performed single-cell RNA sequencing (scRNA-seq) to screen candidates for age-associated genes using young and aged rat primary hepatocytes. To remove animal species specificity, gene expression analyses in mouse livers were performed, confirming age-associated increases in the mRNA expression levels of
Glipr1
,
Clec12a
, and
Phlda3
. Moreover, the mRNA expression levels of
Glipr1
and
Phlda3
were increased by stress-induced premature senescence using doxorubicin in primary hepatocytes and livers of young mice. Transcriptome data of aged rat hepatocytes suggested that
Glipr1
,
Clec12a
, and
Phlda3
were expressed in almost identical cells. Fluorescence in situ hybridization (FISH) confirmed the presence of cells with abundant
Glipr1
,
Clec12a
, and
Phlda3
mRNA in 27-month-old mouse primary hepatocytes, which are considered to be senescent cells. This study is the first to identify
Glipr1
,
Clec12a
, and
Phlda3
as age-associated genes in the mouse liver.
Adipose-derived stem cells (ASCs) exhibit self-renewal and pluripotency. The differentiation potency of ASCs has been reported to deteriorate with aging; however, relevant studies used ASCs that were ...isolated and subcultured several times. It is still unclear whether subcultured ASCs accurately reflect the in vivo state. To address this question, we used freshly isolated stromal vascular fractions (SVFs) and performed comprehensive single-cell transcriptome analysis. In this study, we identified three cell populations as putative ASC candidates in SVFs and three novel ASC-related genes: Adamts7, Snai2, and Tgfbr1, that are reported to be negative regulators of cell differentiation. Moreover, we identified age-associated high gene expression levels of Adamts7, Egfr, and Igfbp4 in the earliest differentiation stage of ASCs. These results suggest that aging may make it impossible to maintain the stringency of the regulation of the expression of some genes related to ASC differentiation.
Background
Hiatal hernia is defined by the permanent or intermittent prolapse of any abdominal structure into the chest through the diaphragmatic esophageal hiatus. Prolapse of the stomach, ...intestine, transverse colon, and spleen is relatively common, but herniation of the pancreas is a rare condition. We describe a case of acute pancreatitis and bile duct dilatation secondary to a massive hiatal hernia of pancreatic body and tail.
Case presentation
An 86-year-old woman with hiatal hernia who complained of epigastric pain and vomiting was admitted to our hospital. Blood tests revealed a hyperamylasemia and abnormal liver function test. Computed tomography revealed prolapse of the massive hiatal hernia, containing the stomach and pancreatic body and tail, with peripancreatic fluid in the posterior mediastinal space as a sequel to pancreatitis. In addition, intrahepatic and extrahepatic bile ducts were seen to be dilated and deformed. After conservative treatment for pancreatitis, an elective operation was performed. There was a strong adhesion between the hernial sac and the right diaphragmatic crus. After the stomach and pancreas were pulled into the abdominal cavity, the hiatal orifice was closed by silk thread sutures (primary repair), and the mesh was fixed in front of the hernial orifice. Toupet fundoplication and intraoperative endoscopy were performed. The patient had an uneventful postoperative course post-procedure.
Conclusion
A rare massive hiatal hernia, involving the stomach and pancreatic body and tail, can cause acute pancreatitis with bile duct dilatation. The etiology can be flexure of the main pancreatic and extrahepatic bile ducts. Symptomatic herniation is best treated with surgery. Elective surgery is thought to be safer than emergent surgery in patients with serious complications.
Conquering immunosuppression in tumor microenvironments is crucial for effective cancer immunotherapy. It is well known that interleukin (IL)‐6, a pleiotropic cytokine, is produced in the ...tumor‐bearing state. In the present study, we investigated the precise effects of IL‐6 on antitumor immunity and the subsequent tumorigenesis in tumor‐bearing hosts. CT26 cells, a murine colon cancer cell line, were intradermally injected into wild‐type and IL‐6‐deficient mice. As a result, we found that tumor growth was decreased significantly in IL‐6‐deficient mice compared with wild‐type mice and the reduction was abrogated by depletion of CD8+ T cells. We further evaluated the immune status of tumor microenvironments and confirmed that mature dendritic cells, helper T cells and cytotoxic T cells were highly accumulated in tumor sites under the IL‐6‐deficient condition. In addition, higher numbers of interferon (IFN)‐γ‐producing T cells were present in the tumor tissues of IL‐6‐deficient mice compared with wild‐type mice. Surface expression levels of programmed death‐ligand 1 (PD‐L1) and MHC class I on CT26 cells were enhanced under the IL‐6‐deficient condition in vivo and by IFN‐γ stimulation in vitro. Finally, we confirmed that in vivo injection of an anti‐PD‐L1 antibody or a Toll‐like receptor 3 ligand, polyinosinic‐polycytidylic acid, effectively inhibited tumorigenesis under the IL‐6‐deficient condition. Based on these findings, we speculate that a lack of IL‐6 produced in tumor‐bearing host augments induction of antitumor effector T cells and inhibits tumorigenesis in vivo, suggesting that IL‐6 signaling may be a promising target for the development of effective cancer immunotherapies.
IL‐6 produced in the tumor hosts suppresses antitumor immunity involving the activation of effector T cells and dendritic cells. Lack of IL‐6 facilitates cancer immunotherapies using immune checkpoint inhibitors and immunological adjuvants.
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