CAF-associated genes putatively representing distinct prognosis by in silico landscape of stromal components of colon cancer.

Comprehensive understanding prognostic relevance of distinct tumor microenvironment (TME) remained elusive in colon cancer. In this study, we performed in silico analysis of the stromal components of primary colon cancer, with a focus on the markers of cancer-associated fibroblasts (CAF) and tumor-associated endothelia (TAE), as well as immunological infiltrates like tumor-associated myeloid cells (TAMC) and cytotoxic T lymphocytes (CTL). The relevant CAF-associated genes (CAFG)(representing R index = 0.9 or beyond with SPARC) were selected based on stroma specificity (cancer stroma/epithelia, cS/E = 10 or beyond) and expression amounts, which were largely exhibited negative prognostic impacts. CAFG were partially shared with TAE-associated genes (TAEG)(PLAT, ANXA1, and PTRF) and TAMC-associated genes (TAMCG)(NNMT), but not with CTL-associated genes (CTLG). Intriguingly, CAFG were prognostically subclassified in order of fibrosis (representing COL5A2, COL5A1, and COL12A1) followed by exclusive TAEG and TAMCG. Prognosis was independently stratified by CD8A, a CTL marker, in the context of low expression of the strongest negative prognostic CAFG, COL8A1. CTLG were comprehensively identified as IFNG, B2M, and TLR4, in the group of low S/E, representing good prognosis. Our current in silico analysis of the micro-dissected stromal gene signatures with prognostic relevance clarified comprehensive understanding of clinical features of the TME and provides deep insights of the landscape.

A Novel Thyroglobulin Immunoassay Using the Specimen-Pretreatment Process Improves the Accuracy of Thyroglobulin Measurements in Anti-Thyroglobulin Positive Specimens.

BACKGROUND: Recently, second-generation thyroglobulin (Tg) sandwich immunoassays have been used in clinical laboratories to measure the serum Tg levels, which is a tumor marker used to monitor postoperative patients with differentiated thyroid cancers. However, these immunoassays are often subject to Tg autoantibody (TgAb) interference. TgAb interference is inevitable for almost all Tg immunoassays, resulting in unreliable Tg measurement values of TgAb-positive samples. METHODS: To address TgAb interference, we have developed a novel immunoassay based on a fully automated chemiluminescent enzyme immunoassay system using the effective specimen-pretreatment process to inactivate TgAb in blood and evaluated its assay performance. RESULTS: The developed assay was traceable to BCR457 IRMM reference material with a limit of quantification of 0.03 ng/mL. The pretreatment process inactivated almost all TgAb in specimens and allowed accurate Tg measurements in TgAb-positive samples in which TgAb interference was observed using the immunoassays. Size-exclusion chromatography analysis of immunoreactive Tg molecule in a TgAb-positive serum verified disruption of the Tg-TgAb immune complex by the pretreatment process. Good correlation of Tg values in TgAb-negative specimens was observed between the new Tg immunoassay and the second-generation sandwich immunoassays. However, there were numerous discrepant samples on bias plots between the new Tg immunoassay and the second-generation sandwich immunoassays for TgAb-positive specimens. CONCLUSIONS: This study indicates the new Tg immunoassay with the specimen-pretreatment process is both robust and free from interference by TgAb. Thus, this novel assay is superior to second-generation sandwich immunoassays and gives accurate Tg concentrations even for TgAb-positive cases.

[Spindle cell type anaplastic carcinoma of the pancreas: review of 27 Japanese case reports].

Spindle cell type anaplastic carcinoma of the pancreas is extremely rare and has a very poor prognosis. A previously healthy 68-year-old woman was referred to our hospital due to a large tumor in the body of the pancreas. Abdominal computed tomography revealed an irregular, well-enhanced 140-mm tumor containing a cystic component. The patient underwent distal pancreatectomy for a possible malignant tumor (e.g., mucinous cystic neoplasms). Histological examination showed that the tumor contained spindle-shaped cells and adenocarcinoma with nuclear atypia, and a definitive diagnosis of anaplastic carcinoma spindle cell type was made. A review of 27 cases reported in Japan revealed 43% of these lesions invaded other organs, and 26% were classified in Stage IV at the time of diagnosis. Postoperative recurrence rate was 78.2%, and mortality rate was 59.3%. Early diagnosis and sequential radial surgery would improve the poor prognosis.

Confirmation of the absolute configuration of Stachybotrin C using single-crystal X-ray diffraction analysis of its 4-bromobenzyl ether derivative.

The absolute configuration of Stachybotrin C was confirmed in this study. After synthesizing the dimethyl ethers of Stachybotrin C, the C-8 epimer was analyzed by 1D NOESY. However, the stereochemistry determination was difficult through the NOE correlations. Instead, the di(4-bromobenzyl) ether of Stachybotrin C was derived and used for X-ray diffraction analysis, because its single crystal was easier to obtain than that of the original Stachybotrin C. The stereochemistry of Stachybotrin C was determined to be (8S, 9R). This derivatization approach may also be used to prepare single crystals of the analogues.

Effects of a long-term high-fat diet and switching from a high-fat to low-fat, standard diet on hepatic fat accumulation in Sprague-Dawley rats.

To investigate the effects of a long-term high-fat diet and switching from high-fat to a low-fat diet on hepatic fat accumulation in Sprague-Dawley (SD) rats, 3-week-old male SD rats were fed a high-fat diet (HFD) containing 45% fat (kilocalories) for 43 weeks (HDHD group), an HFD for 23 weeks followed by a low-fat, standard diet (LFD) containing 10% fat for 20 weeks (HDLD group), and an LFD for 43 weeks (LDLD group). Histopathologically, steatosis and lobular inflammation was obvious in the HDLD and HDHD groups at 46 weeks of age, and ballooning hepatocytes and Mallory hyalines were seen in the HDHD group. Mild fibrosis was observed in 5 of 13 (38%) rats in the HDHD or HDLD groups. Our results demonstrate that a long-term high-fat diet can induce nonalcoholic steatohepatitis (NASH) in SD rats. Switching to a low-fat, standard diet prevented the progression of NASH, although steatosis was not improved.