Cells constituting the tumor microenvironment are attractive targets for developing new cancer therapies. Here we show that cancer‐associated fibroblasts (CAFs) support tumor growth in vivo and ...maintain the stemness of cancer stem/initiating cells in an in vitro model using an established CAF cell line. We found that CD44 is abundantly expressed on CAFs. This molecule is a cancer stem cell marker in several tumors, but its role in tumorigenesis when expressed by CAFs has not been investigated. It is generally accepted that hypoxic and hyponutritional conditions are triggers of cancer malignancy. We found that CAFs strongly express CD44 in hypoxic and avascular areas in the tumor and that its expression on established CAFs is upregulated under hypoxic and hyponutritional conditions in vitro. In addition, CAF CD44‐positivity in tumor tissues was increased after treatment with inhibitors of angiogenesis. Using cocultures and tumor sphere formation assays, CAFs from wild‐type mice were found to sustain the stemness of cancer stem/initiating cells, while CD44‐deficient CAFs did not. Furthermore, CD44 was involved in malignant cancer cell drug resistance mechanisms. In conclusion, our study suggests that CD44 on CAFs is a functional molecule contributing to the maintenance of cancer stem cell populations in the tumor microenvironment. Stem Cells 2014;32:145–156
Postharvest qualitative avocado losses attributable to stem-end rot are serious problems in various main production areas. Postharvest inspection of avocadoes is still commonly performed by hand; ...this process depends upon only slight differences in fruit appearance or firmness, and it can lead to misclassification. The development of a non-destructive stem-end rot detection technique would help improve objective inspection and reduce misclassification. Therefore, this study proposes an X-ray machine vision approach to automatically detect stem-end rot in avocados. Four-hundred-and-twenty-two X-ray images of fully ripened ‘Hass’ avocadoes were obtained to develop and validate an automatic classification model. The stem-end rot features visible in the X-ray images were extracted using two image processing operations: image segmentation and fruit-outline evaluation. Then, an extremely randomized trees model classified rot development into two classes (< 20% and ≥ 20%) using two features extracted from the X-ray image. The overall classification accuracy was 0.89 with an area under the curve of 0.93 and a recall of 0.89, which suggests the possibility of performing stem-end rot inspections via X-ray imaging and image processing.
•The internal “stem-end rot” disease of an avocado is visible in X-ray images.•The features were extracted by image segmentation and fruit-outline evaluation.•The classification model predicted severe rot for ‘Hass’ avocado fruit.•The model suggests the possibility of the postharvest inspection of avocado fruit.
Osteoclasts have a unique bone-destroying capacity, playing key roles in steady-state bone remodeling and arthritic bone erosion. Whether the osteoclasts in these different tissue settings arise from ...the same precursor states of monocytoid cells is presently unknown. Here, we show that osteoclasts in pannus originate exclusively from circulating bone marrow-derived cells and not from locally resident macrophages. We identify murine CX
CR1
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macrophages (termed here arthritis-associated osteoclastogenic macrophages (AtoMs)) as the osteoclast precursor-containing population in the inflamed synovium, comprising a subset distinct from conventional osteoclast precursors in homeostatic bone remodeling. Tamoxifen-inducible Foxm1 deletion suppressed the capacity of AtoMs to differentiate into osteoclasts in vitro and in vivo. Furthermore, synovial samples from human patients with rheumatoid arthritis contained CX
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CD11c
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cells that corresponded to mouse AtoMs, and human osteoclastogenesis was inhibited by the FoxM1 inhibitor thiostrepton, constituting a potential target for rheumatoid arthritis treatment.
Lung cancer is a common type of cancer that represents a health problem worldwide; lung adenocarcinoma (LUAD) is a major subtype of lung cancer. Although several treatments for LUAD have been ...developed, the mortality rate remains high because of uncontrollable progression. Further biological and clinicopathological studies are therefore needed. Here, we investigated the role of family with sequence similarity 111 member B (FAM111B), which is highly expressed in papillary‐predominant LUAD; however, its role in cancer is unclear. An immunohistochemical analysis confirmed that papillary‐predominant adenocarcinomas exhibited higher expression of FAM111B, compared with lepidic‐predominant adenocarcinomas. Additionally, FAM111B expression was significantly correlated with clinical progression. In vitro functional analyses using FAM111B‐knockout cells demonstrated that FAM111B plays an important role in proliferation and cell cycle progression of KRAS‐driven LUAD under serum‐starvation conditions. Furthermore, FAM111B regulated cyclin D1‐CDK4‐dependent cell cycle progression by degradation of p16. In summary, we revealed the clinical importance of FAM111B in human tumor tissues, as well as its function as a degradative enzyme. Therefore, FAM111B has potential as a clinicopathological prognostic marker for LUAD.
We screened family with sequence similarity 111 member B (FAM111B), the precise functional role of which in cancers is not clear, as the molecule is highly expressed in papillary‐predominant lung adenocarcinoma. Immunohistochemical analysis confirmed that papillary‐predominant adenocarcinoma had higher expression of FAM111B compared with lepidic‐predominant adenocarcinoma, and FAM111B expression levels were significantly correlated with patients’ clinical progression. In vitro functional analyses using FAM111B‐knockout (FAM111B‐KO) cells demonstrated that FAM111B plays an important role in proliferation and cell cycle progression of LUAD with the KRAS mutation, specifically under the conditions of serum starvation, and it was revealed that FAM111B negatively regulates CyclinD1‐CDK4‐dependent cell cycle progression by functioning as a degrading enzyme to control p16 expression level.
To study the influence of crystal orientation on the electrochemical properties of boron-doped diamond (BDD), electrodes comprising (100) and (111) homoepitaxial single-crystal layers of BDD were ...investigated and these were compared with a thin polycrystalline BDD electrode. The BDD samples with similar amounts of boron of around 1020 cm–3 and resistivity of around 6 × 10–3 Ω cm were prepared. Evaluation of the electrochemical reactivity of each of the samples with both H- and O-terminated surfaces showed that polycrystalline BDD was the most reactive, whereas the (111) samples proved to be more reactive than the (100) ones for single-crystal BDD. Moreover, considering the results of first-principles molecular dynamics simulations, it is proposed that surface transfer doping is the dominating factor for H-terminated surfaces, whereas the degree of band bending and the thickness of the space-charge layer are the dominating factors for O-terminated surfaces.
Most patients with Crohn disease (CD), a chronic inflammatory gastrointestinal disease, experience recurrence despite treatment, including surgical resection. However, methods for predicting ...recurrence remain unclear. This study aimed to predict postoperative recurrence of CD by computational analysis of histopathologic images and to extract histologic characteristics associated with recurrence. A total of 68 patients who underwent surgical resection of the intestine were included in this study and were categorized into two groups according to the presence or absence of postoperative disease recurrence within 2 years after surgery. Recurrence was defined using the CD Activity Index and the Rutgeerts score. Whole-slide images of surgical specimens were analyzed using deep learning model EfficientNet-b5, which achieved a highly accurate prediction of recurrence (area under the curve, 0.995). Moreover, subserosal tissue images with adipose cells enabled highly accurate prediction. Adipose cell morphology showed significant between-group differences in adipose cell size, cell-to-cell distance, and cell flattening values. These findings suggest that adipocyte shrinkage is an important histologic characteristic associated with recurrence. Moreover, there was a significant between-group difference in the degree of mast cell infiltration in the subserosa. These findings show the importance of mesenteric adipose tissue in patient prognosis and CD pathophysiology. These findings also suggest that deep learning–based artificial intelligence enables the extraction of meaningful histologic features.
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