• Title/Summary/Keyword: Tumor differentiation

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Multiregion Comprehensive Genomic Profiling of a Gastric Mixed Neuroendocrine-Nonneuroendocrine Neoplasm with Trilineage Differentiation

  • Farooq, Faheem;Zarrabi, Kevin;Sweeney, Keith;Kim, Joseph;Bandovic, Jela;Patel, Chiraag;Choi, Minsig
    • Journal of Gastric Cancer
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    • v.18 no.2
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    • pp.200-207
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    • 2018
  • Mixed neuroendocrine-nonneuroendocrine neoplasms (MiNENs) are a group of rare tumors previously known as mixed adenoneuroendocrine carcinomas (MANECs). The neuroendocrine component is high-grade and may consist of small-cell carcinoma or large-cell neuroendocrine carcinoma. The nonneuroendocrine component may consist of adenocarcinoma or squamous cell carcinoma. We report a unique case of a MiNEN with trilineage differentiation: large-cell neuroendocrine carcinoma, squamous cell carcinoma, and adenocarcinoma. The reported patient presented with symptoms of an upper gastrointestinal bleed and was ultimately diagnosed with a MiNEN with trilineage differentiation. This is the first report of this exceedingly rare tumor type to include next-generation sequencing of the 3 separate tumor entities. In addition, we review the current literature and discuss the role of next-generation sequencing in classifying and treating MiNEN tumors.

Clinicopathological Factors and Gastric Cancer Prognosis in the Iranian Population: a Meta-analysis

  • Somi, Mohammad Hossein;Ghojazadeh, Morteza;Bagheri, Masood;Tahamtani, Taraneh
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.3
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    • pp.853-857
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    • 2015
  • Background: Gastric cancer is the most common cancer in the Iranian population. The aim of this study was to determine the effect of clinicopathological factors on prognosis by meta-analysis. Materials and Methods: A literature search was conducted using MEDLINE, EMBASE and Cochrane library and extensive literature search using the Persian databases until February 2011. Prospective follow up studies with multivariate analysis of overall survival of the patients with gastric cancer were included in this review. The data were analyzed by CMA.2. Publication bias are checked by funnel plot and data are shown as Forest plots. Results: From a total of 63 articles, 14 retrospective studies which examined 5 prognostic factors and involving 10,500 patients were included. Tumor size (>35mm) was the main significant factor predicting an unfavorable prognosis for the patients with gastric cancer (RR=1.829, p<0.001) followed by presence of distant metastases (RR=1.607, p<0.001), poor differentiation (RR=1.408, p<0.001) and male sex (RR=1.194, p<0.001). Lymph node metastases (RR=1.058, p=0.698) and moderate differentiation (RR=0.836, p=0.043) were not statistically significant as prognostic factors. Conclusions: This meta-analysis suggests that tumor size>35mm, poor differentiation, presence of distant metastasis and male gender are strongly associated with a poor prognosis in Iranian patients with gastric cancer.

The Relationship between the Expression of Melanoma Differentiation-Associated Gene-7/Interleukin-24 (MDA-7/IL-24) and Clinicopathological Features in Colorectal Adenocarcinomas

  • Seo, Boram;Hong, Young Seob;Youngmin, Youngmin;Roh, Mee Sook
    • Biomedical Science Letters
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    • v.18 no.4
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    • pp.413-419
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    • 2012
  • The melanoma differentiation-associated gene-7 (MDA-7) protein, also known as interleukin-24 (IL-24), is a novel candidate of tumor suppressor that can induce apoptosis experimentally in a variety of human malignant cells. However, there have been few studies about its role in colorectal cancer. We performed immunohistochemical detection of MDA-7/IL-24 in 399 tissue samples from primary colorectal adenocarcinoma patients using a tissue microarray. Western blotting was then done to confirm the immunohistochemical observations. MDA-7/IL-24 immunoreactivity was observed in 116 (29.1%) of the 399 colorectal adenocarcinoma cases. Analysis of the MDA-7/IL-24 expression by Western blotting confirmed the immunohistochemical results. The tumors with a negative MDA-7/IL-24 expression more frequently showed poor differentiation (P=0004), lymph node metastasis (P=0.001), deep invasion (P=0.008) and high stage (P=0.001). A subset of colorectal adenocarcinoma revealed a decreased expression of MDA-7/IL-24, and this was associated with progressive pathologic features. These findings suggest that loss of MDA-7/IL-24 expression may play a role in tumor growth and progression of colorectal adenocarcinomas.

Isolation and identification of goose skeletal muscle satellite cells and preliminary study on the function of C1q and tumor necrosis factor-related protein 3 gene

  • Wang, Han;He, Ke;Zeng, Xuehua;Zhou, Xiaolong;Yan, Feifei;Yang, Songbai;Zhao, Ayong
    • Animal Bioscience
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    • v.34 no.6
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    • pp.1078-1087
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    • 2021
  • Objective: Skeletal muscle satellite cells (SMSCs) are significant for the growth, regeneration, and maintenance of skeletal muscle after birth. However, currently, few studies have been performed on the isolation, culture and inducing differentiation of goose muscle satellite cells. Previous studies have shown that C1q and tumor necrosis factor-related protein 3 (CTRP3) participated in the process of muscle growth and development, but its role in the goose skeletal muscle development is not yet clear. This study aimed to isolate, culture, and identify the goose SMSCs in vitro. Additionally, to explore the function of CTRP3 in goose SMSCs. Methods: Goose SMSCs were isolated using 0.25% trypsin from leg muscle (LM) of 15 to 20 day fertilized goose eggs. Cell differentiation was induced by transferring the cells to differentiation medium with 2% horse serum and 1% penicillin streptomycin. Immunofluorescence staining of Desmin and Pax7 was used to identify goose SMSCs. Quantitative realtime polymerase chain reaction and western blot were applied to explore developmental expression profile of CTRP3 in LM and the regulation of CTRP3 on myosin heavy chains (MyHC), myogenin (MyoG) expression and Notch signaling pathway related genes expression. Results: The goose SMSCs were successfully isolated and cultured. The expression of Pax7 and Desmin were observed in the isolated cells. The expression of CTRP3 decreased significantly during leg muscle development. Overexpression of CTRP3 could enhance the expression of two myogenic differentiation marker genes, MyHC and MyoG. But knockdown of CTRP3 suppressed their expression. Furthermore, CTRP3 could repress the mRNA level of Notch signaling pathway-related genes, notch receptor 1, notch receptor 2 and hairy/enhancer-of-split related with YRPW motif 1, which previously showed a negative regulation in myoblast differentiation. Conclusion: These findings provide a useful cell model for the future research on goose muscle development and suggest that CTRP3 may play an essential role in skeletal muscle growth of goose.

Esophageal GIST : case report (하부식도에서 발생한 GIST 1예)

  • 이상훈;오창권;이기석;조영업;김경래
    • Korean Journal of Bronchoesophagology
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    • v.9 no.1
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    • pp.87-91
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    • 2003
  • Currently gastrointestinal mesenchymal tumors are divided into three major categories: myogenic tumors(leiomyoma, leiomyosarcoma), neurogenic tumors (schwannomas) and neoplasms that belong to neither group, which are known by GIST(gastrointestinal stromal tumors). The stromal tumors are hetrogenous, so that they may show myogenic or neurogenic differentiation or both, or no differentiation at all in some patients. The best defining feature for GIST is their expression of KIT-protein(CD117). Leiomyomas are the most common mesenchymal tumor in esophagus. Esophageal GISTS are very rare in comparision to those of the stomach and intestine. Recently we experieneced one case of the esophageal GIST, so that we describe an esophageal GIST on immunohistochemical analysis. A 70 years old woman complained of dysphagia and nausea for 3 days. FGS showed a huge elevated lesion in lower esophagus 33cm distal to incisor, which was covered with normal mucosa. CT and UGI showed the intramural tumor of lower third of the esophagus. The distal esophagectomy and esophago-gastrostomy were performed. The tumor was located in lower third of esophagus and measured as $6{\times}3.7$cm in size. Immunohistochemically, it showed weakly positive CD117 and diffusely positive S-100. SMA, desmin, NES and chromogranin showed negative immune-reaction. The patient was followed for 15 month after operation. There was no recurrence.

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Expression of Bone Morphogenetic Protein-2 and Histological Differentiation of Oral Squamous Cell Carcinomas

  • Hamasni, Fatme Mouchref;El Hajj, Fady
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.12
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    • pp.5243-5245
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    • 2016
  • Background and Objective : Bone morphogenic protein-2 (BMP-2) plays an essential role in mesenchymal cell differentiation into osteoblasts، through many intracellular pathways which may also be active in tumors. Invasive oral squamous cell carcinomas account for more than 90% of head and neck malignancies in many cancer registries. They are classified into three types according to epithelial cell differentiation. The present study aimed to identify any relation between BMP-2 expression and tumor histology. Materials and methods: BMP-2 expression was compared immunohistochemically among 30 cases (19 male and 11 female, mean age 48 years) of oral squamous cell carcinoma, Division was into 3 groups (each containing 10 cases) according to the histological grade. Results: No significant correlation between BMP-2 expression and histological grade was observed. Changes in localization and cytoplasmic staining were also not apparent. Conclusion: From the results of this study BMP-2 does not appear to have any application as a prognostic marker for oral squamous cell carcinomas.

Low-dose metronomic doxorubicin inhibits mobilization and differentiation of endothelial progenitor cells through REDD1-mediated VEGFR-2 downregulation

  • Park, Minsik;Kim, Ji Yoon;Kim, Joohwan;Lee, Jeong-Hyung;Kwon, Young-Guen;Kim, Young-Myeong
    • BMB Reports
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    • v.54 no.9
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    • pp.470-475
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    • 2021
  • Low-dose metronomic chemotherapy has been introduced as a less toxic and effective strategy to inhibit tumor angiogenesis, but its anti-angiogenic mechanism on endothelial progenitor cells (EPCs) has not been fully elucidated. Here, we investigated the functional role of regulated in development and DNA damage response 1 (REDD1), an endogenous inhibitor of mTORC1, in low-dose doxorubicin (DOX)-mediated dysregulation of EPC functions. DOX treatment induced REDD1 expression in bone marrow mononuclear cells (BMMNCs) and subsequently reduced mTORC1-dependent translation of endothelial growth factor (VEGF) receptor (Vegfr)-2 mRNA, but not that of the mRNA transcripts for Vegfr-1, epidermal growth factor receptor, and insulin-like growth factor-1 receptor. This selective event was a risk factor for the inhibition of BMMNC differentiation into EPCs and their angiogenic responses to VEGF-A, but was not observed in Redd1-deficient BMMNCs. Low-dose metronomic DOX treatment reduced the mobilization of circulating EPCs in B16 melanoma-bearing wild-type but not Redd1-deficient mice. However, REDD1 overexpression inhibited the differentiation and mobilization of EPCs in both wild-type and Redd1-deficient mice. These data suggest that REDD1 is crucial for metronomic DOX-mediated EPC dysfunction through the translational repression of Vegfr-2 transcript, providing REDD1 as a potential therapeutic target for the inhibition of tumor angiogenesis and tumor progression.

Stimulation of Osteogenic Differentiation in Stromal Cells of Giant Cell Tumour of Bone by Zoledronic Acid

  • Yang, Tao;Zheng, Xiao-Fei;Li, Mei;Lin, Xi;Yin, Qing-Shui
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.9
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    • pp.5379-5383
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    • 2013
  • Therapeutic effects of zoledronic acid (ZOL) on giant cell tumour of bone (GCT) have been proven. Apoptosis induction was considered to be one of the mechanisms of ZOL tumour inhibition. In this study, we presented the possibility of an osteogenic differentiation stimulation mechanism of ZOL and further investigated dosage and time effects. We treated stromal cells of GCT (GCTSC) with ZOL for 48 hours at different concentrations ($0{\mu}M$, $0.01{\mu}M$, $0.1{\mu}M$, $1{\mu}M$, 5${\mu}M$, $30{\mu}M$) and assessed apoptotic and osteogenic differentiation markers with immunohistochemical techniques and real-time quantitative RT-PCR. Our results suggested that ZOL enhanced mRNA expression of Cbfa-1, osterix and osteocalcin genes with a maximum effect at $1{\mu}M$ in GCTSC. Time course experiments indicated a time dependent osteogenic differentiation effect. In conclusion, ZOL may be considered as an adjuvant in the treatment of GCT not only by inducing apoptosis but also by stimulating osteogenic differentiation of remaining tumor stromal cells after surgery.

Metastasis via Peritumoral Lymphatic Dilation in Oral Squamous Cell Carcinoma

  • Kim, Han-Seok;Park, Young-Wook
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.36 no.3
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    • pp.85-93
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    • 2014
  • Purpose: Nodal metastasis is the main prognostic factor in the patients with oral squamous cell carcinoma (OSCC). We investigated the association between tumor-associated lymphatics and OSCC characteristics. Methods: Thirty-four specimens were used for the immunohistochemical staining with the antibody for vascular endothelial growth factor (VEGF)-C, VEGF-D, VEGF receptor (VEGFR)-3, phosphorylated VEGFR-3, D2-40, and matrix metallproteinases (MMPs). We observed the distribution of the lymphangiogenic factors and quantified the degree of expression. We determined lymphatic vessel density (LVD) and lymphatic vessel dilatation with D2-40 immunostaining. We assessed the association of LVD or lymphatic vessel dilatation with tumor progression or tumor differentiation. Results: OSCC cells expressed lymphangiogenic ligands. Lymphangiogenic receptor, VEGFR-3, was expressed and activated in some tumor cells as well as in tumor-associated endothelial cells. LVD was not associated with tumor size or nodal status, but lymphatic vessel dilatation was higher in tumors with nodal metastasis, and also higher in poorly differentiated tumors. In stromal area of OSCC, MMP-1 and MMP-10 were up-regulated and the basement membrane of tumor-associated endothelial cells was destroyed by these collagenases. Conclusion: In the primary tumors with nodal metastasis, especially in poorly differentiated OSCC, tumor cells invaded the dilated lymphatic vessels via ruptured sites. MMP-1 and MMP-10 are important in the lysis of the glycocalyx inside the tumor-associated lymphatic endothelial cells.

A Case of Huge Liposarcoma in Thigh (사지에 발생한 거대 지방육종)

  • Kang, Shin-Taek;Hwang, Tae-Hyok;Park, Boem-Soek;Kim, Tae-Jung;Shin, Hwang-Mi
    • The Journal of the Korean bone and joint tumor society
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    • v.14 no.2
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    • pp.192-197
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    • 2008
  • It is well understood that liposarcoma is most common in soft tissue sarcomas. It usually develop proximally in the extremities and most patients are older than 50 years. We report a case of huge liposarcoma which develop on left thigh of 67-year-old man. There was no evidence of metastasis and the tumor was successfully removed by marginal resection. Patient's height is 153 cm and weight is 43 kg, but the tumor's size is $34{\times}20{\times}9\;cm$ and weight is 2.82 kg. The Mass is severely huge in compare with patient's height and weight. But, There are few reports regarding the correlation between tumor-size and pathologic differentiation. Pathological examination reveals a well differentiated liposarcoma. The patient is still asymptomatic at 6-months follow up.

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