Dysregulation of PI3K/Akt/PTEN Pathway in Canine Mammary Tumor

Abstract Background: Malignant proliferation and chemotherapy resistance are some of the causes of high mortality in pancreatic cancer. MicroRNAs have long been a hot spot in cancer research and are involved in tumor formation and metabolic stress responses. miR-489-3p is involved in inhibiting the growth of many tumors, but its relationship with the growth and metabolism of pancreatic cancer is not clear. Methods：We used RNA in situ hybridization to analyze the differential expression of miR-489-3p in pancreatic cancer tissues and adjacent tissues. The qRT-PCR experiment detected the content of miR-489-3p in pancreatic cancer cell lines and ordinary pancreatic ductal epithelial cells. Then we did experiments in vivo (subcutaneous tumor formation in nude mice) and in vitro (plate cloning, transwell, glycolysis related experiments) experiments to verify that miR-489-3p can continue the invasion and metastasis of pancreatic cancer and glucose metabolism. Furthermore, we confirmed that LDHA and PKM2 are the two targets of miR-489-3p through dual luciferase reporter gene experiments. Finally, several reply experiments were done to verify the regulation mechanism of miR-489-3p.Results: We determined that miR-489-3p is under-expressed in pancreatic cancer tissues by RNA in situ hybridization, and the function acquisition and deletion experiments and glycolysis experiments confirmed that miR-489-3p can inhibit the proliferation and invasion of Glycolysis. We then analyzed the website to find that miR-489-3p can target LDHA and PKM, and then we verified this finding with a luciferase report experiment. Therefore, we proceeded with recovery experiments on LDHA and PKM2, and concluded that miR-489-3p performs its function by targeting LDHA and PKM2. Finally, in vivo experiments confirmed that highly expressed miR-489-3p inhibited the growth of pancreatic cancer. Conclusion: In short, we identified miR-489-3p as a novel chemotherapy target for pancreatic cancer, and its diagnostic value deserves further study.

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Whole-Exome Sequencing Analysis of the Progression from Non–Low-Grade Ductal Carcinoma In Situ to Invasive Ductal Carcinoma

Clinical Cancer Research ◽

10.1158/1078-0432.ccr-19-2563 ◽

2020 ◽

Vol 26 (14) ◽

pp. 3682-3693 ◽

Cited By ~ 3

Author(s):

Fresia Pareja ◽

David N. Brown ◽

Ju Youn Lee ◽

Arnaud Da Cruz Paula ◽

Pier Selenica ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Invasive Ductal Carcinoma ◽

Ductal Carcinoma In Situ ◽

Carcinoma In Situ ◽

Ductal Carcinoma ◽

Low Grade ◽

Sequencing Analysis ◽

Whole Exome

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Thyroid-Like Low-Grade Nasopharyngeal Papillary Adenocarcinoma

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqz082 ◽

2019 ◽

Vol 152 (5) ◽

pp. 582-589 ◽

Cited By ~ 1

Author(s):

Fengbo Huang ◽

Xueping Xiang ◽

Bo Hong ◽

Jie Min ◽

Jinfan Li

Keyword(s):

Hot Spot ◽

Gene Mutations ◽

Papillary Adenocarcinoma ◽

Morphological Characterization ◽

Low Grade ◽

Ki 67 ◽

Appropriate Treatment ◽

Rule Out

Abstract Objectives Thyroid-like low-grade nasopharyngeal papillary adenocarcinoma (TLLGNPPA) is a relatively rare nasopharyngeal tumor. We performed morphological characterization, immunohistochemical profiling, and investigated gene mutations. We also provide clinical follow-up data and brief review of the literature. Methods Immunohistochemistry was used to evaluate the expression of TTF-1, CK19, CK7, EMA, TG, Pax-8, CK5/6, S100, and Ki-67. Additionally, in situ hybridization was utilized to identify the presence of EBV. We investigated mutations in hot-spot exons of KRAS/NRAS/BRAF to rule out common mutations seen in thyroid tumors. Results Histopathologic examination of four cases identified tumors that were mainly occupied by papillary architectures. One case had a predominantly glandular structure. The tumors expressed TTF-1 and CK19, while TG and Pax-8 were negative. S100 was moderately expressed focally in three cases. Conclusions While TLLGNPPA displays a morphological resemblance to papillary thyroid carcinoma (PTC), it is vital to differentiate nasopharyngeal metastasis from PTC for appropriate treatment.

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Bovine Papillomavirus 1 Gets Out of the Flock: Detection in an Ovine Wart in Sicily

Pathogens ◽

10.3390/pathogens9060429 ◽

2020 ◽

Vol 9 (6) ◽

pp. 429 ◽

Cited By ~ 2

Author(s):

Federica Savini ◽

Laura Gallina ◽

Alice Prosperi ◽

Roberto Puleio ◽

Antonio Lavazza ◽

...

Keyword(s):

Bovine Papillomavirus ◽

Sequencing Analysis ◽

Test Results ◽

Macroscopic Classification ◽

Next Generation Sequencing Analysis ◽

Rna In Situ Hybridization ◽

Negative Staining Electron Microscopy

A proliferative cauliflower lesion was excised from the udder of a sheep. Histological investigation confirmed the macroscopic classification of the lesion as a papilloma, without any fibroblastic proliferation. PCR revealed the presence of bovine papillomavirus (BPV), which was further confirmed by the identification of a Deltapapillomavirus 4 by Next Generation Sequencing analysis. This was subsequently classified as bovine papillomavirus type 1. Negative staining electron microscopy (EM) analyses produced negative test results for papillomavirus particles. RNA in situ hybridization (ISH) confirmed the presence of BPV-1. The results further confirm the ability of BPVs belonging to the Deltapapillomavirus genus to infect distantly related species and to cause lesions that are different from sarcoids.

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MiR-489-3p reduced pancreatic cancer proliferation and metastasis by targeting PKM2 and LDHA involving glycolysis

10.21203/rs.3.rs-58138/v2 ◽

2020 ◽

Author(s):

Dan Zhang ◽

zhiwei He ◽

Yiyi Shen ◽

Jie wang ◽

Tao Liu ◽

...

Keyword(s):

Pancreatic Cancer ◽

In Situ Hybridization ◽

Hot Spot ◽

Tumor Formation ◽

Luciferase Reporter ◽

Regulation Mechanism ◽

Rna In Situ Hybridization ◽

Cancer Tissues

Abstract Background: Malignant proliferation and chemotherapy resistance are some of the causes of high mortality in pancreatic cancer. MicroRNAs have long been a hot spot in cancer research and are involved in tumor formation and metabolic stress responses. miR-489-3p is involved in inhibiting the growth of many tumors, but its relationship with the growth and metabolism of pancreatic cancer is not clear. Methods：We used RNA in situ hybridization to analyze the differential expression of miR-489-3p in pancreatic cancer tissues and adjacent tissues. The qRT-PCR experiment detected the content of miR-489-3p in pancreatic cancer cell lines and ordinary pancreatic ductal epithelial cells. Then we did experiments in vivo (subcutaneous tumor formation in nude mice) and in vitro (plate cloning, transwell, glycolysis related experiments) experiments to verify that miR-489-3p can continue the invasion and metastasis of pancreatic cancer and glucose metabolism. Furthermore, we confirmed that LDHA and PKM2 are the two targets of miR-489-3p through dual luciferase reporter gene experiments. Finally, several reply experiments were done to verify the regulation mechanism of miR-489-3p.Results: We determined that miR-489-3p is under-expressed in pancreatic cancer tissues by RNA in situ hybridization, and the function acquisition and deletion experiments and glycolysis experiments confirmed that miR-489-3p can inhibit the proliferation and invasion of Glycolysis. We then analyzed the website to find that miR-489-3p can target LDHA and PKM, and then we verified this finding with a luciferase report experiment. Therefore, we proceeded with recovery experiments on LDHA and PKM2, and concluded that miR-489-3p performs its function by targeting LDHA and PKM2. Finally, in vivo experiments confirmed that highly expressed miR-489-3p inhibited the growth of pancreatic cancer. Conclusion: In short, we identified miR-489-3p as a novel chemotherapy target for pancreatic cancer, and its diagnostic value deserves further study.

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MiR-489-3p reduced pancreatic cancer proliferation and metastasis by targeting PKM2 and LDHA involving glycolysis

10.21203/rs.3.rs-58138/v3 ◽

2020 ◽

Author(s):

Dan Zhang ◽

zhiwei He ◽

Yiyi Shen ◽

Jie wang ◽

Tao Liu ◽

...

Keyword(s):

Pancreatic Cancer ◽

In Situ Hybridization ◽

Hot Spot ◽

Tumor Formation ◽

Luciferase Reporter ◽

Regulation Mechanism ◽

Rna In Situ Hybridization ◽

Cancer Tissues

Abstract Background: Malignant proliferation and chemotherapy resistance are some of the causes of high mortality in pancreatic cancer. MicroRNAs have for a long period been a hot spot in cancer research and are involved in tumor formation and metabolic stress responses. miR-489-3p is involved in the inhibition of the growth of many tumors. However, its relationship with the growth and metabolism of pancreatic cancer is not clear.Methods：We used RNA in situ hybridization to analyze the differential expression of miR-489-3p in pancreatic cancer tissues and adjacent tissues. The qRT-PCR experiment detected the content of miR-489-3p in pancreatic cancer cell lines and ordinary pancreatic ductal epithelial cells. Then we did experiments in vivo (subcutaneous tumor formation in nude mice) and in vitro (plate cloning, transwell, glycolysis related experiments) experiments to verify that miR-489-3p can continue the invasion and metastasis of pancreatic cancer and glucose metabolism. Furthermore, we confirmed that LDHA and PKM2 are the two targets of miR-489-3p through dual luciferase reporter gene experiments. Finally, several reply experiments were done to verify the regulation mechanism of miR-489-3p.Results: We determined that miR-489-3p was under-expressed in pancreatic cancer tissues by RNA in situ hybridization. The function acquisition and deletion and glycolysis experiments confirmed that miR-489-3p could inhibit the proliferation and invasion of Glycolysis. On the analysis of the website, we found that miR-489-3p could target LDHA and PKM, a finding that we verified through the luciferase report experiment. Therefore, we proceeded with recovery experiments on LDHA and PKM2 and concluded that miR-489-3p performed its function by targeting LDHA and PKM2. Finally, in vivo experiments confirmed that highly expressed miR-489-3p inhibited the growth of pancreatic cancer.Conclusion: In short, this study has identified miR-489-3p as a novel chemotherapy target for pancreatic cancer, but its diagnostic value deserves further study.

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Intra-Cystic (In Situ) Mucoepidermoid Carcinoma: A Clinico-Pathological Study of 14 Cases

Journal of Clinical Medicine ◽

10.3390/jcm9041157 ◽

2020 ◽

Vol 9 (4) ◽

pp. 1157

Author(s):

Saverio Capodiferro ◽

Giuseppe Ingravallo ◽

Luisa Limongelli ◽

Mauro Mastropasqua ◽

Angela Tempesta ◽

...

Keyword(s):

Alcian Blue ◽

Tumor Invasion ◽

Conservative Surgery ◽

Low Grade ◽

Mucin Production ◽

Cystic Component ◽

Early Growth Phase ◽

Hematoxylin Eosin

Aims: To report on the clinico-pathological features of a series of 14 intra-oral mucoepidermoid carcinomas showing exclusive intra-cystic growth. Materials and methods: All mucoepidermoid carcinomas diagnosed in the period 1990–2012 were retrieved; the original histological preparations were reviewed to confirm the diagnosis and from selected cases, showing exclusive intra-cystic neoplastic components, additional sections were cut at three subsequent 200 m intervals and stained with Hematoxylin–Eosin, PAS, Mucicarmine and Alcian Blue, to possibly identify tumor invasion of the adjacent tissues, which could have been overlooked in the original histological preparations. Additionally, pertinent findings collected from the clinical charts and follow-up data were analyzed. Results: We identified 14 intraoral mucoepidermoid carcinomas treated by conservative surgery and with a minimum follow up of five years. The neoplasms were located in the hard palate (nine cases), the soft palate (two), the cheek (two) and the retromolar trigone (one). In all instances, histological examination revealed the presence of a single cystic space, containing clusters of columnar, intermediate, epidermoid, clear and mucous-producing cells, the latter exhibiting distinct intra-cytoplasmic mucin production, as confirmed by PAS, Mucicarmine and Alcian Blue stains. The cysts were entirely circumscribed by fibrous connective tissue, and no solid areas or infiltrating tumor cell clusters were detected. Conservative surgical resection was performed in all cases, and no recurrences or nodal metastases were observed during follow up. Conclusions: Mucoepidermoid carcinomas showing prominent (>20%) intra-cystic proliferation currently are considered low-grade tumors. In addition, we also unveil the possibility that mucoepidermoid carcinomas, at least in their early growth phase, may display an exclusive intra-cystic component and might be considered as in situ carcinomas, unable to infiltrate adjacent tissues and metastasize.

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In situ differentiation of iridophore crystallotypes underlies zebrafish stripe patterning

Nature Communications ◽

10.1038/s41467-020-20088-1 ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Dvir Gur ◽

Emily J. Bain ◽

Kory R. Johnson ◽

Andy J. Aman ◽

H. Amalia Pasoili ◽

...

Keyword(s):

Skin Color ◽

Cell Types ◽

Color Pattern ◽

Single Type ◽

Sequencing Analysis ◽

X Ray Diffraction ◽

X Ray ◽

Cryogenic Scanning Electron Microscopy ◽

Different Cell Types

AbstractSkin color patterns are ubiquitous in nature, impact social behavior, predator avoidance, and protection from ultraviolet irradiation. A leading model system for vertebrate skin patterning is the zebrafish; its alternating blue stripes and yellow interstripes depend on light-reflecting cells called iridophores. It was suggested that the zebrafish’s color pattern arises from a single type of iridophore migrating differentially to stripes and interstripes. However, here we find that iridophores do not migrate between stripes and interstripes but instead differentiate and proliferate in-place, based on their micro-environment. RNA-sequencing analysis further reveals that stripe and interstripe iridophores have different transcriptomic states, while cryogenic-scanning-electron-microscopy and micro-X-ray diffraction identify different crystal-arrays architectures, indicating that stripe and interstripe iridophores are different cell types. Based on these results, we present an alternative model of skin patterning in zebrafish in which distinct iridophore crystallotypes containing specialized, physiologically responsive, organelles arise in stripe and interstripe by in-situ differentiation.

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Overexpression of Mucin 1 Suppresses the Therapeutical Efficacy of Disulfiram against Canine Mammary Tumor

Animals ◽

10.3390/ani11010037 ◽

2020 ◽

Vol 11 (1) ◽

pp. 37

Author(s):

Ying Zhao ◽

Zixiang Lin ◽

Zhaoyan Lin ◽

Chaoyu Zhou ◽

Gang Liu ◽

...

Keyword(s):

Mammary Tumor ◽

Mammary Tumors ◽

Expression Level ◽

Canine Mammary Tumor ◽

Wild Type ◽

Mucin 1 ◽

Mammary Tumor Cell ◽

Mammary Tumor Cell Line ◽

Canine Mammary Tumors ◽

Wild Type Control

Mucin 1 (MUC1), a transmembrane protein, is closely associated with the malignancy and metastasis of canine mammary tumors; however, the role of overexpressed MUC1 in the development of cancer cells and response to drug treatment remains unclear. To address this question, we developed a new canine mammary tumor cell line, CIPp-MUC1, with an elevated expression level of MUC1. In vitro studies showed that CIPp-MUC1 cells are superior in proliferation and migration than wild-type control, which was associated with the upregulation of PI3K, p-Akt, mTOR, Bcl-2. In addition, overexpression of MUC1 in CIPp-MUC1 cells inhibited the suppressing activity of disulfiram on the growth and metastasis of tumor cells, as well as inhibiting the pro-apoptotic effect of disulfiram. In vivo studies, on the other side, showed more rapid tumor growth and stronger resistance to disulfiram treatment in CIPp-MUC1 xenograft mice than in wild-type control. In conclusion, our study demonstrated the importance of MUC1 in affecting the therapeutical efficiency of disulfiram against canine mammary tumors, indicating that the expression level of MUC1 should be considered for clinical use of disulfiram or other drugs targeting PI3K/Akt pathway.

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