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https://www.readbyqxmd.com/read/28731148/molecular-genetics-and-targeted-therapy-of-wnt-related-human-diseases-review
#1
Masuko Katoh, Masaru Katoh
Canonical WNT signaling through Frizzled and LRP5/6 receptors is transduced to the WNT/β-catenin and WNT/stabilization of proteins (STOP) signaling cascades to regulate cell fate and proliferation, whereas non-canonical WNT signaling through Frizzled or ROR receptors is transduced to the WNT/planar cell polarity (PCP), WNT/G protein-coupled receptor (GPCR) and WNT/receptor tyrosine kinase (RTK) signaling cascades to regulate cytoskeletal dynamics and directional cell movement. WNT/β-catenin signaling cascade crosstalks with RTK/SRK and GPCR-cAMP-PKA signaling cascades to regulate β-catenin phosphorylation and β-catenin-dependent transcription...
July 19, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28731132/mir-374-mediates-the-malignant-transformation-of-gastric-cancer-associated-mesenchymal-stem-cells-in-an-experimental-rat-model
#2
Runbi Ji, Xu Zhang, Hui Qian, Hongbing Gu, Zixun Sun, Fei Mao, Yongmin Yan, Jingyan Chen, Zhaofeng Liang, Wenrong Xu
Mesenchymal stem cells (MSCs) are a critical component of the tumor microenvironment. Upon distinct pathological stimulus, MSCs show phenotypic and functional changes. Gastric cancer is one of the leading causes of cancer‑related deaths worldwide. The roles and mechanisms of MSCs in gastric cancer have not been well characterized. In the present study, we investigated the roles of MSCs in the malignant transformation from gastritis to gastric cancer using an N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric cancer model...
July 18, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28721818/eurycoma-longifolia-a-potential-phytomedicine-for-the-treatment-of-cancer-evidence-of-p53-mediated-apoptosis-in-cancerous-cells
#3
Hnin Ei Thu, Zahid Hussain, Isa Naina Mohamed, Ahmad Nazrun Shuid
BACKGROUND: Eurycoma longifolia is a well-documented herbal medicine that has gained widespread recognition due to its versatile pharmacological activities including anticancer, anti-malarial, antimicrobial, antioxidant, aphrodisiac, anti-inflammatory, anxiolytic, anti-diabetic, anti-rheumatism and anti-ulcer. Plethora of in vitro and in vivo studies evidenced their excellent anti-proliferative and anticancer efficacy against various types of human cancers. OBJECTIVE: This review was aimed to critically analyze the therapeutic viability and anticancer efficacy of Eurycoma longifolia in the treatment of cancer and also to propose its molecular and translational mechanism of cytotoxicity against cancerous cells...
July 18, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28707966/targeted-molecular-ablation-of-cancer-stem-cells-for-curing-gastrointestinal-cancers
#4
Yong Seok Kim, Ho Jae Lee, Jong-Min Park, Young-Min Han, Napapan Kangwan, Ji Young Oh, Dong Yoon Lee, Ki Baik Hahm
Abundance of the ATPase-binding cassette (ABC) transporters and deranged self-renewal pathways characterize the presence of cancer stem cells (CSCs) in gastrointestinal cancers (GI cancers), which play crucial roles in tumorigenesis, chemotherapy resistance, tumor recurrence, and cancer metastasis. Therefore, in order to ensure high cure rates, chemoquiescence, CSCs should be ablated. Recent advances in either understanding CSCs or biomarker identification enable scientists to develop techniques for ablating CSCs and clinicians to provide cancer cure, especially in GI cancers characterized by inflammation-driven carcinogenesis...
July 14, 2017: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28693796/regulatory-effects-of-berberine-on-micrornome-in-cancer-and-other-conditions
#5
REVIEW
Seyed Hasan Ayati, Badrieh Fazeli, Amir Abbas Momtazi-Borojeni, Arrigo F G Cicero, Matteo Pirro, Amirhossein Sahebkar
Berberine (BBR) is an isoquinoline alkaloid found in different plant families such as Berberidaceae, Ranunculaceae, and Papaveraceae. BBR is well-known for its anti-inflammatory, lipid-modifying, anticancer, anti-diabetic, antibacterial, antiparasitic and fungicide activities. Multiple pharmacological actions of BBR stem from different molecular targets of this phytochemical. MicroRNAs (miRs) are single-stranded, evolutionary conserved, small non-coding RNA molecules with a length of 19-23 nucleotides that are involved in RNA silencing and post-transcriptional regulation of gene expression through binding to the 3'-untranslated region (3'UTR) of target mRNA...
August 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28692437/codelivery-of-salinomycin-and-docetaxel-using-poly-d-l-lactic-co-glycolic-acid-poly-ethylene-glycol-nanoparticles-to-target-both-gastric-cancer-cells-and-cancer-stem-cells
#6
Lan Li, Dejun Cui, Limin Ye, Yu Li, Liyi Zhu, Lanqun Yang, Banjun Bai, Zhao Nie, Jie Gao, Yu Cao
Cancer stem cells (CSCs) in gastric cancer (GC) have been established recently as key therapeutic targets for the successful treatment of GC. Emerging evidence suggests that both CSCs and cancer cells should be eradicated to achieve optimal therapeutic efficacy. In the present study, salinomycin, which has been reported to kill CSCs, was used in combination with docetaxel, a chemotherapeutic drug that is used as first-line therapy in GC, to eradicate both GC stem cells (SCs) and cancer cells. Salinomycin and docetaxel were loaded separately into poly(D,L-lactic-co-glycolic acid)-poly(ethylene glycol) nanoparticles of ∼140 nm with a narrow size distribution, high drug loading, and sustained drug release...
July 7, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28659641/lgr5-joins-the-club-of-gastric-stem-cell-markers-in-the-corpus
#7
Toby J Phesse, Owen J Sansom
Several markers of gastric stem cells have been identified in recent years. Now a study demonstrates that Lgr5 marks a population of reserve stem cells located at the base of the corpus glands of the gastric epithelium, and that these cells can also act as a cell-of-origin for gastric tumorigenesis.
June 29, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28649475/solid-pseudopapillary-tumor-of-the-pancreas-an-unusual-cause-of-abdominal-pain
#8
Talal El Imad, Fady G Haddad, Mayurathan Kesavan, Liliane Deeb, Sherif Andrawes
Solid-pseudopapillary neoplasm (SPN) of the pancreas is a rare tumor that accounts for less than one percent of pancreatic tumors. The diagnosis could be challenging as SPN tend to manifest with nonspecific abdominal symptoms, variable radiological features, and inconsistent morphology. The cellular origin of SPN is unclear and might involve ductal, acinar and endocrine stem cells.  We report a rare case of a 27-year-old female who presented with intermittent abdominal pain for two years, associated with a decrease in appetite...
May 16, 2017: Curēus
https://www.readbyqxmd.com/read/28648364/differentiation-of-human-pluripotent-stem-cells-into-colonic-organoids-via-transient-activation-of-bmp-signaling
#9
Jorge O Múnera, Nambirajan Sundaram, Scott A Rankin, David Hill, Carey Watson, Maxime Mahe, Jefferson E Vallance, Noah F Shroyer, Katie L Sinagoga, Adrian Zarzoso-Lacoste, Jonathan R Hudson, Jonathan C Howell, Praneet Chatuvedi, Jason R Spence, John M Shannon, Aaron M Zorn, Michael A Helmrath, James M Wells
Gastric and small intestinal organoids differentiated from human pluripotent stem cells (hPSCs) have revolutionized the study of gastrointestinal development and disease. Distal gut tissues such as cecum and colon, however, have proved considerably more challenging to derive in vitro. Here we report the differentiation of human colonic organoids (HCOs) from hPSCs. We found that BMP signaling is required to establish a posterior SATB2+ domain in developing and postnatal intestinal epithelium. Brief activation of BMP signaling is sufficient to activate a posterior HOX code and direct hPSC-derived gut tube cultures into HCOs...
July 6, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28642169/a-novel-method-to-quantify-base-substitution-mutations-at-the-10-6-per-bp-level-in-dna-samples
#10
Satoshi Yamashita, Naoko Iida, Hideyuki Takeshima, Naoko Hattori, Masahiro Maeda, Takayoshi Kishino, Reiko Nagano, Taichi Shimazu, Shoichiro Tsugane, Toshikazu Ushijima
Somatic base substitution mutations of frequencies at the 10(-6)/bp level are expected to be present in many biomedical samples, such as tissues exposed to carcinogenic factors and exhausted stem cells. However, measurement of such rare mutations has been very difficult in human DNA samples. Here, we invented the use of 100 copies of genomic DNA as a template for amplicon deep sequencing so that a real mutation in a single DNA molecule would be detected at a variant allele frequency of 1% while sequencing errors have less frequency...
June 19, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28621241/hedgehog-signaling-pathway-as-a-potential-target-in-the-treatment-of-advanced-gastric-cancer
#11
Dae-Hee Lee, Suk-Young Lee, Sang Cheul Oh
The sonic hedgehog signaling pathway is critical for cell proliferation, cell differentiation, and organ development during embryogenesis. Aberrant activation of the sonic hedgehog pathway has been associated with a variety of human cancers. Currently, there is no target molecular drug that clinically affects sonic hedgehog activation in patients with gastric cancer. In this review, we will focus on the current clinical treatment options for advanced gastric cancer and discuss the sonic hedgehog signaling pathway...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28615312/stem-cells-in-repair-of-gastrointestinal-epithelia
#12
REVIEW
Amanda Andersson-Rolf, Matthias Zilbauer, Bon-Kyoung Koo, Hans Clevers
Among the endodermal tissues of adult mammals, the gastrointestinal (GI) epithelium exhibits the highest turnover rate. As the ingested food moves along the GI tract, gastric acid, digestive enzymes, and gut resident microbes aid digestion as well as nutrient and mineral absorption. Due to the harsh luminal environment, replenishment of new epithelial cells is essential to maintain organ structure and function during routine turnover and injury repair. Tissue-specific adult stem cells in the GI tract serve as a continuous source for this immense regenerative activity...
July 2017: Physiology
https://www.readbyqxmd.com/read/28611977/clinicopathology-of-early-gastric-carcinoma-an-update-for-pathologists-and-gastroenterologists
#13
REVIEW
Qin Huang, Xiaoping Zou
BACKGROUND: The WHO defines early gastric carcinoma (EGC) as invasive carcinoma up to the submucosal layer, regardless of nodal metastasis. The recent study results indicate that EGC varies in location, histology, nodal metastasis, and prognosis. SUMMARY: The heterogeneity in EGC may be related to various types of epithelial stem cells. The most important stem cells include Lgr5(+) cells at the base of a gastric unit in the antrum-pylorus-cardia, Mist1(+) cells at the isthmus/Troy(+) cells at the base in the corpus-fundus, and Sox2(+) cells at the base in almost all regions...
March 2017: Gastrointestinal Tumors
https://www.readbyqxmd.com/read/28600348/loss-of-the-wnt-receptor-frizzled7-in-the-gastric-epithelium-is-deleterious-and-triggers-rapid-repopulation-in-vivo
#14
Dustin J Flanagan, Nicholas Barker, Cameron Nowell, Hans Clevers, Matthias Ernst, Toby J Phesse, Elizabeth Vincan
The gastric epithelium consists of tubular glandular units each containing several differentiated cells types, and populations of stem cells, which enable the stomach to secrete the acid, mucus and various digestive enzymes required for its function. Cell signalling provides cues to regulate development and homeostasis of adult tissues, however very little is known about which cell signalling pathways are required for homeostasis of the gastric epithelium. Many diseases, such as cancer, arise as a result of deregulation to signalling pathways that regulate homeostasis of the diseased organ...
June 9, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28599471/mir-200b-inhibits-cd133-glioma-cells-by-targeting-the-akt-pathway
#15
Aiqun Liu, Qingyun Yu, Zhongxing Peng, Yeqing Huang, Shengpeng Diao, Jing Cheng, Wentao Wang, Mingfan Hong
MicroRNA-200b (miR-200b) is a tumor suppressor in multiple tumor types, including gastric cancer, breast cancer, ovarian cancer and glioma. The biological significance of a known normal and cancer stem cell marker, CD133, remains elusive. The aim of the present study was to identify the function and mechinism of miR-200b in suppressing CD133(+) glioma cells. CD133(+) glioma cells were sorted by flow cytometry. The expression of miR-200b, Ki67, GAP43, GFAP and CD133 were tested by reverse transcription-quantitative polymerase chain reaction...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28599424/wnt10b-is-critical-for-the-progression-of-gastric-cancer
#16
Xiao-Dan Wu, Qing-Li Bie, Bin Zhang, Zi-He Yan, Zhi-Jun Han
The family of Wnt proteins have been implicated in embryogenesis by regulation of cell fate and pattern formation, and also in human carcinogenesis. Wnt10B was previously shown to be involved in breast cancer development. The present study assessed the association of Wnt10B expression in human gastric cancer tissue specimens with clinicopathological data from these patients. Wnt10B expression in the regulation of gastric cancer cell proliferation and migration capacity in vitro was then investigated. The data revealed that Wnt10B mRNA and protein were upregulated in gastric cancer tissue samples and the upregulated Wnt10B mRNA was associated with gastric cancer metastasizing to lymph nodes...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28595915/predictive-value-for-lymph-node-metastasis-of-epithelial-mesenchymal-transition-and-cancer-stem-cell-marker-expression-in-early-gastric-cancer
#17
Kyung Han Nam, Hyuk Yoon, Kyungbun Lee, Do Joong Park, Hyung-Ho Kim, Hye Seung Lee, Eun Shin
BACKGROUND: Minimally invasive therapies, including endoscopic mucosal resection or sentinel node navigation surgery, have been widely applied in early gastric cancer because of their benefits in promoting patient quality of life. However, lymph node dissection is beyond the capability of endoscopic therapy, and in sentinel node navigation surgery, the potential for skip metastasis is not negligible. Therefore, the possibility of lymph node metastasis is the most important factor to consider when deciding whether to apply the minimally invasive therapies...
March 21, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28581476/lgr5-expressing-chief-cells-drive-epithelial-regeneration-and-cancer-in-the-oxyntic-stomach
#18
Marc Leushacke, Si Hui Tan, Angeline Wong, Yada Swathi, Amin Hajamohideen, Liang Thing Tan, Jasmine Goh, Esther Wong, Simon L I J Denil, Kazuhiro Murakami, Nick Barker
The daily renewal of the corpus epithelium is fuelled by adult stem cells residing within tubular glands, but the identity of these stem cells remains controversial. Lgr5 marks homeostatic stem cells and 'reserve' stem cells in multiple tissues. Here, we report Lgr5 expression in a subpopulation of chief cells in mouse and human corpus glands. Using a non-variegated Lgr5-2A-CreERT2 mouse model, we show by lineage tracing that Lgr5-expressing chief cells do not behave as corpus stem cells during homeostasis, but are recruited to function as stem cells to effect epithelial renewal following injury by activating Wnt signalling...
June 5, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28562343/the-role-of-notch-signaling-in-gastric-carcinoma-molecular-pathogenesis-and-novel-therapeutic-targets
#19
REVIEW
Yizheng Yao, Ying Ni, Jiawen Zhang, Hua Wang, Shihe Shao
Notch signaling, an evolutionarily conserved signaling cascade system, is involved in promoting the progression of different types of cancers. Within the past decades, the Notch signaling pathway has increasingly been shown to have a primary role in deciding the fate of cancer cells and cancer stem cells in the stomach. Most components of Notch signaling are strongly expressed at different levels in gastric carcinoma tissue samples and are associated with a considerable number of clinical parameters. Moreover, crosstalk signaling between the Notch pathway and the Wnt, Ras, and NF-κB pathways promotes the process of gastric carcinogenesis...
May 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28560293/isthmus-stem-cells-are-the-origins-of-metaplasia-in-the-gastric-corpus
#20
Yoku Hayakawa, James G Fox, Timothy C Wang
The acquisition of genetic/epigenetic mutations in long-lived gastrointestinal stem cells leads to the development of cancer, as well as precancerous lesions such as metaplasia and dysplasia. In the proximal stomach corpus, this model of progression from stem cells has been supported by studies in mice and human beings, showing abundant proliferation in the isthmus and clonal expansion of mutated cells from the stem cell region. An alternative theory proposes that gastric metaplasia arises from mature differentiated chief cells...
July 2017: Cellular and Molecular Gastroenterology and Hepatology
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