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https://www.readbyqxmd.com/read/28621236/dynamic-soluble-changes-in-svegfr1-hgf-and-vegf-promote-chemotherapy-and-bevacizumab-resistance-a-prospective-translational-study-in-the-becox-gemcad-09-01-trial
#1
Estela Pineda, A Salud, E Vila-Navarro, M J Safont, Beatriz Llorente, J Aparicio, R Vera, P Escudero, E Casado, C Bosch, U Bohn, R Pérez-Carrión, A Carmona, J R Ayuso, T Ripollés, R Bouzas, M Gironella, X García-Albéniz, J Feliu, J Maurel
Despite initial responsiveness, acquired resistance to both bevacizumab and chemotherapy in metastatic colorectal cancer is universal. We have recently published that in vitro, chronically oxaliplatin resistance upregulates soluble vascular endothelial growth factor receptor 1, downregulates vascular endothelial growth factor, and also promotes c-MET, b-catenin/transcription factor 4, and AKT activation. We tested whether variation in three serum biomarkers such as the natural c-MET ligand (hepatocyte growth factor), soluble vascular endothelial growth factor receptor 1, and vascular endothelial growth factor-A was associated with efficacy in metastatic colorectal cancer patients treated in the prospective BECOX study...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28618047/focal-b-catenin-mutation-identified-on-formalin-fixed-and-paraffin-embedded-inflammatory-hepatocellular-adenomas
#2
Joan Saldarriaga, Bettina Bisig, Gabrielle Couchy, Claire Castain, Jessica Zucman-Rossi, Charles Balabaud, Christine Sempoux, Paulette Bioulac-Sage
The identification of hepatocellular adenoma (HCA) with mutation in exon 3 of the CTNNB1 gene encoding for b-catenin is clinically relevant due to higher risk of malignant transformation. Inflammatory HCA (IHCA) can exhibit b-catenin activation (b-IHCA). We report 2 cases with multiple IHCA in which focal b-catenin activation has been found in one of the IHCA. In both cases, the diagnosis of IHCA was confirmed on the resected nodules by routine stains, immunohistochemical detection of C-reactive protein (CRP), and molecular biology on frozen material...
June 15, 2017: Histopathology
https://www.readbyqxmd.com/read/28611108/wnt-%C3%AE-catenin-signaling-contributes-to-tumor-malignancy-and-is-targetable-in-gastrointestinal-stromal-tumor
#3
Shan Zeng, Adrian M Seifert, Jennifer Q Zhang, Michael J Cavnar, Teresa S Kim, Vinod P Balachandran, Juan A Santamaria-Barria, Noah A Cohen, Michael J Beckman, Benjamin Medina, Ferdinand Rossi, Megan H Crawley, Jennifer K Loo, Joanna H Maltbaek, Peter Besmer, Cristina R Antonescu, Ronald P DeMatteo
Gastrointestinal stromal tumor (GIST) is the most common type of sarcoma and usually harbors either a KIT or PDGFRA mutation. However, the molecular basis for tumor malignancy is not well defined. While the Wnt/b-catenin signaling pathway is important in a variety of cancers, its role in GIST is uncertain. Through analysis of nearly 150 human GIST specimens, we found that some human GISTs expressed b-catenin and contained active, dephosphorylated nuclear b-catenin. Furthermore, advanced human GISTs expressed reduced levels of the Wnt antagonist DKK4...
June 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28600477/targeting-the-wnt-pathway-and-cancer-stem-cells-with-anti-progastrin-humanized-antibodies-a-major-breakthrough-for-k-ras-mutated-colorectal-cancer-treatment
#4
Alexandre Prieur, Monica Cappellini, Guillaume Habif, Marie-Paule Lefranc, Thibault Mazard, Eric Morency, Jean-Marc Pascussi, Maud Flaceliere, Nathalie Cahuzac, Berengere Vire, Benjamin Dubuc, Amandine Durochat, Pierre Liaud, Jérémy Ollier, Caroline Pfeiffer, Sophie Poupeau, Véronique Saywell, Chris Planque, Eric Assenat, Frédéric Bibeau, Jean-François Bourgaux, Pascal Pujol, Alain Sézeur, Marc Ychou, Dominique Joubert
<p>Patients with metastatic colorectal cancer (CRC) suffer from disease relapse mainly due to cancer stem cells (CSC). Interestingly, they have an increased level of blood progastrin, a tumor-promoting peptide essential for the self-renewal of colon CSCs, which is also a direct b-catenin/Tcf4 target gene. In this study we aimed to develop a novel targeted therapy to neutralize secreted progastrin in order to inhibit Wnt signaling, CSCs and reduce relapses.</p> Experimental Design: <p>Antibodies (monoclonal and humanized) directed against progastrin were produced and selected for target specificity and affinity...
June 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28472810/the-long-non-coding-rna-crnde-promotes-colorectal-carcinoma-progression-by-competitively-binding-mir-217-with-tcf7l2-and-enhancing-the-wnt-%C3%AE-catenin-signaling-pathway
#5
Bo Yu, Xuan Ye, Qiong Du, Bin Zhu, Qing Zhai, Xin-Xiang Li
BACKGROUND/AIMS: The long non-coding RNA colorectal neoplasia differentially expressed (CRNDE) contributes to the proliferation and migration of tumors. However, its molecular mechanism underlying gastric cancer remains unknown. In the present study, we investigated whether CRNDE was involved in the development of colorectal cancer via the binding of microRNA (miR)-217 with transcription factor 7-like 2 (TCF7L2) to enhance the Wnt signaling pathway. METHODS: Quantitative polymerase chain reaction was used to detect CRNDE, miR-217 and TCF7L2 in colorectal cancer tissues and cells...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28382841/hepatocellular-carcinoma-in-fanconi-bickel-syndrome
#6
Jennifer Pogoriler, Allison F O'Neill, Stephan D Voss, Robert C Shamberger, Antonio R Perez-Atayde
Fanconi-Bickel syndrome is a rare autosomal recessive disorder due to mutations in the facilitative glucose transporter 2 ( GLUT2 or SLC2A2) gene resulting in excessive glycogen storage predominantly in the liver and kidney. Previous case reports of this condition have described liver biopsies with glycogen storage and variable steatosis and/or fibrosis. Unlike in other types of glycogen storage disease, hepatocellular adenomas and carcinomas have not been described to date in this syndrome. A 6-year-old boy with consanguineous parents had short stature, poorly controlled rickets, hepatosplenomegaly, and renal tubular dysfunction clinically consistent with Fanconi-Bickel Syndrome...
January 1, 2017: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/28314302/kras-mutant-status-may-be-associated-with-distant-recurrence-in-early-stage-rectal-cancer
#7
Michail Sideris, Jane Moorhead, Salvador Diaz-Cano, Amyn Haji, Savvas Papagrigoriadis
BACKGROUND/AIM: Total mesorectal excision combined with neo-adjuvant chemoradiotherary (CRT) and adjuvant chemotherapy, has been the standard treatment of locally advanced rectal cancer (LARC). Although TNM (Tumor, Node, Metastasis) classification for malignant Tumors is still the cornerstone in rectal cancer staging, there has been an effort to identify molecular biomarkers with additional prognostic or predictive value. MATERIALS AND METHODS: We retrospectively analyzed molecular biomarkers on prospectively collected histological specimens and clinical data from a cohort of 135 consecutive rectal cancer cases who underwent radical excision in a tertiary center between 2011-2014 (males=87, females=48, age range=22-89 years, mean=64,67 years, SD=13...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28210516/immunohistochemical-investigation-of-her-akt-mtor-pathway-and-cellular-adhesion-molecules-in-urothelial-carcinomas
#8
Nikolaos Koletsas, Triantafyllia Koletsa, Spyros Choidas, Konstantinos Anagnostopoulos, Stavros Touloupidis, Thomas Zaramboukas, Georgia Raptou, Nikolaos Papadopoulos, Maria Lambropoulou
Background. Several investigators have suggested the possibility that the expression of both EGFR and HER2 could be utilized for molecularly targeted therapy in urinary bladder cancer. We tried to evaluate the expression of HER2 and EGFR and activation of the AKT/PTEN/mTOR pathway in urothelial carcinomas and if there is any association between them and cellular adhesion molecules (CAMs). Materials and Methods. Forty-one paraffin-embedded urothelial cancer tissue blocks were collected. Immunostains for HER2, EGFR, MIB1, phospho-AKT, PTEN, phospho-mTOR, e-cadherin, p-cadherin, and b-catenin were performed on tissue microarrays sections...
2017: Pathology Research International
https://www.readbyqxmd.com/read/28209947/forkhead-box-protein-j1-foxj1-is-overexpressed-in-colorectal-cancer-and-promotes-nuclear-translocation-of-%C3%AE-catenin-in-sw620-cells
#9
Kuiliang Liu, Jianghao Fan, Jing Wu
BACKGROUND FOXJ1, which is a forkhead transcription factor, has been previously studied mostly as a ciliary transcription factor. The role of FOXJ1 in cancer progression is still elusive and controversial. In the present study, the effect of FOXJ1 in progression of colorectal cancer (CRC) was investigated. MATERIAL AND METHODS The pattern of FOXJ1 expression was investigated using the method of immunohistochemistry (IHC) in a tissue microarray (TMA) incorporating 50 pairs of colon cancer specimens and adjacent normal tissue...
February 17, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28133318/-a-case-report-of-an-undifferentiated-pancreatic-carcinoma-diagnosed-as-a-solid-pseudopapillary-neoplasm-before-surgery
#10
Hisataka Matsuo, Hisashi Ikoma, Ryo Morimura, Tomohiro Arita, Toshiyuki Kosuga, Hirotaka Konishi, Yasutoshi Murayama, Shuhei Komatsu, Atsushi Shiozaki, Yoshiaki Kuriu, Masayoshi Nakanishi, Daisuke Ichikawa, Hitoshi Fujiwara, Kazuma Okamoto, Eigo Otsuji
A 37-year-old man visited a previous hospital because of left abdominal pain. A contrast-enhanced CT scan revealed a 7 cm solid tumor in the pancreas body, and the patient was referred to our hospital. EUS-FNA showed that the tumor cells were positive for b-catenin in the nuclei, as well as for CD10 and CD56. On the other hand, the cells were negative for chromogranin A and synaptophysin. This is the typical immunohistochemical pattern of a solid pseudopapillary neoplasm(SPN). Therefore, we diagnosed this case as SPN before surgery...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28133149/-a-case-of-mesenteric-fibromatosis-after-robot-assisted-total-gastrectomy-for-gastric-cancer
#11
Makoto Nakai, Toshiyuki Tazawa, Naoki Wajima, Takahiro Muroya, Katsuya Mikami, Kenichi Hakamada
The patient underwent robot-assisted total gastrectomy for an early gastric cancer. Thirty-four months later, he was admitted to another hospital because of abdominal discomfort. Computed tomography scans showed a giant solid mass approximately 13 cm in diameter in the lower abdomen. We performed a resection of the tumor; operative findings showed a giant solid tumor, without adhesion, in the mesentery of the jejunum. The tumor did not involve other parts of the small intestine. The resected tumor had a smooth surface with an elastic hard consistency...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28092101/the-cross-regulation-between-sox15-and-wnt-signaling-pathway
#12
REVIEW
Ali Moradi, Faezeh Ghasemi, Kazem Anvari, Seyed Mahdi Hassanian, Saeideh Ahmadi Simab, Safieh Ebrahimi, Amirreza Hesari, Mohammad Mahdi Forghanifard, Mohammad Taher Boroushaki, Soodabeh ShahidSales, Amir Avan
WNT/B-CATENIN signaling pathway is one of the key dysregulated pathways in different tumor types, which regulate the expression of several genes involved in cell proliferation, differentiation, and survival. This pathway is being modulated by sex-determining region Y-box (SOX) family genes. The functions of these genes are suggested as tumor suppressor or oncogene. SOX genes transcribe a group of transcription factors that play important roles in embryonic development and carcinogenesis. Among them, SOX15 is recently been identified as a novel tumor suppressor in pancreatic and esophagus cancers with a potential role in modulating Wnt/b-catenin signaling...
January 16, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28090074/targeting-of-wnt-%C3%AE-catenin-by-anthelmintic-drug-pyrvinium-enhances-sensitivity-of-ovarian-cancer-cells-to-chemotherapy
#13
Chongyuan Zhang, Zhenge Zhang, Shuirong Zhang, Wenrong Wang, Ping Hu
BACKGROUND Aberrant activation of Wnt/β-catenin has been shown to promote ovarian cancer proliferation and chemoresistance. Pyrvinium, an FDA-approved anthelmintic drug, has been identified as a potent Wnt inhibitor. Pyrvinium may sensitize ovarian cancer cells to chemotherapy. MATERIAL AND METHODS The effect of pyrvinium alone and its combination with paclitaxel in ovarian cancer was investigated using an in vitro culture system and in vivo xenograft models. The mechanisms of its action were also analyzed, focusing on the Wnt/β-catenin pathway...
January 16, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28077837/curcumin-inhibits-gastric-carcinoma-cell-growth-and-induces-apoptosis-by-suppressing-the-wnt-%C3%AE-catenin-signaling-pathway
#14
Ruzhen Zheng, Qinghua Deng, Yuehua Liu, Pengjun Zhao
BACKGROUND Curcumin has well-known, explicit biological anti-tumor properties. The Wnt/β-catenin signaling pathway plays a central role in tumor cell proliferation and curcumin can regulate the Wnt/b-catenin signaling pathway of several carcinomas. The aim of this study was to investigate the impact of curcumin on the Wnt/β-catenin signaling pathway in human gastric cancer cells. MATERIAL AND METHODS We used 3 gastric cancer cell lines: SNU-1, SNU-5, and AGS. Research methods used were MTT assay, flow cytometry, clonogenic assay, annexin V/PI method, Western blotting analysis, tumor formation assay, and in vivo in the TUNEL assay...
January 12, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28057768/tert-biology-and-function-in-cancer-beyond-immortalization
#15
Ana Pestana, João Vinagre, M Sobrinho-Simões, P Soares
Evasion of replicative senescence and proliferation without restriction, sometimes designated as immortalization, is one of cancer hallmarks that may be attained through reactivation of telomerase in somatic cells. In contrast to most normal cells in which there is lack of telomerase activity, upregulation of TERT transcription/activity is detected in 80 to 90% of malignant tumours. In several types of cancer there is a relationship between the presence of TERTp mutations, TERT mRNA expression and clinico-pathological features but the biological bridge between the occurrence of TERTp mutations and the aggressive/invasive features displayed by the tumours remains unidentified...
January 5, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28054306/circulating-dickkopf-1-and-sclerostin-in-patients-with-paget-s-disease-of-bone
#16
Luca Idolazzi, Angelo Fassio, Gaia Tripi, Vania Braga, Ombretta Viapiana, Giovanni Adami, Maurizio Rossini, Davide Gatti
Paget disease of bone is a chronic metabolic bone disorder characterized by increased bone resorption and new bone formation. The aim of this study is defining the role of inhibitors of canonical Wnt/b-catenin signaling pathway in patients with Paget disease of bone. Scarce and contrasting results have been reported in literature. We studied 40 patients (15 females and 25 males) with radiological and scintigraphic evidence of Paget disease of bone and 40 healthy subjects matched by age and sex. N-propeptide of type I collagen, C-terminal telopeptide of type I collagen, sclerostin, and Dickkopf-related protein 1 (DKK1) were evaluated by blood samples in our laboratory...
January 5, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/27984126/malignant-transformation-of-a-%C3%AE-catenin-inflammatory-adenoma-due-to-an-s45-%C3%AE-catenin-activating-mutation-present-12-years-before
#17
Christine Sempoux, Bettina Bisig, Gabrielle Couchy, Charles Balabaud, Jessica Zucman-Rossi, Paulette Bioulac-Sage
In 1984, a 24-year-old woman underwent a right hepatectomy after a 17-cm nodule, diagnosed as a hepatocellular adenoma with some atypia. The resection was incomplete. Follow-up was interrupted. In 1996, a computed tomographic scan revealed a large multifocal hepatocellular carcinoma confirmed on biopsies. The patient died the same year. We reviewed these nodules using immunohistochemistry and gene sequencing. C-reactive protein was overexpressed in the tumor resected in 1984. Glutamine synthetase was heterogeneous in the tumor, with a few tumor nuclei expressing β-catenin...
April 2017: Human Pathology
https://www.readbyqxmd.com/read/27737536/long-non-coding-rna-hoxa11-antisense-promotes-cell-proliferation-and-invasion-and-predicts-patient-prognosis-in-serous-ovarian-cancer
#18
Ga Won Yim, Hee Jung Kim, Lee Kyung Kim, Sang Wun Kim, Sunghoon Kim, Eun Ji Nam, Young Tae Kim
Purpose: The biological function of long non-coding RNAs (lncRNAs) is only partially understood; therefore, in this study, we investigated the expression of the novel HOXA11 antisense (HOXA11as) lncRNA and its oncogenic role in serous ovarian cancer (SOC). Materials and Methods: HOXA11as expression was examined in 129 serous ovarian cancer tissue samples by real time RT-PCR. Clinicopathological factors and patient survival were compared between the high (N = 27) and low HOXA11as expression group (N = 102)...
October 11, 2016: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/27733685/microvesicle-mediated-wnt-%C3%AE-catenin-signaling-promotes-interspecies-mammary-stem-progenitor-cell-growth
#19
Leen Bussche, Gat Rauner, Marc Antonyak, Bethany Syracuse, Melissa McDowell, Anthony M C Brown, Richard A Cerione, Gerlinde R Van de Walle
Signaling mechanisms that regulate mammary stem/progenitor cell (MaSC) self-renewal are essential for developmental changes that occur in the mammary gland during pregnancy, lactation, and involution. We observed that equine MaSCs (eMaSCs) maintain their growth potential in culture for an indefinite period, whereas canine MaSCs (cMaSCs) lose their growth potential in long term cultures. We then used this system to investigate the role of microvesicles (MVs) in promoting self-renewal properties. We found that Wnt3a and Wnt1 were expressed at higher levels in MVs isolated from eMaSCs compared with those from cMaSCs...
November 18, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27715343/curcumin-reduces-lung-inflammation-via-wnt-%C3%AE-catenin-signaling-in-mouse-model-of-asthma
#20
Xia Yang, Jian-Ning Lv, Hui Li, Bo Jiao, Qiu-Hong Zhang, Yong Zhang, Jie Zhang, Yan-Qin Liu, Ming Zhang, Hu Shan, Jin-Zhao Zhang, Run-Miao Wu, Ya-Li Li
OBJECTIVES: Asthma is a chronic inflammatory, heterogeneous airway disease affecting millions of people around the world. Curcumin has been found to have anti-inflammatory and antifibrosis effects. Researchers reported that curcumin regulated Wnt/β-catenin signaling in lots of cells. However, whether curcumin regulates the levels of Wnt/β-Catenin signaling in lung tissues and DCs (dendritic cells) remains unclear. In this study, we assessed the effects of curcumin on DCs and asthma...
May 2017: Journal of Asthma: Official Journal of the Association for the Care of Asthma
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