scholarly journals ASF-4-1 fibroblast-rich culture increases chemoresistance and mTOR expression of pancreatic cancer BxPC-3 cells at the invasive front in vitro, and promotes tumor growth and invasion in vivo

2016 ◽  
Vol 11 (4) ◽  
pp. 2773-2779 ◽  
Author(s):  
MASAYA FUJIWARA ◽  
KAZUKI KANAYAMA ◽  
YOSHIFUMI S. HIROKAWA ◽  
TAIZO SHIRAISHI
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Growth ◽  
Invasive Front ◽  
Tumor Growth And Invasion

scholarly journals TGF-βRII Knock-down in Pancreatic Cancer Cells Promotes Tumor Growth and Gemcitabine Resistance. Importance of STAT3 Phosphorylation on S727

Cancers ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 254 ◽  
Author(s):  
Vincent Drubay ◽  
Nicolas Skrypek ◽  
Lucie Cordiez ◽  
Romain Vasseur ◽  
Céline Schulz ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Locally Advanced ◽  
Western World ◽  
Pancreatic Cancer Cells ◽  
Stat3 Phosphorylation ◽  
The Impact

Pancreatic adenocarcinoma (PDAC) is one of the most deadly cancers in the Western world because of a lack of early diagnostic markers and efficient therapeutics. At the time of diagnosis, more than 80% of patients have metastasis or locally advanced cancer and are therefore not eligible for surgical resection. Pancreatic cancer cells also harbour a high resistance to chemotherapeutic drugs such as gemcitabine that is one of the main palliative treatments for PDAC. Proteins involved in TGF-β signaling pathway (SMAD4 or TGF-βRII) are frequently mutated in PDAC (50–80%). TGF-β signalling pathway plays antagonistic roles during carcinogenesis by initially inhibiting epithelial growth and later promoting the progression of advanced tumors and thus emerged as both tumor suppressor and oncogenic pathways. In order to decipher the role of TGF-β in pancreatic carcinogenesis and chemoresistance, we generated CAPAN-1 and CAPAN-2 cell lines knocked down for TGF-βRII (first actor of TGF-β signaling). The impact on biological properties of these TGF-βRII-KD cells was studied both in vitro and in vivo. We show that TGF-βRII silencing alters tumor growth and migration as well as resistance to gemcitabine. TGF-βRII silencing also leads to S727 STAT3 and S63 c-Jun phosphorylation, decrease of MRP3 and increase of MRP4 ABC transporter expression and induction of a partial EMT phenotype. These markers associated with TGF-β signaling pathways may thus appear as potent therapeutic tools to better treat/manage pancreatic cancer.

PCL20-116: Can Antisense Oligonucleotides Targeted to K-Ras Gene Inhibit the Tumor Growth, Invasiveness and Expression of MMP-2 and MMP-9 In Vitro and In Vivo in Hamster Experimental Pancreatic Cancer Model?

2020 ◽  
Vol 18 (3.5) ◽  
pp. PCL20-116
Author(s):  
Cintia Yoko Morioka ◽  
Marcel Cerqueira Cesar Machado ◽  
Jose Pinhata Otoch ◽  
Luma Princess Schneider ◽  
Edgard Mesquita Rodrigues Lima ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Growth ◽  
Antisense Oligonucleotides ◽  
Cancer Model ◽  
Ras Gene ◽  
Experimental Pancreatic Cancer

scholarly journals A novel taspine derivative suppresses human liver tumor growth and invasion in vitro and in vivo

2013 ◽  
Vol 6 (3) ◽  
pp. 855-859 ◽  
Author(s):  
NAN WANG ◽  
LEI ZHENG ◽  
YINGZHUAN ZHAN ◽  
YANMIN ZHANG
Keyword(s):  
Tumor Growth ◽  
Liver Tumor ◽  
Human Liver ◽  
Tumor Growth And Invasion

scholarly journals Engineered Resistant-Starch (ERS) Diet Shapes Colon Microbiota Profile in Parallel with the Retardation of Tumor Growth in In Vitro and In Vivo Pancreatic Cancer Models

Nutrients ◽  
2017 ◽  
Vol 9 (4) ◽  
pp. 331 ◽  
Author(s):  
Concetta Panebianco ◽  
Kaarel Adamberg ◽  
Signe Adamberg ◽  
Chiara Saracino ◽  
Madis Jaagura ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Growth ◽  
Resistant Starch ◽  
Cancer Models

Signal transducer and activator of transcription 5b (STAT5b) as a novel target for anti-neoplastic therapy in human pancreatic cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 217-217
Author(s):  
C. Moser ◽  
P. Ruemle ◽  
H. Schenk ◽  
E. K. Geissler ◽  
H. J. Schlitt ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Growth ◽  
Cell Motility ◽  
Cancer Cell ◽  
Human Pancreatic Cancer ◽  
Signal Transducer ◽  
Tumor Vascularization ◽  
Knock Down

217 Background: Activation of signal transducer and activator of transcription 5b (STAT5b) has been associated with tumor growth and metastases in various tumor entities. A number of cytokines, growth factors, and oncogenes that can induce STAT5b activity are also implicated in pancreatic cancer growth and metastases. Hence, we sought to determine STAT5b expression in human pancreatic cancer specimen and effects of selective STAT5b inhibition on pancreatic cancer cells. Methods: Expression of STAT5b in human pancreatic adenocarcinomas was determined by immunohistochemistry. For in vitro experiments, human pancreatic cancer cell lines (BxPC-3, HPAF-II, L3.6pl) were used. Cancer cells were transfected with STAT5b shRNA plasmid to create stable STAT5b knock-down. Effects of STAT5b inhibition on growth and motility of tumor cells was investigated by MTT and modified Boyden chamber assays. In vivo effects of STAT5b blockade were determined in subcutaneous mouse model. Results: Nuclear expression of STAT5b was detected in 42/80 human pancreatic adenocarcinomas. In human cancer cell lines, stable knock-down of STAT5b had no effect on growth of tumor cells in vitro. However, tumor cell motility was significantly reduced upon STAT5b blockade (p<0.05). Moreover, expression of various signaling intermediates and transcription factors including c-myc was impaired upon STAT5b knock-down. In a subcutaneous tumor model, inhibition of STAT5b led to significantly reduced tumor growth (p<0.05) which was also reflected by final tumor weights (p<0.05). Furthermore, as revealed by immunohistochemistry, blockade of STAT5b significantly reduced tumor vascularization in vivo (p<0.05). Conclusions: STAT5b is expressed in human pancreatic adenocarcinomas. Blockade of STAT5b impairs cancer cell motility in vitro, suggesting antimetastatic potential. Moreover, inhibition of STAT5b significantly reduces tumor growth and tumor vascularization in vivo. Hence, STAT5b might be an interesting target for antineoplastic therapy in human pancreatic cancer. No significant financial relationships to disclose.

Effect of trametinib in combination with panitumumab and trastuzumab on tumor growth in an orthotopic xenograft model of human pancreatic cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 190-190
Author(s):  
James M. Lindberg ◽  
Sara J Adair ◽  
Timothy E. Newhook ◽  
Alison Kim ◽  
J Thomas Parsons ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Growth ◽  
Western Blot ◽  
Growth Inhibition ◽  
Triple Therapy ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Ras Pathway

190 Background: Aberrant MAPK and EGFR family signaling are key drivers of pancreatic ductal adenocarcinoma(PDAC). We hypothesized that combination trametinib(MEK1/2 inhibitor), panitumumab(EGFR inhibitor) and trastuzumab(Her2 inhibitor) would more effectively suppress tumor growth than any of these monotherapies. Methods: Patient-derived PDAC cell line MAD09-366 was exposed to trametinib, panitumumab, trastuzumab, and combination therapies in vitro. Western blot analysis was performed on treated cell lysates. Athymic, nude mice were orthotopically implanted with patient-derived PDAC xenografts(MAD09-366, 08-608, and 08-738). Established murine tumors were treated with control, trametinib (0.3mg/kg, qDay), panitumumab (500ug, BIW), trastuzumab (200ug, BIW) or in combination. MRI was used to assess tumor response. Results: Two of 3 PDACs were Kras mutant, 2 of 3 demonstrated increased Her2 activity, and all 3 showed increased EGFR activity. In vitro studies showed increased growth inhibition of triple-therapy-treated cells relative to control or each inhibitor alone. Western blot analysis revealed that EGF stimulation increased Ras pathway signaling in this Kras-mutant cell line. With EGF stimulation, the greatest Ras pathway signaling inhibition was seen in triple-therapy-treated cells. In vivo studies in all PDAC xenografts revealed that triple therapy significantly decreased tumor growth rate relative to control, trametinib alone, panitumumab alone, or panitumumab plus trastuzumab. In 2 of 3 PDACs assessed, triple therapy was superior to trametinib plus panitumumab. Average tumor size in MAD08-738 triple-therapy-treated mice decreased by 9.3%. Conclusions: Triple therapy with trametinib, panitumumab, and trastuzumab demonstrated the greatest in vitro Ras signaling blockade. In vivo, this combination produced significant tumor growth inhibition or regression in all PDAC tumors studied. This regimen should be considered for a future clinical trial in pancreatic cancer patients.

S100A3 Suppression Inhibits In Vitro and In Vivo Tumor Growth and Invasion of Human Castration-resistant Prostate Cancer Cells

Urology ◽  
2015 ◽  
Vol 85 (1) ◽  
pp. 273.e9-273.e15 ◽  
Author(s):  
Minyong Kang ◽  
Hye Sun Lee ◽  
Young Ju Lee ◽  
Woo Suk Choi ◽  
Yong Hyun Park ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Castration Resistant Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Castration Resistant ◽  
Tumor Growth And Invasion

scholarly journals P2RY12-Inhibitors Reduce Cancer-Associated Thrombosis and Tumor Growth in Pancreatic Cancers

2021 ◽  
Vol 11 ◽  
Author(s):  
Ana Luisa Palacios-Acedo ◽  
Soraya Mezouar ◽  
Diane Mège ◽  
Lydie Crescence ◽  
Christophe Dubois ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Growth ◽  
Survival Rates ◽  
Cancer Growth ◽  
Primary Tumors ◽  
Trousseau’S Syndrome ◽  
Pancreatic Cancers ◽  
Cancer Associated Thrombosis

Platelet function can be modified by cancer cells to support tumor growth, causing alterations in the delicate hemostatic equilibrium. Cancer-cell and platelet interactions are one of the main pillars of Trousseau’s syndrome: a paraneoplastic syndrome with recurring and migrating episodes of thrombophlebitis. Altogether, this leads to a four-fold risk of thrombotic events in cancer patients, which in turn, portend a poor prognosis. We previously demonstrated that anti-P2RY12 drugs inhibit cancer-associated-thrombosis and formation of tumor metastasis in pancreatic cancer models. Here, we aimed to (1) compare the effects of aspirin and clopidogrel on pancreatic cancer prevention, (2) characterize the effects of clopidogrel (platelet P2RY12 inhibitor) on cancer-associated thrombosis and cancer growth in vivo, (3) determine the effect of P2RY12 across different digestive-tract cancers in vitro, and (4) analyze the expression pattern of P2RY12 in two different cancer types affecting the digestive system. Clopidogrel treatment resulted in better survival rates with smaller primary tumors and less metastasis than aspirin treatment. Clopidogrel was also more effective than aspirin at dissolving spontaneous endogenous thrombi in our orthotopic advanced cancer mouse model. P2RY12 expression gives pancreatic adenocarcinomas proliferative advantages. In conclusion, we propose the hypothesis that clopidogrel should be further studied to target and prevent Trousseau’s syndrome; as well as diminish cancer growth and spread. However, more studies are required to determine the implicated pathways and effects of these drugs on cancer development.

HMGB1 Derived from Macrophages Acts as an Angiogenic Factor.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3852-3852
Author(s):  
Ikuro Maruyama ◽  
Ko-ichi Kawahara ◽  
Takashi Ito ◽  
Yoko Oyama ◽  
Kazunori Takenouchi ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Advanced Glycation Endproducts ◽  
High Mobility ◽  
Cellular Migration ◽  
Angiogenic Factor ◽  
Hmgb1 Protein ◽  
Glycation Endproducts ◽  
Tumor Growth And Invasion

Abstract High Mobility Group Box-1 (HMGB1) protein, released from the most of necrotic cells and activated macrophages, has been identified as a novel cytokine through the receptor for advanced glycation endproducts (RAGE) and Toll-like receptor(TLR)-2 and -4. The HMGB1-RAGE and TLRs-2, -4 interactions contribute to cellular migration and the production of proinflammatory cytokines, and participate in pathomechanisms in tumor growth and invasion, in which an angiogenesis development is an important aspect. We here show that HMGB1 stimulates the expression of Vascular Endothelial Growth Factor (VEGF), the most potent angiogenic factor in tumors, through the HMGB1-RAGE, but neither TLR-2 nor TLR-4 in macrophage-lineage cells in vitro. The mechanism of VEGF production is mediated through the Akt pathway, which is linked to tumor growth and invasion. Furthermore, HMGB1 induced angiogenesis was also observed in an in vivo rabbit corneal assay (Fig). These results suggest that HMGB1, released from the tumor-associated macrophages, may act as a key cytokine in the development of angiogenesis by producing VEGF in tumor growth and invasion. Thus the tumor-associated HMGB1/RAGE system may contribute to our understanding of the mechanism of cancer cell escape from macrophage-associated acceleration of inflammation.

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