Journal of Experimental & Clinical Cancer Research

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Inhibitory effects of low intensity pulsed ultrasound on osteoclastogenesis induced in vitro by breast cancer cells
Journal of Experimental & Clinical Cancer Research - Tập 37 - Trang 1-11 - 2018
Valeria Carina, Viviana Costa, Stefania Pagani, Angela De Luca, Lavinia Raimondi, Daniele Bellavia, Stefania Setti, Milena Fini, Gianluca Giavaresi
Bone tissue is one of the main sites for breast metastasis; patients diagnosed with advanced breast cancer mostly develop bone metastasis characterized by severe osteolytic lesions, which heavily influence their life quality. Low Intensity Pulsed Ultrasound (LIPUS) is a form of mechanical energy able to modulate various molecular pathways both in cancer and in health cells. The purpose of the present study was to evaluate for the first time, the ability of LIPUS to modulate osteolytic capability of breast cancer cells. Two different approaches were employed: a) Indirect method -conditioned medium obtained by MDA-MB-231 cell line treated or untreated with LIPUS was used to induce osteoclast differentiation of murine macrophage Raw264.7 cell line; and b) Direct method -MDA-MB-231 were co-cultured with Raw264.7 cells and treated or untreated with LIPUS. LIPUS treatment impaired MDA-MB-231 cell dependentosteoclast differentiation and produced a reduction of osteoclast markers such as Cathepsin K, Matrix Metalloproteinase 9 and Tartrate Resistant Acid Phosphatase, suggesting its role as an effective and safe adjuvant in bone metastasis management. LIPUS treatment could be a good and safety therapeutic adjuvant in osteolyitic bone metastasis not only for the induction properties of bone regeneration, but also for the reduction of osteolysis.
Role of the nervous system in cancer metastasis
Journal of Experimental & Clinical Cancer Research - Tập 37 - Trang 1-12 - 2018
Nyanbol Kuol, Lily Stojanovska, Vasso Apostolopoulos, Kulmira Nurgali
Cancer remains as one of the leading cause of death worldwide. The development of cancer involves an intricate process, wherein many identified and unidentified factors play a role. Although most studies have focused on the genetic abnormalities which initiate and promote cancer, there is overwhelming evidence that tumors interact within their environment by direct cell-to-cell contact and with signaling molecules, suggesting that cancer cells can influence their microenvironment and bidirectionally communicate with other systems. However, only in recent years the role of the nervous system has been recognized as a major contributor to cancer development and metastasis. The nervous system governs functional activities of many organs, and, as tumors are not independent organs within an organism, this system is integrally involved in tumor growth and progression.
Collagen triple helix repeat containing-1 negatively regulated by microRNA-30c promotes cell proliferation and metastasis and indicates poor prognosis in breast cancer
Journal of Experimental & Clinical Cancer Research - Tập 36 - Trang 1-15 - 2017
Yuan-hui Lai, Jian Chen, Xiao-ping Wang, Yan-qing Wu, Hai-tao Peng, Xiao-hong Lin, Wen-jian Wang
Collagen triple helix repeat containing-1 (CTHRC1), which was firstly identified overexpressed in the adventitia and neointima of injured rat arteries, could inhibit collagen expression and increase cell migration. It was then found to be ubiquitously expressed in numerous cell types such as fibroblasts and smooth muscle cells, and aberrantly up-regulated in several malignant tumors. However, the functional role of CTHRC1 and its related mechanism in breast cancer still remains unclear. CTHRC1 expressions in breast cancer tissues and cells were assessed by qRT-PCR, western blot and immunohistochemistry. The relative expression level of miR-134, miR-155, miR-30c and miR-630 in breast cancer cells respectively was detected by qRT-PCR. Wild type (Wt) and Mutant type (Mut) CTHRC1 3’UTR sequences were cloned into a psi-CHECK2 reporter vector, and the relative luciferase activity was detected by dual-luciferase reporter assay in indicated cells. The effect of ectopic expression of miR-30c or gain and loss of CTHRC1 on cell viability, cell proliferation, cell cycle progression and apoptosis, cell invasion and migration was respectively detected by CCK-8 assay, colony formation assay, flow cytometry analysis, transwell invasion/migration assay. Protein levels of β-catenin, active β-catenin, normal and phosphorylated form of GSK-3β were detected by western blot in indicated cells. Immunofluorescence staining of β-catenin was performed to observe nuclear localization. We found CTHRC1 was frequently up-regulated in human breast cancer cells and tissues. Then our cohort study and further meta-analysis validated high expression of CTHRC1 was associated with aggressive clinicopathological features and poor clinical outcome of breast cancer patients. In addition, CTHRC1 promoted cell proliferation, invasion and migration and suppressed cell apoptosis in breast cancer, which might be by activating GSK-3β/β-catenin signaling and inhibiting Bax/Caspase-9/Caspase-3 signaling respectively; and these biological functions of CTHRC1 could be directly negatively regulated by miR-30c. Taken together, we identified the role of miR-30c/CTHRC1 axis in breast cancer progression and demonstrated CTHRC1 may serve as a prognostic biomarker and therapeutic target for breast cancer.
Attenuation of hedgehog/GLI signaling by NT1721 extends survival in pancreatic cancer
Journal of Experimental & Clinical Cancer Research - Tập 38 - Trang 1-15 - 2019
Claudia M. Kowolik, Min Lin, Jun Xie, Larry E. Overman, David A. Horne
Pancreatic cancer is one of the most lethal malignancies due to frequent late diagnosis, aggressive tumor growth and metastasis formation. Continuously raising incidence rates of pancreatic cancer and a lack of significant improvement in survival rates over the past 30 years highlight the need for new therapeutic agents. Thus, new therapeutic agents and strategies are urgently needed to improve the outcome for patients with pancreatic cancer. Here, we evaluated the anti-tumor activity of a new natural product-based epidithiodiketopiperazine, NT1721, against pancreatic cancer. We characterized the anticancer efficacy of NT1721 in multiple pancreatic cancer cell lines in vitro and in two orthotopic models. We also compared the effects of NT1721 to clinically used hedgehog inhibitors and the standard-of-care drug, gemcitabine. The effect of NT1721 on hedgehog/GLI signaling was assessed by determining the expression of GLI and GLI target genes both in vitro and in vivo. NT1721 displayed IC50 values in the submicromolar range in multiple pancreatic cancer cell lines, while largely sparing normal pancreatic epithelial cells. NT1721 attenuated hedgehog/GLI signaling through downregulation of GLI1/2 transcription factors and their downstream target genes, which reduced cell proliferation and invasion in vitro and significantly decreased tumor growth and liver metastasis in two preclinical orthotopic mouse models of pancreatic cancer. Importantly, treatment with NT1721 significantly improved survival times of mice with pancreatic cancer compared to the standard-of-care drug, gemcitabine. Favorable therapeutics properties, i.e. 10-fold lower IC50 values than clinically used hedgehog inhibitors (vismodegib, erismodegib), a 90% reduction in liver metastasis and significantly better survival times compared to the standard-of-care drug, gemcitabine, provide a rational for testing NT1721 in the clinic either as a single agent or possibly in combination with gemcitabine or other therapeutic agents in PDAC patients overexpressing GLI1/2. This could potentially result in promising new treatment options for patients suffering from this devastating disease.
Enhancement of radiation response with bevacizumab
Journal of Experimental & Clinical Cancer Research - Tập 31 Số 1 - 2012
Tien Hoang, Shyhmin Huang, Eric A. Armstrong, Jens Eickhoff, Paul M. Harari
The expression profile of microRNAs in a model of 7,12-dimethyl-benz[a]anthrance-induced oral carcinogenesis in Syrian hamster
Journal of Experimental & Clinical Cancer Research - Tập 28 - Trang 1-10 - 2009
Tao Yu, Xiao-yi Wang, Ren-guo Gong, An Li, Sen Yang, Yu-tang Cao, Yu-ming Wen, Chang-mei Wang, Xin-zhu Yi
Non-coding RNA molecules, such as microRNAs, may play an important role in carcinogenesis. Recent studies have indicated that microRNAs are involved in initiation and progression of various malignancies. However, little work has been done to compare the microRNA expression patterns in oral cancer. In this study, we constructed an animal model of oral squamous cell carcinoma to investigate expression profiles of microRNAs in oral carcinogenesis. The animal model of oral squamous cell carcinoma was conducted by tri-weekly (Monday, Wednesday, and Friday) painting with 5% DMBA in acetone. Six Syrian hamsters, including three from the treated group and three from the control group, were used as a training group for microRNA microarray analysis. All microarray data were analyzed by Significance Analysis of Microarrays (SAM) and CLUSTER 3.0 software, and this result was further confirmed by qRT-PCR assay. Seventeen microRNAs were differentially expressed in oral squamous cell carcinoma. Five microRNAs (hsa-miR-21, hsa-miR-200b, hsa-miR-221, hsa-miR-338, and mmu-miR-762) were significantly upregulated and twelve microRNAs (hsa-miR-16, hsa-miR-26a, hsa-miR-29a, hsa-miR-124a, hsa-miR-125b, mmu-miR-126-5p, hsa-miR-143, hsa-miR-145, hsa-miR-148b, hsa-miR-155, hsa-miR-199a, and hsa-miR-203) were down-regulated in cancer tissues. The expression levels of hsa-miR-21 and hsa-miR-16 seen with Stem-loop qRT-PCR were also seen in microarray analysis in all samples. Our findings identified specific microRNA expression in oral squamous cell carcinoma and suggested that microRNAs have a role in oral carcinogenesis.
Correction to: Current status of ctDNA in precision oncology for hepatocellular carcinoma
Journal of Experimental & Clinical Cancer Research - Tập 40 - Trang 1-1 - 2021
Yan Li, Yuanyuan Zheng, Liwei Wu, Jingjing Li, Jie Ji, Qiang Yu, Weiqi Dai, Jiao Feng, Jianye Wu, Chuanyong Guo
Elevated kinesin family member 26B is a prognostic biomarker and a potential therapeutic target for colorectal cancer
Journal of Experimental & Clinical Cancer Research - Tập 34 - Trang 1-10 - 2015
Jingtao Wang, Feifei Cui, Xiao Wang, Yingming Xue, Jian Chen, Yang Yu, Huijun Lu, Meng Zhang, Huamei Tang, Zhihai Peng
Kinesins play a key role in the development and progression of many human cancers. The present study investigated the expression and clinical significance of kinesin family member 26B (KIF26B) in colorectal cancer (CRC). Using quantitative real-time PCR and Western blot analyses as well as immunohistochemical staining of a tissue microarray we examined KIF26B mRNA and protein levels in CRC tumor tissues and paired adjacent normal mucosa. Moreover, the effect of KIF26B knockdown on CRC cell proliferation was investigated using Cell Counting Kit-8 assays. Expression of KIF26B was found to be elevated in CRC. Suppression of KIF26B inhibited CRC cell proliferation. Furthermore, upregulated expression of KIF26B was significantly correlated with tumor size (P = 0.020), American Joint Committee on Cancer (AJCC) stage (P = 0.018), T stage (P = 0.026), N stage (P = 0.013), and differentiation histology (P = 0.047). KIF26B was also shown to be an independent prognostic indicator of overall survival for CRC patients (HR 5.621; 95% CI 2.302–13.730; P < 0.001). Our data indicate that KIF26B plays an important role in colorectal carcinogenesis and functions as a novel prognostic indicator and a potential therapeutic target for CRC.
CD44+/CD24- phenotype contributes to malignant relapse following surgical resection and chemotherapy in patients with invasive ductal carcinoma
Journal of Experimental & Clinical Cancer Research - - 2012
Lin Yang, Ying Zhong, Heng Guan, Xiaohui Zhang, Qiang Sun
AbstractBackgroundInvasive ductal carcinoma is the most common type of breast malignancy, with varying molecular features and resistance to treatment. Although CD44+/CD24- cells are believed to act as breast cancer stem cells and to be linked to poor prognosis in some patients, the association between these cells and tumor recurrence or metastasis in all or some types of invasive ductal carcinoma is unclear.MethodsA total of 147 randomly selected primary and secondary invasive ductal carcinoma samples were assayed for expression of CD44, CD24, ER, PR, and Her2. The association between the proportions of CD44+/CD24- tumor cells and the clinico-pathological features of these patients was evaluated.ResultsCD44+/CD24- tumor cells were detected in 70.1% of the tumors, with a median proportion of 5.8%. The proportion of CD44+/CD24- tumor cells was significantly associated with lymph node involvement (P = 0.026) and PR status (P = 0.038), and was correlated with strong PR status in patients with recurrent or metastatic tumors (P = 0.046) and with basal-like features (p = 0.05). The median disease-free survival (DFS) of patients with and without CD44+/CD24-/lowtumor cells were 22.9 ± 2.2 months and 35.9 ± 3.8 months, and the median overall survival (OS) of patients with and without CD44+/CD24-/lowtumor cells were 39.3 ± 2.6 months and 54.0 ± 3.5 months, respectively, and with both univariate and multivariate analyses showing that the proportion of CD44+/CD24-/lowtumor cells was strongly correlated with DFS and OS.ConclusionThe prevalence of CD44+/CD24- tumor cells varied greatly in invasive ductal carcinomas, with the occurrence of this phenotype high in primary tumors with high PR status and in secondary tumors. Moreover, this phenotype was significantly associated with shorter cumulative DFS and OS. Thus, the CD44+/CD24-phenotype may be an important factor for malignant relapse following surgical resection and chemotherapy in patients with invasive ductal carcinoma.
The LAT1 inhibitor JPH203 reduces growth of thyroid carcinoma in a fully immunocompetent mouse model
Journal of Experimental & Clinical Cancer Research - Tập 37 - Trang 1-15 - 2018
Pascal Häfliger, Julien Graff, Matthias Rubin, Amandine Stooss, Matthias S. Dettmer, Karl-Heinz Altmann, Jürg Gertsch, Roch-Philippe Charles
The L-type amino acid transporter 1 (LAT1/SLC7A5) transports essential amino acids across the plasma membrane. While LAT1 is overexpressed in a variety of human neoplasms, its expression and its role in thyroid cancer is currently unknown. Anaplastic thyroid carcinoma (ATC) is a highly aggressive malignancy for which no effective therapy exists. The purpose of this study was to explore whether the inhibition of LAT1 in ATC would affect tumor growth both in vitro and in vivo. LAT1 was pharmacologically blocked by JPH203 in human ATC and papillary thyroid cancer (PTC) cell lines. The effects on proliferation and mTORC1 activity were addressed in vitro. A genetically engineered mouse model of ATC was used to address the effect of blocking LAT1 on tumor growth in vivo. SLC7A5 transcription was measured in patient-derived ATC samples to address the clinical relevance of the findings. LAT1 block by JPH203 reduced proliferation and mTORC1 signaling in human thyroid cancer cell lines. SLC7A5 transcription was upregulated in ATC tissues derived from a genetically engineered mouse model and in ATC samples recovered from patients. JPH203 treatment induced thyroid tumor growth arrest in vivo in a fully immunocompetent mouse model of thyroid cancer. Additionally, analysis of publicly available datasets of thyroid carcinomas revealed that high LAT1 expression is associated with potentially untreatable PTC presenting reduced NIS/SLC5A5 transcription and with ATC. These preclinical results show that LAT1 inhibition is a novel therapeutic approach in the context of thyroid cancers, and more interestingly in untreatable thyroid cancers.
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