scholarly journals BDE-209 Becreases the Efficacy of Dacarbazine Treatment for Melanoma in C57BL/6 Mice

2021 ◽  
Author(s):  
Patricia Manuitt-Brito ◽  
Tugstênio Lima de Souza ◽  
Francisco Filipak Neto ◽  
Joelma Leão-Buchir ◽  
Stellee Marcela Petris Biscaia ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Polybrominated Diphenyl Ethers ◽  
Lung Metastases ◽  
Alkylating Agents ◽  
Poor Response ◽  
Metastatic Potential ◽  
Public Health Care ◽  
Melanoma Metastasis ◽  
Environmental Chemical ◽  
Bde 209

Abstract Humans are widely exposed to environmental chemical toxicants potentially related to disease susceptibility. Polybrominated diphenyl ethers (PBDEs) present a proven risk associated with cancer, but no studies are related with the tumor progression. The decabromodiphenyl ether (BDE-209) is a flame-retardant detected in human plasma, breast milk and umbilical cord. Melanoma is a skin cancer with high metastatic potential and poor response to therapies. The use of alkylating agents such as dacarbazine is still a common protocol for the treatment of melanoma, mainly in Brazilian Public Health Care System. Recently, we reported the role of BDE-209 on the incidence of melanoma metastasis in different organs of mice after inoculation of B16-F10 cells. In the current study, we describe the effects of BDE-209 on dacarbazine treatment for melanoma. Adult male and female C57BL6 mice were exposed to BDE-209 for 45 days, inoculated with B16-F10 cells and treated with dacarbazine for 21 days (five doses of 40 mg.kg− 1). At 66th day, the animals were euthanized, and the blood, lung, liver, kidney and brain were sampled for hematological, biochemical and metastasis counting analyses. The results showed a decrease of lung metastases in animals treated with dacarbazine and a significant increase in mice previously exposed to BDE-209. Foremost, BDE-209 impaired dacarbazine treatment. These findings demonstrate the effect of BDE-209 and the decreased efficacy of dacarbazine treatment, favoring cancer progression and affecting the disease prognosis.

scholarly journals Iron-Bound Lipocalin-2 from Tumor-Associated Macrophages Drives Breast Cancer Progression Independent of Ferroportin

Metabolites ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 180
Author(s):  
Christina Mertens ◽  
Matthias Schnetz ◽  
Claudia Rehwald ◽  
Stephan Grein ◽  
Eiman Elwakeel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Progression ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Lung Metastases ◽  
Expression Profiles ◽  
The Cancer Genome Atlas ◽  
Lipocalin 2 ◽  
Tumor Associated Macrophages

Macrophages supply iron to the breast tumor microenvironment by enforced secretion of lipocalin-2 (Lcn-2)-bound iron as well as the increased expression of the iron exporter ferroportin (FPN). We aimed at identifying the contribution of each pathway in supplying iron for the growing tumor, thereby fostering tumor progression. Analyzing the expression profiles of Lcn-2 and FPN using the spontaneous polyoma-middle-T oncogene (PyMT) breast cancer model as well as mining publicly available TCGA (The Cancer Genome Atlas) and GEO Series(GSE) datasets from the Gene Expression Omnibus database (GEO), we found no association between tumor parameters and Lcn-2 or FPN. However, stromal/macrophage-expression of Lcn-2 correlated with tumor onset, lung metastases, and recurrence, whereas FPN did not. While the total iron amount in wildtype and Lcn-2−/− PyMT tumors showed no difference, we observed that tumor-associated macrophages from Lcn-2−/− compared to wildtype tumors stored more iron. In contrast, Lcn-2−/− tumor cells accumulated less iron than their wildtype counterparts, translating into a low migratory and proliferative capacity of Lcn-2−/− tumor cells in a 3D tumor spheroid model in vitro. Our data suggest a pivotal role of Lcn-2 in tumor iron-management, affecting tumor growth. This study underscores the role of iron for tumor progression and the need for a better understanding of iron-targeted therapy approaches.

scholarly journals Exosomal S100A4 derived from highly metastatic hepatocellular carcinoma cells promotes metastasis by activating STAT3

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Haoting Sun ◽  
Chaoqun Wang ◽  
Beiyuan Hu ◽  
Xiaomei Gao ◽  
Tiantian Zou ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Progression ◽  
Calcium Binding ◽  
Tumor Metastasis ◽  
Metastatic Potential ◽  
Functional Roles ◽  
Stat3 Phosphorylation ◽  
Hcc Cells

AbstractIntercellular cross-talk plays important roles in cancer progression and metastasis. Yet how these cancer cells interact with each other is still largely unknown. Exosomes released by tumor cells have been proved to be effective cell-to-cell signal mediators. We explored the functional roles of exosomes in metastasis and the potential prognostic values for hepatocellular carcinoma (HCC). Exosomes were extracted from HCC cells of different metastatic potentials. The metastatic effects of exosomes derived from highly metastatic HCC cells (HMH) were evaluated both in vitro and in vivo. Exosomal proteins were identified with iTRAQ mass spectrum and verified in cell lines, xenograft tumor samples, and functional analyses. Exosomes released by HMH significantly enhanced the in vitro invasion and in vivo metastasis of low metastatic HCC cells (LMH). S100 calcium-binding protein A4 (S100A4) was identified as a functional factor in exosomes derived from HMH. S100A4rich exosomes significantly promoted tumor metastasis both in vitro and in vivo compared with S100A4low exosomes or controls. Moreover, exosomal S100A4 could induce expression of osteopontin (OPN), along with other tumor metastasis/stemness-related genes. Exosomal S100A4 activated OPN transcription via STAT3 phosphorylation. HCC patients with high exosomal S100A4 in plasma also had a poorer prognosis. In conclusion, exosomes from HMH could promote the metastatic potential of LMH, and exosomal S100A4 is a key enhancer for HCC metastasis, activating STAT3 phosphorylation and up-regulating OPN expression. This suggested exosomal S100A4 to be a novel prognostic marker and therapeutic target for HCC metastasis.

scholarly journals Nuclear-Biased DUSP6 Expression is Associated with Cancer Spreading Including Brain Metastasis in Triple-Negative Breast Cancer

2019 ◽  
Vol 20 (12) ◽  
pp. 3080 ◽  
Author(s):  
Fan Wu ◽  
Robert D. McCuaig ◽  
Christopher R. Sutton ◽  
Abel H. Y. Tan ◽  
Yoshni Jeelall ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Cancer Progression ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Lung Metastases ◽  
Her2 Positive ◽  
Pathway Gene ◽  
Dual Specificity ◽  
The Brain

DUSP6 is a dual-specificity phosphatase (DUSP) involved in breast cancer progression, recurrence, and metastasis. DUSP6 is predominantly cytoplasmic in HER2+ primary breast cancer cells, but the expression and subcellular localization of DUSPs, especially DUSP6, in HER2-positive circulating tumor cells (CTCs) is unknown. Here we used the DEPArray system to identify and isolate CTCs from metastatic triple negative breast cancer (TNBC) patients and performed single-cell NanoString analysis to quantify cancer pathway gene expression in HER2-positive and HER2-negative CTC populations. All TNBC patients contained HER2-positive CTCs. HER2-positive CTCs were associated with increased ERK1/ERK2 expression, which are direct DUSP6 targets. DUSP6 protein expression was predominantly nuclear in breast CTCs and the brain metastases but not pleura or lung metastases of TNBC patients. Therefore, nuclear DUSP6 may play a role in the association with cancer spreading in TNBC patients, including brain metastasis.

Ewing's tumors with primary lung metastases: survival analysis of 114 (European Intergroup) Cooperative Ewing's Sarcoma Studies patients.

1998 ◽  
Vol 16 (9) ◽  
pp. 3044-3052 ◽  
Author(s):  
M Paulussen ◽  
S Ahrens ◽  
A W Craft ◽  
J Dunst ◽  
B Fröhlich ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Primary Tumor ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Lung Metastases ◽  
Local Treatment ◽  
Poor Response ◽  
Chemotherapy Response ◽  
Treatment Intensification ◽  
Lung Irradiation

PURPOSE To analyze event-free survival (EFS) and prognostic factors in patients who present with Ewing's tumors (ET) of bone and synchronous pulmonary and/or pleural metastases (ppm). PATIENTS AND METHODS Of 1,270 patients (pts) registered at the continental office of the German/European Intergroup Cooperative Ewing's Sarcoma Studies (CESS81, CESS86, EICESS92), 114 were diagnosed ET with ppm. Patients underwent neoadjuvant therapy and local treatment of the primary tumor. Whole-lung irradiation 15 to 18 Gy was applied to 75 ppm-pts. EFS and 95% confidence intervals (CIs) were estimated according to the Kaplan-Meier method, and prognostic factors were analyzed by log-rank tests and Cox and logistic regression procedures. RESULTS On November 1, 1997, at a median time under study of 5.9 years, the 5-year EFS was 0.36 (95% CI, 0.26 to 0.46) and the 10-year EFS was 0.30 (95% CI, 0.19 to 0.41). Thirty-seven of 59 (63%) first relapses involved lung and/or pleura, and the lungs were the only site of relapse in 26 of 59 (44%) ppm-pts. Risk factors identified in univariate and multivariate tests were poor response of the primary tumor toward chemotherapy, metastatic lesions in both lungs, and treatment without additional lung irradiation. CONCLUSION Chemotherapy response of the primary tumor is a prognostic factor in patients with ET with ppm. Strategies of treatment intensification warrant further evaluation.

scholarly journals Non-Mucinous Lepidic Predominant Adenocarcinoma Presenting with Extensive Aerogenous Spread

Rare Tumors ◽  
2016 ◽  
Vol 8 (4) ◽  
pp. 169-172 ◽  
Author(s):  
Yusuke Takanashi ◽  
Shogo Tajima ◽  
Masaru Tsukui ◽  
Kazuya Shinmura ◽  
Takamitsu Hayakawa ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Histopathological Examination ◽  
Periodic Acid ◽  
Lower Lobe ◽  
Poor Response ◽  
Clara Cells ◽  
Invasive Adenocarcinoma ◽  
Rare Presentation ◽  
Periodic Acid Schiff ◽  
The Right

An extremely rare case of non-mucinous lepidic-predominant invasive adenocarcinoma (LPA) showing extensive aerogenous spread with a pneumonic presentation is reported. A 73-year-old woman was referred to our hospital because of an infiltrative shadow on chest xray. Chest computed tomography revealed extensive ground glass opacities in the right lower lobe, which was accompanied by infiltrative shadow with a pneumonic presentation. Invasive mucinous adenocarcinoma was presumed, and a partial resection of the right lower lobe was done. Histopathological examination revealed lepidic growth-predominant invasive adenocarcinoma with Clara type tumor cells, and there were innumerable aerogenous metastases also consisting of Clara cells. Because Alcian Blue and periodic acid-Schiff staining disclosed no mucus, the tumor was diagnosed as a non-mucinous LPA. The patient showed a poor response to 5 courses of pemetrexed, and she died one year after the diagnosis due to cancer progression. Nonmucinous LPA showed a rare presentation characterized by extensive aerogenous spread followed by a poor prognosis.

scholarly journals Insight toward the MicroRNA Profiling of Laryngeal Cancers: Biological Role and Clinical Impact

2020 ◽  
Vol 21 (10) ◽  
pp. 3693 ◽  
Author(s):  
Takashi Takeuchi ◽  
Hiromichi Kawasaki ◽  
Amalia Luce ◽  
Alessia Maria Cossu ◽  
Gabriella Misso ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Multimodality Treatment ◽  
Metastatic Potential ◽  
Clinical Impact ◽  
Overall Survival Rate ◽  
Therapeutic Approaches ◽  
Great Opportunity ◽  
Non Coding Rnas ◽  
Mirna Deregulation

Head and neck squamous cell carcinoma (HNSCC), a heterogeneous disease arising from various anatomical locations including the larynx, is a leading cause of death worldwide. Despite advances in multimodality treatment, the overall survival rate of the disease is still largely dismal. Early and accurate diagnosis of HNSCC is urgently demanded in order to prevent cancer progression and to improve the quality of the patient’s life. Recently, microRNAs (miRNAs), a family of small non-coding RNAs, have been widely reported as new robust tools for prediction, diagnosis, prognosis, and therapeutic approaches of human diseases. Abnormally expressed miRNAs are strongly associated with cancer development, resistance to chemo-/radiotherapy, and metastatic potential through targeting a large variety of genes. In this review, we summarize on the recent reports that emphasize the pivotal biological roles of miRNAs in regulating carcinogenesis of HNSCC, particularly laryngeal cancer. In more detail, we report the characterized miRNAs with an evident either oncogenic or tumor suppressive role in the cancers. In addition, we also focus on the correlation between miRNA deregulation and clinical relevance in cancer patients. On the basis of intriguing findings, the study of miRNAs will provide a new great opportunity to access better clinical management of the malignancies.

scholarly journals Dissecting the Lymphatic System to Predict Melanoma Metastasis

2020 ◽  
Vol 10 ◽  
Author(s):  
Rishi Suresh ◽  
Arturas Ziemys ◽  
Ashley M. Holder
Keyword(s):  
Cutaneous Melanoma ◽  
Lymphatic System ◽  
Survival Rates ◽  
Metastatic Potential ◽  
The United States ◽  
Molecular Characteristics ◽  
High Survival ◽  
Melanoma Metastasis ◽  
Metastatic Risk ◽  
Ajcc Staging

Melanoma is the most lethal form of skin cancer in the United States. Current American Joint Committee on Cancer (AJCC) staging uses Breslow depth and ulceration as the two primary tumor factors that predict metastatic risk in cutaneous melanoma. Early disease stages are generally associated with high survival rates. However, in some cases, patients with thin melanomas develop advanced disease, suggesting other factors may contribute to the metastatic potential of an individual patient’s melanoma. This review focuses on the role of the lymphatic system in the metastasis of cutaneous melanoma, from recent discoveries in mechanisms of lymphangiogenesis to elements of the lymphatic system that ultimately may aid clinicians in determining which patients are at highest risk. Ultimately, this review highlights the need to integrate pathological, morphological, and molecular characteristics of lymphatics into a “biomarker” for metastatic potential.

scholarly journals Role of Heparan Sulfate 2-O-Sulfotransferase in Prostate Cancer Cell Proliferation, Invasion, and Growth Factor Signaling

2011 ◽  
Vol 2011 ◽  
pp. 1-14 ◽  
Author(s):  
Brent W. Ferguson ◽  
Sumana Datta
Keyword(s):  
Prostate Cancer ◽  
Growth Factor ◽  
Heparan Sulfate ◽  
Cancer Progression ◽  
Metastatic Potential ◽  
Growth Factor Signaling ◽  
Cancer Cell Proliferation ◽  
Determining Factors ◽  
Proliferation And Invasion

Heparan-sulfate proteoglycans (HSPGs) are required for maximal growth factor signaling in prostate cancer progression. The degree of sulfate modification on the covalently attached heparan sulfate (HS) chains is one of the determining factors of growth factor-HSPG interactions. Sulfate groups are transferred to HS chains via a series of O-sulfotransferases. In the present study, we demonstrate that Heparan sulfate 2-O-sulfotransferase (2OST) is essential for maximal proliferation and invasion of prostate cancer cells in the LNCaP-C4-2B model. We also show that a decrease in invasion due to 2OST siRNA is associated with an increase in actin and E-cadherin accumulation at the cell surface. 2OST expression correlates with increasing metastatic potential in this model. We demonstrate that 2OST expression is upregulated by the stress-inducible transcription factors HIF1α, ATF2, and NFκB. Chromatin immunoprecipitation analysis suggests that HIF1αand ATF2 act directly on the 2OST promoter, while NFκB acts indirectly.

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