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Sample records for metastasis biology section

  1. Emerging Biological Principles of Metastasis.

    PubMed

    Lambert, Arthur W; Pattabiraman, Diwakar R; Weinberg, Robert A

    2017-02-09

    Metastases account for the great majority of cancer-associated deaths, yet this complex process remains the least understood aspect of cancer biology. As the body of research concerning metastasis continues to grow at a rapid rate, the biological programs that underlie the dissemination and metastatic outgrowth of cancer cells are beginning to come into view. In this review we summarize the cellular and molecular mechanisms involved in metastasis, with a focus on carcinomas where the most is known, and we highlight the general principles of metastasis that have begun to emerge. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. [Biology of cancer metastasis].

    PubMed

    Robert, Jacques

    2013-04-01

    Metastatic dissemination represents the true cause of the malignant character of cancers. Its targeting is much more difficult than that of cell proliferation, because metastasis, like angiogenesis, involves a number of complex interactions between tumour and stroma; the contribution of adhesion and motility pathways is added to that of proliferation and survival pathways. Long distance extension, discontinuous in respect to the primitive tumour, is a major feature of cancer and the main cause of patients' death. Cancer cells use two main dissemination pathways: the lymphatic pathway, leading to the invasion of the lymph nodes draining the organs where the tumour evolves; and the blood pathway, leading to the invasion of distant organs such as liver, brain, bone or lung. Metastasis is inscribed within the properties of the primitive tumour, as shown by the comparative molecular analysis of the primitive tumour and its own metastases: their similarity is always more important than what could be expected from the general activation of "metastasis genes" or the inhibition of "metastasis suppressor genes". Among the signalling pathways involved in metastasis, one can mention the integrin pathway, the transforming growth factor beta (TGFβ) pathway, the chemokine pathway, the dependence receptor pathway and many others. These pathways allow the possibility of therapeutic targeting, thanks to therapeutic antibodies or small molecules inhibiting the kinases involved in these signalling pathways, but not a single properly anti-metastatic drug has yet been proposed: the complexity and the diversity of the processes allowing metastasis emergence, as well as the fact that the activation mechanisms are more often epigenetic than genetic and are generally physiological processes misled by the malignant cell, render especially difficult the therapeutic approach of metastasis.

  3. Computational systems biology in cancer brain metastasis.

    PubMed

    Peng, Huiming; Tan, Hua; Zhao, Weiling; Jin, Guangxu; Sharma, Sambad; Xing, Fei; Watabe, Kounosuke; Zhou, Xiaobo

    2016-01-01

    Brain metastases occur in 20-40% of patients with advanced malignancies. A better understanding of the mechanism of this disease will help us to identify novel therapeutic strategies. In this review, we will discuss the systems biology approaches used in this area, including bioinformatics and mathematical modeling. Bioinformatics has been used for identifying the molecular mechanisms driving brain metastasis and mathematical modeling methods for analyzing dynamics of a system and predicting optimal therapeutic strategies. We will illustrate the strategies, procedures, and computational techniques used for studying systems biology in cancer brain metastases. We will give examples on how to use a systems biology approach to analyze a complex disease. Some of the approaches used to identify relevant networks, pathways, and possibly biomarkers in metastasis will be reviewed into details. Finally, certain challenges and possible future directions in this area will also be discussed.

  4. The Molecular Biology of Brain Metastasis

    PubMed Central

    Rahmathulla, Gazanfar; Toms, Steven A.; Weil, Robert J.

    2012-01-01

    Metastasis to the central nervous system (CNS) remains a major cause of morbidity and mortality in patients with systemic cancers. Various crucial interactions between the brain environment and tumor cells take place during the development of the cancer at its new location. The rapid expansion in molecular biology and genetics has advanced our knowledge of the underlying mechanisms involved, from invasion to final colonization of new organ tissues. Understanding the various events occurring at each stage should enable targeted drug delivery and individualized treatments for patients, with better outcomes and fewer side effects. This paper summarizes the principal molecular and genetic mechanisms that underlie the development of brain metastasis (BrM). PMID:22481931

  5. AACR Centennial Series: The Biology of Cancer Metastasis: Historical Perspective

    PubMed Central

    Talmadge, James E; Fidler, Isaiah J

    2014-01-01

    Metastases resistant to therapy is the major cause of death from cancer. Despite almost 200 years of study, the process of tumor metastasis remains controversial. Stephen Paget initially identified the role of host-tumor interactions on the basis of a review of autopsy records. His “seed and soil” hypothesis was substantiated a century later with experimental studies and numerous reports have confirmed these seminal observations. Inarguably, an improved understanding of the metastatic process and the attributes of the cells selected by this process are critical to the treatment of patients with systemic disease. In many patients, metastasis has occurred by the time of diagnosis, such that metastasis prevention may not be relevant, and treatment of systemic disease, as well as the identity of patients with early disease, should be our goal. During the last three decades, revitalized research has focused on new discoveries in the biology of metastasis. While our understanding of the molecular events that regulate metastasis has improved; nonetheless, the relevant contributions and timing of molecular lesion(s) potentially involved in its pathogenesis remain unclear. The history of pioneering observations and discussion of current controversies should help investigators understand the complex and multifactorial interactions between the host and selected tumor cells that contribute to fatal metastasis and allow for the design of successful therapy. PMID:20610625

  6. Predicting Brain Metastasis in Breast Cancer Patients: Stage Versus Biology.

    PubMed

    Azim, Hamdy A; Abdel-Malek, Raafat; Kassem, Loay

    2017-08-18

    Brain metastasis (BM) is a life-threatening event in breast cancer patients. Identifying patients at a high risk for BM can help to adopt screening programs and test preventive interventions. We tried to identify the incidence of BM in different stages and subtypes of breast cancer. We reviewed the clinical records of 2193 consecutive breast cancer patients who presented between January 1999 and December 2010. We explored the incidence of BM in relation to standard clinicopathological factors, and determined the cumulative risk of BM according to the disease stage and phenotype. Of the 2193 included women, 160 (7.3%) developed BM at a median follow-up of 5.8 years. Age younger than 60 years (P = .015), larger tumors (P = .004), lymph node (LN) positivity (P < .001), high tumor grade (P = .012), and HER2 positivity (P < .001) were associated with higher incidence of BM in the whole population. In patients who presented with locoregional disease, 3 factors independently predicted BM: large tumors (hazard ratio [HR], 3.60; 95% confidence interval [CI], 1.54-8.38; P = .003), axillary LN metastasis (HR, 4.03; 95% CI, 1.91-8.52; P < .001), and HER2 positivity (HR, 1.89; 95% CI, 1.0-3.41; P = .049). A Brain Relapse Index was formulated using those 3 factors, with 5-year cumulative incidence of BM of 19.2% in those having the 2 or 3 risk factors versus 2.5% in those with no or 1 risk factor (P < .001). In metastatic patients, 3 factors were associated with higher risk of BM: HER2 positivity (P = .007), shorter relapse-free interval (P < .001), and lung metastasis (P < .001). Disease stage and biological subtypes predict the risk for BM and subsequent treatment outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Metastasis

    MedlinePlus

    ... Trials Database Supporting Research Raising Awareness Our Blog Patient Education Pancreas News Basics of Pancreatic Cancer FAQs The ... Detection- Goggins Lab Sol Goldman Center Discussion Board Patient Education / Diagnosis Metastasis A major concern when diagnosing a ...

  8. Physical biology in cancer. 1. Cellular physics of cancer metastasis.

    PubMed

    Moore, Nicole M; Nagahara, Larry A

    2014-01-15

    One of the major challenges in cancer research today is developing new therapeutic strategies to control metastatic disease, the spread of cancer cells from a primary tumor to seed in a distant site. Advances in diagnosis and treatment options have increased the survival rate for most patients with local tumors; however, less progress has been made in treatment of disseminated disease. According to the SEER Cancer Statistics Review, 1975-2010, in the case of breast and prostate cancers, only one in four patients diagnosed with distant metastatic disease will survive more than five years. Current research efforts largely focus on identifying biological targets, such as specific genes and signaling pathways that drive two key steps of metastasis, invasion from the primary tumor and growth in the secondary site. On the other hand, there are phenotypic traits and dynamics in the metastatic process that are not encoded by single genes or signaling pathways but, rather, a larger system of events and biophysical characteristics. Connecting genomic and pathway investigations with quantitative physical phenotypic characteristics of cells, the physical microenvironment, and the physical spatiotemporal interactions of the metastatic process provides a stronger complementary understanding of the disease.

  9. Biomechanical forces in the skeleton and their relevance to bone metastasis: biology and engineering considerations

    PubMed Central

    Lynch, Maureen; Fischbach, Claudia

    2014-01-01

    Bone metastasis represents the leading cause of breast cancer related-deaths. However, the effect of skeleton-associated biomechanical signals on the initiation, progression, and therapy response of breast cancer bone metastasis is largely unknown. This review seeks to highlight possible functional connections between skeletal mechanical signals and breast cancer bone metastasis and their contribution to clinical outcome. It provides an introduction to the physical and biological signals underlying bone functional adaptation and discusses the modulatory roles of mechanical loading and breast cancer metastasis in this process. Following a definition of biophysical design criteria, in vitro and in vivo approaches from the fields of bone biomechanics and tissue engineering will be reviewed that may be suitable to investigate breast cancer bone metastasis as a function of varied mechano-signaling. Finally, an outlook of future opportunities and challenges associated with this newly emerging field will be provided. PMID:25174311

  10. [Prediction of Post-operative Lymph Node Metastasis with a Molecular Biological Test in Head and Neck Cancer].

    PubMed

    Takahashi, Katsumasa; Nakajima, Kyoko; Shino, Masato; Toyoda, Minoru; Takayasu, Yukihiro; Chikamatsu, Kazuaki

    2015-02-01

    We assessed herein the post-operative lymph node metastasis in head and neck cancer, using the One-step nucleotide amplification (OSNA) method targeting matrix metalloproteinase 7 (MMP-7). Compared with the pathological test, the molecular biological test revealed more lymph node metastasis, resulting in poor prognosis. Six cases, of which the number of lymph node metastasis was the same between pathological and molecular biological test, survived. On the other hand, three of four cases, in which number of lymph node metastasis in the molecular biological test were larger than the pathological test, died from metastasis. We concluded that the pathological test underestimated metastasis, and OSNA with MMP-7 was useful for the prediction of post-operative lymph node metastasis.

  11. Effect of age and biological subtype on the risk and timing of brain metastasis in breast cancer patients.

    PubMed

    Hung, Man-Hsin; Liu, Chun-Yu; Shiau, Cheng-Ying; Hsu, Chin-Yi; Tsai, Yi-Fang; Wang, Yu-Ling; Tai, Ling-Chen; King, Kuang-Liang; Chao, Ta-Chung; Chiu, Jen-Hwey; Su, Cheng-Hsi; Lo, Su-Shun; Tzeng, Cheng-Hwai; Shyr, Yi-Ming; Tseng, Ling-Ming

    2014-01-01

    Brain metastasis is a major complication of breast cancer. This study aimed to analyze the effect of age and biological subtype on the risk and timing of brain metastasis in breast cancer patients. We identified subtypes of invasive ductal carcinoma of the breast by determining estrogen receptor, progesterone receptor and HER2 status. Time to brain metastasis according to age and cancer subtype was analyzed by Cox proportional hazard analysis. Of the 2248 eligible patients, 164 (7.3%) developed brain metastasis over a median follow-up of 54.2 months. Age 35 or younger, HER2-enriched subtype, and triple-negative breast cancer were significant risk factors of brain metastasis. Among patients aged 35 or younger, the risk of brain metastasis was independent of biological subtype (P = 0.507). Among patients aged 36-59 or >60 years, those with triple-negative or HER2-enriched subtypes had consistently increased risk of brain metastasis, as compared with those with luminal A tumors. Patients with luminal B tumors had higher risk of brain metastasis than luminal A only in patients >60 years. Breast cancer subtypes are associated with differing risks of brain metastasis among different age groups. Patients age 35 or younger are particularly at risk of brain metastasis independent of biological subtype.

  12. The Biology of Brain Metastasis: Challenges for Therapy.

    PubMed

    Fidler, Isaiah J

    2015-01-01

    Many patients with lung cancer, breast cancer, and melanoma develop brain metastases that are resistant to conventional therapy. The median survival for untreated patients is 1 to 2 months, which may be extended to 6 months with surgery, radiotherapy, and chemotherapy. The outcome of metastasis depends on multiple interactions of unique metastatic cells with host homeostatic mechanisms which the tumor cells exploit for their survival and proliferation. The blood-brain barrier is leaky in metastases that are larger than 0.5-mm diameter because of production of vascular endothelial growth factor by metastatic cells. Brain metastases are surrounded and infiltrated by microglia and activated astrocytes. The interaction with astrocytes leads to up-regulation of multiple genes in the metastatic cells, including several survival genes that are responsible for the increased resistance of tumor cells to cytotoxic drugs. These findings substantiate the importance of the "seed and soil" hypothesis and that successful treatment of brain metastases must include targeting of the organ microenvironment.

  13. Biological Ablation of Sentinel Lymph Node Metastasis in Submucosally Invaded Early Gastrointestinal Cancer

    PubMed Central

    Kikuchi, Satoru; Kishimoto, Hiroyuki; Tazawa, Hiroshi; Hashimoto, Yuuri; Kuroda, Shinji; Nishizaki, Masahiko; Nagasaka, Takeshi; Shirakawa, Yasuhiro; Kagawa, Shunsuke; Urata, Yasuo; Hoffman, Robert M; Fujiwara, Toshiyoshi

    2015-01-01

    Currently, early gastrointestinal cancers are treated endoscopically, as long as there are no lymph node metastases. However, once a gastrointestinal cancer invades the submucosal layer, the lymph node metastatic rate rises to higher than 10%. Therefore, surgery is still the gold standard to remove regional lymph nodes containing possible metastases. Here, to avoid prophylactic surgery, we propose a less-invasive biological ablation of lymph node metastasis in submucosally invaded gastrointestinal cancer patients. We have established an orthotopic early rectal cancer xenograft model with spontaneous lymph node metastasis by implantation of green fluorescent protein (GFP)-labeled human colon cancer cells into the submucosal layer of the murine rectum. A solution containing telomerase-specific oncolytic adenovirus was injected into the peritumoral submucosal space, followed by excision of the primary rectal tumors mimicking the endoscopic submucosal dissection (ESD) technique. Seven days after treatment, GFP signals had completely disappeared indicating that sentinel lymph node metastasis was selectively eradicated. Moreover, biologically treated mice were confirmed to be relapse-free even 4 weeks after treatment. These results indicate that virus-mediated biological ablation selectively targets lymph node metastasis and provides a potential alternative to surgery for submucosal invasive gastrointestinal cancer patients. PMID:25523761

  14. Biological ablation of sentinel lymph node metastasis in submucosally invaded early gastrointestinal cancer.

    PubMed

    Kikuchi, Satoru; Kishimoto, Hiroyuki; Tazawa, Hiroshi; Hashimoto, Yuuri; Kuroda, Shinji; Nishizaki, Masahiko; Nagasaka, Takeshi; Shirakawa, Yasuhiro; Kagawa, Shunsuke; Urata, Yasuo; Hoffman, Robert M; Fujiwara, Toshiyoshi

    2015-03-01

    Currently, early gastrointestinal cancers are treated endoscopically, as long as there are no lymph node metastases. However, once a gastrointestinal cancer invades the submucosal layer, the lymph node metastatic rate rises to higher than 10%. Therefore, surgery is still the gold standard to remove regional lymph nodes containing possible metastases. Here, to avoid prophylactic surgery, we propose a less-invasive biological ablation of lymph node metastasis in submucosally invaded gastrointestinal cancer patients. We have established an orthotopic early rectal cancer xenograft model with spontaneous lymph node metastasis by implantation of green fluorescent protein (GFP)-labeled human colon cancer cells into the submucosal layer of the murine rectum. A solution containing telomerase-specific oncolytic adenovirus was injected into the peritumoral submucosal space, followed by excision of the primary rectal tumors mimicking the endoscopic submucosal dissection (ESD) technique. Seven days after treatment, GFP signals had completely disappeared indicating that sentinel lymph node metastasis was selectively eradicated. Moreover, biologically treated mice were confirmed to be relapse-free even 4 weeks after treatment. These results indicate that virus-mediated biological ablation selectively targets lymph node metastasis and provides a potential alternative to surgery for submucosal invasive gastrointestinal cancer patients.

  15. Impact of tumor chronology and tumor biology on lymph node metastasis in breast cancer.

    PubMed

    Smeets, Ann; Ryckx, Andries; Belmans, Ann; Wildiers, Hans; Neven, Patrick; Floris, Giuseppe; Schöffski, Patrick; Christiaens, Marie-Rose

    2013-01-01

    The significance of nodal metastasis in breast cancer is under discussion. We investigated the impact of variables of tumor chronology and tumor biology on the presence of lymph node metastases. Lymph node involvement is the main prognostic factor in breast cancer. However, it is under discussion whether nodal metastasis in breast cancer only reflects the chronological age of the tumor or whether it is also a marker of tumor biology. The goal of our study was to investigate the impact of variables of tumor chronology and biology on the presence of lymph node metastases. We performed a retrospective analysis of data from 3002 patients with an early invasive breast carcinoma. All patients underwent primary surgery at the University Hospitals Leuven between 2001 and 2009. First, the impact of tumor size on the presence of lymph node metastasis was evaluated as the chronological age of a tumor is supposed to be reflected in its size. Next, the impact of tumor grade, lymphovascular invasion and the hormone receptor status, which are all variables of tumor biology, was studied. Logistic regression analyses were performed and the area under the ROC curve (AUC) was calculated as a measure of discrimination between logistic regression models. Using pathological tumor size the AUC of prediction was 0.67. Based on variables of tumor biology, axillary lymph node positivity could be predicted with an AUC of 0.68. Combining variables of tumor chronology and biology an AUC of 0.74 for the prediction of axillary lymph node (ALN) positivity was calculated. According to our data variables of tumor chronology and tumor biology have a similar impact on the presence of lymph node metastasis.

  16. Activation of the CXCR4 chemokine receptor enhances biological functions associated with B16 melanoma liver metastasis.

    PubMed

    Mendt, Mayela; Cardier, Jose E

    2017-08-01

    The CXCR4 chemokine receptor plays an essential role in the homing of cells to organs expressing its ligand, CXCL12. CXCR4 expressed on tumor cells might regulate their traffic during metastasis. Here, we investigated whether the activation of CXCR4 on B16 murine melanoma cells regulates biological functions associated with metastasis, in vitro and in vivo. Flow cytometry and PCR analysis showed that B16 constitutively expresses high levels of CXCR4 (CXCR4-B16). Biological assays showed that the activation of CXCR4, by its ligand CXCL12, increases the migration, invasion, and proliferation of CXCR4-B16. AMD3100 significantly inhibited the stimulatory migrating effect induced by CXCL12. Treatment of CXCR4-B16 with CXCL12 increases their adhesion to liver sinusoidal endothelial cell (LSEC) monolayers. LSEC, expressing CXCL12, increased the migration of CXCR4-B16. In a liver metastasis model, CXCR4-B16 metastasis was associated with an increased expression of CXCL12 in LSEC territories. CXCR4-B16 cells were located close to LSEC microenvironments expressing CXCL12. Increased liver metastasis was observed after injecting CXCR4-B16 cells previously treated with CXCL12. Our results provide evidence showing that CXCR4 plays an important role in regulating biological functions associated with B16 liver metastasis.

  17. Recent advances in the biology of human circulating tumour cells and metastasis

    PubMed Central

    Gkountela, Sofia; Szczerba, Barbara; Donato, Cinzia; Aceto, Nicola

    2016-01-01

    The development of a metastatic disease is recognised as the cause of death of over 90% of patients diagnosed with cancer. Understanding the biological features of metastasis has been hampered for a long time by the difficulties to study widespread cancerous lesions in patients, and by the absence of reliable methods to isolate viable metastatic cells during disease progression. These difficulties negatively impact on our ability to develop new agents that are tailored to block the spread of cancer. Yet, recent advances in specialised devices for the isolation of circulating tumour cells (CTCs), hand-in-hand with technologies that enable single cell resolution interrogation of their genome and transcriptome, are now paving the way to understanding those molecular mechanisms that drive the formation of metastasis. In this review, we aim to summarise some of the latest discoveries in CTC biology in the context of several types of cancer, and to highlight those findings that have a potential to improve the clinical management of patients with metastatic cancer. PMID:27843628

  18. Recent advances in the biology of human circulating tumour cells and metastasis.

    PubMed

    Gkountela, Sofia; Szczerba, Barbara; Donato, Cinzia; Aceto, Nicola

    2016-01-01

    The development of a metastatic disease is recognised as the cause of death of over 90% of patients diagnosed with cancer. Understanding the biological features of metastasis has been hampered for a long time by the difficulties to study widespread cancerous lesions in patients, and by the absence of reliable methods to isolate viable metastatic cells during disease progression. These difficulties negatively impact on our ability to develop new agents that are tailored to block the spread of cancer. Yet, recent advances in specialised devices for the isolation of circulating tumour cells (CTCs), hand-in-hand with technologies that enable single cell resolution interrogation of their genome and transcriptome, are now paving the way to understanding those molecular mechanisms that drive the formation of metastasis. In this review, we aim to summarise some of the latest discoveries in CTC biology in the context of several types of cancer, and to highlight those findings that have a potential to improve the clinical management of patients with metastatic cancer.

  19. Clinicopathologic characteristics and survival of patients with bone metastasis in Yazd, Iran: a cross-sectional retrospective study.

    PubMed

    Shabani, Masood; Binesh, Fariba; Behniafard, Nasim; Nasiri, Faezeh; Shamsi, Farimah

    2014-12-01

    To evaluate the clinico-pathological and survival characteristics in patients with bone metastasis. This cross-sectional study was conducted on patients with bone metastasis who referred to Shahid Ramezanzadeh radiation oncology center. For all of the patients studied, demographic and survival information was recorded. SPSS was used to analyze the data. In this study, 89 men (53.3%) and 78 women (46.7%) with bone metastasis were examined. Most of the patients were in the 66 to 87 age range. Breast cancer was the most common type of cancer in women and prostate cancer was the commonest in men. In most patients, pain was the first manifestation of the disease, and the spine has been most frequently involved areas. The disease was diagnosed by isotope bone scan in the most cases. The mean survival was 31.1 months for patients with breast cancer, 12.9 months for patients with prostate cancer, 13.7 months for patients with lung cancer and the overall survival was 22.5. There was only a meaningful correlation between sex, type of cancer, radiation dose, and survival in patients. We found that age was more effective than the variable of cancer type in survival of patients with bone metastasis. The prognosis of patients with bone metastasis in our center is fair. There was a significant correlation between sex, type of cancer, radiation dose, and survival. Cox proportional hazards model showed that age was a predictor of death.

  20. [The biological essence of golden sections].

    PubMed

    Radiuk, M S

    2001-01-01

    Using the examples of phyllotaxis and the process of graduated development of plant photosynthetic apparatus the author shows that the principle of golden section is an implication of the principle of optimal construction (maximal simplicity). The principle of optimal construction is characterized by minimum of numerical relations between integer and its parts, that indicate the fractal character of studied objects and processes organized according to the golden section principle.

  1. A systems biology approach to invasive behavior: comparing cancer metastasis and suburban sprawl development

    PubMed Central

    2010-01-01

    Background Despite constant progress, cancer remains the second leading cause of death in the United States. The ability of tumors to metastasize is central to this dilemma, as many studies demonstrate successful treatment correlating to diagnosis prior to cancer spread. Hence a better understanding of cancer invasiveness and metastasis could provide critical insight. Presentation of the hypothesis We hypothesize that a systems biology-based comparison of cancer invasiveness and suburban sprawl will reveal similarities that are instructive. Testing the hypothesis We compare the structure and behavior of invasive cancer to suburban sprawl development. While these two systems differ vastly in dimension, they appear to adhere to scale-invariant laws consistent with invasive behavior in general. We demonstrate that cancer and sprawl have striking similarities in their natural history, initiating factors, patterns of invasion, vessel distribution and even methods of causing death. Implications of the hypothesis We propose that metastatic cancer and suburban sprawl provide striking analogs in invasive behavior, to the extent that conclusions from one system could be predictive of behavior in the other. We suggest ways in which this model could be used to advance our understanding of cancer biology and treatment. PMID:20181145

  2. Towards the Biological Understanding of CTC: Capture Technologies, Definitions and Potential to Create Metastasis

    PubMed Central

    Barradas, Ana M.C.; Terstappen, Leon W.M.M.

    2013-01-01

    Circulating Tumor Cells (CTC) are rare cells originated from tumors that travel into the blood stream, extravasate to different organs of which only a small fraction will develop into metastasis. The presence of CTC enumerated with the CellSearch system is associated with a relative short survival and their continued presence after the first cycles of therapy indicates a futile therapy in patients with metastatic carcinomas. Detailed characterization of CTC holds the promise to enable the choice of the optimal therapy for the individual patients during the course of the disease. The phenotype, physical and biological properties are however not well understood making it difficult to assess the merit of recent technological advancements to improve upon the capture of CTC or to evaluate their metastatic potential. Here we will discuss the recent advances in the classification of CTC captured by the CellSearch system, the implications of their features and numbers. Latest capture platforms are reviewed and placed in the light of technology improvements needed to detect CTC. Physical properties, phenotype, viability and proliferative potential and means to assess their proliferation and metastatic capacity will be summarized and placed in the context of the latest CTC capture platforms. PMID:24305653

  3. Handbook to the Conservation Section of the International Biological Programme.

    ERIC Educational Resources Information Center

    Nicholson, E. M.

    Dealing with the organization and activities of one section of the International Biological Programme (IBP), the Conservation Section (CT - Conservation of Terrestrial Communities), this handbook provides an overview of one scientific effort within the worldwide conservation movement. Requirements for a World Conservation Program are described to…

  4. DCB - Tumor Metastasis Research

    Cancer.gov

    Tumor metastasis research examines the mechanisms that allow cancer cells to leave the primary tumor and spread to another part of the body. Learn about recent tumor metastasis research studies supported by the Division of Cancer Biology.

  5. Distant metastasis from oral cancer: A review and molecular biologic aspects

    PubMed Central

    Irani, Soussan

    2016-01-01

    Oral squamous cell carcinoma (OSCC) has been estimated to be the sixth most common cancer worldwide. The distant metastasis plays a critical role in the management and prognosis in oral cancer patients. Regarding the distant metastasis from the oral cancer, the hypopharynx is the most common primary site, followed by the base of tongue and anterior tongue. The present review article analyzes the characteristics of the distant metastases from the oral cavity from 1937 to 2015. PMID:27583211

  6. Extinction and backscatter cross sections of biological materials

    NASA Astrophysics Data System (ADS)

    Thomas, M. E.; Hahn, D. V.; Carr, A. K.; Limsui, D.; Carter, C. C.; Boggs, N. T.; Jackman, J.

    2008-04-01

    Aerosol backscatter and extinction cross-sections are required to model and evaluate the performance of both active and passive detection systems. A method has been developed that begins with laboratory measurements of thin films and suspensions of biological material to obtain the complex index refraction of the biological material from the UV to the LWIR. Using that result with particle size distribution and shape information as inputs to T-matrix or discrete dipole approximation (DDA) calculations yields the extinction cross-section and backscatter cross section as a function of wavelength. These are important inputs to the lidar equation. In a continuing effort to provide validated optical cross-sections, measurements have been made on a number of high purity biological species in the laboratory as well as measurements of material released at recent field tests. The resulting observed differences between laboratory and field measurements aid in distinguishing between intrinsic and extrinsic effects, which can affect the characteristic signatures of important biological aerosols. A variety of biological and test aerosols are examined, including Bacillus atrophaeus (BG), and Erwina, ovalbumin, silica and polystyrene.

  7. The Biological Effects of Dickkopf1 on Small Cell Lung Cancer Cells and Bone Metastasis.

    PubMed

    Pang, Hailin; Ma, Ningqiang; Jiao, Mi; Shen, Weiwei; Xin, Bo; Wang, Tongfei; Zhang, Feng; Liu, Lili; Zhang, Helong

    2017-01-02

    The bone is among the most common sites of metastasis in patients with lung cancer. Over 30%-40% of lung cancers can develop bone metastasis, and no effective therapeutic methods exist in clinic cases. Wnt/β-catenin signaling and Dickkopf1 (DKK1) play important roles in the progression of lung cancer, which preferentially metastasizes to the skeleton. However, the role of DKK1 in osteotropism of small cell lung cancer (SCLC) remains to be elucidated. This study aimed to define the role of DKK1 in SCLC bone metastasis and investigate the underlying mechanisms. Our results demonstrated that the expression level of DKK1 was dramatically higher in bone metastatic SCLC cells (SBC-5 cell line) compared with that in cells without bone metastatic ability (SBC-3 cell line). Therefore, we hypothesized that DKK1 was involved in the bone metastasis of SCLC. We then suppressed the DKK1 expression in SBC-5 cells by RNAi and found that downregulation of DKK1 can inhibit cell proliferation, colony formation, cell migration, and invasion, but increase the apoptosis rate. Downregulation of DKK1 did not affect the cell cycle progression of SBC-5 cells in vitro. In vivo, downregulated DKK1 in SBC-5 cells resulted in attenuated bone metastasis. These results indicated that DKK1 may be an important regulator in bone metastases of SCLC, and targeting DKK1 may be an effective method to prevent and treat skeleton metastases in SCLC cases.

  8. A Systems Biology Approach Identifies FUT8 as a Driver of Melanoma Metastasis.

    PubMed

    Agrawal, Praveen; Fontanals-Cirera, Barbara; Sokolova, Elena; Jacob, Samson; Vaiana, Christopher A; Argibay, Diana; Davalos, Veronica; McDermott, Meagan; Nayak, Shruti; Darvishian, Farbod; Castillo, Mireia; Ueberheide, Beatrix; Osman, Iman; Fenyö, David; Mahal, Lara K; Hernando, Eva

    2017-06-12

    Association of aberrant glycosylation with melanoma progression is based mainly on analyses of cell lines. Here we present a systems-based study of glycomic changes and corresponding enzymes associated with melanoma metastasis in patient samples. Upregulation of core fucosylation (FUT8) and downregulation of α-1,2 fucosylation (FUT1, FUT2) were identified as features of metastatic melanoma. Using both in vitro and in vivo studies, we demonstrate FUT8 is a driver of melanoma metastasis which, when silenced, suppresses invasion and tumor dissemination. Glycoprotein targets of FUT8 were enriched in cell migration proteins including the adhesion molecule L1CAM. Core fucosylation impacted L1CAM cleavage and the ability of L1CAM to support melanoma invasion. FUT8 and its targets represent therapeutic targets in melanoma metastasis. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. An Integrated Systems Biology Approach Identifies TRIM25 as a Key Determinant of Breast Cancer Metastasis.

    PubMed

    Walsh, Logan A; Alvarez, Mariano J; Sabio, Erich Y; Reyngold, Marsha; Makarov, Vladimir; Mukherjee, Suranjit; Lee, Ken-Wing; Desrichard, Alexis; Turcan, Şevin; Dalin, Martin G; Rajasekhar, Vinagolu K; Chen, Shuibing; Vahdat, Linda T; Califano, Andrea; Chan, Timothy A

    2017-08-15

    At the root of most fatal malignancies are aberrantly activated transcriptional networks that drive metastatic dissemination. Although individual metastasis-associated genes have been described, the complex regulatory networks presiding over the initiation and maintenance of metastatic tumors are still poorly understood. There is untapped value in identifying therapeutic targets that broadly govern coordinated transcriptional modules dictating metastatic progression. Here, we reverse engineered and interrogated a breast cancer-specific transcriptional interaction network (interactome) to define transcriptional control structures causally responsible for regulating genetic programs underlying breast cancer metastasis in individual patients. Our analyses confirmed established pro-metastatic transcription factors, and they uncovered TRIM25 as a key regulator of metastasis-related transcriptional programs. Further, in vivo analyses established TRIM25 as a potent regulator of metastatic disease and poor survival outcome. Our findings suggest that identifying and targeting keystone proteins, like TRIM25, can effectively collapse transcriptional hierarchies necessary for metastasis formation, thus representing an innovative cancer intervention strategy. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Optical properties and cross-sections of biological aerosols

    NASA Astrophysics Data System (ADS)

    Thrush, E.; Brown, D. M.; Salciccioli, N.; Gomes, J.; Brown, A.; Siegrist, K.; Thomas, M. E.; Boggs, N. T.; Carter, C. C.

    2010-04-01

    There is an urgent need to develop standoff sensing of biological agents in aerosolized clouds. In support of the Joint Biological Standoff Detection System (JBSDS) program, lidar systems have been a dominant technology and have shown significant capability in field tests conducted in the Joint Ambient Breeze Tunnel (JABT) at Dugway Proving Ground (DPG). The release of biological agents in the open air is forbidden. Therefore, indirect methods must be developed to determine agent cross-sections in order to validate sensor against biological agents. A method has been developed that begins with laboratory measurements of thin films and liquid suspensions of biological material to obtain the complex index of refraction from the ultraviolet (UV) to the long wave infrared (LWIR). Using that result and the aerosols' particle size distribution as inputs to Mie calculations yields the backscatter and extinction cross-sections as a function of wavelength. Recent efforts to model field measurements from the UV to the IR have been successful. Measurements with aerodynamic and geometric particle sizers show evidence of particle clustering. Backscatter simulations of these aerosols show these clustered particles dominate the aerosol backscatter and depolarization signals. In addition, these large particles create spectral signatures in the backscatter signal due to material absorption. Spectral signatures from the UV to the IR have been observed in simulations of field releases. This method has been demonstrated for a variety of biological simulant materials such as Ovalbumin (OV), Erwinia (EH), Bacillus atrophaeus (BG) and male specific bacteriophage (MS2). These spectral signatures may offer new methods for biological discrimination for both stand-off sensing and point detection systems.

  11. Process of hepatic metastasis from pancreatic cancer: biology with clinical significance.

    PubMed

    Shi, Haojun; Li, Ji; Fu, Deliang

    2016-06-01

    Pancreatic cancer shows a remarkable preference for the liver to establish secondary tumors. Selective metastasis to the liver is attributed to the development of potential microenvironment for the survival of pancreatic cancer cells. This review aims to provide a full understanding of the hepatic metastatic process from circulating pancreatic cancer cells to their settlement in the liver, serving as a basic theory for efficient prediction and treatment of metastatic diseases. A systematic search of relevant original articles and reviews was performed on PubMed, EMBASE and Cochrane Library for the purpose of this review. Three interrelated phases are delineated as the contributions of the interaction between pancreatic cancer cells and the liver to hepatic metastasis process. Chemotaxis of disseminated pancreatic cancer cells and simultaneous defensive formation of platelets or neutrophils facilitate specific metastasis toward the liver. Remodeling of extracellular matrix and stromal cells in hepatic lobules and angiogenesis induced by proangiogenic factors support the survival and growth of clinical micrometastasis colonizing the liver. The bimodal role of the immune system or prevalence of cancer cells over the immune system makes metastatic progression successfully proceed from micrometastasis to macrometastasis. Pancreatic cancer is an appropriate research object of cancer metastasis representing more than a straight cascade. If any of the successive or simultaneous phases, especially tumor-induced immunosuppression, is totally disrupted, hepatic metastasis will be temporarily under control or even cancelled forever. To shrink cancers on multiple fronts and prolong survival for patients, novel oral or intravenous anti-cancer agents covering one or different phases of metastatic pancreatic cancer are expected to be integrated into innovative strategies on the premise of safety and efficacious biostability.

  12. Chemotherapy and biological treatment options in breast cancer patients with brain metastasis: an update.

    PubMed

    Arslan, Cagatay; Dizdar, Omer; Altundag, Kadri

    2014-08-01

    Breast cancer (BC) is the second most common cause of CNS metastasis. Ten to 20% of all, and 38% of human epidermal growth factor-2(+), metastatic BC patients experience brain metastasis (BM). Prolonged survival with better control of systemic disease and limited penetration of drugs to CNS increased the probability of CNS metastasis as a sanctuary site of relapse. Treatment of CNS disease has become an important component of overall disease control and quality of life. Current standard therapy for BM is whole-brain radiotherapy, surgery, stereotactic body radiation therapy for selected cases, corticosteroids and systemic chemotherapy. Little progress has been made in chemotherapy for the treatment of BM in patients with BC. Nevertheless, new treatment choices have emerged. In this review, we aimed to update current and future treatment options in systemic treatment for BM of BC. Cornerstone local treatment options for BM of BC are radiotherapy and surgery in selected cases. Efficacy of cytotoxic chemotherapeutics is limited. Among targeted therapies, lapatinib has activity in systemic treatment of BM particularly when used in combination with capecitabine. Novel agents are currently investigated.

  13. Frozen section is superior to imprint cytology for the intra-operative assessment of sentinel lymph node metastasis in Stage I Breast cancer patients

    PubMed Central

    Mori, Miki; Tada, Keiichiro; Ikenaga, Motoko; Miyagi, Yumi; Nishimura, Seiichiro; Takahashi, Kaoru; Makita, Masujiro; Iwase, Takuji; Kasumi, Fujio; Koizumi, Mituru

    2006-01-01

    Background A standard intra-operative procedure for assessing sentinel lymph node metastasis in breast cancer patients has not yet been established. Patients and methods One hundred and thirty-eight patients with stage I breast cancer who underwent sentinel node biopsy using both imprint cytology and frozen section were analyzed. Results Seventeen of the 138 patients had sentinel node involvement. Results of imprint cytology included nine false negative cases (sensitivity, 47.1%). In contrast, only two cases of false negatives were found on frozen section (sensitivity, 88.2%). There were two false positive cases identified by imprint cytology (specificity, 98.3%). On the other hand, frozen section had 100% specificity. Conclusion These findings suggest that frozen section is superior to imprint cytology for the intra-operative determination of sentinel lymph node metastasis in stage I breast cancer patients. PMID:16707007

  14. Integrins and metastasis

    PubMed Central

    Ganguly, Kirat Kumar; Pal, Sekhar; Moulik, Shuvojit; Chatterjee, Amitava

    2013-01-01

    Metastasis is a combination of biological events that makes the difference between cancer and other diseases. Metastasis requires flow of erroneous but precisely coordinated basic cellular activities like cell migration–invasion, cell survival–apoptosis, cell proliferation, etc. All of these processes require efficient regulation of cell attachment and detachment, which recruit integrin receptors in this flow of events. World literatures show several aspects of interrelation of integrins and metastasis. Integrin molecules are being used as prime target to battle metastasis. In this review we are collating the observations showing importance of integrin biology in regulation of metastasis and the strategies where integrin receptors are being used as targets to regulate metastasis. PMID:23563505

  15. Protease-activated receptors (PARs)--biology and role in cancer invasion and metastasis.

    PubMed

    Wojtukiewicz, Marek Z; Hempel, Dominika; Sierko, Ewa; Tucker, Stephanie C; Honn, Kenneth V

    2015-12-01

    Although many studies have demonstrated that components of the hemostatic system may be involved in signaling leading to cancer progression, the potential mechanisms by which they contribute to cancer dissemination are not yet precisely understood. Among known coagulant factors, tissue factor (TF) and thrombin play a pivotal role in cancer invasion. They may be generated in the tumor microenvironment independently of blood coagulation and can induce cell signaling through activation of protease-activated receptors (PARs). PARs are transmembrane G-protein-coupled receptors (GPCRs) that are activated by a unique proteolytic mechanism. They play important roles in vascular physiology, neural tube closure, hemostasis, and inflammation. All of these agents (TF, thrombin, PARs-mainly PAR-1 and PAR-2) are thought to promote cancer invasion and metastasis at least in part by facilitating tumor cell migration, angiogenesis, and interactions with host vascular cells, including platelets, fibroblasts, and endothelial cells lining blood vessels. Here, we discuss the role of PARs and their activators in cancer progression, focusing on TF- and thrombin-mediated actions. Therapeutic options tailored specifically to inhibit PAR-induced signaling in cancer patients are presented as well.

  16. Brain metastasis in human epidermal growth factor receptor 2-positive breast cancer: from biology to treatment

    PubMed Central

    Koo, Taeryool

    2016-01-01

    Overexpression of human epidermal growth factor receptor 2 (HER2) is found in about 20% of breast cancer patients. With treatment using trastuzumab, an anti-HER2 monoclonal antibody, systemic control is improved. Nonetheless, the incidence of brain metastasis does not be improved, rather seems to be increased in HER2-positive breast cancer. The mainstay treatment for brain metastases is radiotherapy. According to the number of metastatic lesions and performance status of patients, radiosurgery or whole brain radiotherapy can be performed. The concurrent use of a radiosensitizer further improves intracranial control. Due to its large molecular weight, trastuzumab has a limited ability to cross the blood-brain barrier. However, small tyrosine kinase inhibitors such as lapatinib, has been noted to be a promising agent that can be used as a radiosensitizer to affect HER2-positive breast cancer. This review will outline general management of brain metastases and will focus on preclinical findings regarding the radiosensitizing effect of small molecule HER2 targeting agents. PMID:27104161

  17. Multiple biological activities of lactic acid in cancer: influences on tumor growth, angiogenesis and metastasis.

    PubMed

    Dhup, Suveera; Dadhich, Rajesh Kumar; Porporato, Paolo Ettore; Sonveaux, Pierre

    2012-01-01

    High rate of glycolysis is a metabolic hallmark of cancer. While anaerobic glycolysis promotes energy production under hypoxia, aerobic glycolysis, the Warburg effect, offers a proliferative advantage through redirecting carbohydrate fluxes from energy production to biosynthetic pathways. To fulfill tumor cell needs, the glycolytic switch is associated with elevated glucose uptake and lactic acid release. Altered glucose metabolism is the basis of positron emission tomography using the glucose analogue tracer [18F]- fluorodeoxyglucose, a widely used clinical application for tumor diagnosis and monitoring. On the other hand, high levels of lactate have been associated with poor clinical outcome in several types of human cancers. Although lactic acid was initially considered merely as an indicator of the glycolytic flux, many evidences originally from the study of normal tissue physiology and more recently transposed to the tumor situation indicate that lactic acid, i.e. the lactate anion and protons, directly contributes to tumor growth and progression. Here, we briefly review the current knowledge pertaining to lactic acidosis and metastasis, lactate shuttles, the influence of lactate on redox homeostasis, lactate signaling and lactate-induced angiogenesis in the cancer context. The monocarboxylate transporters MCT1 and MCT4 have now been confirmed as prominent facilitators of lactate exchanges between cancer cells with different metabolic behaviors and between cancer and stromal cells. We therefore address the function and regulation of MCTs, highlighting MCT1 as a novel anticancer target. MCT1 inhibition allows to simultaneously disrupt metabolic cooperativity and angiogenesis in cancer with a same agent, opening a new path for novel anticancer therapies.

  18. [Cancer research program performed by surgeons invade the biology field - from dormancy to metastasis].

    PubMed

    Pocard, Marc; Eveno, Clarisse; Allaire, Eric

    2012-12-01

    Cancer research program was analyzed. This research was identified using the "master of science in surgery" performed by the majority of surgical resident and fellow. It was analyzed as three axes studying: (i) how to improve the technical practice; (ii) the contribution of surgical skills in basic research, in particular via orthotopic animal models as microenvironment; and (iii) the research in basic biology, testing hypotheses and strategies not confined to surgery but totally multidisciplinary. This research is active with more than half of the fellowships grant in urology sponsored via the French Urologist Association, for projects studying cancer and more than a third of subjects pertaining to the master oncology.

  19. Light and heavy ion beam analysis of thin biological sections

    NASA Astrophysics Data System (ADS)

    Lee, Joonsup; Siegele, Rainer; Pastuovic, Zeljko; Hackett, Mark J.; Hunt, Nicholas H.; Grau, Georges E.; Cohen, David D.; Lay, Peter A.

    2013-07-01

    The application of ion beam analysis (IBA) techniques to thin biological sections (ThBS) presents unique challenges in sample preparation, data acquisition and analysis. These samples are often the end product of expensive, time-consuming experiments, which involve many steps that require careful attention. Analysis via several techniques can maximise the information that is collected from these samples. Particle-induced X-ray emission (PIXE) and Rutherford backscattering (RBS) spectroscopy are two generally non-destructive IBA techniques that use the same MeV ions and can be performed simultaneously. The use of heavy ion PIXE applied to thick samples has, in the past, resulted in X-ray spectra of a poorer quality when compared to those obtained with proton beams. One of the reasons for this is the shorter probing depth of the heavy ions, which does not affect thin sample analysis. Therefore, we have investigated and compared 3-MeV proton and 36-MeV carbon ion beams on 7-μm thick mouse brain sections at the ANSTO Heavy ion microprobe (HIMP). The application of a 36-MeV C4+ ion beam for PIXE mapping of ThBS on thin Si3N4 substrate windows produced spectra of high quality that displayed close to a nine-times gain in signal yield (Z2/q) when compared to those obtained for 3-MeV protons for P, S, Cl and K but not for Fe, Cu and Zn. Image quality was overall similar; however, some elements showed better contrast and features with protons whilst others showed improved contrast with a carbon ion beam. RBS spectra with high enough counting statistics were easily obtained with 3-MeV proton beams resulting in high resolution carbon maps, however, the count rate for nitrogen and oxygen was too low. The results demonstrate that on thin samples, 36-MeV C4+ will produce good quality PIXE spectra in less time; therefore, carbon ions may be advantageous depending on which element is being studied. However, these advantages may be outweighed by the inherent disadvantages including

  20. Fluorescence cross section measurements of biological agent simulants

    SciTech Connect

    Stephens, J.R.

    1996-11-01

    Fluorescence is a powerful technique that has potential uses in detection and characterization of biological aerosols both in the battlefield and in civilian environments. Fluorescence techniques can be used with ultraviolet (UV) light detection and ranging (LIDAR) equipment to detect biological aerosol clouds at a distance, to provide early warning of a biological attack, and to track an potentially noxious cloud. Fluorescence can also be used for detection in a point sensor to monitor biological materials and to distinguish agents from benign aerosols. This work is part of a continuing program by the Army`s Chemical and Biological Defense Command to characterized the optical properties of biological agents. Reported here are ultraviolet fluorescence measurements of Bacillus megaterium and Bacillus Globigii aerosols suspended in an electrodynamic particle trap. Fluorescence spectra of a common atmospheric aerosol, pine pollen, are also presented.

  1. Aspergillus section Nidulantes (formerly Emericella): Polyphasic taxonomy, chemistry and biology.

    PubMed

    Chen, A J; Frisvad, J C; Sun, B D; Varga, J; Kocsubé, S; Dijksterhuis, J; Kim, D H; Hong, S-B; Houbraken, J; Samson, R A

    2016-06-01

    Aspergillus section Nidulantes includes species with striking morphological characters, such as biseriate conidiophores with brown-pigmented stipes, and if present, the production of ascomata embedded in masses of Hülle cells with often reddish brown ascospores. The majority of species in this section have a sexual state, which were named Emericella in the dual name nomenclature system. In the present study, strains belonging to subgenus Nidulantes were subjected to multilocus molecular phylogenetic analyses using internal transcribed spacer region (ITS), partial β-tubulin (BenA), calmodulin (CaM) and RNA polymerase II second largest subunit (RPB2) sequences. Nine sections are accepted in subgenus Nidulantes including the new section Cavernicolus. A polyphasic approach using morphological characters, extrolites, physiological characters and phylogeny was applied to investigate the taxonomy of section Nidulantes. Based on this approach, section Nidulantes is subdivided in seven clades and 65 species, and 10 species are described here as new. Morphological characters including colour, shape, size, and ornamentation of ascospores, shape and size of conidia and vesicles, growth temperatures are important for identifying species. Many species of section Nidulantes produce the carcinogenic mycotoxin sterigmatocystin. The most important mycotoxins in Aspergillus section Nidulantes are aflatoxins, sterigmatocystin, emestrin, fumitremorgins, asteltoxins, and paxillin while other extrolites are useful drugs or drug lead candidates such as echinocandins, mulundocandins, calbistrins, varitriols, variecolins and terrain. Aflatoxin B1 is produced by four species: A. astellatus, A. miraensis, A. olivicola, and A. venezuelensis.

  2. The new follow-on-biologics law: a section by section analysis of the patent litigation provisions in the Biologics Price Competition and Innovation Act of 2009.

    PubMed

    Dougherty, Michael P

    2010-01-01

    An abbreviated pathway for the approval of biosimilar biological products, often called "follow-on biologics," has been enacted into law as part of the health care legislation recently passed by Congress and signed by the President. The subtitle of the health care bill establishing this approval pathway, the Biologics Price Competition and Innovation Act of 2009, includes many provisions governing the identification of patents relevant to a given biosimilar biological product and the assertion of those patents in infringement suits. This article provides a section-by-section analysis of the patent-related provisions of the new approval pathway for biosimilar biological products, and points out several ways in which the new law differs fundamentally from the Hatch-Waxman Act, which provides the approval pathway for generic versions of small molecule drugs.

  3. Targeting Breast Cancer Metastasis

    PubMed Central

    Jin, Xin; Mu, Ping

    2015-01-01

    Metastasis is the leading cause of breast cancer-associated deaths. Despite the significant improvement in current therapies in extending patient life, 30–40% of patients may eventually suffer from distant relapse and succumb to the disease. Consequently, a deeper understanding of the metastasis biology is key to developing better treatment strategies and achieving long-lasting therapeutic efficacies against breast cancer. This review covers recent breakthroughs in the discovery of various metastatic traits that contribute to the metastasis cascade of breast cancer, which may provide novel avenues for therapeutic targeting. PMID:26380552

  4. Aspects of Theme in the Method and Discussion Sections of Biology Journal Articles in English.

    ERIC Educational Resources Information Center

    Martinez, Iliana A.

    2003-01-01

    Analyzes the thematic structure of the method and Discussion section of biology research articles. A corpus of 30 journal articles was analyzed using the categories of systematic functional linguistics and a semantic categorization for unmarked themes realized by subject. Revealed differences in the semantic construction of the sections. (VWL)

  5. A simple formula for estimation of the absorption cross section of biological suspensions

    SciTech Connect

    Paramonov, L.E.

    1994-10-01

    A simple formula for the absorption cross section of biological suspensions is suggested. The error introduced by the formula into the measurements of absorption cross sections of polydisperse spherical particles described by the power, quasi-Gaussian, and gamma distributions, as well as of randomly oriented spheroidal particles is estimated. A formula for the dependence of the absorption cross section on the dispersion composition of a medium is given. 16 refs., 5 tabs.

  6. A case of advanced mycosis fungoides with comprehensive skin and visceral organs metastasis: sensitive to chemical and biological therapy.

    PubMed

    Liu, Yi-Qian; Zhu, Wei-You; Shu, Yong-Qian; Gu, Yan-Hong

    2012-08-01

    Mycosis fungoides is a common cutaneous T-cell lymphoma, which is usually characterized by chronic, indolence progression, with absence of typical symptoms in early stage, metastasis to lymph nodes, bone marrow and visceral organs in later stage and ultimately progression to systemic lymphoma. It can result in secondary skin infection which is a frequent cause of death. At present, no curative therapy existed. Therapeutic purpose is to induce remission, reduce tumor burden and protect immune function of patients. A case of patient with advanced severe mycosis fungoides receiving CHOP plus interferon α-2a was reported here, with disease-free survival of 7 months and overall survival of over 17.0 months, and current status as well as developments of mycosis fungoides were briefly introduced.

  7. Metastasis 'systems' biology: how are macro-environmental signals transmitted into microenvironmental cues for disseminated tumor cells?

    PubMed

    Grzelak, Candice Alexandra; Ghajar, Cyrus Michael

    2017-10-01

    Disseminated breast tumor cells reside on or near stable microvascular endothelium. Currently, the cues that disrupt DTC dormancy and facilitate outgrowth are largely unknown. This article explores the hypothesis that specific patient lifestyle exposures (e.g., alcohol abuse) may disrupt the microenvironments that maintain disseminated tumor cell (DTC) dormancy in a tissue-specific fashion. We suggest that such exposures are 'transmitted' to the dormant niche in the form of injury. Thus, we discuss the relationship between wound healing and metastasis using liver as an example to illustrate how injury steers the phenotype of liver endothelium and perivascular hepatic stellate cells to a potentially pro-metastatic one. We posit further that non-steroidal anti-inflammatory drugs (NSAIDs) - recently shown to prevent metastatic relapse - may act by preserving the dormant niche. We conclude by suggesting that maintenance of the dormant niche - either through patient lifestyle or via development of therapeutics that mimic local molecular cues/responses that coincide with a healthy lifestyle - is a means to prevent metastatic relapse, and should be the subject of far greater research. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Effects of Scoring by Section and Independent Scorers' Patterns on Scorer Reliability in Biology Essay Tests

    ERIC Educational Resources Information Center

    Ebuoh, Casmir N.; Ezeudu, S. A.

    2015-01-01

    The study investigated the effects of scoring by section, use of independent scorers and conventional patterns on scorer reliability in Biology essay tests. It was revealed from literature review that conventional pattern of scoring all items at a time in essay tests had been criticized for not being reliable. The study was true experimental study…

  9. Meeting report: Metastasis Research Society-Chinese Tumor Metastasis Society joint conference on metastasis.

    PubMed

    Bankaitis, Katherine; Borriello, Lucia; Cox, Thomas; Lynch, Conor; Zijlstra, Andries; Fingleton, Barbara; Gužvić, Miodrag; Anderson, Robin; Neman, Josh

    2017-04-01

    During September 16th-20th 2016, metastasis experts from around the world convened for the 16th Biennial Congress of the Metastasis Research Society and 12th National Congress of the Chinese Tumor Metastasis Society in Chengdu, China to share most current data covering basic, translational, and clinical metastasis research. Presentations of the more than 40 invited speakers of the main congress and presentations from the associated Young Investigator Satellite Meeting are summarized in this report by session topic. The congress program also included three concurrent short talk sessions, an advocacy forum with Chinese and American metastatic patient advocates, a 'Meet the Professors Roundtable' session for young investigators, and a 'Meet the Editors' session with editors from Cancer Cell and Nature Cell Biology. The goal of integrating expertise and exchanging the latest findings, ideas, and practices in cancer metastasis research was achieved magnificently, thanks to the excellent contributions of many leaders in the field.

  10. Metastasis: an early event in cancer progression.

    PubMed

    Hu, Yijun; Yu, Xiya; Xu, Guixia; Liu, Shanrong

    2017-05-01

    Metastasis is the leading cause of death for a majority of cancer patients, and thus the need to understand the biology of metastasis becomes increasingly acute. When metastasis is initiated in tumor progression remains obscure. Better understanding of mechanisms regulating acquisition of metastatic ability in tumor cells will provide novel therapeutic targets and prevention of metastasis in clinics accompanied with the treatment of the primary tumor might be helpful in reducing metastasis-related mortality. A literature search was performed in multiple electronic databases. Research papers from clinical reports to experimental studies on metastasis were analyzed. The article discusses tumor heterogeneity and genomic instability in the context of metastasis and tumor cell dissemination. And then we review biological mechanism of metastasis at an early stage in both intracellular (CSCs and CTCs) and extracellular (microenvironment) context. Finally, current development of anti-metastatic therapies is summarized. Metastasis could be initiated at an early point of tumor progression. Therefore, early intervention on metastasis should be applied among cancer patients in clinical settings.

  11. Single ionization and capture cross sections from biological molecules by bare projectile impact*

    NASA Astrophysics Data System (ADS)

    Quinto, Michele A.; Monti, Juan M.; Montenegro, Pablo D.; Fojón, Omar A.; Champion, Christophe; Rivarola, Roberto D.

    2017-02-01

    We report calculations on single differential and total cross sections for single ionization and single electron capture from biological targets, namely, vapor water and DNA nucleobasese molecules, by bare projectile impact: H+, He2+, and C6+. They are performed within the Continuum Distorted Wave - Eikonal Initial State approximation and compared to several existing experimental data. This study is oriented to the obtention of a reliable set of theoretical data to be used as input in a Monte Carlo code destined to micro- and nano- dosimetry.

  12. Intramedullary metastasis.

    PubMed

    Moffie, D; Stefanko, S Z

    1980-01-01

    Three cases of intramedullary metastases and one of a metastasis into the medulla oblongata are described. In two cases the primary tumour was a bronchial carcinoma and in one case a carcinoma of the breast. In one patient a primary tumour could not be found. The literature on this condition is reviewed and the difficulties of clinical diagnosis are discussed. The question remains unanswered as to the mechanism by which these tumour-cells reach the spinal cord and there is, as yet, no satisfactory explanation for the relative rare occurrence of these metastases.

  13. New caged coumarin fluorophores with extraordinary uncaging cross sections suitable for biological imaging applications.

    PubMed

    Zhao, YuRui; Zheng, Quan; Dakin, Kenneth; Xu, Ke; Martinez, Manuel L; Li, Wen-Hong

    2004-04-14

    Photocaged fluorescent molecules are important research tools for tracking molecular dynamics with high spatiotemporal resolution in biological systems. We have designed and synthesized a new class of caged coumarin fluorophores. These coumarin cages displayed more than 200-fold fluorescence enhancement after UV photolysis. Remarkably, the uncaging cross section of a 1-(2-nitrophenyl)ethyl (NPE)-caged coumarin is 6600 at wavelength of 365 nm, about 2 orders of magnitude higher than previously described caged fluorophores. Product analysis of the photolytic reaction showed clean conversion of NPE-caged coumarin to 2-nitrosoacetophenone and the parent coumarin, suggesting that the mechanism of the photolysis follows the known photochemical reaction pathway of the 2-nitrobenzyl group. We have also measured the two-photon uncaging cross sections of NPE-caged coumarins 2a and 5 at 740 nm to be near 1 Goeppert-Mayer (GM). The mechanistic study, together with the two-photon uncaging data, suggested that the coumarin moiety serves as an antenna to enhance the light harvesting efficiency of the coumarin cage and that the photonic energy absorbed by coumarin was utilized efficiently to photolyze the NPE group. Future explorations of this type of "substrate-assisted photolysis" may yield other cages of high uncaging cross sections. For cellular imaging applications, we prepared a cell permeable and caged coumarin fluorophore, NPE-HCCC2/AM (10), which can be loaded into fully intact cells to high concentrations. Initial tests of this probe in a number of cultured mammalian cells showed desired properties for the in vivo imaging applications. The combined advantages of robust fluorescence contrast enhancement, remarkably high uncaging cross sections, noninvasive cellular delivery, and flexible chemistry for bioconjugations should generate broad applications of these caged coumarins in biochemical and biological research.

  14. IFLA General Conference, 1987. Division of Special Libraries. Biological and Medical Science Libraries Section. Social Science Libraries Section. Papers.

    ERIC Educational Resources Information Center

    International Federation of Library Associations, The Hague (Netherlands).

    Six of the nine papers in this collection focus on biological and medical science libraries; the remaining three are concerned with social science libraries. The papers on biological and medical science libraries appear first in this list: (1) "Standards for Medical and Health Care Libraries: Canada" (Jan Greenwood, Canada); (2) "Standards for…

  15. Tumour progression and metastasis

    PubMed Central

    Arvelo, Francisco; Sojo, Felipe; Cotte, Carlos

    2016-01-01

    The two biological mechanisms that determine types of malignancy are infiltration and metastasis, for which tumour microenvironment plays a key role in developing and establishing the morphology, growth and invasiveness of a malignancy. The microenvironment is formed by complex tissue containing the extracellular matrix, tumour and non-tumour cells, a signalling network of cytokines, chemokines, growth factors, and proteases that control autocrine and paracrine communication among individual cells, facilitating tumour progression. During the development of the primary tumour, the tumour stroma and continuous genetic changes within the cells makes it possible for them to migrate, having to count on a pre-metastatic niche receptor that allows the tumour’s survival and distant growth. These niches are induced by factors produced by the primary tumour; if it is eradicated, the active niches become responsible for activating the latent disseminated cells. Due to the importance of these mechanisms, the strategies that develop tumour cells during tumour progression and the way in which the microenvironment influences the formation of metastasis are reviewed. It also suggests that the metastatic niche can be an ideal target for new treatments that make controlling metastasis possible. PMID:26913068

  16. Tumour progression and metastasis.

    PubMed

    Arvelo, Francisco; Sojo, Felipe; Cotte, Carlos

    2016-01-01

    The two biological mechanisms that determine types of malignancy are infiltration and metastasis, for which tumour microenvironment plays a key role in developing and establishing the morphology, growth and invasiveness of a malignancy. The microenvironment is formed by complex tissue containing the extracellular matrix, tumour and non-tumour cells, a signalling network of cytokines, chemokines, growth factors, and proteases that control autocrine and paracrine communication among individual cells, facilitating tumour progression. During the development of the primary tumour, the tumour stroma and continuous genetic changes within the cells makes it possible for them to migrate, having to count on a pre-metastatic niche receptor that allows the tumour's survival and distant growth. These niches are induced by factors produced by the primary tumour; if it is eradicated, the active niches become responsible for activating the latent disseminated cells. Due to the importance of these mechanisms, the strategies that develop tumour cells during tumour progression and the way in which the microenvironment influences the formation of metastasis are reviewed. It also suggests that the metastatic niche can be an ideal target for new treatments that make controlling metastasis possible.

  17. The calculation of radial dose from heavy ions: predictions of biological action cross sections

    NASA Astrophysics Data System (ADS)

    Katz, Robert; Cucinotta, Francis A.; Zhang, C. X.

    1996-02-01

    The track structure model of heavy ion cross sections was developed by Katz and co-workers in the 1960s. In this model the action cross section is evaluated by mapping the dose-response of a detector to γ rays (modeled from biological target theory) onto the radial dose distribution from δ rays about the path of the ion. This is taken to yield the radial distribution of probability for a "hit" (an interaction leading to an observable end-point). Radial integration of the probability yields the cross section. When different response from ions of different Z having the same stopping power is observed this model may be indicated. Since the 1960s there have been several developments in the computation of the radial dose distribution, in the measurement of these distributions, and in new radiobiological data against which to test the model. The earliest model, by Butts and Katz, made use of simplified δ ray distribution functions, of simplified electron range-energy relations, and neglected angular distributions. Nevertheless it made possible the calculation of cross sections for the inactivation of enzymes and viruses, and allowed extension to tracks in nuclear emulsions and other detectors and to biological cells. It set the pattern for models of observable effects in the matter through which the ion passed. Here we outline subsequent calculations of radial dose which make use of improved knowledge of the electron emission spectrum, the electron range-energy relation, the angular distribution, and some considerations of molecular excitation, of particular interest both close to the path of the ion and the outer limits of electron penetration. These are applied to the modeling of action cross sections for the inactivation of several strains of E-coli and B. subtilis spores where extensive measurements in the "thin-down" region have been made with heavy ion beams. Such calculations serve to test the radial dose calculations at the outer limit of electron penetration

  18. The calculation of radial dose from heavy ions: predictions of biological action cross sections

    NASA Technical Reports Server (NTRS)

    Katz, R.; Cucinotta, F. A.; Zhang, C. X.; Wilson, J. W. (Principal Investigator)

    1996-01-01

    The track structure model of heavy ion cross sections was developed by Katz and co-workers in the 1960s. In this model the action cross section is evaluated by mapping the dose-response of a detector to gamma rays (modeled from biological target theory) onto the radial dose distribution from delta rays about the path of the ion. This is taken to yield the radial distribution of probability for a "hit" (an interaction leading to an observable end-point). Radial integration of the probability yields the cross section. When different response from ions of different Z having the same stopping power is observed this model may be indicated. Since the 1960s there have been several developments in the computation of the radial dose distribution, in the measurement of these distributions, and in new radiobiological data against which to test the model. The earliest model, by Butts and Katz made use of simplified delta ray distribution functions, of simplified electron range-energy relations, and neglected angular distributions. Nevertheless it made possible the calculation of cross sections for the inactivation of enzymes and viruses, and allowed extension to tracks in nuclear emulsions and other detectors and to biological cells. It set the pattern for models of observable effects in the matter through which the ion passed. Here we outline subsequent calculations of radial dose which make use of improved knowledge of the electron emission spectrum, the electron range-energy relation, the angular distribution, and some considerations of molecular excitation, of particular interest both close to the path of the ion and the outer limits of electron penetration. These are applied to the modeling of action cross sections for the inactivation of several strains of E-coli and B. subtilis spores where extensive measurements in the "thin-down" region have been made with heavy ion beams. Such calculations serve to test the radial dose calculations at the outer limit of electron

  19. The calculation of radial dose from heavy ions: predictions of biological action cross sections

    NASA Technical Reports Server (NTRS)

    Katz, R.; Cucinotta, F. A.; Zhang, C. X.; Wilson, J. W. (Principal Investigator)

    1996-01-01

    The track structure model of heavy ion cross sections was developed by Katz and co-workers in the 1960s. In this model the action cross section is evaluated by mapping the dose-response of a detector to gamma rays (modeled from biological target theory) onto the radial dose distribution from delta rays about the path of the ion. This is taken to yield the radial distribution of probability for a "hit" (an interaction leading to an observable end-point). Radial integration of the probability yields the cross section. When different response from ions of different Z having the same stopping power is observed this model may be indicated. Since the 1960s there have been several developments in the computation of the radial dose distribution, in the measurement of these distributions, and in new radiobiological data against which to test the model. The earliest model, by Butts and Katz made use of simplified delta ray distribution functions, of simplified electron range-energy relations, and neglected angular distributions. Nevertheless it made possible the calculation of cross sections for the inactivation of enzymes and viruses, and allowed extension to tracks in nuclear emulsions and other detectors and to biological cells. It set the pattern for models of observable effects in the matter through which the ion passed. Here we outline subsequent calculations of radial dose which make use of improved knowledge of the electron emission spectrum, the electron range-energy relation, the angular distribution, and some considerations of molecular excitation, of particular interest both close to the path of the ion and the outer limits of electron penetration. These are applied to the modeling of action cross sections for the inactivation of several strains of E-coli and B. subtilis spores where extensive measurements in the "thin-down" region have been made with heavy ion beams. Such calculations serve to test the radial dose calculations at the outer limit of electron

  20. Micro-PIXE analyses of frozen-hydrated semi-thick biological sections

    NASA Astrophysics Data System (ADS)

    Wang, Y. D.; Mesjasz-Przybylowicz, J.; Tylko, G.; Barnabas, A. D.; Przybylowicz, W. J.

    2013-07-01

    Cryo-micro-PIXE system and methodology of microanalysis of frozen-hydrated semi-thick biological sections is described. A commercially available cryotransfer system used in electron microscopy has been adapted for this purpose. The analyzed material was frozen by metal-mirror method and sections of 20-50 micron thickness were prepared. Micro-PIXE and simultaneous proton backscattering was performed using 3 MeV proton beam. Monitoring of water vapour composition during the proton bombardment showed good stability of the analyzed material. The results of repetitive analyses of standards prepared from gelatin-glycerol solution with added known concentrations of K, Ni, Cu, Zn were in good agreement with expected, calculated values. Mass losses and changes of elemental composition were monitored. Elemental maps obtained for frozen-hydrated semi-thick section of Ni hyperaccumulator Senecio coronatus showed excellent preservation of leaf morphology and the distribution of elements. Quantitative elemental mapping of frozen-hydrated specimens compared with subsequent analysis of the same areas after freeze-drying revealed similar distribution pattern in both cases. It is clear, however, that freeze-drying induces some distortion of cell morphology and specimen shrinkage.

  1. Staining sectioned biological specimens for transmission electron microscopy: conventional and en bloc stains.

    PubMed

    Ellis, E Ann

    2014-01-01

    Post-staining of ultrathin sections and/or en bloc staining of specimens is necessary for differential contrast and improved resolution of cellular structures. Often specimens are fixed and stained with osmium tetroxide during fixation, but additional contrast is the result of additional heavy metal stains on the sections. The most common post-staining of sections is done on grids by aqueous uranyl acetate followed by lead citrate. When it is apparent that simple, aqueous uranium and lead post-staining is not adequate, other stains are invoked. These procedures can be as simple as en bloc staining with uranyl acetate after primary fixation and osmication. Over the years, several other treatments have been developed for use with the primary fixation or during dehydration. Tannic acid, paraphenylenediamine (PPD), and malachite green can all serve as en bloc stains and can contribute to overall improved visualization of ultrastructural details in biological specimens. Tannic acid and PPD improve membrane preservation, and malachite green is a phospholipid stain. All of these stains are compatible with aqueous fixatives and should be considered when the usual stains are not satisfactory. Marinozzi rings and microwave-assisted post-staining offer alternatives to traditional grid staining. In addition, stain precipitates on grids often can be removed by treatment with 10 % (v/v) acetic acid.

  2. Metastasis to a spinal meningioma.

    PubMed

    Bansil, Rohit; Walia, Bipin S; Khan, Zahid; Abrari, Andleeb

    2017-01-01

    Metastasis of one cancer to another is rare. Here, we report a spinal meningioma that was infiltrated by metastatic deposits from another cancer. A 62-year-old male presented with a progressive spastic paraparesis. Magnetic resonance (MR) imaging of the spine suggested a well-defined intradural extramedullary (IDEM) T8 mass in the dorsal spinal canal. When excised, it proved histologically to be a meningothelial meningioma infiltrated by metastatic deposits from an adenocarcinoma. Tumor to tumor metastasis rarely occurs, and meningioma, owing to its biological character and increased vascularity, is one of the most common recipients of a metastases from other lesions.

  3. The challenge of targeting metastasis.

    PubMed

    Fidler, Isaiah J; Kripke, Margaret L

    2015-12-01

    Metastases that are resistant to conventional therapy are the major cause of death from cancer. In most patients, metastasis has already occurred by the time of diagnosis. Thus, the prevention of metastasis is unlikely to be of therapeutic benefit. The biological heterogeneity of metastases presents a major obstacle to treatment. However, the growth and survival of metastases depend on interactions between tumor cells and host homeostatic mechanisms. Targeting these interactions, in addition to the tumor cells, can produce synergistic therapeutic effects against existing metastases.

  4. Ground truth methods for optical cross-section modeling of biological aerosols

    NASA Astrophysics Data System (ADS)

    Kalter, J.; Thrush, E.; Santarpia, J.; Chaudhry, Z.; Gilberry, J.; Brown, D. M.; Brown, A.; Carter, C. C.

    2011-05-01

    Light detection and ranging (LIDAR) systems have demonstrated some capability to meet the needs of a fastresponse standoff biological detection method for simulants in open air conditions. These systems are designed to exploit various cloud signatures, such as differential elastic backscatter, fluorescence, and depolarization in order to detect biological warfare agents (BWAs). However, because the release of BWAs in open air is forbidden, methods must be developed to predict candidate system performance against real agents. In support of such efforts, the Johns Hopkins University Applied Physics Lab (JHU/APL) has developed a modeling approach to predict the optical properties of agent materials from relatively simple, Biosafety Level 3-compatible bench top measurements. JHU/APL has fielded new ground truth instruments (in addition to standard particle sizers, such as the Aerodynamic particle sizer (APS) or GRIMM aerosol monitor (GRIMM)) to more thoroughly characterize the simulant aerosols released in recent field tests at Dugway Proving Ground (DPG). These instruments include the Scanning Mobility Particle Sizer (SMPS), the Ultraviolet Aerodynamic Particle Sizer (UVAPS), and the Aspect Aerosol Size and Shape Analyser (Aspect). The SMPS was employed as a means of measuring smallparticle concentrations for more accurate Mie scattering simulations; the UVAPS, which measures size-resolved fluorescence intensity, was employed as a path toward fluorescence cross section modeling; and the Aspect, which measures particle shape, was employed as a path towards depolarization modeling.

  5. Force per cross-sectional area from molecules to muscles: a general property of biological motors.

    PubMed

    Rospars, Jean-Pierre; Meyer-Vernet, Nicole

    2016-07-01

    We propose to formally extend the notion of specific tension, i.e. force per cross-sectional area-classically used for muscles, to quantify forces in molecular motors exerting various biological functions. In doing so, we review and compare the maximum tensions exerted by about 265 biological motors operated by about 150 species of different taxonomic groups. The motors considered range from single molecules and motile appendages of microorganisms to whole muscles of large animals. We show that specific tensions exerted by molecular and non-molecular motors follow similar statistical distributions, with in particular, similar medians and (logarithmic) means. Over the 10(19) mass (M) range of the cell or body from which the motors are extracted, their specific tensions vary as M(α) with α not significantly different from zero. The typical specific tension found in most motors is about 200 kPa, which generalizes to individual molecular motors and microorganisms a classical property of macroscopic muscles. We propose a basic order-of-magnitude interpretation of this result.

  6. Force per cross-sectional area from molecules to muscles: a general property of biological motors

    PubMed Central

    Meyer-Vernet, Nicole

    2016-01-01

    We propose to formally extend the notion of specific tension, i.e. force per cross-sectional area—classically used for muscles, to quantify forces in molecular motors exerting various biological functions. In doing so, we review and compare the maximum tensions exerted by about 265 biological motors operated by about 150 species of different taxonomic groups. The motors considered range from single molecules and motile appendages of microorganisms to whole muscles of large animals. We show that specific tensions exerted by molecular and non-molecular motors follow similar statistical distributions, with in particular, similar medians and (logarithmic) means. Over the 1019 mass (M) range of the cell or body from which the motors are extracted, their specific tensions vary as Mα with α not significantly different from zero. The typical specific tension found in most motors is about 200 kPa, which generalizes to individual molecular motors and microorganisms a classical property of macroscopic muscles. We propose a basic order-of-magnitude interpretation of this result. PMID:27493785

  7. Metastasis Suppressors and Their Roles in Breast Carcinoma

    PubMed Central

    Vaidya, Kedar. S.; Welch, Danny. R.

    2007-01-01

    Metastasis remains the most deadly aspect of cancer and still evades direct treatment. Clinically and experimentally, primary tumor development and metastasis are distinct processes—locally growing tumors can progress without the development of metastases. The discovery of endogenous molecules that exclusively inhibit metastasis suggests that metastasis is an amenable therapeutic target. By definition, metastasis suppressors inhibit metastasis without inhibiting tumorigenicity and are thus distinct from tumor suppressors. As the biology underlying functional mechanisms of metastasis suppressors becomes clearer, it is evident that metastasis suppressors could be harnessed as direct drug targets, prognostic markers, and to understand the fundamental biology of the metastatic process. Metastasis suppressors vary widely in their cellular localization: they are found in every cellular compartment and some are secreted. In general, metastasis suppressors appear to regulate selectively how cells respond to exogenous signals, by affecting signaling cascades which regulate downstream gene expression. This review briefly summarizes current functional and biochemical data on metastasis suppressors implicated in breast cancer. We also present a schematic integrating known mechanisms for these metastasis suppressors highlighting potential targets for therapeutic intervention. PMID:17587154

  8. Review of photon interaction cross section data in the medical and biological context.

    PubMed

    Hubbell, J H

    1999-01-01

    The probability of a photon (x-ray, gamma-ray, bremsstrahlung, etc) of a given energy E undergoing absorption or scattering when traversing a layer of material Z can be expressed quantitatively in terms of a linear attenuation coefficient mu (cm(-1)). Since mu is dependent on the material's density, rho (g cm(-3)), which can be variable, the quantity usually tabulated is the mass attenuation coefficient mu/rho (cm2 g(-1)) in which the dependence on the density has been removed. Mu/rho, in turn, can be obtained as the sum of the different types of possible interactions of photons with atoms of the material. For photon energies below 1 MeV the major interaction processes to be considered are incoherent (Compton) scattering, coherent (Rayleigh) scattering and atomic photoeffect absorption. Above 1 MeV one must also include nuclear-field pair production and atomic-field (triplet) production, and above 5 MeV one in principle should include photonuclear absorption, although the latter is neglected in data tabulations up to the present time. This review includes a selective history of measurements and theory relating to mu/rho from the turn of the century up to the present time, and is intended to provide a basis for further calculations and critical tabulations of photon cross section data, particularly as required by users in radiation medicine and biology. The mass energy-absorption coefficient mu(en)/rho is also briefly discussed.

  9. Discussion on microcosmic derivation of biological golden section phenomena from DNA geometric structure and snow flower generation.

    PubMed

    Chen, Zhao-Xue; Wang, Zhi-Zhen; Sun, Ying; Bei, Feng-Li

    2011-03-01

    As a mysterious and most universal mathematical constant, the ratio of golden section exists in biological organism widely either from microstructure to macrostructure or from anatomical structure to functional features, and the DNA is the most universal germ plasm throughout all life world. In this paper, by analyzing the DNA microstructure and generating process of snow flowers, such a fact is disclosed that biological golden section phenomena derives from the DNA structure at the molecular layer based on the complex nonlinear interaction with the inner environments.

  10. Imaging of bone metastasis: An update.

    PubMed

    O'Sullivan, Gerard J; Carty, Fiona L; Cronin, Carmel G

    2015-08-28

    Early detection of skeletal metastasis is critical for accurate staging and optimal treatment. This paper briefly reviews our current understanding of the biological mechanisms through which tumours metastasise to bone and describes the available imaging methods to diagnose bone metastasis and monitor response to treatment. Among the various imaging modalities currently available for imaging skeletal metastasis, hybrid techniques which fuse morphological and functional data are the most sensitive and specific, and positron emission tomography (PET)/computed tomography and PET/magnetic resonance imaging will almost certainly continue to evolve and become increasingly important in this regard.

  11. A compact and versatile microfluidic probe for local processing of tissue sections and biological specimens

    NASA Astrophysics Data System (ADS)

    Cors, J. F.; Lovchik, R. D.; Delamarche, E.; Kaigala, G. V.

    2014-03-01

    The microfluidic probe (MFP) is a non-contact, scanning microfluidic technology for local (bio)chemical processing of surfaces based on hydrodynamically confining nanoliter volumes of liquids over tens of micrometers. We present here a compact MFP (cMFP) that can be used on a standard inverted microscope and assist in the local processing of tissue sections and biological specimens. The cMFP has a footprint of 175 × 100 × 140 mm3 and can scan an area of 45 × 45 mm2 on a surface with an accuracy of ±15 μm. The cMFP is compatible with standard surfaces used in life science laboratories such as microscope slides and Petri dishes. For ease of use, we developed self-aligned mounted MFP heads with standardized "chip-to-world" and "chip-to-platform" interfaces. Switching the processing liquid in the flow confinement is performed within 90 s using a selector valve with a dead-volume of approximately 5 μl. We further implemented height-compensation that allows a cMFP head to follow non-planar surfaces common in tissue and cellular ensembles. This was shown by patterning different macroscopic copper-coated topographies with height differences up to 750 μm. To illustrate the applicability to tissue processing, 5 μm thick M000921 BRAF V600E+ melanoma cell blocks were stained with hematoxylin to create contours, lines, spots, gradients of the chemicals, and multiple spots over larger areas. The local staining was performed in an interactive manner using a joystick and a scripting module. The compactness, user-friendliness, and functionality of the cMFP will enable it to be adapted as a standard tool in research, development and diagnostic laboratories, particularly for the interaction with tissues and cells.

  12. Metastasis Detection in Sentinel Lymph Nodes: Comparison of a Limited Widely Spaced (NSABP protocol B-32) and a Comprehensive Narrowly Spaced Paraffin Block Sectioning Strategy

    PubMed Central

    Weaver, Donald L.; Le, U. Phuong; Dupuis, Stacey L.; Weaver, Katherine A. E.; Harlow, Seth P.; Ashikaga, Takamaru; Krag, David N.

    2009-01-01

    The NSABP B-32 trial is examining whether patients with initially negative sentinel lymph nodes (SLNs) who have occult metastases detected on deeper levels and cytokeratin immunohistochemistry (CK-IHC) stains are at risk for regional or distant metastases. The experimental B-32 protocol was designed to detect metastases larger than 1.0 mm by examining sections approximately 0.5 and 1.0 mm deeper into the paraffin blocks (2 levels; wide spacing). This pilot quality assurance study compares detection rates to a comprehensive protocol designed to detect metastases larger than 0.2 mm (multilevel; narrow spacing). All SLNs were sectioned grossly at close to 2.0 mm and all sections embedded in paraffin blocks. For clinical treatment, a single H&E section was examined from each block. For 54 cases with 1–5 SLNs and all SLNs negative, additional CK-IHC sections were evaluated every 0.18 mm through the block until no tissue remained. 20 of 176 (11.4%) blocks harbored occult metastases; the B-32 protocol detected metastases in 11 blocks (6.3%) and 9 additional blocks (5.1%) with metastases were detected on sections that would not have been evaluated (p=0.002; correlated proportions). Median number of levels examined per block on the comprehensive protocol was 11 (range 3–26); the B-32 protocol was fixed at 2 levels (median 2; range 1–2). Median thickness of node sections in the block was 2.1 mm (range 0.7–4.8 mm) and the modal thickness was 2.3 mm. Although more comprehensive sectioning of SLNs detects additional micrometastases, the data suggest diminishing returns and reduced cost effectiveness for the comprehensive strategy. PMID:19730364

  13. IFLA General Conference, 1990. Division of Special Libraries: Section of Administrative Libraries; Section of Social Science Libraries; Section of Science and Technology Libraries; Section of Biological and Medical Sciences Libraries; Section of Art Libraries. Booklet 2.

    ERIC Educational Resources Information Center

    International Federation of Library Associations, The Hague (Netherlands).

    The 23 papers in this collection were presented at 5 sections of the Division of Special Libraries: (1) "Principles of Government Librarianship" (Hans H. van der Neut); (2) "Strategic Planning as an Instrument of Improving Library Quality" (Maurice B. Line); (3) "Library Staff Development Consultancy: A Means to Achieve a…

  14. IFLA General Conference, 1990. Division of Special Libraries: Section of Administrative Libraries; Section of Social Science Libraries; Section of Science and Technology Libraries; Section of Biological and Medical Sciences Libraries; Section of Art Libraries. Booklet 2.

    ERIC Educational Resources Information Center

    International Federation of Library Associations, The Hague (Netherlands).

    The 23 papers in this collection were presented at 5 sections of the Division of Special Libraries: (1) "Principles of Government Librarianship" (Hans H. van der Neut); (2) "Strategic Planning as an Instrument of Improving Library Quality" (Maurice B. Line); (3) "Library Staff Development Consultancy: A Means to Achieve a…

  15. Prediction of Metastasis Using Second Harmonic Generation

    DTIC Science & Technology

    2016-07-01

    photon focal volume and the thin tissue section), producing a single F and B image for each sample. Then an arbitrary threshold was chosen by a blinded...AWARD NUMBER: W81XWH-15-1-0040 TITLE: Prediction of Metastasis Using Second Harmonic Generation PRINCIPAL INVESTIGATOR: Edward Brown...ABOVE ADDRESS. 1. REPORT DATE July 2016 2. REPORT TYPE Final 3. DATES COVERED 1May2015 - 30Apr2016 Prediction of Metastasis Using Second Harmonic

  16. Mouse models for studying prostate cancer bone metastasis

    PubMed Central

    Dai, Jinlu; Hensel, Janine; Wang, Ning; Kruithof-de Julio, Marianna; Shiozawa, Yusuke

    2016-01-01

    Once tumor cells metastasize to the bone, the prognosis for prostate cancer patients is generally very poor. The mechanisms involved in bone metastasis, however, remain elusive, because of lack of relevant animal models. In this manuscript, we describe step-by-step protocols for the xenograft mouse models that are currently used for studying prostate cancer bone metastasis. The different routes of tumor inoculation (intraosseous, intracardiac, intravenous and orthotopic) presented are useful for exploring the biology of bone metastasis. PMID:26916039

  17. IFLA General Conference, 1985. Division on Special Libraries. Section on Biological and Medical Science Libraries. Papers.

    ERIC Educational Resources Information Center

    International Federation of Library Associations, The Hague (Netherlands).

    Papers on biological and medical science libraries which were presented at the 1985 International Federation of Library Associations (IFLA) conference include: (1) "The International Programs of the National Library of Medicine" (Lois Ann Colaianni, United States); (2) "Information Needs for International Health. A CDC (Centers for Disease…

  18. IFLA General Conference, 1985. Division on Special Libraries. Section on Biological and Medical Science Libraries. Papers.

    ERIC Educational Resources Information Center

    International Federation of Library Associations, The Hague (Netherlands).

    Papers on biological and medical science libraries which were presented at the 1985 International Federation of Library Associations (IFLA) conference include: (1) "The International Programs of the National Library of Medicine" (Lois Ann Colaianni, United States); (2) "Information Needs for International Health. A CDC (Centers for Disease…

  19. IFLA General Conference, 1986. Special Libraries Division. Section: Biological and Medical Sciences Libraries. Papers.

    ERIC Educational Resources Information Center

    International Federation of Library Associations and Institutions, The Hague (Netherlands).

    Four papers on biological and medical sciences libraries were presented at the 1986 International Federation of Library Associations (IFLA) conference. "Activities and Services of Medical Libraries in Japan--Past, Present, and Future" (Kazuo Urata and Toshinobu Suga, Japan) discusses the inauguration of the Japan Medical Library…

  20. Metastasis and AKT activation.

    PubMed

    Sheng, Shijie; Qiao, Meng; Pardee, Arthur B

    2009-03-01

    Metastasis, responsible for 90% of cancer patient deaths, is an inefficient process because many tumor cells die. The survival of metastatic tumor cells should be considered as a critical therapeutic target. This review provides a new perspective regarding the role of AKT in tumor survival, and the rationale to target AKT in anti-metastasis therapies.

  1. HGF–MET Cascade, a Key Target for Inhibiting Cancer Metastasis: The Impact of NK4 Discovery on Cancer Biology and Therapeutics

    PubMed Central

    Mizuno, Shinya; Nakamura, Toshikazu

    2013-01-01

    Hepatocyte growth factor (HGF) was discovered in 1984 as a mitogen of rat hepatocytes in a primary culture system. In the mid-1980s, MET was identified as an oncogenic mutant protein that induces malignant phenotypes in a human cell line. In the early 1990s, wild-type MET was shown to be a functional receptor of HGF. Indeed, HGF exerts multiple functions, such as proliferation, morphogenesis and anti-apoptosis, in various cells via MET tyrosine kinase phosphorylation. During the past 20 years, we have accumulated evidence that HGF is an essential conductor for embryogenesis and tissue regeneration in various types of organs. Furthermore, we found in the mid-1990s that stroma-derived HGF is a major contributor to cancer invasion at least in vitro. Based on this background, we prepared NK4 as an antagonist of HGF: NK4 inhibits HGF-mediated MET tyrosine phosphorylation by competing with HGF for binding to MET. In vivo, NK4 treatments produced the anti-tumor outcomes in mice bearing distinct types of malignant cancers, associated with the loss in MET activation. There are now numerous reports showing that HGF-antagonists and MET-inhibitors are logical for inhibiting tumor growth and metastasis. Additionally, NK4 exerts anti-angiogenic effects, partly through perlecan-dependent cascades. This paper focuses on the chronology and significance of HGF-antagonisms in anti-tumor researches, with an interest in NK4 discovery. Tumor HGF–MET axis is now critical for drug resistance and cancer stem cell maintenance. Thus, oncologists cannot ignore this cascade for the future success of anti-metastatic therapy. PMID:23296269

  2. Bioluminescence imaging of bone metastasis in rodents.

    PubMed

    Snoeks, Thomas J A; van Beek, Ermond; Que, Ivo; Kaijzel, Eric L; Löwik, Clemens W G M

    2012-01-01

    Optical imaging is a valuable technique for visualizing and quantifying biological processes in living -organisms. Optical imaging can be divided into two main imaging modalities: bioluminescence imaging and fluorescence imaging. This chapter describes the use of these imaging techniques to image tumour cells in mouse models of cancer and to detect early bone metastasis.

  3. Potential biological pathways linking Type-D personality and poor health: A cross-sectional investigation.

    PubMed

    Jandackova, Vera K; Koenig, Julian; Jarczok, Marc N; Fischer, Joachim E; Thayer, Julian F

    2017-01-01

    Type-D personality, defined as a combination of high negative affect and high social isolation, has been associated with poor health outcomes. However, pathways underlying this association are largely unknown. We investigated the relationship between Type-D personality and several biological and behavioral pathways including the autonomic nervous system, the immune system, glucose regulation and sleep in a large, apparently healthy sample. Data from a total of 646 respondents (age 41.6±11.5, 12,2% women) were available for analysis. Persons with Type-D (negative affect and social isolation score ≥10) were contrasted with those without Type-D. Measures of plasma fibrinogen levels, white blood cell count, high sensitivity C-reactive protein, fasting plasma glucose (FPG), cholesterol, high-density and low-density lipoprotein, glycated hemoglobin (HbA1c), creatinine, triglycerides, and albumin were derived from fasting blood samples. Urine norepinephrine and free cortisol were determined by high-performance liquid chromatography. Time-domain heart rate variability (HRV) measures were calculated for the 24hr recording period and for nighttime separately. Persons with Type-D had higher HbA1c, FPG, and fibrinogen, and lower nighttime HRV than those without Type-D, suggesting worse glycemic control, systemic inflammation and poorer autonomic nervous system modulation in Type-D persons. In addition, those with Type-D reported less social support and greater sleep difficulties while no group differences were observed for alcohol and cigarette consumption, physical activity and body mass index. Findings provide some of the first evidence for multiple possible biological and behavioral pathways between Type-D personality and increased morbidity and mortality.

  4. Cutaneous Metastasis From Sacral Chordoma.

    PubMed

    Gleghorn, Kristyna; Goodwin, Brandon; Sanchez, Ramon

    2017-04-01

    Chordoma is a rare primary bone malignancy of notochord origin, representing 1-4% of malignant bone tumors., Typically, chordomas follow a slow progressive course with aggressive local extension, multiple recurrences, and metastases. Of particular interest to this case, cutaneous metastasis is exceedingly rare. Diagnosis of this entity can be a challenge due to the rarity of chordoma, as well as the infrequent presentation of distant cutaneous metastasis and non-specific clinical skin findings. We report a case of a 61-year-old male with a history of sacral chordoma treated by wide local excision 8 years prior to presentation developed a nodule on his scalp for 6 weeks. Physical examination revealed a 1 cm rubbery, pink, shiny dome-shaped nodule on his left occipital scalp. Hematoxylin and eosin sections revealed a lobular dermal proliferation of small ovoid cells and larger physaliferous cells with hyperchromatic, displaced nuclei and finely vacuolated "soap-bubble" cytoplasm in a myxoid stroma. Immunohistochemistry of tumor cells showed positivity for both S-100 protein and pancytokeratin (AE1/AE3), while smooth muscle actin (SMA), P63, and CK7 were negative. Additionally, tumor cells stained positive for brachyury. The medical history, clinical presentation, histopathological appearance and immunohistochemical profile are consistent with cutaneous metastasis from sacral chordoma, known as chordoma cutis. This case illustrates the integral role of dermatopathology in the diagnosis of a rare and critical condition.

  5. Measured Infrared Optical Cross Sections For a Variety Of Chemical and Biological Aerosol Simulants

    NASA Astrophysics Data System (ADS)

    Gurton, Kristan P.; Ligon, David; Dahmani, Rachid

    2004-08-01

    We conducted a series of spectral extinction measurements on a variety of aerosolized chemical and biological simulants over the spectral range 3-13 µm using conventional Fourier-transform IR (FTIR) aerosol spectroscopy. Samples consist of both aerosolized particulates and atomized liquids. Materials considered include Bacillus subtilis endospores, lyophilized ovalbumin, polyethylene glycol, dimethicone (SF-96), and three common background materials: kaolin clay (hydrated aluminum silicate), Arizona road dust (primarily SiO2), and diesel soot. Aerosol size distributions and mass density were measured simultaneously with the FTIR spectra. As a result, all optical parameters presented here are mass normalized, i.e., in square meters per gram. In an effort to establish the utility of using Mie theory to predict such parameters, we conducted a series of calculations. For materials in which the complex indices of refraction are known, e.g., silicone oil (SF-96) and kaolin, measured size distributions were convolved with Mie theory and the resultant spectral extinction calculated. Where there was good agreement between measured and calculated extinction spectra, absorption, total scattering, and backscatter were also calculated.

  6. Determination of resonance Raman cross-sections for use in biological SERS sensing with femtosecond stimulated Raman spectroscopy.

    PubMed

    Silva, W Ruchira; Keller, Emily L; Frontiera, Renee R

    2014-08-05

    Surface-enhanced Raman spectroscopy (SERS) is a promising technique for in vivo bioanalyte detection, but accurate characterization of SERS biosensors can be challenging due to difficulties in differentiating resonance and surface enhancement contributions to the Raman signal. Here, we quantitate the resonance Raman cross-sections for a commonly used near-infrared SERS dye, 3,3'-diethylthiatricarbocyanine (DTTC). It is typically challenging to measure resonance Raman cross-sections for fluorescent dye molecules due to the overwhelming isoenergetic fluorescence signal. To overcome this issue, we used etalon-based femtosecond stimulated Raman spectroscopy, which is intrinsically designed to acquire a stimulated Raman signal without strong fluorescence or interference from signals resulting from other four-wave mixing pathways. Using this technique, we found that the cross-sections for most of the resonantly enhanced modes in DTTC exceed 10(-25) cm(2)/molecule. These cross-sections lead to high signal magnitude SERS signals from even weakly enhancing SERS substrates, as much of what appears to be a SERS signal is actually coming from the intrinsically strong resonance Raman signal. Our work will lead to a more accurate determination of SERS enhancement factors and SERS substrate characterization in the biologically relevant near-infrared region, ultimately leading to a more widespread use of SERS for biosensing and bioimaging applications.

  7. Targeting Prostate Cancer Metastasis

    DTIC Science & Technology

    2015-09-01

    drug t oxi c i t y and the e ffect i ve dose i n zebrafish and found the best perf ormi ng s t rat egi es usi ng zebrafish - metastasi s model s...CLASSIFICATION OF: a. REPORT b. ABSTRACT c . THIS PAGE Unclassified Unclassified Unclassified screen, zebrafish , mouse, 17. LIMITATION 18. NUMBER OF... zebrafish -metastasis models and mouse models of prostate cancer, we aim to investigate whether FDA approved drugs that target these pathways can be

  8. IFLA General Conference, 1991. Division of Special Libraries Services: Section of Social Science Libraries; Section of Geography and Map Libraries; Section of Biological and Medical Sciences Libraries; Section of Art Libraries. Booklet 2.

    ERIC Educational Resources Information Center

    International Federation of Library Associations and Institutions, The Hague (Netherlands).

    The 10 papers in this booklet were presented at meetings of 4 sections within the Division of Special Libraries: (1) "Information Ensurance of a Scientist" (V. Matveyev, USSR); (2) "Linguistic Barriers and Machine Translation" (Stanley Kalkus, USA); (3) "Maps for Planning" (V. I. Zhukov and L. G. Rudenko, USSR); (4)…

  9. IFLA General Conference, 1991. Division of Special Libraries Services: Section of Social Science Libraries; Section of Geography and Map Libraries; Section of Biological and Medical Sciences Libraries; Section of Art Libraries. Booklet 2.

    ERIC Educational Resources Information Center

    International Federation of Library Associations and Institutions, The Hague (Netherlands).

    The 10 papers in this booklet were presented at meetings of 4 sections within the Division of Special Libraries: (1) "Information Ensurance of a Scientist" (V. Matveyev, USSR); (2) "Linguistic Barriers and Machine Translation" (Stanley Kalkus, USA); (3) "Maps for Planning" (V. I. Zhukov and L. G. Rudenko, USSR); (4)…

  10. Autophagy in Cancer Metastasis

    PubMed Central

    Mowers, Erin E.; Sharifi, Marina N.; Macleod, Kay F.

    2016-01-01

    Autophagy is a highly conserved self-degradative process that plays a key role in cellular stress responses and survival. Recent work has begun to explore the function of autophagy in cancer metastasis, which is of particular interest given the dearth of effective therapeutic options for metastatic disease. Autophagy is induced upon progression of various human cancers to metastasis and together with data from genetically engineered mice and experimental metastasis models, a role for autophagy at nearly every phase of the metastatic cascade has been identified. Specifically, autophagy has been shown to be involved in modulating tumor cell motility and invasion, cancer stem cell viability and differentiation, resistance to anoikis, epithelial-to-mesenchymal transition, tumor cell dormancy and escape from immune surveillance, with emerging functions in establishing the pre-metastatic niche and other aspects of metastasis. In this review, we provide a general overview of how autophagy modulates cancer metastasis and discuss the significance of new findings for disease management. PMID:27593926

  11. Hypoxia-mediated metastasis.

    PubMed

    Chang, Joan; Erler, Janine

    2014-01-01

    Metastasis is responsible for more than 90 % of deaths among cancer patient. It is a highly complex process that involves the interplay between cancer cells, the tumor microenvironment, and even noncancerous host cells. Metastasis can be seen as a step-wise process: acquisition of malignant phenotype, invasion into surrounding tissue, intravasation into blood vessels, survival in circulation, extravasation to distant sites, and colonization of new organs. Before the actual metastatic process, the secondary site is also prepared for the arrival of the cancer cells through formation of "premetastatic niches." Hypoxia (low oxygen tension) is commonly found in solid tumors more than a few millimeters cubed and often is associated with a poor prognosis. Hypoxia increases angiogenesis, cancer cell survival, and metastasis. This chapter described how hypoxia regulates each step of the metastatic process and how blocking hypoxia-driven metastasis through targeting hypoxia-inducible factor 1, or downstream effector molecules such as the lysyl oxidase family may represent highly effective preventive strategies against metastasis in cancer patients.

  12. Genomics screens for metastasis genes

    PubMed Central

    Yan, Jinchun; Huang, Qihong

    2014-01-01

    Metastasis is responsible for most cancer mortality. The process of metastasis is complex, requiring the coordinated expression and fine regulation of many genes in multiple pathways in both the tumor and host tissues. Identification and characterization of the genetic programs that regulate metastasis is critical to understanding the metastatic process and discovering molecular targets for the prevention and treatment of metastasis. Genomic approaches and functional genomic analyses can systemically discover metastasis genes. In this review, we summarize the genetic tools and methods that have been used to identify and characterize the genes that play critical roles in metastasis. PMID:22684367

  13. Brominated 7-hydroxycoumarin-4-ylmethyls: Photolabile protecting groups with biologically useful cross-sections for two photon photolysis

    PubMed Central

    Furuta, Toshiaki; Wang, Samuel S.-H.; Dantzker, Jami L.; Dore, Timothy M.; Bybee, Wendy J.; Callaway, Edward M.; Denk, Winfried; Tsien, Roger Y.

    1999-01-01

    Photochemical release (uncaging) of bioactive messengers with three-dimensional spatial resolution in light-scattering media would be greatly facilitated if the photolysis could be powered by pairs of IR photons rather than the customary single UV photons. The quadratic dependence on light intensity would confine the photolysis to the focus point of the laser, and the longer wavelengths would be much less affected by scattering. However, previous caged messengers have had very small cross sections for two-photon excitation in the IR region. We now show that brominated 7-hydroxycoumarin-4-ylmethyl esters and carbamates efficiently release carboxylates and amines on photolysis, with one- and two-photon cross sections up to one or two orders of magnitude better than previously available. These advantages are demonstrated on neurons in brain slices from rat cortex and hippocampus excited by glutamate uncaged from N-(6-bromo-7-hydroxycoumarin-4-ylmethoxycarbonyl)-l-glutamate (Bhc-glu). Conventional UV photolysis of Bhc-glu requires less than one-fifth the intensities needed by one of the best previous caged glutamates, γ-(α-carboxy-2-nitrobenzyl)-l-glutamate (CNB-glu). Two-photon photolysis with raster-scanned femtosecond IR pulses gives the first three-dimensionally resolved maps of the glutamate sensitivity of neurons in intact slices. Bhc-glu and analogs should allow more efficient and three-dimensionally localized uncaging and photocleavage, not only in cell biology and neurobiology but also in many technological applications. PMID:9990000

  14. Ovarian Cancer Development and Metastasis

    PubMed Central

    Lengyel, Ernst

    2010-01-01

    The biology of ovarian carcinoma differs from that of hematogenously metastasizing tumors because ovarian cancer cells primarily disseminate within the peritoneal cavity and are only superficially invasive. However, since the rapidly proliferating tumors compress visceral organs and are only temporarily chemosensitive, ovarian carcinoma is a deadly disease, with a cure rate of only 30%. There are a number of genetic and epigenetic changes that lead to ovarian carcinoma cell transformation. Ovarian carcinoma could originate from any of three potential sites: the surfaces of the ovary, the fallopian tube, or the mesothelium-lined peritoneal cavity. Ovarian cacinoma tumorigenesis then either progresses along a stepwise mutation process from a slow growing borderline tumor to a well-differentiated carcinoma (type I) or involves a genetically unstable high-grade serous carcinoma that metastasizes rapidly (type II). During initial tumorigenesis, ovarian carcinoma cells undergo an epithelial-to-mesenchymal transition, which involves a change in cadherin and integrin expression and up-regulation of proteolytic pathways. Carried by the peritoneal fluid, cancer cell spheroids overcome anoikis and attach preferentially on the abdominal peritoneum or omentum, where the cancer cells revert to their epithelial phenotype. The initial steps of metastasis are regulated by a controlled interaction of adhesion receptors and proteases, and late metastasis is characterized by the oncogene-driven fast growth of tumor nodules on mesothelium covered surfaces, causing ascites, bowel obstruction, and tumor cachexia. PMID:20651229

  15. Identification of intramural metastasis in esophageal cancer using multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Xu, Jian; Kang, Deyong; Zhuo, Shuangmu; Zhu, Xiaoqin; Lin, jiangbo; Chen, Jianxin

    2017-02-01

    Intramural metastasis (IM) of esophageal cancer is defined as metastasis from a primary lesion to the esophageal wall without intraepithelial cancer extension. Esophageal cancer with IM is more common and such cases indicate a poor prognosis. In esophageal surgery, if curative resection is possible, the complete removal of both primary tumor and associated IMs is required. Therefore, accurate diagnosis of IMs in esophageal cancer prior to surgery is of particular importance. Multiphoton microscopy (MPM) with subcellular resolution is well-suited for deep tissue imaging since many endogenous fluorophores of fresh biological tissues are excited through two-photon excited fluorescence (TPEF) and second harmonic generation (SHG). Here, a study to identify IM in fresh tissue section using MPM is reported. In this study, the morphological and spectral differences between IM and surrounding tissue are described. These results show that MPM has the ability to accurately identify IM in esophageal tissues. With improvement of the penetration depth of MPM and the development of multiphton microendoscope, MPM may be a promising imaging technique for preoperative diagnosis of IMs in esophageal cancer in the future.

  16. Clinical and biological correlates of resilience in patients with schizophrenia and bipolar disorder: A cross-sectional study.

    PubMed

    Mizuno, Yuya; Hofer, Alex; Suzuki, Takefumi; Frajo-Apor, Beatrice; Wartelsteiner, Fabienne; Kemmler, Georg; Saruta, Juri; Tsukinoki, Keiichi; Mimura, Masaru; Fleischhacker, W Wolfgang; Uchida, Hiroyuki

    2016-08-01

    The concept of resilience is relevant in understanding the heterogeneous outcomes noted in schizophrenia and bipolar disorder. However, clinical and biological correlates of resilience in these populations have rarely been investigated. We aimed to identify key correlates of subjective resilience in such patients using comprehensive assessments and to explore associations between resilience levels and peripheral biomarkers. 180 subjects with DSM-IV schizophrenia, bipolar disorder, and healthy controls (60 per group) were included. Demographic and clinical variables were assessed by means of interview and various psychometric scales. Furthermore, blood and saliva samples were obtained for the assessment of brain-derived neurotrophic factor, adrenocorticotropic hormone, cortisol, high sensitivity C-reactive protein, and alpha-amylase levels. Cross-sectional associations with resilience, as assessed by the 25-item Resilience Scale were sought. Resilience Scale total scores were significantly higher in healthy individuals (130.1, 95% confidence intervals (CI): 124.8-135.4) compared to subjects with schizophrenia (109.9, 95% CI: 104.6-115.2, p<0.001) and bipolar disorder (119.0, 95% CI: 113.8-124.3, p=0.012), while the difference between patient groups was non-significant (p=0.055). Self-esteem, spirituality, quality of life, and hopelessness were correlated with resilience in all three groups. In addition, internalized stigma and depression were relevant factors in the schizophrenia and bipolar disorder group, respectively. Correlations between resilience levels and peripheral biomarkers did not reach significance. Although causal relationships must be confirmed in prospective studies, our results have implications in developing psychological interventions to enhance resilience in patients with schizophrenia and bipolar disorder. The biological correlates of resilience in these populations warrant further investigations. Copyright © 2016 Elsevier B.V. All rights

  17. Vaginal metastasis of pancreatic cancer.

    PubMed

    Benhayoune, Khadija; El Fatemi, Hinde; El Ghaouti, Meryem; Bannani, Abdelaziz; Melhouf, Abdelilah; Harmouch, Taoufik

    2015-01-01

    Vaginal metastasis from pancreatic cancer is an extreme case and often indicates a poor prognosis. We present a case of pancreatic carcinoma with metastasis to the vagina that was discovered by vaginal bleeding. To our knowledge, this is the third case in the world of a primary pancreatic adenocarcinoma discovered of symptoms from a vaginal metastasis.

  18. Breast Cancer Metastasis

    PubMed Central

    Marino, Natascia; Woditschka, Stephan; Reed, L. Tiffany; Nakayama, Joji; Mayer, Musa; Wetzel, Maria; Steeg, Patricia S.

    2014-01-01

    Despite important progress in adjuvant and neoadjuvant therapies, metastatic disease often develops in breast cancer patients and remains the leading cause of their deaths. For patients with established metastatic disease, therapy is palliative, with few breaks and with mounting adverse effects. Many have hypothesized that a personalized or precision approach (the terms are used interchangeably) to cancer therapy, in which treatment is based on the individual characteristics of each patient, will provide better outcomes. Here, we discuss the molecular basis of breast cancer metastasis and the challenges in personalization of treatment. The instability of metastatic tumors remains a leading obstacle to personalization, because information from a patient’s primary tumor may not accurately reflect the metastasis, and one metastasis may vary from another. Furthermore, the variable presence of tumor subpopulations, such as stem cells and dormant cells, may increase the complexity of the targeted treatments needed. Although molecular signatures and circulating biomarkers have been identified in breast cancer, there is lack of validated predictive molecular markers to optimize treatment choices for either prevention or treatment of metastatic disease. Finally, to maximize the information that can be obtained, increased attention to clinical trial design in the metastasis preventive setting is needed. PMID:23895915

  19. The Biology of Breast Cancer Metastasis

    DTIC Science & Technology

    2002-10-01

    Breast cancer is the second most common cause of brain metastases, diagnosed in 10 to 15% of breast cancer patients and found at autopsy in 20 to 30...Relatively little is known about how breast cancer cells metastasize to the brain , and what phenotypes characterize these cells. This is due in...breast cancer brain metastases, using intra-carotid artery injection of breast cancer cells into nude mice.

  20. A linear laser scanner to measure cross-sectional shape and area of biological specimens during mechanical testing.

    PubMed

    Vergari, Claudio; Pourcelot, Philippe; Holden, Laurène; Ravary-Plumioën, Bérangère; Laugier, Pascal; Mitton, David; Crevier-Denoix, Nathalie

    2010-10-01

    Measure of the cross-sectional area (CSA) of biological specimens is a primary concern for many biomechanical tests. Different procedures are presented in literature but besides the fact that noncontact techniques are required during mechanical testing, most of these procedures lack accuracy or speed. Moreover, they often require a precise positioning of the specimen, which is not always feasible, and do not enable the measure of the same section during tension. The objective of this study was to design a noncontact, fast, and accurate device capable of acquiring CSA of specimens mounted on a testing machine. A system based on the horizontal linear displacement of two charge-coupled device reflectance laser devices next to the specimen, one for each side, was chosen. The whole measuring block is mounted on a vertical linear guide to allow following the measured zone during sample tension (or compression). The device was validated by measuring the CSA of metallic rods machined with geometrical shapes (circular, hexagonal, semicircular, and triangular) as well as an equine superficial digital flexor tendon (SDFT) in static condition. We also performed measurements during mechanical testing of three SDFTs, obtaining the CSA variations until tendon rupture. The system was revealed to be very fast with acquisition times in the order of 0.1 s and interacquisition time of about 1.5 s. Measurements of the geometrical shapes yielded mean errors lower than 1.4% (n=20 for each shape) while the tendon CSA at rest was 90.29 ± 1.69 mm(2) (n=20). As for the tendons that underwent tension, a mean of 60 measures were performed for each test, which lasted about 2 min until rupture (at 20 mm/min), finding CSA variations linear with stress (R(2)>0.85). The proposed device was revealed to be accurate and repeatable. It is easy to assemble and operate and capable of moving to follow a defined zone on the specimen during testing. The system does not need precise centering of the sample

  1. Solitary midbrain metastasis.

    PubMed

    Ongerboer de Visser, B W; Moffie, D

    1981-01-01

    The available clinical and pathological data of 5 cases with solitary midbrain metastasis including 2 of the present study are reviewed. Progressive dementia occurred in one case and mild dementia in another who also developed ocular symptoms. Ocular symptoms with sensory and coordination disturbances were seen in one, and only ocular symptoms in another case. Right-sided hemiplegia of 5 years duration occurred in the remaining case. Survival in tegmentum lesions is short.

  2. Lymphangiogenesis and Lymphatic Metastasis in Breast Cancer

    PubMed Central

    Ran, Sophia; Volk, Lisa; Hall, Kelly; Flister, Michael J.

    2009-01-01

    Lymphatic metastasis is the main prognostic factor for survival of patients with breast cancer and other epithelial malignancies. Mounting clinical and experimental data suggest that migration of tumor cells into the lymph nodes is greatly facilitated by lymphangiogenesis, a process that generates new lymphatic vessels from pre-existing lymphatics with the aid of circulating lymphatic endothelial progenitor cells. The key protein that induces lymphangiogenesis is vascular endothelial growth factor receptor-3 (VEGFR-3), which is activated by vascular endothelial growth factor-C and -D (VEGF-C and VEGF-D). These lymphangiogenic factors are commonly expressed in malignant, tumor-infiltrating and stromal cells, creating a favorable environment for generation of new lymphatic vessels. Clinical evidence demonstrates that increased lymphatic vessel density in and around tumors is associated with lymphatic metastasis and reduced patient survival. Recent evidence shows that breast cancers induce remodeling of the local lymphatic vessels and the regional lymphatic network in the sentinel and distal lymph nodes. These changes include an increase in number and diameter of tumor-draining lymphatic vessels. Consequently, lymph flow away from the tumor is increased, which significantly increases tumor cell metastasis to draining lymph nodes and may contribute to systemic spread. Collectively, recent advances in the biology of tumor-induced lymphangiogenesis suggest that chemical inhibitors of this process may be an attractive target for inhibiting tumor metastasis and cancer-related death. Nevertheless, this is a relatively new field of study and much remains to be established before the concept of tumor-induced lymphangiogenesis is accepted as a viable anti-metastatic target. This review summarizes the current concepts related to breast cancer lymphangiogenesis and lymphatic metastasis while highlighting controversies and unanswered questions. PMID:20036110

  3. Metastasis and AKT activation.

    PubMed

    Qiao, Meng; Sheng, Shijie; Pardee, Arthur B

    2008-10-01

    Metastasis is responsible for 90% of cancer patient deaths. More information is needed about the molecular basis for its potential detection and treatment. The activated AKT kinase is necessary for many events of the metastatic pathway including escape of cells from the tumor's environment, into and then out of the circulation, activation of proliferation, blockage of apoptosis, and activation of angiogenesis. A series of steps leading to metastatic properties can be initiated upon activation of AKT by phosphorylation on Ser-473. These findings lead to the question of how this activation is connected to metastasis. Activated AKT phosphorylates GSK-3beta causing its proteolytic removal. This increases stability of the negative transcription factor SNAIL, thereby decreasing transcription of the transmembrane protein E-cadherin that forms adhesions between adjacent cells, thereby permitting their detachment. How is AKT hyperactivated in metastatic cells? Increased PI3K or TORC2 kinase activity- or decreased PHLPP phosphatase could be responsible. Furthermore, a positive feedback mechanism is that the decrease of E-cadherin lowers PTEN and thereby increases PIP3, further activating AKT and metastasis.

  4. Invasive cancer cells and metastasis

    NASA Astrophysics Data System (ADS)

    Mierke, Claudia Tanja

    2013-12-01

    The physics of cancer is a relatively new emerging field of cancer research. In the last decade it has become a focus of biophysical research as well as becoming a novel focus for classical cancer research. This special section of Physical Biology focusing on invasive cancer cells and metastasis (physical oncology) will give greater insight into the different subfields where physical approaches are being applied to cancer research. This focus on the physical aspects of cancer is necessary because novel approaches in the field of genomics and proteomics have not altered the field of cancer research dramatically, due to the fact that few breakthroughs have been made. It is still not understood why some primary tumors metastasize and thus have a worse outcome compared to others that do not metastasize. As biophysicists, we and others suggest that the mechanical properties of the cancer cells, which possess the ability to transmigrate, are quite different compared to non-metastatic and non-invasive cancer cells. Furthermore, we hypothesize that these cancer cells undergo a selection process within the primary tumor that enables them to weaken their cell-cell adhesions and to alter their cell-matrix adhesions in order to be able to cross the outermost boundary of the primary tumor, as well as the surrounding basement membrane, and to invade the connective tissue. This prerequisite may also help the cancer cells to enter blood or lymph vessels, get transported with the vessel flow and form secondary tumors either within the vessel, directly on the endothelium, or in a different organ after crossing the endothelial lining a second time. This special section begins with a paper by Mark F Coughlin and Jeffrey J Fredberg on the changes in cytoskeletal dynamics and nonlinear rheology due to the metastatic capability of cancer cells from different cancer tissue types such as skin, bladder, prostate and kidney [1]. The hypothesis was that the metastatic outcome is impacted by

  5. [Late neck metastasis in esthesioneuroblastoma: a case report].

    PubMed

    Damar, Murat; Başerer, Nermin; Ozkara, Selvinaz; Yılmazer, Rasim

    2012-01-01

    Esthesioneuroblastoma is a rare malignancy of olfactory neuroepithelium arising from sinonasal region. It has biologically an aggressive behavior. The tumor is characterised by common local recurrence, atypic distant metastasis and poor long-term prognosis. Cervical metastasis accounts for 20-30% of the patients. Late metastases are seen particularly six months or later following primary treatment. In this article, we present a 43-year-old female case with Kadish B stage esthesioneuroblastoma who underwent extracranial tumor resection and postoperative radiotherapy. Eleven years later (at 132 months) right neck cervical metastasis was occurred and we applied right functional neck dissection and adjuvant radiotherapy to treat. We also review the treatment of late neck metastasis in the light of the current literature data.

  6. A Report on the Implementation of the Blooming Biology Tool: Aligning Course Learning Outcomes with Assessments and Promoting Consistency in a Large Multi-Section First-Year Biology Course

    ERIC Educational Resources Information Center

    O'Neill, Angie; Birol, Gülnur; Pollock, Carol

    2010-01-01

    The objectives of this study were to investigate the alignment of exam questions with course learning outcomes in a first year biology majors course, to examine gaps and overlaps in assessment of content amongst the sections of the course, and to use this information to provide feedback to the teaching team to further improve the course. Our…

  7. MicroRNA-421 inhibits breast cancer metastasis by targeting metastasis associated 1.

    PubMed

    Pan, Yongqin; Jiao, Genlong; Wang, Cunchuan; Yang, Jingge; Yang, Wah

    2016-10-01

    Dysregulation of microRNAs is involved in the initiation and progression of several human cancers, including breast cancer, as strong evidence of miRNAs acting as oncogenes or tumour suppressor genes has been found. This study was performed to investigate the biological functions of microRNA-421 (miR-421) in breast cancer and the underlying mechanisms. The expression level of miR-421 was detected in 50 pairs of surgical specimens and human breast cancer cell lines. The results showed that miR-421 is downregulated in breast cancer tissues and metastatic cell lines. In addition, the decrease in miR-421 levels was significantly associated with lymph node metastasis, recurrence/metastasis, or pTNM stage. Functions of miR-421 in cell migration and invasion were assessed through its silencing and overexpression. The results showed that miR-421 knockdown promotes invasion and metastasis in MCF-7 cells and its overexpression suppresses invasion and metastasis in MDA-MB-231 cells. The specific target genes of miR-421 were predicted by TargetScan algorithm and determined by dual luciferase reporter assay, quantitative reverse transcriptase PCR, and western blot analysis. miR-421 could suppress luciferase activity of the reporter containing 3'-untranslated region of metastasis associated 1 (MTA1), a potent oncogene. miR-421 overexpression or knockdown had no effect on the mRNA expression of MTA1, but it could modulate MTA1 protein level. Furthermore, MTA1 knockdown receded the effect of miR-421 inhibitor on invasion and metastasis of MCF-7 cells, and its overexpression receded the effect of miR-421 on invasion and metastasis of MDA-MB-231 cells. Our findings clearly demonstrate that miR-421 suppresses breast cancer metastasis by directly inhibiting MTA1 expression. The present study provides a new insight into the tumour suppressor roles of miR-421 and suggests that miR-421/MTA1 pathway is a putative therapeutic target in breast cancer. Copyright © 2016 Elsevier Masson SAS

  8. Tocotrienol and cancer metastasis.

    PubMed

    De Silva, Leanne; Chuah, Lay Hong; Meganathan, Puvaneswari; Fu, Ju-Yen

    2016-01-01

    Tumor metastasis involves some of the most complex and dynamic processes in cancer, often leading to poor quality of life and inevitable death. The search for therapeutic compounds and treatment strategies to prevent and/or manage metastasis is the ultimate challenge to fight cancer. In the past two decades, research focus on vitamin E has had a shift from saturated tocopherols to unsaturated tocotrienols (T3). Despite sharing structural similarities with tocopherols, T3 strive to gain scientific prominence due to their anti-cancer effects. Recent studies have shed some light on the anti-metastatic properties of T3. In this review, the roles of T3 in each step of the metastatic process are discussed. During the invasion process, signaling pathways that regulate the extracellular matrix and tumor cell motility have been reported to be modulated by T3. Although studies on T3 and tumor cell migration are fairly limited, they were shown to play a vital role in the suppression of angiogenesis. Furthermore, the anti-inflammatory effect of T3 could be highly promising in the regulation of tumor microenvironment, which is crucial in supporting tumor growth in distant organs.

  9. Floricultural Insects and Related Pests - Biology and Control, Section I. Florogram - Specialty Manual Issue for Commercial Greenhouse Growers.

    ERIC Educational Resources Information Center

    Gentile, A. G.; Scanlon, D. T.

    This manual is designed by the Massachusetts Cooperative Extension Service as a guide for the control of the most common insects and related pests of floricultural crops grown commercially in glass and plastic houses in Massachusetts. The publication consists of two sections. The first section presents a description of the major pests of…

  10. Floricultural Insects and Related Pests - Biology and Control, Section I. Florogram - Specialty Manual Issue for Commercial Greenhouse Growers.

    ERIC Educational Resources Information Center

    Gentile, A. G.; Scanlon, D. T.

    This manual is designed by the Massachusetts Cooperative Extension Service as a guide for the control of the most common insects and related pests of floricultural crops grown commercially in glass and plastic houses in Massachusetts. The publication consists of two sections. The first section presents a description of the major pests of…

  11. Syndecan-1 and Metastasis Dormancy

    DTIC Science & Technology

    2015-09-01

    Breast neoplasms, breast cancer , metastasis, dormancy, stroma, matrix, proteoglycans, migration, invasion, lung, syndecans 16. SECURITY CLASSIFICATION...disease overwhelmingly is the cause of death of breast cancer patients, it becomes imperative to understand the mechanisms that govern maintenance and...2. KEYWORDS Breast neoplasms, breast cancer , metastasis, dormancy, stroma, matrix, proteoglycans, migration, invasion, lung, syndecans 3

  12. Interleukin-5 Facilitates Lung Metastasis by Modulating the Immune Microenvironment

    PubMed Central

    Gleaves, Linda A.; McLoed, Allyson G.; Saxon, Jamie A.; Habermann, Arun C.; Connelly, Linda; Dulek, Daniel; Peebles, R. Stokes; Fingleton, Barbara; Yull, Fiona E.; Stathopoulos, Georgios T.; Blackwell, Timothy S.

    2015-01-01

    Although the lung is the most common metastatic site for cancer cells, biological mechanisms regulating lung metastasis are not fully understood. Using heterotopic and intravenous injection models of lung metastasis in mice, we found that IL-5, a cytokine involved in allergic and infectious diseases, facilitates metastatic colonization through recruitment of sentinel eosinophils and regulation of other inflammatory/immune cells in the microenvironment of the distal lung. Genetic IL-5 deficiency offered marked protection of the lungs from metastasis of different types of tumor cells, including lung cancer, melanoma and colon cancer. IL-5 neutralization protected subjects from metastasis, whereas IL-5 reconstitution or adoptive transfer of eosinophils into IL-5 deficient mice exerted pro-metastatic effects. However, IL-5 deficiency did not affect the growth of the primary tumor or the size of metastatic lesions. Mechanistic investigations revealed that eosinophils produce CCL22, which recruits regulatory T cells (Treg) to the lungs. During early stages of metastasis Treg created a pro-tumorigenic microenvironment, potentially by suppressing IFNγ-producing natural killer cells and M1-polarized macrophages. Together, our results establish a network of allergic inflammatory circuitry that can be co-opted by metastatic cancer cells to facilitate lung colonization, suggesting interventions to target this pathway may offer therapeutic benefits to prevent or treat lung metastasis. PMID:25691457

  13. Interleukin-5 facilitates lung metastasis by modulating the immune microenvironment.

    PubMed

    Zaynagetdinov, Rinat; Sherrill, Taylor P; Gleaves, Linda A; McLoed, Allyson G; Saxon, Jamie A; Habermann, Arun C; Connelly, Linda; Dulek, Daniel; Peebles, R Stokes; Fingleton, Barbara; Yull, Fiona E; Stathopoulos, Georgios T; Blackwell, Timothy S

    2015-04-15

    Although the lung is the most common metastatic site for cancer cells, biologic mechanisms regulating lung metastasis are not fully understood. Using heterotopic and intravenous injection models of lung metastasis in mice, we found that IL5, a cytokine involved in allergic and infectious diseases, facilitates metastatic colonization through recruitment of sentinel eosinophils and regulation of other inflammatory/immune cells in the microenvironment of the distal lung. Genetic IL5 deficiency offered marked protection of the lungs from metastasis of different types of tumor cells, including lung cancer, melanoma, and colon cancer. IL5 neutralization protected subjects from metastasis, whereas IL5 reconstitution or adoptive transfer of eosinophils into IL5-deficient mice exerted prometastatic effects. However, IL5 deficiency did not affect the growth of the primary tumor or the size of metastatic lesions. Mechanistic investigations revealed that eosinophils produce CCL22, which recruits regulatory T cells to the lungs. During early stages of metastasis, Treg created a protumorigenic microenvironment, potentially by suppressing IFNγ-producing natural killer cells and M1-polarized macrophages. Together, our results establish a network of allergic inflammatory circuitry that can be co-opted by metastatic cancer cells to facilitate lung colonization, suggesting interventions to target this pathway may offer therapeutic benefits to prevent or treat lung metastasis.

  14. Identification of the potential biomarkers for the metastasis of rectal adenocarcinoma.

    PubMed

    Hua, Yang; Ma, Xiukun; Liu, Xianglong; Yuan, Xiangfei; Qin, Hai; Zhang, Xipeng

    2017-02-01

    Rectal cancer is a common malignant tumor of the digestive tract, with a high incidence and high mortality. This study aimed to identify the potential biomarkers and therapeutic targets for rectal adenocarcinoma (RAC) metastasis. The expression profiling of RAC patients with metastasis and RAC patients without metastasis was downloaded from The Cancer Genome Atlas (TCGA) database. The datasets were used to identify the genes associated with RAC metastasis. Fifty up-regulated genes and seventeen down-regulated genes were identified in the primary tumor loci of RAC metastasis compared with non-metastasis. Sixty-seven dysregulated gens were conducted to construct the protein-protein network, and CCND3 was the hub protein. The dysregulated genes were significantly enriched in pancreatic secretion, cell adhesion molecules pathways, response to vitamin D of biological process, and retinoid binding of molecular function. Quantitative real-time polymerase chain reaction results demonstrated that CCND3, AQP3, PEG10, and RAB27B had the up-regulated tendency in RAC metastasis; ADCY1 had the down-regulated tendency in RAC metastasis. CCND3, AQP3, PEG10, RAB27B, and ADCY1 might play essential roles in the metastasis process of RAC through pancreatic secretion and cell adhesion molecules pathways. The five genes could be potential diagnosis biomarkers or therapeutic targets for RAC metastasis. © 2016 APMIS. Published by John Wiley & Sons Ltd.

  15. Molecular Mechanisms of Bone Metastasis.

    PubMed

    Weidle, Ulrich H; Birzele, Fabian; Kollmorgen, Gwendlyn; Rüger, Rüdiger

    2016-01-01

    Metastasis of breast and prostate cancer as well as multiple myeloma to the bones represents a significant medical problem. We herein discuss the molecular basis of the creation of pre-metastatic niches, the process of bone metastasis and the phenomenon of tumor dormancy in the bone marrow as well as its regulation. We describe the identification and validation of genes mediating bone metastasis by use of pre-clinical models of bone metastasis. Additionally, we discuss the role of small integrin binding N-linked glycoproteins (SIBLINGS), the chemokine/chemokine receptor CXCL12/CXCR4 pathway and the role of micro RNAs (miRNAs) as mediators of bone metastasis. Finally, we summarize clinical achievements for the treatment of bone metastases.

  16. Measured Infrared Absorption and Extinction Cross Sections for a Variety of Chemically and Biologically Derived Aerosol Simulants

    DTIC Science & Technology

    2004-06-01

    Aerosols considered are categorized as biological, chemical, and inorganic in origin, i.e., bacillus subtilis endospores, dimethicone silicone oil...achieved. The materials considered for this study include dimethicone silicone oil (SF-96 grade 50), bacillus subtilis endospores (BG), and Kaolin

  17. Toward decoding the principles of cancer metastasis circuits.

    PubMed

    Lu, Mingyang; Jolly, Mohit Kumar; Onuchic, Jose'; Ben-Jacob, Eshel

    2014-09-01

    Understanding epithelial-mesenchymal transitions (EMT) during cancer metastasis remains a major challenge in modern biology. Recent observations of cell behavior together with progress in mapping the underlying regulatory genetic networks led to new understandings of carcinoma metastasis. It is now established that the genetic network that regulates the EMT also enables an epithelial-mesenchymal hybrid phenotype. These hybrid cells possess mixed carcinoma epithelial and mesenchymal characteristics that enable specialized capabilities such as collective cell migration. On the gene network perspective, a four-component decision unit composed of two highly interconnected chimeric modules--the miR34/SNAIL and the miR200/ZEB mutual-inhibition feedback circuits--regulates the coexistence of and transitions between the different phenotypes. Here, we present a new tractable theoretical framework to model and decode the underlying principles governing the operation of the regulatory unit. Our approach connects the knowledge about intracellular pathways with observations of cellular behavior and advances toward understanding the logic of cancer decision-making. We found that the miR34/SNAIL module acts as an integrator while the miR200/ZEB module acts as a three-way switch. Consequently, the combined unit can give rise to three phenotypes (stable states): (i) a high miR200 and low ZEB, or (1, 0) state; (ii) a low miR200 and high ZEB, or (0, 1) state; and (iii) a medium miR200 and medium ZEB, or (½, ½) state. We associate these states with the epithelial, mesenchymal, and hybrid phenotypes, respectively. We reflect on the consistency between our theoretical predictions and recent observations in several types of carcinomas and suggest new testable predictions. See all articles in this Cancer Research section, ©2014 American Association for Cancer Research.

  18. Anaplastic thyroid carcinoma, thyroid lymphoma, and metastasis to thyroid.

    PubMed

    Untch, Brian R; Olson, John A

    2006-07-01

    Anaplastic thyroid carcinoma, thyroid lymphoma, and secondary metastasis to the thyroid gland are uncommon thyroid malignancies. They represent significant challenges for the surgeon owing to difficulties in diagnosis, aggressive biology, and the infrequency of their presentation. An awareness and appreciation of multimodality treatment strategies is essential for their management.

  19. Does It Matter if Students Have the Same Instructor for Lecture and Lab Sections? An Analysis of Introductory Biology Students

    ERIC Educational Resources Information Center

    Wise, Michael J.

    2017-01-01

    With the goal of increasing the immediacy of the relationship between tenure-track professors and students, science departments in liberal arts colleges may try to arrange their curriculum so that students have the same professor in both the lecture and the lab section of introductory courses. While this goal seems laudable, empirical data are…

  20. Galectin-3 as a Potential Target to Prevent Cancer Metastasis

    PubMed Central

    Ahmed, Hafiz; AlSadek, Dina M. M.

    2015-01-01

    Interactions between two cells or between cell and extracellular matrix mediated by protein–carbohydrate interactions play pivotal roles in modulating various biological processes such as growth regulation, immune function, cancer metastasis, and apoptosis. Galectin-3, a member of the β-galactoside-binding lectin family, is involved in fibrosis as well as cancer progression and metastasis, but the detailed mechanisms of its functions remain elusive. This review discusses its structure, carbohydrate-binding properties, and involvement in various aspects of tumorigenesis and some potential carbohydrate ligands that are currently investigated to block galectin-3 activity. PMID:26640395

  1. Chemokines: key players in cancer progression and metastasis

    PubMed Central

    Singh, Rajesh; Lilladr, James W.; Singh, Shailesh

    2013-01-01

    Instructed cell migration is a fundamental component of various biological systems and is critical to the pathogenesis of many diseases including cancer. Role of chemokines in providing navigational cues to migrating cancer cells bearing specific receptors is well established. However, functional mechanisms of chemokine are not well implicit, which is crucial for designing new therapeutics to control tumor growth and metastasis. Multiple functions and mode of actions have been advocated for chemokines and their receptors in the progression of primary and secondary tumors. In this review, we have discussed current advances in understanding the role of the chemokines and their corresponding receptor in tumor progression and metastasis. PMID:21622291

  2. Novel Aptamers to Target Metastasis

    DTIC Science & Technology

    2012-11-01

    AD_________________ Award Number: W81XWH-09-1-0154 TITLE: Novel Aptamers To Target Metastasis...August 2012 4. TITLE AND SUBTITLE Novel Aptamers to Target Metastasis 5a. CONTRACT NUMBER . 5b. GRANT NUMBER W81XWH-09-1-0154 5c. PROGRAM ELEMENT...problems. Aptamers , which have proven clinical efficacy for non-neoplastic disease and are generally more specific and stable than antibodies, may have

  3. Hypoxia and the extracellular matrix: drivers of tumour metastasis

    PubMed Central

    Gilkes, Daniele M.; Semenza, Gregg L.; Wirtz, Denis

    2014-01-01

    Of the deaths attributed to cancer, 90% are due to metastasis, and treatments that prevent or cure metastasis remain elusive. Emerging data indicate that hypoxia and the extracellular matrix (ECM) might have crucial roles in metastasis. During tumour evolution, changes in the composition and the overall content of the ECM reflect both its biophysical and biological properties and these strongly influence tumour and stromal cell properties, such as proliferation and motility. Originally thought of as independent contributors to metastatic spread, recent studies have established a direct link between hypoxia and the composition and the organization of the ECM, which suggests a new model in which multiple microenvironmental signals might converge to synergistically influence metastatic outcome. PMID:24827502

  4. CD44 and HCELL: Preventing Hematogenous Metastasis at Step 1

    PubMed Central

    Jacobs, Pieter P.; Sackstein, Robert

    2011-01-01

    Despite great strides in our knowledge of the genetic and epigenetic changes underlying malignancy, we have limited information on the molecular basis of metastasis. Over 90% of cancer deaths are caused by spread of tumor cells from a primary site to distant organs and tissues, highlighting the pressing need to define the molecular effectors of cancer metastasis. Mounting evidence suggests that circulating tumor cells home to specific tissues by hijacking the normal leukocyte trafficking mechanisms. Cancer cells characteristically express CD44, and there is increasing evidence that HCELL, a sialofucosylated glycoform of CD44, serves as the major selectin ligand on cancer cells, allowing interaction of tumor cells with endothelium, leukocytes, and platelets. Here, we review the structural biology of CD44 and of HCELL, and present current data on the function of these molecules in mediating organ-specific homing/metastasis of circulating tumor cells. PMID:21827751

  5. Targeting Phosphatidylserine for Radioimmunotherapy of Breast Cancer Brain Metastasis

    DTIC Science & Technology

    2014-10-01

    signal intensity lesions (arrowheads) on four consecutive coronal sections of a representative mouse brain . Only a few of the lesions (arrowheads...To radiolabel the PS-targeting antibody, mch635, with β- emitters and evaluate its biodistribution and pharmacokinetics in breast cancer brain ...Award Number: W81XWH-12-1-0317 TITLE: Targeting Phosphatidylserine for Radioimmunotherapy of Breast Cancer Brain Metastasis PRINCIPAL

  6. Matricellular proteins as regulators of cancer metastasis to bone

    PubMed Central

    Trotter, Timothy N.; Yang, Yang

    2016-01-01

    Metastasis is the major cause of the death in cancer patients, and a frequent site of metastasis for many cancers is the bone marrow. Therefore, understanding the mechanisms underlying the metastatic process is necessary for future prevention and treatment. The tumor microenvironment is now known to play a role in the metastatic cascade, both at the primary tumor and in metastatic sites, and includes both cellular and non-cellular components. The extracellular matrix (ECM) provides structural support and signaling cues to cells. One particular group of molecules associated with the ECM, known as matricellular proteins, modulate multiple aspects of tumor biology, including growth, migration, invasion, angiogenesis and metastasis. These proteins are also important for normal function in the bone by regulating bone formation and bone resorption. Recent studies have described a link between some of these proteins and metastasis of various tumors to the bone. The aim of this review is to summarize what is currently known about matricellular protein influence on bone metastasis. Particular attention to the contribution of both tumor cells and non-malignant cells in the bone has been given. PMID:26807761

  7. Synthesis, crystals of centrosymmetric triphenylamine chromophores bearing prodigious two-photon absorption cross-section and biological imaging

    NASA Astrophysics Data System (ADS)

    Wang, Shichao; Xu, Shasha; Wang, Yiming; Tian, Xiaohe; Zhang, Yujin; Wang, Chuankui; Wu, Jieying; Yang, Jiaxiang; Tian, Yupeng

    2017-02-01

    Two centrosymmetric D-π-D type triphenylamine chromophores with long π-conjugated bridge and strong electron-donating moiety were designed, synthesized and fully characterized. The crystal analysis revealed that multiple Csbnd H ⋯ π interactions existed in two chromophores, which played a crucial role in generating molecular 1D chains and 2D layers structures. Linear and nonlinear optical properties of the chromophores were systematically investigated with the aid of theoretical calculations. Two chromophores both exhibited intense and wide-dispersed one-photon/two-photon excited fluorescence, bear prodigious 2PA cross section (δ). Especially for Dye2, with ethyoxyl groups, displayed the strong 2PA activity, large cross-sections (δmax > 16,000 GM) and high NLO efficiency (δmax/MW > 16 GM/(g·mol)) in the range of 680-830 nm in DMF. In addition, one- and two-photon fluorescence microscopy images of HepG2 cells incubated with Dye2 were obtained and found that Dye2 could effectively uptake toward living cells and display a uniformly localized in cytosolic space.

  8. Synthesis, crystals of centrosymmetric triphenylamine chromophores bearing prodigious two-photon absorption cross-section and biological imaging.

    PubMed

    Wang, Shichao; Xu, Shasha; Wang, Yiming; Tian, Xiaohe; Zhang, Yujin; Wang, Chuankui; Wu, Jieying; Yang, Jiaxiang; Tian, Yupeng

    2017-02-15

    Two centrosymmetric D-π-D type triphenylamine chromophores with long π-conjugated bridge and strong electron-donating moiety were designed, synthesized and fully characterized. The crystal analysis revealed that multiple CH⋯π interactions existed in two chromophores, which played a crucial role in generating molecular 1D chains and 2D layers structures. Linear and nonlinear optical properties of the chromophores were systematically investigated with the aid of theoretical calculations. Two chromophores both exhibited intense and wide-dispersed one-photon/two-photon excited fluorescence, bear prodigious 2PA cross section (δ). Especially for Dye2, with ethyoxyl groups, displayed the strong 2PA activity, large cross-sections (δmax>16,000GM) and high NLO efficiency (δmax/MW>16GM/(g·mol)) in the range of 680-830nm in DMF. In addition, one- and two-photon fluorescence microscopy images of HepG2 cells incubated with Dye2 were obtained and found that Dye2 could effectively uptake toward living cells and display a uniformly localized in cytosolic space.

  9. Metastasis-associated in colon cancer-1 in gastric cancer: Beyond metastasis

    PubMed Central

    Wu, Zhen-Zhen; Chen, Li-Shan; Zhou, Rui; Bin, Jian-Ping; Liao, Yu-Lin; Liao, Wang-Jun

    2016-01-01

    Metastasis-associated in colon cancer-1 (MACC1) is an oncogene that was first identified in colon cancer. The upstream and downstream of MACC1 form a delicate regulatory network that supports its tumorigenic role in cancers. Multiple functions of MACC1 have been discovered in many cancers. In gastric cancer (GC), MACC1 has been shown to be involved in oncogenesis and tumor progression. MACC1 overexpression adversely affects the clinical outcomes of GC patients. Regarding the mechanism of action of MACC1 in GC, studies have shown that it promotes the epithelial-to-mesenchymal transition and accelerates cancer metastasis. MACC1 is involved in many hallmarks of GC in addition to metastasis. MACC1 promotes vasculogenic mimicry (VM) via TWIST1/2, and VM increases the tumor blood supply, which is necessary for tumor progression. MACC1 also facilitates GC lymphangiogenesis by upregulating extracellular secretion of VEGF-C/D, indicating that MACC1 may be an important player in GC lymphatic dissemination. Additionally, MACC1 supports GC growth under metabolic stress by enhancing the Warburg effect. In conclusion, MACC1 participates in multiple biological processes inside and outside of GC cells, making it an important mediator of the tumor microenvironment. PMID:27547006

  10. Intravital imaging of metastasis in adult Zebrafish.

    PubMed

    Benjamin, David C; Hynes, Richard O

    2017-09-25

    Metastasis is a major clinical problem whose biology is not yet fully understood. This lack of understanding is especially true for the events at the metastatic site, which include arrest, extravasation, and growth into macrometastases. Intravital imaging is a powerful technique that has shown great promise in increasing our understanding of these events. To date, most intravital imaging studies have been performed in mice, which has limited its adoption. Zebrafish are also a common system for the intravital imaging of metastasis. However, as imaging in embryos is technically simpler, relatively few studies have used adult zebrafish to study metastasis and none have followed individual cells at the metastatic site over time. The aim of this study was to demonstrate that adult casper zebrafish offer a convenient model system for performing intravital imaging of the metastatic site over time with single-cell resolution. ZMEL1 zebrafish melanoma cells were injected into 6 to 10-week-old casper fish using an intravenous injection protocol. Because casper fish are transparent even as adults, they could be imaged without surgical intervention. Individual cells were followed over the course of 2 weeks as they arrested, extravasated, and formed macroscopic metastases. Our injection method reliably delivered cells into circulation and led to the formation of tumors in multiple organs. Cells in the skin and sub-dermal muscle could be imaged at high resolution over 2 weeks using confocal microscopy. Arrest was visualized and determined to be primarily due to size restriction. Following arrest, extravasation was seen to occur between 1 and 6 days post-injection. Once outside of the vasculature, cells were observed migrating as well as forming protrusions. Casper fish are a useful model for studying the events at the metastatic site using intravital imaging. The protocols described in this study are relatively simple. Combined with the reasonably low cost of zebrafish, they

  11. IL-17A/IL-17RA interaction promoted metastasis of osteosarcoma cells

    PubMed Central

    Wang, Mingmin; Wang, Luanqiu; Ren, Tao; Xu, Lin; Wen, Zhenke

    2013-01-01

    Osteosarcoma (OS) is the most common human primary malignant bone tumor in children and young adults with poor prognosis because of their high metastatic potential. Identification of key factors that could regulate the aggressive biologic behavior of OS, particularly with respect to metastasis, would be necessary if significant improvements in therapeutic outcome are to occur. In this study, we carefully evaluated the potential role of IL-17A/IL-17RA interaction in metastasis of OS. We found that serum IL-17A was higher in OS patients with metastasis and was associated with their clinical stage. The elevated expression of IL-17RA was observed in tumor tissue from OS patients with metastasis. Of note, we showed that IL-17A could promote the metastasis of U-2 OS cells which expression high IL-17RA, but not MG63 cells which expression low IL-17RA. Further, we revealed that downregulation of IL-17RA in U-2 cells could abrogated the enhanced metastasis induced by IL-17A, while upregulation of IL-17RA in MG63 cells could elevate their response to IL-17A and exerted enhanced metastasis. We observed that IL-17A/IL-17RA interaction promoted the expression of VEGF, MMP9 and CXCR4 in OS cells, which might partly explain the enhanced metastasis of OS cells. Furthermore, we showed that Stat3 activity was crucial for IL-17A/IL-17RA interaction to promote OS metastasis. Finally, we confirmed that IL-17A/IL-17RA interaction promoted the metastasis of OS in nude mice. Our findings might provide a mechanistic explanation for metastasis of OS in vivo, and suggested that targeting IL-17A signaling was a novel promising strategy to treat patients with OS. PMID:23192273

  12. Clinicopathological factors associated with survival in patients with breast cancer brain metastasis.

    PubMed

    Li, Rong; Zhang, Kui; Siegal, Gene P; Wei, Shi

    2017-06-01

    Brain metastasis from breast cancer generally represents a catastrophic event yet demonstrates substantial biological heterogeneity. There have been limited studies solely focusing on the prognosis of patients with such metastasis. In this study, we carried out a comprehensive analysis in 108 consecutive patients with breast cancer brain metastases between 1997 and 2012 to further define clinicopathological factors associated with early onset of brain metastasis and survival outcomes after development of them. We found that lobular carcinoma, higher clinical stages at diagnosis, and lack of coexisting bone metastasis were significantly associated with a worse brain relapse-free survival when compared with brain-only metastasis. High histologic grade, triple-negative breast cancer, and absence of visceral involvement were unfavorable prognostic factors after brain metastasis. Furthermore, high histologic grade, advanced tumor stages, and lack of coexisting bone involvement indicated a worse overall survival. Thus, the previously established prognostic factors in early stage or advanced breast cancers may not entirely apply to patients with brain metastases. Furthermore, the prognostic significance of the clinicopathological factors differed before and after a patient develops brain metastasis. This knowledge might help in establishing an algorithm to further stratify patients with breast cancer into prognostically significant categories for optimal prevention, screening, and treatment of their brain metastasis. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. RARRES3 suppresses breast cancer lung metastasis by regulating adhesion and differentiation.

    PubMed

    Morales, Mònica; Arenas, Enrique J; Urosevic, Jelena; Guiu, Marc; Fernández, Esther; Planet, Evarist; Fenwick, Robert Bryn; Fernández-Ruiz, Sonia; Salvatella, Xavier; Reverter, David; Carracedo, Arkaitz; Massagué, Joan; Gomis, Roger R

    2014-07-01

    In estrogen receptor-negative breast cancer patients, metastatic relapse usually occurs in the lung and is responsible for the fatal outcome of the disease. Thus, a better understanding of the biology of metastasis is needed. In particular, biomarkers to identify patients that are at risk of lung metastasis could open the avenue for new therapeutic opportunities. Here we characterize the biological activity of RARRES3, a new metastasis suppressor gene whose reduced expression in the primary breast tumors identifies a subgroup of patients more likely to develop lung metastasis. We show that RARRES3 downregulation engages metastasis-initiating capabilities by facilitating adhesion of the tumor cells to the lung parenchyma. In addition, impaired tumor cell differentiation due to the loss of RARRES3 phospholipase A1/A2 activity also contributes to lung metastasis. Our results establish RARRES3 downregulation as a potential biomarker to identify patients at high risk of lung metastasis who might benefit from a differentiation treatment in the adjuvant programme. © 2014 The Authors. Published under the terms of the CC BY 4.0 license.

  14. RARRES3 suppresses breast cancer lung metastasis by regulating adhesion and differentiation

    PubMed Central

    Morales, Mònica; Arenas, Enrique J; Urosevic, Jelena; Guiu, Marc; Fernández, Esther; Planet, Evarist; Fenwick, Robert Bryn; Fernández-Ruiz, Sonia; Salvatella, Xavier; Reverter, David; Carracedo, Arkaitz; Massagué, Joan; Gomis, Roger R

    2014-01-01

    In estrogen receptor-negative breast cancer patients, metastatic relapse usually occurs in the lung and is responsible for the fatal outcome of the disease. Thus, a better understanding of the biology of metastasis is needed. In particular, biomarkers to identify patients that are at risk of lung metastasis could open the avenue for new therapeutic opportunities. Here we characterize the biological activity of RARRES3, a new metastasis suppressor gene whose reduced expression in the primary breast tumors identifies a subgroup of patients more likely to develop lung metastasis. We show that RARRES3 downregulation engages metastasis-initiating capabilities by facilitating adhesion of the tumor cells to the lung parenchyma. In addition, impaired tumor cell differentiation due to the loss of RARRES3 phospholipase A1/A2 activity also contributes to lung metastasis. Our results establish RARRES3 downregulation as a potential biomarker to identify patients at high risk of lung metastasis who might benefit from a differentiation treatment in the adjuvant programme. PMID:24867881

  15. Mitochondria in relation to cancer metastasis.

    PubMed

    Bhandary, Bidur; Marahatta, Anu; Kim, Hyung-Ryong; Chae, Han-Jung

    2012-12-01

    Mitochondria, also known as "Power House of cell," are crucial organelles, regulating energy metabolism. Recently, an involvement of mitochondria in cancer occurrence and metastasis has been proposed. The roles of mitochondria in cancer progression/metastasis include alteration of glycolysis, regulation of ROS and suppression of intrinsic apoptosis. This mini-review explains the specific mitochondrial characteristics during cancer metastasis with past and recent findings. It may contribute to understanding mitochondria-related mechanisms of cancer metastasis.

  16. Characterization of surface sediments from the Beijing-Hangzhou Grand Canal (Zaozhuang section), China: assessment of beryllium enrichment, biological effect, and mobility.

    PubMed

    Zhuang, Wen; Chen, Qing; Gao, Xuelu; Zhou, Fengxia; Wang, Mantang; Liu, Yongxia

    2016-07-01

    The South-to-North Water Diversion Project is one of the world's largest water diversion projects, benefiting seven million people in China. The Zaozhuang section of the Beijing-Hangzhou Grand Canal is an important part of this project. This paper investigated the enrichment, biological effect, and mobility of beryllium (Be) in surface sediments of the Zaozhuang section. Results showed that high values were found in Tai'erzhuang District, Zaozhuang city, and the areas near the inlet of the Nansihu Lake, which might have been influenced by local human activities including metallurgy, burning of fossil fuels, and transportation. Four geochemical fractions of Be were obtained: acid-soluble fraction, reducible fraction, oxidizable fraction, and residual fraction. The non-residual fractions (the sum of the first three) accounted for 72.5 ∼ 96.1 % of the total amount of Be. Acid-soluble fraction might be mainly influenced by human activities, with the strongest mobility and bio-availability, accounting for 4.1 ∼ 44.7 % of the total amount, with an average of 20.2 %. Enrichment factor (EF) showed minor to moderate enrichment in some regions; adverse effect index (AEI) also showed that there were high levels of Be in some regions, which might have negative impacts on organisms. Generally, mobility, EF, and AEI of elements are carried out separately. But the results of this study indicated that a comprehensive assessment on the enrichment, mobility, and biological effects of Be caused by human activities is necessary in understanding the environmental risks of Be.

  17. Movers and shakers: cell cytoskeleton in cancer metastasis.

    PubMed

    Fife, C M; McCarroll, J A; Kavallaris, M

    2014-12-01

    Metastasis is responsible for the greatest number of cancer deaths. Metastatic disease, or the movement of cancer cells from one site to another, is a complex process requiring dramatic remodelling of the cell cytoskeleton. The various components of the cytoskeleton, actin (microfilaments), microtubules (MTs) and intermediate filaments, are highly integrated and their functions are well orchestrated in normal cells. In contrast, mutations and abnormal expression of cytoskeletal and cytoskeletal-associated proteins play an important role in the ability of cancer cells to resist chemotherapy and metastasize. Studies on the role of actin and its interacting partners have highlighted key signalling pathways, such as the Rho GTPases, and downstream effector proteins that, through the cytoskeleton, mediate tumour cell migration, invasion and metastasis. An emerging role for MTs in tumour cell metastasis is being unravelled and there is increasing interest in the crosstalk between key MT interacting proteins and the actin cytoskeleton, which may provide novel treatment avenues for metastatic disease. Improved understanding of how the cytoskeleton and its interacting partners influence tumour cell migration and metastasis has led to the development of novel therapeutics against aggressive and metastatic disease. This article is part of a themed section on Cytoskeleton, Extracellular Matrix, Cell Migration, Wound Healing and Related Topics. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-24. © 2014 The British Pharmacological Society.

  18. Movers and shakers: cell cytoskeleton in cancer metastasis

    PubMed Central

    Fife, C M; McCarroll, J A; Kavallaris, M

    2014-01-01

    Metastasis is responsible for the greatest number of cancer deaths. Metastatic disease, or the movement of cancer cells from one site to another, is a complex process requiring dramatic remodelling of the cell cytoskeleton. The various components of the cytoskeleton, actin (microfilaments), microtubules (MTs) and intermediate filaments, are highly integrated and their functions are well orchestrated in normal cells. In contrast, mutations and abnormal expression of cytoskeletal and cytoskeletal-associated proteins play an important role in the ability of cancer cells to resist chemotherapy and metastasize. Studies on the role of actin and its interacting partners have highlighted key signalling pathways, such as the Rho GTPases, and downstream effector proteins that, through the cytoskeleton, mediate tumour cell migration, invasion and metastasis. An emerging role for MTs in tumour cell metastasis is being unravelled and there is increasing interest in the crosstalk between key MT interacting proteins and the actin cytoskeleton, which may provide novel treatment avenues for metastatic disease. Improved understanding of how the cytoskeleton and its interacting partners influence tumour cell migration and metastasis has led to the development of novel therapeutics against aggressive and metastatic disease. Linked Articles This article is part of a themed section on Cytoskeleton, Extracellular Matrix, Cell Migration, Wound Healing and Related Topics. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-24 PMID:24665826

  19. Undergraduate teaching on biological weapons and bioterrorism at medical schools in the UK and the Republic of Ireland: results of a cross-sectional study

    PubMed Central

    Green, Stephen T; Cladi, Lorenzo; Morris, Paul; Forde, Donall

    2013-01-01

    Objective To determine if individual undergraduate schools of medicine in the UK and the Republic of Ireland provide any teaching to medical students about biological weapons, bioterrorism, chemical weapons and weaponised radiation, if they perceive them to be relevant issues and if they figure them in their future plans. Design A cross-sectional study utilising an internet-based questionnaire sent to key figures responsible for leading on the planning and delivery of undergraduate medical teaching at all schools of medicine in the UK and Ireland. Setting All identified undergraduate schools of medicine in the UK and Ireland between August 2012 and December 2012. Outcome measures Numerical data and free text feedback about relevant aspects of undergraduate teaching. Results Of the 38 medical schools approached, 34 (28 in UK, 6 in Ireland) completed the questionnaire (89.47%). 4 (all in UK) chose not to complete it. 6/34 (17.65%) included some specific teaching on biological weapons and bioterrorism. 7/34 (20.59%) had staff with bioterrorism expertise (mainly in microbiological and syndromic aspects). 4/34 (11.76%) had plans to introduce some specific teaching on bioterrorism. Free text responses revealed that some felt that because key bodies (eg, UK's General Medical Council) did not request teaching on bioterrorism, then it should not be included, while others regarded this field of study as a postgraduate subject and not appropriate for undergraduates, or argued that the curriculum was too congested already. 4/34 (11.76%) included some specific teaching on chemical weapons, and 3/34 (8.82%) on weaponised radiation. Conclusions This study provides evidence that at the present time there is little teaching at the undergraduate level in the UK and Ireland on the subjects of biological weapons and bioterrorism, chemical weapons and weaponised radiation and signals that this situation is unlikely to change unless there were to be high-level policy guidance. PMID

  20. Undergraduate teaching on biological weapons and bioterrorism at medical schools in the UK and the Republic of Ireland: results of a cross-sectional study.

    PubMed

    Green, Stephen T; Cladi, Lorenzo; Morris, Paul; Forde, Donall

    2013-06-20

    To determine if individual undergraduate schools of medicine in the UK and the Republic of Ireland provide any teaching to medical students about biological weapons, bioterrorism, chemical weapons and weaponised radiation, if they perceive them to be relevant issues and if they figure them in their future plans. A cross-sectional study utilising an internet-based questionnaire sent to key figures responsible for leading on the planning and delivery of undergraduate medical teaching at all schools of medicine in the UK and Ireland. All identified undergraduate schools of medicine in the UK and Ireland between August 2012 and December 2012. Numerical data and free text feedback about relevant aspects of undergraduate teaching. Of the 38 medical schools approached, 34 (28 in UK, 6 in Ireland) completed the questionnaire (89.47%). 4 (all in UK) chose not to complete it. 6/34 (17.65%) included some specific teaching on biological weapons and bioterrorism. 7/34 (20.59%) had staff with bioterrorism expertise (mainly in microbiological and syndromic aspects). 4/34 (11.76%) had plans to introduce some specific teaching on bioterrorism. Free text responses revealed that some felt that because key bodies (eg, UK's General Medical Council) did not request teaching on bioterrorism, then it should not be included, while others regarded this field of study as a postgraduate subject and not appropriate for undergraduates, or argued that the curriculum was too congested already. 4/34 (11.76%) included some specific teaching on chemical weapons, and 3/34 (8.82%) on weaponised radiation. This study provides evidence that at the present time there is little teaching at the undergraduate level in the UK and Ireland on the subjects of biological weapons and bioterrorism, chemical weapons and weaponised radiation and signals that this situation is unlikely to change unless there were to be high-level policy guidance.

  1. Improving Signal to Noise in Labeled Biological Specimens using Energy-Filtered TEM of sections with a Drift Correction Strategy and a Direct Detection Device

    PubMed Central

    Ramachandra, Ranjan; Bouwer, James C.; Mackey, Mason R.; Bushong, Eric; Peltier, Steven T.; Xuong, Nguyen-Huu; Ellisman, Mark H.

    2014-01-01

    Energy filtered transmission electron microscopy techniques are regularly used to build elemental maps of spatially distributed nanoparticles in materials and biological specimens. When working with thick biological sections, EELS techniques involving core-loss electrons often require exposures exceeding several minutes to provide sufficient signal to noise. Image quality with these long exposures is often compromised by specimen drift, which results in blurring and reduced resolution. To mitigate drift artifacts, a series of short exposure images can be acquired, aligned, and merged to form a single image. For samples where the target elements have extremely low signal yields, the use of CCD based detectors for this purpose can be problematic. At short acquisition times, the images produced by CCDs can be noisy and may contain fixed pattern artifacts that impact subsequent correlative alignment. Here we report on the use of direct electron detection devices (DDD’s) to increase the signal to noise as compared to CCD’s. A 3x improvement in signal is reported with a DDD vs. a comparably formatted CCD, with equivalent dose on each detector. With the fast rolling-readout design of the DDD, the duty cycle provides a major benefit, as there is no dead time between successive frames. PMID:24641915

  2. Metastasis genetics, epigenetics, and the tumor microenvironment

    USDA-ARS?s Scientific Manuscript database

    KISS1 is a member of a family of genes known as metastasis suppressors, defined by their ability to block metastasis without blocking primary tumor development and growth. KISS1 re-expression in multiple metastatic cell lines of diverse cellular origin suppresses metastasis; yet, still allows comple...

  3. Right ventricular metastasis of leiomyosarcoma.

    PubMed

    Dencker, Magnus; Valind, Sven; Stagmo, Martin

    2009-05-05

    Metastatic presentation of leiomyosarcoma in the heart is very rare. We present transthoracic echocardiography and combined PET/CT images of a case with a large right ventricular metastasis of leiomyosarcoma. The patient was placed on cytostatic drugs for palliative purposes, but passed away one month later because of an untreatable ventricular tackycardia.

  4. Intracranial tuberculoma mimicking brain metastasis.

    PubMed

    Salaskar, Abhijit L; Hassaneen, Wael; Keenan, Cheryl H; Suki, Dima

    2015-01-01

    To our knowledge, this is the first report of an intracranial tuberculoma in an immunocompetent patient with a solid primary tumor outside the central nervous system. This case is important because the patient underwent treatment for a presumed brain metastasis, based on the knowledge that a solid extracranial primary tumor was present, but before the brain lesion pathology was determined.

  5. Lectin binding to cutaneous malignant melanoma: HPA is associated with metastasis formation

    PubMed Central

    Thies, A; Moll, I; Berger, J; Schumacher, U

    2001-01-01

    Changes in protein glycosylation of tumour cells, as detected by lectin histochemistry, have been associated with metastasis formation in several human malignancies. This study analysed the association between lectin binding and metastasis in cutaneous malignant melanoma. In a 10-year retrospective study, sections of 100 primary cutaneous malignant melanomas were histochemically stained for the following 5 lectins: HPA, SNA-I, MAA, WGA and PHA-L, differing in their carbohydrate specificity. Since differences in the results of HPA binding depending on methodology have been reported, an indirect and a biotinylated method were employed for HPA. Kaplan–Meier analysis of time to first metastasis revealed a positive correlation between HPA binding and metastasis for both methods, with the biotinylated HPA method (P< 0.0001) being superior to the ‘indirect’ method (P = 0.0006). Cox regression analysis demonstrated that even after adjustment for stage, HPA positivity is an independent predictor for metastasis. The results of the present study indicate that N -acetyl-galactosamine/-glucosamine residues, recognized by HPA, are linked to metastasis in malignant melanoma. In contrast, β1-6 branched oligosaccharides or sialic acid residues, both of which were correlated with metastasis in other malignancies, are of no functional importance for metastasis formation in malignant melanoma. Thus, HPA proved to be a useful and independent prognostic marker for the metastatic phenotype of melanoma. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11259098

  6. Metabolism in cancer metastasis.

    PubMed

    Weber, Georg F

    2016-05-01

    Cancer metabolism has regained substantial research interest over recent years. The focus has been mostly on the primary tumor, while metabolic adjustments during dissemination have been less extensively researched. Deadhesion impairs glucose transport and brings about an ATP deficit that leads to apoptosis. To survive, metastasizing cancer cells need to increase ATP synthesis, which involves mitochondrial activity and is accomplished in part through peroxide signaling. This change in metabolism, associated with cancer spread, is different from the Warburg effect. Therefore it is important to distinguish between the metabolic adjustments in primary tumor cells and those in disseminating tumor cells. In general, it is likely that metabolic responses to environmental cues commonly occur in cell biology. © 2015 UICC.

  7. A New Paradigm for Mechanobiological Mechanisms in Tumor Metastasis

    PubMed Central

    Torzilli, Peter A.; Bourne, Jonathan W.; Cigler, Tessa; Vincent, C.Theresa

    2012-01-01

    Tumor metastases and epithelial to mesenchymal transition (EMT) involve tumor cell invasion and migration through the dense collagen-rich extracellular matrix surrounding the tumor. Little is known about the mechanobiological mechanisms involved in this process, nor the role of the mechanical forces generated by the cells in their effort to invade and migrate through the stroma. In this paper we propose a new fundamental mechanobiological mechanism involved in cancer growth and metastasis, which can be both protective or destructive depending on the magnitude of the forces generated by the cells. This new mechanobiological mechanism directly challenges current paradigms that are focused mainly on biological and biochemical mechanisms associated with tumor metastasis. Our new mechanobiological mechanism describes how tumor expansion generates mechanical forces within the stroma to not only resist tumor expansion but also inhibit or enhance tumor invasion by, respectively, inhibiting or enhancing matrix metalloproteinase (MMP) degradation of the tensed interstitial collagen. While this mechanobiological mechanism has not been previously applied to the study of tumor metastasis and EMT, it may have the potential to broaden our understanding of the tumor invasive process and assist in developing new strategies for preventing or treating cancer metastasis. PMID:22613484

  8. Gene Expression Profiling of Breast Cancer Brain Metastasis

    PubMed Central

    Lee, Ji Yun; Park, Kyunghee; Lee, Eunjin; Ahn, TaeJin; Jung, Hae Hyun; Lim, Sung Hee; Hong, Mineui; Do, In-Gu; Cho, Eun Yoon; Kim, Duk-Hwan; Kim, Ji-Yeon; Ahn, Jin Seok; Im, Young-Hyuck; Park, Yeon Hee

    2016-01-01

    The biology of breast cancer brain metastasis (BCBM) is poorly understood. We aimed to explore genes that are implicated in the process of brain metastasis of primary breast cancer (BC). NanoString nCounter Analysis covering 252 target genes was used for comparison of gene expression levels between 20 primary BCs that relapsed to brain and 41 BCBM samples. PAM50-based intrinsic subtypes such as HER2-enriched and basal-like were clearly over-represented in BCBM. A panel of 22 genes was found to be significantly differentially expressed between primary BC and BCBM. Five of these genes, CXCL12, MMP2, MMP11, VCAM1, and MME, which have previously been associated with tumor progression, angiogenesis, and metastasis, clearly discriminated between primary BC and BCBM. Notably, the five genes were significantly upregulated in primary BC compared to BCBM. Conversely, SOX2 and OLIG2 genes were upregulated in BCBM. These genes may participate in metastatic colonization but not in primary tumor development. Among patient-matched paired samples (n = 17), a PAM50 molecular subtype conversion was observed in eight cases (47.1%), with a trend toward unfavorable subtypes in patients with the distinct gene expression. Our findings, although not conclusive, reveal differentially expressed genes that might mediate the brain metastasis process. PMID:27340107

  9. MicroRNAs in gastric cancer metastasis.

    PubMed

    Shi, Zhaoqi; Wei, Qingxia; She, Junjun

    2014-01-01

    Gastric cancer (GC) is common worldwide and has a high rate of metastasis. The underlying molecular mechanism of metastasis are not entirely clear. MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene expression post-transcriptionally and are reported to be involved in multiple steps of tumor metastasis. Clarifying their roles in GC metastasis will improve understanding of this disease. Here, we review the involvement of miRNAs in multiple steps of GC metastasis, including epithelial-mesenchymal transitions, anoikis, angiogenesis, invasion, and migration. The clinical application of miRNAs as prognostic biomarkers in GC is also discussed.

  10. Critical Roles of p53 in Epithelial-Mesenchymal Transition and Metastasis of Hepatocellular Carcinoma Cells

    PubMed Central

    Wang, Zheng; Jiang, Yuhui; Guan, Dongxian; Li, Jingjing; Yin, Hongkun; Pan, Yi; Xie, Dong; Chen, Yan

    2013-01-01

    Hepatocellular carcinoma (HCC) is one of the most malignant tumors and the biggest obstacle in curing HCC is its high metastasis potential. Alteration of p53 is the most frequent genetic change found in HCC. Although the biological function of p53 in tumor initiation and progression has been well characterized, whether or not p53 is implicated in metastasis of HCC is largely unknown. In this study, we analyzed the potential functions of p53 in epithelial-mesenchymal transition (EMT) and metastasis of HCC cells. Both insulin- and TGF-β1-induced changes of critical EMT markers were greatly enhanced by p53 knockdown in HCC cells. The insulin- and TGF-β1-stimulated migration of HCC cells were enhanced by p53 knockdown. Furthermore, in vivo metastasis of HCC cells using different mouse models was robustly enhanced by p53 knockdown. In addition, we found that p53 regulation on EMT and metastasis involves β-catenin signaling. The nuclear accumulation and transcriptional activity of β-catenin was modulated by p53. The enhanced EMT phenotype, cell migration and tumor metastasis of HCC cells by p53 knockdown were abrogated by inhibiting β-catenin signal pathway. In conclusion, this study reveals that p53 plays a pivotal role in EMT and metastasis of HCC cells via its regulation on β-catenin signaling. PMID:24023784

  11. Animal Models of Bone Metastasis

    PubMed Central

    Simmons, J. K.; Hildreth, B. E.; Supsavhad, W.; Elshafae, S. M.; Hassan, B. B.; Dirksen, W. P.; Toribio, R. E.; Rosol, T. J.

    2015-01-01

    Bone is one of the most common sites of cancer metastasis in humans and is a significant source of morbidity and mortality. Bone metastases are considered incurable and result in pain, pathologic fracture, and decreased quality of life. Animal models of skeletal metastases are essential to improve the understanding of the molecular pathways of cancer metastasis and growth in bone and to develop new therapies to inhibit and prevent bone metastases. The ideal animal model should be clinically relevant, reproducible, and representative of human disease. Currently, an ideal model does not exist; however, understanding the strengths and weaknesses of the available models will lead to proper study design and successful cancer research. This review provides an overview of the current in vivo animal models used in the study of skeletal metastases or local tumor invasion into bone and focuses on mammary and prostate cancer, lymphoma, multiple myeloma, head and neck squamous cell carcinoma, and miscellaneous tumors that metastasize to bone. PMID:26021553

  12. [Bone metastasis of gastric cancer].

    PubMed

    Sudo, Hideo; Takagi, Yu; Katayanagi, So; Hoshino, Sumito; Suda, Takeshi; Hibi, Yasuhiro; Ito, Kazushige; Tsutida, Akihiko; Aoki, Tatsuya

    2006-08-01

    We evaluated 19 patients with bone metastasis after surgery for gastric cancer. In a number of cases, the located in the tumor was U and M region, of macroscopic 3, and the histological type was poorly-differentiated adenocarcinoma with high-grade of lymphatic invasion. The major symptom was lumbago and back pain. The serum AFP level was high in 73.7% of the cases, and LDH was high in 47.7%. The metastatic lesion was predominantly seen in the bone with red pulp such as lumbar and thoracic vertebra and rib. The median survival time was 189 days (range: 24-509) with a poor prognosis. However, newly developed anticancer drugs were very effective for some cases, indicating that such chemotherapy should be tried for cases with bone metastasis.

  13. [Uterine metastasis revealing gastric adenocarcinoma].

    PubMed

    Mambrini, P; Giovanini, M; Seitz, J F; Perrier, H; Allemand, I; Rabia, I; Monges, G; Lebreuil, G

    1995-01-01

    We report a case of metastasis to the uterine corpus revealing a primary gastric adenocarcinoma. A 26-year-old woman suffered from weight loss, vaginal bleeding, abdominal pain. An endometrial curettage showed apparently metastatic adenocarcinoma. The primary site of the tumour was gastric. The upper gastrointestinal endoscopy revealed an ulcus and aspect of linitis plastica in the fundus. Biopsies showed diffuse type adenocarcinoma. Because of extensive disease, laparotomy was not performed and exclusive palliative chemotherapy was started. The patient died 10 months after the diagnosis. Metastasis from primary gastric cancer to the female genital tract are rare and are usually observed in young premenopausal women with diffuse type gastric adenocarcinoma. This case report underlines the interest, for those patients of careful gynaecologic examination at the initial staging and after treatment.

  14. Dissecting and Targeting Latent Metastasis

    DTIC Science & Technology

    2013-09-01

    bone metastasis seed pre-selection by a mesenchymal-rich stroma in the mammary tumor. Blue and grey cells represent mesenchymal and non -mesenchymal...proliferate in vitro but have the capacity to enter a state of long-term latency after infiltrating target organs including lungs, the bone marrow...survival of breast cancer cells that infiltrated the bone marrow. The studies and progress in the first year therefore represent highly promising

  15. Dissecting and Targeting Latent Metastasis

    DTIC Science & Technology

    2015-09-01

    activators of natural killer (NK) lymphocytes, thus leading to evasion of NK cell-mediated cancer cell clearance. By expressing a Sox-dependent stem-like...receptors regulate cancer metastasis via natural killer cells. Nature 507, 508-512 (2014). 29. M. J. Smyth, G. P. Dunn, R. D. Schreiber, Cancer...Zhong, J. M. Chase, P. B. Rothman, J. Yu, J. K. Riley, J. Zhu, Z. Tian, W. M. Yokoyama, Tissue-resident natural killer (NK) cells are cell lineages

  16. Colorectal hepatic metastasis: Evolving therapies

    PubMed Central

    Macedo, Francisco Igor B; Makarawo, Tafadzwa

    2014-01-01

    The approach for colorectal hepatic metastasis has advanced tremendously over the past decade. Multidrug chemotherapy regimens have been successfully introduced with improved outcomes. Concurrently, adjunct multimodal therapies have improved survival rates, and increased the number of patients eligible for curative liver resection. Herein, we described major advancements of surgical and oncologic management of such lesions, thereby discussing modern chemotherapeutic regimens, adjunct therapies and surgical aspects of liver resection. PMID:25067997

  17. Raman spectroscopy of bone metastasis

    NASA Astrophysics Data System (ADS)

    Esmonde-White, Karen A.; Sottnik, Joseph; Morris, Michael; Keller, Evan

    2012-02-01

    Raman spectroscopy of bone has been used to characterize chemical changes occurring in diseases such as osteoporosis, osteoarthritis and osteomyelitis. Metastasis of cancer into bone causes changes to bone quality that are similar to those observed in osteoporosis, such as decreased bone strength, but with an accelerated timeframe. In particular, osteolytic (bone degrading) lesions in bone metastasis have a marked effect on patient quality of life because of increased risk of fractures, pain, and hypercalcemia. We use Raman spectroscopy to examine bone from two different mouse models of osteolytic bone metastasis. Raman spectroscopy measures physicochemical information which cannot be obtained through standard biochemical and histological measurements. This study was reviewed and approved by the University of Michigan University Committee on the Care and Use of Animals. Two mouse models of prostate cancer bone metastasis, RM1 (n=3) and PC3-luc (n=4) were examined. Tibiae were injected with RM1 or PC3-luc cancer cells, while the contralateral tibiae received a placebo injection for use as controls. After 2 weeks of incubation, the mice were sacrificed and the tibiae were examined by Raman microspectroscopy (λ=785 nm). Spectroscopic markers corresponding to mineral stoichiometry, bone mineralization, and mineral crystallinity were compared in spectra from the cancerous and control tibiae. X-ray imaging of the tibia confirmed extensive osteolysis in the RM1 mice, with tumor invasion into adjoining soft tissue and moderate osteolysis in the PC3-luc mice. Raman spectroscopic markers indicate that osteolytic lesions are less mineralized than normal bone tissue, with an altered mineral stoichiometry and crystallinity.

  18. Biological and clinical manifestations of Huntington’s disease in the longitudinal TRACK-HD study: cross-sectional analysis of baseline data

    PubMed Central

    Tabrizi, Sarah J; Langbehn, Douglas R; Leavitt, Blair R; Roos, Raymund A C; Durr, Alexandra; Craufurd, David; Kennard, Christopher; Hicks, Stephen L; Fox, Nick C; Scahill, Rachael I; Borowsky, Beth; Tobin, Allan J; Rosas, H Diana; Johnson, Hans; Reilmann, Ralf; Landwehrmeyer, Bernhard; Stout, Julie C

    2010-01-01

    Summary Background Huntington’s disease (HD) is an autosomal dominant, fully penetrant, neurodegenerative disease that most commonly affects adults in mid-life. Our aim was to identify sensitive and reliable biomarkers in premanifest carriers of mutated HTT and in individuals with early HD that could provide essential methodology for the assessment of therapeutic interventions. Methods This multicentre study uses an extensive battery of novel assessments, including multi-site 3T MRI, clinical, cognitive, quantitative motor, oculomotor, and neuropsychiatric measures. Blinded analyses were done on the baseline cross-sectional data from 366 individuals: 123 controls, 120 premanifest (pre-HD) individuals, and 123 patients with early HD. Findings The first participant was enrolled in January, 2008, and all assessments were completed by August, 2008. Cross-sectional analyses identified significant changes in whole-brain volume, regional grey and white matter differences, impairment in a range of voluntary neurophysiological motor, and oculomotor tasks, and cognitive and neuropsychiatric dysfunction in premanifest HD gene carriers with normal motor scores through to early clinical stage 2 disease. Interpretation We show the feasibility of rapid data acquisition and the use of multi-site 3T MRI and neurophysiological motor measures in a large multicentre study. Our results provide evidence for quantifiable biological and clinical alterations in HTT expansion carriers compared with age-matched controls. Many parameters differ from age-matched controls in a graded fashion and show changes of increasing magnitude across our cohort, who range from about 16 years from predicted disease diagnosis to early HD. These findings might help to define novel quantifiable endpoints and methods for rapid and reliable data acquisition, which could aid the design of therapeutic trials. Funding CHDI/High Q Foundation. PMID:19646924

  19. Cancer stem cells and metastasis.

    PubMed

    Sampieri, Katia; Fodde, Riccardo

    2012-06-01

    Cancer stem cells (CSCs) represent a subpopulation of tumour cells endowed with self-renewal and multi-lineage differentiation capacity but also with an innate resistance to cytotoxic agents, a feature likely to pose major clinical challenges towards the complete eradication of minimal residual disease in cancer patients. Operationally, CSCs are defined by their tumour-propagating ability when serially transplanted into immune-compromised mice and by their capacity to fully recapitulate the original heterogeneity of cell types observed in the primary lesions they are derived from. CSCs were first identified in haematopoietic malignancies and later in a broad spectrum of solid tumours including those of the breast, colon and brain. Notably, several CSC characteristics are relevant to metastasis, such as motility, invasiveness and, as mentioned above, resistance to DNA damage-induced apoptosis. Here, we have reviewed the current literature on the relation between CSCs and metastasis formation. Preliminary studies on cancer cell lines and patient-derived material suggest a rate-limiting role for stem-like cells in the processes of tumour cell dissemination and metastasis formation. However, additional studies are needed to deliver formal proof of their identity as the cell of origin of recurrences at distant organ sites. Nevertheless, several studies have already provided pre-clinical evidence of the efficacy of novel therapies directed against disseminated CSCs.

  20. Unusual Metastasis from Carcinoma Cervix.

    PubMed

    Bhandari, Virendra; Kausar, Mehlam; Naik, Ayush; Batra, Manika

    2016-10-01

    Although the incidence of cancer cervix has reduced in India during the last two decades, still most of the patients presenting in tertiary care centers are in advanced stages. At this center, we see 6% of cancer cervix cases every year, and most of these cases are in stage III and IVa. All these patients have squamous cell carcinoma and were treated with a combination of external and intracavitary radiotherapy along with concurrent cisplatin given once weekly. Eighty-nine point nine % patients had achieved a complete response. Local recurrence was seen in 17.9% at a median duration of 10.5 months, and 8.17% developed distant metastasis involving lung, liver, bone, and supraclavicular lymph nodes. Three patients developed metastasis at unusual sites involving breast, paraspinal muscles, and duodenum which are very rarely involved. These patients were treated with chemotherapy using carboplatin and Paclitaxel combination but succumbed within 8-10 months of development of metastasis. The cause of involvement of these unusual sites is not clear, but it may be hematological spread, and we want to share these reports such that these sites are seen during follow-up of patients of cancer cervix.

  1. Prevalence of metastasis at diagnosis of osteosarcoma: an international comparison

    PubMed Central

    Marko, Tracy A.; Diessner, Brandon J.; Spector, Logan G.

    2016-01-01

    Background Osteosarcoma is the most common primary malignant bone tumor in many countries, with metastatic disease responsible for most patient deaths. This study compares the prevalence of metastatic osteosarcoma at diagnosis across countries to inform the critical question of whether diagnostic delay or tumor biology drives metastases development prior to diagnosis. Procedure A literature search of the PubMed database was conducted to compare the prevalence of metastatic disease at the time of OS diagnosis between countries. A pooled prevalence with 95% confidence intervals was calculated for each study meeting inclusion criteria. Studies were grouped for analysis based on human development index (HDI) scores. Results Our analysis found an 18% (95% CI: 15%, 20%) average global pooled proportion of metastasis at osteosarcoma diagnosis. The average prevalence of metastasis at diagnosis increased as HDI groupings decreased, with very high HDI, high HDI, and medium/ low HDI groups found to be 15% (95% CI: 13%, 17%), 20% (95% CI: 14%, 28%), and 31% (95% CI: 15%, 52%), respectively. Conclusions Our evidence suggests there is a biological baseline for metastatic OS at diagnosis, which is observed in countries with very high HDI. In countries with medium/ low HDI, where there are more barriers to accessing healthcare, the higher prevalence of metastasis may result from treatment delay or an artificial prevalence inflation due to patients with less severe symptoms not presenting to clinic. Additional research in countries with medium/ low HDI may reveal that earlier detection and treatment could improve patient outcomes in those countries. PMID:26929018

  2. The cancer diaspora: Metastasis beyond the seed and soil hypothesis.

    PubMed

    Pienta, Kenneth J; Robertson, Bruce A; Coffey, Donald S; Taichman, Russell S

    2013-11-01

    Do cancer cells escape the confinement of their original habitat in the primary tumor or are they forced out by ecologic changes in their home niche? Describing metastasis in terms of a simple one-way migration of cells from the primary to the target organs is an insufficient concept to cover the nuances of cancer spread. A diaspora is the scattering of people away from an established homeland. To date, "diaspora" has been a uniquely human term used by social scientists; however, the application of the diaspora concept to metastasis may yield new biologic insights as well as therapeutic paradigms. The diaspora paradigm takes into account, and models, several variables including: the quality of the primary tumor microenvironment, the fitness of individual cancer cell migrants as well as migrant populations, the rate of bidirectional migration of cancer and host cells between cancer sites, and the quality of the target microenvironments to establish metastatic sites. Ecologic scientific principles can be applied to the cancer diaspora to develop new therapeutic strategies. For example, ecologic traps - habitats that lead to the extinction of a species - can be developed to attract cancer cells to a place where they can be better exposed to treatments or to cells of the immune system for improved antigen presentation. Merging the social science concept of diaspora with ecologic and population sciences concepts can inform the cancer field to understand the biology of tumorigenesis and metastasis and inspire new ideas for therapy.

  3. Inhibition of cancer cell invasion and metastasis by genistein

    PubMed Central

    Pavese, Janet M.; Farmer, Rebecca L.

    2010-01-01

    Genistein is a small, biologically active flavonoid that is found in high amounts in soy. This important compound possesses a wide variety of biological activities, but it is best known for its ability to inhibit cancer progression. In particular, genistein has emerged as an important inhibitor of cancer metastasis. Consumption of genistein in the diet has been linked to decreased rates of metastatic cancer in a number of population-based studies. Extensive investigations have been performed to determine the molecular mechanisms underlying genistein’s antimetastatic activity, with results indicating that this small molecule has significant inhibitory activity at nearly every step of the metastatic cascade. Reports have demonstrated that, at high concentrations, genistein can inhibit several proteins involved with primary tumor growth and apoptosis, including the cyclin class of cell cycle regulators and the Akt family of proteins. At lower concentrations that are similar to those achieved through dietary consumption, genistein can inhibit the prometastatic processes of cancer cell detachment, migration, and invasion through a variety of mechanisms, including the transforming growth factor (TGF)-β signaling pathway. Several in vitro findings have been corroborated in both in vivo animal studies and in early-phase human clinical trials, demonstrating that genistein can both inhibit human cancer metastasis and also modulate markers of metastatic potential in humans, respectively. Herein, we discuss the variety of mechanisms by which genistein regulates individual steps of the metastatic cascade and highlight the potential of this natural product as a promising therapeutic inhibitor of metastasis. PMID:20730632

  4. Intracarotid Cancer Cell Injection to Produce Mouse Models of Brain Metastasis.

    PubMed

    Zhang, Chenyu; Lowery, Frank J; Yu, Dihua

    2017-02-08

    Metastasis, the spread and growth of malignant cells at secondary sites within a patient's body, accounts for > 90% of cancer-related mortality. Recently, impressive advances in novel therapies have dramatically prolonged survival and improved quality of life for many cancer patients. Sadly, incidence of brain metastatic recurrences is fast rising, and all current therapies are merely palliative. Hence, good experimental animal models are urgently needed to facilitate in-depth studies of the disease biology and to assess novel therapeutic regimens for preclinical evaluation. However, the standard in vivo metastasis assay via tail vein injection of cancer cells produces predominantly lung metastatic lesions; animals usually succumb to the lung tumor burden before any meaningful outgrowth of brain metastasis. Intracardiac injection of tumor cells produces metastatic lesions to multiple organ sites including the brain; however, the variability of tumor growth produced with this model is large, dampening its utility in evaluating therapeutic efficacy. To generate reliable and consistent animal models for brain metastasis study, here we describe a procedure for producing experimental brain metastasis in the house mouse (Mus musculus) via intracarotid injection of tumor cells. This approach allows one to produce large number of brain metastasis-bearing mice with similar growth and mortality characteristics, thus facilitating research efforts to study basic biological mechanisms and to assess novel therapeutic agents.

  5. The impact of hypoxia in pancreatic cancer invasion and metastasis

    PubMed Central

    Yuen, Angela; Díaz, Begoña

    2014-01-01

    Intratumoral hypoxia is a common feature of solid tumors. Recent advances in cancer biology indicate that hypoxia is not only a consequence of unrestrained tumor growth, but also plays an active role in promoting tumor progression, malignancy, and resistance to therapy. Hypoxia signaling is mediated by the hypoxia-inducible factors (HIFs), which are not only stabilized under hypoxia, but also by activated oncogenes or inactivated tumor suppressors under normoxia. Hypoxia is a prominent feature of the tumor microenvironment of pancreatic tumors, also characterized by the presence of a fibrotic reaction that promotes, and is also modulated by, hypoxia. As the mechanisms by which hypoxia signaling impacts invasion and metastasis in pancreatic cancer are being elucidated, hypoxia is emerging as a key determinant of pancreatic cancer malignancy as well as an important target for therapy. Herein we present an overview of recent advances in the understanding of the impact that hypoxia has in pancreatic cancer invasion and metastasis. PMID:27774469

  6. Portal venous gas following chemotherapy for colorectal cancer liver metastasis.

    PubMed

    Zalinski, S; Scatton, O; Jacqmin, S; Tacher, V; Brézault, C; Soubrane, O

    2009-05-01

    The standard of care for patients with colorectal liver metastases is a combination of chemotherapy and surgery. New chemotherapy regimens with biologic agents (cetuximab, bevacizumab) have been shown to increase tumor response rates. Although this might be beneficial and this is an expected endpoint, it should be noted that patients with synchronous colorectal and liver metastases are at risk of septic complications. We recently encountered a case of hepatic portal venous gas after two cycles of chemotherapy in a patient with right colon cancer liver metastases. Complete necrosis of the liver metastasis subsequently turned into a liver abscess, which fistulized in the right portal vein. Infection of the necrotized metastasis was thought to be promoted by the colic tumor. Although this is a dramatic situation, it does not contraindicate a curative surgical resection.

  7. A Large, First-Year, Introductory, Multi-Sectional Biological Concepts of Health Course Designed to Develop Skills and Enhance Deeper Learning

    ERIC Educational Resources Information Center

    Murrant, Coral L.; Dyck, David J.; Kirkland, James B.; Newton, Genevieve S.; Ritchie, Kerry L.; Tishinsky, Justine M.; Bettger, William J.; Richardson, Nicolette S.

    2015-01-01

    Large first-year biology classes, with their heavy emphasis on factual content, contribute to low student engagement and misrepresent the dynamic, interdisciplinary nature of biological science. We sought to redesign a course to deliver fundamental biology curriculum through the study of health, promote skills development, and encourage a deeper…

  8. Unusual late extrapulmonary metastasis in osteosarcoma.

    PubMed

    Hirota, T; Konno, K; Fujimoto, T; Ohta, H; Kato, S; Hara, K

    1999-01-01

    The major site of metastasis from osteosarcoma is the lung, and over 90% of fatalities in patients with this disease die from pulmonary metastases. Extrapulmonary disease is developing in an increasing proportion of patients, usually after pulmonary metastasis. This study reports three cases of patients with osteosarcoma that metastasized to the brain, mediastinum, intramuscular site, and pelvic cavity. The physician must be aware that extrapulmonary metastases may be present at the time a pulmonary metastasis becomes evident.

  9. Zosteriform skin metastasis of lung cancer.

    PubMed

    Li, Wen-Hao; Tu, Chih-Yen; Hsieh, Te-Chun; Wu, Po-Yuan

    2012-12-01

    Skin metastasis from internal organ malignancy has a 5% to about 10% incidence, and zosteriform metastasis is much rarer. We present the case of a 51-year-old male smoker initially given a diagnosis of right lower lung adenocarcinoma T2N3M0 who developed new-onset zosteriform skin metastasis over the right-side T3∼T5 dermatomes documented by skin biopsy specimen. The probable mechanism for this band-distributed skin metastasis is the retrograde flow of lymph after obstruction by cancer cells. Such a phenomenon may be demonstrated by lymphoscintigraphy.

  10. Roles of Fyn in pancreatic cancer metastasis.

    PubMed

    Chen, Zhi-Yu; Cai, Lei; Bie, Ping; Wang, Shu-Guang; Jiang, Yan; Dong, Jia-Hong; Li, Xiao-Wu

    2010-02-01

    Src family kinases have been suggested to be associated with the metastasis of tumors, but their related mechanisms remain unclear. The aims of the present study were to assess the possible mechanisms by which the inhibition of Fyn activation regulates pancreatic cancer metastasis. We examined the expressions of Fyn in human pancreatic cancer tissues by immunohistochemistry and systematically investigated the relationship between Fyn expression and pancreatic cancer metastasis. A nude mouse xenograft model induced by BxPC3 cells with or without the inhibition of Fyn activation was used to explore the effect of the inhibition of Fyn on metastasis in vivo. Methyl thiazolyl tetrazolium and terminal deoxynucleotidyl transferase-labeling assays were used to examine the effect of the inhibition of Fyn on the cell proliferation of BxPC3 pancreatic cancer cells in vitro. Reverse transcription polymerase chain reaction and Western blot analysis were performed to explore the possible mechanism of Fyn-induced metastasis. We found that the upregulation of Fyn expression was correlated with human pancreatic cancer metastasis. In BxPC3 pancreatic cancer cells, the inhibition of Fyn activation by kinase-dead Fyn transfection decreased liver metastasis in nude mice. Further analyses showed that Fyn activity modulated pancreatic cell metastasis through the regulation of proliferation and apoptosis. Our results suggest a possible mechanism by which Fyn activity regulates cell proliferation and apoptosis that exerts an effect on pancreatic cancer metastasis.

  11. Endocannabinoids as Guardians of Metastasis

    PubMed Central

    Tegeder, Irmgard

    2016-01-01

    Endocannabinoids including anandamide and 2-arachidonoylglycerol are involved in cancer pathophysiology in several ways, including tumor growth and progression, peritumoral inflammation, nausea and cancer pain. Recently we showed that the endocannabinoid profiles are deranged during cancer to an extent that this manifests in alterations of plasma endocannabinoids in cancer patients, which was mimicked by similar changes in rodent models of local and metastatic cancer. The present topical review summarizes the complexity of endocannabinoid signaling in the context of tumor growth and metastasis. PMID:26875980

  12. A review of penile metastasis

    PubMed Central

    Mearini, Luigi; Colella, Renato; Zucchi, Alessandro; Nunzi, Elisabetta; Porrozzi, Carlo; Porena, Massimo

    2012-01-01

    Penile cancer as primary disease is relatively rare in developed countries. The penis is a rare site of metastases in spite of its rich vascularization. Approximately 500 cases have been reported in the literature; almost 70% of primary lesions are of pelvic origin (from genitourinary or recto-sigmoid primary tumors). We describe a case of penile metastasis from lung cancer. The rarity of the event prompted us to also explore related reviews and discuss the incidence, physiopathology, diagnosis and therapy of penile secondary cancer. PMID:25992200

  13. Immune cell promotion of metastasis

    PubMed Central

    Kitamura, Takanori; Qian, Bin-Zhi; Pollard, Jeffrey W.

    2015-01-01

    Metastatic disease is the major cause of death from cancer, and immunotherapy and chemotherapy have had limited success in reversing its progression. Data from mouse models suggest that the recruitment of immunosuppressive cells to tumours protects metastatic cancer cells from surveillance by killer cells, which nullifies the effects of immunotherapy and thus establishes metastasis. Furthermore, in most cases, tumour-infiltrating immune cells differentiate into cells that promote each step of the metastatic cascade and thus are novel targets for therapy. In this Review, we describe how tumour-infiltrating immune cells contribute to the metastatic cascade and we discuss potential therapeutic strategies to target these cells. PMID:25614318

  14. On a Rare Cutaneous Metastasis from a Sacrococcygeal Chordoma

    PubMed Central

    Brunelli, Matteo; Floccari, Federica; De Caro, Francesco

    2017-01-01

    Chordomas are rare malignant tumors of notochordal origin and are rare locally aggressive ones with a metastatic potential. The skin rarely is seen as metastatic site. We describe a case of an adult woman with cutaneous metastasis of a primary sacral chordoma excised ten years before, which appeared as a painless cutaneous mass located in the dorsal region. Once removed, the surgical specimen was formalin fixed and in paraffin embedded. Sections were stained with haematoxylin-eosin, and histochemical and immunohistochemical investigations were performed. Histologically, the neoplasia was characterized by cords or single tumor cells with an abundant myxoid stroma, conspicuous pale vacuolated cytoplasm (the classic “physaliphorous cells”), and mild nuclear atypia. Mitotic activity was scanty. At immunohistochemistry, the tumor cells were diffusely positive for S-100 protein, pan-keratins, EMA, and vimentin. A diagnosis of cutaneous metastasis of chordoma was performed. This case illustrates a diagnostic challenge because of the unusual presentation of an already rare tumor. PMID:28409046

  15. Anti-Metastasis Effect of Fucoidan from Undaria pinnatifida Sporophylls in Mouse Hepatocarcinoma Hca-F Cells

    PubMed Central

    Wang, Peisheng; Liu, Zhichao; Liu, Xianli; Teng, Hongming; Zhang, Cuili; Hou, Lin; Zou, Xiangyang

    2014-01-01

    Metastasis is one of the major causes of cancer-related death. It is a complex biological process involving multiple genes, steps, and phases. It is also closely connected to many biological activities of cancer cells, such as growth, invasion, adhesion, hematogenous metastasis, and lymphatic metastasis. Fucoidan derived from Undaria pinnatifida sporophylls (Ups-fucoidan) is a sulfated polysaccharide with more biological activities than other fucoidans. However, there is no information on the effects of Ups-fucoidan on tumor invasion and metastasis. We used the mouse hepatocarcinoma Hca-F cell line, which has high invasive and lymphatic metastasis potential in vitro and in vivo, to examine the effect of Ups-fucoidan on cancer cell invasion and metastasis. Ups-fucoidan exerted a concentration- and time-dependent inhibitory effect on tumor metastasis in vivo and inhibited Hca-F cell growth, migration, invasion, and adhesion capabilities in vitro. Ups-fucoidan inhibited growth and metastasis by downregulating vascular endothelial growth factor (VEGF) C/VEGF receptor 3, hepatocyte growth factor/c-MET, cyclin D1, cyclin-dependent kinase 4, phosphorylated (p) phosphoinositide 3-kinase, p-Akt, p-extracellular signal regulated kinase (ERK) 1/2, and nuclear transcription factor-κB (NF-κB), and suppressed adhesion and invasion by downregulating L-Selectin, and upregulating protein levels of tissue inhibitor of metalloproteinases (TIMPs). The results suggest that Ups-fucoidan suppresses Hca-F cell growth, adhesion, invasion, and metastasis capabilities and that these functions are mediated through the mechanism involving inactivation of the NF-κB pathway mediated by PI3K/Akt and ERK signaling pathways. PMID:25162296

  16. Anti-metastasis effect of fucoidan from Undaria pinnatifida sporophylls in mouse hepatocarcinoma Hca-F cells.

    PubMed

    Wang, Peisheng; Liu, Zhichao; Liu, Xianli; Teng, Hongming; Zhang, Cuili; Hou, Lin; Zou, Xiangyang

    2014-01-01

    Metastasis is one of the major causes of cancer-related death. It is a complex biological process involving multiple genes, steps, and phases. It is also closely connected to many biological activities of cancer cells, such as growth, invasion, adhesion, hematogenous metastasis, and lymphatic metastasis. Fucoidan derived from Undaria pinnatifida sporophylls (Ups-fucoidan) is a sulfated polysaccharide with more biological activities than other fucoidans. However, there is no information on the effects of Ups-fucoidan on tumor invasion and metastasis. We used the mouse hepatocarcinoma Hca-F cell line, which has high invasive and lymphatic metastasis potential in vitro and in vivo, to examine the effect of Ups-fucoidan on cancer cell invasion and metastasis. Ups-fucoidan exerted a concentration- and time-dependent inhibitory effect on tumor metastasis in vivo and inhibited Hca-F cell growth, migration, invasion, and adhesion capabilities in vitro. Ups-fucoidan inhibited growth and metastasis by downregulating vascular endothelial growth factor (VEGF) C/VEGF receptor 3, hepatocyte growth factor/c-MET, cyclin D1, cyclin-dependent kinase 4, phosphorylated (p) phosphoinositide 3-kinase, p-Akt, p-extracellular signal regulated kinase (ERK) 1/2, and nuclear transcription factor-κB (NF-κB), and suppressed adhesion and invasion by downregulating L-Selectin, and upregulating protein levels of tissue inhibitor of metalloproteinases (TIMPs). The results suggest that Ups-fucoidan suppresses Hca-F cell growth, adhesion, invasion, and metastasis capabilities and that these functions are mediated through the mechanism involving inactivation of the NF-κB pathway mediated by PI3K/Akt and ERK signaling pathways.

  17. Experimental Models to Study Lymphatic and Blood Vascular Metastasis

    PubMed Central

    Chen, Lu; Wu, Lily

    2011-01-01

    As a model system for the understanding of human cancer, the mouse has proved immensely valuable. Indeed, studies of mouse models have helped to define the nature of cancer as a genetic disease and demonstrated the causal role of genetic events found in tumors. As an experimental platform, they have provided critical insight into the process of tumor metastasis in the lymphovascular system. Once viewed with skepticism, mouse models are now an integral arm of basic and clinical cancer research. The use of a genetically tractable organism that shares organ systems and an immense degree of genetic similarity to humans provides a means to examine multiple features of human disease. Mouse models enable development and testing of new approaches to disease prevention and treatment, identification of early diagnostic markers and novel therapeutic targets, and an understanding of the in vivo biology and genetics of tumor initiation, promotion, progression, and metastasis. This review summarizes recent mouse models for lymphangiogenesis and the process of lymphovascular metastasis, focusing on the use of the cornea as an experimental platform for lymphangiogenesis in inflammation and immunity, and on the use of molecular and viral vector mediated imaging and to identify and monitor lymph node metastases of prostate cancer. PMID:21480239

  18. Intramedullary spinal metastasis of a carcinoid tumor.

    PubMed

    Kumar, Jay I; Yanamadala, Vijay; Shin, John H

    2015-12-01

    We report an intramedullary spinal cord metastasis from a bronchial carcinoid, and discuss its mechanisms and management. Intramedullary spinal cord metastases from any cancer are rare, and bronchial carcinoids account for only a small fraction of lung cancers. To our knowledge, an intramedullary spinal cord metastasis from a bronchial carcinoid has been described only once previously.

  19. Heparanase Mechanisms in Melanoma Brain Metastasis

    DTIC Science & Technology

    2014-08-01

    Melanoma Brain Metastasis PRINCIPAL INVESTIGATOR: Dr. Dario Marchetti RECIPIENT: Baylor College of Medicine REPORT DATE...Annual 3. DATES COVERED 1 Aug 2013-31 Jul 2014 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Heparanase Mechanisms in Melanoma Brain...brain. This emphasizes the potential for therapeutically targeting this enzyme in brain metastasis in general, brain-metastatic melanoma (BMM) in

  20. Phyllodes tumor of the breast: role of CD10 in predicting metastasis.

    PubMed

    Al-Masri, Mahmoud; Darwazeh, Ghaleb; Sawalhi, Samer; Mughrabi, Ayman; Sughayer, Maher; Al-Shatti, Marwa

    2012-04-01

    Phyllodes tumors are classified as benign, borderline, and malignant according to a group of histological features. The expression of many biological markers has been explored to discriminate between different grades of phyllodes tumor and to predict their behavior. The immunohistochemical expression of CD10 has been shown to discriminate between benign and other grades of phyllodes tumor but has not been evaluated as a predictor of metastasis. The purpose of this study was to evaluate the usefulness of immunohistochemical staining of stromal CD10 in predicting the likelihood of metastasis in phyllodes tumors. The expression of CD10 was studied in 43 phyllodes tumors (16 benign, 10 borderline, and 17 malignant) using immunohistochemistry to evaluate whether differences in expression correlated with the presence of, and or, development of distant metastasis. Metastasis occurred in six malignant phyllodes tumors. The expression of CD10 significantly (P<0.05) correlated with the occurrence of distant metastasis. The expression of CD10 can be used to predict the occurrence of distant metastasis in phyllodes tumors of the breast.

  1. Galectin-3 in angiogenesis and metastasis

    PubMed Central

    Funasaka, Tatsuyoshi; Raz, Avraham; Nangia-Makker, Pratima

    2014-01-01

    Galectin-3 is a member of the family of β-galactoside-binding lectins characterized by evolutionarily conserved sequences defined by structural similarities in their carbohydrate-recognition domains. Galectin-3 is a unique, chimeric protein consisting of three distinct structural motifs: (i) a short NH2 terminal domain containing a serine phosphorylation site; (ii) a repetitive proline-rich collagen-α-like sequence cleavable by matrix metalloproteases; and (iii) a globular COOH-terminal domain containing a carbohydrate-binding motif and an NWGR anti-death motif. It is ubiquitously expressed and has diverse biological functions depending on its subcellular localization. Galectin-3 is mainly found in the cytoplasm, also seen in the nucleus and can be secreted by non-classical, secretory pathways. In general, secreted galectin-3 mediates cell migration, cell adhesion and cell–cell interactions through the binding with high affinity to galactose-containing glycoproteins on the cell surface. Cytoplasmic galectin-3 exhibits anti-apoptotic activity and regulates several signal transduction pathways, whereas nuclear galectin-3 has been associated with pre-mRNA splicing and gene expression. Its unique chimeric structure enables it to interact with a plethora of ligands and modulate diverse functions such as cell growth, adhesion, migration, invasion, angiogenesis, immune function, apoptosis and endocytosis emphasizing its significance in the process of tumor progression. In this review, we have focused on the role of galectin-3 in tumor metastasis with special emphasis on angiogenesis. PMID:25138305

  2. Roles of the cyclooxygenase 2 matrix metalloproteinase 1 pathway in brain metastasis of breast cancer.

    PubMed

    Wu, Kerui; Fukuda, Koji; Xing, Fei; Zhang, Yingyu; Sharma, Sambad; Liu, Yin; Chan, Michael D; Zhou, Xiaobo; Qasem, Shadi A; Pochampally, Radhika; Mo, Yin-Yuan; Watabe, Kounosuke

    2015-04-10

    Brain is one of the major sites of metastasis in breast cancer; however, the pathological mechanism of brain metastasis is poorly understood. One of the critical rate-limiting steps of brain metastasis is the breaching of blood-brain barrier, which acts as a selective interface between the circulation and the central nervous system, and this process is considered to involve tumor-secreted proteinases. We analyzed clinical significance of 21 matrix metalloproteinases on brain metastasis-free survival of breast cancer followed by verification in brain metastatic cell lines and found that only matrix metalloproteinase 1 (MMP1) is significantly correlated with brain metastasis. We have shown that MMP1 is highly expressed in brain metastatic cells and is capable of degrading Claudin and Occludin but not Zo-1, which are key components of blood-brain barrier. Knockdown of MMP1 in brain metastatic cells significantly suppressed their ability of brain metastasis in vivo, whereas ectopic expression of MMP1 significantly increased the brain metastatic ability of the cells that are not brain metastatic. We also found that COX2 was highly up-regulated in brain metastatic cells and that COX2-induced prostaglandins were directly able to promote the expression of MMP1 followed by augmenting brain metastasis. Furthermore, we found that COX2 and prostaglandin were able to activate astrocytes to release chemokine (C-C motif) ligand 7 (CCL7), which in turn promoted self-renewal of tumor-initiating cells in the brain and that knockdown of COX2 significantly reduced the brain metastatic ability of tumor cells. Our results suggest the COX2-MMP1/CCL7 axis as a novel therapeutic target for brain metastasis. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Complexity and Dynamic Heterogeneity of the Process of Cancer Metastasis

    NASA Astrophysics Data System (ADS)

    Chambers, Ann

    2010-03-01

    Cancer metastasis -- the spread of cancer from a primary tumor to distant parts of the body -- is responsible for most cancer deaths. If cancer is detected early, before it has spread, it can often be treated with local therapies like surgery and radiation. If cancer is detected after it has already spread, it is much harder to treat successfully. Cancer cells may be distributed to many organs, may be present as tiny micrometastases that are hard to detect, and cancer cells can be in a dormant state that may be resistant to treatment that is directed against actively dividing cells. A better understanding of the process of metastasis thus is needed in order to improve survival from cancer. Cancer is not a static disease, but one that can undergo stepwise evolution and progression from early, treatable cancer to aggressive cancer that is harder to treat. Furthermore, cancers are made up of many cells, and there is considerable heterogeneity among the cells in a tumor. Thus, cancer is ``plastic,'' with heterogeneity among cancer cells and changes over time. Understanding this ``dynamic heterogeneity'' has proven to be difficult. Input from physical sciences disciplines may help to shed light on this complex aspect of cancer biology. Here the process of cancer metastasis will be discussed, and experimental models for imaging the process described. The concept of ``dynamic heterogeneity'' of the metastatic process will be discussed, and some of the questions that need to be addressed for better understanding of metastasis will be outlined. An evolving dialogue between cancer biologists and physical scientists may lead to new ways of studying and understanding this lethal aspect of cancer.

  4. FLT1 signaling in metastasis-associated macrophages activates an inflammatory signature that promotes breast cancer metastasis

    PubMed Central

    Zhang, Hui; Li, Jiufeng; He, Tianfang; Yeo, Eun-Jin; Soong, Daniel Y.H.; Carragher, Neil O.; Munro, Alison; Chang, Alvin; Bresnick, Anne R.; Lang, Richard A.

    2015-01-01

    Although the link between inflammation and cancer initiation is well established, its role in metastatic diseases, the primary cause of cancer deaths, has been poorly explored. Our previous studies identified a population of metastasis-associated macrophages (MAMs) recruited to the lung that promote tumor cell seeding and growth. Here we show that FMS-like tyrosine kinase 1 (Flt1, also known as VEGFR1) labels a subset of macrophages in human breast cancers that are significantly enriched in metastatic sites. In mouse models of breast cancer pulmonary metastasis, MAMs uniquely express FLT1. Using several genetic models, we show that macrophage FLT1 signaling is critical for metastasis. FLT1 inhibition does not affect MAM recruitment to metastatic lesions but regulates a set of inflammatory response genes, including colony-stimulating factor 1 (CSF1), a central regulator of macrophage biology. Using a gain-of-function approach, we show that CSF1-mediated autocrine signaling in MAMs is downstream of FLT1 and can restore the tumor-promoting activity of FLT1-inhibited MAMs. Thus, CSF1 is epistatic to FLT1, establishing a link between FLT1 and inflammatory responses within breast tumor metastases. Importantly, FLT1 inhibition reduces tumor metastatic efficiency even after initial seeding, suggesting that these pathways represent therapeutic targets in metastatic disease. PMID:26261265

  5. Factors associated with HIV testing among male injecting drug users: findings from a cross-sectional behavioural and biological survey in Manipur and Nagaland, India.

    PubMed

    Ganju, Deepika; Ramesh, Sowmya; Saggurti, Niranjan

    2016-06-21

    Although targeted interventions in India require all high-risk groups, including injecting drug users (IDUs), to test for HIV every 6 months, testing uptake among IDUs remains far from universal. Our study estimates the proportion of IDUs who have taken an HIV test and identifies the factors associated with HIV testing uptake in Nagaland and Manipur, two high HIV prevalence states in India where the epidemic is driven by injecting drug use. Data are drawn from the cross-sectional Integrated Behavioural and Biological Assessment (2009) of 1650 male IDUs from two districts each of Manipur and Nagaland. Participants were recruited using respondent-driven sampling (RDS). Descriptive data were analysed using RDSAT 7.1. Multivariate logistic regression analysis was undertaken using STATA 11 to examine the association between HIV testing and socio-demographic, behavioural and programme exposure variables. One third of IDUs reported prior HIV testing, of whom 8 % had tested HIV-positive. Among those without prior testing, 6.2 % tested HIV-positive in the current survey. IDUs aged 25-34 years (adjusted odds ratio (OR) = 1.41; 95 % confidence interval (CI) = 1.03-1.93), married (Adjusted OR = 1.56; 95 % CI = 1.15-2.12), had a paid sexual partner (Adjusted OR = 1.64; 95 % CI = 1.24-2.18), injected drugs for more than 36 months (Adjusted OR = 1.38; 95 % CI = 1.06-1.81), injected frequently (Adjusted OR = 1.49; 95 % CI = 1.12-1.98) and had high-risk perception (Adjusted OR = 1.68; 95 % CI = 1.32-2.14) were more likely than others to test for HIV. Compared to those with no programme exposure, IDUs who received counselling, or counselling and needle/syringe services, were more likely to test for HIV. HIV testing uptake among IDUs is low in Manipur and Nagaland, and a critical group of HIV-positive IDUs who have never tested for HIV are being missed by current programmes. This study identifies key sub

  6. Awareness of physical activity in healthy middle-aged adults: a cross-sectional study of associations with sociodemographic, biological, behavioural, and psychological factors.

    PubMed

    Godino, Job G; Watkinson, Clare; Corder, Kirsten; Sutton, Stephen; Griffin, Simon J; van Sluijs, Esther M F

    2014-05-02

    Interventions to promote physical activity have had limited success. One reason may be that inactive adults are unaware that their level of physical activity is inadequate and do not perceive a need to change their behaviour. We aimed to assess awareness of physical activity, defined as the agreement between self-rated and objective physical activity, and to investigate associations with sociodemographic, biological, behavioural, and psychological factors. We conducted an exploratory, cross-sectional analysis of awareness of physical activity using baseline data collected from 453 participants of the Feedback, Awareness and Behaviour study (Cambridgeshire, UK). Self-rated physical activity was measured dichotomously by asking participants if they believed they were achieving the recommended level of physical activity. Responses were compared to objective physical activity, measured using a combined accelerometer and heart rate monitor (Actiheart®). Four awareness groups were created: overestimators, realistic inactives, underestimators, and realistic actives. Logistic regression was used to assess associations between awareness group and potential correlates. The mean (standard deviation) age of participants was 47.0 (6.9) years, 44.4% were male, and 65.1% were overweight (body mass index ≥ 25). Of the 258 (57.0%) who were objectively classified as inactive, 130 (50.4%) misperceived their physical activity by incorrectly stating that they were meeting the guidelines (overestimators). In a multivariable logistic regression model adjusted for age and sex, those with a lower body mass index (Odds Ratio (OR) = 0.95, 95% Confidence Interval (CI) = 0.90 to 1.00), higher physical activity energy expenditure (OR = 1.03, 95% CI = 1.00 to 1.06) and self-reported physical activity (OR = 1.13, 95% CI = 1.07 to 1.19), and lower intention to increase physical activity (OR = 0.69, 95% CI = 0.48 to 0.99) and response efficacy (OR = 0

  7. Awareness of physical activity in healthy middle-aged adults: a cross-sectional study of associations with sociodemographic, biological, behavioural, and psychological factors

    PubMed Central

    2014-01-01

    Background Interventions to promote physical activity have had limited success. One reason may be that inactive adults are unaware that their level of physical activity is inadequate and do not perceive a need to change their behaviour. We aimed to assess awareness of physical activity, defined as the agreement between self-rated and objective physical activity, and to investigate associations with sociodemographic, biological, behavioural, and psychological factors. Methods We conducted an exploratory, cross-sectional analysis of awareness of physical activity using baseline data collected from 453 participants of the Feedback, Awareness and Behaviour study (Cambridgeshire, UK). Self-rated physical activity was measured dichotomously by asking participants if they believed they were achieving the recommended level of physical activity. Responses were compared to objective physical activity, measured using a combined accelerometer and heart rate monitor (Actiheart®). Four awareness groups were created: overestimators, realistic inactives, underestimators, and realistic actives. Logistic regression was used to assess associations between awareness group and potential correlates. Results The mean (standard deviation) age of participants was 47.0 (6.9) years, 44.4% were male, and 65.1% were overweight (body mass index ≥ 25). Of the 258 (57.0%) who were objectively classified as inactive, 130 (50.4%) misperceived their physical activity by incorrectly stating that they were meeting the guidelines (overestimators). In a multivariable logistic regression model adjusted for age and sex, those with a lower body mass index (Odds Ratio (OR) = 0.95, 95% Confidence Interval (CI) = 0.90 to 1.00), higher physical activity energy expenditure (OR = 1.03, 95% CI = 1.00 to 1.06) and self-reported physical activity (OR = 1.13, 95% CI = 1.07 to 1.19), and lower intention to increase physical activity (OR = 0.69, 95% CI = 0.48 to 0.99) and

  8. Crosstalk between TGF-β signaling and miRNAs in breast cancer metastasis.

    PubMed

    Chen, Wei; Zhou, Siying; Mao, Ling; Zhang, Heda; Sun, Dawei; Zhang, Junying; Li, JIan; Tang, Jin-Hai

    2016-08-01

    Transforming growth factor-β (TGF-β) signaling pathway is a key regulator of various cancer biologies, including cancer cell migration, invasion, angiogenesis, proliferation, as well as apoptosis, and it is one of indispensable signaling pathways during cancer metastasis. TGF-β signaling pathway can regulate and be regulated by a series of molecular and signaling pathways where microRNAs (miRNAs) seem to play important roles. miRNAs are small non-coding RNAs that can regulate expressions of their target genes. Emerging evidence suggest that miRNAs participate in various biological and pathologic processes such as cancer cells apoptosis, proliferation, invasion, migration, and metastasis by influencing multiple signaling pathways. In this article, we focus on the interaction between miRNAs and TGF-β in breast cancer (BC) metastasis through modulating invasion-metastasis-related factors, including epithelial-to-mesenchymal transition (EMT), cancer stem cells (CSCs), matrix metalloproteinase (MMP), tissue inhibitors of MMPs (TIMPs), cell adhesion molecules (CAMs), and tumor microenvironment (TME). Through a clear understanding of the complicated links between TGF-β pathway and miRNAs, it may provide a novel and safer therapeutic target to prevent BC metastasis.

  9. Role of Magnetic Resonance Imaging in Differentiating Spondylitis from Vertebral Metastasis

    PubMed Central

    Widhiasi, Dhanti Erma

    2015-01-01

    Study Design Observational analytic design with a cross-sectional approach. Purpose To analyze the suitability of magnetic resonance imaging (MRI) in distinguishing radiology images with a corresponding delineation of spondylitis and vertebral metastasis confirmed by histology results. Overview of Literature MRI is an accurate modality for assessing vertebrae and their disorders. Infections and metastasis are most commonly found in the vertebrae. It is difficult to differentiate between these two disorders both clinically and radiographically, particularly in atypical cases. Methods McNemar statistical test was used to analyze the data. Samples were chosen using the consecutive method. There were 35 samples (14 males and 21 females), consisting of 22 samples of spondylitis and 13 samples of metastasis confirmed on histology examination. Results Nineteen (86%) out of the 22 samples of histological spondylitis were diagnosed as having spondylitis on MRI, whereas all 13 samples of metastasis were 100% accurately diagnosed on MRI. Conclusions There was no statistically significant difference between diagnostic radiology using MRI and histological diagnosis with a p=0.250 (p>0.05). In this respect, MRI was more precise in diagnosing metastasis. Typical MRI description of spondylitis was the involvement of anterior vertebrae and components of intervertebral discs, stiffening of discs, paravertebral abscess, and involvement of the vertebral segment sequence. Typical MRI delineation of metastasis was involvement of the anterior posterior vertebral component, paravertebral mass, and skip lesions. PMID:26435798

  10. Treatment of brain metastasis from lung cancer.

    PubMed

    Kawabe, Takuya; Phi, Ji Hoon; Yamamoto, Masaaki; Kim, Dong Gyu; Barfod, Bierta E; Urakawa, Yoichi

    2012-01-01

    Brain metastasis from lung cancer occupies a significant portion of all brain metastases. About 15-20% of patients with non-small cell lung cancer (NSCLC) develop brain metastasis during the course of the disease. The prognosis of brain metastasis is poor with median survival of less than 1 year. Whole-brain radiation therapy (WBRT) is widely used for the treatment of brain metastasis. WBRT can also be used as adjuvant treatment along with surgery and stereotactic radiosurgery (SRS).Surgery provides a rapid relief of mass effects and may be the best choice for a large single metastasis. SRS confers local control rates comparable to those for surgery with minimal toxicities and versatility that makes it applicable to multiple lesions, deep-seated lesions, and to patients with poor medical conditions. Recursive partitioning analysis (RPA) classes are widely used for prognostic stratification. However, the validity of RPA classes, especially for NSCLC, has been questioned and other scoring systems are being developed. Synchronous presentation of primary NSCLC and brain metastases is a special situation in which surgery for the lung lesion and surgery or SRS for brain lesions are recommended if the thoracic disease is in early stages. Small cell lung cancer (SCLC) has a higher likelihood for brain metastasis than NSCLC and prophylactic cranial irradiation and subsequent WBRT are usually recommended. Recently, SRS for brain metastasis from SCLC has been tried, but requires further verification.

  11. Mechanisms of Ovarian Cancer Metastasis: Biochemical Pathways

    PubMed Central

    Nakayama, Kentaro; Nakayama, Naomi; Katagiri, Hiroshi; Miyazaki, Kohji

    2012-01-01

    Ovarian cancer is the most lethal gynecologic malignancy. Despite advances in chemotherapy, the five-year survival rate of advanced ovarian cancer patients with peritoneal metastasis remains around 30%. The most significant prognostic factor is stage, and most patients present at an advanced stage with peritoneal dissemination. There is often no clearly identifiable precursor lesion; therefore, the events leading to metastatic disease are poorly understood. This article reviews metastatic suppressor genes, the epithelial-mesenchymal transition (EMT), and the tumor microenvironment as they relate to ovarian cancer metastasis. Additionally, novel chemotherapeutic agents targeting the metastasis-related biochemical pathways are discussed. PMID:23109879

  12. Metaplastic Breast Carcinoma With Multiple Muscle Metastasis

    PubMed Central

    Liu, Chung Hsiung; Chang, Chen; Sy, Edgar; Lai, Hung-Wen; Kuo, Yao-Lung

    2015-01-01

    Abstract Metaplastic breast carcinoma (MBC) is a rare type of breast carcinoma. Recurrence presenting as chest wall invasion is common but rarely as metastasis to distal skeletal muscle in which most patients present with a painful mass. Herein, we report a rare case of 65-year-old woman, with MBC and recurrence presenting as distal multiple muscle metastasis. The patient received surgical excision for symptomatic relief. Unfortunately, she died 12 months postoperatively due to disease progression with multiple lung metastasis. In addition to radiotherapy and chemotherapy, surgical excision is an alternative option in selected patients such as those with painful, isolated, and easily approachable mass. PMID:25929895

  13. Breast cancer metastasis to the pituitary gland.

    PubMed

    Magalhães, Julia Fragoso; Bacchin, Renata Prota; Costa, Priscila Scatena; Alves, Gisele Malavazi; Fraige Filho, Fadlo; Stella, Lenira Cristina

    2014-11-01

    Metastatic tumors to the pituitary gland are an unusual complication typically seen in elderly patients with diffuse malignant disease. Breast and lung are the commonest sites of the primary tumor. Prognosis of patients with breast cancer metastasis is poor and depends on the primary neoplastic extension. We report a 54 year-old woman with breast cancer metastasis to the pituitary stalk first diagnosed because of visual disturbance with no other symptoms. Pituitary gland stalk metastasis is a very uncommon find and this case report includes a literature review.

  14. Preparation of biological material for X-ray microanalysis of diffusible elements. I. Rapid freezing of biological tissue in nitrogen slush and preparation of ultrathin frozen sections in the absence of trough liquid.

    PubMed

    Sevéus, L

    1978-04-01

    Any method used for the analysis of diffusible elements within a cell should involve conditions which eliminate the redistribution of those elements. Redistribution of diffusible substances is caused by (a) ice damage during freezing, (b) thawing during sectioning, and (c) thawing during handling of sections. To eliminate this sections were cut (a) in the 5-8 micrometer ice crystal free surface layer obtained by freezing in melting nitrogen, (b) at a specimen temperature of 133 K and a knife temperature of 173 K to 153 K, and the temperature of the chamber was kept low by evaporating nitrogen from an extra reservoir inside the chamber, by regulating the output of a foil heater. A grid carrier was designed to simplify the section collection and the sections were affixed on to the grid in a press assembly. The sections were hard and translucent, and showed faint interference colours.

  15. [Cervical lymph node metastasis in clinical N0 papillary thyroid carcinoma].

    PubMed

    Yan, Dan-gui; Zhang, Bin; An, Chang-ming; Zhang, Zong-min; Li, Zheng-jiang; Xu, Zhen-gang; Tang, Ping-zhang

    2011-11-01

    To study the patterns of cervical lymph nodes metastasis and the surgical managements of cervical lymph nodes in clinical N0 (cN0) papillary thyroid carcinoma. Fifty-one consecutive patients with papillary carcinomas without clinical evidence of cervical lymph node involvement were included in the study between August 2007 and September 2010, in which 53 sides underwent neck lymph node dissection. Preoperative lymphoscintigraphy intra-operative hand-held gamma probe detecting and blue dye technique were used to detect the sentinel lymph node (SLN). SLNs were sent to frozen-section and the results were compared with specimen of routine selective neck dissection. All the pathologic specimens were reviewed by pathologists, counting the numbers of pathologic positive nodes and mapping the localization of positive nodes in level II, III, IV, V and VI respectively. The following criteria were used to study the predictive value of lateral neck compartment lymph node metastasis: age, multifocality of the tumor, extracapsular spread (ECS), tumor size, and the number of central compartment metastasis nodes. Univariate analysis with the χ2 test was used to analyze the statistical correlation between lateral neck compartment lymph node metastasis and the other clinical factors. Multiple logistic regression analysis was used to identify the multivariate correlates of lateral neck compartment metastasis. The occult lymph node metastasis and lateral neck metastasis rates were 77.4% and 58.5% respectively, central compartment metastasis ≥3 nodes was the only independent predictive factor for the metastasis in lateral neck. Twelve sides were pN0 and other 41 sides were pN+ in all 53 side specimens. Of 41 sides with pN+, 17 sides (41.5%) involved single site and 24 sides (58.5%) involved multi-sites. The distribution of metastasis lymph nodes:level VI 62.3%, level III 52.8%, level IV 30.2%, level II 18.9%, and level V 0%. Cervical occult lymph node metastasis in cN0 papillary

  16. [Metastasis tumors of the central nervous system: molecular biology].

    PubMed

    Bello, M Josefa; González-Gómez, P; Rey, J A

    2004-12-01

    Metastases in the nervous system represent an important and growing problem in the clinical practice, being the cause of a great mortality in the developed countries. This article reviews the few data available on the molecular mechanisms involved in the pathogenesis of these tumours, leading to oncogene activation, inactivation of tumour suppressor genes, not only by the classical mechanisms, but also by the tumour cell epigenetic balance alteration. We conclude that all this knowledge will lead in the future to a better diagnosis, treatment and clinic evolution of these patients.

  17. Diagnosis of bone metastasis: recent comparative studies of imaging modalities.

    PubMed

    Talbot, J N; Paycha, F; Balogova, S

    2011-08-01

    Various imaging modalities are currently available to diagnose bone metastasis. The two main anatomical modalities are computed tomography (CT) and magnetic resonance imaging (MRI), with many variants proposed for the MRI procedure, including diffusion-weighted imaging. The two main functional modalities are scintigraphy and PET, also with many variants in the radiopharmaceutical, from the "all purpose" 99mTc labelled bisphosphonates to very selective radiopharmaceuticals for rare neoplasia. The diagnostic strategy will become more and more individually tailored according to the patient's clinical and biological data (primary cancer type, phase of the evolution, markers of aggressiveness, serum levels of biological tracers of bone metabolism, circulating or disseminating tumour cells …). If imaging is indicated, the diagnostic strategy will also depend on the availability and the diagnostic performance of the imaging modalities. Assessment of diagnostic performance requires comparative studies, performed with an adequate methodology. The main methodological weaknesses encountered in studies intending to compare imaging modalities for diagnosing bone metastasis are summarised. Comparative studies have been reviewed, which address the initial diagnosis of skeletal metastases in solid tumours except primary bone cancers. The results of more than 140 such comparative studies are then summarised and briefly commented, according to the type of the primary cancer, and according to the compared imaging modalities.

  18. Raman spectroscopy for cancer detection and characterization in metastasis models

    NASA Astrophysics Data System (ADS)

    Koga, Shigehiro; Oshima, Yusuke; Sato, Mitsunori; Ishimaru, Kei; Yoshida, Motohira; Yamamoto, Yuji; Matsuno, Yusuke; Watanabe, Yuji

    2017-02-01

    Raman spectroscopy provides a wealth of diagnostic information to the surgeon with in situ cancer detection and label-free histopathology in clinical practice. Raman spectroscopy is a developing optical technique which can analyze biological tissues with light scattering. The difference in frequencies between the incident light and the scattering light are called Raman shifts, which correspond to the vibrational energy of the molecular bonds. Raman spectrum gives information about the molecular structure and composition in biological specimens. We had been previously reported that Raman spectroscopy could distinguish various histological types of human lung cancer cells from normal cells in vitro. However, to identify and detect cancer diagnostic biomarkers in vivo on Raman spectroscopy is still challenging, because malignancy can be characterized not only by the cancer cells but also by the environmental factors including immune cells, stroma cells, secretion vesicles and extracellular matrix. Here we investigate morphological and molecular dynamics in both cancer cells and their environment in xenograft models and spontaneous metastasis models using Raman spectroscopy combined with fluorescence microscopy and photoluminescence imaging. We are also constructing a custom-designed Raman spectral imaging system for both in vitro and in vivo assay of tumor tissues to reveal the metastasis process and to evaluate therapeutic effects of anti-cancer drugs and their drug delivery toward the clinical application of the technique.

  19. Cell and Signal Components of the Microenvironment of Bone Metastasis Are Affected by Hypoxia

    PubMed Central

    Bendinelli, Paola; Maroni, Paola; Matteucci, Emanuela; Desiderio, Maria Alfonsina

    2016-01-01

    Bone metastatic cells release bone microenvironment proteins, such as the matricellular protein SPARC (secreted protein acidic and rich in cysteine), and share a cell signaling typical of the bone metabolism controlled by Runx2. The megakaryocytes in the bone marrow engrafted by the metastases seem to be one of the principal microenvironment sources of the biological stimuli, implicated in the formation of an osteoblastic niche, and affecting metastasis phenotype and colonization. Educated platelets in the circulation might derive from megakaryocytes in bone metastasis. The evaluation of predictive markers in the circulating platelets might be useful for the stratification of patients for therapeutic purposes. The hypoxic environment in bone metastasis is one of the key regulators of the network of the biological soluble and structural components of the matrix. In bone metastatic cells under hypoxia, similar patterns of Runx2 and SPARC are observed, both showing downregulation. Conversely, hypoxia induces Endothelin 1, which upregulates SPARC, and these biological stimuli may be considered prognostic markers of bone metastasis in breast carcinoma patients. PMID:27187355

  20. Invasion and metastasis in pancreatic cancer.

    PubMed

    Keleg, Shereen; Büchler, Peter; Ludwig, Roman; Büchler, Markus W; Friess, Helmut

    2003-01-22

    Pancreatic cancer remains a challenging disease with an overall cumulative 5-year survival rate below 1%. The process of cancer initiation, progression and metastasis is still not understood well. Invasion and tumor metastasis are closely related and both occur within a tumour-host microecology, where stroma and tumour cells exchange enzymes and cytokines that modify the local extracellular matrix, stimulate cell migration, and promote cell proliferation and tumor cell survival. During the last decade considerable progress has been made in understanding genetic alterations of genes involved in local and systemic tumor growth. The most important changes occur in genes which regulate cell cycle progression, extracellular matrix homeostasis and cell migration. Furthermore, there is growing evidence that epigenetic factors including angiogenesis and lymphangiogenesis may participate in the formation of tumor metastasis. In this review we highlight the most important genetic alterations involved in tumor invasion and metastasis and further outline the role of tumor angiogenesis and lymphangiogenesis in systemic tumor dissemination.

  1. Ovarian carcinoma presenting as cutaneous nasal metastasis*

    PubMed Central

    António, Ana Marta; Alves, João Vitor; Goulão, João; Bártolo, Elvira

    2016-01-01

    Metastatic ovarian cancer uncommonly presents with skin metastasis. When present, skin metastases of ovarian cancer are usually localized in the vicinity of the primary tumor. We report a case of a 58-year-old woman with a rapid growing erythematous, well-defined nodule localized on the left nasal ala. A skin biopsy was performed and histopathological and immunohistochemical findings were compatible with a cutaneous metastasis of adenocarcinoma. A systematic investigation revealed a bilateral ovarian cystadenocarcinoma associated with visceral dissemination, likely associated with nose cutaneous metastasis. We report a very uncommon case because of the presentation of ovarian carcinoma as cutaneous metastasis. To our knowledge, this atypical localization on the nose has not been described yet in the literature. PMID:28300910

  2. Organotropic metastasis: role of tumor exosomes.

    PubMed

    Liu, Yang; Cao, Xuetao

    2016-02-01

    A recent paper in Nature shows that tumor exosomes expressing unique integrins can determine organotropic metastasis by preparing pre-metastatic niche through their integrins-mediated fusion with and fertilization of organ-specific resident cells.

  3. Three-dimensional context regulation of metastasis.

    PubMed

    Erler, Janine T; Weaver, Valerie M

    2009-01-01

    Tumor progression ensues within a three-dimensional microenvironment that consists of cellular and non-cellular components. The extracellular matrix (ECM) and hypoxia are two non-cellular components that potently influence metastasis. ECM remodeling and collagen cross-linking stiffen the tissue stroma to promote transformation, tumor growth, motility and invasion, enhance cancer cell survival, enable metastatic dissemination, and facilitate the establishment of tumor cells at distant sites. Matrix degradation can additionally promote malignant progression and metastasis. Tumor hypoxia is functionally linked to altered stromal-epithelial interactions. Hypoxia additionally induces the expression of pro-migratory, survival and invasion genes, and up-regulates expression of ECM components and modifying enzymes, to enhance tumor progression and metastasis. Synergistic interactions between matrix remodeling and tumor hypoxia influence common mechanisms that maximize tumor progression and cooperate to drive metastasis. Thus, clarifying the molecular pathways by which ECM remodeling and tumor hypoxia intersect to promote tumor progression should identify novel therapeutic targets.

  4. Psoralen inhibits bone metastasis of breast cancer in mice.

    PubMed

    Wu, Chunyu; Sun, Zhenping; Ye, Yiyi; Han, Xianghui; Song, Xiaoyun; Liu, Sheng

    2013-12-01

    Breast cancer is the most common female malignancy and it frequently metastasizes to bone. Metastatic breast cancer continues to be the primary cause of death for women in East and Southeast Asia. Psoralen is a furocoumarin that can be isolated from the seeds of Psoralea corylifolia L. Psoralen exhibits a wide range of biological properties and has been demonstrated as an antioxidant, antidepressant, anticancer, antibacterial, and antiviral agent. Additionally, it is involved in the formation and regulation of bone. This study investigated whether psoralen can inhibit metastasis of breast cancer to bone in vivo. Histological, molecular biological, and imaging analyses revealed that psoralen inhibits bone metastases in mice. Psoralen may function to inhibit breast cancer cell growth in the bone microenvironment and regulate the function of osteoblasts and osteoclasts in tumor-bearing mice. The results of this study suggest that psoralen is a bone-modifying agent and a potential therapeutic to treat patients with bone metastases. © 2013.

  5. Breast cancer and metastasis: on the way toward individualized therapy.

    PubMed

    Trapé, Adriana Priscila; Gonzalez-Angulo, Ana Maria

    2012-01-01

    Breast cancer (BC) remains the most common cancer type diagnosed in women. Although targeted therapies have improved patient survival for advanced BC, these tumors frequently relapse due to drug resistance mechanisms. A systems biology approach integrates DNA, RNA and protein alterations generated from multidimensional platforms to better understand the mechanisms that regulate the metastatic process. Downstream functional analyses in pre-clinical studies might integrate the role of these aberrations into the cell, leading to discovery of new therapeutic targets. In the present report, we review relevant findings associated with genomic, transcriptomic and proteomic analyses and the contribution of the systems biology concept to the interpretation of these data in the metastatic context. Also, we highlight the importance of re-designing clinical trials towards metastasis prevention for improvement of personalized care.

  6. Patterns and clinical significance of cervical lymph node metastasis in papillary thyroid cancer patients with Delphian lymph node metastasis.

    PubMed

    Zheng, Guibin; Zhang, Hua; Hao, Shaolong; Liu, Chengxin; Xu, Jie; Ning, Jinyao; Wu, Guochang; Jiang, Lixin; Li, Guojun; Zheng, Haitao; Song, Xicheng

    2017-08-22

    Although the roles of Delphian lymph node (DLN) metastasis in papillary thyroid cancer (PTC) have been previously reported, there are still limited data on correlations of clinicopathologic factors with DLN metastasis and unique patterns of cervical node subsite metastasis in PTC patients with DLN metastasis. We retrospectively reviewed medical records of 320 patients with a diagnosis of PTC who underwent primary surgery. Clinicopathologic features and DLN metastasis patterns were analyzed for predicting extensive cervical lymph node metastasis. Both univariate and multivariate Cox regression analyses were used to identify independent factors for cervical lymph node metastasis. DLN metastasis was significantly associated with multifocality, tumor size > 1 cm, extrathyroid extension, BRAF(V600E) mutation, central neck node metastasis (CNNM), and lateral neck nodes metastases. Patients with DLN metastasis had more lymph node metastases in the central compartment. CNNM number and tumor size > 1 cm were independent risk factors for DLN metastasis. DLN metastasis was highly predictive of lateral lymph node metastasis with moderate sensitivity and high specificity. DLN metastasis is associated with several poor prognostic factors, including extensive cervical lymph node metastasis, and can serve as a predictor of advanced PTC. The presence of DLN metastasis should prompt surgeons to perform an aggressive surgery approach.

  7. Native and Non-Native Writers' Use of First Person Pronouns in the Different Sections of Biology Research Articles in English

    ERIC Educational Resources Information Center

    Martinez, Iliana A.

    2005-01-01

    Various authors have shown the first person to play a key role in the construction of the writer's persona in research articles. This paper compares the use of first person in a corpus of biology articles produced by native English-speaking (NES) writers and a corpus of research article manuscripts produced by non-native English-speaking (NNES)…

  8. Heparanase Mechanisms in Melanoma Brain Metastasis

    DTIC Science & Technology

    2015-10-01

    recently reported the HPSE inhibition by microRNA 1258 which resulted in a suppression of brain metastasis in in xenograft models of breast cancer ...Goodman J.C., Marchetti, D. MicroRNA-1258 suppresses breast cancer brain metastasis by targeting heparanase. Cancer Research – Priority Report, 71(3...levels of exosomes, microvescicles that were found to be significantly implicated in the metastatic cancer events, notably to brain (6). Exosomes

  9. Metastasis Suppressors and the Tumor Microenvironment

    PubMed Central

    Cook, Leah M.; Hurst, Douglas R.; Welch, Danny R.

    2011-01-01

    The most lethal and debilitating attribute of cancer cells is their ability to metastasize. Throughout the process of metastasis, tumor cells interact with other tumor cells, host cells and a variety of molecules. Tumor cells are also faced with a number of insults, such as hemodynamic sheer pressure and immune selection. This brief review explores how metastasis suppressor proteins regulate interactions between tumor cells and the microenvironments in which tumor cells find themselves. PMID:21168504

  10. Cardiac metastasis of oral squamous cell carcinoma.

    PubMed

    Pattni, Neeraj; Rennie, Andrew; Hall, Timothy; Norman, Aidan

    2015-09-09

    We present a case of isolated cardiac metastasis of oral squamous cell carcinoma. An 89-year-old woman was due to undergo curative resection of a histologically proven squamous cell carcinoma of the retromolar region. On admission, it was noted that there were ECG changes, and following further investigations, the patient was diagnosed with a cardiac metastasis of her oral malignancy. The presentation, including the diagnostic difficulties, as well as the clinical features of this rare case, are discussed.

  11. Gastric metastasis by lung small cell carcinoma

    PubMed Central

    Casella, Giovanni; Bella, Camillo Di; Cambareri, Antonino Roberto; Buda, Carmelo Antonio; Corti, Gianluigi; Magri, Filippo; Crippa, Stefano; Baldini, Vittorio

    2006-01-01

    Metastatic tumors of the gastrointestinal tract are rare. We describe a case of gastric metastasis due to primary lung cancer, revealed by an upper gastrointestinal endoscopy (UGIE). Haematogenous metastases to the stomach are a rare event. To our knowledge, only 55 cases have been described in the international literature. In these patients, the prognosis is very poor. We report herein a case of gastric metastasis by lung small cell carcinoma, with a review of the literature about this rare entity. PMID:16810769

  12. Symptomatic intracranial metastasis in penile carcinoma

    PubMed Central

    Moiyadi, Aliasgar V.; Tongaonkar, Hemant B.; Bakshi, Ganesh K.

    2010-01-01

    Distant metastases in penile cancers are rare, especially metachronous symptomatic intracranial metastasis. A middle-aged patient presented to us with an intracranial mass 2 years after being treated for penile cancer. Given the rarity of metastasis and the diagnostic dilemma along with the need for relief of neurological symptoms, it was excised and found to be a metastatic deposit. We discuss the case and review the relevant literature. PMID:21369397

  13. Lysyl oxidase mediates hypoxic control of metastasis.

    PubMed

    Erler, Janine T; Giaccia, Amato J

    2006-11-01

    Hypoxic cancer cells pose a great challenge to the oncologist because they are especially aggressive, metastatic, and resistant to therapy. Recently, we showed that elevation of the extracellular matrix protein lysyl oxidase (LOX) correlates with metastatic disease and is essential for hypoxia-induced metastasis. In an orthotopic rodent model of breast cancer, a small-molecule or antibody inhibitor of LOX abolished metastasis, offering preclinical validation of this enzyme as a therapeutic target.

  14. Factors predicting 'time to distant metastasis' in radically treated head and neck cancer.

    PubMed

    Krishnatry, R; Gupta, T; Murthy, V; Ghosh-Laskar, S; Budrukkar, A; Chaturvedi, P; Nair, S; Nair, D; Kumar, P; Joshi, A; Agarwal, J P

    2014-01-01

    Context: Various studies have shown the important risk factors for distant metastasis in head and neck cancer (HNC) which are present in most of the patients in developing countries. Identification of factors on the basis of time to distant metastasis (TDM) can help in future trials targeting smaller subgroups. Aims and Objectives: To identify the factors that predict TDM in radically treated HNC patients. Settings and Design: Retrospective audit. Materials and Methods: Retrospective audit of the prospectively maintained electronic database of a single HNC radiotherapy clinic from 1990 to 2010 was done to identify radically treated patients of HNC who developed distant metastasis. Univariate and multivariate analysis were done to identify baseline (demographic, clinical, pathological, and treatment) factors which could predict TDM, early time to metastasis (ETM; <12 months), intermediate time to metastasis (ITM; 12-24 months), and late time to metastasis (LTM; >2 years) using Kaplan Meier and Cox regression analysis, respectively. Results: One hundred patients with distant metastasis were identified with a median TDM of 7.4 months; 66 had ETM, 17 had ITM, and 17 had LTM. On multivariate analysis, the nodal stage 2-3 (N2/3) was the only baseline factor independently predicting TDM, ETM, and ITM, whereas none of the baseline factors predicted LTM. Conclusions: Higher nodal burden (N2/3) is associated with both ETM and ITM, and calls for aggressive screening, systemic therapy options, and surveillance. It is difficult to predict patients who are at a risk of developing LTM with baseline factors alone and evaluation of biological data is needed.

  15. C-type lectins facilitate tumor metastasis

    PubMed Central

    Ding, Dongbing; Yao, Yao; Zhang, Songbai; Su, Chunjie; Zhang, Yonglian

    2017-01-01

    Metastasis, a life-threatening complication of cancer, leads to the majority of cases of cancer-associated mortality. Unfortunately, the underlying molecular and cellular mechanisms of cancer metastasis remain to be fully elucidated. C-type lectins are a large group of proteins, which share structurally homologous carbohydrate-recognition domains (CRDs) and possess diverse physiological functions, including inflammation and antimicrobial immunity. Accumulating evidence has demonstrated the contribution of C-type lectins in different steps of the metastatic spread of cancer. Notably, a substantial proportion of C-type lectins, including selectins, mannose receptor (MR) and liver and lymph node sinusoidal endothelial cell C-type lectin, are important molecular targets for the formation of metastases in vitro and in vivo. The present review summarizes what has been found regarding C-type lectins in the lymphatic and hematogenous metastasis of cancer. An improved understanding the role of C-type lectins in cancer metastasis provides a comprehensive perspective for further clarifying the molecular mechanisms of cancer metastasis and supports the development of novel C-type lectins-based therapies the for prevention of metastasis in certain types of cancer. PMID:28123516

  16. Magnetic Resonance Imaging of Liver Metastasis.

    PubMed

    Karaosmanoglu, Ali Devrim; Onur, Mehmet Ruhi; Ozmen, Mustafa Nasuh; Akata, Deniz; Karcaaltincaba, Musturay

    2016-12-01

    Liver magnetic resonance imaging (MRI) is becoming the gold standard in liver metastasis detection and treatment response assessment. The most sensitive magnetic resonance sequences are diffusion-weighted images and hepatobiliary phase images after Gd-EOB-DTPA. Peripheral ring enhancement, diffusion restriction, and hypointensity on hepatobiliary phase images are hallmarks of liver metastases. In patients with normal ultrasonography, computed tomography (CT), and positron emission tomography (PET)-CT findings and high clinical suspicion of metastasis, MRI should be performed for diagnosis of unseen metastasis. In melanoma, colon cancer, and neuroendocrine tumor metastases, MRI allows confident diagnosis of treatment-related changes in liver and enables differential diagnosis from primary liver tumors. Focal nodular hyperplasia-like nodules in patients who received platinum-based chemotherapy, hypersteatosis, and focal fat can mimic metastasis. In cancer patients with fatty liver, MRI should be preferred to CT. Although the first-line imaging for metastases is CT, MRI can be used as a problem-solving method. MRI may be used as the first-line method in patients who would undergo curative surgery or metastatectomy. Current limitation of MRI is low sensitivity for metastasis smaller than 3mm. MRI fingerprinting, glucoCEST MRI, and PET-MRI may allow simpler and more sensitive diagnosis of liver metastasis. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. C-type lectins facilitate tumor metastasis.

    PubMed

    Ding, Dongbing; Yao, Yao; Zhang, Songbai; Su, Chunjie; Zhang, Yonglian

    2017-01-01

    Metastasis, a life-threatening complication of cancer, leads to the majority of cases of cancer-associated mortality. Unfortunately, the underlying molecular and cellular mechanisms of cancer metastasis remain to be fully elucidated. C-type lectins are a large group of proteins, which share structurally homologous carbohydrate-recognition domains (CRDs) and possess diverse physiological functions, including inflammation and antimicrobial immunity. Accumulating evidence has demonstrated the contribution of C-type lectins in different steps of the metastatic spread of cancer. Notably, a substantial proportion of C-type lectins, including selectins, mannose receptor (MR) and liver and lymph node sinusoidal endothelial cell C-type lectin, are important molecular targets for the formation of metastases in vitro and in vivo. The present review summarizes what has been found regarding C-type lectins in the lymphatic and hematogenous metastasis of cancer. An improved understanding the role of C-type lectins in cancer metastasis provides a comprehensive perspective for further clarifying the molecular mechanisms of cancer metastasis and supports the development of novel C-type lectins-based therapies the for prevention of metastasis in certain types of cancer.

  18. Galectin-3 binding and metastasis.

    PubMed

    Nangia-Makker, Pratima; Balan, Vitaly; Raz, Avraham

    2012-01-01

    Galectin-3 is a member of a family of carbohydrate-binding proteins. It is present in the nucleus, the -cytoplasm, and also the extracellular matrix (ECM) of many normal and neoplastic cell types. Reports show an upregulation of this protein in transformed and metastatic cell lines (Raz and Lotan Cancer Metastasis Rev 6: 433-452, 1987; Raz et al. Int J Cancer 46: 871-877, 1990). Moreover, in many human carcinomas, an increased expression of galectin-3 correlates with progressive tumor stages (Lotan et al. Int J Cancer 56: 474-480, 1994; Bresalier et al. Gastroenterology 115: 287-296, 1998; Nangia-Makker et al. Int J Oncol 7: 1079-1087, 1995; Xu et al. Am J Pathol 147: 815-822, 1995).Several lines of analysis have demonstrated that the galectins participate in cell-cell and cell-matrix interactions by recognizing and binding complementary glycoconjugates and thereby play a crucial role in normal and pathological processes. Elevated expression of the protein is associated with an increased capacity for anchorage-independent growth, homotypic aggregation, and tumor cell lung colonization (Lotan et al. Cancer Res 45: 4349-4353, 1985; Lotan and Raz J Cell Biochem 37: 107-117, 1988; Meromsky et al. Cancer Res 46: 5270-5275, 1986). In this chapter we describe the methods of purification of galectin-3 from transformed Escherichia coli and some of the commonly used functional assays for analyzing galectin-3 binding.

  19. Ion Channels in Brain Metastasis

    PubMed Central

    Klumpp, Lukas; Sezgin, Efe C.; Eckert, Franziska; Huber, Stephan M.

    2016-01-01

    Breast cancer, lung cancer and melanoma exhibit a high metastatic tropism to the brain. Development of brain metastases severely worsens the prognosis of cancer patients and constrains curative treatment options. Metastasizing to the brain by cancer cells can be dissected in consecutive processes including epithelial–mesenchymal transition, evasion from the primary tumor, intravasation and circulation in the blood, extravasation across the blood–brain barrier, formation of metastatic niches, and colonization in the brain. Ion channels have been demonstrated to be aberrantly expressed in tumor cells where they regulate neoplastic transformation, malignant progression or therapy resistance. Moreover, many ion channel modulators are FDA-approved drugs and in clinical use proposing ion channels as druggable targets for future anti-cancer therapy. The present review article aims to summarize the current knowledge on the function of ion channels in the different processes of brain metastasis. The data suggest that certain channel types involving voltage-gated sodium channels, ATP-release channels, ionotropic neurotransmitter receptors and gap junction-generating connexins interfere with distinct processes of brain metastazation. PMID:27618016

  20. Conflicting Biomedical Assumptions for Mathematical Modeling: The Case of Cancer Metastasis

    PubMed Central

    Divoli, Anna; Mendonça, Eneida A.; Evans, James A.; Rzhetsky, Andrey

    2011-01-01

    Computational models in biomedicine rely on biological and clinical assumptions. The selection of these assumptions contributes substantially to modeling success or failure. Assumptions used by experts at the cutting edge of research, however, are rarely explicitly described in scientific publications. One can directly collect and assess some of these assumptions through interviews and surveys. Here we investigate diversity in expert views about a complex biological phenomenon, the process of cancer metastasis. We harvested individual viewpoints from 28 experts in clinical and molecular aspects of cancer metastasis and summarized them computationally. While experts predominantly agreed on the definition of individual steps involved in metastasis, no two expert scenarios for metastasis were identical. We computed the probability that any two experts would disagree on k or fewer metastatic stages and found that any two randomly selected experts are likely to disagree about several assumptions. Considering the probability that two or more of these experts review an article or a proposal about metastatic cascades, the probability that they will disagree with elements of a proposed model approaches 1. This diversity of conceptions has clear consequences for advance and deadlock in the field. We suggest that strong, incompatible views are common in biomedicine but largely invisible to biomedical experts themselves. We built a formal Markov model of metastasis to encapsulate expert convergence and divergence regarding the entire sequence of metastatic stages. This model revealed stages of greatest disagreement, including the points at which cancer enters and leaves the bloodstream. The model provides a formal probabilistic hypothesis against which researchers can evaluate data on the process of metastasis. This would enable subsequent improvement of the model through Bayesian probabilistic update. Practically, we propose that model assumptions and hunches be harvested

  1. Asporin enhances colorectal cancer metastasis through activating the EGFR/Src/cortactin signaling pathway

    PubMed Central

    He, Yonggang; Hu, Lei; Wu, Haoxuan; Ye, Feng; Zhao, Ren

    2016-01-01

    Asporin has been implicated as an oncogene in various types of human cancers; however, the roles of asporin in the development and progression of colorectal cancer (CRC) have not yet been determined. With clinical samples, we found that asporin was highly expressed in CRC tissues compared to adjacent normal tissues and the asporin expression levels were significantly associated with lymph node metastasis status and TNM stage of the patients. Through knockdown of asporin in CRC cell lines RKO and SW620 or overexpression of asporin in cell lines HT-29 and LoVo, we found that asporin could enhance wound healing, migration and invasion abilities of the CRC cells. Further more, with the human umbilical vein endothelial cells (HUVECs) tube formation assays and the xenograft model, we found that asporin promoted the tumor growth through stimulating the VEGF signaling pathway. The portal vein injection models suggested that asporin overexpression stimulated the liver metastasis of HT29 cell line, while asporin knockdown inhibited the liver metastasis of RKO cell line. In addition, asporin was found to augment the phosphorylation of EGFR/Src/cortactin signaling pathway, which might be contributed to the biological functions of asporin in CRC metastasis. These results suggested that asporin promoted the tumor growth and metastasis of CRC, and it could be a potential therapeutic target for CRC patients in future. PMID:27705916

  2. Molecular Mechanisms and Metabolomics of Natural Polyphenols Interfering with Breast Cancer Metastasis.

    PubMed

    Ci, Yingqian; Qiao, Jinping; Han, Mei

    2016-12-17

    Metastatic cancers are the main cause of cancer-related death. In breast primary cancer, the five-year survival rate is close to 100%; however, for metastatic breast cancer, that rate drops to a mere 25%, due in part to the paucity of effective therapeutic options for treating metastases. Several in vitro and in vivo studies have indicated that consumption of natural polyphenols significantly reduces the risk of cancer metastasis. Therefore, this review summarizes the research findings involving the molecular mechanisms and metabolomics of natural polyphenols and how they may be blocking breast cancer metastasis. Most natural polyphenols are thought to impair breast cancer metastasis through downregulation of MMPs expression, interference with the VEGF signaling pathway, modulation of EMT regulator, inhibition of NF-κB and mTOR expression, and other related mechanisms. Intake of natural polyphenols has been shown to impact endogenous metabolites and complex biological metabolic pathways in vivo. Breast cancer metastasis is a complicated process in which each step is modulated by a complex network of signaling pathways. We hope that by detailing the reported interactions between breast cancer metastasis and natural polyphenols, more attention will be directed to these promising candidates as effective adjunct therapies against metastatic breast cancer in the clinic.

  3. Thioredoxin-1 promotes colorectal cancer invasion and metastasis through crosstalk with S100P.

    PubMed

    Lin, Feiyan; Zhang, Peili; Zuo, Zhigui; Wang, Fule; Bi, Ruichun; Shang, Wenjing; Wu, Aihua; Ye, Ju; Li, Shaotang; Sun, Xuecheng; Wu, Jianbo; Jiang, Lei

    2017-08-10

    Thioredoxin-1 (Trx-1) is a small redox-regulating protein, which plays an important role in several cellular functions. Despite recent advances in understanding the biology of Trx-1, the role of Trx-1 and its underlying signaling mechanism in colorectal cancer (CRC) metastasis have not been extensively studied. In this study, we observed that Trx-1 expression is increased in CRC tissues compared to the paired non-cancerous tissues and is significantly correlated with clinical staging, lymph node metastasis and poor survival. Overexpression of Trx-1 enhanced CRC cell invasion and metastasis in vitro and in vivo. Conversely, suppression of Trx-1 expression decreased cell invasion and metastasis in vitro and in vivo. Moreover, Trx-1 activates S100P gene transcription. S100P, in turn, promotes Trx-1 expression and nuclear localization by upregulating p-ERK1/2 and downregulating TXNIP expression. Our finding provides new insight into the mechanism of Trx-1/S100P axis in the promotion of CRC metastasis, and suggests that the Trx-1/S100P axis and their related signaling pathways could be novel targets for the treatment of metastatic CRC. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. FOXP3 suppresses breast cancer metastasis through downregulation of CD44.

    PubMed

    Zhang, Cun; Xu, Yujin; Hao, Qiang; Wang, Shuning; Li, Hong; Li, Jialin; Gao, Yuan; Li, Meng; Li, Weina; Xue, Xiaochang; Wu, Shouzhen; Zhang, Yingqi; Zhang, Wei

    2015-09-15

    Forkhead box protein 3 (FOXP3) plays an important role in breast cancer as an X-linked tumor suppressor gene. However, the biological functions and significance of FOXP3 in breast cancer metastasis remain unclear. Here, we find that, clinically, nuclear FOXP3 expression is inversely correlated with breast cancer metastasis. Moreover, we demonstrate that FOXP3 significantly inhibits adhesion, invasion and metastasis of breast cancer cells in vivo and in vitro. In addition, the adhesion molecule CD44 is found to be suppressed by FOXP3 through transcriptome sequence analysis (RNA-seq). A luciferase reporter assay, chromatin immunoprecipitation and electrophoretic mobility shift assay identify CD44 as a direct target of FOXP3. The expression of CD44 is downregulated by FOXP3 in breast cancer cells. Importantly, anti-CD44 antibody reverses the FOXP3 siRNA-induced effects on the breast cancer cells in vitro and FOXP3 expression level in the nucleus of breast cancer cells is inversely correlated with CD44 expression level in clinic breast cancer tissues. Taken together, the results from the present study suggest that FOXP3 is a suppressor of breast cancer metastasis. FOXP3 directly binds to the promoter of CD44 and inhibits its protein expression, thereby suppressing adhesion and invasion of human breast cancer cells. This finding highlights the therapeutic potential of FOXP3-CD44 signaling to inhibit breast cancer metastasis. © 2015 UICC.

  5. Direct Measurement of the Aerosol Absorption and Extinction Cross Section for a Variety of Chemical and Biological Simulants in the LWIR

    DTIC Science & Technology

    2005-10-01

    for chemical and biological simulants using flow-through aerosol photoacoustics Electret Acoustic dampeners IR detector Modulated IR laser Aerosol out...microphone Acoustic dampeners Aerosol filter holder/substrate Inner cavity IR window with fresh air flush Aerosol spectroscopy using flow-through...emission spectroscopy”. coherent IR source (1-5 watts) ZnSe lens Levitated 1-30um particle spherical-void (or ring) electrodynamic trap Gold

  6. Environmental noise exposure, early biological risk and mental health in nine to ten year old children: a cross-sectional field study

    PubMed Central

    2011-01-01

    Background Previous research suggests that children born prematurely or with a low birth weight are more vulnerable to the mental health effects of ambient neighbourhood noise; predominantly road and rail noise, at home. This study used data from the Road Traffic and Aircraft Noise Exposure and Children's Cognition and Health (RANCH) study to see if this finding extends to aircraft and road traffic noise at school. Methods Children and their parents from schools around three European airports were selected to represent a range of aircraft and road traffic noise exposure levels. Birth weight and gestation period were merged to create a dichotomous variable assessing 'early biological risk'. Mental health was assessed using the Strengths and Difficulties Questionnaire (SDQ). Complete data were available for 1900 primary school children. Results Children who were 'at risk' (i.e. low birth weight or premature birth) were rated as having more conduct problems and emotional symptoms and poorer overall mental health than children not at risk. However, there was no interaction between aircraft or road traffic noise exposure at school and early biological risk. Conclusions Data from the RANCH study suggests that children with early biological risk are not more vulnerable to the effects of aircraft or road traffic noise at school on mental health than children without this risk; however they are more likely to have mental ill-health. PMID:21569605

  7. Biological warfare agents.

    PubMed

    Pohanka, Miroslav; Kuca, Kamil

    2010-01-01

    Biological warfare agents are a group of pathogens and toxins of biological origin that can be potentially misused for military or criminal purposes. The present review attempts to summarize necessary knowledge about biological warfare agents. The historical aspects, examples of applications of these agents such as anthrax letters, biological weapons impact, a summary of biological warfare agents and epidemiology of infections are described. The last section tries to estimate future trends in research on biological warfare agents.

  8. An evidence-based knowledgebase of metastasis suppressors to identify key pathways relevant to cancer metastasis

    PubMed Central

    Zhao, Min; Li, Zhe; Qu, Hong

    2015-01-01

    Metastasis suppressor genes (MS genes) are genes that play important roles in inhibiting the process of cancer metastasis without preventing growth of the primary tumor. Identification of these genes and understanding their functions are critical for investigation of cancer metastasis. Recent studies on cancer metastasis have identified many new susceptibility MS genes. However, the comprehensive illustration of diverse cellular processes regulated by metastasis suppressors during the metastasis cascade is lacking. Thus, the relationship between MS genes and cancer risk is still unclear. To unveil the cellular complexity of MS genes, we have constructed MSGene (http://MSGene.bioinfo-minzhao.org/), the first literature-based gene resource for exploring human MS genes. In total, we manually curated 194 experimentally verified MS genes and mapped to 1448 homologous genes from 17 model species. Follow-up functional analyses associated 194 human MS genes with epithelium/tissue morphogenesis and epithelia cell proliferation. In addition, pathway analysis highlights the prominent role of MS genes in activation of platelets and coagulation system in tumor metastatic cascade. Moreover, global mutation pattern of MS genes across multiple cancers may reveal common cancer metastasis mechanisms. All these results illustrate the importance of MSGene to our understanding on cell development and cancer metastasis. PMID:26486520

  9. A case of intracerebral metastasis in osteosarcoma without active pulmonary metastasis.

    PubMed

    Onodera, Hidetaka; Yoshida, Yasuyuki; Sakakibara, Yohtaro; Kono, Takao; Uchida, Masashi; Tanaka, Yuichiro; Hashimoto, Takuo

    2012-02-01

    Intracerebral metastasis in osteosarcoma is extremely rare. A 14-year-old girl who had previously been operated upon for osteosarcoma of the femur presented with seizures and left hemiparesis. A right parietal lesion with calcification and brain oedema was found. After resection of the mass, pathology revealed an osteosarcoma metastasis.

  10. An evidence-based knowledgebase of metastasis suppressors to identify key pathways relevant to cancer metastasis.

    PubMed

    Zhao, Min; Li, Zhe; Qu, Hong

    2015-10-21

    Metastasis suppressor genes (MS genes) are genes that play important roles in inhibiting the process of cancer metastasis without preventing growth of the primary tumor. Identification of these genes and understanding their functions are critical for investigation of cancer metastasis. Recent studies on cancer metastasis have identified many new susceptibility MS genes. However, the comprehensive illustration of diverse cellular processes regulated by metastasis suppressors during the metastasis cascade is lacking. Thus, the relationship between MS genes and cancer risk is still unclear. To unveil the cellular complexity of MS genes, we have constructed MSGene (http://MSGene.bioinfo-minzhao.org/), the first literature-based gene resource for exploring human MS genes. In total, we manually curated 194 experimentally verified MS genes and mapped to 1448 homologous genes from 17 model species. Follow-up functional analyses associated 194 human MS genes with epithelium/tissue morphogenesis and epithelia cell proliferation. In addition, pathway analysis highlights the prominent role of MS genes in activation of platelets and coagulation system in tumor metastatic cascade. Moreover, global mutation pattern of MS genes across multiple cancers may reveal common cancer metastasis mechanisms. All these results illustrate the importance of MSGene to our understanding on cell development and cancer metastasis.

  11. Mitochondrial metabolism in cancer metastasis

    PubMed Central

    Whitaker-Menezes, Diana; Martinez-Outschoorn, Ubaldo E; Flomenberg, Neal; Birbe, Ruth C; Witkiewicz, Agnieszka K; Howell, Anthony; Philp, Nancy J; Pestell, Richard G

    2012-01-01

    We have recently proposed a new two-compartment model for understanding the Warburg effect in tumor metabolism. In this model, glycolytic stromal cells produce mitochondrial fuels (L-lactate and ketone bodies) that are then transferred to oxidative epithelial cancer cells, driving OXPHOS and mitochondrial metabolism. Thus, stromal catabolism fuels anabolic tumor growth via energy transfer. We have termed this new cancer paradigm the “reverse Warburg effect,” because stromal cells undergo aerobic glycolysis, rather than tumor cells. To assess whether this mechanism also applies during cancer cell metastasis, we analyzed the bioenergetic status of breast cancer lymph node metastases, by employing a series of metabolic protein markers. For this purpose, we used MCT4 to identify glycolytic cells. Similarly, we used TOMM20 and COX staining as markers of mitochondrial mass and OXPHOS activity, respectively. Consistent with the “reverse Warburg effect,” our results indicate that metastatic breast cancer cells amplify oxidative mitochondrial metabolism (OXPHOS) and that adjacent stromal cells are glycolytic and lack detectable mitochondria. Glycolytic stromal cells included cancer-associated fibroblasts, adipocytes and inflammatory cells. Double labeling experiments with glycolytic (MCT4) and oxidative (TOMM20 or COX) markers directly shows that at least two different metabolic compartments co-exist, side-by-side, within primary tumors and their metastases. Since cancer-associated immune cells appeared glycolytic, this observation may also explain how inflammation literally “fuels” tumor progression and metastatic dissemination, by “feeding” mitochondrial metabolism in cancer cells. Finally, MCT4(+) and TOMM20(-) “glycolytic” cancer cells were rarely observed, indicating that the conventional “Warburg effect” does not frequently occur in cancer-positive lymph node metastases. PMID:22395432

  12. First description of cervical intradural thymoma metastasis.

    PubMed

    Marotta, Nicola; Mancarella, Cristina; Colistra, Davide; Landi, Alessandro; Dugoni, Demo Eugenio; Delfini, Roberto

    2015-11-16

    Thymoma and thymic carcinoma are rare epithelial tumors, which originate from the thymus gland. According to the World Health Organization there are "organotypic" (types A, AB, B1, B2, and B3) and "non-organotypic" (thymic carcinomas) thymomas. Type B3 thymomas are aggressive tumors, which can metastasize. Due to the rarity of these lesions, only 7 cases of extradural metastasis are described in the literature. We report the first and unique case of a man with cervical intradural B3 thymoma metastasis. A 46-year-old man underwent thymoma surgical removal. The year after the procedure he was treated for a parietal pleura metastasis. In 2006 he underwent cervical-dorsal extradural metastasis removal and C5-Th1 stabilization. Seven years after he came to our observation complaining left cervicobrachialgia and a reduction of strength of the left arm. He underwent a cervical spine magnetic resonance imaging, which showed a new lesion at the C5-C7 level. The patient underwent a surgery for the intradural B3 thymoma metastasis. Neurological symptoms improved although the removal was subtotal. He went through postoperative radiation therapy with further mass reduction. Spinal metastases are extremely rare. To date, only 7 cases of spinal extradural metastasis have been described in the literature. This is the first case of spinal intradural metastasis. Early individuation of these tumors and surgical treatment improve neurological outcome in patients with spinal cord compression. A multimodal treatment including neoadjuvant chemotherapy, surgery and postoperative radiation therapy seems to improve survival in patients with metastatic thymoma.

  13. First description of cervical intradural thymoma metastasis

    PubMed Central

    Marotta, Nicola; Mancarella, Cristina; Colistra, Davide; Landi, Alessandro; Dugoni, Demo Eugenio; Delfini, Roberto

    2015-01-01

    Thymoma and thymic carcinoma are rare epithelial tumors, which originate from the thymus gland. According to the World Health Organization there are “organotypic” (types A, AB, B1, B2, and B3) and “non-organotypic” (thymic carcinomas) thymomas. Type B3 thymomas are aggressive tumors, which can metastasize. Due to the rarity of these lesions, only 7 cases of extradural metastasis are described in the literature. We report the first and unique case of a man with cervical intradural B3 thymoma metastasis. A 46-year-old man underwent thymoma surgical removal. The year after the procedure he was treated for a parietal pleura metastasis. In 2006 he underwent cervical-dorsal extradural metastasis removal and C5-Th1 stabilization. Seven years after he came to our observation complaining left cervicobrachialgia and a reduction of strength of the left arm. He underwent a cervical spine magnetic resonance imaging, which showed a new lesion at the C5-C7 level. The patient underwent a surgery for the intradural B3 thymoma metastasis. Neurological symptoms improved although the removal was subtotal. He went through postoperative radiation therapy with further mass reduction. Spinal metastases are extremely rare. To date, only 7 cases of spinal extradural metastasis have been described in the literature. This is the first case of spinal intradural metastasis. Early individuation of these tumors and surgical treatment improve neurological outcome in patients with spinal cord compression. A multimodal treatment including neoadjuvant chemotherapy, surgery and postoperative radiation therapy seems to improve survival in patients with metastatic thymoma. PMID:26601098

  14. Spinal metastasis in head and neck cancer

    PubMed Central

    2012-01-01

    Background The incidence of head and neck cancer is relatively low in developed countries and highest in South East Asia. Notwithstanding advances in surgery and radiotherapy over the past several decades, the 5-year survival rate for head and neck cancer has stagnated and remains at 50–55%. This is due, in large part, to both regional and distant disease spread, including spinal metastasis. Spinal metastasis from head and neck cancer is rare, has a poor prognosis and can significantly impede end-stage quality of life; normally only palliative care is given. This study aims to conduct a systematic review of the evidence available on management of spinal metastasis from head and neck cancer and to use such evidence to draw up guiding principles in the management of the distant spread. Methods Systematic review of the electronic literature was conducted regarding the management of spinal metastasis of head and neck malignancies. Results Due to the exceptional rarity of head and neck cancers metastasizing to the spine, there is a paucity of good randomized controlled trials into the management of spinal metastasis. This review produced only 12 case studies/reports and 2 small retrospective cohort studies that lacked appropriate controls. Conclusion Management should aim to improve end-stage quality of life and maintain neurological function. This review has found that radiotherapy +/− medical adjuvant is considered the principle treatment of spinal metastasis of head and neck cancers. There is an absence of a definitive treatment protocol for head and neck cancer spinal metastasis. Our failure to find and cite high-quality scientific evidence only serves to stress the need for good quality research in this area. PMID:22716187

  15. A rapid imageable in vivo metastasis assay for circulating tumor cells.

    PubMed

    Menen, Rhiana S; Pinney, Emmett; Kolostova, Katerina; Bobek, Vladimir; Suetsugu, Atsushi; Zhang, Nan; Bouvet, Michael; Hoffman, Robert M

    2011-10-01

    Circulating tumor cells (CTCs) are of great importance for cancer diagnosis, prognosis and treatment. It is necessary to improve the ability to image and analyze them for their biological properties which determine their behavior in the patient. In the present study, using immunomagnetic beads, CTCs were rapidly isolated from the circulation of mice orthotopically implanted with human PC-3 prostate cancer cells stably expressing green fluorescent protein (GFP). The PC-3-GFP CTCs were then expanded in culture in parallel with the parental PC-3-GFP cell line. Both cell types were then inoculated onto the chorioallentoic membrane (CAM) of chick embryos. Eight days later, embryos were harvested and the brains were processed for frozen sections. The IV-100 intravital laser scanning microscope enabled rapid identification of fluorescent metastatic foci within the chick embryonic brain. Inoculation of embryos with PC-3-GFP CTCs resulted in a 3 to 10-fold increase in brain metastasis when compared to those with the parental PC-3-GFP cells (p<0.05 in all animals). Thus, PC-3-GFP CTCs have increased metastatic potential compared to their parental counterparts. Furthermore, the chick embryo represents a rapid, sensitive, imageable assay of metastatic potential for CTCs. The chick embryo assay has future clinical application for individualizing patient therapy based on the metastatic profile of their CTCs.

  16. Noninvasive visualization of retinoblastoma growth and metastasis via bioluminescence imaging.

    PubMed

    Ji, Xunda; Cheng, Lin; Wei, Fang; Li, Huiming; Wang, Mengyun; Tian, Yuhua; Chen, Xiafang; Wang, Yufei; Wolf, Frank; Li, Chuanyuan; Huang, Qian

    2009-12-01

    To establish human retinoblastoma (RB) animal models that allow sensitive, noninvasive and continuous monitoring of tumor growth and metastasis in vivo. The human RB tumor cell lines HXO-Rb44 and Y79 were engineered to express a fusion reporter gene allowing for bioluminescence and fluorescence imaging. Intraocular and metastatic tumors were induced in immunodeficient nude mice by injection of bioluminescent RB cells into eye compartments and into the left ventricle or tail vein. The growth kinetics of intraocular and metastatic tumors was quantitatively and continuously monitored via bioluminescence imaging (BLI). Intraocular injection of HXO-Rb44-GFP-luc cells resulted in 100%, 80%, and 80% successful RB tumor development in the anterior chamber, vitreal cavity and subretinal space, respectively. The subretinal injection of Y79-GFP-luc cells resulted in 100% tumor development. BLI signal intensity correlated with the number of tumor cells injected as well as the weight of the tumor-bearing eyes. After bilateral subretinal injection of HXO-Rb44-GFP-luc cells, one of six RB tumor mice developed brain metastasis. Intracardiac injection of HXO-Rb44-GFP-luc cells resulted in metastatic disease in 9 of 15 nude mice, whereas tail vein injection resulted in metastasis in 1 of 16. Metastases were developed in multiple organs, including lymph nodes, bone, and brain, resembling the metastatic profile in patients with RB. BLI allowed sensitive, noninvasive, and quantitative localization and monitoring of intraocular and metastatic RB tumor growth in vivo and thus may be a useful tool to study RB biology as well as anti-RB therapies.

  17. Fucoidan Suppresses Hypoxia-Induced Lymphangiogenesis and Lymphatic Metastasis in Mouse Hepatocarcinoma.

    PubMed

    Teng, Hongming; Yang, Yazong; Wei, Hengyun; Liu, Zundong; Liu, Zhichao; Ma, Yanhong; Gao, Zixiang; Hou, Lin; Zou, Xiangyang

    2015-06-03

    Metastasis, the greatest clinical challenge associated with cancer, is closely connected to multiple biological processes, including invasion and adhesion. The hypoxic environment in tumors is an important factor that causes tumor metastasis by activating HIF-1α. Fucoidan, extracted from brown algae, is a sulfated polysaccharide and, as a novel marine biological material, has been used to treat various disorders in China, Korea, Japan and other countries. In the present study, we demonstrated that fucoidan derived from Undaria pinnatifida sporophylls significantly inhibits the hypoxia-induced expression, nuclear translocation and activity of HIF-1α, the synthesis and secretion of VEGF-C and HGF, cell invasion and lymphatic metastasis in a mouse hepatocarcinoma Hca-F cell line. Fucoidan also suppressed lymphangiogenesis in vitro and in vivo. In addition, accompanied by a reduction in the HIF-1α nuclear translocation and activity, fucoidan significantly reduced the levels of p-PI3K, p-Akt, p-mTOR, p-ERK, NF-κB, MMP-2 and MMP-9, but increased TIMP-1 levels. These results indicate strongly that the anti-metastasis and anti-lymphangiogenesis activities of fucoidan are mediated by suppressing HIF-1α/VEGF-C, which attenuates the PI3K/Akt/mTOR signaling pathways.

  18. Imaging of surgical margin in pancreatic metastasis using two-photon excited fluorescence microscopy

    NASA Astrophysics Data System (ADS)

    Chen, Jing; Hong, Zhipeng; Chen, Hong; Chen, Youting; Xu, Yahao; Zhu, Xiaoqin; Zhuo, Shuangmu; Shi, Zheng; Chen, Jianxin

    2014-09-01

    Two-photon excited fluorescence (TPEF) microscopy, has become a powerful tool for imaging unstained tissue samples at subcellular level in biomedical research. The purpose of this study was to determine whether TPEF imaging of histological sections without H-E staining can be used to identify the boundary between normal pancreas and pancreatic metastasis from renal cell carcinoma (RCC). The typical features such as the significant increase of cancerous nests, the absence of pancreatic ductal, the appearance of cancer cells were observed to present the boundary between normal pancreas and pancreatic metastasis from RCC. These results correlated well with the corresponding histological outcomes. With the advent of clinically miniaturized TPEF microscopy and integrative endoscopy, TPEF microscopy has the potential application on surgical location of pancreatic metastasis from RCC in the near future.

  19. Tumour exosome integrins determine organotropic metastasis

    PubMed Central

    Hoshino, Ayuko; Costa-Silva, Bruno; Shen, Tang-Long; Rodrigues, Goncalo; Hashimoto, Ayako; Mark, Milica Tesic; Molina, Henrik; Kohsaka, Shinji; Di Giannatale, Angela; Ceder, Sophia; Singh, Swarnima; Williams, Caitlin; Soplop, Nadine; Uryu, Kunihiro; Pharmer, Lindsay; King, Tari; Bojmar, Linda; Davies, Alexander E.; Ararso, Yonathan; Zhang, Tuo; Zhang, Haiying; Hernandez, Jonathan; Weiss, Joshua M.; Dumont-Cole, Vanessa D.; Kramer, Kimberly; Wexler, Leonard H.; Narendran, Aru; Schwartz, Gary K.; Healey, John H.; Sandstrom, Per; Labori, Knut Jørgen; Kure, Elin H.; Grandgenett, Paul M.; Hollingsworth, Michael A.; de Sousa, Maria; Kaur, Sukhwinder; Jain, Maneesh; Mallya, Kavita; Batra, Surinder K.; Jarnagin, William R.; Brady, Mary S.; Fodstad, Oystein; Muller, Volkmar; Pantel, Klaus; Minn, Andy J.; Bissell, Mina J.; Garcia, Benjamin A.; Kang, Yibin; Rajasekhar, Vinagolu K.; Ghajar, Cyrus M.; Matei, Irina; Peinado, Hector; Bromberg, Jacqueline; Lyden, David

    2015-01-01

    Ever since Stephen Paget’s 1889 hypothesis, metastatic organotropism has remained one of cancer’s greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6β4 and α6β1 were associated with lung metastasis, while exosomal integrin αvβ5 was linked to liver metastasis. Targeting the integrins α6β4 and αvβ5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis. PMID:26524530

  20. Tumour exosome integrins determine organotropic metastasis

    SciTech Connect

    Hoshino, Ayuko; Costa-Silva, Bruno; Shen, Tang-Long; Rodrigues, Goncalo; Hashimoto, Ayako; Tesic Mark, Milica; Molina, Henrik; Kohsaka, Shinji; Di Giannatale, Angela; Ceder, Sophia; Singh, Swarnima; Williams, Caitlin; Soplop, Nadine; Uryu, Kunihiro; Pharmer, Lindsay; King, Tari; Bojmar, Linda; Davies, Alexander E.; Ararso, Yonathan; Zhang, Tuo; Zhang, Haiying; Hernandez, Jonathan; Weiss, Joshua M.; Dumont-Cole, Vanessa D.; Kramer, Kimberly; Wexler, Leonard H.; Narendran, Aru; Schwartz, Gary K.; Sandstrom, Per; Jørgen Labori, Knut; Kure, Elin H.; Grandgenett, Paul M.; Hollingsworth, Michael A.; de Sousa, Maria; Kaur, Sukhwinder; Jain, Maneesh; Mallya, Kavita; Batra, Surinder K.; Jarnagin, William R.; Brady, Mary S.; Fodstad, Oystein; Muller, Volkmar; Pantel, Klaus; Minn, Andy J.; Bissell, Mina J.; Garcia, Benjamin A.; Kang, Yibin; Rajasekhar, Vinagolu K.; Ghajar, Cyrus M.; Matei, Irina; Peinado, Hector; Bromberg, Jacqueline; Lyden, David

    2015-10-28

    Ever since Stephen Paget’s 1889 hypothesis, metastatic organotropism has remained one of cancer’s greatest mysteries. In this paper, we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6β4 and α6β1 were associated with lung metastasis, while exosomal integrin αvβ5 was linked to liver metastasis. Targeting the integrins α6β4 and αvβ5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. In conclusion, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.

  1. Tumour exosome integrins determine organotropic metastasis

    DOE PAGES

    Hoshino, Ayuko; Costa-Silva, Bruno; Shen, Tang-Long; ...

    2015-10-28

    Ever since Stephen Paget’s 1889 hypothesis, metastatic organotropism has remained one of cancer’s greatest mysteries. In this paper, we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6β4 and α6β1 were associated with lung metastasis,more » while exosomal integrin αvβ5 was linked to liver metastasis. Targeting the integrins α6β4 and αvβ5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. In conclusion, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.« less

  2. Tumour exosome integrins determine organotropic metastasis.

    PubMed

    Hoshino, Ayuko; Costa-Silva, Bruno; Shen, Tang-Long; Rodrigues, Goncalo; Hashimoto, Ayako; Tesic Mark, Milica; Molina, Henrik; Kohsaka, Shinji; Di Giannatale, Angela; Ceder, Sophia; Singh, Swarnima; Williams, Caitlin; Soplop, Nadine; Uryu, Kunihiro; Pharmer, Lindsay; King, Tari; Bojmar, Linda; Davies, Alexander E; Ararso, Yonathan; Zhang, Tuo; Zhang, Haiying; Hernandez, Jonathan; Weiss, Joshua M; Dumont-Cole, Vanessa D; Kramer, Kimberly; Wexler, Leonard H; Narendran, Aru; Schwartz, Gary K; Healey, John H; Sandstrom, Per; Labori, Knut Jørgen; Kure, Elin H; Grandgenett, Paul M; Hollingsworth, Michael A; de Sousa, Maria; Kaur, Sukhwinder; Jain, Maneesh; Mallya, Kavita; Batra, Surinder K; Jarnagin, William R; Brady, Mary S; Fodstad, Oystein; Muller, Volkmar; Pantel, Klaus; Minn, Andy J; Bissell, Mina J; Garcia, Benjamin A; Kang, Yibin; Rajasekhar, Vinagolu K; Ghajar, Cyrus M; Matei, Irina; Peinado, Hector; Bromberg, Jacqueline; Lyden, David

    2015-11-19

    Ever since Stephen Paget's 1889 hypothesis, metastatic organotropism has remained one of cancer's greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6β4 and α6β1 were associated with lung metastasis, while exosomal integrin αvβ5 was linked to liver metastasis. Targeting the integrins α6β4 and αvβ5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.

  3. Surgical treatment of brain metastasis: a review.

    PubMed

    Mut, Melike

    2012-01-01

    Brain metastasis is the most common intracranial tumor in adults. Currently, treatment of brain metastasis requires multidisciplinary approach tailored for each individual patient. Surgery has an indispensible role in relieving intracranial mass effect, improving neurological status and survival while providing or confirming neuropathological diagnosis with low mortality and morbidity rates. Besides the resection of a single brain metastasis in patients with accessible lesions, good functional status, and absent/controlled extracranial disease; surgery is proven to play a role in management of multiple metastases. Surgical technique has an impact on the outcome since piecemeal resection rather than en bloc resection and leaving infiltrative zone behind around resection cavity may have a negative influence on local control. Best local control of brain metastasis can be accomplished with optimal surgical resection involving current armamentarium of preoperative structural and functional imaging, intraoperative neuromonitoring, and advanced microneurosurgical techniques; followed by adjunct therapies like stereotactic radiosurgery, whole brain radiotherapy, or intracavitary therapies. Here, treatment options for brain metastasis are discussed with controversies about surgery.

  4. Bone metastasis risk factors in breast cancer

    PubMed Central

    Pulido, Catarina; Vendrell, Inês; Ferreira, Arlindo R; Casimiro, Sandra; Mansinho, André; Alho, Irina; Costa, Luís

    2017-01-01

    Bone is the single most frequent site for bone metastasis in breast cancer patients. Patients with bone-only metastasis have a fairly good prognosis when compared with patients with visceral disease. Nevertheless, cancer-induced bone disease carries an important risk of developing skeletal related events that impact quality of life (QoL). It is therefore particularly important to stratify patients according to their risk of developing bone metastasis. In this context, several risk factors have been studied, including demographic, clinicopathological, genetic, and metabolic factors. Most of them show conflicting or non-definitive associations and are not validated for clinical use. Nonetheless, tumour intrinsic subtype is widely accepted as a major risk factor for bone metastasis development and luminal breast cancer carries an increased risk for bone disease. Other factors such as gene signatures, expression of specific cytokines (such as bone sialoprotein and bone morphogenetic protein 7) or components of the extracellular matrix (like bone crosslinked C-telopeptide) might also influence the development of bone metastasis. Knowledge of risk factors related with bone disease is of paramount importance as it might be a prediction tool for triggering the use of targeted agents and allow for better patient selection for future clinical trials. PMID:28194227

  5. Brain metastasis: Unique challenges and open opportunities.

    PubMed

    Lowery, Frank J; Yu, Dihua

    2017-01-01

    The metastasis of cancer to the central nervous system (CNS) remains a devastating clinical reality, carrying an estimated survival time of less than one year in spite of recent therapeutic breakthroughs for other disease contexts. Advances in brain metastasis research are hindered by a number of factors, including its complicated nature and the difficulty of modeling metastatic cancer growth in the unique brain microenvironment. In this review, we will discuss the clinical challenge, and compare the merits and limitations of the available models for brain metastasis research. Additionally, we will specifically address current knowledge on how brain metastases take advantage of the unique brain environment to benefit their own growth. Finally, we will explore the distinctive metabolic and chemical characteristics of the brain and how these paradoxically represent barriers to establishment of brain metastasis, but also provide ample supplies for metastatic cells' growth in the brain. We envision that multi-disciplinary innovative approaches will open opportunities for the field to make breakthroughs in tackling unique challenges of brain metastasis. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Nanotechnology-based intelligent drug design for cancer metastasis treatment.

    PubMed

    Gao, Yu; Xie, Jingjing; Chen, Haijun; Gu, Songen; Zhao, Rongli; Shao, Jingwei; Jia, Lee

    2014-01-01

    Traditional chemotherapy used today at clinics is mainly inherited from the thinking and designs made four decades ago when the Cancer War was declared. The potency of those chemotherapy drugs on in-vitro cancer cells is clearly demonstrated at even nanomolar levels. However, due to their non-specific effects in the body on normal tissues, these drugs cause toxicity, deteriorate patient's life quality, weaken the host immunosurveillance system, and result in an irreversible damage to human's own recovery power. Owing to their unique physical and biological properties, nanotechnology-based chemotherapies seem to have an ability to specifically and safely reach tumor foci with enhanced efficacy and low toxicity. Herein, we comprehensively examine the current nanotechnology-based pharmaceutical platforms and strategies for intelligent design of new nanomedicines based on targeted drug delivery system (TDDS) for cancer metastasis treatment, analyze the pros and cons of nanomedicines versus traditional chemotherapy, and evaluate the importance that nanomaterials can bring in to significantly improve cancer metastasis treatment.

  7. Regulation of microRNAs in Cancer Metastasis

    PubMed Central

    Bouyssou, Juliette M.C.; Manier, Salomon; Huynh, Daisy; Issa, Samar; Roccaro, Aldo M.; Ghobrial, Irene M.

    2014-01-01

    Metastasis is a phenomenon of crucial importance in defining prognosis in patients with cancer and is often responsible for cancer-related mortality. It is known that several steps are necessary for clonal cells to disseminate from their primary tumor site and colonize distant tissues, thus originating metastatic lesions. Therefore, investigating the molecular actors regulating this process may provide helpful insights in the development of efficient therapeutic responses. Recent evidences have indicated the role of microRNAs (miRNAs) in modulating the metastatic process in solid tumors. miRNAs are small regulatory non-coding RNAs that bind specific target mRNAs, leading to translational repression. miRNAs are known to act as negative regulators of gene expression and are involved in the regulation of biological processes, including cell growth, differentiation and apoptosis, both in physiological conditions and during diseases, such as tumors. In the specific field of tumorigenesis, miRNAs play an important role in mediating oncogenesis and favoring tumor progression, as a result of their ability to modulate epithelial-to-mesenchymal transition (EMT) and other series of events facilitating the formation of metastasis. The role of miRNAs in cancer development has been widely studied and has helped elucidate events such as the change in expression of oncogenes, tumor-suppressors and cancer-related proteins. This review focuses on the mechanisms underlying the role of miRNAs as part of the metastatic process. PMID:24569228

  8. [Sacral metastasis simulating aneurysmal bone cyst].

    PubMed

    Sanromán-Álvarez, Pablo; Simal-Julián, Juan Antonio; Miranda-Lloret, Pablo; Pérez-Borredá, Pedro; Botella-Asunción, Carlos

    2014-01-01

    Cystic spinal lesions with characteristic patterns, such as the presence of haematic fluid-fluid levels (H-FFL), have been associated with many tumoral lineages, more frequently with aneurysmal bone cyst (ABC) and exceptionally with metastasis. We present the case of a 60-year-old man with the finding of a sacral cystic bone lesion with H-FFL, with initial suspicion of ABC and confirmed diagnosis of metastasis. The case presented is, to our knowledge, the second case published of spinal cystic bone metastasis with H-FFL pattern with unknown primary tumour at the time of diagnosis and the only one that received resective surgical treatment, achieving pulmonary and metastatic disease control with good quality of life after 1 year of follow up.

  9. Control of Metastasis by NK Cells.

    PubMed

    López-Soto, Alejandro; Gonzalez, Segundo; Smyth, Mark J; Galluzzi, Lorenzo

    2017-08-14

    The metastatic spread of malignant cells to distant anatomical locations is a prominent cause of cancer-related death. Metastasis is governed by cancer-cell-intrinsic mechanisms that enable neoplastic cells to invade the local microenvironment, reach the circulation, and colonize distant sites, including the so-called epithelial-to-mesenchymal transition. Moreover, metastasis is regulated by microenvironmental and systemic processes, such as immunosurveillance. Here, we outline the cancer-cell-intrinsic and -extrinsic factors that regulate metastasis, discuss the key role of natural killer (NK) cells in the control of metastatic dissemination, and present potential therapeutic approaches to prevent or target metastatic disease by harnessing NK cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. miR-29c suppresses pancreatic cancer liver metastasis in an orthotopic implantation model in nude mice and affects survival in pancreatic cancer patients.

    PubMed

    Zou, Yongkang; Li, Jianwei; Chen, Zhiyu; Li, Xiaowu; Zheng, Shuguo; Yi, Dong; Zhong, Ai; Chen, Jian

    2015-06-01

    We investigated mechanisms of pancreatic cancer metastasis and defined the biological role of miR-29c in pancreatic cancer metastasis. After two rounds of cell selection in vivo, pancreatic cancer cells with various metastatic potentials derived from spontaneous liver metastases were used as a model of pancreatic cancer to determine the role of miR-29c in pancreatic cancer metastasis. Pancreatic cancer samples were analyzed for miRNA-29c expression, and these levels were associated with survival between groups. miR-29c suppresses cell migration and invasion by targeting the MMP2 3'UTR. Overexpression of miR-29c suppresses pancreatic cancer liver metastasis in a nude mouse orthotopic implantation model. miR-29c expression was associated with metastasis and pancreatic cancer patient survival. miR-29c plays an important role in mediating pancreatic cancer metastasis to the liver by targeting MMP2. Therefore, miR-29c may serve as a novel marker of pancreatic cancer metastasis and possibly as a therapeutic target to treat pancreatic cancer liver metastasis.

  11. Osteosarcoma metastasis causing ileo-ileal intussusception.

    PubMed

    Abbo, Olivier; Pinnagoda, Kalitha; Micol, Lionel A; Beck-Popovic, Maya; Joseph, Jean-Marc

    2013-08-12

    Osteosarcoma metastasis causing intussusception is a very rare entity, with a pejorative prognosis. Based on a case, we performed a literature review in order to better assess this situation. We conclude that, in patients with a history of osteosarcoma lung metastasis, echographic and/or computed tomography scan evidence of a small bowel obstruction with intussusception should lead to an open surgical procedure if the laparoscopic approach does not allow to accurately explore and resect the lesion, in order to prevent misdiagnosis and to avoid further delay in the management.

  12. Crossing the endothelial barrier during metastasis.

    PubMed

    Reymond, Nicolas; d'Água, Bárbara Borda; Ridley, Anne J

    2013-12-01

    During metastasis, cancer cells disseminate to other parts of the body by entering the bloodstream in a process that is called intravasation. They then extravasate at metastatic sites by attaching to endothelial cells that line blood vessels and crossing the vessel walls of tissues or organs. This Review describes how cancer cells cross the endothelial barrier during extravasation and how different receptors, signalling pathways and circulating cells such as leukocytes and platelets contribute to this process. Identification of the mechanisms that underlie cancer cell extravasation could lead to the development of new therapies to reduce metastasis.

  13. [Surgical managment of colorectal liver metastasis].

    PubMed

    Prot, Thomas; Halkic, Nermin; Demartines, Nicolas

    2007-06-27

    Surgery offer the only curative treatment for colorectal hepatic metastasis. Nowadays, five-year survival increases up to 58% in selected cases, due to the improvement and combination of chemotherapy, surgery and ablative treatment like embolisation, radio-frequency or cryoablation. Surgery should be integrated in a multi disciplinary approach and initial work-up must take in account patient general conditions, tumor location, and possible extra hepatic extension. Thus, a surgical resection may be performed immediately or after preparation with chemotherapy or selective portal embolization. Management of liver metastasis should be carried out in oncological hepato-biliary centre.

  14. Cranial computed tomographic abnormalities in leptomeningeal metastasis

    SciTech Connect

    Lee, Y.Y.; Glass, J.P.; Geoffray, A.; Wallace, S.

    1984-11-01

    Sixty-four (57.6%) of 111 cancer patients with cerebrospinal fluid cytology positive for malignant cells had cranial computed tomographic (CT) scans within 2 weeks before or after a lumbar puncture. Twenty-two (34.3%) of the 64 had abnormal CT findings indicative of leptomeningeal metastasis. Thirteen (59.6%) of these 22 patients had associated parenchymal metastases. Recognition of leptomeningeal disease may alter the management of patients with parenchymal metastases. Communicating hydrocephalus in cancer patients should be considered to be related to leptomeningeal metastasis until proven otherwise.

  15. The Multiple Roles of Exosomes in Metastasis

    PubMed Central

    WEIDLE, H. ULRICH; BIRZELE, FABIAN; KOLLMORGEN, GWEN; RÜGER, RÜDIGER

    2016-01-01

    Exosomes are important contributors to cell−cell communication and their role as diagnostic markers for cancer and the pathogenesis for cancer is under intensive investigation. Here, we focus on their role in metastasis-related processes. We discuss their impact regarding promotion of invasion and migration of tumor cells, conditioning of lymph nodes, generation of premetastatic niches and organotropism of metastasis. Furthermore, we highlight interactions of exosomes with bone marrow and stromal components such as fibroblasts, endothelial cells, myeloid- and other immune-related cells in the context of metastases. For all processes as described above, we outline molecular and cellular components for therapeutic intervention with metastatic processes. PMID:28031234

  16. Surviving at a distance: organ specific metastasis

    PubMed Central

    Obenauf, Anna C.; Massagué, Joan

    2015-01-01

    The clinical manifestation of metastasis in a vital organ is the final stage of cancer progression and the main culprit of cancer related mortality. Once established, metastasis is devastating, yet only a small proportion of the cancer cells that leave a tumor succeed at infiltrating, surviving, and ultimately overtaking a distant organ. The bottlenecks that challenge cancer cells in newly invaded microenvironments are organ specific and consequently demand distinct mechanisms for metastatic colonization. Here we review the metastatic traits that allow cancer cells to colonize distinct organ sites. PMID:26693180

  17. Metastasis from oral cancer: an overview.

    PubMed

    Noguti, Juliana; De Moura, Carolina Foot Gomes; De Jesus, Gustavo Protasio Pacheco; Da Silva, Victor Hugo Pereira; Hossaka, Thais Ayako; Oshima, Celina Tijuko Fujiyama; Ribeiro, Daniel Araki

    2012-01-01

    Oral cancer is a common neoplasm worldwide. Its incidence and mortality have also increased over the past decades. It is characterized by poor prognosis and a low survival rate despite sophisticated surgical and radiotherapeutic modalities. Metastasis of oral cancer is a complex process involving detachment of cells from tumor tissue, regulation of cell motility and invasion, proliferation and evasion through the lymphatic system or blood vessels. In this review, we will focus on the current knowledge in metastasis from oral cancer regarding facts, such as incidence; stage, histopathology and grade of primary tumor; clinical manifestations; diagnosis; and treatment. Certainly, such information will contribute to the understanding of oral cancer pathogenesis.

  18. The Multiple Roles of Exosomes in Metastasis.

    PubMed

    Weidle, Ulrich H; Birzele, Fabian; Kollmorgen, Gwen; Rüger, Rüdiger

    2017-01-02

    Exosomes are important contributors to cell-cell communication and their role as diagnostic markers for cancer and the pathogenesis for cancer is under intensive investigation. Here, we focus on their role in metastasis-related processes. We discuss their impact regarding promotion of invasion and migration of tumor cells, conditioning of lymph nodes, generation of premetastatic niches and organotropism of metastasis. Furthermore, we highlight interactions of exosomes with bone marrow and stromal components such as fibroblasts, endothelial cells, myeloid- and other immune-related cells in the context of metastases. For all processes as described above, we outline molecular and cellular components for therapeutic intervention with metastatic processes.

  19. Quantifying spontaneous metastasis in a syngeneic mouse melanoma model using real time PCR.

    PubMed

    Deng, Wentao; McLaughlin, Sarah L; Klinke, David J

    2017-08-07

    Modeling metastasis in vivo with animals is a priority for both revealing mechanisms of tumor dissemination and developing therapeutic methods. While conventional intravenous injection of tumor cells provides an efficient and consistent system for studying tumor cell extravasation and colonization, studying spontaneous metastasis derived from orthotopic tumor sites has the advantage of modeling more aspects of the metastatic cascade, but is challenging as it is difficult to detect small numbers of metastatic cells. In this work, we developed an approach for quantifying spontaneous metastasis in the syngeneic mouse B16 system using real time PCR. We first transduced B16 cells with lentivirus expressing firefly luciferase Luc2 gene for bioluminescence imaging. Next, we developed a real time quantitative PCR (qPCR) method for the detection of luciferase-expressing, metastatic tumor cells in mouse lungs and other organs. To illustrate the approach, we quantified lung metastasis in both spontaneous and experimental scenarios using B16F0 and B16F10 cells in C57BL/6Ncrl and NOD-Scid Gamma (NSG) mice. We tracked B16 melanoma metastasis with both bioluminescence imaging and qPCR, which were found to be self-consistent. Using this assay, we can quantitatively detect one Luc2 positive tumor cell out of 10(4) tissue cells, which corresponds to a metastatic burden of 1.8 × 10(4) metastatic cells per whole mouse lung. More importantly, the qPCR method was at least a factor of 10 more sensitive in detecting metastatic cell dissemination and should be combined with bioluminescence imaging as a high-resolution, end-point method for final metastatic cell quantitation. Given the rapid growth of primary tumors in many mouse models, assays with improved sensitivity can provide better insight into biological mechanisms that underpin tumor metastasis.

  20. Establishment and characterization of a metastasis model of human gastric cancer in nude mice.

    PubMed

    Li, Kesheng; Du, Huifen; Lian, Xiaowen; Chai, Dandan; Li, Xinwen; Yang, Rong; Wang, Chunya

    2016-02-03

    A mouse model of metastasis of human gastric cancer is one of the most important tools for studying the biological mechanisms underlying human gastric cancer metastasis. In this paper, we established a mouse model of metastatic human gastric cancer in nude mice that has a higher rate of tumor formation and metastasis than existing models. To generate the mouse model of metastatic human gastric cancer, fresh tumor tissues from patients that have undergone surgery for gastric cancer were subcutaneously implanted in the right and left groins of nude mice. When the implanted tissue grew to 1 cubic centimeter, the mice were killed, and the tumor tissues were examined and resected. The tumor tissues were implanted into nude mice and subjected to pathological examination, immunohistochemical staining, and real-time PCR for cytokeratin 8/18 (CK8/18), E-cadherin, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). The mice were also analyzed for metastasis in their peritoneum, abdominal cavity, and internal organs by histopathological examination. Tissues collected from these organs were examined for pathology. After ten generations of implantation, all mice developed tumor growth at the implanted position, 94% of the mice developed metastasis to the retroperitoneum and viscera. The implanted and metastatic tumor maintained the same histological features across all generations, and metastasis was observed in the esophagus, stomach, spleen, liver, kidney, adrenal, intestine, and pancreas. These metastatic tumors revealed no detectable expression of CK8/18, E-cadherin, VCAM-1, and ICAM-1. This model will serve as valuable tool for understanding the metastatic process of human gastric cancer.

  1. Differential combinatorial regulatory network analysis related to venous metastasis of hepatocellular carcinoma

    PubMed Central

    2012-01-01

    Background Hepatocellular carcinoma (HCC) is one of the most fatal cancers in the world, and metastasis is a significant cause to the high mortality in patients with HCC. However, the molecular mechanism behind HCC metastasis is not fully understood. Study of regulatory networks may help investigate HCC metastasis in the way of systems biology profiling. Methods By utilizing both sequence information and parallel microRNA(miRNA) and mRNA expression data on the same cohort of HBV related HCC patients without or with venous metastasis, we constructed combinatorial regulatory networks of non-metastatic and metastatic HCC which contain transcription factor(TF) regulation and miRNA regulation. Differential regulation patterns, classifying marker modules, and key regulatory miRNAs were analyzed by comparing non-metastatic and metastatic networks. Results Globally TFs accounted for the main part of regulation while miRNAs for the minor part of regulation. However miRNAs displayed a more active role in the metastatic network than in the non-metastatic one. Seventeen differential regulatory modules discriminative of the metastatic status were identified as cumulative-module classifier, which could also distinguish survival time. MiR-16, miR-30a, Let-7e and miR-204 were identified as key miRNA regulators contributed to HCC metastasis. Conclusion In this work we demonstrated an integrative approach to conduct differential combinatorial regulatory network analysis in the specific context venous metastasis of HBV-HCC. Our results proposed possible transcriptional regulatory patterns underlying the different metastatic subgroups of HCC. The workflow in this study can be applied in similar context of cancer research and could also be extended to other clinical topics. PMID:23282077

  2. Suppression of death receptor 5 enhances cancer cell invasion and metastasis through activation of caspase-8/TRAF2-mediated signaling.

    PubMed

    Oh, You-Take; Yue, Ping; Wang, Dongsheng; Tong, Jing-Shan; Chen, Zhuo G; Khuri, Fadlo R; Sun, Shi-Yong

    2015-12-01

    The role of death receptor 5 (DR5), a well-known cell surface pro-apoptotic protein, in the negative regulation of invasion and metastasis of human cancer cells and the underlying mechanisms are largely unknown and were hence the focus of this study. In this report, we have demonstrated that DR5 functions to suppress invasion and metastasis of human cancer cells, as evidenced by enhanced cancer cell invasion and metastasis upon genetic suppression of DR5 either by gene knockdown or knockout. When DR5 is suppressed, FADD and caspase-8 may recruit and stabilize TRAF2 to form a metastasis and invasion signaling complex, resulting in activation of ERK and JNK/AP-1 signaling that mediate the elevation and activation of matrix metalloproteinase-1 (MMP1) and eventual promotion of cancer invasion and metastasis. Our findings thus highlight a novel non-apoptotic function of DR5 as a suppressor of human cancer cell invasion and metastasis and suggest a basic working model elucidating the underlying biology.

  3. Examining self-reported and biological stress and near misses among Emergency Medicine residents: a single-centre cross-sectional assessment in the USA.

    PubMed

    Arnetz, Bengt B; Lewalski, Philip; Arnetz, Judy; Breejen, Karen; Przyklenk, Karin

    2017-08-15

    To examine the relationship between perceived and biological stress and near misses among Emergency Medicine residents. Self-rated stress and stress biomarkers were assessed in residents in Emergency Medicine before and after a day shift. The supervising physicians and residents reported numbers of near misses. The study took place in the Emergency Department of a large trauma 1 centre, located in Detroit, USA. Residents in Emergency Medicine volunteered to participate. The sample consisted of 32 residents, with complete data on 28 subjects. Residents' supervising physicians assessed the clinical performance of each resident. Participants' preshift and postshift stress, biological stress (salivary cortisol, plasma interleukin-6, tumour necrosis factor-alpha (TNF-α) and high-sensitivity C-reactive protein), residents' and supervisors' reports of near misses, number of critically ill and patients with trauma seen during the shift. Residents' self-reported stress increased from an average preshift level of 2.79 of 10 (SD 1.81) to a postshift level of 5.82 (2.13) (p<0.001). Residents cared for an average of 2.32 (1.52) critically ill patients and 0.68 (1.06) patients with trauma. Residents reported a total of 7 near misses, compared with 11 reported by the supervising physicians. After controlling for baseline work-related exhaustion, residents that cared for more patients with trauma and had higher levels of TNF-α reported a higher frequency of near misses (R(2)=0.72; p=0.001). Residents' preshift ratings of how stressful they expected the shift to be were related to the supervising physicians' ratings of residents' near misses during the shift. Residents' own ratings of near misses were associated with residents' TNF-α, a biomarker of systemic inflammation and the number of patients with trauma seen during the shift. In contrast, supervisor reports on residents' near misses were related only to the residents' preshift expectations of how stressful the shift would

  4. Relationship of Serum Vitamin D Concentrations and Allostatic Load as a Measure of Cumulative Biological Risk among the US Population: A Cross-Sectional Study

    PubMed Central

    Frei, Regina; Haile, Sarah R.; Mutsch, Margot; Rohrmann, Sabine

    2015-01-01

    Introduction The allostatic load (AL) index is a multi-systemic measure of physiologic dysregulation known to be associated with chronic exposure to stress and adverse health outcomes. We examined the relationship between AL and serum 25-hydroxyvitamin D (25(OH)D) concentration in non-institutionalized US adults. Methods Data from the Third National Health and Nutrition Examination Survey (NHANES III, 1988–94) were used to calculate two versions of AL including 9 biomarkers and another two with 14 biomarkers (systolic and diastolic blood pressure, pulse rate, serum cholesterol, serum HDL-cholesterol, glycated hemoglobin, sex-specific waist-to-hip ratio, serum albumin, and serum C-reactive protein for AL1, and, additionally body mass index, serum triglyceride, serum creatinine, and serum herpes I & II antibodies for AL2), each set defined by predefined cut-offs or by quartiles. Serum vitamin D concentration was ranked into quartiles. Logistic regression, Poisson regression and linear regression were used to examine the association of serum 25(OH)D concentrations on AL, after adjusting for biological, physiological, socioeconomic, lifestyle, and health variables. Results Odds Ratios (OR) for high AL of the lowest 25(OH)D serum quartile were between 1.45 (95% CI: 1.28, 1.67) and 1.79 (95% CI: 1.39, 2.32) for the fully adjusted model, depending on AL version. Inverse relationships between vitamin D serum concentrations were observed for all AL versions and every adjustment. This relationship was consistent after stratification by sex, age or ethnic background. Sensitivity to low 25(OH)D concentrations was highest among the youngest group (20–39 years) with an OR of 2.11 (95% CI: 1.63, 2.73) for the lowest vitamin D quartile Q1. Conclusions Vitamin D had a consistent and statistically significant inverse association with all tested models of high AL, which remained consistent after adjusting for biological, socioeconomic, lifestyle and health variables. Our study

  5. Mutational profiling of brain metastasis from breast cancer: matched pair analysis of targeted sequencing between brain metastasis and primary breast cancer.

    PubMed

    Lee, Ji Yun; Park, Kyunghee; Lim, Sung Hee; Kim, Hae Su; Yoo, Kwai Han; Jung, Ki Sun; Song, Haa-Na; Hong, Mineui; Do, In-Gu; Ahn, TaeJin; Lee, Se Kyung; Bae, Soo Youn; Kim, Seok Won; Lee, Jeong Eon; Nam, Seok Jin; Kim, Duk-Hwan; Jung, Hae Hyun; Kim, Ji-Yeon; Ahn, Jin Seok; Im, Young-Hyuck; Park, Yeon Hee

    2015-12-22

    Although breast cancer is the second most common cause of brain metastasis with a notable increase of incidence, genes that mediate breast cancer brain metastasis (BCBM) are not fully understood. To study the molecular nature of brain metastasis, we performed gene expression profiling of brain metastasis and matched primary breast cancer (BC). We used the Ion AmpliSeq Cancer Panel v2 covering 2,855 mutations from 50 cancer genes to analyze 18 primary BC and 42 BCBM including 15 matched pairs. The most common BCBM subtypes were triple-negative (42.9%) and basal-like (36.6%). In a total of 42 BCBM samples, 32 (76.2%) harbored at least one mutation (median 1, range 0-7 mutations). Frequently detected somatic mutations included TP53 (59.5%), MLH1 (14.3%), PIK3CA (14.3%), and KIT (7.1%). We compared BCBM with patient-matched primary BC specimens. There were no significant differences in mutation profiles between the two groups. Notably, gene expression in BCBM such as TP53, PIK3CA, KIT, MLH1, and RB1 also seemed to be present in primary breast cancers. The TP53 mutation frequency was higher in BCBM than in primary BC (59.5% vs 38.9%, respectively). In conclusion, we found actionable gene alterations in BCBM that were maintained in primary BC. Further studies with functional testing and a delineation of the role of these genes in specific steps of the metastatic process should lead to a better understanding of the biology of metastasis and its susceptibility to treatment.

  6. Biological control of AFB1-producing Aspergillus section Flavi strains isolated from brewer's grains, alternative feed intended for swine production in Argentina.

    PubMed

    Asurmendi, Paula; García, María J; Ruíz, Francisco; Dalcero, Ana; Pascual, Liliana; Barberis, Lucila

    2016-07-02

    The aim of the present study was to investigate the inhibitory activity of lactic acid bacteria (LAB) isolated from brewer's grains on Aspergillus section Flavi growth and aflatoxin B1 production. The Aspergillus strains tested were inhibited by all the LAB strains assayed. The isolates Lactobacillus brevis B20, P. pentosaceus B86, Lactococcus lactis subsp. lactis B87, L. brevis B131, and Lactobacillus sp. B144 completely suppressed the fungal growth and reduced aflatoxin B1 production. In conclusion, LAB isolated from brewer's grains show a high inhibitory activity on fungal growth and aflatoxin biosynthesis by Aspergillus flavus and Aspergillus parasiticus. Further studies must be conducted to evaluate the success of in vitro assays under food environment conditions and to elucidate the antifungal mechanism of these strains.

  7. Melanoma Stem Cells and Metastasis: Mimicking Hematopoietic Cell Trafficking?

    PubMed Central

    Lee, Nayoung; Barthel, Steven R.; Schatton, Tobias

    2014-01-01

    Malignant melanoma is a highly metastatic cancer that bears responsibility for the majority of skin cancer-related deaths. Amidst the research efforts to better understand melanoma progression, there has been increasing evidence that hints at a role for a subpopulation of virulent cancer cells, termed malignant melanoma stem or initiating cells (MMICs), in metastasis formation. MMICs are characterized by their preferential ability to initiate and propagate tumor growth and their selective capacity for self-renewal and differentiation into less tumorigenic melanoma cells. The frequency of MMICs has been shown to correlate with poor clinical prognosis in melanoma. Additionally, MMICs are enriched among circulating tumor cells (CTCs) in the peripheral blood of cancer patients, suggesting that MMICs may be a critical player in the metastatic cascade. Although these links exist between MMICs and metastatic disease, the mechanisms by which MMICs may advance metastatic progression are only beginning to be elucidated. Recent studies have shown that MMICs express molecules critical for hematopoietic cell maintenance and trafficking, providing a possible explanation for how circulating MMICs could drive melanoma dissemination. We therefore propose that MMICs might fuel melanoma metastasis by exploiting homing mechanisms commonly utilized by hematopoietic cells. Here we review the biological properties of MMICs and the existing literature on their metastatic potential. We will discuss possible mechanisms by which MMICs might initiate metastases in the context of established knowledge of cancer stem cells (CSCs) in other cancers and of hematopoietic homing molecules, with a particular focus on selectins, integrins, chemokines, and chemokine receptors known to be expressed by melanoma cells. Biological understanding of how these molecules might be utilized by MMICs to propel the metastatic cascade could critically impact the development of more effective therapies for advanced

  8. Tuberculosis cervical lymphadenopathy mimics lateral neck metastasis from papillary thyroid carcinoma.

    PubMed

    Kim, Seok-Mo; Jun, Hak Hoon; Chang, Ho-Jin; Chun, Ki Won; Kim, Bup-Woo; Lee, Yong Sang; Chang, Hang-Seok; Park, Cheong Soo

    2016-06-01

    Tuberculosis (TB) lymphadenitis is a frequent cause of lymphadenopathy in areas in which TB is endemic. Cervical lymphadenopathy in TB can mimic lateral neck metastasis (LNM) from papillary thyroid carcinoma (PTC). This study evaluated the clinicopathological features of patients with PTC and TB lateral neck lymphadenopathy. Of the 9098 thyroid cancer patients who underwent thyroid cancer surgery at the Thyroid Cancer Center of Gangnam Severance Hospital between January 2009 and April 2013, 28 had PTC and showed TB lymphadenopathy of the lateral neck node. The clinicopathological features of these 28 patients were evaluated. Preoperatively, all 28 patients were diagnosed with PTC and showed cervical lymphadenopathy. All had radiological characteristics suspicious of metastasis in lateral neck nodes. Based upon the results from intraoperative frozen sections, lymph node dissection (LND) was not performed on 19 patients. Seven of eight patients who underwent LND had metastasis combined with tuberculous lymphadenopathy, with the remaining patient negative for LNM. Intraoperative sampling and frozen sectioning of lymph nodes suspicious of metastasis can help avoid unnecessary LND for tuberculous lymphadenopathy. © 2014 Royal Australasian College of Surgeons.

  9. Intra-abdominal metastasis in osteosarcoma: survey and literature review.

    PubMed

    Rejin, Kebudi; Aykan, Ozgüven A; Omer, Görgün; Ensar, Yekeler; Bilge, Bilgiç; Inci, Ayan; Harzem, Ozger

    2011-10-01

    Extrapulmonary metastasis, particularly abdominal metastasis from osteogenic sarcoma, are rare and generally appear as a solid mass of calcification as the primary tumor. The aim of this case report is to document the incidence, characteristics, treatment, and prognosis of abdominal metastasis in osteosarcomas in a single institution and to review the literature. From September 1989 to December 2002, 94 children ≤16 years of age with osteosarcomas were diagnosed and treated in the Division of Pediatric Oncology, Oncology Institute, Istanbul University. Patients with abdominal metastasis were assessed. Two girls of 94 patients (2.1%) with osteosarcoma developed abdominal metastasis. One had pulmonary metastasis at diagnosis and the other had developed lung metastasis 15 months after diagnosis. They developed abdominal metastasis 4 and 3 years after diagnosis during therapy or relapse at a median duration of 16 months (1-70 months) from initial diagnosis. All patients had metastasis to various sites, mostly lung, at the time the abdominal metastasis were detected. Treatment included surgery, chemotherapy, and radiotherapy in one and only surgery in the other patient. Both patients died at a median time of 4 months (2-6 months) from the time of abdominal metastasis with progressive disease. Abdominal metastasis in osteosarcoma is a rare event, but abdomen should be investigated in case of recurrence from osteosarcoma. The outcome for these patients is dismal in this series and in the literature.

  10. Breast metastasis of anaplastic oligodendroglioma: a case report.

    PubMed

    Alacacioglu, Ahmet; Unal, Serkan; Canpolat, Selin; Yurt, Alaattin; Oztekin, Ozgur; Coskun, Ali; Karatas, Ayse; Postaci, Hakan; Sop, Gulten

    2012-11-01

    Extracranial metastasis of primary brain tumors is rarely observed. Of all brain malignancies, glioblastomas, medulloblastomas and astrocytomas metastasize most frequently. Metastasis of oligondendroglioma is rare. We present a case of breast metastasis in a 58-year-old man with an anaplastic oligodendroglioma.

  11. [Single prostatic metastasis of a small cell lung carcinoma].

    PubMed

    Gonzalez Yañez, Isabel; Perez Lopez, Maria Eva; Rodriguez Lopez, Jose Angel; Arias Santos, Maria Dolores; Garcia Gomez, Jesus; Garcia Mata, Jesus

    2009-03-01

    To make the difference between two uncommon entities, small cell prostate carcinoma and prostatic metastasis of small cell lung cancer. We describe a case of single extrapulmonar metastasis in the prostate from small lung carcinoma. We describe a case of single extrapulmonar metastasis in the prostate from small lung carcinoma. Clinical and radiographic findings and inmunohistochemistry allow differential diagnosis.

  12. Recreational drug use in the Oslo nightlife setting: study protocol for a cross-sectional time series using biological markers, self-reported and qualitative data

    PubMed Central

    Nordfjærn, Trond; Edland-Gryt, Marit; Bretteville-Jensen, Anne Line; Buvik, Kristin; Gripenberg, Johanna

    2016-01-01

    Introduction Recreational drug use in the nightlife setting carries the risk of many negative consequences, such as violence, injuries, aberrant driving and sexual risk-taking. The aim of this study is to investigate recreational drug use and user characteristics among people visiting licensed premises, for example, nightclubs and bars, by using self-reports and biological markers. Staff of licensed premises will be asked to report drug use observations. Further, by using qualitative data, we will examine the motives, consequences and culture associated with recreational drug use. An additional aim is to compare self-reported drug use with oral fluid test (OFT) results in order to validate the different measurement methods in this context. Methods and analyses Data collection will be conducted among patrons (n=1000) outside licensed premises. On consent, patrons will be asked to anonymously complete a questionnaire, a breath alcohol concentration test and an OFT. Patrons who report use of recreational drugs in the previous 12 months will be asked to leave their contact information for a subsequent qualitative in-depth interview (n=30–40). Staff from licensed premises (n=500) will be invited during Responsible Beverage Service Training to participate in an anonymous survey. Survey data will be analysed by univariate and multivariate statistical methods and the oral fluids will be analysed for a large number of drugs using biochemical methods. Cohen's κ will be used as a measure of agreement between self-reported drug use and OFT. In-depth interviews will be coded in HyperRESEARCH and analysed using an inductive approach. Data collection will be repeated on a biannual basis until at least 2020, allowing for examination of trends in recreational drug use. Ethics and dissemination This study has been approved by the Regional Committee for Medical and Health Research Ethics. Results will be disseminated in research journals, conferences and the media. PMID:27105710

  13. Radial secondary electron dose profiles and biological effects in light-ion beams based on analytical and Monte Carlo calculations using distorted wave cross sections.

    PubMed

    Wiklund, Kristin; Olivera, Gustavo H; Brahme, Anders; Lind, Bengt K

    2008-07-01

    To speed up dose calculation, an analytical pencil-beam method has been developed to calculate the mean radial dose distributions due to secondary electrons that are set in motion by light ions in water. For comparison, radial dose profiles calculated using a Monte Carlo technique have also been determined. An accurate comparison of the resulting radial dose profiles of the Bragg peak for (1)H(+), (4)He(2+) and (6)Li(3+) ions has been performed. The double differential cross sections for secondary electron production were calculated using the continuous distorted wave-eikonal initial state method (CDW-EIS). For the secondary electrons that are generated, the radial dose distribution for the analytical case is based on the generalized Gaussian pencil-beam method and the central axis depth-dose distributions are calculated using the Monte Carlo code PENELOPE. In the Monte Carlo case, the PENELOPE code was used to calculate the whole radial dose profile based on CDW data. The present pencil-beam and Monte Carlo calculations agree well at all radii. A radial dose profile that is shallower at small radii and steeper at large radii than the conventional 1/r(2) is clearly seen with both the Monte Carlo and pencil-beam methods. As expected, since the projectile velocities are the same, the dose profiles of Bragg-peak ions of 0.5 MeV (1)H(+), 2 MeV (4)He(2+) and 3 MeV (6)Li(3+) are almost the same, with about 30% more delta electrons in the sub keV range from (4)He(2+)and (6)Li(3+) compared to (1)H(+). A similar behavior is also seen for 1 MeV (1)H(+), 4 MeV (4)He(2+) and 6 MeV (6)Li(3+), all classically expected to have the same secondary electron cross sections. The results are promising and indicate a fast and accurate way of calculating the mean radial dose profile.

  14. Murine models of breast cancer bone metastasis

    PubMed Central

    Wright, Laura E; Ottewell, Penelope D; Rucci, Nadia; Peyruchaud, Olivier; Pagnotti, Gabriel M; Chiechi, Antonella; Buijs, Jeroen T; Sterling, Julie A

    2016-01-01

    Bone metastases cause significant morbidity and mortality in late-stage breast cancer patients and are currently considered incurable. Investigators rely on translational models to better understand the pathogenesis of skeletal complications of malignancy in order to identify therapeutic targets that may ultimately prevent and treat solid tumor metastasis to bone. Many experimental models of breast cancer bone metastases are in use today, each with its own caveats. In this methods review, we characterize the bone phenotype of commonly utilized human- and murine-derived breast cell lines that elicit osteoblastic and/or osteolytic destruction of bone in mice and report methods for optimizing tumor-take in murine models of bone metastasis. We then provide protocols for four of the most common xenograft and syngeneic inoculation routes for modeling breast cancer metastasis to the skeleton in mice, including the intra-cardiac, intra-arterial, orthotopic and intra-tibial methods of tumor cell injection. Recommendations for in vivo and ex vivo assessment of tumor progression and bone destruction are provided, followed by discussion of the strengths and limitations of the available tools and translational models that aid investigators in the study of breast cancer metastasis to bone. PMID:27867497

  15. Gallbladder metastasis: spectrum of imaging findings.

    PubMed

    Barretta, Maria Luisa; Catalano, Orlando; Setola, Sergio Venanzio; Granata, Vincenza; Marone, Ugo; D'Errico Gallipoli, Adolfo

    2011-12-01

    The objective of this study is to report the diagnostic features of hematogenous gallbladder metastasis using various imaging modalities. We carried out a single-center retrospective analysis of 13 patients with gallbladder metastasis. The primary malignancy was cutaneous melanoma (11 cases), hepatocellular carcinoma (1 case), and non-Hodgkin lymphoma (1 case). All patients underwent sonography (US), with color-power-Doppler assessment in 11 cases. Contrast-enhanced US (CEUS) was performed in 8 patients, MDCT in 8, and MR imaging in 1. Four subjects studied by whole-body PET. The gallbladder lesions were first detected with US in 9 cases and with MDCT in 3 cases. The remaining patient was investigated because of hepatic fluorodeoxyglucose uptake at PET; CEUS failed to detect any liver metastasis in this subject but identified a gallbladder lesion. Typical findings included multiplicity of gallbladder vegetations, broad base, limited mural thickening, presence of contrast enhancement, absence of gallstones and gallbladder bed infiltration, presence of combined lesions within other organs. Only two patients presented an isolated location in the gallbladder and were successfully treated with surgery. Gallbladder metastasis is a rare but possible occurrence. Knowledge of the typical imaging features and careful evaluation of the gallbladder may avoid an incorrect or false negative diagnosis.

  16. Opening a Chromatin Gate to Metastasis

    PubMed Central

    Minna, John D.; Johnson, Jane E.

    2017-01-01

    What changes need to occur in a primary tumor to make it metastatic? Denny et al. address this question for small cell lung cancer (SCLC), finding that changes in genomic accessibility mediated by a single transcription factor, NFIB, comprise at least one mechanism influencing metastasis. PMID:27419866

  17. Opening a Chromatin Gate to Metastasis.

    PubMed

    Minna, John D; Johnson, Jane E

    2016-07-14

    What changes need to occur in a primary tumor to make it metastatic? Denny et al. address this question for small cell lung cancer (SCLC), finding that changes in genomic accessibility mediated by a single transcription factor, NFIB, comprise at least one mechanism influencing metastasis. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Stereotactic radiosurgery of brain metastasis from melanoma.

    PubMed

    Marchan, Edward M; Sheehan, Jason

    2012-01-01

    Brain metastasis represents the most common intracranial neoplasm in adult patients. Melanoma is the third most frequent cancer histology and consequently comprises a significant portion of brain metastasis patients. Unlike the more frequent lung and breast cancers, melanoma represents a particularly challenging entity because of its radioresistant nature. Stereotactic radiosurgery appears to overcome the inherent radioresistance of brain metastasis from melanoma and, thereby, affords a high rate of local tumor control. Reports from leading centers indicate a favorable benefit to risk profile for radiosurgery in melanoma patients. Local tumor control after radiosurgery generally exceeds 80%, and neurological complications as a result of radiosurgery are infrequent. A higher performance status and lower intracranial tumor burden in melanoma patients at the time of radiosurgery are associated with longer survival. Radiosurgery may be used in conjunction upfront with radiotherapy, resection, and chemotherapy or as a salvage therapy in selected melanoma patients. Careful radiological and neurological follow-up is required to assess local tumor control and distant intracranial disease progression. Further clinical studies will be required to better define the role of upfront and salvage radiosurgery in selected cohorts of patients with brain metastasis from melanoma. However, it appears likely that radiosurgery will play an expanded role in the overall management of these patients.

  19. Presumed choroidal metastasis of Merkel cell carcinoma

    SciTech Connect

    Small, K.W.; Rosenwasser, G.O.; Alexander, E. III; Rossitch, G.; Dutton, J.J. )

    1990-05-01

    Merkel cell carcinoma is a rare skin tumor of neural crest origin and is part of the amine precursor uptake and decarboxylase system. It typically occurs on the face of elderly people. Distant metastasis is almost uniformly fatal. Choroidal metastasis, to our knowledge, has not been described. We report a patient with Merkel cell carcinoma who had a synchronous solid choroidal tumor and a biopsy-proven brain metastasis. Our 56-year-old patient presented with a rapidly growing, violaceous preauricular skin tumor. Computed tomography of the head disclosed incidental brain and choroidal tumors. Light and electron microscopy of biopsy specimens of both the skin and the brain lesions showed Merkel cell carcinoma. Ophthalmoscopy, fluorescein angiography, and A and B echography revealed a solid choroidal mass. The brain and skin tumors responded well to irradiation. A radioactive episcleral plaque was applied subsequently to the choroidal tumor. All tumors regressed, and the patient was doing well 28 months later. To our knowledge this is the first case of presumed choroidal metastasis of Merkel cell carcinoma.

  20. Cerebral metastasis from malignant pleural mesothelioma.

    PubMed

    El Molla, Mohamed; Gragnaniello, Cristian; Al-Khawaja, Darweesh; Chiribao-Negri, Concepcion; Eftekhar, Behzad

    2013-09-26

    Malignant mesothelioma is an uncommon, highly invasive tumor derived from the mesothelial cells of pleura or peritoneum characterized by poor outcome. Mesothelioma was thought to metastasize locally only via direct invasion and not have distant spread. Distant metastases were discovered mostly on post-mortem examination. The authors present a case of 62-year-old man with pleural mesothelioma and brain metastasis.

  1. Breast cancer metastasis and the lymphatic system

    PubMed Central

    RAHMAN, MUNAZZAH; MOHAMMED, SULMA

    2015-01-01

    Breast cancer remains the leading cause of cancer mortality worldwide, despite a significant decline in death rates due to early detection. The majority of cancer mortalities are due to the metastasis of tumor cells to other organs. Metastasis or tumor cell dissemination occurs via the hematogenous and lymphatic systems. For many carcinomas, the dissemination of tumor cells via lymphatic drainage of the tumor is the most common metastatic route. Such lymphatic drainage collects at the regional lymph nodes and the dissection and pathological examination of these nodes for lodged cancer cells is the gold standard procedure to detect metastasis. The present report provides an overview of the lymphatic system and its clinical significance as a prognostic factor, in addition to the interactions between the primary tumor and its microenvironment, and the influence of genomic subtypes on the resulting organ-specific pattern of tumor cell dissemination. It also examines the seemingly protracted asymptomatic period, during which the disseminated cells remain dormant, leading to the manifestation of metastasis decades after the successful treatment of the primary tumor. PMID:26622656

  2. Altered Tumor-Cell Glycosylation Promotes Metastasis

    PubMed Central

    Häuselmann, Irina; Borsig, Lubor

    2014-01-01

    Malignant transformation of cells is associated with aberrant glycosylation presented on the cell-surface. Commonly observed changes in glycan structures during malignancy encompass aberrant expression and glycosylation of mucins; abnormal branching of N-glycans; and increased presence of sialic acid on proteins and glycolipids. Accumulating evidence supports the notion that the presence of certain glycan structures correlates with cancer progression by affecting tumor-cell invasiveness, ability to disseminate through the blood circulation and to metastasize in distant organs. During metastasis tumor-cell-derived glycans enable binding to cells in their microenvironment including endothelium and blood constituents through glycan-binding receptors – lectins. In this review, we will discuss current concepts how tumor-cell-derived glycans contribute to metastasis with the focus on three types of lectins: siglecs, galectins, and selectins. Siglecs are present on virtually all hematopoietic cells and usually negatively regulate immune responses. Galectins are mostly expressed by tumor cells and support tumor-cell survival. Selectins are vascular adhesion receptors that promote tumor-cell dissemination. All lectins facilitate interactions within the tumor microenvironment and thereby promote cancer progression. The identification of mechanisms how tumor glycans contribute to metastasis may help to improve diagnosis, prognosis, and aid to develop clinical strategies to prevent metastasis. PMID:24592356

  3. Neural Regulation of Breast Cancer Metastasis

    DTIC Science & Technology

    2009-10-01

    and F. Entschladen, The norepinephrine-driven metastasis development of PC-3 human prostate cancer cells in BALB/c nude mice is inhibited by beta ... blockers . Int J Cancer, 2006. 118(11): p. 2744-9. 8. Draoui, A, B. Vandewalle, L. Hornez, F. Revillion, and J. Lefebvre, Beta-adrenergic receptors in

  4. Three-dimensional context regulation of metastasis

    PubMed Central

    Erler, Janine T.; Weaver, Valerie M.

    2009-01-01

    Tumor progression ensues within a three-dimensional microenvironment that consists of cellular and non-cellular components. The extracellular matrix (ECM) and hypoxia are two non-cellular components that potently influence metastasis. ECM remodeling and collagen cross-linking stiffen the tissue stroma to promote transformation, tumor growth, motility and invasion, enhance cancer cell survival, enable metastatic dissemination, and facilitate the establishment of tumor cells at distant sites. Matrix degradation can additionally promote malignant progression and metastasis. Tumor hypoxia is functionally linked to altered stromal-epithelial interactions. Hypoxia additionally induces the expression of pro-migratory, survival and invasion genes, and up-regulates expression of ECM components and modifying enzymes, to enhance tumor progression and metastasis. Synergistic interactions between matrix remodeling and tumor hypoxia influence common mechanisms that maximize tumor progression and cooperate to drive metastasis. Thus, clarifying the molecular pathways by which ECM remodeling and tumor hypoxia intersect to promote tumor progression should identify novel therapeutic targets. PMID:18814043

  5. Characteristics of a thyroid carcinoma cell line derived from spinal metastasis

    PubMed Central

    Zhou, Zhenhua; Li, Yan; Yan, Xu; Wang, Xudong; Chen, Su; Xiao, Jianru

    2016-01-01

    A thyroid carcinoma cell line named THY28 was established through primary culture of the surgical specimens, which were derived from a Chinese patient with spinal metastasis. The cell morphology, growth kinetics, cell cycle, chromosome number, cell capability of migration, tumorigenicity and cytogenetic features of the cell line were investigated. THY28 cells were subcultured in vitro for more than 50 passages with a human karyotype. The modal number of its chromosomes was mainly from 67 to 85. The doubling time of THY28 cells was 56 hours. The histopathological features of xenograft induced by THY28 cells were consistent with the characteristics of thyroid cancer. The biological and molecular properties of THY28 cells were not entirely consistent with those of other thyroid carcinoma cells such as SW579 and TT cells, indicating biological differences between primary and metastatic thyroid carcinoma cell lines. We have established a novel thyroid carcinoma cell line derived from spinal metastasis, which will provide a useful model for biological or therapeutic studies of thyroid carcinoma metastasis. PMID:27811013

  6. S100A4 in Cancer Metastasis: Wnt Signaling-Driven Interventions for Metastasis Restriction

    PubMed Central

    Dahlmann, Mathias; Kobelt, Dennis; Walther, Wolfgang; Mudduluru, Giridhar; Stein, Ulrike

    2016-01-01

    The aberrant activity of Wnt signaling is an early step in the transformation of normal intestinal cells to malignant tissue, leading to more aggressive tumors, and eventually metastases. In colorectal cancer (CRC), metastasis accounts for about 90% of patient deaths, representing the most lethal event during the course of the disease and is directly linked to patient survival, critically limiting successful therapy. This review focuses on our studies of the metastasis-inducing gene S100A4, which we identified as transcriptional target of β-catenin. S100A4 increased migration and invasion in vitro and metastasis in mice. In patient CRC samples, high S100A4 levels predict metastasis and reduced patient survival. Our results link pathways important for tumor progression and metastasis: the Wnt signaling pathway and S100A4, which regulates motility and invasiveness. S100A4 suppression by interdicting Wnt signaling has potential for therapeutic intervention. As proof of principle, we applied S100A4 shRNA systemically and prevented metastasis in mice. Furthermore, we identified small molecule inhibitors from high-throughput screens of pharmacologically active compounds employing an S100A4 promoter-driven reporter. Best hits act, as least in part, via intervening in the Wnt pathway and restricted metastasis in mouse models. We currently translate our findings on restricting S100A4-driven metastasis into clinical practice. The repositioned FDA-approved drug niclosamide, targeting Wnt signaling, is being tested in a prospective phase II clinical trial for treatment of CRC patients. Our assay for circulating S100A4 transcripts in patient blood is used to monitor treatment success. PMID:27331819

  7. Recreational drug use in the Oslo nightlife setting: study protocol for a cross-sectional time series using biological markers, self-reported and qualitative data.

    PubMed

    Nordfjærn, Trond; Edland-Gryt, Marit; Bretteville-Jensen, Anne Line; Buvik, Kristin; Gripenberg, Johanna

    2016-04-22

    Recreational drug use in the nightlife setting carries the risk of many negative consequences, such as violence, injuries, aberrant driving and sexual risk-taking. The aim of this study is to investigate recreational drug use and user characteristics among people visiting licensed premises, for example, nightclubs and bars, by using self-reports and biological markers. Staff of licensed premises will be asked to report drug use observations. Further, by using qualitative data, we will examine the motives, consequences and culture associated with recreational drug use. An additional aim is to compare self-reported drug use with oral fluid test (OFT) results in order to validate the different measurement methods in this context. Data collection will be conducted among patrons (n=1000) outside licensed premises. On consent, patrons will be asked to anonymously complete a questionnaire, a breath alcohol concentration test and an OFT. Patrons who report use of recreational drugs in the previous 12 months will be asked to leave their contact information for a subsequent qualitative in-depth interview (n=30-40). Staff from licensed premises (n=500) will be invited during Responsible Beverage Service Training to participate in an anonymous survey. Survey data will be analysed by univariate and multivariate statistical methods and the oral fluids will be analysed for a large number of drugs using biochemical methods. Cohen's κ will be used as a measure of agreement between self-reported drug use and OFT. In-depth interviews will be coded in HyperRESEARCH and analysed using an inductive approach. Data collection will be repeated on a biannual basis until at least 2020, allowing for examination of trends in recreational drug use. This study has been approved by the Regional Committee for Medical and Health Research Ethics. Results will be disseminated in research journals, conferences and the media. Published by the BMJ Publishing Group Limited. For permission to use

  8. Predictive factors for lymph node metastasis in early gastric cancer with lymphatic invasion after endoscopic resection.

    PubMed

    Park, Ji Won; Ahn, Sangjeong; Lee, Hyuk; Min, Byung-Hoon; Lee, Jun Haeng; Rhee, Poong-Lyul; Kim, Kyoung-Mee; Kim, Jae J

    2017-04-04

    Lymph node (LN) metastasis is found in only about 5-10% of the patients who undergo additional surgery after non-curative endoscopic resection. Lymphatic invasion after endoscopic submucosal dissection (ESD) is regarded as non-curative resection due to risk of reginal LN metastasis. This study was aimed to identify clinicopathologic predictive factors for LN metastasis in early gastric cancer (EGC) with lymphatic invasion after endoscopic resection. Among a total of 2036 patients who underwent endoscopic resection for EGC at Samsung Medical Center from April 2000 to May 2011, 146 patients were diagnosed with lymphatic invasion. And 123 patients who had gastrectomy with LN dissection due to presence of lymphatic invasion as one of the non-curative factors were included in this study. Demographics, endoscopic tumor findings, histological findings, surgical findings with pathologic reports, and follow-up data were collected from the patient's medical records. Pathological re-evaluation of resected specimens was performed. Among a total of 123 patients, LN metastases were found in seven patients (5.7%). The univariate analysis revealed that the LN metastasis was significantly more frequent in patients with certain morphology of lymphatic invasion that shows adhesion to endothelium of lymphatic tumor emboli (p = 0.016), higher number of lymphatic tumor emboli in whole section (p < 0.001) and papillary adenocarcinoma component (p = 0.024). In multivariate analysis, the number of lymphatic tumor emboli [OR 93.5, 95% CI (2.62-3330.81)] and the presence of papillary adenocarcinoma component [OR 552.5, 95% CI (1.20-254871.81)] were identified as independent predictors of LN metastasis in patients with lymphatic invasion after endoscopic resection. The number of lymphatic tumor emboli and the presence of papillary adenocarcinoma component were significant predictors for LN metastasis in patients with lymphatic invasion after endoscopic resection.

  9. Genomic Alteration During Metastasis of Lung Adenocarcinoma.

    PubMed

    Tan, Qiang; Cui, Jian; Huang, Jia; Ding, Zhengping; Lin, Hao; Niu, Xiaomin; Li, Zhiming; Wang, Guan; Luo, Qingquan; Lu, Shun

    2016-01-01

    Recurrent gene mutation has been identified by the analysis of exonic DNA from lung adenocarcinoma, but its progression has not been extensively profiled. The investigation of the mutational landscape of tumors provides new insights into cancer genome evolution and further discovers the interplay of somatic mutation, adaptation of clones to their environment and natural selection. Cancer development involves cycles of genomic damage, epigenetic deregulation, and increased cellular proliferation that eventually culminate in the carcinoma phenotype. Comparative whole exome sequencing of both primary and metastatic tumor tissues from four patients of stage IV lung adenocarcinoma patients with chest wall metastasis was performed. Both primary and metastatic tumors were diagnosed through biopsy followed by surgical resection. All tumor specimens were cut into several pieces to assess potential heterogenic clones within the tumor tissue. Adjacent normal lung tissue was also obtained to provide germline mutation background. By modeling and analyzing progression of the cancer metastasis based on non-synonymous variants, we defined the extent of heterogeneity of cancer genomes and identified similar cancer evolution pattern in the four patients: metastasis was an early event occurring right after the primary cancer formation and evolution in the metastatic tumor was continuously and simultaneously in progression with that in the primary tumor. By characterizing the clonal hierarchy of genetic lesions, we further charted a pathway of oncogenic events along which genes may drive lung adenocarcinoma metastasis, such as TAS2R31 and UMODL1, involving in G-protein coupled receptor protein signaling pathway. The candidate genes identified in this study may become targets for the treatment of lung adenocarcinoma metastasis. © 2016 S. Karger AG, Basel.

  10. A case report of thyroid gland metastasis associated with lung metastasis from colon cancer.

    PubMed

    Nakamura, Keisuke; Nozawa, Keijiro; Aoyagi, Yoshiko; Ishihara, Soichiro; Matsuda, Keiji; Fukushima, Junichi; Watanabe, Toshiaki

    2011-01-01

    Thyroid gland metastasis of malignant tumors is observed in 1.9% to 9.5% of histologically examined autopsy cases. Thyroid metastasis from colon cancer is extremely rare and the prognosis is poor. Here we report a case of lung metastasis and thyroid gland metastasis following sigmoid colon cancer surgery. In 2000, a 58-year-old woman underwent a sigmoid colectomy for sigmoid colon cancer. In 2005, a metastatic lung tumor was detected by chest CT. The patient underwent a partial thoracoscopic resection of the left lung in April 2005. On a CT scan taken 3 years and 4 months after the lung resection, a tumor mass was observed in the left lung and a low-absorption region with an unclear border was seen in the left lobe of the thyroid gland. Thyroid aspiration cytology showed adenocarcinoma, and a diagnosis of thyroid gland metastasis from sigmoid colon cancer was made. In April 2008 a subtotal thyroidectomy was performed. Following surgery, the patient underwent chemotherapy with mFOLFOX6 and bevacizumab. Nevertheless a number of lung metastases and expressions of lung metastasis were subsequently observed. Histopathological examination revealed a number of metastases of differentiated papillary adenocarcinoma in the thyroid gland from colon cancer.

  11. Organ Preference of Cancer Metastasis and Metastasis-Related Cell Adhesion Molecules Including Carbohydrates.

    PubMed

    Kawaguchi, Takanori

    2016-01-01

    This review starts on one of our special interests, the organ preference of metastasis. We examined data on 1,117 autopsy cases and found that the organ distribution of metastasis of cancers of the lung, pancreas, stomach, colon, rectum, uterine cervix, liver, bile duct, and esophagus involved the lung, liver, adrenal gland, bone/bone marrow, lymph node, and pleura/peritoneum. Cancers of the kidney, thyroid, ovary, choriocarcinoma, and breast, however, manifested different metastatic patterns. The distribution of leukemia and lymphoma metastases was quite different from that of epithelial cancers. On the basis of experimental studies, we believe that the anatomical-mechanical hypothesis should be replaced by the microinjury hypothesis, which suggests that tissue microinjury induced by temporal tumor cell embolization is crucial for successful metastasis. This hypothesis may actually reflect the so-called inflammatory oncotaxis concept. To clarify the mechanisms underlying metastasis, we developed an experimental model system of a rat hepatoma AH7974 that embraced substrate adhesiveness. This model did not prove a relationship between substrate-adhesion potential and metastatic lung-colonizing potential of tumor cells, but metastatic potential was correlated with the expression of the laminin carbohydrate that was recognized by Griffonia (Bandeiraea) simplicifolia isolectin G4. Therefore, we investigated the relationship between carbohydrate expression profiles and metastasis and prognosis. We indeed found an intimate relationship between the carbohydrate expression of cancer cells and the progression of malignant tumors, organ preference of metastasis, metastatic potential of tumor cells, and prognosis of patients.

  12. Evolution & the Cesarean Section Rate

    ERIC Educational Resources Information Center

    Walsh, Joseph A.

    2008-01-01

    "Nothing in biology makes sense except in the light of evolution." This was the title of an essay by geneticist Theodosius Dobzhansky writing in 1973. Many causes have been given for the increased Cesarean section rate in developed countries, but biologic evolution has not been one of them. The C-section rate will continue to rise, because the…

  13. Evolution & the Cesarean Section Rate

    ERIC Educational Resources Information Center

    Walsh, Joseph A.

    2008-01-01

    "Nothing in biology makes sense except in the light of evolution." This was the title of an essay by geneticist Theodosius Dobzhansky writing in 1973. Many causes have been given for the increased Cesarean section rate in developed countries, but biologic evolution has not been one of them. The C-section rate will continue to rise, because the…

  14. KIAA1377 is associated with lymph node metastasis in esophageal squamous cell carcinoma.

    PubMed

    Zheng, Shu-Tao; Yang, Chen-Chen; Liu, Qing; Liu, Tao; Lu, Mang; Dai, Fang; Gao, Xiang-Peng; Sheyhidin, Ilyar; Lu, Xiao-Mei

    2016-12-01

    KIAA1377, of which there are few studies regarding cell biology and neurological diseases, has been found to be significantly amplified in esophageal squamous cell carcinoma (ESCC) with lymph node metastasis compared with ESCC without lymph node metastasis. This suggests that KIAA1377 may play a role in the lymph node metastasis of ESCC. There has, to the best of our knowledge, been no study performed to investigate the role of KIAA1377 in ESCC. In the present study, the expression of KIAA1377 was detected by immunohistochemistry, and its expression was statistically analyzed with clinicopathological parameters, using commercially obtained tissue arrays consisting of 86 cases of ESCC and 79 paired controls. KIAA1377 was knocked down ex vivo using transient transfection with specific small hairpin RNA (shRNA) vectors into ESCC TE-1 and EC9706 cell lines whose endogenous KIAA1377 level was highest. The variation of proliferation, migration and invasion were evaluated using methyl thiazolyl tetrazolium, wound healing and Transwell assay, respectively. It was found in vivo that KIAA1377 expression was significantly associated with lymph node metastasis and differentiation, and ex vivo that knockdown of KIAA1377 cannot significantly affect proliferation and mobility in the ESCC cell line TE-1. Overall, this is the first study suggesting that KIAA1377 may play a role in the lymph node micrometastasis of ESCC.

  15. Engineering a biomimetic three-dimensional nanostructured bone model for breast cancer bone metastasis study.

    PubMed

    Zhu, Wei; Wang, Mian; Fu, Yebo; Castro, Nathan J; Fu, Sidney W; Zhang, Lijie Grace

    2015-03-01

    Traditional breast cancer (BrCa) bone metastasis models contain many limitations with regards to controllability, reproducibility and flexibility of design. In this study, a novel biomimetic bone microenvironment was created by integrating hydroxyapatite (HA) and native bioactive factors deposited by osteogenic induction of human bone marrow mesenchymal stem cells (MSCs) within a cytocompatible chitosan hydrogel. It was found that a 10% nanocrystalline HA (nHA) chitosan scaffold exhibited the highest BrCa adhesion and proliferation when compared to chitosan scaffolds with 20% nHA, 10% and 20% microcrystalline HA as well as amorphous HA. This 3-D tunable bone scaffold can provide a biologically relevant environment, increase cell-cell and cell-matrix interactions as found in native bone, and retain the behavior of BrCa cells with different metastasis potential (i.e. highly metastatic MDA-MB-231, less metastatic MCF-7 and transfected MDA-MB-231). The co-culture of MSCs and MDA-MB-231 in this bone model illustrated that MSCs have the capacity to upregulate the expression of the well-known metastasis-associated gene metadherin within BrCa cells. In summary, this study illustrates the ability of our 3-D bone model to create a biomimetic environment conducive to recapitulating the behavior of metastatic BrCa cells, making it a promising tool for in vitro BrCa cell bone metastasis study and for the discovery of potential therapeutics.

  16. KIAA1377 is associated with lymph node metastasis in esophageal squamous cell carcinoma

    PubMed Central

    Zheng, Shu-Tao; Yang, Chen-Chen; Liu, Qing; Liu, Tao; Lu, Mang; Dai, Fang; Gao, Xiang-Peng; Sheyhidin, Ilyar; Lu, Xiao-Mei

    2016-01-01

    KIAA1377, of which there are few studies regarding cell biology and neurological diseases, has been found to be significantly amplified in esophageal squamous cell carcinoma (ESCC) with lymph node metastasis compared with ESCC without lymph node metastasis. This suggests that KIAA1377 may play a role in the lymph node metastasis of ESCC. There has, to the best of our knowledge, been no study performed to investigate the role of KIAA1377 in ESCC. In the present study, the expression of KIAA1377 was detected by immunohistochemistry, and its expression was statistically analyzed with clinicopathological parameters, using commercially obtained tissue arrays consisting of 86 cases of ESCC and 79 paired controls. KIAA1377 was knocked down ex vivo using transient transfection with specific small hairpin RNA (shRNA) vectors into ESCC TE-1 and EC9706 cell lines whose endogenous KIAA1377 level was highest. The variation of proliferation, migration and invasion were evaluated using methyl thiazolyl tetrazolium, wound healing and Transwell assay, respectively. It was found in vivo that KIAA1377 expression was significantly associated with lymph node metastasis and differentiation, and ex vivo that knockdown of KIAA1377 cannot significantly affect proliferation and mobility in the ESCC cell line TE-1. Overall, this is the first study suggesting that KIAA1377 may play a role in the lymph node micrometastasis of ESCC. PMID:28144289

  17. MicroRNA-374a activates Wnt/β-catenin signaling to promote breast cancer metastasis.

    PubMed

    Cai, Junchao; Guan, Hongyu; Fang, Lishan; Yang, Yi; Zhu, Xun; Yuan, Jie; Wu, Jueheng; Li, Mengfeng

    2013-02-01

    Tumor metastasis involves a series of biological steps during which the tumor cells acquire the ability to invade surrounding tissues and survive outside the original tumor site. During the early stages, the cancer cells undergo an epithelial-mesenchymal transition (EMT). Wnt/β-catenin signaling is known to drive EMT and metastasis. Here we report that Wnt/β-catenin signaling is hyperactivated in metastatic breast cancer cells that express microRNA 374a (miR-374a). In breast cancer cell lines, ectopic overexpression of miR-374a promoted EMT and metastasis both in vitro and in vivo. Furthermore, miR-374a directly targeted and suppressed multiple negative regulators of the Wnt/β-catenin signaling cascade, including WIF1, PTEN, and WNT5A. Notably, miR-374a was markedly upregulated in primary tumor samples from patients with distant metastases and was associated with poor metastasis-free survival. These results demonstrate that miR-374a maintains constitutively activated Wnt/β-catenin signaling and may represent a therapeutic target for early metastatic breast cancer.

  18. A zebrafish xenograft model for studying human cancer stem cells in distant metastasis and therapy response.

    PubMed

    Chen, L; Groenewoud, A; Tulotta, C; Zoni, E; Kruithof-de Julio, M; van der Horst, G; van der Pluijm, G; Ewa Snaar-Jagalska, B

    2017-01-01

    Lethal and incurable bone metastasis is one of the main causes of death in multiple types of cancer. A small subpopulation of cancer stem/progenitor-like cells (CSCs), also known as tumor-initiating cells from heterogenetic cancer is considered to mediate bone metastasis. Although over the past decades numerous studies have been performed in different types of cancer, it is still difficult to track small numbers of CSCs during the onset of metastasis. With use of noninvasive high-resolution imaging, transparent zebrafish embryos can be employed to dynamically visualize cancer progression and reciprocal interaction with stroma in a living organism. Recently we established a zebrafish CSC-xenograft model to visually and functionally analyze the role of CSCs and their interactions with the microenvironment at the onset of metastasis. Given the highly conserved human and zebrafish genome, transplanted human cancer cells are able to respond to zebrafish cytokines, modulate the zebrafish microenvironment, and take advantage of the zebrafish stroma during cancer progression. This chapter delineates the zebrafish CSC-xenograft model as a useful tool for both CSC biological study and anticancer drug screening. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Effects of Chemotherapy-Induced Alterations in Cell Mechanical Properties on Cancer Metastasis

    NASA Astrophysics Data System (ADS)

    Prathivadhi, Sruti; Ekpenyong, Andrew; Nichols, Michael; Taylor, Carolyn; Ning, Jianhao

    Biological cells can modulate their mechanical properties to suit their functions and in response to changes in their environment. Thus, mechanical phenotyping of cells has been employed for tracking stem cell differentiation, bacterial infection, cell death, etc. Malignant transformation of cells also involves changes in mechanical properties. However, the extent to which mechanical properties of cancer cells contribute to metastasis is not well understood. Yet, more than 90% of all cancer deaths are directly related to metastasis. Transit of cells through the microcirculation is one of the key features of metastasis. We hypothesize that cancer treatment regimens do inadvertently alter cell mechanical properties in ways that might promote cancer metastasis. We use a microfluidic microcirculation mimetic (MMM) platform which mimics the capillary constrictions of the pulmonary and peripheral microcirculation to determine if in-vivo-like mechanical stimuli can evoke different responses from cells subjected to various cancer drugs. In particular, we show that cancer cells treated with chemotherapeutic drugs such as daunorubicin, become more deformable at short timescales (0.1 s) and transit faster through the device. Our results are first steps in evaluating the pro- or anti-metastatic effects of chemotherapeutic drugs based on their induced alterations in cell mechanical properties.

  20. Characterization of long non-coding RNA expression profiles in lymph node metastasis of early-stage cervical cancer

    PubMed Central

    SHANG, CHUNLIANG; ZHU, WENHUI; LIU, TIANYU; WANG, WEI; HUANG, GUANGXIN; HUANG, JIAMING; ZHAO, PEIZHEN; ZHAO, YUNHE; YAO, SHUZHONG

    2016-01-01

    Pelvic lymph node metastasis (PLNM) is an independent prognostic parameter and determines the treatment strategies of cervical cancer. Increasing evidence indicates that long non-coding RNAs (lncRNAs) play a crucial role in the process of tumor biological functions. This study aimed to mine lymph node metastasis-associated lncRNAs and investigate their potential pathophysiological mechanism in cervical cancer lymph node metastasis. We applied the lncRNA-mining approach to identify lncRNA transcripts represented on Affymetrix human genome U133 plus 2.0 microarrays from Gene Expression Omnibus (GEO) and then by validation in clinical specimens. The biological role and molecular mechanism of these lncRNAs were predicted by bioinformatic analysis. Subsequently, a receiver operating characteristic (ROC) curve and survival curve were conducted to evaluate the diagnostic and prognostic value of candidate lncRNAs. In total, 234 differentially expressed lncRNAs were identified to significantly associate with pelvic lymph node metastasis in early-stage cervical cancer. Our qRT-PCR results were consistent with the mining analysis (P<0.05). The functional enrichment analysis suggested that these lncRNAs may be involved in the biological process of lymph node metastasis. The ROC curves demonstrated satisfactory discrimination power of MIR100HG and AC024560.2 with areas under the curve of 0.801 and 0.837, respectively. Survival curve also indicated that patients with high MIR100HG expression had a tendency of poor prognosis. This is the first study to successfully mine the lncRNA expression patterns in PLNM of early-stage cervical cancer. MIR100HG and AC024560.2 may be a potential biomarkers of PLNM and these lncRNAs may provide broader perspective for combating cervical cancer metastasis. PMID:27035672

  1. Characterization of long non-coding RNA expression profiles in lymph node metastasis of early-stage cervical cancer.

    PubMed

    Shang, Chunliang; Zhu, Wenhui; Liu, Tianyu; Wang, Wei; Huang, Guangxin; Huang, Jiaming; Zhao, Peizhen; Zhao, Yunhe; Yao, Shuzhong

    2016-06-01

    Pelvic lymph node metastasis (PLNM) is an independent prognostic parameter and determines the treatment strategies of cervical cancer. Increasing evidence indicates that long non-coding RNAs (lncRNAs) play a crucial role in the process of tumor biological functions. This study aimed to mine lymph node metastasis-associated lncRNAs and investigate their potential pathophysiological mechanism in cervical cancer lymph node metastasis. We applied the lncRNA-mining approach to identify lncRNA transcripts represented on Affymetrix human genome U133 plus 2.0 microarrays from Gene Expression Omnibus (GEO) and then by validation in clinical specimens. The biological role and molecular mechanism of these lncRNAs were predicted by bioinformatic analysis. Subsequently, a receiver operating characteristic (ROC) curve and survival curve were conducted to evaluate the diagnostic and prognostic value of candidate lncRNAs. In total, 234 differentially expressed lncRNAs were identified to significantly associate with pelvic lymph node metastasis in early-stage cervical cancer. Our qRT-PCR results were consistent with the mining analysis (P<0.05). The functional enrichment analysis suggested that these lncRNAs may be involved in the biological process of lymph node metastasis. The ROC curves demonstrated satisfactory discrimination power of MIR100HG and AC024560.2 with areas under the curve of 0.801 and 0.837, respectively. Survival curve also indicated that patients with high MIR100HG expression had a tendency of poor prognosis. This is the first study to successfully mine the lncRNA expression patterns in PLNM of early-stage cervical cancer. MIR100HG and AC024560.2 may be a potential biomarkers of PLNM and these lncRNAs may provide broader perspective for combating cervical cancer metastasis.

  2. Section 3--selected biological properties of tissues: potential determinants of susceptibility to ultrasound-induced bioeffects. American Institute of Ultrasound in Medicine.

    PubMed

    2000-02-01

    hemorrhage, data from studies using pulsed ultrasound are less abundant but suggest that species differences in susceptibility to pulsed ultrasound-induced lung hemorrhage may also possibly exist. Species differences in susceptibility to ultrasound-induced lung hemorrhage appear inversely related to the thickness of the visceral pleura of the lung. Although pulsed ultrasound can induce hemorrhage in the intestine of mice, there are no data from intestinal studies currently available suggesting there are species differences in susceptibility to pulsed ultrasound. There exists, for the intestine, information similar to that reported in the lung, which documents innate tissue and organ differences among mammalian species that could influence susceptibility to pulsed ultrasound. The analysis, interpretation, and speculation regarding bioeffects and tissue properties documented in this section and the conclusions presented likely will mature and evolve as new information becomes available through additional in vivo bioeffects research.

  3. P62: An emerging oncotarget for osteolytic metastasis

    PubMed Central

    Zhang, Jing; Yang, Zuozhang; Dong, Jian

    2016-01-01

    Bone metastasis occurs in the majority of late-stage tumors with poor prognosis. It is mainly classified as osteoblastic metastasis and osteolytic metastasis. The pathogenesis of osteolytic metastasis is a “vicious cycle” between tumor cells and bone cells (primarily the osteoclasts), which is mediated by secretory factors. The P62 adapter protein is a versatile multitasker between tumor cells and bone cells. The overexpression of P62 has been detected among a variety of tumors, playing positive roles in both tumorigenesis and metastasis. Moreover, P62 is an important modulator of the osteoclastogenesis pathway. Therefore, the ability of P62 to modulate tumors and osteoclasts suggests that it may be a feasible oncotarget for bone metastasis, especially for osteolytic metastasis. Recent research has shown that a P62 DNA vaccine triggered effective anti-tumor, anti-metastatic and anti-osteoporotic activities. Growing lines of evidence point to P62 as an emerging oncotarget for osteolytic metastasis. In this review, we outline the different roles of P62 in tumor cells and osteoclasts, focusing on the P62-related signaling pathway in key steps of osteolytic metastasis, including tumorigenesis, metastasis and osteoclastogenesis. Finally, we discuss the newest observations on P62 as an oncotarget for osteolytic metastasis treatment. PMID:26998424

  4. P62: An emerging oncotarget for osteolytic metastasis.

    PubMed

    Zhang, Jing; Yang, Zuozhang; Dong, Jian

    2016-03-01

    Bone metastasis occurs in the majority of late-stage tumors with poor prognosis. It is mainly classified as osteoblastic metastasis and osteolytic metastasis. The pathogenesis of osteolytic metastasis is a "vicious cycle" between tumor cells and bone cells (primarily the osteoclasts), which is mediated by secretory factors. The P62 adapter protein is a versatile multitasker between tumor cells and bone cells. The overexpression of P62 has been detected among a variety of tumors, playing positive roles in both tumorigenesis and metastasis. Moreover, P62 is an important modulator of the osteoclastogenesis pathway. Therefore, the ability of P62 to modulate tumors and osteoclasts suggests that it may be a feasible oncotarget for bone metastasis, especially for osteolytic metastasis. Recent research has shown that a P62 DNA vaccine triggered effective anti-tumor, anti-metastatic and anti-osteoporotic activities. Growing lines of evidence point to P62 as an emerging oncotarget for osteolytic metastasis. In this review, we outline the different roles of P62 in tumor cells and osteoclasts, focusing on the P62-related signaling pathway in key steps of osteolytic metastasis, including tumorigenesis, metastasis and osteoclastogenesis. Finally, we discuss the newest observations on P62 as an oncotarget for osteolytic metastasis treatment.

  5. Experimental model of pulmonary metastasis treatment with IFNalpha.

    PubMed

    Martínez, Cristina; Vicente, Vicente; Yáñez, M Josefa; García, Juana M; Canteras, Manuel; Alcaraz, Miguel

    2005-07-08

    Melanoma shows the high rates of mortality, preferentially by metastasis, and the failure of chemotherapy. We inoculated 30 B16F10 Swiss mice with 5 x 10(5) melanocytes. The mice were then inoculated with 150,000; 300,000; 600,000 and 1,200,000 IU/mouse of interferon alpha. A count of the metastatic nodules of the lung surface and the microscopic study were made by image analysis on five histological sections, calculating the implantation percentage and tumoral growth and invasion index. Treatment with the three highest doses of interferon alpha resulted in a dose-dependent reduction of the number of metastatic nodules and invaded area. A correlation existing between the parameters studied and the different antitumoral effects observed.

  6. Basosquamous carcinoma with systemic metastasis in a miniature Pinscher.

    PubMed

    Shin, Sang-Kyung; Kim, Tae-Wang; Youm, So-Young; Kim, Gonhyung; Na, Ki-Jeong; Chang, Dongwoo; Ahn, Byeongwoo

    2011-11-01

    Basosquamous carcinoma (BSCC) is a rare malignancy, primarily composed of basal cells with foci of squamous differentiation. It is considered to be histologically an intermediate type between basal cell carcinoma and squamous cell carcinoma, and is known to have aggressive behaviors. BSCC occurred in a 17-year-old female minipin with a history of surgical excision for a mammary tumor. The right upper hindlimb was severely enlarged to 8 x 5 cm. Cross-section showed a homogenous white to yellow-white mass compressing the surrounding muscular tissues. The tumor metastasized also to the lungs, heart, abdominal cavity, liver and salivary gland. Microscopically, basaloid cells were crowded into solid nests or lobules separated by well-developed fibrous tissues with occasional keratinizations. Since there was no skin lesions, the tumor is assumed to be originated from the formerly present tumor in mammary gland. To our literature review, this case is the first BSCC with systemic metastasis in a dog.

  7. Unusual presentation of a pancreatic cyst resulting from osteosarcoma metastasis.

    PubMed

    Akpinar, Burcu; Obuch, Joshua; Fukami, Norio; Pokharel, Sajal S

    2015-07-21

    Pancreatic metastases are uncommon. They have been reported in lung cancer, gastrointestinal malignancies, breast cancer, renal cell carcinoma, melanoma, lymphoma and sarcoma, and usually have solid morphology. Cystic metastasis to the pancreas is even more rare with few case reports in the literature. However, with the increasing use of computed tomography and magnetic resonance imaging as well as endoscopic ultrasound, more such lesions may be detected. Metastasis to the pancreas from osteosarcoma is highly unusual, but can be seen with the increasing survival of patients with osteosarcoma. We present an extremely rare case of a predominantly cystic lesion of the pancreas, which was diagnosed as metastasis from osteosarcoma. The pathophysiology of the cystic component of the metastasis of osteosarcoma is unknown. Cystic necrotic degeneration of the solid metastasis or pancreatitis secondary to the metastasis with development of associated fluid collection can be considered. Metastasis should remain a differential consideration even for primarily cystic lesions of the pancreas.

  8. Unusual presentation of a pancreatic cyst resulting from osteosarcoma metastasis

    PubMed Central

    Akpinar, Burcu; Obuch, Joshua; Fukami, Norio; Pokharel, Sajal S

    2015-01-01

    Pancreatic metastases are uncommon. They have been reported in lung cancer, gastrointestinal malignancies, breast cancer, renal cell carcinoma, melanoma, lymphoma and sarcoma, and usually have solid morphology. Cystic metastasis to the pancreas is even more rare with few case reports in the literature. However, with the increasing use of computed tomography and magnetic resonance imaging as well as endoscopic ultrasound, more such lesions may be detected. Metastasis to the pancreas from osteosarcoma is highly unusual, but can be seen with the increasing survival of patients with osteosarcoma. We present an extremely rare case of a predominantly cystic lesion of the pancreas, which was diagnosed as metastasis from osteosarcoma. The pathophysiology of the cystic component of the metastasis of osteosarcoma is unknown. Cystic necrotic degeneration of the solid metastasis or pancreatitis secondary to the metastasis with development of associated fluid collection can be considered. Metastasis should remain a differential consideration even for primarily cystic lesions of the pancreas. PMID:26217098

  9. Redox regulation of cancer metastasis: molecular signaling and therapeutic opportunities.

    PubMed

    Yang, Wenyong; Zou, Linzhi; Huang, Canhua; Lei, Yunlong

    2014-08-01

    Cancer metastasis is the major cause of cancer-related mortality. Accumulated evidence has shown that high-metastasis potential cancer cells have more reactive oxygen species (ROS) accumulation compared with low-metastasis potential cancer cells. ROS can function as second messengers to regulate multiple cancer metastasis-related signaling pathways via reversible oxidative posttranslational modifications of cysteine in key redox-sensitive proteins, which leads to the structural and functional change of these proteins. Because ROS can promote cancer metastasis, therapeutic strategies aiming at inducing/reducing cellular ROS level or targeting redox sensors involved in metastasis hold great potential in developing new efficient approaches for anticancer therapy. In this review, we summarize recent findings on regulation of tumor metastasis by key redox sensors and describe the potential of targeting redox signaling pathways for cancer therapy.

  10. Cholangiocarcinoma Presenting as Uterine Metastasis

    PubMed Central

    Dendas, W.; Cappelle, L.; Verguts, J.; Orye, G.

    2014-01-01

    Metastases to the female genital tract are rare, with metastatic disease restricted to the uterus being even less frequent. The primary tumor is most often intragenital rather than extragenital. The diagnosis is usually made after occurrence of gynecological symptoms. We describe the case of a 26-year-old female, in whom a curettage for menorrhagia revealed a uterine malignancy, at first thought to be a carcinosarcoma. Biochemistry only showed iron deficiency anemia. Imaging showed discrepant results with liver lesions, suspect of neoplastic or inflammatory disease. She underwent an abdominal hysterectomy and, peroperatively, a frozen section of a mass in the liver hilus demonstrated a cholangiocarcinoma. The diagnosis of a uterine metastasized cholangiocarcinoma was made. We emphasize the fact that uterine metastases have to be excluded in every woman with abnormal uterine bleeding and a personal history of malignancy. However, our case also indicates that gynecological metastatic disease may be the first presentation of an extragenital primary neoplasm. PMID:25610676

  11. Tetraspanins as regulators of the tumour microenvironment: implications for metastasis and therapeutic strategies

    PubMed Central

    Detchokul, S; Williams, E D; Parker, M W; Frauman, A G

    2014-01-01

    One of the hallmarks of cancer is the ability to activate invasion and metastasis. Cancer morbidity and mortality are largely related to the spread of the primary, localized tumour to adjacent and distant sites. Appropriate management and treatment decisions based on predicting metastatic disease at the time of diagnosis is thus crucial, which supports better understanding of the metastatic process. There are components of metastasis that are common to all primary tumours: dissociation from the primary tumour mass, reorganization/remodelling of extracellular matrix, cell migration, recognition and movement through endothelial cells and the vascular circulation and lodgement and proliferation within ectopic stroma. One of the key and initial events is the increased ability of cancer cells to move, escaping the regulation of normal physiological control. The cellular cytoskeleton plays an important role in cancer cell motility and active cytoskeletal rearrangement can result in metastatic disease. This active change in cytoskeletal dynamics results in manipulation of plasma membrane and cellular balance between cellular adhesion and motility which in turn determines cancer cell movement. Members of the tetraspanin family of proteins play important roles in regulation of cancer cell migration and cancer-endothelial cell interactions, which are critical for cancer invasion and metastasis. Their involvements in active cytoskeletal dynamics, cancer metastasis and potential clinical application will be discussed in this review. In particular, the tetraspanin member, CD151, is highlighted for its major role in cancer invasion and metastasis. Linked Articles This article is part of a themed section on Cytoskeleton, Extracellular Matrix, Cell Migration, Wound Healing and Related Topics. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-24 PMID:23731188

  12. FRZB up-regulation is correlated with hepatic metastasis and poor prognosis in colon carcinoma patients with hepatic metastasis.

    PubMed

    Shen, Yanping; Zhang, Fang; Lan, Huanrong; Chen, Ke; Zhang, Qi; Xie, Guoming; Teng, Lisong; Jin, Ketao

    2015-01-01

    Frizzled-related protein (FRZB) was up-regulated in hepatic metastasis samples compared with primary colon cancer samples in our previous work. However, the clinical relevance of FRZB in colon cancer hepatic metastasis remains uncertain. The aim of this study was to assess the prognostic value of FRZB in patients with colon carcinoma hepatic metastasis after hepatic resection. FRZB expression was evaluated by immunohistochemistry in formalin-fixed paraffin embedded (FFPE) primary colon carcinoma and paired hepatic metastasis tissues from 136 patients with liver metastasis from colon carcinoma that underwent hepatic resection. The relation between FRZB expression and clinicopathologic factors and long-term prognosis in these 136 patients was retrospectively examined. The prognostic significance of negative or positive FRZB expression in colon carcinoma hepatic metastasis was assessed using Kaplan-Meier survival analysis and log-rank tests. Positive expression of FRZB was correlated with liver metastasis of colon cancer. Univariate analysis indicated significantly worse overall survival (OS) for patients with a positive FRZB expression in colon carcinoma hepatic metastasis than for patients with a negative FRZB expression. Multivariate analysis showed positive-FRZB in colon carcinoma hepatic metastasis to be an independent prognostic factor for OS after hepatic resection (P = 0.001). Positive expression of FRZB was statistically significantly associated with poor prognosis of patients with colon carcinoma hepatic metastasis. FRZB could be a novel predictor for poor prognosis of patients with colon carcinoma hepatic metastasis after hepatic resection.

  13. Cervical chordoma in a domestic ferret (Mustela putorius furo) with pulmonary metastasis.

    PubMed

    Frohlich, Jennifer R; Donovan, Taryn A

    2015-09-01

    A 4-year-old, male neutered domestic ferret (Mustela putorius furo) was evaluated for a mass in the left cervical region. The owner elected humane euthanasia, and an autopsy was performed, revealing a neoplasm with infiltration into the left cranial articular fovea of the atlas and cervical vertebrae, with regional compression of the spinal cord. Histologic evaluation was consistent with cervical chordoma. At autopsy, a left cranial lung lobe nodule was observed. Additional sectioning and histologic evaluation revealed multiple foci of metastatic chordoma at this site. A small focus of micrometastasis was also detected in a section from the right lung lobes. Chordoma is the most common musculoskeletal neoplasm of ferrets, arising from remnant fetal notochord. To our knowledge, pulmonary chordoma metastasis has not been previously reported in the ferret. This case demonstrates the potential for visceral metastasis of chordoma in the ferret, as has been reported in other species. © 2015 The Author(s).

  14. Gli1 promotes colorectal cancer metastasis in a Foxm1-dependent manner by activating EMT and PI3K-AKT signaling

    PubMed Central

    Zhang, Yue; Ji, Bing; Wang, Sen; Sun, Ye; Zhu, Chunyan; Zhang, Dongsheng; Sun, Yueming

    2016-01-01

    Colorectal cancer(CRC) is one of the most commonly diagnosed cancers in human beings and metastasis is the main death reason. Recently, Gli1 has been reported to be a key regulator of various cancer biologies and genes expressions. However, the detailed molecular mechanism of Gli1 in CRC metastasis remains largely unknown. In this study, we aimed to investigate the role of Gli1 in CRC metastasis. We used qRT-PCR, Immunohistochemistry and Western blot to test the expression levels of Gli1, Foxm1 and other target genes in the tissues and cells; Lentivirus stable transfection to change the expression levels of Gli1 and Foxm1; Wound-healing, cell invasion, migration assays and tail vein metastatic assay to test the role of Gli1 in CRC metastasis in vitro and vivo. We demonstrated that Gli1 was significantly overexpressed in colorectal cancer tissues and cells. Foxm1 level had a positive correlation with Gli1. Furthermore, we found that Gli1 promotes colorectal cancer cells metastasis in a Foxm1-dependent manner by activating EMT and PI3K-AKT signaling. Thus, we proved that Gli1 plays important role in CRC metastasis and provided a new visual field on the therapy of CRC metastasis. PMID:27863385

  15. Melanoma metastasis to the spleen: Laparoscopic approach

    PubMed Central

    Trindade, Manoel Roberto Maciel; Blaya, Rodrigo; Trindade, Eduardo Neubarth

    2009-01-01

    We report a case of minimally invasive surgery in the management of metastasis to the spleen. A 67-year-old male patient with possible splenic soft tissue melanoma metastasis was referred to our hospital. He had a history of an excised soft tissue melanoma from his back eight months earlier, and the control abdominal computer tomography (CT) scan revealed a hypodense spleen lesion. The patient underwent laparoscopic surgery to diagnose and treat the splenic lesion. The splenectomy was performed and the histological examination revealed a melanoma. The patient had a good postoperative course and was discharged on the second postoperative day. On his 12-month follow-up there was no sign of recurrence. The laparoscopic approach is a safe and effective alternative for treatment of splenic metastases. PMID:19547681

  16. Colonic adenocarcinoma with metastasis to the gingiva.

    PubMed

    Alvarez-Alvarez, Carlos; Iglesias-Rodríguez, Begoña; Pazo-Irazu, Susana; Delgado-Sánchez-Gracián, Carlos

    2006-01-01

    Metastatic tumors involve the oral cavity, and the most common primary sites are the breast and lung. Most cases affect the mandible and maxilla in that order, although some of them can be located in the soft perioral tissues. We report the case of a 62-year-old male who had been diagnosed with sigmoid adenocarcinoma with nodal and liver metastasis, who presented 6 months later with a gingival polypoid tumor, at first considered as a primary neoplasm of gingiva, that was diagnosed in a biopsy as metastatic intestinal adenocarcinoma. The histological evaluation is essential to separate adenocarcinoma from the commoner in this site squamous cell carcinoma, and the immunohistochemical techniques are useful to distinguish metastatic tumor versus primary adenocarcinoma from the minor salivary glands of the area. The intraoral spread of a disseminated neoplasm is generally a sign of bad prognosis, although a longer survival can be expected if a radical surgical treatment of a solitary metastasis is carried out.

  17. Macroscopic Stiffness of Breast Tumors Predicts Metastasis

    PubMed Central

    Fenner, Joseph; Stacer, Amanda C.; Winterroth, Frank; Johnson, Timothy D.; Luker, Kathryn E.; Luker, Gary D.

    2014-01-01

    Mechanical properties of tumors differ substantially from normal cells and tissues. Changes in stiffness or elasticity regulate pro-metastatic behaviors of cancer cells, but effects have been documented predominantly in isolated cells or in vitro cell culture systems. To directly link relative stiffness of tumors to cancer progression, we combined a mouse model of metastatic breast cancer with ex vivo measurements of bulk moduli of freshly excised, intact tumors. We found a high, inverse correlation between bulk modulus of resected tumors and subsequent local recurrence and metastasis. More compliant tumors were associated with more frequent, larger local recurrences and more extensive metastases than mice with relatively stiff tumors. We found that collagen content of resected tumors correlated with bulk modulus values. These data establish that relative differences in tumor stiffness correspond with tumor progression and metastasis, supporting further testing and development of tumor compliance as a prognostic biomarker in breast cancer. PMID:24981707

  18. Genetic factors conferring metastasis in osteosarcoma.

    PubMed

    Maximov, Vadim V; Aqeilan, Rami I

    2016-07-01

    Osteosarcoma (OS) is a deadly bone malignancy affecting mostly children and adolescents. OS has outstandingly complex genetic alterations likely due to p53-independent genomic instability. Based on analysis of recent published research we claim existence of various genetic mechanisms of osteosarcomagenesis conferring great variability to different OS properties including metastatic potential. We also propose a model explaining how diverse genetic mechanisms occur and providing a framework for future research. P53-independent preexisting genomic instability, which precedes and frequently causes TP53 genetic alterations, is central in our model. In addition, our analyses reveal a possible cooperation between aberrantly activated HIF-1α and AP-1 genetic pathways in OS metastasis. We also review the involvement of noncoding RNA genes in OS metastasis.

  19. Microenvironmental regulation of tumor progression and metastasis

    PubMed Central

    Quail, DF; Joyce, JA

    2014-01-01

    Cancers develop in complex tissue environments, which they depend upon for sustained growth, invasion and metastasis. Unlike tumor cells, stromal cell types within the tumor microenvironment (TME) are genetically stable, and thus represent an attractive therapeutic target with reduced risk of resistance and tumor recurrence. However, specifically disrupting the pro-tumorigenic TME is a challenging undertaking, as the TME has diverse capacities to induce both beneficial and adverse consequences for tumorigenesis. Furthermore, many studies have shown that the microenvironment is capable of normalizing tumor cells, suggesting that reeducation of stromal cells, rather than targeted ablation per se, may be an effective strategy for treating cancer. Here, we will discuss the paradoxical roles of the TME during specific stages of cancer progression and metastasis, and recent therapeutic attempts to re-educate stromal cells within the TME to have anti-tumorigenic effects. PMID:24202395

  20. Progression and metastasis of lung cancer.

    PubMed

    Popper, Helmut H

    2016-03-01

    Metastasis in lung cancer is a multifaceted process. In this review, we will dissect the process in several isolated steps such as angiogenesis, hypoxia, circulation, and establishment of a metastatic focus. In reality, several of these processes overlap and occur even simultaneously, but such a presentation would be unreadable. Metastasis requires cell migration toward higher oxygen tension, which is based on changing the structure of the cell (epithelial-mesenchymal transition), orientation within the stroma and stroma interaction, and communication with the immune system to avoid attack. Once in the blood stream, cells have to survive trapping by the coagulation system, to survive shear stress in small blood vessels, and to find the right location for extravasation. Once outside in the metastatic locus, tumor cells have to learn the communication with the "foreign" stroma cells to establish vascular supply and again express molecules, which induce immune tolerance.

  1. Renal Clear Cell Carcinoma and Tonsil Metastasis

    PubMed Central

    Marcotullio, Dario; Iannella, Giannicola; Zelli, Melissa; Magliulo, Giuseppe

    2013-01-01

    Renal cell carcinoma is the most common renal tumor in adults. Clear cell carcinoma represents 85% of all histological subtypes. In February 2012 a 72-year-old woman came to our department due to the appearance of massive hemoptysis and pharyngodinia. Previously, this patient was diagnosed with a renal cell carcinoma treated with left nephrectomy. We observed an exophytic, grayish, and ulcerated mass in the left tonsillar lodge and decided to subject the patient to an immediate tonsillectomy. Postoperative histology showed nests of cells with highly hyperchromatic nuclei and clear cytoplasm. These features enabled us to make the diagnosis of renal clear cell carcinoma metastasis. Only few authors described metastasis of renal cell carcinoma in this specific site. PMID:24455373

  2. Renal clear cell carcinoma and tonsil metastasis.

    PubMed

    Marcotullio, Dario; Iannella, Giannicola; Macri, Gian Franco; Marinelli, Caterina; Zelli, Melissa; Magliulo, Giuseppe

    2013-01-01

    Renal cell carcinoma is the most common renal tumor in adults. Clear cell carcinoma represents 85% of all histological subtypes. In February 2012 a 72-year-old woman came to our department due to the appearance of massive hemoptysis and pharyngodinia. Previously, this patient was diagnosed with a renal cell carcinoma treated with left nephrectomy. We observed an exophytic, grayish, and ulcerated mass in the left tonsillar lodge and decided to subject the patient to an immediate tonsillectomy. Postoperative histology showed nests of cells with highly hyperchromatic nuclei and clear cytoplasm. These features enabled us to make the diagnosis of renal clear cell carcinoma metastasis. Only few authors described metastasis of renal cell carcinoma in this specific site.

  3. Distinctive properties of metastasis-initiating cells

    PubMed Central

    Celià-Terrassa, Toni; Kang, Yibin

    2016-01-01

    Primary tumors are known to constantly shed a large number of cancer cells into systemic dissemination, yet only a tiny fraction of these cells is capable of forming overt metastases. The tremendous rate of attrition during the process of metastasis implicates the existence of a rare and unique population of metastasis-initiating cells (MICs). MICs possess advantageous traits that may originate in the primary tumor but continue to evolve during dissemination and colonization, including cellular plasticity, metabolic reprogramming, the ability to enter and exit dormancy, resistance to apoptosis, immune evasion, and co-option of other tumor and stromal cells. Better understanding of the molecular and cellular hallmarks of MICs will facilitate the development and deployment of novel therapeutic strategies. PMID:27083997

  4. Thymoma Metastasis to the Semimembranosus Muscle

    PubMed Central

    Taniguchi, Kenta; Susa, Michiro; Ogata, Sho; Ozeki, Yuichi; Chiba, Kazuhiro

    2017-01-01

    Thymoma is the most common thymic epithelial tumor whose classification was first introduced in 1999. Type B2 thymoma is considered a moderate/high-risk tumor; however, extrathoracic metastases are extremely rare with limited reports to date. In this report, we present a rare thymoma metastasis to the semimembranosus muscle, which was resected with a wide margin after confirmation by open biopsy. At the final follow-up after 1 year, no local recurrence has been observed. PMID:28203162

  5. Prostate Cancer Presenting with Parietal Bone Metastasis

    PubMed Central

    Pare, Abdoul Karim; Abubakar, Babagana Mustapha; Kabore, Moussa

    2017-01-01

    Bone metastases from prostate cancer are very common. They are usually located on the axial skeleton. However, cranial bone metastases especially to the parietal bone are rare. We report a case of metastatic prostate cancer presenting with left parietal bone metastasis in a patient with no urological symptoms or signs. We should consider prostate cancer in any man above 60 years presenting unusual bone lesions.

  6. Targeting Neuromimicry in Prostate Cancer Metastasis

    DTIC Science & Technology

    2016-10-01

    metastasis to distant organs, including intestine, liver and lung, in different orthotopic xenograft mouse models. In addition , we showed that MAOA...validated by Western blot (Figure 1). In addition , these cells were stably labeled with GFP/RFP and Luc, which were detected by fluorescence microscopy...treated mice by qPCR. In addition , orthotopic xenograft models were established by using PC-3 (vector and MAOA-overexpression) and ARCaPM (control and

  7. Epigenetic Control of Prostate Cancer Metastasis: Role of Runx2 Phosphorylation

    DTIC Science & Technology

    2015-05-01

    Metastasis: Role of Runx2 Phosphorylation Study Site Information: PI: Renny T. Franceschi, Ph.D. Department of Periodontics and Oral Medicine University...COLLABORATING ORGANIZATIONS What individuals have worked on project? Name Renny Franceschi Project Role PI, Professor of Periodontics and Oral Medicine...equally 1 Department of Periodontics and Oral Medicine, University of Michigan, Ann Arbor, USA 2 Department of Surgical Sciences, Section of Anatomic

  8. Identification and Validation of a Five MicroRNA Signature Predictive of Prostate Cancer Recurrence and Metastasis: A Cohort Study.

    PubMed

    Nam, Robert K; Amemiya, Yutaka; Benatar, Tania; Wallis, Christopher J D; Stojcic-Bendavid, Jessica; Bacopulos, Stephanie; Sherman, Christopher; Sugar, Linda; Naeim, Magda; Yang, Wenyi; Zhang, Aiguo; Klotz, Laurence H; Narod, Steven A; Seth, Arun

    2015-01-01

    MicroRNA (miRNA) have been shown to be important in regulating gene expression in prostate cancer. We used next generation miRNA sequencing to conduct a whole miRNome analysis to identify miRNAs associated with prostate cancer metastasis. We conducted discovery and validation analyses of miRNAs among a total of 546 men who underwent surgery for prostate cancer using the development of metastasis as an endpoint. Genome wide analysis was conducted among the discovery group (n=31) to identify new miRNAs associated with prostate cancer metastasis. Selected miRNAs were then analyzed using qPCR on prostatectomy specimens from an independent cohort (n=515) to determine whether their expression could predict the development of metastasis after surgery. To examine the biology underlying these associations, we created prostate cancer cell lines which overexpressed miR-301a for in vitro and in vivo functional assays. We identified 33 miRNAs associated with prostate cancer metastasis and selected a panel comprising miRs-301a, 652, 454, 223 and 139 which strongly predicted metastasis (AUC=95.3%, 95%C.I.:84%-99%). Among the validation cohort, the 15-year metastasis-free survival was 77.5% (95% C.I.:63.9%-86.4%) for patients with a high miRNA panel score and 98.8% (95% C.I.:94.9%-99.7%, p<0.0001 for difference) for those with a low score. After adjusting for grade, stage, and PSA, the hazard ratio for metastasis was 4.3 (95% C.I.: 1.7-11.1, p=0.002) for patients with a high miRNA panel score, compared to those with a low score. Prostate cancer cell lines overexpressing miR-301a had in significantly higher tumor growth and metastasis in a xenograft mouse model. A panel of miRNAs is associated with prostate cancer metastasis. These could be used as potential new prognostic factors in the surgical management of prostate cancer.

  9. pH-Responsive Wormlike Micelles with Sequential Metastasis Targeting Inhibit Lung Metastasis of Breast Cancer.

    PubMed

    He, Xinyu; Yu, Haijun; Bao, Xiaoyue; Cao, Haiqiang; Yin, Qi; Zhang, Zhiwen; Li, Yaping

    2016-02-18

    Cancer metastasis is the main cause for the high mortality in breast cancer patients. Herein, we first report succinobucol-loaded pH-responsive wormlike micelles (PWMs) with sequential targeting capability to inhibit lung metastasis of breast cancer. PWMs can in a first step be delivered specifically to the sites of metastases in the lungs and then enable the intracellular pH-stimulus responsive drug release in cancer cells to improve the anti-metastatic effect. PWMs are identified as nanofibrillar assemblies with a diameter of 19.9 ± 1.9 nm and a length within the 50-200 nm range, and exhibited pH-sensitive drug release behavior in response to acidic intracellular environments. Moreover, PWMs can obviously inhibit the migration and invasion abilities of metastatic 4T1 breast cancer cells, and reduce the expression of the metastasis-associated vascular cell adhesion molecule-1 (VCAM-1) at 400 ng mL(-1) of succinobucol. In particular, PWMs can induce a higher specific accumulation in lung and be specifically delivered to the sites of metastases in lung, thereby leading to an 86.6% inhibition on lung metastasis of breast cancer. Therefore, the use of sequentially targeting PWMs can become an encouraging strategy for specific targeting and effective treatment of cancer metastasis.

  10. Metastasis of Prostate Adenocarcinoma to the Testis

    PubMed Central

    Campara, Zoran; Simic, Dejan; Aleksic, Predrag; Spasic, Aleksandar; Milicevic, Snjezana

    2016-01-01

    Introduction: Prostate carcinoma is the most frequently diagnosed carcinoma in the male population. The most typical places of the metastases are pelvic lymphatic glands, bones and lungs, and very rarely it metastasizes into a testis. The prognostic importance of testicular metastasis of prostate cancer is not yet well-known, due to a very few published cases. According to the known facts, it is certain that a metastasis of the prostate carcinoma into a testis is a sign of an advanced disease. Case report: This work presents a 48-year-old patient, to whom an adenocarcinoma of the prostate has been proven by the pathohistological finding of transrectal biopsy, performed due to the elevated level of prostate-specific antigen (PSA). Nine years after the initial diagnosis, due to a gradual rise of PSA and tumorous enlargement of the left testis, left inguinal orchectomy and right orchectomy were performed. Metastatic dissemination of prostate adenocarcinoma into a testis was determined by a pathohistological analysis of the left testis. Conclusion: The metastasis of the prostate carcinoma into a testis, as a rare localization of the metastatic dissemination, after additionally performed orchectomy along with further oncological therapy, can provide a continuation of a good life quality as well as a control of the disease in a longer time period. PMID:27703299

  11. Imaging pH and Metastasis

    PubMed Central

    Hashim, Arig Ibrahim; Zhang, Xiaomeng; Wojtkowiakk, Jonathan W.; Gillies, Robert J.

    2013-01-01

    Metastasis is a multistep process that culminates in the spread of cells from a primary tumor to a distant site or organs. For tumor cells to be able to metastasize, they have to locally invade through basement membrane into the lymphatic and the blood vasculatures. Eventually they extravasate from the blood and colonize in the secondary organ. This process involves multiple interactions between the tumor cells and their microenvironments. The microenvironment surrounding tumors has a significant impact on tumor development and progression. A key factor in the microenvironment is an acidic pH. The extracellular pH of solid tumors is more acidic in comparison to normal tissue as a consequence of high glycolysis and poor perfusion. It plays an important role in almost all steps of metastasis. The past decades have seen development of technologies to non-invasively measure intra- and/or extracellular pH. Most successful measurements are MR-based, and sensitivity and accuracy have dramatically improved. Quantitatively imaging the distribution of acidity helps us understand the role of the tumor microenvironment in cancer progression. This review discusses different MR methods in measuring tumor pH along with emphasizing the importance of extracelluar tumor low pH on different steps of metastasis; more specifically focusing on Epithelial to Mesenchymal transition (EMT), and anti cancer immunity. PMID:21387439

  12. Cancer metastasis - tricks of the trade.

    PubMed

    Zeeshan, Rabia; Mutahir, Zeeshan

    2017-08-20

    Decades of cancer research have unraveled genetic, epigenetic and molecular pathways leading to plausible therapeutic targets; many of which hold great promise in improving clinical outcomes. Metastatic tumors become evident early on and are one of the major causes of cancer-related fatalities worldwide. This review depicts the sequential events of cancer metastasis. Genetic and epigenetic heterogeneity influences local tumor cell invasion, intravasation, survival in circulation, extravasation and colonization to distant sites. Each sequential event is associated with heterogeneous tumor microenvironment, gain of competence, unique population of cancer stem cells (CSCs), circulatory pathway, compatible niche and immune system support. A tight regulation of metastasis-promoting mechanisms and, in parallel, evading inhibitory mechanisms contribute to the severity and site of metastasis. A comprehensive understanding of tumor cell fate as an individual entity, as well as in combination with different promoting factors and associated molecular mechanisms, is anticipated in the coming years. This will enable scientists to depict design strategies for targeted cancer therapies.

  13. Chemokines: novel targets for breast cancer metastasis

    PubMed Central

    Ali, Simi; Lazennec, Gwendal

    2007-01-01

    Recent studies have highlighted the possible involvement of chemokines and their receptors in breast cancer progression and metastasis. Chemokines and their receptors constitute a superfamily of signalling factors whose prognosis value in breast cancer progression remains unclear. We will examine here the expression pattern of chemokines and their receptors in mammary gland physiology and carcinogenesis. The nature of the cells producing chemokines or harboring chemokine receptors appears to be crucial in certain conditions for example, the infiltration of the primary tumor by leukocytes and angiogenesis. In addition, chemokines, their receptors and the interaction with glycosaminoglycan (GAGs) are key players in the homing of cancer cells to distant metastasis sites. Several lines of evidence, including in vitro and in vivo models, suggest that the mechanism of action of chemokines in cancer development involves the modulation of proliferation, apoptosis, invasion, leukocyte recruitment or angiogenesis. Furthermore, we will discuss the regulation of chemokine network in tumor neovascularity by decoy receptors. The reasons accounting for the deregulation of chemokines and chemokine receptors expression in breast cancer are certainly crucial for the comprehension of chemokine role in breast cancer and are in several cases linked to estrogen receptor status. The targeting of chemokines and chemokine receptors by antibodies, small molecule antagonists, viral chemokine binding proteins and heparins appears as promising tracks to develop therapeutic strategies. Thus there is significant interest in developing strategies to antagonize the chemokine function, and an opportunity to interfere with metastasis, the leading cause of death in most patients. PMID:17717637

  14. Hepatic metastasis complicated by abscess formation.

    PubMed

    Yi, Liao; Lihua, Qiu; Xianming, Diao; Qiyong, Gong

    2015-01-01

    Hepatic abscesses and hepatic metastasis are common diseases. However, hepatic abscesses seldom occur in patients with hepatic metastases. We describe a case of a 67-year-old female patient with abdominal pain in the right upper quadrant. Magnetic resonance imaging revealed several lesions, with the largest lesion displaying features of both hepatic pyogenic abscess and liver metastasis. These features included iso- or hypointense signaling on T1WI and T2WI, hyperintense signaling on diffusion weighted imaging of the thick wall, and mixed hyperintense signal in the center on DWI, as well as dramatic and irregular peripheral enhancement was detected on LAVA dynamic contrast scanning. Aspiration and culture of the largest lesions revealed Klebsiella pneumoniae and a pathologic diagnosis of adenocarcinoma. At this point, the patient admitted a history of colon adenocarcinoma 9 years ago treated with hemicolectomy. Therefore, this patient was considered to have a hepatic pyogenic abscesses complicated by hepatic metastasis. The patient began treatment for the responsible pathogens and underwent chemoembolization of the liver lesions. In special cases, we could attempt to pursue a more detailed search for coexistence of microorganism infection and tumor.

  15. Actin-like protein 6A is a novel prognostic indicator promoting invasion and metastasis in osteosarcoma.

    PubMed

    Sun, Wei; Wang, Wanchun; Lei, Jian; Li, Hui; Wu, Yi

    2017-04-01

    Osteosarcoma harbors highly metastatic properties, accounting for postoperative recurrence and metastasis. Actin-like protein 6A (ACTL6A) regulates cell proliferation, migration and differentiation. However, the biologic role of ACTL6A in osteosarcoma remains unknown. In this study, the results showed that, by analysis of frozen fresh primary tumor tissues, matched non-cancerous bone tissues (NCBTs) and biopsy lung metastatic nodule tissues from 30 osteosarcoma patients after radical surgical resection, ACTL6A was overexpressed in osteosarcoma tissues compared with matched NCBTs, and its expression level was associated with osteosarcoma metastasis. Immunohistochemical analyses of osteosarcoma tissue samples from two independent cohorts of formaldehyde-fixed, paraffin-embedded osteosarcoma tissue samples from total of 186 osteosarcoma patients showed that high ACTL6A expression correlated with malignant clinicopathological features such as larger tumor size, high Ennecking grade, high histologic grade, and advanced tumor node metastasis stage. High ACTL6A expression was associated with poor prognosis for patients with osteosarcoma, and an independent and significant risk factor for disease-free survival and overall survival after radical tumor resection. Both in vitro and in vivo assays showed that ACTL6A overexpression promoted osteosarcoma cell invasion and metastasis, whereas knockdown of ACTL6A expression reduced osteosarcoma cell malignant behavior such as invasion and metastasis. Furthermore, we proved that ACTL6A promoted osteosarcoma cells of metastasis through facilitating epithelial-mesenchymal transition (EMT). In conclusion, data from the present study demonstrated that ACTL6A was associated with poor survival and promoted osteosarcoma cell metastasis through EMT, suggesting that ACTL6A may be a novel prognostic biomarker and therapeutic target for osteosarcoma.

  16. Expression of IL-1α correlates with distant metastasis in patients with head and neck squamous cell carcinoma

    PubMed Central

    León, Xavier; Bothe, Carolina; García, Jacinto; Parreño, Matilde; Alcolea, Sonia; Quer, Miquel

    2015-01-01

    The presence of IL-1 in human cancers is associated with aggressive tumor biology but its prognostic value is unknown. We studied whether IL-1α expression is a prognostic marker of distant metastasis in patients with head and neck squamous cell carcinoma (HNSCC). IL-1α mRNA and protein levels were determined in tumor samples and cancer cell lines using RT-PCR and ELISA. The effects of constitutive IL-1α expression by tumor lines were characterized. IL-1α mRNA and protein secretion were higher in tumor samples from patients who later developed distant metastasis than in patients who did not. By using distant metastasis as a dependent variable, patients were classified into two categories of IL-1α transcript-levels. The high-IL-1α group had a significantly lower five-year distant metastasis-free survival than the low-IL-1α group [70.0% (CI 95%: 55.9-84.1%) vs 94.7% (CI 95%:90.2-99.2%)]. When IL-1α transcript-levels were combined with clinical factors related to tumor metastasis, the predictive power of the model increased significantly. Additionally, transcript levels of IL-1α correlated significantly with those of the IL-1 family genes and genes related to the metastatic process. IL-1 treatment of microvascular endothelial cells increased adhesion of HNSCC cells but no differences were found based on constitutive IL-1α expression by tumor cells. Nevertheless, IL-1α produced by tumor cells effectively increased their transmigration across the endothelium. We found a significant relationship between IL-1α expression and development of distant metastasis in HNSCC patients. IL-1α expression could help to define a subset of patients at high risk of distant metastasis who could benefit from adjuvant treatment. PMID:26460957

  17. Decorin is responsible for progression of non-small-cell lung cancer by promoting cell proliferation and metastasis.

    PubMed

    Shi, Xuefei; Liang, Wenjun; Yang, Wen; Xia, Rui; Song, Yong

    2015-05-01

    Decorin, a member of the small leucine-rich proteoglycans family, exists and plays multifunctional roles in stromal and epithelial cells. Emerging evidences showed that decorin is dysregulated expression in a wide variety of human tumors and affects a broad biology process of cancer cells, including growth, metastasis, and angiogenesis. Recent studies demonstrated that decorin could affect A549 proliferation though decreasing TGF-β1, cycling D1 expression and increasing P53 and P21 expression. However, limited data are available on the effect of decorin on metastasis of non-small-cell lung cancer (NSCLC) cell lines and how decorin impacts metastasis is still unknown. In this study, we identified decorin mRNA expression through Oncomine database and verified the expression of decorin mRNA and protein in 50 patients who underwent primary surgical resection of a NSCLC in the Department of Thoracic Surgery, Jinling Hospital, Nanjing University School of Medicine, China, between September 2013 and March 2014 by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and Western blot. Also, the correlationship between decorin and the NSCLC patients' clinical characteristics or survival ( www.kmplot.com ) was analyzed. Via ectopic expression analyses and Western blot, the roles of decorin in proliferation, metastasis, and the underline mechanism for decorin expression were further explored. We found that decorin was downregulated in NSCLC tissues compared with the adjacent normal lung tissues or normal tissues. Additionally, the expression of decorin was correlated with tumor size, lymph node metastasis, tumor stage, and prognosis. We also showed that overexpression of decorin could inhibit NSCLC cell lines proliferation and metastasis. Through Western blot analysis, we identified that E-cadherin and vascular endothelial growth factor (VEGF) are two key factors responsible for the growth arrest and metastasis inhibition induced by decorin in NSCLC. Our

  18. The histone demethylase KDM3A, and its downstream target MCAM, promote Ewing Sarcoma cell migration and metastasis.

    PubMed

    Sechler, M; Parrish, J K; Birks, D K; Jedlicka, P

    2017-07-20

    Ewing Sarcoma is the second most common solid pediatric malignant neoplasm of bone and soft tissue. Driven by EWS/Ets, or rarely variant, oncogenic fusions, Ewing Sarcoma is a biologically and clinically aggressive disease with a high propensity for metastasis. However, the mechanisms underpinning Ewing Sarcoma metastasis are currently not well understood. In the present study, we identify and characterize a novel metastasis-promotional pathway in Ewing Sarcoma, involving the histone demethylase KDM3A, previously identified by our laboratory as a new cancer-promoting gene in this disease. Using global gene expression profiling, we show that KDM3A positively regulates genes and pathways implicated in cell migration and metastasis, and demonstrate, using functional assays, that KDM3A promotes migration in vitro and experimental, post-intravasation, metastasis in vivo. We further identify the melanoma cell adhesion molecule (MCAM) as a novel KDM3A target gene in Ewing Sarcoma, and an important effector of KDM3A pro-metastatic action. Specifically, we demonstrate that MCAM depletion, like KDM3A depletion, inhibits cell migration in vitro and experimental metastasis in vivo, and that MCAM partially rescues impaired migration due to KDM3A knock-down. Mechanistically, we show that KDM3A regulates MCAM expression both through a direct mechanism, involving modulation of H3K9 methylation at the MCAM promoter, and an indirect mechanism, via the Ets1 transcription factor. Finally, we identify an association between high MCAM levels in patient tumors and poor survival, in two different Ewing Sarcoma clinical cohorts. Taken together, our studies uncover a new metastasis-promoting pathway in Ewing Sarcoma, with therapeutically targetable components.

  19. Section candidates

    NASA Astrophysics Data System (ADS)

    Eos has carried biographies and photographs of candidates for President-Elect of the Union and for President-Elect and Secretary of each section. In addition, statements by the candidates for Union and Section President-Elect have appeared. T h e material for the petition candidate for President-Elect of the Solar-Planetary Relationships Section and a correction to the biography of one candidate for President-Elect of t h e Geodesy Section appear below. The material for the original slate for Solar-Planetary Relationships appeared in the August 6 issue, that for the Seismology Section in the August 13 issue, that for the Geodesy Section in the August 20 issue, that for the Atmospheric Sciences Section in the August 27 issue, that for the Hydrology Section in the September 3 issue, that for the Tectonophysics Section in the September 10 issue, that for the Volcanology, Geochemistry, and Petrology Section in the September 17 issue, that for the Planetology Section in the September 24 issue, that for the Ocean Sciences Section in the October 1 issue, that for the Geomagnetism and Paleomagnetism Section in the October 8 issue, and that for Union President-Elect in the October 15 issue. T h e slate of candidates for all offices was carried in the July 2 issue.

  20. Functional Annotation of Metastasis-associated MicroRNAs of Melanoma: A Meta-analysis of Expression Profiles

    PubMed Central

    Li, Jing-Yi; Zheng, Li-Li; Wang, Ting-Ting; Hu, Min

    2016-01-01

    Background: Melanoma is a type of cancer that develops from the pigment-containing cells. Until now, its pathological mechanisms remain largely unknown. The aim of this study was to identify metastasis-related microRNA (miRNAs) and gain an understanding of the biological functions in the metastasis of melanoma. Methods: We searched the PubMed and Gene Expression Omnibus database to collect miRNA expression profiling datasets about melanoma, with key words of “melanoma”, “miRNA”, “microarray”, and “gene expression profiling”. Only the original experimental works published before June 2016 for analyzing the metastasis of melanoma were retained, other nonhuman studies, reviews, and meta-analyses were removed. We performed a meta-analysis to explore the differentially expressed miRNA between metastatic and nonmetastatic samples. Moreover, we predicted target genes of the miRNAs to study their biological roles for these miRNAs. Results: We identified a total of 63 significantly differentially expressed miRNAs by meta-analysis of the melanoma expression profiling data. The regulatory network constructed by using these miRNAs and the predicted targets identified several key genes involved in the metastasis of melanoma. Functional annotation of these genes indicated that they are mainly enriched in some biological pathways such as mitogen-activated protein kinase signaling pathway, cell junction, and focal adhesion. Conclusions: By collecting the miRNA expression datasets from different platforms, multiple biological markers were identified for the metastasis of melanoma. This study provided novel insights into the molecular mechanisms underlying this disease, thereby aiding the diagnosis and treatment of the disease. PMID:27748342

  1. A Review of the Association between Osteosarcoma Metastasis and Protein Translation

    PubMed Central

    Osborne, T. S.; Khanna, C.

    2012-01-01

    Summary The malignant transformation of mesenchymal cells within the bone leads to the development of osteosarcoma (OS), but the genetic underpinnings of these events are not understood. From a clinical perspective, primary tumour management can be achieved successfully in most patients. However, the development of metastasis to the lungs represents the most common cause of death in OS patients. A clearer understanding of metastasis biology is required to improve cancer mortality and improve outcomes. Modelling the genetics, biology and therapy of OS can be accomplished through research involving a number of species. Most notable is the naturally occurring form of OS that develops in dogs. Through a cross-species and comparative approach important questions can be asked within specific and suitable models to advance our understanding of this disease and its common metastatic outcome. A comparative perspective on the problem of OS metastasis that utilizes a cross-species approach may offer unique opportunities to assist in this prioritization and generate new hypotheses related to this important clinical problem. PMID:22297074

  2. Breast cancer osteomimicry and its role in bone specific metastasis; an integrative, systematic review of preclinical evidence.

    PubMed

    Awolaran, Olugbenga; Brooks, Susan A; Lavender, Verna

    2016-12-01

    Metastasis accounts for most of the deaths from breast cancer and the preference of invasive breast cancer metastasising to bone has been widely reported. However, the biological basis of breast cancer osteotropism is not fully understood. This paper provides, for the first time, an integrative, systematic review of evidence of molecular factors that have functional roles in the homing of metastatic breast cancer to the bone. Pubmed, Web of Science and EBSCOhost were searched using keywords and synonyms for molecular, metastasis, breast cancer and bone to identify articles published between January 2004 and August 2016. 4491 potentially relevant citations were retrieved. 63 articles met the inclusion criteria, which were primary studies reporting evidence of molecular factors that have functional roles in predisposing breast cancer bone metastasis in vivo. 12 of those 63 articles that additionally met quality criteria were included in the review. Extracted data were tabulated and key findings that indicated biological mechanisms involved in breast cancer metastasis to bone were synthesised. 15 proteins expressed by breast cancer cells were identified as factors that mediate breast cancer bone metastasis: ICAM-1, cadherin-11, osteoactivin, bone sialoprotein, CCN3, IL-11, CCL2, CITED2, CXCR4, CTGF, OPN, CX3CR1, TWIST1, adrenomedullin and Enpp1. Upregulation or overexpression of one or more of them by breast cancer cells resulted in increased breast cancer metastasis to bone in vivo, except for CCL2 where bone-metastatic cells showed a reduced expression of this factor. All factors identified, here expressed by breast cancer cells, are proteins that are normally expressed in the bone microenvironment and linked to physiologic bone functions. All have a functional role in one of more of the following: cell proliferation and differentiation, bone mineralization and remodelling, cell adhesion and/or chemokine signalling. Six of them (cadherin-11, ICAM-1, OPN, CX3CR1

  3. Developmental therapeutics for patients with breast cancer and central nervous system metastasis: current landscape and future perspectives.

    PubMed

    Costa, R; Carneiro, B A; Wainwright, D A; Santa-Maria, C A; Kumthekar, P; Chae, Y K; Gradishar, W J; Cristofanilli, M; Giles, F J

    2016-10-03

    Breast cancer is the second-leading cause of metastatic disease in the central nervous system (CNS). Recent advances in the biological understanding of breast cancer have facilitated an unprecedented increase of survival in a subset of patients presenting with metastatic breast cancer. Patients with HER2 positive (HER2+) or triple negative breast cancer are at highest risk of developing CNS metastasis, and typically experience a poor prognosis despite treatment with local and systemic therapies. Among the obstacles ahead in the realm of developmental therapeutics for breast cancer CNS metastasis is the improvement of our knowledge on its biological nuances and on the interaction of the blood brain barrier with new compounds. This manuscript reviews recent discoveries related to the underlying biology of breast cancer brain metastases, clinical progress to date and suggests rational approaches for investigational therapies.

  4. Cesarean Section

    MedlinePlus

    A Cesarean section (C-section) is surgery to deliver a baby. The baby is taken out through the mother's abdomen. In the United ... three women has their babies this way. Some C-sections are planned, but many are done when ...

  5. Cutaneous metastasis from lung cancer. Case report.

    PubMed

    Fratus, Giorgio; Tagliabue, Fabio; Mariani, Pierpaolo; Bottazzi, Enrico Coppola; Spinelli, Luisella; Novellino, Lorenzo

    2014-07-21

    Il cancro del polmone rappresenta la patologia maligna maggiormente diagnosticata a livello mondiale. La diffusione metastatica della malattia è piuttosto frequente. Oltre ai classici siti di metastatizzazione (ossea, surreni, fegato, cervello) un sito particolare è rappresentato dalla cute. Il caso presentato riguarda appunto un paziente di 66 anni con metastasi cutanea da neoplasia del polmone. Un uomo di 66 anni, con anamnesi positiva per anuerisma aortico sottorenale, BPCO, cardiopatico e diabetico, giunge alla nostra osservazione per neoplasia del lobo inferiore del polmone sinistro. Dopo un accurato staging preoperatorio, il paziente viene sottoposto a lobectomia inferiore sinistra. L’esito dell’esame istologico è di carcinoma squamocellulare moderatamente e scarsamente differenziato G2-3 pT2bN0. Il paziente viene pertanto inviato al collega oncologo per il regolare follow up. Dopo circa 6 mesi il paziente ritorna alla nostra attenzione per la comparsa a livello del fianco/fossa iliaca di destra di nodulo cutaneo, duro, discromico, dolente ed ulcerato. Le biopsie eseguite, hanno dato esito di carcinoma squamocellulare moderatamente e scarsamente differenziato. Il paziente veniva sottoposto a un TC torace- addome che evidenziava in sede della parete addominale l’assenza d’infiltrazione dei piani muscolo-aponeurotici da parte della neoformazione. Il paziente è stato quindi sottoposto ad intervento chirurgico di asportazione della lesione cutanea. L’esame istologico del pezzo operatorio ha confermato trattarsi di carcinoma squamocellulare metastatico. Le metastasi cutanee da carcinoma del polmone si presentano nel 2,5 - 7,5% dei casi. La sopravvivenza mediana di questi pazienti è di circa 2,9 mesi. L’istotipo maggiormente coinvolto, secondo autori Giapponesi, è l’adenocarcinoma seguito dal carcinoma squamocellulare. Alcuni studi hanno dimostrato la validità dell’approccio chirurgico seguito dalla chemioterapia nei casi di metastasi singole

  6. RNA Sequencing Analysis Reveals Interactions between Breast Cancer or Melanoma Cells and the Tissue Microenvironment during Brain Metastasis.

    PubMed

    Sato, Ryo; Nakano, Teppei; Hosonaga, Mari; Sampetrean, Oltea; Harigai, Ritsuko; Sasaki, Takashi; Koya, Ikuko; Okano, Hideyuki; Kudoh, Jun; Saya, Hideyuki; Arima, Yoshimi

    2017-01-01

    Metastasis is the main cause of treatment failure and death in cancer patients. Metastasis of tumor cells to the brain occurs frequently in individuals with breast cancer, non-small cell lung cancer, or melanoma. Despite recent advances in our understanding of the causes and in the treatment of primary tumors, the biological and molecular mechanisms underlying the metastasis of cancer cells to the brain have remained unclear. Metastasizing cancer cells interact with their microenvironment in the brain to establish metastases. We have now developed mouse models of brain metastasis based on intracardiac injection of human breast cancer or melanoma cell lines, and we have performed RNA sequencing analysis to identify genes in mouse brain tissue and the human cancer cells whose expression is associated specifically with metastasis. We found that the expressions of the mouse genes Tph2, Sspo, Ptprq, and Pole as well as those of the human genes CXCR4, PLLP, TNFSF4, VCAM1, SLC8A2, and SLC7A11 were upregulated in brain tissue harboring metastases. Further characterization of such genes that contribute to the establishment of brain metastases may provide a basis for the development of new therapeutic strategies and consequent improvement in the prognosis of cancer patients.

  7. RNA Sequencing Analysis Reveals Interactions between Breast Cancer or Melanoma Cells and the Tissue Microenvironment during Brain Metastasis

    PubMed Central

    Hosonaga, Mari; Koya, Ikuko

    2017-01-01

    Metastasis is the main cause of treatment failure and death in cancer patients. Metastasis of tumor cells to the brain occurs frequently in individuals with breast cancer, non–small cell lung cancer, or melanoma. Despite recent advances in our understanding of the causes and in the treatment of primary tumors, the biological and molecular mechanisms underlying the metastasis of cancer cells to the brain have remained unclear. Metastasizing cancer cells interact with their microenvironment in the brain to establish metastases. We have now developed mouse models of brain metastasis based on intracardiac injection of human breast cancer or melanoma cell lines, and we have performed RNA sequencing analysis to identify genes in mouse brain tissue and the human cancer cells whose expression is associated specifically with metastasis. We found that the expressions of the mouse genes Tph2, Sspo, Ptprq, and Pole as well as those of the human genes CXCR4, PLLP, TNFSF4, VCAM1, SLC8A2, and SLC7A11 were upregulated in brain tissue harboring metastases. Further characterization of such genes that contribute to the establishment of brain metastases may provide a basis for the development of new therapeutic strategies and consequent improvement in the prognosis of cancer patients. PMID:28210624

  8. MicroRNA-543 suppresses colorectal cancer growth and metastasis by targeting KRAS, MTA1 and HMGA2

    PubMed Central

    Liu, Allan Yi; Ma, Handong; Yu, Donghong; Maitikabili, Alaiyi; Xiao, Hongjun; Zhang, Chuankai; Liu, Fan; Luo, Qi; Ouyang, Gaoliang

    2016-01-01

    miR-543 has been implicated as having a critical role in the development of breast cancer, endometrial cancer and hepatocellular carcinoma. However, the exact clinical significance and biological functions of miR-543 in colorectal cancer (CRC) remain unclear. Here, we found that miR-543 expression significantly downregulated in tumors from patients with CRC, APCMin mice and a mouse model of colitis-associated colon cancer. miR-543 level was inversely correlated with the metastatic status of patients with CRC and the metastatic potential of CRC cell lines. Moreover, ectopic expression of miR-543 inhibited the proliferation and metastasis of CRC cells in vitro and in vivo by targeting KRAS, MTA1 and HMGA2. Conversely, miR-543 knockdown promoted the proliferation, migration and invasion of CRC cells in vitro and augmented tumor growth and metastasis in vivo. Furthermore, we found that miR-543 expression was negatively correlated with the levels of KRAS, MTA1 and HMGA2 in clinical samples. Collectively, these data show that miR-543 inhibits the proliferation and metastasis of CRC cells by targeting KRAS, MTA1 and HMGA2. Our study highlights a pivotal role for miR-543 as a suppressor in the regulation of CRC growth and metastasis and suggests that miR-543 may serve as a novel diagnostic and prognostic biomarker for CRC metastasis. PMID:26968810

  9. A cytokine signal inhibitor for rheumatoid arthritis enhances cancer metastasis via depletion of NK cells in an experimental lung metastasis mouse model of colon cancer.

    PubMed

    Shimaoka, Hideki; Takeno, Shinsuke; Maki, Kenji; Sasaki, Takahide; Hasegawa, Suguru; Yamashita, Yuichi

    2017-09-01

    Current therapy for rheumatoid arthritis (RA) relies on global suppression of the immune response or specific blockade of inflammatory cytokines. However, it is unclear how immunosuppressants affect patients with cancer. Therefore, in the present study, the effect of three biological agents, tofacitinib, anti-mouse IL-6 receptor antibody (MR16-1) and etanercept, which are used for the treatment of RA diseases, on a tumor-bearing mouse model was investigated. The effect of the three agents was examined using a mouse lung-metastasis model with the murine colon 26 cancer cell line. Lymphocyte subsets and natural killer (NK) cells in peripheral blood and spleen were analyzed using fluorescence-activated cell sorting, and the number of lung surface nodules was examined. In the continuous tofacitinib administration (15 mg/kg/day) group, the number of lung surface nodules was significantly increased compared with that of the vehicle-treated group (vehicle, 1.20±0.58; tofacitinib, 35.6±10.81; P<0.01). NK cell number in the blood and spleen of tofacitinib-treated mice was decreased 10-fold, and the percentage of cluster of differentiation (CD)11(+)CD27(-) NK cells was significantly reduced. MR16-1 [8 mg/mouse; once a week; intraperitoneal (i.p.)] or etanercept (1 mg/mouse; 3 times a week; i.p.) treatment did not affect the number of NK cells or lung metastasis. In the present study, immunosuppressants that target cytokines, including tofacitinib, were demonstrated to inhibit the proliferation and differentiation of NK cells, and exhibit the potential to promote cancer metastasis using a mouse model of lung metastasis.

  10. Generation of a syngeneic orthotopic transplant model of prostate cancer metastasis

    PubMed Central

    Ellis, Leigh; Lehet, Kristin; Ku, ShengYu; Azabdaftari, Gissou; Pili, Roberto

    2014-01-01

    Progression to metastatic disease is the primary cause of mortality in men with prostate cancer (PCa). Mouse models which progress with spontaneous metastasis are limited. Such models would allow for extensive studies of molecular mechanisms of metastasis, and more definite pre- clinical therapy trials. Orthotopic murine models have been described; however a limiting biology of these models is their lack of an intact immune system. Within, we describe the development of an androgen sensitive and castrate resistant tractable orthotopic murine syngeneic (immune competent) model of prostate cancer. Both models develop primary tumors which spontaneously progress to metastatic disease in lymph tissue. These models will allow for more complete mechanistic and therapeutic studies in a short time period. PMID:25485289

  11. A Rare Tumor with a Very Rare Initial Presentation: Thymic Carcinoma as Bone Marrow Metastasis

    PubMed Central

    Dawson, Leelavathi

    2017-01-01

    Tumors of thymus gland are rare and account for 0.2% to 1.5% of all the neoplasms. They constitute a heterogeneous group that has an unknown etiology and a complex as well as varied biology. This has led to difficulty in their histological classification and in predicting their prognostic and survival markers. Among them, thymic carcinoma is the most aggressive thymic epithelial tumor exhibiting cytological malignant features and a diversity of clinicopathological characteristics that can cause diagnostic dilemmas, misdiagnosis, and therapeutic challenge. We herein describe a case of a 60-year-old man who while undergoing evaluation for the cause of pancytopenia was discovered having bone marrow metastasis from an asymptomatic thymic carcinoma. Bone marrow metastasis is an extremely rare initial presentation of thymic carcinoma with only few cases reported in the literature. PMID:28116199

  12. Role of Akt2 in regulation of metastasis suppressor 1 expression and colorectal cancer metastasis.

    PubMed

    Agarwal, E; Robb, C M; Smith, L M; Brattain, M G; Wang, J; Black, J D; Chowdhury, S

    2017-06-01

    Survival signaling is critical for the metastatic program of cancer cells. The current study investigated the role of Akt survival proteins in colorectal cancer (CRC) metastasis and explored potential mechanisms of Akt-mediated metastasis regulation. Using an orthotopic implantation model in mice, which uniquely recapitulates the entire multistep process of CRC metastasis, combined with an inducible system of short hairpin RNA-mediated Akt isoform knockdown in human CRC cells, our studies confirm a role of Akt2 in CRC cell dissemination to distant organs in vivo. Akt2 deficiency profoundly inhibited the development of liver lesions in mice, whereas Akt1 had no effect under the experimental conditions used in the study. Array analysis of human metastatic genes identified the scaffolding protein metastasis suppressor 1 (MTSS1) as a novel Akt2-regulated gene. Inducible loss of Akt2 in CRC cells robustly upregulated MTSS1 at the messenger RNA and protein level, and the accumulated protein was functionally active as shown by its ability to engage an MTSS1-Src-cortactin inhibitory axis. MTSS1 expression led to a marked reduction in levels of functional cortacin (pcortactin Y421), an actin nucleation-promoting factor that has a crucial role in cancer cell invasion and metastasis. MTSS1 was also shown to mediate suppressive effects of Akt2 deficiency on CRC cell viability, survival, migration and actin polymerization in vitro. The relevance of these findings to human CRC is supported by analysis of The Cancer Genome Atlas (TCGA) and NCBI GEO data sets, which demonstrated inverse changes in expression of Akt2 and MTSS1 during CRC progression. Taken together, the data identify MTSS1 as a new Akt2-regulated gene, and point to suppression of MTSS1 as a key step in the metastasis-promoting effects of Akt2 in CRC cells.

  13. Clinical implications of bilateral lateral cervical lymph node metastasis in papillary thyroid cancer: a risk factor for lung metastasis.

    PubMed

    Lee, Yoon Se; Lim, Yun Sung; Lee, Jin-Choon; Wang, Soo-Geun; Kim, In-Ju; Son, Seok-Man; Lee, Byung-Joo

    2011-11-01

    Distant metastasis to the lung in papillary thyroid cancer (PTC) is rarely detected, but it is known to be an important prognostic factor associated with survival. We investigated risk factors for lung metastasis in PTC. We performed a retrospective review of patients with PTC (n=977) who were treated from January 2006 to August 2009. Enrolled patients received radioablation therapy followed by a radioiodine whole body scan. Lung metastasis was screened out with whole body scan or positron emission tomography/computed tomography (PET/CT) and confirmed with chest CT. Age, gender, extrathyroidal extension, central lymph node metastasis, lateral lymph node metastasis, and bilateral lateral cervical lymph node metastasis (BLNM) were investigated to analyze the relationship with lung metastasis. In total, 949 patients were enrolled. The median age was 49 years (±13 years) with 829 women. Lung metastasis was found in 20 patients (2.1%). Patients were divided into three groups by tumor size (≤1 cm, 1-2 cm, >2 cm); the groups comprised 47.3%, 28.5%, and 24.1% of the patients, respectively. BLNM was identified in 4.4% (n=43). In a univariate analysis, male gender, old age, large tumor, extrathyroidal extension, lymph node metastasis, lateral lymph node metastasis, and BLNM were significantly related to lung metastasis (P<0.05). In a multivariate analysis, BLNM appeared to be the only significant risk factor for lung metastasis (P=0.026; odds ratio=10.219). BLNM may be a risk factor for lung metastasis. This indicates that careful examinations, including chest CT and positron emission tomography (PET), are recommended during the follow-up period when BLNM is suspected.

  14. Relationship Between P15 Gene Mutation and Formation and Metastasis of Malignant Osteosarcoma.

    PubMed

    Yu, ChangShui; Wang, WenBo

    2016-02-27

    BACKGROUND As a type of primary malignant bone tumor, osteosarcoma has high incidence and poor prognosis, and is predisposed for pulmonary metastasis. The abnormal expression of P15 gene directly participates in the invasion of various cancers. Therefore, this study investigated the gene mutation of P15 in both primary lesion and pulmonary metastasis lesion of osteosarcoma in a rat model, in an attempt to elucidate the value of P15 gene as a biological marker. MATERIAL AND METHODS A total of 60 SD rats were randomly divided into 2 groups. Model rats had injection of osteosarcoma UMR-106 cells (5×106) inoculated underneath the right forelimb skin, while control rats received saline injection instead. Six rats were sacrificed after 0, 1, 2, 4, and 6 weeks of the inoculation. Tissue samples from inoculation sites and lungs were extracted for measuring the tumor size. SP immunohistochemical (IHC) staining was used to detect the positive expression rate, while P15 gene mutation was detected by PCR method. RESULTS With the elongation of inoculation time, tumor size was significantly increased (p<0.05). The positive expression rates in both primary and pulmonary metastasis lesions were also significantly elevated (p<0.05). The occurrence rate of P15 gene mutation in model rats was significantly elevated and showed a correlation with the tumor formation (r=0.998, p<0.05). CONCLUSIONS The P15 gene mutation was significantly correlated with osteosarcoma formation and metastasis towards the pulmonary tissue, suggesting its potency as a novel biological marker for early diagnosis of osteosarcoma.

  15. Human Subperitoneal Fibroblast and Cancer Cell Interaction Creates Microenvironment That Enhances Tumor Progression and Metastasis

    PubMed Central

    Yokota, Mitsuru; Ishii, Genichiro; Saito, Norio; Aoyagi, Kazuhiko; Sasaki, Hiroki; Ochiai, Atsushi

    2014-01-01

    Backgrounds Peritoneal invasion in colon cancer is an important prognostic factor. Peritoneal invasion can be objectively identified as periotoneal elastic laminal invasion (ELI) by using elastica stain, and the cancer microenvironment formed by the peritoneal invasion (CMPI) can also be observed. Cases with ELI more frequently show distant metastasis and recurrence. Therefore, CMPI may represent a particular milieu that facilitates tumor progression. Pathological and biological investigations into CMPI may shed light on this possibly distinctive cancer microenvironment. Methods We analyzed area-specific tissue microarrays to determine the pathological features of CMPI, and propagated subperitoneal fibroblasts (SPFs) and submucosal fibroblasts (SMFs) from human colonic tissue. Biological characteristics and results of gene expression profile analyses were compared to better understand the peritoneal invasion of colon cancer and how this may form a special microenvironment through the interaction with SPFs. Mouse xenograft tumors, derived by co-injection of cancer cells with either SPFs or SMFs, were established to evaluate their active role on tumor progression and metastasis. Results We found that fibrosis with alpha smooth muscle actin (α-SMA) expression was a significant pathological feature of CMPI. The differences in proliferation and gene expression profile analyses suggested SPFs and SMFs were distinct populations, and that SPFs were characterized by a higher expressions of extracellular matrix (ECM)-associated genes. Furthermore, compared with SMFs, SPFs showed more variable alteration in gene expressions after cancer-cell-conditioned medium stimulation. Gene ontology analysis revealed that SPFs-specific upregulated genes were enriched by actin-binding or contractile-associated genes including α-SMA encoding ACTA2. Mouse xenograft tumors derived by co-injection of cancer cells with SPFs showed enhancement of tumor growth, metastasis, and capacity for

  16. Relationship Between P15 Gene Mutation and Formation and Metastasis of Malignant Osteosarcoma

    PubMed Central

    Yu, ChangShui; Wang, WenBo

    2016-01-01

    Background As a type of primary malignant bone tumor, osteosarcoma has high incidence and poor prognosis, and is predisposed for pulmonary metastasis. The abnormal expression of P15 gene directly participates in the invasion of various cancers. Therefore, this study investigated the gene mutation of P15 in both primary lesion and pulmonary metastasis lesion of osteosarcoma in a rat model, in an attempt to elucidate the value of P15 gene as a biological marker. Material/Methods A total of 60 SD rats were randomly divided into 2 groups. Model rats had injection of osteosarcoma UMR-106 cells (5×106) inoculated underneath the right forelimb skin, while control rats received saline injection instead. Six rats were sacrificed after 0, 1, 2, 4, and 6 weeks of the inoculation. Tissue samples from inoculation sites and lungs were extracted for measuring the tumor size. SP immunohistochemical (IHC) staining was used to detect the positive expression rate, while P15 gene mutation was detected by PCR method. Results With the elongation of inoculation time, tumor size was significantly increased (p<0.05). The positive expression rates in both primary and pulmonary metastasis lesions were also significantly elevated (p<0.05). The occurrence rate of P15 gene mutation in model rats was significantly elevated and showed a correlation with the tumor formation (r=0.998, p<0.05). Conclusions The P15 gene mutation was significantly correlated with osteosarcoma formation and metastasis towards the pulmonary tissue, suggesting its potency as a novel biological marker for early diagnosis of osteosarcoma. PMID:26921270

  17. Eight proteins play critical roles in RCC with bone metastasis via mitochondrial dysfunction.

    PubMed

    Wang, Jiang; Zhao, Xiaolin; Qi, Jun; Yang, Caihong; Cheng, Hao; Ren, Ye; Huang, Lei

    2015-08-01

    Most kidney cancers are renal cell carcinomas (RCC). RCC lacks early warning signs and 70 % of patients with RCC develop metastases. Among them, 50 % of patients having skeletal metastases developed a dismal survival of less than 10 % at 5 years. Therefore, exploring the key driving proteins and pathways involved in RCC bone metastasis could benefit patients' therapy and prolong their survival. We examined the difference between the OS-RC-2 cells and the OS-RC-2-BM5 cells (subpopulation from OS-RC-2) of RCC with proteomics. Then we employed Western-blot, immunohistochemistry and the clinical database (oncomine) to screen and verify the key proteins and then we analyzed the functions and the related pathways of selected key proteins with system biology approaches. Our proteomic data revealed 26 significant changed spots (fold change <0.5 and >1.9, P < 0.05) between two cells. The Western blotting results validated for these identified spots were consistent with the proteomics'. From the public clinical database, 23 out of 26 proteins were connected with RCC metastases and 9 out of 23 with survival time directly (P < 0.05). Finally, only 8 out of 9 proteins had significantly positive results in tissues of RCC patients with bone metastasis compared with primary tumor (P < 0.05). System biology analyzing results showed these eight proteins mainly distributed in oxidative phosphorylation which indicates that mitochondria dysfunction played the critical role to regulate cells metastasis. Our article used a variety of experimental techniques to find eight proteins which abnormally regulated mitochondrial function to achieve a successful induction for RCC metastasis to bone.

  18. Brain metastasis: new opportunities to tackle therapeutic resistance.

    PubMed

    Seoane, Joan; De Mattos-Arruda, Leticia

    2014-09-12

    Brain metastasis is a devastating complication of cancer with unmet therapeutic needs. The incidence of brain metastasis has been rising in cancer patients and its response to treatment is limited due to the singular characteristics of brain metastasis (i.e., blood-brain-barrier, immune system, stroma). Despite improvements in the treatment and control of extracranial disease, the outcomes of patients with brain metastasis remain dismal. The mechanisms that allow tumor cells to promulgate metastases to the brain remain poorly understood. Further work is required to identify the molecular alterations inherent to brain metastasis in order to identify novel therapeutic targets and explicate the mechanisms of resistance to systemic therapeutics. In this article, we review current knowledge of the unique characteristics of brain metastasis, implications in therapeutic resistance, and the possibility of developing biomarkers to rationally guide the use of targeted agents.

  19. Diet, nutrients, phytochemicals, and cancer metastasis suppressor genes.

    PubMed

    Meadows, Gary G

    2012-12-01

    The major factor in the morbidity and mortality of cancer patients is metastasis. There exists a relative lack of specific therapeutic approaches to control metastasis, and this is a fruitful area for investigation. A healthy diet and lifestyle not only can inhibit tumorigenesis but also can have a major impact on cancer progression and survival. Many chemicals found in edible plants are known to inhibit metastatic progression of cancer. While the mechanisms underlying antimetastatic activity of some phytochemicals are being delineated, the impact of diet, dietary components, and various phytochemicals on metastasis suppressor genes is underexplored. Epigenetic regulation of metastasis suppressor genes promises to be a potentially important mechanism by which dietary components can impact cancer metastasis since many dietary constituents are known to modulate gene expression. The review addresses this area of research as well as the current state of knowledge regarding the impact of diet, dietary components, and phytochemicals on metastasis suppressor genes.

  20. The Role of Megakaryocytes in Breast Cancer Metastasis to Bone

    DTIC Science & Technology

    2011-05-01

    and TPO -/- mice, and femurs collected over time. Bone cytokines also will be assessed. 15. SUBJECT TERMS Megakaryocytes, breast cancer, bone...conditions of metastasis or non-metastasis. Thrombopoietin ( TPO -/-) knockout mice will be used to test metastasis in mice with a megakaryocyte deficiency...1. Begin the process of creating TPO -/-mice on a Balb/c background. We had received permission from Genentech to obtain frozen embryos of TPO

  1. Mechanisms of CTC Biomarkers in Breast Cancer Brain Metastasis

    DTIC Science & Technology

    2015-10-01

    AWARD NUMBER: W81XWH-14-1-0214 TITLE: Mechanisms of CTC Biomarkers in Breast Cancer Brain Metastasis PRINCIPAL INVESTIGATOR: Dario...5a. CONTRACT NUMBER Mechanisms of CTC Biomarkers in Breast Cancer Brain Metastasis 5b. GRANT NUMBER W81XWH-14-1-0214 5c. PROGRAM ELEMENT NUMBER 6...SUPPLEMENTARY NOTES None 14. ABSTRACT Breast cancer brain metastasis (BCBM) is devastating and increasing in frequency, however, BCBM mechanisms are

  2. Tumor-Host Interaction in Breast Cancer Bone Metastasis

    DTIC Science & Technology

    2006-01-01

    sites where breast cancer metastases are found include the liver, lungs and brain. However, the most common site of breast cancer metastasis is the...increased expression in lung metastasis derived variants of the GI101A breast cancer cell line 21. Thus, the increased expression of CTGF may be more...therapy exists for bone metastasis , and clinical management is generally palliative. Treatment options include surgery or radiation to prevent or repair

  3. Regulation of Prostate Cancer Bone Metastasis by DKK1

    DTIC Science & Technology

    2012-09-01

    0030 TITLE: Regulation of Prostate Cancer Bone Metastasis by DKK1 PRINCIPAL INVESTIGATOR: Gregory A. Clines, MD, PhD CONTRACTING...of Prostate Cancer Bone Metastasis by DKK1 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-08-1-0030 5c. PROGRAM ELEMENT...Osteoblastic bone metastasis is a common complication of advanced prostate cancer, resulting in pain and pathologic fracture. Dickkopf homolog 1 ( DKK1 ) is a

  4. Regulation of Prostate Cancer Bone Metastasis by DKK1

    DTIC Science & Technology

    2010-04-01

    0030 TITLE: Regulation of Prostate Cancer Bone Metastasis by DKK1 PRINCIPAL INVESTIGATOR: Gregory A. Clines, MD, PhD CONTRACTING...AND SUBTITLE Regulation of Prostate Cancer Bone Metastasis by DKK1 5a. CONTRACT NUMBER W81XWH-08-1-0030 5b. GRANT NUMBER...metastasis is a common complication of advanced prostate cancer, resulting in pain and pathologic fracture. Dickkopf homolog 1 ( DKK1 ) is a secreted

  5. Brain metastasis in patients with uterine cervical cancer.

    PubMed

    Hwang, Jong Ha; Yoo, Heon Jong; Lim, Myong Cheol; Seo, Sang-Soo; Kang, Sokbom; Kim, Joo-Young; Park, Sang-Yoon

    2013-01-01

    The purpose of this study was to describe the features of patients with brain metastasis from cervical cancer. The medical records of patients with cervical cancer between February 2001 and June 2011 were reviewed retrospectively. Clinical characteristics, symptoms, treatment and survival in patients with brain metastasis were analyzed.   Eleven patients with brain metastasis from cervical cancer were identified, representing an incidence of brain metastasis in the study population of 0.45%. Median patient age at initial diagnosis of cervical cancer was 50 years (range 33-75 years). Non-squamous cell carcinoma was diagnosed in six (54.5%) of the 11 patients, with small cell carcinoma diagnosed in two patients. Ten of the 11 patients had lung-related metastasis at presentation; eight patients had lung metastasis, one had mediastinal lymph node metastasis, and one had pleural metastasis. The median interval from diagnosis of cervical cancer to identification of brain metastasis was 15.4 months (range 3.4-83.3 months). Nine patients presented with neurologic symptoms, such as headache, nausea, vomiting, seizure and extremity weakness. Initially, six patients received whole brain radiotherapy: three patients received chemotherapy; one underwent surgery; and one patient refused treatment. The median survival time after diagnosis of the brain metastases was 5.9 months (range 0.7-19 months). The prognosis after diagnosis of the brain metastasis in patients with uterine cervical cancer is poor. The small cell type and lung metastasis seem to be related with brain metastasis and may be regarded as risk factors. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

  6. Targeting Phosphatidylserine for Radioimmunotherapy of Breast Cancer Brain Metastasis

    DTIC Science & Technology

    2015-12-01

    Award Number: W81XWH-12-1-0316 TITLE: Targeting Phosphatidylserine for Radioimmunotherapy of Breast Cancer Brain Metastasis PRINCIPAL...Cancer Brain Metastasis 5b. GRANT NUMBER W81XWH-12-1-0316 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Rolf A. Brekken...DISTRIBUTION / AVAILABILITY STATEMENT Approved for public release; distribution unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Brain metastasis occurs in

  7. Targeting Phosphatidylserince for Radioimmunotherapy of Breast Cancer Brain Metastasis

    DTIC Science & Technology

    2014-10-01

    Targeting Phosphatidylserine for Radioimmunotherapy of Breast Cancer Brain Metastasis 5b. GRANT NUMBER W81XWH-12-1-0316 5c. PROGRAM ELEMENT NUMBER 6...SUPPLEMENTARY NOTES 14. ABSTRACT Brain metastasis occurs in ~30% of metastatic breast cancer patients. The prognosis is extremely poor, with a...Introduction Brain metastasis is the most common intracranial malignancy in adults. The prognosis is extremely poor, with a median survival of 4-6 months even

  8. [Adenocarcinoma of lung cancer with solitary metastasis to the stomach].

    PubMed

    Koh, Sung Ae; Lee, Kyung Hee

    2014-09-25

    Although hematogenous metastasis of cancer to the gastrointestinal track is rare, it sometime has been reported in patients with malignant melanoma and breast cancer. However, it is extremely rare for lung cancer to metastasize to the stomach, not to mention solitary gastric metastasis. Herein, the authors report a case of a 69-year-old man who was initially diagnosed with lung cancer with synchronous primary gastric cancer which proved to be lung cancer with solitary gastric metastasis after the operation.

  9. [Research progress on mechanisms of modern medicine in cancer metastasis].

    PubMed

    Chen, Hui; Qu, Jing-Lian; Gong, Jie-Ning

    2014-08-01

    Cancer metastasis is the most dangerous stage of tumorigenesis and evolution, the primary cause of death in cancer patients. Clinically, more than 60% of cancer patients have found metastasis at the time of examination. Modern medicine has made significant progress on the mechanisms of cancer metastasis in recent years, from the simple "anatomy and machinery" theory forward to the "seed and soil" theory, then to the "microenvironmental" theory and the "cancer stem cell" theory. The emerging "cancer stem cell" theory successfully explains phenomenon such as tumor genetic heterogeneity, anoikis resistance, tumor dormancy, providing more new targets and ideas for the diagnosis and treatment of cancer metastasis.

  10. Skeletal metastasis: treatments, mouse models, and the Wnt signaling

    PubMed Central

    Valkenburg, Kenneth C.; Steensma, Matthew R.; Williams, Bart O.; Zhong, Zhendong

    2013-01-01

    Skeletal metastases result in significant morbidity and mortality. This is particularly true of cancers with a strong predilection for the bone, such as breast, prostate, and lung cancers. There is currently no reliable cure for skeletal metastasis, and palliative therapy options are limited. The Wnt signaling pathway has been found to play an integral role in the process of skeletal metastasis and may be an important clinical target. Several experimental models of skeletal metastasis have been used to find new biomarkers and test new treatments. In this review, we discuss pathologic process of bone metastasis, the roles of the Wnt signaling, and the available experimental models and treatments. PMID:23327798

  11. Isolated pancreatic metastasis of hepatocellular carcinoma after curative resection.

    PubMed

    Woo, Sang Myung; Park, Joong-Won; Han, Sung-Sik; Choi, Joon-Il; Lee, Woo Jin; Park, Sang Jae; Hong, Eun Kyung; Kim, Chang-Min

    2010-04-15

    Hepatocellular carcinoma (HCC) is a highly malignant tumor and extrahepatic metastasis is not rare. The most common organ of HCC metastasis is lung, followed by bone and adrenal gland. To the best of our knowledge, isolated pancreatic metastasis of HCC that developed after curative resection has not been described previously. We report a case of solitary pancreatic metastasis of HCC, which was found 28 mo after left hemihepatectomy for HCC. The lesion was successfully resected with the pancreas, and no other metastatic lesions have been found in follow-up.

  12. Metastasis of prostate adenocarcinoma to the frontal and ethmoid sinus

    PubMed Central

    Akdemir, Fatih; Aldemir, Mustafa; Çakar, Hasan; Güler, Gülnur

    2016-01-01

    Intracranial metastasis of prostate cancer is rarely seen, and there are few studies in this regard in the literature. Most of these studies in the literature comprise the metastasis of prostate cancer to the sphenoid sinus, and metastasis to the frontal and ethmoid sinus is a much rare entity. Association of visual symptoms, epistaxis, headache, and hematuria may indicate a urologic malignancy in terms of the origin of the primary tumor. This study was aimed to present the prostate cancer case of a 73-year-old patient whose paranasal sinus tomograms revealed the presence of frontal and ethmoid sinus metastasis. PMID:27909626

  13. Thinking outside the box: using metastasis suppressors as molecular tools.

    PubMed

    Thiolloy, Sophie; Rinker-Schaeffer, Carrie W

    2011-04-01

    Metastasis, the process in which tumor cells move from a primary tumor through the circulation, lodge, and grow in distant locations, is a significant contributor to cancer patient morbidity and mortality, yet remains poorly understood. The molecular processes regulating tumorigenicity and metastasis are distinguishable, suggesting that it is possible to design therapeutic interventions to specifically control metastasis formation. Metastasis suppressors, which specifically regulate metastasis, are being used in "reverse genetics" approaches to discover the phenotypic alterations caused by modulating their levels and/or activity. This strategy is allowing the identification of tumor-host interactions that are crucial for efficient colonization and their disruption can be targeted to suppress metastases formation. In this review we discuss studies addressing invasion and migration, key functions for both early and late in the metastatic process. Metastasis suppressor functions, which modulate lodging and subsequent colonization of the secondary site, are also described. In sum this review focuses on metastasis suppressors that have yielded insight into mechanisms controlling metastasis formation. These serve as platform for out of the box thinking which will enable the discovery of new paradigms in metastasis research. Copyright © 2011. Published by Elsevier Ltd.

  14. Port-site metastasis after laparoscopic surgery for gastrointestinal cancer.

    PubMed

    Emoto, Shigenobu; Ishigami, Hironori; Yamaguchi, Hironori; Ishihara, Soichiro; Sunami, Eiji; Kitayama, Joji; Watanabe, Toshiaki

    2017-03-01

    Although the incidence of port-site metastasis after laparoscopic surgery for colorectal cancer has markedly decreased since laparoscopic colectomy was first reported in 1991, it still has not reached zero. In colorectal cancer, the safety of laparoscopic surgery, including the low incidence of port-site metastasis, has been proven in large, randomized trials. In gastric cancer, reports of port-site metastasis are extremely rare, but we should await the results of ongoing trials. This brief review summarizes the current knowledge regarding port-site metastasis after laparoscopic surgery for colorectal and gastric cancer.

  15. An Autopsy Case of Lepidic Pulmonary Metastasis from Cholangiocarcinoma

    PubMed Central

    Nagayoshi, Yohsuke; Yamamoto, Kazuko; Hashimoto, Satoru; Hisatomi, Keiko; Doi, Seiji; Nagashima, Seiji; Kurohama, Hirokazu; Ito, Masahiro; Takazono, Takahiro; Nakamura, Shigeki; Miyazaki, Taiga; Kohno, Shigeru

    2016-01-01

    We herein report the first case of pulmonary metastasis with lepidic growth that originated from cholangiocarcinoma. A 77-year-old man was admitted to our hospital due to exertional dyspnea and liver dysfunction. Computed tomography showed widespread infiltration and a ground-glass opacity in the lung and dilation of the intrahepatic bile duct. The pulmonary lesion progressed rapidly, and the patient died of respiratory failure. Cholangiocarcinoma and lepidic pulmonary metastasis were pathologically diagnosed by an autopsy. Lepidic pulmonary growth is an atypical pattern of metastasis, and immunopathological staining is useful to distinguish pulmonary metastasis from extrapulmonary cancer and primary pulmonary adenocarcinoma. PMID:27725547

  16. Pathway-related molecules of VEGFC/D-VEGFR3/NRP2 axis in tumor lymphangiogenesis and lymphatic metastasis.

    PubMed

    Wang, Jingwen; Huang, Yuhong; Zhang, Jun; Wei, Yuanyi; Mahoud, Salma; Bakheet, Ahmed Musa Hago; Wang, Li; Zhou, Shuting; Tang, Jianwu

    2016-10-01

    Precondition for tumor lymphatic metastasis is that tumor cells induce formation of original and newborn lymphatic vessels and invade surrounding lymphatic vessels in tumor stroma, while some pathway-related molecules play an important role in mechanisms associated with proliferation and migration of lymphatic endothelial cells (LECs) and tumor cells. In lymphangiogenesis and lymphatic metastasis, the pathway-related molecules of VEGFC/D-VEGFR3/NRP2 axis, such as Furin-like enzyme, CNTN1, Prox1, LYVE-1, Podoplanin, SOX18, SDF1 and CXCR4, are direct constitutors as a portion of VEGFC/D-VEGFR3/NRP2 axis, and their biological activities rely on this ligand-receptor system. These axis-related signal molecules could gradually produce waterfall-like cascading effects, mediate differentiation and maturation of LECs, remodel original and neonatal lymphatic vessels, as well as ultimately promote tumor cell chemotaxis, migration, invasion and metastasis to lymphoid tracts. This review summarizes the structure and function features of pathway-related molecules of VEGFC/D-VEGFR3/NRP2 axis, the expression changes of these molecules in different anatomic organs or histopathologic types or development stages of various tumors, the characteristics of transduction, implementation, integration of signal networks, the interactive effects on biological behaviors between tumor cells and lymphatic endothelial cells, and their molecular mechanisms and significances in tumor lymphangiogenesis and lymphatic metastasis.

  17. An orthotopic xenograft model with survival hindlimb amputation allows investigation of the effect of tumor microenvironment on sarcoma metastasis.

    PubMed

    Goldstein, Seth D; Hayashi, Masanori; Albert, Catherine M; Jackson, Kyle W; Loeb, David M

    2015-10-01

    Overall survival rates for pediatric high-grade sarcoma have improved greatly in the past few decades, but prevention and treatment of distant metastasis remain the most compelling problems facing these patients. Traditional preclinical mouse models have not proven adequate to study the biology and treatment of spontaneous distant sarcoma metastasis. To address this deficit, we developed an orthotopic implantation/amputation model in which patient-derived sarcoma xenografts are surgically implanted into mouse hindlimbs, allowed to grow, then subsequently amputated and the animals observed for development of metastases. NOD/SCID/IL-2Rγ-null mice were implanted with either histologically intact high grade sarcoma patient-derived xenografts or cell lines in the pretibial space and affected limbs were amputated after tumor growth. In contrast to subcutaneous flank tumors, we were able to consistently detect spontaneous distant spread of the tumors using our model. Metastases were seen in 27-90 % of animals, depending on the xenograft, and were repeatable and predictable. We also demonstrate the utility of this model for studying the biology of metastasis and present preliminary new insights suggesting the role of arginine metabolism and macrophage phenotype polarization in creating a tumor microenvironment that facilitates metastasis. Subcutaneous tumors express more arginase than inducible nitric oxide synthase and demonstrate significant macrophage infiltration, whereas orthotopic tumors express similar amounts of inducible nitric oxide synthase and arginase and have only a scant macrophage infiltrate. Thus, we present a model of spontaneous distant sarcoma metastasis that mimics the clinical situation and is amenable to studying the biology of the entire metastatic cascade.

  18. Tumor budding is an independent prognostic factor for prediction of lymph node metastasis in oral squamous cell carcinoma.

    PubMed

    Angadi, Punnya V; Patil, Prakash V; Hallikeri, Kaveri; Mallapur, M D; Hallikerimath, Seema; Kale, Alka D

    2015-04-01

    Despite the enormous advances in diagnostic and management modalities of oral squamous cell carcinoma (OSCC), the mortality rates have remained stagnant with a 5-year survival rate of <50% challenging the available methods of prognostic assessment. Presence of tumor budding has been associated with aggressive behavior and is correlated with lymph node metastasis, recurrence, distant metastasis, and decreased survival in several cancers. However, the prognostic significance of this apparently simple to evaluate parameter is sparse in OSCC. A total of 75 cases of surgically excised OSCC were analyzed for tumor budding along with other clinicopathologic parameters. Tumor budding was graded as high and low intensity based on presence and absence of ≥10 or <10 budding foci in hematoxylin and eosin-stained sections. An association between the clinicopathological parameters, lymph node metastases with the budding index was examined using univariate and multivariate analyses. Tumor budding was evident in 89% of cases with around 45.3% of the cases demonstrated high-intensity budding. High-intensity tumor budding was significantly associated with lymph node metastasis and depth of invasion. Multivariate analysis demonstrated that tumor budding and depth of invasion were significant independent predictors for lymph node metastasis. Tumor budding is frequently encountered histologic marker in OSCC. High-intensity tumor budding is a strong independent prognostic factor for prediction of lymph node metastasis. © The Author(s) 2015.

  19. iTRAQ analysis of colorectal cancer cell lines suggests Drebrin (DBN1) is overexpressed during liver metastasis.

    PubMed

    Lin, Qifeng; Tan, Hwee Tong; Lim, Teck Kwang; Khoo, Avery; Lim, Kiat Hon; Chung, Maxey C M

    2014-06-01

    Colorectal cancer is currently the third in cancer incidence worldwide and the fourth most common cause of cancer deaths. Mortality in colorectal cancer is often ascribed to liver metastasis. In an effort to elucidate the proteins involved in colorectal cancer liver metastasis, we compared the proteome profiles of the human colon adenocarcinoma cell line HCT-116 with its metastatic derivative E1, using the iTRAQ labelling technology, coupled to 2D-LC and MALDI-TOF/TOF MS. A total of 547 proteins were identified, of which 31 of them were differentially expressed in the E1 cell line. Among these proteins, the differential expressions of translationally controlled tumour protein 1, A-kinase anchor protein 12 and Drebrin (DBN1) were validated using Western blot. In particular, DBN1, a protein not previously known to be involved in colorectal cancer metastasis, was found to be overexpressed in E1 as compared to HCT-116 cells. The overexpression of DBN1 was further validated using immunohistochemistry on colorectal cancer tissue sections with matched lymph node and liver metastasis tissues. DBN1 is currently believed to be involved in actin cytoskeleton reorganisation and suppresses actin filament cross-linking and bundling. Since actin reorganisation is an important process for tumour cell migration and invasion, DBN1 may have an important role during colorectal cancer metastasis.

  20. Metastasis-associated gene, mag-1 improves tumour microenvironmental adaptation and potentiates tumour metastasis.

    PubMed

    Wang, Yan; Jia, Haiquan; Lin, Huiyun; Tan, Xiaogang; Du, Zhiyan; Chen, Huihua; Xu, Yuanji; Han, Xiaoxi; Zhang, Jiakai; Zhao, Siyang; Yu, Xiaodan; Lu, Yinglin

    2012-12-01

    Metastasis is a major cause of death from malignant diseases, and the underlying mechanisms are still largely not known. A detailed probe into the factors which may regulate tumour invasion and metastasis contributes to novel anti-metastatic therapies. We previously identified a novel metastasis-associated gene 1 (mag-1) by means of metastatic phenotype cloning. Then we characterized the gene expression profile of mag-1 and showed that it promoted cell migration, adhesion and invasion in vitro. Importantly, the disruption of mag-1 via RNA interference not only inhibited cellular metastatic behaviours but also significantly reduced tumour weight and restrained mouse breast cancer cells to metastasize to lungs in spontaneous metastatic assay in vivo. Furthermore, we proved that mag-1 integrates dual regulating mechanisms through the stabilization of HIF-1α and the activation of mTOR signalling pathway. We also found that mag-1-induced metastatic promotion could be abrogated by mTOR specific inhibitor, rapamycin. Taken together, the findings identified a direct role that mag-1 played in metastasis and implicated its function in cellular adaptation to tumour microenvironment.

  1. Thin Sections

    PubMed Central

    Peachey, Lee D.

    1958-01-01

    Knowledge of the thickness of sections is important for proper interpretation of electron micrographs. Therefore, the thicknesses of sections of n-butyl methacrylate polymer were determined by ellipsometry, and correlated with the color shown in reflected light. The results are: gray, thinner than 60 mµ; silver, 60 to 90 mµ; gold, 90 to 150 mµ; purple, 150 to 190 mµ; blue, 190 to 240 mµ; green, 240 to 280 mµ; and yellow, 280 to 320 mµ. These results agree well with optical theory and with previous published data for thin films. Sections, after cutting, are 30 to 40 per cent shorter than the face of the block from which they were cut. Only a small improvement results from allowing the sections to remain in the collecting trough at room temperature. Heating above room temperature, however, reduces this shortening, with a corresponding improvement in dimensions and spatial relationships in the sections. When the thickness of the section is considered in interpreting electron micrographs instead of considering the section to be two-dimensional, a more accurate interpretation is possible. The consideration of electron micrographs as arising from projections of many profiles from throughout the whole thickness of the section explains the apparent lack of continuity often observed in serial sections. It is believed that serial sections are actually continuous, but that the change in size of structure through the thickness of one section and the consideration of only the largest profile shown in the micrograph can account for the lack of continuity previously observed. PMID:13549493

  2. Monoclonal Antibody Testing for Cancer Metastasis

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Malignant cells are characterized by the ability to invade surrounding normal tissues. Tumor invasion is abetted by proteolytic enzymes that have been correlated with recurrent disease and metastasis. These enzymes are involved in a cascade of proteolytic interactions with other enzymes and inhibitors which allow cancer cells to dissolve surrounding extracellular matrix, thereby enabling the cells to rapidly invade adjacent tissues and migrate to metastatic sites distant from the primary tumor. Among these proteases are the plasminogen activators (PA), collagenase IV, faminase, and in some cases cathepsin D, which together mediate key steps in the invasion process of metastasis. Cells which have the selective advantage for invasion and metastasis are those capable of regulating their proteolytic activity and proliferation. Cells in the process of invasion would be probably down-regulated for proliferation, but subsequent to attachment and adhesion at a distant site, would then be in a proliferative mode, up-regulating DNA replication. Urokinase (uPA) can be present in the tissues in several molecular forms. The inactive proenzyme is a single chain protein (scuPA) that is cleaved at Lys. 158 to form the double chain, high molecular weight active form (HMW-uPA) of 54 kD. A low molecular weight form (LMW-uPA) can also be produced by cleavage of the HMW-U PA at Lys. 135 - Lys. 136 giving a 35 kD active enzyme. Recently, it has been shown that the HMW active form of urokinase, bound to the tumor cell membrane, is responsible for the local lysis of the extracellular matrix, hence the tissue invasion mechanism for metastasis (Andreasen et al, 19861. Receptor- (membrane) bound uPA is twice as efficient (catalytically) as free fluid-phase uPA. Tho unbound uPA and the LMW form is not responsible for most of the local dissolution of extracellular matrix in the immediate vicinity of the metastatic tumor cell. High levels of urokinase (greater than 3.49 ng/mg of total protein

  3. Isolated Abdominal Wall Metastasis of Endometrial Carcinoma

    PubMed Central

    Simões, Jorge; Gonçalves, Matilde; Matos, Isabel

    2014-01-01

    A woman in her mid-60s presented with a bulky mass on the anterior abdominal wall. She had a previous incidental diagnosis of endometrial adenocarcinoma FIGO stage IB following a vaginal hysterectomy. Physical exam and imaging revealed a well circumscribed bulging tumour at the umbilical region, measuring 10 × 9 × 9 cm, with overlying intact skin and subcutaneous tissue. Surgical resection was undertaken, and histological examination showed features of endometrial carcinoma. She began chemotherapy and is alive with no signs of recurrent disease one year after surgery. This case brings up to light an atypical location of a solitary metastasis of endometrial carcinoma. PMID:25349753

  4. [Orthopaedic management of long bones metastasis].

    PubMed

    Fleury, Thierry Rod; Holzer, Nicolas; Fleury, Mapi; Hoffmeyer, Pierre J

    2012-12-19

    The recent progress in oncologic management of patients with metastatic disease has permitted a significant improvement of their life expectancy. Many of these patients will suffer from complications related to bone metastasis. Unfortunately an orthopaedic treatment is seldom offered to them, mainly because of the misconception that this would not bring them any benefice. However these patients are often good candidates for an orthopaedic management, which objectives are to relieve pain and to re-establish their quality of life. The available surgical techniques are well described and the management protocols are clearly defined, as are the expectable complications and the errors that must not be done.

  5. Intracardiac metastasis from germ cell testicular tumor.

    PubMed

    Jonjev, Z S; Rajić, J; Majin, M; Donat, D

    2012-09-01

    Intracardiac metastases of germ cell testicular tumors are not commonly seen in clinical practice. The clinical presentation of right-sided heart metastases ranges widely. Depending upon its size and intracardiac location, it could be highly symptomatic, leading to a congestive heart failure, pulmonary embolism, and death, or completely asymptomatic. Improved imaging techniques and treatment strategies demonstrate that right-sided heart metastasis should be considered a potentially dangerous but treatable disease. Presented is the case of a 24-year-old man with a testicular nonseminomatous germ cell tumor, which after metastasizing in the right atrium differentiated into a teratoma and resulted in an inflow obstruction of the right ventricle.

  6. Meningioma with metastasis from follicular carcinoma thyroid.

    PubMed

    Chaturvedi, Sujata; Gupta, Sanjeev; Kumari, Rima

    2010-01-01

    A 45-year-old female presented with loss of vision in the left eye, numbness on left half of face and left-sided hemicrania for two months. On the basis of radiological investigations, provisional diagnosis of basal meningioma was made. Tissue sent for histopathological evaluation revealed a dual tumor-meningioma with metastasis from follicular carcinoma, thyroid. To the best of authors' knowledge, this is the first report of a tumor metastasizing to another tumor, where a follicular carcinoma thyroid metastasized to meningioma.

  7. NDPKA is not just a metastasis suppressor - be aware of its metastasis-promoting role in neuroblastoma.

    PubMed

    Tan, Choon-Yee; Chang, Christina L

    2017-10-09

    NDPK-A, encoded by nm23-H1 (also known as NME1) was the first metastasis suppressor discovered. Much of the attention has been focused on the metastasis-suppressing role of NDPK-A in human tumors, including breast carcinoma and melanoma. However, compelling evidence points to a metastasis-promoting role of NDPK-A in certain tumors such as neuroblastoma and lymphoma. To balance attention on this contrariety of NDPK-A in different cancer types, this review addresses the metastasis-promoting role of NDPK-A in neuroblastoma. Neuroblastoma is an embryonic tumor, arising from neural crest cells that fail to differentiate into the sympathetic nervous system. We summarize and discuss nm23-H1 genetics and the prognosis of neuroblastoma, structural and functional changes associated with the S120G mutation of NDPK-A, as well as the evidence supporting the role of NDPK-A as a metastasis promoter. Also discussed are the NDPK-A relevant molecular determinants of neuroblastoma metastasis, and metastasis-relevant neural crest development. Because of NDPK-A's dichotomous role in tumor metastasis as both a suppressor and a promoter, tumor genome/exome profiles are necessary to identify the molecular drivers of metastasis in the NDPK-A network for developing tumor-specific therapies.Laboratory Investigation advance online publication, 9 October 2017; doi:10.1038/labinvest.2017.105.

  8. Clinical and radiological pictures of hepatocellular carcinoma with intracranial metastasis.

    PubMed

    Yen, F S; Wu, J C; Lai, C R; Sheng, W Y; Kuo, B I; Chen, T Z; Tsay, S H; Lee, S D

    1995-01-01

    Hepatocellular carcinoma (HCC) with extrahepatic spreading is not uncommon. In order to delineate the clinical and radiological pictures of HCC with intracranial metastasis, 33 documented cases were analysed. Eighteen had brain parenchymal metastasis without skull involvement; the other 15 cases disclosed skull metastasis with brain invasion. The underlying HCC are mainly of expanding (13/33, 39.4%) and multifocal (13/33, 39.4%) types. Eighteen cases (18/33, 54.5%) had mental changes not related to hypoglycaemia or hepatic encephalopathy. Eighteen cases (18/20, 90%) disclosed hyperdense mass lesions by non-contrast computed tomography (CT) scans and 17 cases showed homogeneous enhancement (17/22, 77.3%) by post-contrast CT images. In the non-skull involved group, five cases (5/12, 41.7%) disclosed ring-shape enhancement and 14 cases (14/16, 87.5%) had perifocal oedema, which were not seen in the skull involved group. Eight cases (8/33, 24.2%) presented as intracerebral haemorrhage. Twelve (12/33, 36.4%) died of brain herniation. Most (14/18, 77.8%) non-skull involved cases had simultaneous lung metastasis without bony metastasis, while the skull involved group often (10/15, 66.7%) disclosed extracranial bony metastasis without lung metastasis. The difference in extracranial metastasis was statistically significant (P < 0.05). The multivariate survival analysis disclosed that lower lactate dehydrogenase level (< or = 316 U/L, P = 0.029) and treatments (surgery or radiation, P = 0.001) were positively associated with longer survival. In conclusion, HCC with intracranial metastasis is symptomatic and life-threatening. Half the cases may come from pulmonary metastasis and the other half may be from bony metastasis. Brain irradiation or surgery can prolong their survival.

  9. Enhanced MAF Oncogene Expression and Breast Cancer Bone Metastasis

    PubMed Central

    Pavlovic, Milica; Arnal-Estapé, Anna; Rojo, Federico; Bellmunt, Anna; Tarragona, Maria; Guiu, Marc; Planet, Evarist; Garcia-Albéniz, Xabier; Morales, Mónica; Urosevic, Jelena; Gawrzak, Sylwia; Rovira, Ana; Prat, Aleix; Nonell, Lara; Lluch, Ana; Jean-Mairet, Joël; Coleman, Robert; Albanell, Joan

    2015-01-01

    Background: There are currently no biomarkers for early breast cancer patient populations at risk of bone metastasis. Identification of mediators of bone metastasis could be of clinical interest. Methods: A de novo unbiased screening approach based on selection of highly bone metastatic breast cancer cells in vivo was used to determine copy number aberrations (CNAs) associated with bone metastasis. The CNAs associated with bone metastasis were examined in independent primary breast cancer datasets with annotated clinical follow-up. The MAF gene encoded within the CNA associated with bone metastasis was subjected to gain and loss of function validation in breast cancer cells (MCF7, T47D, ZR-75, and 4T1), its downstream mechanism validated, and tested in clinical samples. A multivariable Cox cause-specific hazard model with competing events (death) was used to test the association between 16q23 or MAF and bone metastasis. All statistical tests were two-sided. Results: 16q23 gain CNA encoding the transcription factor MAF mediates breast cancer bone metastasis through the control of PTHrP. 16q23 gain (hazard ratio (HR) for bone metastasis = 14.5, 95% confidence interval (CI) = 6.4 to 32.9, P < .001) as well as MAF overexpression (HR for bone metastasis = 2.5, 95% CI = 1.7 to 3.8, P < .001) in primary breast tumors were specifically associated with risk of metastasis to bone but not to other organs. Conclusions: These results suggest that MAF is a mediator of breast cancer bone metastasis. 16q23 gain or MAF protein overexpression in tumors may help to select patients at risk of bone relapse. PMID:26376684

  10. Risk factors for distant metastasis of dermatofibrosarcoma protuberans.

    PubMed

    Hayakawa, Keiko; Matsumoto, Seiichi; Ae, Keisuke; Tanizawa, Taisuke; Gokita, Tabu; Funauchi, Yuki; Motoi, Noriko

    2016-09-01

    Dermatofibrosarcoma protuberans (DFSP) may recur locally but rarely metastasizes. Fibrosarcomatous transformation in dermatofibrosarcoma protuberans (FS-DFSP) is said to have worse prognosis compared with ordinary DFSP (O-DFSP). Since DFSP rarely metastasizes, there have been few reports summarizing data on distant metastasis cases at single institution. The aim of this retrospective study is to review DFSP cases in order to analyze risk factors for metastasis. This retrospective study involved 67 patients. We analyzed O-DFSP and FS-DFSP metastasis rates, metastasis sites, time to metastasis, the relationship between frequency of local recurrence and metastasis, and the relationship between primary tumor size and metastasis. Distant metastasis was found in 5 (7.4 %) of 67 cases with DFSP. Of the five cases, the histopathological diagnosis was FS-DFSP in four cases and O-DFSP in one case. Out of five cases with metastasis, three had not recurred and two had recurred twice. No clear correlation was identified (Fisher's exact test: p = 0.216). The primary tumor diameters in the metastatic cases were 15.0, 12.6, 20.5, 13.0, and 5.0 cm, respectively. The tumor diameters in metastatic cases were significantly larger (Fisher's exact test: p < 0.0001). In this study, we identified a stronger correlation between DFSP metastasis and tumor size. There was a high possibility that the cases with large tumors might be FS-DFSP, having high rate of metastasis and poor prognosis. In treatment of DFSP, early diagnosis before primary tumor growth and wide resection is considered important.

  11. Panax notoginseng saponins (PNS) inhibits breast cancer metastasis.

    PubMed

    Wang, Peiwei; Cui, Jingang; Du, Xiaoye; Yang, Qinbo; Jia, Chenglin; Xiong, Minqi; Yu, Xintong; Li, Li; Wang, Wenjian; Chen, Yu; Zhang, Teng

    2014-07-03

    Panax notoginseng (Burkill) F.H. Chen (Araliaceae) has been extensively used as a therapeutic agent to treat a variety of diseases. Panax notoginseng saponins (PNS) consist of major therapeutically active components of Panax notoginseng. PNS inhibit the growth of a variety of tumor cells in vitro and in vivo. The aim of the study is to investigate the effects and underlying mechanisms of PNS on breast cancer metastasis. 4T1 cell, a highly metastatic mouse breast carcinoma cell line, was utilized for in vitro and in vivo assays. In vitro assays were first performed to examine the effects of PNS on 4T1 cell viability, migration and invasion, respectively. Real-time PCR analyses were also performed to examine the effects of PNS on the expression of genes associated with tumor metastasis. The effect of PNS on 4T1 tumor cell metastasis was further assessed in spontaneous and experimental metastasis models in vivo. PNS treatment exhibited a dose-dependent effect on impairing 4T1 cell viability in vitro. However, when examined at a lower dose that did not affect cell viability, the migration and invasion of 4T1 cell was remarkably inhibited in vitro. Meanwhile, PNS treatment led to upregulated expression of genes known to inhibit metastasis and downregulated expression of genes promoting metastasis in cultured 4T1 cells. These results suggested a selective effect of PNS on 4T1 migration and invasion. This hypothesis was further addressed in 4T1 metastasis models in vivo. The results showed that the lung metastasis was significantly inhibited by PNS treatment in both spontaneous and experimental metastasis models. Taken together, our results demonstrated an inhibitory effect of PNS on 4T1 tumor metastasis, warranting further evaluation of PNS as a therapeutic agent for treating breast cancer metastasis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. An isolated vaginal metastasis from rectal cancer.

    PubMed

    Sadatomo, Ai; Koinuma, Koji; Horie, Hisanaga; Lefor, Alan K; Sata, Naohiro

    2016-02-01

    Isolated vaginal metastases from colorectal cancer are extremely rare. There are only a few reported cases in the English literature, and the characteristics of such cases of metastasis remain relatively unknown. We present a case of isolated vaginal metastasis from rectal cancer in a 78-year-old female patient. The patient had no symptoms related to vaginal tumor. Magnetic resonance imaging (MRI) showed thickening of the middle rectum and a vaginal tumor. Biopsy from the vaginal tumor showed adenocarcinoma, similar to the rectal lesion. Low anterior resection with ileostomy, hystero-oophorectomy, and transvaginal tumor resection was performed. After nineteen months, computed tomography scan revealed multiple lung metastases and recurrent tumor in the pelvis. The patient refused chemotherapy and is alive three months after developing recurrent disease. Most cases of primary vaginal carcinoma are squamous cell carcinoma. Other histologic types such as adenocarcinoma are usually metastatic lesions. Primary lesions associated with metastatic vaginal adenocarcinoma are most often the uterus, and are very rarely from the colon or rectum. We review previous case reports of isolated vaginal metastases from colorectal cancer and discuss their symptoms, treatments, and outcomes. We should keep the vagina within the field of view of pelvic MRI, which is one of the preoperative diagnostic tools for colorectal cancer. If female patients show gynecological symptoms, gynecological examination should be recommended. Isolated vaginal metastases are an indication for surgical resection, and adjuvant chemotherapy is also recommended.

  13. Hypothyroidism Enhances Tumor Invasiveness and Metastasis Development

    PubMed Central

    Martínez-Iglesias, Olaia; García-Silva, Susana; Regadera, Javier; Aranda, Ana

    2009-01-01

    Background Whereas there is increasing evidence that loss of expression and/or function of the thyroid hormone receptors (TRs) could result in a selective advantage for tumor development, the relationship between thyroid hormone levels and human cancer is a controversial issue. It has been reported that hypothyroidism might be a possible risk factor for liver and breast cancer in humans, but a lower incidence of breast carcinoma has been also reported in hypothyroid patients Methodology/Principal Findings In this work we have analyzed the influence of hypothyroidism on tumor progression and metastasis development using xenografts of parental and TRβ1–expressing human hepatocarcinoma (SK-hep1) and breast cancer cells (MDA-MB-468). In agreement with our previous observations tumor invasiveness and metastasis formation was strongly repressed when TRβ–expressing cells were injected into euthyroid nude mice. Whereas tumor growth was retarded when cells were inoculated into hypothyroid hosts, tumors had a more mesenchymal phenotype, were more invasive and metastatic growth was enhanced. Increased aggressiveness and tumor growth retardation was also observed with parental cells that do not express TRs. Conclusions/Significance These results show that changes in the stromal cells secondary to host hypothyroidism can modulate tumor progression and metastatic growth independently of the presence of TRs on the tumor cells. On the other hand, the finding that hypothyroidism can affect differentially tumor growth and invasiveness can contribute to the explanation of the confounding reports on the influence of thyroidal status in human cancer. PMID:19641612

  14. Gastric metastasis of bilateral breast cancer

    PubMed Central

    Belaïd, Asma; Mghirbi, Fahmi; Béhi, Khalil; Doghri, Raoudha; Benna, Farouk

    2017-01-01

    Breast cancer is the most common malignancy in women. The most frequent metastatic sites are lung, bone, liver and brain. On the other hand, gastric metastases are rare. Synchronous bilateral breast cancer (SBBC) occurs rarely. Lobular carcinoma is the histological type most often associated with bilateral breast carcinomas and gastric metastases. We made a retrospective study including four patients followed in the Salah Azaiez Institute, for a bilateral breast cancer with gastric metastases. We analyzed the epidemiological, anatomoclinical and therapeutic particularities of this rare entity. Symptoms were unspecific. The diagnosis of gastric metastasis of the SBBC was confirmed by a histopathological examination of an endoscopic biopsy. The median age was 46.2 years (range, 36–51 years) and the median time until the gastric involvement was 19 months (range, 0–41 months). None of patients had a surgical treatment for the gastric location. All Patients received at least one line of chemotherapy and radiotherapy. Median survival following the detection of gastric involvement was 22 months (range, 1–56 months). Gastric metastases from breast cancer are rare and frequently associated with other distant metastasis. Symptoms are unspecific and endoscopy may not be contributive. Therefore, gastric involvement is underestimated. Lobular infiltrating carcinoma (LIC) is the most histological type incriminated in its occurrence. The supply of immunohistochemistry is crucial to distinguish between primary or metastatic gastric cancer. PMID:28280631

  15. Apelin promotes lymphangiogenesis and lymph node metastasis

    PubMed Central

    Laszlo, Viktoria; Rozsas, Anita; Garay, Tamas; Torok, Szilvia; Grusch, Michael; Berger, Walter; Paku, Sandor; Renyi-Vamos, Ferenc; Masri, Bernard; Tovari, Jozsef; Groger, Marion; Klepetko, Walter; Hegedus, Balazs; Dome, Balazs

    2014-01-01

    Whereas the role of the G-protein-coupled APJ receptor and its ligand, apelin, in angiogenesis has been well documented, the ability of the apelin/APJ system to induce lymphangiogenesis and lymphatic metastasis has been largely unexplored. To this end, we first show that APJ is expressed in lymphatic endothelial cells (LECs) and, moreover, that it responds to apelin by activating the apelinergic signaling cascade. We find that although apelin treatment does not influence the proliferation of LECs in vitro, it enhances their migration, protects them against UV irradiation-induced apoptosis, increases their spheroid numbers in 3D culture, stimulates their in vitro capillary-like tube formation and, furthermore, promotes the invasive growth of lymphatic microvessels in vivo in the matrigel plug assay. We also demonstrate that apelin overexpression in malignant cells is associated with accelerated in vivo tumor growth and with increased intratumoral lymphangiogenesis and lymph node metastasis. These results indicate that apelin induces lymphangiogenesis and, accordingly, plays an important role in lymphatic tumor progression. Our study does not only reveal apelin as a novel lymphangiogenic factor but might also open the door for the development of novel anticancer therapies targeting lymphangiogenesis. PMID:24962866

  16. von Willebrand factor expression in osteosarcoma metastasis.

    PubMed

    Eppert, Kolja; Wunder, Jay S; Aneliunas, Vicky; Kandel, Rita; Andrulis, Irene L

    2005-03-01

    A number of genes are implicated in the initiation and progression of osteosarcoma; however, cytogenetic and comparative genomic hybridization studies indicate the involvement of additional unidentified genes. An examination of gene expression profiles in 22 high-grade osteosarcoma tumor specimens from 15 patients (including paired primary and metastatic samples from five patients) indicated that von Willebrand factor (vWF) mRNA expression may increase during tumor progression. vWF, a large glycoprotein previously considered to be expressed exclusively by endothelial cells and megakaryocytes, is involved in platelet aggregation and adhesion to the subendothelial matrix, processes critical to hematogenous tumor cell metastasis to the lung. Analysis of paired primary and metastatic osteosarcoma tumor samples from 10 patients revealed an increase in vWF gene expression in metastases (P=0.005). Immunohistochemistry showed that, in addition to the endothelial cells, vWF protein was also detected in osteosarcoma cells in vivo in 13 of 29 tumor specimens as well as in SAOS2, an osteosarcoma cell line. The tumor cell staining correlated positively with high vWF expression in the sample (P=0.006). Although vascular endothelial cells contribute to the vWF mRNA detected in the tumor samples, there was neither any correlation between vascular density (VD) and vWF mRNA expression nor between VD and clinical outcome. These findings suggest that vWF expression is deregulated in osteosarcoma tumors, potentially contributing to metastasis.

  17. Anaplastic extramedullary cervical ependymoma with leptomeningeal metastasis.

    PubMed

    Pomeraniec, I J; Dallapiazza, R F; Sumner, H M; Lopes, M B; Shaffrey, C I; Smith, J S

    2015-12-01

    We present a rare extramedullary ependymoma with diffuse spinal metastatic disease, and review the previous reports of extramedullary spinal ependymomas. Ependymomas are the most common intramedullary spinal cord tumor in adults. These tumors rarely present as extramedullary masses. We treated a 23-year-old man with a history of progressive neck, shoulder and arm pain, with sensory and motor symptoms in the C7 dermatome. MRI of the cervical spine demonstrated a ventral contrast-enhancing lesion with evidence of enhancement along the dura and spinal cord of the upper cervical spine, thoracic spine, and cauda equina. He underwent a tumor debulking procedure without complications. Following surgery, he received craniospinal radiation to treat the remaining tumor and diffuse leptomeningeal disease. The final pathology of the tumor revealed that is was a World Health Organization Grade III anaplastic ependymoma. At the 1 year follow-up, the patient had stable imaging and had returned to his preoperative functional status. Of the 19 reported patients with primary intradural, extramedullary spinal ependymomas, two had extradural components and seven had anaplastic grades. Only one tumor with an anaplastic grade resulted in metastatic disease, but without spinal recurrence. To our knowledge, this is the first report of an intradural, extramedullary spinal ependymoma with an anaplastic grade, presenting with concomitant diffuse, nodular leptomeningeal metastasis involving the upper cervical spine, thoracic spine, conus medullaris, and cauda equina. Similar to the treatment of intramedullary ependymomas with metastasis, this patient underwent an aggressive debulking procedure followed by radiation therapy to the entire neuroaxis.

  18. Supratentorial extraventricular anaplastic ependymoma with extracranial metastasis.

    PubMed

    Pachella, Laura A; Kamiya-Matsuoka, Carlos; Lee, Eva Lu T; Olar, Adriana; Yung, W K Alfred

    2015-03-01

    Ependymoma is a relatively rare malignancy accounting for 2.0% of all primary central nervous system tumors in adults. Extracranial metastasis is a very uncommon complication of gliomas, especially of anaplastic ependymomas. The objective of this paper is to show that ependymomas can metastasize to soft tissue and lymph nodes as well as to share our approach to this challenge. We report a male patient with anaplastic ependymoma that recurred, metastasizing to the neck and lymph nodes. Metastatic disease was diagnosed based on clinical presentation of a palpable nodule on the right neck and diffuse cervical lymphadenopathies. A biopsy was obtained and pathology revealed anaplastic ependymoma. Whole-body fluorodeoxyglucose positron emission tomography scan showed metastatic disease in the right mastoid region with diffuse uptake in the cervical lymph nodes. Clinical and radiologic response was achieved after three chemotherapy cycles of etoposide, cisplatin, vincristine, and cyclophosphamide. This case highlights extracranial metastasis to the soft tissue as an atypical presentation of recurrent anaplastic ependymoma. Other reported instances of extracranial metastatic ependymoma with this presentation are discussed. The possible metastatic pathways of intracranial disease are discussed. It also illustrates how extracranial disease remains stable with systemic chemotherapy.

  19. Inhibitory Effects of Dopamine Receptor D1 Agonist on Mammary Tumor and Bone Metastasis

    PubMed Central

    Minami, Kazumasa; Liu, Shengzhi; Liu, Yang; Chen, Andy; Wan, Qiaoqiao; Na, Sungsoo; Li, Bai-Yan; Matsuura, Nariaki; Koizumi, Masahiko; Yin, Yukun; Gan, Liangying; Xu, Aihua; Li, Jiliang; Nakshatri, Harikrishna; Yokota, Hiroki

    2017-01-01

    Dopaminergic signaling plays a critical role in the nervous system, but little is known about its potential role in breast cancer and bone metabolism. A screening of ~1,000 biologically active compounds revealed that a selective agonist of dopamine receptor D1 (DRD1), A77636, inhibited proliferation of 4T1.2 mammary tumor cells as well as MDA-MB-231 breast cancer cells. Herein, we examined the effect of A77636 on bone quality using a mouse model of bone metastasis from mammary tumor. A77636 inhibited migration of cancer cells in a DRD1-dependent fashion and suppressed development of bone-resorbing osteoclasts by downregulating NFATc1 through the elevation of phosphorylation of eIF2α. In the mouse model of bone metastasis, A77636 reduced osteolytic lesions and prevented mechanical weakening of the femur and tibia. Collectively, we expect that dopaminergic signaling might provide a novel therapeutic target for breast cancer and bone metastasis. PMID:28374823

  20. Inhibition of autophagy promotes metastasis and glycolysis by inducing ROS in gastric cancer cells.

    PubMed

    Qin, Wenjie; Li, Chao; Zheng, Wen; Guo, Qingqu; Zhang, Yuefeng; Kang, Muxing; Zhang, Bo; Yang, Bin; Li, Baozhong; Yang, Haijun; Wu, Yulian

    2015-11-24

    Autophagy defect has been shown to be correlated with malignant phenotype and poor prognosis of human cancers, however, the detailed mechanisms remain obscure. In this study, we investigated the biological changes induced by autophagy inhibition in gastric cancer. We showed that inhibition of autophagy in gastric cancer cells promotes epithelial-mesenchymal transition (EMT) and metastasis, alters metabolic phenotype from mitochondrial oxidative phosphorylation to aerobic glycolysis and converts cell phenotype toward malignant, which maybe further contribute to chemoresistance and poor prognosis of gastric cancer. We also identified that the EMT and metabolism alterations induced by autophagy inhibition were dependent on ROS-NF-κB-HIF-1α pathway. More importantly, scavenging of ROS by the antioxidant N-acetylcysteine (NAC) attenuated activation of NF-κB and HIF-1α in autophagy-deficient gastric cancer cells, and autophagy inhibition induced metastasis and glycolysis were also diminished by NAC in vivo. Taken together, our findings suggested that autophagy defect promotes metastasis and glycolysis of gastric cancer, and antioxidants could be used to improve disease outcome for gastric cancer patients with autophagy defect.

  1. Targeting vascular pericytes in hypoxic tumors increases lung metastasis via angiopoietin-2

    PubMed Central

    Keskin, Doruk; Kim, Jiha; Cooke, Vesselina G.; Wu, Chia-Chin; Sugimoto, Hikaru; Gu, Chenghua; De Palma, Michele; Kalluri, Raghu; LeBleu, Valerie S.

    2015-01-01

    Summary Strategies to target angiogenesis include inhibition of the vessel-stabilizing properties of vascular pericytes. Pericyte depletion in early-stage non-hypoxic tumors suppressed nascent angiogenesis, tumor growth and lung metastasis. In contrast, pericyte depletion in advanced-stage hypoxic tumors with pre-established vasculature resulted in enhanced intra-tumoral hypoxia, decreased tumor growth and increased lung metastasis. Further, depletion of pericytes in post-natal retinal blood vessels resulted in abnormal and leaky vasculature. Tumor transcriptome profiling and biological validation revealed that angiopoietin signaling is a key regulatory pathway associated with pericyte targeting. Indeed, pericyte targeting in established mouse tumors increased angiopoietin-2 (ANG2/Angpt2) expression. Depletion of pericytes, coupled with targeting of ANG2 signaling, restored vascular stability in multiple model systems and decreased tumor growth and metastasis. Importantly, ANGPT2 expression correlated with poor outcome in patients with breast cancer. These results emphasize the potential utility of therapeutic regimens that target pericytes and ANG2 signaling in metastatic breast cancer. PMID:25704811

  2. Evidence that the process of murine melanoma metastasis is sequential and selective and contains stochastic elements.

    PubMed

    Price, J E; Aukerman, S L; Fidler, I J

    1986-10-01

    Malignant neoplasms are heterogeneous for many different biological characteristics, including invasion and metastasis. The pathogenesis of metastasis involves a series of sequential steps which must be completed by metastatic cells. In the present study we examined the metastatic behavior of three highly metastatic and three nonmetastatic subpopulations isolated from the K-1735 melanoma syngeneic to the C3H/HeN mouse. Cells were labeled with [125I]iodo-2'-deoxyuridine, and their initial organ distribution, fate, and production of experimental metastases were determined. Highly metastatic cells survived in lung parenchyma to produce metastases, whereas nonmetastatic cells did not. However, even with the highly metastatic cells only 2% of the original inoculum was responsible for the final production of metastases. The results support the concept that the fate of tumor cells released into the bloodstream is determined by sequential and selective events and introduces a third regulatory factor. Cells endowed with metastatic properties have a higher probability of forming metastases than cells not so endowed, but this probability is not 100%. Hence, metastasis should be considered as a sequential, selective, and stochastic process.

  3. An Integrative Platform for Three-dimensional Quantitative Analysis of Spatially Heterogeneous Metastasis Landscapes

    NASA Astrophysics Data System (ADS)

    Guldner, Ian H.; Yang, Lin; Cowdrick, Kyle R.; Wang, Qingfei; Alvarez Barrios, Wendy V.; Zellmer, Victoria R.; Zhang, Yizhe; Host, Misha; Liu, Fang; Chen, Danny Z.; Zhang, Siyuan

    2016-04-01

    Metastatic microenvironments are spatially and compositionally heterogeneous. This seemingly stochastic heterogeneity provides researchers great challenges in elucidating factors that determine metastatic outgrowth. Herein, we develop and implement an integrative platform that will enable researchers to obtain novel insights from intricate metastatic landscapes. Our two-segment platform begins with whole tissue clearing, staining, and imaging to globally delineate metastatic landscape heterogeneity with spatial and molecular resolution. The second segment of our platform applies our custom-developed SMART 3D (Spatial filtering-based background removal and Multi-chAnnel forest classifiers-based 3D ReconsTruction), a multi-faceted image analysis pipeline, permitting quantitative interrogation of functional implications of heterogeneous metastatic landscape constituents, from subcellular features to multicellular structures, within our large three-dimensional (3D) image datasets. Coupling whole tissue imaging of brain metastasis animal models with SMART 3D, we demonstrate the capability of our integrative pipeline to reveal and quantify volumetric and spatial aspects of brain metastasis landscapes, including diverse tumor morphology, heterogeneous proliferative indices, metastasis-associated astrogliosis, and vasculature spatial distribution. Collectively, our study demonstrates the utility of our novel integrative platform to reveal and quantify the global spatial and volumetric characteristics of the 3D metastatic landscape with unparalleled accuracy, opening new opportunities for unbiased investigation of novel biological phenomena in situ.

  4. microRNAs, Gap Junctional Intercellular Communication and Mesenchymal Stem Cells in Breast Cancer Metastasis

    PubMed Central

    Gregory, Larissa A.; Ricart, Rachel A.; Patel, Shyam A.; Lim, Philip K.; Rameshwar, Pranela

    2010-01-01

    The failed outcome of autologous bone marrow transplantation for breast cancer opens the field for investigations. This is particularly important because the bone marrow could be a major source of cancer cells during tertiary metastasis. This review discusses subsets of breast cancer cells, including those that enter the bone marrow at an early period of disease development, perhaps prior to clinical detection. This population of cells evades chemotherapeutic damage even at high doses. An understanding of this population might be crucial for the success of bone marrow transplants for metastatic breast cancer and for the eradication of cancer cells in bone marrow. In vivo and in vitro studies have demonstrated gap junctional intercellular communication (GJIC) between bone marrow stroma and breast cancer cells. This review discusses GJIC in cancer metastasis, facilitating roles of mesenchymal stem cells (MSCs). In addition, the review addresses potential roles for miRNAs, including those already linked to cancer biology. The literature on MSCs is growing and their links to metastasis are beginning to be significant leads for the development of new drug targets for breast cancer. In summary, this review discusses interactions among GJIC, miRNAs and MSCs as future consideration for the development of cancer therapies. PMID:21886602

  5. DIXDC1 activates the Wnt signaling pathway and promotes gastric cancer cell invasion and metastasis.

    PubMed

    Tan, Cong; Qiao, Fan; Wei, Ping; Chi, Yayun; Wang, Weige; Ni, Shujuan; Wang, Qifeng; Chen, Tongzhen; Sheng, Weiqi; Du, Xiang; Wang, Lei

    2016-04-01

    DIXDC1 (Dishevelled-Axin domain containing 1) is a DIX (Dishevelled-Axin) domain-possessing protein that promotes colon cancer cell proliferation and increases the invasion and migration ability of non-small-cell lung cancer via the PI3K pathway. As a positive regulator of the Wnt/β-catenin pathway, the biological role of DIXDC1 in human gastric cancer and the relationship between DIXDC1 and the Wnt pathway are unclear. In the current study, the upregulation of DIXDC1 was detected in gastric cancer and was associated with advanced TNM stage cancer, lymph node metastasis, and poor prognosis. We also found that the overexpression of DIXDC1 could promote the invasion and migration of gastric cancer cells. The upregulation of MMPs and the downregulation of E-cadherin were found to be involved in the process. DIXDC1 enhanced β-catenin nuclear accumulation, which activated the Wnt pathway. Additionally, the inhibition of β-catenin in DIXDC1-overexpressing cells reversed the metastasis promotion effects of DIXDC1. These results demonstrate that the expression of DIXDC1 is associated with poor prognosis of gastric cancer patients and that DIXDC1 promotes gastric cancer invasion and metastasis through the activation of the Wnt pathway; E-cadherin and MMPs are also involved in this process. © 2015 Wiley Periodicals, Inc.

  6. An Integrative Platform for Three-dimensional Quantitative Analysis of Spatially Heterogeneous Metastasis Landscapes.

    PubMed

    Guldner, Ian H; Yang, Lin; Cowdrick, Kyle R; Wang, Qingfei; Alvarez Barrios, Wendy V; Zellmer, Victoria R; Zhang, Yizhe; Host, Misha; Liu, Fang; Chen, Danny Z; Zhang, Siyuan

    2016-04-12

    Metastatic microenvironments are spatially and compositionally heterogeneous. This seemingly stochastic heterogeneity provides researchers great challenges in elucidating factors that determine metastatic outgrowth. Herein, we develop and implement an integrative platform that will enable researchers to obtain novel insights from intricate metastatic landscapes. Our two-segment platform begins with whole tissue clearing, staining, and imaging to globally delineate metastatic landscape heterogeneity with spatial and molecular resolution. The second segment of our platform applies our custom-developed SMART 3D (Spatial filtering-based background removal and Multi-chAnnel forest classifiers-based 3D ReconsTruction), a multi-faceted image analysis pipeline, permitting quantitative interrogation of functional implications of heterogeneous metastatic landscape constituents, from subcellular features to multicellular structures, within our large three-dimensional (3D) image datasets. Coupling whole tissue imaging of brain metastasis animal models with SMART 3D, we demonstrate the capability of our integrative pipeline to reveal and quantify volumetric and spatial aspects of brain metastasis landscapes, including diverse tumor morphology, heterogeneous proliferative indices, metastasis-associated astrogliosis, and vasculature spatial distribution. Collectively, our study demonstrates the utility of our novel integrative platform to reveal and quantify the global spatial and volumetric characteristics of the 3D metastatic landscape with unparalleled accuracy, opening new opportunities for unbiased investigation of novel biological phenomena in situ.

  7. Novel Biomarker Candidates for Colorectal Cancer Metastasis: A Meta-analysis of In Vitro Studies

    PubMed Central

    Long, Nguyen Phuoc; Lee, Wun Jun; Huy, Nguyen Truong; Lee, Seul Ji; Park, Jeong Hill; Kwon, Sung Won

    2016-01-01

    Colorectal cancer (CRC) is one of the most common and lethal cancers. Although numerous studies have evaluated potential biomarkers for early diagnosis, current biomarkers have failed to reach an acceptable level of accuracy for distant metastasis. In this paper, we performed a gene set meta-analysis of in vitro microarray studies and combined the results from this study with previously published proteomic data to validate and suggest prognostic candidates for CRC metastasis. Two microarray data sets included found 21 significant genes. Of these significant genes, ALDOA, IL8 (CXCL8), and PARP4 had strong potential as prognostic candidates. LAMB2, MCM7, CXCL23A, SERPINA3, ABCA3, ALDH3A2, and POLR2I also have potential. Other candidates were more controversial, possibly because of the biologic heterogeneity of tumor cells, which is a major obstacle to predicting metastasis. In conclusion, we demonstrated a meta-analysis approach and successfully suggested ten biomarker candidates for future investigation. PMID:27688707

  8. Papillary thyroid carcinoma metastasizing to anaplastic meningioma: an unusual case of tumor-to-tumor metastasis.

    PubMed

    Das, Sumit; Chaudhary, Navjot; Ang, Lee-Cyn; Megyesi, Joseph S

    2017-07-01

    Tumor-to-tumor metastasis is a relatively uncommon entity, whereby the so-called 'recipient' tumor is involved by another biologically unrelated 'donor' tumor. Intracranially, meningioma (WHO grade 1) is the most common recipient tumor, while breast and lung cancers are the most common donor tumors. We present an unusual case of intracranial tumor-to-tumor metastasis involving papillary thyroid carcinoma (PTC) believed to have metastasized to an anaplastic meningioma (WHO grade 3). The patient is a 64-year-old female with a history of PTC, whose neuroimaging, performed as part of her staging workup, revealed a right parietal scalp lesion. The lesion was resected to reveal metastatic PTC with spindle cell component believed to represent sarcomatoid differentiation. Follow-up neuroimaging 2 months later revealed regrowth of the lesion under the previous craniotomy site. PET scan showed increased uptake in this area consistent with metastasis. Resection of this lesion revealed primarily features of an anaplastic meningioma. The combination of pathologic findings from both resections in conjunction with findings from the PET scan led to the suggestion that the PTC had metastasized into the anaplastic meningioma. To the authors' knowledge, this is the first example in the literature of a donor tumor metastasizing to a high-grade recipient tumor.

  9. An Integrative Platform for Three-dimensional Quantitative Analysis of Spatially Heterogeneous Metastasis Landscapes

    PubMed Central

    Guldner, Ian H.; Yang, Lin; Cowdrick, Kyle R.; Wang, Qingfei; Alvarez Barrios, Wendy V.; Zellmer, Victoria R.; Zhang, Yizhe; Host, Misha; Liu, Fang; Chen, Danny Z.; Zhang, Siyuan

    2016-01-01

    Metastatic microenvironments are spatially and compositionally heterogeneous. This seemingly stochastic heterogeneity provides researchers great challenges in elucidating factors that determine metastatic outgrowth. Herein, we develop and implement an integrative platform that will enable researchers to obtain novel insights from intricate metastatic landscapes. Our two-segment platform begins with whole tissue clearing, staining, and imaging to globally delineate metastatic landscape heterogeneity with spatial and molecular resolution. The second segment of our platform applies our custom-developed SMART 3D (Spatial filtering-based background removal and Multi-chAnnel forest classifiers-based 3D ReconsTruction), a multi-faceted image analysis pipeline, permitting quantitative interrogation of functional implications of heterogeneous metastatic landscape constituents, from subcellular features to multicellular structures, within our large three-dimensional (3D) image datasets. Coupling whole tissue imaging of brain metastasis animal models with SMART 3D, we demonstrate the capability of our integrative pipeline to reveal and quantify volumetric and spatial aspects of brain metastasis landscapes, including diverse tumor morphology, heterogeneous proliferative indices, metastasis-associated astrogliosis, and vasculature spatial distribution. Collectively, our study demonstrates the utility of our novel integrative platform to reveal and quantify the global spatial and volumetric characteristics of the 3D metastatic landscape with unparalleled accuracy, opening new opportunities for unbiased investigation of novel biological phenomena in situ. PMID:27068335

  10. Thrombospondin 2 expression is correlated with inhibition of angiogenesis and metastasis of colon cancer

    PubMed Central

    Tokunaga, T; Nakamura, M; Oshika, Y; Abe, Y; Ozeki, Y; Fukushima, Y; Hatanaka, H; Sadahiro, S; Kijima, H; Tsuchida, T; Yamazaki, H; Tamaoki, N; Ueyama, Y

    1999-01-01

    Two subtypes of thrombospondin (TSP-1 and TSP-2) have inhibitory roles in angiogenesis in vitro, although the biological significance of these TSP isoforms has not been determined in vivo. We examined TSP-1 and TSP-2 gene expression by reverse transcription polymerase chain reaction (RT-PCR) analysis in 61 colon cancers. Thirty-eight of these 61 colon cancers were positive for TSP-2 expression and showed hepatic metastasis at a significantly lower incidence than those without TSP-2 expression (P = 0.02). TSP-2 expression was significantly associated with M0 stage in these colon cancers (P = 0.03), whereas TSP-1 expression showed no apparent correlation with these factors. The colon cancer patients with TSP-2 expression showed a significantly low frequency of liver metastasis correlated with the cell-associated isoform of vascular endothelial growth factor (VEGF-189) (P = 0.0006). Vascularity was estimated by CD34 staining, and TSP-2(–)/VEGF-189(+) colon cancers showed significantly increased vessel counts and density in the stroma (P < 0.0001). TSP-2(–)/VEGF-189(+) colon cancer patients also showed significantly poorer prognosis compared with those with TSP-2(+) / VEGF-189(–) (P = 0.0014). These results suggest that colon cancer metastasis is critically determined by angiogenesis resulting from the balance between the angioinhibitory factor TSP-2 and angiogenic factor VEGF-189. © 1999 Cancer Research Campaign PMID:9888480

  11. Synchronous contralateral adrenal metastasis of colorectal cancer: case report.

    PubMed

    Raices, Micaela; Boccalatte, Luis; Rossi, Gustavo; Wright, Fernando

    2017-06-01

    The most frequent sites of distant metastasis of colorectal cancer (CRC) are primarily liver and lung, followed by brain and bone metastases. Infrequently, metastases are found in the adrenal glands. They usually have a metachronous and homolateral character. We present a case of contralateral synchronic adrenal metastasis of CRC and its surgical resolution.

  12. Synchronous contralateral adrenal metastasis of colorectal cancer: case report

    PubMed Central

    Raices, Micaela; Boccalatte, Luis; Wright, Fernando

    2017-01-01

    Abstract The most frequent sites of distant metastasis of colorectal cancer (CRC) are primarily liver and lung, followed by brain and bone metastases. Infrequently, metastases are found in the adrenal glands. They usually have a metachronous and homolateral character. We present a case of contralateral synchronic adrenal metastasis of CRC and its surgical resolution. PMID:28616158

  13. [Metastasis of hepatocellular carcinoma to the urinary bladder].

    PubMed

    Kurimoto, S; Komatsu, H; Doi, N; Wakumoto, Y; Tominaga, T; Nishimura, Y

    1993-01-01

    We report a case of metastasis of a hepatocellular carcinoma to the bladder. Clinically the tumor was suspected to be a primary bladder tumor with subsequent metastasis to the liver. However, the pathological diagnosis yielded different results. The tumor cells resembled liver cells and sometimes bile production was even observed. No therapy was available and the patient died of cachexia 6 months later.

  14. Bilateral Cystic Adrenal Neuroblastoma with Cystic Liver metastasis

    PubMed Central

    Aslan, Mine; Kalyoncu, Ayse Ucar; Habibi, Hatice Arioz; Ozdemir, Gul Nihal; Koc, Basak; Adaletli, Ibrahim

    2017-01-01

    Bilateral congenital cystic adrenal neuroblastoma (NB) with cystic liver metastasis is a very rare condition and only few cases have been reported in the literature. Herein we report a case of a congenital bilateral cystic adrenal NB with cystic liver metastasis and briefly discuss characteristic imaging features of cystic NB. PMID:28163998

  15. Isolated mucinous adrenal metastasis in a breast cancer patient.

    PubMed

    Demirci, Umut; Buyukberber, Suleyman; Cakir, Tansel; Poyraz, Aylar; Baykara, Meltem; Karakus, Esra; Tufan, Gulnihal; Benekli, Mustafa; Coskun, Ugur

    2011-12-01

    Mucinous breast carcinoma (MBC) is a rare histological type of breast cancer and rarely associated with advanced disease. We report a case that had MBC with an isolated adrenal metastasis which was removed by laparoscopic adrenelectomy. This case is unique due to the unexpected metastasis of pure mucinous carcinoma developed after 4 years of hormone therapy.

  16. A single cervical lymph node metastasis of malignant ameloblastoma.

    PubMed

    Kim, Yoori; Choi, Sung-Weon; Lee, Jong-Ho; Ahn, Kang-Min

    2014-12-01

    Cervical node metastasis of malignant ameloblastoma is extremely rare. Because of its rarity, there is no standard treatment modality in a single lymph node metastasis in malignant ameloblastoma. Eleven patients of malignant ameloblastoma involving a single cervical lymph node metastasis and one new case were reviewed. Neck treatment was classified into neck dissection and simple excision. Local nodal recurrence, distant metastasis and follow-up periods were investigated. Eight patients were treated with neck dissection (group A) and four patients underwent a simple node excision (group B). Two patients in group A experienced multiple organ metastases such as liver and lung seven months and 13 years after neck dissection respectively. The other patients showed no recurrence and metastasis. In group B, there was no report of a regional neck recurrence and distant metastasis during follow-up of 1-7 years. Multiple nodes metastasis requires a radical neck dissection; however, simple excision with close follow-up may be used in a single node metastasis in malignant ameloblastoma. Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  17. Preventing Prostate Cancer Metastasis by Targeting Exosome Secretion

    DTIC Science & Technology

    2014-10-01

    Exosome Secretion PRINCIPAL INVESTIGATOR: Christine Vogel CONTRACTING ORGANIZATION: New York University, New York, NY 10012...30 Sep 2013 - 29 Sep 2014 4. TITLE AND SUBTITLE Preventing Prostate Cancer Metastasis by Targeting Exosome Secretion 5a. CONTRACT...NUMBER Preventing Prostate Cancer Metastasis by Targeting Exosome Secretion 5b. GRANT NUMBER W81XWH-13-1-0467 5c. PROGRAM ELEMENT

  18. Global secretome analysis identifies novel mediators of bone metastasis

    PubMed Central

    Blanco, Mario Andres; LeRoy, Gary; Khan, Zia; Alečković, Maša; Zee, Barry M; Garcia, Benjamin A; Kang, Yibin

    2012-01-01

    Bone is the one of the most common sites of distant metastasis of solid tumors. Secreted proteins are known to influence pathological interactions between metastatic cancer cells and the bone stroma. To comprehensively profile secreted proteins associated with bone metastasis, we used quantitative and non-quantitative mass spectrometry to globally analyze the secretomes of nine cell lines of varying bone metastatic ability from multiple species and cancer types. By comparing the secretomes of parental cells and their bone metastatic derivatives, we identified the secreted proteins that were uniquely associated with bone metastasis in these cell lines. We then incorporated bioinformatic analyses of large clinical metastasis datasets to obtain a list of candidate novel bone metastasis proteins of several functional classes that were strongly associated with both clinical and experimental bone metastasis. Functional validation of selected proteins indicated that in vivo bone metastasis can be promoted by high expression of (1) the salivary cystatins CST1, CST2, and CST4; (2) the plasminogen activators PLAT and PLAU; or (3) the collagen functionality proteins PLOD2 and COL6A1. Overall, our study has uncovered several new secreted mediators of bone metastasis and therefore demonstrated that secretome analysis is a powerful method for identification of novel biomarkers and candidate therapeutic targets. PMID:22688892

  19. Unusual location of a urinary bladder cancer metastasis.

    PubMed

    Forte, Serafino; Kos, Sebastian; Hoffmann, Adrienne

    2009-01-01

    Bladder cancer is the fourth most common malignancy among men in the Western world. Bone metastasis occurs in 27 % of the cases. Usually, the location is the spine. The present report describes the first case of a proven distant bone metastasis to the acromion from a urinary bladder carcinoma in a patient with shoulder pain.

  20. Probing the Fifty Shades of EMT in Metastasis.

    PubMed

    Li, Wenyang; Kang, Yibin

    2016-02-01

    The involvement of epithelial-to-mesenchymal transition (EMT) in metastasis has long been under debate. Recent efforts to probe the occurrence and functional significance of EMT in clinical samples and animal models have produced exciting but sometimes conflicting findings. The diversity of EMT underlies the challenge in studying its role in metastasis.

  1. Systemic inflammation: Cancer's long-distance reach to maximize metastasis

    PubMed Central

    Coffelt, Seth B.; de Visser, Karin E.

    2016-01-01

    ABSTRACT While major improvements have been made in targeting primary tumor growth, metastasis and combating cancer spread remain an enigma. We recently identified a systemic inflammatory cascade involving IL17-producing γδ T cells and neutrophils that advance breast cancer metastasis. These data provide insights into how immune cells promote cancer spread. PMID:27057449

  2. Systemic inflammation: Cancer's long-distance reach to maximize metastasis.

    PubMed

    Coffelt, Seth B; de Visser, Karin E

    2016-02-01

    While major improvements have been made in targeting primary tumor growth, metastasis and combating cancer spread remain an enigma. We recently identified a systemic inflammatory cascade involving IL17-producing γδ T cells and neutrophils that advance breast cancer metastasis. These data provide insights into how immune cells promote cancer spread.

  3. Platelet aggregation in the formation of tumor metastasis

    PubMed Central

    Tsuruo, Takashi; Fujita, Naoya

    2008-01-01

    Metastasis is the major cause of death from cancer, yet the optimal strategy against it remains uncertain. The pathogenesis of hematogenous metastasis is dynamic and consists of the following steps: 1) detachment of tumor cells from the primary site, 2) invasion into the host’s blood vessels, 3) migration in the host’s blood stream, 4) transport along the circulation, 5) arrest in or adhesion to the capillary in a distant organ, 6) extravasation, and 7) proliferation within the foreign tissues. A key to successful hematogenous metastasis is tumor survival in the bloodstream because most circulating tumor cells are rapidly destroyed by the shear forces or are attacked by the immune system. Less than 0.01% of these cells result in metastasis. Tumor cell–induced platelet aggregation has been reported to facilitate hematogenous metastasis by increasing the arrest of tumor cell emboli in the microcirculation. Platelet aggregation is also believed to protect tumor cells from immunological assault in the circulation. We have identified Aggrus as a platelet–aggregating factor expressed on a number of human cancers. Because hematogenous metastasis is reduced when neutralizing antibodies or eliminating carbohydrates attenuates Aggrus function, Aggrus’s main contribution to hematogenous metastasis of Aggrus–expressing cells, then, is by promoting platelet aggregation. Aggrus could serve as an ideal target for drug development to block metastasis. PMID:18941298

  4. New genes potentially involved in breast cancer metastasis.

    PubMed

    Schwirzke, M; Schiemann, S; Gnirke, A U; Weidle, U H

    1999-01-01

    Identification of new genes involved in the pathogenesis of breast cancer opens new avenues for improved diagnostic markers and new molecular targets for improved treatment of this malignancy. In the following we review genes with proved involvement in invasion and metastasis of breast cancer as well as genes which exhibit an expression pattern that correlates with invasion and metastasis.

  5. Isolated metastasis of testicular seminoma to extralobar pulmonary sequestration.

    PubMed

    Fudulu, Daniel; Casali, Gianluca; Sohail, Muhammed; Krishnadas, Rakesh

    2016-05-01

    This case report describes a 46-year-old patient with a very unusual pattern of isolated metastasis to an extralobar pulmonary sequestration following orchidectomy for seminoma. The patient underwent uncomplicated video-assisted thoracoscopic resection of the metastasis, involving the whole of the sequestration mass. © The Author(s) 2016.

  6. Muc1 promotes migration and lung metastasis of melanoma cells

    PubMed Central

    Wang, Xiaoli; Lan, Hongwen; Li, Jun; Su, Yushu; Xu, Lijun

    2015-01-01

    Early stages of melanoma can be successfully treated by surgical resection of the tumor, but there is still no effective treatment once it is progressed to metastatic phases. Although growing family of both melanoma metastasis promoting and metastasis suppressor genes have been reported be related to metastasis, the molecular mechanisms governing melanoma metastatic cascade are still not completely understood. Therefore, defining the molecules that govern melanoma metastasis may aid the development of more effective therapeutic strategies for combating melanoma. In the present study, we found that muc1 is involved in the metastasis of melanoma cells and demonstrated that muc1 disruption impairs melanoma cells migration and metastasis. The requirement of muc1 in the migration of melanoma cells was further confirmed by gene silencing in vitro. In corresponding to this result, over-expression of muc1 significantly promoted the migratory of melanoma cells. Moreover, down-regulation of muc1 expression strikingly inhibits melanoma cellular metastasis in vivo. Finally, we found that muc1 promotes melanoma migration through the protein kinase B (Akt) signaling pathway. To conclude, our findings suggest a novel mechanism underlying the metastasis of melanoma cells which might serve as a new intervention target for the treatment of melanoma. PMID:26609470

  7. GPR116, an adhesion G-protein-coupled receptor, promotes breast cancer metastasis via the Gαq-p63RhoGEF-Rho GTPase pathway.

    PubMed

    Tang, Xiaolong; Jin, Rongrong; Qu, Guojun; Wang, Xiu; Li, Zhenxi; Yuan, Zengjin; Zhao, Chen; Siwko, Stefan; Shi, Tieliu; Wang, Ping; Xiao, Jianru; Liu, Mingyao; Luo, Jian

    2013-10-15

    Adhesion G-protein-coupled receptors (GPCR), which contain adhesion domains in their extracellular region, have been found to play important roles in cell adhesion, motility, embryonic development, and immune response. Because most adhesion molecules with adhesion domains have vital roles in cancer metastasis, we speculated that adhesion GPCRs are potentially involved in cancer metastasis. In this study, we identified GPR116 as a novel regulator of breast cancer metastasis through expression and functional screening of the adhesion GPCR family. We found that knockdown of GPR116 in highly metastatic (MDA-MB-231) breast cancer cells suppressed cell migration and invasion. Conversely, ectopic GPR116 expression in poorly metastatic (MCF-7 and Hs578T) cells promoted cell invasion. We further showed that knockdown of GPR116 inhibited breast cancer cell metastasis in two mammary tumor metastasis mouse models. Moreover, GPR116 modulated the formation of lamellipodia and actin stress fibers in cells in a RhoA- and Rac1-dependent manner. At a molecular level, GPR116 regulated cell motility and morphology through the Gαq-p63RhoGEF-RhoA/Rac1 pathway. The biologic significance of GPR116 in breast cancer is substantiated in human patient samples, where GPR116 expression is significantly correlated with breast tumor progression, recurrence, and poor prognosis. These findings show that GPR116 is crucial for the metastasis of breast cancer and support GPR116 as a potential prognostic marker and drug target against metastatic human breast cancer.

  8. MiR-630 inhibits invasion and metastasis in esophageal squamous cell carcinoma.

    PubMed

    Jin, Li; Yi, Jun; Gao, Yanping; Han, Siqi; He, Zhenyue; Chen, Longbang; Song, Haizhu

    2016-09-01

    Esophageal squamous cell carcinoma (ESCC) is among the most aggressive malignancies and has a high incidence in China. MicroRNAs (miRNAs) are small endogenous RNAs that regulate multiple tumorigenic processes, including proliferation, invasion, metastasis and prognosis. Using miRNA expression profiling analysis, we found that miR-630 was markedly down-regulated in three ESCC tissue samples compared with that in paired normal esophageal tissues. Differential miR-630 expression was subsequently confirmed using quantitative real-time PCR. To determine whether miR-630 down-regulation could be considered as a diagnostic indicator and adverse prognostic factor, we investigated the association between miR-630 and clinicopathological characteristics in patients with ESCC. It was found that decreased miR-630 expression was associated with poor overall survival in these patients. In addition, we also explored the biological function of miR-630 by targeting Slug and investigated the correlation between miR-630 expression and epithelial-mesenchymal transition (EMT) progression in vivo and in vitro Ectopic miR-630 expression could inhibit proliferation, invasion and metastasis, whereas miR-630 knockdown induced proliferation, invasion, metastasis and EMT traits. Overall, our study supports a role for miR-630 as a critical novel modulator in ESCC. © The Author 2016. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Mandible ameloblastoma with lung metastasis: a rare case report

    PubMed Central

    Yang, Rui-Na; Wang, Xin-Shuai; Ren, Jing; Xie, Yan-Fei; Zhou, Dan; Ge, Dong-Feng; Feng, Xiao-Shan; Gao, She-Gan

    2015-01-01

    Background: The ameloblastoma is the most common odontogenic epithelial tumor, which belong to benign neoplasms that present a painless course, and usually occur in the oromaxillo-facial region. Although the histopathological manifestation of ameloblastoma is benign, it has unique biological behavior, for example local invasion and recurrence repeatedly. A few case of ameloblastoma was locally aggressive growth, and rarely metastasis to other tissue, for example the lungs, lymph nodes, and spine. Case report: A 64-year-old Chinese man, diagnosed with metastatic ameloblastoma, was treated with palliative chemotherapy consisting of cyclophosphamide, doxorubicin, and cisplatin for six cycles, and radiotherapy for 50 Gy after the last cycle chemotherapy. During the surveillance CT scan after the therapy, the tissues of the tumor were nearly complete response. Conclusion: The purpose of this study was to report a case of a patient with a right mandible ameloblastoma that recurred repeatedly and metastasized into bilateral lung. After the chemotherapy and radiotherapy, the tissues of the tumor were nearly complete response. This case is interesting because it investigated the diagnosis and treatment of the malignancy ameloblastoma, as this may help diagnose and treatment for clinician to the metastatic ameloblastoma. PMID:26261564

  10. Mandible ameloblastoma with lung metastasis: a rare case report.

    PubMed

    Yang, Rui-Na; Wang, Xin-Shuai; Ren, Jing; Xie, Yan-Fei; Zhou, Dan; Ge, Dong-Feng; Feng, Xiao-Shan; Gao, She-Gan

    2015-01-01

    The ameloblastoma is the most common odontogenic epithelial tumor, which belong to benign neoplasms that present a painless course, and usually occur in the oromaxillo-facial region. Although the histopathological manifestation of ameloblastoma is benign, it has unique biological behavior, for example local invasion and recurrence repeatedly. A few case of ameloblastoma was locally aggressive growth, and rarely metastasis to other tissue, for example the lungs, lymph nodes, and spine. A 64-year-old Chinese man, diagnosed with metastatic ameloblastoma, was treated with palliative chemotherapy consisting of cyclophosphamide, doxorubicin, and cisplatin for six cycles, and radiotherapy for 50 Gy after the last cycle chemotherapy. During the surveillance CT scan after the therapy, the tissues of the tumor were nearly complete response. The purpose of this study was to report a case of a patient with a right mandible ameloblastoma that recurred repeatedly and metastasized into bilateral lung. After the chemotherapy and radiotherapy, the tissues of the tumor were nearly complete response. This case is interesting because it investigated the diagnosis and treatment of the malignancy ameloblastoma, as this may help diagnose and treatment for clinician to the metastatic ameloblastoma.

  11. Dynamics of tissue topology during cancer invasion and metastasis

    NASA Astrophysics Data System (ADS)

    Munn, Lance L.

    2013-12-01

    During tumor progression, cancer cells mix with other cell populations including epithelial and endothelial cells. Although potentially important clinically as well as for our understanding of basic tumor biology, the process of mixing is largely a mystery. Furthermore, there is no rigorous, analytical measure available for quantifying the mixing of compartments within a tumor. I present here a mathematical model of tissue repair and tumor growth based on collective cell migration that simulates a wide range of observed tumor behaviors with correct tissue compartmentalization and connectivity. The resulting dynamics are analyzed in light of the Euler characteristic number (χ), which describes key topological features such as fragmentation, looping and cavities. The analysis predicts a number of regimes in which the cancer cells can encapsulate normal tissue, form a co-interdigitating mass, or become fragmented and encapsulated by endothelial or epithelial structures. Key processes that affect the topological changes are the production of provisional matrix in the tumor, and the migration of endothelial or epithelial cells on this matrix. Furthermore, the simulations predict that topological changes during tumor invasion into blood vessels may contribute to metastasis. The topological analysis outlined here could be useful for tumor diagnosis or monitoring response to therapy and would only require high resolution, 3D image data to resolve and track the various cell compartments.

  12. Dynamics of tissue topology during cancer invasion and metastasis.

    PubMed

    Munn, Lance L

    2013-12-01

    During tumor progression, cancer cells mix with other cell populations including epithelial and endothelial cells. Although potentially important clinically as well as for our understanding of basic tumor biology, the process of mixing is largely a mystery. Furthermore, there is no rigorous, analytical measure available for quantifying the mixing of compartments within a tumor. I present here a mathematical model of tissue repair and tumor growth based on collective cell migration that simulates a wide range of observed tumor behaviors with correct tissue compartmentalization and connectivity. The resulting dynamics are analyzed in light of the Euler characteristic number (χ), which describes key topological features such as fragmentation, looping and cavities. The analysis predicts a number of regimes in which the cancer cells can encapsulate normal tissue, form a co-interdigitating mass, or become fragmented and encapsulated by endothelial or epithelial structures. Key processes that affect the topological changes are the production of provisional matrix in the tumor, and the migration of endothelial or epithelial cells on this matrix. Furthermore, the simulations predict that topological changes during tumor invasion into blood vessels may contribute to metastasis. The topological analysis outlined here could be useful for tumor diagnosis or monitoring response to therapy and would only require high resolution, 3D image data to resolve and track the various cell compartments.

  13. Hepatoblastoma of the adult with pericardial metastasis: A case report

    PubMed Central

    Celotti, Andrea; Baiocchi, Gian Luca; Ceresoli, Marco; Bartoli, Michele; Ulinici, Silvia; Portolani, Nazario

    2016-01-01

    Background Hepatoblastoma is the most frequent liver tumor in children, but very rare in the adult and associated with an unfavorable prognosis. The diagnosis is always postoperative or post mortem and biopsy is not useful. Surgery is the only accepted treatment. Case presentation Our patient underwent surgery in the suspect of liver metastasis from a previous gastric cancer. Surgery consisted in left lobectomy with partial diaphragm resection and partial pericardiectomy for a pericardial lesion, found after the opening of the thorax. The diaphragm defect was corrected with a biological mesh. Results The histopathological examination indicated hepatoblastoma of the adult with pericardial metastases. The patient was asymptomatic and without recurrence after 21 months of follow up. Conclusion The hepatoblastoma of the adult is related to a poor prognosis with median survival time less than 5 months. Surgery is the only curative treatment, but in many cases tumor resection requires complex operations. Vascular and thoracic expertise could be useful in the management of hepatoblastoma. PMID:26826931

  14. The role of exosomes in tumor progression and metastasis (Review).

    PubMed

    Suchorska, Wiktoria M; Lach, Michal S

    2016-03-01

    Tumor cells have developed various mechanisms in defense against applied treatment, which prevent their total elimination from an organism. One of the underestimated mechanisms of defense is secretion of highly specialized double-membrane structures called exosomes. They play a crucial role in the control of the local microenvironment and intracellular communication. It has been shown that the exosomes can be carriers of various proteins, lipids, miRNAs and mRNAs. There are extensive data concerning the influence and participation by exosomes in metastasis and cancer progression. It has been demonstrated that exosomes are involved in multidrug resistance mechanisms, radiation-induced bystander effect and epithelial-mesenchymal transition. Furthermore, exosomes are able to form a premetastatic niche and enable the escape of cancer cells from recognition by host immune cells. Moreover, exosomes are responsible for the formation of vessels. This indicates the significance of secreted extracellular vesicles in the development and prognosis of cancer. The aim of the present review is to briefly describe the role of exosomes in tumor biology.

  15. Cesarean Sections

    MedlinePlus

    ... the uterus itself. This incision can also be vertical or horizontal. Doctors usually use a horizontal incision ... especially if the incision on the uterus was vertical rather than horizontal. A C-section can also ...

  16. [Cervical lymph node metastasis in medullary thyroid carcinoma].

    PubMed

    Yan, Dangui; Zhang, Bin; Li, Zhengjiang; Wu, Yuehuang; Liu, Shaoyan; Liu, Wensheng; Xu, Zhengang; Tang, Pingzhang

    2015-04-01

    To study the patterns of cervical lymph node metastasis of medullary thyroid carcinoma. Ninety-one patients with medullary thyroid carcinoma first treated between January 1999 and October 2014 were analyzed retrospectively. Of 91 patients, 39 cases presented with clinical negative node (cN0) and 52 cases with clinical positive node (cN+). Central compartment dissection was performed in all cases. Lateral neck dissection was performed in 52 cN+ cases (71 sides). All neck dissection specimens were obtained and analyzed for lymph node (LN) involvement with respect to neck levels. The distribution of LN with metastasis was studied in cN+ patients and the following factors were used to study the predictive value of central compartment LN metastasis: sex, age, family history, tumor size, bilateral tumor, multifocality of the tumor, extracapsular spread, and remote metastasis. Univariate analysis with the χ(2) test was used to analyze the statistical correlation between central compartment LN metastasis and other clinical factors. Multiple logistic regression analysis was used to identify the factors related to central compartment metastasis. Neck and bilateral neck metastasis rates were 73.6%, 19.8% respectively. Metastasis rates in central compartment and superior mediastinal region were 68.1% and 27.5% respectively. The central compartment metastasis rate was 33.3% in cN0 patients and 94.2% in cN+ patients. The superior mediastinal metastasis rate was 2.6% in cN0 patients and 46.2% in cN+ patients. Extracapsular spread was an independent predictive factor for central compartment metastasis (χ(2)=15.592, P=0.000, OR=12.876). The incidences of LN metastases at level II, III, IV, V were 62.9%,84.5%,83.1%,50.0% in cN+ patient, respectively. Multi-sites were involved. The possibility of lateral neck metastasis was higher when preoperative value of calcitonin was higher than 300 ng/L (66.7% vs 28.6%, χ(2)=5.771, P=0.016). Cervical lymph node metastasis of medullary

  17. [Clinical analysis of cervical lymph node metastasis of hypopharyngeal carcinoma].

    PubMed

    Chen, Xinglong; Xu, Jian

    2011-10-01

    To investigate the pattern of cervical lymph node metastasis in hypopharyngeal carcinoma. Forty-five cases of hypopharyngeal squamous cell carcinoma were analyzed retrospectively. (1) The total rate of lymph node metastasis was 75.56%. 11.11% metastases for bilateral neck and 4.44% did unilateral neck in 10 bilateral neck dissection. The total distance metastasis rate out of lymph node were 79.41%. The rate of bilateral distance metastasis and unilateral distance metastasis were both 5.88% in 10 bilateral neck dissection. (2) 163 of 411 lymph nodes (39.66%) were positive. The percentage of positive lymph node were 0.61%, 49.08%, 25.77%, 21.47% and 3.07% in region I, II, III, IV and V respectively. The rates of lymph node metastasis were 3.57%, 62.02%, 37.17%, 42.17% and 8.62% in region I, II, III, NV and V respectively. (3) The statistical significant differences were found between region I + V and II + III and IV (P < 0.05), among II, III and IV (P < 0.05), between II and III + IV (P < 0.05), between II and III (P < 0.05), between II and IV (P < 0.05), among I, II, III, IV and II + III + IV (P < 0.05), among V, II, III, IV and II + III + IV (P < 0.05). There were not statistical significant differences in region between III and IV (P > 0.05), between I and V (P > 0.05). (4) There were not statistical significant differences in the rates of lymph node metastasis and capsule invasion between T1 + T2 and T3 + T4 (P > 0.05), among T1, T2, T3 and T4 (P > 0.05). (5) There were not statistical significant differences in the rates of lymph node metastasis and distance metastasis between pyriform sinus and out of it (P > 0.05). (6) There were not statistical significant differences in the rates of lymph node metastasis and distance metastasis between cervical esophagus invasion and not (P > 0.05). (7) There were not statistical significant differences in the rates of lymph node metastasis and distance metastasis among N1, N2, N3 (P > 0.05). (8) There were statistical

  18. Choroid Melanoma Metastasis to Spine: A Rare Case Report

    PubMed Central

    Mandaliya, Hiren; Singh, Nandini; George, Sanila; George, Mathew

    2016-01-01

    Metastatic choroid melanoma is a highly malignant disease with a limited life expectancy. The liver is the most common site for metastasis of uveal melanoma followed by lung, bone, skin, and subcutaneous tissue. Metastasis from choroidal melanoma usually occurs within the first five years of treatment for primary tumours. Metastatic choroid melanoma to the spine/vertebrae is extremely rare. We report the first case of spinal metastasis from choroid melanoma in a 61-year-old man who had been treated for primary ocular melanoma three years earlier with radioactive plaque brachytherapy. Synchronously, at the time of metastasis, he was also diagnosed as having a new primary lung adenocarcinoma as well. The only other case reported on vertebral metastasis from malignant melanoma of choroid in literature in which primary choroid melanoma was enucleated. PMID:26989537

  19. GDF15 promotes EMT and metastasis in colorectal cancer.

    PubMed

    Li, Chen; Wang, Jingyu; Kong, Jianlu; Tang, Jinlong; Wu, Yihua; Xu, Enping; Zhang, Honghe; Lai, Maode

    2016-01-05

    Metastasis is the major cause of cancer deaths, and the epithelial-mesenchymal transition (EMT) has been considered to be a fundamental event in cancer metastasis. However, the role of growth differentiation factor 15 (GDF15) in colorectal cancer (CRC) metastasis and EMT remains poorly understood. Here, we showed that GDF15 promoted CRC cell metastasis both in vitro and in vivo. In addition, the EMT process was enhanced by GDF15 through binding to TGF-β receptor to activate Smad2 and Smad3 pathways. Clinical data showed GDF15 level in tumor tissues, and the serum was significantly increased, in which high GDF15 level correlated with a reduced overall survival in CRC. Thus, GDF15 may promote colorectal cancer metastasis through activating EMT. Promisingly, GDF15 could be considered as a novel prognostic marker for CRC in the clinic.

  20. Potential Anti-metastasis Natural Compounds for Lung Cancer.

    PubMed

    Chanvorachote, Pithi; Chamni, Supakarn; Ninsontia, Chuanpit; Phiboonchaiyanan, Preeyaporn Plaimee

    2016-11-01

    As lung cancer is the most common malignancy worldwide and high mortalities are the result of metastasis, novel information surpassing the treatment strategies and therapeutic agents focusing on cancer dissemination are of interest. Lung cancer metastasis involves increased motility, survival in circulation and ability to form new tumors. Metastatic cells increase their aggressive features by utilizing several mechanisms to overcome hindrances of metastasis, including epithelial to mesenchymal transition (EMT), increased in cellular survival and migratory signals. Sufficient amounts of natural product-derived compounds have been shown to have promising anti-metastasis activities by suppressing key molecular features upholding such cell aggressiveness. The knowledge regarding molecular mechanisms rendering cell dissemination together with the anti-metastasis information of natural product-derived compounds may lead to development of novel therapeutic strategies. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  1. Mammalian mediator 19 mediates H1299 lung adenocarcinoma cell clone conformation, growth, and metastasis.

    PubMed

    Xu, Lu-Lu; Guo, Shu-Liang; Ma, Su-Ren; Luo, Yong-Ai

    2012-01-01

    Mammalian mediator (MED) is a multi-protein coactivator that has been identified by several research groups. The involvement of the MED complex subunit 19 (MED 19) in the metastasis of lung adenocarcinoma cell line (H1299), which expresses the MED 19 subunit, was here investigated. When MED 19 expression was decreased by RNA interference H1299 cells demonstrated reduced clone formation, arrest in the S phase of the cell cycle, and lowered metastatic capacity. Thus, MED 19 appears to play important roles in the biological behavior of non-small cell lung carcinoma cells. These findings may be important for the development of novel lung carcinoma treatments.

  2. Chemotherapy-enhanced inflammation may lead to the failure of therapy and metastasis.

    PubMed

    Vyas, Dinesh; Laput, Gieric; Vyas, Arpitak K

    2014-01-01

    The lack of therapy and the failure of existing therapy has been a challenge for clinicians in treating various cancers. Doxorubicin, 5-fluorouracil, cisplatin, and paclitaxel are the first-line therapy in various cancers; however, toxicity, resistance, and treatment failure limit their clinical use. Their status leads us to discover and investigate more targeted therapy with more efficacy. In this article, we dissect literature from the patient perspective, the tumor biology perspective, therapy-induced metastasis, and cell data generated in the laboratory.

  3. Transforming growth factor β as regulator of cancer stemness and metastasis

    PubMed Central

    Bellomo, Claudia; Caja, Laia; Moustakas, Aristidis

    2016-01-01

    Key elements of cancer progression towards metastasis are the biological actions of cancer stem cells and stromal cells in the tumour microenvironment. Cross-communication between tumour and stromal cells is mediated by secreted cytokines, one of which, the transforming growth factor β (TGFβ), regulates essentially every cell within the malignant tissue. In this article, we focus on the actions of TGFβ on cancer stem cells, cancer-associated fibroblasts and immune cells that assist the overall process of metastatic dissemination. We aim at illustrating intricate connections made by various cells in the tumour tissue and which depend on the action of TGFβ. PMID:27537386

  4. CD133+CD54+CD44+ circulating tumor cells as a biomarker of treatment selection and liver metastasis in patients with colorectal cancer

    PubMed Central

    Wang, Cun; Huang, Qiaorong; Meng, Wentong; Yu, Yongyang; Yang, Lie; Peng, Zhihai; Hu, Jiankun; Li, Yuan; Mo, Xianming; Zhou, Zongguang

    2016-01-01

    Introduction Liver is the most common site of distant metastasis in colorectal cancer (CRC). Early diagnosis and appropriate treatment selection decides overall prognosis of patients. However, current diagnostic measures were basically imaging but not functional. Circulating tumor cells (CTCs) known as hold the key to understand the biology of metastatic mechanism provide a novel and auxiliary diagnostic strategy for CRC with liver metastasis (CRC-LM). Results The expression of CD133+ and CD133+CD54+CD44+ cellular subpopulations were higher in the peripheral blood of CRC-LM patients when compared with those without metastasis (P<0.001). Multivariate analysis proved the association between the expression of CD133+CD44+CD54+ cellular subpopulation and the existence of CRC-LM (P<0.001). The combination of abdominal CT/MRI, CEA and the CD133+CD44+CD54+ cellular subpopulation showed increased detection and discrimination rate for liver metastasis, with a sensitivity of 88.2% and a specificity of 92.4%. Meanwhile, it also show accurate predictive value for liver metastasis (OR=2.898, 95% C.I.1.374–6.110). Materials and Method Flow cytometry and multivariate analysis was performed to detect the expression of cancer initiating cells the correlation between cellular subpopulations and liver metastasis in patients with CRC. The receiver operating characteristic curves combined with the area under the curve were generated to compare the predictive ability of the cellular subpopulation for liver metastasis with current CT and MRI images. Conclusions The identification, expression and application of CTC subpopulations will provide an ideal cellular predictive marker for CRC liver metastasis and a potential marker for further investigation. PMID:27764803

  5. Hypoxic regulation of RIOK3 is a major mechanism for cancer cell invasion and metastasis

    PubMed Central

    Singleton, Dean C.; Rouhi, Pegah; Zois, Christos E.; Haider, Syed; Li, Ji-Liang; Kessler, Benedikt M.; Cao, Yihai; Harris, Adrian L.

    2014-01-01

    Hypoxia is a common feature of locally advanced breast cancers and is associated with increased metastasis and poorer survival. Stabilisation of Hypoxia-Inducible Factor-1α (HIF1α) in tumours causes transcriptional changes in numerous genes that function at distinct stages of the metastatic cascade. We demonstrate that expression of RIOK3 was increased during hypoxic exposure in a HIF1α-dependent manner. RIOK3 was localised to distinct cytoplasmic aggregates in normoxic cells and underwent redistribution to the leading edge of the cell in hypoxia with a corresponding change in the organisation of the actin cytoskeleton. Depletion of RIOK3 expression caused MDA-MB-231 to become elongated and this morphological change was due to a loss of protraction at the trailing edge of the cell. This phenotypic change resulted in reduced cell migration in 2D cultures and inhibition of cell invasion through 3D extracellular matrix. Proteomic analysis identified interactions of RIOK3 with actin and several actin-binding factors including tropomyosins (TPM3 and TPM4) and tropomodulin 3 (TMOD3). Depletion of RIOK3 in cells resulted in fewer and less organised actin filaments. Analysis of these filaments showed reduced association of TPM3, particularly during hypoxia, suggesting that RIOK3 regulates actin filament specialisation. RIOK3 depletion reduced the dissemination of MDA-MB-231 cells in both a zebrafish model of systemic metastasis and a mouse model of pulmonary metastasis. These findings demonstrate that RIOK3 is necessary for maintaining actin cytoskeletal organisation required for migration and invasion, biological processes that are necessary for hypoxia-driven metastasis. PMID:25486436

  6. Matrix Metalloproteinase 1 promotes tumor formation and lung metastasis in an intratibial injection osteosarcoma mouse model.

    PubMed

    Husmann, Knut; Arlt, Matthias J E; Muff, Roman; Langsam, Bettina; Bertz, Josefine; Born, Walter; Fuchs, Bruno

    2013-02-01

    Proteolytic degradation of the extracellular matrix (ECM) is an important process during tumor invasion. Matrix Metalloproteinase 1 (MMP-1) is one of the proteases that degrade collagen type I, a major component of bone ECM. In the present study, the biological relevance of MMP-1 in osteosarcoma (OS) tumor growth and metastasis was investigated in vitro and in vivo. Human OS cells in primary culture expressed MMP-1 encoding mRNA at considerably higher levels than normal human bone cells. In addition, MMP-1 mRNA and protein expression in the highly metastatic human osteosarcoma 143-B cell line was remarkably higher than in the non-metastatic parental HOS cell line. Stable shRNA-mediated downregulation of MMP-1 in 143-B cells impaired adhesion to collagen I and anchorage-independent growth, reflected by a reduced ability to grow in soft agar. Upon intratibial injection into SCID mice, 143-B cells with shRNA-downregulated MMP-1 expression formed smaller primary tumors and significantly lower numbers of lung micro- and macrometastases than control cells. Conversely, HOS cells stably overexpressing MMP-1 showed an enhanced adhesion capability to collagen I and accelerated anchorage-independent growth compared to empty vector-transduced control cells. Furthermore, and most importantly, individual MMP-1 overexpression in HOS cells enabled the formation of osteolytic primary tumors and lung metastasis while the HOS control cells did not develop any tumors or metastases after intratibial injection. The findings of the present study reveal an important role of MMP-1 in OS primary tumor and metastasis formation to the lung, the major organ of OS metastasis. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Identification of differentially expressed genes in salivary adenoid cystic carcinoma cells associated with metastasis

    PubMed Central

    Liu, Bing-Yao; Zhang, Xiang; Zhao, Xiao-Ge; Cao, Gang; Dong, Zhen

    2016-01-01

    Introduction Salivary adenoid cystic carcinoma (SACC) is a frequent type of salivary gland cancer which is characterized by slow growth but high incidence of distant metastasis. We aimed to identify therapeutic targets which are associated with metastasis of SACC. Material and methods Total RNA was isolated from a low metastatic SACC cell line (ACC-2) and a highly metastatic SACC cell line (ACC-M), which was screened from ACC-2 by combination of in vivo selection and cloning in vitro. Then the total RNA was subjected to microarray analysis. Differentially expressed genes (DEGs) were screened from ACC-M compared with ACC-2, followed by Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Function annotation for DEGs also was performed. A protein-protein interaction network (PPI) was constructed for DEGs. Results A total of 1128 DEGs were identified from ACC-M cells compared with ACC-2 cells. Both up- and down-regulated DEGs were enriched in different functions in biological process (BP), cellular component (CC) and molecular function (MF). Additionally, down-regulated DEGs were mainly enriched in “Apoptosis” and “Cytokine-cytokine receptor interaction” pathways which involved IFN-α1, NTRK1 and TGF-β1. In the PPI network, PIK3CA, PTPN11 and PIK3R1 had a number of nodes greater than 10. Conclusions Transforming growth factor β1 might play a pivotal role during lung metastasis of SACC and be selected as a candidate target for treatment of metastatic SACC. IFNA1, NTRK1 and PIK3CA were also associated with tumor metastasis. PMID:27478471

  8. Pituitary Metastasis from Renal Cell Carcinoma: Description of a Case Report

    PubMed Central

    Wendel, Chloé; Campitiello, Marco; Plastino, Francesca; Eid, Nada; Hennequin, Laurent; Quétin, Philippe; Longo, Raffaele

    2017-01-01

    Patient: Male, 61 Final Diagnosis: Pituitary metastasis from renal cell carcinoma Symptoms: Deterioration of visual acuity and field • persisting headache • excess thirst • polyuria Medication: — Clinical Procedure: Total body CT-scan • brain MRI • trans-sphenoidal endoscopical surgery • radiotherapy • anti-angiogenic therapy Specialty: Oncology Objective: Rare disease Background: Pituitary metastasis is uncommon, breast and lung cancers being the most frequent primary tumors. Renal cell carcinoma (RCC) is a rare cause of pituitary metastases, with only a few cases described to date. Case Report: We report a case of a 61-year-old man who presented with a progressive deterioration of visual acuity and field associated with a bitemporal hemianopsia. Two years ago, he underwent radical right nephrectomy for a clear cell RCC (ccRCC). The biological tests showed pan-hypopituitarism and diabetes insipidus. Brain MRI revealed a large sellar tumor lesion bilaterally infiltrating the cavernous sinuses, which was surgically resected. Histology confirmed a ccRCC pituitary metastasis. The patient received post-surgical radiotherapy. Considering the presence of concomitant extra-pituitary metastases, treatment with sunitinib was started, followed by several lines of therapy with axitinib, everolimus, and sorafenib because of tumor progression. The patient also presented with a pituitary tumor recurrence, which was treated by stereotaxic radiotherapy. He died five years after the initial diagnosis of RCC and 30 months after the diagnosis of the pituitary metastasis. Conclusions: There are no standardized treatment guidelines for management of pituitary metastases. Pituitary surgery plays a role in symptom palliation, and it does not have any relevant impact on survival. Exclusive radiotherapy or stereotaxic radiotherapy could be an alternative to surgery in patients whose general condition is poor or who have concomitant extra-pituitary metastases. PMID:28044054

  9. Coordinate regulation of microenvironmental stimuli and role of methylation in bone metastasis from breast carcinoma.

    PubMed

    Matteucci, Emanuela; Maroni, Paola; Disanza, Andrea; Bendinelli, Paola; Desiderio, Maria Alfonsina

    2016-01-01

    The pathogenesis of bone metastasis is unclear, and much focus in metastatic biology and therapy relays on epigenetic alterations. Since DNA-methyltransferase blockade with 5-aza-2'-deoxycytidine (dAza) counteracts tumour growth, here we utilized dAza to clarify whether molecular events undergoing epigenetic control were critical for bone metastatization. In particular, we investigated the patterns of secreted-protein acidic and rich in cysteine (SPARC) and of Endothelin 1, affected by DNA methyltransferases in tumours, with the hypothesis that in bone metastasis a coordinate function of SPARC and Endothelin 1, if any occurs, was orchestrated by DNA methylation. To this purpose, we prepared a xenograft model with the clone 1833, derived from human-MDA-MB231 cells, and dAza administration slowed-down metastasis outgrowth. This seemed consequent to the reductions of SPARC and Endothelin 1 at invasive front and in the bone marrow, mostly due to loss of Twist. In the metastasis bulk Snail, partly reduced by dAza, might sustain Endothelin 1-SPARC cooperativity. Both SPARC and Endothelin 1 underwent post-translational control by miRNAs, a molecular mechanism that might explain the in vivo data. Ectopic miR29a reduced SPARC expression also under long-term dAza exposure, while Endothelin 1 down-regulation occurred in the presence of endogenous-miR98 expression. Notably, dAza effects differed depending on in vivo and in vitro conditions. In 1833 cells exposed to 30-days dAza, SPARC-protein level was practically unaffected, while Endothelin 1 induction depended on the 3'-UTR functionality. The blockade of methyltransferases leading to SPARC reduction in vivo, might represent a promising strategy to hamper early steps of the metastatic process affecting the osteogenic niche. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Establishment of an ovarian metastasis model and possible involvement of E-cadherin down-regulation in the metastasis.

    PubMed

    Kuwabara, Yoshiko; Yamada, Taketo; Yamazaki, Ken; Du, Wen-Lin; Banno, Kouji; Aoki, Daisuke; Sakamoto, Michiie

    2008-10-01

    Clinical observations of cases of ovarian metastasis suggest that there may be a unique mechanism underlying ovarian-specific metastasis. This study was undertaken to establish an in vivo model of metastasis to the ovary, and to investigate the mechanism of ovarian-specific metastasis. We examined the capacity for ovarian metastasis in eight different human carcinoma cell lines by implantation in female NOD/SCID mice transvenously and intraperitoneally. By transvenous inoculation, only RERF-LC-AI, a poorly differentiated carcinoma cell line, frequently demonstrated ovarian metastasis. By intraperitoneal inoculation, four of the eight cell lines (HGC27, MKN-45, KATO-III, and RERF-LC-AI) metastasized to the ovary. We compared E-cadherin expression among ovarian metastatic cell lines and others. All of these four ovarian metastatic cell lines and HSKTC, a Krukenberg tumor cell line, showed E-cadherin down-regulation and others did not. E-cadherin was then forcibly expressed in RERF-LC-AI, and inhibited ovarian metastasis completely. The capacity for metastasizing to the other organs was not affected by E-cadherin expression. We also performed histological investigation of clinical ovarian-metastatic tumor cases. About half of all ovarian-metastatic tumor cases showed loss or reduction of E-cadherin expression. These data suggest that E-cadherin down-regulation may be involved in ovarian-specific metastasis.

  11. Cadm1 is a metastasis susceptibility gene that suppresses metastasis by modifying tumor interaction with the cell-mediated immunity.

    PubMed

    Faraji, Farhoud; Pang, Yanli; Walker, Renard C; Nieves Borges, Rosan; Yang, Li; Hunter, Kent W

    2012-09-01

    Metastasis is a complex process utilizing both tumor-cell-autonomous properties and host-derived factors, including cellular immunity. We have previously shown that germline polymorphisms can modify tumor cell metastatic capabilities through cell-autonomous mechanisms. However, how metastasis susceptibility genes interact with the tumor stroma is incompletely understood. Here, we employ a complex genetic screen to identify Cadm1 as a novel modifier of metastasis. We demonstrate that Cadm1 can specifically suppress metastasis without affecting primary tumor growth. Unexpectedly, Cadm1 did not alter tumor-cell-autonomous properties such as proliferation or invasion, but required the host's adaptive immune system to affect metastasis. The metastasis-suppressing effect of Cadm1 was lost in mice lacking T cell-mediated immunity, which was partially phenocopied by depleting CD8(+) T cells in immune-competent mice. Our data show a novel function for Cadm1 in suppressing metastasis by sensitizing tumor cells to immune surveillance mechanisms, and this is the first report of a heritable metastasis susceptibility gene engaging tumor non-autonomous factors.

  12. Therapeutic opportunities from tumour biology in metastatic colon cancer.

    PubMed

    McLeod, H L; McKay, J A; Collie-Duguid, E S; Cassidy, J

    2000-08-01

    Tumour metastasis is the major cause of morbidity and mortality from colorectal cancer. While improvements in quality of life and patient survival have been made over the past 10 years, the majority of patients with metastatic colorectal cancer will die from their disease. As knowledge of the biology of colon cancer and its invasion/metastasis programme evolve, this presents new therapeutic opportunities for pharmacological and genetic intervention. This review discusses the current approaches to metastatic colorectal cancer therapy, details genomic and biological variance between primary and metastatic tumours, and highlights approaches for harnessing these differences to improve therapy.

  13. Tongue metastasis as an initial manifestation of Distant metastasis in Oesophageal Adenocarcinoma

    PubMed Central

    Tunio, Mutahir A.; AlAsiri, Mushabbab; Fareed, Muhammad Mohsin; Ali, Nagoud Mohamed Omar

    2014-01-01

    Metastasis to the head and neck region from primary is rarest manifestation. Lung and breast carcinomas are the commonest malignancies to metastasize to the head and neck region. Oesophageal adenocarcinoma with metastasis to the oral cavity is a rarest presentation and is associated with dismal prognosis. Only few related case reports have been published so far. Her-in we report a case of 55 years old male who underwent radical oesophagectomy for adenocarcinoma of lower oesophagus twelve months back, now presented with hard mass in the right margin of tongue which was suspected as primary tongue carcinoma; subsequently was confirmed as metastatic oesophageal adenocarcinoma following excision. Two months after tongue excision, patient died of progressive metastatic disease. PMID:25097546

  14. Patterns of metastasis and survival in breast cancer patients: a preliminary study in an Iranian population.

    PubMed

    Ziaei, Jamal Eivazi; Pourzand, Ali; Bayat, Amrollah; Vaez, Jalil

    2012-01-01

    Due to lack of sufficient data on characteristics of breast cancer patients and risk factors for developing metastasis in Iran this study was designed to understand clinical aspects impacting on survival. A cross-sectional study on breast cancer patients was conducted in an oncology clinic of the university hospital between 1995 and 2010. Data were retrieved from medical records and included age, menopausal status, tumor diameter, number of involved nodes, histopathological type, estrogen and progesterone receptor expression, c-erbB-2, primary and secondary metastasis sites, overall survival, disease free interval and type of chemotherapy protocol. The results were analyzed with SPSS 13 software.The mean age of the patients was 49.2 (27-89) years. The primary tumors were mainly ER positive (48%) and PR negative (49.3%). The status of lymph nodes dissected and examined in these patients was unknown in 19 patients (25.3%) while 18 patients (24%) had positive lymph nodes with no report on the number of involved nodes. All of the patients had received antracyclin based chemotherapy in an adjuvant or metastatic setting. Adjuvant hormonal therapy was administered to receptor positive patients. In average, overall survival after recurrence was 30 months (95%CI 24.605-35.325) for non-skeletal versus 42 months (95%CI 31.211-52.789) for skeletal metastasis (P= 0.002). The median survival was also greater for receptor positive patients; 39 months (95%CI 33.716-44.284) for PR+ versus 26 months (95%CI 19.210-32.790) for PR- (P=0.047) and 38 months (95%CI 32.908-43.092) for ER+ versus 27 months (95%CI 18.780-35.220) for ER- patients (P=0.016). No relation was found between site of first metastasis and hormone receptor, age, tumor diameter, DFI and menopausal status. Sites of metastasis were independent of age, size of the tumor, menopausal and hormone receptor status in this study. Overall survival provided significant relations with respect to receptor status and bone

  15. Determination of radiotherapeutic target zones for thoracic esophageal squamous cell cancer with lower cervical lymph node metastasis according to CT-images

    PubMed Central

    Li, Xingde; Zhao, Jin; Liu, Ming; Zhai, Fushan; Zhu, Zhengfei; Yu, Feng; Zhang, Mingyun; Han, Lijie; Zhao, Yue; Wang, Haiyan

    2016-01-01

    Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer-related deaths worldwide. And radical synchronized chemoradiotherapy has become an important treatment measures for this disease. It is necessary to define the therapeutic target zone based on computer tomography(CT)-images for precise radiotherapy. Therefore, we retrospectively analyzed the regularity of lymph node metastasis in lower cervical section of thoracic esophageal cancer based on CT-images and discussed the range of radiotherapy in supraclavicular zone. The lower cervical lymphatic drainage area was divided into cervical tracheoesophageal groove (CTG), medial supraclavicular zone (MSC zone) and lateral supraclavicular zone (LSC zone) based on CT-images. We found that the rate of lymph node metastasis to medial CTG and MSC zone was relatively high. And rate of lymph node metastasis to the above two zones from middle thoracic section was on an increasing trend with the progress of T stage. Patients at stage T3 and T4 with lymph node metastasis in tracheoesophageal groove in middle thoracic section showed a higher rate of lymph node metastasis in MSC zone. These results demonstrated that the CTG and MSC zone should be clinically included in the supraclavicular target zone for radical radiotherapy, and the T-stage and tumor location should be considered simultaneously. PMID:27147581

  16. [Thyroid metastasis due to right colonic carcinoma].

    PubMed

    Rauber, E; Pancrazio, F; Spivach, A; Stanta, G

    1998-12-01

    Clinical evident metastases to the thyroid gland are rarely found antemortem. A case of a 62 year-old man with a history of right colonic carcinoma, who presented a mass in the right lobe of his thyroid gland one year after the removal of a metachronous metastasis in his right lung, is presented. The tumour of the thyroid was found to be metastatic adenocarcinoma from his previous colonic cancer. The clinical finding of metastases to the thyroid gland is rare, particularly from a colorectal primary neoplasm. However, the possibility of a tumour of the thyroid gland representing a secondary malignancy is to be considered in any patient with a prior history of cancer.

  17. Diaphragmatic Hernia Masquerading as a Pulmonary Metastasis

    PubMed Central

    Appiah, S; Tcherveniakov, P; Krysiak, P

    2015-01-01

    Iatrogenic injury accounts for the second most common cause of acquired diaphragmatic hernias after penetrating trauma. An increased incidence of these hernias has been observed with the widespread use of laparoscopic surgery. We present the case of a 65-year-old woman who initially underwent sigmoid resection for an adenocarcinoma and a subsequent liver resection for metastasis. She was noted to have a left lower lobe pulmonary nodule on surveillance computed tomography, for which she underwent a mini-thoracotomy for a planned resection. At the time of surgery, the pulmonary nodule was discovered to be a diaphragmatic hernia, most probably of iatrogenic origin. We discuss the difficulty in diagnosis given her history and the location of such a lesion. PMID:25723679

  18. Bone metastasis: mechanisms and therapeutic opportunities

    PubMed Central

    Suva, Larry J.; Washam, Charity; Nicholas, Richard W.; Griffin, Robert J.

    2011-01-01

    The skeleton is one of the most common sites for metastatic cancer, and tumors arising from the breast or prostate possess an increased propensity to spread to this site. The growth of disseminated tumor cells in the skeleton requires tumor cells to inhabit the bone marrow, from which they stimulate local bone cell activity. Crosstalk between tumor cells and resident bone and bone marrow cells disrupts normal bone homeostasis, which leads to tumor growth in bone. The metastatic tumor cells have the ability to elicit responses that stimulate bone resorption, bone formation or both. The net result of these activities is profound skeletal destruction that can have dire consequences for patients. The molecular mechanisms that underlie these painful and often incurable consequences of tumor metastasis to bone are beginning to be recognized, and they represent promising new molecular targets for therapy. PMID:21200394

  19. Pinworm infection masquerading as colorectal liver metastasis

    PubMed Central

    Roberts, KJ; Hubscher, S; Mangat, K; Sutcliffe, R; Marudanayagam, R

    2012-01-01

    Enterobius vermicularis is responsible for a variety of diseases but rarely affects the liver. Accurate characterisation of suspected liver metastases is essential to avoid unnecessary surgery. In the presented case, following a diagnosis of rectal cancer, a solitary liver nodule was diagnosed as a liver metastasis due to typical radiological features and subsequently resected. At pathological assessment, however, a necrotic nodule containing E vermicularis was identified. Solitary necrotic nodules of the liver are usually benign but misdiagnosed frequently as malignant due to radiological features. It is standard practice to diagnose colorectal liver metastases solely on radiological evidence. Without obtaining tissue prior to liver resection, misdiagnosis of solitary necrotic nodules of the liver will continue to occur. PMID:22943320

  20. Primary Intracranial Malignant Melanoma with Extracranial Metastasis

    PubMed Central

    Hirota, Kengo; Yoshimura, Chika; Kubo, Osami; Kasuya, Hidetoshi

    2017-01-01

    We report a case of primary intracranial malignant melanoma (PIMM) with extracranial metastases. The patient was an 82-year-old woman diagnosed with PIMM under the left cerebellar tentorium. We performed a tumor resection followed by gamma knife surgery. An magnetic resonance imaging at 11 months after surgery showed a local intracranial recurrence. At 12 months, vertebral metastasis was suspected, and 2-[fluorine-18]-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) showed multiple extracranial metastases. She died at 13 months after surgery. Although extracranial metastases of PIMM are extremely rare, we should carefully follow up extracranial metastases together with intracranial ones, especially by FDG-PET/CT, even at an early asymptomatic stage. PMID:28061499

  1. Rare Endobronchial metastasis from uterine leiomyosarcoma

    PubMed Central

    Ghosh, Saswata; Kundu, Susmita; Pal, Amitava; Paul, Suman

    2015-01-01

    Uterine sarcomas are rare and represent approximately 3.2% of all invasive uterine cancers. The annual incidence rate is less than two per 100,000 women. The median age at which uterine sarcoma diagnosed is 56 years. The most common histologic pattern is leiomyosarcoma (LMS) which originates from the myometrium or myometrial vessels. Uterine LMSs are aggressive tumors with high rates of recurrence. The most common mode of spread is hematogenous, with lymphatic spread being rare. Recurrences of up to 70% are reported in stage I and II disease with the site of recurrence being distal, most commonly the lungs or the upper abdomen. But the intra bronchial spread is extremely rare. Here we are reporting a case of uterine LMS with endobronchial metastasis causing whole lung collapse. PMID:25814801

  2. Adrenal Metastasis from Uterine Papillary Serous Carcinoma

    PubMed Central

    Lubana, Sandeep Singh; Singh, Navdeep; Tuli, Sandeep S.; Seligman, Barbara

    2016-01-01

    Patient: Female, 60 Final Diagnosis: UPSC with adrenal metastasis Symptoms: Post menopausal bleeding Medication: — Clinical Procedure: Adrenalectomy Specialty: Oncology Objective: Rare disease Background: Uterine papillary serous carcinoma (UPSC) is a highly malignant form of endometrial cancer with a high propensity for metastases and recurrences even when there is minimal or no myometrial invasion. It usually metastasizes to the pelvis, retroperitoneal lymph nodes, upper abdomen, and peritoneum. However, adrenal metastases from UPSC is extremely rare. Here, we present a case of UPSC with adrenal metastasis that occurred 6 years after the initial diagnosis. Case Report: A 60-year-old woman previously diagnosed with uterine papillary serous carcinoma at an outside facility presented in September of 2006 with postmenopausal bleeding. She underwent comprehensive surgical staging with FIGO (International Federation of Gynecology and Obstetrics) stage 2. Post-operatively, the patient was treated with radiation and chemotherapy. The treatment was completed in April of 2007. The patient had no evidence of disease until July 2009 when she was found to have a mass highly suspicious for malignancy. Subsequently, she underwent right upper lobectomy. The morphology of the carcinoma was consistent with UPSC. She refused chemotherapy due to a previous history of chemotherapy-induced neuropathy. The patient was followed up with regular computed tomography (CT) scans. In October 2012 a new right adrenal nodule was seen on CT, which showed intense metabolic uptake on positron emission tomography (PET)/CT scan. The patient underwent right adrenalectomy. Pathology of the surgical specimen was consistent with UPSC. Conclusions: UPSC is an aggressive variant of endometrial cancer associated with high recurrence rate and poor prognoses. Long-term follow-up is needed because there is a possibility of late metastases, as in this case. PMID:27117594

  3. Hand1 overexpression inhibits medulloblastoma metastasis

    SciTech Connect

    Asuthkar, Swapna; Guda, Maheedhara R.; Martin, Sarah E.; Antony, Reuben; Fernandez, Karen; Lin, Julian; Tsung, Andrew J.; Velpula, Kiran K.

    2016-08-19

    Medulloblastoma (MB) is the most frequent malignant pediatric brain tumor. Current treatment includes surgery, radiation and chemotherapy. However, ongoing treatment in patients is further classified according to the presence or absence of metastasis. Since metastatic medulloblastoma are refractory to current treatments, there is need to identify novel biomarkers that could be used to reduce metastatic potential, and more importantly be targeted therapeutically. Previously, we showed that ionizing radiation-induced uPAR overexpression is associated with increased accumulation of β-catenin in the nucleus. We further demonstrated that uPAR protein act as cytoplasmic sequestration factor for a novel basic helix-loop-helix transcription factor, Hand1. Among the histological subtypes classical and desmoplastic subtypes account for the majority while large cell/anaplastic variant is most commonly associated with metastatic disease. In this present study using immunohistochemical approach and patient data mining for the first time, we demonstrated that Hand1 expression is observed to be downregulated in all the subtypes of medulloblastoma. Previously we showed that Hand1 overexpression regulated medulloblastoma angiogenesis and here we investigated the role of Hand1 in the context of Epithelial-Mesenchymal Transition (EMT). Moreover, UW228 and D283 cells overexpressing Hand1 demonstrated decreased-expression of mesenchymal markers (N-cadherin, β-catenin and SOX2); metastatic marker (SMA); and increased expression of epithelial marker (E-cadherin). Strikingly, human pluripotent stem cell antibody array showed that Hand1 overexpression resulted in substantial decrease in pluripotency markers (Nanog, Oct3/4, Otx2, Flk1) suggesting that Hand1 expression may be essential to attenuate the EMT and our findings underscore a novel role for Hand1 in medulloblastoma metastasis. - Highlights: • Hand1 expression is downregulated in Medulloblastoma. • Hand1 over expression reduce

  4. Orbital metastasis of endocervical stromal sarcoma: a rare tumor and an uncommon metastasis.

    PubMed

    Seker, Mehmet Metin; Uslu, Ali Ugur; Ozer, Hatice; Seker, Ayse; Kacan, Turgut; Babacan, Nalan; Aker, Handan; Elagoz, Sahande

    2014-12-01

    Endocervical stromal sarcoma (ECSS) is a very rare uterine sarcoma. The most common presentation is pelvic mass and vaginal bleeding. The mainstay of treatment is surgery. There is no consensus on the adjuvant treatment. Relapses are usually in the pelvic and abdominal regions. To a lesser extent, lung, liver and bone metastases may be seen. A 46-year-old woman had total abdominal hysterectomy (TAH) with bilateral salpingo-oophorectomy (BSO) performed due to endometrial polyp and leiomyoma. Six months after the TAH-BSO, she was admitted to the hospital with cough and hemoptysis. A thoracic mass was detected, and a biopsy was done. The diagnosis was low-grade ECSS metastasis. One week after thoracotomy, she was admitted to the hospital with loss of vision in the left eye. An orbital mass was detected with magnetic resonance imaging. Endometrial and cervical pathology preparations were reassessed and were compatible with ECSS. We performed mammography, thorax, and abdomen and cranial imaging to rule out other malignancies that may cause lung and orbital metastasis. Partial remission was achieved with systemic chemotherapy and orbital radiotherapy. Orbital metastasis may be seen in ECSS patients. Although we have less knowledge about the choice of chemotherapeutic agents, ifosfamide and doxorubicin are effective in treating ECSS.

  5. Orbital metastasis of endocervical stromal sarcoma: a rare tumor and an uncommon metastasis

    PubMed Central

    Uslu, Ali Ugur; Ozer, Hatice; Seker, Ayse; Kacan, Turgut; Babacan, Nalan; Aker, Handan; Elagoz, Sahande

    2014-01-01

    Endocervical stromal sarcoma (ECSS) is a very rare uterine sarcoma. The most common presentation is pelvic mass and vaginal bleeding. The mainstay of treatment is surgery. There is no consensus on the adjuvant treatment. Relapses are usually in the pelvic and abdominal regions. To a lesser extent, lung, liver and bone metastases may be seen. A 46-year-old woman had total abdominal hysterectomy (TAH) with bilateral salpingo-oophorectomy (BSO) performed due to endometrial polyp and leiomyoma. Six months after the TAH-BSO, she was admitted to the hospital with cough and hemoptysis. A thoracic mass was detected, and a biopsy was done. The diagnosis was low-grade ECSS metastasis. One week after thoracotomy, she was admitted to the hospital with loss of vision in the left eye. An orbital mass was detected with magnetic resonance imaging. Endometrial and cervical pathology preparations were reassessed and were compatible with ECSS. We performed mammography, thorax, and abdomen and cranial imaging to rule out other malignancies that may cause lung and orbital metastasis. Partial remission was achieved with systemic chemotherapy and orbital radiotherapy. Orbital metastasis may be seen in ECSS patients. Although we have less knowledge about the choice of chemotherapeutic agents, ifosfamide and doxorubicin are effective in treating ECSS. PMID:26327880

  6. Brain tumor imaging: imaging brain metastasis using a brain-metastasizing breast adenocarcinoma.

    PubMed

    Madden, Kelley S; Zettel, Martha L; Majewska, Ania K; Brown, Edward B

    2013-03-01

    Brain metastases from primary or secondary breast tumors are difficult to model in the mouse. When metastatic breast cancer cell lines are injected directly into the arterial circulation, only a small fraction of cells enter the brain to form metastatic foci. To study the molecular and cellular mechanisms of brain metastasis, we have transfected MB-231BR, a brain-homing derivative of a human breast adenocarcinoma line MDA-MB-231, with the yellow fluorescent protein (YFP) variant Venus. MB-231BR selectively enters the brain after intracardiac injection into the arterial circulation, resulting in accumulation of fluorescent foci of cells in the brain that can be viewed by standard fluorescence imaging procedures. We describe how to perform the intracardiac injection and the parameters used to quantify brain metastasis in brain sections by standard one-photon fluorescence imaging. The disadvantage of this model is that the kinetics of growth over time cannot be determined in the same animal. In addition, the injection technique does not permit precise placement of tumor cells within the brain. This model is useful for determining the molecular determinants of brain tumor metastasis.

  7. Support vector machine model for diagnosis of lymph node metastasis in gastric cancer with multidetector computed tomography: a preliminary study

    PubMed Central

    2011-01-01

    Background Lymph node metastasis (LNM) of gastric cancer is an important prognostic factor regarding long-term survival. But several imaging techniques which are commonly used in stomach cannot satisfactorily assess the gastric cancer lymph node status. They can not achieve both high sensitivity and specificity. As a kind of machine-learning methods, Support Vector Machine has the potential to solve this complex issue. Methods The institutional review board approved this retrospective study. 175 consecutive patients with gastric cancer who underwent MDCT before surgery were included. We evaluated the tumor and lymph node indicators on CT images including serosal invasion, tumor classification, tumor maximum diameter, number of lymph nodes, maximum lymph node size and lymph nodes station, which reflected the biological behavior of gastric cancer. Univariate analysis was used to analyze the relationship between the six image indicators with LNM. A SVM model was built with these indicators above as input index. The output index was that lymph node metastasis of the patient was positive or negative. It was confirmed by the surgery and histopathology. A standard machine-learning technique called k-fold cross-validation (5-fold in our study) was used to train and test SVM models. We evaluated the diagnostic capability of the SVM models in lymph node metastasis with the receiver operating characteristic (ROC) curves. And the radiologist classified the lymph node metastasis of patients by using maximum lymph node size on CT images as criterion. We compared the areas under ROC curves (AUC) of the radiologist and SVM models. Results In 175 cases, the cases of lymph node metastasis were 134 and 41 cases were not. The six image indicators all had statistically significant differences between the LNM negative and positive groups. The means of the sensitivity, specificity and AUC of SVM models with 5-fold cross-validation were 88.5%, 78.5% and 0.876, respectively. While the

  8. Golden Sections

    ERIC Educational Resources Information Center

    Stuart, Stephen N.

    2006-01-01

    In this article, the author states that architects, musicians and other thoughtful people have, since the time of Pythagoras, been fascinated by various harmonious proportions. One, is the visual harmony attributed to Euclid, called "the golden section". He explores this concept in geometries of one, two and three dimensions. He added, that in…

  9. miR-135b Stimulates Osteosarcoma Recurrence and Lung Metastasis via Notch and Wnt/β-Catenin Signaling.

    PubMed

    Jin, Hua; Luo, Song; Wang, Yun; Liu, Chang; Piao, Zhenghao; Xu, Meng; Guan, Wei; Li, Qing; Zou, Hua; Tan, Qun-You; Yang, Zhen-Zhou; Wang, Yan; Wang, Dong; Xu, Cheng-Xiong

    2017-09-15

    Cancer stem cells (CSCs) play an important role in osteosarcoma (OS) metastasis and recurrence, and both Wnt/β-catenin and Notch signaling are essential for the development of the biological traits of CSCs. However, the mechanism that underlies the simultaneous hyperactivation of both Wnt/β-catenin and Notch signaling in OS remains unclear. Here, we report that expression of miR-135b correlates with the overall and recurrence-free survival of OS patients, and that miR-135b has an activating effect on both Wnt/β-catenin and Notch signaling. The overexpression of miR-135b simultaneously targets multiple negative regulators of the Wnt/β-catenin and Notch signaling pathways, including glycogen synthase kinase-3 beta (GSK3β), casein kinase 1a (CK1α), and ten-eleven translocation 3 (TET3). Therefore, upregulated miR-135b promotes CSC traits, lung metastasis, and tumor recurrence in OS. Notably, antagonizing miR-135b potently inhibits OS lung metastasis, cancer cell stemness, CSC-induced tumor formation, and recurrence in xenograft animal models. These findings suggest that miR-135b mediates the constitutive activation of Wnt/β-catenin and Notch signaling, and that the inhibition of miR-135b is a novel strategy to inhibit tumor metastasis and prevent CSC-induced recurrence in OS. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  10. An approach for the identification of targets specific to bone metastasis using cancer genes interactome and gene ontology analysis.

    PubMed

    Vashisht, Shikha; Bagler, Ganesh

    2012-01-01

    Metastasis is one of the most enigmatic aspects of cancer pathogenesis and is a major cause of cancer-associated mortality. Secondary bone cancer (SBC) is a complex disease caused by metastasis of tumor cells from their primary site and is characterized by intricate interplay of molecular interactions. Identification of targets for multifactorial diseases such as SBC, the most frequent complication of breast and prostate cancers, is a challenge. Towards achieving our aim of identification of targets specific to SBC, we constructed a 'Cancer Genes Network', a representative protein interactome of cancer genes. Using graph theoretical methods, we obtained a set of key genes that are relevant for generic mechanisms of cancers and have a role in biological essentiality. We also compiled a curated dataset of 391 SBC genes from published literature which serves as a basis of ontological correlates of secondary bone cancer. Building on these results, we implement a strategy based on generic cancer genes, SBC genes and gene ontology enrichment method, to obtain a set of targets that are specific to bone metastasis. Through this study, we present an approach for probing one of the major complications in cancers, namely, metastasis. The results on genes that play generic roles in cancer phenotype, obtained by network analysis of 'Cancer Genes Network', have broader implications in understanding the role of molecular regulators in mechanisms of cancers. Specifically, our study provides a set of potential targets that are of ontological and regulatory relevance to secondary bone cancer.

  11. [The highly expressed secreted phosphoprotein 1 gene in prostate cancer metastasis: a microarray-based bioinformatic analysis].

    PubMed

    Li, Tie-qiu; Teng, Yi-li; Zou, Ya-guang; Yang, Yu; Li, Qi; Mao, Xiang-ming

    2014-11-01

    To investigate the composition, function, and regulatory mechanisms of the secreted phosphoprotein 1 (SPP1) gene in metastatic prostate cancer. We obtained the data about the whole genomic expression profiles on prostate cancer metastasis from the GEO database, and performed data-mining and bioinformatic analysis using BRB-Array Tools and such softwares as Protparam, MotifScan, SignalP 4.0, TMHMM, NetPhos2.0, PredictProtein, GO, KEGG, and STRING. Totally, 73 co-expressed differential genes in prostate cancer metastasis were identified, 21 up-regulated and 52 down-regulated (P <0.01). Bioinformatic analysis indicated that the highly expressed SPP1 gene encoded 314 amino acids and contained 2 N-glycosylation sites, 8 casein kinase II phosphorylation sites and 3 protein kinase C phosphorylation sites, playing essential roles in extracellular matrix (ECM) binding, ossification, osteoblast differentiation, cell adhesion, PI3K-Akt signaling pathway, focal adhesion, Toll-like receptor signaling pathway, and ECM-receptor interaction. The bioinformatic method showed a high efficiency in analyzing microarray data and revealing internal biological information. SPP1 may play an important role in prostate cancer metastasis and become a novel biomarker for the diagnosis of prostate cancer metastasis and a new target for its treatment.

  12. Phosphatase of regenerating liver-3 (PRL-3) is associated with metastasis and poor prognosis in gastric carcinoma

    PubMed Central

    2013-01-01

    Background PRL-3 is a member of phosphatases of regenerating liver family, characterized by phosphatase active domain and C-terminal prenylation motif. Overexpression of PRL-3 has been implicated in multiple cancers. Here we examined the clinical significance of PRL-3 in gastric cancer together with its metastatic biological functions utilizing different structural mutants. Methods PRL-3 expression was analyzed immunohistochemically in 196 gastric cancer patients and 21 cases of liver metastasis. A series of wild type PRL-3 or its mutant plasmids were expressed in BGC823 cells to investigate the relationship between its catalytic activity, cellular localization and metastatic potential in vitro. Results Positive staining of PRL-3 was observed in 19.4% (38/196) gastric cancer tissues compared with 76.2% (16/21) in liver metastasis. Statistical analysis revealed that PRL-3 expression correlated with lymph node metastasis and vascular invasion (P < 0.05). Patients with high PRL-3 expression showed poorer 5-year overall survival (P = 0.011). Wild type PRL-3 expressing cells resulted in enhanced migration and invasion ability, which were greatly crippled in form of PRL-3(C104S) or PRL-3(ΔCAAX) mutants accompanied with its alteration in subcellular localization. Conclusions Metastasis associated protein PRL-3 may serve as a potential prognostic biomarker in human gastric cancer. Both the phosphatase catalytic activity and cellular localization are critical for its function. PMID:24330843

  13. An Approach for the Identification of Targets Specific to Bone Metastasis Using Cancer Genes Interactome and Gene Ontology Analysis

    PubMed Central

    Vashisht, Shikha; Bagler, Ganesh

    2012-01-01

    Metastasis is one of the most enigmatic aspects of cancer pathogenesis and is a major cause of cancer-associated mortality. Secondary bone cancer (SBC) is a complex disease caused by metastasis of tumor cells from their primary site and is characterized by intricate interplay of molecular interactions. Identification of targets for multifactorial diseases such as SBC, the most frequent complication of breast and prostate cancers, is a challenge. Towards achieving our aim of identification of targets specific to SBC, we constructed a ‘Cancer Genes Network’, a representative protein interactome of cancer genes. Using graph theoretical methods, we obtained a set of key genes that are relevant for generic mechanisms of cancers and have a role in biological essentiality. We also compiled a curated dataset of 391 SBC genes from published literature which serves as a basis of ontological correlates of secondary bone cancer. Building on these results, we implement a strategy based on generic cancer genes, SBC genes and gene ontology enrichment method, to obtain a set of targets that are specific to bone metastasis. Through this study, we present an approach for probing one of the major complications in cancers, namely, metastasis. The results on genes that play generic roles in cancer phenotype, obtained by network analysis of ‘Cancer Genes Network’, have broader implications in understanding the role of molecular regulators in mechanisms of cancers. Specifically, our study provides a set of potential targets that are of ontological and regulatory relevance to secondary bone cancer. PMID:23166660

  14. Early versus late distant metastasis and adjuvant chemotherapy alone versus both radiotherapy and chemotherapy in molecular apocrine breast cancer.

    PubMed

    Liu, Xiaozhen; Yang, Yang; Feng, Xiaolong; Shen, Honghong; Liu, Jian; Liu, Xia; Niu, Yun

    2016-08-02

    As a new subtype of breast cancer, molecular apocrine breast cancer (MABC) is estrogen receptor (ER) and progesterone receptor (PR) negative expression, but androgen receptor (AR) positive expression. The prognostic significance and clinical biological behavior of MABC have remained unclear up to now. This study aimed to analysis the distant metastasis behavior and response to adjuvant radiotherapy and chemotherapy of MABC subgroup. The report showed that there were significant differences between early and late distant metastasizing tumors with respect to Ki67, epidermal growth factor receptor 2 (HER2) and vascular endothelial growth factor (VEGF) expressions by a retrospective analysis consisting of 410 invasive breast cancer patients, which included 205 MABC and 205 nonMABC cases. MABC subgroup metastasized earlier than nonMABC subgroup, and MABC showed a tendency for a higher metastasis rate in lung, liver and brain, but lower in bone. HER2-positive or VEGF-positive tumors were more inclined to develop bone metastasis within MABC subgroup. The survival rate was superior for patients undergone both adjuvant radiotherapy and chemotherapy than those undergone chemotherapy alone in nonMABC subgroup, but there was no significant difference in MABC subgroup. Our data suggested that MABC subgroup seemed to develop distant metastasis earlier than nonMABC subgroup, and patients with MABC indicated poor prognosis. This study might also provide a foundation for helping patients receive reasonable treatments according to molecular subtype.

  15. Early versus late distant metastasis and adjuvant chemotherapy alone versus both radiotherapy and chemotherapy in molecular apocrine breast cancer

    PubMed Central

    Liu, Xiaozhen; Yang, Yang; Feng, Xiaolong; Shen, Honghong; Liu, Jian; Liu, Xia; Niu, Yun

    2016-01-01

    As a new subtype of breast cancer, molecular apocrine breast cancer (MABC) is estrogen receptor (ER) and progesterone receptor (PR) negative expression, but androgen receptor (AR) positive expression. The prognostic significance and clinical biological behavior of MABC have remained unclear up to now. This study aimed to analysis the distant metastasis behavior and response to adjuvant radiotherapy and chemotherapy of MABC subgroup. The report showed that there were significant differences between early and late distant metastasizing tumors with respect to Ki67, epidermal growth factor receptor 2 (HER2) and vascular endothelial growth factor (VEGF) expressions by a retrospective analysis consisting of 410 invasive breast cancer patients, which included 205 MABC and 205 nonMABC cases. MABC subgroup metastasized earlier than nonMABC subgroup, and MABC showed a tendency for a higher metastasis rate in lung, liver and brain, but lower in bone. HER2-positive or VEGF-positive tumors were more inclined to develop bone metastasis within MABC subgroup. The survival rate was superior for patients undergone both adjuvant radiotherapy and chemotherapy than those undergone chemotherapy alone in nonMABC subgroup, but there was no significant difference in MABC subgroup. Our data suggested that MABC subgroup seemed to develop distant metastasis earlier than nonMABC subgroup, and patients with MABC indicated poor prognosis. This study might also provide a foundation for helping patients receive reasonable treatments according to molecular subtype. PMID:27340922

  16. Reduced adenosine-to-inosine miR-455-5p editing promotes melanoma growth and metastasis.

    PubMed

    Shoshan, Einav; Mobley, Aaron K; Braeuer, Russell R; Kamiya, Takafumi; Huang, Li; Vasquez, Mayra E; Salameh, Ahmad; Lee, Ho Jeong; Kim, Sun Jin; Ivan, Cristina; Velazquez-Torres, Guermarie; Nip, Ka Ming; Zhu, Kelsey; Brooks, Denise; Jones, Steven J M; Birol, Inanc; Mosqueda, Maribel; Wen, Yu-ye; Eterovic, Agda Karina; Sood, Anil K; Hwu, Patrick; Gershenwald, Jeffrey E; Robertson, A Gordon; Calin, George A; Markel, Gal; Fidler, Isaiah J; Bar-Eli, Menashe

    2015-03-01

    Although recent studies have shown that adenosine-to-inosine (A-to-I) RNA editing occurs in microRNAs (miRNAs), its effects on tumour growth and metastasis are not well understood. We present evidence of CREB-mediated low expression of ADAR1 in metastatic melanoma cell lines and tumour specimens. Re-expression of ADAR1 resulted in the suppression of melanoma growth and metastasis in vivo. Consequently, we identified three miRNAs undergoing A-to-I editing in the weakly metastatic melanoma but not in strongly metastatic cell lines. One of these miRNAs, miR-455-5p, has two A-to-I RNA-editing sites. The biological function of edited miR-455-5p is different from that of the unedited form, as it recognizes a different set of genes. Indeed, wild-type miR-455-5p promotes melanoma metastasis through inhibition of the tumour suppressor gene CPEB1. Moreover, wild-type miR-455 enhances melanoma growth and metastasis in vivo, whereas the edited form inhibits these features. These results demonstrate a previously unrecognized role for RNA editing in melanoma progression.

  17. Metastasis of osteosarcoma to the trapezius muscle: a case report.

    PubMed

    Sakamoto, Yuichiro; Yokouchi, Masahiro; Nagano, Satoshi; Shimada, Hirofumi; Nakamura, Shunsuke; Setoguchi, Takao; Kawamura, Ichiro; Ishidou, Yasuhiro; Tanimoto, Akihide; Komiya, Setsuro

    2014-06-04

    Metastasis of a primary osteosarcoma to the muscles is extremely rare. As there have been few reported cases, the necessity of surgical treatment for such metastatic lesions remains controversial. We present the case of a primary osteosarcoma with development of a solitary metastasis to the trapezius muscle during chemotherapy for pulmonary metastasis. The patient was a 51-year-old man diagnosed with osteosarcoma of the right tibia. After undergoing chemotherapy and femoral amputation, he developed pulmonary metastasis. Chemotherapy was reinitiated, however, after approximately 1 year a palpable tumor was identified in the patient's right shoulder. This tumor grew and was associated with pain in the right shoulder. It was surgically removed 3 years after the re-initiation of chemotherapy. The pathological diagnosis was osteosarcoma with metastasis to the trapezius muscle. Although the patient died of respiratory failure due to pulmonary metastasis 14 months after resection of the metastatic lesion in the trapezius muscle, no new extrapulmonary metastasis was observed after the resection.

  18. NRF2 activation by antioxidant antidiabetic agents accelerates tumor metastasis.

    PubMed

    Wang, Hui; Liu, Xiufei; Long, Min; Huang, Yi; Zhang, Linlin; Zhang, Rui; Zheng, Yi; Liao, Xiaoyu; Wang, Yuren; Liao, Qian; Li, Wenjie; Tang, Zili; Tong, Qiang; Wang, Xiaocui; Fang, Fang; Rojo de la Vega, Montserrat; Ouyang, Qin; Zhang, Donna D; Yu, Shicang; Zheng, Hongting

    2016-04-13

    Cancer is a common comorbidity of diabetic patients; however, little is known about the effects that antidiabetic drugs have on tumors. We discovered that common classes of drugs used in type 2 diabetes mellitus, the hypoglycemic dipeptidyl peptidase-4 inhibitors (DPP-4i) saxagliptin and sitagliptin, as well as the antineuropathic α-lipoic acid (ALA), do not increase tumor incidence but increase the risk of metastasis of existing tumors. Specifically, these drugs induce prolonged activation of the nuclear factor E2-related factor 2 (NRF2)-mediated antioxidant response through inhibition of KEAP1-C151-dependent ubiquitination and subsequent degradation of NRF2, resulting in up-regulated expression of metastasis-associated proteins, increased cancer cell migration, and promotion of metastasis in xenograft mouse models. Accordingly, knockdown of NRF2 attenuated naturally occurring and DPP-4i-induced tumor metastasis, whereas NRF2 activation accelerated metastasis. Furthermore, in human liver cancer tissue samples, increased NRF2 expression correlated with metastasis. Our findings suggest that antioxidants that activate NRF2 signaling may need to be administered with caution in cancer patients, such as diabetic patients with cancer. Moreover, NRF2 may be a potential biomarker and therapeutic target for tumor metastasis.

  19. Reduced ING1 levels in breast cancer promotes metastasis

    PubMed Central

    Chen, Jie; Tran, Uyen; Yang, Yang; Salazar, Carolina; Magliocco, Anthony; Klimowicz, Alexander; Jirik, Frank R.; Riabowol, Karl

    2014-01-01

    INhibitor of Growth 1 (ING1) expression is repressed in breast carcinomas, but its role in breast cancer development and metastasis is unknown. ING1 levels were quantified in >500 patient samples using automated quantitative fluorescence immunohistochemistry, and data were analysed for correlations to patient outcome. Effects of altering ING levels were examined in microarrays and metastasis assays in vitro, and in a mouse metastasis model in vivo. ING1 levels were lower in tumors compared to adjacent normal breast tissue and correlated with tumor size (p=0.019) and distant recurrence (p=0.001) in ER- or Her2+ patients. In these patients ING1 predicted disease-specific and distant metastasis-free survival. Transcriptome analysis showed that the pathway most affected by ING1 was breast cancer (p = 0.0008). Decreasing levels of ING1 increased, and increasing levels decreased, migration and invasion of MDA-MB231 cells in vitro. ING1 overexpression also blocked cancer cell metastasis in vivo and eliminated tumor-induced mortality in mouse models. Our data show that ING1 protein levels are downregulated in breast cancer and for the first time, we show that altering their levels regulates metastasis in vitro and in vivo, which indicates that ING1 may have a therapeutic role for inhibiting metastasis of breast cancer. PMID:24962136

  20. Encouraging Student Biological Research.

    ERIC Educational Resources Information Center

    Frame, Kathy, Ed.; Hays, Rachel, Ed.; Mack, Alison, Ed.

    This publication encourages student involvement in biological research through student research with the cooperation of teachers and scientists. The contents of the book are divided into two sections. The first section introduces students to research investigations and includes: (1) "How the Investigations Are Set Up and the Rationale Behind…

  1. Creative Biology Teaching.

    ERIC Educational Resources Information Center

    Harding, Delma E.; And Others

    The first section of this book discusses modern approaches to teaching biology, including theoretical approaches (such as "teaching form and function together") and the use of educational technology. The second part gives guidelines for planning and stocking science centers and laboratories. The third section deals with the use of materials: use…

  2. Encouraging Student Biological Research.

    ERIC Educational Resources Information Center

    Frame, Kathy, Ed.; Hays, Rachel, Ed.; Mack, Alison, Ed.

    This publication encourages student involvement in biological research through student research with the cooperation of teachers and scientists. The contents of the book are divided into two sections. The first section introduces students to research investigations and includes: (1) "How the Investigations Are Set Up and the Rationale Behind…

  3. Cutaneous metastasis revealing a relapse of gastric linitis: Another case

    PubMed Central

    Kairouani, Mouna; Perrin, Julie; Dietemann-Barabinot, Anne; Diab, Rafiq; Ruck, Stephane

    2012-01-01

    INTRODUCTION Cutaneous metastasis from gastric cancer is a rare occurrence. The linitis gastric carcinoma accounts only 8.7% of all gastric cancers. PRESENTATION OF CASE We report a case of female patient who was followed for linits cancer with peritoneal metastasis treated by six cycles of chemotherapy. After seventeen months of control, the relapse of the disease revealed by occurrence of cutaneous metastatsis. DISCUSSION Cutaneous metastasis from linit gastric is rare and the prognostic remains poor. The treatment is palliative. CONCLUSION This rare presentation should encourage the practitioners to biopsy any suspicion skin lesion. PMID:23276763

  4. Cutaneous metastasis revealing a relapse of gastric linitis: Another case.

    PubMed

    Kairouani, Mouna; Perrin, Julie; Dietemann-Barabinot, Anne; Diab, Rafiq; Ruck, Stephane

    2013-01-01

    Cutaneous metastasis from gastric cancer is a rare occurrence. The linitis gastric carcinoma accounts only 8.7% of all gastric cancers. We report a case of female patient who was followed for linits cancer with peritoneal metastasis treated by six cycles of chemotherapy. After seventeen months of control, the relapse of the disease revealed by occurrence of cutaneous metastatsis. Cutaneous metastasis from linit gastric is rare and the prognostic remains poor. The treatment is palliative. This rare presentation should encourage the practitioners to biopsy any suspicion skin lesion. Copyright © 2012 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

  5. Tumorigenesis and spontaneous metastasis by luciferase-labeled human xenograft osteosarcoma cells in nude mice.

    PubMed

    Du, Lin; Xu, Wen-ting; Fan, Qi-ming; Tu, Bing; Shen, Yang; Yan, Wei; Tang, Ting-ting; Wang, You

    2012-11-01

    Osteosarcoma (OS) is the most common primary malignant tumor of bone. Mouse models of human OS can invariably provide greater insight into the complex mechanisms that underlie the development and pathogenesis of this aggressive tumor. Bioluminescence technology favored tracing cancer cells in vivo. In this study, an OS model was described and evaluated using human OS cell line, Saos2, labeled with luciferase (Saos2-luc). Saos2 cells were infected by lentivirus loading a firefly luciferase gene. Luciferase expression of Saos2-luc cells was characterized both in vitro and in vivo. Specific biologic and oncologic features of Saos2-luc cells were analyzed. The OS was established as orthotopic xenografts in nude mice. Both orthotopic tumors and spontaneous lung metastasis were analyzed. Tumorigenesis and spontaneous lung metastasis in nude mice could be monitored in vivo through in vivo imaging system. The enhancement in proliferation, migration and invasion abilities and the attenuation in adhesion ability were observed in Saos2-luc cells compared with Saos2 cells. Furthermore, there were the up-regulation of Osteocalcin, CCR10, CXCR1 and ID1 and the down-regulation of ALP, collagen I, CCR1, CCR3, CXCR3, NID and N-cadherin in Saos2-luc cells compare to Saos2 cells. The rate of spontaneous lung metastasis in Saos2-luc cells was higher than that in Saos2 cells, although without significant difference. Lentivirus transfection may cause alteration of gene expression profiles and further biological functions. This model can be used in the elucidation of molecular mechanisms of tumorigenesis and the screening of new therapeutic agents.

  6. Overexpression of DNA repair genes is associated with metastasis: a new hypothesis.

    PubMed

    Sarasin, Alain; Kauffmann, Audrey

    2008-01-01

    Tumorigenesis is a multistep process, where it is believed that the transformation of normal cells into tumoral cells needs a succession of genetic and epigenetic changes, such as point mutations, chromosomal rearrangements, and changes in gene expression level. All these modifications are supposed to confer a selective advantage and to generate highly malignant cancer cells. Until recently, the same selection procedure of rare cells in the tumour mass was believed to be necessary for the metastatic process. Using gene expression profiling, several recent publications report that a gene expression signature could discriminate between primary tumours with high metastatic potentiality and poor clinical outcome, and primary tumours that are not going to metastasize. Analysis of the biological pathways associated with metastatic potential points to cell adhesion, angiogenesis, cell cycle regulation, initiation of DNA synthesis, and DNA repair. Analysing human primary malignant melanoma and various biological processes, we have shown that the overexpression of DNA repair pathways, particularly those involved in double-stand break repair and surveillance of the DNA replication forks, is associated with metastasis and poor patient survival [V. Winnepenninckx, V. Lazar, S. Michiels, P. Dessen, M. Stas, S.R. Alonso, M.F. Avril, P.L. Ortiz Romero, T. Robert, O. Balacescu, A.M. Eggermont, G. Lenoir, A. Sarasin, T. Tursz, J.J. van den Oord, A. Spatz, Gene expression profiling of primary cutaneous melanoma and clinical outcome, J. Natl. Cancer Inst. 98 (2006) 472-482]. These results, also found by analysing other types of human tumours, such as breast or bladder cancers, would clearly explain the high resistance of metastasis towards chemo- and radiotherapies. Our hypothesis is that genetic instability is absolutely necessary to go from normal cells to tumoral cells, but one needs some type of genetic stabilization, which can be obtained by overexpressing specific DNA repair

  7. All biology is computational biology.

    PubMed

    Markowetz, Florian

    2017-03-01

    Here, I argue that computational thinking and techniques are so central to the quest of understanding life that today all biology is computational biology. Computational biology brings order into our understanding of life, it makes biological concepts rigorous and testable, and it provides a reference map that holds together individual insights. The next modern synthesis in biology will be driven by mathematical, statistical, and computational methods being absorbed into mainstream biological training, turning biology into a quantitative science.

  8. All biology is computational biology

    PubMed Central

    2017-01-01

    Here, I argue that computational thinking and techniques are so central to the quest of understanding life that today all biology is computational biology. Computational biology brings order into our understanding of life, it makes biological concepts rigorous and testable, and it provides a reference map that holds together individual insights. The next modern synthesis in biology will be driven by mathematical, statistical, and computational methods being absorbed into mainstream biological training, turning biology into a quantitative science. PMID:28278152

  9. [Value of jugulo-omohyoid lymph nodes in predicting lateral cervical occult metastasis in patients with papillary thyroid carcinoma].

    PubMed

    An, C M; Wang, Y; Wang, S X; Yin, Y L; Chen, M Q; Xu, Z G; Tang, P Z; Li, Z J

    2017-03-23

    Objective: To investigate the value of jugulo-omohyoid lymph nodes (JOHLN) in predicting occult lateral cervical lymph node metastasis in patients with papillary thyroid carcinoma (PTC). Methods: The clinicopathological data of 136 out of 2 100 PTC patients, who had a high risk of lateral neck lymph node metastasis and treated by us from January 2010 to December 2015, were retrospectively analyzed. Super selective neck dissection (SSND, level Ⅲ and Ⅳ)was performed and JOHLNs were sent for frozen section in all the 136 cases. The clinicopathological data was analyzed and the significance of JOHLN in predicting lateral cervical LNM was calculated using the SPSS software package. Results: Of the 136 patients, total thyroidectomy was performed in 76 cases (55.9%) and unilateral lobectomy plus isthmus was performed in the other 60 cases (44.1%). SSND was performed in 72 patients (52.9%), level Ⅱ-Ⅳ dissection in 15 (11.0%), and level Ⅱ-Ⅴ dissection in 49 (36.0%). According to the pathological results, 38 patients were pN0(27.9%), 18 (13.2%) were pN1a and 80 (58.8%) were pN1b. The lymph node metastasis(LNM) rates at level Ⅱ-Ⅵ were 19.9%, 43.4%, 42.6%, 2.9%, and 59.6%, respectively. The sensitivity, specificity and accuracy of JOHLN in predicting lateral neck metastasis were 58.8%, 62.9%, and 76.7%, respectively. The rates for predicting level Ⅱ metastasis were 81.5%, 43.2%, and 59.4%, respectively. None of the patients died in the follow-up. Only 1 recurrence was found in level Ⅱ and regional control was achieved after level Ⅱ and Ⅴ dissection. Conclusions: JOHLN has a high accuracy for predicting lateral cervical lymph node metastasis and high sensitivity for level Ⅱ metastasis. For patients with high risk of lateral cervival metastasis, super-selective neck dissection including level Ⅲ and Ⅳ can confirm the stage and reduce the risk of reoperation. Dissection for level Ⅱ, Ⅲ, and Ⅳ is recommended.

  10. Oncostatin M Promotes Mammary Tumor Metastasis to Bone and Osteolytic Bone Degradation

    PubMed Central

    Bolin, Celeste; Tawara, Ken; Sutherland, Caleb; Redshaw, Jeff; Aranda, Patrick; Moselhy, Jim; Anderson, Robin

    2012-01-01

    Oncostatin M (OSM) is an interleukin-6 (IL-6) family cytokine that has been implicated in a number of biological processes including inflammation, hematopoiesis, immune responses, development, and bone homeostasis. Recent evidence suggests that OSM may promote breast tumor invasion and metastasis. We investigated the role of OSM in the formation of bone metastases in vivo using the 4T1.2 mouse mammary tumor model in which OSM expression was knocked down using shRNA (4T1.2-OSM). 4T1.2-OSM cells were injected orthotopically into Balb/c mice, resulting in a greater than 97% decrease in spontaneous metastasis to bone compared to control cells. Intratibial injection of these same 4T1.2-OSM cells also dramatically reduced the osteolytic destruction of trabecular bone volume compared to control cells. Furthermore, in a tumor resection model, mice bearing 4T1.2-OSM tumors showed an increase in survival by a median of 10 days. To investigate the specific cellular mechanisms important for OSM-induced osteolytic metastasis to bone, an in vitro model was developed using the RAW 264.7 preosteoclast cell line co-cultured with 4T1.2 mouse mammary tumor cells. Treatment of co-cultures with OSM resulted in a 3-fold induction of osteoclastogenesis using the TRAP assay. We identified several tumor cell–induced factors including vascular endothelial growth factor, IL-6, and a previously uncharacterized OSM-regulated bone metastasis factor, amphiregulin (AREG), which increased osteoclast differentiation by 4.5-fold. In addition, pretreatment of co-cultures with an anti-AREG neutralizing antibody completely reversed OSM-induced osteoclastogenesis. Our results suggest that one mechanism for OSM-induced osteoclast differentiation is via an AREG autocrine loop, resulting in decreased osteoprotegerin secretion by the 4T1.2 cells. These data provide evidence that OSM might be an important therapeutic target for the prevention of breast cancer metastasis to bone. PMID:23050044

  11. Breast metastasis from esophagogastric junction cancer: a case report.

    PubMed

    Jena, Sanghamitra; Bhattacharya, Samir; Gupta, Arnab; Roy, Shravasti; Sinha, Neetesh Kumar

    2014-01-01

    Metastasis to breast from nonmammary malignancy is only about 1.3-2.7%. A few cases of squamous cell carcinoma of esophagus and adenocarcinoma of stomach metastasizing to breast have been reported, but this is probably the first report of breast metastasis from esophagogastric junction (EGJ) cancer in the English literature. Herein we report a case of a 32-year-old patient diagnosed as adenocarcinoma of gastroesophageal junction, presenting with left breast metastasis two years after treatment. Given unusual site of metastasis in a follow-up case of EGJ cancer, not only it is challenging to differentiate it from primary carcinoma of breast but also it is important from treatment point of view. In our case, clinical data, radiology, histopathology, and immunohistochemistry (IHC) led us to reach the diagnosis.

  12. Hypoxia-inducible factor 1 and breast cancer metastasis*

    PubMed Central

    Liu, Zhao-ji; Semenza, Gregg L.; Zhang, Hua-feng

    2015-01-01

    Accumulating evidence has shown that the hypoxic microenvironment, which is critical during cancer development, plays a key role in regulating breast cancer progression and metastasis. The effects of hypoxia-inducible factor 1 (HIF-1), a master regulator of the hypoxic response, have been extensively studied during these processes. In this review, we focus on the roles of HIF-1 in regulating breast cancer cell metastasis, specifically its effects on multiple key steps of metastasis, such as epithelial-mesenchymal transition (EMT), invasion, extravasation, and metastatic niche formation. We also discuss the roles of HIF-1-regulated non-coding RNAs in breast cancer metastasis, and therapeutic opportunities for breast cancer through targeting the HIF-1 pathway. PMID:25559953

  13. Solitary skull metastasis as initial manifestation of hepatocellular carcinoma.

    PubMed

    Shim, Yu Shik; Ahn, Jung Yong; Cho, Jun Hyung; Lee, Kyu Sung

    2008-06-21

    A solitary skull metastasis from hepatocellular carcinoma (HCC) prior to diagnosis of the primary tumor without liver dysfunction is a very rare event. A 71-year-old male, without known liver disease, presented to our institution with a palpable occipital scalp mass. On brain magnetic resonance imaging (MRI), a highly enhanced and osteolytic skull tumor was observed. The histological diagnosis obtained from the percutaneous needle biopsy was a cranial metastasis from HCC. The metastatic tumor was removed via occipital craniectomy, and the two primary liver mass lesions were subsequently treated by transarterial chemoembolization. An isolated skull metastasis may be the sole initial presentation of HCC. Early diagnosis is essential in order to treat the primary disease. A skull metastasis from HCC should be considered in the differential diagnosis in patients with subcutaneous scalp mass and osteolytic defects on X-ray.

  14. Patrolling monocytes control tumor metastasis to the lung.

    PubMed

    Hanna, Richard N; Cekic, Caglar; Sag, Duygu; Tacke, Robert; Thomas, Graham D; Nowyhed, Heba; Herrley, Erica; Rasquinha, Nicole; McArdle, Sara; Wu, Runpei; Peluso, Esther; Metzger, Daniel; Ichinose, Hiroshi; Shaked, Iftach; Chodaczek, Grzegorz; Biswas, Subhra K; Hedrick, Catherine C

    2015-11-20

    The immune system plays an important role in regulating tumor growth and metastasis. Classical monocytes promote tumorigenesis and cancer metastasis, but how nonclassical "patrolling" monocytes (PMo) interact with tumors is unknown. Here we show that PMo are enriched in the microvasculature of the lung and reduce tumor metastasis to lung in multiple mouse metastatic tumor models. Nr4a1-deficient mice, which specifically lack PMo, showed increased lung metastasis in vivo. Transfer of Nr4a1-proficient PMo into Nr4a1-deficient mice prevented tumor invasion in the lung. PMo established early interactions with metastasizing tumor cells, scavenged tumor material from the lung vasculature, and promoted natural killer cell recruitment and activation. Thus, PMo contribute to cancer immunosurveillance and may be targets for cancer immunotherapy. Copyright © 2015, American Association for the Advancement of Science.

  15. Durable response of breast cancer leptomeningeal metastasis to capecitabine monotherapy

    PubMed Central

    Rogers, Lisa R.; Remer, Sandra E.; Tejwani, Sheela

    2004-01-01

    We report a durable (12-month) response to capecitabine monotherapy, shown clinically, by MRI, and by cerebrospinal fluid analysis, in a patient with leptomeningeal metastasis from breast cancer. PMID:14769142

  16. Malignant intraventricular meningioma with craniospinal dissemination and concurrent pulmonary metastasis

    PubMed Central

    2014-01-01

    Background Malignant intraventricular meningiomas are quite rare and may spread along the craniospinal axis or extraneurally. However, simultaneous cerebrospinal dissemination and distal extraneural metastasis has seldom been reported. Case presentation A 51-year-old woman presented with recurrent anaplastic meningioma in the trigone of right lateral ventricle over a 1.5-year period. Suggested radiotherapy was refused after each operation. The patient showed a local relapse and dissemination around the previous tumoral cavity and along the spinal canal during the last recurrence. Left pulmonary metastasis was also found. She died despite multiple lesion resections. Conclusions Malignant intraventricular meningiomas are an uncommon subset of intracranial meningiomas, and have a great potential for intraneural and extraneural metastasis. Systemic investigation for metastasis is required after surgery, especially for those without adjuvant therapies. PMID:25073808

  17. Patrolling Monocytes Control Tumor Metastasis to the Lung

    PubMed Central

    Hanna, Richard N.; Cekic, Caglar; Sag, Duygu; Tacke, Robert; Thomas, Graham D.; Nowyhed, Heba; Herrley, Erica; Rasquinha, Nicole; McArdle, Sara; Wu, Runpei; Peluso, Esther; Metzger, Daniel; Ichinose, Hiroshi; Shaked, Iftach; Chodaczek, Grzegorz; Biswas, Subhra K.; Hedrick, Catherine C.

    2016-01-01

    The immune system plays an important role in regulating tumor growth and metastasis. For example, classical monocytes promote tumorigenesis and cancer metastasis; however, how nonclassical “patrolling” monocytes interact with tumors is unknown. Here we show that patrolling monocytes are enriched in the microvasculature of the lung and reduce tumor metastasis to lung in multiple mouse metastatic tumor models. Nr4a1-deficient mice, which specifically lack patrolling monocytes, showed increased lung metastasis in vivo. Transfer of Nr4a1-proficient patrolling monocytes into Nr4a1-deficient mice prevented tumor invasion in lung. Patrolling monocytes established early interactions with metastasizing tumor cells, scavenged tumor material from the lung vasculature and promoted natural killer cell recruitment and activation. Thus, patrolling monocytes contribute to cancer immunosurveillance and may be targets for cancer immunotherapy. PMID:26494174

  18. Two cases of pancreatic ductal adenocarcinoma with intrapancreatic metastasis

    PubMed Central

    Fujita, Yusuke; Kitago, Minoru; Masugi, Yohei; Itano, Osamu; Shinoda, Masahiro; Abe, Yuta; Hibi, Taizo; Yagi, Hiroshi; Fujii-Nishimura, Yoko; Sakamoto, Michiie; Kitagawa, Yuko

    2016-01-01

    There are no standardized diagnostic criteria for intrapancreatic metastasis of pancreatic ductal adenocarcinoma (PDAC). Here, we report two cases of patients with PDAC who were pathologically diagnosed as harboring intrapancreatic metastasis. In both cases, the main lesions were located in the pancreatic body, and no other lesion was detected preoperatively. The patients were diagnosed with pancreatic body cancers and distal pancreatectomy was performed. Pathological findings revealed microscopic cancer nests, which had connections to neither the main lesion nor the premalignant lesion in the pancreatic tail parenchyma. In both cases, the histological type of the daughter lesion was quite similar to that of the main lesion. Hence, we diagnosed the daughter lesions as metastatic foci in the pancreas. Although intrapancreatic metastasis of PDAC has been regarded as a poor prognostic factor, few reports of intrapancreatic metastasis are available. This article reports two such cases and provides a review of the literature. PMID:27895409

  19. Imaging TGFβ Signaling in Mouse Models of Cancer Metastasis.

    PubMed

    Kang, Yibin

    2016-01-01

    Metastatic spread of cancer cells from the primary tumors to distant vital organs, such as lung, liver, brain, and bone, is responsible for the majority of cancer-related deaths. Development of metastatic lesions is critically dependent on the interaction of tumor cells with the stromal microenvironment. As a multifunctional paracrine signaling factor that is abundantly produced by both tumor and stromal cells, TGFβ has been well established as an important mediator of tumor-stromal interaction during cancer metastasis. Imaging the in vivo dynamic of TGFβ signaling activity during cancer metastasis is critical for understanding the pathogenesis of the disease, and for the development of effective anti-metastasis treatments. In this chapter, I describe several xenograft methods to introduce human breast cancer cells into nude mice in order to generate spontaneous and experimental metastases, as well as the luciferase-based bioluminescence imaging method for quantitative imaging analysis of TGFβ signaling in tumor cells during metastasis.

  20. Gastric Metastasis of Breast Cancer: A Case Series.

    PubMed

    Dos Santos Fernandes, Gustavo; Batista Bugiato Faria, Luiza D; de Assis Pereira, Isadora; Neves, Natália C Moreira; Vieira, Yasmine Oliveira; Leal, Alessandro I Cavalcanti

    2016-09-05

    Gastric metastasis is rare but it can be the initial symptom of cancer. The second leading cause of this type of metastasis is breast cancer. A lack of clinical signs and nonspecific side effects of the treatment of primary tumors can lead to the misdiagnosis of metastatic gastric cancer. Upper gastrointestinal endoscopy with biopsy and immunohistochemistry should be used for diagnosis. Treatment is palliative; it includes chemo, endocrine, and radiation therapies. Four patients with breast cancer and gastric metastasis were identified. All the patients tested positive for estrogen and progesterone receptors, and received chemotherapy and hormone therapy. One patient underwent surgery and two received radiation therapy. Patients with breast cancer and gastrointestinal symptoms should be investigated for gastric metastasis, given its morbidity and negative impact on quality of life.