WorldWideScience

Sample records for brain metastasis

  1. Brain metastasis from esophageal carcinoma

    Directory of Open Access Journals (Sweden)

    Almasi Saeid

    2004-10-01

    Full Text Available Brain metastasis from esophageal carcinoma is rare. In our center, among 301 cases of esophageal cancer referred for radiotherapy during a 14-year period, brain metastasis from esophageal carcinoma was detected in one case. An unusual case of esophageal carcinoma that presented with brain metastasis is reported.

  2. [Diagnosis and treatment of brain metastasis].

    Science.gov (United States)

    Sajama, Carlos; Lorenzoni, José; Tagle, Patricio

    2008-10-01

    Cerebral metastasis occur in 20 to 30 percent of patients with systemic cancer and are the most common type of intracranial tumor. The median survival of untreated patients is one month with a slightly longer survival in those treated with steroids. Patients treated with whole brain radiation therapy survive between 3 to 6 months. In selected cases survival can increase to 10 to 12 months with combination of surgery and radiotherapy or stereotactic radiosurgery alone or associated to radiotherapy. Most brain metastasis arise from lung, breast and melanomas. The most important criteria for selecting patients who will benefit from surgery or stereotactic radiosurgery are a Karnofsky score of 70 or more, systemic control of the cancer and absence of leptomeningeal involvement. Surgery is indicated in patients with a single lesion located in an accessible zone and stereotactic radiosurgery is indicated for lesions up to 3 cm of diameter, and in patients with up to 3 or 4 metastasis, no matter their location. The survival benefit of chemotherapy in brain metastasis has not been demonstrated.

  3. Computational systems biology in cancer brain metastasis.

    Science.gov (United States)

    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. Leptomeningeal metastasis after surgical resection of brain metastases

    NARCIS (Netherlands)

    T.C. van der Ree; D.W.J. Dippel (Diederik); C.J.J. Avezaat (Cees); C.J. Vecht; M.J. van den Bent (Martin); P.A.E. Sillevis Smitt (Peter)

    1999-01-01

    textabstractOBJECTIVE: To determine the incidence and risk factors for leptomeningeal metastasis after surgery for brain metastasis of solid tumors. METHODS: Review of the records of all patients operated on for brain metastasis between January 1990 and August 1995. RES

  5. Brain metastasis: new opportunities to tackle therapeutic resistance.

    Science.gov (United States)

    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.

  6. Heparanase Mechanisms in Melanoma Brain Metastasis

    Science.gov (United States)

    2015-10-01

    with HPSE- mediated cell signaling and actions, and ultimately affecting the modulation of BMM. Accordingly, this, by employing the pINDUCER lentiviral...found that HPSE plays important roles in mechanisms modulating BMM onset. A new molecular mechanism was also identified by which HPSE mediates an... mediated by enzymatically active heparanase. Our work has implicated heparanase as a promoter of brain metastasis since the enzyme is most active in cells

  7. Targeting Phosphatidylserine for Radioimmunotherapy of Breast Cancer Brain Metastasis

    Science.gov (United States)

    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

  8. Mixed adenoneuroendocrine carcinoma with brain metastasis

    Directory of Open Access Journals (Sweden)

    Xiao-ling YAN

    2015-05-01

    Full Text Available Objective To study clinicopathological features, diagnosis, differential diagnosis and prognosis of mixed adenoneuroendocrine carcinoma (MANEC.  Methods One case of MANEC with brain metastasis was reported focusing on the following aspects: clinical manifestations, histopathological features and immunophenotypes, and the relevant literatures were reviewed.  Results A 35-year-old male presented headache and vomiting, and his head CT scan showed a lesion located in the right temporal lobe. The tumor was detected after separating the cerebral cortex during the surgery. The tumor diameter was 3 cm. The tumor was soft and rubbery with ill-defined margins, and rich in blood supply. Under optical microscopy, the tumor was consisted of small round cells of the same size, with focal tumor cells arranged around blood vessels in a pseudorosette manner or papillary manner with brisk mitotic activity. The boundary between tumor and brain tissue was ill-defined. By using immunohistochemical staining, the tumor cells were diffusely positive for synaptophysin (Syn and CD56, and negative for glial fibrillary acidic protein (GFAP, pan cytokeratin (PCK, CD3, CD20, vimentin (Vim, leukocyte common antigen (LCA, thyroid transcription factor-1 (TTF-1, S-100 protein (S-100, neurofilament (NF, nestin (Nes, CK5/6, CK8/18 and CD99. Ki-67 labeling index was about 62%. Sigmoidoscopy was performed later in another hospital and showed a mass in the patient's colon. The colon tumor was biphasic in appearance, and was consisted of two distinct components: isomorphic small round cells and low-middle differentiated adenocarcinoma cells. The small round tumor cells were diffusely positive for Syn and CD56, and negative for PCK. The adenocarcinoma cells showed opposite results.  Conclusions MANEC is a rare tumor, which is defined in 2010 by WHO Classification of Digestive, and to the best of our knowledge, MANEC of the colon with brain metastasis has never been described

  9. Incidence of brain metastasis in patients with esophageal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Ron S Smith; Robert C Miller

    2011-01-01

    AIM: To determine the incidence of brain metastasis in a contemporary group of patients with carcinoma of the esophagus. METHODS: Retrospective analysis of 53 patients with esophageal carcinoma who received radiotherapy as a component of treatment between 1998 and 2007, including patient and tumor characteristics, and subsequent diagnosis of brain metastasis. The association between the histological type of esophageal cancer and the incidence of brain metastasis was assessed using Fisher's exact test. RESULTS: Forty-four of the fifty-three patients in this study had adenocarcinoma and nine had squamous cell carcinoma, ranging from stage ⅡA-ⅣB. Primary treatment was surgery with neoadjuvant chemoradiotherapy (trimodality therapy) in 19% of patients; chemoradiotherapy in 42%; and surgery and adjuvant radiotherapy in 7%. Twenty-five percent of patients in this study received palliative radiotherapy. The overall incidence of brain metastasis in this cohort was 13%. Adenocarcinoma was the primary tumor histology in all of the patients who developed brain metastasis, representing an incidence of 16% in this subgroup. No patients with squamous cell carcinoma received trimodality therapy. The association between histology and brain metastasis was not statistically significant. CONCLUSION: The incidence of brain metastasis in this contemporary cohort of patients with esophageal carcinoma is higher than previously reported and was confined to those with adenocarcinoma.

  10. Therapy for non-small-cell lung cancer patients with brain metastasis Therapy for non-small-cell lung cancer patients with brain metastasis

    Institute of Scientific and Technical Information of China (English)

    Bing Li; Yuchen Bao Co-first author; Bin Chen; Songwen Zhou

    2014-01-01

    Brain metastasis is a major cause of poor prognosis and high mortality for non-smal celllung cancer patients. The prognosis of non-smal-celllung cancer (NSCLC) patients with brain metastasis is generaly poor and more efective treatment is required to improve their prognosis. Whole-brain radiotherapy, surgery, stereotactic radiosurgery, chemotherapy and targeted therapy are the main treatment for brain metastasis. This review focuses on the five therapeutic strategy and in particular, on targeted therapy.

  11. BRAIN METASTASIS FROM HEPATOCELLULAR CARCINOMA: A RARE CASE

    Directory of Open Access Journals (Sweden)

    A. Kh. Bekyashev

    2012-01-01

    Full Text Available Hepatocellular carcinoma ranks 5th in prevalence and 3rd in cancer mortality worldwide. The prognosis of this disease is very poor: the 5-year survival rate was not more than 3–5%. Metastases generally occur in the lung, in the lymph nodes of the abdomen, chest, and neck, in the vertebrae, kidneys, and adrenals. The cases of brain metastasis from hepatocellular cancer are very rare. Overall, the prognosis is very poor for patients with brain metastases from hepatocellular carcinoma. Nevertheless, solitary brain metastases and good hepatic function are favorable survival criteria; thus, the treatment of this group of patients may lead to their better survival. The paper describes a clinical case of brain metastasis from hepatocellular carcinoma in a patient receiving the combination treatment involving neurosurgical treatment and targeted therapy. 

  12. Mechanisms of CTC Biomarkers in Breast Cancer Brain Metastasis

    Science.gov (United States)

    2015-10-01

    represents the most devastating and feared consequence of breast cancer . BCBM is usually fatal and is increasing in frequency with occult brain...metastatic breast cancer (stage IV) patients with or without clinically diagnosed BCBM employing multiparametric flow cytometry (FACS; ARIA IIID system)(10...AWARD NUMBER: W81XWH-14-1-0214 TITLE: Mechanisms of CTC Biomarkers in Breast Cancer Brain Metastasis PRINCIPAL INVESTIGATOR: Dario

  13. Melanoma Brain Metastasis: Mechanisms, Models, and Medicine.

    Science.gov (United States)

    Kircher, David A; Silvis, Mark R; Cho, Joseph H; Holmen, Sheri L

    2016-09-02

    The development of brain metastases in patients with advanced stage melanoma is common, but the molecular mechanisms responsible for their development are poorly understood. Melanoma brain metastases cause significant morbidity and mortality and confer a poor prognosis; traditional therapies including whole brain radiation, stereotactic radiotherapy, or chemotherapy yield only modest increases in overall survival (OS) for these patients. While recently approved therapies have significantly improved OS in melanoma patients, only a small number of studies have investigated their efficacy in patients with brain metastases. Preliminary data suggest that some responses have been observed in intracranial lesions, which has sparked new clinical trials designed to evaluate the efficacy in melanoma patients with brain metastases. Simultaneously, recent advances in our understanding of the mechanisms of melanoma cell dissemination to the brain have revealed novel and potentially therapeutic targets. In this review, we provide an overview of newly discovered mechanisms of melanoma spread to the brain, discuss preclinical models that are being used to further our understanding of this deadly disease and provide an update of the current clinical trials for melanoma patients with brain metastases.

  14. Brain metastasis detection by resonant Raman optical biopsy method

    Science.gov (United States)

    Zhou, Yan; Liu, Cheng-hui; Cheng, Gangge; Zhou, Lixin; Zhang, Chunyuan; Pu, Yang; Li, Zhongwu; Liu, Yulong; Li, Qingbo; Wang, Wei; Alfano, Robert R.

    2014-03-01

    Resonant Raman (RR) spectroscopy provides an effective way to enhance Raman signal from particular bonds associated with key molecules due to changes on a molecular level. In this study, RR is used for detection of human brain metastases of five kinds of primary organs of lung, breast, kidney, rectal and orbital in ex-vivo. The RR spectra of brain metastases cancerous tissues were measured and compared with those of normal brain tissues and the corresponding primary cancer tissues. The differences of five types of brain metastases tissues in key bio-components of carotene, tryptophan, lactate, alanine and methyl/methylene group were investigated. The SVM-KNN classifier was used to categorize a set of RR spectra data of brain metastasis of lung cancerous tissues from normal brain tissue, yielding diagnostic sensitivity and specificity at 100% and 75%, respectively. The RR spectroscopy may provide new moleculebased optical probe tools for diagnosis and classification of brain metastatic of cancers.

  15. Integrated genomic and epigenomic analysis of breast cancer brain metastasis.

    Directory of Open Access Journals (Sweden)

    Bodour Salhia

    Full Text Available The brain is a common site of metastatic disease in patients with breast cancer, which has few therapeutic options and dismal outcomes. The purpose of our study was to identify common and rare events that underlie breast cancer brain metastasis. We performed deep genomic profiling, which integrated gene copy number, gene expression and DNA methylation datasets on a collection of breast brain metastases. We identified frequent large chromosomal gains in 1q, 5p, 8q, 11q, and 20q and frequent broad-level deletions involving 8p, 17p, 21p and Xq. Frequently amplified and overexpressed genes included ATAD2, BRAF, DERL1, DNMTRB and NEK2A. The ATM, CRYAB and HSPB2 genes were commonly deleted and underexpressed. Knowledge mining revealed enrichment in cell cycle and G2/M transition pathways, which contained AURKA, AURKB and FOXM1. Using the PAM50 breast cancer intrinsic classifier, Luminal B, Her2+/ER negative, and basal-like tumors were identified as the most commonly represented breast cancer subtypes in our brain metastasis cohort. While overall methylation levels were increased in breast cancer brain metastasis, basal-like brain metastases were associated with significantly lower levels of methylation. Integrating DNA methylation data with gene expression revealed defects in cell migration and adhesion due to hypermethylation and downregulation of PENK, EDN3, and ITGAM. Hypomethylation and upregulation of KRT8 likely affects adhesion and permeability. Genomic and epigenomic profiling of breast brain metastasis has provided insight into the somatic events underlying this disease, which have potential in forming the basis of future therapeutic strategies.

  16. Integrated genomic and epigenomic analysis of breast cancer brain metastasis.

    Science.gov (United States)

    Salhia, Bodour; Kiefer, Jeff; Ross, Julianna T D; Metapally, Raghu; Martinez, Rae Anne; Johnson, Kyle N; DiPerna, Danielle M; Paquette, Kimberly M; Jung, Sungwon; Nasser, Sara; Wallstrom, Garrick; Tembe, Waibhav; Baker, Angela; Carpten, John; Resau, Jim; Ryken, Timothy; Sibenaller, Zita; Petricoin, Emanuel F; Liotta, Lance A; Ramanathan, Ramesh K; Berens, Michael E; Tran, Nhan L

    2014-01-01

    The brain is a common site of metastatic disease in patients with breast cancer, which has few therapeutic options and dismal outcomes. The purpose of our study was to identify common and rare events that underlie breast cancer brain metastasis. We performed deep genomic profiling, which integrated gene copy number, gene expression and DNA methylation datasets on a collection of breast brain metastases. We identified frequent large chromosomal gains in 1q, 5p, 8q, 11q, and 20q and frequent broad-level deletions involving 8p, 17p, 21p and Xq. Frequently amplified and overexpressed genes included ATAD2, BRAF, DERL1, DNMTRB and NEK2A. The ATM, CRYAB and HSPB2 genes were commonly deleted and underexpressed. Knowledge mining revealed enrichment in cell cycle and G2/M transition pathways, which contained AURKA, AURKB and FOXM1. Using the PAM50 breast cancer intrinsic classifier, Luminal B, Her2+/ER negative, and basal-like tumors were identified as the most commonly represented breast cancer subtypes in our brain metastasis cohort. While overall methylation levels were increased in breast cancer brain metastasis, basal-like brain metastases were associated with significantly lower levels of methylation. Integrating DNA methylation data with gene expression revealed defects in cell migration and adhesion due to hypermethylation and downregulation of PENK, EDN3, and ITGAM. Hypomethylation and upregulation of KRT8 likely affects adhesion and permeability. Genomic and epigenomic profiling of breast brain metastasis has provided insight into the somatic events underlying this disease, which have potential in forming the basis of future therapeutic strategies.

  17. Brain metastasis reirradiation in patients with advanced breast cancer

    Science.gov (United States)

    Huang, Zhou; Sun, Bing; Shen, Ge; Cha, Lei; Meng, Xiangying; Wang, Junliang; Zhou, Zhenshan; Wu, Shikai

    2017-01-01

    The outcome of recurrent brain metastasis is dismal. This study aims to assess the clinical outcomes and toxicity of reirradiation as a salvage treatment for progressive brain metastasis in patients with advanced breast cancer. Between July 2005 and September 2014, the medical records of 56 patients with brain metastasis from breast cancer were retrospectively reviewed. Of these patients, 39 received whole-brain radiotherapy (WBRT) followed by stereotactic radiosurgery (SRS) reirradiation (Group 1), and 17 received SRS followed by WBRT reirradiation (Group 2). Overall survival (OS) and brain progression-free survival rates/times were calculated using the Kaplan–Meier method. Prognostic factors were evaluated using the Cox proportional hazards model. Change in neurologic function was also assessed. The median OS was 10.8 months (range, 1.3–56.8 months). In Group 1, the median PFS time (PFS-1) was 6.5 months and the OS time was 11.4 months. Multivariate analysis revealed that longer OS was significantly associated with a high Karnofsky performance score (KPS) (P = 0.004), controlled extracranial metastasis (P = 0.001) and a good response to reirradiation (P = 0.034). In Group 2, the median PFS time (PFS-2) after reirradiation was 8.5 months and the OS time was 10.8 months. Multivariate analysis revealed that longer OS was significantly associated with a high KPS (P = 0.018). The majority of the patients had improved or stable neurological function. Reirradiation is an effective and a safe treatment for patients with brain metastases from breast cancer. It might delay the progression of intracranial disease and improve neurological function. A suitable patient selection for reirradiation was suggested. PMID:27707842

  18. A rare metastasis from a rare brain tumour

    DEFF Research Database (Denmark)

    Aabenhus, Kristine; Hahn, Christoffer Holst

    2014-01-01

    This case report presents the story of a patient with an oligodendroglioma metastasizing to the bone marrow and to lymph nodes of the neck. The patient had undergone primary brain surgery 13 years prior to the discovery of metastases and radiotherapy directed at the brain tumour two months prior........ Oligodendroglioma are rare primary brain tumours of which extraneural metastasis is even more rare. The incidence of cases like this may be increasing because of better treatment and thus longer survival of patients with oligodendroglioma....

  19. Brain metastasis from breastcancer. Effect of radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Kaasa, S.; Melsom, H.; Lund, E.

    1988-04-01

    Cerebral metastases often lead to considerable morbidity with development of neurological symptoms. The expected survival is short and treatment should be considered as symptomatic. A retrospective analysis of 39 patients with breastcancer and brain metastases was undertaken. The patients were treated with total cranial irradiation. The median survival was 5.3 months. In five patients the tumor was resected before radiotheraphy. This group of patients had a median survival of 13.5 months. Selected groups of patients with long relapse-free interval solitary brain metastases and no other systemic disease, should be considered for neurosurgery. Dexamethasone may be effective as initial treatment. Patients with relatively long expected survival, assessed from the extracranial disease, should be considered for cranial irradiation.

  20. [Brain metastasis: clinical and cognitive assessments].

    Science.gov (United States)

    Ramirez, Carole; Blonski, Marie; Belin, Catherine; Carpentier, Antoine; Taillia, Hervé

    2013-01-01

    The incidence of brain metastases (BM) has increased due to the improvement of therapeutics and diagnostic imaging, but also to an aging population. The initial symptoms may develop suddenly or insidiously over weeks or months. The symptoms depend on the location of the BM and related complications (hydrocephalus, tumor hemorrhage, cerebral herniation). Headaches are the most frequent symptoms (50%); they are related to intracranial hypertension. Cognitive deficits are commonly described at diagnosis (67 to 90.5%). Cognitive assessment is essential because of its impact on patients' prognosis and quality of life. Nevertheless, these deficits remain underestimated. The Karnofsky Perfomance Scale and the Mini Mental State Examination (MMSE) seem inadequate. A short battery was proposed and internationally validated, assessing seven domains: attention (Digit Symbol Test WAIS-III), episodic memory (Hopkins Verbal Learning Test [HVLT]), working memory (Digit Span Test WAIS-III), verbal fluency (Controlled Oral Word Association Test [COWA]), fine motor dexterity (Grooved Pegboard Test), information processing speed (Trail Making Test [TMT] A) and executive functions (TMT B). This battery is relevant, feasible and associated with a good compliance. These cognitive tests are currently recommended to assess cognitive functions in patients with BM.

  1. Cognition in patients with newly diagnosed brain metastasis: profiles and implications.

    Science.gov (United States)

    Gerstenecker, Adam; Nabors, Louis B; Meneses, Karen; Fiveash, John B; Marson, Daniel C; Cutter, Gary; Martin, Roy C; Meyers, Christina A; Triebel, Kristen L

    2014-10-01

    Cognitive impairment is a common symptom in patients with brain metastasis, and significant cognitive dysfunction is prevalent in a majority of patients who are still able to engage in basic self-care activities. In the current study, the neurocognitive performance of 32 patients with brain metastasis and 32 demographically-matched controls was examined using a battery of standardized neuropsychological tests, with the goal of comprehensively examining the cognitive functioning of newly diagnosed brain metastasis patients. The cognition of all patients was assessed within 1 week of beginning treatment for brain metastasis. Results indicated impairments in verbal memory, attention, executive functioning, and language in relation to healthy controls. Performance in relation to appropriate normative groups was also examined. Overall, cognitive deficits were prevalent and memory was the most common impairment. Given that cognitive dysfunction was present in this cohort of patients with largely minimal functional impairment, these results have implications for patients, caregivers and health care providers treating patients with brain metastasis.

  2. Serpins promote cancer cell survival and vascular co-option in brain metastasis.

    Science.gov (United States)

    Valiente, Manuel; Obenauf, Anna C; Jin, Xin; Chen, Qing; Zhang, Xiang H-F; Lee, Derek J; Chaft, Jamie E; Kris, Mark G; Huse, Jason T; Brogi, Edi; Massagué, Joan

    2014-02-27

    Brain metastasis is an ominous complication of cancer, yet most cancer cells that infiltrate the brain die of unknown causes. Here, we identify plasmin from the reactive brain stroma as a defense against metastatic invasion, and plasminogen activator (PA) inhibitory serpins in cancer cells as a shield against this defense. Plasmin suppresses brain metastasis in two ways: by converting membrane-bound astrocytic FasL into a paracrine death signal for cancer cells, and by inactivating the axon pathfinding molecule L1CAM, which metastatic cells express for spreading along brain capillaries and for metastatic outgrowth. Brain metastatic cells from lung cancer and breast cancer express high levels of anti-PA serpins, including neuroserpin and serpin B2, to prevent plasmin generation and its metastasis-suppressive effects. By protecting cancer cells from death signals and fostering vascular co-option, anti-PA serpins provide a unifying mechanism for the initiation of brain metastasis in lung and breast cancers.

  3. Welcoming Treat: Astrocyte-Derived Exosomes Induce PTEN Suppression to Foster Brain Metastasis.

    Science.gov (United States)

    Alečković, Maša; Kang, Yibin

    2015-11-09

    Metastasis to distant organs depends on pathological crosstalk between tumor cells and various tissue-specific stromal components. Zhang and colleagues recently demonstrated that astrocyte-derived exosomal miR-19a reversibly downregulated PTEN expression in cancer cells, thereby increasing their CCL2 secretion and recruitment of myeloid cell to promote brain metastasis.

  4. Significance of Primary Tumor Location and Histology for Brain Metastasis Development and Peritumoral Brain Edema in Lung Cancer

    DEFF Research Database (Denmark)

    Fabian, Katalin; Gyulai, Marton; Furak, Jozsef;

    2016-01-01

    Background: Brain metastasis of lung cancer adversely affects overall survival (OS) and quality of life, while peritumoral brain edema is responsible for life-threatening complications. Methods: We retrospectively analyzed the clinicopathological and cerebral radiological data of 575 consecutive...... lung cancer patients with brain metastases. Results: In adenocarcinoma and squamous cell carcinoma, peritumoral brain edema was more pronounced than in small-cell lung cancer (p ... of peritumoral brain edema (p

  5. Oxidative Stress Increases the Blood Brain Barrier Permeability Resulting in Increased Incidence of Brain Metastasis in BRCA Mutation Carriers

    Science.gov (United States)

    2014-08-01

    Increased Incidence of Brain Metastasis in BRCA Mutation Carriers PRINCIPAL INVESTIGATOR: Hava Avraham, Ph.D. CONTRACTING ORGANIZATION: Beth Israel...Permeability Resulting in Increased Incidence of Brain Metastasis in BRCA Mutation Carriers 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-11-1-0172 5c...significantly up-regulated with a decrease in cellular sensitivity to paclitaxel. Cells that harbor endogenous mutant or defective BRCA l (such as MDA-MB-436

  6. Pertuzumab, trastuzumab and docetaxel reduced the recurrence of brain metastasis from breast cancer: a case report.

    Science.gov (United States)

    Senda, Noriko; Yamaguchi, Ayane; Nishimura, Hideaki; Shiozaki, Toshiki; Tsuyuki, Shigeru

    2016-03-01

    The CLEOPATRA trial reported the survival benefit of pertuzumab with trastuzumab plus docetaxel in HER2-positive metastatic breast cancer patients. However, there are a few case reports concerning the effects of a pertuzumab-containing regimen on brain metastases. A 55-year-old woman, who underwent curative surgery for breast cancer after neoadjuvant chemotherapy 5 years previously, developed repeated solitary brain metastasis in her right occipital lobe. Whole brain radiation therapy, stereotactic radiosurgery and 3 times of surgical resection were performed. Lapatinib and capecitabine plus tamoxifen were administered. The metastasis recurred in the stump of the previous surgery. Pertuzumab with trastuzumab plus docetaxel was initiated as second-line chemotherapy. A complete response of the brain metastasis was achieved, which persisted for 5 months. Pertuzumab with trastuzumab plus docetaxel was effective in reducing the brain metastases from breast cancer. Further studies are warranted to confirm the effect of this regimen on brain metastases.

  7. Exercise maintains blood-brain barrier integrity during early stages of brain metastasis formation.

    Science.gov (United States)

    Wolff, Gretchen; Davidson, Sarah J; Wrobel, Jagoda K; Toborek, Michal

    2015-08-07

    Tumor cell extravasation into the brain requires passage through the blood-brain barrier, which is a highly protected microvascular environment fortified with tight junction (TJ) proteins. TJ integrity can be regulated under physiological and pathophysiological conditions. There is evidence that exercise can modulate oxidation status within the brain microvasculature and protect against tumor cell extravasation and metastasis formation. In order to study these events, mature male mice were given access to voluntary exercise on a running wheel (exercise) or access to a locked wheel (sedentary) for five weeks. The average running distance was 9.0 ± 0.2 km/day. Highly metastatic tumor cells (murine Lewis lung carcinoma) were then infused into the brain microvasculature through the internal carotid artery. Analyses were performed at early stage (48 h) and late stage (3 weeks) post tumor cell infusion. Immunohistochemical analysis revealed fewer isolated tumor cells extravasating into the brain at both 48 h and 3 weeks post surgery in exercised mice. Occludin protein levels were reduced in the sedentary tumor group, but maintained in the exercised tumor group at 48 h post tumor cell infusion. These results indicate that voluntary exercise may participate in modulating blood-brain barrier integrity thereby protecting the brain during metastatic progression.

  8. Brain metastasis as initial presentation of papillary adenocarcinoma of the lung: case report

    Energy Technology Data Exchange (ETDEWEB)

    Bispo, Irving Gabriel Araujo; Nascimento, Diego Teixeira; Ferreira, Karina Oliveira; Fakhouri, Ricardo; Godinho, Atilano Salvador; Ferrao, Thiago de Oliveira, E-mail: irvingbispo@yahoo.com.br [Universidade Federal de Sergipe (HU-UFS), Aracaju, SE (Brazil). Hospital Universitario

    2013-09-15

    The authors describe the case of a 33-year-old patient with history of seizures alone without any previous symptom, being diagnosed with brain metastases from primary papillary adenocarcinoma of the lung. Emphasis is given to the diagnostic investigation for brain metastasis and prognostic evaluation of papillary adenocarcinoma of the lung, and a brief literature review on such diseases is performed. (author)

  9. Selective Permeabilization of the Blood–Brain Barrier at Sites of Metastasis

    OpenAIRE

    Sibson, NR; Vallis, KA; Hamilton, A.; Seymour, L.; Anthony, DC; Connell, JJ; Chatain, G

    2013-01-01

    BACKGROUND: Effective chemotherapeutics for primary systemic tumors have limited access to brain metastases because of the blood-brain barrier (BBB). The aim of this study was to develop a strategy for specifically permeabilizing the BBB at sites of cerebral metastases. METHODS: BALB/c mice were injected intracardially to induce brain metastases. After metastasis induction, either tumor necrosis factor (TNF) or lymphotoxin (LT) was administered intravenously, and 2 to 24 hours later gadoliniu...

  10. [Targeted Therapy and Immunotherapy for Non-small Cell Lung Cancer 
with Brain Metastasis].

    Science.gov (United States)

    Song, Qi; Jiao, Shunchang; Li, Fang

    2016-08-20

    Brain metastasis, a common complication of non-small cell lung cancer (NSCLC) with an incidence rate of 30%-50%, significantly affects the patients' quality of life. The prognosis of patients of NSCLC with brain metastasis is extremely poor, the average median survival is only 1 m-2 m without treatment. The targeted therapy based on lung cancer driven gene is a new treatment. Besides, the immunotherapy which can enhance the effect of anti-cancer by simulating the immune system is a new approach. The combination of targeted therapy and immunotherapy can greatly benefit patients in clinical work.

  11. Targeted Therapy and Immunotherapy for Non-small Cell Lung Cancer 
with Brain Metastasis

    Directory of Open Access Journals (Sweden)

    Qi SONG

    2016-08-01

    Full Text Available Brain metastasis, a common complication of non-small cell lung cancer (NSCLC with an incidence rate of 30%-50%, significantly affects the patients’ quality of life. The prognosis of patients of NSCLC with brain metastasis is extremely poor, the average median survival is only 1 m-2 m without treatment. The targeted therapy based on lung cancer driven gene is a new treatment. Besides, the immunotherapy which can enhance the effect of anti-cancer by simulating the immune system is a new approach. The combination of targeted therapy and immunotherapy can greatly benefit patients in clinical work.

  12. Targeted Therapy and Immunotherapy for Non-small Cell Lung Cancer 
with Brain Metastasis

    OpenAIRE

    Song, Qi; Jiao, Shunchang; Li, Fang

    2016-01-01

    Brain metastasis, a common complication of non-small cell lung cancer (NSCLC) with an incidence rate of 30%-50%, significantly affects the patients’ quality of life. The prognosis of patients of NSCLC with brain metastasis is extremely poor, the average median survival is only 1 m-2 m without treatment. The targeted therapy based on lung cancer driven gene is a new treatment. Besides, the immunotherapy which can enhance the effect of anti-cancer by simulating the immune system is a new approa...

  13. MicroRNA and protein profiling of brain metastasis competent cell-derived exosomes.

    Directory of Open Access Journals (Sweden)

    Laura Camacho

    Full Text Available Exosomes are small membrane vesicles released by most cell types including tumor cells. The intercellular exchange of proteins and genetic material via exosomes is a potentially effective approach for cell-to-cell communication and it may perform multiple functions aiding to tumor survival and metastasis. We investigated microRNA and protein profiles of brain metastatic (BM versus non-brain metastatic (non-BM cell-derived exosomes. We studied the cargo of exosomes isolated from brain-tropic 70W, MDA-MB-231BR, and circulating tumor cell brain metastasis-selected markers (CTC1BMSM variants, and compared them with parental non-BM MeWo, MDA-MB-231P and CTC1P cells, respectively. By performing microRNA PCR array we identified one up-regulated (miR-210 and two down-regulated miRNAs (miR-19a and miR-29c in BM versus non-BM exosomes. Second, we analyzed the proteomic content of cells and exosomes isolated from these six cell lines, and detected high expression of proteins implicated in cell communication, cell cycle, and in key cancer invasion and metastasis pathways. Third, we show that BM cell-derived exosomes can be internalized by non-BM cells and that they effectively transport their cargo into cells, resulting in increased cell adhesive and invasive potencies. These results provide a strong rationale for additional investigations of exosomal proteins and miRNAs towards more profound understandings of exosome roles in brain metastasis biogenesis, and for the discovery and application of non-invasive biomarkers for new therapies combating brain metastasis.

  14. Treatment for brain metastasis from lung cancer in the era of radiosurgery

    Energy Technology Data Exchange (ETDEWEB)

    Yamanaka, Kazuhiro; Iwai, Yoshiyasu; Nakajima, Hideki [Osaka City General Hospital (Japan)] (and others)

    2001-07-01

    The treatment for brain metastasis has undergone remarkable changes since the development of radiosurgery. We investigated the results of treatment for brain metastasis from lung cancer since the initiation of gamma knife radiosurgery (GKRS) and we discuss the usefulness of GKRS combined with other treatments in cases with recurrence. We treated 142 patients with brain metastasis from lung cancer. Sixteen patients were treated surgically, 11 patients were treated with whole brain radiation therapy (WBRT), and 115 patients were treated with GKRS. Our treatment plan is to use GKRS in cases with less than 5 lesions and lesions less than 3 cm in mean diameter. We use WBRT in cases with 5 or more lesions, and surgery in cases with lesions 3 cm or larger. If new lesions or tumor regrowth appeared after the initial treatment, we retreated them with one of the methods mentioned above. Twice or three-time treatments were performed in 30 patients. Median survival including all cases was 10 months and the number of deaths due to local treatment failure was only 5 (6.5%) out of the total 77 deaths which occurred. We were able to carry out less invasive treatment for brain metastasis from lung cancer by utilizing GKRS. Though we have to consider the indications for other treatments, we can say that radiosurgery is usually the treatment of first choice for brain metastasis from lung caner. When new lesions appear in cases where a particular initial treatment was used, it is possible to maintain or improve the quality of life by retreatment, using a combination of GKRS, surgery or WBRT, to prolong the patient's life. (author)

  15. MicroRNA and protein profiling of brain metastasis competent cell-derived exosomes.

    Science.gov (United States)

    Camacho, Laura; Guerrero, Paola; Marchetti, Dario

    2013-01-01

    Exosomes are small membrane vesicles released by most cell types including tumor cells. The intercellular exchange of proteins and genetic material via exosomes is a potentially effective approach for cell-to-cell communication and it may perform multiple functions aiding to tumor survival and metastasis. We investigated microRNA and protein profiles of brain metastatic (BM) versus non-brain metastatic (non-BM) cell-derived exosomes. We studied the cargo of exosomes isolated from brain-tropic 70W, MDA-MB-231BR, and circulating tumor cell brain metastasis-selected markers (CTC1BMSM) variants, and compared them with parental non-BM MeWo, MDA-MB-231P and CTC1P cells, respectively. By performing microRNA PCR array we identified one up-regulated (miR-210) and two down-regulated miRNAs (miR-19a and miR-29c) in BM versus non-BM exosomes. Second, we analyzed the proteomic content of cells and exosomes isolated from these six cell lines, and detected high expression of proteins implicated in cell communication, cell cycle, and in key cancer invasion and metastasis pathways. Third, we show that BM cell-derived exosomes can be internalized by non-BM cells and that they effectively transport their cargo into cells, resulting in increased cell adhesive and invasive potencies. These results provide a strong rationale for additional investigations of exosomal proteins and miRNAs towards more profound understandings of exosome roles in brain metastasis biogenesis, and for the discovery and application of non-invasive biomarkers for new therapies combating brain metastasis.

  16. A case of leukoencephalopathy caused by radiation and chemotherapy for brain metastasis of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Shigeru; Sonoo, Hiroshi; Nomura, Tsunehisa; Ohkubo, Sumiko; Yamamoto, Yutaka; Tanaka, Katsuhiro; Kurebayashi, Junichi; Hiratsuka, Junichi [Kawasaki Medical School, Kurashiki, Okayama (Japan)

    2002-08-01

    A case of treatment-related leukoencephalopathy is presented. A patient with breast cancer metastasis to the brain, liver, bone and distant lymph nodes was treated with whole brain radiation and docetaxcel. Eleven months after radiation, magnetic resonance imaging showed diffuse leukoencephalopathy. Twenty-two months after radiation, the patient had gait disturbance, parkinsonism, dementia and urinary incontinence. From this experience, stereotactic radiosurgery such as cyber knife and gamma knife therapy, representing a new modality for delivering intense focal radiation, should be come preferred techniques for treating patients with brain metastases, to avoid the potential cognitive side effects of fractionated whole-brain radiotherapy. (author)

  17. Management of brain metastasis: past lessons, modern management, and future considerations.

    Science.gov (United States)

    Koay, Eugene; Sulman, Erik P

    2012-02-01

    Brain metastasis is a major challenge for patients, physicians, and the broader health care system, with approximately 170,000 new cases per year. After a diagnosis of brain metastasis, patients have a poor prognosis, but modern management has made significant advances in the past two decades to improve palliative efficacy and patient survival through a multidisciplinary approach. A number of factors must be taken into consideration in the treatment approach, including the number of intracranial lesions, the control of extracranial disease, and the patient's overall health, while weighing the benefits of treatment against the toxicities, both acute and chronic. With quality of life as an emphasis, emerging concepts for modern management of brain metastasis have sought to minimize long-term toxicities. The economic impact of such strategies for patients and the health care system has been demonstrated in some studies, but has not been a consistent area of focus. Each of these strategies, as well as novel therapeutics, has embraced the concept of personalized treatment. This review will discuss the current knowledge of modern multidisciplinary management of brain metastasis and look forward to emerging concepts.

  18. Brain metastasis as initial presentation of papillary adenocarcinoma of the lung: case report

    Directory of Open Access Journals (Sweden)

    Irving Gabriel Araujo Bispo

    2013-09-01

    Full Text Available The authors describe the case of a 33-year-old patient with history of seizures alone without any previous symptom, being diagnosed with brain metastases from primary papillary adenocarcinoma of the lung. Emphasis is given to the diagnostic investigation for brain metastasis and prognostic evaluation of papillary adenocarcinoma of the lung, and a brief literature review on such diseases is performed.

  19. Role of KCNMA1 gene in breast cancer invasion and metastasis to brain

    Directory of Open Access Journals (Sweden)

    Couraud Pierre-Olivier

    2009-07-01

    Full Text Available Abstract Background The prognosis for patients with breast tumor metastases to brain is extremely poor. Identification of prognostic molecular markers of the metastatic process is critical for designing therapeutic modalities for reducing the occurrence of metastasis. Although ubiquitously present in most human organs, large-conductance calcium- and voltage-activated potassium channel (BKCa channels are significantly upregulated in breast cancer cells. In this study we investigated the role of KCNMA1 gene that encodes for the pore-forming α-subunit of BKCa channels in breast cancer metastasis and invasion. Methods We performed Global exon array to study the expression of KCNMA1 in metastatic breast cancer to brain, compared its expression in primary breast cancer and breast cancers metastatic to other organs, and validated the findings by RT-PCR. Immunohistochemistry was performed to study the expression and localization of BKCa channel protein in primary and metastatic breast cancer tissues and breast cancer cell lines. We performed matrigel invasion, transendothelial migration and membrane potential assays in established lines of normal breast cells (MCF-10A, non-metastatic breast cancer (MCF-7, non-brain metastatic breast cancer cells (MDA-MB-231, and brain-specific metastatic breast cancer cells (MDA-MB-361 to study whether BKCa channel inhibition attenuates breast tumor invasion and metastasis using KCNMA1 knockdown with siRNA and biochemical inhibition with Iberiotoxin (IBTX. Results The Global exon array and RT-PCR showed higher KCNMA1 expression in metastatic breast cancer in brain compared to metastatic breast cancers in other organs. Our results clearly show that metastatic breast cancer cells exhibit increased BKCa channel activity, leading to greater invasiveness and transendothelial migration, both of which could be attenuated by blocking KCNMA1. Conclusion Determining the relative abundance of BKCa channel expression in breast

  20. A Phase I trial of dose escalation of topotecan combined with whole brain radiotherapy for brain metastasis in lung cancer

    Institute of Scientific and Technical Information of China (English)

    Xiaohui Ge; Wenyan Zhao; Xiaocang Ren; Yongqiang Wang; Zhigang Li; Yanqi Li; Yuee Liu; Qiang Lin

    2012-01-01

    Objective: The aim of this study was to define the maximum-tolerated dose (MTD) and observe the toxicity of escalating topotecan combined whole brain radiotherapy for brain metastasis in lung cancer. Methods: Patients with brain metastasis of lung cancer received conventional fractionation radiotherapy, with 5 daily fractions of 2 Gy per week, the total radiation dose was 40 Gy, while the larger lesions were boosted to 50-60 Gy. The initial dose of topotecan was 1.0 mg/m2. Escalation dose was 0.25 mg/m2. Every cohort contained at least 3 patients.If no dose-limiting toxicity (DLT) was observed,the next dose level was opened for entry. These courses were repeated until DLT appeared. MTD was declared as one dose level below which DLT appeared. Results: Eighteen patients were recruited. Two cases of grade 3 leucopenia/neutropenia was observed as DLT at the level of topotecan 2.0 mg/m2. MTD of topotecan was defined as 1.75 mg/m2.The major side effects were leucopenia/neutropenia, nausea and vomiting. Conclusion: Topotecan combined with whole brain radiotherapy for brain metastasis in lung cancer is well tolerated. Maximum-tolerated dose of topotecan is 1.75 mg/m2, once a week of a total of four.

  1. Endoscopy-verified occult subependymal dissemination of glioblastoma and brain metastasis undetected by MRI: prognostic significance

    Directory of Open Access Journals (Sweden)

    Iacoangeli M

    2012-12-01

    Full Text Available Maurizio Iacoangeli,1 Alessandro Di Rienzo,1 Roberto Colasanti,1 Antonio Zizzi,2 Maurizio Gladi,1 Lorenzo Alvaro,1 Niccolò Nocchi,1 Lucia Giovanna Maria Di Somma,1 Marina Scarpelli,2 Massimo Scerrati11Department of Neurosurgery, 2Department of Pathology, Università Politecnica delle Marche, Umberto I General Hospital, Ancona, ItalyAbstract: Although various prognostic indices exist for patients with malignant brain tumors, the prognostic significance of the subependymal spread of intracranial tumors is still a matter of debate. In this paper, we report the cases of two intraventricular lesions, a recurrent glioblastoma multiforme (GBM and a brain metastasis, each successfully treated with a neuroendoscopic approach. Thanks to this minimally invasive approach, we achieved good therapeutic results: we obtained a histological diagnosis; we controlled intracranial hypertension by treating the associated hydrocephalus and, above all, compared with a microsurgical approach, we reduced the risks related to dissection and brain retraction. Moreover, in both cases, neuroendoscopy enabled us to identify an initial, precocious subependymal tumor spreading below the threshold of magnetic resonance imaging (MRI detection. This finding, undetected in pre-operative MRI scans, was then evident during follow-up neuroimaging studies. In light of these data, a neuroendoscopic approach might play a leading role in better defining the prognosis and optimally tailored management protocols for GBM and brain metastasis.Keywords: subependymal spreading, glioblastoma, brain metastasis, endoscopy, minimally invasive surgery, prognosis

  2. [Brain metastasis from papillary thyroid carcinoma with acute intracerebral hemorrhage: a surgical case report].

    Science.gov (United States)

    Chonan, Masashi; Mino, Masaki; Yoshida, Masahiro; Sakamoto, Kazuhiro

    2012-05-01

    We report a rare case of brain metastasis from papillary thyroid carcinoma with intracerebral hemorrhage. A 79-year-old woman presented with sudden headache and monoplegia of the right upper limb 10 years after diagnosis of thyroid papillary adenocarcinoma. Despite the known metastatic lesions in the cervical lymph nodes and lungs, she had been well for 10 years since thyroidectomy, focal irradiation and internal radiation of 131I. CT demonstrated intracerebral hemorrhage in the left temporal lobe. Magnetic resonance imaging showed marked signal heterogeneity. She underwent radical surgery on the day of the onset and the histological diagnosis was metastatic brain tumor of thyroid papillary carcinoma. Postoperative course was uneventful, and the monoplegia was improved. Papillary thyroid carcinoma has a relatively benign course, and surgical removal of the brain metastasis is able to contribute to longer survival times for patients.

  3. Targeting Phosphatidylserine for Radioimmunotherapy of Breast Cancer Brain Metastasis

    Science.gov (United States)

    2013-10-01

    antibodies to the endothelial marker, CD31 (Serotec, Raleigh, NC) followed by Cy3-conjugated secondary antibody ( Jackson Immunoresearch Laboratories...in the brain. Cancer Res 67, 4190-4198, doi:67/9/4190 [pii] 10.1158/0008-5472.CAN-06- 3316 (2007). 7 Percy , D. B. et al. In vivo characterization of

  4. Oncocytic-type intraductal papillary mucinous neoplasm (IPMN-derived invasive oncocytic pancreatic carcinoma with brain metastasis - a case report

    Directory of Open Access Journals (Sweden)

    Chiang Kun-Chun

    2012-07-01

    Full Text Available Abstract Pancreatic cancer is a lethal disease without effective treatments at present. It ranks as s as 4th and 5th in cancer-related mortality in the western countries and worldwide. Locally advanced pancreatic duct carcinoma (PDAC and metastatic PDAC, usually found the metastases over liver, peritoneum, or lung, have been shown to be with dismal prognosis. Brain metastasis is a rare entity and most cases reported before were found post-mortem. Intraductal papillary mucinous neoplasms of the pancreas (IPMN has been deemed as a precursor of PDAC with very slow progression rate. Here we reported a case diagnosed with IPMN-derived PDAC with brain metastasis. After surgeries for PDAC and brain metastasis, subsequent chemotherapy and radiotherapy were also given. One and half year after surgery, this patient is still living with good performance status, which may warrant individualization of therapeutic strategy for PDAC with only brain metastasis.

  5. Oncocytic-type intraductal papillary mucinous neoplasm (IPMN)-derived invasive oncocytic pancreatic carcinoma with brain metastasis - a case report.

    Science.gov (United States)

    Chiang, Kun-Chun; Yu, Chi-Chang; Chen, Jim-Ray; Huang, Yu-Ting; Huang, Cheng-Cheng; Yeh, Chun-Nan; Tsai, Chien-Sheng; Chen, Li-Wei; Chen, Hsien-Cin; Hsu, Jun-Te; Wang, Cheng-Hsu; Chen, Huang-Yang

    2012-07-09

    Pancreatic cancer is a lethal disease without effective treatments at present. It ranks as s as 4th and 5th in cancer-related mortality in the western countries and worldwide. Locally advanced pancreatic duct carcinoma (PDAC) and metastatic PDAC, usually found the metastases over liver, peritoneum, or lung, have been shown to be with dismal prognosis. Brain metastasis is a rare entity and most cases reported before were found post-mortem. Intraductal papillary mucinous neoplasms of the pancreas (IPMN) has been deemed as a precursor of PDAC with very slow progression rate. Here we reported a case diagnosed with IPMN-derived PDAC with brain metastasis. After surgeries for PDAC and brain metastasis, subsequent chemotherapy and radiotherapy were also given. One and half year after surgery, this patient is still living with good performance status, which may warrant individualization of therapeutic strategy for PDAC with only brain metastasis.

  6. A pilot study of accelerated irradiation for brain metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Michinao; Tokuuye, Koichi; Akine, Yasuyuki; Akimoto, Tetsuo; Ogino, Takashi; Tsukiyama, Iwao; Ono, Ryosuke; Egawa, Sunao (National Cancer Center, Tokyo (Japan). Hospital)

    1992-12-01

    Twenty-eight patients with brain metastases received brain radiotherapy with a total dose of 48 Gy, at 2 Gy per fraction, twice a day with a minimum interfractional period of 4 hours, and 5 days per week. This was intended to shorten the treatment period without increasing the morbidity, since most of these patients had a limited survival expectancy. Twenty-six of the 28 patients completed the radiotherapy. Three of the 26 patients experienced nausea and/or vomiting during the treatment. Radiotherapy was interrupted in two patients: one developed hemiplegia, and the other somnolence, both of which resulted from the progressive intracerebral disease. This radiotherapy regimen appears to be comparable to the conventional scheme in alleviation of symptoms. No patient needed interruption of the planned course of treatment because of acute irradiation toxicity. Based on these results, a multi-institutional randomized trial has been initiated to compare the twice-a-day and once-a-day radiotherapy schemes on patients with brain metastases. (author).

  7. A case report of thyroid carcinoma with multiple organ metastasis including brain metastasis effectively treated by surgery and [sup 131]I treatment

    Energy Technology Data Exchange (ETDEWEB)

    Shibata, Masahito; Yoshida, Satoru; Kubota, Masahiro; Tsuda, Takatoshi; Morita, Kazuo (Sapporo Medical Coll. (Japan))

    1993-12-01

    Reported is a case of a multiple organ metastases that also included a brain metastasis from a thyroid cancer for which surgery, followed by [sup 131]I therapy, proved very effective and enabled the patient to live for over 15 more years. The treatment for a differentiated thyroid cancer has somewhat been established. The outcome of this case, however, is considered extremely rare, in that a bone metastasis that was surgically removed resulted in no paraplegia and [sup 131]I therapy appeared to cause the disappearance of the brain metastasis. The authors report the encouraging news that for 15 years that followed the initial thyroidectomy, the patient's condition remained good. (author).

  8. SU-E-T-56: Brain Metastasis Treatment Plans for Contrast-Enhanced Synchrotron Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Obeid, L; Adam, J [Grenoble Institut des Neurosciences, La Tronche, Rhone-Alpes (France); Tessier, A [Centre Hospitalier Universitaire, La Tronche, Rhone-Alpes (France); Vautrin, M; Benkebil, M [DOSIsoft, Cachan, Ile de France (France); Sihanath, R [Centre Hospitalier Universitaire, La Tronche, Rhone- Alpes (France)

    2014-06-01

    Purpose: Iodine-enhanced radiotherapy is an innovative treatment combining the selective accumulation of an iodinated contrast agent in brain tumors with irradiations using monochromatic medium energy x-rays. The aim of this study is to compare dynamic stereotactic arc-therapy and iodineenhanced SSRT. Methods: Five patients bearing brain metastasis received a standard helical 3D-scan without iodine. A second scan was acquired 13 min after an 80 g iodine infusion. Two SSRT treatment plans (with/without iodine) were performed for each patient using a dedicated Monte Carlo (MC) treatment planning system (TPS) based on the ISOgray TPS. Ten coplanar beams (6×6 cm2, shaped with collimator) were simulated. MC statistical error objective was less than 5% in the 50% isodose. The dynamic arc-therapy plan was achieved on the Iplan Brainlab TPS. The treatment plan validation criteria were fixed such that 100% of the prescribed dose is delivered at the beam isocentre and the 70% isodose contains the whole target volume. The comparison elements were the 70% isodose volume, the average and maximum doses delivered to organs at risk (OAR): brainstem, optical nerves, chiasma, eyes, skull bone and healthy brain parenchyma. Results: The stereotactic dynamic arc-therapy remains the best technique in terms of dose conformation. Iodine-enhanced SSRT presents similar performances to dynamic arc-therapy with increased brainstem and brain parenchyma sparing. One disadvantage of SSRT is the high dose to the skull bone. Iodine accumulation in metastasis may increase the dose by 20–30%, allowing a normal tissue sparing effect at constant prescribed dose. Treatment without any iodine enhancement (medium-energy stereotactic radiotherapy) is not relevant with degraded HDVs (brain, parenchyma and skull bone) comparing to stereotactic dynamic arc-therapy. Conclusion: Iodine-enhanced SSRT exhibits a good potential for brain metastasis treatment regarding the dose distribution and OAR criteria.

  9. Afatinib in Treatment-Naive Patients With EGFR-Mutated Lung Adenocarcinoma With Brain Metastasis: A Case Series.

    Science.gov (United States)

    Li, Shih-Hong; Hsieh, Meng-Heng; Fang, Yueh-Fu

    2015-10-01

    Tyrosine kinase inhibitors (TKIs) of epidermal growth factor receptor (EGFR) were previously the standard first-line treatments for lung cancers with activating EGFR mutations. The first-generation reversible EGFR TKIs, gefitinib and erlotinib, demonstrated substantial efficacy in the treatment of brain metastases from EGFR-mutated lung adenocarcinoma. However, the efficacy of afatinib, the second-generation irreversible EGFR TKI, as the first-line treatment in lung adenocarcinoma patients with brain metastasis has yet to be evaluated.Here, we report cases of 3 patients who received afatinib alone as the first-line treatment in combination with whole-brain radiotherapy or following surgical resection of brain metastases. All 3 patients had EGFR L858R mutation. The first patient had lung adenocarcinoma with brain metastasis and no neurologic symptoms. After consultation, she received afatinib as a first-line treatment. Chest computed tomography and brain magnetic resonance imaging (MRI) showed partial response. The second patient had lung adenocarcinoma accompanied with a metastatic brain lesion associated with seizures. This patient received whole-brain radiotherapy and afatinib treatment following brain MRI and subsequently showed significant regression of the brain metastasis. The third patient had strabismus of the right eye, and brain MRI showed a single tumor at the cerebellar pontine angle. This patient underwent surgical resection of the tumor followed by afatinib treatment. He refused adjuvant radiotherapy after surgery for brain metastasis. The brain MRI showed no recurrent brain metastasis, and the patient had relatively less neurologic deficiency.This series of 3 cases indicate that afatinib may be an appropriate first-line treatment alternative in patients having lung adenocarcinoma with EGFR mutations. Further retrospective analyses and prospective clinical trials are required to substantiate the efficacy of afatinib in the treatment of brain

  10. Low Expression of Slit2 and Robo1 is Associated with Poor Prognosis and Brain-specific Metastasis of Breast Cancer Patients.

    Science.gov (United States)

    Qin, Fengxia; Zhang, Huikun; Ma, Li; Liu, Xiaoli; Dai, Kun; Li, Wenliang; Gu, Feng; Fu, Li; Ma, Yongjie

    2015-09-24

    Brain metastasis is a significant unmet clinical problem in breast cancer treatment. It is always associated with poor prognosis and high morbidity. Recently, Slit2/Robo1 pathway has been demonstrated to be involved in the progression of breast carcinoma. However, until present, there are no convincing reports that suggest whether the Slit2/Robo1 axis has any role in brain metastasis of breast cancer. In this study, we investigated the correlation between Slit2/Robo1 signaling and breast cancer brain metastasis for the first time. Our results demonstrated that (1) Invasive ductal carcinoma patients with low expression of Slit2 or Robo1 exhibited worse prognosis and brain-specific metastasis, but not liver, bone or lung. (2) Lower expression of Slit2 and Robo1 were observed in patients with brain metastasis, especially in their brain metastasis tumors, compared with patients without brain metastasis. (3) The interval from diagnosis of breast cancer to brain metastasis and brain metastasis to death were both much shorter in patients with low expression of Slit2 or Robo1 compared with the high expression group. Overall, our findings indicated that Slit2/Robo1 axis possibly be regarded as a significant clinical parameter for predicting brain metastasis in breast cancer patients.

  11. Targeting Phosphatidylserine for Radioimmunotherapy of Breast Cancer Brain Metastasis

    Science.gov (United States)

    2015-12-01

    for these patients is whole brain radiotherapy (WBRT). WBRT, however, is often associated with neurological complications that preclude sufficient...an opportunity to selectively radiate tumor cells while sparing normal tissues. The high energy β- emitter, Yttrium-90 (90Y), a FDA approved...3.71 2.54 muscle 1.40 7.75 0.43 10.03 skin 3.24 6.66 5.20 8.13 heart 3.90 4.91 6.59 8.74 lung 15.10 21.39 2.22 3.10 colon 3.16 2.21 1.28 0.60

  12. Identification and analysis of signaling networks potentially involved in breast carcinoma metastasis to the brain.

    Directory of Open Access Journals (Sweden)

    Feng Li

    Full Text Available Brain is a common site of breast cancer metastasis associated with significant neurologic morbidity, decreased quality of life, and greatly shortened survival. However, the molecular and cellular mechanisms underpinning brain colonization by breast carcinoma cells are poorly understood. Here, we used 2D-DIGE (Difference in Gel Electrophoresis proteomic analysis followed by LC-tandem mass spectrometry to identify the proteins differentially expressed in brain-targeting breast carcinoma cells (MB231-Br compared with parental MDA-MB-231 cell line. Between the two cell lines, we identified 12 proteins consistently exhibiting greater than 2-fold (p<0.05 difference in expression, which were associated by the Ingenuity Pathway Analysis (IPA with two major signaling networks involving TNFα/TGFβ-, NFκB-, HSP-70-, TP53-, and IFNγ-associated pathways. Remarkably, highly related networks were revealed by the IPA analysis of a list of 19 brain-metastasis-associated proteins identified recently by the group of Dr. A. Sierra using MDA-MB-435-based experimental system (Martin et al., J Proteome Res 2008 7:908-20, or a 17-gene classifier associated with breast cancer brain relapse reported by the group of Dr. J. Massague based on a microarray analysis of clinically annotated breast tumors from 368 patients (Bos et al., Nature 2009 459: 1005-9. These findings, showing that different experimental systems and approaches (2D-DIGE proteomics used on brain targeting cell lines or gene expression analysis of patient samples with documented brain relapse yield highly related signaling networks, suggest strongly that these signaling networks could be essential for a successful colonization of the brain by metastatic breast carcinoma cells.

  13. Analysis of radiation therapy in a model of triple-negative breast cancer brain metastasis.

    Science.gov (United States)

    Smart, DeeDee; Garcia-Glaessner, Alejandra; Palmieri, Diane; Wong-Goodrich, Sarah J; Kramp, Tamalee; Gril, Brunilde; Shukla, Sudhanshu; Lyle, Tiffany; Hua, Emily; Cameron, Heather A; Camphausen, Kevin; Steeg, Patricia S

    2015-10-01

    Most cancer patients with brain metastases are treated with radiation therapy, yet this modality has not yet been meaningfully incorporated into preclinical experimental brain metastasis models. We applied two forms of whole brain radiation therapy (WBRT) to the brain-tropic 231-BR experimental brain metastasis model of triple-negative breast cancer. When compared to sham controls, WBRT as 3 Gy × 10 fractions (3 × 10) reduced the number of micrometastases and large metastases by 87.7 and 54.5 %, respectively (both p < 0.01); whereas a single radiation dose of 15 Gy × 1 (15 × 1) was less effective, reducing metastases by 58.4 % (p < 0.01) and 47.1 % (p = 0.41), respectively. Neuroinflammation in the adjacent brain parenchyma was due solely to a reaction from metastases, and not radiotherapy, while adult neurogenesis in brains was adversely affected following both radiation regimens. The nature of radiation resistance was investigated by ex vivo culture of tumor cells that survived initial WBRT ("Surviving" cultures). The Surviving cultures surprisingly demonstrated increased radiosensitivity ex vivo. In contrast, re-injection of Surviving cultures and re-treatment with a 3 × 10 WBRT regimen significantly reduced the number of large and micrometastases that developed in vivo, suggesting a role for the microenvironment. Micrometastases derived from tumor cells surviving initial 3 × 10 WBRT demonstrated a trend toward radioresistance upon repeat treatment (p = 0.09). The data confirm the potency of a fractionated 3 × 10 WBRT regimen and identify the brain microenvironment as a potential determinant of radiation efficacy. The data also nominate the Surviving cultures as a potential new translational model for radiotherapy.

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

    Directory of Open Access Journals (Sweden)

    Ryo Sato

    2017-01-01

    Full Text Available 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.

  15. Endoscopy-verified occult subependymal dissemination of glioblastoma and brain metastasis undetected by MRI: prognostic significance

    Science.gov (United States)

    Iacoangeli, Maurizio; Di Rienzo, Alessandro; Colasanti, Roberto; Zizzi, Antonio; Gladi, Maurizio; Alvaro, Lorenzo; Nocchi, Niccolò; Di Somma, Lucia Giovanna Maria; Scarpelli, Marina; Scerrati, Massimo

    2012-01-01

    Although various prognostic indices exist for patients with malignant brain tumors, the prognostic significance of the subependymal spread of intracranial tumors is still a matter of debate. In this paper, we report the cases of two intraventricular lesions, a recurrent glioblastoma multiforme (GBM) and a brain metastasis, each successfully treated with a neuroendoscopic approach. Thanks to this minimally invasive approach, we achieved good therapeutic results: we obtained a histological diagnosis; we controlled intracranial hypertension by treating the associated hydrocephalus and, above all, compared with a microsurgical approach, we reduced the risks related to dissection and brain retraction. Moreover, in both cases, neuroendoscopy enabled us to identify an initial, precocious subependymal tumor spreading below the threshold of magnetic resonance imaging (MRI) detection. This finding, undetected in pre-operative MRI scans, was then evident during follow-up neuroimaging studies. In light of these data, a neuroendoscopic approach might play a leading role in better defining the prognosis and optimally tailored management protocols for GBM and brain metastasis. PMID:23271915

  16. Expression of metastasis-associated protein 3 in human brain glioma related to tumor prognosis.

    Science.gov (United States)

    Shan, Shouqin; Hui, Guangyan; Hou, Fanggao; Shi, Hua; Zhou, Guoqing; Yan, Han; Wang, Lu; Liu, Jinfeng

    2015-10-01

    Glioma represents a disparate group of tumors characterized by high invasion ability, and therefore it is of clinical significance to identify molecular markers and therapeutic targets for better clinical management. Previously, metastasis-associated protein family (MTA) is considered to promote tumor cell invasion and metastasis of human malignancies. Recently, the newly identified MTA3 has been shown to play conflicting roles in human malignancies, while the expression pattern and potential clinical significance of MTA3 in human glioma have not been addressed yet. In the present study, we investigated the protein expression of MTA3 by immunohistochemistry assay and analyzed its association with glioma prognosis in 186 cases of patients. Results showed that MTA3 expression was decreased in glioma compared with that in normal brain (P human glioma and negatively associated with prognosis of patients, suggesting that MTA3 may play a tumor suppressor role in glioma.

  17. Are capecitabine and the active metabolite 5-Fu CNS penetrable to treat breast cancer brain metastasis?

    Science.gov (United States)

    Zhang, Jinqiang; Zhang, Lingli; Yan, Yumei; Li, Shaorong; Xie, Liang; Zhong, Wei; Lv, Jing; Zhang, Xiuhua; Bai, Yu; Cheng, Ziqiang

    2015-03-01

    Brain metastasis (BM) is increasingly diagnosed in Her2 positive breast cancer (BC) patients. Lack of effective treatment to breast cancer brain metastases (BCBMs) is probably due to inability of the current therapeutic agents to cross the blood-brain barrier. The central nervous system (CNS) response rate in BCBM patients was reported to improve from 2.6%-6% (lapatinib) to 20%-65% (lapatinib in combination with capecitabine). Lapatinib is a poor brain penetrant. In this study, we evaluated the CNS penetration of capecitabine and hoped to interpret the mechanism of the improved CNS response from the pharmacokinetic (PK) perspective. Capecitabine does not have antiproliferative activity and 5-fluorouracil (5-FU) is the active metabolite. Capecitabine was orally administered to mouse returning an unbound brain-to-blood ratio (Kp,uu,brain) at 0.13 and cerebrospinal fluid (CSF)-to-unbound blood ratio (Kp,uu,CSF) at 0.29 for 5-FU. Neither free brain nor CSF concentration of 5-FU can achieve antiproliferative concentration for 50% of maximal inhibition of cell proliferation of 4.57 µM. BCBM mice were treated with capecitabine monotherapy or in combination with lapatinib. The Kp,uu,brain value of 5-FU increased to 0.17 in the brain tumor in the presence of lapatinib, which is still far below unity. The calculated free concentration of 5-FU and lapatinib in the brain tumor did not reach the antiproliferative potency and neither treatment showed antitumor activity in the BCBM mice. The CNS penetration of 5-FU in human was predicted based on the penetration in preclinical brain tumor, CSF, and human PK and the predicted free CNS concentration was below the antiproliferative potency. These results suggest that CNS penetration of 5-FU and lapatinib are not desirable and development of a true CNS penetrable therapeutic agent will further improve the response rate for BCBM.

  18. The role of MMP-1 in breast cancer growth and metastasis to the brain in a xenograft model

    Directory of Open Access Journals (Sweden)

    Liu Hui

    2012-12-01

    Full Text Available Abstract Background Brain metastasis is an increasingly common complication for breast cancer patients; approximately 15– 30% of breast cancer patients develop brain metastasis. However, relatively little is known about how these metastases form, and what phenotypes are characteristic of cells with brain metastasizing potential. In this study, we show that the targeted knockdown of MMP-1 in breast cancer cells with enhanced brain metastatic ability not only reduced primary tumor growth, but also significantly inhibited brain metastasis. Methods Two variants of the MDA-MB-231 human breast cancer cell line selected for enhanced ability to form brain metastases in nude mice (231-BR and 231-BR3 cells were found to express high levels of matrix metalloproteinase-1 (MMP-1. Short hairpin RNA-mediated stable knockdown of MMP-1 in 231-BR and 231-BR3 cells were established to analyze tumorigenic ability and metastatic ability. Results Short hairpin RNA-mediated stable knockdown of MMP-1 inhibited the invasive ability of MDA-MB 231 variant cells in vitro, and inhibited breast cancer growth when the cells were injected into the mammary fat pad of nude mice. Reduction of MMP-1 expression significantly attenuated brain metastasis and lung metastasis formation following injection of cells into the left ventricle of the heart and tail vein, respectively. There were significantly fewer proliferating cells in brain metastases of cells with reduced MMP-1 expression. Furthermore, reduced MMP-1 expression was associated with decreased TGFα release and phospho-EGFR expression in 231-BR and BR3 cells. Conclusions Our results show that elevated expression of MMP-1 can promote the local growth and the formation of brain metastases by breast cancer cells.

  19. Impact of CT/MRI Image Registration on Target Delineation of Radiotherapy for Lung Cancer with Brain Metastasis

    Directory of Open Access Journals (Sweden)

    Yang LI

    2012-08-01

    Full Text Available Background and objective Accurate target delineation in radiation therapy is a key component of the treatment regimen for brain metastasis for which CT/MRI fusion technology provides a feasible method. The aim of this study is to explore the role of CT/MRI image registration in target delineation for lung cancer with brain metastasis. Methods The image data of 31 patients were processed using Oncentra MasterPlan. The GTVs were delineated on CT and CT/MRI images, and their differences were compared to analyze the impact of the maximum average error and tumor edema on target delineation. Results The GTVs delineated on CT/MRI images were markedly smaller than those delineated on CT images. Target delineation was clearly influenced by edema. Conclusion The technology of CT/MRI image registration can improve the accuracy of target delineation for lung cancer with brain metastasis.

  20. Multi-platform genome-wide analysis of melanoma progression to brain metastasis

    Directory of Open Access Journals (Sweden)

    Diego M. Marzese

    2014-12-01

    Full Text Available Melanoma has a high tendency to metastasize to brain tissue. The understanding about the molecular alterations of early-stage melanoma progression to brain metastasis (MBM is very limited. Identifying MBM-specific genomic and epigenomic alterations is a key initial step in understanding its aggressive nature and identifying specific novel druggable targets. Here, we describe a multi-platform dataset generated with different stages of melanoma progression to MBM. This data includes genome-wide DNA methylation (Illumina HM450K BeadChip, gene expression (Affymetrix HuEx 1.0 ST array, single nucleotide polymorphisms (SNPs and copy number variation (CNV; Affymetrix SNP 6.0 array analyses of melanocyte cells (MNCs, primary melanoma tumors (PRMs, lymph node metastases (LNMs and MBMs. The analysis of this data has been reported in our recently published study (Marzese et al., 2014.

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

    Energy Technology Data Exchange (ETDEWEB)

    Koo, Tae Ryool [Dept. of Radiation Oncology, Hallym University Chuncheon Sacred Heart Hospital, Chuncheon (Korea, Republic of); Kim, In Ah [Dept. of Radiation Oncology, Seoul National University Bundang Hospital, Seongnam (Korea, Republic of)

    2016-03-15

    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.

  2. Clinical Significance of KISS1 Protein Expression for Brain Invasion and Metastasis

    Science.gov (United States)

    Ulasov, Ilya V.; Kaverina, Natalya V.; Pytel, Peter; Thaci, Bart; Liu, FeiFei; Hurst, Douglas R.; Welch, Danny R.; Sattar, Husein A.; Olopade, Olufunmilayo I.; Baryshnikov, Anatoly Y.; Kadagidze, Zaira G.; Lesniak, Maciej S.

    2013-01-01

    BACKGROUND Metastases to the brain represent a feared complication and contribute to the morbidity and mortality of breast cancer. Despite improvements in therapy, prognostic factors for development of metastases are lacking. KISS1 is a metastasis suppressor that demonstrates inhibition of metastases formation in several types of cancer. The purpose of this study was to determine the importance of KISS1 expression in breast cancer progression and the development of intracerebral lesions. METHODS In this study, we performed a comparative analysis of 47 brain metastases and 165 primary breast cancer specimens by using the antihuman KISS1 antibody. To compare KISS1 expression between different groups, we used a 3-tier score and the automated score computer software (ACIS) evaluation. To reveal association between mRNA and protein expression, we used quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis. Significance of immunohistochemistry stainings was correlated with clinicopathological data. RESULTS We identified that KISS1 expression is significantly higher in primary breast cancer compared with brain metastases (P < .05). The mRNA analysis performed on 33 selected ductal carcinoma brain metastatic lesions and 36 primary ductal carcinomas revealed a statistically significant down-regulation of KISS1 protein in metastatic cases (P = .04). Finally, we observed a significant correlation between expression of KISS1 and metastasis-free survival (P = .04) along with progression of breast cancer and expression of KISS1 in primary breast cancer specimens (P = .044). CONCLUSIONS In conclusion, our study shows that breast cancer expresses KISS1. Cytoplasmic expression of KISS1 may be used as a prognostic marker for increased risk of breast cancer progression. PMID:21928364

  3. Primary monophasic synovial sarcoma lung with brain metastasis diagnosed on transthoracic FNAC: Report of a case with literature review

    Directory of Open Access Journals (Sweden)

    Paras Nuwal

    2012-01-01

    Full Text Available Synovial sarcoma is highly malignant tumor of soft tissues, occurring chiefly in the extremities and limb girdle with a propensity for local recurrence and sometimes metastases to the lungs. Primary synovial sarcoma arising in the lungs is rare and brain metastasis as presentation is further uncommon. We report a case of primary monophasic synovial sarcoma lung presenting with brain metastasis in a 35-year-old male patient. The diagnosis was made on percutaneous transthoracic needle aspiration from left-sided pulmonary mass and later confirmed by immunohistochemistry. The utility of preoperative diagnosis by percutaneous aspiration cytology is also stressed.

  4. Surgery Versus Stereotactic Radiosurgery for Single Synchronous Brain Metastasis from Non-Small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    Hui LI; Sheng-cai HOU; Bin HU; Tong LI; Yang Wang; Jin-bai Miao; Bin You; Yi-li Fu

    2009-01-01

    Objective: The aim of this study is to compare the effectiveness of surgery with stereotactic radiosurgery (SRS) for patients with a single synchronous brain metastasis from successfully treated non-small cell lung cancer.Methods: Between 1995 and 2002, 53 patients underwent resection of both primary non-small cell lung cancer and the associated single brain metastasis. There were 33 men and 20 women with a mean age of 57 years (range, 32(85 years). At the time of diagnosis, 42 patients experienced lung cancer related symptoms, whereas 11 patients experienced brain metastases-related symptoms. 42 patients had received thoracic surgery first, and 11 patients had undergone neurosurgery or radiosurgery first. Pneumonectomy was performed in 9 out of 42 patients (21.4%), lobectomies in 30 (71.4%), and wedge resection in 3 (7.2%). 48 patients (90.5%) underwent complete lymphadenectomy. 35 patients underwent brain metastasectomy. 18 underwent SRS.Results: There was no postoperative mortality and severe complications after either lung or brain surgery. Histology showed 34 adenocarcinomas, 16 squamous cell carcinomas, and 3 large cell lung cancers. 15 patients (28.3%) had no evidence of lymph node metastases (N0), 20 patients (37.7%) had hilar metastases (N1), and 18 patients (34%) had mediastinal metastases (N2). The 1-, 2-, 3- and 5-year overall survival rates were 49%, 19%, 10%, and 5%, respectively. The corresponding data for neurosurgery group were 55%, 17%, 11%, and 6%, respectively. The median survival time was 13 months. For SRS group the corresponding data were 44.8%, 20.9% 10.5%, and 2%, respectively. The median survival time was 14 months. The differences between the two groups were not significant (P>0.05). In lymph node negative patients (N0), the overall 5-year survival rate was 10%, as compared with a 1% survival rate in patients with lymph node metastases (N1(2). The difference was significant (P0.05).Conclusion: Although the overall survival rate for

  5. Growth inhibition in a brain metastasis model by antibody delivery using focused ultrasound-mediated blood-brain barrier disruption.

    Science.gov (United States)

    Kobus, Thiele; Zervantonakis, Ioannis K; Zhang, Yongzhi; McDannold, Nathan J

    2016-09-28

    HER2-targeting antibodies (i.e. trastuzumab and pertuzumab) prolong survival in HER2-positive breast cancer patients with extracranial metastases. However, the response of brain metastases to these drugs is poor, and it is hypothesized that the blood-brain barrier (BBB) limits drug delivery to the brain. We investigated whether we could improve the response by temporary disruption of the BBB using focused ultrasound in combination with microbubbles. To study this, we inoculated 30 nude rats with HER2-positive cells derived from a brain metastasis of a breast cancer patient (MDA-MB-361). The animals were divided into three groups: a control-group that received no treatment; an antibody-only group that received six weekly treatments of trastuzumab and pertuzumab; and an ultrasound+antibody group that received trastuzumab and pertuzumab in combination with six weekly sessions of BBB disruption using focused ultrasound. In two animals, the leakiness of the tumors before disruption was evaluated using contrast-enhanced T1-weighted magnetic resonance imaging and found that the tumors were not leaky. The same technique was used to evaluate the effectiveness of BBB disruption, which was successful in all sessions. The tumor in the control animals grew exponentially with a growth constant of 0.042±0.011mm(3)/day. None of the antibody-only animals responded to the treatment and the growth constant was 0.033±0.009mm(3)/day during the treatment period. Four of the ten animals in the ultrasound+antibody-group showed a response to the treatment with an average growth constant of 0.010±0.007mm(3)/day, compared to a growth constant 0.043±0.013mm(3)/day for the six non-responders. After the treatment period, the tumors in all groups grew at similar rates. As the tumors were not leaky before BBB disruption and there were no responders in the antibody-only group, these results show that at least in some cases disruption of the BBB is necessary for a response to the antibodies in

  6. Management of brain metastasis in a patient with advanced epithelial ovarian carcinoma by gamma-knife radiosurgery

    Directory of Open Access Journals (Sweden)

    Nikolaou Marinos

    2015-01-01

    Full Text Available Introduction. Brain metastases from epithelial ovarian cancer (EOC are rare events. We present a rare case of single ovarian cancer metastasis to the brain treated with gamma-knife radiosurgery (GKRS. Case Outline. A 65-year-old woman with advanced EOC presented with severe neurologic symptoms. A single brain metastasis of 3.2 cm with surrounding edema in the left parietal lobe was detected by brain magnetic resonance imaging (MRI scan during the work-up. The decision to perform GKRS was due to a surgical inaccessibility of intracranial lesion. Twelve weeks after the procedure, the MRI scan showed reduction in the diameter of brain metastasis and surrounding edema and the patient returned to good mental and motor performance. The patient survived for 22 months following treatment and died from a progressive intra-abdominal disease. Prognosis of ovarian cancer patients with brain metastases is generally poor regardless of treatment. Conclusion. Our case shows that GKRS as primary treatment modality for the control of ovarian cancer metastases to the brain was effective and can be considered as a treatment of choice if international selection criteria are followed.

  7. Prognostic factors to predict survival in non-small-cell lung cancer with brain metastasis

    Institute of Scientific and Technical Information of China (English)

    Tiantian Li; Xuezhen Ma; Yuan Yao

    2014-01-01

    Objective:The purpose of the study was to assess prognostic factors to predict overal survival (OS) and progres-sion-free survival (PFS) in non-smal-celllung cancer (NSCLC) with brain metastasis (BM). Methods:From November 2011 to March 2013, the clinical data of 31 NSCLC cases with BM treated with multiple modalities including brain radiotherapy alone, systemic chemotherapy, whole brain radiotherapy (WBRT) combined with tyrosine kinase inhibitor (TKIs). The ef icacy and adverse reaction were evaluated after treatment. Results:In terms of intracranial lesions, the objective response rate (ORR) and the disease control rate (DCR) were 22.6%and 90.3%, respectively. As for systemic disease, ORR and DCR were 32.3%and 93.5%, respectively. The median time to progression-free survival (PFS) was 298 days (95%CI:258.624-337.376 days), whereas in the epidermal growth factor receptor (EGFR) mutation patients was 331 days. Patients who received EGFR-TKIs combined with brain radiation had better response rate (RR) than those only brain radiation. Univariate analysis showed that the EGFR-mutations could predictive factors for PFS, and not to other clinical pathological features. The most common toxici-ties were rash and diarrhea, but al were wel-tolerated. Conclusion:EGFR-mutations is the independent prognostic factors af ecting the survival rates of NSCLC patients with BM. Through the clinical observation, icotinib combined with WBRT may be ef ective on brain metastases in NSCLC patients, and toxicities are tolerable, which worth further study.

  8. Peptic ulcer disease and other complications in patients receiving dexamethasone palliation for brain metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Penzner, R.D.; Lipsett, J.A.

    1982-11-01

    A retrospective analysis was done of 106 patients who received radiation therapy for brain metastasis. Dexamethasone therapy was instituted in 97 patients. Peptic ulcer disease developed in 5 of 89 patients (5.6 percent) who received a dosage of at least 12 mg a day, but did not occur in patients who received a lower dose or in those who did not receive steroids. The interval between institution of dexamethasone therapy and the development of peptic ulcer disease ranged from three to nine weeks. Two patients had perforated ulcers, one of whom required surgical resection. Peptic ulcer disease contributed to the general deterioration and death of three of the five patients. Overall, in 14 of the 89 patients (15.7 percent) a complication of steroid therapy developed in the form of peptic ulcer disease, steroid myopathy or diabetes mellitus (or a combination of these).

  9. Solitary epidural brain metastasis of Neuroepithelioma (a Primitive Neuroectodermal Tumor: case report

    Directory of Open Access Journals (Sweden)

    Farnaz Farshidfar

    2008-08-01

    Full Text Available A 14 years old male was referred to Computerized tomography scan (CT of our hospital for evaluation of headache. The patient was known case of cervical soft tissue Primitive neuroectodermal tumor (PNET which has undergone surgery and radiotherapy 4 years ago. The CT scan showed large solitary extra axial, epidural lesion in right parietal region, with mass effect and bony involvement. Then surgery was done for him and the resultant biopsy was Neuroepithelioma. After diagnosis the patient has undergone chemotherapy and radiotherapy. He has no signs or symptoms of malignancy, and also follow up CT scan of the brain, chest, and abdomen were normal after two years of surgery. This is the first reported case of epidural metastasis of a head and neck PNET in an adolescent.

  10. Brain Metastasis in Bone and Soft Tissue Cancers: A Review of Incidence, Interventions, and Outcomes

    Directory of Open Access Journals (Sweden)

    Faris Shweikeh

    2014-01-01

    Full Text Available Bone and soft tissue malignancies account for a small portion of brain metastases. In this review, we characterize their incidence, treatments, and prognosis. Most of the data in the literature is based on case reports and small case series. Less than 5% of brain metastases are from bone and soft tissue sarcomas, occurring most commonly in Ewing’s sarcoma, malignant fibrous tumors, and osteosarcoma. Mean interval from initial cancer diagnosis to brain metastasis is in the range of 20–30 months, with most being detected before 24 months (osteosarcoma, Ewing sarcoma, chordoma, angiosarcoma, and rhabdomyosarcoma, some at 24–36 months (malignant fibrous tumors, malignant peripheral nerve sheath tumors, and alveolar soft part sarcoma, and a few after 36 months (chondrosarcoma and liposarcoma. Overall mean survival ranges between 7 and 16 months, with the majority surviving < 12 months (Ewing’s sarcoma, liposarcoma, malignant fibrous tumors, malignant peripheral nerve sheath tumors, angiosarcoma and chordomas. Management is heterogeneous involving surgery, radiosurgery, radiotherapy, and chemotherapy. While a survival advantage may exist for those given aggressive treatment involving surgical resection, such patients tended to have a favorable preoperative performance status and minimal systemic disease.

  11. Prognostic predictors for non-small cell lung cancer patients with brain metastasis after radiotherapy

    Directory of Open Access Journals (Sweden)

    Qiuhong FAN

    2008-06-01

    Full Text Available Background and objective Brain metastasis (BM is often found in the patients with lung cancer. Radiotherapy is regular and effective means of therapy and it aims at palliating symptoms and prolonging survival time. However, now there are different viewpoints on protocols of radiotherapy and prognostic factors. A retrospective analysis is used to evaluate the results of treatment for 82 cases with brain metastasis from non-small cell lung cancer (NSCLC and explore the prognostic factors to establish a prognostic index (PI model. Methods From Feb.1995 to Oct. 2006, 82 patients irradiated for BM from NSCLC, with both complete medical charts and follow-up data available, were eligible for this retrospective analysis. A number of potential factors which might affect prognosis after irradiation were evaluated. The significance of prognostic variables in the survival resulted from both univariate analysis by Kaplan-Meier combining with log-rank test and multivariate Cox regression model. The prognostic index (PI was established based on Cox regression analysis and subgrouping values. Results The follow-up time was 1-120 months. For the entire cohort, the median survival from the start of radiation for BM was 10.5 months, and the actuarial overall survival rate was 50.8%, 23.7% and 5.1% at 0.5, 1 and 2 years respectively. Univariate analysis showed KPS, control of primary tumor, interval from the beginning of diagnostic to BM, extracranial systemic metastasis, counts of lymphocyte and solitary BM were predictors of prognosis. However, in the Cox multivariate analysis, only KPS, control of primary tumor, interval from the beginning of diagnostic to BM and solitary BM were significant prognostic factors. The prognostic index was established based on Cox regression analysis and 82 patients were stratified good, intermediate and poor prognostic sub-groups. The difference of survival rate among 3 subgroups is significant (P<0.001. Conclusion Radiotherapy is

  12. Deploying swarm intelligence in medical imaging identifying metastasis, micro-calcifications and brain image segmentation.

    Science.gov (United States)

    al-Rifaie, Mohammad Majid; Aber, Ahmed; Hemanth, Duraiswamy Jude

    2015-12-01

    This study proposes an umbrella deployment of swarm intelligence algorithm, such as stochastic diffusion search for medical imaging applications. After summarising the results of some previous works which shows how the algorithm assists in the identification of metastasis in bone scans and microcalcifications on mammographs, for the first time, the use of the algorithm in assessing the CT images of the aorta is demonstrated along with its performance in detecting the nasogastric tube in chest X-ray. The swarm intelligence algorithm presented in this study is adapted to address these particular tasks and its functionality is investigated by running the swarms on sample CT images and X-rays whose status have been determined by senior radiologists. In addition, a hybrid swarm intelligence-learning vector quantisation (LVQ) approach is proposed in the context of magnetic resonance (MR) brain image segmentation. The particle swarm optimisation is used to train the LVQ which eliminates the iteration-dependent nature of LVQ. The proposed methodology is used to detect the tumour regions in the abnormal MR brain images.

  13. Brain metastasis from cutaneous squamous cell carcinoma of the dorsum. Case report.

    Science.gov (United States)

    Salvati, Maurizio; Caroli, Emanuela; Paone, Cristina; Frati, Alessandro; Ferrante, Luigi; Giangaspero, Felice; Delfini, Roberto

    2005-06-01

    The majority of cutaneous squamous cell carcinoma (SCC) are diagnosed early and cured using local treatment, although a minority of cases metastasize to regional structures. In this report the authors describe an unknown feature of skin SCC, namely, distant brain metastasis. This 54-year-old man, who had undergone surgery for moderately differentiated SCC of the dorsum (T2NOM0 stage), was admitted to our institution 11 months later with headache, vomiting, and ataxia. A magnetic resonance image documented a cerebellar lesion, which was totally removed. Results of histological studies revealed SCC. The patient received whole-brain radiotherapy (30 Gy over 2 weeks using a linear accelerator). A metastatic work-up showed enlarged inguinal and para-aortic lymph nodes that were histologically examined using excisional biopsy. Inguinal lymph nodes were tumor-positive and were dissected. The patient was subjected to two cycles of chemotherapy with cisplatin (75 mg/m2). After 3 months, a significant reduction in the size of the para-aortic lymph nodes was documented on control computerized tomography studies. Although the described case is unique, knowledge of the potential for this uncommon behavior in cutaneous SCC may be useful, especially because of its increasing incidence.

  14. MRI diagnosis of solitary brain metastasis%单发脑转移瘤的MRI诊断

    Institute of Scientific and Technical Information of China (English)

    许思祥

    2015-01-01

    目的::探讨单发脑转移瘤( solitary brain metastasis,SBM)的MRI表现,提高对其诊断的准确性。方法:回顾性分析经临床综合确诊的38例SBM的MRI平扫及增强表现,分析病灶的部位、大小、瘤周水肿程度和瘤体的强化特点。结果:本组38例SBM中,发生于幕上31例,其中位于脑皮质和皮质下区28例;幕下7例。瘤体直径3.0cm 7例。增强扫描所有病灶均出现强化,其中结节型强化19例,环型强化11例,混合型强化8例。瘤周无水肿7例,轻度水肿11例,中度水肿13例,重度水肿7例。结论:SBM的MRI表现具有一定的特征性,MRI增强扫描对其诊断和鉴别诊断具有重要价值。%Objective:To evaluate the MRI performance of solitary brain metastasis( SBM) ,and to improve the di-agnostic and differential diagnosis accuracy of SBM. Methods:Retrospectively review the MRI scan and enhanced scan of 38 cases of SBM by clinical comprehensive diagnosis. Analyze the location of tumor,size,peritumoral edema as well as findings after contrast enhancement. Results:In 38 cases,31 lesions were located at supratentorial regions,in which 28 tumors were located in cortex and subcortex. Seven lesions located at infratentorial regions. The diameter was less than 1. 0 cm in 12 cases,between 1. 0 cm to 3. 0 cm in 19 cases,and larger than 3 cm in 7 cases. All lesions showed enhancement,among which nodular enhancement was in 19 lesions,ring-like enhancement in 11 lesions,and mixed-shape enhancement in 8 lesions. Seven cases had no peritumoral edema,11 cases with mild edema,13 cases with moderate edema,and 7 cases with severe edema. Conclusion:The MRI performance of SBM had certain charac-teristics,and MRI enhanced scan had important value for the diagnosis and differential diagnosis of SBM.

  15. The relevance of serum carcinoembryonic antigen as an indicator of brain metastasis detection in advanced non-small cell lung cancer.

    Science.gov (United States)

    Lee, Dong-Soo; Kim, Yeon-Sil; Jung, So-Lyoung; Lee, Kyo-Young; Kang, Jin-Hyoung; Park, Sarah; Kim, Young-Kyoon; Yoo, Ie-Ryung; Choi, Byung-Ock; Jang, Hong-Seok; Yoon, Sei-Chul

    2012-08-01

    Although many biomarkers have emerged in non-small cell lung cancer (NSCLC), the predictive value of site-specific spread is not fully defined. We designed this study to determine if there is an association between serum biomarkers and brain metastasis in advanced NSCLC. We evaluated 227 eligible advanced NSCLC patients between May 2005 and March 2010. Patients who had been newly diagnosed with stage IV NSCLC but had not received treatment previously, and had available information on at least one of the following pretreatment serum biomarkers were enrolled: carcinoembryonic antigen (CEA), cytokeratin 19 fragments (CYFRA 21-1), cancer antigen 125 (CA 125), cancer antigen 19-9, and squamous cancer cell antigen. Whole body imaging studies and magnetic resonance imaging of the brain were reviewed, and the total number of metastatic regions was scored. Brain metastasis was detected in 66 (29.1%) patients. Although serum CEA, CYFRA 21-1, and CA 125 levels were significantly different between low total metastatic score group (score 1-3) and high total metastatic score group (score 4-7), only CEA level was significantly different between patients with brain metastasis and those without brain metastasis (p present study demonstrated that the pretreatment serum CEA level was significantly correlated with brain metastasis in advanced NSCLC. These findings suggested the possible role of CEA in the pathogenesis of brain invasion. More vigilant surveillance would be warranted in the high-risk group of patients with high serum CEA level and multiple synchronous metastasis.

  16. Serum S100B, lactate dehydrogenase and brain metastasis are prognostic factors in patients with distant melanoma metastasis and systemic therapy.

    Directory of Open Access Journals (Sweden)

    Benjamin Weide

    Full Text Available BACKGROUND: Prognostic factors of melanoma with distant metastasis and systemic treatment are only poorly established. This study aimed to analyse the impact of S100B, lactate dehydrogenase (LDH and the type of treatment on survival in advanced patients receiving systemic treatment. PATIENTS AND METHODS: We analysed overall survival of 499 patients from the university department of dermatology in Tuebingen, Germany, with unresectable melanoma at the time point of initiation of first-line systemic therapy. Only patients who started treatment between the years 2000 and 2010 were included. Disease-specific survival was calculated by bivariate Kaplan Meier survival probabilities and multivariate Cox hazard regression analysis. RESULTS: In univariate analysis LDH, S100B, the site of distant metastasis (soft tissue vs. lung vs. other visceral, the presence of brain metastases and the type of treatment (monochemotherapy, polychemotherapy, immunotherapy or biochemotherapy were associated with overall survival (all p<0.001. In multivariate analysis LDH (Hazard ratio [HR] 1.6 [1.3-2.1]; p<0.001, S100B (HR 1.6 [1.2-2.1]; p<0.001 and the presence of brain metastases (HR 1.5 [1.1-1.9]; p = 0.009, but not the type of treatment had significant independent impact. Among those factors normal S100B was the best indicator of long-term survival, which was 12.3% after 5 years for this subgroup. CONCLUSION: Serum S100B is a prognostic marker predicting survival at the time of initiation of first-line treatment in unresectable melanoma patients. Compared to the other independent factors LDH and the presence of brain metastases it is most appropriate to predict long-term survival and requires further prospective investigation in patients treated with new and more potent drugs in metastatic melanoma.

  17. Crizotinib Treatment Combined with Resection and Whole-brain Radiation Therapy 
in A ROS1 Rearranged Lung Adenocarcinoma with Brain Metastasis: 
Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Min ZHANG

    2016-08-01

    Full Text Available Background and objective Lung cancer with brain metastasis had poor prognosis. Crizotinib had been confirmed to be used in ROS1 (C-ros oncogene 1 receptor tyrosine kinase rearranged lung adenocarcinoma, but its efficacy in lung cancer with brain metastasis was poor due to the blood brain barrier. In the present study, we reported one case of ROS1 fusion lung adenocarcinoma with symptomatic brain matastasis, who was treated with brain metastases resection, crizotinib, and whole brain radiotherapy plus boost to residual brain metastasis. The safety and efficacy was summarized. Methods At first, surgical resection was used to relive mass effect and to biopsy. Then crizotinib (250 mg, bid was chosen for the existence of ROS1 fusion gene. Whole brain radiotherapy plus boost to residual brain metastasis were used after surgery. Objective response was evaluated by Response Evaluation Criteriation in Solid Tumours (RECIST v1.1 and brain metastasis were evaluated by computer tomography (CT/magnetic resonance imaging (MRI image. Adverse events were evaluated according to Common Terminology Criteria for Adverse Events (CTC AE v4.0. Results After taking crizotinib for 3 months, the lung lesions were close to complete response (CR, the brain metastasis were partial response (PR, the abdomen metastasis were CR and the symptom of blurred vision relieved. Conclusion Crizotinib combined with palliative operation and radiation therapy (WBRT plus boost to residual brain metastasis in the treatment of ROS1 fusion gene positive lung adenocarcinoma with symptomatic brain metastases, can effectively control intracranial lesions with good tolerance.

  18. Integrating Structure to Protein-Protein Interaction Networks That Drive Metastasis to Brain and Lung in Breast Cancer

    OpenAIRE

    H Billur Engin; Emre Guney; Ozlem Keskin; Baldo Oliva; Attila Gursoy

    2013-01-01

    Integrating Structure to Protein-Protein Interaction Networks That Drive Metastasis to Brain and Lung in Breast Cancer H. Billur Engin1, Emre Guney2, Ozlem Keskin1, Baldo Oliva2, Attila Gursoy1* 1 Center for Computational Biology and Bioinformatics and College of Engineering, Koc University, Istanbul, Turkey, 2 Structural Bioinformatics Group (GRIB), Universitat Pompeu Fabra Abstract Blocking specific protein interactions can lead to human diseases. Accordingly, protein i...

  19. Prognostic factors and survival of patients with brain metastasis from breast cancer who underwent craniotomy.

    Science.gov (United States)

    Leone, José Pablo; Lee, Adrian V; Brufsky, Adam M

    2015-07-01

    Brain metastasis (BM) in patients with breast cancer is a catastrophic event that results in poor prognosis. Identification of prognostic factors associated with breast cancer brain metastases (BCBM) could help to identify patients at risk. The aim of this study was to assess clinical characteristics, prognostic factors, and survival of patients with BCBM who had craniotomy and resection in a series of patients treated with modern multimodality therapy. We analyzed 42 patients with BCBM who underwent resection. Patients were diagnosed with breast cancer between April 1994 and May 2010. Cox proportional hazards regression was selected to describe factors associated with time to BM, survival from the date of first recurrence, and overall survival (OS). Median age was 51 years (range 24-74). Median follow-up was 4.2 years (range 0.6-18.5). The proportion of the biological subtypes of breast cancer was ER+/HER2- 25%, ER+/HER2+ 15%, ER-/HER2+ 30%, and ER-/HER2- 30%. Median OS from the date of primary diagnosis was 5.74 years. Median survival after diagnosis of BM was 1.33 years. In multivariate Cox regression analyses, stage was the only factor associated with shorter time to the development of BM (P = 0.033), whereas age was the only factor associated with survival from the date of recurrence (P = 0.027) and with OS (P = 0.037). Stage at primary diagnosis correlated with shorter time to the development of BM, while age at diagnosis was associated with shorter survival in BCBM. None of the other clinical factors had influence on survival.

  20. Optical pathology of human brain metastasis of lung cancer using combined resonance Raman and spatial frequency spectroscopies

    Science.gov (United States)

    Zhou, Yan; Liu, Cheng-hui; Pu, Yang; Cheng, Gangge; Zhou, Lixin; Chen, Jun; Zhu, Ke; Alfano, Robert R.

    2016-03-01

    Raman spectroscopy has become widely used for diagnostic purpose of breast, lung and brain cancers. This report introduced a new approach based on spatial frequency spectra analysis of the underlying tissue structure at different stages of brain tumor. Combined spatial frequency spectroscopy (SFS), Resonance Raman (RR) spectroscopic method is used to discriminate human brain metastasis of lung cancer from normal tissues for the first time. A total number of thirty-one label-free micrographic images of normal and metastatic brain cancer tissues obtained from a confocal micro- Raman spectroscopic system synchronously with examined RR spectra of the corresponding samples were collected from the identical site of tissue. The difference of the randomness of tissue structures between the micrograph images of metastatic brain tumor tissues and normal tissues can be recognized by analyzing spatial frequency. By fitting the distribution of the spatial frequency spectra of human brain tissues as a Gaussian function, the standard deviation, σ, can be obtained, which was used to generate a criterion to differentiate human brain cancerous tissues from the normal ones using Support Vector Machine (SVM) classifier. This SFS-SVM analysis on micrograph images presents good results with sensitivity (85%), specificity (75%) in comparison with gold standard reports of pathology and immunology. The dual-modal advantages of SFS combined with RR spectroscopy method may open a new way in the neuropathology applications.

  1. Evaluating the significance of density, localization, and PD-1/PD-L1 immunopositivity of mononuclear cells in the clinical course of lung adenocarcinoma patients with brain metastasis

    DEFF Research Database (Denmark)

    Téglási, Vanda; Reiniger, Lilla; Fabian, Katalin

    2017-01-01

    therapeutic strategies with these agents. The aim of this study was to characterize the distribution of ICs and determine the expression of the checkpoint molecules programmed death protein 1 (PD-1) and its ligand, PD-L1, in brain metastasis of lung adenocarcinoma (LUAD) patients and to analyze......Background. Management of lung cancer patients who suffer from brain metastases represents a major challenge. Considering the promising results with immune checkpoint inhibitor treatment, evaluating the status of immune cell (IC) infiltrates in the prognosis of brain metastasis may lead to better...... their clinicopathological correlations. Methods. We determined the presence of peritumoral mononuclear cells (mononuclear ring) and the density of intratumoral stromal mononuclear cells on brain metastasis tissue sections of 208 LUAD patients. PD-L1/PD-1 expressions were analyzed by immunohistochemistry. Results...

  2. Nosocomial infection in patients with brain metastasis%脑转移瘤患者医院感染分析

    Institute of Scientific and Technical Information of China (English)

    丁维军; 杨伟芳; 于长辉

    2012-01-01

    目的 探讨脑转移瘤患者医院感染的相关因素.方法 回顾性分析510例脑转移瘤患者医院感染的临床资料.结果 78例患者并发医院感染,感染率为15.3%;其中呼吸道感染53例,占67.9%.结论 脑转移瘤患者年龄大、血糖增高、留置导尿易导致医院感染,必须加强医院感染的管理,积极控制血糖,减少留置导尿,规范抗菌药物的应用,减少医院感染的发生.%OBJECTIVE To analyze the clinical features of nosocomial infection in patients with brain metastasis. METHODS The clinical data of 510 brain metastasis tumor patients were retrospectively analyzed. RESULTS Nosocomial infection occurred in 78 patients with the infection rate of 15. 3%. The respiratory infection was the major infection which accounting for 67. 9%. CONCLUSION The incidence of nosocomial infection in brain metastasis patients is high. The elder age, hyperglycemia, and indwelling catheterization are important risk factors for nosocomial infection. To reduce the occurrence of nosocomial infection, the following strategies need to be strengthened including treating hyperglycemia with standard care, reducing indwelling caterterization and rationally using the antibiotics.

  3. Lapatinib-loaded human serum albumin nanoparticles for the prevention and treatment of triple-negative breast cancer metastasis to the brain

    Science.gov (United States)

    Wan, Xu; Zheng, Xiaoyao; Pang, Xiaoyin; Pang, Zhiqing; Zhao, Jingjing; Zhang, Zheming; Jiang, Tao; Xu, Wei; Zhang, Qizhi; Jiang, Xinguo

    2016-01-01

    Brain metastasis from triple-negative breast cancer (TNBC) has continued to lack effective clinical treatments until present. However, the feature of epidermal growth factor receptor (EGFR) frequently overexpressed in TNBC offers the opportunity to employ lapatinib, a dual-tyrosine kinase inhibitor of human epidermal growth factor receptor-2 (HER2) and EGFR, in the treatment of brain metastasis of TNBC. Unfortunately, the low oral bioavailability of lapatinib and drug efflux by blood-brain barrier have resulted in low drug delivery efficiency into the brain and limited therapeutic effects for patients with brain metastasis in clinical trials. To overcome such disadvantages, we developed lapatinib-loaded human serum albumin (HSA) nanoparticles, named LHNPs, by modified nanoparticle albumin-bound (Nab) technology. LHNPs had a core-shell structure and the new HSA/phosphatidylcholine sheath made LHNPs stable in bloodstream. Compared to free lapatinib, LHNPs could inhibit the adhesion, migration and invasion ability of high brain-metastatic 4T1 cells more effectively in vitro. Tissue distribution following intravenous administration revealed that LHNPs (i.v., 10 mg/kg) achieved increased delivery to the metastatic brain at 5.43 and 4.36 times the levels of Tykerb (p.o., 100 mg/kg) and lapatinib solution (LS, i.v., 10 mg/kg), respectively. Compared to the marketed Tykerb group, LHNPs had markedly better inhibition effects on brain micrometastasis and significantly extended the median survival time of 4T1 brain metastatic mice in consequence. The improved anti-tumor efficacy of LHNPs could be partly ascribed to down-regulating metastasis-related proteins. Therefore, these results clearly indicated that LHNPs could become a promising candidate for clinical applications against brain metastasis of TNBC. PMID:27086917

  4. The role of postoperative radiotherapy after resection of a single brain metastasis. Combined analysis of 643 patients

    Energy Technology Data Exchange (ETDEWEB)

    Nieder, C. [Nordlandssykehuset HF, Bodo (Norway). Radiation Oncology Unit; Astner, S.T.; Andratschke, N.H.; Molls, M. [Klinikum rechts der Isar, Munich (Germany). Dept. of Radiation Oncology; Grosu, A.L. [Universitaetsklinikum Freiburg (Germany). Klinik fuer Strahlenheilkunde

    2007-10-15

    Background and Purpose: The extent of treatment in patients with single brain metastasis is a controversial topic. Especially the issue of whole-brain radiotherapy (WBRT) after local treatment of the lesion is largely unresolved. Therefore, the authors performed a pooled analysis of all available clinical data, based on a comprehensive literature search and on prospectively defined inclusion criteria and endpoints (in particular local brain control at the original site and development of new brain metastases). Material and Methods: Overall, 643 patients from ten publications met the inclusion criteria. 106 patients were treated with surgery alone, 66 with surgery plus local radiotherapy, and the others with surgery plus WBRT. Results: Both types of additional radiotherapy significantly improved local control at the original site (relative risk of local failure < 0.5). WBRT also reduced new lesions significantly (relative risk 0.6). Within the available range of doses, no significant dose-response relationship was observed. Even after WBRT, new lesions remained the predominant type of brain failure. One of the underlying causes might be continuous reseeding of cells from active extracranial sites. Toxicity and quality of life were not well described in the publications. Conclusion: The present data favor moderate-dose WBRT, but the pros and cons of each option should be discussed with each patient. Higher radiation doses or local boost treatment are not supported by these data, but might be considered under certain circumstances, e.g., after incomplete resection. (orig.)

  5. SU-E-T-306: Dosimetric Comparison of Leaf with Or Without Interdigitation in Multiple Brain Metastasis VMAT Treatment Planning

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2015-06-15

    Purpose: To evaluate the effects of leaf with or without interdigitation in multiple brain metastasis volumetric modulated arc therapy (VMAT) plans. Methods: Twenty patients with 2 to 6 brain metastases of our hospital were retrospectively studied to be planned with dual arc VMAT using Monaco 3.3 TPS on the Elekta Synergy linear accelerator. The prescription dose of PTV was 60Gy/30 fractions. Two plans with or without leaf interdigitation were designed. The homogeneity index (HI), conformity index (CI), dose volume histograms (DVHs), monitor unit (MU), treatment time (T), the segments, the dose coverage of the target, were all evaluated. Results: The plans with leaf interdigitation could achieve better CI (p<0.05) than without leaf interdigitation, while no significant difference were found in HI (p> 0.05) and the dose coverage of the target (p> 0.05).The MU,T, and the segments of the plan with leaf interdigitation were more than the plan without leaf interdigitation (p<0.05). There was no significant difference found in radiation dose of spinal cord, lenses and parotids, while the maximum dose of brain stem of leaf without interdigitation was higher than leaf with interdigitation (p< 0.05). It was worth noting that the areas of low dose regions with leaf interdigitation plan were much less than the without leaf interdigitation plan in the doublication planes (p< 0.05). Conclusion: This study shows that leaf with interdigitation has some advantages than leaf without interdigitation in multiple brain metastasis VMAT plans although the clinical relevance remains to be proven.

  6. In Vitro Treatment of Melanoma Brain Metastasis by Simultaneously Targeting the MAPK and PI3K Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Inderjit Daphu

    2014-05-01

    Full Text Available Malignant melanoma is the most lethal form of skin cancer, with a high propensity to metastasize to the brain. More than 60% of melanomas have the BRAFV600E mutation, which activates the mitogen-activated protein kinase (MAPK pathway [1]. In addition, increased PI3K (phosphoinositide 3-kinase pathway activity has been demonstrated, through the loss of activity of the tumor suppressor gene, PTEN [2]. Here, we treated two melanoma brain metastasis cell lines, H1_DL2, harboring a BRAFV600E mutation and PTEN loss, and H3, harboring WT (wild-type BRAF and PTEN loss, with the MAPK (BRAF inhibitor vemurafenib and the PI3K pathway associated mTOR inhibitor temsirolimus. Combined use of the drugs inhibited tumor cell growth and proliferation in vitro in H1_DL2 cells, compared to single drug treatment. Treatment was less effective in the H3 cells. Furthermore, a strong inhibitory effect on the viability of H1_DL2 cells, when grown as 3D multicellular spheroids, was seen. The treatment inhibited the expression of pERK1/2 and reduced the expression of pAKT and p-mTOR in H1_DL2 cells, confirming that the MAPK and PI3K pathways were inhibited after drug treatment. Microarray experiments followed by principal component analysis (PCA mapping showed distinct gene clustering after treatment, and cell cycle checkpoint regulators were affected. Global gene analysis indicated that functions related to cell survival and invasion were influenced by combined treatment. In conclusion, we demonstrate for the first time that combined therapy with vemurafenib and temsirolimus is effective on melanoma brain metastasis cells in vitro. The presented results highlight the potential of combined treatment to overcome treatment resistance that may develop after vemurafenib treatment of melanomas.

  7. Hepatocellular carcinoma metastasis to the brain mimicking primary pituitary tumor around the sella turcica.

    Science.gov (United States)

    Tamura, Tetsuo; Kawamura, Yusuke; Ikeda, Kenji; Seko, Yuya; Fukushima, Taito; Kumada, Hiromitu; Yamada, Shozo; Matumaru, Yuji

    2013-08-01

    We report on two cases of hepatocellular carcinoma (HCC) with metastasis to the cavernous sinus and sphenoid sinus. Both cases presented with diplopia and retro-orbital headache and both underwent surgery for a primary pituitary gland tumor. After surgery, both cases were diagnosed with metastases from HCC. Case 1 was a 67-year-old male with a history of HCC who was referred to our hospital for pituitary tumor surgery. The tumor appeared to be in the sella turcica and to invade the sphenoid sinus and right cavernous sinus. Transnasal transsphenoidal surgery (TSS) was performed. The tumor was postoperatively diagnosed by histology to be a metastatic pituitary tumor from HCC. Radiotherapy was administered to the metastatic site. Case 2 was a 58-year-old male with a history of TSS for a pituitary tumor 16 years previously. He was referred to our hospital for TSS for a recurrent pituitary adenoma. TSS was performed twice in 3 months. During a preoperative general examination, HCC and chronic hepatitis B were revealed. TSS was performed initially, followed by arterial infusion chemotherapy. After TSS, the pituitary tumor was diagnosed by histology to be a metastasis from HCC. As with Case 1, radiotherapy was administered to the metastasis. Most tumors in the sella turcica are pituitary adenomas, although some cases of metastatic pituitary tumors and skull base metastases have been reported. Distant metastases generally have a poor prognosis; however, surgery to the metastatic site can effectively control symptoms caused by the metastatic tumor.

  8. Overexpression of adenylate cyclase-associated protein 1 may predict brain metastasis in non-small cell lung cancer.

    Science.gov (United States)

    Xie, Shuan-Shuan; Tan, Min; Lin, Hai-Yan; Xu, Lei; Shen, Chang-Xing; Yuan, Qing; Song, Xiao-Lian; Wang, Chang-Hui

    2015-01-01

    This study was designed to establish a biomarker risk model for predicting brain metastasis (BM) in non-small cell lung cancer (NSCLC). The model comprises 120 cases of NSCLC that were treated and followed up for 4 years. The patients were divided into the BM (n=50) and non-BM (other visceral metastasis and those without recurrence) (n=70) groups. Immunohistochemical and western blot analyses were performed in metastatic tissues of NSCLC. Multivariate regression analysis was performed to correlate the immunoreactive cyclase-associated protein 1 (CAP1) signal with BM. Survival analyses were performed by using the Kaplan-Meier method. CAP1 protein content and immunoreactivity were significantly increased in BM specimens compared to other-metastatic specimens. The survival analysis revealed that CAP1 overexpression was significantly associated with survival (P<0.05). The ROC test suggested that the area under the curve was 73.33% (P<0.001; 95% CI, 63.5-83.2%). When P=0.466, the sensitivity and specificity reached 79.5 and 67.1%, respectively. These findings suggested that CAP1 is involved in the BM of NSCLC, and that elevated levels of CAP1 expression may indicate a poor prognosis for patients with BM. The CAP1 molecular model may be useful in the prediction of the risk of BM in NSCLC.

  9. Development of Magnetic Nanovectors for Treatment and Imaging of Breast Cancer Metastasis to the Brain

    Science.gov (United States)

    2014-10-01

    knockdown the pro metastasis gene MENA) also are conjugated to the NP polymer overcoat. 15. SUBJECT TERMS Nanotechnology , Targeted Therapies...Page 1. Introduction …………………………………………………………. 4 2...11 11. Appendices…………………………………………………………. 14   4   Introduction The aim of this research project is to develop a

  10. Comparison of Clinical Outcomes of Surgery Followed by Local Brain Radiotherapy and Surgery Followed by Whole Brain Radiotherapy in Patients With Single Brain Metastasis: Single-Center Retrospective Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Kenji [Division of Neurosurgery, National Cancer Center Hospital, Tokyo (Japan); Narita, Yoshitaka, E-mail: yonarita@ncc.go.jp [Division of Neurosurgery, National Cancer Center Hospital, Tokyo (Japan); Miyakita, Yasuji; Ohno, Makoto [Division of Neurosurgery, National Cancer Center Hospital, Tokyo (Japan); Sumi, Minako; Mayahara, Hiroshi [Division of Radiation Oncology, National Cancer Center Hospital, Tokyo (Japan); Kayama, Takamasa; Shibui, Soichiro [Division of Neurosurgery, National Cancer Center Hospital, Tokyo (Japan)

    2011-11-15

    Purpose: Data comparing the clinical outcomes of local brain radiotherapy (LBRT) and whole brain RT (WBRT) in patients with a single brain metastasis after tumor removal are limited. Patients and Methods: A retrospective analysis was performed to compare the patterns of treatment failure, cause of death, progression-free survival, median survival time, and Karnofsky performance status for long-term survivors among patients who underwent surgery followed by either LBRT or WBRT between 1990 and 2008 at the National Cancer Center Hospital. Results: A total of 130 consecutive patients were identified. The median progression-free survival period among the patients who received postoperative LBRT (n = 64) and WBRT (n = 66) was 9.7 and 11.5 months, respectively (p = .75). The local recurrence rates (LBRT, 9.4% vs. WBRT, 12.1%) and intracranial new metastasis rate (LBRT, 42.2% vs. WBRT, 33.3%) were similar in each arm. The incidence of leptomeningeal metastasis was also equivalent (LBRT, 9.4% vs. WBRT, 10.6%). The median survival time for the LBRT and WBRT patients was 13.9 and 16.7 months, respectively (p = .88). A neurologic cause of death was noted in 35.6% of the patients in the LBRT group and 36.7% of the WBRT group (p = .99). The Karnofsky performance status at 2 years was comparable between the two groups. Conclusions: The clinical outcomes of LBRT and WBRT were similar. A prospective evaluation is warranted.

  11. The metastasis-promoting S100A4 protein confers neuroprotection in brain injury

    DEFF Research Database (Denmark)

    Dmytriyeva, Oksana; Pankratova, Stanislava; Owczarek, Sylwia

    2012-01-01

    Identification of novel pro-survival factors in the brain is paramount for developing neuroprotective therapies. The multifunctional S100 family proteins have important roles in many human diseases and are also upregulated by brain injury. However, S100 functions in the nervous system remain...... unclear. Here we show that the S100A4 protein, mostly studied in cancer, is overexpressed in the damaged human and rodent brain and released from stressed astrocytes. Genetic deletion of S100A4 exacerbates neuronal loss after brain trauma or excitotoxicity, increasing oxidative cell damage...... and downregulating the neuroprotective protein metallothionein I+II. We identify two neurotrophic motifs in S100A4 and show that these motifs are neuroprotective in animal models of brain trauma. Finally, we find that S100A4 rescues neurons via the Janus kinase/STAT pathway and, partially, the interleukin-10...

  12. Exercise modulates redox-sensitive small GTPase activity in the brain microvasculature in a model of brain metastasis formation.

    Science.gov (United States)

    Wolff, Gretchen; Balke, Jordan E; Andras, Ibolya E; Park, Minseon; Toborek, Michal

    2014-01-01

    Tumor cell extravasation into the brain requires passage through the blood-brain barrier (BBB). There is evidence that exercise can alter the oxidation status of the brain microvasculature and protect against tumor cell invasion into the brain, although the mechanisms are not well understood. In the current study, we focused on the role of microenvironment generated by exercise and metastasizing tumor cells at the levels of brain microvessels, influencing oxidative stress-mediated responses and activation of redox-sensitive small GTPases. Mature male mice were exercised for four weeks using a running wheel with the average voluntary running distance 9.0 ± 0.3 km/day. Mice were then infused with 1.0 × 10(6) D122 (murine Lewis lung carcinoma) cells into the brain microvasculature, and euthanized either 48 hours (in short-term studies) or 2-3 weeks (in long-term studies) post tumor cell administration. A significant increase in the level of reactive oxygen species was observed following 48 hours or 3 weeks of tumor cells growth, which was accompanied by a reduction in MnSOD expression in the exercised mice. Activation of the small GTPase Rho was negatively correlated with running distance in the tumor cell infused mice. Together, these data suggest that exercise may play a significant role during aggressive metastatic invasion, especially at higher intensities in pre-trained individuals.

  13. Exercise modulates redox-sensitive small GTPase activity in the brain microvasculature in a model of brain metastasis formation.

    Directory of Open Access Journals (Sweden)

    Gretchen Wolff

    Full Text Available Tumor cell extravasation into the brain requires passage through the blood-brain barrier (BBB. There is evidence that exercise can alter the oxidation status of the brain microvasculature and protect against tumor cell invasion into the brain, although the mechanisms are not well understood. In the current study, we focused on the role of microenvironment generated by exercise and metastasizing tumor cells at the levels of brain microvessels, influencing oxidative stress-mediated responses and activation of redox-sensitive small GTPases. Mature male mice were exercised for four weeks using a running wheel with the average voluntary running distance 9.0 ± 0.3 km/day. Mice were then infused with 1.0 × 10(6 D122 (murine Lewis lung carcinoma cells into the brain microvasculature, and euthanized either 48 hours (in short-term studies or 2-3 weeks (in long-term studies post tumor cell administration. A significant increase in the level of reactive oxygen species was observed following 48 hours or 3 weeks of tumor cells growth, which was accompanied by a reduction in MnSOD expression in the exercised mice. Activation of the small GTPase Rho was negatively correlated with running distance in the tumor cell infused mice. Together, these data suggest that exercise may play a significant role during aggressive metastatic invasion, especially at higher intensities in pre-trained individuals.

  14. [A Case of Brain Metastasis from Rectal Cancer with Synchronous Liver and Lung Metastases after Multimodality Treatment--A Case Report].

    Science.gov (United States)

    Udagawa, Masaru; Tominaga, Ben; Kobayashi, Daisuke; Ishikawa, Yuuya; Watanabe, Shuuichi; Adikrisna, Rama; Okamoto, Hiroyuki; Yabata, Eiichi

    2015-11-01

    We report a case of brain metastasis from rectal cancer a long time after the initial resection. A 62-year-old woman, diagnosed with lower rectal cancer with multiple synchronous liver and lung metastases, underwent abdominoperineal resection after preoperative radiochemotherapy (40 Gy at the pelvis, using the de Gramont regimen FL therapy: 1 kur). The histological diagnosis was a moderately differentiated adenocarcinoma. Various regimens of chemotherapy for unresectable and metastatic colorectal cancer were administered, and a partial response was obtained; thereby, the metastatic lesions became resectable. The patient underwent partial resection of the liver and lung metastases. Pathological findings confirmed that both the liver and lung lesions were metastases from the rectal cancer. A disease-free period occurred for several months; however, there were recurrences of the lung metastases, so we started another round of chemotherapy. After 8 months, she complained of vertigo and dizziness. A left cerebellar tumor about 3 cm in diameter was revealed by MRI and neurosurgical excision was performed. Pathological findings confirmed a cerebellar metastasis from the rectal cancer. Twenty months after resection of the brain tumor, the patient complained of a severe headache. A brain MRI showed hydrocephalia, and carcinomatous meningitis from rectal cancer was diagnosed by a spinal fluid cytology test. A ventriculo-peritoneal shunt was inserted, but the cerebrospinal pressure did not decreased and she died 20 months after the first surgery. Although brain metastasis from colorectal cancer is rare, the number of patients with brain metastasis is thought to increase in the near future. Chemotherapy for colorectal cancer is effective enough to prolong the survival period even if multiple metastases have occurred. However, after a long survival period with lung metastases such as in our case, there is a high probability of developing brain metastases.

  15. The Largest Known Survival Analysis of Patients with Brain Metastasis from Thyroid Cancer Based on Prognostic Groups.

    Directory of Open Access Journals (Sweden)

    Jinhyun Choi

    Full Text Available To analyze the clinical features and prognostic factors associated with the survival of patients with a very rare occurrence of brain metastasis (BM from differentiated thyroid cancer (DTC.A total of 37 patients with DTC who were diagnosed with BM between 1995 and 2014 were included. We reviewed the clinical characteristics, treatment modalities, and image findings of BM. Factors associated with survival were evaluated, and the patients were divided into three prognostic groups (Groups A, B, and C for comparative analysis.The median age at BM was 63 years, and the median time from initial thyroid cancer diagnosis to BM was 3.8 years. The median survival and the 1-year actuarial survival rate after BM were 8.8 months and 47%, respectively. According to univariate and multivariate analyses, four good prognostic factors (GPFs were identified including age ≤ 60 years, PS ≤ ECOG 2, ≤ 3 BM sites, and without extracranial metastasis prior to BM. Three prognostic groups were designed based on age and number of remaining GPFs: patients ≤ 60 years of age with at least 2 GPFs (Group A had the most favorable prognosis with a median survival of 32.8 months; patients ≤ 60 years of age with fewer than 2 GPFs and those > 60 years of age with at least 2 GPFs (Group B had an intermediate prognosis with a median survival of 9.4 months; and patients > 60 years of age with fewer than 2 GPFs (Group C had the least favorable prognosis with a median survival of 1.5 months.The survival of patients with BM form DTC differed among the prognostic groups based on the total number of good prognostic factors.

  16. Response of brain metastasis from lung cancer patients to an oral nutraceutical product containing silibinin.

    Science.gov (United States)

    Bosch-Barrera, Joaquim; Sais, Elia; Cañete, Noemí; Marruecos, Jordi; Cuyàs, Elisabet; Izquierdo, Angel; Porta, Rut; Haro, Manel; Brunet, Joan; Pedraza, Salvador; Menendez, Javier A

    2016-05-31

    Despite multimodal treatment approaches, the prognosis of brain metastases (BM) from non-small cell lung cancer (NSCLC) remains poor. Untreated patients with BM have a median survival of about 1 month, with almost all patients dying from neurological causes. We herein present the first report describing the response of BM from NSCLC patients to an oral nutraceutical product containing silibinin, a flavonoid extracted from the seeds of the milk thistle. We present evidence of how the use of the silibinin-based nutraceutical Legasil® resulted in significant clinical and radiological improvement of BM from NSCLC patients with poor performance status that progressed after whole brain radiotherapy and chemotherapy. The suppressive effects of silibinin on progressive BM, which involved a marked reduction of the peritumoral brain edema, occurred without affecting the primary lung tumor outgrowth in NSCLC patients. Because BM patients have an impaired survival prognosis and are in need for an immediate tumor control, the combination of brain radiotherapy with silibinin-based nutraceuticals might not only alleviate BM edema but also prove local control and time for either classical chemotherapeutics with immunostimulatory effects or new immunotherapeutic agents such as checkpoint blockers to reveal their full therapeutic potential in NSCLC BM patients. New studies aimed to illuminate the mechanistic aspects underlying the regulatory effects of silibinin on the cellular and molecular pathobiology of BM might expedite the entry of new formulations of silibinin into clinical testing for progressive BM from lung cancer patients.

  17. Uncommon case of brain metastasis in a patient with a history of heavy smoking.

    Science.gov (United States)

    Scharl, M; Bode, B; Rushing, E; Knuth, A; Rordorf, T

    2014-10-01

    Primary sarcomas of the aorta are extremely uncommon. Depending on histomorphology and immunohistochemical pattern, intimal sarcomas can show angiosarcomatous differentiation. Here, we describe the case of a 60-year-old woman with a primary intimal sarcoma of the aortic arch and signs of cerebral metastatic disease as the initial manifestation. After the patient experienced the onset of severe headaches, ataxia, and left-sided weakness, magnetic resonance imaging showed several brain lesions. Histologic assessment of a brain biopsy specimen revealed a malignant tumour composed of large pleomorphic cells that were positive for pancytokeratin and CD10. Radiation to the brain did not significantly improve the patient's symptoms, and cranial computed tomography (ct) imaging revealed several metastases, indicating lack of response. Because of the patient's smoking history, the presence of central nervous system and skeletal metastases on combined positron-emission tomography and ct imaging, and the focal pan-cytokeratin positivity of the tumour, carcinoma of the lung was favoured as the primary tumour. Despite chemotherapy with cisplatin and etoposide, the patient's neurologic symptoms and general condition deteriorated rapidly, and she died within a few days. At autopsy, an undifferentiated intimal sarcoma of the aortic arch was diagnosed. The primary tumour in the aorta consisted of large pleomorphic cells. Immunohistochemical analysis of the aortic tumour and brain metastases demonstrated diffuse positivity for vimentin and p53 and focal S-100 staining. In summary, we report a challenging case of advanced intimal sarcoma of the aortic arch with brain and bone metastases at initial presentation. Our report demonstrates the difficulties in diagnosing and treating this disease, and the need for multicentre studies to accrue more patients for investigations of optimal therapy.

  18. Comparison of prognostic indices in patients who undergo melanoma brain metastasis radiosurgery.

    Science.gov (United States)

    Kano, Hideyuki; Morales-Restrepo, Alejandro; Iyer, Aditya; Weiner, Gregory M; Mousavi, Seyed H; Kirkwood, John M; Tarhini, Ahmad A; Flickinger, John C; Lunsford, L Dade

    2017-01-20

    OBJECTIVE The goal of this study was to use 4 prognostic indices to compare survival times of patients who underwent Gamma Knife stereotactic radiosurgery (SRS) to treat melanoma brain metastases. METHODS The authors analyzed 422 consecutive patients (1440 brain metastases) who underwent Gamma Knife SRS. The median total brain tumor volume was 4.7 cm(3) (range 0.3-69.3 cm(3)), and the median number of metastases was 2 (range 1-32). One hundred thirty-two patients underwent whole-brain radiation therapy. Survival times were compared using recursive partitioning analysis (RPA), the Score Index for Radiosurgery (SIR), the Basic Score for Brain Metastases (BSBM), and the Diagnosis-Specific Graded Prognostic Assessment (DS-GPA). RESULTS The overall survival times after SRS were compared. With the RPA index, survival times were 2.6 months (Class III, n = 27), 5.5 months (Class II, n = 348), and 13.0 months (Class I, n = 47). With the DS-GPA index, survival times were 2.8 months (Scores 0-1, n = 67), 4.2 months (Scores 1.5-2.0, n = 143), 6.6 months (Scores 2.5-3.0, n = 111), and 9.4 months (Scores 3.5-4.0, n = 101). With the SIR, survival times were 3.2 months (Scores 0-3, n = 56), 5.8 months (Scores 4-7, n = 319), and 12.7 months (Scores 8-10, n = 47). With the BSBM index, survival times were 2.6 months (BSBM0, n = 47), 5.4 months (BSBM1, n = 282), 11.0 months (BSBM2, n = 86), and 8.8 months (BSBM3, n = 7). The DS-GPA index was the most balanced by case numbers in each class and provided the overall best prognostic index for overall survival. CONCLUSIONS The DS-GPA index proved most balanced and predictive of survival for patients with melanoma who underwent SRS as part of management for brain metastases. Patients whose DS-GPA score was ≥ 2.5 had predictably improved survival times after SRS.

  19. Concomitant treatment of brain metastasis with Whole Brain Radiotherapy [WBRT] and Temozolomide [TMZ] is active and improves Quality of Life

    Directory of Open Access Journals (Sweden)

    Montella Liliana

    2007-01-01

    Full Text Available Abstract Background Brain metastases (BM represent one of the most frequent complications related to cancer, and their treatment continues to evolve. We have evaluated the activity, toxicity and the impact on Quality of Life (QoL of a concomitant treatment with whole brain radiotherapy (WBRT and Temozolomide (TMZ in patients with brain metastases from solid tumors in a prospective Simon two stage study. Methods Fifty-nine patients were enrolled and received 30 Gy WBRT with concomitant TMZ (75 mg/m2/day for ten days, and subsequently TMZ (150 mg/m2/day for up to six cycles. The primary end points were clinical symptoms and radiologic response. Results Five patients had a complete response, 21 patients had a partial response, while 18 patients had stable disease. The overall response rate (45% exceeded the target activity per study design. The median time to progression was 9 months. Median overall survival was 13 months. The most frequent toxicities included grade 3 neutropenia (15% and anemia (13%, and only one patient developed a grade 4 thrombocytopenia. Age, Karnofsky performance status, presence of extracranial metastases and the recursive partitioning analysis (RPA were found to be predictive factors for response in patients. Overall survival (OS and progression-free survival (PFS were dependent on age and on the RPA class. Conclusion We conclude that this treatment is well tolerated, with an encouraging objective response rate, and a significant improvement in quality of life (p

  20. The identification and characterization of breast cancer CTCs competent for brain metastasis

    OpenAIRE

    2013-01-01

    Brain metastatic breast cancer (BMBC) is uniformly fatal and increasing in frequency. Despite its devastating outcome, mechanisms causing BMBC remain largely unknown. The mechanisms that implicate circulating tumor cells (CTCs) in metastatic disease, notably in BMBC, remain elusive. Here we characterize CTCs isolated from peripheral blood mononuclear cells (PBMCs) of patients with breast cancer, and also develop CTC lines from three of these patients. In epithelial cell adhesion molecule (EpC...

  1. Metástase cerebral: tratamento paliativo com radiocirurgia Brain metastasis: palliative treatment with radiosurgery

    Directory of Open Access Journals (Sweden)

    Sérgio L. Faria

    1995-09-01

    Full Text Available O artigo faz avaliação de 52 pacientes com metástase cerebral tratados com radiocirurgia estereotática na Universidade McGill, em Montreal. A radiocirurgia foi realizada com a técnica dinâmica em que, ao mesmo tempo, giram a mesa e a cabeça do acelerador linear de 10 MV. Todos os pacientes (56 tratamentos ao todo foram tratados com um único isocentro e uma dose única mediana de 1800 cGy na periferia da metástase. Em 88% dos casos a radiocirurgia foi usada após falha de tratamento radioterápico fracionado em todo cérebro. Todos os 52 casos tiveram avaliação com CT pós radiocirurgia. O seguimento mediano foi de 6 meses (variou entre 1 e 37 meses e a taxa de resposta, parcial ou completa, foi de 64%. Apenas 4 pacientes (7% tiveram algum tipo de complicação tardia relacionada ao tratamento. Estes achados vão de encontro com dados da literatura. A radiocirurgia é tratamento pouco agressivo, bem tolerado e com alta taxa de resposta para lesões locais e pode ser útil para pacientes selecionados. O seu valor definitivo, como tratamento único ou combinado com radioterapia em todo cérebro, está sendo avaliado de forma prospectiva e randomizada.This is a retrospective review of 52 patients with metastatic brain disease who underwent stereotactic radiosurgery at McGill University in Montreal. The radiosurgical treatment was performed with the dynamic rotation technique in which there is continuous and simultaneous movement of treatment couch and machine gantry of a 10 MV linac. All patients were treated with a single isocenter and a median dose of 1800 cGy was delivered. In 88% of the cases radiosurgery was given after failure from whole brain conventional irradiation. All 52 cases were assessed with brain CT post radiosurgery. The median follow up time was 6 months (range 1 -37 months and the response rate (partial or complete was 64%. Only 4 patientes (7% developed late complications related to the treatment. These findings are

  2. Differentiation of solitary brain metastasis from glioblastoma multiforme: a predictive multiparametric approach using combined MR diffusion and perfusion

    Energy Technology Data Exchange (ETDEWEB)

    Bauer, Adam Herman; Moser, Franklin G.; Maya, Marcel [Cedars-Sinai Medical Center, Department of Medical Imaging, Los Angeles, CA (United States); Erly, William; Nael, Kambiz [University of Arizona Medical Center, Department of Medical Imaging, Tucson, AZ (United States)

    2015-07-15

    Solitary brain metastasis (MET) and glioblastoma multiforme (GBM) can appear similar on conventional MRI. The purpose of this study was to identify magnetic resonance (MR) perfusion and diffusion-weighted biomarkers that can differentiate MET from GBM. In this retrospective study, patients were included if they met the following criteria: underwent resection of a solitary enhancing brain tumor and had preoperative 3.0 T MRI encompassing diffusion tensor imaging (DTI), dynamic contrast-enhanced (DCE), and dynamic susceptibility contrast (DSC) perfusion. Using co-registered images, voxel-based fractional anisotropy (FA), mean diffusivity (MD), K{sup trans}, and relative cerebral blood volume (rCBV) values were obtained in the enhancing tumor and non-enhancing peritumoral T2 hyperintense region (NET2). Data were analyzed by logistic regression and analysis of variance. Receiver operating characteristic (ROC) analysis was performed to determine the optimal parameter/s and threshold for predicting of GBM vs. MET. Twenty-three patients (14 M, age 32-78 years old) met our inclusion criteria. Pathology revealed 13 GBMs and 10 METs. In the enhancing tumor, rCBV, K{sup trans}, and FA were higher in GBM, whereas MD was lower, neither without statistical significance. In the NET2, rCBV was significantly higher (p = 0.05) in GBM, but MD was significantly lower (p < 0.01) in GBM. FA and K{sup trans} were higher in GBM, though not reaching significance. The best discriminative power was obtained in NET2 from a combination of rCBV, FA, and MD, resulting in an area under the curve (AUC) of 0.98. The combination of MR diffusion and perfusion matrices in NET2 can help differentiate GBM over solitary MET with diagnostic accuracy of 98 %. (orig.)

  3. Estimating the need for palliative radiotherapy for brain metastasis: a benchmarking approach.

    Science.gov (United States)

    Kong, W; Jarvis, C; Mackillop, W J

    2015-02-01

    Palliative radiotherapy (PRT) is useful in the management of many patients with brain metastases, but the need for this treatment in the general cancer population is unknown. The objective of this study was to estimate the appropriate rate of use of PRT for brain metastases (PRT.Br). Ontario's population-based cancer registry was used to identify patients who died of cancer. Radiotherapy records from all the province's radiotherapy centres were linked to Ontario's cancer registry to identify patients who received PRT.Br in the last 2 years of life. Multivariate analysis was used to identify social and health system-related barriers to the use of PRT.Br and to identify a subpopulation of patients with unimpeded access to PRT.Br. The rate of use of PRT.Br was measured in this benchmark subpopulation. The benchmark rate was standardised to the case mix of the overall cancer population. The study population included 231,397 patients who died of cancer in Ontario between 1998 and 2007. Overall, 13,944 patients received at least one course of PRT.Br in the last 2 years of life (6.0%). Multivariate analysis showed that the use of PRT.Br was strongly associated with: the availability of radiotherapy at the diagnosing hospital; the socioeconomic status of the community where the patient lived; and the distance from his/her home to the nearest radiotherapy centre. The benchmark subpopulation was defined as patients diagnosed in a hospital with radiotherapy facilities on site and who resided in a high income community, within 50 km of the nearest radiotherapy centre. The standardised benchmark rate of PRT.Br was 8.0% (95% confidence interval 7.5%, 8.5%). The overall shortfall between the actual rate and the benchmark was 25%, but varied by primary cancer site: lung, 27.6%; melanoma, 19.4%; breast, 13.9%. The magnitude of the shortfall in the use of PRT.Br varied widely across the province. At least 8.0% of patients who die of cancer require PRT.Br at least once in the last 2

  4. Nanotrastuzumab in combination with radioimmunotherapy: Can it be a viable treatment option for patients with HER2-positive breast cancer with brain metastasis?

    Science.gov (United States)

    Wang, Xuefei; Sun, Qiang; Shen, Songjie; Xu, Yali; Huang, Likun

    2016-03-01

    Brain metastasis of primary breast cancer (BCBM) has been rising during the last couple of decades. Approximately 25% of the patients with BCBM have a hormone receptor-negative, HER2-positive disease. Given the short life expectancy in patients with BCBM, researchers have tried many new approaches, including cesium-131(131Cs) brachytherapy, radretumab radioimmunotherapy and nanoparticles. Novel biological drug delivery techniques have successfully delivered nanobioconjugates across the blood-brain barrier (BBB). However, nanobioconjugates have significant toxicities and other drawbacks that prevent therapeutic concentrations of the active drug from being delivered to the brain lesions. Radretumab radioimmunotherapy combined with nanotrastruzumab can theoretically overcome this challenge. Radiotherapy can increase the BBB permeability, which can promote the transport and effect of nanotrastuzumab, reduce radretumab radioimmunotherapy dose and target patients with HER2-positive BCBM lesions more specifically. In this article, we propose that nanotrastuzumab in combination with radioimmunotherapy could be a viable treatment option for patients with HER2-positive breast cancer with brain metastasis.

  5. Neurocognitive function and quality of life in patients with newly diagnosed brain metastasis after treatment with intra-operative cesium-131 brachytherapy: a prospective trial.

    Science.gov (United States)

    Pham, Anthony; Yondorf, Menachem Z; Parashar, Bhupesh; Scheff, Ronald J; Pannullo, Susan C; Ramakrishna, Rohan; Stieg, Philip E; Schwartz, Theodore H; Wernicke, A Gabriella

    2016-03-01

    Intraoperative permanent Cesium-131 (Cs-131) brachytherapy can provide a viable alternative to WBRT with excellent response rates and minimal toxicity. This study reports the results of the prospective trial of the impact of intraoperative Cs-131 on neurocognitive function and quality of life (QoL) in patients with resected brain metastases. Between 2010 and 2012, 24 patients with newly diagnosed metastasis to the brain were accrued on a prospective protocol and treated with Cs-131 brachytherapy seeds after surgical resection. Physicians administered the mini-mental status examination (MMSE) and functional assessment of cancer therapy-brain (FACT-Br) questionnaire to all patients before treatment and again every 2 months for the duration of 6 months with additional follow-up again at 12 months. Wilcoxon rank sum test was used to analyze statistically significant changes in MMSE over time and paired t test was used to analyze changes in FACT-BR. There was a statistical improvement in overall FACT-BR score at 4 and 6 months of follow-up when compared to baseline (162 vs. 143, P = 0.004; 164 vs. 143, P = 0.005 respectively) with a non-significant trend toward improvement at 2 and 12 months (154 vs. 143, P = 0.067; 159 vs. 149, P = 0.4). MMSE score was statistically improved at 4 and up to 12 months compared to pre-treatment MMSE (30 vs. 29, P = 0.017; 30 vs. 29, P = 0.001 respectively). Patients with brain metastasis who received intra-operative permanent Cs-131 brachytherapy implants saw an improvement of their neurocognitive status and self-assessment of QoL. In addition to the excellent local control of metastasis, this approach may contribute to the improvements in cognitive function and QOL.

  6. The treatment on multiple brain metastasis by stereotactic gamma knife%多发性脑转移瘤的立体定向伽玛刀治疗

    Institute of Scientific and Technical Information of China (English)

    张永权; 巴特尔; 刘文力

    2004-01-01

    多发性脑转移瘤(multiple brain metastasis,MBM)由于瘤体散在、多发,成为神经外科疾病治疗难点,近年来,随着立体定向伽玛刀治疗技术的广泛应用,其逐渐成为MBM的首选治疗方法.本文主要对立体定向伽玛刀治疗MBM的机制、预后因素及治疗新进展进行综述.

  7. Activity of pemetrexed and high-dose gefitinib in an EGFR-mutated lung adenocarcinoma with brain and leptomeningeal metastasis after response to gefitinib

    Directory of Open Access Journals (Sweden)

    Yuan Ying

    2012-11-01

    Full Text Available Abstract About 20% to 40% of patients with non-small cell lung cancer (NSCLC will develop brain metastases during the natural course of their disease. The prognosis for such patients is very poor with limited survival. In addition to the standard whole brain radiation therapy (WBRT, some studies have shown that chemotherapy drugs and/or epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI can improve the outcome of these patients. Here, we report a stage IIIA patient who developed multiple brain metastases one year after operation. Oral gefitinib with concurrent WBRT were given as first-line therapy. Complete response and a 50-month progression-free survival (PFS were obtained. Double dosage of gefitinib (500 mg per day together with pemetrexed were given as the second-line therapy after the patient developed new brain lesions and leptomeningeal metastasis during the maintenance therapy of gefitinib. The PFS for the second-line therapy was six months. In total, the patient obtained an overall survival of 59 months since the first diagnosis of brain metastases. Mutational analysis showed a 15-nucleotide deletion and a missense mutation in exon 19 of the EGFR gene, and a missense mutation at codon 12 of the K-ras gene. These underlying genetic changes might partially explain the long-term survival of this patient after brain metastases when treated with concurrent or sequential therapies of EGFR-TKI, radiotherapy and chemotherapy.

  8. Pharmacologic inhibition of MLK3 kinase activity blocks the in vitro migratory capacity of breast cancer cells but has no effect on breast cancer brain metastasis in a mouse xenograft model.

    Directory of Open Access Journals (Sweden)

    Kun Hyoe Rhoo

    Full Text Available Brain metastasis of breast cancer is an important clinical problem, with few therapeutic options and a poor prognosis. Recent data have implicated mixed lineage kinase 3 (MLK3 in controlling the in vitro migratory capacity of breast cancer cells, as well as the metastasis of MDA-MB-231 breast cancer cells from the mammary fat pad to distant lymph nodes in a mouse xenograft model. We therefore set out to test whether MLK3 plays a role in brain metastasis of breast cancer cells. To address this question, we used a novel, brain penetrant, MLK3 inhibitor, URMC099. URMC099 efficiently inhibited the migration of breast cancer cells in an in vitro cell monolayer wounding assay, and an in vitro transwell migration assay, but had no effect on in vitro cell growth. We also tested the effect of URMC099 on tumor formation in a mouse xenograft model of breast cancer brain metastasis. This analysis showed that URMC099 had no effect on the either the frequency or size of breast cancer brain metastases. We conclude that pharmacologic inhibition of MLK3 by URMC099 can reduce the in vitro migratory capacity of breast cancer cells, but that it has no effect on either the frequency or size of breast cancer brain metastases, in a mouse xenograft model.

  9. Epigenome-wide DNA methylation landscape of melanoma progression to brain metastasis reveals aberrations on homeobox D cluster associated with prognosis.

    Science.gov (United States)

    Marzese, Diego M; Scolyer, Richard A; Huynh, Jamie L; Huang, Sharon K; Hirose, Hajime; Chong, Kelly K; Kiyohara, Eiji; Wang, Jinhua; Kawas, Neal P; Donovan, Nicholas C; Hata, Keisuke; Wilmott, James S; Murali, Rajmohan; Buckland, Michael E; Shivalingam, Brindha; Thompson, John F; Morton, Donald L; Kelly, Daniel F; Hoon, Dave S B

    2014-01-01

    Melanoma brain metastasis (MBM) represents a frequent complication of cutaneous melanoma. Despite aggressive multi-modality therapy, patients with MBM often have a survival rate of MBM. In this study, we generated a comprehensive DNA methylation landscape through the use of genome-wide copy number, DNA methylation and gene expression data integrative analysis of melanoma progression to MBM. A progressive genome-wide demethylation in low CpG density and an increase in methylation level of CpG islands according to melanoma progression were observed. MBM-specific partially methylated domains (PMDs) affecting key brain developmental processes were identified. Differentially methylated CpG sites between MBM and lymph node metastasis (LNM) from patients with good prognosis were identified. Among the most significantly affected genes were the HOX family members. DNA methylation of HOXD9 gene promoter affected transcript and protein expression and was significantly higher in MBM than that in early stages. A MBM-specific PMD was identified in this region. Low methylation level of this region was associated with active HOXD9 expression, open chromatin and histone modifications associated with active transcription. Demethylating agent induced HOXD9 expression in melanoma cell lines. The clinical relevance of this finding was verified in an independent large cohort of melanomas (n = 145). Patients with HOXD9 hypermethylation in LNM had poorer disease-free and overall survival. This epigenome-wide study identified novel methylated genes with functional and clinical implications for MBM patients.

  10. SU-E-QI-21: Iodinated Contrast Agent Time Course In Human Brain Metastasis: A Study For Stereotactic Synchrotron Radiotherapy Clinical Trials

    Energy Technology Data Exchange (ETDEWEB)

    Obeid, L; Esteve, F; Adam, J [Grenoble Institut des Neurosciences, La Tronche, Isere (France); Tessier, A; Balosso, J [Centre Hospitalier Universitaire, La Tronche, Isere (France)

    2014-06-15

    Purpose: Synchrotron stereotactic radiotherapy (SSRT) is an innovative treatment combining the selective accumulation of heavy elements in tumors with stereotactic irradiations using monochromatic medium energy x-rays from a synchrotron source. Phase I/II clinical trials on brain metastasis are underway using venous infusion of iodinated contrast agents. The radiation dose enhancement depends on the amount of iodine in the tumor and its time course. In the present study, the reproducibility of iodine concentrations between the CT planning scan day (Day 0) and the treatment day (Day 10) was assessed in order to predict dose errors. Methods: For each of days 0 and 10, three patients received a biphasic intravenous injection of iodinated contrast agent (40 ml, 4 ml/s, followed by 160 ml, 0.5 ml/s) in order to ensure stable intra-tumoral amounts of iodine during the treatment. Two volumetric CT scans (before and after iodine injection) and a multi-slice dynamic CT of the brain were performed using conventional radiotherapy CT (Day 0) or quantitative synchrotron radiation CT (Day 10). A 3D rigid registration was processed between images. The absolute and relative differences of absolute iodine concentrations and their corresponding dose errors were evaluated in the GTV and PTV used for treatment planning. Results: The differences in iodine concentrations remained within the standard deviation limits. The 3D absolute differences followed a normal distribution centered at zero mg/ml with a variance (∼1 mg/ml) which is related to the image noise. Conclusion: The results suggest that dose errors depend only on the image noise. This study shows that stable amounts of iodine are achievable in brain metastasis for SSRT treatment in a 10 days interval.

  11. A new strategy of CyberKnife treatment system based radiosurgery followed by early use of adjuvant bevacizumab treatment for brain metastasis with extensive cerebral edema.

    Science.gov (United States)

    Wang, Yang; Wang, Enmin; Pan, Li; Dai, Jiazhong; Zhang, Nan; Wang, Xin; Liu, Xiaoxia; Mei, Guanghai; Sheng, Xiaofang

    2014-09-01

    Bevacizumab blocks the effects of vascular endothelial growth factor in leakage-prone capillaries and has been suggested as a new treatment for cerebral radiation edema and necrosis. CyberKnife is a new, frameless stereotactic radiosurgery system. This work investigated the safety and efficacy of CyberKnife followed by early bevacizumab treatment for brain metastasis with extensive cerebral edema. The eligibility criteria of the patients selected for radiosurgery followed by early use of adjuvant bevacizumab treatment were: (1) brain tumors from metastasis with one solitary brain lesion and symptomatic extensive cerebral edema; (2) >18 years of age; (3) the patient refused surgery due to the physical conditions and the risk of surgery; (4) no contraindications for bevacizumab. (5) bevacizumab was applied for a minimum of 2 injections and a maximum of 6 injections with a 2-week interval between treatments, beginning within 2 weeks of the CyberKnife therapy; (6) Karnofsky performance status (KPS) ≥30. Tumor size and edema were monitored by magnetic resonance imaging (MRI). Dexamethasone dosage, KPS, adverse event occurrence and associated clinical outcomes were also recorded. Eight patients were accrued for this new treatment. Radiation dose ranged from 20 to 33 Gy in one to five sessions, prescribed to the 61-71 % isodose line. Bevacizumab therapy was administered 3-10 days after completion of CyberKnife treatment for a minimum of two cycles (5 mg/kg, at 2-week intervals). MRI revealed average reductions of 55.8 % (post-gadolinium) and 63.4 % (T2/FLAIR). Seven patients showed significant clinical neurological improvements. Dexamethasone was reduced in all patients, with five successfully discontinuing dexamethasone treatment 4 weeks after bevacizumab initiation. Hypertension, a bevacizumab-related adverse event, occurred in one patient. After 3-8 months, all patients studied were alive and primary brain metastases were under control, 2 developed new brain

  12. A Melanoma Brain Metastasis with a Donor-Patient Hybrid Genome following Bone Marrow Transplantation: First Evidence for Fusion in Human Cancer.

    Directory of Open Access Journals (Sweden)

    Rossitza Lazova

    Full Text Available Tumor cell fusion with motile bone marrow-derived cells (BMDCs has long been posited as a mechanism for cancer metastasis. While there is much support for this from cell culture and animal studies, it has yet to be confirmed in human cancer, as tumor and marrow-derived cells from the same patient cannot be easily distinguished genetically.We carried out genotyping of a metastatic melanoma to the brain that arose following allogeneic bone-marrow transplantation (BMT, using forensic short tandem repeat (STR length-polymorphisms to distinguish donor and patient genomes. Tumor cells were isolated free of leucocytes by laser microdissection, and tumor and pre-transplant blood lymphocyte DNAs were analyzed for donor and patient alleles at 14 autosomal STR loci and the sex chromosomes.All alleles in the donor and patient pre-BMT lymphocytes were found in tumor cells. The alleles showed disproportionate relative abundances in similar patterns throughout the tumor, indicating the tumor was initiated by a clonal fusion event.Our results strongly support fusion between a BMDC and a tumor cell playing a role in the origin of this metastasis. Depending on the frequency of such events, the findings could have important implications for understanding the generation of metastases, including the origins of tumor initiating cells and the cancer epigenome.

  13. Clinical outcomes of HER2-positive metastatic breast cancer patients with brain metastasis treated with lapatinib and capecitabine: an open-label expanded access study in Korea

    Directory of Open Access Journals (Sweden)

    Ro Jungsil

    2012-07-01

    Full Text Available Abstract Background To evaluate efficacy in patients with brain metastasis (BM on entry into the lapatinib expanded access program (LEAP. Methods LEAP is a worldwide, single-arm, open-label study. HER2-positive, locally-advanced or metastatic breast cancer patients with progression after an anthracycline, taxane, and trastuzumab were eligible. Patients received capecitabine 2000 mg/m2 daily in two divided doses, days 1–14, every 21 days and lapatinib 1250 mg once daily. Results Among 186 patients enrolled in 6 Korean centers, 58 had BM. Progression-free survival (PFS was 18.7 weeks in patients with BM and 19.4 weeks without BM (P = 0.88. In patients with BM, brain response was synchronized with systemic responses (P = 0.0001. Overall survival (OS was 48.9 weeks in patients with BM and 64.6 weeks without BM (P = 0.23. Multivariable analysis found hormone receptor positivity (P = 0.003 and clinical benefit rate (CBR of combined systemic and brain disease (P  Conclusion Lapatinib plus capecitabine is equally effective in patients with or without BM. Trial registration ClinicalTrials.gov (NCT00338247

  14. [Biology of cancer metastasis].

    Science.gov (United States)

    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.

  15. Brain metastasis of hepatocellular carcinoma detected after liver transplantation Metástase cerebral de carcinoma hepatocelular após transplante de fígado

    Directory of Open Access Journals (Sweden)

    Alex Vianey Callado França

    2004-09-01

    Full Text Available AIM: We report the case of a patient with hepatocellular carcinoma submitted to liver transplantation, who subsequently manifested tumor recurrence initially as brain metastasis. CASE DESCRIPTION: A 48-year-old male cirrhotic patient with hepatitis C infection, and two focal hepatic lesions, had a cytologic and histologic diagnosis of hepatocellular carcinoma. Before transplant, he was submitted to adjuvant treatment with a combination of arterial embolization and intratumoral ethanol injection. In the 3rd month post-liver transplantation, the patient developed headache, nausea and vomiting, without any neurological impairment. Brain computed tomography and magnetic resonance imaging identified an expansive hypervascular lesion with internal bleeding. Evaluation of the surgical explant revealed macroscopic invasion of portal vessels. CONCLUSION: Brain metastasis of a hepatocellular carcinoma after liver transplantation may occur. This metastasis may have occurred before or soon after the transplant. Patients with hepatocellular carcinoma, awaiting liver transplant, should be screened for cerebral metastasis. Vascular invasion may indicate hematogenic dissemination of the tumor.OBJETIVO: Relatar o caso de paciente com carcinoma hepatocelular submetido a transplante de fígado, que subseqüentemente manifestou recurrência tumoral em cérebro após o transplante. DESCRIÇÃO DO CASO: Homem de 48 anos de idade, com cirrose hepática secundária à infecção pelo vírus da hepatite C, com duas lesões focais hepáticas diagnosticadas como carcinoma hepatocelular pela citologia e histologia. Antes do transplante, foi submetido a tratamento coadjuvante com embolização da artéria hepática e injeção intra-tumoral de etanol. No terceiro mês pós-transplante, o paciente apresentou cefaléia, náuseas e vômitos, sem déficit neurológico focal. Tomografia computadorizada e ressonância magnética de crânio identificaram lesão expansiva

  16. Targeting Neuronal-like Metabolism of Metastatic Tumor Cells as a Novel Therapy for Breast Cancer Brain Metastasis

    Science.gov (United States)

    2016-03-01

    1 AWARD NUMBER: W81XWH-15-1-0021 TITLE: Targeting Neuronal -like Metabolism of Metastatic Tumor Cells as a Novel Therapy for Breast Cancer Brain ...functional importance of key neuronal -like changes during metastatic evolution and target metastatic colonization of the brain with BBB-permeable...DATES COVERED 1 Mar 2015 - 28 Feb 2016 4. TITLE AND SUBTITLE Targeting Neuronal -like Metabolism of Metastatic Tumor Cells as a Novel Therapy for Breast

  17. The role of cancer stem cells and miRNAs in defining the complexities of brain metastasis

    OpenAIRE

    2013-01-01

    Researchers and clinicians have been challenged with the development of therapies for the treatment of cancer patients whose tumors metastasized to the brain. Among the most lethal weapons known today, current management of brain metastases involves multiple therapeutic modalities that provide little, if any, for improving the quality of life and overall survival. Recently the role of cancer stem cells (CSCs) in the development of cancer has been studied extensively, and thus its role in the ...

  18. Feasibility on using composite gel-alanine dosimetry on the validation of a multiple brain metastasis radiosurgery VMAT technique

    Science.gov (United States)

    Pavoni, J. F.; Neves-Junior, W. F. P.; Silveira, M. A.; Ramos, P. A. M. M.; Haddad, C. M. K.; Baffa, O.

    2015-01-01

    This work presents an end-to-end test using a composite Gel-Alanine phantom, in order to validate 3-dimensionally the dose distribution delivered by a single isocenter VMAT technique on the simultaneous treatment of multiple brain metastases. The results obtained with the gel and alanine dosimeters are consistent with the expected by the treatment planning system, showing the potential of this multidosimetric approach and validating dosimetrically the multiple brain metastases treatment using VMAT.

  19. Intra-arterial administration improves temozolomide delivery and efficacy in a model of intracerebral metastasis, but has unexpected brain toxicity.

    Science.gov (United States)

    Muldoon, Leslie L; Pagel, Michael A; Netto, Joao Prola; Neuwelt, Edward A

    2016-02-01

    We tested the hypothesis that intra-arterial (IA) infusion of temozolomide into the internal carotid artery would safely improve drug delivery to brain and enhance chemotherapy efficacy in a chemosensitive rat brain tumor model. Quantitative autoradiography after 25 µCi (14)C-temozolomide was given by oral, intravenous, or IA route of administration, or IA with osmotic blood-brain barrier disruption (BBBD) (n = 5-7 per group) showed that both IA and IA/BBBD administration increased drug delivery in tumor by over threefold compared to normal brain (P Temozolomide (20 mg/kg; ~150 mg/m(2)) increased median survival when given by oral (25.5 days), intravenous (25.5 days), or IA (33 days) route of administration, compared to 17.5 days in untreated controls (n = 8 per group; overall P temozolomide was significantly longer than all other groups (P temozolomide was toxic in the efficacy study, but there was no evidence of symptomatic neurotoxicity in rats given IA temozolomide. After these promising animal results, a 49 year old male with glioblastoma multiforme who failed all standard therapy received temozolomide 100 mg/m(2) IA. Upon initiation of the second course of IA infusion the patient had increased heart rate, blood pressure, and rash, and the procedure was terminated without sequelae. Follow up IA infusion of temozolomide diluent in normal rats showed damaged cerebrovasculature as determined by dye leakage. These results demonstrate that IA infusion of temozolomide was toxic, with or without BBBD. We conclude that under the current formulation temozolomide is not safe for IA infusion in patients.

  20. Brain metastasis is predetermined in early stages of cutaneous melanoma by CD44v6 expression through epigenetic regulation of the spliceosome.

    Science.gov (United States)

    Marzese, Diego M; Liu, Michelle; Huynh, Jamie L; Hirose, Hajime; Donovan, Nicholas C; Huynh, Kelly T; Kiyohara, Eiji; Chong, Kelly; Cheng, David; Tanaka, Ryo; Wang, Jinhua; Morton, Donald L; Barkhoudarian, Garni; Kelly, Daniel F; Hoon, Dave S B

    2015-01-01

    Melanoma brain metastasis (MBM) is frequent and has a very poor prognosis with no current predictive factors or therapeutic molecular targets. Our study unravels the molecular alterations of cell-surface glycoprotein CD44 variants during melanoma progression to MBM. High expression of CD44 splicing variant 6 (CD44v6) in primary melanoma (PRM) and regional lymph node metastases from AJCC Stage IIIC patients significantly predicts MBM development. The expression of CD44v6 also enhances the migration of MBM cells by hyaluronic acid and hepatocyte growth factor exposure. Additionally, CD44v6-positive MBM migration is reduced by blocking with a CD44v6-specific monoclonal antibody or knocking down CD44v6 by siRNA. ESRP1 and ESRP2 splicing factors correlate with CD44v6 expression in PRM, and ESRP1 knockdown significantly decreases CD44v6 expression. However, an epigenetic silencing of ESRP1 is observed in metastatic melanoma, specifically in MBM. In advanced melanomas, CD44v6 expression correlates with PTBP1 and U2AF2 splicing factors, and PTBP1 knockdown significantly decreases CD44v6 expression. Overall, these findings open a new avenue for understanding the high affinity of melanoma to progress to MBM, suggesting CD44v6 as a potential MBM-specific factor with theranostic utility for stratifying patients.

  1. A multimodality imaging model to track viable breast cancer cells from single arrest to metastasis in the mouse brain

    Science.gov (United States)

    Parkins, Katie M.; Hamilton, Amanda M.; Makela, Ashley V.; Chen, Yuanxin; Foster, Paula J.; Ronald, John A.

    2016-10-01

    Cellular MRI involves sensitive visualization of iron-labeled cells in vivo but cannot differentiate between dead and viable cells. Bioluminescence imaging (BLI) measures cellular viability, and thus we explored combining these tools to provide a more holistic view of metastatic cancer cell fate in mice. Human breast carcinoma cells stably expressing Firefly luciferase were loaded with iron particles, injected into the left ventricle, and BLI and MRI were performed on days 0, 8, 21 and 28. The number of brain MR signal voids (i.e., iron-loaded cells) on day 0 significantly correlated with BLI signal. Both BLI and MRI signals decreased from day 0 to day 8, indicating a loss of viable cells rather than a loss of iron label. Total brain MR tumour volume on day 28 also correlated with BLI signal. Overall, BLI complemented our sensitive cellular MRI technologies well, allowing us for the first time to screen animals for successful injections, and, in addition to MR measures of cell arrest and tumor burden, provided longitudinal measures of cancer cell viability in individual animals. We predict this novel multimodality molecular imaging framework will be useful for evaluating the efficacy of emerging anti-cancer drugs at different stages of the metastatic cascade.

  2. A multimodality imaging model to track viable breast cancer cells from single arrest to metastasis in the mouse brain

    Science.gov (United States)

    Parkins, Katie M.; Hamilton, Amanda M.; Makela, Ashley V.; Chen, Yuanxin; Foster, Paula J.; Ronald, John A.

    2016-01-01

    Cellular MRI involves sensitive visualization of iron-labeled cells in vivo but cannot differentiate between dead and viable cells. Bioluminescence imaging (BLI) measures cellular viability, and thus we explored combining these tools to provide a more holistic view of metastatic cancer cell fate in mice. Human breast carcinoma cells stably expressing Firefly luciferase were loaded with iron particles, injected into the left ventricle, and BLI and MRI were performed on days 0, 8, 21 and 28. The number of brain MR signal voids (i.e., iron-loaded cells) on day 0 significantly correlated with BLI signal. Both BLI and MRI signals decreased from day 0 to day 8, indicating a loss of viable cells rather than a loss of iron label. Total brain MR tumour volume on day 28 also correlated with BLI signal. Overall, BLI complemented our sensitive cellular MRI technologies well, allowing us for the first time to screen animals for successful injections, and, in addition to MR measures of cell arrest and tumor burden, provided longitudinal measures of cancer cell viability in individual animals. We predict this novel multimodality molecular imaging framework will be useful for evaluating the efficacy of emerging anti-cancer drugs at different stages of the metastatic cascade. PMID:27767185

  3. 肿瘤标志物与非小细胞肺癌脑转移的相关性%Relationship between serum tumor markers and brain metastasis in patients with ad-vanced non - small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    刘艳萍; 曾爱屏; 宋向群; 周韶璋; 于起涛

    2015-01-01

    Objective:To explore the relationship between serum tumor markers and brain metastasis in patients with advanced non - small cell lung cancer(NSCLC). Methods:The clinical data of 289 advanced NSCLC patients hospitalized from April 2009 to October 2013 were retrospectively analyzed. All the enrolled patients were newly diag-nosed NSCLC with stage Ⅳ and not received treatment previously. Of those patients,223 had no brain metastasis. The rest were diagnosed with brain metastasis. Results:The incidence of brain metastasis was 22. 8%(66 / 289),the medi-an survival time of patients with the brain metastasis was 9. 4 months. The 1 - year and 2 - year survival rates were 37% and 15% respectively. The serum level of carcinoembryonic antigen(CEA)was significantly different between no brain metastasis patients and those who had(P = 0. 001). The median value of CEA of patients with and without brain metastasis was 6. 8ng/ ml,16. 0ng/ ml respectively. Overall survival was significantly shorter among patients with elevated serum CEA(median survival 15 months vs. 8 months,P = 0. 027)or CA125(median survival 13 months vs. 7 months,P = 0. 008). In multivariate analysis,CA125,radiotherapy and sex were independent prognostic factors for brain metastasis(P < 0. 05). Conclusion:The high serum CEA level may be potentially used as an indicator to predict the probability of brain metastasis in patients with NSCLC. The high serum CA125 may be used as reference index of the prognosis of brain metastasis in patients with NSCLC.%目的:探讨血清 CEA、CA125、CA153、CA199、CA724和 CYFRA21-1水平与晚期非小细胞肺癌(NSCLC)脑转移发生和预后的相关性。方法:回顾性分析我院2009年4月至2013年10月289例(非脑转移223例,脑转移66例)未进行过任何治疗的Ⅳ期 NSCLC 患者临床资料。结果:全组病例脑转移发生率为22.8%(66/289),66例脑转移的中位生存期为9.4个月,1年、2年生存率分别为37%、15

  4. Intramedullary metastasis.

    Science.gov (United States)

    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.

  5. Definitive Chemoradiation Therapy Following Surgical Resection or Radiosurgery Plus Whole-Brain Radiation Therapy in Non-Small Cell Lung Cancer Patients With Synchronous Solitary Brain Metastasis: A Curative Approach

    Energy Technology Data Exchange (ETDEWEB)

    Parlak, Cem, E-mail: cemparlak@gmail.com [Department of Radiation Oncology, Baskent University, Adana Medical Faculty, Adana (Turkey); Mertsoylu, Hüseyin [Department of Medical Oncology, Baskent University, Adana Medical Faculty, Adana (Turkey); Güler, Ozan Cem; Onal, Cem; Topkan, Erkan [Department of Radiation Oncology, Baskent University, Adana Medical Faculty, Adana (Turkey)

    2014-03-15

    Purpose/Objectives: The aim of this study was to evaluate the impact of definitive thoracic chemoradiation therapy following surgery or stereotactic radiosurgery (SRS) and whole-brain radiation therapy (WBRT) on the outcomes of patients with non-small cell lung cancer (NSCLC) with synchronous solitary brain metastasis (SSBM). Methods and Materials: A total of 63 NSCLC patients with SSBM were retrospectively evaluated. Patients were staged using positron emission tomography-computed tomography in addition to conventional staging tools. Thoracic radiation therapy (TRT) with a total dose of 66 Gy in 2 Gy fractions was delivered along with 2 cycles of cisplatin-based chemotherapy following either surgery plus 30 Gy of WBRT (n=33) or SRS plus 30 Gy of WBRT (n=30) for BM. Results: Overall, the treatment was well tolerated. All patients received planned TRT, and 57 patients (90.5%) were also able to receive 2 cycles of chemotherapy. At a median follow-up of 25.3 months (7.1-52.1 months), the median months of overall, locoregional progression-free, neurological progression-free, and progression-free survival were 28.6, 17.7, 26.4, and 14.6, respectively. Both univariate and multivariate analyses revealed that patients with a T1-T2 thoracic disease burden (P=.001), a nodal stage of N0-N1 (P=.003), and no weight loss (P=.008) exhibited superior survival. Conclusions: In the present series, surgical and radiosurgical treatments directed toward SSBM in NSCLC patients were equally effective. The similarities between the present survival outcomes and those reported in other studies for locally advanced NSCLC patients indicate the potentially curative role of definitive chemoradiation therapy for highly selected patients with SSBM.

  6. Whole brain radiation with supplementary boost for patients for unique brain metastasis from a primitive lung cancer; Experience de l'irradiation encephalique totale avec escalade de dose focalisee pour le traitement des metastases cerebrales uniques d'un carcinome bronchopulmonaire

    Energy Technology Data Exchange (ETDEWEB)

    Levy, A.; Lamproglou, I. [Service de radiotherapie, groupe hospitalier Pitie-Salpetriere, 47-83, boulevard de l' Hopital, 75013 Paris (France); Chargari, C. [Service de radiotherapie, groupe hospitalier Pitie-Salpetriere, 47-83, boulevard de l' Hopital, 75013 Paris (France); Service de radiotherapie, hopital d' instruction des armees Val-de-Grace, 75005 Paris (France); Mazeron, J.J. [Service de radiotherapie, groupe hospitalier Pitie-Salpetriere, 47-83, boulevard de l' Hopital, 75013 Paris (France); Universite Pierre-et-Marie-Curie Paris 6, 4, place Jussieu, 75005 Paris (France); Krzisch, C. [Service de radiotherapie, CHU d' Amiens-Picardie, place Victor-Pauchet, 80054 Amiens cedex (France); Assouline, A. [Service de radiotherapie, groupe hospitalier Pitie-Salpetriere, 47-83, boulevard de l' Hopital, 75013 Paris (France); Universite Pierre-et-Marie-Curie Paris 6, 4, place Jussieu, 75005 Paris (France); Service de radiotherapie, CHU d' Amiens-Picardie, place Victor-Pauchet, 80054 Amiens cedex (France)

    2011-08-15

    Purpose. - To assess the potential benefit of a boost in patients treated with whole brain irradiation by a conventional linear accelerator for lung cancer solitary brain metastasis. Patients and methods. - From 2002 to 2006, a retrospective analysis was carried out from 64 unselected consecutive patients with secondary brain metastasis from lung cancer, treated with whole brain irradiation without surgical resection. Thirty patients (47%) received a boost in their brain metastases. Three potential prognostic factors were studied: sex, RPA score and improvement of neurological symptoms after radiotherapy. An analysis was conducted to determine whether an additional dose may improve survival in the absence of surgical resection. Results. - The mean follow-up was 4.9 months. The median overall survival was 8.5 months (6.4 to 10.7 months). The total dose of radiotherapy was the only significant prognostic factor for overall survival. The median overall survival was 6.2 months for patients without additional radiation versus 11.2 months for patients receiving a boost dose (p = 0.011). Sex, RPA score and improvement of neurological symptoms after radiotherapy were not found as prognostic factors for overall survival. Conclusions. - Boost delivered after whole brain radiation therapy by a conventional particle accelerator may provide a benefit in selected patients, especially for centres that do not have radiotherapy techniques in stereotactic conditions. This warrants further prospective assessment. (authors)

  7. Metastasis of Pregnancy-Associated Breast Cancer (Suspected to Be Hereditary Breast and Ovarian Cancer to the Brain, Diagnosed at 18 Weeks’ Gestation: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Tomohiro Okuda

    2016-01-01

    Full Text Available We report a case of pregnancy-associated breast cancer with metastasis to the brain, likely resulting from hereditary breast and ovarian cancer (HBOC. A 35-year-old woman (gravida 2, para 0-1-0-1 underwent a right mastectomy and right axillary dissection after a cesarean section at 30 years of age; her mother died at 47 years of age due to breast cancer. Histopathological examination indicated an invasive ductal carcinoma with triple-negative cancer (cancer stage 2B [pT3N0M0]. The patient refused adjuvant therapy because of the risk of infertility. After 4 years, she became pregnant naturally. At 18 weeks’ gestation, she experienced aphasia and dyslexia due to brain metastasis. The pregnancy was terminated at 21 weeks’ gestation after thorough counseling. Her family history, young-onset disease, and histopathological findings suggested HBOC. She declined genetic testing for BRCA1/2, though genetic counseling was provided. In cases of pregnancy-related breast cancer, consideration must be given to whether the pregnancy should be continued and to posttreatment fertility. HBOC should also be considered. Genetic counseling should be provided and the patient should be checked for the BRCA mutation, as it is meaningful for the future of any potential children. Genetic counseling should be provided even if the cancer is advanced or recurrent.

  8. Slit2在乳腺组织的表达与乳腺癌脑转移的关系%Slit2 Expression in breast cancer and its relationship to brain metastasis

    Institute of Scientific and Technical Information of China (English)

    王乐; 马勇杰; 孙增峰; 刘芳芳; 付丽; 李文良; 谷峰

    2010-01-01

    Objective To detect the expression of Slit2 in breast tumors and its association with the breast cancer brain metastasis. Methods Immunohistochemistry staining was performed for Slit2 expression on specimens from 24 cases of invasive ductal carcinoma (IDC) with brain metastasis, 71 cases of IDC without brain metastasis, 22 cases of ductal carcinoma in situ (DCIS) and 23 cases of fibroadenoma.Results ( 1 ) The expression level of Slit2 in IDC with brain metastasis ( 13% ) was significantly lower than that in IDC without brain metastasis ( 59% ), P < 0. 05. (2) The expression level of Slit2 in IDC (48%) and DCIS (59%) was significantly lower than that in adenofibroma (87%),P <0.05. The expression of Slit2 in IDC was lower than that in DCIS, but had no significant difference,P > 0.05. (3) The expression of Slit2 was significantly higher in more than 50 year-old-group (62%) than that in less than 50 year-old-group (34%) of IDC patients, and highly related with the duration of IDC patients,P <0.05. No correlation was found between the Slit2 expression and the tumor size, lymph node metastasis, pathologic stage and histological grade, P > 0.05. Conclusion The Slit2 expression correlates negatively with IDC brain metastasis, and positively with the age and duration of IDC patients. Slit2 could be applied as a marker in evaluating the IDC invasiveness and brain metastasis, and could be a new therapeutic target.%目的 检测神经轴突导向蛋白2(Slit2)在不同乳腺肿瘤组织中的表达,探讨Slit2与乳腺癌脑转移的相关性.方法 采用免疫组织化学LSAB法检测对24例发生脑转移的乳腺浸润性导管癌(IDC)、71例未发生脑转移的乳腺浸润性导管癌、22例乳腺导管内癌和23例乳腺腺纤维瘤组织中Slit2的表达.结果 Slit2在浸润性导管癌中有脑转移患者的阳性表达率(13%)明显低于无脑转移患者(59%)(P<0.05);在乳腺导管内癌和浸润性导管癌中的阳性表达率(59%和48%)

  9. Decoding Melanoma Metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Damsky, William E. Jr. [Department of Dermatology, Yale School of Medicine, New Haven, Connecticut (United States); Department of Pathology, University of Vermont College of Medicine, Burlington, Vermont (United States); Rosenbaum, Lara E.; Bosenberg, Marcus, E-mail: Marcus.Bosenberg@yale.edu [Department of Dermatology, Yale School of Medicine, New Haven, Connecticut (United States)

    2010-12-30

    Metastasis accounts for the vast majority of morbidity and mortality associated with melanoma. Evidence suggests melanoma has a predilection for metastasis to particular organs. Experimental analyses have begun to shed light on the mechanisms regulating melanoma metastasis and organ specificity, but these analyses are complicated by observations of metastatic dormancy and dissemination of melanocytes that are not yet fully malignant. Additionally, tumor extrinsic factors in the microenvironment, both at the site of the primary tumor and the site of metastasis, play important roles in mediating the metastatic process. As metastasis research moves forward, paradigms explaining melanoma metastasis as a step-wise process must also reflect the temporal complexity and heterogeneity in progression of this disease. Genetic drivers of melanoma as well as extrinsic regulators of disease spread, particularly those that mediate metastasis to specific organs, must also be incorporated into newer models of melanoma metastasis.

  10. Decoding Melanoma Metastasis

    Directory of Open Access Journals (Sweden)

    Marcus Bosenberg

    2010-12-01

    Full Text Available Metastasis accounts for the vast majority of morbidity and mortality associated with melanoma. Evidence suggests melanoma has a predilection for metastasis to particular organs. Experimental analyses have begun to shed light on the mechanisms regulating melanoma metastasis and organ specificity, but these analyses are complicated by observations of metastatic dormancy and dissemination of melanocytes that are not yet fully malignant. Additionally, tumor extrinsic factors in the microenvironment, both at the site of the primary tumor and the site of metastasis, play important roles in mediating the metastatic process. As metastasis research moves forward, paradigms explaining melanoma metastasis as a step-wise process must also reflect the temporal complexity and heterogeneity in progression of this disease. Genetic drivers of melanoma as well as extrinsic regulators of disease spread, particularly those that mediate metastasis to specific organs, must also be incorporated into newer models of melanoma metastasis.

  11. RARE CASE OF COLONIC METASTASIS

    Directory of Open Access Journals (Sweden)

    Vinod Kumar

    2015-04-01

    Full Text Available Colon cancer is the second most common type of cancer in females and the third in males worldwide. The most common sites of colon cancer metastasis are the regional lymph nodes, liver, lung, bone and brain. In this case report, an extremely rare case of colon adenocarcinoma with metastasis to the philtrum with extensive peritoneal and bowel involvement is presented. A 44 year old male presented with a change in bowel habits, melena and weight loss . Diagnosed to have carcinoma rectum underwent Abdominoperenial resection (APR two y ears back. Biopsies were consistent with the diagnosis of invasive moderately differentiated adenocarcinoma. Now presented with swelling over philtrum . Fine needle aspiration (FNAC was done suggestive of adenocarcinoma. This case presented for its uncommon presentation.

  12. 非小细胞肺癌脑转移的靶向和免疫治疗%Targeted Therapy and Immunotherapy for Non-small Cell Lung Cancer with Brain Metastasis

    Institute of Scientific and Technical Information of China (English)

    宋琪; 焦顺昌; 李方

    2016-01-01

    Brain metastasis, a common complication of non-small cell lung cancer (NSCLC) with an incidence rate of 30%-50%, signiifcantly affects the patients’ quality of life. hTe prognosis of patients of NSCLC with brain metastasis is ex-tremely poor, the average median survival is only 1 m-2 m without treatment. hTe targeted therapy based on lung cancer driven gene is a new treatment. Besides, the immunotherapy which can enhance the effect of anti-cancer by simulating the immune system is a new approach. The combination of targeted therapy and immunotherapy can greatly benefit patients in clinical work.%脑转移是非小细胞肺癌(non-small cell lung cancer, NSCLC)常见并发症,发生率为30%-50%,大大影响了患者的生存质量。NSCLC一旦发生脑转移预后极差,未经治疗者的中位生存期仅为1个月-2个月。基于肺癌驱动基因的靶向治疗为肺癌脑转移提供了新的方法。目前免疫治疗已成为肿瘤治疗的新方向,它能通过刺激机体免疫系统提高抗肿瘤免疫效应。临床上靶向治疗和免疫治疗的结合运用可使患者获益。

  13. Factors Affecting the Risk of Brain Metastasis in Small Cell Lung Cancer With Surgery: Is Prophylactic Cranial Irradiation Necessary for Stage I-III Disease?

    Energy Technology Data Exchange (ETDEWEB)

    Gong Linlin; Wang, Q.I.; Zhao Lujun; Yuan Zhiyong; Li Ruijian [Department of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, and Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin (China); Wang Ping, E-mail: Doctorwang66@yahoo.cn [Department of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, and Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin (China)

    2013-01-01

    Purpose: The use of prophylactic cranial irradiation (PCI) in small cell lung cancer (SCLC) with surgical resection has not been fully identified. This study undertook to assess the factors affecting the risk of brain metastases in patients with stage I-III SCLC after surgical resection. The implications of PCI treatment for these patients are discussed. Methods and Materials: One hundred twenty-six patients treated with surgical resection for stage I-III SCLC from January 1998-December 2009 were retrospectively analyzed to elucidate the risk factors of brain metastases. Log-rank test and Cox regression model were used to determine the risk factors of brain metastases. Results: The median survival time for this patient population was 34 months, and the 5-year overall survival rate was 34.9%. For the whole group, 23.0% (29/126) of the patients had evidence of metastases to brain. Pathologic stage not only correlated with overall survival but also significantly affected the risk of brain metastases. The 5-year survival rates for patients with pathologic stages I, II, and III were 54.8%, 35.6%, and 14.1%, respectively (P=.001). The frequency of brain metastases in patients with pathologic stages I, II, and III were 6.25% (2/32), 28.2% (11/39), and 29.1% (16/55) (P=.026), respectively. A significant difference in brain metastases between patients with complete resection and incomplete resection was also observed (20.5% vs 42.9%, P=.028). The frequency of brain metastases was not found to be correlated with age, sex, pathologic type, induction chemotherapy, adjuvant chemotherapy, or adjuvant radiation therapy. Conclusions: Stage I SCLC patients with complete resection had a low incidence of brain metastases and a favorable survival rate. Stage II-III disease had a higher incidence of brain metastases. Thus, PCI might have a role for stage II-III disease but not for stage I disease.

  14. Intracranial metastasis from a sacrococcygeal chordoma. Case report.

    LENUS (Irish Health Repository)

    Kamel, Mahmoud Hamdy

    2012-02-03

    Chordoma is a locally invasive tumor of low metastatic potential. Only six cases of chordoma that metastasized to the brain are found in the English literature. Most of these lesions were clinically silent and all were associated with extraneural metastases. The authors report a case of symptomatic brain metastasis from a sacrococcygeal chordoma in the absence of other metastases. The incidence, sites, and factors predictive of chordoma metastasis are discussed.

  15. Cancer stem cells and metastasis.

    Science.gov (United States)

    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.

  16. Tumour exosome integrins determine organotropic metastasis.

    Science.gov (United States)

    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.

  17. 伽玛刀分次治疗脑转移瘤的疗效评估%Evaluation of Clinical Efficacy of Fractionated Gamma Knife for the Treatment for Brain Metastasis Tumor

    Institute of Scientific and Technical Information of China (English)

    王宗烨; 戴卓捷; 王建峰; 马慧珍; 任晔

    2011-01-01

    [Objective] To evaluate the clinical efficacy of fractionated gamma knife for the treatment of brain metastasis tumor. [Methods] Thirty two patients who suffered {rom brain metastasis tumor were treated with factionated gamma knife(cobalt 60-gyro rotating radiation therapy system, Gyro Knife). The fractionated dose of 50~70% isodose curve were 2.5~5Gy, and the total dose of tumor periphery were 30~40 Gy. Periodical follow up after treatment was performed with MR scan to evaluate the clinical efficacy as well as record the side effects. [Results]Thirty two patients were followed up for 1~15 months and the number of tumor in one patient was 1 to 3. According to WHO standards for the clinical evaluation, 10 cases were the complete remission(CR) of the tumor, and 15 cases were partial remission(PR), and 6 cases were in a stable condition(SD). The clinical symptoms in all cases were much improved. The short term effect(PR + CR) in this group was up to 78.2% and the one-year survival rate was 66.7%. No obvious long term side-effects were observed in the follow up period. [Conclusion]Compared with previous studies, fractionated gamma knife for the treatment of brain metastasis tumor has high local control rate, less adverse reaction and no long term side effects.%[目的]评价伽玛刀分次治疗脑转移瘤的临床疗效.[方法] 32例脑转移瘤患者,应用伽玛刀(陀螺旋转式钴60放射治疗系统,陀螺刀)进行分次治疗,采用每次分次剂量50%~70%等剂量曲线2.5~5 Gy,肿瘤周边总剂量30~40 Gy,治疗结束后定期复查MR并评价疗效,记录毒副作用.[结果]32例患者,随访1~15个月 ,肿瘤数量1~3个,按WHO标准评价,肿瘤消失(CR)10例,肿瘤缩小(PR)15例,稳定(SD)6例,临床症状明显好转,本组治疗的近期有效率(PR+CR)达78.2%,一年存活率为66.7%.未出现明显的远期副作用.[结论] 与文献对比,伽玛刀分次治疗脑转移瘤局部控制率提高,不良反应减少,未出现远期毒副反应.

  18. Research-progression of Temozolomide in Brain Metastasis%替莫唑胺应用于脑转移瘤的研究进展

    Institute of Scientific and Technical Information of China (English)

    韦燕(综述); 赵善琳(审校)

    2015-01-01

    Brain metastases are most common intracranial malignant tumors in adults, with the progress of tumor treatment means, the better curative effect of malignant tumor and the longer survival time, the incidence of brain metastases increase. That will be serious impact on quality of life. Treatment of brain metastases is limited, radiation therapy is the traditional one. As a new generation of alkylating agent temozolomide, which show antitumor effects by through the blood-brain barrier, widely used in the treatment of glioma. In recent years attempts to using temozolomide therapy metastatic cancer also effective. This paper summarize using temozolomide in the treatment of brain metastases.%脑转移性肿瘤是成人最常见的颅内恶性肿瘤,治疗手段有限,传统的治疗方法主要以放射治疗为主。替莫唑胺是新一代的烷化剂,具有透过血脑屏障起到抗肿瘤的作用,在脑胶质瘤的治疗上应用广泛,疗效确切。近年来尝试在脑转移性肿瘤上使用替莫唑胺治疗亦得到肯定疗效,替莫唑胺与其他化疗药物或放疗联合可能有助于控制肿瘤,使患者得到生存获益。本文就国内外使用替莫唑胺治疗脑转移瘤的现状进展进行综述。

  19. Physiopathology of Spine Metastasis

    Directory of Open Access Journals (Sweden)

    Giulio Maccauro

    2011-01-01

    Full Text Available The metastasis is the spread of cancer from one part of the body to another. Two-thirds of patients with cancer will develop bone metastasis. Breast, prostate and lung cancer are responsible for more than 80% of cases of metastatic bone disease. The spine is the most common site of bone metastasis. A spinal metastasis may cause pain, instability and neurological injuries. The diffusion through Batson venous system is the principal process of spinal metastasis, but the dissemination is possible also through arterial and lymphatic system or by contiguity. Once cancer cells have invaded the bone, they produce growth factors that stimulate osteoblastic or osteolytic activity resulting in bone remodeling with release of other growth factors that lead to a vicious cycle of bone destruction and growth of local tumour.

  20. Dosimetry study of volumetric-modulated arc therapy for single brain metastasis%容积调强弧形治疗用于单发脑转移瘤的剂量学研究

    Institute of Scientific and Technical Information of China (English)

    徐英杰; 肖建平; 马攀; 门阔; 张永谦; 戴建荣

    2015-01-01

    目的 通过与立体定向拉弧(S_ARC)计划剂量学参数比较,研究VMAT用于单发脑转移瘤剂量学特点,为其临床应用提供指导.方法 收集2012年在本院治疗的单发脑转移瘤31例,分别设计VMAT单双弧计划和S_ARC计划,要求处方剂量(40 Gy分4次)覆盖95%靶体积.计划评价参数包括靶区适形、梯度指数,正常脑组织Dmean及低剂量体积、机器跳数和计划执行时间.配对t检验或Wilcoxon符号秩检验不同计划间差别.结果 VMAT单弧、双弧计划的CI值高于S_ARC计划,其中位数分别为0.815、0.818、0.779(P =0.000、0.000),3种计划的梯度指数中位数均不同,分别为5.865、5.706、3.133(P=0.000、0.000、0.000),VMAT计划具有更好靶区适形性但剂量梯度略差.VMAT计划的正常脑组织Dmean更大、低剂量受照体积更大(P=0.000、0.000).VMAT单弧和双弧计划及SARC计划的治疗时间分别为(2.7±0.1)、(2.8±0.1)、(7.6±0.2)min,VMAT计划执行时间短于S_ARC计划(P =0.000、0.000).结论 VMAT用于单发脑转移瘤,计划执行时间短,剂量分布能满足临床要求.%Objective To evaluate the plan quality of volumetric modulated arc therapy (VMAT) in single brain metastasis compared with the stereotactic arc therapy (S_ARC).Methods 31 patients were replanned using VMAT and S_ARC technique.Prescription dose is 40 Gy delivered in 4 fractions covering at least 95% of the target volume while keeping minimum doses to the volume of normal brain tissue.The plans were assessed and compared using the conformity indexes (CI),gradient indexes (GI),the mean dose of normal brain tissue,the volumes of normal brain tissue receiving 4 Gy doses,the number of monitor unit and treatment times.A paired t test or non-parametric Wilcoxon signed rank test was performed to analyze the difference between these two plans.Results VMAT plans increased dose conformity,but not dose gradient,compared with S_ARC plans.The median dose conformity index values were

  1. Targeting Prostate Cancer Metastasis

    Science.gov (United States)

    2015-09-01

    AWARD NUMBER: W81XWH-14-1-0412 TITLE: "Targeting Prostate Cancer Metastasis " PRINCIPAL INVESTIGATOR: Yong Teng CONTRACTING ORGANIZATION: REPORT...ng Prost a t e Cancer Metastasi s Sb. GRANT NUMBER W81XWH- 14- 1- 0 41 2 Sc. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Sd. PROJECT NUMBER YongTeng Se...r egulator in contr olling metastasis of p r ost a t e cancer and i nhi b i t i ng i t prevent s met ast asis . There are no drugs available to tar

  2. Robo1蛋白在非小细胞肺癌和肺癌脑转移组织中的表达及意义%Robo1 expression in non-small cell lung cancer and its brain metastasis

    Institute of Scientific and Technical Information of China (English)

    李晓霞; 金玲; 孙增峰; 谷峰; 李文良; 马勇杰

    2013-01-01

    目的 探讨Robo1蛋白的表达与非小细胞肺癌(NSCLC)脑转移的关系.方法 采用免疫组化SP法检测80例NSCLC和52例癌旁组织中Robo1蛋白的表达情况,同时检测72例NSCLC脑转移患者(无其他脏器转移,脑转移灶为单发)脑转移瘤组织中Robo1蛋白的表达情况.另选取17例自身对照患者,检测肺癌和脑转移瘤组织中Robo1蛋白的表达情况.采用Kaplan-Meier法绘制生存曲线,并行Log rank检验.结果 Robo1蛋白在癌旁组织、肺癌组织和脑转移瘤组织中的阳性表达率分别为1.9%(1/52)、13.8%(11/80)和40.3%(29/72),差异有统计学意义(P<0.05).在17例自身对照患者中,Robo1蛋白在肺癌和脑转移瘤组织中的阳性表达率分别为17.6%和64.7%,差异有统计学意义(P<0.01).72例肺癌脑转移患者中,Robo1蛋白阳性表达患者的中位生存时间为10个月,明显短于阴性表达的患者(17个月,P <0.05).结论 Robo1蛋白在癌旁组织、肺癌组织和肺癌脑转移瘤组织中的表达依次增高,Robo1蛋白在肺癌脑转移瘤中的表达与脑转移患者的预后呈负相关.Robo1可能作为促癌基因促进了肺癌和脑转移瘤的发生和发展.%Objective To detect the expression of Robo1 in lung cancer tissues,adjacent noncancerous tissues as well as lung cancer brain metastasis,and explore the correlation of Robo1 expression to lung cancer brain metastasis.Methods SP (streptavidin-peroxidase) staining method was used to examine the Robo1 expression in specimens from 80 cases of NSCLC,52 cases of adjacent non-cancerous tissues and 72 cases of lung cancer with single brain metastasis (without metastasis in other organs).The Robo1 expression was further examined in 17 self control cases with lung cancer tissues and their brain metastasis tissues.The results were assessed by Kaplan-Meier analysis and log-rank test.Results The positive expression rate of Robo1 among adjacent non-cancerous tissues,lung cancers tissues and the

  3. Brain metastases from colorectal cancer

    DEFF Research Database (Denmark)

    Vagn-Hansen, Chris Aksel; Rafaelsen, Søren Rafael

    2001-01-01

    Brain metastases from colorectal cancer are rare. The prognosis for patients with even a single resectable brain metastasis is poor. A case of surgically treated cerebral metastasis from a rectal carcinoma is reported. The brain tumour was radically resected. However, cerebral, as well...... as extracerebral, disease recurred 12 months after diagnosis. Surgical removal of colorectal metastatic brain lesions in selected cases results in a longer survival time....

  4. Targeting Breast Cancer Metastasis

    OpenAIRE

    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 me...

  5. Brain metastasis of ALK positive anaplastic large cell lymphoma after a long-term disease free survival in an old adult

    Science.gov (United States)

    Wang, Cai-Xia; Wang, Hai; Li, Jie; Ma, Heng-Hui; Yu, Bo; Shi, Shan-Shan; Zhou, Xiao-Jun; Shi, Qun-Li

    2014-01-01

    Anaplastic large cell lymphoma (ALCL) is a subtype of non-Hodgkin lymphoma composed of CD30-positive cells and now recognized as three different entities: primary cutaneous ALCL, primary systemic anaplastic lymphoma kinase (ALK)-positive (ALK+) ALCL and primary ALK-negative (ALK-) ALCL. ALK+ ALCL is supposed to have a better prognosis than ALK- ALCL. It is rarely metastasized to other sites, especially to the central nervous system (CNS). Herein, we present a rare case of systemic ALK+ ALCL which metastasized to the brain after a long-term disease free survival in an adult. Neuroimaging revealed a well-enhanced mass in the left frontal lobe. And it was completely resected. The results of the pathological and immunohistochemical studies were consistent with the metastasized ALK+ ALCL. The clinical findings, pathologic characteristics and treatment are described. PMID:24696735

  6. Solitary brain metastasis of an occult and stable small-cell lung cancer in a schizophrenic patient: a 3-year control.

    Science.gov (United States)

    Jesien-Lewandowicz, Emilia; Spych, Michal; Fijuth, Jacek; Kordek, Radzislaw

    2010-08-01

    Small-cell lung cancer is a highly aggressive carcinoma, with poorer prognosis in patients with brain metastases. We present the case of a 49-year-old woman diagnosed with a cerebellar tumour which, following surgery, was revealed to be a metastatic small-cell lung carcinoma. Subsequent CT and PET scanning showed a small, isolated 8 mm nodule in the upper lobe of the right lung. The patient was suffering from schizophrenia and has been treated with clozapine for 17 years. Because of the unusual presentation, there was no therapy given for the primary tumour at the time, and systemic therapy or surgery was discussed. However, 18 months later, the nodule was slightly larger (14 mm), and surgery was performed. On pathology examination, the tumour was presented as a typical small-cell carcinoma. Standard chest irradiation with systemic chemotherapy was given. At the time of writing, 39 months after diagnosis of metastatic small-cell carcinoma, the patient is disease free. However, this case is unusual in that a long-term observation of a small stable primary tumour in the lung took place without any therapy being given. This case strongly supports the thesis that small-cell lung cancer may comprise a heterogeneous group of tumours with different biological properties. The proapoptotic effect of clozapine may be also taken into account.

  7. Hypoxia-mediated metastasis.

    Science.gov (United States)

    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.

  8. Soft tissue sarcoma with metastasis to the stomach: A case report

    Institute of Scientific and Technical Information of China (English)

    Lemuel; Leon; Dent; Cesar; Yamil; Cardona; Michael; Clause; Buchholz; Roosevelt; Peebles; Julie; Denise; Scott; Derrick; Jerome; Beech; Billy; Ray; Ballard

    2010-01-01

    Soft tissue sarcomas are unusual malignancies comprising 1% of cancer diagnoses in the United States. Undifferentiated pleomorphic sarcoma accounts for approximately 5% of sarcomas occurring in adults. The most common site of metastasis is the lung, with other sites being bone, the brain, and the liver. Metastasis to the gastrointestinal tract has rarely been documented. We present an unusual case of high-grade pleomorphic sarcoma with metastasis to the stomach, complicated by upper gastrointestinal bleedin...

  9. Metastasis Is Cell Motility Disease

    Institute of Scientific and Technical Information of China (English)

    Kazuyuki ITOH

    2009-01-01

    @@ Multidisciplinary approach (surgery, chemotherapy and radiation) for the primary site of cancer is now almost established, however, recurrence, inva-sion and metastasis are still life threatening, thus the effort of fighting against metastasis is critical and crucial.

  10. Cerebral metastasis from hepatoid adenocarcinoma of the stomach

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    We first report a rare case of metastasis from gastric hepatoid adenocarcinoma (HAC) to cerebral parenchyma, in a 50-year-old Chinese patient. He complained of a one-month history of a paroxysm of headache in the left temple and pars parietalis accompanied with binocular caligation caligo, insensible feeling of limbs and transient anepia. Magnetic resonance (MR) imaging revealed a spherical occupying lesion in the left posterior-temple lobe which was clinically diagnosed as a metastatic tumor. Three years ago, the patient accepted total gastrectomy as he was pathologically diagnosed at gastroscopy having an adenocarcinoma. Eight months after gastrectomy, the occupying lesion in liver was detected by ultrasound and CT, and he accepted transcatheter arterial embolization. Before operation of the brain metastasis, no obvious abnormality was found in liver by ultrasound. Histopathological characteristics of the brain tumor were identical to those of stomach tumor. The growth pattern of both tumors showed solid cell nests. The tumor cells were polygonal, and had abundant eosinophilic cytoplasm and round nuclei with obvious nucleoli. Sinusoid-like blood spaces were located between nodular tumor cells. Immunohistochemistrystained tumor cells were positive for AFP and negative for Hep-Par-1. According to these histopathological findings, both tumors were diagnosed as HAC and metastatic HAC. The patient remained alive 16 mo after tumorectomy of the cerebral metastasis. The differential diagnosis of brain metastasis from metastatic tumors should use a panel of antibodies to avoid confusing with the brain metastasis of hepatocellular carcinoma (HCC). This paper describes this rare case of metastasis from gastric hepatoid adenocarcinoma to cerebral parenchyma, and provides a review of the literature concerning its histopathological and immunohistochemical characteristics.

  11. Cathepsins mediate tumor metastasis

    Institute of Scientific and Technical Information of China (English)

    Gong-Jun; Tan; Zheng-Ke; Peng; Jin-Ping; Lu; Fa-Qing; Tang

    2013-01-01

    Cathepsins are highly expressed in various human cancers, associated with tumor metastasis. It is superfamily, concluding A, B, C, D, E, F, G, H, L, K, O, S, V, and W family members. As a group of lysosomal proteinases or endopeptidases, each member has a different function, playing different roles in distinct tumorigenic processes such as proliferation, angiogenesis, metastasis, and invasion. Cathepsins belong to a diverse number of enzyme subtypes, including cysteine proteases, serine proteases and aspartic proteases. The contribution of cathepsins to invasion in human cancers is well documented, although the precise mechanisms by which cathepsins exert their effects are still not clear. In the present review, the role of cathepsin family members in cancer is discussed.

  12. Testicular leiomyosarcoma with metastasis

    Directory of Open Access Journals (Sweden)

    Venkatesh Giridhar

    2011-01-01

    Full Text Available Primary leiomyosarcoma of testis is a rare entity with few cases reported in literature. Primary leiomyosarcoma of testis usually occurs following radiotherapy or long-term anabolic steroid use. Without these predisposing factors, its occurrence is rare. In the present study, we present a rare case of primary leiomyosarcoma of testis occurring in an elderly patient, with an unusual presentation mimicking epididymo-orchitis and metastasis eight months following high inguinal orchidectomy.

  13. Solitary midbrain metastasis.

    Science.gov (United States)

    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.

  14. Intracranial metastasis from carcinoma of the cervix: A rare case report

    Directory of Open Access Journals (Sweden)

    Tanvi Aggarwal

    2014-01-01

    Full Text Available Brain metastasis from cervical carcinoma is very rare and have poor prognosis. We report an interesting and rare case of cervical carcinoma who developed brain metastasis following total hysterectomy with bilateral salpingoophorectomy and radiotherapy, within 6 months of primary diagnosis. Since patient prognosis is very poor, oncology physicians should anticipate the presence of this condition in order to give prompt and comprehensive treatment.

  15. AMELANOTIC MELANOMA WITH ATYPICAL CLINICAL PRESENTATION AND MULTIPLE METASTASIS

    Directory of Open Access Journals (Sweden)

    Revathy

    2014-11-01

    Full Text Available A 52 year old woman presented with a history of asymptomatic skin lesions over left leg for the past 4 months. On examination she had multiple skin coloured papules and plaques over left leg. Oedema was also seen over left leg. Histopathology and immunohistochemistry proved the diagnosis of malignant melanoma. Radiological investigation showed metastasis to lung, liver and brain. The patient was asymptomatic at the time of admission but she developed rapid metastasis within a very short span of time. This case is reported for the rare atypical presentation of malignant melanoma.

  16. Clinical Observation and Basic Study of Erlotinib Combined Radiotherapy in the Treatment of Non-Small Cell Lung Cancer with Brain Metastasis%厄洛替尼联合放疗治疗肺癌脑转移的临床及基础研究

    Institute of Scientific and Technical Information of China (English)

    张清琴; 靳彩玲; 崔艳慧; 苗战会; 寇小格; 李小瑞

    2011-01-01

    Objective To study the efficacy of erlotinib combined with whole brain radiotherapy(WBRT) for non-small cell lung cancer(NSCLC) patients with brain metastasis and investigate gene mutations of EGFR and erlotinib efficacy. Methods Forty NSCLC patients with brain metastasis received conventional WBRT of 30 Gy concurrently with 150 mg oral doses of erlotinib once daily until disease progression. Gene sequencing was used to detect the EGFR of all patients, MRI was evaluated 3 months after radiation. Results In NSCLC patients with brain metastasis, the overall response rate and clinical benefit rate of erlotinib combined with WBRT were 90.0% and 100% respectively( complete response, CR in 4 patients, partial response, PR in 30 patients ,and stable disease SD in 6patients). Overall median survival was 10.2 months. Its efficacy in exon 19 and 21 of EGFR was 90.3%. Conclusion Erlotinib combined with radiotherapy was effective for Non-small cell lung cancer patients with multiple brain metastasis,especially patients with 19 and 21 of EGFR.%目的 观察厄洛替尼联合全脑放疗(WBRT)治疗非小细胞肺癌(non-small cell lung cancer,NSCLC)的有效性,并探讨其与表皮生长因子(epidermal growth factor receptor,EGFR)基因突变的关系.方法 40例均为不能接受化疗或化疗失败的NSCLC脑转移患者,接受全脑放疗(whole brain radi otherapy,WBRT)30 Gy/10 Fx,共2周,同时口服厄洛替尼150 mg,1次/d,直至疾病进展,所有患者均经基因测序法检查EGFR突变.放疗结束后3个月复查脑MRI,每3个月复查1次,进行临床疗效评价,直至疾病进展,并统计1年生存情况.结果 厄洛替尼联合WBRT对NSCLC脑转移的客观缓解率(完全缓解+部分缓解)为85.0%,临床症状缓解率100%,中位生存时间10.2月,EGFR突变的外显子19和2l突变的有效率为90.3%.结论 厄洛替尼联合WBRT对NSCLC脑转移EGFR突变的患者有较好的疗效,尤其是外显子19和2l突变的患者.生存期明显延

  17. Impact of CT/MRI Image Registration on Target Delineation of Radiotherapy for Lung Cancer with Brain Metastasis%CT/MRI影像融合对肺癌脑转移放射治疗靶区勾画的影响

    Institute of Scientific and Technical Information of China (English)

    李洋; 李香兰; 王业伟; 周洋

    2012-01-01

    背景与目的 脑转移瘤靶区勾画的准确性一直是放射治疗的关键,CT/MRI融合技术提供了可行的方法,本研究旨在探讨CT/MRI图像融合技术在肺癌脑转移靶区勾画中的作用.方法 将31例肺癌脑转移患者的增强CT和MRI图像传送至图像处理工作站,分别在CT和CT/MRI融合图像上勾画GTV,比较勾画后的GTV体积,分析最大平均误差及瘤周水肿对靶区勾画的影响.结果 CT/MRI融合图像上勾画的GTV明显小于CT图像上勾画的GTV;瘤周水肿对靶区勾画存在明显影响.结论 CT/MRI图像融合技术可以提高肺癌脑转移靶区勾画的准确性.%Background and objective Accurate target delineation in radiation therapy is a key component of the treatment regimen for brain metastasis for which CT/MRI fusion technology provides a feasible method. The aim of this study is to explore the role of CT/MRI image registration in target delineation for lung cancer with brain metastasis. Methods The image data of 31 patients were processed using Oncentra MasterPlan. The GTVs were delineated on CT and CT/MRI images, and their differences were compared to analyze the impact of the maximum average error and tumor edema on target delineation. Results The GTVs delineated on CT/MRI images were markedly smaller than those delineated on CT images. Target delineation was clearly influenced by edema. Conclusion The technology of CT/MRI image registration can improve the accuracy of target delineation for lung cancer with brain metastasis.

  18. Metastatic Brain Tumors

    Directory of Open Access Journals (Sweden)

    Ersin Haciyakupoglu

    2014-04-01

    Full Text Available Metastatic tumor is secondary spread to the central nervous system of primer systemic cancers originating from tissues other than the central nervous system. In adults; there are metastases respectively from lungs, breasts, malign melanoma, renal cell carcinoma, colon and thyroid cancers. 30-60% of lung cancers metastasis to the brain. In children there are quite a few cerebral metastases. Most commonly leukemia, lymphoma, osteogenic sarcoma, rhabdomyosarcoma and germ cell tumors metastasis to the brain. %50 of malign melanoma, lung, breast and colon cancers intend to make multipl metastases but renal cell cancers intend to make solitary metastasis.While lung cancers metastasis to brain in 6-9 months after the definitive diagnosis, renal cancers in 1 year, colon cancers in 2 years, breast cancers and malign melanoma in 3 years metastasis to brain. In 6% of cases there are cerebral metastasis while there isn’t a symptom of a primary tumor. For treatment corticosteroids, surgery, Radiotherapy(RT, Chemotherapy(CT and Stereotactic Radiosurgery(SRS can be implemented. Small cell lung cancers, lymphoma, germ cell tumors are sensitive to RT and CT. Non small cell lung cancers, renal, colon cancers and malign melanoma are radioresistant. The purposes in the surgery of the metastatic brain tumors are; total resection of tumors without neurologic deficits, decreasing the intracranial pressure and decreasing the dose of postoperative radiotherapy. Key Words: Metastatic brain tumors, Stereotactic radiosurgery, Malign melanoma, Lung cancers, Renal cell carcinoma, Radiotherapy, Chemotherapy [Cukurova Med J 2014; 39(2.000: 191-202

  19. Papillary thyroid microcarcinoma presenting as skull base metastasis

    Institute of Scientific and Technical Information of China (English)

    YAN Bo; LIU Dian-gang; L(U) Hai-li; ZHANG Qiu-hang

    2010-01-01

    @@ Papillary thyroid carcinoma (PTC) is the most common type of well-differentiated thyroid cancer and is considered to be a relatively indolent tumor in which distant metastasis and death are rare.1 The metastasis of PTC is usually to regional lymph nodes, especially the cervical and mediastinal nodes. Metastases to the brain are rare, and constitute 0.1%-5.0% of distant metastases of papillary carcinoma.2 Skull metastasis is uncommon,and is found in 2.5%-5.8% of cases of thyroid cancer.3 Skull base metastasis of PTC is extremely rare, with only eight reported cases in the literature involving the clivus,cavernous sinus, sella turcica, and the petrous apex and ridge.4 A metastatic lesion can arise from histologically benign and silent thyroid neoplasms,5 and differential diagnosis between ectopic and metastatic thyroid cancer can be difficult,6 therefore, the management of thyroid cancer is controversial after removal of metastatic disease.Here we reported a case of papillary thyroid microcarcinoma (PTMC) that was manifested as a solitary clivus metastasis and discussed the diagnostic and therapeutic management strategies. The 73-year-old patient presented with visual impairment in the right eye,and epistaxis. The patient subsequently underwent complete total thyroidectomy after a diagnosis of papillary microcarcinoma. This finding emphasizes that clinically significant metastases can arise from thyroid papillary microcarcinoma. Total thyroidectomy and careful review of the histology are necessary to prevent delay in proper diagnosis.

  20. Is Selenium a Potential Treatment for Cancer Metastasis?

    Directory of Open Access Journals (Sweden)

    Yu-Chi Chen

    2013-04-01

    Full Text Available Selenium (Se is an essential micronutrient that functions as a redox gatekeeper through its incorporation into proteins to alleviate oxidative stress in cells. Although the epidemiological data are somewhat controversial, the results of many studies suggest that inorganic and organic forms of Se negatively affect cancer progression, and that several selenoproteins, such as GPXs, also play important roles in tumor development. Recently, a few scientists have examined the relationship between Se and metastasis, a late event in cancer progression, and have evaluated the potential of Se as an anti-angiogenesis or anti-metastasis agent. In this review, we present the current knowledge about Se compounds and selenoproteins, and their effects on the development of metastasis, with an emphasis on cell migration, invasion, and angiogenesis. In the cancers of breast, prostate, colorectal, fibrosarcoma, melanoma, liver, lung, oral squamous cell carcinoma, and brain glioma, there is either clinical evidence linking selenoproteins, such as thioredoxin reductase-1 to lymph node metastasis; in vitro studies indicating that Se compounds and selenoproteins inhibited cell motility, migration, and invasion, and reduced angiogenic factors in some of these cancer cells; or animal studies showing that Se supplementation resulted in reduced microvessel density and metastasis. Together, these data support the notion that Se may be an anti-metastastatic element in addition to being a cancer preventative agent.

  1. Is selenium a potential treatment for cancer metastasis?

    Science.gov (United States)

    Chen, Yu-Chi; Prabhu, K Sandeep; Mastro, Andrea M

    2013-04-08

    Selenium (Se) is an essential micronutrient that functions as a redox gatekeeper through its incorporation into proteins to alleviate oxidative stress in cells. Although the epidemiological data are somewhat controversial, the results of many studies suggest that inorganic and organic forms of Se negatively affect cancer progression, and that several selenoproteins, such as GPXs, also play important roles in tumor development. Recently, a few scientists have examined the relationship between Se and metastasis, a late event in cancer progression, and have evaluated the potential of Se as an anti-angiogenesis or anti-metastasis agent. In this review, we present the current knowledge about Se compounds and selenoproteins, and their effects on the development of metastasis, with an emphasis on cell migration, invasion, and angiogenesis. In the cancers of breast, prostate, colorectal, fibrosarcoma, melanoma, liver, lung, oral squamous cell carcinoma, and brain glioma, there is either clinical evidence linking selenoproteins, such as thioredoxin reductase-1 to lymph node metastasis; in vitro studies indicating that Se compounds and selenoproteins inhibited cell motility, migration, and invasion, and reduced angiogenic factors in some of these cancer cells; or animal studies showing that Se supplementation resulted in reduced microvessel density and metastasis. Together, these data support the notion that Se may be an anti-metastastatic element in addition to being a cancer preventative agent.

  2. Diagnostic examination performance by using microvascular leakage, cerebral blood volume, and blood flow derived from 3-T dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging in the differentiation of glioblastoma multiforme and brain metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Server, Andres; Nakstad, Per H. [Oslo University Hospital-Ullevaal, Section of Neuroradiology, Department of Radiology and Nuclear Medicine, Oslo (Norway); University of Oslo, Oslo (Norway); Orheim, Tone E.D. [Oslo University Hospital, Interventional Centre, Oslo (Norway); Graff, Bjoern A. [Oslo University Hospital-Ullevaal, Department of Radiology and Nuclear Medicine, Oslo (Norway); Josefsen, Roger [Oslo University Hospital-Ullevaal, Department of Neurosurgery, Oslo (Norway); Kumar, Theresa [Oslo University Hospital-Ullevaal, Department of Pathology, Oslo (Norway)

    2011-05-15

    Conventional magnetic resonance (MR) imaging has limited capacity to differentiate between glioblastoma multiforme (GBM) and metastasis. The purposes of this study were: (1) to compare microvascular leakage (MVL), cerebral blood volume (CBV), and blood flow (CBF) in the distinction of metastasis from GBM using dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging (DSC-MRI), and (2) to estimate the diagnostic accuracy of perfusion and permeability MR imaging. A prospective study of 61 patients (40 GBMs and 21 metastases) was performed at 3 T using DSC-MRI. Normalized rCBV and rCBF from tumoral (rCBVt, rCBFt), peri-enhancing region (rCBVe, rCBFe), and by dividing the value in the tumor by the value in the peri-enhancing region (rCBVt/e, rCBFt/e), as well as MVL were calculated. Hemodynamic and histopathologic variables were analyzed statistically and Spearman/Pearson correlations. Receiver operating characteristic curve analysis was performed for each of the variables. The rCBVe, rCBFe, and MVL were significantly greater in GBMs compared with those of metastases. The optimal cutoff value for differentiating GBM from metastasis was 0.80 which implies a sensitivity of 95%, a specificity of 92%, a positive predictive value of 86%, and a negative predictive value of 97% for rCBVe ratio. We found a modest correlation between rCBVt and rCBFt ratios. MVL measurements in GBMs are significantly higher than those in metastases. Statistically, both rCBVe, rCBVt/e and rCBFe, rCBFt/e were useful in differentiating between GBMs and metastases, supporting the hypothesis that perfusion MR imaging can detect infiltration of tumor cells in the peri-enhancing region. (orig.)

  3. 人肺腺癌脑转移动物模型建立及显像的研究%An Experimental Study on the Chinese Lung Adenocarcinoma Cell Clone CPA-Yang1-BR with Brain Metastasis Potency in Nude Mice and In Vivo Imaging Research

    Institute of Scientific and Technical Information of China (English)

    雷贝; 曹杰; 沈杰; 赵兰香; 梁胜; 孟庆刚; 谢文晖; 杨顺芳

    2013-01-01

    Background and objective Lung cancer is the leading cause of cancer-related death in men and wom-en. It is also the most common cause of brain metastases. A brain metastasis model is diffcult to be established because of the presence of the blood-brain barrier (BBB) and the lack of optimal methods for detecting brain metastasis in nude mice. hTus, the establishment of a Chinese lung adenocarcinoma cell line and its animal model with brain metastasis potency and in vivo research is of great signiifcance. Methods CPA-Yang1 cells were obtained from a patient with human lung adeno-carcinoma by lentiviral vector-mediated transfection of green lfuorescence protein. Intracardiac inoculation of the cells was performed in nude mice, and brain metastatic lesions were detected using micro 18F FDG-PET/CT scanners, small animal in vivo imaging system for lfuorescence, radionuclide and X ray fused imaging, magnetic resonance imaging (MRI) with sense body detection, and resection. hTe samples were divided into two parts for cell culture and histological diagnosis. hTe process was repeated in vivo and in vitro for four cycles to obtain a novel cell clone, CPA-Yang1-BR. Results A novel cell clone, CPA-Yang1-BR, was obtained with a brain metastatic rate of 50%. hTe use of MRI for the detection of brain metasta-ses has obvious advantages. Conclusion An experimental Chinese lung adenocarcinoma cell clone (CPA-Yang1-BR) and its animal model with brain metastasis potency in nude mice were established. MRI with sense body or micro MRI may be used as a sensitive, accurate, and noninvasive method to detect experimental brain metastases in intact live immunodeifcient mice. hTe results of this study may serve as a technical platform for brain metastases from lung adenocarcinoma.%背景与目的肺癌脑转移是临床常见的严重并发症,由于脑部结构和功能的特殊性、脑转移检测方法的局限性,预后很差。本研究旨在筛选人肺腺

  4. [Ocular metastasis heralding gastric adenocarcinoma].

    Science.gov (United States)

    Chekrine, T; Tawfiq, N; Bouchbika, Z; Benchakroun, N; Jouhadi, H; Sahraoui, S; Benider, A

    2010-10-01

    Ocular metastasis is a rare presenting feature of gastric adenocarcinoma. We report a 48-year-old woman who presented with a decrease in visual acuity of the right eye leading to the discovery of an ocular metastasis. Diagnostic work-up identified a gastric adenocarcinoma with pulmonary metastases. She received four cycles of chemotherapy combining epirubicin, cisplatin and fluorouracil. The patient died 6 months after the diagnosis of respiratory failure.

  5. Cutaneous metastasis in anorectal adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Krishnendra Varma

    2015-01-01

    Full Text Available Cutaneous metastasis in anorectal adenocarcinoma is a rare entity. Here, we report the case of a 40-year-old female who presented with yellowish-brown, irregular, solid, elevated rashes over the pubis with a recent history off palliative colostomy for anorectal adenocarcinoma. Clinically, we suspected metastasis that was proved on biopsy. We report this case due to the rare presenting site (i.e., perineum of a metastatic adenocarcinoma.

  6. Gastric metastasis of bilateral breast cancer

    Science.gov (United States)

    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

  7. Intracranial metastasis from primary transitional cell carcinoma of female urethra: case report & review of the literature

    Directory of Open Access Journals (Sweden)

    Kim In-Young

    2011-01-01

    Full Text Available Abstract Background Transitional cell carcinoma (TCC of the female urethra is a rare urological malignancy, and intracranial metastasis of this cancer has not yet been reported in the literature. This review is intended to present a case of multiple intracranial metastasis in a female patient with a remote history of primary urethral TCC. Case Presentation A 49-year-old woman, presented with a prolapsed mass in urethral orifice that was diagnosed as primary urethral TCC with distant lung and multiple bone metastases. The patient subsequently underwent chemotherapy under various regimens. A year later, the patient developed headache and vomiting which as was found to be due to multiple intracranial metastasis. The patient underwent surgical resection of the largest lesion located on the cerebellum, and consecutively gamma knife radiosurgery was performed for other small-sized lesions. Pathological examination of the resected mass revealed a metastatic carcinoma from a known urethral TCC. Serial work-up of systemic metastasis revealed concomitant aggravation of lung, spleen, and liver metastasis. The patient died of lung complication 2 months after the diagnosis of brain metastasis. Conclusion To the best of our knowledge, this is the first reported case of cerebral metastasis from primary urethral TCC, with pathological confirmation. As shown in intracranial metastasis of other urinary tract carcinoma, this case occurred in the setting of uncontrolled systemic disease and led to dismal prognosis in spite of aggressive interventional modalities.

  8. Medullary metastasis of a malignant peripheral nerve sheath tumor: A case report

    Science.gov (United States)

    Hagi, Tomohito; Nakamura, Tomoki; Yokoji, Ayumu; Matsumine, Akihiko; Sudo, Akihiro

    2016-01-01

    The present study reports a case of medullary metastasis without lung metastasis that occurred as a result of a malignant peripheral nerve sheath tumor (MPNST). An 81-year-old woman presented with a MPNST in the left brachial plexus, arising from the cervical nerve root. The patient underwent carbon ion radiotherapy; however, tumor recurrence was identified in the left shoulder. Subsequently, the patient underwent wide excision. Three weeks subsequent to surgery, imbalance and dysarthria developed suddenly. Dysphagia emerged and left upper limb pain disappeared on the day after symptom development. Magnetic resonance imaging (MRI) revealed that this was due to metastasis to the medulla. Five days subsequent to the onset of dysarthria, the patient succumbed due to respiratory failure. To the best of our knowledge, no previous cases of medullary metastasis arising from a MPNST in the absence of lung metastasis have been reported. MRI is a useful examination tool for the identification of brain metastases; however, the high cost of MRI as a routine examination must be considered due to the rarity of brain metastases. Therefore, methods to detect brain metastasis warrant further investigation. PMID:27588138

  9. Intra-cranial metastasis of gastrointestinal stromal tumor

    Institute of Scientific and Technical Information of China (English)

    WONG Chun-sing; CHU Yiu-ching

    2011-01-01

    With the evolution of immunochemical staining techniques and better imaging modalities with better image resolution and whole body coverage,gastrointestinal stromal tumor (GIST),the most common mesenchymal tumor of the gastrointestinal tract,is often encountered in clinical practice.Metastasis is common with malignant GIST and can be found in up to 50% of patients at presentation.Liver and peritoneum are the two most common sites of metastasis and accounted for 95% of cases.Lymphatics,bone and lung metastasis are rare.Malignant GIST with intracranial metastasis is even rarer,with only a few cases reported in the literature,and most of these had earlier metastasis elsewhere.Radiological features for GISTs are not specific but it does contribute to confirming early and accurate diagnosis of malignant GISTs by judging the tumor size,enhancement pattern and the invasion of adjacent structures.We report a case of a 26-year-old male with metastatic GIST to the liver and subsequently to the brain and skull vault.This is the first case reported in our locality and he is the youngest patient reported with this disease entity.The clinical progress,radiological features and the role of imaging will be discussed further in this paper.The radiological and clinical features of the primary tumor will specifically be addressed.The purpose of this paper is to enrich the current database of this rare disease entity and to alert both radiologists and clinicians about the imaging features of GIST with intracranial metastasis.

  10. [Orbital metastasis in malignant melanoma].

    Science.gov (United States)

    Pedroli, G L; Hamedani, M; Barraco, P; Oubaaz, A; Morax, S

    2001-03-01

    We report the case of a 60-year-old man presenting bilateral progressive proptosis with diplopia, weight loss, tachycardia, nervosity, and stomach pain. These signs seemed at first to favor a diagnosis of Graves'ophthalmopathy. Thyroid tests were negative and the initial orbital CT scan was considered normal. A new radiological investigation 4 months later in our hospital revealed typical hypertrophy of the extraocular muscles compatible with orbital metastasis. The systemic investigations demonstrated a pulmonary tumor, multiple hepatic lesions, and several pigmented nodules of gastric mucosa. The pathology of pulmonary and gastric specimens confirmed the diagnosis of malignant melanoma. The primary lesion remains unknown. The authors discuss the differential diagnoses of orbital metastasis and the radiological characteristics of orbital metastasis in malignant melanoma.

  11. The challenge of targeting metastasis.

    Science.gov (United States)

    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.

  12. 伽玛刀同步贝伐珠单抗治疗伴广泛脑水肿的结直肠癌脑转移瘤:5例病例报道%Concurrent gamma knife radiosu rgery and bevacizumab treatment for brain metastasis from colorectal cancer with extensive cerebral edema:5 cases report

    Institute of Scientific and Technical Information of China (English)

    汤旭群; 江华; 魏立晨; 张南; 戴嘉中; 吴瀚峰; 潘力

    2016-01-01

    Objective To explore the efficacy and safety of concurrent gamma knife radiosurgery and bevacizumab treatment for brain metastasis from colorectal cancer with extensive cerebral edema. Methods Five patients with brain metastasis from colorectal cancer were included in this prospective investigation from March 2013 to October 2014. Bevacizumab therapy (5 mg/kg, at 2 to 3 week intervals) was administered the next day after completion of gamma knife radiosurgery for the median treatment cycle of 4. The patients were followed up for median period of 13 months, ranged from 7 to 18 months. Results Compared with the pretreatment, the lesions decreased by median of 42.85%, ranged from 29.51%to 100%on enhanced MRI T1WI sequence, and edema area decreased by median of 86.60%, ranged from 69.03%to 97.51%on T2WI sequence during short-term follow-up period after the treatment. Clinical symptoms were improved in all the 5 patients, and the KPS increased by a median of 30, ranged from 20 to 40 scores. At last follow-up, two patients died, one progressed and the other two kept tumor progression free. No symptomatic radiation or severe bevacizumab-related adverse events occurred. Conclusion Coadministration of gamma knife radiosurgery and bevacizumab as a promising salvage treatment is safe and effective for brain metastasis from colorectal cancer with extensive cerebral edema.%目的:探讨伽玛刀同步贝伐珠单抗治疗伴广泛脑水肿的结直肠癌脑转移瘤的有效性和安全性。方法2013年3月-2014年10月期间共5例结直肠癌脑转移瘤病人纳入该前瞻性研究。所有病人在伽玛刀治疗后第2天给予贝伐珠单抗静脉滴注(5 mg/kg,每2~3周重复1次),贝伐珠单抗中位治疗周期数为4。伽玛刀和贝伐珠单抗同步治疗后随访7~18个月(中位时间13个月)。结果近期随访显示:MRI T1WI 增强序列上病灶较治疗前缩小29.51%~100%(中位数42.85%),T2WI序列上病灶水肿区域缩小69.03%~97.51%(

  13. Urethral metastasis of lung carcinoma with germinative cell features

    Directory of Open Access Journals (Sweden)

    Tefilli Marcos V.

    2003-01-01

    Full Text Available INTRODUCTION: We present the case of a patient with urethral metastasis of a lung carcinoma with germinative cell features. CASE REPORT: A White, 57-year old man underwent urologic assessment due to gross hematuria. Patient was being treated with chemotherapy and radiotherapy during the past 3 months due to primary carcinoma of the lung with brain metastasis. Urethrocistoscopy and nuclear magnetic resonance imaging revealed a stenosing mass invading the bulbomembranous urethra. No other tumor was found. Biopsy specimens, obtained from the lung, brain and urethra tumors, revealed the same neoplasia, with definitive diagnosis being undifferentiated giant cell carcinoma of the lung with germinative features. Considering his clinical condition and poor prognosis, a decision was made to treat the patient only clinically. Clinical conditions deteriorated and the patient evolved to death within 3 months. COMMENTS: As far as we were able to access, urethral metastasis from lung carcinoma had never been described in the indexed literature. Due to the extremely limited experience with these tumors, there is not a defined treatment and the prognosis remains quite poor.

  14. Metastasis genetics, epigenetics, and the tumor microenvironment

    Science.gov (United States)

    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...

  15. Cerebral Metastasis from a Previously Undiagnosed Appendiceal Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Antonio Biroli

    2012-01-01

    Full Text Available Brain metastases arise in 10%–40% of all cancer patients. Up to one third of the patients do not have previous cancer history. We report a case of a 67-years-old male patient who presented with confusion, tremor, and apraxia. A brain MRI revealed an isolated right temporal lobe lesion. A thorax-abdomen-pelvis CT scan showed no primary lesion. The patient underwent a craniotomy with gross-total resection. Histopathology revealed an intestinal-type adenocarcinoma. A colonoscopy found no primary lesion, but a PET-CT scan showed elevated FDG uptake in the appendiceal nodule. A right hemicolectomy was performed, and the specimen showed a moderately differentiated mucinous appendiceal adenocarcinoma. Whole brain radiotherapy was administrated. A subsequent thorax-abdomen CT scan revealed multiple lung and hepatic metastasis. Seven months later, the patient died of disease progression. In cases of undiagnosed primary lesions, patients present in better general condition, but overall survival does not change. Eventual identification of the primary tumor does not affect survival. PET/CT might be a helpful tool in detecting lesions of the appendiceal region. To the best of our knowledge, such a case was never reported in the literature, and an appendiceal malignancy should be suspected in patients with brain metastasis from an undiagnosed primary tumor.

  16. Pulmonary Metastasis from Pseudomyxoma Peritonei

    Directory of Open Access Journals (Sweden)

    Toshiyuki Kitai

    2012-01-01

    Full Text Available Pseudomyxoma peritonei (PMP is a rare clinical condition, where copious mucinous ascites accumulate in the peritoneal cavity due to dissemination of mucin-producing tumor. Because of this disseminating, yet nonmetastasizing, behavior, PMP attracts much interest from surgical oncologists in that aggressive locoregional therapy can give the opportunity of long survival and even cure. Although extra-abdominal metastasis is exceptionally rare, the lung is the most likely site in such a case. In this paper, the clinical findings and treatment of eleven cases with pulmonary metastasis from PMP were reviewed, including ten cases in the literature and one case which we experienced. The clinical features of PMP cases with pulmonary metastasis were similar to cases without pulmonary metastasis. The histological type was low-grade mucinous neoplasm in most cases. Pulmonary lesions were resected in seven cases in which abdominal lesions were controlled by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy or another therapeutic modality. Disease-free state was maintained in five cases at the end of the follow-up period. However, it should be noted that rapid progression after resection was seen in two cases, suggesting that biological features may have changed by surgical intervention.

  17. Right ventricular metastasis of leiomyosarcoma

    Directory of Open Access Journals (Sweden)

    Stagmo Martin

    2009-05-01

    Full Text Available Abstract 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.

  18. Genome remodelling in a basal-like breast cancer metastasis and xenograft.

    Science.gov (United States)

    Ding, Li; Ellis, Matthew J; Li, Shunqiang; Larson, David E; Chen, Ken; Wallis, John W; Harris, Christopher C; McLellan, Michael D; Fulton, Robert S; Fulton, Lucinda L; Abbott, Rachel M; Hoog, Jeremy; Dooling, David J; Koboldt, Daniel C; Schmidt, Heather; Kalicki, Joelle; Zhang, Qunyuan; Chen, Lei; Lin, Ling; Wendl, Michael C; McMichael, Joshua F; Magrini, Vincent J; Cook, Lisa; McGrath, Sean D; Vickery, Tammi L; Appelbaum, Elizabeth; Deschryver, Katherine; Davies, Sherri; Guintoli, Therese; Lin, Li; Crowder, Robert; Tao, Yu; Snider, Jacqueline E; Smith, Scott M; Dukes, Adam F; Sanderson, Gabriel E; Pohl, Craig S; Delehaunty, Kim D; Fronick, Catrina C; Pape, Kimberley A; Reed, Jerry S; Robinson, Jody S; Hodges, Jennifer S; Schierding, William; Dees, Nathan D; Shen, Dong; Locke, Devin P; Wiechert, Madeline E; Eldred, James M; Peck, Josh B; Oberkfell, Benjamin J; Lolofie, Justin T; Du, Feiyu; Hawkins, Amy E; O'Laughlin, Michelle D; Bernard, Kelly E; Cunningham, Mark; Elliott, Glendoria; Mason, Mark D; Thompson, Dominic M; Ivanovich, Jennifer L; Goodfellow, Paul J; Perou, Charles M; Weinstock, George M; Aft, Rebecca; Watson, Mark; Ley, Timothy J; Wilson, Richard K; Mardis, Elaine R

    2010-04-15

    Massively parallel DNA sequencing technologies provide an unprecedented ability to screen entire genomes for genetic changes associated with tumour progression. Here we describe the genomic analyses of four DNA samples from an African-American patient with basal-like breast cancer: peripheral blood, the primary tumour, a brain metastasis and a xenograft derived from the primary tumour. The metastasis contained two de novo mutations and a large deletion not present in the primary tumour, and was significantly enriched for 20 shared mutations. The xenograft retained all primary tumour mutations and displayed a mutation enrichment pattern that resembled the metastasis. Two overlapping large deletions, encompassing CTNNA1, were present in all three tumour samples. The differential mutation frequencies and structural variation patterns in metastasis and xenograft compared with the primary tumour indicate that secondary tumours may arise from a minority of cells within the primary tumour.

  19. OVARIAN METASTASIS IN PATIENT WITH ENDOMETRIAL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    ZHOU Feng-zhi; CHEN Yi-nan; ZHANG Guo-nan

    2005-01-01

    Objective: To study the clinical pathological characteristics of ovarian metastasis of endometrial carcinoma and the factors affecting prognosis. Methods: Retrospective analysis was made to the clinical pathological outcome of endometrial carcinoma patients receiving surgical treatment in our hospital from January 1990 to December 2002. Results:Among the 191 cases of endometrial carcinoma patients, 17 cases (8.9%) had ovarian metastasis and young patients were more likely to have ovarian metastasis. The multiple factor analysis showed that the independent risk factors of ovarian metastasis in endometrial carcinoma included the depth of myometrial invasion, lymph node metastasis and pathological types. Conclusion: Ovarian metastasis in patients with endometrial carcinoma is associated with poor prognosis, the depth of myometrial invasion, lymph node metastasis and histologic types are independent risk factors affecting the prognosis. For young patients at early stage of the disease, it should be prudent as to whether to retain the ovary.

  20. Breast Cancer Metastasis to Pituitary Infandibulum

    Directory of Open Access Journals (Sweden)

    Maryam Poursadegh Fard

    2011-06-01

    Full Text Available Metastasis from breast cancer to other parts of the body is very common, but the spread of the tumor to pituitary gland, especially to infandibulum, is a rare presentation. At the time of pituitary metastasis, a majority of the patients have clinical and radiological evidence of the disease. It seems that the posterior area of the gland is the most common site of metastasis, probably due to highly rich blood supply through the hypophyseal artery. The present report introduces a case of a 55-years-old woman presented with diabetes insipidus resulting from metastasis of the tumor to pituitary infandibulum, which is a rare site for metastasis, without significant complaint resulting from metastasis to other part of the body, or other primary diseases. Further evaluation revealed that in spite of previous reports, which metastasis usually happens in end stage of cancer, the patients had primary breast cancer. In subsequent evaluations of the case, hypofunction of adenohypophysis was also detected

  1. Design and Construction of a Multi-Organ Microfluidic Chip Mimicking the in vivo Microenvironment of Lung Cancer Metastasis.

    Science.gov (United States)

    Xu, Zhiyun; Li, Encheng; Guo, Zhe; Yu, Ruofei; Hao, Hualong; Xu, Yitong; Sun, Zhao; Li, Xiancheng; Lyu, Jianxin; Wang, Qi

    2016-10-05

    Metastasis is a complex pathophysiological process. As the main cause of cancer mortality in humans it represents a serious challenge to both basic researchers and clinicians. Here we report the design and construction of a multi-organ microfluidic chip that closely mimics the in vivo microenvironment of lung cancer metastasis. This multi-organs-on-a-chip includes an upstream "lung" and three downstream "distant organs", with three polydimethylsiloxane (PDMS) layers and two thin PDMS microporous membranes bonded to form three parallel microchannels. Bronchial epithelial, lung cancer, microvascular endothelial, mononuclear, and fibroblast cells were grown separated by the biomembrane in upstream "lung", while astrocytes, osteocytes, and hepatocytes were grown in distant chambers, to mimic lung cancer cell metastasis to the brain, bone, and liver. After culture in this system, lung cancer cells formed a "tumor mass", showed epithelial-mesenchymal transition (with altered expression of E-cadherin, N-cadherin, Snail1, and Snail2) and invasive capacity. A549 cells co-cultured with astrocytes overexpressed CXCR4 protein, indicating damage of astrocytes after cancer cell metastasis to the brain. Osteocytes overexpressed RANKL protein indicates damage of osteocytes after cancer cell metastasis to the bone, and hepatocytes overexpressed AFP protein indicates damage to hepatocytes after cancer cell metastasis to the liver. Finally, in vivo imaging of cancer growth and metastasis in a nude mice model validated the performance of metastasis in the organs-on-chip system. This system provides a useful tool to mimic the in vivo microenvironment of cancer metastasis and to investigate cell-cell interactions during metastasis.

  2. Pericytes limit tumor cell metastasis

    DEFF Research Database (Denmark)

    Xian, Xiaojie; Håkansson, Joakim; Ståhlberg, Anders

    2006-01-01

    Previously we observed that neural cell adhesion molecule (NCAM) deficiency in beta tumor cells facilitates metastasis into distant organs and local lymph nodes. Here, we show that NCAM-deficient beta cell tumors grew leaky blood vessels with perturbed pericyte-endothelial cell-cell interactions...... and deficient perivascular deposition of ECM components. Conversely, tumor cell expression of NCAM in a fibrosarcoma model (T241) improved pericyte recruitment and increased perivascular deposition of ECM molecules. Together, these findings suggest that NCAM may limit tumor cell metastasis by stabilizing...... the microvessel wall. To directly address whether pericyte dysfunction increases the metastatic potential of solid tumors, we studied beta cell tumorigenesis in primary pericyte-deficient Pdgfb(ret/ret) mice. This resulted in beta tumor cell metastases in distant organs and local lymph nodes, demonstrating a role...

  3. Raman spectroscopy of bone metastasis

    Science.gov (United States)

    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.

  4. Endocannabinoids as Guardians of Metastasis.

    Science.gov (United States)

    Tegeder, Irmgard

    2016-02-10

    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.

  5. Brain metastases from gestational trophoblastic neoplasia: review of pertinent literature.

    Science.gov (United States)

    Piura, E; Piura, B

    2014-01-01

    Brain metastasis from gestational trophoblastic neoplasia (GTN) is rare with about 222 cases documented in the literature and an incidence of about 11% in living GTN patients. Brain metastasis from GTN was part of a disseminated disease in 90% of patients, single metastases in the brain - 80% and located in the cerebrum - 90%. Brain metastasis was the only manifestation of metastatic GTN in 11.3% of patients, appeared synchronously with metastatic GTN in other sites of the body - 30.6% and was diagnosed from 0.3 to 60 months after diagnosis of metastatic GTN in other sites (most often in the lung) - 58.1%. Overall, 83.9% of patients with brain metastases from GTN had also lung metastases from GTN. Brain metastases from GTN showed a greater tendency to be hemorrhagic compared to brain metastases from other primaries. In patients with brain metastases from GTN, the best outcome was achieved with multimodal therapy including craniotomy, whole brain radiotherapy, and EP-EMA or EMA-CO chemotherapy. Nonetheless, brain metastasis from GTN is a grave disease with a median survival time from diagnosis of brain metastasis of about 12 months.

  6. A Bone Metastasis Nude Mouse Model Created by Ultrasound Guided Intracardiac Injection of Breast Cancer Cells: the Micro-CT, MRI and Bioluminescence Imaging Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Park, Young Jin; Song, Eun Hye; Kim, Seol Hwa; Song, Ho Taek; Suh, Jin Suck [Yonsei University College of Medicine, Seoul (Korea, Republic of); Choi, Sang Hyun [Korean Minjok Leadership Academy, Heongsung (Korea, Republic of)

    2011-01-15

    The purpose of this study was to develop a nude mouse model of bone metastasis by performing intracardiac injection of breast cancer cells under ultrasonography guidance and we wanted to evaluate the development and the distribution of metastasis in vivo using micro-CT, MRI and bioluminescence imaging. Animal experiments were performed in 6-week-old female nude mice. The animals underwent left ventricular injection of 2x105 MDA-MB-231Bo-Luc cells. After injection of the tumor cells, serial bioluminescence imaging was performed for 7 weeks. The findings of micro-CT, MRI and the histology were correlated with the 'hot' lesions seen on the bioluminescence imaging. Metastasis was found in 62.3% of the animals. Two weeks after intracardiac injection, metastasis to the brain, spine and femur was detected with bioluminescence imaging with an increasing intensity by week 7. Micro-CT scan confirmed multiple osteolytic lesions at the femur, spine and skull. MRI and the histology were able to show metastasis in the brain and extraskeletal metastasis around the femur. The intracardiac injection of cancer cells under ultrasonography guidance is a safe and highly reproducible method to produce bone metastasis in nude mice. This bone metastasis nude mouse model will be useful to study the mechanism of bone metastasis and to validate new therapeutics

  7. Blocking the adhesion cascade at the premetastatic niche for prevention of breast cancer metastasis.

    Science.gov (United States)

    Kang, Shin-Ae; Hasan, Nafis; Mann, Aman P; Zheng, Wei; Zhao, Lichao; Morris, Lynsie; Zhu, Weizhu; Zhao, Yan D; Suh, K Stephen; Dooley, William C; Volk, David; Gorenstein, David G; Cristofanilli, Massimo; Rui, Hallgeir; Tanaka, Takemi

    2015-06-01

    Shear-resistant adhesion and extravasation of disseminated cancer cells at the target organ is a crucial step in hematogenous metastasis. We found that the vascular adhesion molecule E-selectin preferentially promoted the shear-resistant adhesion and transendothelial migration of the estrogen receptor (ER)(-)/CD44(+) hormone-independent breast cancer cells, but not of the ER(+)/CD44(-/low) hormone-dependent breast cancer cells. Coincidentally, CD44(+) breast cancer cells were abundant in metastatic lung and brain lesions in ER(-) breast cancer, suggesting that E-selectin supports hematogenous metastasis of ER(-)/CD44(+) breast cancer. In an attempt to prevent hematogenous metastasis through the inhibition of a shear-resistant adhesion of CD44(+) cancer cells to E-selectin-expressing blood vessels on the premetastatic niche, an E-selectin targeted aptamer (ESTA) was developed. We demonstrated that a single intravenous injection of ESTA reduced metastases to a baseline level in both syngeneic and xenogeneic forced breast cancer metastasis models without relocating the site of metastasis. The effect of ESTA was absent in E-selectin knockout mice, suggesting that E-selectin is a molecular target of ESTA. Our data highlight the potential application of an E-selectin antagonist for the prevention of hematogenous metastasis of ER(-)/CD44(+) breast cancer.

  8. Macrophage Efferocytosis and Prostate Cancer Bone Metastasis

    Science.gov (United States)

    2015-10-01

    AWARD NUMBER: W81XWH-14-1-0408 TITLE: Macrophage Efferocytosis and Prostate Cancer Bone Metastasis PRINCIPAL INVESTIGATOR: Jacqueline D. Jones...0408 Macrophage Efferocytosis and Prostate Cancer Bone Metastasis 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER...efferocytosis. The translation of this functional role during pathophysiological states such as tumor metastasis to the skeleton is unknown. The purpose of this

  9. Prostate cancer and metastasis initiating stem cells

    Institute of Scientific and Technical Information of China (English)

    Kathleen Kelly; Juan Juan Yin

    2008-01-01

    Androgen refractory prostate cancer metastasis is a major clinical challenge.Mechanism-based approaches to treating prostate cancer metastasis require an understanding of the developmental origin of the metastasis-initiating cell.Properties of prostate cancer metastases such as plasticity with respect to differentiated phenotype and androgen independence are consistent with the transformation of a prostate epithelial progenitor or stem cell leading to metastasis.This review focuses upon current evidence and concepts addressing the identification and properties of normal prostate stem or progenitor cells and their transformed counterparts.

  10. Simultaneous in-field boost for patients with 1 to 4 brain metastasis/es treated with volumetric modulated arc therapy: a prospective study on quality-of-life

    Directory of Open Access Journals (Sweden)

    Malek Karim

    2011-06-01

    Full Text Available Abstract Purpose To assess treatment toxicity and patients' survival/quality of life (QoL after volumetric modulated arc therapy (VMAT with simultaneous in-field boost (SIB for cancer patients with 1 - 4 brain metastases (BM treated with or without surgery. Methods and Materials Between March and December 2010, 29 BM patients (total volume BM, 3 aged Results As of April 2011 and after a mean FU of 5.4 ± 2.8 months, 14 (48.3% patients died. The 6-month overall survival was 55.1%. Alopecia was only observed in 9 (31% patients. In 3-month survivors, KPS was significantly (p = 0.01 decreased. MMSE score remained however stable (p = 0.33. Overall, QoL did decrease after VMAT. The mean QLQ-C30 global health status (p = 0.72 and emotional functional (p = 0.91 scores were decreased (low QoL. Physical (p = 0.05 and role functioning score (p = 0.01 were significantly worse and rapidly decreased during treatment. The majority of BN20 domains and single items worsened 3 months after VMAT except headaches (p = 0.046 and bladder control (p = 0.26 which improved. Conclusions The delivery of 40 Gy in 10 fractions to 1 - 4 BM using VMAT was achieved with no significant toxicity. QoL, performance status, but not MMSE, was however compromised 3 months after treatment in this selected cohort of BM patients.

  11. Pancreatic Metastasis from Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Julian Jacob

    2010-01-01

    Full Text Available The pancreas is an unusual location for metastases from other primary cancers. Rarely, pancreatic metastases from kidney or colorectal cancers have been reported. However, a variety of other cancers may also spread to the pancreas. We report an exceptional case of pancreatic metastasis from prostate cancer. Differences in management between primary and secondary pancreatic tumors make recognition of metastases to the pancreas an objective of first importance. Knowledge of unusual locations for metastatic spread will reduce diagnostic delay and lead to a timely delivery of an appropriate treatment.

  12. Sigmoid adenocarcinoma with renal metastasis

    Directory of Open Access Journals (Sweden)

    Carini Dagnoni

    2011-11-01

    Full Text Available We report a case of a 75-year-old man submitted to a rectosigmoidectomy and partial cystectomy because of a sigmoid cancer and colovesical fistula. Seven months later and after four cycles of adjuvant chemotherapy, a lesion was detected in the kidney. Histology revealed tubular adenocarcinoma, which meant sigmoid cancer metastasis. Kidney metastases are very rare in colorectal cancer (CRC, but may be generally associated with an unfavorable prognosis. Thus, patients with metastatic CRC and kidney tumors are a diagnostic and therapeutic challenge.

  13. Vesical metastasis of gastric adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Alberto A. Antunes

    2004-10-01

    Full Text Available Metastatic vesical tumors are rare, and constitute approximately 1% of all neoplasias affecting this organ. The authors report the case of a 63-year old woman with vesical metastasis of gastric adenocarcinoma. Patient presented signs of cachexia and complained of left lumbar pain and dysuria unresponsive to antibiotic therapy for approximately 5 months. She reported a previous partial gastrectomy due to ulcerative undifferentiated gastric adenocarcinoma 1 year and 9 months before. Cystoscopy revealed an extensive vegetative lesion in bladder, occupying its entire mucosal surface. The biopsy revealed metastatic signet-ring cell adenocarcinoma.

  14. Gestational Choriocarcinoma Presenting with Lacrimal Gland Metastasis: A First Reported Case

    Directory of Open Access Journals (Sweden)

    Naushad A. B. Ahamed

    2015-01-01

    Full Text Available Background. Gestational choriocarcinoma (GC is a recognized clinicopathological subtype of gestational trophoblastic neoplasia that usually metastasizes hematogenously to highly vascular organs like the lung, liver, and brain. However, orbital metastasis to the choroid and lacrimal gland is a rare occurrence. Case Presentation. A 21-year-old female presented with headache and left orbital swelling one year after resection of a complete hydatidiform mole followed by adjuvant methotrexate chemotherapy. A metastatic imaging screening revealed multiple metastases in the lungs, brain, and adrenal gland, in addition to the choroid and lacrimal gland. Based on her modified WHO risk factors scoring she was started on chemotherapy and whole brain radiotherapy, which resulted in a complete response. At two-year follow-up, serum b-HCG level was with normal limits; imaging surveillance was uneventful. Conclusion. We present the first case of lacrimal gland metastasis in a young girl from GC relapse.

  15. Contiguous spinal metastasis mimicking infectious spondylodiscitis

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Chul Min; Lee, Seung Hun [Dept. of Radiology, Hanyang University Hospital, Seoul (Korea, Republic of); Bae, Ji Yoon [Dept. of Pathology, National Police Hospital, Seoul (Korea, Republic of)

    2015-12-15

    Differential diagnosis between spinal metastasis and infectious spondylodiscitis is one of the occasional challenges in daily clinical practice. We encountered an unusual case of spinal metastasis in a 75-year-old female breast cancer patient that mimicked infectious spondylodiscitis. Magnetic resonance imaging (MRI) showed diffuse bone marrow infiltrations with paraspinal soft tissue infiltrative changes in 5 contiguous cervical vertebrae without significant compression fracture or cortical destruction. These MRI findings made it difficult to differentiate between spinal metastasis and infectious spondylodiscitis. Infectious spondylodiscitis such as tuberculous spondylodiscitis was regarded as the more appropriate diagnosis due to the continuous involvement of > 5 cervical vertebrae. The patient's clinical presentation also supported the presumptive diagnosis of infectious spondylodiscitis rather than spinal metastasis. Intravenous antibiotics were administered, but clinical symptoms worsened despite treatment. After pathologic confirmation by computed tomography-guided biopsy, we were able to confirm a final diagnosis of spinal metastasis.

  16. The Current and Future Treatment of Brain Metastases

    Directory of Open Access Journals (Sweden)

    Douglas A Hardesty

    2016-05-01

    Full Text Available Brain metastases are the most common intracranial malignancy, accounting for significant morbidity and mortality in oncology patients. The current treatment paradigm for brain metastasis depends on the patient’s overall health status, the primary tumor pathology, and the number and location of brain lesions. Herein, we review the modern management options for these tumors, including surgical resection, radiotherapy, and chemotherapy. Recent operative advances, such as fluorescence, confocal microscopy, and brachytherapy, are highlighted. With an increased understanding of the pathophysiology of brain metastasis come increased future therapeutic options. Therapy targeted to specific tumor molecular pathways, such as those involved in blood-brain barrier transgression, cell-cell adhesion, and angiogenesis, are also reviewed. A personalized plan for each patient, based on molecular characterizations of the tumor that are used to better target radiotherapy and chemotherapy, is undoubtedly the future of brain metastasis treatment.

  17. The Current and Future Treatment of Brain Metastases.

    Science.gov (United States)

    Hardesty, Douglas A; Nakaji, Peter

    2016-01-01

    Brain metastases are the most common intracranial malignancy, accounting for significant morbidity and mortality in oncology patients. The current treatment paradigm for brain metastasis depends on the patient's overall health status, the primary tumor pathology, and the number and location of brain lesions. Herein, we review the modern management options for these tumors, including surgical resection, radiotherapy, and chemotherapy. Recent operative advances, such as fluorescence, confocal microscopy, and brachytherapy, are highlighted. With an increased understanding of the pathophysiology of brain metastasis come increased future therapeutic options. Therapy targeted to specific tumor molecular pathways, such as those involved in blood-brain barrier transgression, cell-cell adhesion, and angiogenesis, are also reviewed. A personalized plan for each patient, based on molecular characterizations of the tumor that are used to better target radiotherapy and chemotherapy, is undoubtedly the future of brain metastasis treatment.

  18. Paclitaxel liposome combined with cisplatin chemotherapy in non-small cell lung cancer with brain metastasis%紫杉醇脂质体联合顺铂治疗非小细胞肺癌脑转移的临床观察

    Institute of Scientific and Technical Information of China (English)

    刘娜; 程俊; 孟令占; 刘勇

    2015-01-01

    Objective To evaluate the clinical efficacy and toxicity of paclitaxel liposome combined with cisplatin chemotherapy in NSCLC with brain metastasis. Methods Twenty-eight patients were newly diag-nosed NSCLC with brain metastasis(confirmed by pathology or cytology). The patients were treated with pacli-taxel liposome(135 mg/ m2 )on day 1 intravenous drip for 3 hours,cisplatin,25 mg/ m2 on day 1-3. The course of treatment was 21 days. The patients accepted the anti-allergy treatment before chemotherapy. Results Twenty-eight patients could be evaluated,and 101 treatment cycles were completed( 3. 6 cycles per patient). General lesion assessment presented that no patient got complete remission( CR),13 patients (46. 43% )got a partial response(PR),11(39. 28% )had a stable disease(SD)and 4(14. 29% )had a progressive disease( PD). The objective response rate( RR)was 46. 43% ,and the disease control rate (DCR) was 85. 71% . Local cerebral response assessment showed that no patient got CR,6 patients (21. 43% )got a PR,15(53. 58% )had a SD and 4(14. 29% )had a PD. The RR was 21. 43% ,and the DCR was 85. 71% . There was a significant difference in the RR(χ2 = 3. 90,P = 0. 03)but not in the DCR (χ2 = 0. 15,P = 0. 3)between the local cerebral disease and the general lesion. The median time to disease progression(TTP)for general lesion and local cerebral were 7. 2 months and 6. 2 months,respectively(χ2 =6. 43,P < 0. 05). The adverse reactions included bone marrow suppression,gastrointestinal reactions,elevated transaminases,alopecia,neurotoxicity,etc. All of these could be well controlled. Conclusion Paclitaxel liposome combined with cisplatin regimen demonstrates a higher efficacy and well tolerable against main metas-tasis of NSCLC,and the adverse effects are minor.%目的:观察紫杉醇脂质体联合顺铂治疗非小细胞肺癌( NSCLC)脑转移的疗效和不良反应。方法对28例经病理或细胞学检查确诊的 NSCLC 脑转移初治患者采用紫杉醇

  19. Imaging of bone metastasis: An update

    Institute of Scientific and Technical Information of China (English)

    Gerard; J; O’Sullivan; Fiona; L; Carty; Carmel; G; Cronin

    2015-01-01

    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 whichfuse 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.

  20. Primary brain tumours, meningiomas and brain metastases in pregnancy

    DEFF Research Database (Denmark)

    Verheecke, Magali; Halaska, Michael J; Lok, Christianne A

    2014-01-01

    to obtain better insight into outcome and possibilities of treatment in pregnancy. METHODS: We collected all intracranial tumours (primary brain tumour, cerebral metastasis, or meningioma) diagnosed during pregnancy, registered prospectively and retrospectively by international collaboration since 1973......, respectively. Eight patients (30%) underwent brain surgery, seven patients (26%) had radiotherapy and in three patients (11%) chemotherapy was administered during gestation. Two patients died during pregnancy and four pregnancies were terminated. In 16 (59%) patients elective caesarean section was performed...... were reassuring. CONCLUSION: Adherence to standard protocol for the treatment of brain tumours during pregnancy appears to allow a term delivery and a higher probability of a vaginal delivery....

  1. Efifcacy of Gamma Knife Radiation Therapy in Lung Cancer Patients with Brain Metastasis Lesions and Whole Brain Radiation Therapy%肺癌脑转移病灶患者伽马刀放射治疗及全脑放射治疗的疗效

    Institute of Scientific and Technical Information of China (English)

    刘敬聘; 秦坤明; 王仁生; 阮林

    2015-01-01

    Objective: To investigate the efficacy analysis of lung lesions in patients with brain metastases Gamma Knife radiation therapy and whole brain radiation therapy.Methods:March 2002~ March 2013 in our hospital diagnosis and treatment of 500 cases of lung cancer patients with brain metastases as the research object. According to the specific circumstances of the patient decided to use the gamma knife radiation therapy or whole brain radiation therapy.Gamma Knife radiotherapy group and whole brain radiotherapy group in gender, age was not significantly different,P>0.05,comparable.Results:The Gamma Knife radiotherapy group and whole brain radiotherapy efficacy in the near future, with a median survival time and 1-year progression-free survival without brain lesions was no significant difference; 1-year survival rate was significantly higher than the gamma knife radiotherapy whole brain radiotherapy; adverse reaction rate of gamma knife radiotherapy group was significantly higher than the whole-brain radiotherapy.Conclusion:The adverse reaction rates using the gamma knife radiation is small, good effect, and thus overall due to the whole brain radiotherapy, but in clinical practice should also consider the specific circumstances of the patient treatment decisions for patients with larger tumors may be two were combined to achieve a more satisfactory outcome.%目的:探讨分析肺癌脑转移病灶患者伽马刀放射治疗(放疗)及全脑放射治疗的疗效。方法:选取2002年3月~2013年3月在我院接受诊断和治疗的500例肺癌脑转移患者作为研究对象。根据患者具体情况决定使用伽马刀放射治疗或全脑放射治疗。伽马刀放疗组和全脑放疗组患者在性别、年龄方面差异不明显,P>0.05,具有可比性。结果:伽马刀放疗组和全脑放疗组在近期疗效、中位生存期和1年无颅脑病灶进展生存率方面无明显差异;伽马刀放疗组的1年生存率明显高于全脑

  2. Cutaneous metastasis from a myoepithelial carcinoma of submandibular salivary gland.

    Science.gov (United States)

    Chougule, Abhijit; Barwad, Adarsh; Bal, Amanjit; Dey, Pranab

    2015-01-01

    Myoepithelial carcinoma is a rare malignant tumor of salivary gland with locally aggressive nature and potential for distant metastasis. It is composed of tumor cells with myoepithelial differentiation showing varied cytomorphology. Lungs and kidneys are the commonest sites for distant metastasis. Cutaneous metastasis of myoepithelial carcinoma is very rare. In this report, we described cutaneous metastasis of myoepithelial carcinoma arising from submandibular gland.

  3. Clinical Research of Temozolomide Combined with Radiotherapy in the Treatment of Brain Metastasis in Patients with Non-small Cell Lung Cancer%替莫唑胺联合放疗在非小细胞肺癌脑转移中的临床研究

    Institute of Scientific and Technical Information of China (English)

    周蕾; 安广宇; 岳振东; 陈力; 宋雨光; 姜妮

    2011-01-01

    OBJECTIVE: To investigate the therapeutic efficacy and safety of temozolomide combined with radiotherapy in the treatment of brain metastasis in patients with non-small cell lung cancer and its effect on overall survival time.METHODS: 42 brain metastases patients with non-small cell lung cancer were randomized into temozolomide combined with radiotherapy group and radiotherapy group: Temozolomide combined with radiotherapy group was given temozolomide 75 mg·m-2·d-1 and conventional head radiotherapy of a total dose of 40 Gy fractionated (2 Gy, 5 d/week) for 4 weeks while radiotherapy group was given radiotherapy of a total dose of 40 Gy alone.Temozolomide combined with radiotherapy group received temozolomide therapy (first cycle: 150 mg·m-2·d-1;second to the sixth cycles:200 mg·m-2·d-1) for 5 days every 28 days for an additional six cycles.RESULTS: The objective response rates of temozolomide combined with radiotherapy group and radiotherapy group were 75% and 64% (P=0.017), there was significant difference.The incidence rates of neutropenia in two groups were 40% and 27% (P=0.019), those of thrombocytopenia was 10% and 5% (P=0.045) and those of hemochrome decreasing were 25% and 18% (P=0.024), respectively.There were significant differences.Overall survival time of two groups were 9.2 and 7.9, there was no significant difference (P=0.449).CONCLUSION: Temozolomide combined with radiotherapy is safe and effective in the treatment of brain metastasis in patients with non-small cell lung cancer.%目的:探讨替莫唑胺联合放疗在非小细胞肺癌脑转移治疗中的疗效、安全性及对总生存期的影响.方法:42例非小细胞肺癌脑转移的患者随机分为替莫唑胺联合放疗组与单纯放疗组:替莫唑胺联合放疗组给予替莫唑胺(75 mg·m-2·d-1)联合4周总剂量40Gy常规头部放疗(2Gy,5 d/周);单纯放疗组仅予40Gy常规头部放疗.替莫唑胺联合放疗组放疗结束后继续给予6

  4. Ovarian carcinoma presenting as cutaneous nasal metastasis*

    Science.gov (United States)

    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.

  5. Invasion and metastasis in pancreatic cancer.

    Science.gov (United States)

    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.

  6. Three-dimensional context regulation of metastasis.

    Science.gov (United States)

    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.

  7. Biology of cancer invasion and metastasis.

    Science.gov (United States)

    Mareel, M M; Crombez, R

    1992-01-01

    Current concepts of invasion eventually leading to metastasis are discussed and exemplified by cancers of the head and neck mucosa. Invasion occurs at a number of steps, each step making an ecosystem comprising not only the neoplastic cells but also their normal counterparts, a variety of host cells and the extracellular matrix. The ecosystem concept may explain aspects of metastasis such as site-dependence and organ-specificity of cancer metastasis as well as invasiveness of normal leucocytes. Genes implicated in invasion and metastasis are actively searched for. Recently, the epithelial cell-cell adhesion molecule E-cadherin has been identified as an i- (invasion suppressor) gene product, i.e. a molecule the expression of which counterbalances i+ (invasion promotor) gene activity. Downregulation of E-cadherin in human head and neck cancers may account for their invasive and metastatic behaviour.

  8. Organotropic metastasis: role of tumor exosomes.

    Science.gov (United States)

    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.

  9. Targeting Phosphatidylserine for Radioimmunotherapy of Breast Cancer Brain Metastasis

    Science.gov (United States)

    2013-10-01

    Center, Dallas, TX). These cell lines were maintained in RPMI-1640 supplemented with 10% v/v heat- inactivated FBS (Hyclone) without antibiotics . All cell...and removal by macro- phages . J Immunol 1992;148:2207–16. 21. McDonald PP, Fadok VA, Bratton D, Henson PM. Transcriptional and translational

  10. Mechanisms of CTC Biomarkers in Breast Cancer Brain Metastasis

    Science.gov (United States)

    2015-10-01

    obtained at the middle of vein puncture after the first 5 ml of blood was discarded to avoid contamination by normal epithelial cells . All samples (25...Supplementary Fig. 1) in which the endomembrane furrow separates the daughter and mother cell during cell -division events18. Biomarker profiling of...gating parameters to select for DAPI− (4′ , 6-diamidino-2-phenylindole)/ EpCAM−/CD45−/CD44+/CD24− cells . Cells were then subsequently sorted to obtain

  11. Gastric metastasis by lung small cell carcinoma

    Institute of Scientific and Technical Information of China (English)

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

    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.

  12. Molecular mechanisms of metastasis in prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Noel W.Clarke; Claire A.Hart; Mick D.Brown

    2009-01-01

    Prostate cancer (PCa) preferentially metastasizes to the bone marrow stroma of the axial skeleton.This activity is the principal cause of PCa morbidity and mortality.The exact mechanism of PCa metastasis is currently unknown,although considerable progress has been made in determining the key players in this process.In this review,we present the current understanding of the molecular processes driving PCa metastasis to the bone.

  13. Isolated malignant melanoma metastasis to the pancreas

    DEFF Research Database (Denmark)

    Larsen, Anne K; Krag, Christen; Geertsen, Poul

    2013-01-01

    SUMMARY: Malignant melanomas rarely develop isolated pancreatic metastases. We describe a unique patient who is still alive 22 years following an isolated pancreatic melanoma metastasis, and we review the sparse literature in the field.......SUMMARY: Malignant melanomas rarely develop isolated pancreatic metastases. We describe a unique patient who is still alive 22 years following an isolated pancreatic melanoma metastasis, and we review the sparse literature in the field....

  14. Gastric metastasis by lung small cell carcinoma

    Science.gov (United States)

    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

  15. Three-dimensional context regulation of metastasis

    DEFF Research Database (Denmark)

    Erler, Janine Terra; Weaver, Valerie M

    2009-01-01

    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...

  16. Cellular Plasticity in Prostate Cancer Bone Metastasis

    Directory of Open Access Journals (Sweden)

    Dima Y. Jadaan

    2015-01-01

    Full Text Available Purpose. Experimental data suggest that tumour cells can reversibly transition between epithelial and mesenchymal states (EMT and MET, a phenomenon known as cellular plasticity. The aim of this review was to appraise the clinical evidence for the role of cellular plasticity in prostate cancer (PC bone metastasis. Methods. An electronic search was performed using PubMed for studies that have examined the differential expression of epithelial, mesenchymal, and stem cell markers in human PC bone metastasis tissues. Results. The review included nineteen studies. More than 60% of the studies used ≤20 bone metastasis samples, and there were several sources of heterogeneity between studies. Overall, most stem cell markers analysed, except for CXCR4, were positively expressed in bone metastasis tissues, while the expression of EMT and MET markers was heterogeneous between and within samples. Several EMT and stemness markers that are involved in osteomimicry, such as Notch, Met receptor, and Wnt/β pathway, were highly expressed in bone metastases. Conclusions. Clinical findings support the role of cellular plasticity in PC bone metastasis and suggest that epithelial and mesenchymal states cannot be taken in isolation when targeting PC bone metastasis. The paper also highlights several challenges in the clinical detection of cellular plasticity.

  17. Roles of TGFβ in metastasis

    Institute of Scientific and Technical Information of China (English)

    David Padua; Joan Massagué

    2009-01-01

    The TGFβ signaling pathway is conserved from flies to humans and has been shown to regulate such diverse pro-cesses as cell proliferation,differentiation,motility,adhesion,organization,and programmed cell death.Both in vitro and in vivo experiments suggest that TGFβ can utilize these varied programs to promote cancer metastasis through its effects on the tumor microenvironment,enhanced invasive properties,and inhibifion of immune cell function.Recent clinical evidence demonstrating a link between TGFβ signaling and cancer progression is fostering interest in this signaling pathway as a therapeutic target.Anti-TGFβ therapies are currently being developed and tested in pre-clinical studies.However,targeting TGFβ carries a substantial risk as this pathway is implicated in multiple homeo-static processes and is also known to have tumor-suppressor functions.Additionally,clinical and experimental results show that TGFβ has diverse and often conflicting roles in tumor progression even within the same tumor types.The development of TGFβ inhibitors for clinical use will require a deeper understanding of TGFβ signaling,its conse- quences,and the contexts in which it acts.

  18. A case of peritoneal metastasis during treatment for hypopharyngeal squamous cell carcinoma

    OpenAIRE

    Wakasaki, Takahiro; Omori, Hirofumi; Sueyoshi, Shintaro; Rikimaru, Fumihide; Toh, Satoshi; Taguchi, Kenichi; Higaki, Yuichiro; Morita, Masaru; Masuda, Muneyuki

    2016-01-01

    Background Advanced head and neck squamous cell carcinomas frequently develop distant metastases to limited organs, including the lungs, bone, mediastinal lymph nodes, brain, and liver. Peritoneal carcinomatosis as an initial distant metastasis from hypopharyngeal squamous cell carcinoma is quite rare. Case presentation A 75-year-old man diagnosed with hypopharyngeal squamous cell carcinoma and his clinical stage was determined as T2N2cM0. Notably, the right retropharyngeal lymph node surroun...

  19. Cutaneous metastasis as a first presentation for lung adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Yazan Abdeen

    2016-01-01

    Full Text Available Context: According to the recent World Health Organization reports, lung cancer has become the most common type of malignancy and the leading cause of death from cancer. Lung cancer frequently metastasizes to hilar lymphnodes, brain, adrenal glands, bone, but rarely to skin. Case Report: We report a case of a 72-year-old male with a past medical history of pulmonary fibrosis and no prior history of smoking who presented to the emergency room for progressive dyspnea over three weeks. The patient reported having a rapidly growing scalp lesion as well. A computed tomography (CT scan of the chest showed diffuse fibrotic changes and multiple densities of different diameters; a CT guided biopsy of lung revealed a poorly differentiated adenocarcinoma. Excision of right scalp lesion was performed, and pathology revealed poorly differentiated malignant neoplasm favoring adenocarcinoma. Conclusion: We are presenting a rare case of lung adenocarcinoma presenting with skin metastasis, which was simultaneously diagnosed during the same hospitalization. Although cutaneous metastasis from the lung is rare, it must be ruled out in patients with suspicious skin lesions, smoking history, or lung cancer.

  20. Rectal carcinoid tumor metastasis to a skull base meningioma

    Science.gov (United States)

    Huang, Jennifer; Gupta, Amit; Badve, Chaitra; Cohen, Mark L; Wolansky, Leo J

    2016-01-01

    Carcinoid tumors are rare, slow-growing neuroendocrine tumors that most frequently develop in the gastrointestinal tract or lungs and have high potential for metastasis. Metastasis to the brain is rare, but to another intracranial tumor is extremely rare. Of the intracranial tumors, meningiomas are the most common to host metastases, which may be related to its rich vascularity and E-cadherin expression. We describe the case of a 65-year-old female with active chemotherapy-treated neuroendocrine carcinoma who presented with left-sided facial numbness, headaches, and blurry vision. Initial imaging revealed a 1 cm irregular dural-based left petrous apex mass suggestive of a meningioma that was re-imaged four months later as a rapidly enlarging, extra-axial, mass extending into the cavernous sinus, effacing Meckel’s cave that resembled a trigeminal schwannoma. Pathology revealed a carcinoid tumor metastatic to meningioma. While the mass displayed characteristic imaging findings of a schwannoma, rapid growth in the setting of known active malignancy should prompt the clinician to consider mixed pathology from metastatic disease or a more aggressive meningioma. PMID:26825133

  1. Screening and Establishment of Human Lung Cancer Cell Lines 
with Organ-specific Metastasis Potential

    Directory of Open Access Journals (Sweden)

    Qinghua ZHOU

    2014-03-01

    Full Text Available Background and objective Cancer metastasis is not only the malignant marker and characteristics, but also the main cause of failure to cure and lose their life in the patients with lung cancer. Lung cancer metastasis has organ-specific characteristics. The most common sites of lung cancer metastasis are mediastinal lymph node, brain, bone, liver and adrenal gland. The aim of this study is to screen and establish lung cancer cell model with organ-specific metastasis potential with human high-metastatic large cell lung cancer cell line L9981 established by our laboratory previously, and to provide cell models for studying the mechanisms and signal regulation of organ-specific metastasis of lung cancer. Materials and methods The parent lung cancer cell line, L9981-Luc, was inoculated in the armpit of nude mice. The live animal imaging system, IVIS-200, was used to detect the lung cancer organ-specific metastasis every week. When the organ-specific metastasis were established, the nude mices bearing the lung cancer were sacrificed when they became moribund. Under sterile conditions, the organs (mediastinal lymph nodes, lung, spinal column and brain with lung cancer organ-specific metastasis were removed and the metastasized nodules were dissected free of connective tissue and blood clots, and rinsed twice with medium. The metastasized nodules were finely minced using sterile scalpel blades in medium, and the cells were seeded in tissue culture dishes. Then, the cells with organ-specific metastasis potential were reinoculated into the armpit of nude mice, respectively. This processes were repeated to establish the organ-specific metastatic sublines of L9981-Luc cell line more than 10 times. Finally, the organ-specific metastasis sublines of L9981-Luc were screened and established, which the four cell lines have the characteristics only metastasized to brian, lung, bone and mediastinal lymph node. Results A group of organ-specific metastasis cell

  2. Leptomeningeal metastasis of an intradural malignant peripheral nerve sheath tumor.

    Science.gov (United States)

    Stark, Andreas M; Mehdorn, H Maximilian

    2013-08-01

    Malignant peripheral nerve sheath tumors (MPNST) are defined as any malignant tumor arising from or differentiating towards the peripheral nerve sheath. Intradural MPNST metastases are very rare. We report, to our knowledge, the first case of leptomeningeal metastasis of a MPNST to the spine and intracranial space. A 56-year-old woman with primary intradural MPNST of the S1 nerve root developed leptomeningeal metastases as well as brain metastases 19 months after diagnosis. The patient had a history of non-Hodgkins lymphoma for which she had received irradiation to the spine 15 years prior to this presentation. She had no stigmata of neurofibromatosis type 1. Patients with MPNST may also develop leptomeningeal metastases as demonstrated in this patient with intradural post-radiation MPNST.

  3. Mouse models of advanced spontaneous metastasis for experimental therapeutics.

    Science.gov (United States)

    Francia, Giulio; Cruz-Munoz, William; Man, Shan; Xu, Ping; Kerbel, Robert S

    2011-02-01

    An enduring problem in cancer research is the failure to reproduce highly encouraging preclinical therapeutic findings using transplanted or spontaneous primary tumours in mice in clinical trials of patients with advanced metastatic disease. There are several reasons for this, including the failure to model established, visceral metastatic disease. We therefore developed various models of aggressive multi-organ spontaneous metastasis after surgical resection of orthotopically transplanted human tumour xenografts. In this Opinion article we provide a personal perspective summarizing the prospect of their increased clinical relevance. This includes the reduced efficacy of certain targeted anticancer drugs, the late emergence of spontaneous brain metastases and the clinical trial results evaluating a highly effective therapeutic strategy previously tested using such models.

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

    Science.gov (United States)

    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.

  5. First description of cervical intradural thymoma metastasis.

    Science.gov (United States)

    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.

  6. Radiosurgery for brain metastases and cerebral edema.

    Science.gov (United States)

    Gazit, Inbal; Har-Nof, Sagi; Cohen, Zvi R; Zibly, Zion; Nissim, Uzi; Spiegelmann, Roberto

    2015-03-01

    The objective of this study was to assess reduction in cerebral edema following linear accelerator radiosurgery (LINAC) as first line therapy for brain metastasis. We reviewed the medical records of all patients who underwent LINAC radiosurgery for brain metastasis at our institution during 2010-2012, and who had not previously undergone either surgery or whole brain radiotherapy. Data were analyzed for 55 brain metastases from 46 patients (24 males), mean age 59.9 years. During the 2 months following LINAC radiosurgery, the mean steroid dose decreased from 4.8 to 2.6 mg/day, the mean metastasis volume decreased from 3.79±4.12 cc to 2.8±4.48 cc (p=0.001), and the mean edema volume decreased from 16.91±30.15 cc to 12.85±24.47 cc (p=0.23). The 17 patients with reductions of more than 50% in brain edema volume had single metastases. Edema volume in the nine patients with two brain metastases remained stable in five patients (volume change 10%, 2-14 cc). In a subanalysis of eight metastases with baseline edema volume greater than 40 cc, edema volume decreased from 77.27±37.21 cc to 24.84±35.6 cc (p=0.034). Reductions in brain edema were greater in metastases for which non-small-cell lung carcinoma and breast cancers were the primary diseases. Overall, symptoms improved in most patients. No patients who were without symptoms or who had no signs of increased intracranial pressure at baseline developed signs of intracranial pressure following LINAC radiosurgery. In this series, LINAC stereotactic radiosurgery for metastatic brain lesions resulted in early reduction in brain edema volume in single metastasis patients and those with large edema volumes, and reduced the need for steroids.

  7. Bio-luminescent imaging and characterization of organ-specific metastasis of human cancer in NOD/SCID mice

    Science.gov (United States)

    Chun, Nicole A. L.; Murakami, Takashi

    2010-02-01

    Many clinical evidences demonstrate that the sites of distant metastasis are not random and certain malignant tumors show a tendency to develop metastases in specific organs (e.g., brain, liver, and lungs). However, an appropriate animal model to characterize the metastatic nature of transplantable human cancer cell lines has not been reported well. Recent advances in bio-luminescent imaging (BLI) technologies have facilitated the quantitative analysis of various cellular processes in vivo. To visualize the fate of tumor progression in the living mice, we are constructing a luciferaseexpressing human cancer cell library (including melanoma, colon, breast, and prostate cancer). Herein we demonstrate that the BLI technology in couple with a fine ultrasonic guidance realizes cancer cell-type dependent metastasis to the specific organs. For example, some melanoma cell lines showed frequent metastasis to brain, lungs, and lymph nodes in the mouse model. Notably, reflecting the clinical features of melanoma, breast, and prostate cancer, some of the cell lines showed preferential metastasis to the brain. Moreover, these cellular resources for BLI allow a high throughput screening for potential anti-cancer drugs. Thus, this BLI-mediated additional strategy with the luciferase-expressing cancer cell resources should promote many translational studies for human cancer therapy.

  8. Repeat stereotactic radiosurgery in the management of brain metastases from NSCLC: A case report and review of the literature

    OpenAIRE

    2013-01-01

    The aims of radiotherapeutic treatment of brain metastases include maintaining neurocognitive function and improvement of survival. Based on these premises, we present a case report in which the role of repeat stereotactic radiosurgery (SRS) was investigated in a patient with a recurrent brain metastasis from non-small cell lung cancer in the same area as previously treated with radiosurgery. A 40-year-old male caucasian patient was diagnosed with brain metastasis from non-small cell lung can...

  9. Breast metastasis from carcinoma of gall bladder

    Directory of Open Access Journals (Sweden)

    Ajaz Ahmad Malik

    2013-01-01

    Full Text Available Carcinoma of gall bladder has early lymphatic and haematogenous spread. Most common extra abdominal site of metastasis is the lung. Metastasis to breast from carcinoma of breast is very rare. Our case describes an interesting case of carcinoma of gall bladder metastising to breast. A 50-year-old female presented to our outpatient department with a small nodule on upper outer quadrant of left breast. Patient had a history of cholecystectomy done for symptomatic gall stones 2 years back. Histopathological examination of the gall bladder specimen showed adenocarcinoma of the gall bladder with invasion to lamina propria. No additional treatment was offered to the patient. The breast nodule was excised and sent for histopathological examination. Histopathological examination revealed metastising adenocarcinoma. Patient was subjected to palliative chemotherapy (Gamcitabine and carboplatin. However, patient died of hepatic encephalopathy after 5 months. Our case reports an unusual site of metastasis from carcinoma of gall bladder which is very rare.

  10. Plakoglobin: Role in Tumorigenesis and Metastasis

    Directory of Open Access Journals (Sweden)

    Zackie Aktary

    2012-01-01

    Full Text Available Plakoglobin (γ-catenin is a member of the Armadillo family of proteins and a homolog of β-catenin. As a component of both the adherens junctions and desmosomes, plakoglobin plays a pivotal role in the regulation of cell-cell adhesion. Furthermore, similar to β-catenin, plakoglobin is capable of participating in cell signaling. However, unlike β-catenin that has well-documented oncogenic potential through its involvement in the Wnt signaling pathway, plakoglobin generally acts as a tumor/metastasis suppressor. The exact roles that plakoglobin plays during tumorigenesis and metastasis are not clear; however, recent evidence suggests that it may regulate gene expression, cell proliferation, apoptosis, invasion, and migration. In this paper, we describe plakoglobin, its discovery and characterization, its role in regulating cell-cell adhesion, and its signaling capabilities in regulation of tumorigenesis and metastasis.

  11. Intracranial Dural Metastasis of Ewing's Sarcoma: a Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eung Yeop; Lee, Seung Koo; Kim, Dong Joon; Kim, Jin Na; Lee, Kyu Sung; Jung, Woo Hee; Kim, Dong Ik [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2008-02-15

    Ewing's sarcoma is a malignant bone tumor that can occur anywhere in the body, but it is most commonly observed in the long bones of the arms and legs, the pelvis and in the chest. The predominant sites of metastasis include the lung (38%), bone (including the spine; 31%), and the bone marrow (11%). Metastasis of Ewing's sarcoma to the central nervous system (CNS) is relatively rare, and most of the previous reports have demonstrated involvement of the bony calvarium or brain parenchyma. We describe here the imaging findings of dural metastasis of Ewing's sarcoma, and these imaging findings have not been previously reported on in the medical literature. In conclusion, dural metastasis of Ewing's sarcoma is very rare and its imaging characteristics are similar to those of a primary tumor, which mimic the findings of a schwannoma or meningioma. Despite its rarity, secondary Ewing's sarcoma may be included in the differential diagnosis of extra-axial dural masses.

  12. Homonymous Quadrantanopsia as the First Manifestation of Cerebral Metastasis of Invasive Mole: a case report

    Directory of Open Access Journals (Sweden)

    Song De-Lu

    2012-04-01

    Full Text Available Abstract Introduction Homonymous quadrantanopsia results from retrochiasmal lesions in the visual pathway. Invasive mole is a benign tumor that arises from myometrial invasion of a hydatidiform mole via direct extension through tissue or venous channels. Cerebral metastasis of invasive mole is rare and there has been no report demonstrating homonymous quadrantanopsia as the first manifestation of metastasis in any trophoblastic neoplasms. Case presentation We report the case of a 31-year-old Asian woman who presented with right homonymous inferior quadrantanopsia from the mass effect of a solitary cerebral metastasis from an invasive mole. A magnetic resonance image (MRI of the brain showed a metastatic tumor in the left occipital lobe. The visual field improved slightly after chemotherapy. There was a reduction in the tumor size and the surrounding edema. This is the first case report demonstrating that homonymous quadrantanopsia should be included in the manifestations of the metastasis of an invasive mole. Conclusions The presentation of homonymous quadrantanopsia must alert ophthalmologists to conduct a complete medical history and arrange specialist consultation.

  13. Cranial computed tomographic abnormalities in leptomeningeal metastasis

    Energy Technology Data Exchange (ETDEWEB)

    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.

  14. Cutaneous metastasis from carcinoma of tonsil.

    Directory of Open Access Journals (Sweden)

    Dasmajumdar S

    2002-01-01

    Full Text Available Hematogenous spread from carcinoma of tonsil is an uncommon event and skin is an extremely rare site of metastasis. We encountered a 40-year-old male patient who initially presented with carcinoma of the tonsil with T3N2cMO disease and treated by curative radiotherapy. After about 2 years, he developed a skin lesion in the periorbital region which on cytological examination turned out to be metastasis from tonsillar carcinoma. The present paper describes this rare case report along with a brief review of the literature.

  15. The Multiple Roles of Exosomes in Metastasis.

    Science.gov (United States)

    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.

  16. Revisiting the Seed-and-soil Theory of Cancer Metastasis

    Institute of Scientific and Technical Information of China (English)

    Chaonan QIAN

    2009-01-01

    @@ In 1889, Paget proposed a "Seed-and-Soil" theory for cancer metastasis.According to this theory, cancer metastasis is not random, and one remote organ is more prone to be the seat of secondary tumor growth than another.

  17. Popliteal lymph node metastasis of tibial osteoblastic osteosarcoma

    Directory of Open Access Journals (Sweden)

    Yalın Dirik

    2014-01-01

    CONCLUSION: Lymph node metastasis of osteosarcoma is a rare entity and metastatic patterns could not be clearly explained. On the other hand, the effects of lymph node metastasis on prognosis are also not clearly defined and further studies are needed.

  18. Brain Basics

    Medline Plus

    Full Text Available ... News About Us Home > Health & Education > Educational Resources Brain Basics Introduction The Growing Brain The Working Brain ... to mental disorders, such as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are ...

  19. Brain Basics

    Science.gov (United States)

    ... News About Us Home > Health & Education > Educational Resources Brain Basics Introduction The Growing Brain The Working Brain ... to mental disorders, such as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are ...

  20. Metastasis in renal cell carcinoma: Biology and implications for therapy

    Directory of Open Access Journals (Sweden)

    Jun Gong

    2016-10-01

    Full Text Available Although multiple advances have been made in systemic therapy for renal cell carcinoma (RCC, metastatic RCC remains incurable. In the current review, we focus on the underlying biology of RCC and plausible mechanisms of metastasis. We further outline evolving strategies to combat metastasis through adjuvant therapy. Finally, we discuss clinical patterns of metastasis in RCC and how distinct systemic therapy approaches may be considered based on the anatomic location of metastasis.

  1. Invasive cancer cells and metastasis

    Science.gov (United States)

    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

  2. An Integrative Platform for Three-dimensional Quantitative Analysis of Spatially Heterogeneous Metastasis Landscapes

    Science.gov (United States)

    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.

  3. Imaging of Pelvic Bone Metastasis from Malignant Phyllodes Breast Tumor

    OpenAIRE

    Nguyen, Ba D.

    2015-01-01

    The author reports a patient with a malignant phyllodes breast tumor, who then had a ten-year disease free interval before she developed a left pelvic bone metastasis and soft tissue invasion. Cross-sectional and radionuclide imaging of its musculoskeletal metastasis is presented. Literature concerning bone metastasis from phyllodes tumor is also briefly reviewed and discussed, along with its epidemiology.

  4. Bilateral Choroidal Metastasis from Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Tariq Namad

    2014-01-01

    Full Text Available Breast and lung cancers are the most common primary neoplasms to manifest with choroidal metastases. The incidence of choroidal metastases from metastatic lung cancer was reported to be 2–6.7%. We report a case of bilateral choroidal metastasis from non-small cell lung cancer. A 59-year-old Caucasian female patient, never a smoker, was diagnosed with stage IV lung adenocarcinoma metastatic to the pleura, bones, and the brain. Her initial scan of the chest showed innumerable soft tissue nodules and mediastinal adenopathy compatible with metastatic disease. Her initial brain MRI showed numerous small enhancing lesions consistent with extensive disease. Unfortunately, during her follow-up visits, she presented with bulge on her left eye. Simultaneously, her follow-up chest scan showed increase in the size of the lung nodules. She continued to have a reasonable performance status at that time, except for mild increase in her dyspnea. The choroidal metastases require a multidisciplinary care and should be among the differential patients with malignancy who present with ocular symptoms.

  5. Inguinal lymph node metastasis of colon cancer

    Directory of Open Access Journals (Sweden)

    Sloane McGraw

    2011-01-01

    Full Text Available We present a case of adenocarcinoma of colon with unusual metastasis to inguinal lymph nodes. Our patient is a young male with bilateral inguinal lymphadenopathy, bone pains, and jaundice who presented as carcinoma of unknown primary. He was diagnosed as widely metastatic adenocarcinoma of colon for which he received chemotherapy and has had a good response to the treatment.

  6. Diagnosis of bone metastasis from thyroid carcinoma

    DEFF Research Database (Denmark)

    Bechsgaard, Thor; Lelkaitis, Giedrius; Jensen, Karl E;

    2015-01-01

    (MRI), but histology revealed a metastasis from thyroid carcinoma, although the patient had no previous history of thyroid malignancy and resection of the thyroid gland was without malignancy. Ultrasound-guided biopsy was possible due to cortical destruction and the multidisciplinary approach with re...

  7. A new protein Girdin in tumor metastasis

    Institute of Scientific and Technical Information of China (English)

    WANG Jing; FU Li; GU Feng; MA Yong-jie

    2010-01-01

    @@ The phosphatidylinositol 3-kinase/Akt serine/threonine kinase system regulates multiple cellular processes through the phosphorylation of a great number of downstream substrates and has been recognized as an important pathway for signal transduction, and in cancer invasion and metastasis.

  8. Severe Hyperkalemia and Bilateral Adrenal Metastasis

    Directory of Open Access Journals (Sweden)

    Michael Nagler

    2009-01-01

    Full Text Available Adrenal metastases are a common finding in metastatic lung and breast cancer. Often there are no clinical symptoms suggesting them. In this paper, we present a case of a 66-year-old man with metastatic lung cancer suffering from severe hyperkaliemia due to hypoaldosteronism as a result of bilateral adrenal metastasis.

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

    Science.gov (United States)

    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.

  10. Distant skeletal muscle metastasis from intrahepatic cholangiocarcinoma presenting as Budd-Chiari syndrome

    Institute of Scientific and Technical Information of China (English)

    Oh Sung Kwon; Young Sook Park; Jong Eun Joo; Dae Won Jun; Sang Heum Kim; Mee Yeon Chung; Nam In Kim; Moon Hee Song; Han Hyo Lee; Seung Hwan Kim; Yoon Ju Jo

    2007-01-01

    Intrahepatic cholangiocarcinoma is a malignant neoplasm arising from the biliary epithelium, which frequently invades adjacent organs or metastasizes to other visceral organs such as the lungs, bones, adrenals, and brain. However, distant skeletal muscle metastasis of cholangiocarcinoma has never been described before to the best of our knowledge and, furthermore, Budd-Chiari syndrome secondary to intrahepatic cholangiocarcinoma is also extremely rare. Here we present the first case overall of distant muscle metastasis from intrahepatic cholangiocarcinoma presenting as Budd-Chiari syndrome. A 44-year-old man admitted to the hospital with complaints of abdominal distension, edema of both legs, back pain and anorexia of 30 o" duration. Computed tomography and ultrasonography-guided percutaneous muscle biopsy established intrahepatic cholangiocarcinoma with disseminated thrombosis from inferior vena cava to bilateral iliac and femoral veins, and multiple skeletal muscle metastases in bilateral buttock and erector spinal muscle.

  11. Pituitary Metastasis from Renal Cell Carcinoma: Description of a Case Report

    Science.gov (United States)

    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

  12. Brain herniation

    Science.gov (United States)

    ... herniation; Uncal herniation; Subfalcine herniation; Tonsillar herniation; Herniation - brain ... Brain herniation occurs when something inside the skull produces pressure that moves brain tissues. This is most ...

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

    Science.gov (United States)

    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.

  14. Efficiency and prognosis of whole brain irradiation combined with precise radiotherapy on triple-negative breast cancer

    Directory of Open Access Journals (Sweden)

    Xinhong Wu

    2013-01-01

    Conclusion: After whole brain irradiation followed by IMRT or 3DCRT treatment, TN phenotype breast cancer patients with intracranial metastasis had high objective response rates but shorter survival time. With respect to survival in breast cancer patients with intracranial metastasis, the TN phenotype represents a significant adverse prognostic factor.

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

    Science.gov (United States)

    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.

  16. Clinical significance of intraventricular metastasis in patients with concomitant leptomeningeal metastasis from lung cancer%肺癌脑室内转移瘤对伴发脑膜转移的提示意义

    Institute of Scientific and Technical Information of China (English)

    潘振宇; 袁婷婷; 杨国姿; 王爱林; 石硙岩; 董丽华

    2013-01-01

    Objective To investigate the significance of intraventricular metastasis in the diagnosis of leptomeningeal metastasis from lung cancer.Methods Nineteen lung cancer patients with intraventricular metastasis,admitted to and confirmed by brain MRI in our hospital from May 2010 to December 2012,were selected in our study.All of the patients accepted cerebrospinal fluid (CSF)examination.The clinical and imaging findings and CSF examination results were analyzed.Results All 19 patients had cerebral parenehyma metastasis; the lesions of 16 patients located in the lateral ventricle,4 in the third ventricle and 8 in the fourth ventricle and aquaeductus cerebra; 9 patients had 2 metastatic lesions of intraventricular,which were disseminated.According to the disease history,imaging manifestation,clinical features and CSF examination results,13 patients (68%) were diagnosed with leptomeningeal metastasis.Conclusions Referring to the mechanism of leptomeningeal metastasis and imaging findings,intraventricular metastasis can lead to leptomeningeal metastasis; while tumor cells implantation caused by leptomeningeal metastasis can also form intraventricular metastasis.Therefore,intraventricular metastasis has the suggestive role for the diagnosis of leptomeningeal metastasis from lung cancer; intraventricular metastasis is one of the imaging characteristics in leptomeningeal metastasis from lung cancer.%目的 探讨肺癌患者磁共振(MRI)检查显示脑室内转移瘤是否对可能同时存在的脑膜转移具有提示作用.方法 选取吉林大学第一医院放疗科自2010年12月至2013年1月收治的19例头部MRI检查证实存在脑室内转移病灶,并具有脑脊液相关检查的肺癌患者,分析其临床及影像学表现、脑脊液检查结果等相关临床资料. 结果 19例患者均合并脑实质内转移病灶;16例患者脑室内病灶位于侧脑室,4例位于第三脑室,8例位于第四脑室及中脑导水管;其中9例同时存在脑室内2

  17. Modeling tumor invasion and metastasis in Drosophila.

    Science.gov (United States)

    Miles, Wayne O; Dyson, Nicholas J; Walker, James A

    2011-11-01

    Conservation of major signaling pathways between humans and flies has made Drosophila a useful model organism for cancer research. Our understanding of the mechanisms regulating cell growth, differentiation and development has been considerably advanced by studies in Drosophila. Several recent high profile studies have examined the processes constraining the metastatic growth of tumor cells in fruit fly models. Cell invasion can be studied in the context of an in vivo setting in flies, enabling the genetic requirements of the microenvironment of tumor cells undergoing metastasis to be analyzed. This Perspective discusses the strengths and limitations of Drosophila models of cancer invasion and the unique tools that have enabled these studies. It also highlights several recent reports that together make a strong case for Drosophila as a system with the potential for both testing novel concepts in tumor progression and cell invasion, and for uncovering players in metastasis.

  18. Modeling tumor invasion and metastasis in Drosophila

    Directory of Open Access Journals (Sweden)

    Wayne O. Miles

    2011-11-01

    Full Text Available Conservation of major signaling pathways between humans and flies has made Drosophila a useful model organism for cancer research. Our understanding of the mechanisms regulating cell growth, differentiation and development has been considerably advanced by studies in Drosophila. Several recent high profile studies have examined the processes constraining the metastatic growth of tumor cells in fruit fly models. Cell invasion can be studied in the context of an in vivo setting in flies, enabling the genetic requirements of the microenvironment of tumor cells undergoing metastasis to be analyzed. This Perspective discusses the strengths and limitations of Drosophila models of cancer invasion and the unique tools that have enabled these studies. It also highlights several recent reports that together make a strong case for Drosophila as a system with the potential for both testing novel concepts in tumor progression and cell invasion, and for uncovering players in metastasis.

  19. Melanoma metastasis to the spleen: Laparoscopic approach

    Directory of Open Access Journals (Sweden)

    Trindade Manoel Roberto

    2009-01-01

    Full Text Available 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.

  20. Melanoma metastasis to the spleen: Laparoscopic approach

    Science.gov (United States)

    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

  1. Progression and metastasis of lung cancer.

    Science.gov (United States)

    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.

  2. Breast carcinoma metastasis to the lacrimal gland

    DEFF Research Database (Denmark)

    Nickelsen, Marie N.; Von Holstein, Sarah; Hansen, Alastair B.;

    2015-01-01

    A 77-year-old female, with proptosis, reduced eye motility and diplopia which had developed over two to three months and a 69-year-old female with proptosis, oedema of the eyelid, reduced motility and ptosis, which had developed over three weeks, are presented in the present study. Computed tomog...... study aimed to describe two such cases and draw attention to breast carcinomas as a differential diagnosis and the most frequent cause of lacrimal gland metastasis....

  3. Isolated penile metastasis from bladder carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Demuren, O.A. [Department of Radiology and Imaging, Armed Forces Hospital, Riyadh (Saudi Arabia); Koriech, O. [Department of Oncology, Armed Forces Hospital, Riyadh (Saudi Arabia)

    1999-10-01

    Metastases of the penis are uncommon, with only approximately 300 cases reported since 1870. In up to 70 % of patients, the primary tumour is located in the urogenital tract. Furthermore, isolated metastases of the penis are exceptionally rare. We report a case of solitary squamous cell metastasis of the penis presenting with painful swelling initially thought to be inflammatory in origin. The CT and MR imaging findings are presented with a short review of the literature. (orig.) With 2 figs., 9 refs.

  4. Thymoma Metastasis to the Semimembranosus Muscle

    Science.gov (United States)

    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

    Science.gov (United States)

    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. [Intrascrotal metastasis in a renal cell carcinoma].

    Science.gov (United States)

    Calleja Escudero, J; Pascual Samaniego, M; Martín Blanco, S; de Castro Olmedo, C; Gonzalo, V; Fernández del Busto, E

    2004-04-01

    The present article reports a case of intrascrotal metastasis of renal adenocarcinoma. This is an unusual case. A 66-year-old male patient undewent right radical nephrectomy and cavotomy for renal cell carcinoma with renal vein infiltration and thrombus in cava. Six months later the patient present with a nodulous enlargement intrascrotal and roots of penis. And he died 15 moths after nephrectomy. Usually intrascrotal metastases are a late event in the course after detection of a renal carcinoma.

  7. Mandibular metastasis of cholangiocarcinoma: A case report

    Energy Technology Data Exchange (ETDEWEB)

    You, Tae Min [Dept. of Advanced General Dentistry, Dankook University, Cheonan (Korea, Republic of); Kim, Kee Dong; Jeong, Ho Gui; Park, Won Se [Advanced General Dentistry, Dankook University, Cheonan (Korea, Republic of)

    2015-12-15

    Tumors metastasizing from distant regions to the oral and maxillofacial region are uncommon, comprising only 1%-2% of all malignancies. Cholangiocarcinoma is a malignancy that arises from cholangiocytes, which are epithelial cells that line the bile ducts. These cancers are difficult to diagnose and have a poor prognosis. In this paper, we report a rare case of mandibular metastasis of cholangiocarcinoma diagnosed at the primary site and discuss the radiographic findings observed in this case.

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

    Science.gov (United States)

    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.

  9. Metastasis of Prostate Adenocarcinoma to the Testis

    Science.gov (United States)

    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

  10. Therapy for bone metastasis from different cancers

    Institute of Scientific and Technical Information of China (English)

    Zheng Zhang; Peng Tan; Baoguo Mi; Chao Song; Yi Deng; Hanfeng Guan

    2016-01-01

    The bone is the most common target organ of cancer metastasis. Bone metastasis leads to considerable morbidity due to skeletal-related events (SREs). These include bone pain, hypercalcemia, pathologic frac-tures, and compression of the spinal cord. Cancers such as those of the lung, breast, prostate, and kidney are more likely to cause SREs than other cancer types. Additionaly, some blood cancers, including multiple myeloma and lymphoma, frequently cause SREs. In this article, we review the conventional therapies for metastatic bone disease, including drug therapy, radiotherapy, and surgery. Among osteoclast-targeting agents, bisphosphonates and nuclear factor kappa-B ligand inhibitors are the most widely used agents to prevent cancer-related bone loss. Unsealed radioisotopes are also considered promising in cancer therapy. Currently, iodine-131, strontium-89, and radium-223 are available for the treatment of bone metastasis. However, the treatments for blood cancers with SREs are diferent from those of other cancers. In those cases, new classes of agents including proteasome inhibitors, immunomodulatory drugs, monoclonal anti-bodies, and histone deacetylase inhibitors have shown remarkable eficacy. We also discuss the potential development of new therapies for these diseases.

  11. Spinal Intramedullary Metastasis of Breast Cancer

    Directory of Open Access Journals (Sweden)

    Recep Basaran

    2014-01-01

    Full Text Available Objective. Breast cancer accounts for approximately one-third of all cancers in females. Approximately 8.5 % of all central nervous system metastases are located in the spinal cord. These patients have rapidly progressing neurological deficits and require immediate examination. The aim of surgery is decompression of neural tissue and histological evaluation of the tumor. In this paper, we present a case of breast cancer metastasis in thoracic spinal intramedullary area which had been partially excised and then given adjuvant radiotherapy. Case. A 43-year-old female patient with breast cancer for 8 years was admitted to our hospital with complaints of weakness in both legs. Eight years ago, she received chemotherapy and radiotherapy. On her neurological examination, she had paraparesis (left lower extremity: 2/5, right lower extremity: 3/5 and urinary incontinence. Spinal MRI revealed a gadolinium enhancing intramedullary lesion. Pathologic examination of the lesion was consistent with breast carcinoma metastasis. The patient has been taken into radiotherapy. Conclusion. Spinal intramedullary metastasis of breast cancer is an extremely rare situation, but it has a high morbidity and mortality rate. Microsurgical resection is necessary for preservation or amelioration of neurological state and also for increased life expectancy and quality.

  12. Pathobiology of cancer metastasis: a short account

    Directory of Open Access Journals (Sweden)

    Feller Liviu

    2012-06-01

    Full Text Available Abstract Cancer-initiating cells display aberrant functional and phenotypic characteristics of normal stem cells from which they evolved by accumulation of multiple cytogenetic and/or epigenetic alterations. Signal transduction pathways which are essential for normal stem cell function are abnormally expressed by cancer cells, with a cancer cell phenotype playing an essential role in cancerization and metastasis. Local tumour progression, metastasis and metastatic tumour growth are mediated by direct cell-to-cell and paracrine reciprocal interactions between cancer cells and various stromal cells including fibroblasts, macrophages, bone marrow derived stem cells and progenitor cells. These interactions mediate breakdown of basement membrane barriers and angiogenesis both locally at the invasive front of the primary tumour and at the distant metastatic site; attract primary tumour cells to the candidate metastatic site; and promote proliferation, survival and growth of primary tumour cells and of metastatic cells at their distant site. It is the purpose of this article to highlight the analogies between some of the genetic programs of normal stem cells, and of cancer cells participating in the process of metastasis.

  13. Rational Operation for Primary Gastric Carcinoma with Liver Metastasis

    Institute of Scientific and Technical Information of China (English)

    Caigang Liu; Ping Lu; Jinsong Gu; Junqing Chen

    2007-01-01

    OBJECTIVE To investigate the prognosis of advanced gastric carcinoma patients with liver metastasis, and provide a foundation for rational operations.METHODS The operations and prognosis of 102 primary gastric carcinoma patients with liver metastasis were studied retrospectively. RESULTS In gastric carcinoma patients with H1 metastasis who under went a resection operation, the 6-month, 1- and 2-year post-operative survival rates were 61%, 42% and 7%. There was a statistically significant difference in survival between resected and non-resected patients (P=0.000) In gastric carcinoma cases with H2 metastasis, resection operations resulted in 54%,16% and 8% respective survival rates, with no significant difference compared to patients not receiving a resection (P=0.132). Gastric carcinoma patients with H3 metastasis who received a resection operation showed 25%, 13% and 0% respective survivals with no significantly better prognosis compared to the non-resected cases (P=0.135). There was no statistically significant difference in survival between the cases with or without peritoneal metastasis (P=0.152).CONCLUSION A resection operation provides a better prognosis for gastric carcinoma patients with H1 metastasis independent of peritoneal metastasis, but resection has no benefit for gastric carcinoma cases with H2 or H3 metastasis. Peritoneal metastases are not the significant influencing factor for the prognosis of gastric cancer with liver metastasis.

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

    Science.gov (United States)

    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.

  15. Molecular Mechanism Underlying Lymphatic Metastasis in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Zhiwen Xiao

    2014-01-01

    Full Text Available As the most challenging human malignancies, pancreatic cancer is characterized by its insidious symptoms, low rate of surgical resection, high risk of local invasion, metastasis and recurrence, and overall dismal prognosis. Lymphatic metastasis, above all, is recognized as an early adverse event in progression of pancreatic cancer and has been described to be an independent poor prognostic factor. It should be noted that the occurrence of lymphatic metastasis is not a casual or stochastic but an ineluctable and designed event. Increasing evidences suggest that metastasis-initiating cells (MICs and the microenvironments may act as a double-reed style in this crime. However, the exact mechanisms on how they function synergistically for this dismal clinical course remain largely elusive. Therefore, a better understanding of its molecular and cellular mechanisms involved in pancreatic lymphatic metastasis is urgently required. In this review, we will summarize the latest advances on lymphatic metastasis in pancreatic cancer.

  16. Cutaneous metastasis from squamous carcinoma of the base of tongue

    Directory of Open Access Journals (Sweden)

    Tashnin Rahman

    2015-01-01

    Full Text Available Context: Cutaneous metastasis from head and neck cancer is uncommon and it is seen from laryngeal cancer. Cutaneous metastasis from the base of tongue is relatively rare. Case Report: A 55-year-old male, who was a treated case of squamous carcinoma of the base of tongue presented with metastatic nodule on the skin of face and thigh. But, there was complete resolution of the tumor at the primary site. In the present case, clinically obvious cutaneous nodules with metastasis appeared soon after the completion of treatment with concurrent chemo-radiotherapy. The metastasis to the skin of face clinically appeared like an inflammatory lesion. Fine needle aspiration cytology confirmed the diagnosis of metastasis to skin at both the sites. Conclusion: Our case has highlighted that there could be associated occult skin metastasis at the time of diagnosis in squamous carcinoma of the base of tongue.

  17. MicroRNA regulation network in colorectal cancer metastasis

    Institute of Scientific and Technical Information of China (English)

    Jiao-Jiao; Zhou; Shu; Zheng; Li-Feng; Sun; Lei; Zheng

    2014-01-01

    Colorectal cancer is the third most common cancer worldwide. Metastasis is a major cause of colorectal cancer-related death. Mechanisms of metastasis remain largely obscure. MicroRNA is one of the most important epigenetic regulators by targeting mRNAs posttranscriptionally. Accumulated evidence has supported its significant role in the metastasis of colorectal cancer, including epithelial-mesenchymal transition and angiogenesis. Dissecting microRNAome potentially identifies specific microRNAs as biomarkers of colorectal cancer metastasis. Better understanding of the complex network of microRNAs in colorectal cancer metastasis provide new insights in the biological process of metastasis and in the potential targets for colorectal cancer therapies and for diagnosis of recurrent and metastatic colorectal cancer.

  18. Patrolling Monocytes Control Tumor Metastasis to the Lung

    OpenAIRE

    Hanna, Richard N.; Cekic, Caglar; Sag, Duygu; Tacke, Robert; Graham D. Thomas; Nowyhed, Heba; Herrley, Erica; Rasquinha, Nicole; McArdle, Sara; Wu, Runpei; Peluso, Esther; Metzger, Daniel; Ichinose, Hiroshi; Shaked, Iftach; Chodaczek, Grzegorz

    2015-01-01

    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 ...

  19. [Orbital metastasis from mucinous adenocarcinoma of the rectum].

    Science.gov (United States)

    Chekrine, T; Hassouni, A; Hatime, M; Jouhadi, H; Benchakroun, N; Bouchbika, Z; Tawfiq, N; Sahraoui, S; Benider, A

    2013-05-01

    Orbital metastasis from colorectal cancer are extremely rare. Only six cases are described in the literature. The discrepancy between the frequency of colorectal cancer and the rarity of metastasis to the eye and orbit remains paradoxical and enigmatic. We report the case of an 18-year-old young woman with orbital metastasis as the presenting sign of rectal cancer. Proptosis is the most frequent presenting clinical sign. Once the diagnosis is made, the prognosis is poor and treatment is palliative.

  20. [Adenocarcinoma of lung cancer with solitary metastasis to the stomach].

    Science.gov (United States)

    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.

  1. The role of GAGE cancer/testis antigen in metastasis

    DEFF Research Database (Denmark)

    Gjerstorff, Morten Frier; Terp, Mikkel Green; Hansen, Malene Bredahl;

    2016-01-01

    with migratory and invasive properties and were found to be upregulated in cancer cells with metastasizing potential in a gastric cancer model. METHODS: We have addressed the direct role of GAGE proteins in supporting metastasis using an isogenic metastasis model of human cancer, consisting of 4 isogenic cell......) and moderately metastatic clones (LM3), stable downregulation of GAGE expression did not affect the ability of CL16 cells to establish primary tumors and form metastasis in the lungs of immunodeficient mice. CONCLUSIONS: These results suggest that GAGE proteins per se do not support metastasis and that further...

  2. Brain Basics

    Medline Plus

    Full Text Available ... Basics will introduce you to some of this science, such as: How the brain develops How genes and the environment affect the brain The basic structure of the brain How different parts of the brain communicate and work with each other How changes in the brain ...

  3. Brain Fingerprinting

    Directory of Open Access Journals (Sweden)

    Ravi Kumar

    2012-12-01

    Full Text Available Brain Fingerprinting is a scientific technique to determine whether or not specific information is stored in an individual's brain by measuring a electrical brain wave response to Word, phrases, or picture that are presented on computer screen. Brain Fingerprinting is a controversial forensic science technique that uses electroencephalography (EEG to determine whether specific information is stored in a subject's brain.

  4. Brain Fingerprinting

    Directory of Open Access Journals (Sweden)

    ravi kumar

    2012-12-01

    Full Text Available Brain Fingerprinting is a scientific technique to determine whether or not specific information is stored in an individual's brain by measuring a electrical brain wave response to Word, phrases, or picture that are presented on computer screen. Brain Fingerprinting is a controversial forensic science technique that uses electroencephalograph y (EEG to determine whether specific information is stored in a subject's brain

  5. Brain Tumors

    Science.gov (United States)

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

  6. Contemporary approaches for imaging skeletal metastasis

    Institute of Scientific and Technical Information of China (English)

    David Ulmert; Lilja Solnes; Daniel LJ Thorek

    2015-01-01

    The skeleton is a common site of cancer metastasis. Notably high incidences of bone lesions are found for breast, prostate, and renal carcinoma. Malignant bone tumors result in significant patient morbidity. Identification of these lesions is a critical step to accurately stratify patients, guide treatment course, monitor disease progression, and evaluate response to therapy. Diagnosis of cancer in the skeleton typically relies on indirect bone-targeted radiotracer uptake at sites of active bone remodeling. In this manuscript, we discuss established and emerging tools and techniques for detection of bone lesions, quantification of skeletal tumor burden, and current clinical challenges.

  7. Orbital Metastasis of Multiple Myeloma: Case Report

    Directory of Open Access Journals (Sweden)

    Mustafa Vatansever

    2016-06-01

    Full Text Available A 68-year-old woman with a history of multiple myeloma presented to the clinic with pain and vision loss in her right eye. Proptosis was observed in her right eye and eye movements were restricted in all directions. Best corrected visual acuity was 3/10 in her right eye. On biomicroscopic examination, hyperemia and subconjunctival hemorrhage were present. Fundus examination of the right eye revealed optic disc edema and choroidal folds. In magnetic resonance imaging two orbital masses were detected. Based on the patient’s history and ocular examination, we evaluated the masses as orbital metastasis of multiple myeloma. Palliative radiotherapy was recommended.

  8. Diagnostic value of lymph node metastasis by diffusion-weighted magnetic resonance imaging in cervical cancer

    Directory of Open Access Journals (Sweden)

    Xiang-Qin He

    2016-01-01

    Conclusion: The ADC values in CC tissues with LN metastasis were significantly lower than those without LN metastasis, suggesting that DWI appears to improve diagnostic performance and can be a useful adjunct imaging for identifying LN metastasis in CC patients.

  9. Identification of a seasonal pattern to brain metastases

    Directory of Open Access Journals (Sweden)

    Sakellakis M

    2016-03-01

    Full Text Available Minas Sakellakis,1 Angelos Koutras,1 Maria Pittaka,2 Dimitrios Kardamakis,2 Melpomeni Kalofonou,1 Haralabos P Kalofonos,1 Despina Spyropoulou2 1Division of Oncology, Department of Medicine, 2Department of Radiation Oncology, University Hospital, Patras Medical School, Rion, Patras, GreeceWe have previously tested our hypothesis that there is a seasonality in the incidence of carcinomatous meningitis.1 Although further validation is needed in a larger cohort, we found that leptomeningeal metastasis occurred more often during warm months of the year which, in the case of Greece, is the period generally marked with the larger daytime length.1 Carcinomatous meningitis is closely related to brain metastasis, and a logical question is whether warm season is marked by a greater propensity also for brain metastasis.2 

  10. Brain components

    Science.gov (United States)

    ... can make complex movements without thinking. The brain stem connects the brain with the spinal cord and is composed of ... structures: the midbrain, pons, and medulla oblongata. The brain stem provides us with automatic functions that are necessary ...

  11. Brain surgery

    Science.gov (United States)

    Craniotomy; Surgery - brain; Neurosurgery; Craniectomy; Stereotactic craniotomy; Stereotactic brain biopsy; Endoscopic craniotomy ... cut depends on where the problem in the brain is located. The surgeon creates a hole in ...

  12. Brain Malformations

    Science.gov (United States)

    Most brain malformations begin long before a baby is born. Something damages the developing nervous system or causes it ... medicines, infections, or radiation during pregnancy interferes with brain development. Parts of the brain may be missing, ...

  13. Brain Basics

    Medline Plus

    Full Text Available ... science, such as: How the brain develops How genes and the environment affect the brain The basic ... that with brain development in people mental disorders. Genes and environmental cues both help to direct this ...

  14. Brain Basics

    Medline Plus

    Full Text Available ... can lead to mental disorders, such as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits ... tailored treatments, and possibly prevention of such illnesses. The Working Brain Neurotransmitters Everything we do relies on ...

  15. Solitary Spinal Epidural Metastasis from Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Taisei Sako

    2016-01-01

    Full Text Available Solitary epidural space metastasis of a malignant tumor is rare. We encountered a 79-year-old male patient with solitary metastatic epidural tumor who developed paraplegia and dysuria. The patient had undergone total gastrectomy for gastric cancer followed by chemotherapy 8 months priorly. The whole body was examined for suspected metastatic spinal tumor, but no metastases of the spine or important organs were observed, and a solitary mass was present in the thoracic spinal epidural space. The mass was excised for diagnosis and treatment and was histopathologically diagnosed as metastasis from gastric cancer. No solitary metastatic epidural tumor from gastric cancer has been reported in English. Among the Japanese, 3 cases have been reported, in which the outcome was poor in all cases and no definite diagnosis could be made before surgery in any case. Our patient developed concomitant pneumonia after surgery and died shortly after the surgery. When a patient has a past medical history of malignant tumor, the possibility of a solitary metastatic tumor in the epidural space should be considered.

  16. Global secretome analysis identifies novel mediators of bone metastasis

    Institute of Scientific and Technical Information of China (English)

    Mario Andres Blanco; Gary LeRoy; Zia Khan; Ma(s)a Ale(c)kovi(c); Barry M Zee; Benjamin A Garcia; Yibin Kang

    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.

  17. Calvarial Mass Confused With Trichilemmal Cyst: Hepatocellular Cancer Metastasis.

    Science.gov (United States)

    Polat, Gökhan; Sade, Recep

    2017-03-01

    The hepatocellular cancer calvarial metastasis is a rare condition that commonly presents cranial swelling. Therefore, calvarial swelling may confuse with frequent lesions of the scalp. The authors' patient was operated as trichilemmal cyst. But, intracranial extension was seen in operation. Calvarial metastasis of hepatocellular cancer was observed by examination of the patient.

  18. Bioinformatics analysis of metastasis-related proteins in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Pei-Ming Song; Yang Zhang; Yu-Fei He; Hui-Min Bao; Jian-Hua Luo; Yin-Kun Liu; Peng-Yuan Yang; Xian Chen

    2008-01-01

    AIM: To analyze the metastasis-related proteins in hepatocellular carcinoma (HCC) and discover the biomark-er candidates for diagnosis and therapeutic intervention of HCC metastasis with bioinformatics tools.METHODS: Metastasis-related proteins were determined by stable isotope labeling and MS analysis and analyzed with bioinformatics resources, including Phobius, Kyoto encyclopedia of genes and genomes (KEGG), online mendelian inheritance in man (OHIH) and human protein reference database (HPRD).RESULTS: All the metastasis-related proteins were linked to 83 pathways in KEGG, including MAPK and p53 signal pathways. Protein-protein interaction network showed that all the metastasis-related proteins were categorized into 19 function groups, including cell cycle, apoptosis and signal transcluction. OMIM analysis linked these proteins to 186 OMIM entries.CONCLUSION: Metastasis-related proteins provide HCC cells with biological advantages in cell proliferation, migration and angiogenesis, and facilitate metastasis of HCC cells. The bird's eye view can reveal a global charac-teristic of metastasis-related proteins and many differen-tially expressed proteins can be identified as candidates for diagnosis and treatment of HCC.

  19. Molecular Mechanisms of Metastasis Suppression in Human Breast Cancer

    Science.gov (United States)

    2000-07-01

    and breast carcinoma metastasis, Wake Forest University Cancer Center, July 28 Molecular mechanisms controlling melanoma and breast carcinoma...Bowman Show, August 17 Molecular regulation of melanoma and breast carcinoma metastasis, Wake Forest University Cancer Center, July 28 Molecular...Institute, April 20, Pathology ofNeoplasia Cumberland Unit, American Cancer Society, April 19; Breast Cancer Research Ministerio de Sanidad y

  20. Evaluate the Mechanism of Enhanced Metastasis Induced by Arthritis

    Science.gov (United States)

    2012-09-01

    Genes that mediate breast ca ncer metastasis to lung . Nature 2005, 436(7050):518-524. 6. Das Roy L, Pathangey L, Tinder T, Schettini J, Gruber H...7. Das Roy L, Ghosh S, Pathangey LB, Tinder TL, Gruber HE, Mukherjee P: Collagen induced arthritis increases s econdary metastasis in MMTV-PyV

  1. AACR centennial series: the biology of cancer metastasis: historical perspective.

    Science.gov (United States)

    Talmadge, James E; Fidler, Isaiah J

    2010-07-15

    Metastasis 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. An improved understanding of the metastatic process and the attributes of the cells selected by this process is critical for the treatment of patients with systemic disease. In many patients, metastasis has occurred by the time of diagnosis, so metastasis prevention may not be relevant. Treating systemic disease and identifying patients with early disease should be our goal. Revitalized research in the past three decades has focused on new discoveries in the biology of metastasis. Even though our understanding of molecular events that regulate metastasis has improved, the contributions and timing of molecular lesion(s) involved in metastasis pathogenesis remain unclear. Review of the history of pioneering observations and discussion of current controversies should increase understanding of the complex and multifactorial interactions between the host and selected tumor cells that contribute to fatal metastasis and should lead to the design of successful therapy.

  2. Probing the Fifty Shades of EMT in Metastasis.

    Science.gov (United States)

    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.

  3. Post site metastasis of breast cancer after video-assisted thoracic surgery for pulmonary metastasis of breast cancer: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Park, Mee Hyun; Hwang, Ji Young; Hyun, Su Jeong; Lee, Yul; Woo, Ji Young; Yang, Ik; Hong, Hye Sook; Kim, Han Myun [Dept. of Radiology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul (Korea, Republic of)

    2016-05-15

    We reported a case of port site metastasis in a 57-year-old patient who underwent video-assisted thoracic surgery (VATS) resection of pulmonary metastasis from breast cancer. Port site metastasis after VATS is very rare in patients with breast cancer. However, when suspicious lesions are detected near the port site in patients who have undergone VATS for pulmonary metastasis, port site metastasis should be considered in the differential diagnosis.

  4. Potential Anti-metastasis Natural Compounds for Lung Cancer.

    Science.gov (United States)

    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.

  5. Application of Proteomics in the Study of Tumor Metastasis

    Institute of Scientific and Technical Information of China (English)

    Zhen Cai; Jen-Fu Chiu; Qing-Yu He

    2004-01-01

    Tumor metastasis is the dominant cause of death in cancer patients. However, the molecular and cellular mechanisms underlying tumor metastasis are still elusive.The identification of protein molecules with their expressions correlated to the metastatic process would help to understand the metastatic mechanisms and thus facilitate the development of strategies for the therapeutic interventions and clinical management of cancer. Proteomics is a systematic research approach aiming to provide the global characterization of protein expression and function under given conditions. Proteomic technology has been widely used in biomarker discovery and pathogenetic studies including tumor metastasis. This article provides a brief review of the application of proteomics in identifying molecular factors in tumor metastasis process. The combination of proteomics with other experimental approaches in biochemistry, cell biology, molecular genetics and chemistry, together with the development of new technologies and improvements in existing method ologies will continue to extend its application in studying cancer metastasis.

  6. Carcinoma prostate with gastric metastasis: A rare case report

    Directory of Open Access Journals (Sweden)

    Virendra Bhandari

    2015-01-01

    Full Text Available Prostate carcinoma is the most common malignancy in males and it commonly manifests with bony metastasis in India, but occasionally visceral metastasis to lungs and liver may also be seen. Metastasis to the gastrointestinal tract is very rare. In literature, we could find six cases only. We present here 7 th patient of carcinoma prostate, which metastasized to stomach. He had epigastric pain, which was mistaken initially with analgesic induced acid peptic disease abut later, on endoscopy a gastric nodule was seen. Histopathology and immunohistochemistry of this confirmed it to be metastasis from prostate. This visceral metastasis to stomach usually spreads through lymphatic′s rather than by hematogenous route. This case is being presented because of its rare occurrence.

  7. Optimization of brain metastases radiotherapy with TomoHDA.

    Science.gov (United States)

    Yartsev, Slav; Bauman, Glenn

    2017-01-01

    An upgrade of the helical tomotherapy technology by introducing variable fan-field width (dynamic jaws) reduced the penumbra in superior-inferior direction for the target. Possible implementation of this upgrade even for the cases of the targets with different dose prescriptions is proposed. An example of brain metastasis in proximity to the optical apparatus in need of the whole brain irradiation of 30 Gy and higher dose to the lesion is considered.

  8. Establishment of an ovarian metastasis model and possible involvement of E-cadherin down-regulation in the metastasis.

    Science.gov (United States)

    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.

  9. Potential applications of image-guided radiotherapy for brain metastases and glioblastoma to improve patient quality of life

    Directory of Open Access Journals (Sweden)

    Nam Phong Nguyen

    2013-11-01

    Full Text Available Treatment of glioblastoma multiforme (GBM and brain metastasis remains a challenge because of the poor survival and the potential for brain damage following radiation. Despite concurrent chemotherapy and radiation dose escalation, local recurrence remains the predominant pattern of failure in GBM most likely secondary to repopulation of cancer stem cells. Even though radiotherapy is highly effective for local control of radio-resistant tumors such as melanoma and renal cell cancer, systemic disease progression is the cause of death in most patients with brain metastasis. Preservation of quality of life of cancer survivors is the main issue for patients with brain metastasis. Image-guided radiotherapy (IGRT by virtue of precise radiation dose delivery may reduce treatment time of patients with GBM without excessive toxicity and potentially improve neurocognitive function with preservation of local control in patients with brain metastasis. Future prospective trials for primary brain tumors or brain metastasis should include IGRT to assess its efficacy to improve patient quality of life.

  10. Anatomy of the Brain

    Science.gov (United States)

    ... Menu Brain Tumor Information Brain Anatomy Brain Structure Neuron Anatomy Brain Tumor Symptoms Diagnosis Types of Tumors Risk Factors ... form Brain Tumor Information Brain Anatomy Brain Structure Neuron Anatomy Brain Tumor Symptoms Diagnosis Types of Tumors Risk Factors ...

  11. [Management of brain metastases from urological malignancies].

    Science.gov (United States)

    Gaillard, S; Lebret, T; Scarone, P; Lepeintre, J-F; Méjean, A; Aldea, S

    2008-11-01

    Brain metastases account for 30 to 40% of all brain tumors in adults. Even if urological carcinomas are not very common, anti-angiogenic drugs have transformed their prognosis, leading physicians to consider their specific treatment. For the majority of cases, surgery is quite simple with low associated morbidity. Depending on the size and the location, surgery or stereotaxic radiotherapy should be discussed. As soon as the metastasis is suspected a neurosurgerical opinion must be sought before beginning any treatment to coordinate the global management.

  12. [Vaginal metastasis of renal carcinoma (author's transl)].

    Science.gov (United States)

    Carl, P; Marx, F J

    1977-11-01

    Four cases of vaginal metastases of renal carcinoma are reported. This is an incidence of 1.3% in 313 operated patients (from 1/1/70 to 12/31/76). A surgical treatment of primary renal carcinoma and vaginal metastasis seems to be reasonable in there cases. Since in accordance with the literature metastatic involvement of vagina and vulva seems not to be a very rare finding, the diagnostic in renal carcinoma should imply a gynecologic examination. Although in carcinoma of the left kidney metastatic spreading into the external female genitalia most probably occurs by a retrograde venous pathway (left ovarian vein), the way of dissemination in carcinoma of the right side is unclear.

  13. Oncoprotein metastasis and its suppression revisited

    Directory of Open Access Journals (Sweden)

    Radulescu Razvan T

    2010-04-01

    Full Text Available Abstract The past two decades have witnessed an increasing appreciation of the role of the tumor microenvironment, of genetic and epigenetic alterations in normal cells adjacent to tumors and of the migration of normal cells with aberrant intrinsic properties in cancer pathophysiology. Aside from these insights, a novel concept termed "oncoprotein metastasis" (OPM has recently been advanced and proposed to reflect protein-based neoplastic phenomena that might occur even before any modifications relating to the morphology, location or (epigenetic outfit of cells during the malignant process. Here, evidence is presented that supports the OPM perception and thus should contribute not only to further rethink the definition of a normal cell, but also the treatment of cancer disease in the years to come.

  14. Axillary node metastasis from primary ovarian carcinoma

    Directory of Open Access Journals (Sweden)

    Trupti S Patel

    2014-01-01

    Full Text Available Metastasization and distinction from mammary carcinoma is of great clinical importance because of different treatment modalities. Here, we discuss a case of stage IIIC ovarian serous carcinoma, presenting with bilateral axillary nodes metastasis after 25 months interval of its initial presentation. Increased serum CA-125 level caused clinical suspicion. Computed tomography scan of abdomen and pelvis showed no residual disease or any abdominal lymphadenopathy. Mammography of both breast were normal. Bilateral axillary nodes were noted. Guided fine needle aspiration cytology (FNAC and biopsy of ovarian carcinoma to axillary node is a rare event. Its recogn done. Cytomorphology revealed poorly differentiated carcinoma, compatible to that of primary ovarian tumor. Thus, metastatic carcinoma to axillary node from ovary was confirmed. This case illustrates a rare metastatic presentation of ovarian carcinoma and unequivocal role of FNAC to provide rapid diagnosis and preferred to be first line diagnostic procedure.

  15. Breast metastasis from small cell lung carcinoma

    Institute of Scientific and Technical Information of China (English)

    Shi-ping LUH; Chih KUO; Thomas Chang-yao TSAO

    2008-01-01

    Breast metastases from extramammary neoplasms are very rare. We presented a 66 year-old female with metastasis of small cell lung carcinoma to the breast. She presented with consolidation over the left upper lobe of her lung undetermined after endobronchial or video-assisted thoracoscopic surgery (VATS) biopsy, and this was treated effectively after antibiotic therapy at initial stage. The left breast lumps were noted 4 months later, and she underwent a modified radical mastectomy under the impression of primary breast carcinoma. However, the subsequent chest imaging revealed re-growing mass over the left mediastinum and hilum, and cells with the same morphological and staining features were found from specimens of transbronchial brushing and biopsy. An accurate diagnosis to distinguish a primary breast carcinoma from metastatic one is very important because the therapeutic planning and the outcome between them are different.

  16. Ventricular metastasis resulting in disseminated intravascular coagulation

    Directory of Open Access Journals (Sweden)

    Davis Ian D

    2005-05-01

    Full Text Available Abstract Background Disseminated Intravascular Coagulation (DIC complicates up to 7% of malignancies, the commonest solid organ association being adenocarcinoma. Transitional Cell Carcinoma (TCC has rarely been associated with DIC. Case presentation A 74-year-old woman with TCC bladder and DIC was found to have a cardiac lesion suspicious for metastatic disease. The DIC improved with infusion of plasma and administration of Vitamin K, however the cardiac lesion was deemed inoperable and chemotherapy inappropriate; given the patients functional status. We postulate that direct activation of the coagulation cascade by the intraventricular metastasis probably triggered the coagulopathy in this patient. Conclusion Cardiac metastases should be considered in cancer patients with otherwise unexplained DIC. This may influence treatment choices.

  17. Exercise, natural immunity, and tumor metastasis.

    Science.gov (United States)

    Hoffman-Goetz, L

    1994-02-01

    Exercise has been shown to reduce the growth of primary tumors and to enhance certain aspects of host natural immunity. The question of whether these are independent phenomena or are casually related has not been systematically evaluated. This paper presents information concerning the methodological difficulties in studying proposed relationships between exercise and cancer, focusing specifically on tumor metastasis, the process by which malignant cells disseminate to distant organs and establish new colonies. This paper also focuses on how natural immune processes and tumor cells exert bidirectional influences on each other. It is suggested that the direction of the impact of exercise on the control of metastatic spread of neoplastic cells will reflect, in part, the sensitivity of the specific tumor to cytolysis by natural immune mechanisms, the route of dissemination, the timing of exercise relative to tumor exposure, and whether exercise acts as a distress or eustress state.

  18. A link between inflammation and metastasis

    DEFF Research Database (Denmark)

    Hansen, M. T.; Forst, B.; Cremers, N.

    2015-01-01

    S100A4 is implicated in metastasis and chronic inflammation, but its function remains uncertain. Here we establish an S100A4-dependent link between inflammation and metastatic tumor progression. We found that the acute-phase response proteins serum amyloid A (SAA) 1 and SAA3 are transcriptional...... targets of S100A4 via Toll-like receptor 4 (TLR4)/nuclear factor-κB signaling. SAA proteins stimulated the transcription of RANTES (regulated upon activation normal T-cell expressed and presumably secreted), G-CSF (granulocyte-colony-stimulating factor) and MMP2 (matrix metalloproteinase 2), MMP3, MMP9...... and MMP13. We have also shown for the first time that SAA stimulate their own transcription as well as that of proinflammatory S100A8 and S100A9 proteins. Moreover, they strongly enhanced tumor cell adhesion to fibronectin, and stimulated migration and invasion of human and mouse tumor cells...

  19. NRF2 activation by antioxidant antidiabetic agents accelerates tumor metastasis.

    Science.gov (United States)

    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.

  20. Evaluation of inoperable pancreatic carcinoma based on tumor metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Miura, Yasuhiko; Ueda, Michio; Kubota, Toru; Endo, Itaru; Sekido, Hitoshi; Togo, Shinji; Shimada, Hiroshi [Yokohama City Univ. (Japan). School of Medicine

    2002-05-01

    Many pancreatic cancers are detected only after they are far advanced, and thus show a poor prognosis. We evaluated the survival of patients with inoperable pancreatic carcinoma, and strategy treatment. Subjects were 72 persons with advanced inoperable pancreatic carcinoma selected from among 144 examined at our department from May 1992 to March 2001. Patient factors (age, gender, and nutrition), tumor factors (hepatic metastasis, peritoneal dissemination, and distant metastasis), and treatment (radiotherapy, systemic chemotherapy, and hepatic arterial infusion therapy (HAI)) were studied and survival evaluated statistically. Overall mean survival was 175 days and the 1-year survival ratio was 13.5%. With multivariate analysis, prognostic factors were hepatic metastasis and radiotherapy. We therefore re-evaluated 56 patients treated with radiotherapy. In the group with no hepatic metastasis whose mean survival was 247 days, the prognostic factor was systemic chemotherapy. In the group with hepatic metastasis, mean survival was 140 days and the prognostic factor was the prognostic nutritional index (PNI) on admission. HAI was also a significant factor, which prolonged survival time with univariate analysis. Radiotherapy will be conducted for all inoperable pancreatic carcinomas. For the group with no hepatic metastasis, systemic chemotherapy is effective and for the group with hepatic metastasis. HAI will be selected. (author)

  1. N-glycans and metastasis in galectin-3 transgenic mice.

    Science.gov (United States)

    More, Shyam K; Srinivasan, Nithya; Budnar, Srikanth; Bane, Sanjay M; Upadhya, Archana; Thorat, Rahul A; Ingle, Arvind D; Chiplunkar, Shubhada V; Kalraiya, Rajiv D

    2015-05-01

    Poly-N-acetyl-lactosamine (polyLacNAc) on N-glycans facilitate lung specific metastasis of melanoma cells by serving as high affinity ligands for galectin-3, expressed in highest amounts in the lungs, on almost all its tissue compartments including on the surface of vascular endothelium. PolyLacNAc not only aids in initial arrest on the organ endothelium but in all the events of extravasation. Inhibition of polyLacNAc synthesis, or competitive inhibition of its interaction with galectin-3 all inhibited these processes and experimental metastasis. Transgenic galectin-3 mice, viz., gal-3(+/+) (wild type), gal-3(+/-) (hemizygous) and gal-3(-/-) (null) have been used to prove that galectin-3/polyLacNAc interactions are indeed critical for lung specific metastasis. Gal-3(+/-) mice which showed metastasis. However, surprisingly, the number and size of metastatic colonies in gal-3(-/-) mice was very similar as that seen in gal-3(+/+) mice. The levels of lactose binding lectins on the lungs and the transcripts of other galectins (galectin-1, -8 and -9) which are expressed on lungs and have similar sugar binding specificities as galectins-3, remain unchanged in gal-3(+/+) and gal-3(-/-) mice. Further, inhibition of N-glycosylation with Swainsonine (SW) which drastically reduces metastasis of B16F10 cells in gal-3(+/+) mice, did not affect lung metastasis when assessed in gal-3(-/-) mice. Together, these results rule out the possibility of some other galectin taking over the function of galectin-3 in gal-3(-/-) mice. Chimeric mice generated to assess if absence of any effect on metastasis is due to compromised tumor immunity by replacing bone marrow of gal-3(-/-) mice with that from gal-3(+/+) mice, also failed to impact melanoma metastasis. As galectin-3 regulates several immune functions including maturation of different immune cells, compromised tumor immunity could be the major determinant of melanoma metastasis in gal-3(-/-) mice and warrants thorough investigation.

  2. Dissecting Tumor-Stromal Interactions in Breast Cancer Bone Metastasis

    Directory of Open Access Journals (Sweden)

    Yibin Kang

    2016-06-01

    Full Text Available Bone metastasis is a frequent occurrence in breast cancer, affecting more than 70% of late stage cancer patients with severe complications such as fracture, bone pain, and hypercalcemia. The pathogenesis of osteolytic bone metastasis depends on cross-communications between tumor cells and various stromal cells residing in the bone microenvironment. Several growth factor signaling pathways, secreted micro RNAs (miRNAs and exosomes are functional mediators of tumor-stromal interactions in bone metastasis. We developed a functional genomic approach to systemically identified molecular pathways utilized by breast cancer cells to engage the bone stroma in order to generate osteolytic bone metastasis. We showed that elevated expression of vascular cell adhesion molecule 1 (VCAM1 in disseminated breast tumor cells mediates the recruitment of pre-osteoclasts and promotes their differentiation to mature osteoclasts during the bone metastasis formation. Transforming growth factor β (TGF-β is released from bone matrix upon bone destruction, and signals to breast cancer to further enhance their malignancy in developing bone metastasis. We furthered identified Jagged1 as a TGF-β target genes in tumor cells that engaged bone stromal cells through the activation of Notch signaling to provide a positive feedback to promote tumor growth and to activate osteoclast differentiation. Substantially change in miRNA expression was observed in osteoclasts during their differentiation and maturation, which can be exploited as circulating biomarkers of emerging bone metastasis and therapeutic targets for the treatment of bone metastasis. Further research in this direction may lead to improved diagnosis and treatment strategies for bone metastasis.

  3. Cell proliferation index predicts relapse of brain metastases in non-irradiated patients

    DEFF Research Database (Denmark)

    Peev, N A; Tonchev, A B; Penkowa, M

    2008-01-01

    BACKGROUND: Brain metastasis is a common complication and a major cause of morbidity and mortality in human malignancies. We investigated whether the proliferating cell index of surgically treated single brain metastasis would predict the relapse at a location remote from the initial resection site...... within 2 months of the excision in patients with uncontrolled systemic disease and not subjected to adjuvant whole brain radio-therapy. MATERIALS AND METHODS: Tissue biopsies derived from 25 patients with brain metastases specifically selected to be a single totally resected lesion and not treated...... subsequently by radiotherapy to the whole brain were stained by immunohistochemistry for the marker CDC47 and the proliferation index was calculated. The index was then analysed with respect to clinical parameters, including the incidence of brain relapse within 2 months of the first resection, the timing...

  4. BRAIN METASTASES OF GERM CELL TUMORS. THE RUSSIAN CANCER RESEARCH CENTER'S EXPERIENCE

    Directory of Open Access Journals (Sweden)

    A. A. Tryakin

    2014-07-01

    Full Text Available This paper analyzes the experience in treating 20 patients with nonseminomatous germ cell tumors metastasizing to the brain. It presents brain metastasis-associated factors: multiple lung metastases; IGCCCG poor prognosis; and a baseline human chorionic gonadotropin level of > 50000 mIU/ml. The authors have identified a group to be screened for brain metastasis, which includes patients with intermediate/poor prognosis and multiple lung metastases. Long-term survival was achieved in 45 % of patients with baseline brain damage and in 22 % of those with metastases revealed after first-line chemotherapy. The positive prognostic factors associated with long-term survival were a single brain lesion, no neurological symptoms, and achievement of clinical complete personse in the brain.

  5. Advances in TCM Treatment for Metastasis of Tumors

    Institute of Scientific and Technical Information of China (English)

    牛红梅; 刘嘉湘

    2003-01-01

    @@ As one of the basic biologic features of malignant tumors and a major cause leading to failure of treatment and even death, metastasis has aroused a great interest among the medical researchers. To date, convincing evidence is still lacking as to whether metastasis could be controlled by surgery, radio- or chemotherapy. However, TCM measures have proved to be advantageous in improving the survival quality and prolonging the survival period by decreasing the rate of distant metastasis of tumors. The following is a brief summary on the advances in this field.

  6. Cutaneous metastasis of prostate carcinoma to neck and upper chest

    Directory of Open Access Journals (Sweden)

    Nitin Abrol

    2011-01-01

    Full Text Available Prostate adenocarcinoma is the most common urologic malignant neoplasm in men. Metastasis to skin is rarely reported and usually occurs late. The incidence and appearance of cutaneous metastasis are not well established in patients with prostate adenocarcinoma and their recognition remains poor among practicing urologists. Their clinical appearance may mimic other common dermatologic disorders. Definitive diagnosis requires a high index of suspicion. Immunohistochemical staining helps in establishing the diagnosis. We report a case of prostate adenocarcinoma presenting with widespread metastasis, including those to dermis and subcutaneous tissue of neck and upper chest.

  7. Isolated renal metastasis from squamous cell lung cancer

    Directory of Open Access Journals (Sweden)

    Cai Jun

    2013-01-01

    Full Text Available Abstract Renal metastasis from non-small cell lung cancer is rather uncommon. The mechanism underlying the occurrence of metastasis in this site is still not well understood. We report a case of a 53-year-old Chinese woman who had moderately differentiated squamous cell carcinoma of the lung. After a ten months post-surgery interval of disease free survival, computed tomography (CT scan found that left renal parenchymal was occupied by a mass, confirmed by kidney biopsy to be a metastasis from squamous cell lung carcinoma. Based on this case, we are warned to be cautious in diagnosis and treatment when renal lesion are detected.

  8. Lymphatics and cancer : VEGF-C and nitric oxide in lymphatic function, lymphangiogenesis, and metastasis

    NARCIS (Netherlands)

    Hagendoorn, Jeroen

    2006-01-01

    The lymphatics are a primary route for cancer metastasis and lymph node metastasis is an important clinical prognostic factor. The process of lymphatic metastasis is, however, not well understood. This thesis examines the function of lymphatic vessels in relation to cancer progression and metastasis

  9. File list: ALL.Bld.05.AllAg.Lymph_node_metastasis [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.05.AllAg.Lymph_node_metastasis hg19 All antigens Blood Lymph node metastasi...s SRX861687 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Bld.05.AllAg.Lymph_node_metastasis.bed ...

  10. File list: ALL.Bld.50.AllAg.Lymph_node_metastasis [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.50.AllAg.Lymph_node_metastasis hg19 All antigens Blood Lymph node metastasi...s SRX861687 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Bld.50.AllAg.Lymph_node_metastasis.bed ...

  11. File list: ALL.Bld.20.AllAg.Lymph_node_metastasis [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.20.AllAg.Lymph_node_metastasis hg19 All antigens Blood Lymph node metastasi...s SRX861687 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Bld.20.AllAg.Lymph_node_metastasis.bed ...

  12. File list: Unc.Bld.05.AllAg.Lymph_node_metastasis [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Bld.05.AllAg.Lymph_node_metastasis hg19 Unclassified Blood Lymph node metastasi...s http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Bld.05.AllAg.Lymph_node_metastasis.bed ...

  13. File list: ALL.Bld.10.AllAg.Lymph_node_metastasis [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.10.AllAg.Lymph_node_metastasis hg19 All antigens Blood Lymph node metastasi...s SRX861687 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Bld.10.AllAg.Lymph_node_metastasis.bed ...

  14. File list: Unc.Bld.20.AllAg.Lymph_node_metastasis [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Bld.20.AllAg.Lymph_node_metastasis hg19 Unclassified Blood Lymph node metastasi...s http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Bld.20.AllAg.Lymph_node_metastasis.bed ...

  15. File list: Unc.Bld.50.AllAg.Lymph_node_metastasis [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Bld.50.AllAg.Lymph_node_metastasis hg19 Unclassified Blood Lymph node metastasi...s http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Bld.50.AllAg.Lymph_node_metastasis.bed ...

  16. File list: Unc.Bld.10.AllAg.Lymph_node_metastasis [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Bld.10.AllAg.Lymph_node_metastasis hg19 Unclassified Blood Lymph node metastasi...s http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Bld.10.AllAg.Lymph_node_metastasis.bed ...

  17. Multiple cutaneous melanomas associated with gastric and brain metastases*

    Science.gov (United States)

    Grander, Lara Caroline; Cabral, Fernanda; Lisboa, Alice Paixão; Vale, Gabrielle; Barcaui, Carlos Baptista; Maceira, Juan Manuel Pineiro

    2016-01-01

    The occurrence of multiple primary melanomas in a single individual is rare. Most commonly, malignant melanocytic lesions subsequent to the initial diagnosis of melanoma are secondary cutaneous metastases. We report a patient with gastrointestinal bleeding from gastric metastasis of cutaneous melanoma. During clinical evaluation and staging, we discovered a brain metastasis associated with 3 synchronous primary cutaneous melanomas. We suggest the research on the mutation in the cyclin-dependent kinase inhibitor 2A (CDKN2A) (INK4a) in such cases. We also emphasize the importance of clinical examination and dermoscopy of the entire tegument, even after a malignant melanocytic lesion is identified.

  18. Spontaneous metastasis in matrix metalloproteinase 3-deficient mice

    DEFF Research Database (Denmark)

    Juncker-Jensen, Anna; Rømer, John; Pennington, Caroline J;

    2009-01-01

    in tumorigenesis and metastatic growth. In this model the stromal expression of MMP-3 mRNA resembles the predominant MMP-3 expression pattern observed in human ductal breast carcinomas. We studied a cohort of 63 PyMT transgenic mice, either deficient for MMP-3 or wild-type controls. The degree of metastasis did...... not differ significantly between the two groups of mice, although the median lung metastasis volume was more than threefold increased in MMTV-PyMT mice deficient in MMP-3. Likewise, primary tumor growth rate and lymph node metastasis were not significantly affected by MMP-3-deficiency. By comparing m......RNA levels in MMP-3-deficient PyMT tumors with PyMT wild-type tumors we excluded compensatory transcriptional changes of other MMPs or their specific inhibitors. Thus, we conclude that genetic ablation of MMP-3 does not significantly affect tumor growth and metastasis in the MMTV-PyMT model....

  19. Contribution to Study About Metastasis of Oral Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Fernanda Ferreira LOPES

    2006-09-01

    Full Text Available Objective: This paper is a retrospective study with aim of collecting information about neoplasm metastasis of oral squamous cell carcinoma. Method: The registry of patients with the histopathology diagnose of oral squamous cell carcinoma in Oncology Institute Aldenora Belo (IMOAB in São Luis - MA, from 1992 to 2004, was analyzed and 18 cases were selected. Results: The most common anatomical region of primary neoplasm was tongue, following by buccal floor and cheek. In related to anatomical area compromised by metastasis, the cervical ones were the most frequent, followed by tongue and buccal floor. Conclusion: It concluded that the tongue was the most common site of oral squamous cell carcinoma, where frequently, shows metastasis, and the most common loco-regional metastasis was on cervical area, especially.

  20. Skeletal metastasis: treatments, mouse models,and the Wnt signaling

    Institute of Scientific and Technical Information of China (English)

    Kenneth C.Valkenburg; Matthew R.Steensma; Bart O.Williams; Zhendong Zhong

    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.

  1. Hypoxia-regulated target genes implicated in tumor metastasis

    Directory of Open Access Journals (Sweden)

    Tsai Ya-Ping

    2012-12-01

    Full Text Available Abstract Hypoxia is an important microenvironmental factor that induces cancer metastasis. Hypoxia/hypoxia-inducible factor-1α (HIF-1α regulates many important steps of the metastatic processes, especially epithelial-mesenchymal transition (EMT that is one of the crucial mechanisms to cause early stage of tumor metastasis. To have a better understanding of the mechanism of hypoxia-regulated metastasis, various hypoxia/HIF-1α-regulated target genes are categorized into different classes including transcription factors, histone modifiers, enzymes, receptors, kinases, small GTPases, transporters, adhesion molecules, surface molecules, membrane proteins, and microRNAs. Different roles of these target genes are described with regards to their relationship to hypoxia-induced metastasis. We hope that this review will provide a framework for further exploration of hypoxia/HIF-1α-regulated target genes and a comprehensive view of the metastatic picture induced by hypoxia.

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

    Science.gov (United States)

    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.

  3. Gastric Metastasis of Breast Cancer: A Case Series

    Science.gov (United States)

    dos Santos Fernandes, Gustavo; Batista Bugiato Faria, Luiza D.; de Assis Pereira, Isadora; Neves, Natália C. Moreira; Vieira, Yasmine Oliveira; Leal, Alessandro I. Cavalcanti

    2016-01-01

    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.

  4. Treatment of multiple liver metastasis from gastric carcinoma

    Directory of Open Access Journals (Sweden)

    Nishida Yasuji

    2007-06-01

    Full Text Available Abstract Background The efficacy of operative resection of liver metastasis from colorectal cancer has been established. However, a treatment for liver metastasis from gastric cancer has not yet been established. In this study, we evaluated the efficacy of hepatic arterial infusion for synchronous hepatic metastasis from gastric cancer. Patients and methods This study consisted of 37 patients [HAI group; 18 and non-HAI group; 19] with synchronous multiple liver metastases from gastric cancer at Gunma Prefecture Saiseikai-Maebashi Hospital. We retrospectively analyzed the efficacy of HAI. Results Response rate (CR + PR of HAI was 83%. However, HAI treatment did not affect any improvement in the survival rate. Conclusion HAI is an effective treatment for control of liver metastasis specifically. The factor effective for an improvement in the survival rate was possibly that of gastrectomy.

  5. Breast Metastasis from Esophagogastric Junction Cancer: A Case Report

    Directory of Open Access Journals (Sweden)

    Sanghamitra Jena

    2014-01-01

    Full Text Available 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.

  6. Patrolling Monocytes Control Tumor Metastasis to the Lung

    Science.gov (United States)

    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

  7. Activation of PPARγ in myeloid cells promotes lung cancer progression and metastasis.

    Directory of Open Access Journals (Sweden)

    Howard Li

    Full Text Available Activation of peroxisome proliferator-activated receptor-γ (PPARγ inhibits growth of cancer cells including non-small cell lung cancer (NSCLC. Clinically, use of thiazolidinediones, which are pharmacological activators of PPARγ is associated with a lower risk of developing lung cancer. However, the role of this pathway in lung cancer metastasis has not been examined well. The systemic effect of pioglitazone was examined in two models of lung cancer metastasis in immune-competent mice. In an orthotopic model, murine lung cancer cells implanted into the lungs of syngeneic mice metastasized to the liver and brain. As a second model, cancer cells injected subcutaneously metastasized to the lung. In both models systemic administration of pioglitazone increased the rate of metastasis. Examination of tissues from the orthotopic model demonstrated increased numbers of arginase I-positive macrophages in tumors from pioglitazone-treated animals. In co-culture experiments of cancer cells with bone marrow-derived macrophages, pioglitazone promoted arginase I expression in macrophages and this was dependent on the expression of PPARγ in the macrophages. To assess the contribution of PPARγ in macrophages to cancer progression, experiments were performed in bone marrow-transplanted animals receiving bone marrow from Lys-M-Cre+/PPARγ(flox/flox mice, in which PPARγ is deleted specifically in myeloid cells (PPARγ-Mac(neg, or control PPARγ(flox/flox mice. In both models, mice receiving PPARγ-Mac(neg bone marrow had a marked decrease in secondary tumors which was not significantly altered by treatment with pioglitazone. This was associated with decreased numbers of arginase I-positive cells in the lung. These data support a model in which activation of PPARγ may have opposing effects on tumor progression, with anti-tumorigenic effects on cancer cells, but pro-tumorigenic effects on cells of the microenvironment, specifically myeloid cells.

  8. Matrix metalloproteinases in the brain and blood-brain barrier: Versatile breakers and makers.

    Science.gov (United States)

    Rempe, Ralf G; Hartz, Anika Ms; Bauer, Björn

    2016-09-01

    Matrix metalloproteinases are versatile endopeptidases with many different functions in the body in health and disease. In the brain, matrix metalloproteinases are critical for tissue formation, neuronal network remodeling, and blood-brain barrier integrity. Many reviews have been published on matrix metalloproteinases before, most of which focus on the two best studied matrix metalloproteinases, the gelatinases MMP-2 and MMP-9, and their role in one or two diseases. In this review, we provide a broad overview of the role various matrix metalloproteinases play in brain disorders. We summarize and review current knowledge and understanding of matrix metalloproteinases in the brain and at the blood-brain barrier in neuroinflammation, multiple sclerosis, cerebral aneurysms, stroke, epilepsy, Alzheimer's disease, Parkinson's disease, and brain cancer. We discuss the detrimental effects matrix metalloproteinases can have in these conditions, contributing to blood-brain barrier leakage, neuroinflammation, neurotoxicity, demyelination, tumor angiogenesis, and cancer metastasis. We also discuss the beneficial role matrix metalloproteinases can play in neuroprotection and anti-inflammation. Finally, we address matrix metalloproteinases as potential therapeutic targets. Together, in this comprehensive review, we summarize current understanding and knowledge of matrix metalloproteinases in the brain and at the blood-brain barrier in brain disorders.

  9. ["Clown nose"--skin metastasis of breast cancer].

    Science.gov (United States)

    Soyer, H P; Cerroni, L; Smolle, J; Kerl, H

    1990-10-01

    We report on a 74-year-old woman showing a reddish infiltration of the tip of the nose, which had appeared 3 months ago. Clinically, we considered the following differential diagnoses: sarcoidosis, rosacea, pseudolymphoma, and metastasis. Histological and immunohistological investigation proved a cutaneous metastasis of carcinoma of the breast. Our case report gives evidence of the fact that cutaneous metastases of systemic malignancies are frequently located in acral regions of the skin.

  10. Targeting ROR1 inhibits epithelial-mesenchymal transition and metastasis.

    Science.gov (United States)

    Cui, Bing; Zhang, Suping; Chen, Liguang; Yu, Jianqiang; Widhopf, George F; Fecteau, Jessie-F; Rassenti, Laura Z; Kipps, Thomas J

    2013-06-15

    Metastasis is responsible for 90% of cancer-related deaths. Strategies are needed that can inhibit the capacity of cancer cells to migrate across the anatomic barriers and colonize distant organs. Here, we show an association between metastasis and expression of a type I receptor tyrosine kinase-like orphan receptor, ROR1, which is expressed during embryogenesis and by various cancers, but not by normal postpartum tissues. We found that expression of ROR1 associates with the epithelial-mesenchymal transition (EMT), which occurs during embryogenesis and cancer metastasis. Breast adenocarcinomas expressing high levels of ROR1 were more likely to have gene expression signatures associated with EMT and had higher rates of relapse and metastasis than breast adenocarcinomas expressing low levels of ROR1. Suppressing expression of ROR1 in metastasis-prone breast cancer cell lines, MDA-MB-231, HS-578T, or BT549, attenuated expression of proteins associated with EMT (e.g., vimentin, SNAIL-1/2, and ZEB1), enhanced expression of E-cadherin, epithelial cytokeratins (e.g., CK-19), and tight junction proteins (e.g., ZO-1), and impaired their migration/invasion capacity in vitro and the metastatic potential of MDA-MB-231 cells in immunodeficient mice. Conversely, transfection of MCF-7 cells to express ROR1 reduced expression of E-cadherin and CK-19, but enhanced the expression of SNAIL-1/2 and vimentin. Treatment of MDA-MB-231 with a monoclonal antibody specific for ROR1 induced downmodulation of vimentin and inhibited cancer cell migration and invasion in vitro and tumor metastasis in vivo. Collectively, this study indicates that ROR1 may regulate EMT and metastasis and that antibodies targeting ROR1 can inhibit cancer progression and metastasis.

  11. Targeting ROR1 Inhibits Epithelial-Mesenchymal Transition and Metastasis

    OpenAIRE

    Cui, Bing; Zhang, Suping; Chen, Liguang; Yu, Jianqiang; Widhopf, George F.; Fecteau, Jessie-F.; Rassenti, Laura Z.; Kipps, Thomas J.

    2013-01-01

    Metastasis is responsible for 90% of cancer-related deaths. Strategies are needed that can inhibit the capacity of cancer cells to migrate across anatomic barriers and colonize distant organs. Here we show an association between metastasis and expression of a type I receptor-tyrosine-kinase-like orphan receptor, ROR1, which is expressed during embryogenesis and by various cancers, but not by normal post-partum tissues. We found that expression of ROR1 associates with the epithelial-mesenchyma...

  12. Pericardial Metastasis Induced Tamponade from Urothelial Carcinoma: A Rare Entity

    OpenAIRE

    Rafay Khan; Waqas Jehangir; Sunil Tulpule; Mohamed Osman; Shilpi Singh; Shuvendu Sen

    2016-01-01

    Urothelial carcinoma in a few cases may result in cardiac metastasis. A rare presentation of this condition is its diagnosis as a result of cardiac tamponade. Tamponade is an unusual entity as a result of urothelial carcinoma and has only been reported in four cases. There have also been only a total of fifteen cases of cardiac metastasis from this form of malignancy. It is through this discussion that we emphasize the importance of early detection and monitoring of cardiac symptoms with the ...

  13. Preoperative diagnosis of lymph node metastasis in thoracic esophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Eguchi, Reiki; Yamada, Akiyoshi; Ueno, Keiko; Murata, Yoko [Tokyo Women`s Medical Coll. (Japan)

    1996-10-01

    From 1994 to 1995, to evaluate the utility of preoperative CT, EUS (endoscopic ultrasonography) and US in the diagnosis of lymph node metastasis in thoracic esophageal cancer, 94 patients with thoracic esophageal cancer who underwent esophagectomy were studied clinicopathologically. The sensitivity of EUS diagnosis of upper mediastinal lymph node metastasis (85%), left-sided paragastrin lymph node metastasis (73-77%), and especially lower paraesophageal lymph node metastasis (100%) were good. But due to their low-grade specificity in EUS diagnosis, their overall accuracy was not very good. On the other hand, the overall accuracy of the CT diagnosis of lymph node metastasis was fine. However, sensitivity, the most important clinical factor in the CT diagnosis of lymph node metastasis was considerably inferior to EUS. The assessment of the diagnosis of lymph node metastasis around the tracheal bifurcation and the pulmonary hilum and the left para-cardial lesion by CT or EUS was poor. It was concluded that lymph node metastasis of these area must be the pitfall in preoperative diagnosis. The average diameter of the lymph nodes and the proportion of cancerous tissue in the lymph nodes diagnosed as metastatic lymph nodes by CT was larger than that of the false negative lymph nodes. However, the lymph nodes diagnosed as true positives by EUS showed no such tendency. This must be the reason the sensitivity of the EUS diagnosis and specificity of the CT diagnosis were favorable, but the specificity of the EUS diagnosis and especially the sensitivity of the CT diagnosis were not as good. (author)

  14. A niche role for cancer exosomes in metastasis.

    Science.gov (United States)

    Zhang, Yun; Wang, Xiao-Fan

    2015-06-01

    Cancer cells are known to secrete exosomes with pro-metastatic effects. Pancreatic-cancer-derived exosomes are now shown to promote liver metastasis by eliciting pre-metastatic niche formation through a multi-step process. This involves uptake of exosome-derived factors by liver Kupffer cells and hepatic stellate cell activation to generate a fibrotic microenvironment with immune cell infiltrates that favours metastasis.

  15. Patients with brain metastases from gastrointestinal tract cancer treated with whole brain radiation therapy:Prognostic factors and survival

    Institute of Scientific and Technical Information of China (English)

    Susanne Bartelt; Felix Momm; Christian Weissenberger; Johannes Lutterbach

    2004-01-01

    AIM: To identify the prognostic factors with regard to survival for patients with brain metastasis from primary tumors of the gastrointestinal tract.METHODS: Nine hundred and sixteen patients with brain metastases, treated with whole brain radiation therapy (WBRT) between January 1985 and December 2000 at the Department of Radiation Oncology, University Hospital Freiburg, were analyzed retrospectively.RESULTS: Fifty-seven patients presented with a primary tumor of the gastrointestinal tract (esophagus: n = 0, stomach:n = 10, colorectal: n = 47). Twenty-six patients had a solitary brain metastasis, 31 patients presented with multiple brain metastases. Surgical resection was performed in 25 patients.WBRTwas applied with daily fractions of 2 Gray (Gy) or 3 Gy to a total dose of 50 Gy or 30 Gy, respectively. The interval between diagnoses of the primary tumors and brain metastases was 22.6 mo vs8.0 mo for patients with primary tumors of the colon/rectum vs other primary tumors,respectively (P<0.01, log-rank). Median overall survival for all patients with brain metastases (n = 916) was 3.4 mo and 3.2 mo for patients with gastrointestinal neoplasms.Patients with gastrointestinal primary tumors presented significantly more often with a solitary brain metastasis than patients with other primary tumors (P<0.05, log-rank). In patients with gastrointestinal neoplasms (n = 57), the median overall survival was 5.8 mo for patients with solitary brain metastasis vs 2.7 mo for patients with multiple brain metastases (P<0.01, log-rank). The median overall survival for patients with a Karnofsky performance status (KPS) ≥70was 5.5 mo vs2.1 mo for patients with KPS <70 (P<0.01,log-rank). At multivariate analysis (Cox Model) the performance status and the number of brain metastases were identified as independent prognostic factors for overall survival.CONCLUSION: Brain metastases occur late in the course of gastrointestinal tumors. Pretherapeutic variables like KPS and the

  16. Brain Basics

    Medline Plus

    Full Text Available ... have been linked to many mental disorders, including autism , obsessive compulsive disorder (OCD) , schizophrenia , and depression . Brain ... studies show that brain growth in children with autism appears to peak early. And as they grow ...

  17. Brain Basics

    Medline Plus

    Full Text Available ... depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are the basic working unit of ... but sometimes give rise to disabilities or diseases. neural circuit —A network of neurons and their interconnections. ...

  18. Brain Basics

    Medline Plus

    Full Text Available ... than ever before. Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses ... depression experience when starting treatment. Gene Studies Advanced technologies are also making it faster, easier, and more ...

  19. Brain Basics

    Medline Plus

    Full Text Available ... Real Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah is a ... blues" from time to time. In contrast, major depression is a serious disorder that lasts for weeks. ...

  20. Brain Basics

    Medline Plus

    Full Text Available ... the brain cannot effectively coordinate the billions of cells in the body, the results can affect many ... unit of the brain and nervous system. These cells are highly specialized for the function of conducting ...

  1. Brain Diseases

    Science.gov (United States)

    The brain is the control center of the body. It controls thoughts, memory, speech, and movement. It regulates the function of many organs. When the brain is healthy, it works quickly and automatically. However, ...

  2. Brain Basics

    Medline Plus

    Full Text Available ... related to changes in the anatomy, physiology, and chemistry of the nervous system. When the brain cannot ... their final destination. Chemical signals from other cells guide neurons in forming various brain structures. Neighboring neurons ...

  3. Brain Basics

    Medline Plus

    Full Text Available ... in the anatomy, physiology, and chemistry of the nervous system. When the brain cannot effectively coordinate the billions ... the basic working unit of the brain and nervous system. These cells are highly specialized for the function ...

  4. Brain Basics

    Medline Plus

    Full Text Available ... affect many aspects of life. Scientists are continually learning more about how the brain grows and works ... early brain development. It may also assist in learning and memory. Problems in making or using glutamate ...

  5. Olanzapine and Betamethasone Are Effective for the Treatment of Nausea and Vomiting due to Metastatic Brain Tumors of Rectal Cancer

    Directory of Open Access Journals (Sweden)

    M. Suzuki

    2014-01-01

    Full Text Available Brain lesions originating from metastasis of colorectal cancer represent 3-5% of all brain metastases and are relatively rare. Of all distant metastases of colorectal cancer, those to the liver are detected in 22-29% of cases, while those to the lungs are detected in 8-18% of cases. In contrast, brain metastasis is quite rare, with a reported incidence ranging from 0.4 to 1.8%. Treatments for metastatic brain tumors include surgery, radiotherapy, chemotherapy and supportive care with steroids, etc. Untreated patients exhibit a median survival of only approximately 1 month. The choice of treatment for brain metastasis depends on the number of lesions, the patient's general condition, nerve findings and presence of other metastatic lesions. We herein report the case of a 78-year-old male who presented with brain metastases originating from rectal carcinoma. He suffered from nausea, vomiting, anorexia and vertigo during body movement. He received antiemetics, glycerol and whole brain radiation therapy; however, these treatments proved ineffective. Olanzapine therapy was started at a dose of 1.25 mg every night. The persistent nausea disappeared the next day, and the frequency of vomiting subsequently decreased. The patient was able to consume solid food. Olanzapine is an antipsychotic that has recently been used as palliative therapy for refractory nausea and vomiting in patients receiving chemotherapy. We consider that olanzapine was helpful as a means of supportive care for the treatment of nausea and vomiting due to brain metastasis.

  6. Matrix metalloproteinase 13-containing exosomes promote nasopharyngeal carcinoma metastasis.

    Science.gov (United States)

    You, Yiwen; Shan, Ying; Chen, Jing; Yue, Huijun; You, Bo; Shi, Si; Li, Xingyu; Cao, Xiaolei

    2015-12-01

    Nasopharyngeal cancer (NPC) is an endemic type of head and neck cancer with a high rate of cervical lymph node metastasis. Metastasis is the major cause of death in NPC patients. Increasing evidence indicates that exosomes play a pivotal role in promoting cancer metastasis by enhancing angiogenesis and ECM degradation. Matrix metalloproteinase 13 is an important kind of matrix proteinase that is often overexpressed in various tumors and increases the risk of metastasis. However, little is known about the potential role of MMP13-containing exosomes in NPC. In this study, we found that MMP13 was overexpressed in NPC cells and exosomes purified from conditioned medium (CM) as well as NPC patients' plasma. Transwell analysis revealed that MMP13-containing exosomes facilitated the metastasis of NPC cells. Furthermore, siRNA inhibited the effect of MMP13-containing exosomes on tumor cells metastasis as well as angiogenesis. The current findings provided novel insight into the vital role of MMP13-containing exosomes in NPC progression which might offer unique insights for potential therapeutic strategies for NPC progressions.

  7. Remodeling of the methylation landscape in breast cancer metastasis.

    Directory of Open Access Journals (Sweden)

    Marsha Reyngold

    Full Text Available The development of breast cancer metastasis is accompanied by dynamic transcriptome changes and dramatic alterations in nuclear and chromatin structure. The basis of these changes is incompletely understood. The DNA methylome of primary breast cancers contribute to transcriptomic heterogeneity and different metastatic behavior. Therefore we sought to characterize methylome remodeling during regional metastasis. We profiled the DNA methylome and transcriptome of 44 matched primary breast tumors and regional metastases. Striking subtype-specific patterns of metastasis-associated methylome remodeling were observed, which reflected the molecular heterogeneity of breast cancers. These divergent changes occurred primarily in CpG island (CGI-poor areas. Regions of methylome reorganization shared by the subtypes were also observed, and we were able to identify a metastasis-specific methylation signature that was present across the breast cancer subclasses. These alterations also occurred outside of CGIs and promoters, including sequences flanking CGIs and intergenic sequences. Integrated analysis of methylation and gene expression identified genes whose expression correlated with metastasis-specific methylation. Together, these findings significantly enhance our understanding of the epigenetic reorganization that occurs during regional breast cancer metastasis across the major breast cancer subtypes and reveal the nature of methylome remodeling during this process.

  8. Metastasis and bone loss: advancing treatment and prevention.

    Science.gov (United States)

    Coleman, Robert E; Lipton, Allan; Roodman, G David; Guise, Theresa A; Boyce, Brendon F; Brufsky, Adam M; Clézardin, Philippe; Croucher, Peter I; Gralow, Julie R; Hadji, Peyman; Holen, Ingunn; Mundy, Gregory R; Smith, Matthew R; Suva, Larry J

    2010-12-01

    Tumor metastasis to the skeleton affects over 400,000 individuals in the United States annually, more than any other site of metastasis, including significant proportions of patients with breast, prostate, lung and other solid tumors. Research on the bone microenvironment and its role in metastasis suggests a complex role in tumor growth. Parallel preclinical and clinical investigations into the role of adjuvant bone-targeted agents in preventing metastasis and avoiding cancer therapy-induced bone loss have recently reported exciting and intriguing results. A multidisciplinary consensus conference convened to review recent progress in basic and clinical research, assess gaps in current knowledge and prioritize recommendations to advance research over the next 5 years. The program addressed three topics: advancing understanding of metastasis prevention in the context of bone pathophysiology; developing therapeutic approaches to prevent metastasis and defining strategies to prevent cancer therapy-induced bone loss. Several priorities were identified: (1) further investigate the effects of bone-targeted therapies on tumor and immune cell interactions within the bone microenvironment; (2) utilize and further develop preclinical models to study combination therapies; (3) conduct clinical studies of bone-targeted therapies with radiation and chemotherapy across a range of solid tumors; (4) develop biomarkers to identify patients most likely to benefit from bone-targeted therapies; (5) educate physicians on bone loss and fracture risk; (6) define optimal endpoints and new measures of efficacy for future clinical trials; and (7) define the optimum type, dose and schedule of adjuvant bone-targeted therapy.

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

    Science.gov (United States)

    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.

  10. Advances in understanding the molecular mechanism of pancreatic cancer metastasis

    Institute of Scientific and Technical Information of China (English)

    Yong-Xing Du; Zi-Wen Liu; Lei You; Wen-Ming Wu; Yu-Pei Zhao

    2016-01-01

    BACKGROUND: Pancreatic cancer (PC) is usually diagnosed at the late-stage and therefore, has widespread metastasis and a very high mortality rate. The mechanisms underlying PC metastasis are not well understood. Recent advances in genomic sequencing have identiifed groups of gene mutations that affect PC metastasis, but studies elucidating their roles are lacking. The present review was to investigate the molecu-lar mechanisms of PC metastasis. DATA SOURCES: Relevant articles on PC metastasis were searched in MEDLINE via PubMed prior to April 2015. The search was limited in English publications. RESULTS: PC metastatic cascades are multi-factorial events including both intrinsic and extrinsic elements. This review highlights the most important genetic alterations and other mechanisms that account for PC invasion and metastasis, with particular regard to epithelial-mesenchymal transition, inlfammation, stress response, and circulating tumor cells. CONCLUSIONS: Analyses of relevant gene functions and signaling pathways are needed to establish the gene regula-tory network and to deifne the pivotal modulators. Another promising area of study is the genotyping and phenotyping of circulating tumor cells, which could lead to a new era of per-sonalized therapy by identifying speciifc markers and targets.

  11. Inhibitory effect of ginsenoside Rg3 on ovarian cancer metastasis

    Institute of Scientific and Technical Information of China (English)

    XU Tian-min; CUI Man-hua; XIN Ying; GU Li-ping; JIANG Xin; SU Man-man; WANG Ding-ding; WANG Wen-jia

    2008-01-01

    Background Ginsenosides are main components extracted from ginseng, and ginsenoside Rg3 is one of the most important parts. Ginsenoside Rg3 has been found to inhibit several kinds of tumor growth and metastasis. The present study was undertaken to investigate the effect of ginsenoside Rg3 on human ovarian cancer metastasis and the possible mechanism.Methods The experimental lung metastasis models of ovarian cancer SKOV-3 and the assay of tumor-induced angiogenesis were used to observe the inhibitory effects of Rg3 on tumor metastasis and angiogenesis. The effect of Rg3 on invasive ability of SKOV-3 cells in vitro was detected by Boyden chamber, and immunofluorescence staining was used to recognize the expression of matrix metalloproteinase 9 (MMP-9) in SKOV-3 cells.Results In the experimental lung metastasis models of ovarian cancer, the number of tumor colonies in the lung and vessels oriented toward the tumor mass in each ginsenoside Rg3 group, was lower than that of control group. The invasive ability and MMP-9 expression of SKOV-3 cells decreased significantly after treatment with ginsenoside Rg3.Conclusions Ginsenoside Rg3 can significantly inhibit the metastasis of ovarian cancer. The inhibitory effect is partially due to inhibition of tumor-induced angiogenesis and decrease of invasive ability and MMP-9 expression of SKOV-3 cells.

  12. Metastasis and bone loss: Advancing treatment and prevention

    Science.gov (United States)

    Coleman, Robert E.; Lipton, Allan; Roodman, G. David; Guise, Theresa A.; Boyce, Brendon F.; Brufsky, Adam M.; Clézardin, Philippe; Croucher, Peter I.; Gralow, Julie R.; Hadji, Peyman; Holen, Ingunn; Mundy, Gregory R.; Smith, Matthew R.; Suva, Larry J.

    2011-01-01

    Tumor metastasis to the skeleton affects over 400,000 individuals in the United States annually, more than any other site of metastasis, including significant proportions of patients with breast, prostate, lung and other solid tumors. Research on the bone microenvironment and its role in metastasis suggests a complex role in tumor growth. Parallel preclinical and clinical investigations into the role of adjuvant bone-targeted agents in preventing metastasis and avoiding cancer therapy-induced bone loss have recently reported exciting and intriguing results. A multidisciplinary consensus conference convened to review recent progress in basic and clinical research, assess gaps in current knowledge and prioritize recommendations to advance research over the next 5 years. The program addressed three topics: advancing understanding of metastasis prevention in the context of bone pathophysiology; developing therapeutic approaches to prevent metastasis and defining strategies to prevent cancer therapy-induced bone loss. Several priorities were identified: (1) further investigate the effects of bone-targeted therapies on tumor and immune cell interactions within the bone microenvironment; (2) utilize and further develop preclinical models to study combination therapies; (3) conduct clinical studies of bone-targeted therapies with radiation and chemotherapy across a range of solid tumors; (4) develop biomarkers to identify patients most likely to benefit from bone-targeted therapies; (5) educate physicians on bone loss and fracture risk; (6) define optimal endpoints and new measures of efficacy for future clinical trials; and (7) define the optimum type, dose and schedule of adjuvant bone-targeted therapy. PMID:20478658

  13. Effects of vascular targeting photodynamic therapy on lymphatic tumor metastasis

    Science.gov (United States)

    Fateye, B.; He, C.; Chen, B.

    2009-06-01

    Vascular targeting photodynamic therapy (vPDT) is currently in clinical trial for prostate cancer (PCa) treatment. In order to study the effect of vPDT on tumor metastasis, GFP-PC3 or PC-3 xenografts were treated with verteporfin (BPD) PDT. Vascular function was assessed by ultrasound imaging; lymph node and lung metastasis were assessed by fluorescence imaging. vPDT significantly reduced tumor blood flow within 30minutes to 2 hours of treatment. Sub-curative treatment resulted in re-perfusion within 2 weeks of treatment and increased lymph node metastasis. With curative doses, no metastasis was observed. In order to identify cellular or matrix factors and cytokines implicated, conditioned medium from BPD PDTtreated endothelial cells was incubated with PC3 cells in vitro. Tumor cell proliferation and migration was assessed. By immunoblotting, we evaluated the change in mediators of intracellular signaling or that may determine changes in tumor phenotype. Low sub-curative dose (200ng/ml BPD) of endothelial cells was associated with ~15% greater migration in PC3 cells when compared with control. This dose was also associated with sustained activation of Akt at Ser 473, an upstream effector in the Akt/ mTOR pathway that has been correlated with Gleason scores in PCa and with survival and metastasis in vitro and in vivo. In conclusion, the study implicates efficacy of PDT of endothelial cells as an important determinant of its consequences on adjacent tumor proliferation and metastasis.

  14. Skeletal metastasis: the effect on immature skeleton

    Energy Technology Data Exchange (ETDEWEB)

    Ogden, J.A.; Ogden, D.A.

    1982-12-01

    The unique opportunity to study the entire appendicular skeleton of a child who died from metastatic angiosarcoma allowed detailed assessment of radiographically evident involvement. Virtually every portion of the appendicular skeleton had evidence of metastatic disease. However, the extent of involvement was extremely variable, especially when contralateral regions were assessed. The most likely region of metastasis, the metaphysis, is normally a fenestrated cortex of woven bone in the young child, rather than a well demarcated cortex formed by osteon (lamellar) bone, as it is in the adult. The pattern of destruction is such that less extensive areas may be involved before becoming radiographically evident, and trabecular bone involvement may be evident even without cortical damage. The metaphyseal metastatic spread supports the concept of arterial hematogeneous dissemination, comparable to osteomyelitis in the child. Pathologic metaphyseal fractures involved both proximal humeri; the fracture also extended along a portion of the methaphyseal-physeal interface in one humerus. In one distal femur the physis readily separated from the metaphysis; this was a nondisplaced type 1 growth mechanism injury.

  15. Galectin-3 in angiogenesis and metastasis

    Science.gov (United States)

    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

  16. Brain Basics

    Medline Plus

    Full Text Available ... such as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are the basic working unit ... final destination. Chemical signals from other cells guide neurons in forming various brain structures. Neighboring neurons make connections with each other ...

  17. Brain Aneurysm

    Science.gov (United States)

    A brain aneurysm is an abnormal bulge or "ballooning" in the wall of an artery in the brain. They are sometimes called berry aneurysms because they ... often the size of a small berry. Most brain aneurysms produce no symptoms until they become large, ...

  18. The Brain.

    Science.gov (United States)

    Hubel, David H.

    1979-01-01

    This article on the brain is part of an entire issue about neurobiology and the question of how the human brain works. The brain as an intricate tissue composed of cells is discussed based on the current knowledge and understanding of its composition and structure. (SA)

  19. Intracranial Metastasis in a Patient with Hepatocellular Carcinoma and Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Akinobu Tawada

    2014-03-01

    Full Text Available A 76-year-old man was referred to our hospital with visual disturbance, weakness of the left upper and lower limbs, and gait disturbance. He had previously received transarterial chemoembolization for hepatocellular carcinoma (HCC 3 and 10 years ago. When he had received radiofrequency ablation for HCC recurrence 2 years ago, total gastrectomy was also performed for his gastric cancer. Subsequently, sorafenib had been administrated for concomitant lung metastatic tumors. On admission, MRI revealed an intra-axial tumor with perifocal edema. The level of carcinoembryonic antigen, but not alpha-fetoprotein, markedly increased. The tumor was successfully removed by craniotomy and pathological examination revealed that it was composed of adenocarcinoma, which was consistent with the primary gastric cancer. After surgery, his neurological disturbances rapidly resolved. Additional gamma-knife treatment was also performed for another small brain metastasis detected after craniotomy. Subsequently, sorafenib administration was discontinued and S-1 was administered postoperatively. Successful treatment of intracranial metastasis of gastric cancer is important and meaningful, even in patients with multiple primary malignancies.

  20. Stereotactic radiosurgery for multiple brain metastases

    Science.gov (United States)

    Lee, Anna; (Josh Yamada, Yoshiya

    2017-01-01

    Whole brain radiation therapy has been the traditional treatment of choice for patients with multiple brain metastases. Although stereotactic radiosurgery is widely accepted for the management to up to 4 brain metastases, its use is still controversial in cases of 5 or more brain metastases. Randomized trials have suggested that stereotactic radiosurgery alone is appropriate in up to 4 metastases without concomitant whole brain radiation. Level 1 evidence also suggests that withholding whole brain radiation may also reduce the impact of radiation on neurocognitive function and also may even offer a survival advantage. A recent analysis of a large multicentre prospective database has suggested that there are no differences in outcomes such as the likelihood of new metastasis or leptomeningeal disease in cases of 2-10 brain metastases, nor in overall survival. Hence in the era of prolonged survival with stage IV cancer, stereotactic radiosurgery is a reasonable alternative to whole brain radiation in order to minimize the impact of treatment upon quality of life without sacrificing overall survival.

  1. [Factors significant for cerebral circulacion in patients with supratentorial brain tumors].

    Science.gov (United States)

    Sboev, A Yu; Dolgih, V T; Larkin, V I

    2013-01-01

    Using the Doppler ultrasonography method the condition of brain blood circulation of 90 patients with supratentorial brain tumors (gliomas--43, meningiomas--34, metastasis--9) during pre-surgical period was studied. The factors changing brain blood circulation at patients with with supratentorial brain tumors were brain displacement, increase of intracranial pressure, histologic structure and the first symptoms duration of illness. Localization (for an exception of an occipital lobe) and the size of a tumor directly didn't render influence on blood circulation parameters.

  2. Recurrent isolated oculomotor nerve palsy after radiation of a mesencephalic metastasis. Case report and mini-review.

    Directory of Open Access Journals (Sweden)

    Olga eGrabau

    2014-07-01

    Full Text Available Introduction: Recurrent oculomotor nerve palsies are extremely rare clinical conditions. Case report: Here, we report on a unique case of a short-lasting recurrent unilateral incomplete external and complete internal oculomotor nerve palsy. The episodic palsies were probably caused by an ipsilateral mesencephalic metastasis of a breast carcinoma and occurred after successful brain radiation therapy. Discussion: While the pathogenic mechanism remains unclear, the recurrent sudden onset and disappearance of the palsies and their decreasing frequency after antiepileptic treatment suggest the occurrence of epilepsy-like brainstem seizures. A review of case reports of spontaneous reversible oculomotor nerve palsies is presented.

  3. Cellular and molecular processes in ovarian cancer metastasis. A Review in the Theme: Cell and Molecular Processes in Cancer Metastasis.

    Science.gov (United States)

    Yeung, Tsz-Lun; Leung, Cecilia S; Yip, Kay-Pong; Au Yeung, Chi Lam; Wong, Stephen T C; Mok, Samuel C

    2015-10-01

    Ovarian cancer is the most lethal gynecological malignancy. It is usually diagnosed at a late stage, with a 5-yr survival rate of metastasis. Although metastasis plays a crucial role in promoting ovarian tumor progression and decreasing patient survival rates, the underlying mechanisms of ovarian cancer spread have yet to be thoroughly explored. For many years, researchers have believed that ovarian cancer metastasizes via a passive mechanism by which ovarian cancer cells are shed from the primary tumor and carried by the physiological movement of peritoneal fluid to the peritoneum and omentum. However, the recent discovery of hematogenous metastasis of ovarian cancer to the omentum via circulating tumor cells instigated rethinking of the mode of ovarian cancer metastasis and the importance of the "seed-and-soil" hypothesis for ovarian cancer metastasis. In this review we discuss the possible mechanisms by which ovarian cancer cells metastasize from the primary tumor to the omentum, the cross-talk signaling events between ovarian cancer cells and various stromal cells that play crucial roles in ovarian cancer metastasis, and the possible clinical implications of these findings in the management of this deadly, highly metastatic disease.

  4. Classification of glioblastoma and metastasis for neuropathology intraoperative diagnosis: a multi-resolution textural approach to model the background

    Science.gov (United States)

    Ahmad Fauzi, Mohammad Faizal; Gokozan, Hamza Numan; Elder, Brad; Puduvalli, Vinay K.; Otero, Jose J.; Gurcan, Metin N.

    2014-03-01

    Brain cancer surgery requires intraoperative consultation by neuropathology to guide surgical decisions regarding the extent to which the tumor undergoes gross total resection. In this context, the differential diagnosis between glioblastoma and metastatic cancer is challenging as the decision must be made during surgery in a short time-frame (typically 30 minutes). We propose a method to classify glioblastoma versus metastatic cancer based on extracting textural features from the non-nuclei region of cytologic preparations. For glioblastoma, these regions of interest are filled with glial processes between the nuclei, which appear as anisotropic thin linear structures. For metastasis, these regions correspond to a more homogeneous appearance, thus suitable texture features can be extracted from these regions to distinguish between the two tissue types. In our work, we use the Discrete Wavelet Frames to characterize the underlying texture due to its multi-resolution capability in modeling underlying texture. The textural characterization is carried out in primarily the non-nuclei regions after nuclei regions are segmented by adapting our visually meaningful decomposition segmentation algorithm to this problem. k-nearest neighbor method was then used to classify the features into glioblastoma or metastasis cancer class. Experiment on 53 images (29 glioblastomas and 24 metastases) resulted in average accuracy as high as 89.7% for glioblastoma, 87.5% for metastasis and 88.7% overall. Further studies are underway to incorporate nuclei region features into classification on an expanded dataset, as well as expanding the classification to more types of cancers.

  5. The metastasis suppressor RARRES3 as an endogenous inhibitor of the immunoproteasome expression in breast cancer cells

    Science.gov (United States)

    Anderson, Alison M.; Kalimutho, Murugan; Harten, Sarah; Nanayakkara, Devathri M.; Khanna, Kum Kum; Ragan, Mark A.

    2017-01-01

    In breast cancer metastasis, the dynamic continuum involving pro- and anti-inflammatory regulators can become compromised. Over 600 genes have been implicated in metastasis to bone, lung or brain but how these genes might contribute to perturbation of immune function is poorly understood. To gain insight, we adopted a gene co-expression network approach that draws on the functional parallels between naturally occurring bone marrow-derived mesenchymal stem cells (BM-MSCs) and cancer stem cells (CSCs). Our network analyses indicate a key role for metastasis suppressor RARRES3, including potential to regulate the immunoproteasome (IP), a specialized proteasome induced under inflammatory conditions. Knockdown of RARRES3 in near-normal mammary epithelial and breast cancer cell lines increases overall transcript and protein levels of the IP subunits, but not of their constitutively expressed counterparts. RARRES3 mRNA expression is controlled by interferon regulatory factor IRF1, an inducer of the IP, and is sensitive to depletion of the retinoid-related receptor RORA that regulates various physiological processes including immunity through modulation of gene expression. Collectively, these findings identify a novel regulatory role for RARRES3 as an endogenous inhibitor of IP expression, and contribute to our evolving understanding of potential pathways underlying breast cancer driven immune modulation.

  6. Targeting type Iγ phosphatidylinositol phosphate kinase inhibits breast cancer metastasis.

    Science.gov (United States)

    Chen, C; Wang, X; Xiong, X; Liu, Q; Huang, Y; Xu, Q; Hu, J; Ge, G; Ling, K

    2015-08-27

    Most deaths from breast cancer are caused by metastasis, a complex behavior of cancer cells involving migration, invasion, survival and microenvironment manipulation. Type Iγ phosphatidylinositol phosphate kinase (PIPKIγ) regulates focal adhesion assembly and its phosphorylation at Y639 is critical for cell migration induced by EGF. However, the role of this lipid kinase in tumor metastasis remains unclear. Here we report that PIPKIγ is vital for breast cancer metastasis. Y639 of PIPKIγ can be phosphorylated by stimulation of EGF and hepatocyte growth factor (HGF), two promoting factors for breast cancer progression. Histological analysis revealed elevated Y639 phosphorylation of PIPKIγ in invasive ductal carcinoma lesions and suggested a positive correlation with tumor grade. Orthotopically transplanted PIPKIγ-depleted breast cancer cells showed substantially reduced growth and metastasis, as well as suppressed expression of multiple genes related to cell migration and microenvironment manipulation. Re-expression of wild-type PIPKIγ in PIPKIγ-depleted cells restored tumor growth and metastasis, reinforcing the importance of PIPKIγ in breast cancer progression. Y639-to-F or a kinase-dead mutant of PIPKIγ could not recover the diminished metastasis in PIPKIγ-depleted cancer cells, suggesting that Y639 phosphorylation and lipid kinase activity are both required for development of metastasis. Further analysis with in vitro assays indicated that depleting PIPKIγ inhibited cell proliferation, MMP9 secretion and cell migration and invasion, lending molecular mechanisms for the eliminated cancer progression. These results suggest that PIPKIγ, downstream of EGF and/or HGF receptor, participates in breast cancer progression from multiple aspects and deserves further studies to explore its potential as a therapeutic target.

  7. Therapy of leptomeningeal metastasis in solid tumors.

    Science.gov (United States)

    Mack, F; Baumert, B G; Schäfer, N; Hattingen, E; Scheffler, B; Herrlinger, U; Glas, M

    2016-02-01

    Leptomeningeal metastasis (LM), i.e. the seeding of tumor cells to the cerebrospinal fluid (CSF) and the leptomeninges, is a devastating and mostly late-stage complication of various solid tumors. Clinical signs and symptoms may include cranial nerve palsies, radicular symptoms, signs of increased intracranial pressure such as headache, nausea and vomiting, and cognitive dysfunction. In cases of suspected LM, the highest diagnostic sensitivity is provided by the combination of CSF cytology and contrast-enhanced MRI (cranial as well as complete spine). The therapeutic spectrum includes radiotherapy of the clinically involved region as well as systemic and intrathecal chemotherapy. The choice of treatment modalities depends on the type of LM (non-adherent tumor cells in the CSF vs. nodular contrast-enhancing tumor growth), additional systemic involvement (uncontrolled vs. controlled systemic disease) and additional involvement of the CNS parenchyma (LM as the only CNS involvement vs. LM+parenchymal CNS metastases). Larger contrast-enhancing nodular LM or symptomatic lesions of the spine may be treated with radiotherapy. In case of uncontrolled systemic disease, the treatment regimen should include systemic chemotherapy. The choice of systemic treatment should take into account the histology of the primary tumor. Intrathecal chemotherapy is most important in cases of LM of the non-adherent type. There are three substances for routine use for intrathecal chemotherapy: methotrexate, cytarabine, and thiotepa. Liposomal cytarabine shows advantages in terms of longer injection intervals, a sufficient distribution in the entire subarachnoid space after lumbar administration and improved quality-of-life. The role of new agents (e.g. rituximab and trastuzumab) for intrathecal therapy is still unclear.

  8. ZBTB7A suppresses melanoma metastasis by transcriptionally repressing MCAM

    Science.gov (United States)

    Liu, Xue-Song; Genet, Matthew D; Haines, Jenna E; Mehanna, Elie K; Wu, Shaowei; Chen, Hung-I Harry; Chen, Yidong; Qureshi, Abrar A; Han, Jiali; Chen, Xiang; Fisher, David E; Pandolfi, Pier Paolo; Yuan, Zhi-Min

    2015-01-01

    The excessive metastatic propensity of melanoma makes it the most deadly form of skin cancer, yet the underlying mechanism of metastasis remains elusive. Here, mining of cancer genome datasets discovered a frequent loss of chromosome 19p13.3 and associated down-regulation of the zinc finger transcription factor ZBTB7A in metastatic melanoma. Functional assessment of ZBTB7A-regulated genes identified MCAM, which encodes an adhesion protein key to melanoma metastasis. Using an integrated approach, it is demonstrated that ZBTB7A directly binds to the promoter and transcriptionally represses the expression of MCAM, establishing ZBTB7A as a bona fide transcriptional repressor of MCAM. Consistently, down-regulation of ZBTB7A results in marked upregulation of MCAM and enhanced melanoma cell invasion and metastasis. An inverse correlation of ZBTB7A and MCAM expression in association with melanoma metastasis is further validated with data from analysis of human melanoma specimens. Implications Together these results uncover a previously unrecognized role of ZBTB7A in negative regulation of melanoma metastasis and have important clinical implications. PMID:25995384

  9. Ventriculoperitoneal shunt for hydrocephalus caused by central nervous system metastasis.

    Science.gov (United States)

    Lee, Seung Hoon; Kong, Doo Sik; Seol, Ho Joon; Nam, Do-Hyun; Lee, Jung-Il

    2011-09-01

    The development of better diagnostic tools and therapeutic modalities has increased the incidence of central nervous system (CNS) metastasis in malignant tumor patients. Hydrocephalus can result from CNS metastasis and frustrate cancer treatment. The authors sought to investigate the outcomes and the roles of ventriculoperitoneal shunts (VPS) in patients with CNS metastasis. The medical records of 50 consecutive patients who underwent VPS for hydrocephalus related to CNS metastasis were analyzed retrospectively. Data included features of primary malignancies, CNS involvement, clinical course and surgical outcome. Median patient age was 55.0 years (range 25-77), and 30 female and 20 male patients were included in the study. At the time of VPS, 10 patients had parenchymal metastases only and 40 patients had leptomeningeal seeding (LMS). Symptom improvement was observed postoperatively in 40 patients (80%), mean Karnofsky performance status (KPS) scale change was from 37.8 to 46.0, and median survival from VPS was 3.0 months (2 days to 54 months). A ventricular opening pressure of >30 cmH(2)O (HR 6.44, 95% CI 1.26-32.9, P = 0.02) and further cancer treatment after VPS (HR 0.17, 95% CI 0.07-0.42, P Hydrocephalus in CNS metastasis requiring VPS is commonly associated with LMS. VPS is an effective palliative measure and an adequate cancer treatment after VPS may provide the best means of improving survival.

  10. Gastric metastasis from primary lung adenocarcinomamimicking primary gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Min Ji Kim; Ji Hyung Hong; Eun Su Park; Jae Ho Byun

    2015-01-01

    Gastric metastases from lung adenocarcinoma arerare. Because gastric metastasis grossly resemblesadvanced gastric cancer, it is difficult to diagnose gastricmetastasis especially when the histology of the primarylung cancer is adenocarcinoma. We describe a case ofgastric metastasis from primary lung adenocarcinomamimicking Borrmann type Ⅳ primary gastric cancer.A 68-year-old man with known lung adenocarcinomawith multiple bone metastases had been experiencingprogressive epigastric pain and dyspepsia over one year.Esophagogastroduodenoscopy revealed linitis plasticalikelesions in the fundus of the stomach. Pathologicexamination revealed a moderately differentiatedadenocarcinoma with submucosal infiltration. Positiveimmunohistochemical staining for thyroid transcriptionfactor-1 (TTF-1) and napsin A (Nap-A) confirmed thatthe metastasis was pulmonary in origin. The patienthad been treated with palliative chemotherapy for thelung cancer and had lived for over fifteen months afterthe diagnosis of gastric metastasis. Clinicians should beaware of the possibility of gastric metastasis in patientswith primary lung adenocarcinoma, and additionalimmunohistochemical staining for Nap-A as well as TTF-1may help in differentiating its origin.

  11. Epithelioid sarcoma with muscle metastasis detected by positron emission tomography

    Directory of Open Access Journals (Sweden)

    Oya Masafumi

    2008-08-01

    Full Text Available Abstract Background Epithelioid sarcoma is an uncommon high-grade sarcoma, mostly involving the extremities. Case presentation A 33-year-old man was referred to our institute with a diagnosis of Volkmann's contracture with the symptom of flexion contracture of the fingers associated with swelling in his left forearm. Magnetic resonance imaging (MRI showed abnormal signal intensity, comprising iso-signal intensity on T1- and high-signal intensity on T2-weighted images surrounding the flexor tendons in the forearm. Diagnosis of epithelioid sarcoma was made by open biopsy, and amputation at the upper arm was then undertaken. [18F]-2-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET detected multiple lesions with an increased uptake in the right neck, the bilateral upper arms and the right thigh, as well as in the left axillary lymph nodes, with maximum standardized uptake value (SUVmax ranging from 2.0 to 5.5 g/ml. Magnetic resonance imaging confirmed that there was a lesion within the right thigh muscle which was suggestive of metastasis, even though the lesion was occult clinically. Conclusion Increased uptake on FDG-PET might be representative of epithelioid sarcoma, and for this reason FDG-PET may be useful for detecting metastasis. Muscle metastasis is not well documented in epithelioid sarcoma. Accordingly, the frequency of muscle metastasis, including occult metastasis, needs to be further analyzed.

  12. A Case of Conjunctival Melanoma Presenting with Breast Metastasis

    Directory of Open Access Journals (Sweden)

    Mustafa Canhoroz

    2014-03-01

    Full Text Available Most breast masses arise from the breast. Metastasis to the breast is fairly uncommon, but can occur in breast skin and parenchyma. In particular, leukemia and lung cancers, and MM may metastasize to the breast. Breast metastasis might be the first symptom or may occur during the course of other malignancies. Our case presented with a fixed mass in the upper-medial quadrant of her left breast during regular follow-up visits. The mean time to breast metastasis in patients with MM is 62 months (13-178. In our case this time was 48 months. In a case series with 7 patients hematological malignancies (Hodgkin lymphoma, non-Hodgkin lymphoma, and leukemia were the leading cause of breast metastasis, whereas in only 1 case the cause was MM. In another case series of 15 MM patients with metastasis to the breast, the primary tumor was frequently localized to the upper extremities and trunk. In a report of 250 conjunctival MM cases the mortality rate was significantly higher in patients with tumors >4 mm in vertical thickness. In another 45-case MM series tumors with a diameter >10 mm were associated with higher mortality rates. In our case the thickness of the tumor was 5 mm. In conclusion, histopathological evaluation should be mandatory in patients with known primary malignancies in order to differentiate new primary tumors, metastases, and benign tumors.

  13. Simultaneous laparoscopic excision for rectal carcinoma and synchronous hepatic metastasis

    Institute of Scientific and Technical Information of China (English)

    CHEN Kai-yun; XIANG Guo-an; WANG Han-ning; XIAO Fang-lian

    2011-01-01

    Background Rectal carcinoma patients are often accompanied by hepatic metastasis. The aim of this study was to evaluate the therapeutic efficacy of simultaneous laparoscopic excision for rectal carcinoma with synchronous hepatic metastasis.Methods A total of 41 patients with rectal carcinoma and synchronous hepatic metastasis detected by CT scan were included in this study. Among them, 23 patients underwent laparoscopic surgery and 18 patients underwent traditional open surgery to simultaneously remove the rectal tumor and hepatic metastasis lesions. All patients received postoperative adjuvant chemotherapy. All the patients were followed up from 36 to 72 months (mean 45.3 months).Results All the operations were performed successfully and no patient was turned to open surgery in laparoscopic group. The mean blood loss, the mean postoperative hospital stay, the mean blood transfusion and the mean intestinal functional recovery time showed a significant difference between the two groups (P<0.05). The 1-, 3- and 5-year survival rates were 82.6%, 43.5% and 8.6% in the laparoscopic group, without significant difference compared with the open group (77.8%, 38.9% and 0) (P>0.05).Conclusions Simultaneous laparoscopic excision for rectal carcinoma and synchronous hepatic metastasis is safe and effective with similar survival achieved by the traditional open abdominal surgery.

  14. Incidence of bone metastasis in carcinoma buccal mucosa

    Directory of Open Access Journals (Sweden)

    Virendra Bhandari

    2016-01-01

    Full Text Available Introduction: Head and neck cancer is a leading health problem in India due to the habit of chewing tobacco and bad oral and dental hygiene. Carcinoma buccal mucosa is more common and is 2.5% of all malignancies at our center. Most of the patients present in stage III and IV and the survival in these cases is not very good. Bone metastasis in advanced cases of carcinoma buccal mucosa is rarely reported in the world literature. Materials and Methods: We present here cases developing bone metastasis in carcinoma buccal mucosa in last 5 years. These patients were young with loco-regionally advanced disease where bone metastasis developed within 1-year of definitive treatment. Results: The flat bones and vertebrae were mainly involved and the survival was also short after diagnosis of metastasis despite the treatment with local Radiotherapy and chemotherapy. Conclusion: The exact cause of metastasis cannot be proved, but the probability of subclinical seedling of malignant cells before the eradication of the primary tumor should be considered along with advanced local and nodal disease with high grade of tumor.

  15. Carcinoma-associated fibroblasts provide operational flexibility in metastasis.

    Science.gov (United States)

    De Wever, Olivier; Van Bockstal, Mieke; Mareel, Marc; Hendrix, An; Bracke, Marc

    2014-04-01

    Malignant cancer cells do not act as lone wolves to achieve metastasis, as they exist within a complex ecosystem consisting of an extracellular matrix scaffold populated by carcinoma-associated fibroblasts (CAFs), endothelial cells and immune cells. We recognize local (primary tumor) and distant ecosystems (metastasis). CAFs, also termed myofibroblasts, may have other functions in the primary tumor versus the metastasis. Cellular origin and tumor heterogeneity lead to the expression of specific markers. The molecular characteristics of a CAF remain in evolution since CAFs show operational flexibility. CAFs respond dynamically to a cancer cell's fluctuating demands by shifting profitable signals necessary in metastasis. Local, tissue-resident fibroblasts and mesenchymal stem cells (MSCs) coming from reservoir sites such as bone marrow and adipose tissue are the main progenitor cells of CAFs. CAFs may induce awakening from metastatic dormancy, a major cause of cancer-specific death. Cancer management protocols influence CAF precursor recruitment and CAF activation. Since CAF signatures represent early changes in metastasis, including formation of pre-metastatic niches, we discuss whether liquid biopsies, including exosomes, may detect and monitor CAF reactions allowing optimized prognosis of cancer patients.

  16. Cancer-associated fibroblast promote transmigration through endothelial brain cells in three-dimensional in vitro models.

    Science.gov (United States)

    Choi, Yoon Pyo; Lee, Joo Hyun; Gao, Ming-Qing; Kim, Baek Gil; Kang, Suki; Kim, Se Hoon; Cho, Nam Hoon

    2014-11-01

    Brain metastases are associated with high morbidity as well as with poor prognosis and survival in breast cancer patients. Despite its clinical importance, metastasis of breast cancer cells through the blood-brain barrier (BBB) is poorly understood. The objective of our study was to investigate whether cancer-associated fibroblasts (CAFs) play crucial roles in breast cancer brain metastasis. Using a cell adhesion assays, in vitro BBB permeability and transmigration assays and soft agar colony formation assays, we investigated the physical roles of CAFs in breast cancer brain metastasis. We also performed immunofluorescence, flow cytometric analysis, Droplet Digital PCR and Simon™ Simple Western System to confirm changes in expression levels. We established two novel three-dimensional (3D) culture systems using a perpendicular slide chamber and applying 3D embedded culture method to reflect brain metastasis conditions. With a newly developed device, CAFs was proven to promote cell adhesion to human brain microvascular endothelial cells, in vitro BBB permeability and transmigration and colony formation of breast cancer cells. Furthermore, CAFs enhanced the invasive migration of breast cancer cells in two kinds of 3D cultures. These 3D models also reliably recapitulate the initial steps of BBB transmigration, micro-metastasis and colonization. Expression of integrin α5β1 and αvβ3, c-MET and α2,6-siayltransferase was increased in breast cancer cells that migrated through the BBB. In conclusion, based on our in vitro BBB and co-culture models, our data suggest that CAFs may play a role in breast cancer brain metastasis.

  17. Bone sialoprotein and osteopontin in bone metastasis of osteotropic cancers.

    Science.gov (United States)

    Kruger, Thomas E; Miller, Andrew H; Godwin, Andrew K; Wang, Jinxi

    2014-02-01

    The mechanisms underlying malignant cell metastasis to secondary sites such as bone are complex and no doubt multifactorial. Members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) family, particularly bone sialoprotein (BSP) and osteopontin (OPN), exhibit multiple activities known to promote malignant cell proliferation, detachment, invasion, and metastasis of several osteotropic cancers. The expression level of BSP and OPN is elevated in a variety of human cancers, particularly those that metastasize preferentially to the skeleton. Recent studies suggest that the "osteomimicry" of malignant cells is not only conferred by transmembrane receptors bound by BSP and OPN, but includes the "switch" in gene expression repertoire typically expressed in cells of skeletal lineage. Understanding the role of BSP and OPN in tumor progression, altered pathophysiology of bone microenvironment, and tumor metastasis to bone will likely result in development of better diagnostic approaches and therapeutic regimens for osteotropic malignant diseases.

  18. Neutrophils: important contributors to tumor progression and metastasis.

    Science.gov (United States)

    Swierczak, Agnieszka; Mouchemore, Kellie A; Hamilton, John A; Anderson, Robin L

    2015-12-01

    The presence of neutrophils in tumors has traditionally been considered to be indicative of a failed immune response against cancers. However, there is now evidence showing that neutrophils can promote tumor growth, and increasingly, the data support an active role for neutrophils in tumor progression to distant metastasis. Neutrophils have been implicated in promoting metastasis in cancer patients, where neutrophil numbers and neutrophil-related factors and functions have been associated with progressive disease. Nevertheless, the role of neutrophils in tumors, both at the primary and secondary sites, remains controversial, with some studies reporting their anti-tumor functions. This review will focus on the data demonstrating a role for neutrophils in both tumor growth and metastasis and will attempt to clarify the discrepancies in the literature.

  19. Metastasis at the colostomy site: a rare case report.

    Science.gov (United States)

    Kuo, Yi-Hung; Chin, Chih-Chien; Lee, Kam-Fai

    2012-08-01

    Metastasis at the colostomy site is rare. Most reported patients with such metastases undergo abdominoperineal resection and this kind of metastases happened after a longer period post-cancer surgery. In our patient, because it happened during a short interval between rectal cancer surgery and stoma closure, colostomy site metastasis probably occurred owing to ablative cancer cell reflux and seeding from the obstruction during decompressive colostomy rather than local, lymphatic or haematogenous spread. Meticulous histologic analyses to rule out undetected, concomitant polyps and metachronous cancer are very important for patients with obstructive colorectal cancer who undergo decompressive colostomy. The potential risk of colostomy site metastasis during staged surgery for obstructive colorectal cancer remains uncertain; however, the result from this case report raises the question of such a risk for further studies in a greater number of patients.

  20. Epithelial-mesenchymal transition in breast cancer progression and metastasis

    Institute of Scientific and Technical Information of China (English)

    Yifan Wang; Binhua P. Zhou

    2011-01-01

    Breast cancer is the most common cancer in women,and approximately 90% of breast cancer deaths are caused by local invasion and distant metastasis of tumor cells.Epithelial-mesenchymal transition (EMT) is a vital process for large-scale cell movement during morphogenesis at the time of embryonic development.Tumor cells usurp this developmental program to execute the multi-step process of tumorigenesis and metastasis.Several transcription factors and signals are involved in these events.In this review,we summarize recent advances in breast cancer researches that have provided new insights in the molecular mechanisms underlying EMT regulation during breast cancer progression and metastasis.We especially focus on the molecular pathways that control EMT.

  1. Anal metastasis from recurrent breast lobular carcinoma: A case report

    Institute of Scientific and Technical Information of China (English)

    Maria Puglisi; Emanuela Varaldo; Michela Assalino; Gianluca Ansaldo; Giancarlo Torre; Giacomo Borgonovo

    2009-01-01

    We report a case of isolated gastrointestinal metastasis from breast lobular carcinoma, which mimicked primary anal cancer. In July 2000, an 88-year-old woman presented with infiltrating lobular cancer (pT1/G2/N2). The patient received postoperative radiotherapy and hormonal therapy. Four years later,she presented with an anal polypoid lesion. The mass was removed for biopsy. Immunohistochemical staining suggested a breast origin. Radiotherapy was chosen for this patient, which resulted in complete regression of the lesion. The patient died 3 years after the first manifestation of gastrointestinal metastasis.According to the current literature, we consider the immunohistochemistry features that are essential to support the suspicion of gastrointestinal breast metastasis, and since we consider the gastrointestinal involvement as a sign of systemic disease, the therapy should be less aggressive and systemic.

  2. Role of STAT3 in Cancer Metastasis and Translational Advances

    Directory of Open Access Journals (Sweden)

    Mohammad Zahid Kamran

    2013-01-01

    Full Text Available Signal transducer and activator of transcription 3 (STAT3 is a latent cytoplasmic transcription factor, originally discovered as a transducer of signal from cell surface receptors to the nucleus. It is activated by tyrosine phosphorylation at position 705 leading to its dimerization, nuclear translocation, DNA binding, and activation of gene transcription. Under normal physiological conditions, STAT3 activation is tightly regulated. However, compelling evidence suggests that STAT3 is constitutively activated in many cancers and plays a pivotal role in tumor growth and metastasis. It regulates cellular proliferation, invasion, migration, and angiogenesis that are critical for cancer metastasis. In this paper, we first describe the mechanism of STAT3 regulation followed by how STAT3 is involved in cancer metastasis, then we summarize the various small molecule inhibitors that inhibit STAT3 signaling.

  3. Role of STAT3 in Cancer Metastasis and Translational Advances

    Science.gov (United States)

    Patil, Prachi; Gude, Rajiv P.

    2013-01-01

    Signal transducer and activator of transcription 3 (STAT3) is a latent cytoplasmic transcription factor, originally discovered as a transducer of signal from cell surface receptors to the nucleus. It is activated by tyrosine phosphorylation at position 705 leading to its dimerization, nuclear translocation, DNA binding, and activation of gene transcription. Under normal physiological conditions, STAT3 activation is tightly regulated. However, compelling evidence suggests that STAT3 is constitutively activated in many cancers and plays a pivotal role in tumor growth and metastasis. It regulates cellular proliferation, invasion, migration, and angiogenesis that are critical for cancer metastasis. In this paper, we first describe the mechanism of STAT3 regulation followed by how STAT3 is involved in cancer metastasis, then we summarize the various small molecule inhibitors that inhibit STAT3 signaling. PMID:24199193

  4. Active Roles of Tumor Stroma in Breast Cancer Metastasis

    Directory of Open Access Journals (Sweden)

    Zahraa I. Khamis

    2012-01-01

    Full Text Available Metastasis is the major cause of death for breast cancer patients. Tumors are heterogenous cellular entities composed of cancer cells and cells of the microenvironment in which they reside. A reciprocal dynamic interaction occurs between the tumor cells and their surrounding stroma under physiological and pathological conditions. This tumor-host communication interface mediates the escape of tumor cells at the primary site, survival of circulating cancer cells in the vasculature, and growth of metastatic cancer at secondary site. Each step of the metastatic process is accompanied by recruitment of stromal cells from the microenvironment and production of unique array of growth factors and chemokines. Stromal microenvironment may play active roles in breast cancer metastasis. Elucidating the types of cells recruited and signal pathways involved in the crosstalk between tumor cells and stromal cells will help identify novel strategies for cotargeting cancer cells and tumor stromal cells to suppress metastasis and improve patient outcome.

  5. The pre-metastatic niche: is metastasis random?

    Science.gov (United States)

    Cox, Thomas R; Gartland, Alison; Erler, Janine T

    2012-01-01

    The metastasis of solid tumours is a vastly complex, dynamic and systemic process involving both primary tumour cells as well as a wide array of stromal and vascular cells. The recruitment and activation of host cells by tumours at both the primary and metastatic sites is crucial for successful metastatic dissemination highlighting the systemic nature of disease progression. The appropriation of distant metastatic sites by primary tumours and the generation of so-called pre-metastatic niches have gained much interest in the last decade complementing the century old 'seed and soil' hypothesis. The idea that tumours are capable of pre-defining future sites of metastasis is both exciting and terrifying as we try to understand the dynamic networks associated with solid tumour metastasis. Exactly how a tumour cell can alter the distant metastatic microenvironment is of great importance and will unlock novel strategies for successfully targeting these processes.

  6. The pre-metastatic niche: is metastasis random?

    Science.gov (United States)

    Cox, Thomas R; Gartland, Alison; Erler, Janine T

    2012-01-01

    The metastasis of solid tumours is a vastly complex, dynamic and systemic process involving both primary tumour cells as well as a wide array of stromal and vascular cells. The recruitment and activation of host cells by tumours at both the primary and metastatic sites is crucial for successful metastatic dissemination highlighting the systemic nature of disease progression. The appropriation of distant metastatic sites by primary tumours and the generation of so-called pre-metastatic niches have gained much interest in the last decade complementing the century old 'seed and soil' hypothesis. The idea that tumours are capable of pre-defining future sites of metastasis is both exciting and terrifying as we try to understand the dynamic networks associated with solid tumour metastasis. Exactly how a tumour cell can alter the distant metastatic microenvironment is of great importance and will unlock novel strategies for successfully targeting these processes. PMID:27127624

  7. Symptomatic spinal cord metastasis from cerebral oligodendroglioma.

    Science.gov (United States)

    Elefante, A; Peca, C; Del Basso De Caro, M L; Russo, C; Formicola, F; Mariniello, G; Brunetti, A; Maiuri, F

    2012-06-01

    Spinal subarachnoid spread is not uncommon in brain oligodendrogliomas; on the other hand, symptomatic involvement of the spinal cord and cauda is very rare, with only 16 reported cases. We report the case of a 41-year-old man who underwent resection of a low-grade frontal oligodendroglioma 4 years previously. He was again observed because of bilateral sciatic pain followed by left leg paresis. A spine MRI showed an intramedullary T12-L1 tumor with root enhancement. At operation, an intramedullary anaplastic oligodendroglioma with left exophytic component was found and partially resected. Two weeks later, a large left frontoparietal anaplastic oligodendroglioma was diagnosed and completely resected. The patient was neurologically stable for 8 months and died 1 year after the spinal surgery because of diffuse brain and spinal leptomeningeal spread. The review of the reported cases shows that spinal symptomatic metastases can occur in both low-grade and anaplastic oligodendrogliomas, even many years after surgery of the primary tumor; however, they exceptionally occur as first clinical manifestation or as anaplastic progression. The spinal seeding represents a negative event leading to a short survival.

  8. A cell-based fascin bioassay identifies compounds with potential anti-metastasis or cognition-enhancing functions

    Directory of Open Access Journals (Sweden)

    Robert Kraft

    2013-01-01

    The actin-bundling protein fascin is a key mediator of tumor invasion and metastasis and its activity drives filopodia formation, cell-shape changes and cell migration. Small-molecule inhibitors of fascin block tumor metastasis in animal models. Conversely, fascin deficiency might underlie the pathogenesis of some developmental brain disorders. To identify fascin-pathway modulators we devised a cell-based assay for fascin function and used it in a bidirectional drug screen. The screen utilized cultured fascin-deficient mutant Drosophila neurons, whose neurite arbors manifest the ‘filagree’ phenotype. Taking a repurposing approach, we screened a library of 1040 known compounds, many of them FDA-approved drugs, for filagree modifiers. Based on scaffold distribution, molecular-fingerprint similarities, and chemical-space distribution, this library has high structural diversity, supporting its utility as a screening tool. We identified 34 fascin-pathway blockers (with potential anti-metastasis activity and 48 fascin-pathway enhancers (with potential cognitive-enhancer activity. The structural diversity of the active compounds suggests multiple molecular targets. Comparisons of active and inactive compounds provided preliminary structure-activity relationship information. The screen also revealed diverse neurotoxic effects of other drugs, notably the ‘beads-on-a-string’ defect, which is induced solely by statins. Statin-induced neurotoxicity is enhanced by fascin deficiency. In summary, we provide evidence that primary neuron culture using a genetic model organism can be valuable for early-stage drug discovery and developmental neurotoxicity testing. Furthermore, we propose that, given an appropriate assay for target-pathway function, bidirectional screening for brain-development disorders and invasive cancers represents an efficient, multipurpose strategy for drug discovery.

  9. Calcium-activated potassium channels mediated blood-brain tumor barrier opening in a rat metastatic brain tumor model

    Directory of Open Access Journals (Sweden)

    Ong John M

    2007-03-01

    Full Text Available Abstract Background The blood-brain tumor barrier (BTB impedes the delivery of therapeutic agents to brain tumors. While adequate delivery of drugs occurs in systemic tumors, the BTB limits delivery of anti-tumor agents into brain metastases. Results In this study, we examined the function and regulation of calcium-activated potassium (KCa channels in a rat metastatic brain tumor model. We showed that intravenous infusion of NS1619, a KCa channel agonist, and bradykinin selectively enhanced BTB permeability in brain tumors, but not in normal brain. Iberiotoxin, a KCa channel antagonist, significantly attenuated NS1619-induced BTB permeability increase. We found KCa channels and bradykinin type 2 receptors (B2R expressed in cultured human metastatic brain tumor cells (CRL-5904, non-small cell lung cancer, metastasized to brain, human brain microvessel endothelial cells (HBMEC and human lung cancer brain metastasis tissues. Potentiometric assays demonstrated the activity of KCa channels in metastatic brain tumor cells and HBMEC. Furthermore, we detected higher expression of KCa channels in the metastatic brain tumor tissue and tumor capillary endothelia as compared to normal brain tissue. Co-culture of metastatic brain tumor cells and brain microvessel endothelial cells showed an upregulation of KCa channels, which may contribute to the overexpression of KCa channels in tumor microvessels and selectivity of BTB opening. Conclusion These findings suggest that KCa channels in metastatic brain tumors may serve as an effective target for biochemical modulation of BTB permeability to enhance selective delivery of chemotherapeutic drugs to metastatic brain tumors.

  10. Phase transitions in tumor growth: III vascular and metastasis behavior

    Science.gov (United States)

    Llanos-Pérez, J. A.; Betancourt-Mar, J. A.; Cocho, G.; Mansilla, R.; Nieto-Villar, José Manuel

    2016-11-01

    We propose a mechanism for avascular, vascular and metastasis tumor growth based on a chemical network model. Vascular growth and metastasis, appear as a hard phase transition type, as "first order", through a supercritical Andronov-Hopf bifurcation, emergence of limit cycle and then through a cascade of bifurcations type saddle-foci Shilnikov's bifurcation. Finally, the thermodynamics framework developed shows that the entropy production rate, as a Lyapunov function, indicates the directional character and stability of the dynamical behavior of tumor growth according to this model.

  11. Intracortical bone metastasis mimicking intracortical osteoid osteoma: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Yu Ri; Kim, Jee Young [St. Vincent' s Hospital, The Catholic University of Korea, Suwon (Korea, Republic of)

    2007-08-15

    Cortical metastasis usually occurs in the diaphysis of the long bones with the appearance of a cookie-bite pattern; this is associated with cortical destruction extending into the soft tissue as well as into the medullary cavity, or there can be a periosteal reaction. We report here on a 66-year-old woman who was diagnosed with intracortical metastasis in the proximal metaphysis of the right femur as an initial metastatic focus from primary lung cancer. CT detected an intracortical osteolytic lesion without cortical destruction or thickening. The MR images showed extensive peritumoral edema in the surrounding soft tissue and adjacent bone marrow edema, and this all mimicked osteoid osteoma.

  12. Malar Bone Metastasis Revealing a Papillary Thyroid Carcinoma

    Directory of Open Access Journals (Sweden)

    Ihsen Slim

    2012-01-01

    Full Text Available Papillary thyroid carcinoma is the most common form of differentiated thyroid carcinoma. It is generally confined to the neck with or without spread to regional lymph nodes. Metastatic thyroid carcinomas are uncommon and mainly include lung and bone. Metastases involving oral and maxillofacial region are extremely rare. We described a case of malar metastasis revealing a follicular variant of papillary thyroid carcinoma, presenting with pain and swelling of the left cheek in a 67-years-old female patient with an unspecified histological left lobo-isthmectomy medical history. To our knowledge, this is the first recorded instance of a malar metastasis from a follicular variant of papillary thyroid carcinoma.

  13. Ureteral Metastasis Secondary to Prostate Cancer: A Case Report

    Directory of Open Access Journals (Sweden)

    I. Morales

    2016-03-01

    Full Text Available Prostate cancer is very frequent, but secondary ureteral metastasis are extremely rare. We present a 55 year old man with a 2 month history of right flank pain and lower urinary tract symptoms. Prostatic specific antigen of 11.3 ng/mL. Computed tomography showed right hydroureteronephrosis, a developing urinoma and right iliac adenopathies. He underwent right ureteronephrectomy, iliac lymphadenectomy and prostate biopsy. Pathology revealed prostatic carcinoma infiltrating the ureteral muscularis propria, without mucosal involvement. There are 46 reported cases of prostate cancer with ureteral metastases. Ureteral metastasis are a rare cause of renal colic and need of a high index of suspicion.

  14. Mechanism of Warburg Effect and Its Effect on Tumor Metastasis

    Directory of Open Access Journals (Sweden)

    Huijun WEI

    2015-03-01

    Full Text Available Cancer cells exhibit altered glucose metabolism characterized by a preference for aerobic glycolysis even when the oxygen content is normal, a phenomenon termed “Warburg effect”. However the definite molecular mechanisms of Warburg effect remains unclear, recent works indicated that it might be related to the abnormal activity of the oncogene and tumor suppressor genes, also the change of tumor microenvironment, the abnormal expression of glucose metabolic enzyme and so on. Warburg effect has a relationship with tumor progression and provide suitable conditions for tumor metastasis. This review will summarizes the mechanism of Warburg effect and its effect on tumor metastasis.

  15. A Rare Cause of Testicular Metastasis: Upper Tract Urothelial Carcinoma

    Directory of Open Access Journals (Sweden)

    Alper Nesip Manav

    2014-01-01

    Full Text Available Metastatic testicular cancers are rare. Primary tumor sources are prostate, lung, and gastrointestinal tract for metastatic testicular cancers. Metastasis of urothelial carcinoma (UC to the testis is extremely rare. Two-thirds of upper tract urothelial carcinoma (UTUC is of invasive stage at diagnosis and metastatic sites are the pelvic lymph nodes, liver, lung, and bone. We report a rare case of metastatic UTUC to the testis which has not been reported before, except one case in the literature. Testicular metastasis of UC should be considered in patients with hematuria and testicular swelling.

  16. GP140/CDCPI in the Development of Prostate Cancer Metastasis

    Science.gov (United States)

    2013-09-01

    RM: The pluripotency of hair follicle stem cells. Cell Cycle 2006, 5:232–233 54. Hirst CE, Ng ES, Azzola L, Voss AK, Thomas T, Stanley EG, Elefanty...analyze the role of gp140/CDCP1 in prostate cancer metastasis and to determine whether targeting gp140/CDCP1 could serve as a treatment against...KS, Xin H: Targeting CUB domain-containing protein 1 with a monoclonal antibody inhibits metastasis in a prostate cancer model. Cancer Res 2008, 68

  17. Laparoscopic resection of colon cancer and synchronous liver metastasis.

    Science.gov (United States)

    Geiger, Timothy M; Tebb, Zachary D; Sato, Erika; Miedema, Brent W; Awad, Ziad T

    2006-02-01

    The recommended surgical approach to synchronous colorectal metastasis has not been clarified. Simultaneous open liver and colon resection for synchronous colorectal carcinoma has been shown beneficial when compared to staged resections. A review of the literature has shown the benefits of both laparoscopic colon resection for colorectal cancer and laparoscopic left lateral segmentectomy in liver disease. We present the case of a 60-year-old male with sigmoid colon carcinoma and a synchronous solitary liver metastasis localized to the left lateral segment. Using laparoscopic techniques, we were able to achieve simultaneous resection of the sigmoid colon and left lateral liver segment.

  18. Isolated axillary lymph node metastasis in oesophageal adenocarcinoma.

    Science.gov (United States)

    Toh, Vi Vien; Shirley, Rebecca; Duffy, John; Starley, Ian Francis

    2015-03-01

    Oesophageal adenocarcinoma metastatic to the axilla is a rare occurrence. The authors present a case of a woman who developed an axillary metastasis from a completely excised oesophageal adenocarcinoma with no prior evidence of nodal disease. With aggressive local treatment, including multiple local operations and radiotherapy, she remains alive and disease-free 12 years after her diagnosis following surgical resection of her axillary metastasis with adjuvant radiotherapy. This case report suggests that there are occasions when aggressive local treatment of apparently isolated metastases can result in a cure.

  19. Brain Autopsy

    Science.gov (United States)

    ... why a family should consider arranging for a brain autopsy upon the death of their loved one. To get a definitive ... study of tissue removed from the body after death. Examination of the whole brain is important in understanding FTD because the patterns ...

  20. Brain Basics

    Medline Plus

    Full Text Available ... Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses magnetic fields to take pictures of ... to slow or stop them from progressing. Functional magnetic resonance imaging (fMRI) is another important research tool in understanding ...

  1. Brain Basics

    Medline Plus

    Full Text Available ... and are working to compare that with brain development in people mental disorders. Genes and environmental cues both help to direct ... comparing such children to those with normal brain development may help scientists to pinpoint when and where mental disorders begin and perhaps how to slow or stop ...

  2. Choroidal metastasis from early rectal cancer: Case report and literature review

    Directory of Open Access Journals (Sweden)

    Mitsuyoshi Tei

    2014-01-01

    CONCLUSION: This is the first report of choroidal metastasis from early rectal cancer. We consider it important to enforce systemic chemotherapy in addition to radiotherapy for choroidal metastasis from colorectal cancer.

  3. In vivo magnetic resonance imaging investigating the development of experimental brain metastases due to triple negative breast cancer.

    Science.gov (United States)

    Hamilton, Amanda M; Foster, Paula J

    2017-02-01

    Triple negative breast cancer (TNBC), when associated with poor outcome, is aggressive in nature with a high incidence of brain metastasis and the shortest median overall patient survival after brain metastasis development compared to all other breast cancer subtypes. As therapies that control primary cancer and extracranial metastatic sites improve, the incidence of brain metastases is increasing and the management of patients with breast cancer brain metastases continues to be a significant clinical challenge. Mouse models have been developed to permit in depth evaluation of breast cancer metastasis to the brain. In this study, we compare the efficiency and metastatic potential of two experimental mouse models of TNBC. Longitudinal MRI analysis and end point histology were used to quantify initial cell arrest as well as the number and volume of metastases that developed in mouse brain over time. We showed significant differences in MRI appearance, tumor progression and model efficiency between the syngeneic 4T1-BR5 model and the xenogeneic 231-BR model. Since TNBC does not respond to many standard breast cancer treatments and TNBC brain metastases lack effective targeted therapies, these preclinical TNBC models represent invaluable tools for the assessment of novel systemic therapeutic approaches. Further pursuits of therapeutics designed to bypass the blood tumor barrier and permit access to the brain parenchyma and metastatic cells within the brain will be paramount in the fight to control and treat lethal metastatic cancer.

  4. Brain peroxisomes.

    Science.gov (United States)

    Trompier, D; Vejux, A; Zarrouk, A; Gondcaille, C; Geillon, F; Nury, T; Savary, S; Lizard, G

    2014-03-01

    Peroxisomes are essential organelles in higher eukaryotes as they play a major role in numerous metabolic pathways and redox homeostasis. Some peroxisomal abnormalities, which are often not compatible with life or normal development, were identified in severe demyelinating and neurodegenerative brain diseases. The metabolic roles of peroxisomes, especially in the brain, are described and human brain peroxisomal disorders resulting from a peroxisome biogenesis or a single peroxisomal enzyme defect are listed. The brain abnormalities encountered in these disorders (demyelination, oxidative stress, inflammation, cell death, neuronal migration, differentiation) are described and their pathogenesis are discussed. Finally, the contribution of peroxisomal dysfunctions to the alterations of brain functions during aging and to the development of Alzheimer's disease is considered.

  5. The role of lysyl oxidase in SRC-dependent proliferation and metastasis of colorectal cancer

    DEFF Research Database (Denmark)

    Baker, Ann-Marie; Cox, Thomas Robert; Bird, Demelza;

    2011-01-01

    Emerging evidence implicates lysyl oxidase (LOX), an extracellular matrix-modifying enzyme, in promoting metastasis of solid tumors. We investigated whether LOX plays an important role in the metastasis of colorectal cancer (CRC).......Emerging evidence implicates lysyl oxidase (LOX), an extracellular matrix-modifying enzyme, in promoting metastasis of solid tumors. We investigated whether LOX plays an important role in the metastasis of colorectal cancer (CRC)....

  6. Metachronous Bilateral Isolated Adrenal Metastasis from Rectal Adenocarcinoma: A Case Report

    Science.gov (United States)

    Jabir, H.; Tawfiq, N.; Moukhlissi, M.; Akssim, M.; Guensi, A.; Kadiri, B.; Bouchbika, Z.; Taleb, A.; Benchekroun, N.; Jouhadi, H.; Sahraoui, S.; Zamiati, S.; Benider, A.

    2014-01-01

    We report a case of adrenal metastasis from colorectal cancer in a 54-year-old woman. Nine months after resection for advanced rectal carcinoma, a computed tomography scan revealed bilateral adrenal metastasis. The level of serum carcinoembryonic antigen was normal. A bilateral adrenalectomy was performed after chemotherapy. Histopathological examination showed adenocarcinoma, compatible with metastasis from the rectal cancer. Adrenal metastasis should be considered in the patients' follow-up for colorectal cancer. PMID:24860684

  7. Metachronous bilateral isolated adrenal metastasis from rectal adenocarcinoma: a case report.

    Science.gov (United States)

    Jabir, H; Tawfiq, N; Moukhlissi, M; Akssim, M; Guensi, A; Kadiri, B; Bouchbika, Z; Taleb, A; Benchekroun, N; Jouhadi, H; Sahraoui, S; Zamiati, S; Benider, A

    2014-01-01

    We report a case of adrenal metastasis from colorectal cancer in a 54-year-old woman. Nine months after resection for advanced rectal carcinoma, a computed tomography scan revealed bilateral adrenal metastasis. The level of serum carcinoembryonic antigen was normal. A bilateral adrenalectomy was performed after chemotherapy. Histopathological examination showed adenocarcinoma, compatible with metastasis from the rectal cancer. Adrenal metastasis should be considered in the patients' follow-up for colorectal cancer.

  8. Metastin has potential as a suitable biomarker and novel effective therapy for cancer metastasis (Review)

    OpenAIRE

    SHOJI, SUNAO; TANG, XIAN YANG; SATO, HARUHIRO; Usui, Yukio; UCHIDA, TOYOAKI; Terachi, Toshiro

    2010-01-01

    Cancer metastasis is a leading cause of death in cancer patients and is a multistep process involving complex interactions between tumor and host cells. To metastasize, tumor cells must invade or migrate from the primary tumor and be transported to close or distant secondary sites. A tumor cell should successfully accomplish each step of the pathway or metastasis may not develop. KiSS-1 is a human metastasis suppressor gene that inhibits metastasis of human melanomas and breast carcinomas wit...

  9. Metachronous Bilateral Isolated Adrenal Metastasis from Rectal Adenocarcinoma: A Case Report

    Directory of Open Access Journals (Sweden)

    H. Jabir

    2014-01-01

    Full Text Available We report a case of adrenal metastasis from colorectal cancer in a 54-year-old woman. Nine months after resection for advanced rectal carcinoma, a computed tomography scan revealed bilateral adrenal metastasis. The level of serum carcinoembryonic antigen was normal. A bilateral adrenalectomy was performed after chemotherapy. Histopathological examination showed adenocarcinoma, compatible with metastasis from the rectal cancer. Adrenal metastasis should be considered in the patients’ follow-up for colorectal cancer.

  10. Matrix metalloproteinase 13‐containing exosomes promote nasopharyngeal carcinoma metastasis

    OpenAIRE

    2015-01-01

    Nasopharyngeal cancer (NPC) is an endemic type of head and neck cancer with a high rate of cervical lymph node metastasis. Metastasis is the major cause of death in NPC patients. Increasing evidence indicates that exosomes play a pivotal role in promoting cancer metastasis by enhancing angiogenesis and ECM degradation. Matrix metalloproteinase 13 is an important kind of matrix proteinase that is often overexpressed in various tumors and increases the risk of metastasis. However, little is kno...

  11. A case report of neck, chest and upper limb cutaneous metastasis from synchronous colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    WANG Jian; SHI Yu-qian; WU Zhi-yong

    2009-01-01

    Cutaneous metastasis from colorectal carcinoma is uncommon, occurring in less than 4% of the whole patients.' The most frequently involved are incision scar or abdominal skin,24 while cutaneous metastasis to neck and chest is very rare. We hereby report a case of synchronous, postoperative cutaneous metastasis from colorectal carcinoma to neck, upper limb and chest skin, which were confirmed by biopsy.

  12. Synthesis of RGD-aPEG-lactoside, a Potential Anti-metastasis Glycoconjugate

    Institute of Scientific and Technical Information of China (English)

    Shu Chun LI; Li Min NIU; Hui LI; Zhong Jun LI; Qing LI

    2004-01-01

    The adhesive interaction between tumor cells and host cells or the extra cellular matrix plays a crucial role in metastasis. Due to the anti-metastasis effects of RGD (arginyl-glycyl -aspartic acid) and some oligosaccharides, RGD-aPEG-Lactoside was prepared which will be used on anti-metastasis.

  13. Occipital lymph node metastasis from nasopharyngeal carcinoma:a special case report and literature review

    Institute of Scientific and Technical Information of China (English)

    Jing Yang; Wei-Xiong Xia; Yan-Qun Xiang; Xing Lv; Liang-Ru Ke; Ya-Hui Yu; Xiang Guo

    2016-01-01

    Cervical lymph node metastasis is common in patients with nasopharyngeal carcinoma (NPC), but occipital lymph node metastasis in NPC patients has not yet been reported. In this case report, we describe an NPC patient with occipital lymph node metastasis. The clinical presentation, diagnostic procedure, treatment, and outcome of this case were presented, with a review of the related literature.

  14. File list: His.Bld.10.AllAg.Lymph_node_metastasis [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.10.AllAg.Lymph_node_metastasis hg19 Histone Blood Lymph node metastasis htt...p://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Bld.10.AllAg.Lymph_node_metastasis.bed ...

  15. File list: Oth.Bld.05.AllAg.Lymph_node_metastasis [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.05.AllAg.Lymph_node_metastasis hg19 TFs and others Blood Lymph node metasta...sis http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Bld.05.AllAg.Lymph_node_metastasis.bed ...

  16. File list: Oth.Bld.50.AllAg.Lymph_node_metastasis [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.50.AllAg.Lymph_node_metastasis hg19 TFs and others Blood Lymph node metasta...sis http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Bld.50.AllAg.Lymph_node_metastasis.bed ...

  17. File list: His.Bld.05.AllAg.Lymph_node_metastasis [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.05.AllAg.Lymph_node_metastasis hg19 Histone Blood Lymph node metastasis htt...p://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Bld.05.AllAg.Lymph_node_metastasis.bed ...

  18. File list: Pol.Bld.10.AllAg.Lymph_node_metastasis [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Bld.10.AllAg.Lymph_node_metastasis hg19 RNA polymerase Blood Lymph node metasta...sis http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Bld.10.AllAg.Lymph_node_metastasis.bed ...

  19. File list: Pol.Bld.20.AllAg.Lymph_node_metastasis [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Bld.20.AllAg.Lymph_node_metastasis hg19 RNA polymerase Blood Lymph node metasta...sis http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Bld.20.AllAg.Lymph_node_metastasis.bed ...

  20. File list: DNS.Bld.05.AllAg.Lymph_node_metastasis [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Bld.05.AllAg.Lymph_node_metastasis hg19 DNase-seq Blood Lymph node metastasis h...ttp://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.Bld.05.AllAg.Lymph_node_metastasis.bed ...

  1. File list: DNS.Bld.10.AllAg.Lymph_node_metastasis [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Bld.10.AllAg.Lymph_node_metastasis hg19 DNase-seq Blood Lymph node metastasis h...ttp://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.Bld.10.AllAg.Lymph_node_metastasis.bed ...

  2. File list: Oth.Bld.10.AllAg.Lymph_node_metastasis [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.10.AllAg.Lymph_node_metastasis hg19 TFs and others Blood Lymph node metasta...sis http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Bld.10.AllAg.Lymph_node_metastasis.bed ...

  3. File list: Oth.Bld.20.AllAg.Lymph_node_metastasis [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.20.AllAg.Lymph_node_metastasis hg19 TFs and others Blood Lymph node metasta...sis http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Bld.20.AllAg.Lymph_node_metastasis.bed ...

  4. File list: His.Bld.50.AllAg.Lymph_node_metastasis [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.50.AllAg.Lymph_node_metastasis hg19 Histone Blood Lymph node metastasis htt...p://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Bld.50.AllAg.Lymph_node_metastasis.bed ...

  5. File list: DNS.Bld.50.AllAg.Lymph_node_metastasis [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Bld.50.AllAg.Lymph_node_metastasis hg19 DNase-seq Blood Lymph node metastasis h...ttp://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.Bld.50.AllAg.Lymph_node_metastasis.bed ...

  6. File list: DNS.Bld.20.AllAg.Lymph_node_metastasis [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Bld.20.AllAg.Lymph_node_metastasis hg19 DNase-seq Blood Lymph node metastasis h...ttp://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.Bld.20.AllAg.Lymph_node_metastasis.bed ...

  7. File list: Pol.Bld.05.AllAg.Lymph_node_metastasis [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Bld.05.AllAg.Lymph_node_metastasis hg19 RNA polymerase Blood Lymph node metasta...sis http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Bld.05.AllAg.Lymph_node_metastasis.bed ...

  8. File list: His.Bld.20.AllAg.Lymph_node_metastasis [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.20.AllAg.Lymph_node_metastasis hg19 Histone Blood Lymph node metastasis htt...p://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Bld.20.AllAg.Lymph_node_metastasis.bed ...

  9. 双相型肺母细胞瘤并肋骨转移一例报道%Biphasic pulmonary blastoma with metastasis to adjacent rib: one case report

    Institute of Scientific and Technical Information of China (English)

    Li Tian; Lizhi Liu

    2008-01-01

    @@ Pulmonary blastoma (PB) is a relatively rare intratho-racic neoplasm that is composed of immature malignant epithelial and/or mesenchymal tissues whose features may resemble early embryological lung tissues [1,2]. They have been divided into three subgroups - classic biphasic pulmonary blastoma (BPB), well-differentiated fetal adenocarcinoma (WDFA) and pleuropulmonary blastoma (PPB) [2,3], among which BPB is the most common subtype and its prognosis is fairly poor, especially in case of accompanying local infiltration or distant metastasis. There have been several case reports about BPB with distant metastasis to brain, lung, kidney, even to pancrea. Here we reported a case of biphasic pulmonary blastoma with metastasis to adjacent rib.

  10. MicroRNAs in Brain Metastases: Potential Role as Diagnostics and Therapeutics

    Directory of Open Access Journals (Sweden)

    Samer Alsidawi

    2014-06-01

    Full Text Available Brain metastases remain a daunting adversary that negatively impact patient survival. Metastatic brain tumors affect up to 45% of all cancer patients with systemic cancer and account for ~20% of all cancer-related deaths. A complex network of non-coding RNA molecules, microRNAs (miRNAs, regulate tumor metastasis. The brain micro-environment modulates metastatic tumor growth; however, defining the precise genetic events that promote metastasis in the brain niche represents an important, unresolved problem. Understanding these events will reveal disease-based targets and offer effective strategies to treat brain metastases. Effective therapeutic strategies based upon the biology of brain metastases represent an urgent, unmet need with immediate potential for clinical impact. Studies have demonstrated the ability of miRNAs to distinguish normal from cancerous cells, primary from secondary brain tumors, and correctly categorize metastatic brain tumor tissue of origin based solely on miRNA profiles. Interestingly, manipulation of miRNAs has proven effective in cancer treatment. With the promise of reduced toxicity, increased efficacy and individually directed personalized anti-cancer therapy, using miRNA in the treatment of metastatic brain tumors may prove very useful and improve patient outcome. In this review, we focus on the potential of miRNAs as diagnostic and therapeutic targets for the treatment of metastatic brain lesions.

  11. Evaluation of TAZ expression and its effect on tumor invasion and metastasis in human glioma

    Institute of Scientific and Technical Information of China (English)

    Pei-Dong Li; Xin-Jun Wang; Qiao Shan; Yue-Hui Wu; Zhen Wang

    2014-01-01

    Objective:To evaluate the expression ofTAZ and its role in tumor invasion and metastasis in human glioma.Methods:The expression ofTAZ protein was measured in48 samples of surgically resected human glioma and13 samples of normal brain tissues using immunohistochemistry. TAZ was knocked down by a retrovirus-mediatedTAZ shRNA in a glioma cell line,SNB19. Transwell cell migration and invasion assays were used to determine migration and invasion ofSNB19 cells.Results:The positive expression rate ofTAZ protein in glioma tissues was significantly higher than that in normal brain tissues(79.2%vs.15.4%,P<0.001).Furthermore, clinical analysis suggested that the positive expression rate ofTAZ protein in poorly differentiated tumor tissues was significantly higher as compared with that in well differentiated tissues(96.0%vs.60.9%,P<0.01).TAZ was significantly knocked down byTAZ shRNA(P<0.001), andTAZ knockdown significantly reduced cell migration and invasion(P<0.01, respectively) inSNB19 cells.Conclusions:TAZ protein overexpression is observed in human glioma and its elevated expression is significantly correlated with poor differentiation.TAZ knockdown prominently reduces cell migration and invasion inSNB19 cells, suggesting thatTAZ may play a key role in the initiation and progression of human glioma.

  12. Cognitive Predictors of Reasoning through Treatment Decisions in Patients with Newly Diagnosed Brain Metastases.

    Science.gov (United States)

    Gerstenecker, Adam; Duff, Kevin; Meneses, Karen; Fiveash, John B; Nabors, Louis B; Triebel, Kristen L

    2015-07-01

    To examine the association between reasoning through medical treatment decisions and cognition in a sample of patients with brain metastasis. The association between reasoning and cognition was examined using data from 41 patients with diagnosed brain metastasis. All diagnoses were made by a board-certified radiation oncologist and were verified histologically. In total, 41 demographically matched, cognitively healthy controls were also included to aid in classifying patients with brain metastasis according to reasoning status (i.e., intact or impaired). Results indicate that measures of episodic memory and processing speed were associated with reasoning. Using these two predictors, actuarial equations were constructed that can be used to help screen for impaired reasoning ability in patients' with brain metastasis. The equations presented in this study have clinical significance as they can be used to help identify patients at risk for possessing a diminished ability to reason through medical treatment decisions and, thus, are in need of a more comprehensive evaluation of their medical decision-making capacity.

  13. Management approach for recurrent brain metastases following upfront radiosurgery may affect risk of subsequent radiation necrosis

    Directory of Open Access Journals (Sweden)

    Ali Rae, BS

    2016-10-01

    Conclusion: Our results suggest that initial management approach for recurrent brain metastasis after upfront SRS does not affect the rate of RN. However, the risk of RN significantly increases when patients are treated with both repeat SRS and salvage WBRT. Methods to improve prediction of toxicity and optimize patient selection for salvage treatments are needed.

  14. Metastasis regulation by PPARD expression in cancer cells

    Science.gov (United States)

    Zuo, Xiangsheng; Xu, Weiguo; Xu, Min; Tian, Rui; Moussalli, Micheline J.; Mao, Fei; Zheng, Xiaofeng; Wang, Jing; Morris, Jeffrey S.; Eng, Cathy; Maru, Dipen M.; Rashid, Asif; Broaddus, Russell; Wei, Daoyan; Hung, Mien-Chie; Sood, Anil K.

    2017-01-01

    Peroxisome proliferator–activated receptor–δ (PPARD) is upregulated in many major human cancers, but the role that its expression in cancer cells has in metastasis remains poorly understood. Here, we show that specific PPARD downregulation or genetic deletion of PPARD in cancer cells significantly repressed metastasis in various cancer models in vivo. Mechanistically, PPARD promoted angiogenesis via interleukin 8 in vivo and in vitro. Analysis of transcriptome profiling of HCT116 colon cancer cells with or without genetic deletion of PPARD and gene expression patterns in The Cancer Genome Atlas colorectal adenocarcinoma database identified novel pro-metastatic genes (GJA1, VIM, SPARC, STC1, SNCG) as PPARD targets. PPARD expression in cancer cells drastically affected epithelial-mesenchymal transition, migration, and invasion, further underscoring its necessity for metastasis. Clinically, high PPARD expression in various major human cancers (e.g., colorectal, lung, breast) was associated with significantly reduced metastasis-free survival. Our results demonstrate that PPARD, a druggable protein, is an important molecular target in metastatic cancer. PMID:28097239

  15. Hypoxia-induced metastasis model in embryonic zebrafish

    DEFF Research Database (Denmark)

    Rouhi, Pegah; Jensen, Lasse D.; Cao, Ziquan

    2010-01-01

    I-labeled human or mouse tumor cells are implanted into the perivitelline cavity of 48-h-old zebrafish embryos, which are subsequently placed in hypoxic water for 3 d. Tumor cell invasion, metastasis and pathological angiogenesis are detected under fluorescent microscopy in the living fish. The average...

  16. Oxygen and Metastasis: A Conversation with Dr. Nick Restifo

    Science.gov (United States)

    Dr. Nick Restifo, a senior investigator in NCI’s Center for Cancer Research, discusses his recently published study finding that Oxygen, a molecule necessary for life, paradoxically aids cancer metastasis to the lung by impairing cancer-killing immune cells.

  17. GAGE12 mediates human gastric carcinoma growth and metastasis.

    Science.gov (United States)

    Lee, Eun Kyung; Song, Kyung-A; Chae, Ji-Hye; Kim, Kyoung-Mee; Kim, Seok-Hyung; Kang, Myung-Soo

    2015-05-15

    The spontaneous metastasis from human gastric carcinoma (GC) remains poorly reproduced in animal models. Here, we established an experimental mouse model in which GC progressively developed in the orthotopic stomach wall and metastasized to multiple organs; the tumors colonized in the ovary exhibited typical characteristics of Krukenberg tumor. The expression of mesenchymal markers was low in primary tumors and high in those in intravasating and extravasating veins. However, the expression of epithelial markers did not differ, indicating that the acquisition of mesenchymal markers without a concordant loss of typical epithelial markers was associated with metastasis. We identified 35 differentially expressed genes (DEGs) in GC cells metastasized to ovary, among which overexpression of GAGE12 family genes, the top-ranked DEGs, were validated. In addition, knockdown of the GAGE12 gene family affected transcription of many of the aforementioned 35 DEGs and inhibited trans-well migration, tumor sphere formation in vitro and tumor growth in vivo. In accordance, GAGE12 overexpression augmented migration, tumor sphere formation and sustained in vivo tumor growth. Taken together, the GAGE12 gene family promotes GC growth and metastasis by modulating the expression of GC metastasis-related genes.

  18. Survival in patients with breast cancer with bone metastasis

    DEFF Research Database (Denmark)

    Cetin, Karynsa; Christiansen, Christian Fynbo; Sværke, Claus;

    2015-01-01

    OBJECTIVES: Since population-based data on prognostic factors affecting survival in patients with breast cancer with bone metastasis (BM) are currently limited, we conducted this nationwide retrospective cohort study to examine the prognostic role of disease stage at breast cancer diagnosis...

  19. The effect of bone morphogenetic protein-2 on osteosarcoma metastasis

    Science.gov (United States)

    Gill, Jonathan; Connolly, Patrick; Roth, Michael; Chung, So Hak; Zhang, Wendong; Piperdi, Sajida; Hoang, Bang; Yang, Rui; Guzik, Hillary; Gorlick, Richard; Geller, David S.

    2017-01-01

    Purpose Bone Morphogenetic Protein-2 (BMP-2) may offer the potential to enhance allograft-host osseous union in limb-salvage surgery following osteosarcoma resection. However, there is concern regarding the effect of locally applied BMP-2 on tumor recurrence and metastasis. The purpose of this project was to evaluate the effect of exogenous BMP-2 on osteosarcoma migration and invasion across a panel of tumor cell lines in vitro and to characterize the effect of BMP-2 on pulmonary osteosarcoma metastasis within a xenograft model. Experimental design The effect of BMP-2 on in vitro tumor growth and development was assessed across multiple standard and patient-derived xenograft osteosarcoma cell lines. Tumor migration capacity, invasion, and cell proliferation were characterized. In addition, the effect on metastasis was measured using a xenograft model following tail-vein injection. The effect of exogenous BMP-2 on the development of metastases was measured following both single and multiple BMP-2 administrations. Results There was no significant difference in migration capacity, invasion, or cell proliferation between the BMP-2 treated and the untreated osteosarcoma cell lines. There was no significant difference in pulmonary metastases between either the single-dose or multi-dose BMP-2 treated animals and the untreated control animals. Conclusions In the model systems tested, the addition of BMP-2 does not increase osteosarcoma proliferation, migration, invasion, or metastasis to the lungs. PMID:28264040

  20. Adaptive hypofractionated gamma knife radiosurgery for a large brainstem metastasis

    DEFF Research Database (Denmark)

    Sinclair, Georges; Bartek, Jiri; Martin, Heather;

    2016-01-01

    BACKGROUND: To demonstrate how adaptive hypofractionated radiosurgery by gamma knife (GK) can be successfully utilized to treat a large brainstem metastasis - a novel approach to a challenging clinical situation. CASE DESCRIPTION: A 42-year-old woman, diagnosed with metastatic nonsmall cell lung ...

  1. A Quantitative System for Studying Metastasis Using Transparent Zebrafish

    DEFF Research Database (Denmark)

    Heilmann, Silja; Ratnakumar, Kajan; Langdon, Erin M

    2015-01-01

    of transgenic mitfa-BRAF(V600E);p53(-/-) fish. We then transplanted the melanoma cells into the transparent casper strain to enable highly quantitative measurement of the metastatic process at single-cell resolution. Using computational image analysis of the resulting metastases, we generated a metastasis score...

  2. Paeoniflorin inhibits macrophage-mediated lung cancer metastasis.

    Science.gov (United States)

    Wu, Qi; Chen, Gang-Ling; Li, Ya-Juan; Chen, Yang; Lin, Fang-Zhen

    2015-12-01

    Alternatively activated macrophages are more frequently involved in tumor growth, angiogenesis, and immunosuppression. A previous study showed that paeoniflorin, the major active constituent of Paeonia lactiflora Pallas, can inhibit tumor growth and lung metastases of Lewis lung tumor-bearing mice. This study tried to investigate whether paeoniflorin inhibited lung cancer metastasis by inhibiting the alternative activation of macrophages (M2 macrophage). Using a viability assay, the cytotoxicity of paeoniflorin on Lewis lung cancer cells and peritoneal macrophages were investigated. In vitro scratch wound and in vivo lung metastasis experiments were used to test the ability to inhibit the migration of paeoniflorin and the function of M2 macrophages. Flow cytometry was performed to test the cell cycle of Lewis lung cancer cells, and to test the M2 macrophages in peritoneal macrophages and subcutaneous transplantable tumor. It was found that paeoniflorin showed no inhibitory effect on the growth of Lewis lung cancer cells and peritoneal macrophages of mouse in vitro. Paeoniflorin could attenuate the migration of LLC stimulated by alternatively activated macrophages (stimulated for 24 h and 48 h, paeoniflorin 1, 3, 10, 30, 100 μmol·L(-1), P lung cancer cells (paeoniflorin 100 μmol·L(-1), P lung metastasis of Lewis lung cancer cells xenograft and decrease the numbers of M2 macrophages in subcutaneous xenograft tumour in vivo (paeoniflorin 20, 40 mg·kg(-1), P lung metastasis of Lewis lung cancer cells xenograft partly through inhibiting the alternative activation of macrophages.

  3. Integrin signaling modes controlling cell migration and metastasis

    NARCIS (Netherlands)

    Truong, Hoa Hoang

    2011-01-01

    The aim of this thesis is to address how integrin-mediated signaling regulates cellular processes that have profound effects on cell morphology, motility, cancer metastasis, and FN fibrillogenesis, and how these findings can be utilized for relevant medical purposes or advancement of drug discovery.

  4. STRIPAK components determine mode of cancer cell migration and metastasis

    DEFF Research Database (Denmark)

    Madsen, Chris D; Hooper, Steven; Tozluoglu, Melda;

    2015-01-01

    and MST4 kinases, which promote the co-localization of the contractile actomyosin machinery with the Ezrin/Radixin/Moesin family proteins by phosphorylating the inhibitors of PPP1CB, PPP1R14A-D. Using computational modelling, in vitro cell migration assays and in vivo breast cancer metastasis assays we...

  5. Adenocarcinoma of urethra presenting metastasis to eyes: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Lages, Rafael Bandeira; Sousa, Rodrigo Beserra; Santos, Lina Gomes dos; Vieira, Sabas Carlos, E-mail: rafaelblages@gmail.co [Universidade Federal do Piaui (UFPI), Teresina, PI (Brazil); Tavares, Marilia Buenos Aires Cabral [Universidade Federal do Ceara (UFC), Fortaleza, CE (Brazil). Hospital Universitario Walter Cantidio; Valenca, Rodrigo Jose de Vasconcelos [Hospital Sao Marcos (HSM), Teresina, PI (Brazil)

    2010-07-01

    Primary urethral carcinoma is extremely rare, accounting for less than 1% of all female genitourinary tract cancers. To the best of our knowledge, this patient is the first reported case of primary urethral carcinoma presenting metastasis to eyes. The diagnosis of metastasis involving the choroids should be suspected in patient with history of carcinoma and a decreased visual acuity or any other visual symptom. Case presentation: A 43-year-old woman underwent a total hysterectomy, cystectomy and bilateral pelvic lymphadenectomy due a primary adenocarcinoma of the proximal urethra. Adjuvant pelvic radiotherapy and six cycles of chemotherapy using cisplatin were performed. The patient made follow-up with no evidence of oncologic disease. However, nine months later, the patient reported visual alterations. Ophthalmoloscopic examination showed choroid lesions in both eyes that were compatible with metastatic choroids tumor and nuclear magnetic resonance suggested bilateral retinal metastasis and left meningioma parasagittal in parietal region. She was undergoing a new palliative chemotherapy, but the disease developed and there were metastasis to bone four months later. The patient died fourteen months after the surgery. (author)

  6. Leukemia stem cells in drug resistance and metastasis

    Institute of Scientific and Technical Information of China (English)

    DENG Chao-hua; ZHANG Qiu-ping

    2010-01-01

    Objective To review the central role of leukemia stem cells (LSCs) in drug resistance and metastasis, aiming to provide key insights into leukemogenic pathology and developing novel therapeutic strategies against the relapse of leukemia.Data sources The data used in this review were obtained mainly from the studies reported in PubMed using the key terms "tumor-initiating cells", "leukemia stem cells", "drug resistance" and "metastasis".Study selection Relevant articles on studies of leukemia stem cells were selected.Results Increasing numbers of studies have suggested the importance of cancer stem cells (CSCs) in the initiation and maintenance of cancer, especially in leukemia. This review has summarized the origin, characteristics, isolation and identification of LSCs. It highlights the crucial role of LSCs in drug resistance and metastasis of leukemia by illustrating possible mechanisms and aims to provide novel therapeutic strategies for LSCs-targeted treatment.Conclusion LSCs play a crucial role in drug resistance and metastasis of leukemia and new promising LSCs-targeted therapies warrant investigation in both experimental models and clinical practice.

  7. Mechanism of Tumor Metastasis Suppression by the KAI1 Gene

    Science.gov (United States)

    2008-02-01

    Genomics 41, 25–32. Dunon, D., Piali, L., Imhof , B.A., 1996. To stick or not to stick: the new leukocyte homing paradigm. Curr. Opin. Cell Biol. 8, 714–723...Eur. J. Immunol. 26, 2657–2665. Ruiz, P., Dunon, D., Sonnenberg, A., Imhof , B.A., 1993. Suppression of mouse melanoma metastasis by EA-1, a

  8. Hepatoma with cardiac metastasis: An advanced cancer requiring advanced treatment

    Institute of Scientific and Technical Information of China (English)

    Yu-Sheng Lin; Shih-Ming Jung; Feng-Chun Tsai; Chun-Nan Yeh; Tzu-Fang Shiu; Hsueh-Hua Wu; Pyng-Jing Lin; Pao-Hsien Chu

    2007-01-01

    AIM: To investigate the clinical and pathologic findings,and to discuss the pathophysiology of hepatocellular carcinoma with cardiac metastasis.METHODS: Eight hepatoma patients with cardiac metastasis, who were treated by surgical excision from 1993 to 2006, were retrospectively studied. Detailed clinical parameters were analyzed.RESULTS: Of those eight patients, two (25%) were women and six (75%) were men, with the mean age of 50 years (range, 40-70 years). The presentations included: asymptomatic (75%), heart failure (25%), and pulmonary embolism (12.5%). All lesions involved the right atrium, and extended to the lung (12.5%), inferior vena cava (25%), and left atrium (12.5%). The level of tumor marker, alpha-fetal protein, was not correlated with the severity of metastasis or disease prognosis.Moreover, the availably estimated doubling time was less than 3 mo. The pathological findings included variable hemorrhage and necrosis. The survival time following surgery also varied from one month to more than 30 mo.CONCLUSION: Hepatoma metastasis to the heart was detected in all eight patients. This study demonstrates that surgery might help the outcome in such cases.

  9. Disrupting Ovarian Cancer Metastatic Colonization: Insights from Metastasis Suppressor Studies

    Directory of Open Access Journals (Sweden)

    Shaheena Khan

    2010-01-01

    Full Text Available Ovarian cancer affects approximately 25,000 women in the United States each year and remains one of the most lethal female malignancies. A standard approach to therapy is surgical cytoreduction, after which the remaining microscopic residual disease is treated with chemotherapy. The vast majority of patients have disease recurrence, underscoring the crucial need for approaches to control the regrowth, or colonization, of tissues after local treatment. Improved therapies require mechanistic information about the process of metastatic colonization, the final step in metastasis, in which cancer cells undergo progressive growth at secondary sites. Studies of metastasis suppressors are providing insights into events controlling metastatic colonization. This paper reviews our laboratory's approach to the identification, characterization, and functional testing of the JNKK1/MKK4 metastasis suppressor in ovarian cancer metastatic colonization. Specifically, we demonstrate that interaction of ovarian caner cells with the omental microenvironment activates JNKK1/MKK4 resulting in decreased proliferation without affecting apoptosis. The potential role of the omental microenvironment, specifically milky spot structures, is also described. It is our goal to provide this work as a usable paradigm that will enable others to study metastasis suppressors in clinical and experimental ovarian cancer metastases.

  10. Review of Animal Models of Prostate Cancer Bone Metastasis

    Directory of Open Access Journals (Sweden)

    Jessica K. Simmons

    2014-06-01

    Full Text Available Prostate cancer bone metastases are associated with a poor prognosis and are considered incurable. Insight into the formation and growth of prostate cancer bone metastasis is required for development of new imaging and therapeutic strategies to combat this devastating disease. Animal models are indispensable in investigating cancer pathogenesis and evaluating therapeutics. Multiple animal models of prostate cancer bone metastasis have been developed, but few effectively model prostatic neoplasms and osteoblastic bone metastases as they occur in men. This review discusses the animal models that have been developed to investigate prostate cancer bone metastasis, with a focus on canine models and also includes human xenograft and rodent models. Adult dogs spontaneously develop benign prostatic hyperplasia and prostate cancer with osteoblastic bone metastases. Large animal models, such as dogs, are needed to develop new molecular imaging tools and effective focal intraprostatic therapy. None of the available models fully reflect the metastatic disease seen in men, although the various models have provided important insight into the metastatic process. As additional models are developed and knowledge from the different models is combined, the molecular mechanisms of prostate cancer bone metastasis can be deciphered and targeted for development of novel therapies and molecular diagnostic imaging.

  11. Cutaneous metastasis from gastrointestinal adenocarcinoma of unknown primary origin.

    Science.gov (United States)

    Junqueira, Ana Lucia Ariano; Corbett, Ana Maria França; Oliveira Filho, Jayme de; Nasser, Kassila da Rosa; Haddad, Natalie Nejem; Tebet, Ana Carolina Franco

    2015-01-01

    Cutaneous metastasis is a rare manifestation of visceral malignancies that indicates primarily advanced disease. Due to its low incidence and similarity to other cutaneous lesions, it is not uncommon to have a delayed diagnosis and a shortened prognosis. We describe the case of a patient who presented with a cutaneous nodule in the sternal region as a first sign of malignancy.

  12. Rectal metastasis from Breast cancer: A rare entity

    Directory of Open Access Journals (Sweden)

    Cho Ee Ng

    2015-01-01

    Conclusion: There should be high clinical suspicion of bowel metastasis in patients presenting with positive faecal occult blood with or without bowel symptoms even if the incidence is less <1% of metastases, particularly in cases where the initial breast tumour was large, with positive axillary nodes.

  13. Testicular Metastasis of Prostate Cancer: A Case Report

    Directory of Open Access Journals (Sweden)

    Ayumu Kusaka

    2014-09-01

    Full Text Available The incidence of secondary neoplasms of the testis during autopsies is approximately 2.5%. Although most secondary testicular metastases are due to prostate cancer, only a few patients with prostate cancer have clinically manifested testicular metastasis. We report the case of a prostate cancer patient with testicular metastasis who was diagnosed after the presence of a palpable mass in the right testis. A 56-year-old Japanese male presented to our hospital with an elevated serum prostate-specific antigen (PSA level of 137 ng/ml. He was diagnosed with stage IV (T3N1M1b prostate cancer and received androgen deprivation therapy, followed by various hormonal manipulations. His serum PSA level was undetectable for 1 year. No distant metastases were detected during imaging examinations. He received radiation therapy; however, his serum PSA level increased gradually. Four months later, he presented with right testicular swelling. Computed tomography revealed a heterogenous mass in the right testis and a right high inguinal orchiectomy was performed. Histopathological analysis showed that the right testis was infiltrated with metastatic adenocarcinoma with a Gleason score of 8. This is a rare case of right testicular metastasis in a patient with prostate cancer. Testicular metastasis of prostate cancer can be aggressive and metastasize.

  14. Immunosuppressive cells in tumor immune escape and metastasis.

    Science.gov (United States)

    Liu, Yang; Cao, Xuetao

    2016-05-01

    Tumor immune escape and the initiation of metastasis are critical steps in malignant progression of tumors and have been implicated in the failure of some clinical cancer immunotherapy. Tumors develop numerous strategies to escape immune surveillance or metastasize: Tumors not only modulate the recruitment and expansion of immunosuppressive cell populations to develop the tumor microenvironment or pre-metastatic niche but also switch the phenotype and function of normal immune cells from a potentially tumor-reactive state to a tumor-promoting state. Immunosuppressive cells facilitate tumor immune escape by inhibiting antitumor immune responses and furthermore promote tumor metastasis by inducing immunosuppression, promoting tumor cell invasion and intravasation, establishing a pre-metastatic niche, facilitating epithelial-mesenchymal transition, and inducing angiogenesis at primary tumor or metastatic sites. Numerous translational studies indicate that it is possible to inhibit tumor immune escape and prevent tumor metastasis by blocking immunosuppressive cells and eliminating immunosuppressive mechanisms that are induced by either immunosuppressive cells or tumor cells. Furthermore, many clinical trials targeting immunosuppressive cells have also achieved good outcome. In this review, we focus on the underlying mechanisms of immunosuppressive cells in promoting tumor immune escape and metastasis, discuss our current understanding of the interactions between immunosuppressive cells and tumor cells in the tumor microenvironment, and suggest future research directions as well as potential clinical strategies in cancer immunotherapy.

  15. Left ventricular metastasis from a primary lung carcinoma

    Institute of Scientific and Technical Information of China (English)

    CHE Guo-wei; LIU Lun-xu; ZHANG Er-yong; ZHOU Qing-hua

    2007-01-01

    @@ The most common tumors associated with cardiac metastases are lung carcinoma and melanoma.1 Although the cardiac involvement of lung cancer is common(lung cancer usually directly invades into the pericardium and/or left/right atrium),the primary lung cancer accompanied with metastasis to the left ventricle is extremely rare.

  16. Metastatic transitional cell carcinoma presenting with skin metastasis.

    Science.gov (United States)

    Açıkgöz, Onur; Ölçücüoğlu, Erkan; Kasap, Yusuf; Yığman, Metin; Güneş, Zeki Ender; Gazel, Eymen

    2015-01-01

    Transitional cell carcinomas (TCC) of upper urinary system account for 5% of all TCCs. The incidence of such metastases ranges from 0.18% to 2%. Experimental studies reported a general unsatisfactory survival time following skin metastasis. We report in this paper a case of metastatic urinary system TCC, which had become evident with a skin lesion in the right hypogastric region. A 60-year-old female patient with a history of being operated upon due to renal pelvic TCC was admitted to our outpatient clinic with complaints of red skin lesion in the near vicinity of the operational incision scar for 3 months. Her medical history revealed nothing but nephroureterectomy operation on the upper urinary system; moreover, it was learned that she had been ignoring what was recommended to her for routine controls. Thoraco-abdominal computed tomographic (CT) examination performed on the basis of aforementioned findings depicted a mass lesion of 24*20 mm dimension with high contrast uptake detected within the subcutaneous fat tissue in the right abdominal wall. The skin lesion depicted in CT was surgically excised. The pathological examination of the excised material was reported to be compatible with TCC. The patient was referred due to abdominal lesion to medical oncology after the operation. Followed up under chemotherapy protocol, the patient died 3 months after the metastasectomy operation. Skin metastasis of upper urinary system TCCs, especially renal pelvic TCCs, are quite rare conditions. Among the likely skin sites of metastasis for genitourinary system TCCs are head, face, extremities, suprapubic region and abdomen. Taking into consideration the low survival rates, the importance of early diagnosis of recurrences and/or distant metastases should be better appreciated. These patients die soon after the skin metastasis even with the administration of aggressive therapy. Similarly, our patient died 90 days after the diagnosis of skin metastasis despite the oncologic

  17. Angiotensin II facilitates breast cancer cell migration and metastasis.

    Directory of Open Access Journals (Sweden)

    Sylvie Rodrigues-Ferreira

    Full Text Available Breast cancer metastasis is a leading cause of death by malignancy in women worldwide. Efforts are being made to further characterize the rate-limiting steps of cancer metastasis, i.e. extravasation of circulating tumor cells and colonization of secondary organs. In this study, we investigated whether angiotensin II, a major vasoactive peptide both produced locally and released in the bloodstream, may trigger activating signals that contribute to cancer cell extravasation and metastasis. We used an experimental in vivo model of cancer metastasis in which bioluminescent breast tumor cells (D3H2LN were injected intra-cardiacally into nude mice in order to recapitulate the late and essential steps of metastatic dissemination. Real-time intravital imaging studies revealed that angiotensin II accelerates the formation of metastatic foci at secondary sites. Pre-treatment of cancer cells with the peptide increases the number of mice with metastases, as well as the number and size of metastases per mouse. In vitro, angiotensin II contributes to each sequential step of cancer metastasis by promoting cancer cell adhesion to endothelial cells, trans-endothelial migration and tumor cell migration across extracellular matrix. At the molecular level, a total of 102 genes differentially expressed following angiotensin II pre-treatment were identified by comparative DNA microarray. Angiotensin II regulates two groups of connected genes related to its precursor angiotensinogen. Among those, up-regulated MMP2/MMP9 and ICAM1 stand at the crossroad of a network of genes involved in cell adhesion, migration and invasion. Our data suggest that targeting angiotensin II production or action may represent a valuable therapeutic option to prevent metastatic progression of invasive breast tumors.

  18. Selectins mediate small cell lung cancer systemic metastasis.

    Directory of Open Access Journals (Sweden)

    Franziska Heidemann

    Full Text Available Metastasis formation is the major reason for the extremely poor prognosis in small cell lung cancer (SCLC patients. The molecular interaction partners regulating metastasis formation in SCLC are largely unidentified, however, from other tumor entities it is known that tumor cells use the adhesion molecules of the leukocyte adhesion cascade to attach to the endothelium at the site of the future metastasis. Using the human OH-1 SCLC line as a model, we found that these cells expressed E- and P-selectin binding sites, which could be in part attributed to the selectin binding carbohydrate motif sialyl Lewis A. In addition, protein backbones known to carry these glycotopes in other cell lines including PSGL-1, CD44 and CEA could be detected in in vitro and in vivo grown OH1 SCLC cells. By intravital microscopy of murine mesenterial vasculature we could capture SCLC cells while rolling along vessel walls demonstrating that SCLC cells mimic leukocyte rolling behavior in terms of selectin and selectin ligand interaction in vivo indicating that this mechanism might indeed be important for SCLC cells to seed distant metastases. Accordingly, formation of spontaneous distant metastases was reduced by 50% when OH-1 cells were xenografted into E-/P-selectin-deficient mice compared with wild type mice (p = 0.0181. However, as metastasis formation was not completely abrogated in selectin deficient mice, we concluded that this adhesion cascade is redundant and that other molecules of this cascade mediate metastasis formation as well. Using several of these adhesion molecules as interaction partners presumably make SCLC cells so highly metastatic.

  19. Brain radiation - discharge

    Science.gov (United States)

    Radiation - brain - discharge; Cancer-brain radiation; Lymphoma - brain radiation; Leukemia - brain radiation ... Decadron) while you are getting radiation to the brain. It may make you hungrier, cause leg swelling ...

  20. Brain tumor - primary - adults

    Science.gov (United States)

    ... Vestibular schwannoma (acoustic neuroma) - adults; Meningioma - adults; Cancer - brain tumor (adults) ... Primary brain tumors include any tumor that starts in the brain. Primary brain tumors can start from brain cells, ...

  1. Multiple extraneural metastasis of glioblastoma multiforme

    Directory of Open Access Journals (Sweden)

    J. Undabeitia

    2015-04-01

    Full Text Available Introduction. Glioblastoma multiforme is the most frequent primary tumor in the brain. Despite improvements in its surgical, chemotherapy and radiotherapy treatment, prognosis remains poor. Extracranial metastases of glioblastoma are a rare complication in this disease. Its appearance has been described in lung, liver, bone or lymph nodes. Case report. We describe the case of a 20 year-old patient who complained of a subacute-onset headache. In the MRI an enhancing right temporal lesion was detected suggesting a high grade glioma as first diagnosis. Surgery was performed, obtaining a gross total resection of the lesion. Our patient underwent adjuvant radiotherapy and chemotherapy treatment, according to our hospital´s protocol. Five months after initial surgery our patient complained of chest pain and a hacking cough. A thoracic-abdominal-pelvic CT scan was obtained, which showed bilateral lung infiltrates with pleural effusion, a pancreatic nodule and several vertebral lytic lesions. The lung lesions were biopsied. The pathologic diagnosis was metastatic glioblastoma multiforme. The patient died eight months after initial diagnosis. Conclusion. Extracranial metastases of glioblastoma remain a rare event although its incidence is increasing, probably due to the improvement in survival among these patients and better imaging techniques. The mechanisms for extracranial dissemination of glioblastoma are not entirely known, as several theories exist in this regard. Physicians must be aware of this complication and keep it in mind as a differential diagnosis to improve the quality of life of our patients.

  2. Capecitabine-related intracranial hypotension syndrome mimicking dural metastasis in a breast cancer patient: Case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Cosar-Alas Rusen

    2010-01-01

    Full Text Available Spontaneous intracranial hypotension (SICH is an entity, which is secondary to iatrogenic manipulation and breaching of dura. Postural headache in patients should be suspected, cranial magnetic resonance imaging (MRI is essential for precise diagnosis. Hallmark of MRI is regular shape of pachymeningeal gadolinium enhancement and subdural effusion. It may mimic central nervous system (CNS metastasis. Prevention of such cases from receiving cranial radiotherapy by misinterpretation of the gadolinium enhancement as CNS metastasis is an important issue. Capecitabine is an antineoplastic agent, of which metabolites can cross blood-brain barrier in CNS via epithelial tissue. It may cause decrease in CSF production. SICH might be the clinical reflection of this decrease in CSF production. Review of the English literature revealed limited data because of the very little experience with oncologic patients suffering from intracranial hypotension. We report a case of spontaneous intracranial hypotension during capecitabine treatment. Patient was completely well following drug discontinuation and supportive treatment.

  3. Brain Basics

    Medline Plus

    Full Text Available ... highly developed area at the front of the brain that, in humans, plays a role in executive functions such as ... Higher Death Rate Among Youth with Psychosis Delayed Walking Link ...

  4. Brain Basics

    Medline Plus

    Full Text Available ... the brain, which is linked to thought and emotion. It is also linked to reward systems in ... or-flight response and is also involved in emotions and memory. anterior cingulate cortex —Is involved in ...

  5. Brain Basics

    Medline Plus

    Full Text Available ... Some people who develop a mental illness may recover completely; others may have repeated episodes of illness ... in early detection, more tailored treatments, and possibly prevention of such illnesses. The Working Brain Neurotransmitters Everything ...

  6. Brain Basics

    Medline Plus

    Full Text Available ... that contains codes to make proteins and other important body chemicals. DNA also includes information to control ... cells required for normal function and plays an important role during early brain development. It may also ...

  7. Brain Basics

    Medline Plus

    Full Text Available ... of the cell from its surrounding environment and controls what enters and leaves the cell, and responds ... via axons) to form brain circuits. These circuits control specific body functions such as sleep and speech. ...

  8. Brain Basics

    Medline Plus

    Full Text Available ... in early detection, more tailored treatments, and possibly prevention of such illnesses. The Working Brain Neurotransmitters Everything ... can cause tremors or symptoms found in Parkinson's disease. Serotonin —helps control many functions, such as mood, ...

  9. Brain Basics

    Medline Plus

    Full Text Available ... Offices and Divisions Careers@NIMH Advisory Boards and Groups Staff Directories Getting to NIMH National Institutes of ... electrical signals. The brain begins as a small group of cells in the outer layer of a ...

  10. Brain Basics

    Medline Plus

    Full Text Available ... These circuits control specific body functions such as sleep and speech. The brain continues maturing well into ... factors that can affect our bodies, such as sleep, diet, or stress. These factors may act alone ...

  11. Lingual metastasis from renal cell carcinoma: a case report and literature review

    Directory of Open Access Journals (Sweden)

    Camillo Porta

    2012-06-01

    Full Text Available Renal cell carcinoma (RCC accounts for the 3% of all solid tumors. Despite continuous improvement in the therapy regimen, less has been achieved in terms of enabling an earlier diagnosis: the neoplasia usually reveals its presence at an advanced stage, obviously affecting prognosis. The most frequent sites of secondary disease are shown to be lungs (50-60%, bone (30-40%, liver (30-40% and brain (5%; while the head and neck district seems to account for less than 1% of patients with primary kidney lesion. We report here the case of a 70-year old man who presented with acute renal failure due to abdominal recurrence of RCC 18 years post nephrectomy. After a few months of follow up without any systemic therapy due to the renal impairment, the patient presented a vascularized tongue lesion that was demonstrated to be a secondary localization of the RCC. This lesion has, therefore, been treated with microsphere embolization to stop the frequent bleeding and to lessen the unbearable concomitant symptoms it caused, such as dysphagia and pain. A tongue lesion that appears in a RCC patient should always be considered suspect and a multidisciplinary study should be conducted both to assess whether it is a metastasis or a primary new lesion and to understand which method should be selected, if necessary, to treat it (surgery, radiation or embolization. Lingual metastasis should be examined accurately not only because they seem to implicate a poor prognosis, but also because they carry a burden of symptoms that not only threatens patients’ lives but also has a strong impact on their quality of life.

  12. Tumor microenvironment regulates metastasis and metastasis genes of mouse MMTV-PymT mammary cancer cells in vivo.

    Science.gov (United States)

    Werbeck, J L; Thudi, N K; Martin, C K; Premanandan, C; Yu, L; Ostrowksi, M C; Rosol, T J

    2014-07-01

    Metastasis is the primary cause of death in breast cancer patients, yet there are challenges to modeling this process in vivo. The goal of this study was to analyze the effects of injection site on tumor growth and metastasis and gene expression of breast cancer cells in vivo using the MMTV-PymT breast cancer model (Met-1 cells). Met-1 cells were injected into 5 sites (subcutaneous, mammary fat pad, tail vein, intracardiac, and intratibial), and tumors and metastases were monitored using bioluminescent imaging and confirmed with gross necropsy and histopathology. Met-1 tumors were analyzed based on morphology and changes in gene expression in each tissue microenvironment. There were 6 permissible sites of Met-1 tumor growth (mammary gland, subcutis, lung, adrenal gland, ovary, bone). Met-1 cells grew faster in the subcutis compared to mammary fat pad tumors (highest Ki-67 index). Morphologic differences were evident in each tumor microenvironment. Finally, 7 genes were differentially expressed in the Met-1 tumors in the 6 sites of growth or metastasis. This investigation demonstrates that breast cancer progression and metastasis are regulated by not only the tumor cells but also the experimental model and unique molecular signals from the tumor microenvironment.

  13. Colorectal cancer manifesting with metastasis to prolactinoma: report of a case involving symptoms mimicking pituitary apoplexy.

    Science.gov (United States)

    Thewjitcharoen, Yotsapon; Shuangshoti, Shanop; Lerdlum, Sukalaya; Siwanuwatn, Rungsak; Sunthornyothin, Sarat

    2014-01-01

    Pituitary metastasis is an uncommon first presentation of systemic malignancy. The most common presenting symptom of pituitary metastasis is diabetes insipidus reflecting involvement of the stalk and/or posterior pituitary. We herein present a unique case of the coexistence of both a functioning pituitary adenoma (prolactinoma) and pituitary metastasis of advanced colorectal cancer with pituitary apoplexy as the first manifestation of underlying malignancy. The present case emphasizes the need to consider pituitary metastasis as a differential diagnosis in patients presenting with pituitary lesions and be aware that tumor-to-tumor metastasis can occur unexpectedly in those with pituitary metastases.

  14. Late (> 5 years) regional lymph node metastasis of oral squamous cell carcinoma (SCC), proven by p53 mutation analysis

    NARCIS (Netherlands)

    Kummer, J. Alain; Van Es, Robert J. J.; Hoekstra, J.W.M.

    2008-01-01

    Background: A late (>5 years) neck nodal metastasis of oral cancer, poses a problem to the clinician: is it a late metastasis or a metastasis of a (unknown) second primary tumour? Methods: A 50-year-old male was seen with a contralateral lymph node metastasis, 51/2 years after treatment of a pT2N1M0

  15. Intracerebral metastasis showing restricted diffusion: Correlation with histopathologic findings

    Energy Technology Data Exchange (ETDEWEB)

    Duygulu, G. [Radiology Department, Ege University Medicine School, Izmir (Turkey); Ovali, G. Yilmaz [Radiology Department, Celal Bayar University Medicine School, Manisa (Turkey)], E-mail: gulgun.yilmaz@bayar.edu.tr; Calli, C.; Kitis, O.; Yuenten, N. [Radiology Department, Ege University Medicine School, Izmir (Turkey); Akalin, T. [Pathology Department, Ege University Medicine School, Izmir (Turkey); Islekel, S. [Neurosurgery Department, Ege University Medicine School, Izmir (Turkey)

    2010-04-15

    Objective: We aimed to detect the frequency of restricted diffusion in intracerebral metastases and to find whether there is correlation between the primary tumor pathology and diffusion-weighted MR imaging (DWI) findings of these metastases. Material and methods: 87 patients with intracerebral metastases were examined with routine MR imaging and DWI. 11 hemorrhagic metastatic lesions were excluded. The routine MR imaging included three plans before and after contrast enhancement. The DWI was performed with spin-echo EPI sequence with three b values (0, 500 and 1000), and ADC maps were calculated. 76 patients with metastases were grouped according to primary tumor histology and the ratios of restricted diffusion were calculated according to these groups. ADCmin values were measured within the solid components of the tumors and the ratio of metastases with restricted diffusion to that which do not show restricted diffusion were calculated. Fisher's exact and Mann-Whitney U tests were used for the statistical analysis. Results: Restricted diffusion was observed in a total of 15 metastatic lesions (19, 7%). Primary malignancy was lung carcinoma in 10 of these cases (66, 6%) (5 small cell carcinoma, 5 non-small cell carcinoma), and breast carcinoma in three cases (20%). Colon carcinoma and testicular teratocarcinoma were the other two primary tumors in which restricted diffusion in metastasis was detected. There was no statistical significant difference between the primary pathology groups which showed restricted diffusion (p > 0.05). ADCmin values of solid components of the metastasis with restricted diffusion and other metastasis without restricted diffusion also showed no significant statistical difference (0.72 {+-} 0.16 x 10{sup -3} mm{sup 2}/s and 0.78 {+-} 21 x 10{sup -3} mm{sup 2}/s respectively) (p = 0.325). Conclusion: Detection of restricted diffusion on DWI in intracerebral metastasis is not rare, particularly if the primary tumor is lung or breast

  16. Targeting breast to brain metastatic tumours with death receptor ligand expressing therapeutic stem cells.

    Science.gov (United States)

    Bagci-Onder, Tugba; Du, Wanlu; Figueiredo, Jose-Luiz; Martinez-Quintanilla, Jordi; Shah, Khalid

    2015-06-01

    Characterizing clinically relevant brain metastasis models and assessing the therapeutic efficacy in such models are fundamental for the development of novel therapies for metastatic brain cancers. In this study, we have developed an in vivo imageable breast-to-brain metastasis mouse model. Using real time in vivo imaging and subsequent composite fluorescence imaging, we show a widespread distribution of micro- and macro-metastasis in different stages of metastatic progression. We also show extravasation of tumour cells and the close association of tumour cells with blood vessels in the brain thus mimicking the multi-foci metastases observed in the clinics. Next, we explored the ability of engineered adult stem cells to track metastatic deposits in this model and show that engineered stem cells either implanted or injected via circulation efficiently home to metastatic tumour deposits in the brain. Based on the recent findings that metastatic tumour cells adopt unique mechanisms of evading apoptosis to successfully colonize in the brain, we reasoned that TNF receptor superfamily member 10A/10B apoptosis-inducing ligand (TRAIL) based pro-apoptotic therapies that induce death receptor signalling within the metastatic tumour cells might be a favourable therapeutic approach. We engineered stem cells to express a tumour selective, potent and secretable variant of a TRAIL, S-TRAIL, and show that these cells significantly suppressed metastatic tumour growth and prolonged the survival of mice bearing metastatic breast tumours. Furthermore, the incorporation of pro-drug converting enzyme, herpes simplex virus thymidine kinase, into therapeutic S-TRAIL secreting stem cells allowed their eradication post-tumour treatment. These studies are the first of their kind that provide insight into targeting brain metastasis with stem-cell mediated delivery of pro-apoptotic ligands and have important clinical implications.

  17. Brain death.

    Science.gov (United States)

    Wijdicks, Eelco F M

    2013-01-01

    The diagnosis of brain death should be based on a simple premise. If every possible confounder has been excluded and all possible treatments have been tried or considered, irreversible loss of brain function is clinically recognized as the absence of brainstem reflexes, verified apnea, loss of vascular tone, invariant heart rate, and, eventually, cardiac standstill. This condition cannot be reversed - not even partly - by medical or surgical intervention, and thus is final. Many countries in the world have introduced laws that acknowledge that a patient can be declared brain-dead by neurologic standards. The U.S. law differs substantially from all other brain death legislation in the world because the U.S. law does not spell out details of the neurologic examination. Evidence-based practice guidelines serve as a standard. In this chapter, I discuss the history of development of the criteria, the current clinical examination, and some of the ethical and legal issues that have emerged. Generally, the concept of brain death has been accepted by all major religions. But patients' families may have different ideas and are mostly influenced by cultural attitudes, traditional customs, and personal beliefs. Suggestions are offered to support these families.

  18. New insights of epithelial-mesenchymal transition in cancer metastasis

    Institute of Scientific and Technical Information of China (English)

    Yadi Wu; Binhua P.Zhou

    2008-01-01

    Epithelial-mesenchymal transition (EMT) is a key step during embryonic morphogenesis,heart development,chronic degenerative fibrosis,and cancer metastasis.Several distinct traits have been conveyed by EMT,including cell motility,invasiveness,resistance to apoptosis,and some properties of stem cells.Many signal pathways have contributed to the induction of EMT,such as transforming growth factor-β,Wnt,Hedgehog,Notch,and nuclear factor-κB.Over the last few years,increasing evidence has shown that EMT plays an essential role in tumor progression and metastasis.Understanding the molecular mechanism of EMT has a great effect in unraveling the metastatic cascade and may lead to novel interventions for metastatic disease.

  19. RECURRENT MARJOLIN’S ULCER WITH REGIONAL LYMPH NODE METASTASIS

    Directory of Open Access Journals (Sweden)

    Anjali

    2012-11-01

    Full Text Available ABSTRACT: Marjolin’s ulcer is a malignant tumour developing in a chronic skin lesion (burn scar, vaccination scar, non-healing wound etc.. Th e majority of cases reported are squamous cell carcinoma. Surgery remains the first treatment of choice (resection with 2cms. safety margin of healthy skin for primary squamous cell car cinoma Marjolin ulcers and 2.5cms. safety margin for recurrent cases. Recurrence after surge ry and regional lymph node metastasis are not uncommon (17% & 30% respectively.We presents a c ase report and literature review of Recurrent Marjolin’s Ulcer with regional Lymph Node Metastasis. Marjolin's ulcer should be considered as a significant post-burn complication; i t should be treated with full emphasis on adequate local clearance and regular follow up for m any years; if not treated adequately, it may lead to complicated recurrence.

  20. A Case of Patella Metastasis of Papillary Thyroid Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Han, Eun Ji; Choi, Woo Hee; Chung, Yong An; Sohn, Hyung Sun; Kang, Chang Suk [College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of)

    2009-02-15

    A 73-year-old man presented with a chief complaint of progressive left knee pain for two months. He had a history of total thyroidectomy and central lymph node dissection due to papillary thyroid carcinoma three months ago. MRI images revealed a solid mass in the left patella. A solid mass demonstrated low signal on T1 weighed image, and high signal on T2 weighed image. And whole body bone scan showed focal photon defect in same lesion of left patella. The histologic result of left knee lesion was adenocarcinoma, consistent with metastatic papillary thyroid carcinoma. Although patellar metastasis of papillary thyroid carcinoma is very rare, when knee pain and radiologic abnormality are noted, differential diagnosis of metastasis is necessary.