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Sample records for spontaneous lung metastasis

  1. Integrin α3β1 can function to promote spontaneous metastasis and lung colonization of invasive breast carcinoma.

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    Zhou, Bo; Gibson-Corley, Katherine N; Herndon, Mary E; Sun, Yihan; Gustafson-Wagner, Elisabeth; Teoh-Fitzgerald, Melissa; Domann, Frederick E; Henry, Michael D; Stipp, Christopher S

    2014-01-01

    Significant evidence implicates α3β1 integrin in promoting breast cancer tumorigenesis and metastasis-associated cell behaviors in vitro and in vivo. However, the extent to which α3β1 is actually required for breast cancer metastasis remains to be determined. We used RNA interference to silence α3 integrin expression by approximately 70% in 4T1 murine mammary carcinoma cells, a model of aggressive, metastatic breast cancer. Loss of α3 integrin reduced adhesion, spreading, and proliferation on laminin isoforms, and modestly reduced the growth of orthotopically implanted cells. However, spontaneous metastasis to lung was strikingly curtailed. Experimental lung colonization after tail vein injection revealed a similar loss of metastatic capacity for the α3-silenced (α3si) cells, suggesting that critical, α3-dependent events at the metastatic site could account for much of α3β1's contribution to metastasis in this model. Reexpressing α3 in the α3si cells reversed the loss of metastatic capacity, and silencing another target, the small GTPase RhoC, had no effect, supporting the specificity of the effect of silencing α3. Parental, α3si, and α3-rescued cells, all secreted abundant laminin α5 (LAMA5), an α3β1 integrin ligand, suggesting that loss of α3 integrin might disrupt an autocrine loop that could function to sustain metastatic growth. Analysis of human breast cancer cases revealed reduced survival in cases where α3 integrin and LAMA5 are both overexpressed. α3 integrin or downstream effectors may be potential therapeutic targets in disseminated breast cancers, especially when laminin α5 or other α3 integrin ligands are also over-expressed. ©2013 AACR.

  2. Unusual case of cavitary lung metastasis from squamous cell ...

    African Journals Online (AJOL)

    Spontaneous excavation of primary lung cancer is common; however cavitation of metastatic lung lesions is rare and usually confused with benign lesions. In Moroccan context tuberculosis is the first suspected diagnosis of lung excavations. We report a rare case of cavitary lung metastasis of a uterine cervix cancer, treated ...

  3. Lung Metastasis Mimicking Fingertip Infection

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    Soylemez, Salih; Demiroglu, Murat; Yayla, Mehmet Ali; Ozkan, Korhan; Alpan, Bugra; Ozger, Harzem

    2015-01-01

    Metastasis fingers (acral metastasis) are finding a poor prognosis. Past medical history should be questioned and metastasis from primary tumor should be kept in mind in patients with pain, swelling, and hyperemia in fingers. Successful surgical treatment on acral metastasis does not extend the life expectancy; however, it reduces the patient's pain during his terminal period, saves the functions of the limb, and increases life comfort. PMID:26236517

  4. Lung Metastasis Mimicking Fingertip Infection

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    Salih Soylemez

    2015-01-01

    Full Text Available Metastasis fingers (acral metastasis are finding a poor prognosis. Past medical history should be questioned and metastasis from primary tumor should be kept in mind in patients with pain, swelling, and hyperemia in fingers. Successful surgical treatment on acral metastasis does not extend the life expectancy; however, it reduces the patient’s pain during his terminal period, saves the functions of the limb, and increases life comfort.

  5. Genomic Alteration During Metastasis of Lung Adenocarcinoma

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    Qiang Tan

    2016-02-01

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

  6. Laryngeal metastasis from lung cancer

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    Kalai, Umasankar; Madan, Karan; Jain, Deepali; Mohan, Anant; Guleria, Randeep

    2015-01-01

    Metastatic tumors of the larynx are rare. The most common tumors metastasizing to the larynx are melanoma and renal cell carcinoma. Bronchogenic carcinoma metastasizing to the larynx has been rarely described. Herein, we report the case of a 49-year-old, chronic smoker, who incidentally had a laryngeal growth detected during flexible bronchoscopy examination for evaluation of suspected lung cancer. Histopathological examination of the laryngeal nodule and the biopsy obtained from the main bronchus growth confirmed the diagnosis of metastatic squamous cell carcinoma to the larynx from primary lung cancer. PMID:25983415

  7. Laryngeal metastasis from lung cancer

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    Umasankar Kalai

    2015-01-01

    Full Text Available Metastatic tumors of the larynx are rare. The most common tumors metastasizing to the larynx are melanoma and renal cell carcinoma. Bronchogenic carcinoma metastasizing to the larynx has been rarely described. Herein, we report the case of a 49-year-old, chronic smoker, who incidentally had a laryngeal growth detected during flexible bronchoscopy examination for evaluation of suspected lung cancer. Histopathological examination of the laryngeal nodule and the biopsy obtained from the main bronchus growth confirmed the diagnosis of metastatic squamous cell carcinoma to the larynx from primary lung cancer.

  8. 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...

  9. NSG Mice Provide a Better Spontaneous Model of Breast Cancer Metastasis than Athymic (Nude Mice.

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    Madhavi Puchalapalli

    Full Text Available Metastasis is the most common cause of mortality in breast cancer patients worldwide. To identify improved mouse models for breast cancer growth and spontaneous metastasis, we examined growth and metastasis of both estrogen receptor positive (T47D and negative (MDA-MB-231, SUM1315, and CN34BrM human breast cancer cells in nude and NSG mice. Both primary tumor growth and spontaneous metastases were increased in NSG mice compared to nude mice. In addition, a pattern of metastasis similar to that observed in human breast cancer patients (metastases to the lungs, liver, bones, brain, and lymph nodes was found in NSG mice. Furthermore, there was an increase in the metastatic burden in NSG compared to nude mice that were injected with MDA-MB-231 breast cancer cells in an intracardiac experimental metastasis model. This data demonstrates that NSG mice provide a better model for studying human breast cancer metastasis compared to the current nude mouse model.

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

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    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.

  11. Selectins mediate small cell lung cancer systemic metastasis.

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    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.

  12. An unusual metastasis of lung adenocarcinoma: Biceps brachii muscle

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    Muzaffer Sariaydin

    2016-01-01

    Full Text Available Skeletal muscle metastasis of nonsmall cell lung carcinoma (NSCLC is a rare occurrence, and the most effective treatment modality is currently unknown. In this case presentation, we report a patient with NSCLC who underwent palliative radiotherapy for biceps muscle metastasis of NSLCS. Our case was a 49-year-old woman who had lung adenocarcinoma with biceps muscle metastasis. She had been followed up for 2 years due to Stage IV lung adenocarcinoma from whom a biopsy was taken from a painful mass in right arm that was found to be compatible with metastasis of lung adenocarcinoma. She had palliative radiotherapy for her painful mass and systemic chemotherapy was planned. After palliative radiotherapy, the pain originating from the metastatic mass in right biceps muscle alleviated. Palliative radiotherapy can be a valuable treatment option for cases with skeletal muscle metastasis.

  13. Intramedullary conus metastasis from carcinoma lung

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    Mavani, Sandip B.; Nadkarni, Trimurti D.; Goel, Naina A.

    2013-01-01

    A 46-year-old male presented with progressive paraparesis and sensory impairment in both lower limbs since 2 months. He had urinary and bowel incontinence. On examination he had flaccid paraplegia with a sensory level at 11th dorsal vertebral level. Magnetic resonance imaging (MRI) scans of the lumbosacral spine showed an enhancing intramedullary lesion in the conus. The patient underwent excision of the conus mass. Histopathology confirmed the tumor to represent a poorly differentiated metastatic carcinoma from an unknown primary. A positron emission tomography-computed tomography (PET-CT) scan of the whole body revealed hypermetabolic activity in the hilum of the right lung confirmed to be a lung carcinoma on a CT-guided biopsy. The patient was undergoing chemoradiation at 1 month follow-up. The author's literature search has yielded only four other case reports of conus metastasis of which only one is in English literature. The present case report and review of literature are presented. PMID:24381457

  14. Breast cancer lung metastasis: molecular biology and therapeutic implications.

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    Jin, Liting; Han, Bingchen; Siegel, Emily; Cui, Yukun; Giuliano, Armando; Cui, Xiaojiang

    2018-03-26

    Distant metastasis accounts for the vast majority of deaths in patients with cancer. Breast cancer exhibits a distinct metastatic pattern commonly involving bone, liver, lung, and brain. Breast cancer can be divided into different subtypes based on gene expression profiles, and different breast cancer subtypes show preference to distinct organ sites of metastasis. Luminal breast tumors tend to metastasize to bone while basal-like breast cancer (BLBC) displays a lung tropism of metastasis. However, the mechanisms underlying this organ-specific pattern of metastasis still remain to be elucidated. In this review, we will summarize the recent advances regarding the molecular signaling pathways as well as the therapeutic strategies for treating breast cancer lung metastasis.

  15. Gastric metastasis from small cell lung cancer: a case report.

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    Gao, Song; Hu, Xu-Dong; Wang, Su-Zhen; Liu, Ning; Zhao, Wei; Yu, Qing-Xi; Hou, Wen-Hong; Yuan, Shuang-Hu

    2015-02-07

    Small cell lung cancer (SCLC) represents a group of highly malignant tumors that give rise to early and widespread metastases at the time of diagnosis. The preferential metastatic sites are the brain, liver, adrenal glands, bone, and bone marrow. However, metastases of the gastrointestinal system, especially the stomach, are rare; most cases of stomach metastasis are asymptomatic and, as a result, are usually only discovered at autopsy. We report a case of gastric metastasis originating from SCLC. The patient was a 66-year-old man admitted to our hospital due to abdominal pain. He underwent gastroscopy, with the pathological report of the tissue biopsy proving it to be a small cell cancer. Immunohistochemistry was positive for CD56, synaptophysin, and pan-cytokeratin. These results confirmed the diagnosis of gastric metastasis of a neuroendocrine small cell carcinoma from the lung.

  16. Osteogenic sarcoma presenting with lung metastasis.

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    Staddon, Arthur P; Lackman, Richard; Robinson, Keith; Shrager, Joseph B; Warhol, Michael

    2002-01-01

    A patient with osteogenic sarcoma presenting with lung metastases is discussed with attention to appropriate diagnosis, staging, and treatment. Multimodality treatment options using chemotherapy, orthopedic surgery and thoracic surgery are presented. Physical medicine and rehabilitation evaluation and treatment are included. Current research options are discussed.

  17. Spinal metastasis of occult lung carcinoma causing cauda equina syndrome.

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    Kotil, Kadir; Kilinc, Bekir Mahmut; Bilge, Turgay

    2007-04-01

    Cauda equina syndrome (CES) may be caused by tumor, herniated disc, trauma and spinal infections. However, CES due to occult lung cancer has not been reported in the literature. A 50-year-old man presented with a subacute CES caused by an intradural metastasis of an adenocarcinoma of the lung to the lumbosacral cauda fibers. His lumbosacral magnetic resonance imaging (MRI), showed a well-demarcated, intradural extramedullary mass lesion resembling a neurinoma at the L4/5 level. The patient underwent an L4-L5 laminectomy. The operative findings were also suggestive of neurinoma with involvement of three nerve roots, and a well-demarcated tumor without infiltration into the subarachnoid space. Although the findings of the operation were suggestive of neurinoma, final pathological diagnosis revealed metastatic carcinoma. Immunohistochemistry revealed clear cell adenocarcinoma metastasis. Chest X-ray and high resolution contrasted pulmonary computed tomography were normal. Positron emission tomography (PET) showed a lung mass, at the left apex. The patient was treated with chemotherapy and post-operative spinal radiotherapy was also performed. The CES resolved after the operation and the patient was followed up for 2 years with no recurrence. MRI of intradural cauda equina metastasis may be similar to that of intradural nerve sheath tumor. Surgery and postoperative radiotherapy may be effective for the treatment of CES due to lung carcinoma. Definitive diagnosis is by histopathological examination with immunohistochemistry. If the primary cancer cannot be detected by conventional radiological techniques, PET may be helpful.

  18. Interstitial fluid pressure, vascularity and metastasis in ectopic, orthotopic and spontaneous tumours

    International Nuclear Information System (INIS)

    Lunt, Sarah Jane; Kalliomaki, Tuula MK; Brown, Allison; Yang, Victor X; Milosevic, Michael; Hill, Richard P

    2008-01-01

    High tumour interstitial fluid pressure (IFP) has been adversely linked to poor drug uptake in patients, and to treatment response following radiotherapy in cervix cancer patients. In this study we measured IFP values in a selection of murine and xenograft models, spontaneously arising or transplanted either intramuscularly (i/m) or orthotopically and analysed their relationship to tumour vascularity and metastatic spread. KHT-C murine fibrosarcoma, ME180 and SiHa human cervix carcinoma were grown either intramuscularly (i/m), sub-cutaneously (s/c) or orthotopically. Polyoma middle-T (MMTV-PyMT) transgenic spontaneous mammary tumours were studied either as spontaneous tumours or following orthotopic or i/m transplantation. IFP was measured in all tumours using the wick-in-needle method. Spontaneous metastasis formation in the lungs or lymph nodes was assessed in all models. An immunohistochemical analysis of tumour hypoxia, vascular density, lymphatic vascular density and proliferation was carried out in ME180 tumours grown both i/m and orthotopically. Blood flow was also assessed in the ME180 model using high-frequency micro-ultrasound functional imaging. Tumour IFP was heterogeneous in all the models irrespective of growth site: KHT-C i/m: 2–42 mmHg, s/c: 1–14 mmHg, ME180: i/m 5–68 mmHg, cervix 4–21 mmHg, SiHa: i/m 20–56 mmHg, cervix 2–26 mmHg, MMTV-PyMT: i/m: 13–45 mmHg, spontaneous 2–20 mmHg and transplanted 2–22 mmHg. Additionally, there was significant variation between individual tumours growing in the same mouse, and there was no correlation between donor and recipient tumour IFP values. Metastatic dissemination to the lungs or lymph nodes demonstrated no correlation with tumour IFP. Tumour hypoxia, proliferation, and lymphatic or blood vessel density also showed no relationship with tumour IFP. Speckle variance analysis of ultrasound images showed no differences in vascular perfusion between ME180 tumours grown i/m versus orthotopically

  19. New clinically relevant, orthotopic mouse models of human chondrosarcoma with spontaneous metastasis

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    Dass Crispin R

    2010-06-01

    Full Text Available Abstract Background Chondrosarcoma responds poorly to adjuvant therapy and new, clinically relevant animal models are required to test targeted therapy. Methods Two human chondrosarcoma cell lines, JJ012 and FS090, were evaluated for proliferation, colony formation, invasion, angiogenesis and osteoclastogenesis. Cell lines were also investigated for VEGF, MMP-2, MMP-9, and RECK expression. JJ012 and FS090 were injected separately into the mouse tibia intramedullary canal or tibial periosteum. Animal limbs were measured, and x-rayed for evidence of tumour take and progression. Tibias and lungs were harvested to determine the presence of tumour and lung metastases. Results JJ012 demonstrated significantly higher proliferative capacity, invasion, and colony formation in collagen I gel. JJ012 conditioned medium stimulated endothelial tube formation and osteoclastogenesis with a greater potency than FS090 conditioned medium, perhaps related to the effects of VEGF and MMP-9. In vivo, tumours formed in intratibial and periosteal groups injected with JJ012, however no mice injected with FS090 developed tumours. JJ012 periosteal tumours grew to 3 times the non-injected limb size by 7 weeks, whereas intratibial injected limbs required 10 weeks to achieve a similar tumour size. Sectioned tumour tissue demonstrated features of grade III chondrosarcoma. All JJ012 periosteal tumours (5/5 resulted in lung micro-metastases, while only 2/4 JJ012 intratibial tumours demonstrated metastases. Conclusions The established JJ012 models replicate the site, morphology, and many behavioural characteristics of human chondrosarcoma. Local tumour invasion of bone and spontaneous lung metastasis offer valuable assessment tools to test the potential of novel agents for future chondrosarcoma therapy.

  20. Tumor to tumor metastasis: Adenocarcinoma of lung metastatic to meningioma

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    A Talukdar

    2014-01-01

    Full Text Available Tumor-to-tumor metastasis (T2Tmets is an established entity but often overlooked and underdiagnosed. Merely 84 such cases are reported in literature till date. The authors here describe a 65-year-old man presenting with first episode of focal seizure and incidentally turned out to be a case of adenocarcinoma of lung metastatic to a meningioma. The diagnosis of T2Tmets was based solely on histopathological criteria. Recent advent of brain imaging revolutionized its diagnosis and it has moved from the realm of thologists to that of radiologists. In our case, diagnosis was also established by immunohistochemistry.

  1. Nanodiamonds-mediated doxorubicin nuclear delivery to inhibit lung metastasis of breast cancer.

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    Xiao, Jisheng; Duan, Xiaopin; Yin, Qi; Zhang, Zhiwen; Yu, Haijun; Li, Yaping

    2013-12-01

    Lung metastasis is one of the greatest challenges for breast cancer treatment. Here, a nanodiamonds (NDs)-mediated doxorubicin (DOX) delivery system was first designed to inhibit the lung metastasis of breast cancer effectively. DOX was non-covalently bound to NDs via physical adsorption in an aqueous solution, then DSPE-PEG 2K was coated to the NDs-DOX complex (NDX) to increase the dispersibility and prolong the circulation time. DSPE-PEG 2K coating NDX (DNX) displayed high drug loading and excellent ability to deliver DOX to the nucleus, thereby significantly enhancing cytotoxicity and inducing cell apoptosis. Furthermore, DNX showed good histocompatibility and could improve drug accumulation in lung, as a result, markedly inhibited the lung metastasis of breast cancer. The high anti-metastasis efficacy with the decreased systemic toxicity suggested that DNX could be a promising drug delivery system for the therapy of lung metastasis of breast cancer. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Diffuse Interstitial Infiltrative Lung Metastasis of Malignant Melanoma: a Case Report

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    Shin, Na young; Hong, Yoo Jin; Kim, Ah Hyun; Shim, Hyo Sub; Nam, Ji Eun; Lee, Hye Jeong; Kim, Myung Joon [Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2011-04-15

    A diffuse interstitial infiltrative pattern of lung metastasis in a patient with malignant melanoma is rare and can be confused with benign conditions such as pulmonary edema or drug-induced pneumonitis. We experienced a case of diffuse interstitial infiltrative lung metastasis in malignant melanoma in a 37-year-old man. This case was confirmed by a transbronchial lung biopsy. We herein describe the findings on CT and positron emission tomography scan

  3. TRPM5 mediates acidic extracellular pH signaling and TRPM5 inhibition reduces spontaneous metastasis in mouse B16-BL6 melanoma cells

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    Maeda, Toyonobu; Suzuki, Atsuko; Koga, Kaori; Miyamoto, Chihiro; Maehata, Yojiro; Ozawa, Shigeyuki; Hata, Ryu-Ichiro; Nagashima, Yoji; Nabeshima, Kazuki; Miyazaki, Kaoru; Kato, Yasumasa

    2017-01-01

    Extracellular acidity is a hallmark of solid tumors and is associated with metastasis in the tumor microenvironment. Acidic extracellular pH (pHe) has been found to increase intracellular Ca2+ and matrix metalloproteinase-9 (MMP-9) expression by activating NF-κB in the mouse B16 melanoma model. The present study assessed whether TRPM5, an intracellular Ca2+-dependent monovalent cation channel, is associated with acidic pHe signaling and induction of MMP-9 expression in this mouse melanoma model. Treatment of B16 cells with Trpm5 siRNA reduced acidic pHe-induced MMP-9 expression. Enforced expression of Trpm5 increased the rate of acidic pHe-induced MMP-9 expression, as well as increasing experimental lung metastasis. This genetic manipulation did not alter the pHe critical for MMP-9 induction but simply amplified the percentage of inducible MMP-9 at each pHe. Treatment of tumor bearing mice with triphenylphosphine oxide (TPPO), an inhibitor of TRPM5, significantly reduced spontaneous lung metastasis. In silico analysis of clinical samples showed that high TRPM5 mRNA expression correlated with poor overall survival rate in patients with melanoma and gastric cancer but not in patients with cancers of the ovary, lung, breast, and rectum. These results showed that TRPM5 amplifies acidic pHe signaling and may be a promising target for preventing metastasis of some types of tumor. PMID:29108231

  4. TRPM5 mediates acidic extracellular pH signaling and TRPM5 inhibition reduces spontaneous metastasis in mouse B16-BL6 melanoma cells.

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    Maeda, Toyonobu; Suzuki, Atsuko; Koga, Kaori; Miyamoto, Chihiro; Maehata, Yojiro; Ozawa, Shigeyuki; Hata, Ryu-Ichiro; Nagashima, Yoji; Nabeshima, Kazuki; Miyazaki, Kaoru; Kato, Yasumasa

    2017-10-03

    Extracellular acidity is a hallmark of solid tumors and is associated with metastasis in the tumor microenvironment. Acidic extracellular pH (pH e ) has been found to increase intracellular Ca 2+ and matrix metalloproteinase-9 (MMP-9) expression by activating NF-κB in the mouse B16 melanoma model. The present study assessed whether TRPM5, an intracellular Ca 2+ -dependent monovalent cation channel, is associated with acidic pH e signaling and induction of MMP-9 expression in this mouse melanoma model. Treatment of B16 cells with Trpm5 siRNA reduced acidic pH e -induced MMP-9 expression. Enforced expression of Trpm5 increased the rate of acidic pH e -induced MMP-9 expression, as well as increasing experimental lung metastasis. This genetic manipulation did not alter the pH e critical for MMP-9 induction but simply amplified the percentage of inducible MMP-9 at each pH e . Treatment of tumor bearing mice with triphenylphosphine oxide (TPPO), an inhibitor of TRPM5, significantly reduced spontaneous lung metastasis. In silico analysis of clinical samples showed that high TRPM5 mRNA expression correlated with poor overall survival rate in patients with melanoma and gastric cancer but not in patients with cancers of the ovary, lung, breast, and rectum. These results showed that TRPM5 amplifies acidic pH e signaling and may be a promising target for preventing metastasis of some types of tumor.

  5. Mucoepidermoid carcinoma of the conjunctiva with lung metastasis

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    Rishi, Pukhraj; Sharma, Rashi; Subramanian, Krishnakumar; Subramaniam, Nirmala

    2015-01-01

    A 36-year-old lady presented with redness and decreased vision in right eye since 6 months. She was earlier diagnosed of cavitary lung lesion, presumed secondary to tuberculosis and treated with anti-tubercular treatment for 4 months. Examination of affected right eye revealed nil light perception, conjunctival congestion with an exuberant mass in the inferotemporal bulbar conjunctiva, proptosis, iris neovascularization, 360° closed angles, intraocular pressure of 48 mm Hg, exudative retinal detachment, uveal mass and orbital extension. A diagnostic needle biopsy of uveal mass revealed malignant cells. Computed tomography-guided lung biopsy revealed squamous cell carcinoma (SCC), indicating metastatic spread from the orbit. She underwent lid-sparing exenteration of the right eye. Histopathological examination of the orbital tissue revealed mucoepidermoid carcinoma arising from the conjunctiva with extensive invasion into the orbital tissue, muscle fibers, sclera, choroid and optic nerve. Multiple tumor emboli were seen in the lumen of orbital blood vessels. In conclusion, mucoepidermoid carcinoma of the conjunctiva is a rare, aggressive variant of SCC. Early intervention is essential to prevent intraocular invasion and systemic metastasis. PMID:26139812

  6. Mandible ameloblastoma with lung metastasis: a rare case report.

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    Yang, Rui-Na; Wang, Xin-Shuai; Ren, Jing; Xie, Yan-Fei; Zhou, Dan; Ge, Dong-Feng; Feng, Xiao-Shan; Gao, She-Gan

    2015-01-01

    The ameloblastoma is the most common odontogenic epithelial tumor, which belong to benign neoplasms that present a painless course, and usually occur in the oromaxillo-facial region. Although the histopathological manifestation of ameloblastoma is benign, it has unique biological behavior, for example local invasion and recurrence repeatedly. A few case of ameloblastoma was locally aggressive growth, and rarely metastasis to other tissue, for example the lungs, lymph nodes, and spine. A 64-year-old Chinese man, diagnosed with metastatic ameloblastoma, was treated with palliative chemotherapy consisting of cyclophosphamide, doxorubicin, and cisplatin for six cycles, and radiotherapy for 50 Gy after the last cycle chemotherapy. During the surveillance CT scan after the therapy, the tissues of the tumor were nearly complete response. The purpose of this study was to report a case of a patient with a right mandible ameloblastoma that recurred repeatedly and metastasized into bilateral lung. After the chemotherapy and radiotherapy, the tissues of the tumor were nearly complete response. This case is interesting because it investigated the diagnosis and treatment of the malignancy ameloblastoma, as this may help diagnose and treatment for clinician to the metastatic ameloblastoma.

  7. Management of lung cancer brain metastasis: An overview

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    Himanshu Srivastava

    2017-01-01

    Full Text Available With the improvements in systemic treatment for lung cancer, distant metastasis to sanctuary sites such as brain has become an increasingly more important issue. The management of these patients consists of supportive care and disease-directed treatment. Combined modality treatment (surgical resection or radiosurgery, followed by whole brain radiotherapy of brain metastases has greatly improved the local control of disease in patients with single lesion, good functional performance status, and controlled extracranial disease as demonstrated in prospective randomized studies. For patients with multiple brain metastases, conventional fractionated whole brain radiotherapy continues to be a standard and efficacious treatment. At present, experience with the use of molecularly targeted tyrosine kinase inhibitors in nonsmall cell lung cancer patients with activating mutations in the epidermal growth factor receptor gene and anaplastic lymphoma kinase gene is growing. However, their effectiveness in patients with brain metastases is not well established. In the arena of targeted therapies, vascular endothelial growth factor pathway inhibitors such as bevacizumab have shown some activity in brain metastases. Further prospective studies are necessary to facilitate selection of patient subpopulation for targeted agents in future studies.

  8. Mucoepidermoid carcinoma of the conjunctiva with lung metastasis

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    Pukhraj Rishi

    2015-01-01

    Full Text Available A 36-year-old lady presented with redness and decreased vision in right eye since 6 months. She was earlier diagnosed of cavitary lung lesion, presumed secondary to tuberculosis and treated with anti-tubercular treatment for 4 months. Examination of affected right eye revealed nil light perception, conjunctival congestion with an exuberant mass in the inferotemporal bulbar conjunctiva, proptosis, iris neovascularization, 360° closed angles, intraocular pressure of 48 mm Hg, exudative retinal detachment, uveal mass and orbital extension. A diagnostic needle biopsy of uveal mass revealed malignant cells. Computed tomography-guided lung biopsy revealed squamous cell carcinoma (SCC, indicating metastatic spread from the orbit. She underwent lid-sparing exenteration of the right eye. Histopathological examination of the orbital tissue revealed mucoepidermoid carcinoma arising from the conjunctiva with extensive invasion into the orbital tissue, muscle fibers, sclera, choroid and optic nerve. Multiple tumor emboli were seen in the lumen of orbital blood vessels. In conclusion, mucoepidermoid carcinoma of the conjunctiva is a rare, aggressive variant of SCC. Early intervention is essential to prevent intraocular invasion and systemic metastasis.

  9. Small cell lung cancer with metastasis to the thyroid in a patient with toxic multinodular goiter.

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    Ozgu, Eylem Sercan; Gen, Ramazan; Ilvan, Ahmet; Ozge, Cengiz; Polat, Ayşe; Vayisoglu, Yusuf

    2012-11-01

    Thyroid metastasis of lung cancer is rarely observed in clinical practice. The primary cancers which metastasize to the thyroid gland are mostly renal cell carcinoma, lung cancer, and breast cancer. Transient destructive thyrotoxicosis is caused by massive metastasis of extrathyroid tumors. We herein present a case report of a patient with small cell carcinoma of lung with metastasis to the thyroid and thyrotoxicosis due to toxic multinodular goiter. A 66-year-old man complained of swelling around the right side of the neck, dyspnea, progressive weight loss, and palpitation starting since 3 months before his admission. The patient was diagnosed with small cell carcinoma of lung with metastasis to the thyroid and thyrotoxicosis due to toxic multinodular goiter. The case report presented here illustrates the challenge of making a definitive and adequate diagnosis, particularly if the patient presents with 2 potential causes of thyrotoxicosis. Thyroid scintigraphy is an important tool for differential diagnosis of thyrotoxicosis.

  10. Colonic Metastasis with Anemia Leading to a Diagnosis of Primary Lung Adenocarcinoma

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    Vasa Jevremovic

    2016-01-01

    Full Text Available Metastasis occurs with 50% of lung carcinomas, most commonly to lymph nodes, adrenal glands, liver, bone, and brain. It is extremely rare for lung cancer to present with symptoms of a gastrointestinal metastasis and even more so pertaining to the colon. To the best of our knowledge, only 12 such cases have been reported in the literature. We describe a case of a 71-year-old female presenting with refractory iron deficiency anemia that was found to have a lesion in the transverse colon. Pathology revealed adenocarcinoma of the lung and a subsequent lung lesion was discovered in a retrograde fashion.

  11. Use of αv Integrin Linked to Green Fluorescent Protein in Osteosarcoma Cells and Confocal Microscopy to Image Molecular Dynamics During Lung Metastasis in Nude Mice.

    Science.gov (United States)

    Tome, Yasunori; Yano, Shuya; Sugimoto, Naotoshi; Mii, Sumiyuki; Uehara, Fuminari; Miwa, Shinji; Bouvet, Michael; Tsuchiya, Hiroyuki; Kanaya, Fuminori; Hoffman, Robert M

    2016-08-01

    We report here imaging of the behavior of αv integrin linked to green fluorescent protein (GFP) in human osteosarcoma cells colonizing the lung of nude mice. 143B osteosarcoma cells expressing αv integrin-GFP were generated by transfection of an αv integrin-GFP fusion-gene vector pCMV-AC- ITGAV-GFP. In order to generate experimental lung metastases, 143B osteosarcoma cells (1×10(6)), stably expressing αv integrin-GFP, were injected intravenously via the tail vein. The osteosarcoma cells were transplanted orthotopically in the tibia of nude mice in order to generate spontaneous metastases. Lungs were harvested and imaged by confocal microscopy within 1 hour. In the experimental lung-metastasis model, extravasating and deformed osteosarcoma cells expressing αv integrin-GFP were observed. Pseudopodia of the osteosarcoma cells contained small puncta of αv integrin-GFP. In early-stage spontaneous lung metastasis, tumor emboli were observed in pulmonary vessels. At high magnification, small αv integrin-GFP puncta were observed in the tumor embolus. In late-stage spontaneous metastasis, tumor emboli were also observed in pulmonary vessels. Invading cancer cells with strong expression of αv integrin-GFP were observed at the margin of the tumor emboli. The results of this study demonstrate that molecular dynamics of αv integrin-GFP can be imaged in lung metastasis, which will allow further understanding of the role of αv integrin in this process. The results also suggest a general concept for imaging molecular behavior in vivo. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  12. Simultaneous thigh muscle metastasis from lung cancer and Escherichia coli gas producing myonecrosis

    International Nuclear Information System (INIS)

    Martinez, Gonzalo E.; Coursey, Courtney A.; Martinez, Salutario; Dodd, Leslie

    2008-01-01

    We present the case of a 41-year-old man with known large cell lung cancer who had undergone left pneumonectomy 7 months prior and who presented with a large intramuscular mass involving the posterior left thigh and upper calf. This thigh mass was ultimately surgically explored, and specimens yielded both Escherichia coli organisms and cells reflecting a skeletal muscle metastasis from the patient's known lung cancer. The patient was also found to have a rectal metastasis from his lung cancer. Intramuscular abscesses produced by gastrointestinal tract flora are a well-known presentation of colon cancer. To our knowledge, this is the first case report of the simultaneous occurrence of a skeletal muscle metastasis and an E. coli abscess in the same anatomic location. We believe the patient's rectal metastasis may have been the intermediate step in this process. (orig.)

  13. Simultaneous thigh muscle metastasis from lung cancer and Escherichia coli gas producing myonecrosis

    Energy Technology Data Exchange (ETDEWEB)

    Martinez, Gonzalo E. [Hospital Italiano, Department of Radiology, Cordoba (Argentina); Coursey, Courtney A.; Martinez, Salutario [Duke University Medical Center, Department of Radiology, Durham, NC (United States); Dodd, Leslie [Duke University Medical Center, Department of Pathology, Durham, NC (United States)

    2008-08-15

    We present the case of a 41-year-old man with known large cell lung cancer who had undergone left pneumonectomy 7 months prior and who presented with a large intramuscular mass involving the posterior left thigh and upper calf. This thigh mass was ultimately surgically explored, and specimens yielded both Escherichia coli organisms and cells reflecting a skeletal muscle metastasis from the patient's known lung cancer. The patient was also found to have a rectal metastasis from his lung cancer. Intramuscular abscesses produced by gastrointestinal tract flora are a well-known presentation of colon cancer. To our knowledge, this is the first case report of the simultaneous occurrence of a skeletal muscle metastasis and an E. coli abscess in the same anatomic location. We believe the patient's rectal metastasis may have been the intermediate step in this process. (orig.)

  14. Lung uptake on I-131 therapy and short-term outcome in patients with lung metastasis from differentiated thyroid cancer

    International Nuclear Information System (INIS)

    Okamoto, Shozo; Shiga, Tohru; Uchiyama, Yuko; Manabe, Osamu; Kobayashi, Kentaro; Yoshinaga, Keiichiro; Tamaki, Nagara

    2014-01-01

    It is sometimes difficult to assess I-131 lung uptake at the initial I-131 therapy because of strong artifacts from I-131 uptake in the thyroid bed. The aim of this study was to analyze the lung uptake at the second I-131 therapy for lung metastasis in patients who did not have lung uptake at the initial therapy from differentiated thyroid carcinoma (DTC). Then, we also analyzed the relationship between the initial lung uptake and short-term outcome after I-131 therapies. This study included 62 DTC patients with lung metastasis. The patients were classified into 2 groups according to the lung uptake at the initial I-131 therapy such as patients with lung uptake (positive uptake group n=31) and those without lung uptake (negative uptake group n=31). The lung uptake was analyzed at the second therapy in both groups. The short-term outcome was also analyzed based on the CT findings of lung metastasis size and serum thyroglobulin level between the two groups. The positive uptake group showed positive lung uptake at the second therapy in 23 patients (74%), whereas none of negative uptake group showed any lung uptake at the second therapy (P < 0.01). The positive uptake group significantly decreased in the size of lung metastasis from the initial therapy to the second therapy (20.0 ± 11.7 to 16.6 ± 9.6 mm, P < 0.01) with further decrease after the second therapy (P < 0.05). The serum thyroglobulin level was also significantly decreased from the initial therapy to the second therapy (4348 ± 7011 to 2931 ± 4484 ng/ml, P < 0.05). In contrast, the negative uptake group significantly increased in the size of lung metastasis from the initial therapy to the second therapy (17.3 ± 12.2 to 19.9 ± 14.3 mm, P < 0.01) with further increase after the second therapy (P < 0.01). No patients without lung uptake at the initial I-131 therapy showed lung uptake at the second therapy, or showed treatment effect. Therefore, second I-131 therapy for these patients with initially

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

    International Nuclear Information System (INIS)

    Bispo, Irving Gabriel Araujo; Nascimento, Diego Teixeira; Ferreira, Karina Oliveira; Fakhouri, Ricardo; Godinho, Atilano Salvador; Ferrao, Thiago de Oliveira

    2013-01-01

    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)

  16. 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)

  17. Frequency of brain metastasis in adenocarcinoma and large cell carcinoma of the lung: correlation with survival

    International Nuclear Information System (INIS)

    Komaki, R.; Cox, J.D.; Stark, R.

    1983-01-01

    From January 1970 through December 1981, 469 patients with histologically or cytologically proven adenocarcinoma (AC) (349) and large cell carcinoma (LC) (120) of the lung were seen at the Department of Radiation Oncology, Medical College of Wisconsin Affiliated Hospitals. One quarter (126/469) of these patients had brain metastasis: 48 patients presented with brain metastasis and 78 patients subsequently developed brain metastasis. Brain was the dominant site of metastasis in 82 patients who received only cranial + thoracic irradiation; 37 patients (17 simultaneous, 20 metachronous) also required irradiation of other sites of metastasis. All 17 patients with LC, and 47/61 (77%) with AC who developed metachronous brain metastasis did so within one year. The cumulative probability of brain metastasis increased with survival to the levels predicted by autopsy studies. Therapeutic brain irradiation may result in long-term survival in patients with single organ brain metastasis. Since patients with AC and LC so frequently develop brain metastasis and the brain may be the only site of metastasis, prophylactic cranial irradiation may significantly reduce morbidity and mortality from these diseases

  18. Diet Modulation is an Effective Complementary Agent in Preventing and Treating Breast Cancer Lung Metastasis

    Science.gov (United States)

    Zhao, Xiangmin; Rezonzew, Gabriel; Wang, Dezhi; Siegal, Gene P.; Hardy, Robert W.

    2014-01-01

    A significant percentage of breast cancer victims will suffer from metastases indicating that new approaches to preventing breast cancer metastasis are thus needed. Dietary stearate and chemotherapy have been shown to reduce breast cancer metastasis. We tested the complementary use of dietary stearate with a taxol-based chemotherapy which work through separate mechanisms to reduce breast cancer metastasis. We therefore carried out a prevention study in which diets were initiated prior to human MDA-MB-435 cancer cells being injected into the host and a treatment study in which diets were combined with paclitaxel (PTX). Using an orthotopic athymic nude mouse model and three diets (corn oil control diet/CO, low fat /LF or stearate/ST) the prevention study demonstrated that the ST diet decreased the incidence of lung metastasis by 50% compared to both the LF and CO diets. The ST diet also reduced the number and size of metastatic lung nodules compared to the LF diet. Results of the treatment study indicated that both the CO and ST diets decreased the number of mice with lung metastasis compared to the LF diet. Both CO and ST also decreased the number of lung metastases per mouse compared to the LF diet however only the ST diet cohort was significant. Histomorphometric analysis of the lung tumor tissue indicated that the ST diet plus PTX decreased angiogenesis compared to the LF diet plus PTX. In conclusion these results support combining diet with chemotherapy in both treatment and prevention settings. PMID:24832758

  19. Metastasis of Lung Adenocarcinoma to the Gingiva: A Rare Case Report

    Directory of Open Access Journals (Sweden)

    M. Rajini Kanth

    2015-05-01

    Full Text Available Metastatic tumors account for 1% of all oral malignancies. Metastasis to jaw bones is common, particularly in the mandible, rare in the oral soft tissues, and account for only 0.1% of oral malignancies. The majority of metastatic cases (70% reported in the literature have primary tumors located in the lung, breast, kidney, and colon. Metastasis is a biological complex process that involves detachment from the surrounding cells, regulation of cell motility, invasion, survival, proliferation, and evasion of the immune system. Clinical presentation of metastatic tumors is variable, which may create diagnostic dilemma or may lead to erroneous diagnosis. Metastatic tumors clinically mimic as dental infections. Metastasis to the oral soft tissue from lung cancer, especially gingiva is a rare condition. Metastasis to the gingiva can affect the oral function, speech, and nutrition. Most of the cases in the literature reported that lesion presented in oral soft tissues before the diagnosis of primary tumors. Here we report a case of 62-year-old male patient with metastasis from lung to the gingiva, where the metastasis was detected before primary tumor.

  20. Analysis of the ultrasonic image of adrenal metastasis in primary lung cancer

    International Nuclear Information System (INIS)

    Bai Ling; Yang Tao; Tang Ying; Mao Jingning; Chen Wei; Wang Yong; Zhang Yan

    2009-01-01

    Objective: To investigate the ultrasonic image of adrenal metastasis in primary lung cancer. Methods: The ultrasonic imaging characteristics of fourteen patients with adrenal metastasis in primary lung cancer were retrospectively reviewed. In all the cases, US-guided percutaneous biopsy was performed for pathological evaluation during the clinical diagnosis. Results and Conclusion: In ultrasonography the adrenal metastatic tumors were manifested as solitary in all the cases, well-defined in 10 cases, irregularly shaped in 10 cases, hypoechoic in 13 cases, and 1 case showed cystoid structure in the tumor. The maximum diameter of the tumor was 3.0-15.3 cm. 9 cases were metastatic adenocarcinoma. The sonographic appearance of adrenal metastasis in primary lung cancer has its characteristics. Ultrasonography can find adrenal metastalic tumors easily and contribute to diagnosis. (authors)

  1. Gastrointestinal metastasis from primary lung cancer. Case series and systematic literature review.

    Science.gov (United States)

    Balla, Andrea; D Subiela, José; Bollo, Jesús; Martínez, Carmen; Rodriguez Luppi, Carlos; Hernández, Pilar; Pascual-González, Yuliana; Quaresima, Silvia; M Targarona, Eduard

    2018-03-19

    Aim of the present study is to report clinical characteristics and outcomes of patients treated in authors' hospital for GI metastasis from primary lung cancer, and to report and analyse the same data concerning patients retrieved from a systematic literature review. We performed a retrospective analysis of prospectively collected data, and a systematic review using the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. Ninety-one patients were included, 5 patients from the authors' hospital and 86 through PubMed database using the keywords "intestinal metastasis" AND "lung cancer". The median time between primary lung cancer diagnosis and GI metastasis diagnosis was 2 months and the median overall survival was 4 months. This group of patients present a poor prognosis and the gold standard treatment is not defined. None of the reported treatments had a significant impact on survival. Copyright © 2018 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  2. Mint3 in bone marrow-derived cells promotes lung metastasis in breast cancer model mice.

    Science.gov (United States)

    Hara, Toshiro; Murakami, Yoshinori; Seiki, Motoharu; Sakamoto, Takeharu

    2017-08-26

    Breast cancer is one of the most common cancers in women in the world. Although breast cancer is well treatable at the early stage, patients with distant metastases show a poor prognosis. Data from recent studies using transplantation models indicate that Mint3/APBA3 might promote breast cancer malignancy. However, whether Mint3 indeed contributes to tumor development, progression, or metastasis in vivo remains unclear. To address this, here we examined whether Mint3 depletion affects tumor malignancy in MMTV-PyMT breast cancer model mice. In MMTV-PyMT mice, Mint3 depletion did not affect tumor onset and tumor growth, but attenuated lung metastases. Experimental lung metastasis of breast cancer Met-1 cells derived from MMTV-PyMT mice also decreased in Mint3-depleted mice, indicating that host Mint3 expression affected lung metastasis of MMTV-PyMT-derived breast cancer cells. Further bone marrow transplant experiments revealed that Mint3 in bone marrow-derived cells promoted lung metastasis in MMTV-PyMT mice. Thus, targeting Mint3 in bone marrow-derived cells might be a good strategy for preventing metastasis and improving the prognosis of breast cancer patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Orbital metastasis as the presenting symptom of extensive stage small cell lung cancer.

    Science.gov (United States)

    Henning, Michelle; Hu, Qiyue; Siegelmann-Danieli, Nava

    2008-01-01

    Detailed herein are two cases of small cell lung cancer first presenting with orbital metastasis. Orbital metastasis from solid tumors is a rare entity. The predominating primaries in Western countries are breast and lung tumors; hepatocellular and gastric malignancies lead in Japanese series. Clinical symptoms and findings reflect the mass effect and the degree of extra-ocular muscle invasion. Treatment is guided by the cancer type and the tumor histology. The prognosis is grim, and with the exception of rare cases secondary to hormone-responsive tumors, the majority of patients succumb to their disease within a year of diagnosis.

  4. Spontaneous rupture of hepatic metastasis from a thymoma: A case report.

    Science.gov (United States)

    Kim, Ho Jae; Park, Yong Eun; Ki, Min Seo; Lee, Se Ju; Beom, Seung Hun; Han, Dai Hoon; Park, Young Nyun; Park, Jun Yong

    2016-11-28

    Bleeding resulting from spontaneous rupture of the liver is an infrequent but potentially life threatening complication that may be associated with an underlying liver disease. A hepatocellular carcinoma or hepatic adenoma is frequently reported is such cases. However, hemoperitoneum resulting from a hepatic metastatic thymoma is extremely rare. Here, we present a case of a 62-year-old man with hypovolemic shock induced by ruptured hepatic metastasis from a thymoma. At the first hospital admission, the patient had a 45-mm anterior mediastinal mass that was eventually diagnosed as a type A thymoma. The mass was excised, and the patient was disease-free for 6 years. He experienced sudden-onset right upper quadrant pain and was again admitted to our hospital. We noted large hemoperitoneum with a 10-cm encapsulated mass in S5/8 and a 2.3-cm nodular lesion in the right upper quadrant of the abdomen. He was diagnosed with hepatic metastasis from the thymoma, and he underwent chemotherapy and surgical excision.

  5. PPARGC1A is upregulated and facilitates lung cancer metastasis.

    Science.gov (United States)

    Li, Jin-Dong; Feng, Qing-Chuan; Qi, Yu; Cui, Guanghui; Zhao, Song

    2017-10-15

    Lung cancer remains a leading cause of cancer-related mortality, with metastatic progression remaining the single largest cause of lung cancer mortality. Hence it is imperative to determine reliable biomarkers for lung cancer prognosis. We performed quantitative real-time PCR (qRT-PCR) analysis to explore epithelial-mesenchymal transition (EMT) inducers that regulate EMT process in three patients with advanced lung cancer disease. Peroxisome proliferator-activated receptor gamma (PPARGC1A) was uniformly the topmost overexpressed gene in all three human non-small cell lung cancer (NSCLC) patient samples. Further evaluation in human normal lung and metastatic lung cancer cell lines revealed that the expression of PPARGC1A was upregulated in metastatic lung cancer cell lines. Metagenomic analysis revealed direct correlation among PPARGC1A, zinc-finger transcription factor snail homolog 1 (SNAI1), and metastatic lung disease. Upregulation of PPARGC1A transcript expression was independent of a differential upregulation of the upstream AMP-dependent protein kinase (AMPK) activation or steady state expression of the silent mating type information regulation 2 homolog 1 (SIRT1). Xenograft tail vein colonization assays proved that the high expression of PPARGC1A was a prerequisite for metastatic progression of lung cancer to brain. Our results indicate that PPARGC1A might be a potential biomarker for lung cancer prognosis. Copyright © 2017. Published by Elsevier Inc.

  6. Faslodex inhibits estradiol-induced extracellular matrix dynamics and lung metastasis in a model of lymphangioleiomyomatosis.

    Science.gov (United States)

    Li, Chenggang; Zhou, Xiaobo; Sun, Yang; Zhang, Erik; Mancini, John D; Parkhitko, Andrey; Morrison, Tasha A; Silverman, Edwin K; Henske, Elizabeth P; Yu, Jane J

    2013-07-01

    Lymphangioleiomyomatosis (LAM) is a destructive lung disease primarily affecting women. Genetic studies indicate that LAM cells carry inactivating tuberous sclerosis complex (TSC)-2 mutations, and metastasize to the lung. We previously discovered that estradiol increases the metastasis of TSC2-deficient cells in mice carrying xenograft tumors. Here, we investigate the molecular basis underlying the estradiol-induced lung metastasis of TSC2-deficient cells, and test the efficacy of Faslodex (an estrogen receptor antagonist) in a preclinical model of LAM. We used a xenograft tumor model in which estradiol induces the lung metastasis of TSC2-deficient cells. We analyzed the impact of Faslodex on tumor size, the extracellular matrix organization, the expression of matrix metalloproteinase (MMP)-2, and lung metastasis. We also examined the effects of estradiol and Faslodex on MMP2 expression and activity in tuberin-deficient cells in vitro. Estradiol resulted in a marked reduction of Type IV collagen deposition in xenograft tumors, associated with 2-fold greater MMP2 concentrations compared with placebo-treated mice. Faslodex normalized the Type IV collagen changes in xenograft tumors, enhanced the survival of the mice, and completely blocked lung metastases. In vitro, estradiol enhanced MMP2 transcripts, protein accumulation, and activity. These estradiol-induced changes in MMP2 were blocked by Faslodex. In TSC2-deficient cells, estradiol increased MMP2 concentrations in vitro and in vivo, and induced extracellular matrix remodeling. Faslodex inhibits the estradiol-induced lung metastasis of TSC2-deficient cells. Targeting estrogen receptors with Faslodex may be of efficacy in the treatment of LAM.

  7. Long noncoding RNA metastasis-associated lung adenocarcinoma ...

    African Journals Online (AJOL)

    Manal S. Fawzy

    2016-09-22

    Sep 22, 2016 ... a Department of Medical Biochemistry, Faculty of Medicine, Suez Canal University, P.O. 41522, Ismailia, Egypt b Departments of ... qRT-PCR, quantitative reverse transcription polymerase chain reaction; ROC, receiver operating characteristic; TBP, tata binding protein ...... colorectal cancer metastasis.

  8. Air-space pattern in lung metastasis from adenocarcinoma of the GI tract

    Energy Technology Data Exchange (ETDEWEB)

    Gaeta, M.; Volta, S.; Scribano, E. [Univ. of Messina (Italy)] [and others

    1996-03-01

    We retrospectively reviewed a series of proven lung metastasis to evaluate the frequency and CT features of metastases showing an air-space (lepidic) pattern of growth. CT examinations of 65 patients with proven lung metastasis from GI carcinomas were reviewed by three observers. Four CT features were used to classify lesions as air-space metastases: (a) air-space nodules; (b) parenchymal consolidation containing air bronchogram and/or showing angiogram sign; (c) focal or extensive ground-glass opacities; and (d) nodule(s) with a {open_quotes}halo{close_quotes} sign. Six of 65 patients showed air-space metastases: three from pancreatic carcinoma. two from colonic carcinoma, and one from jejunal carcinoma. In one case, metastasis appeared as extensive parenchymal consolidation associated with ground-glass opacities; in one as an area of ground-glass opacity; in one as an extensive parenchymal consolidation with air bronchogram; in one as parenchymal consolidations with angiogram sign and multiple nodules, some of these with halo sign; in one as air-space nodules and patchy air-space consolidations; and in one as a solitary nodule with halo sign. Our study shows that air-space lung metastasis from GI carcinomas is uncommon but not rare. On CT as well as microscopically, differential diagnosis between air-space metastasis and bronchioloalveolar carcinoma may be impossible. 13 refs., 5 figs., 1 tab.

  9. Breast metastasis and lung large-cell neuroendocrine carcinoma: first clinical observation.

    Science.gov (United States)

    Papa, Anselmo; Rossi, Luigi; Verrico, Monica; Di Cristofano, Claudio; Moretti, Valentina; Strudel, Martina; Zoratto, Federica; Minozzi, Marina; Tomao, Silverio

    2017-09-01

    The lung large-cell neuroendocrine carcinoma (LCNEC) is a very rare aggressive neuroendocrine tumor with a high propensity to metastasize and very poor prognosis. We report an atypical presentation of lung LCNEC was diagnosed from a metastatic nodule on the breast. Our patient is a 59-years-old woman that presented in March 2014 nonproductive cough. A CT scan showed multiple brain, lung, adrenal gland and liver secondary lesions; moreover, it revealed a breast right nodule near the chest measuring 1.8 cm. The breast nodule and lung lesions were biopsied and their histology and molecular diagnosis were LCNEC of the lung. To our knowledge, this is the first documented case of breast metastasis from LCNEC of the lung. Furthermore, breast metastasis from extramammary malignancy is uncommon and its diagnosis is difficult but important for proper management and prediction of prognosis. Therefore, a careful clinical history with a thorough clinical examination is needed to make the correct diagnosis. Moreover, metastasis to the breast should be considered in any patient with a known primary malignant tumor history who presents with a breast lump. Anyhow, pathological examination should be performed to differentiate the primary breast cancer from metastatic tumor. Therefore, an accurate diagnosis of breast metastases may not only avoid unnecessary breast resection, more importantly it is crucial to determine an appropriate and systemic treatment. © 2015 John Wiley & Sons Ltd.

  10. Arctigenin Inhibits Lung Metastasis of Colorectal Cancer by Regulating Cell Viability and Metastatic Phenotypes.

    Science.gov (United States)

    Han, Yo-Han; Kee, Ji-Ye; Kim, Dae-Seung; Mun, Jeong-Geon; Jeong, Mi-Young; Park, Sang-Hyun; Choi, Byung-Min; Park, Sung-Joo; Kim, Hyun-Jung; Um, Jae-Young; Hong, Seung-Heon

    2016-08-27

    Arctigenin (ARC) has been shown to have an anti-cancer effect in various cell types and tissues. However, there have been no studies concerning metastatic colorectal cancer (CRC). In this study, we investigated the anti-metastatic properties of ARC on colorectal metastasis and present a potential candidate drug. ARC induced cell cycle arrest and apoptosis in CT26 cells through the intrinsic apoptotic pathway via MAPKs signaling. In several metastatic phenotypes, ARC controlled epithelial-mesenchymal transition (EMT) through increasing the expression of epithelial marker E-cadherin and decreasing the expressions of mesenchymal markers; N-cadherin, vimentin, β-catenin, and Snail. Moreover, ARC inhibited migration and invasion through reducing of matrix metalloproteinase-2 (MMP-2) and MMP-9 expressions. In an experimental metastasis model, ARC significantly inhibited lung metastasis of CT26 cells. Taken together, our study demonstrates the inhibitory effects of ARC on colorectal metastasis.

  11. Arctigenin Inhibits Lung Metastasis of Colorectal Cancer by Regulating Cell Viability and Metastatic Phenotypes

    Directory of Open Access Journals (Sweden)

    Yo-Han Han

    2016-08-01

    Full Text Available Arctigenin (ARC has been shown to have an anti-cancer effect in various cell types and tissues. However, there have been no studies concerning metastatic colorectal cancer (CRC. In this study, we investigated the anti-metastatic properties of ARC on colorectal metastasis and present a potential candidate drug. ARC induced cell cycle arrest and apoptosis in CT26 cells through the intrinsic apoptotic pathway via MAPKs signaling. In several metastatic phenotypes, ARC controlled epithelial-mesenchymal transition (EMT through increasing the expression of epithelial marker E-cadherin and decreasing the expressions of mesenchymal markers; N-cadherin, vimentin, β-catenin, and Snail. Moreover, ARC inhibited migration and invasion through reducing of matrix metalloproteinase-2 (MMP-2 and MMP-9 expressions. In an experimental metastasis model, ARC significantly inhibited lung metastasis of CT26 cells. Taken together, our study demonstrates the inhibitory effects of ARC on colorectal metastasis.

  12. Gingival metastasis from the lung through a needle and a pin: a case report

    International Nuclear Information System (INIS)

    Hentati, D.; Chraiet, N.; Kochbati, L.; Maalej, M.

    2007-01-01

    Gingival metastases are very rare. We report the case of a 47 year-old man presenting with a gingival metastasis from a non small cell lung carcinoma. According to the literature, the most probable way of spread of such metastasis is hematogenous. Local implantation of cancer cells, present in patient's expectoration, in a fragile gingival may be an other pathway of lung cancer metastasizing in this region as we will try to describe in this case report. Cytological and/or histological investigation is needed to assess the malignant and the metastatic character of these gingival lesions. A rapid regression is observed after a flash of external beam radiation; nevertheless metastasis prognosis depends on the primary tumour progress. (authors)

  13. Bladder Metastasis of non-Small Cell Lung Cancer : an Unusual Cause of Hematuria

    NARCIS (Netherlands)

    Karatas, O. Faruk; Bayrak, Reyhan; Yildirim, M. Erol; Bayrak, Omer; Cimentepe, Ersin; Unal, Dogan

    2009-01-01

    Approximately 2% of bladder malignancies are metastatic. The lung cancer makes metastasis sporadically to the bladder. A-69-year-old female patient presented with a history of pain in kidneys, vomiting and hematuria. Cystoscopic examination of the patient revealed small bladder capacity and solitary

  14. Risk of intracranial hemorrhage and cerebrovascular accidents in non-small cell lung cancer brain metastasis patients.

    Science.gov (United States)

    Srivastava, Geetika; Rana, Vishal; Wallace, Suzy; Taylor, Sarah; Debnam, Matthew; Feng, Lei; Suki, Dima; Karp, Daniel; Stewart, David; Oh, Yun

    2009-03-01

    Brain metastases confer significant morbidity and a poorer survival in non-small cell lung cancer (NSCLC). Vascular endothelial growth factor-targeted antiangiogenic therapies (AAT) have demonstrated benefit for patients with metastatic NSCLC and are expected to directly inhibit the pathophysiology and morbidity of brain metastases, yet patients with brain metastases have been excluded from most clinical trials of AAT for fear of intracranial hemorrhage (ICH). The underlying risk of ICH from NSCLC brain metastases is low, but needs to be quantitated to plan clinical trials of AAT for NSCLC brain metastases. Data from MD Anderson Cancer Center Tumor Registry and electronic medical records from January 1998 to March 2006 was interrogated. Two thousand one hundred forty-three patients with metastatic NSCLC registering from January 1998 to September 2005 were followed till March 2006. Seven hundred seventy-six patients with and 1,367 patients without brain metastases were followed till death, date of ICH, or last date of study, whichever occurred first. The incidence of ICH seemed to be higher in those with brain metastasis compared with those without brain metastases, in whom they occurred as result of cerebrovascular accidents. However, the rates of symptomatic ICH were not significantly different. All ICH patients with brain metastasis had received radiation therapy for them and had been free of anticoagulation. Most of the brain metastasis-associated ICH's were asymptomatic, detected during increased radiologic surveillance. The rates of symptomatic ICH, or other cerebrovascular accidents in general were similar and not significantly different between the two groups. In metastatic NSCLC patients, the incidence of spontaneous ICH appeared to be higher in those with brain metastases compared with those without, but was very low in both groups without a statistically significant difference. These data suggest a minimal risk of clinically significant ICH for NSCLC

  15. Lung cancer metastasis to the gastrointestinal system: An enigmatic occurrence

    Science.gov (United States)

    Badipatla, Kanthi Rekha; Yadavalli, Niharika; Vakde, Trupti; Niazi, Masooma; Patel, Harish K

    2017-01-01

    Adenocarcinoma of the lung infrequently metastasizes to the gastrointestinal tract. We report a rare case of a 65-year-old male with no respiratory symptoms diagnosed with adenocarcinoma of the lung by histopathological examination of metastatic sites which included an ulcer in the gastric body and a mass in the rectum. Metastatic disease also involved the liver as well. Patient was treated with systemic chemotherapy but unfortunately expired five months after the diagnosis was made. PMID:28344748

  16. Mammalian mediator 19 mediates H1299 lung adenocarcinoma cell clone conformation, growth, and metastasis.

    Science.gov (United States)

    Xu, Lu-Lu; Guo, Shu-Liang; Ma, Su-Ren; Luo, Yong-Ai

    2012-01-01

    Mammalian mediator (MED) is a multi-protein coactivator that has been identified by several research groups. The involvement of the MED complex subunit 19 (MED 19) in the metastasis of lung adenocarcinoma cell line (H1299), which expresses the MED 19 subunit, was here investigated. When MED 19 expression was decreased by RNA interference H1299 cells demonstrated reduced clone formation, arrest in the S phase of the cell cycle, and lowered metastatic capacity. Thus, MED 19 appears to play important roles in the biological behavior of non-small cell lung carcinoma cells. These findings may be important for the development of novel lung carcinoma treatments.

  17. The economic burden of brain metastasis among lung cancer patients in the United States.

    Science.gov (United States)

    Guérin, A; Sasane, M; Dea, K; Zhang, J; Culver, K; Nitulescu, R; Wu, E Q; Macalalad, A R

    2016-01-01

    Brain metastases among lung cancer patients can impair cognitive and functional ability, complicate care, and reduce survival. This study focuses on the economic burden of brain metastasis in lung cancer-direct healthcare costs to payers and indirect costs to patients, payers, and employers-in the US. Retrospective study using claims data from over 60 self-insured Fortune 500 companies across all US census regions (January 1999-March 2013). Adult, non-elderly lung cancer patients with brain metastasis were evaluated over two study periods: (1) pre-diagnosis (≤30 days prior to first observed lung cancer diagnosis to ≤30 days prior to first-observed brain metastasis diagnosis) and (2) post-diagnosis (≤30 days prior to first observed brain metastasis diagnosis to end of continuous eligibility or observation). Healthcare costs to payers and resource utilization, salary loss to patients, disability payouts for payers, and productivity loss to employers. A total of 132 patients were followed for a median of 8.4 and 6.6 months in the pre- and post-diagnosis periods, respectively. At diagnosis of brain metastasis, 21.2% of patients were on leave of absence and 6.1% on long-term disability leave. Substantial differences were observed in the pre- vs post-diagnosis periods. Specifically, patients incurred much greater healthcare utilization in the post-diagnosis period, resulting in $25,579 higher medical costs per-patient-per-6-months (PPP6M). During this period, patients missed significantly more work days, generating an incremental burden of $2853 PPP6M in salary loss for patients, $2557 PPP6M in disability payments for payers, and $4570 PPP6M in productivity loss for employers. Type of primary lung cancer and extent of brain metastasis could not be assessed in the data. The analysis was also limited to patients with comprehensive disability coverage. Development of brain metastasis among lung cancer patients is associated with a substantial economic burden to payers

  18. MYC is a metastasis gene for non-small-cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Ulf R Rapp

    Full Text Available BACKGROUND: Metastasis is a process by which cancer cells learn to form satellite tumors in distant organs and represents the principle cause of death of patients with solid tumors. NSCLC is the most lethal human cancer due to its high rate of metastasis. METHODOLOGY/PRINCIPAL FINDINGS: Lack of a suitable animal model has so far hampered analysis of metastatic progression. We have examined c-MYC for its ability to induce metastasis in a C-RAF-driven mouse model for non-small-cell lung cancer. c-MYC alone induced frank tumor growth only after long latency at which time secondary mutations in K-Ras or LKB1 were detected reminiscent of human NSCLC. Combination with C-RAF led to immediate acceleration of tumor growth, conversion to papillary epithelial cells and angiogenic switch induction. Moreover, addition of c-MYC was sufficient to induce macrometastasis in liver and lymph nodes with short latency associated with lineage switch events. Thus we have generated the first conditional model for metastasis of NSCLC and identified a gene, c-MYC that is able to orchestrate all steps of this process. CONCLUSIONS/SIGNIFICANCE: Potential markers for detection of metastasis were identified and validated for diagnosis of human biopsies. These markers may represent targets for future therapeutic intervention as they include genes such as Gata4 that are exclusively expressed during lung development.

  19. Lentivirus-mediated shRNA interference targeting SLUG inhibits lung cancer growth and metastasis.

    Science.gov (United States)

    Wang, Yao-Peng; Wang, Ming-Zhao; Luo, Yi-Ren; Shen, Yi; Wei, Zhao-Xia

    2012-01-01

    Lung cancer is a deadly cancer, whose kills more people worldwide than any other malignancy. SLUG (SNAI2, Snail2) is involved in the epithelial mesenchymal transition in physiological and in pathological contexts and is implicated in the development and progression of lung cancer. We constructed a lentivirus vector with SLUG shRNA (LV-shSLUG). LV-shSLUG and a control lentivirus were infected into the non-small cell lung cancer cell A549 and real-time PCR, Western blot and IHC were applied to assess expression of the SLUG gene. Cell proliferation and migration were detected using MTT and clony formation methods. Real-time PCR, Western Blot and IHC results confirmed down-regulation of SLUG expression by its shRNA by about 80%~90% at both the mRNA and protein levels. Knockdown of SLUG significantly suppressed lung cancer cell proliferation. Furthermore, knockdown of SLUG significantly inhibited lung cancer cell invasion and metastasis. Finally, knockdown of SLUG induced the down-regulation of Bcl-2 and up-regulation of E-cadherin. These results indicate that SLUG is a newly identified gene associated with lung cancer growth and metastasis. SLUG may serve as a new therapeutic target for the treatment of lung cancer in the future.

  20. Inhibition of Spontaneous Breast Cancer Metastasis by Anti—Thomsen-Friedenreich Antigen Monoclonal Antibody JAA-F11

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    Jamie Heimburg

    2006-11-01

    Full Text Available Thomsen-Friedenreich antigen (TF-Ag is expressed in many carcinomas, including those of the breast, colon, bladder, prostate. TF-Ag is important in adhesion and metastasis and as a potential immunotherapy target. We hypothesized that passive transfer of JAAF11, an anti -TF-Ag monoclonal antibody, may create a survival advantage for patients with TIF-Ag -expressing tumors by cytotoxicity, blocking of tumor cell adhesion, inhibition of metastasis. This was tested using in vitro models of tumor cell growth; cytotoxicity assays; in vitro, ex vivo, in vivo models of cancer metastasis; and, finally, in vivo effects in mice with metastatic breast cancer. Unlike some anti-TF-Ag antibodies, JAA-F11 did not enhance breast carcinoma cell growth. JAA-F11 did not induce the killing of 4T1 tumor cells through complement-dependent cytotoxicity or apoptotic mechanisms. However, JAA-F11 blocked the stages of metastasis that involve the adhesion of human breast carcinoma cells to human endothelial cells (human umbilical vein endothelial cells and human bone marrow endothelial cells 60 in in vitro static adhesion models, in a perfused ex vivo model, in murine lung vasculature in an in vivo metastatic deposit formation assay. JAA-F11 significantly extended the median survival time of animals bearing metastatic 4T1 breast tumors and caused a > 50% inhibition of lung metastasis.

  1. Gastric cancer metastasis mimicking primary lung cancer - case report and review of the literature

    International Nuclear Information System (INIS)

    Escuissato, Dante Luiz; Ledesma, Jorge Alberto; Urban, Linei Augusta Brolini Delle; Liu, Cristhian Bau; Reis Filho, Jorge Sergio; Oliveira Filho, Adilson Gil; Ferri, Mauricio Beller; Hossaka, Marco Aurelio

    2002-01-01

    Gastric cancer frequently presents intraperitoneal spread. Distant metastasis are rare. The authors describe a case of a 47-year-old white man, long-term cigarette smoker, who had a right upper lobe mass seen on plain films and computed tomography of the chest. A gastric adenocarcinoma was concomitantly diagnosed by endoscopic examination. A bronchoscopy guided biopsy showed that the lung mass was in fact a metastasis from gastric adenocarcinoma. In this article, the imaging findings of gastric cancer and the patterns of dissemination to other organs are reviewed. (author)

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

    International Nuclear Information System (INIS)

    Yamanaka, Kazuhiro; Iwai, Yoshiyasu; Nakajima, Hideki

    2001-01-01

    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)

  3. Ang-2 promotes lung cancer metastasis by increasing epithelial-mesenchymal transition

    Science.gov (United States)

    Zheng, Wenjie; Wang, Li; Fang, Miao; Wu, Mengna; Yao, Min; Yao, Dengfu

    2018-01-01

    Lung cancer is the most common malignant tumor with increasing angiopoietin-2 (Ang-2) and a high rate of metastasis. However, the mechanism of Ang-2 enhancing tumor proliferation and facilitating metastasis remains to be clarified. In this study, Ang-2 expression and its gene transcription on effects of biological behaviors and epithelial-mesenchymal transition (EMT) were investigated in lung cancers. Total incidence of Ang-2 expression in the cancerous tissues was up to 91.8 % (112 of 122) with significantly higher (χ2=103.753, P2=7.883, P=0.005), differentiation degree (χ2=4.554, P=0.033), tumor node metastasis (TNM) staging (χ2=5.039, P=0.025), and 5-year survival rate (χ2 =11.220, P2=18.881, P2=0.81, P=0.776) or III & IV (χ2=1.845, P=0.174). Over-expression of Ang-2 or Ang-2 mRNA in lung A549 and NCI-H1975 cells were identified among different cell lines. When silencing Ang-2 in A549 cells with specific shRNA-1 transfection, the cell proliferation was significantly inhibited in a time-dependent manner, with up-regulating E-cadherin, down-regulating Vimentin, Twist, and Snail expression, and decreasing invasion and metastasis of cancer cell abilities, suggesting that Ang-2 promote tumor metastasis through increasing EMT, and it could be a potential target for lung cancer therapy. PMID:29560103

  4. XCR1 promotes cell growth and migration and is correlated with bone metastasis in non-small cell lung cancer

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    Wang, Ting; Han, Shuai; Wu, Zhipeng; Han, Zhitao; Yan, Wangjun; Liu, Tielong; Wei, Haifeng; Song, Dianwen; Zhou, Wang, E-mail: brilliant212@163.com; Yang, Xinghai, E-mail: cnspineyang@163.com; Xiao, Jianru, E-mail: jianruxiao83@163.com

    2015-08-21

    Bone metastasis occurs in approximately 30–40% patients with advanced non-small cell lung cancer (NSCLC), but the mechanism underlying this bone metastasis remains poorly understood. The chemokine super family is believed to play an important role in tumor metastasis in lung cancer. The chemokine receptor XCR1 has been identified to promote cell proliferation and migration in oral cancer and ovarian carcinoma, but the role of XCR1 in lung cancer has not been reported. In this study, we demonstrated for the first time that XCR1 was overexpressed in lung cancer bone metastasis as compared with that in patients with primary lung cancer. In addition, the XCR1 ligand XCL1 promoted the proliferation and migration of lung cancer cells markedly, and knockdown of XCR1 by siRNA abolished the effect of XCL1 in cell proliferation and migration. Furthermore, we identified JAK2/STAT3 as a novel downstream pathway of XCR1, while XCL1/XCR1 increased the mRNA level of the downstream of JAK2/STAT3 including PIM1, JunB, TTP, MMP2 and MMP9. These results indicate that XCR1 is a new potential therapeutic target for the treatment of lung cancer bone metastasis. - Highlights: • XCR1 is overexpressed in bone metastasis compared with primary NSCLC. • XCR1 activation by XCL1 promotes lung cancer cell proliferation and migration. • JAK2/STAT3 is a novel potential downstream pathway of XCR1.

  5. Lung Metastasis of Primary Alveolar Soft-Part Sarcoma Occurring 20 Years after Initial Treatment

    Directory of Open Access Journals (Sweden)

    R. F. Falkenstern-Ge

    2013-01-01

    Full Text Available A 30-year old woman was referred to our center because of suspicion of a primary lung tumor of the right upper lobe. Histological examination of the lung lesion revealed lung metastasis of a previously treated alveolar soft part sarcoma of the musculus vastus medialis of the right femur, which was resected 20 years ago. Alveolar soft-part sarcoma is a rare malignant tumor that occurs most often in the soft tissue of lower limbs. It is a slow-growing malignant soft tissue tumor arising in muscle tissue, usually in young adults. Due to pleural and extensive mediastinal infiltration with bilateral lung metastases, a systemic treatment with chemotherapy doxorubicin and ifosfamide was initiated. Late metastases from previously treated alveolar part sarcoma should be considered in patients with suspicious lung lesions even if surgical treatment was performed a long time ago.

  6. CXCR4/CXCL12 in Non-Small-Cell Lung Cancer Metastasis to the Brain

    Directory of Open Access Journals (Sweden)

    Sebastiano Cavallaro

    2013-01-01

    Full Text Available Lung cancer represents the leading cause of cancer-related mortality throughout the world. Patients die of local progression, disseminated disease, or both. At least one third of the people with lung cancer develop brain metastases at some point during their disease, even often before the diagnosis of lung cancer is made. The high rate of brain metastasis makes lung cancer the most common type of tumor to spread to the brain. It is critical to understand the biologic basis of brain metastases to develop novel diagnostic and therapeutic approaches. This review will focus on the emerging data supporting the involvement of the chemokine CXCL12 and its receptor CXCR4 in the brain metastatic evolution of non-small-cell lung cancer (NSCLC and the pharmacological tools that may be used to interfere with this signaling axis.

  7. Primary Pulmonary Meningioma Mimicking Lung Metastasis: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Su Wan; Choe, Du Hwan; Lee, Byung Hee; Ko, Jae Soo [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    2009-02-15

    Primary pulmonary meningioma is a very rare tumor and it usually presents as a solitary pulmonary nodule. We report here on a case of primary pulmonary meningioma that was first suspected of being a metastatic lesion from lung cancer, but the correct diagnosis was established after resection. The imaging findings together with a brief literature review are described.

  8. Metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Weller, R.E.

    1991-10-01

    Distant metastasis of primary neoplasms is the main factor that limits the success of antineoplastic therapy. It can be regarded as an early or late event in the neoplastic process, and varies considerably with tumor type. The metastatic potential of a given tumor greatly influences prognosis. Tumor metastasis is not a single neoplastic event, rather, it involves several major steps: invasion of cells from the primary tumor into tissue, and penetration of blood and lymph vessels; release of tumor cell emboli into the circulation; arrest of the emboli in capillary beds of distant organs; invasion of the wall of the arresting vessel, infiltration into adjacent tissue, and multiplication; and growth of vascularized stroma into the new tumor as proliferating tumor cells invade the distant organ. Lodgement and invasion are complex events that are not fully defined. Arrest and lodgement appears to require a thromboembolic event in which the metastatic embolis (1 cell) contacts vascular endothelium and adheres to the wall with thrombis formation following aggregation of platelets and fibrin to the tumor cell(s). Invasion may involve: formation of collagenases by tumor cells; mechanical disruption; chemotactic factors. Metastatic patterns depend on the route of metastasis, tumor type, and target organ (favored soil). In general, carcinomas metastasize via lymphatics and sarcomas via hematogenous routes. Others, melanoma, mast cell tumors, etc., show mixed patterns. This knowledge is important when one is attempting to prognostically stage a tumor, especially when thoracic radiographs are negative. The question of enlarged regional lymph nodes will be discussed in lecture relative to specific tumor types. 4 refs., 1 tab.

  9. Inflammation-Generated Extracellular Matrix Fragments Drive Lung Metastasis

    Directory of Open Access Journals (Sweden)

    Sandrine Bekaert

    2017-12-01

    Full Text Available Mechanisms explaining the propensity of a primary tumor to metastasize to a specific site still need to be unveiled, and clinical studies support a link between chronic inflammation and cancer dissemination to specific tissues. Using different mouse models, we demonstrate the role of inflammation-generated extracellular matrix fragments ac-PGP ( N -acetyl-proline-glycine-proline on tumor cells dissemination to lung parenchyma. In mice exposed to cigarette smoke or lipopolysaccharide, lung neutrophilic inflammation produces increased levels of MMP-9 (matrix metalloproteinase 9 that contributes to collagen breakdown and allows the release of ac-PGP tripeptides. By silencing CXCR2 gene expression in tumor cells, we show that these generated ac-PGP tripeptides exert a chemotactic activity on tumor cells in vivo by binding CXCR2.

  10. Acute Abdomen: A Rare Presentation of Lung Cancer Metastasis

    OpenAIRE

    Guérin, E.; Gilbert, O.; Dequanter, D.

    2009-01-01

    Surgical emergencies caused by bowel metastases from carcinoma of the lung are very rare. We describe two cases of symptomatic gastrointestinal metastatic small cell carcinoma: the first one concerns a 69-year-old man with an acute abdomen and the second is a 72-year-old man complaining of a gastric ulcer symptoms. We also discuss the current management and the prognosis of these patients.

  11. Correlations between EGFR gene polymorphisms and pleural metastasis of lung adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Guo HS

    2016-08-01

    Full Text Available Haisheng Guo,1,* Yunhui Xing,2,* Ailan Mu,1 Xia Li,3 Tingshan Li,4 Xia Bian,1 Chunmei Yang,1 Xiaolei Zhang,1 Yuefen Liu,1 Xunguo Wang1 1Department of Oncology, Dongying People’s Hospital, 2Department of Tuberculosis, Shengli Hospital of Shengli Oil Field, 3Department of Health, 4Personnel Department, Dongying People’s Hospital, Dongying, Shandong, People’s Republic of China *These authors contributed equally to this work Abstract: Proliferation, growth, and differentiation of cells are strictly controlled by the signal system of epidermal growth factor receptor (EGFR. If any link of the EGFR signals system is interfered with or damaged, the proliferation, growth, and differentiation of cells would become uncontrolled. EGFR is overexpressed in a variety of malignant tumors, such as non-small-cell lung cancer, colorectal cancer and breast cancer. Results of the study have proved that EGFR overexpression is closely associated with mutations and variants of the EGFR genes, whose mutations and variants are associated with occurrence, metastasis, and prognosis of different types of tumors, including lung cancer. This study is aimed at investigating whether the polymorphisms of CA simple sequence repeat in intron 1 (CA-SSR1, -216G/T, and R497K in the EGFR are able to induce EGFR activation and whether overexpression is associated with pleural metastasis of lung adenocarcinoma. A total of 432 lung adenocarcinoma patients with pleural metastasis (metastasis group and 424 patients with lung adenocarcinoma but without pleural metastasis (nonmetastasis group were enrolled in this study. For all patients, the CA-SSR1 genotypes were determined by capillary electrophoresis, polymerase chain reaction amplification, and direct DNA sequencing, and the R497K and -216G/T genotypes were determined by polymerase chain reaction amplification and direct DNA sequencing. EGFR expression was evaluated by immunohistochemical staining in primary tumor tissues

  12. Resonance Raman Spectroscopy of human brain metastasis of lung cancer analyzed by blind source separation

    Science.gov (United States)

    Zhou, Yan; Liu, Cheng-Hui; Pu, Yang; Cheng, Gangge; Yu, Xinguang; Zhou, Lixin; Lin, Dongmei; Zhu, Ke; Alfano, Robert R.

    2017-02-01

    Resonance Raman (RR) spectroscopy offers a novel Optical Biopsy method in cancer discrimination by a means of enhancement in Raman scattering. It is widely acknowledged that the RR spectrum of tissue is a superposition of spectra of various key building block molecules. In this study, the Resonance Raman (RR) spectra of human metastasis of lung cancerous and normal brain tissues excited by a visible selected wavelength at 532 nm are used to explore spectral changes caused by the tumor evolution. The potential application of RR spectra human brain metastasis of lung cancer was investigated by Blind Source Separation such as Principal Component Analysis (PCA). PCA is a statistical procedure that uses an orthogonal transformation to convert a set of observations of possibly correlated variables into a set of values of linearly uncorrelated variables called principal components (PCs). The results show significant RR spectra difference between human metastasis of lung cancerous and normal brain tissues analyzed by PCA. To evaluate the efficacy of for cancer detection, a linear discriminant analysis (LDA) classifier is utilized to calculate the sensitivity, and specificity and the receiver operating characteristic (ROC) curves are used to evaluate the performance of this criterion. Excellent sensitivity of 0.97, specificity (close to 1.00) and the Area Under ROC Curve (AUC) of 0.99 values are achieved under best optimal circumstance. This research demonstrates that RR spectroscopy is effective for detecting changes of tissues due to the development of brain metastasis of lung cancer. RR spectroscopy analyzed by blind source separation may have potential to be a new armamentarium.

  13. Anesthesia condition for 18F-FDG imaging of lung metastasis tumors using small animal PET

    International Nuclear Information System (INIS)

    Woo, Sang-Keun; Lee, Tae Sup; Kim, Kyeong Min; Kim, June-Youp; Jung, Jae Ho; Kang, Joo Hyun; Cheon, Gi Jeong; Choi, Chang Woon; Lim, Sang Moo

    2008-01-01

    Small animal positron emission tomography (PET) with 18 F-FDG has been increasingly used for tumor imaging in the murine model. The aim of this study was to establish the anesthesia condition for imaging of lung metastasis tumor using small animal 18 F-FDG PET. Methods: To determine the impact of anesthesia on 18 F-FDG distribution in normal mice, five groups were studied under the following conditions: no anesthesia, ketamine and xylazine (Ke/Xy), 0.5% isoflurane (Iso 0.5), 1% isoflurane (Iso 1) and 2% isoflurane (Iso 2). The ex vivo counting, standard uptake value (SUV) image and glucose SUV of 18 F-FDG in various tissues were evaluated. The 18 F-FDG images in the lung metastasis tumor model were obtained under no anesthesia, Ke/Xy and Iso 0.5, and registered with CT image to clarify the tumor region. Results: Blood glucose concentration and muscle uptake of 18 F-FDG in the Ke/Xy group markedly increased more than in the other groups. The Iso 2 group increased 18 F-FDG uptake in heart compared with the other groups. The Iso 0.5 anesthesized group showed the lowest 18 F-FDG uptake in heart and chest wall. The small size of lung metastasis tumor (2 mm) was clearly visualized by 18 F-FDG image with the Iso 0.5 anesthesia. Conclusion: Small animal 18 F-FDG PET imaging with Iso 0.5 anesthesia was appropriate for the detection of lung metastasis tumor. To acquire 18 F-FDG PET images with small animal PET, the type and level of anesthetic should be carefully considered to be suitable for the visualization of target tissue in the experimental model

  14. Micropapillary Lung Cancer with Breast Metastasis Simulating Primary Breast Cancer due to Architectural Distortion on Images

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    Ko, Kyung Ran; Hong, Eun Kyung; Lee, See Yeon [Center for Breast Cancer, National Cancer Center, Goyang (Korea, Republic of); Ro, Jae Yoon [The Methodist Hospital, Weill Medical College of Cornell University, Houston (United States)

    2012-03-15

    A 47-year-old Korean woman with right middle lobe lung adenocarcinoma, malignant pleural effusion, and multiple lymph node and bone metastases, after three months of lung cancer diagnosis, presented with a palpable right breast mass. Images of the right breast demonstrated architectural distortion that strongly suggested primary breast cancer. Breast biopsy revealed metastatic lung cancer with a negative result for estrogen receptor (ER), progesterone receptor (PR) and mammaglobin, and a positive result for thyroid transcription factor-1 (TTF-1). We present a case of breast metastasis from a case of lung cancer with an extensive micropapillary component, which was initially misinterpreted as a primary breast cancer due to unusual image findings with architectural distortion.

  15. Differential CT features between malignant mesothelioma and pleural metastasis from lung cancer or extra thoracic primary tumor mimicking malignant mesothelioma

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sung Il; Ryu, Young Hoon; Lee, Kwang Hun; Choe, Kyu Ok; Kim, Sang Jin [College of Medicine, Yonsei University, Seoul (Korea, Republic of)

    2000-01-01

    To evaluate the differential CT features found among malignant mesothelioma and pleural metastasis from lung cancer and from extra-thoracic primary tumor which on CT mimic malignant mesothelioma. Forty-four patients who on chest CT scans showed pleural thickening suggesting malignant pleural disease and in whom this condition was pathologically confirmed were included in this study. On the basis of their pathologically proven primary disease (malignant mesothelioma (n=3D14), pleural metastasis of lung cancer (n=3D18), extra thoracic primary tumor (n=3D12). They were divided into three groups. Cases of lung which on CT showed a primary lung nodule or endobronchial mass with pleural lesion, or manifested only pleural effusion, were excluded. The following eight CT features were retrospectively analyzed: (1) configuration of pleural lesion (type I, single or multiple separate nodules, type II, localized flat pleural thickening, type III, diffuse flat pleural thickening; type IV, type III with pleural nodules superimposed; type V, mass filling the hemithorax), (2) the presence of pleural effusion, (3) chest wall or rib invasion, (4) the involvement of a major fissure, (5) extra-pleural fat proliferation, (6) calcified plaque, (7) metastatic lymph nodes, (8) metastatic lung modules. In malignant mesothelioma, type IV (8/14) or II (4/14) pleural thickening was relatively frequent. Pleural metastasis of lung cancer favored type IV (8/18) or I (6/18) pleural thickening, while pleural metastasis from extrathoracic primary tumor showed a variable thickening configuration, except type V. Pleural metastasis from lung cancer and extrapleural primary tumor more frequently showed type I configuration than did malignant mesothelioma, and there were significant differences among the three groups. Fissural involvement, on the other hand, was significantly more frequent in malignant mesothelioma than in pleural metastasis from lung cancer or extrapleural primary tumor. Metastatic

  16. Phyllodes tumor of the breast with lung metastasis

    International Nuclear Information System (INIS)

    Arias Beaton, Ernesto; Oca Santiago, Pedro Montes de; Arias Beaton, Martha Beatriz

    2012-01-01

    The case report of a 63-year-old patient is described, who was admitted to 'Dr. Juan Bruno Zayas Alfonso' Teaching General Hospital of Santiago de Cuba due to persistent dry cough, little expectoration (sometimes yellowish), asthenia and loss of weight. On physical examination a tumor was palpated in the right breast, which was confirmed through sonography and mammogram. The results of the fine-needle biopsy were positive for neoplastic cells, consistent with carcinoma. Chest radiography and computerized axial tomography revealed the presence of lung metastatic images, reason why tumor excision with a safety margin of 2 cm was performed. The presence of phyllodes tumor was confirmed by means of the histopathologic study, so that it was necessary to indicate 3 cycles of chemotherapy (CISCYVADACT scheme), of which only two were administered as the old woman had an unfavorable course and she died 3 months later

  17. Relationship between maximum standardized uptake value (SUVmax) of lung cancer and lymph node metastasis on FDG-PET

    International Nuclear Information System (INIS)

    Nambu, Atsushi; Kato, Satoshi; Okuwaki, Hideto; Nishikawa, Keiichi; Ichikawa, Tomoaki; Araki, Tsutomu; Sato, Yoko; Saito, Akitoshi; Matsumoto, Keiko

    2009-01-01

    The purpose of this study was to evaluate the relationship between standardized uptake value (SUV)max of primary lung cancers on fluorodeoxyglucose-positron emission tomography (FDG-PET) and lymph node metastasis. The subjects were a total of consecutive 66 patients with lung cancer who were examined by FDG-PET and subsequently underwent surgery between October 2004 and January 2008. There were 41 males and 25 females, ranging in age from 45 to 83 years with an average of 68 years. The pathological subtypes of the lung cancers consisted of 49 adenocarcinomas, 11 squamous cell carcinomas, 2 adenosquamous carcinomas, 1 large cell carcinoma, 1 small cell carcinoma, 1 pleomorphic carcinoma and 1 mucoepidermoid carcinoma. We statistically compared the mean SUVmax of lung cancer between the groups with and without lymph node metastasis, the frequency of lymph node metastasis between higher and lower SUVmax of lung cancer groups that were classified by using the median SUVmax of lung cancer, and evaluated the relationship between the SUVmax of lung cancer and frequency of lymph node metastases, and correlations between the SUVmax of lung cancer and number of the metastatic lymph nodes and pathological n stages. The difference in the average of the SUVmax of lung cancer between the cases with and without lymph node metastases was statistically significant (p=0.00513). Lymph node metastasis was more frequently seen in the higher SUVmax of lung cancer group (17/33, 52%) than in the lower SUVmax of lung cancer group (7/33, 21%) with a statistically significant difference. There was no lymph node metastasis in lung cancers with an SUVmax of lung cancer less than 2.5, and lung cancers with an SUVmax of lung cancer more than 12 had a 70% frequency of lymph node metastasis. There were moderate correlations between SUVmax of lung cancer, and the number of the metastatic lymph nodes (γ=0.404, p=0.001) and pathological n stage (γ=0.411, p=0.001). The likelihood of lymph node

  18. Nicotine promotes tumor growth and metastasis in mouse models of lung cancer.

    Directory of Open Access Journals (Sweden)

    Rebecca Davis

    2009-10-01

    Full Text Available Nicotine is the major addictive component of tobacco smoke. Although nicotine is generally thought to have limited ability to initiate cancer, it can induce cell proliferation and angiogenesis in a variety of systems. These properties might enable nicotine to facilitate the growth of tumors already initiated. Here we show that nicotine significantly promotes the progression and metastasis of tumors in mouse models of lung cancer. This effect was observed when nicotine was administered through intraperitoneal injections, or through over-the-counter transdermal patches.In the present study, Line1 mouse adenocarcinoma cells were implanted subcutaneously into syngenic BALB/c mice. Nicotine administration either by intraperitoneal (i.p. injection or transdermal patches caused a remarkable increase in the size of implanted Line1 tumors. Once the tumors were surgically removed, nicotine treated mice had a markedly higher tumor recurrence (59.7% as compared to the vehicle treated mice (19.5%. Nicotine also increased metastasis of dorsally implanted Line1 tumors to the lungs by 9 folds. These studies on transplanted tumors were extended to a mouse model where the tumors were induced by the tobacco carcinogen, NNK. Lung tumors were initiated in A/J mice by i.p. injection of NNK; administration of 1 mg/kg nicotine three times a week led to an increase in the size and the number of tumors formed in the lungs. In addition, nicotine significantly reduced the expression of epithelial markers, E-Cadherin and beta-Catenin as well as the tight junction protein ZO-1; these tumors also showed an increased expression of the alpha(7 nAChR subunit. We believe that exposure to nicotine either by tobacco smoke or nicotine supplements might facilitate increased tumor growth and metastasis.Our earlier results indicated that nicotine could induce invasion and epithelial-mesenchymal transition (EMT in cultured lung, breast and pancreatic cancer cells. This study

  19. Brain metastasis from differentiated thyroid cancer in patients treated with radioiodine for bone and lung lesions

    International Nuclear Information System (INIS)

    Misaki, Takashi; Iwata, Masahiro; Kasagi, Kanji; Konishi, Junji

    2000-01-01

    Brain metastasis of differentiated thyroid cancer (DTC) often is detected during treatment of other remote lesions. We examined the prevalence, risk factors and treatment outcome of this disease encountered during nuclear medicine practice. Of the 167 patients with metastasis to lung or bone treated 1-14 times with radioactive iodine (RAI), 9 (5.4%) also had lesions in the brain. Five were males and 4 females, aged 49-84, out of the original population of 49 males and 118 females aged 10-84 (mean 54.7) years. Three of them underwent removal of their brain tumors, 5 received conventional external beam irradiation, and 2 had stereotactic radiosurgery with supervoltage X-ray. None of the brain lesions showed significant uptake of RAI despite demonstrable accumulation in most extracerebral lesions. Seven patients died 4-23 (mean 9.4) months after the discovery of cerebral metastasis, brain damage being the primary or at least a contributing cause. The 8th and 9th patients remained relatively well for more than 42 and 3 months, respectively, without any evidence of intracranial recurrence. Our results confirmed that the brain is a major site of secondary metastasis from DTC. No statistically significant demographic risk factor was detected. Any suspicious neurological symptoms in the course of RAI treatment warrant cerebral computed tomography. As for therapy, from out initial experience, radiosurgery seemed promising as an effective and less invasive alternative to surgical removal. (author)

  20. Screening and identification of lung cancer metastasis-related genes by suppression subtractive hybridization.

    Science.gov (United States)

    Liu, Jiewei; Zhong, Xiaorong; Li, Juan; Liu, Baoxing; Guo, Shanxian; Chen, Jun; Tan, Qingwei; Wang, Qin; Ma, Wei; Wu, Zhihao; Wang, Haisu; Hou, Mei; Zhang, Hong-Tao; Zhou, Qinghua

    2012-08-01

    Lung cancer metastasis is a complicated process in which multiple stages and multiple genes are involved. There is an urgent need to use new molecular biology techniques to get more systematic information and have a general idea of the molecular events that take place in lung cancer metastasis. The object of this study was to construct the subtracted cDNA libraries of different metastatic potential lung cancer cell lines, NL9980 and L9981, which were established and screened from human lung large cell carcinoma cell line, WCQH-9801.   The forward and reverse subtracted cDNA libraries were constructed in the large cell lung cancer cell lines NL9980 and L9981 with the same heredity background but different metastatic potential, by suppression subtractive hybridization (SSH). The positive clones were preliminarily screened by blue-white colony and precisely identified by PCR. The forward and reverse subtracted libraries were screened and identified by dot blot so as to obtain the clones corresponding to gene segments with differential expression. DNA sequencing was performed to analyze the sequences of differential expression segments, which were then searched and compared using the Basic Local Alignment Search Tool from The National Center for Biotechnology Information NCBI BLAST tools. Quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) and western blotting were performed to confirm the differential expressed genes both on RNA and protein levels.   The forward and reverse subtracted cDNA libraries of the different large cell lung cancer cell lines with metastatic potential were successfully constructed. With blue-white colony and dot blot, 307 positive clones in the forward subtracted library and 78 positive clones in the reverse subtracted library were obtained. Fifty-five clones were successfully sequenced in the forward subtracted library while 31 clones were successfully sequenced in the reverse subtracted library. One new

  1. Genome-wide identification of bone metastasis-related microRNAs in lung adenocarcinoma by high-throughput sequencing.

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    Lin Xie

    Full Text Available BACKGROUND: MicroRNAs (miRNAs are a class of small noncoding RNAs that regulate gene expression at the post-transcriptional level. They participate in a wide variety of biological processes, including apoptosis, proliferation and metastasis. The aberrant expression of miRNAs has been found to play an important role in many cancers. RESULTS: To understand the roles of miRNAs in the bone metastasis of lung adenocarcinoma, we constructed two small RNA libraries from blood of lung adenocarcinoma patients with and without bone metastasis. High-throughput sequencing combined with differential expression analysis identified that 7 microRNAs were down-regulated and 21 microRNAs were up-regulated in lung adenocarcinoma with bone metastasis. A total of 797 target genes of the differentially expressed microRNAs were identified using a bioinformatics approach. Functional annotation analysis indicated that a number of pathways might be involved in bone metastasis, survival of the primary origin and metastatic angiogenesis of lung adenocarcinoma. These include the MAPK, Wnt, and NF-kappaB signaling pathways, as well as pathways involving the matrix metalloproteinase, cytoskeletal protein and angiogenesis factors. CONCLUSIONS: This study provides some insights into the molecular mechanisms that underlie lung adenocarcinoma development, thereby aiding the diagnosis and treatment of the disease.

  2. Urinary bladder metastasis from lung adenocarcinoma: A rare cause of hematuria

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    Kan Wai Man Raymond

    2014-01-01

    Full Text Available We presented an unusual case of hematuria caused by a solitary bladder metastasis from lung adenocarcinoma. A confident diagnosis of secondary adenocarcinoma of the bladder was made by clinical suspicion based on patient′s past history, careful examination of tumor morphology, and a directed panel (cytokeratin [CK] 7/CK20/thyroid transcription factor 1 of immunohistochemistry. We sought, through sharing our experience in the investigative and diagnostic process, to contribute to the better understanding of this unusual cause of hematuria.

  3. Spontaneous rupture of an internal carotid artery aneurysm diagnosed as a peritonsillar abscess, a tonsillar and epipharyngeal carcinoma with metastasis.

    Science.gov (United States)

    Karov, I

    1996-01-01

    The author observed a spontaneous rupture of an internal carotid artery aneurysm with initial manifestations of throat pain and subfebrillity. The condition was diagnosed as peritonsillar abscess. Two days later, a swelling appeared on the same side of the neck, which necessitated a revision of the primary diagnosis and acceptance of another one--a carcinoma of the palatine tonsil with metastasis. A third diagnosis was made on hospitalization--epipharyngeal carcinoma with metastasis. Physical examination disclosed an intact skin of the neck with a right-side tumefaction of a walnut size. The right tonsil was displaced anteriorly and medially. The epi- and hypopharynx were restricted. Simultaneous palpation of the displaced tonsil and the neck tumefaction showed that the lesion was single and pulsated. The pulsations were synchronous with the pulse. Contrast angiography showed an internal carotid artery aneurysm reaching the cranial base. The manifestation of the aneurysm by pains at the throat, subfebrillity, the displacement of the palatine tonsil and the appearance of a neck tumefaction were related to a spontaneous rupture. The absence of a skin lividity was most probably due to the barrier function of the neck fasciae concerning the haematoma.

  4. The motor protein KIF14 inhibits tumor growth and cancer metastasis in lung adenocarcinoma.

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    Pei-Fang Hung

    Full Text Available The motor protein kinesin superfamily proteins (KIFs are involved in cancer progression. The depletion of one of the KIFs, KIF14, might delay the metaphase-to-anaphase transition, resulting in a binucleated status, which enhances tumor progression; however, the exact correlation between KIF14 and cancer progression remains ambiguous. In this study, using loss of heterozygosity and array comparative genomic hybridization analyses, we observed a 30% loss in the regions surrounding KIF14 on chromosome 1q in lung adenocarcinomas. In addition, the protein expression levels of KIF14 in 122 lung adenocarcinomas also indicated that approximately 30% of adenocarcinomas showed KIF14 down-regulation compared with the expression in the bronchial epithelial cells of adjacent normal counterparts. In addition, the reduced expression of KIF14 mRNA or proteins was correlated with poor overall survival (P = 0.0158 and <0.0001, respectively, and the protein levels were also inversely correlated with metastasis (P<0.0001. The overexpression of KIF14 in lung adenocarcinoma cells inhibited anchorage-independent growth in vitro and xenograft tumor growth in vivo. The overexpression and silencing of KIF14 also inhibited or enhanced cancer cell migration, invasion and adhesion to the extracellular matrix proteins laminin and collagen IV. Furthermore, we detected the adhesion molecules cadherin 11 (CDH11 and melanoma cell adhesion molecule (MCAM as cargo on KIF14. The overexpression and silencing of KIF14 enhanced or reduced the recruitment of CDH11 in the membrane fraction, suggesting that KIF14 might act through recruiting adhesion molecules to the cell membrane and modulating cell adhesive, migratory and invasive properties. Thus, KIF14 might inhibit tumor growth and cancer metastasis in lung adenocarcinomas.

  5. Foxa2 and Cdx2 cooperate with Nkx2-1 to inhibit lung adenocarcinoma metastasis.

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    Li, Carman Man-Chung; Gocheva, Vasilena; Oudin, Madeleine J; Bhutkar, Arjun; Wang, Shi Yun; Date, Saya R; Ng, Sheng Rong; Whittaker, Charles A; Bronson, Roderick T; Snyder, Eric L; Gertler, Frank B; Jacks, Tyler

    2015-09-01

    Despite the fact that the majority of lung cancer deaths are due to metastasis, the molecular mechanisms driving metastatic progression are poorly understood. Here, we present evidence that loss of Foxa2 and Cdx2 synergizes with loss of Nkx2-1 to fully activate the metastatic program. These three lineage-specific transcription factors are consistently down-regulated in metastatic cells compared with nonmetastatic cells. Knockdown of these three factors acts synergistically and is sufficient to promote the metastatic potential of nonmetastatic cells to that of naturally arising metastatic cells in vivo. Furthermore, silencing of these three transcription factors is sufficient to account for a significant fraction of the gene expression differences between the nonmetastatic and metastatic states in lung adenocarcinoma, including up-regulated expression of the invadopodia component Tks5long, the embryonal proto-oncogene Hmga2, and the epithelial-to-mesenchymal mediator Snail. Finally, analyses of tumors from a genetically engineered mouse model and patients show that low expression of Nkx2-1, Foxa2, and Cdx2 strongly correlates with more advanced tumors and worse survival. Our findings reveal that a large part of the complex transcriptional network in metastasis can be controlled by a small number of regulatory nodes that function redundantly, and loss of multiple nodes is required to fully activate the metastatic program. © 2015 Li et al.; Published by Cold Spring Harbor Laboratory Press.

  6. Metastasis in soft tissue as the first manifestation of lung cancer: a case report

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    Vakhnina-Vassila, O.; Flokatoula, M.; Vlachou, I.; Petrocheilou, G.; Douvlou, E.; Fragopoulou, L.; Stathopoulou, S.; Kokkinis, C.

    2012-01-01

    Full text: Material and methods: A 54-years-old male was admitted to our hospital with a palpable mass in the anterior sub navel abdominal wall. He had shortness of breath, coughing and fatigue since a month. The patient was a heavy smoker for years. Computed tomography (CT) was used for imaging assessment. Results: In the chest a focal lesion (∼1.6 cm) was detected in the right upper lobe of lung, with pleural extrapolations and coexisted sizeable lymph node swelling in the mediastinum. The findings were compatible with a primary lung tumor. In the abdomen, a solid lesion (4 cm diameter) that was enhanced after contrast injection was recognized in the anterior abdominal wall, medial and left of the mid line below the umbilicus, which adhered to the anterior surface of the left rectus abdominis muscle and showcased in the subcutaneous fat. The lesion was suspected to be a metastasis and its biopsy with a fine needle was performed under CT guidance. We preferred not to puncture the lung lesion in order to prevent complications. The diagnosis was confirmed for an adenocarcinoma. Conclusion: Subcutaneous metastases of lung adenocarcinoma is a rare manifestation of the disease. Contrast enhanced CT plays a great role for the first evaluation of the patient and for scheduling a diagnostic plan

  7. Oncological outcome after lung metastasis in patients presenting with localized chondrosarcoma at extremities: Tokai Musculoskeletal Oncology Consortium study

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    Nakamura T

    2016-07-01

    Full Text Available Tomoki Nakamura,1 Akihiko Matsumine,1 Satoshi Yamada,2 Satoshi Tsukushi,3,4 Katsuhisa Kawanami,5 Takatoshi Ohno,6 Hirohisa Katagiri,7 Hideshi Sugiura,3,8 Kenji Yamada,9 Yoshihisa Yamada,10 Akihiro Sudo,1 Yoshihiro Nishida4 1Department of Orthopaedic Surgery, Mie Graduate School of Medicine, Tsu-City, Mie, 2Department of Orthopedic Surgery, Graduate School of Medical Sciences, Nagoya City University, 3Department of Orthopedic Surgery, Aichi Cancer Center Hospital, 4Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 5Department of Orthopaedic Surgery, Aichi Medical University School of Medicine, Nagakute, 6Department of Orthopaedic Surgery, Gifu University Graduate School of Medicine, Gifu, 7Division of Orthopaedic Oncology, Shizuoka Cancer Center Hospital, Nagaizumi, Shizuoka, 8Department of Physical Therapy, Nagoya University Graduate School Medicine, Nagoya, 9Department of Orthopedic Surgery, Aichi Cancer Center, Aichi Hospital, Okazaki, 10Department of Orthopedic Surgery, Nagoya Memorial Hospital, Nagoya, Aichi, Japan Abstract: The oncological outcome after lung metastasis in patients with chondrosarcoma of the extremities has not been reported. Between June 2000 and June 2013, 179 patients with chondrosarcoma in the extremities were treated at eleven hospitals. Twenty consecutive patients (11.2% developed lung metastases after initial treatment of primary chondrosarcoma in the extremities. We investigated the oncological outcome of 20 chondrosarcoma patients with lung metastasis. There were 14 males and six females with a mean age of 49 years. The mean duration between primary surgery and appearance of lung metastases was 34 months. The mean follow-up period was 48 months. We excluded patients with lung metastasis at the time of presentation from this study. At the final follow-up, four of 20 patients had no evidence of disease, four were alive with disease, and twelve had died of disease. The

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

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    Fabian, Katalin; Gyulai, Marton; Furak, Jozsef

    2016-01-01

    of peritumoral brain edema (p tumors (p = 0.019), in younger patients (= 50 years) (p = 0.042), and in females (p = 0.016). The time to development of brain metastasis was shorter in central than in peripheral lung cancer (5.3 vs. 9.0 months, p = 0.035). Early brain......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

  9. Isolated Splenic Metastasis from Non-Small-Cell Lung Cancer: A Case Report and Review of the Literature

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    Nikolaos Mitsimponas

    2017-07-01

    Full Text Available Metastases to the spleen are rare but have been reported for different tumor entities, including breast cancer, lung cancer, colorectal cancer, ovarian cancer, and melanoma. As an isolated event, splenic metastasis from non-small-cell lung cancer (NSCLC is exceedingly rare. Until now, only 28 cases have been reported in the medical literature. We report the case of a 66-year-old woman with NSCLC (adenocarcinoma who presented with a synchronous, isolated splenic metastasis. Operative removal of both primary tumor and metastasis was not possible due to multiple comorbidities. Therefore, treatment was limited to combined systemic chemotherapy and simultaneous radiation of the primary tumor, which led to partial remission of the disease. Isolated metastasis to the spleen in NSCLC has been reported only 28 times in the medical literature, most often in male patients with right-sided lung tumors, most of which were adenocarcinomas. The majority of patients were asymptomatic with respect to splenic metastasis. About half of the reported cases were isolated metachronous splenic metastases. Splenectomy seems to confer a survival advantage. We review the pertinent medical literature.

  10. Sequential Change of Hypometabolic Metastasis from Non-small-cell Lung Cancer on Brain FDG-PET/CT

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    Park, Soon Ah; Yang, Sei Hoon; Yang, Chung Yong; Choi, Keum Ha [Wonkwang Medical Science, Wonkwang University College of Medicine, Iksan (Korea, Republic of)

    2009-10-15

    A 60-year-old woman, who had non-small-cell lung cancer (NSCLC) in left lower lobe underwent brain F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for evaluation of cerebral metastasis. On follow-up FDG-PET/CT, only hypometaolic lesion was detected and progressed in right frontal lobe at 6 months and 10 months, later. Hypermetabolic metastasis was not detected even at last scan time of FDG-PET/CT. Brain MRI showed brain metastasis in right frontal lobe. As might be expected, the physician should take cerebral metastasis into consideration even though there is only hypometabolic change on subsequent FDG-PET/CT in patients with NSCLC.

  11. Nasal Adenocarcinoma in a Horse with Metastasis to Lung, Liver, and Bone and Review of Metastasis in Nine Horses with Sinonasal Tumors

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    Ashley Hanna

    2015-01-01

    Full Text Available Sinonasal neoplasia metastasizing to distant organs is rare in horses. This case report describes the clinical and imaging findings of a horse with sinonasal neoplasia, which had metastasized to the lung, liver, and humerus. Additionally, the prevalence of sinonasal neoplasia and their incidence of distant metastasis among horses that presented to the Oregon State University Veterinary Teaching Hospital (OSU-VTH were estimated. Of 5,558 equine patients who presented to the OSU-VTH in the last nine years, 1.4% were diagnosed with sinonasal disease and 10.3% of these cases had sinonasal neoplasia with only one having confirmed distant metastasis. This case was an eleven-year-old quarter horse which was evaluated due to a history of a right forelimb lameness of three weeks duration. Two and a half months later he presented again, this time for unilateral epistaxis and persistent right forelimb lameness. Radiography of the right elbow noted an increasingly irregular, periosteal response and osteolytic lesion of the right distal humeral condyle. At the time of the second presentation, nasosinal endoscopy identified a lobulated mass in the region of the ethmoid turbinates. Histopathology of this mass revealed an adenocarcinoma of nasal origin with metastasis to the lung, liver, and right humerus.

  12. Differential effects of drugs targeting cancer stem cell (CSC and non-CSC populations on lung primary tumors and metastasis.

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    Leyre Larzabal

    Full Text Available Cancer stem cells (CSCs are thought to be responsible for tumor initiation and recurrence after chemotherapy. Targeting CSCs and non-CSCs with specific compounds may be an effective approach to reduce lung cancer growth and metastasis. The aim of this study was to investigate the effect of salinomycin, a selective inhibitor of CSCs, with or without combination with paclitaxel, in a metastatic model. To evaluate the effect of these drugs in metastasis and tumor microenvironment we took advantage of the immunocompetent and highly metastatic LLC mouse model. Aldefluor assays were used to analyze the ALDH+/- populations in murine LLC and human H460 and H1299 lung cancer cells. Salinomycin reduced the proportion of ALDH+ CSCs in LLC cells, whereas paclitaxel increased such population. The same effect was observed for the H460 and H1299 cell lines. Salinomycin reduced the tumorsphere formation capacity of LLC by more than 7-fold, but paclitaxel showed no effect. In in vivo experiments, paclitaxel reduced primary tumor volume but increased the number of metastatic nodules (p<0.05, whereas salinomycin had no effect on primary tumors but reduced lung metastasis (p<0.05. Combination of both drugs did not improve the effect of single therapies. ALDH1A1, SOX2, CXCR4 and SDF-1 mRNA levels were higher in metastatic lesions than in primary tumors, and were significantly elevated in both locations by paclitaxel treatment. On the contrary, such levels were reduced (or in some cases did not change when mice were administered with salinomycin. The number of F4/80+ and CD11b+ cells was also reduced upon administration of both drugs, but particularly in metastasis. These results show that salinomycin targets ALDH+ lung CSCs, which has important therapeutic effects in vivo by reducing metastatic lesions. In contrast, paclitaxel (although reducing primary tumor growth promotes the selection of ALDH+ cells that likely modify the lung microenvironment to foster

  13. Sevoflurane suppresses hypoxia-induced growth and metastasis of lung cancer cells via inhibiting hypoxia-inducible factor-1α.

    Science.gov (United States)

    Liang, Hua; Yang, Cheng Xiang; Zhang, Bin; Wang, Han Bing; Liu, Hong Zhen; Lai, Xiao Hong; Liao, Mei Juan; Zhang, Tao

    2015-12-01

    Hypoxia promotes the progression of lung cancer cells. Unfortunately, anesthetic technique might aggravate hypoxia of lung cancer cells. Sevoflurane is a commonly used anesthetic. Its effect on hypoxia-induced aggressiveness of lung cancer cells remains unknown. The aim of the study is to investigate the effects of sevoflurane on hypoxia-induced growth and metastasis of lung cancer cells. As hypoxia-inducible factor-1α (HIF-1α) plays a pivotal role in mediating the adaptation and tolerance of cancer cells under hypoxic microenvironment, the role of HIF-1α in the effect of sevoflurane on hypoxia-induced growth and metastasis has also been elucidated. A549 cells were treated with normoxia, hypoxia, co-treatment of sevoflurane and hypoxia, and dimethyloxaloylglycine (DMOG, a HIF-1α agonist) for 4 h, respectively. MTT assay and colony formation assay were used to evaluate cell growth. Transwell assay was performed to detect invasion and migration ability. The protein level of HIF-1α, X-linked inhibitor of apoptosis protein (XIAP), survivin, fascin, heparanase (HPA), and p38 MAPK were determined by Western blotting. Hypoxia enhanced proliferation and metastatic potential of cells. Sevoflurane could suppress hypoxia-induced growth and metastasis ability of cells. Furthermore, HIF-1α, XIAP, survivin, fascin and HPA were down-regulated significantly by the co-treatment of sevoflurane and hypoxia as compared to hypoxia treatment. DMOG abolished the inhibiting effects of sevoflurane on hypoxia-induced growth and metastasis ability of cells. In addition, sevoflurane partly reversed the increase of p38 MAPK activity that was induced by hypoxia. Sevoflurane could suppress hypoxia-induced growth and metastasis of lung cancer cells, which might be associated with modulating HIF-1α and its down-stream genes. Moreover, p38 MAPK signaling pathway was involved in the regulation of HIF-1α by sevoflurane.

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

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    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

  15. Kaempferol modulates the metastasis of human non-small cell lung cancer cells by inhibiting epithelial-mesenchymal transition

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    Meng Hang

    2015-06-01

    Full Text Available The present study was done to determine whether kaempferol, a natural polyphenol of the flavonoid family, affects Epithelial-Mesenchymal Transition (EMT in non-small cell lung cancer cells. Kaempferol not only inhibited cancer cell proliferation and migration in a dose-dependent manner but also modulated the expression of EMT-related proteins E-cadherin and vimentin which are indispensible to cellular motility, invasiveness and metastasis. These results indicate that kaempferol suppresses non-small cell lung cancer migration by modulating the expression of EMT proteins. Therefore, kaempferol may be useful as a potential anticancer agent for non-small cell lung cancer.

  16. miR-135b Stimulates Osteosarcoma Recurrence and Lung Metastasis via Notch and Wnt/β-Catenin Signaling

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    Hua Jin

    2017-09-01

    Full Text Available Cancer stem cells (CSCs play an important role in osteosarcoma (OS metastasis and recurrence, and both Wnt/β-catenin and Notch signaling are essential for the development of the biological traits of CSCs. However, the mechanism that underlies the simultaneous hyperactivation of both Wnt/β-catenin and Notch signaling in OS remains unclear. Here, we report that expression of miR-135b correlates with the overall and recurrence-free survival of OS patients, and that miR-135b has an activating effect on both Wnt/β-catenin and Notch signaling. The overexpression of miR-135b simultaneously targets multiple negative regulators of the Wnt/β-catenin and Notch signaling pathways, including glycogen synthase kinase-3 beta (GSK3β, casein kinase 1a (CK1α, and ten-eleven translocation 3 (TET3. Therefore, upregulated miR-135b promotes CSC traits, lung metastasis, and tumor recurrence in OS. Notably, antagonizing miR-135b potently inhibits OS lung metastasis, cancer cell stemness, CSC-induced tumor formation, and recurrence in xenograft animal models. These findings suggest that miR-135b mediates the constitutive activation of Wnt/β-catenin and Notch signaling, and that the inhibition of miR-135b is a novel strategy to inhibit tumor metastasis and prevent CSC-induced recurrence in OS. Keywords: osteosarcoma, miR-135b, metastasis, recurrence, Wnt/β-catenin

  17. A pH-Responsive Host-guest Nanosystem Loading Succinobucol Suppresses Lung Metastasis of Breast Cancer.

    Science.gov (United States)

    Dan, Zhaoling; Cao, Haiqiang; He, Xinyu; Zhang, Zhiwen; Zou, Lili; Zeng, Lijuan; Xu, Yan; Yin, Qi; Xu, Minghua; Zhong, Dafang; Yu, Haijun; Shen, Qi; Zhang, Pengcheng; Li, Yaping

    2016-01-01

    Cancer metastasis is the leading reason for the high mortality of breast cancer. Herein, we report on a pH-responsive host-guest nanosystem of succinobucol (PHN) with pH-stimuli controlled drug release behavior to improve the therapeutic efficacy on lung metastasis of breast cancer. PHN was composed of the host polymer of β-cyclodextrin linked with multiple arms of N,N-diisopropylethylenediamine (βCD-DPA), the guest polymer of adamantyl end-capped methoxy poly(ethylene glycol) (mPEG-Ad), and the active agent of succinobucol. PHN comprises nanometer-sized homogenous spherical particles, and exhibits specific and rapid drug release in response to the intracellular acidic pH-stimuli. Then, the anti-metastatic efficacy of PHN is measured in metastatic 4T1 breast cancer cells, which effectively confirms the superior inhibitory effects on cell migration and invasion activities, VCAM-1 expression and cell-cell binding of RAW 264.7 to 4T1 cells. Moreover, PHN can be specifically delivered to the sites of metastatic nodules in lungs, and result in an obviously improved therapeutic efficacy on lung metastasis of breast cancer. Thereby, the pH-responsive host-guest nanosystem can be a promising drug delivery platform for effective treatment of cancer metastasis.

  18. Time course of development of metastasis in irradiated Lewis lung carcinoma

    International Nuclear Information System (INIS)

    Ohizumi, Yukio; Maezawa, Hiroshi; Mori, Tomoyuki

    1988-01-01

    The influence of local irradiation on the development of metastases and primary tumor volume was studied in Lewis lung carcinoma growing intramuscularly in the hind leg of C57BL/6 mice. The time course of development of metastases was determined from the size of the lung colonies at autopsy by determining the growth rate of the colonies. Irradiation within five days after tumor cell injection inhibited the incidence of metastases in accordance with irradiation dose. For irradiation more than seven days after the injection, promotion of metastases was observed around the time of the experiment as a function of irradiation dose and tumor volume. After the irradiation phase, the development of metastases was inhibited in accordance with radiation dose. When delay in metastasis was defined as additional days needed to develop two or ten colonies compared with controls, the relationship between delay and dose was linear. At the regrowth phase of the primary tumor, the incidence of metastases from the irradiated tumor was reduced in comparison with that from unirradiated tumors of the same size. Inhibition of metastases was observed only at 5 Gy and showed slight dose-dependency. Mechanisms in the development of metastases as they related to these findings are also discussed. (autho)

  19. Reduction of experimental human fibrosarcoma lung metastasis in mice by adenovirus-mediated cystatin C overexpression in the host.

    Science.gov (United States)

    Kopitz, Charlotte; Anton, Martina; Gansbacher, Bernd; Krüger, Achim

    2005-10-01

    Tumor cell invasion and metastasis are associated with degradation of components of the extracellular matrix by different proteinases. Among those, papain-like cysteine proteases, such as cathepsin B, seem to play an important role, as they are associated with poor clinical outcome in different cancers. In this study, we tested whether cystatin C, a natural extracellular inhibitor of papain-like cysteine proteases, can inhibit metastasis when overexpressed at the tumor-host interface. Local overexpression of cystatin C in liver and lungs of CD1 nu/nu mice was achieved by gene transfer with a novel adenoviral construct, which also led to the presence of 60 ng/mL of cystatin C in the serum. Three days after gene transfer, these mice were challenged by i.v. inoculation of lacZ-tagged human fibrosarcoma cells (HT1080lacZ-K15), leading to the formation of experimental lung and liver metastases. In this model, formation of experimental metastatic foci correlated with expression of cathepsin B in lungs, whereas there was no correlation with metastasis to the liver. In mice overexpressing cystatin C, the number of lung metastases was significantly reduced by 92%, as compared with mice receiving control adenovirus. The efficacy of extravasation of HT1080lacZ-K15 cells into the liver was not affected, indicating the independence of this process from the activity of cysteine-cathepsins. The present report is the first evidence of successful reduction of metastasis by inhibition of cysteine-cathepsins by cystatin C overexpression in the host microenvironment. Furthermore, organ-specific protease expression during tumor-host cell interactions could affect the success of antiproteolytic intervention against metastasis.

  20. Oligo- and polymetastatic progression in lung metastasis(es patients is associated with specific microRNAs.

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    Yves A Lussier

    Full Text Available RATIONALE: Strategies to stage and treat cancer rely on a presumption of either localized or widespread metastatic disease. An intermediate state of metastasis termed oligometastasis(es characterized by limited progression has been proposed. Oligometastases are amenable to treatment by surgical resection or radiotherapy. METHODS: We analyzed microRNA expression patterns from lung metastasis samples of patients with ≤ 5 initial metastases resected with curative intent. RESULTS: Patients were stratified into subgroups based on their rate of metastatic progression. We prioritized microRNAs between patients with the highest and lowest rates of recurrence. We designated these as high rate of progression (HRP and low rate of progression (LRP; the latter group included patients with no recurrences. The prioritized microRNAs distinguished HRP from LRP and were associated with rate of metastatic progression and survival in an independent validation dataset. CONCLUSION: Oligo- and poly- metastasis are distinct entities at the clinical and molecular level.

  1. Oligo- and polymetastatic progression in lung metastasis(es) patients is associated with specific microRNAs.

    Science.gov (United States)

    Lussier, Yves A; Khodarev, Nikolai N; Regan, Kelly; Corbin, Kimberly; Li, Haiquan; Ganai, Sabha; Khan, Sajid A; Gnerlich, Jennifer L; Gnerlich, Jennifer; Darga, Thomas E; Fan, Hanli; Karpenko, Oleksiy; Paty, Philip B; Posner, Mitchell C; Chmura, Steven J; Hellman, Samuel; Ferguson, Mark K; Weichselbaum, Ralph R

    2012-01-01

    Strategies to stage and treat cancer rely on a presumption of either localized or widespread metastatic disease. An intermediate state of metastasis termed oligometastasis(es) characterized by limited progression has been proposed. Oligometastases are amenable to treatment by surgical resection or radiotherapy. We analyzed microRNA expression patterns from lung metastasis samples of patients with ≤ 5 initial metastases resected with curative intent. Patients were stratified into subgroups based on their rate of metastatic progression. We prioritized microRNAs between patients with the highest and lowest rates of recurrence. We designated these as high rate of progression (HRP) and low rate of progression (LRP); the latter group included patients with no recurrences. The prioritized microRNAs distinguished HRP from LRP and were associated with rate of metastatic progression and survival in an independent validation dataset. Oligo- and poly- metastasis are distinct entities at the clinical and molecular level.

  2. Oligo- and Polymetastatic Progression in Lung Metastasis(es) Patients Is Associated with Specific MicroRNAs

    Science.gov (United States)

    Lussier, Yves A.; Ganai, Sabha; Khan, Sajid A.; Gnerlich, Jennifer; Darga, Thomas E.; Fan, Hanli; Karpenko, Oleksiy; Paty, Philip B.; Posner, Mitchell C.; Chmura, Steven J.; Hellman, Samuel; Ferguson, Mark K.; Weichselbaum, Ralph R.

    2012-01-01

    Rationale Strategies to stage and treat cancer rely on a presumption of either localized or widespread metastatic disease. An intermediate state of metastasis termed oligometastasis(es) characterized by limited progression has been proposed. Oligometastases are amenable to treatment by surgical resection or radiotherapy. Methods We analyzed microRNA expression patterns from lung metastasis samples of patients with ≤5 initial metastases resected with curative intent. Results Patients were stratified into subgroups based on their rate of metastatic progression. We prioritized microRNAs between patients with the highest and lowest rates of recurrence. We designated these as high rate of progression (HRP) and low rate of progression (LRP); the latter group included patients with no recurrences. The prioritized microRNAs distinguished HRP from LRP and were associated with rate of metastatic progression and survival in an independent validation dataset. Conclusion Oligo- and poly- metastasis are distinct entities at the clinical and molecular level. PMID:23251360

  3. Pancreatic metastasis in a case of small cell lung carcinoma: Diagnostic role of fine-needle aspiration cytology and immunocytochemistry

    Directory of Open Access Journals (Sweden)

    Dilip K Das

    2011-01-01

    Full Text Available Small cell lung carcinoma represents a group of highly malignant tumors giving rise to early and widespread metastasis at the time of diagnosis. However, the pancreas is a relatively infrequent site of metastasis by this neoplasm, and there are only occasional reports on its fine needle aspiration (FNA cytology diagnosis. A 66-year-old man presented with extensive mediastinal lymphadenopathy and a mass in the pancreatic tail. Ultrasound-guided FNA smears from the pancreatic mass contained small, round tumor cells with extensive nuclear molding. The cytodiagnosis was metastatic small cell carcinoma. Immunocytochemical staining showed that a variable number of neoplastic cell were positive for cytokeratin, chromogranin A, neurone-specific enolase and synaptophysin but negative for leukocyte common antigen. The trans-bronchial needle aspiration was non-diagnostic, but biopsy was suspicious of a small cell carcinoma. This case represents a rare metastatic lesion in the pancreas from small cell lung carcinoma, diagnosed by FNA cytology.

  4. CXCR4-antagonist Peptide R-liposomes for combined therapy against lung metastasis

    Science.gov (United States)

    Ieranò, Caterina; Portella, Luigi; Lusa, Sara; Salzano, Giuseppina; D'Alterio, Crescenzo; Napolitano, Maria; Buoncervello, Maria; Macchia, Daniele; Spada, Massimo; Barbieri, Antonio; Luciano, Antonio; Barone, Maria Vittoria; Gabriele, Lucia; Caraglia, Michele; Arra, Claudio; De Rosa, Giuseppe; Scala, Stefania

    2016-03-01

    The chemokine CXCL12 activates CXCR4, initiating multiple pathways that control immune cell trafficking, angiogenesis and embryogenesis; CXCR4 is also overexpressed in multiple tumors affecting metastatic dissemination. While there has been great enthusiasm for exploiting the CXCR4-CXCL12 axis as a target in cancer therapy, to date the promise has yet to be fulfilled. A new class of CXCR4-antagonist cyclic peptides was recently developed and the compound named Peptide R was identified as the most active. With the intent to improve the efficacy and biodistribution of Peptide R, stealth liposomes decorated with Peptide R were developed (PL-Peptide R). In vitro PL-Peptide R efficiently inhibited CXCR4-dependent migration and in vivo it significantly reduced lung metastases and increased overall survival in B16-CXCR4 injected C57BL/6 mice. To evaluate if PL-Peptide R could also be a drug delivery system for CXCR4 expressing tumors, the PL-Peptide R was loaded with doxorubicin (DOX) (PL-Peptide R-DOX). PL-Peptide R-DOX efficiently delivered DOX to CXCR4 expressing cell lines with a consequent decrease in the DOX IC50 efficient dose. In vivo, B16-CXCR4 injected C57BL/6 mice treated with PL-Peptide R-DOX developed fewer lung metastases compared to PL-DOX treated mice. This work provides the proof-of-concept to prevent metastasis by using combined nanomedicine.The chemokine CXCL12 activates CXCR4, initiating multiple pathways that control immune cell trafficking, angiogenesis and embryogenesis; CXCR4 is also overexpressed in multiple tumors affecting metastatic dissemination. While there has been great enthusiasm for exploiting the CXCR4-CXCL12 axis as a target in cancer therapy, to date the promise has yet to be fulfilled. A new class of CXCR4-antagonist cyclic peptides was recently developed and the compound named Peptide R was identified as the most active. With the intent to improve the efficacy and biodistribution of Peptide R, stealth liposomes decorated with Peptide

  5. Establishment of an animal model of spontaneous cervical lymph node metastasis of laryngeal squamous cell carcinoma and obtaining laryngocarcinoma cells with high metastatic potential.

    Science.gov (United States)

    Chen, L W; Wang, J L; Zhang, L Y; Yang, S M; Li, C S; Yu, N; Zhao W, J D; Zhao, L D; Li, K; Liu, M B; Zhai, S Q

    2013-01-01

    To establish an animal model of spontaneous cervical lymph node metastasis of laryngeal squamous cell carcinoma and obtain laryngocarcinoma cells with high metastatic potential, laryngeal squamous cell carcinoma cell line HEP-2 in logarithmic phase were inoculated under the lingual margin mucosa of nude mice. HEP-2 cells metastasized to the cervical lymph nodes were isolated, cultured, and re-inoculated under the lingual margin mucosa of nude mice twice. The tumor formation in the tongue and in the cervical lymph nodes was confirmed by pathological examination. Carcinoma cells' ability of invasion and migration was detected by transwell assay. Human specific Alu sequences were detected by PCR, which indicated that the tumor cells originated from human laryngeal squamous cell carcinoma cell line HEP-2. Finally, an animal model of spontaneous lymph node metastasis of laryngeal squamous cell carcinoma was successfully established. Laryngeal squamous cell carcinoma cells with high metastatic potential to lymph nodes were obtained through repeated inoculations. .

  6. Anesthesia condition for {sup 18}F-FDG imaging of lung metastasis tumors using small animal PET

    Energy Technology Data Exchange (ETDEWEB)

    Woo, Sang-Keun; Lee, Tae Sup; Kim, Kyeong Min; Kim, June-Youp; Jung, Jae Ho; Kang, Joo Hyun [Division of Nuclear Medicine and RI Application, Korea Institute of Radiological and Medical Sciences (KIRAMS), Nowon-Gu, Seoul 139-706 (Korea, Republic of); Cheon, Gi Jeong [Division of Nuclear Medicine and RI Application, Korea Institute of Radiological and Medical Sciences (KIRAMS), Nowon-Gu, Seoul 139-706 (Korea, Republic of); Department of Nuclear Medicine, Korea Institute of Radiological and Medical Sciences (KIRAMS), Nowon-Gu, Seoul 139-706 (Korea, Republic of)], E-mail: larry@kcch.re.kr; Choi, Chang Woon; Lim, Sang Moo [Division of Nuclear Medicine and RI Application, Korea Institute of Radiological and Medical Sciences (KIRAMS), Nowon-Gu, Seoul 139-706 (Korea, Republic of); Department of Nuclear Medicine, Korea Institute of Radiological and Medical Sciences (KIRAMS), Nowon-Gu, Seoul 139-706 (Korea, Republic of)

    2008-01-15

    Small animal positron emission tomography (PET) with {sup 18}F-FDG has been increasingly used for tumor imaging in the murine model. The aim of this study was to establish the anesthesia condition for imaging of lung metastasis tumor using small animal {sup 18}F-FDG PET. Methods: To determine the impact of anesthesia on {sup 18}F-FDG distribution in normal mice, five groups were studied under the following conditions: no anesthesia, ketamine and xylazine (Ke/Xy), 0.5% isoflurane (Iso 0.5), 1% isoflurane (Iso 1) and 2% isoflurane (Iso 2). The ex vivo counting, standard uptake value (SUV) image and glucose SUV of {sup 18}F-FDG in various tissues were evaluated. The {sup 18}F-FDG images in the lung metastasis tumor model were obtained under no anesthesia, Ke/Xy and Iso 0.5, and registered with CT image to clarify the tumor region. Results: Blood glucose concentration and muscle uptake of {sup 18}F-FDG in the Ke/Xy group markedly increased more than in the other groups. The Iso 2 group increased {sup 18}F-FDG uptake in heart compared with the other groups. The Iso 0.5 anesthesized group showed the lowest {sup 18}F-FDG uptake in heart and chest wall. The small size of lung metastasis tumor (2 mm) was clearly visualized by {sup 18}F-FDG image with the Iso 0.5 anesthesia. Conclusion: Small animal {sup 18}F-FDG PET imaging with Iso 0.5 anesthesia was appropriate for the detection of lung metastasis tumor. To acquire {sup 18}F-FDG PET images with small animal PET, the type and level of anesthetic should be carefully considered to be suitable for the visualization of target tissue in the experimental model.

  7. Brain metastasis from non-small cell lung cancer (NSCLC). Prognostic importance of the number of involved extracranial organs

    Energy Technology Data Exchange (ETDEWEB)

    Gerdan, L. [University of Luebeck, Department of Radiation Oncology, Luebeck (Germany); University of Luebeck, Section of Nuclear Medicine, Luebeck (Germany); Segedin, B. [Institute of Oncology, Department of Radiation Oncology, Ljubljana (Slovenia); Nagy, V. [Oncology Institute Ion Ciricuta, Department of Radiotherapy, Cluj-Napoca (Romania); Khoa, M.T. [Hanoi Medical University, Department of Nuclear Medicine, Hanoi (Viet Nam); Bach Mai Hospital, Nuclear Medicine and Oncology Center, Hanoi (Viet Nam); Trang, N.T. [Bach Mai Hospital, Nuclear Medicine and Oncology Center, Hanoi (Viet Nam); Schild, S.E. [Mayo Clinic Scottsdale, Department of Radiation Oncology, Scottsdale, AZ (United States); Rades, D. [University of Luebeck, Department of Radiation Oncology, Luebeck (Germany)

    2014-01-15

    This study investigated the potential prognostic value of the number of involved extracranial organs in patients with brain metastasis from non-small cell lung cancer (NSCLC). A total of 472 patients who received whole-brain radiotherapy (WBRT) alone with 5 x 4 Gy or 10 x 3 Gy for brain metastasis from NSCLC were included in this retrospective study. In addition to the number of involved extracranial organs, 6 further potential prognostic factors were investigated including WBRT regimen, age, gender, Karnofsky Performance Score (KPS), number of brain metastases, and the interval from cancer diagnosis to WBRT. Subgroup analyses were performed for patients with metastatic involvement of one (lung vs. bone vs. other metastasis) and two (lung+bone vs. lung+lymph nodes vs. other combinations) extracranial organs. The survival rates at 6 months of the patients with involvement of 0, 1, 2, 3, and ≥4 extracranial organs were 52, 27, 17, 4, and 14%, respectively (p<0.001). On multivariate analysis, the number of involved extracranial organs remained significant (risk ratio 1.32; 95% confidence interval 1.19-1.46; p<0.001). Age <65 years (p=0.004), KPS ≥70 (p<0.001), and only 1-3 brain metastases (p=0.022) were also significantly associated with survival in the multivariate analysis. In the separate analyses of patients with involvement of one and two extracranial organs, survival was not significantly different based on the pattern of extracranial organ involvement. The number of involved extracranial organs is an independent prognostic factor of survival in patients with brain metastasis from NSCLC, irrespective of the pattern of extracranial organ involvement. (orig.)

  8. RYBP Inhibits Progression and Metastasis of Lung Cancer by Suppressing EGFR Signaling and Epithelial-Mesenchymal Transition

    Directory of Open Access Journals (Sweden)

    Xiaoxiao Dinglin

    2017-04-01

    Full Text Available Lung cancer (LC is a common lethal malignancy with rapid progression and metastasis, and Ring1 and YY1 binding protein (RYBP has been shown to suppress cell growth in human cancers. This study aimed to investigate the role of RYBP in LC progression and metastasis. In this study, a total of 149 LC patients were recruited, and the clinical stage of their tumors, metastasis status, survival time, presence of epidermal growth factor receptor (EGFR mutation, and RYBP expression levels were measured. RYBP silencing and overexpression were experimentally performed in LC cell lines and in nude mice, and the expressions of genes in EGFR-related signaling pathways and epithelial-mesenchymal transition (EMT were detected. The results showed that RYBP was downregulated in LC compared with adjacent normal tissues, and low RYBP expression was associated with a more severe clinical stage, high mortality, high metastasis risk, and poor survival. Cell proliferation and xenograft growth were inhibited by RYBP overexpression, whereas proliferation and xenograft growth were accelerated by RYBP silencing. EGFR and phosphorylated-EGFR levels were upregulated when RYBP was silenced, whereas EGFR, p-EGFR, p-AKT, and p-ERK were downregulated when RYBP was overexpressed. Low RYBP expression was related to a high metastasis risk, and metastasized tumors showed low RYBP levels. Cell migration and invasion were promoted by silencing RYBP but were inhibited by overexpressed RYBP. In addition, the EMT marker vimentin showed diminished expression, and E-cadherin was promoted by the overexpression of RYBP. In conclusion, our data suggest that RYBP suppresses cell proliferation and LC progression by impeding the EGFR-ERK and EGFR-AKT signaling pathways and thereby inhibiting cell migration and invasion and LC metastasis through the suppression of EMT.

  9. Brain irradiation for metastasis prevention and radiation treatment of small cell lung cancer metastases into the brain

    International Nuclear Information System (INIS)

    Mikhina, Z.P.; Motorina, L.I.; Glekov, I.V.

    1985-01-01

    The report presents the results of cranial irradiation of 44 small cell lung cancer patients with clinically-identified intracranial metastases and 40 patients - for metastatic spread prevention. Whole brain irradiation was carried out with single doses of 2-4 Gy (total dose - 30-40 Gy) in both groups 5 times weekly. Patients irradiated for metastasis prevention revealed a 3.3 - fold decrease in intracranial metastasis frequency and a good post-treatment tolerance. In the other group, radiation failed to reach tumor lesions in 20%; treatment produced a poor effect in 30%. There was a correlation between survival time, initial expansion of process and tumor response to primary treatment. No relationship was observed between survival time and procedure and duration of cranial irradiation. Prophylactic irradiation may be beneficial in responders to therapy

  10. Longitudinally Extensive Transverse Myelitis with Intramedullary Metastasis of Small-Cell Lung Carcinoma: An Autopsy Case Report

    Directory of Open Access Journals (Sweden)

    Kenya Nishioka

    2013-01-01

    Full Text Available Background. Longitudinally extensive transverse myelitis (LETM is characterized by spinal cord inflammation extending vertically through three or more vertebral segments. The widespread use of MRI revealed LETM more frequency than ever. We report the case of a patient with pathologically confirmed small-cell lung carcinoma metastasis into the spinal cord presenting as LETM. Case Presentation. A 74-year-old man developed rapidly progressive sensorimotor disturbance and vesicorectal dysfunction. T2-weighted magnetic resonance imaging of the spine revealed LETM at the level of from T3 to conus medullaris; gadolinium enhancement showed concurrent tumor in the thoracic spinal cord from T10 to T11. Systemic survey identified a nodular mass in the lung that was verified as small-cell carcinoma. Following initial failed treatment by high-dose steroid, the patient underwent an emergent microsurgical tumor resection. Histological examination was identical with the lung carcinoma. The patient died of tumor progression at the 47th day after admission. At autopsy, only changes of edema were found in the gray matter of the cord, while tumor cells were not noted in it. Conclusion. Metastasis may rarely present symptoms of LETM. Prompt identification of underlying etiology by contrast examination and systemic survey is crucial for the patient assumed as LETM.

  11. Malignant pleural disease is highly associated with subsequent peritoneal metastasis in patients with stage IV non-small cell lung cancer independent of oncogene status.

    Science.gov (United States)

    Patil, Tejas; Aisner, Dara L; Noonan, Sinead A; Bunn, Paul A; Purcell, William T; Carr, Laurie L; Camidge, D Ross; Doebele, Robert C

    2016-06-01

    Peritoneal metastasis from lung cancer is an uncommon clinical event and there are limited data on what factors predict peritoneal progression. This study retrospectively investigated whether patterns of metastatic spread and oncogene status in patients with advanced non-small cell lung cancer (NSCLC) are associated with peritoneal metastasis. Patients with metastatic non-squamous NSCLC (n=410) were identified at the University of Colorado Cancer Center. Sites of metastatic disease and baseline oncogene status (EGFR, ALK, KRAS, or triple negative) were documented via a retrospective chart review. In patients with EGFR mutations who developed peritoneal disease, we documented the presence of known resistance mechanisms. Median time to peritoneal metastasis, time from peritoneal disease to death, and overall survival were collected. Eight percent (33/410) patients in this study developed peritoneal metastasis. Malignant pleural disease at baseline was significantly associated with subsequent peritoneal spread. There was no association between oncogene status and peritoneal metastasis. Three patients with EGFR mutations who developed peritoneal metastasis had documented resistance to tyrosine kinase inhibitors (TKIs) in the ascitic fluid. Median time from stage IV disease to peritoneal metastasis was 16.5 months (range 0.6-108 months). There were no differences in overall survival between patients who developed peritoneal metastasis and those who did not. Malignant pleural disease is highly associated with peritoneal metastasis in patients with advanced NSCLC. The underlying mechanism is not clear. The presence of resistance mutations in ascitic fluid implies that poor drug penetration is unlikely to be the dominant mechanism. Despite being a late clinical finding, there were no differences in overall survival between patients who developed peritoneal metastasis and those who did not. Additional studies exploring treatment related factors in patients with malignant

  12. Imaging of lung metastasis tumor mouse model using [{sup 18}F]FDG small animal PET and CT

    Energy Technology Data Exchange (ETDEWEB)

    Kim, June Youp; Woo, Sang Keun; Lee, Tae Sup [Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul (Korea, Republic of)] (and others)

    2007-02-15

    The purpose of this study is to image metastaic lung melanoma model with optimal pre-conditions for animal handling by using [{sup 18}F]FDG small animal PET and clinical CT. The pre-conditions for lung region tumor imaging were 16-22 h fasting and warming temperature at 30 .deg. C. Small animal PET image was obtained at 60 min postinjection of 7.4 MBq [{sup 18}F]FDG and compared pattern of [{sup 18}F]FDG uptake and glucose standard uptake value (SUVG) of lung region between Ketamine/Xylazine (Ke/Xy) and Isoflurane (Iso) anesthetized group in normal mice. Metastasis tumor mouse model to lung was established by intravenous injection of B16-F10 cells in C57BL/6 mice. In lung metastasis tumor model, [{sup 18}F]FDG image was obtained and fused with anatomical clinical CT image. Average blood glucose concentration in normal mice were 128.0 {+-} 22.87 and 86.0 {+-} 21.65 mg/dL in Ke/Xy group and Iso group, respectively. Ke/Xy group showed 1.5 fold higher blood glucose concentration than Iso group. Lung to Background ratio (L/B) in SUVG image was 8.6 {+-} 0.48 and 12.1 {+-}0.63 in Ke/Xy group and Iso group, respectively. In tumor detection in lung region, [{sup 18}F]FDG image of Iso group was better than that of Ke/Xy group, because of high L/B ratio. Metastatic tumor location in [{sup 18}F]FDG small animal PET image was confirmed by fusion image using clinical CT. Tumor imaging in small animal lung region with [{sup 18}F]FDG small animal PET should be considered pre-conditions which fasting, warming and an anesthesia during [{sup 18}F]FDG uptake. Fused imaging with small animal PET and CT image could be useful for the detection of metastatic tumor in lung region.

  13. Spontaneous Chitin Accumulation in Airways and Age-Related Fibrotic Lung Disease.

    Science.gov (United States)

    Van Dyken, Steven J; Liang, Hong-Erh; Naikawadi, Ram P; Woodruff, Prescott G; Wolters, Paul J; Erle, David J; Locksley, Richard M

    2017-04-20

    The environmentally widespread polysaccharide chitin is degraded and recycled by ubiquitous bacterial and fungal chitinases. Although vertebrates express active chitinases from evolutionarily conserved loci, their role in mammalian physiology is unclear. We show that distinct lung epithelial cells secrete acidic mammalian chitinase (AMCase), which is required for airway chitinase activity. AMCase-deficient mice exhibit premature morbidity and mortality, concomitant with accumulation of environmentally derived chitin polymers in the airways and expression of pro-fibrotic cytokines. Over time, these mice develop spontaneous pulmonary fibrosis, which is ameliorated by restoration of lung chitinase activity by genetic or therapeutic approaches. AMCase-deficient epithelial cells express fibrosis-associated gene sets linked with cell stress pathways. Mice with lung fibrosis due to telomere dysfunction and humans with interstitial lung disease also accumulate excess chitin polymers in their airways. These data suggest that altered chitin clearance could exacerbate fibrogenic pathways in the setting of lung diseases characterized by epithelial cell dysfunction. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Adrenalectomy does not improve survival rates of patients with solitary adrenal metastasis from non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Huang S

    2017-03-01

    Full Text Available Shao-Hong Huang,1,* Qing-Lei Kong,2,* Xue-Xia Chen,3 Jin-Yuan He,1 Jie Qin,4 Zhuang-Gui Chen5,6 1Department of Cardiothoracic Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; 2Department of Emergency, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; 3Department of Nursing, Eastern Hospital of The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; 4Department of Radiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; 5Department of Pediatrics, Pediatric Intensive Care Unit, The Third Affiliated Hospital of Sun Yat-sen University, 6Institution of Respiratory Disease of Sun Yat-sen University, Guangzhou, China *These authors contributed equally to this work Background and purpose: Several case reports and studies have suggested that there is an increased survival rate for patients who undergo resection of solitary adrenal metastasis from non-small cell lung cancer (NSCLC. This study aimed to investigate whether NSCLC patients with solitary adrenal metastasis could gain a higher survival rate after adrenalectomy (ADX when compared with those patients undergoing nonsurgical treatment, and to investigate the potential prognostic factors.Patients and methods: A total of 1,302 NSCLC inpatients’ data from 2001 to 2015 were retrospectively reviewed to identify those with solitary adrenal metastasis. Overall survival for those who underwent both primary resection and ADX was compared to those patients with conservative treatment using the log-rank test. Potential prognostic variables were evaluated with univariate and multivariate analyses including clinical, therapeutic, pathologic, primary and metastatic data.Results: A total of 22 NSCLC patients with solitary adrenal metastasis were identified, with an overall median survival of 11 months (95% confidence interval: 9.4–12.6 months and a 1-year survival rate of 51.4% (95% confidence interval: 29.6%

  15. Functional characterization of recombinant snake venom rhodocytin: rhodocytin mutant blocks CLEC-2/podoplanin-dependent platelet aggregation and lung metastasis.

    Science.gov (United States)

    Sasaki, T; Shirai, T; Tsukiji, N; Otake, S; Tamura, S; Ichikawa, J; Osada, M; Satoh, K; Ozaki, Y; Suzuki-Inoue, K

    2018-02-28

    Essentials We generated recombinant rhodocytin that could aggregate platelets via CLEC-2. Recombinant wild-type rhodocytin formed heterooctamer with four α- and β-subunits. Asp 4 in α-subunit of rhodocytin was required for binding to CLEC-2. Inhibitory mutant of rhodocytin blocked podoplanin-dependent hematogenous metastasis. Background Rhodocytin, a disulfide-linked heterodimeric C-type lectin from Calloselasma rhodostoma consisting of α-subunits and β-subunits, induces platelet aggregation through C-type lectin-like receptor 2 (CLEC-2). CLEC-2 is a physiological binding partner of podoplanin (PDPN), which is expressed on some tumor cell types, and is involved in tumor cell-induced platelet aggregation and tumor metastasis. Thus, modified rhodocytin may be a possible source of anti-CLEC-2 drugs for both antiplatelet and antimetastasis therapy. However, its molecular function has not been well characterized, because of the lack of recombinant rhodocytin that induces platelet aggregation. Objective To produce recombinant rhodocytin, in order to verify its function with mutagenesis, and to develop an anti-CLEC-2 drug based on the findings. Methods We used Chinese hamster ovary cells to express recombinant rhodocytin (wild-type [WT] and mutant), which was analyzed for induction/inhibition of platelet aggregation with light transmission aggregometry, the formation of multimers with blue native PAGE, and binding to CLEC-2 with flow cytometry. Finally, we investigated whether mutant rhodocytin could suppress PDPN-induced metastasis in an experimental lung metastasis mouse model. Results Functional WT] rhodocytin (αWTβWT) was obtained by coexpression of both subunits. Asp4 in α-subunits of rhodocytin was required for CLEC-2 binding. αWTβWT formed a heterooctamer similarly to native rhodocytin. Moreover, an inhibitory mutant of rhodocytin (αWTβK53A/R56A), forming a heterotetramer, bound to CLEC-2 without inducing platelet aggregation, and blocked CLEC-2-PDPN

  16. Metastasis of breast cancer cells to the bone, lung, and lymph nodes promotes resistance to ionizing radiation

    International Nuclear Information System (INIS)

    Hara, Takamitsu; Iwadate, Manabu; Tachibana, Kazunoshin; Waguri, Satoshi; Takenoshita, Seiichi; Hamada, Nobuyuki

    2017-01-01

    Metastasis represents the leading cause of breast cancer deaths, necessitating strategies for its treatment. Although radiotherapy is employed for both primary and metastatic breast cancers, the difference in their ionizing radiation response remains incompletely understood. This study is the first to compare the radioresponse of a breast cancer cell line with its metastatic variants and report that such metastatic variants are more radioresistant. A luciferase expressing cell line was established from human basal-like breast adenocarcinoma MDA-MB-231 and underwent in vivo selections, whereby a cycle of inoculations into the left cardiac ventricle or the mammary fat pad of athymic nude mice, isolation of metastases to the bone, lung and lymph nodes visualized with bioluminescence imaging, and expansion of obtained cells was repeated twice or three times. The established metastatic cell lines were assessed for cell proliferation, wound healing, invasion, clonogenic survival, and apoptosis. The established metastatic cell lines possessed an increased proliferative potential in vivo and were more chemotactic, invasive, and resistant to X-ray-induced clonogenic inactivation and apoptosis in vitro. Breast cancer metastasis to the bone, lung, and lymph nodes promotes radioresistance. (orig.) [de

  17. Metastasis of breast cancer cells to the bone, lung, and lymph nodes promotes resistance to ionizing radiation.

    Science.gov (United States)

    Hara, Takamitsu; Iwadate, Manabu; Tachibana, Kazunoshin; Waguri, Satoshi; Takenoshita, Seiichi; Hamada, Nobuyuki

    2017-10-01

    Metastasis represents the leading cause of breast cancer deaths, necessitating strategies for its treatment. Although radiotherapy is employed for both primary and metastatic breast cancers, the difference in their ionizing radiation response remains incompletely understood. This study is the first to compare the radioresponse of a breast cancer cell line with its metastatic variants and report that such metastatic variants are more radioresistant. A luciferase expressing cell line was established from human basal-like breast adenocarcinoma MDA-MB-231 and underwent in vivo selections, whereby a cycle of inoculations into the left cardiac ventricle or the mammary fat pad of athymic nude mice, isolation of metastases to the bone, lung and lymph nodes visualized with bioluminescence imaging, and expansion of obtained cells was repeated twice or three times. The established metastatic cell lines were assessed for cell proliferation, wound healing, invasion, clonogenic survival, and apoptosis. The established metastatic cell lines possessed an increased proliferative potential in vivo and were more chemotactic, invasive, and resistant to X‑ray-induced clonogenic inactivation and apoptosis in vitro. Breast cancer metastasis to the bone, lung, and lymph nodes promotes radioresistance.

  18. Whole brain radiation with supplementary boost for patients for unique brain metastasis from a primitive lung cancer

    International Nuclear Information System (INIS)

    Levy, A.; Lamproglou, I.; Chargari, C.; Mazeron, J.J.; Krzisch, C.; Assouline, A.

    2011-01-01

    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)

  19. Promoter methylation is not associated with FLCN irregulation in lung cyst lesions of primary spontaneous pneumothorax.

    Science.gov (United States)

    Ding, Yibing; Zou, Wei; Zhu, Chengchu; Min, Haiyan; Ma, Dehua; Chen, Baofu; Ye, Minhua; Pan, Yanqing; Cao, Lei; Wan, Yueming; Zhu, Qiuxiang; Xia, Haizhen; Zhang, Wenwen; Feng, Ying; Gao, Qian; Yi, Long

    2015-11-01

    Germline mutations in FLCN are responsible for ~10% of patients with primary spontaneous pneumothorax (PSP), characterized by multiple lung cysts in the middle/lower lobes and recurrent pneumothorax. These clinical features are also observed in a substantial portion of patients with sporadic PSP exhibiting no FLCN coding mutations. To assess the potential underlying mechanisms, 71 patients with PSP were selected, including 69 sporadic and 2 familial cases, who bared FLCN mutation‑like lung cysts, however, harbored no FLCN protein‑altering mutations. Notably, in a significant proportion of the patients, FLCN irregulation was observed at the transcript and protein levels. Genetic analyses of the cis‑regulatory region of FLCN were performed by sequencing and multiplex ligation‑dependent probe amplification assay. No inheritable DNA defect was detected, with the exception of a heterozygous deletion spanning the FLCN promoter, which was identified in a family with PSP. This mutation caused a reduction in the expression of FLCN in the lung cysts. Pedigree analysis demonstrated that haploinsufficiency of FLCN was pathogenic. To determine whether epigenetic mechanisms may be involved in the irregulation of FLCN, the promoter methylation status was measured in the remainder of the patients. No evidence of FLCN promoter methylation was demonstrated. The present study suggested that FLCN irregulation in lung cysts of PSP is not associated with promoter methylation.

  20. Renal Impairment Hampers Bisphosphonate Treatment in a Quarter of Lung Cancer Patients with Bone Metastasis

    DEFF Research Database (Denmark)

    Fabian, Katalin; Puskás, Rita; Kakuk, Tímea

    2017-01-01

    Renal function impairment in lung cancer patients with bone metastases was investigated, as this can limit the application of bisphosphonates representing the gold standard in the management of such cases. Clinicopathological data of 570 lung cancer patients were retrospectively analysed for chan......Renal function impairment in lung cancer patients with bone metastases was investigated, as this can limit the application of bisphosphonates representing the gold standard in the management of such cases. Clinicopathological data of 570 lung cancer patients were retrospectively analysed...

  1. Accelerated Fractionation In The Treatment of Brain Metastasis From Non-Small Cell Carcinoma of The Lung

    International Nuclear Information System (INIS)

    Hong, Seong Eon

    1994-01-01

    Purpose: Metastatic cancer to the brain is a major problem for the patients with bronchogenic carcinoma, and most of these patients have a limited survival expectancy. To increase tumor control and/or to decrease late morbidity with possible shortening in over-all treatment period, multiple daily fraction technique for brain metastasis was performed. The author represented the results of accelerated fractionation radiotherapy in patients with brain metastases from non-small cell lung cancer. Materials and Methods: Twenty-six patients with brain metastases from non-small cell lung cancer between 1991 and 1993 received brain radiotherapy with a total dose of 48 Gy, at 2 Gy per fraction, twice a day with a interfractional period of 6 hours, and delivered 5 days a week. The whole brain was treated to 40 Gy and boost dose escalated to 8 Gy for single metastatic lesion by reduced field. Twenty-four of the 26 patients completed the radiotherapy. Radiotherapy was interrupted in two patients suggesting progressive intracerebral disease. Results: This radiotherapy regimen appears to be comparable to the conventional schema in relief from symptoms. Three of the 24 patients experienced nausea and or vomiting during the course of treatment because of acute irradiation toxicity. The author observed no excessive toxicity with escalating dose of irradiation. An increment in median survival, although not statistically significant (p>0.05), was noted with escalating doses(48 Gy) of accelerated fractionation (7 months) compared to conventional treatment(4.5 months). Median survival also increased in patients with brain solitary metastasis(9 months) compared to multiple extrathoracic sites(4 months), and in patients with good performance status(9 months versus 3.5 months), they were statistically significant(p<0.01). Conclusion: The increment in survival in patients with good prognostic factors such as controlled primary lesion, metastasis in brain only, and good performance status

  2. Risk factors of lymph node metastasis in patients with non-small cell lung cancer ≤ 2 cm in size: A monocentric population-based analysis.

    Science.gov (United States)

    Yu, Xiyan; Li, Yanwen; Shi, Chunlei; Han, Baohui

    2018-01-01

    This study was designed to determine the risk factors of lymph node metastasis in non-small cell lung cancer (NSCLC) patients with tumors ≤ 2 cm, using the Shanghai Chest Hospital Lung Cancer Database. Five hundred and eighteen patients with NSCLC ≤ 2 cm were included in this study, and were classified into lymph node-positive and lymph node-negative groups. Univariate and multivariate logistic regression analyses were performed to select the independent risk factors for lymph node metastasis in NSCLC patients. No evidence of metastasis was found in tumors ≤ 1 cm, all positive results were in tumors sized 1-2 cm. Imaging characteristics, including solid and part-solid nodules, were strongly associated with lymph node metastasis (odds ratio [OR] 24.959, 95% confidence interval [CI] 5.999-103.835, P 1 cm. Size had a great impact on lymph node metastasis, especially tumors of 1-2 cm. Preoperative imaging, non-adeno non-squamous carcinoma, pleural invasion, and carcinoembryonic antigen all indicated lymph node dissection. There was no discrepancy between N1 and N2 positive lymph nodes. © 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

  3. Long-term survival and low effective cumulative radioiodine doses to achieve remission in patients with 131Iodine-avid lung metastasis from differentiated thyroid cancer.

    Science.gov (United States)

    Pitoia, Fabián; Bueno, Fernanda; Cross, Graciela

    2014-09-01

    To evaluate long-term survival and response to RAI treatment in patients with differentiated thyroid cancer (DTC) and 131Iodine-avid metastatic lung disease. A retrospective review of 639 DTC patients followed-up at the Hospital de Clínicas, Buenos Aires, Argentina, showed that 42 (6%) patients had lung metastasis, and 24 patients were included for analysis. Seventeen were women, and 7 were men (F:M=2.4:1). Eighteen patients (75%) had PTC, and 6 (25%) had FTC. The median age at diagnosis was older than 45 years in 50%, and the median follow-up was 13 years. Good response to treatment (GRT: no evidence of disease or biochemical persistence without structural correlate) was observed in 46% of patients (all with diffuse postdose radioiodine uptake and no structural images higher than 1 cm in diameter); and 21% patients died from disseminated lung metastasis. Overall survival at 5 and 10 years was 100% and 88.4%, respectively. The Cox proportional hazard ratio showed that extrathyroidal invasion, positive uptake of 18-FDG, and metachronous diagnosis of the lung metastasis were variables that significantly predicted death. Those patients who had a GRT did with a mean effective cumulative RAI dose of 457.3±29.7 mCi 131I (range, 300-600 mCi 131I). Lung metastasis showed a slow progression with a high long-term overall survival. The presence of synchronous lung metastasis, the absence of nodules larger than 1 cm, and the lack of uptake of FDG were predictive factors for an early response to treatment with RAI cumulative doses lower than 600 mCi 131I.

  4. miRNA-197 and miRNA-184 are associated with brain metastasis in EGFR-mutant lung cancers.

    Science.gov (United States)

    Remon, J; Alvarez-Berdugo, D; Majem, M; Moran, T; Reguart, N; Lianes, P

    2016-02-01

    The prognostic value of EGFR mutation in lung cancer patients with brain metastases is uncertain and therapeutic efficacy with EGFR TKI is limited. Looking for biomarkers closely related with early tumor changes and brain metastases in non-small cell lung cancer is warranted. MicroRNAs (miRNAs) are frequently deregulated in lung cancer. The objective of this study was to investigate whether some miRNAs are related with brain metastasis risk in EGFR-mutant non-small cell lung cancer patients. miRNA quantification was retrospectively performed in formalin-fixed, extracranial paraffin-embedded adenocarcinoma tumor tissue available from 17 human samples of advanced non-small cell lung cancer patients. Samples were classified as brain metastasis group (5 EGFR-mutant patients with initial BM, EGFRm-BM+; and 6 EGFR wild-type patients with initial BM) and the control group (6 EGFR-mutant NSCLC patients without BM). The RNA obtained was preamplified and retro-transcribed, and the miRNA was quantified with the TaqMan OpenArray Human MiRNA Panel in the QuantStudio™ 12 K Flex Real-Time PCR system. miRNA-197 and miRNA-184 showed a significant higher expression in EGFRm-BM+ group than in the control group (p = 0.017 and p = 0.01, for miRNA-197 and miRNA-184, respectively), with a trend toward overexpression in BM group compared with the control group (p = 0.08 and p = 0.065, for miRNA-197 and miRNA-184, respectively), without differences in expression in BM group according to EGFR mutational status (EGFR wild type vs. EGFR-mutant: p = 0.175 and p = 0.117, for miRNA-197, miRNA-184 respectively). miRNA-197 and miRNA-184 are overexpressed in EGFR-mutant patients with BM and they might be a new biomarker for stratifying the risk of BM in this subpopulation.

  5. P38 delta MAPK promotes breast cancer progression and lung metastasis by enhancing cell proliferation and cell detachment.

    Science.gov (United States)

    Wada, M; Canals, D; Adada, M; Coant, N; Salama, M F; Helke, K L; Arthur, J S; Shroyer, K R; Kitatani, K; Obeid, L M; Hannun, Y A

    2017-11-23

    The protein p38 mitogen-activated protein kinase (MAPK) delta isoform (p38δ) is a poorly studied member of the MAPK family. Data analysis from The Cancer Genome Atlas database revealed that p38δ is highly expressed in all types of human breast cancers. Using a human breast cancer tissue array, we confirmed elevation in cancer tissue. The breast cancer mouse model, MMTV-PyMT (PyMT), developed breast tumors with lung metastasis; however, mice deleted in p38δ (PyMT/p38δ -/- ) exhibited delayed primary tumor formation and highly reduced lung metastatic burden. At the cellular level, we demonstrate that targeting of p38δ in breast cancer cells, MCF-7 and MDA-MB-231 resulted in a reduced rate of cell proliferation. In addition, cells lacking p38δ also displayed an increased cell-matrix adhesion and reduced cell detachment. This effect on cell adhesion was molecularly supported by the regulation of the focal adhesion kinase by p38δ in the human breast cell lines. These studies define a previously unappreciated role for p38δ in breast cancer development and evolution by regulating tumor growth and altering metastatic properties. This study proposes MAPK p38δ protein as a key factor in breast cancer. Lack of p38δ resulted in reduced primary tumor size and blocked the metastatic potential to the lungs.

  6. FNAB cytology of extra-cranial metastasis of glioblastoma multiforme may resemble a lung primary: A diagnostic pitfall

    Directory of Open Access Journals (Sweden)

    Dincer HE

    2005-01-01

    Full Text Available Abstract Background As extra-cranial metastasis of glioblastoma multiforme (GBM is rare, it may create a diagnostic dilemma especially during interpretation of fine needle aspiration biopsy (FNAB cytology. Case presentation We present transbronchial FNAB findings in a 62-year-old smoker with lung mass clinically suspicious for a lung primary. The smears of transbronchial FNAB showed groups of cells with ill-defined cell margins and cytological features overlapping with poorly differentiated non-small cell carcinoma. The tumor cells demonstrated lack of immunoreactivity for cytokeratin, thyroid transcription factor-1, and usual neuroendocrine markers, synaptophysin and chromogranin in formalin-fixed cellblock sections. However, they were immunoreactive for the other neuroendocrine immunomarker, CD56, suggesting neural nature of the cells. Further scrutiny of clinical details revealed a history of GBM, 13 months status-post surgical excision with radiation therapy and systemic chemotherapy. The tumor recurred 7 months earlier and was debulked surgically and with intra-cranial chemotherapy. Additional evaluation of tumor cells for glial fibrillary acidic protein (GFAP immunoreactivity with clinical details resulted in final interpretation of metastatic GBM. Conclusion Lack of clinical history and immunophenotyping may lead to a diagnostic pitfall with possible misinterpretation of metastatic GBM as poorly differentiated non-small cell carcinoma of lung in a smoker.

  7. [A Case of Central Diabetes Insipidus That Was Caused by Pituitary Metastasis of Lung Adenocarcinoma and Was Controlled by Radiation Therapy].

    Science.gov (United States)

    Izumi, Yusuke; Masuda, Takeshi; Nabeshima, Shinji; Horimasu, Yasushi; Nakashima, Taku; Miyamoto, Shintaro; Iwamoto, Hiroshi; Fujitaka, Kazunori; Murakami, Yuji; Hamada, Hironobu; Nagata, Yasushi; Hattori, Noboru

    2017-06-01

    Pituitary metastasis of lung cancer is rare; however, it often causes diabetes insipidus. Although the majority of such patients are treated with radiation therapy, it remains unclear whether diabetes insipidus can be controlled by radiation therapy. A 72-year-old man was admitted to our hospital for hemosputum, headache, and polyuria. A chest CT scan showed a 3.0 cm mass in the left upper lobe of his lung. Bronchofiberscopy results confirmed the pathological diagnosis of lung adenocarcinoma. Based on the findings from PET-CT, head MRI, and endocrine tests, the diagnosis of lung adenocarcinoma( cT1bN0M1b, stage IV)accompanied with central diabetes insipidus caused by pituitary metastasis was made. Oral administration of desmopressin reduced urine volumes; however, chemotherapy for achieving stable disease in the primary tumor was ineffective in controlling the symptoms of diabetes insipidus. Chemotherapy was discontinued after 4 months because of severe hematological toxicity. During 2 months after the cessation of chemotherapy, polyuria worsened and, therefore, radiation therapy for pituitary metastasis was started. Following the radiation therapy, an apparent reduction in urine volume was observed. Our experience of this case suggests that radiation therapy for pituitary metastasis should be considered at the time when diabetes insipidus becomes clinically overt.

  8. 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

    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...

  9. Excavated pulmonary nodules: an unusual clinical presentation of lung metastasis in two cases

    Directory of Open Access Journals (Sweden)

    Lalya Issam

    2010-06-01

    Full Text Available Abstract Background Excavated pulmonary metastasis are rare. We present two cases of excavated pulmonary nodules proved to be metastases from osteosarcoma and gallblader lymphoma. Case presentation The first one is 39-year-old man in whom cholecystectomy made the diagnosis of primary non-Hodgkin's lymphoma of the gallbladder. He presented in chest CT scan excavated nodules that had been biopsied and confirmed the diagnosis of non hodgkin lymphoma. He underwent 8 courses of chemotherapy CHOP 21 with complete remission. The second one is an 21 years old man who presented a right leg osteoblastic osteosarcoma with only excavated pulmonary nodules in extension assessment. He had 3 courses of polychemotherapy API (doxorubicin, platinum, and ifosfamide with partial response. Unfortunately, he died following a septic shock. Review of the literature shows that excavated pulmonary nodules as metastasis are rare but we should consider this diagnosis every time we are in front of a cancer. Chest computed tomography is the best diagnosis imaging that could make this diagnosis. Differential diagnosis between benign and malignant bullous lesions is important because surgical excision affects survival in some malignancies. Conclusions Although pulmonary nodules are the most common cancer metastasis, a differential diagnosis of a concurrent primary malignancy should always be considered every time we have excavated lesions, even in patients with known malignant disease. Thorough chest evaluation is important, as multiple primary malignancies may occur concomitantly.

  10. Long noncoding RNA LINC00961 inhibits cell invasion and metastasis in human non-small cell lung cancer.

    Science.gov (United States)

    Jiang, Bin; Liu, Jing; Zhang, Yu-Hong; Shen, Dong; Liu, Shaoping; Lin, Feng; Su, Jun; Lin, Qing-Feng; Yan, Shuai; Li, Yong; Mao, Wei-Dong; Liu, Zhi-Li

    2018-01-01

    Long noncoding RNAs (LncRNAs) expression has been found to be misregulated in multiple human cancers, and a growing number of studies have revealed that lncRNAs can function as important oncogenes or tumor suppressors. In this study, we identified a lncRNA-LINC00961, which was significantly down-regulated in human non-small cell lung cancer tissues. Decreased LINC00961 was associated with NSCLC patients advanced clinical stage, lymph node metastasis, and shorter survival time. Further experiments demonstrated that LSD1 could directly bind to LINC00961 promoter regions and epigenetically repress its transcription in NSCLC cells. Moreover, MTT assays showed that LINC00961 had no influence on NSCLC cell proliferation. Ectopic overexpression of LINC00961 inhibits NSCLC cell migration, invasion in vitro and metastasis in vivo. Finally, qRT-PCR and western blot assays revealed that LINC00961 could act as a tumor suppressor partially via affecting β-catenin expression. Collectively, decreased LINC00961 might play a key role in NSCLC progression, and may serve as a novel prognostic marker in human NSCLC. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  11. Rac1-mediated cytoskeleton rearrangements induced by intersectin-1s deficiency promotes lung cancer cell proliferation, migration and metastasis.

    Science.gov (United States)

    Jeganathan, Niranjan; Predescu, Dan; Zhang, Jin; Sha, Fei; Bardita, Cristina; Patel, Monal; Wood, Stephen; Borgia, Jeffrey A; Balk, Robert A; Predescu, Sanda

    2016-09-14

    The mechanisms involved in lung cancer (LC) progression are poorly understood making discovery of successful therapies difficult. Adaptor proteins play a crucial role in cancer as they link cell surface receptors to specific intracellular pathways. Intersectin-1s (ITSN-1s) is an important multidomain adaptor protein implicated in the pathophysiology of numerous pulmonary diseases. To date, the role of ITSN-1s in LC has not been studied. Human LC cells, human LC tissue and A549 LC cells stable transfected with myc-ITSN-1s construct (A549 + ITSN-1s) were used in correlation with biochemical, molecular biology and morphological studies. In addition scratch assay with time lapse microscopy and in vivo xenograft tumor and mouse metastasis assays were performed. ITSN-1s, a prevalent protein of lung tissue, is significantly downregulated in human LC cells and LC tissue. Restoring ITSN-1s protein level decreases LC cell proliferation and clonogenic potential. In vivo studies indicate that immunodeficient mice injected with A549 + ITSN-1s cells develop less and smaller metastatic tumors compared to mice injected with A549 cells. Our studies also show that restoring ITSN-1s protein level increases the interaction between Cbl E3 ubiquitin ligase and Eps8 resulting in enhanced ubiquitination of the Eps8 oncoprotein. Subsequently, downstream unproductive assembly of the Eps8-mSos1 complex leads to impaired activation of the small GTPase Rac1. Impaired Rac1 activation mediated by ITSN-1s reorganizes the cytoskeleton (increased thick actin bundles and focal adhesion (FA) complexes as well as collapse of the vimentin filament network) in favor of decreased LC cell migration and metastasis. ITSN-1s induced Eps8 ubiquitination and impaired Eps8-mSos1 complex formation, leading to impaired activation of Rac1, is a novel signaling mechanism crucial for abolishing the progression and metastatic potential of LC cells.

  12. Spontaneous chylothorax complicating small cell lung cancer – Review of aetiology and diagnosis

    Directory of Open Access Journals (Sweden)

    S. Hanina

    2015-01-01

    Full Text Available We report the first case of spontaneous chylothorax complicating small cell lung cancer. A 52 year old female presented with exertional dyspnoea, left-sided chest and neck pain, and dysphagia. The chest X-ray on admission revealed a large left-sided pleural effusion. A subsequent CT chest showed a large anterior mediastinal mass with a left brachiocephalic and jugular vein thrombosis. The patient underwent medical thoracoscopy with chest drain insertion, which drained pleural fluid high in triglycerides, consistent with a chylothorax. Due to its uncommon nature, the management of chylothorax is not well defined. Alongside the case report, we provide a review of aetiology, mechanism and diagnosis with a brief summary of treatment options.

  13. Metastasis of breast cancer cells to the bone, lung, and lymph nodes promotes resistance to ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Hara, Takamitsu [Gunma Prefectural College of Health Sciences, Department of Radiological Technology, School of Radiological Technology, Gunma, Maebashi (Japan); Iwadate, Manabu [Fukushima Medical University, Department of Thyroid and Endocrinology, School of Medicine, Fukushima (Japan); Tachibana, Kazunoshin [Fukushima Medical University, Department of Breast Surgery, School of Medicine, Fukushima (Japan); Waguri, Satoshi [Fukushima Medical University, Department of Anatomy and Histology, School of Medicine, Fukushima (Japan); Takenoshita, Seiichi [Fukushima Medical University, Advanced Clinical Research Center, Fukushima Global Medical Science Center, School of Medicine, Fukushima (Japan); Hamada, Nobuyuki [Central Research Institute of Electric Power Industry (CRIEPI), Radiation Safety Research Center, Nuclear Technology Research Laboratory, Tokyo, Komae (Japan)

    2017-10-15

    Metastasis represents the leading cause of breast cancer deaths, necessitating strategies for its treatment. Although radiotherapy is employed for both primary and metastatic breast cancers, the difference in their ionizing radiation response remains incompletely understood. This study is the first to compare the radioresponse of a breast cancer cell line with its metastatic variants and report that such metastatic variants are more radioresistant. A luciferase expressing cell line was established from human basal-like breast adenocarcinoma MDA-MB-231 and underwent in vivo selections, whereby a cycle of inoculations into the left cardiac ventricle or the mammary fat pad of athymic nude mice, isolation of metastases to the bone, lung and lymph nodes visualized with bioluminescence imaging, and expansion of obtained cells was repeated twice or three times. The established metastatic cell lines were assessed for cell proliferation, wound healing, invasion, clonogenic survival, and apoptosis. The established metastatic cell lines possessed an increased proliferative potential in vivo and were more chemotactic, invasive, and resistant to X-ray-induced clonogenic inactivation and apoptosis in vitro. Breast cancer metastasis to the bone, lung, and lymph nodes promotes radioresistance. (orig.) [German] Metastasierung ist die Hauptursache fuer den toedlichen Verlauf von Brustkrebserkrankungen. Darauf muessen spezifische Behandlungsstrategien ausgerichtet werden. Sowohl primaere als auch metastatische Brustkrebsarten koennen mit einer Strahlentherapie behandelt werden, allerdings sind die Unterschiede in der Reaktion auf ionisierende Strahlung bis heute nicht vollstaendig verstanden. In dieser Studie wird zum ersten Mal die Strahlenantwort einer Brustkrebszelllinie mit der ihrer metastatischen Varianten verglichen und die erhoehte Strahlenresistenz der metastatischen Varianten gezeigt. Eine Luciferase-exprimierende Zelllinie wurde aus humanen basaloiden Brustadenokarzinomen

  14. A Rare Case of Sarcomatoid Carcinoma of the Lung with Spine Metastasis, Including a Literature Review.

    Science.gov (United States)

    Arshad, Hafiza Sobia; Dudekula, Rizwan Ahmed; Niazi, Masooma; Malik, Sandeep; Khaja, Misbahuddin

    2017-07-07

    BACKGROUND Sarcomatoid carcinoma is a rare, aggressive, malignant cancer composed of sarcoma and sarcoma-like components, and can occur in different organs such as the thyroid gland, bone, skin, breast, pancreas, liver, urinary tract, and lung. Pulmonary sarcomatoid carcinoma accounts for only a small percentage of lung cancers and has histological variants that include pleomorphic carcinoma, giant cell carcinoma, spindle cell carcinoma, carcinosarcoma, and pulmonary blastoma. CASE REPORT Here, we present a case of sarcomatoid carcinoma in a 63-year-old HIV-positive Hispanic male who presented with back pain, dry cough, and weight loss. A CT scan of his chest showed an ovoid mass in the lower lobe of the left lung, and an MRI of the spine showed a left lateral paraspinal soft tissue mass causing central canal stenosis and mild cord compression. The patient underwent laminectomy and resection of the spinal mass. A transthoracic needle biopsy of the lung and spinal masses had similar histopathology, and were indicative of sarcomatoid carcinoma. CONCLUSIONS We report a rare case of sarcomatoid carcinoma involving both the lung and spinal cord in the same patient. Sarcomatoid carcinomas of the lung have poor prognosis and are aggressive cancers. Moreover, our case also had the co-occurrence of HIV and sarcomatoid carcinoma.

  15. Quantification of B16 Melanoma Cells in Lungs Using Triplex Q-PCR - A New Approach to Evaluate Melanoma Cell Metastasis and Tumor Control

    DEFF Research Database (Denmark)

    Sorensen, Maria R; Pedersen, Sara R; Lindkvist, Annika

    2014-01-01

    of survival once the tumor has metastasized. In the present study, we have developed a new assay for quantitative analysis of B16 melanoma metastasis in the lungs. We have used a triplex Q-PCR to determine the expression of the melanoma genes GP100/Pmel and tyrosinase-related protein 2 (TRP-2), and found...... the outgrowth of subcutaneous melanomas. Results obtained using Q-PCR were compared to conventional counting of metastatic foci under a dissection microscope. A marked reduction in gene expression was observed in the lungs after vaccination with both vectors; however, Ad-Ii-GP showed the highest protection......, and matching results were obtained by enumeration of visible tumor nodules on the lung surfaces. Finally, we could show that inhibition of tumor metastasis required antigen-specific CD8 T cells and IFNγ, but not perforin. In conclusion, the presented results validate triplex Q-PCR as a fast, objective...

  16. Ground-glass opacity in lung metastasis from adenocarcinoma of the stomach: a case report

    International Nuclear Information System (INIS)

    Jung, Mi Ran; Kim, Jeong Kon; Lee, Jin Seong; Song, Koun Sik; Lim, Tae Hwan

    2000-01-01

    Ground-glass opacity is a frequent but nonspecific finding seen on high-resolution CT scans of lung parenchyma. Histologically, this appearance is observed when thickening of the alveolar wall and septal interstitium is minimal or the alveolar lumen is partially filled with fluid, macrophage, neutrophils, or amorphous material. It has been shown that ground-glass opacity may be caused not only by an active inflammatory process but also by fibrotic processes. When a focal area of ground-glass opacity persists or increases in size, the possibility of neoplasm-bronchioloalveolar carcinoma or adenoma, or lymphoma, for example, should be considered. Diffuse nonsegmental ground-glass opacity in both lung fields was incidentally found on follow up abdominal CT in a stomach cancer patient and signet-ring cell-type metastatic lung cancer was confirmed by transbronchial lung biopsy. We report a case of diffuse ground-glass opacity seen in metastatic lung cancer from adenocarcinoma of the stomach. (author)

  17. Whole lung computed tomography for detection of pulmonary metastasis of osteosarcoma confirmed at thoracotomy

    International Nuclear Information System (INIS)

    Ishida, Itsuro; Fukuma, Seigo; Sawada, Kinya; Seki, Yasuo; Tanaka, Fumitaka

    1980-01-01

    Whole lung computed tomography (CT) was performed in patients with osteosarcoma of bone to evaluate its diagnostic efficacy in comparison to that in conventional chest radiography and in whole lung tomography to detect metastatic nodules in the lung. In 11 of the 12 patients with osteosarcoma, CT detected pulmonary nodules and in 6 of the 11 patients pulmonary nodules were detected by CT, conventional chest radiography and whole lung tomography, respectively, and 22 pulmonary nodules were resected at thoracotomy and proved to be metastatic lesions. Nineteen nodules of the 22 nodules resected were detected by CT and nine of the 22 nodules were discovered only by CT, while only 10 of 22 nodules were recognized by the conventional chest radiography and the whole lung tomography. Two pulmonary nodules, measuring 1 mm and 2 mm in diameter, respectively, were not detected by any of these three methods. In three nodules that showed to be false positive in CT in the two patients, two nodules were histologically suture granulomas induced by the previous operation, and a deformed protuberance of the chest wall was erroneously interpreted to be a subpleural and intrapulmonary nodule in the remaining. We conclude that CT is the most efficient method to detect pulmonary nodules in the patients with osteosarcoma, but that the minimal size of the detectable nodule by CT is 3 mm in diameter. But a smaller nodule having a tendency to ossify can be detected by CT. (author)

  18. Evaluation of mediastinal lymph node metastasis of lung cancer by thin-section computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Ishiwa, Naoki; Yamada, Kozo; Nakayama, Haruhiko [Kanagawa Cancer Center (Japan)] (and others)

    2000-10-01

    The aim of this study was to improve the predictive value of evaluation of mediastinal lymph nodes in lung cancer. We reviewed 110 patients with operable lung cancer, and compared preoperative thin-section CT findings and postoperative histo-pathological findings. The positive criteria for a CT diagnosis based on not only node size ({>=}10 mm), but external morphological evaluation (long axislung cancer. (author)

  19. Small RNA sequencing reveals metastasis-related microRNAs in lung adenocarcinoma

    DEFF Research Database (Denmark)

    Daugaard, Iben; Venø, Morten T.; Yan, Yan

    2017-01-01

    The majority of lung cancer deaths are caused by metastatic disease. MicroRNAs (miRNAs) are posttranscriptional regulators of gene expression and miRNA dysregulation can contribute to metastatic progression. Here, small RNA sequencing was used to profile the miRNA and piwi-interacting RNA (pi...

  20. Spontaneous breathing or mechanical ventilation alters lung compliance and tissue association of exogenous surfactant in preterm newborn rabbits.

    Science.gov (United States)

    Bohlin, Kajsa; Bouhafs, Rabea K L; Jarstrand, Connie; Curstedt, Tore; Blennow, Mats; Robertson, Bengt

    2005-05-01

    In preterm infants with respiratory distress syndrome, surfactant administration followed by immediate extubation to spontaneous breathing with nasal continuous positive airway pressure reduces the need for mechanical ventilation. With this treatment approach, repeated doses of surfactant are rarely indicated. We used a rabbit model to test the hypothesis that exogenous surfactant therapy followed by spontaneous breathing results in a more sustained initial treatment response compared with treatment followed by mechanical ventilation. Preterm rabbits (gestational age 28.5 d) were treated with pharyngeal deposition of 200 mg/kg radiolabeled surfactant (14C-Curosurf) and randomized to 4 h of spontaneous breathing or mechanical ventilation or to a control group, killed immediately after surfactant administration. With pharyngeal deposition, 46 +/- 10% (mean +/- SEM) of the administered surfactant reached the lungs. The dynamic lung-thorax compliance was higher in spontaneously breathing compared with mechanically ventilated animals (median, 9.9 and 0.75 ml x cm H2O(-1) x kg(-1), respectively; p mechanically ventilated animals (p mechanically ventilated animals. We conclude that the initial lung tissue association of exogenous surfactant is impaired by mechanical ventilation. This is associated with a reduction of dynamic compliance and evidence of increased surfactant inactivation.

  1. Evaluation of dual-input perfusion in lung cancer using a 320-detector CT: Its correlation with tumor size, location, and presence of metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Eun Ju; Lee, Ki Nam; Roh, Mee Sook; Son, Choon Hee [Dong-A University College of Medicine, Busan (Korea, Republic of); Roh, Mee Sook [Dept. of Radiology, Dongnam Institute of Radiological and Medical Sciences, Busan (Korea, Republic of)

    2016-11-15

    The purposes of our study were to assess the dual blood supply of lung cancer using a computed tomography (CT) perfusion technique, and to analyze the correlations between dual perfusion and various characteristics of lung cancer. Thirty-five consecutive patients with lung tumors highly suggestive of malignancy were included in this study. All subjects underwent a dual-input dynamic perfusion volume scan using a 320-detector-row CT before CT-guided biopsy. The pulmonary trunk and the descending thoracic aorta were selected for the arterial input functions. From the CT data, pulmonary arterial perfusion (PP), aortic perfusion (AP), and the perfusion index [PI = PP / (PP + AP)] were calculated using the dual-input maximum-slope method. We statistically analyzed the relationship of the perfusion data with tumor locations (central, peripheral, and abutting the pleural lesions), tumor volumes, and the presence of lymph node metastasis or distant metastasis. All subjects were pathologically diagnosed with primary lung cancers via CT-guided aspiration biopsy. The overall mean PI was 53.7 ± 7.2%. The PI showed a significant difference according to the tumor location (central, 49.2 ± 3.3%; peripheral, 56.2 ± 6.7%; abutting the pleural lesions, 48.9 ± 7.6%, p = 0.047). In contrast, no significant difference was detected in tumor size or the presence of metastasis (p > 0.05). We found that the proportion of dual perfusion in lung cancer was significantly dependent on the location of the tumor, while tumor size or the presence of metastasis was not distinctly associated with dual perfusion.

  2. [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].

    Science.gov (United States)

    Lei, Bei; Cao, Jie; Shen, Jie; Zhao, Lanxiang; Liang, Sheng; Meng, Qinggang; Xie, Wenhui; Yang, Shunfang

    2013-08-20

    Lung cancer is the leading cause of cancer-related death in men and women. It is also the most common cause of brain metastases. A brain metastasis model is difficult 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. Thus, the establishment of a Chinese lung adenocarcinoma cell line and its animal model with brain metastasis potency and in vivo research is of great significance. CPA-Yang1 cells were obtained from a patient with human lung adenocarcinoma by lentiviral vector-mediated transfection of green fluorescence 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 fluorescence, radionuclide and X ray fused imaging, magnetic resonance imaging (MRI) with sense body detection, and resection. The samples were divided into two parts for cell culture and histological diagnosis. The process was repeated in vivo and in vitro for four cycles to obtain a novel cell clone, CPA-Yang1-BR. A novel cell clone, CPA-Yang1-BR, was obtained with a brain metastatic rate of 50%. The use of MRI for the detection of brain metastases has obvious advantages. 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 immunodeficient mice. The results of this study may serve as a technical platform for brain metastases from lung adenocarcinoma.

  3. Evaluation of dual-input perfusion in lung cancer using a 320-detector CT: Its correlation with tumor size, location, and presence of metastasis

    International Nuclear Information System (INIS)

    Kang, Eun Ju; Lee, Ki Nam; Roh, Mee Sook; Son, Choon Hee; Roh, Mee Sook

    2016-01-01

    The purposes of our study were to assess the dual blood supply of lung cancer using a computed tomography (CT) perfusion technique, and to analyze the correlations between dual perfusion and various characteristics of lung cancer. Thirty-five consecutive patients with lung tumors highly suggestive of malignancy were included in this study. All subjects underwent a dual-input dynamic perfusion volume scan using a 320-detector-row CT before CT-guided biopsy. The pulmonary trunk and the descending thoracic aorta were selected for the arterial input functions. From the CT data, pulmonary arterial perfusion (PP), aortic perfusion (AP), and the perfusion index [PI = PP / (PP + AP)] were calculated using the dual-input maximum-slope method. We statistically analyzed the relationship of the perfusion data with tumor locations (central, peripheral, and abutting the pleural lesions), tumor volumes, and the presence of lymph node metastasis or distant metastasis. All subjects were pathologically diagnosed with primary lung cancers via CT-guided aspiration biopsy. The overall mean PI was 53.7 ± 7.2%. The PI showed a significant difference according to the tumor location (central, 49.2 ± 3.3%; peripheral, 56.2 ± 6.7%; abutting the pleural lesions, 48.9 ± 7.6%, p = 0.047). In contrast, no significant difference was detected in tumor size or the presence of metastasis (p > 0.05). We found that the proportion of dual perfusion in lung cancer was significantly dependent on the location of the tumor, while tumor size or the presence of metastasis was not distinctly associated with dual perfusion

  4. Silencing of advanced glycosylation and glycosylation and product-specific receptor (RAGE) inhibits the metastasis and growth of non-small cell lung cancer.

    Science.gov (United States)

    Yu, Yan Xia; Pan, Wen Chong; Cheng, Yu Feng

    2017-01-01

    Non-small cell lung cancer (NSCLC) constitutes the main cases of lung cancer and is the world's most common and lethal cancer owing to regional invasion or distant metastasis. Growing morbidity and lethality demonstrates that valid molecular target in management of NSCLC metastasis is still absence. The receptor of advanced glycation end-products (RAGE) has been identified as an oncogenic gene and appears to promote the growth and metastasis of various cancers. Here, we investigated if RAGE targeted by RNA interference (RNAi) might have certain effect on the restraint of the growth of NSCLC and tumor metastasis. Wound healing and Transwell invasion assays indicated that RAGE favored the metastatic capabilities of NSCLC H1975 cells. Besides, soft-agar colony assay revealed that silencing RAGE significantly blocked colony-forming capability of H1975 cells in vitro. Furthermore, we observed that RAGE participated in H1975 cells growth, metastasis and epithelial-mesenchymal transition (EMT) by regulating interdict crux intracellular signaling pathways, including phosphatidylinositol-3 kinase/serine-threonine kinase (PI3K/AKT) and V-Ki-ras2 kirsten rat sarcoma viral oncogene homolog/RAF proto-oncogene serine/threonine-protein kinase (KRAS/RAF-1). In xenograft model, significantly reduction intumor growth and Ki67 expression was demonstrated in nude mice inoculation with RAGE down-regulation H1975 cells. To conclude, our study demonstrated that RAGE played a crucial role in the metastasis and growth of NSCLC by regulating PI3K/AKT and KRAS/RAF-1 signaling pathways, thereby might be a promising therapeutic target for NSCLC.

  5. Changes in the relative risk and sites of central nervous system metastasis with effective combined chemotherapy and radiation therapy for small cell carcinoma of the lung

    International Nuclear Information System (INIS)

    Komaki, R.; Cox, J.D.; Holoye, P.Y.; Byhardt, R.W.

    1983-01-01

    Prolongation of survival of patients with small cell carcinoma of the lung with current effective systemic therapy has been accompanied by a marked increase in the frequency of relapse in the central nervous system (CNS). Prophylactic cranial irradiation (PCI) was shown to reduce the frequency of brain metastasis, but there was no increased short-term survival. Therefore, the necessity for PCI early in the course of treatment has been questioned, especially for patients with extensive disease. From January 1974 through March 1982, 205 patients with small cell carcinoma of the lung were treated at the Medical College of Wisconsin Affiliated Hospitals. None had clinical, radioisotopic, or computed tomographic evidence of brain metastasis. Eighty-two patients received radiotherapy and chemotherapy, but no PCI; 123 patients received combination chemotherapy and radiation therapy with PCI. The cumulative probability of brain metastasis without PCI was 36% at 12 months and 47% at 24 months; the probabilities were 6 and 10%, respectively with PCI. The 24-month probability of brain metastasis in patients with limited disease and no PCI was 45%; for those with extensive disease, it was 47%. No patient presented with extracranial central nervous system (ECNS) metastasis and no one without PCI developed it. Twelve patients who received PCI developed ECNS metastasis; the cumulative probabilities rose to 14% at 12 months and 22% at 24 months. The increased frequency of ECNS involvement has led to a phase I trial of PCI followed by six cycles of combination chemotherapy, without maintenance chemotherapy, followed by irradiation of the chest and spinal cord for patients with complete response

  6. FOXA2 functions as a suppressor of tumor metastasis by inhibition of epithelial-to-mesenchymal transition in human lung cancers

    OpenAIRE

    Tang, Yunneng; Shu, Guangwen; Yuan, Xinwang; Jing, Naihe; Song, Jianguo

    2010-01-01

    The forkhead box transcription factor A2 (FOXA2) is an important regulator in animal development and body homeostasis. However, whether FOXA2 is involved in transforming growth factor β1 (TGF-β1)-mediated epithelial-to-mesenchymal transition (EMT) and tumor metastasis remains unknown. The present study showed that in human lung cancer cell lines, the abundance of FOXA2 positively correlates with epithelial phenotypes and negatively correlates with the mesenchymal phenotypes of cells, and TGF-...

  7. The chemotherapeutic effect of essential oil of Plectranthus amboinicus (Lour) on lung metastasis developed by B16F-10 cell line in C57BL/6 mice.

    Science.gov (United States)

    Manjamalai, A; Grace, V M Berlin

    2013-01-01

    Current investigation is to evaluate the anticancer activity of the essential oil of Plectranthus amboinicus (Lour) on B16F-10 melanoma cell line injected C57BL/6 mice, and it was simultaneously treated with the essential oil of P. amboinicus (Lour) (50 μg/dose) via i.p. for 21 days. The present investigation exhibited the potent chemotherapeutic/chemopreventive effect of the essential oil of P. amboinicus (Lour) over lung metastasis that developed. To our knowledge, this is the first report in evaluating the effect of essential oil of P. amboinicus (Lour) using lung cancer model.

  8. A case of cutaneous squamous cell carcinoma associated with small cell carcinoma of lung developing a skin metastasis on previously irradiated area

    International Nuclear Information System (INIS)

    Kohda, Mamoru; Takei, Yoji; Ueki, Hiroaki

    1983-01-01

    Squamous cell carcinoma which occurred in the penis of a 61-year-old male patient was treated surgically and by Linac (a total of 10,400 rad). However, it was not cured. Abnormal shadows in the lung and multiple liver tumor was noted one month before death. Autopsy revealed generalized metastases of pulmonary small-cell carcinoma, and persistent squamous cell carcinoma of the penis with no metastases. Skin metastasis of lung carcinoma occurred only in the area previously irradiated. (Ueda, J.)

  9. Short-term outcomes and safety of computed tomography-guided percutaneous microwave ablation of solitary adrenal metastasis from lung cancer: A multi-center retrospective study

    Energy Technology Data Exchange (ETDEWEB)

    Men, Min; Ye, Xin; Yang, Xia; Zheng, Aimin; Huang, Guang Hui; Wei, Zhigang [Dept. of Oncology, Shandong Provincial Hospital Affiliated with Shandong University, Jinan (China); Fan, Wei Jun [Imaging and Interventional Center, Sun Yat-sen University Cancer Center, Guangzhou (China); Zhang, Kaixian [Dept. of Oncology, Teng Zhou Central People' s Hospital Affiliated with Jining Medical College, Tengzhou (China); Bi, Jing Wang [Dept. of Oncology, Jinan Military General Hospital of Chinese People' s Liberation Army, Jinan (China)

    2016-11-15

    To retrospectively evaluate the short-term outcomes and safety of computed tomography (CT)-guided percutaneous microwave ablation (MWA) of solitary adrenal metastasis from lung cancer. From May 2010 to April 2014, 31 patients with unilateral adrenal metastasis from lung cancer who were treated with CT-guided percutaneous MWA were enrolled. This study was conducted with approval from local Institutional Review Board. Clinical outcomes and complications of MWA were assessed. Their tumors ranged from 1.5 to 5.4 cm in diameter. After a median follow-up period of 11.1 months, primary efficacy rate was 90.3% (28/31). Local tumor progression was detected in 7 (22.6%) of 31 cases. Their median overall survival time was 12 months. The 1-year overall survival rate was 44.3%. Median local tumor progression-free survival time was 9 months. Local tumor progression-free survival rate was 77.4%. Of 36 MWA sessions, two (5.6%) had major complications (hypertensive crisis). CT-guided percutaneous MWA may be fairly safe and effective for treating solitary adrenal metastasis from lung cancer.

  10. A stochastic Markov chain model to describe lung cancer growth and metastasis.

    Science.gov (United States)

    Newton, Paul K; Mason, Jeremy; Bethel, Kelly; Bazhenova, Lyudmila A; Nieva, Jorge; Kuhn, Peter

    2012-01-01

    A stochastic Markov chain model for metastatic progression is developed for primary lung cancer based on a network construction of metastatic sites with dynamics modeled as an ensemble of random walkers on the network. We calculate a transition matrix, with entries (transition probabilities) interpreted as random variables, and use it to construct a circular bi-directional network of primary and metastatic locations based on postmortem tissue analysis of 3827 autopsies on untreated patients documenting all primary tumor locations and metastatic sites from this population. The resulting 50 potential metastatic sites are connected by directed edges with distributed weightings, where the site connections and weightings are obtained by calculating the entries of an ensemble of transition matrices so that the steady-state distribution obtained from the long-time limit of the Markov chain dynamical system corresponds to the ensemble metastatic distribution obtained from the autopsy data set. We condition our search for a transition matrix on an initial distribution of metastatic tumors obtained from the data set. Through an iterative numerical search procedure, we adjust the entries of a sequence of approximations until a transition matrix with the correct steady-state is found (up to a numerical threshold). Since this constrained linear optimization problem is underdetermined, we characterize the statistical variance of the ensemble of transition matrices calculated using the means and variances of their singular value distributions as a diagnostic tool. We interpret the ensemble averaged transition probabilities as (approximately) normally distributed random variables. The model allows us to simulate and quantify disease progression pathways and timescales of progression from the lung position to other sites and we highlight several key findings based on the model.

  11. A stochastic Markov chain model to describe lung cancer growth and metastasis.

    Directory of Open Access Journals (Sweden)

    Paul K Newton

    Full Text Available A stochastic Markov chain model for metastatic progression is developed for primary lung cancer based on a network construction of metastatic sites with dynamics modeled as an ensemble of random walkers on the network. We calculate a transition matrix, with entries (transition probabilities interpreted as random variables, and use it to construct a circular bi-directional network of primary and metastatic locations based on postmortem tissue analysis of 3827 autopsies on untreated patients documenting all primary tumor locations and metastatic sites from this population. The resulting 50 potential metastatic sites are connected by directed edges with distributed weightings, where the site connections and weightings are obtained by calculating the entries of an ensemble of transition matrices so that the steady-state distribution obtained from the long-time limit of the Markov chain dynamical system corresponds to the ensemble metastatic distribution obtained from the autopsy data set. We condition our search for a transition matrix on an initial distribution of metastatic tumors obtained from the data set. Through an iterative numerical search procedure, we adjust the entries of a sequence of approximations until a transition matrix with the correct steady-state is found (up to a numerical threshold. Since this constrained linear optimization problem is underdetermined, we characterize the statistical variance of the ensemble of transition matrices calculated using the means and variances of their singular value distributions as a diagnostic tool. We interpret the ensemble averaged transition probabilities as (approximately normally distributed random variables. The model allows us to simulate and quantify disease progression pathways and timescales of progression from the lung position to other sites and we highlight several key findings based on the model.

  12. The important role of circulating CYFRA21-1 in metastasis diagnosis and prognostic value compared with carcinoembryonic antigen and neuron-specific enolase in lung cancer patients.

    Science.gov (United States)

    Zhang, Li; Liu, Dan; Li, Lei; Pu, Dan; Zhou, Ping; Jing, Yuting; Yu, He; Wang, Yanwen; Zhu, Yihan; He, Yanqi; Li, Yalun; Zhao, Shuang; Qiu, Zhixin; Li, Weimin

    2017-02-02

    The roles of carcinoembryonic antigen (CEA), cytokeratin 19 fragments (CYFRA21-1) and neuron-specific enolase (NSE) in metastases occurrence and poor diagnosis in specific histological classifications of lung cancer need further exploring. In this study, we investigated relationship between elevated levels of three biomarkers of CEA, CYFRA21-1 and NSE (individually and in combination) and metastasis, survival status and prognosis in lung cancer patients. Eight hundred and sixty eight lung cancer patients including adenocarcinoma (ADC, N = 445), squamous cell carcinoma (SCC, N = 215), small cell lung cancer (SCLC, N = 159) and other types (N = 49) were categorized into negative, moderate and high groups according to serum levels of biomarkers, and were then categorized into negative, single, double and triple groups according to any positive combination of three biomarkers. The cutoff values of three biomarkers for groupings were developed on the training group (N = 432) and verified in a validation group (N = 436). Clinical and laboratory characteristics were then assessed for correlation with occurrence of metastasis, survival status and prognosis between the two groups. Further correlation analyses were also conducted by different subtypes (ADC, SCC and SCLC) and tumor stages (I + II, III and IV) of lung cancers. The consistent results between training and validation group confirmed the rationality of grouping methods. CYFRA21-1 levels had stronger association with metastases and survival status than CEA and NSE in all lung cancer patients. When stratified by subtypes, these significances only existed in ADC patients for CYFRA21-1. Cox regression analyses showed that CYFRA21-1 and NSE were independent prognostic factors for lung cancer patients. However, only CYFRA21-1 was an independent prognostic factor in ADC and SCLC patients subtypes. Cox-regression results also indicated that CYFRA21-1 could act as independent prognostic factor

  13. Downregulation of miR-218 contributes to epithelial-mesenchymal transition and tumor metastasis in lung cancer by targeting Slug/ZEB2 signaling.

    Science.gov (United States)

    Shi, Z-M; Wang, L; Shen, H; Jiang, C-F; Ge, X; Li, D-M; Wen, Y-Y; Sun, H-R; Pan, M-H; Li, W; Shu, Y-Q; Liu, L-Z; Peiper, S C; He, J; Jiang, B-H

    2017-05-04

    Epithelial-mesenchymal transition (EMT) has been recognized as a key element of cell migration and invasion in lung cancer; however, the underlying mechanisms are not fully elucidated. Recently, emerging evidence suggest that miRNAs have crucial roles in control of EMT and EMT-associated traits such as migration, invasion and chemoresistance. Here, we found that miR-218 expression levels were significantly downregulated in lung cancer tissues compared with adjacent non-cancerous tissues, and the levels of miR-218 were significantly associated with histological grades and lymph node metastasis. Overexpression of miR-218 inhibited cell migration and invasion as well as the EMT process. Of particular importance, miR-218 was involved in the metastatic process of lung cancer cells in vivo by suppressing local invasion and distant colonization. We identified Slug and ZEB2 as direct functional targets of miR-218. Inverse correlations were observed between miR-218 levels and Slug/ZEB2 levels in cancer tissue samples. In addition, overexpression of miR-218 in H1299 increased chemosensitivity of cells to cisplatin treatment through suppression of Slug and ZEB2. These findings highlight an important role of miR-218 in the regulation of EMT-related traits and metastasis of lung cancer in part by modulation of Slug/ZEB2 signaling, and provide a potential therapeutic strategy by targeting miR-218 in NSCLC.

  14. Inhibition of tumor cell-induced platelet aggregation and lung metastasis by the oral GpIIb/IIIa antagonist XV454.

    Science.gov (United States)

    Amirkhosravi, Ali; Mousa, Shaker A; Amaya, Mildred; Blaydes, Susan; Desai, Hina; Meyer, Todd; Francis, John L

    2003-09-01

    Platelets are known to play a role in blood borne metastasis. Previous experimental studies have suggested that platelet GpIIb/IIIa may be a therapeutic target. However, the need for intravenous administration limits the potential application of current GpIIb/IIIa inhibitors to cancer therapy. The aim of the present study was to assess the efficacy of a novel, non-peptide oral GpIIb/IIIa antagonist (XV454) on tumor cell-induced platelet aggregation in vivo and on experimental metastasis. A Lewis lung carcinoma (LL2) mouse model of experimental metastasis was used in this study. XV454 (100 micro g) was administered intravenously (via tail vein) or orally (gavages) to 20 g mice. To determine the effect of XV454 on platelet aggregation, blood samples were collected by cardiac puncture 10 minutes after intravenous and 1-24 hrs after oral XV454, and platelet function was assessed by aggregometry, thrombelastography and the Platelet Function Analyzer (PFA100). The effect of XV454 on tumor cell-induced thrombocytopenia was determined 10 minutes after intravenous and 3 hrs after oral XV454 administration. Tumor cells (2 x 10(6)) were injected intravenously and 15 minutes after cell injection, platelet count was measured and compared to baseline (pre-injection) counts. To assess the effect on metastasis, XV454 was administered intravenous or orally 10 minutes and 3 hrs before tumor cell injection, respectively. Eighteen days later, surface lung tumor nodules were counted and the total lung tumor burden assessed. In a fourth group, in addition to the initial oral dose (before tumor cell injection), oral XV454 was given daily for the first week and three times in the second week. Administration of XV454 (5 mg/kg) completely inhibited platelet aggregation and this effect persisted for at least 24 hrs after oral delivery. Both intravenous and oral XV454 significantly inhibited tumor cell-induced thrombocytopenia (P < 0.01), the number of surface lung tumor nodules (80-85%; P

  15. LOXL4 knockdown enhances tumor growth and lung metastasis through collagen-dependent extracellular matrix changes in triple-negative breast cancer.

    Science.gov (United States)

    Choi, Sul Ki; Kim, Hoe Suk; Jin, Tiefeng; Moon, Woo Kyung

    2017-02-14

    Lysyl oxidase (LOX) family genes catalyze collagen cross-link formation. To determine the effects of lysyl oxidase-like 4 (LOXL4) expression on breast tumor formation and metastasis, we evaluated primary tumor growth and lung metastasis in mice injected with LOXL4-knockdown MDA-MB-231 triple-negative human breast cancer cells. In addition, we analyzed overall survival in breast cancer patients based on LOXL4 expression using a public online database. In the mouse xenograft model, LOXL4 knockdown increased primary tumor growth and lung colonization as well as collagen I and IV, lysine hydroxylase 1 and 2, and prolyl 4-hydroxylase subunit alpha 1 and 2 levels. Second harmonic generation imaging revealed that LOXL4 knockdown resulted in the thickening of collagen bundles within tumors. In addition, weak LOXL4 expression was associated with poor overall survival in breast cancer patients from the BreastMark dataset, and this association was strongest in triple-negative breast cancer patients. These results demonstrate that weak LOXL4 expression leads to remodeling of the extracellular matrix through induction of collagen synthesis, deposition, and structural changes. These alterations in turn promote tumor growth and metastasis and are associated with poor clinical outcomes in triple-negative breast cancer.

  16. Src Promotes Metastasis of Human Non-Small Cell Lung Cancer Cells through Fn14-Mediated NF-κB Signaling.

    Science.gov (United States)

    Wang, Wei; Liu, Feiyu; Wang, Chaoyang; Wang, Chengde; Tang, Yijun; Jiang, Zhongmin

    2018-03-03

    BACKGROUND Src and Fn14 are implicated in the aggressiveness of non-small cell lung cancer (NSCLC) cells, yet the molecular mechanism is not fully understood. MATERIAL AND METHODS The proliferation, migration, and invasion of HCC827 cells with Src knockdown were examined in vitro. The expression of Fn14 and the activation of NF-κB signaling pathway in Src-silenced HCC827 cells were detected by western blot. The role of Fn14 in Src-regulated cell migration/invasion and activation of NF-κB signaling was investigated by overexpressing Fn14 in Src knockdown NSCLC cells. Furthermore, the pro-metastatic role of Src was validated in a NSCLC metastasis mouse model. RESULTS Knockdown of Src inhibited the proliferation, migration, and invasion of HCC827 cells, which was associated with reduced levels of Fn14, p-IκBα, p-IKKβ, and nuclear NF-κB p65. Overexpression of Fn14 restored the potential of migration and invasion as well as the activation of NF-κB signaling in Src-silenced NSCLC cells. In addition, silencing of Src suppressed lung metastasis of HCC827 cells in mice, and inhibited the expression of Fn14 and nuclear translocation of NF-κB p65 in vivo. CONCLUSIONS The data demonstrated that the Src/Fn14/NF-κB axis plays a critical role in NSCLC metastasis.

  17. Retention index of thallium-201 single photon emission computerised tomography (SPECT) as an indicator of metastasis in adenocarcinoma of the lung.

    Science.gov (United States)

    Takekawa, H.; Itoh, K.; Abe, S.; Ogura, S.; Isobe, H.; Sukou, N.; Furudate, M.; Kawakami, Y.

    1994-01-01

    We examined the relationship between the retention of thallium-201 (201Tl) on a delayed scan and the metastatic potential of adenocarcinomas of the lung. We studied 43 patients with adenocarcinoma of the lung and divided them into two groups according to the presence or absence of lymph node metastasis. 201Tl single photon emission computerised tomography (SPECT) was conducted twice: 15 min (early scan) and 120 min (delayed scan) after intravenous injection of 3 mCi of 201Tl chloride. We calculated the retention index in order to evaluate the degree of 201Tl retention in the primary tumour. The retention indices were significantly higher in the group that was positive for lymph node metastasis than in the negative group. In adenocarcinomas with high metastatic potential, 201Tl SPECT demonstrated slow washout or increased retention on the delayed scan. The retention index of 201Tl SPECT is a useful indicator of metastatic potential, thereby facilitating the prediction of prognosis, and provides insight into the relationship between 201Tl uptake and malignancy. This is the first report demonstrating a significant relationship between the retention of 201Tl SPECT and lymph node metastasis. Images Figure 1 PMID:8054281

  18. Suberoylanilide hydroxamic acid, an inhibitor of histone deacetylase, enhances radiosensitivity and suppresses lung metastasis in breast cancer in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Hui-Wen Chiu

    Full Text Available Triple-negative breast cancer (TNBC, defined by the absence of an estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression, is associated with an early recurrence of disease and poor outcome. Furthermore, the majority of deaths in breast cancer patients are from metastases instead of from primary tumors. In this study, MCF-7 (an estrogen receptor-positive human breast cancer cell line, MDA-MB-231 (a human TNBC cell line and 4T1 (a mouse TNBC cell line were used to investigate the anti-cancer effects of ionizing radiation (IR combined with suberoylanilide hydroxamic acid (SAHA, an inhibitor of histone deacetylase (HDAC and to determine the underlying mechanisms of these effects in vitro and in vivo. We also evaluated the ability of SAHA to inhibit the metastasis of 4T1 cells. We found that IR combined with SAHA showed increased therapeutic efficacy when compared with either treatment alone in MCF-7, MDA-MB-231 and 4T1 cells. Moreover, the combined treatment enhanced DNA damage through the inhibition of DNA repair proteins. The combined treatment was induced primarily through autophagy and ER stress. In an orthotopic breast cancer mouse model, the combination treatment showed a greater inhibition of tumor growth. In addition, SAHA inhibited the migration and invasion abilities of 4T1 cells and inhibited breast cancer cell migration by inhibiting the activity of MMP-9. In an in vivo experimental metastasis mouse model, SAHA significantly inhibited lung metastasis. SAHA not only enhances radiosensitivity but also suppresses lung metastasis in breast cancer. These novel findings suggest that SAHA alone or combined with IR could serve as a potential therapeutic strategy for breast cancer.

  19. Spontaneous breathing with biphasic positive airway pressure attenuates lung injury in hydrochloric acid-induced acute respiratory distress syndrome.

    Science.gov (United States)

    Xia, Jingen; Zhang, Heng; Sun, Bing; Yang, Rui; He, Hangyong; Zhan, Qingyuan

    2014-06-01

    It has been proved that spontaneous breathing (SB) with biphasic positive airway pressure (BIPAP) can improve lung aeration in acute respiratory distress syndrome compared with controlled mechanical ventilation. The authors hypothesized that SB with BIPAP would attenuate lung injury in acute respiratory distress syndrome compared with pressure-controlled ventilation. Twenty male New Zealand white rabbits with hydrochloric acid aspiration-induced acute respiratory distress syndrome were randomly ventilated using the BIPAP either with SB (BIPAP plus SB group) or without SB (BIPAP minus SB group) for 5 h. Inspiration pressure was adjusted to maintain the tidal volume at 6 ml/kg. Both groups received the same positive end-expiratory pressure level at 5 cm H2O for hemodynamic goals. Eight healthy animals without ventilatory support served as the control group. The BIPAP plus SB group presented a lower ratio of dead space ventilation to tidal volume, a lower respiratory rate, and lower minute ventilation. No significant difference in the protein levels of interleukin-6 and interleukin-8 in plasma, bronchoalveolar lavage fluid, and lung tissue were measured between the two experimental groups. However, SB resulted in lower messenger ribonucleic acid levels of interleukin-6 (mean ± SD; 1.8 ± 0.7 vs. 2.6 ± 0.5; P = 0.008) and interleukin-8 (2.2 ± 0.5 vs. 2.9 ± 0.6; P = 0.014) in lung tissues. In addition, lung histopathology revealed less injury in the BIPAP plus SB group (lung injury score, 13.8 ± 4.6 vs. 21.8 ± 5.7; P hydrochloric acid-induced acute respiratory distress syndrome, SB with BIPAP attenuated lung injury and improved respiratory function compared with controlled ventilation with low tidal volume.

  20. Spontaneous pneumothorax

    Directory of Open Access Journals (Sweden)

    Davari R

    1996-07-01

    Full Text Available A case with bilateral spontaneous pneumothorax was presented. Etiology, mechanism, and treatment were discussed on the review of literature. Spontaneous Pneumothorax is a clinical entity resulting from a sudden non traumatic rupture of the lung. Biach reported in 1880 that 78% of 916 patients with spontaneous pneumothorax had tuberculosis. Kjergaard emphasized 1932 the primary importance of subpleural bleb disease. Currently the clinical spectrum of spontaneous pneumothorax seems to have entered a third era with the recognition of the interstitial lung disease and AIDS as a significant etiology. Standard treatment is including: observation, thoracocentesis, tube thoracostomy. Chemical pleurodesis, bullectomy or wedge resection of lung with pleural abrasion and occasionally pleurectomy. Little information has been reported regarding the efficacy of such treatment in spontaneous pneumothorax secondary to non bleb disease

  1. ELF5 Drives Lung Metastasis in Luminal Breast Cancer through Recruitment of Gr1+ CD11b+ Myeloid-Derived Suppressor Cells.

    Directory of Open Access Journals (Sweden)

    David Gallego-Ortega

    2015-12-01

    Full Text Available During pregnancy, the ETS transcription factor ELF5 establishes the milk-secreting alveolar cell lineage by driving a cell fate decision of the mammary luminal progenitor cell. In breast cancer, ELF5 is a key transcriptional determinant of tumor subtype and has been implicated in the development of insensitivity to anti-estrogen therapy. In the mouse mammary tumor virus-Polyoma Middle T (MMTV-PyMT model of luminal breast cancer, induction of ELF5 levels increased leukocyte infiltration, angiogenesis, and blood vessel permeability in primary tumors and greatly increased the size and number of lung metastasis. Myeloid-derived suppressor cells, a group of immature neutrophils recently identified as mediators of vasculogenesis and metastasis, were recruited to the tumor in response to ELF5. Depletion of these cells using specific Ly6G antibodies prevented ELF5 from driving vasculogenesis and metastasis. Expression signatures in luminal A breast cancers indicated that increased myeloid cell invasion and inflammation were correlated with ELF5 expression, and increased ELF5 immunohistochemical staining predicted much shorter metastasis-free and overall survival of luminal A patients, defining a group who experienced unexpectedly early disease progression. Thus, in the MMTV-PyMT mouse mammary model, increased ELF5 levels drive metastasis by co-opting the innate immune system. As ELF5 has been previously implicated in the development of antiestrogen resistance, this finding implicates ELF5 as a defining factor in the acquisition of the key aspects of the lethal phenotype in luminal A breast cancer.

  2. [Multidisciplinary treatment of leptomeningeal metastasis in patients with lung adenocarcinoma: the triple modality combination of EGFR-TKI, VP shunt and irradiation].

    Science.gov (United States)

    Mitsuya, Koichi; Nakasu, Yoko; Mizokami, Yoshihito; Takahashi, Toshiaki; Nakamura, Yukiko; Ono, Akira; Toda, Yoko; Yamamoto, Nobuyuki; Harada, Hideyuki; Nishimura, Tetsuo

    2012-06-01

    Leptomeningeal metastasis (LM) is a devastating complication of systemic cancers. New therapies that have beneficial effects on primary cancers outside the central nervous system (CNS) have underscored the significance of LM. Intrathecal chemotherapy plus radiation therapy are less effective for LM from lung adenocarcinoma. We retrospectively studied outcomes of patients with LM from lung adenocarcinoma who underwent multidisciplinary treatments in our institute. Four patients with LM from lung adenocarcinoma treated with EGFR-TKI, VP shunt and irradiation. Of those four, two presented with increased intracranial pressure, one with epilepsy, and the other with truncal ataxia. Treatment was indicated when LM was confirmed by MR images or cytology, and Karnofsky Performance Status scale was more than 40%, and life expectancy was more than three months if LM was controlled. EGFR mutation was not examined, because of the unsettled approval of Japanese public health insurance at the time of this study. The patients selected for treatment by EGFR-TKI were all Asian women who had never smoked. Treatment sequence was based on clinical symptoms depending on the individual situation. The mean time from diagnosis of lung adenocarcinoma to LM onset was 28 (24 to 36) months. Mean survival time from LM diagnosis was 9 months. All patients died of LM. No patients suffered from peritoneal carcinomatosis or infection after VP shunt. The triple modality combination of EGFR-TKI, VP shunt and radiation therapy may improve outcomes and symptoms of patients with LM from lung adenocarcinoma.

  3. Close correlation between restriction fragment length polymorphism of the L-MYC gene and metastasis of human lung cancer to the lymph nodes and other organs

    International Nuclear Information System (INIS)

    Kawashima, Kazuko; Shikama, Hiroshi; Imoto, Kazuhiko; Izawa, Mitsuo; Nishimura, Susumu; Naruke, Tsuguo; Okabayashi, Kenzo

    1988-01-01

    Restriction length fragment polymorphism of the L-MYC gene was examined in DNAs from lung cancer tissues and normal tissues of 51 Japanese patients with lung cancer. In individual patients, no difference was seen between the restriction length fragments of the two alleles of L-MYC [6-kilobase (kb)] and 10-kb fragments in EcoRI digests in lung cancer tissues and normal tissues. But a striking correlation was found between the restriction length fragment polymorphism pattern of L-MYC and the extent of metastasis, particularly to the lymph nodes at the time of surgery: Patients with only the L band (10 kb) had few lymph node metastatic lesions, whereas patients with either the S band (6 kb) or the S and L bands almost always had lymph node metastatic lesion. A similar correlation was found between the presence of the S band and metastases to other organs. This correlation was particularly marked in cases of adenocarcinoma. These results indicate a clear genetic influence on metastases and a consequent poor prognosis for certain patients of lung cancer; L-MYC restriction length fragment polymorphism is thus shown to be a useful marker for predicting the metastatic potential of human lung cancer

  4. Hypoxia and loss of PHD2 inactivate stromal fibroblasts to decrease tumour stiffness and metastasis

    DEFF Research Database (Denmark)

    Madsen, Chris D; Pedersen, Jesper Thorhauge; Venning, Freja A

    2015-01-01

    , which can be prevented by simultaneous depletion of HIF-1α. Treatment with the PHD inhibitor DMOG in an orthotopic breast cancer model significantly decreases spontaneous metastases to the lungs and liver, associated with decreased tumour stiffness and fibroblast activation. PHD2 depletion in CAFs co......-injected with tumour cells similarly prevents CAF-induced metastasis to lungs and liver. Our data argue that reversion of CAFs towards a less active state is possible and could have important clinical implications....

  5. Detection of retinoblastoma gene deletions in spontaneous and radiation-induced mouse lung adenocarcinomas by polymerase chain reaction

    International Nuclear Information System (INIS)

    Churchill, M.E.; Gemmell, M.A.; Woloschak, G.E.

    1994-01-01

    A polymerase chain reaction (PCR) technique has been developed to detect deletions in the mouse retinoblastoma gene using histological sections from radiation-induced and spontaneous tumors as the DNA source. Six mouse Rb gene exon fragments were amplified in a 40-cycle, 3-temperature PCR protocol. The absence of any of these fragments relative to control PCR products on a Southern blot indicated a deletion of that portion of the mouse Rb gene. Tumors chosen for analysis were lung adenocarcinomas that were judged to be the cause of death. Spontaneous tumors as well as those from irradiated mice (5.69 Gy 60 Co γ rays or 0.6 Gy JANUS neutrons, which have been found to have approximately equal radiobiological effectiveness) were analyzed for mouse Rb deletions. Tumors in 6 neutron-irradiated mice had no mouse Rb deletions. However, 1 of 6 tumors from γ-irradiated mice (17%) and 6 of 18 spontaneous tumors from unirradiated mice (33%) showed a deletion in one or both mouse Rb alleles. All deletions detected were in the 5' region of the mouse Rb gene. 36 refs., 2 figs., 2 tabs

  6. FOXA2 functions as a suppressor of tumor metastasis by inhibition of epithelial-to-mesenchymal transition in human lung cancers.

    Science.gov (United States)

    Tang, Yunneng; Shu, Guangwen; Yuan, Xinwang; Jing, Naihe; Song, Jianguo

    2011-02-01

    The forkhead box transcription factor A2 (FOXA2) is an important regulator in animal development and body homeostasis. However, whether FOXA2 is involved in transforming growth factor β1 (TGF-β1)-mediated epithelial-to-mesenchymal transition (EMT) and tumor metastasis remains unknown. The present study showed that in human lung cancer cell lines, the abundance of FOXA2 positively correlates with epithelial phenotypes and negatively correlates with the mesenchymal phenotypes of cells, and TGF-β1 treatment decreased FOXA2 protein level. Consistently, knockdown of FOXA2 promoted EMT and invasion of lung cancer cells, whereas overexpression of FOXA2 reduced the invasion and suppressed TGF-β1-induced EMT. In addition, knockdown of FOXA2 induced slug expression, and ectopic expression of FOXA2 inhibited slug transcription. Furthermore, we identified that FOXA2 can bind to slug promoter through a conserved binding site, and that the DNA-binding region and transactivation region II of FOXA2 are required for repression of the slug promoter. These data demonstrate that FOXA2 functions as a suppressor of tumor metastasis by inhibition of EMT.

  7. The long non-coding RNA HOTAIR indicates a poor prognosis and promotes metastasis in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Liu, Xiang-hua; Liu, Zhi-li; Sun, Ming; Liu, Jing; Wang, Zhao-xia; De, Wei

    2013-01-01

    The identification of cancer-associated long non-coding RNAs and the investigation of their molecular and biological functions are important for understanding the molecular biology and progression of cancer. HOTAIR (HOX transcript antisense intergenic RNA) has been implicated in several cancers; however, its role in non-small cell lung cancer (NSCLC) is unknown. The aim of the present study was to examine the expression pattern of HOTAIR in NSCLC and to evaluate its biological role and clinical significance in tumor progression. Expression of HOTAIR was analyzed in 42 NSCLC tissues and four NSCLC cell lines by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Over-expression and RNA interference (RNAi) approaches were used to investigate the biological functions of HOTAIR. The effect of HOTAIR on proliferation was evaluated by MTT and colony formation assays, and cell migration and invasion were evaluated by transwell assays. Tail vein injection of cells was used to study metastasis in nude mice. Protein levels of HOTAIR targets were determined by western blot analysis. Differences between groups were tested for significance using Student’s t-test (two-tailed). HOTAIR was highly expressed both in NSCLC samples and cell lines compared with corresponding normal counterparts. HOTAIR upregulation was correlated with NSCLC advanced pathological stage and lymph-node metastasis. Moreover, patients with high levels of HOTAIR expression had a relatively poor prognosis. Inhibition of HOTAIR by RNAi decreased the migration and invasion of NSCLC cells in vitro and impeded cell metastasis in vivo. HOXA5 levels were affected by HOTAIR knockdown or over-expression in vitro. Our findings indicate that HOTAIR is significantly up-regulated in NSCLC tissues, and regulates NSCLC cell invasion and metastasis, partially via the down-regulation of HOXA5. Thus, HOTAIR may represent a new marker of poor prognosis and is a potential therapeutic target for NSCLC

  8. The Platelet Aggregation-Inducing Factor Aggrus/Podoplanin Promotes Pulmonary Metastasis

    Science.gov (United States)

    Kunita, Akiko; Kashima, Takeshi G.; Morishita, Yasuyuki; Fukayama, Masashi; Kato, Yukinari; Tsuruo, Takashi; Fujita, Naoya

    2007-01-01

    Tumor cell-induced platelet aggregation has been reported to facilitate hematogenous metastasis. Aggrus/podoplanin is a platelet aggregation-inducing factor that is up-regulated in a number of human cancers and has been implicated in tumor progression. We studied herein the role of Aggrus in tumor growth, metastasis, and survival in vivo. Aggrus expression in Chinese hamster ovary cells promoted pulmonary metastasis in both an experimental and a spontaneous mouse model. No differences in the size of metastatic foci or in primary tumor growth were found in either set of mice. Aggrus-expressing cells, which were covered with platelets, arrested in the lung microvasculature 30 minutes after injection. In addition, lung metastasis resulting from Aggrus expression decreased the survival of the mice. By generating several Aggrus point mutants, we revealed that point mutation at the platelet aggregation-stimulating domain of Aggrus (Thr34 and Thr52) obliterated both platelet aggregation and metastasis. Furthermore, administration of aspirin to mice reduced the number of metastatic foci. These results indicate that Aggrus contributes to the establishment of metastasis by promoting platelet aggregation without affecting subsequent growth. Thus, Aggrus could serve as an ideal therapeutic target for drug development to block metastasis. PMID:17392172

  9. Sulforaphane suppresses EMT and metastasis in human lung cancer through miR-616-5p-mediated GSK3β/β-catenin signaling pathways.

    Science.gov (United States)

    Wang, Da-Xuan; Zou, Yu-Jiao; Zhuang, Xi-Bin; Chen, Shu-Xing; Lin, Yong; Li, Wen-Lan; Lin, Jun-Jin; Lin, Zhi-Qiang

    2017-02-01

    Sulforaphane is a common antioxidant selectively abundant in cruciferous plants, which exhibits effective anti-cancer actions in control of tumorigenesis or progression of various cancers. A recent study has shown that sulforaphane attenuates the EGFR signaling pathway in non-small cell lung cancer (NSCLC), suggesting its potential anti-metastatic effects. In this study we assessed the involvement of sulforaphane and miR-616-5p in epithelial-mesenchymal transition (EMT) and NSCLC metastasis. Sulforaphane suppressed the cell proliferation in human NSCLC cell lines H1299, 95C and 95D with IC 50 values of 9.52±1.23, 9.04±1.90 and 17.35±2.03 μmol/L, respectively. At low concentrations (1-5 μmol/L), sulforaphane dose-dependently inhibited the migration and invasion of 95D and H1299 cells with relatively high metastatic potential. The anti-metastatic action of sulforaphane was confirmed in 95D and H1299 cell xenografts in vivo. In fresh NSCLC tissue samples from 179 patients, miR-616-5p levels were upregulated in late-stage NSCLCs, and strongly correlated with risk of NSCLC recurrence and metastasis. Consistent with the clinic observation, miR-616-5p levels in the 3 NSCLC cell lines were correlated with their metastatic ability, and were decreased by sulforaphane treatment. Silencing miR-616-5p markedly suppressed the migration and invasion of 95D cells in vitro and NSCLC metastasis in vivo. Further studies revealed that miR-616-5p directly targeted GSK3β and decreased its expression, whereas sulforaphane decreased miR-616-5p levels by histone modification, and followed by inactivation of the GSK3β/β-catenin signaling pathway and inhibition of EMT, which was characterized by loss of epithelial markers and acquisition of a mesenchymal phenotype in NSCLC cells. Our findings suggest that sulforaphane is a potential adjuvant chemotherapeutic agent for the prevention of NSCLC recurrence and metastasis, and miR-616-5p can be clinically utilized as a biomarker or

  10. Long-Term Survival of a Patient with Brainstem and Recurrent Brain Metastasis from Stage IV Nonsmall Cell Lung Cancer Treated with Multiple Gamma Knife Radiosurgeries and Craniotomies: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Andrew F. Lamm

    2012-01-01

    Full Text Available The prognosis of patients diagnosed with stage IV nonsmall cell lung cancer that have brain and brainstem metastasis is very poor, with less than a third surviving a year past their initial date of diagnosis. We present the rare case of a 57-year-old man who is a long-term survivor of brainstem and recurrent brain metastasis, after aggressive treatment. He is now five and a half years out from diagnosis and continues to live a highly functional life without evidence of disease. Four separate Gamma Knife stereotactic radiosurgeries in conjunction with two craniotomies were utilized since his initial diagnosis to treat recurrent brain metastasis while chemoradiation therapy and thoracic surgery were used to treat his primary disease in the right upper lung. In his situation, Gamma Knife radiosurgery proved to be a valuable, safe, and effective tool for the treatment of multiply recurrent brain metastases within critical normal structures.

  11. Radio-photothermal therapy mediated by a single compartment nanoplatform depletes tumor initiating cells and reduces lung metastasis in the orthotopic 4T1 breast tumor model

    Science.gov (United States)

    Zhou, Min; Zhao, Jun; Tian, Mei; Song, Shaoli; Zhang, Rui; Gupta, Sanjay; Tan, Dongfeng; Shen, Haifa; Ferrari, Mauro; Li, Chun

    2015-11-01

    Tumor Initiating Cells (TICs) are resistant to radiotherapy and chemotherapy, and are believed to be responsible for tumor recurrence and metastasis. Combination therapies can overcome the limitation of conventional cancer treatments, and have demonstrated promising application in the clinic. Here, we show that dual modality radiotherapy (RT) and photothermal therapy (PTT) mediated by a single compartment nanosystem copper-64-labeled copper sulfide nanoparticles ([64Cu]CuS NPs) could suppress breast tumor metastasis through eradication of TICs. Positron electron tomography (PET) imaging and biodistribution studies showed that more than 90% of [64Cu]CuS NPs was retained in subcutaneously grown BT474 breast tumor 24 h after intratumoral (i.t.) injection, indicating the NPs are suitable for the combination therapy. Combined RT/PTT therapy resulted in significant tumor growth delay in the subcutaneous BT474 breast cancer model. Moreover, RT/PTT treatment significantly prolonged the survival of mice bearing orthotopic 4T1 breast tumors compared to no treatment, RT alone, or PTT alone. The RT/PTT combination therapy significantly reduced the number of tumor nodules in the lung and the formation of tumor mammospheres from treated 4T1 tumors. No obvious side effects of the CuS NPs were noted in the treated mice in a pilot toxicity study. Taken together, our data support the feasibility of a therapeutic approach for the suppression of tumor metastasis through localized RT/PTT therapy.Tumor Initiating Cells (TICs) are resistant to radiotherapy and chemotherapy, and are believed to be responsible for tumor recurrence and metastasis. Combination therapies can overcome the limitation of conventional cancer treatments, and have demonstrated promising application in the clinic. Here, we show that dual modality radiotherapy (RT) and photothermal therapy (PTT) mediated by a single compartment nanosystem copper-64-labeled copper sulfide nanoparticles ([64Cu]CuS NPs) could suppress

  12. Lung cancer-derived Dickkopf1 is associated with bone metastasis and the mechanism involves the inhibition of osteoblast differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Chu, Tianqing; Teng, Jiajun; Jiang, Liyan; Zhong, Hua; Han, Baohui, E-mail: baohuihan1@163.com

    2014-01-17

    Highlights: •DKK1 level was associated with NSCLC bone metastases. •Lung tumor cells derived DKK1 inhibited osteoblast differentiation. •Lung tumor cells derived DKK1 modulates β-catenin and RUNX2. -- Abstract: Wnt/β-catenin signaling and Dickkopf1 (DKK1) play important roles in the progression of lung cancer, which preferably metastasizes to skeleton. But the role of them in bone dissemination is poorly understood. This study aims to define the role of DKK1 in lung cancer bone metastases and investigate the underlying mechanism. Our results demonstrated that DKK1 over-expression was a frequent event in non-small-cell lung cancer (NSCLC) blood samples, and serous DKK1 level was much higher in bone metastatic NSCLC compared to non-bone metastatic NSCLC. We also found that conditioned medium from DKK1 over-expressing lung cancer cells inhibited the differentiation of osteoblast, determined by alkaline phosphatase activity and osteocalcin secretion, whereas the conditioned medium from DKK1 silencing lung cancer cells exhibited the opposite effects. Mechanistically, DKK1 reduced the level of β-catenin and RUNX2, as well as inhibiting the nuclear translocation of β-catenin. Taken together, these results suggested that lung cancer-produced DKK1 may be an important mechanistic link between NSCLC and bone metastases, and targeting DKK1 may be an effective method to treat bone metastase of NSCLC.

  13. Spontaneous atopic dermatitis is mediated by innate immunity, with the secondary lung inflammation of the atopic march requiring adaptive immunity.

    Science.gov (United States)

    Saunders, Sean P; Moran, Tara; Floudas, Achilleas; Wurlod, Felicity; Kaszlikowska, Agnieszka; Salimi, Maryam; Quinn, Emma M; Oliphant, Christopher J; Núñez, Gabriel; McManus, Ross; Hams, Emily; Irvine, Alan D; McKenzie, Andrew N J; Ogg, Graham S; Fallon, Padraic G

    2016-02-01

    Atopic dermatitis (AD) is an inflammatory skin condition that can occur in early life, predisposing to asthma development in a phenomenon known as the atopic march. Although genetic and environmental factors are known to contribute to AD and asthma, the mechanisms underlying the atopic march remain poorly understood. Filaggrin loss-of-function mutations are a major genetic predisposer for the development of AD and progression to AD-associated asthma. We sought to experimentally address whether filaggrin mutations in mice lead to the development of spontaneous eczematous inflammation and address the aberrant immunologic milieu arising in a mouse model of filaggrin deficiency. Filaggrin mutant mice were generated on the proallergic BALB/c background, creating a novel model for the assessment of spontaneous AD-like inflammation. Independently recruited AD case collections were analyzed to define associations between filaggrin mutations and immunologic phenotypes. Filaggrin-deficient mice on a BALB/c background had profound spontaneous AD-like inflammation with progression to compromised pulmonary function with age, reflecting the atopic march in patients with AD. Strikingly, skin inflammation occurs independently of adaptive immunity and is associated with cutaneous expansion of IL-5-producing type 2 innate lymphoid cells. Furthermore, subjects with filaggrin mutations have an increased frequency of type 2 innate lymphoid cells in the skin in comparison with control subjects. This study provides new insights into our understanding of the atopic march, with innate immunity initiating dermatitis and the adaptive immunity required for subsequent development of compromised lung function. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Paracrine signaling by VEGF-C promotes non-small cell lung cancer cell metastasis via recruitment of tumor-associated macrophages.

    Science.gov (United States)

    Deng, Yanchao; Yang, Yang; Yao, Bei; Ma, Lei; Wu, Qipeng; Yang, Zhicheng; Zhang, Luyong; Liu, Bing

    2018-03-15

    High expression of tumoral vascular endothelial growth factor C (VEGF-C) is correlated with clinical non-small cell lung cancer (NSCLC) metastasis and patient survival. Nevertheless, the comprehensive mechanisms accounting for VEGF-C-mediated cancer progression remain largely unclear. The present study found that VEGF-C expression was upregulated in various NSCLC cell lines. By utilizing transwell migration assay, we found that both recombinant VEGF-C protein and overexpression of VEGF-C in NSCLC cells (A549 and H441 cell lines) could efficiently enhance RAW264.7 cell (murine macrophages) migration. However, recombinant VEGF-C treatment had no effects on both CD206 (an M2 macrophage marker) expression and M1/M2 cytokine profiles of macrophages. Furthermore, additional treatment of recombinant Flt-4/Fc, the specific VEGFR-3 inhibitor or the specific VEGFR-2 inhibitor significantly suppressed macrophage migration compared with A549-CM (conditioned medium) or H441-CM alone group, confirming that NSCLC cells-derived VEGF-C is sufficient to promote macrophage migration. Interestingly, VEGF-C could stimulate the Src/p38 signaling via VEGFR-2/3 axis in macrophages, and inhibition of Src/p38 signaling obviously reversed the enhancement effect of VEGF-C on macrophage migration. Finally, the functional importance of macrophage infiltration induced by tumoral VEGF-C in promoting metastasis was established in a mouse model. In conclusion, our results highlight a novel function of tumoral VEGF-C that paracrinely induces macrophage recruitment, and resultantly promotes NSCLC cell metastasis. Therefore, VEGF-C/VEGFR-2/3 axis may be a promising microenvironmental target against progression of NSCLC. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Brain metastasis from colorectal cancer

    International Nuclear Information System (INIS)

    Bamba, Yoshiko; Itabashi, Michio; Hirosawa, Tomoichiro; Ogawa, Shinpei; Noguchi, Eiichiro; Takemoto, Kaori; Shirotani, Noriyasu; Kameoka, Shingo

    2007-01-01

    The present study was performed to clarify the clinical characteristics of brain metastasis from colorectal cancer. Five patients with brain metastasis from colorectal cancer treated at our institute between 2001 and 2005 were included in the study. Clinical findings and survival time were determined and an appropriate system for follow-up in such cases was considered. Brain metastasis was found after surgery for colorectal cancer in 4 cases. In addition, colorectal cancer was found after diagnosis of brain metastasis in 1 case. At the time of diagnosis of brain metastasis, all patients had lung metastasis and 3 had liver metastasis. The mean periods between surgery for colorectal cancer and lung and brain metastases were 19.5 and 38.2 months, respectively. In all cases, brain metastasis was diagnosed by imaging after the appearance of neurological symptoms. Brain metastases were multiple in 1 case and focal in 4 cases. We performed gamma knife radiation therapy, and the symptoms disappeared or decreased in all cases. Mean survival time after brain metastasis was 3.0 months. Prognosis after brain metastasis is poor, but gamma knife radiation therapy contributed to patients' quality of life. (author)

  16. Lung metastasis fails in MMTV-PyMT oncomice lacking S100A4 due to a T-cell deficiency in primary tumors

    DEFF Research Database (Denmark)

    Grum-Schwensen, Birgitte; Klingelhöfer, Jörg; Grigorian, Mariam

    2010-01-01

    . In contrast, in S100A4(-/-) PyMT tumors, a significant suppression of T-cell infiltration was documented at the transition period. In vitro, the S100A4 protein mediated the attraction of T cells. Moreover, S100A4(+/+), but not S100A4(-/-), fibroblasts stimulated the invasion of T lymphocytes into fibroblast...... monolayers. In vivo, the presence of S100A4(+/+), but not S100A4(-/-), fibroblasts significantly stimulated the attraction of T lymphocytes to the site of the growing tumor. Increased levels of T cells were also observed in the premetastatic lungs of tumor-bearing mice primed to metastasize by S100A4......Interactions between tumor and stroma cells are essential for the progression of cancer from its initial growth at a primary site to its metastasis to distant organs. The metastasis-stimulating protein S100A4 exerts its function as a stroma cell-derived factor. Genetic depletion of S100A4...

  17. Silibinin and Paclitaxel Cotreatment Significantly Suppress the Activity and Lung Metastasis of Triple Negative 4T1 Mammary Tumor Cell in Mice

    Directory of Open Access Journals (Sweden)

    Bing-Ying Ho

    2012-10-01

    Full Text Available The in vitro and in vivo bioactivities of silibinin (SB, paclitaxel (PTX and SB and PTX in combination (SB+PTX against murine metastatic mammary 4T1 cancer cell line were investigated. Isobologram and combination index (CI analyses showed that SB and PTX can function synergistically in the inhibition of 4T1 cell proliferation with a CI value<1. Both SB and PTX alone or SB+PTX treatment inhibited 4T1 cell migration and motility possibly through downregulation of the serpin protease nexin-1 (PN-1 and N-cadherin expression, inhibition of matrix metalloprotease (MMP-9 activity, and upregulation of E-cadherin. Flow cytometry and Western blot analyses demonstrated that both drugs deregulated cell-cycle mediators and induced apoptosis in 4T1 cells. A real-time in vivo bioluminescence imaging system to monitor the breast cancer cell metastasis in syngeneic BALB/c mice was established using a stable 4T1pGL−COX−2/Luc cell clone carrying a COX-2 promoter driven-luciferase reporter gene. In vivo study using the allograft 4T1pGL−COX−2/Luc metastatic mouse model indicated that SB co-treated with PTX can significantly suppress lung metastasis of 4T1 cells likely through inhibiting cell proliferation and angiogenesis. Together, this study demonstrates that SB could act synergistically with PTX in 4T1 cells, providing a therapeutic option for highly metastatic triple negative breast cancer.

  18. Downregulation of Cyclophilin A by siRNA diminishes non-small cell lung cancer cell growth and metastasis via the regulation of matrix metallopeptidase 9

    Directory of Open Access Journals (Sweden)

    Qian Zhe

    2012-10-01

    Full Text Available Abstract Background Cyclophilin A (CypA is a cytosolic protein possessing peptidyl-prolyl isomerase activity that was recently reported to be overexpressed in several cancers. Here, we explored the biology and molecular mechanism of CypA in non-small cell lung cancer (NSCLC. Methods The expression of CypA in human NSCLC cell lines was detected by real-time reverse transcription PCR. The RNA interference-mediated knockdown of CypA was established in two NSCLC cell lines (95C and A549. 239836 CypA inhibitor was also used to suppress CypA activity. Tumorigenesis was assessed based on cellular proliferation, colony formation assays, and anchorage-independent growth assays; metastasis was assessed based on wound healing and transwell assays. Results Suppression of CypA expression inhibited the cell growth and colony formation of A549 and 95C cells. CypA knockdown resulted in the inhibition of cell motility and invasion. Significantly, we show for the first time that CypA increased NSCLC cell invasion by regulating the activity of secreted matrix metallopeptidase 9 (MMP9. Likewise, suppression of CypA with 239836 CypA inhibitor decreased cell proliferation and MMP9 activity. Conclusions The suppression of CypA expression was correlated with decreased NSCLC cell tumorigenesis and metastasis.

  19. Enhanced breast cancer cell adherence to the lung endothelium via PAF acetylhydrolase inhibition: a potential mechanism for enhanced metastasis in smokers.

    Science.gov (United States)

    Kispert, Shannon E; Marentette, John O; McHowat, Jane

    2014-11-15

    Cancer deaths are primarily caused by distant metastases, rather than by primary tumor growth; however, the role of smoking in metastasis remains unclear. We demonstrated previously that endothelial cell platelet-activating factor (PAF) production results in enhanced inflammatory cell recruitment to the lung. We propose that endothelial cell PAF accumulation plays a role in cancer cell migration to distal locations. We used cigarette smoke extract (CSE) to inhibit the activity of endothelial cell PAF acetylhydrolase (PAF-AH), which hydrolyzes and inactivates PAF, and determined whether this results in increased endothelial cell PAF accumulation and breast cancer adherence. Incubation of human lung microvascular endothelial cells (HMVEC-L) with CSE resulted in a significant inhibition of PAF-AH activity that was accompanied by increased PAF production and adherence of highly invasive MDA-MB-231 breast cancer cells. Pretreatment of HMVEC-L with (S)-bromoenol lactone to inhibit calcium-independent phospholipase A2β (iPLA2β, which initiates endothelial cell PAF production) prior to CSE exposure resulted in complete inhibition of MDA-MB-231 cell adherence. Similarly, pretreatment of MDA-MB-231 cells with the PAF receptor antagonist Ginkgo biloba resulted in inhibition of adherence to the endothelium. Immunoblot analysis indicated an increase in MDA-MB-231 cell PAF receptor expression with CSE exposure. Taken together, our data indicate that CSE exposure increases endothelial cell PAF production, resulting in enhanced adherence of tumor cells to the endothelium. Our in vitro data indicate that increased tumor cell adherence would lead to enhanced metastasis formation in smokers. Potential therapeutic targets include endothelial cell iPLA2β or the tumor cell PAF receptor. Copyright © 2014 the American Physiological Society.

  20. RIG-I Helicase-Independent Pathway in Sendai Virus-Activated Dendritic Cells Is Critical for Preventing Lung Metastasis of AT6.3 Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Tomonori Kato

    2010-11-01

    Full Text Available We recently demonstrated highly efficient antitumor immunity against dermal tumors of B16F10 murine melanoma with the use of dendritic cells (DCs activated by replication-competent, as well as nontransmissible-type, recombinant Sendai viruses (rSeV, and proposed a new concept, “immunostimulatory virotherapy,” for cancer immunotherapy. However, there has been little information on the efficacies of thismethod: 1 inmore clinically relevant situations including metastatic diseases, 2 on other tumor types and other animal species, and 3 on the related molecular/cellular mechanisms. In this study, therefore, we investigated the efficacy of vaccinating DCs activated by fusion gene-deleted nontransmissible rSeV on a rat model of lung metastasis using a highly malignant subline of Dunning R-3327 prostate cancer, AT6.3. rSeV/dF-green fluorescent protein (GFP-activated bone marrow-derived DCs (rSeV/dF-GFP-DC, consistent with results previously observed in murine DCs. Vaccination of rSeV/dF-GFP-DC was highly effective at preventing lung metastasis after intravenous loading of R-3327 tumor cells, compared with the effects observed with immature DCs or lipopolysaccharide-activated DCs. Interestingly, neither CTL activity nor DC trafficking showed any apparent difference among groups. Notably, rSeV/dF-DCs expressing a dominant-negative mutant of retinoic acid-inducible gene I (RIG-I (rSeV/dF-RIGIC-DC, an RNA helicase that recognizes the rSeV genome for inducing type I interferons, largely lost the expression of proinflammatory cytokines without any impairment of antitumor activity. These results indicate the essential role of RIG-I-independent signaling on antimetastatic effect induced by rSeV-activated DCs and may provide important insights to DC-based immunotherapy for advanced malignancies.

  1. The role of cytochrome c oxidase subunit Va in non-small cell lung carcinoma cells: association with migration, invasion and prediction of distant metastasis

    Directory of Open Access Journals (Sweden)

    Chen Wen-Liang

    2012-06-01

    Full Text Available Abstract Background Lung cancer is one of the most lethal malignancies worldwide, but useful biomarkers of lung cancer are still insufficient. The aim of this study is to identify some membrane-bound protein(s associated with migration and invasion in human non-small cell lung cancer (NSCLC cells. Methods We classified four NSCLC cell lines into high and low migration/invasion groups by Transwell and Matrigel assays. Using two-dimensional gel electrophoresis and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS, we identified 10 membrane-associated proteins being significantly overexpressed in the high migration/invasion group. The expression of the target protein in the four NSCLC cell lines was then confirmed by reverse transcription polymerase chain reaction (RT-PCR, western blot and immunostaining. RNA interference technique was applied to observe the influence of the target protein on migration and invasion. Gelatin zymography was also performed to evaluate the activities of matrix metalloproteinase (MMP-2 and MMP-9. Expression condition of the target protein on surgical specimens was further examined by immunohistochemical staining and the clinicopathologic data were analyzed. Results We identified a mitochondria-bound protein cytochrome c oxidase subunit Va (COX Va because of its abundant presence found exclusively in tumorous areas. We also demonstrated that migration and invasion of NSCLC cells decreased substantially after knocking down COX Va by siRNA. Meanwhile, we found a positive correlation between COX Va expression, Bcl-2 expression and activities of MMP-2 and MMP-9 in NSCLC cells. Immunohistochemical staining of surgically resected lung adenocarcinomas in 250 consecutive patients revealed that strong COX Va expression was found in 54.8% (137/250 of patients and correlated positively with the status of lymph node metastasis (P = 0.032. Furthermore, strong COX Va expression was

  2. The role of cytochrome c oxidase subunit Va in non-small cell lung carcinoma cells: association with migration, invasion and prediction of distant metastasis

    International Nuclear Information System (INIS)

    Chen, Wen-Liang; Kuo, Kuang-Tai; Chou, Teh-Ying; Chen, Chien-Lung; Wang, Chih-Hao; Wei, Yau-Huei; Wang, Liang-Shun

    2012-01-01

    Lung cancer is one of the most lethal malignancies worldwide, but useful biomarkers of lung cancer are still insufficient. The aim of this study is to identify some membrane-bound protein(s) associated with migration and invasion in human non-small cell lung cancer (NSCLC) cells. We classified four NSCLC cell lines into high and low migration/invasion groups by Transwell and Matrigel assays. Using two-dimensional gel electrophoresis and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), we identified 10 membrane-associated proteins being significantly overexpressed in the high migration/invasion group. The expression of the target protein in the four NSCLC cell lines was then confirmed by reverse transcription polymerase chain reaction (RT-PCR), western blot and immunostaining. RNA interference technique was applied to observe the influence of the target protein on migration and invasion. Gelatin zymography was also performed to evaluate the activities of matrix metalloproteinase (MMP)-2 and MMP-9. Expression condition of the target protein on surgical specimens was further examined by immunohistochemical staining and the clinicopathologic data were analyzed. We identified a mitochondria-bound protein cytochrome c oxidase subunit Va (COX Va) because of its abundant presence found exclusively in tumorous areas. We also demonstrated that migration and invasion of NSCLC cells decreased substantially after knocking down COX Va by siRNA. Meanwhile, we found a positive correlation between COX Va expression, Bcl-2 expression and activities of MMP-2 and MMP-9 in NSCLC cells. Immunohistochemical staining of surgically resected lung adenocarcinomas in 250 consecutive patients revealed that strong COX Va expression was found in 54.8% (137/250) of patients and correlated positively with the status of lymph node metastasis (P = 0.032). Furthermore, strong COX Va expression was associated with the presence of distant metastasis (P = 0

  3. Distinguishing the histological and radiological features of cystic lung disease in Birt-Hogg-Dubé syndrome from those of tobacco-related spontaneous pneumothorax.

    Science.gov (United States)

    Fabre, Aurelie; Borie, Raphael; Debray, Marie Pierre; Crestani, Bruno; Danel, Claire

    2014-04-01

    Birt-Hogg-Dubé syndrome (BHD) is a rare autosomal dominantly inherited genodermatosis that predisposes to cystic lung disease, leading to spontaneous pneumothoraces. This retrospective analysis of five BHD cases (two men, three women) compared lung histology and computed tomography (CT) imaging to a matched cohort of non-BHD patients with spontaneous pneumothoraces (SPN). Lung was sampled during pleurodesis to resect bullae. Recurrent pneumothoraces was seen in two patients. Fourteen sets of histological slides (seven in each group) and 10 CT scans (five in each group) were reviewed. CT scans in BHD showed multiple cysts with a basal predominance and intraparenchymal/peribronchial distribution. On histological examination, BHD lungs showed punch-out cysts with no inflammation, and lacked subpleural fibroelastotic scars and smoking changes. In contrast, all SPN cases showed respiratory bronchiolitis and subpleural fibroelastotic scars. This study emphasizes the importance of smoking history and topography of the lesions in assessing cystic lung disease. Pathologists need to remain alert to the possibility of BHD in the setting of recurrent pneumothoraces in a non-smoker, in particular in a woman, at any age, and should take part in a multidisciplinary approach to the diagnosis of cystic lung disease to obtain clinical and CT scan details. © 2013 John Wiley & Sons Ltd.

  4. Discordant Findings of Skeletal Metastasis Between Tc99m MDP Bone Scans and F18 FDG PET/CT Imaging for Advanced Breast and Lung Cancers—Two Case Reports and Literature Review

    Directory of Open Access Journals (Sweden)

    Yu-Wen Chen

    2007-12-01

    Full Text Available Traditionally, Tc99m methyl diphosphate (MDP bone scintigraphy provides high-sensitivity detection of skeletal metastasis from breast and lung cancers in regular follow-up. Fluorodeoxyglucose (FDG positron emission tomography/computed tomography (PET/CT, based on the glucose metabolism of malignant cells, plays a role in describing rumor growth, proliferation of neoplasm and the extent of metastasis. In general, concordant findings of skeletal metastasis are seen on both types of image, especially in cases of breast and lung cancer. However, there were extremely discordant findings of skeletal metastasis between bone scans and F18 FDG PET/CT imaging in two cases among 300 consecutive F18 FDG PET/CT follow-up exams of patients with malignancies, during the past year, in our center. Both cases, one of breast cancer and one of lung cancer, had negative bone scintigraphic findings, but a diffusely high grade of F18 FDG avid marrow infiltration in the axial spine, leading to the diagnosis of stage IV disease in both cases. Owing to variant genetic aberrance of malignance, F18 FDG PET/CT reveals direct evidence of diffuse, rapid neoplasm metabolism in the bone marrow of the spine, but not of secondary osteoblastic reactions in vivo. F18 FDG PET/CT should always be employed in the follow-up of patients with malignancies.

  5. Gastric cancer metastasis mimicking primary lung cancer - case report and review of the literature; Metastase de cancer gastrico simulando neoplasia primaria de pulmao - relato de caso e revisao da literatura

    Energy Technology Data Exchange (ETDEWEB)

    Escuissato, Dante Luiz; Ledesma, Jorge Alberto; Urban, Linei Augusta Brolini Delle; Liu, Cristhian Bau [Parana Univ., Curitiba, PR (Brazil). Hospital de Clinicas. Servico de Radiologia]. E-mail: info@dapi.com.br; Reis Filho, Jorge Sergio [Parana Univ., Curitiba, PR (Brazil). Hospital de Clinicas. Servico de Patologia; Oliveira Filho, Adilson Gil; Ferri, Mauricio Beller; Hossaka, Marco Aurelio [Parana Univ., Curitiba, PR (Brazil). Hospital de Clinicas

    2002-04-01

    Gastric cancer frequently presents intraperitoneal spread. Distant metastasis are rare. The authors describe a case of a 47-year-old white man, long-term cigarette smoker, who had a right upper lobe mass seen on plain films and computed tomography of the chest. A gastric adenocarcinoma was concomitantly diagnosed by endoscopic examination. A bronchoscopy guided biopsy showed that the lung mass was in fact a metastasis from gastric adenocarcinoma. In this article, the imaging findings of gastric cancer and the patterns of dissemination to other organs are reviewed. (author)

  6. MiR-424 Promotes Non-Small Cell Lung Cancer Progression and Metastasis through Regulating the Tumor Suppressor Gene TNFAIP1

    Directory of Open Access Journals (Sweden)

    Ming Zhang

    2017-05-01

    Full Text Available Background/Aims: This study aimed to investigate the potential roles of miR-424 expression in non-small cell lung cancer (NSCLC metastasis and growth and its underlying mechanism. Methods: The expression of miR-424 in two NSCLC cell lines (A549 and H1975 was altered by transfection with miR-424 mimic and inhibitor. Effects of miR-424 overexpression and suppression on cells migration, invasion and colony formation were analyzed. Target genes for miR-424 were predicted using bioinformatics method and then verified using luciferase assay. Effects of miR-424 expression on cell migration, invasion and proliferation were reanalyzed on the condition of TNFAIP1 was silenced. Moreover, TNFAIP1 silencing and miR-424 modified A549 cells were subcutaneous injected into node BALB/c mice to confirm the regulation of miR-424 on TNFAIP1 in regulating tumor growth. Results: Compared with the control, miR-424 overexpression significantly increased the migrated and invaded cells, as well as the proliferated colonies. TNFAIP1 was a predicted target gene for miR-424, and was negatively regulated by miR-424. TNFAIP1 silence significantly increased the migrated and invaded cells compared to that in control, while these increases were abolished by miR-424 suppression. Animal experiment further evidenced miR-424 affected tumor growth by regulating TNFAIP1. Conclusions: These data demonstrate that miR-424 may be a contributor for NSCLC progression and metastasis through involving in cell migration, invasion and proliferation via inhibiting TNFAIP1. This study may provide theoretical basis for miR-424 in NSCLC target therapeutic treatment.

  7. Long-term survival in patients with non-small cell lung cancer and synchronous brain metastasis treated with whole-brain radiotherapy and thoracic chemoradiation

    International Nuclear Information System (INIS)

    Arrieta, Oscar; Villarreal-Garza, Cynthia; Zamora, Jesús; Blake-Cerda, Mónika; Mata, María D de la; Zavala, Diego G; Muñiz-Hernández, Saé; Garza, Jaime de la

    2011-01-01

    Brain metastases occur in 30-50% of Non-small cell lung cancer (NSCLC) patients and confer a worse prognosis and quality of life. These patients are usually treated with Whole-brain radiotherapy (WBRT) followed by systemic therapy. Few studies have evaluated the role of chemoradiotherapy to the primary tumor after WBRT as definitive treatment in the management of these patients. We reviewed the outcome of 30 patients with primary NSCLC and brain metastasis at diagnosis without evidence of other metastatic sites. Patients were treated with WBRT and after induction chemotherapy with paclitaxel and cisplatin for two cycles. In the absence of progression, concurrent chemoradiotherapy for the primary tumor with weekly paclitaxel and carboplatin was indicated, with a total effective dose of 60 Gy. If disease progression was ruled out, four chemotherapy cycles followed. Median Progression-free survival (PFS) and Overall survival (OS) were 8.43 ± 1.5 and 31.8 ± 15.8 months, respectively. PFS was 39.5% at 1 year and 24.7% at 2 years. The 1- and 2-year OS rates were 71.1 and 60.2%, respectively. Three-year OS was significantly superior for patients with N0-N1 stage disease vs. N2-N3 (60 vs. 24%, respectively; Response rate [RR], 0.03; p= 0.038). Patients with NSCLC and brain metastasis might benefit from treatment with WBRT and concurrent thoracic chemoradiotherapy. The subgroup of N0-N1 patients appears to achieve the greatest benefit. The result of this study warrants a prospective trial to confirm the benefit of this treatment

  8. Bone metastasis in patients with non-small cell lung cancer: The diagnostic role of F-18 FDG PET/CT

    International Nuclear Information System (INIS)

    Liu Ningbo; Ma Li; Zhou Wei; Pang Qingsong; Hu Man; Shi Fang; Fu Zheng; Li Minghuan; Yang Guoren; Yu Jinming

    2010-01-01

    Purpose: To evaluate the performance of F-18 FDG PET/CT in the detection of bone metastasis in non-small cell lung cancer (NSCLC) patients. Materials and methods: Three hundred and sixty-two consecutive NSCLC patients who underwent F-18 FDG PET/CT scanning were retrospectively analyzed. Each image of PET/CT, combined CT, and PET was performed at 10 separate areas and interpreted blindly and separately. The sensitivity, specificity and accuracy of F-18 FDG PET/CT, combined CT and F-18 FDG PET were calculated and the results were statistically analyzed. Results: Bone metastasis was confirmed in 82 patients with 331 positive segments based on the image findings and clinical follow-up. On patient-based analysis, the sensitivity of F-18 FDG PET/CT (93.9%) was significantly higher than those of combined CT (74.4%) and F-18 FDG PET (84.1%), respectively (p < 0.05). The overall specificity and accuracy of combined CT, F-18 FDG PET, and F-18 FDG PET/CT were 90.7%, 93.2%, 98.9% and 87.0%, 91.2%, and 97.8%, respectively (compared with PET/CT, p < 0.05). On segment-based analysis, the sensitivity of the three modalities were 79.5%, 94.3%, and 98.8%, respectively (compared with PET/CT, p < 0.05). The overall specificity and accuracy of the three modalities were 87.9%, 89.2%, 98.6% and 84.5%, 91.2%, 98.7%, respectively (compared with PET/CT, p < 0.05). Conclusion: F-18 FDG PET/CT is superior to F-18 FDG PET or combined CT in detecting bone metastasis of NSCLC patients because of the complementation of CT and PET. It is worth noting that the added value of F-18 FDG PET/CT may beneficially impact the clinical management of NSCLC.

  9. Combination of intravenous dexmedetomidine with topicalization of airway for placement of double lumen tube in a spontaneously breathing patient of giant lung bullae

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    Vikas Karne

    2016-10-01

    Here we present a patient with giant lung bulla in left lower lobe with severely reduced pulmonary reserves and significant air-trapping posted for VAT assisted bullectomy. Anaesthesia challenges including pathological changes, its effects during induction of anaesthesia, and issues related to placement of double lumen tube in a spontaneously breathing patient are discussed with possible advantages of dexmedetomidine in this special group of patients.

  10. Durable recurrence-free survival after pneumonectomy for late lung metastasis from rectal cancer: case report with genetic and epigenetic analyses

    International Nuclear Information System (INIS)

    Imperatori, Andrea; Rotolo, Nicola; Dominioni, Lorenzo; Nardecchia, Elisa; Cattoni, Maria; Cimetti, Laura; Riva, Cristina; Sessa, Fausto; Furlan, Daniela

    2015-01-01

    Treatment of pulmonary recurrence from colorectal cancer involving the main bronchus usually entails palliation using interventional bronchoscopy, because the prognosis is generally very poor. Surgical experience has clarified that in this setting pneumonectomy should only be performed in carefully selected patients showing favorable prognostic profiles (defined by low carcinoembryonic antigen serum levels pre-thoracotomy), solitary and completely resectable pulmonary metastasis, and long disease-free intervals. In the few long-term survivors after pneumonectomy for late-recurrent colorectal cancer, the disease has a relatively indolent metastatic course and genetic and epigenetic profiling may provide further insight regarding tumor evolution. We describe a rare case of late hilar-endobronchial and lymph nodal recurrence of rectal cancer, sequential to hepatic metastasectomy, that we successfully treated with pneumonectomy and chemotherapy (leucovorin, 5-fluorouracil and oxaliplatin regimen); the patient achieved 7-year relapse-free survival after lung metastasectomy and 24-year overall survival after primary rectal cancer resection. To our knowledge, this is the longest survival reported after sequential liver resection and pneumonectomy for recurrent colorectal cancer. In our case the primary rectal cancer and its recurrences showed identical immunohistochemical patterns. The primary rectal cancer and the matched metastases (hepatic, pulmonary and lymph nodal) demonstrated no KRAS, NRAS, BRAF and PIK3CA mutations, a microsatellite stable phenotype, and no tumor protein p53 alterations or recurrent copy number alterations on chromosome 8. High genetic concordances between the paired primary tumor and metastases suggest that the key tumor biological traits remained relatively conserved in the three metastatic sites. Minor differences in gene specific hypermethylation were observed between the primary tumor and lung and nodal metastases. These differences suggest

  11. Systems toxicology approaches enable mechanistic comparison of spontaneous and cigarette smoke-related lung tumor development in the A/J mouse model.

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    Luettich, Karsta; Xiang, Yang; Iskandar, Anita; Sewer, Alain; Martin, Florian; Talikka, Marja; Vanscheeuwijck, Patrick; Berges, An; Veljkovic, Emilija; Gonzalez-Suarez, Ignacio; Schlage, Walter; Hoeng, Julia; Peitsch, Manuel

    2014-06-01

    The A/J mouse is highly susceptible to lung tumor induction and has been widely used as a screening model in carcinogenicity testing and chemoprevention studies. However, the A/J mouse model has several disadvantages. Most notably, it develops lung tumors spontaneously. Moreover, there is a considerable gap in our understanding of the underlying mechanisms of pulmonary chemical carcinogenesis in the A/J mouse. Therefore, we examined the differences between spontaneous and cigarette smoke-related lung tumors in the A/J mouse model using mRNA and microRNA (miRNA) profiling. Male A/J mice were exposed whole-body to mainstream cigarette smoke (MS) for 18 months. Gene expression interaction term analysis of lung tumors and surrounding non-tumorous parenchyma samples from animals that were exposed to either 300 mg/m(3) MS or sham-exposed to fresh air indicated significant differential expression of 296 genes. Ingenuity Pathway Analysis(®) (IPA(®)) indicated an overall suppression of the humoral immune response, which was accompanied by a disruption of sphingolipid and glycosaminoglycan metabolism and a deregulation of potentially oncogenic miRNA in tumors of MS-exposed A/J mice. Thus, we propose that MS exposure leads to severe perturbations in pathways essential for tumor recognition by the immune system, thereby potentiating the ability of tumor cells to escape from immune surveillance. Further, exposure to MS appeared to affect expression of miRNA, which have previously been implicated in carcinogenesis and are thought to contribute to tumor progression. Finally, we identified a 50-gene expression signature and show its utility in distinguishing between cigarette smoke-related and spontaneous lung tumors.

  12. Systems toxicology approaches enable mechanistic comparison of spontaneous and cigarette smoke-related lung tumor development in the A/J mouse model

    Directory of Open Access Journals (Sweden)

    Luettich Karsta

    2014-06-01

    Full Text Available The A/J mouse is highly susceptible to lung tumor induction and has been widely used as a screening model in carcinogenicity testing and chemoprevention studies. However, the A/J mouse model has several disadvantages. Most notably, it develops lung tumors spontaneously. Moreover, there is a considerable gap in our understanding of the underlying mechanisms of pulmonary chemical carcinogenesis in the A/J mouse. Therefore, we examined the differences between spontaneous and cigarette smokerelated lung tumors in the A/J mouse model using mRNA and microRNA (miRNA profiling. Male A/J mice were exposed whole-body to mainstream cigarette smoke (MS for 18 months. Gene expression interaction term analysis of lung tumors and surrounding nontumorous parenchyma samples from animals that were exposed to either 300 mg/m3 MS or sham-exposed to fresh air indicated significant differential expression of 296 genes. Ingenuity Pathway Analysis® (IPA® indicated an overall suppression of the humoral immune response, which was accompanied by a disruption of sphingolipid and glycosaminoglycan metabolism and a deregulation of potentially oncogenic miRNA in tumors of MS-exposed A/J mice. Thus, we propose that MS exposure leads to severe perturbations in pathways essential for tumor recognition by the immune system, thereby potentiating the ability of tumor cells to escape from immune surveillance. Further, exposure to MS appeared to affect expression of miRNA, which have previously been implicated in carcinogenesis and are thought to contribute to tumor progression. Finally, we identified a 50-gene expression signature and show its utility in distinguishing between cigarette smoke-related and spontaneous lung tumors

  13. Stereotactic body radiotherapy for stage I lung cancer and small lung metastasis: evaluation of an immobilization system for suppression of respiratory tumor movement and preliminary results

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    Ayakawa Shiho

    2009-05-01

    Full Text Available Abstract Background In stereotactic body radiotherapy (SBRT for lung tumors, reducing tumor movement is necessary. In this study, we evaluated changes in tumor movement and percutaneous oxygen saturation (SpO2 levels, and preliminary clinical results of SBRT using the BodyFIX immobilization system. Methods Between 2004 and 2006, 53 consecutive patients were treated for 55 lesions; 42 were stage I non-small cell lung cancer (NSCLC, 10 were metastatic lung cancers, and 3 were local recurrences of NSCLC. Tumor movement was measured with fluoroscopy under breath holding, free breathing on a couch, and free breathing in the BodyFIX system. SpO2 levels were measured with a finger pulseoximeter under each condition. The delivered dose was 44, 48 or 52 Gy, depending on tumor diameter, in 4 fractions over 10 or 11 days. Results By using the BodyFIX system, respiratory tumor movements were significantly reduced compared with the free-breathing condition in both craniocaudal and lateral directions, although the amplitude of reduction in the craniocaudal direction was 3 mm or more in only 27% of the patients. The average SpO2 did not decrease by using the system. At 3 years, the local control rate was 80% for all lesions. Overall survival was 76%, cause-specific survival was 92%, and local progression-free survival was 76% at 3 years in primary NSCLC patients. Grade 2 radiation pneumonitis developed in 7 patients. Conclusion Respiratory tumor movement was modestly suppressed by the BodyFIX system, while the SpO2 level did not decrease. It was considered a simple and effective method for SBRT of lung tumors. Preliminary results were encouraging.

  14. [Comparison of the efficacy of gadobutrol and multihance in contrast-enhanced MRI for diagnosis of brain metastasis in lung cancer].

    Science.gov (United States)

    Li, Zhen-Lin; Chen, Xian; Xia, Chun-Chao; Sun, Jia-Yu; Li, Chang-Xian; Tang, He-Han; Song, Bin

    2012-07-01

    To investigate the diagnostic efficacy of gadobutrol for assessing brain metastases in lung cancer patients in comparison with multihance. 21 patients with lung cancer suspected of brain metastasis were enrolled in this study. All patients underwent twice MRI scans on a 3.0T MRI scanner (Siemens MAGENETOM Trio) with 8-channel head coil, first with 0.5 mol/L multihance and then with 1.0 mol/L gadobutrol as contrast agent. The dosage of contrast agent was set at 0.1 mmol/kg body mass. The interval between the two scans was 24-72 hours. The detection and delineation of lesions were evaluated visually. The signal-to-noise ratios (SNR), contrast-to-noise ratios (CNR) of lesion to normal brain white matter and the percentage of lesion enhancement were calculated and compared between the two scans by 2 experienced neuroradiologists. One patient was excluded because he received radiation therapy between the two scans. 15 patients were found to have brain metastases with a total of 35 lesions. There were no statistical differences between the two scans in SNR, CNR and percentage enhancement for both normal brain and lesions (t = 0.545, P = 0.592; t = 1.143, P = 2.267; t = 0.592, P = 0.557; t = 0.473, P = 0.639). Half-dose gadobutrol (1.0 mol/L) can achieve the same enhancement effects compared with full-dose multihance (0.5 mol/L).

  15. Accuracy of diffusion-weighted (DW) MRI with background signal suppression (MR-DWIBS) in diagnosis of mediastinal lymph node metastasis of nonsmall-cell lung cancer (NSCLC).

    Science.gov (United States)

    Xu, Liang; Tian, Jiakai; Liu, Yuhui; Li, Chuanfu

    2014-07-01

    To prospectively evaluate the accuracy of diffusion-weighted (DW) magnetic resonance (MR) imaging with background signal suppression (MR-DWIBS) for detecting mediastinal lymph node metastasis of nonsmall-cell lung cancer (NSCLC). MR-DWIBS was performed in 42 consecutive patients (27 men, 15 women; age range, 42-78 years; median age, 55 years) with histologically proven NSCLC. The visualization rate of metastatic lymph node (MLN) and benign lymph node (BLN) of enlarged lymph nodes (ELN) and normal-sized lymph nodes (NLN) was compared by using a chi-square test or Fisher's exact test on a per-nodal basis. Apparent diffusion coefficient (ADC) of MLN and BLN was measured and compared by using two-tailed unpaired Student's t-test. Receiver operating characteristic (ROC) analysis was used to assess the overall diagnostic accuracy of ADC for ELN and NLN. The optimal cutoff value was determined and the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy was calculated. Thirty-five out of 119 lymph resected nodes were confirmed to be metastatic by histologic examination. The visualization rate of MLN was significantly higher than that of BLN for ELN (P accuracy were 75.0%, 90.9%, 66.7%, 93.8%, and 87.8%, respectively. MR-DWIBS may be clinically useful to visually detect mediastinal lymph nodes and ADC measurement can aid in malignant node discrimination. © 2013 Wiley Periodicals, Inc.

  16. p0071 interacts with E-cadherin in the cytoplasm so as to promote the invasion and metastasis of non-small cell lung cancer.

    Science.gov (United States)

    Zhao, Huanyu; Zhang, Di; Yang, Lianhe; Wang, Enhua

    2018-01-01

    As a member of the p120-catenin (p120ctn) subfamily, the p0071 study in tumor is very limited. We demonstrated the clinicopathological significance of p0071 in non-small cell lung cancer (NSCLC), as well as E-cadherin. Co-immunoprecipitation was used to detect the interaction of p0071 with E-cadherin in A549 and SPC cells (E-cadherin is mainly expressed in the cytoplasm of these cells). p0071 cytoplasmic expression was knocked down by siRNA in these cells and this effect on the RhoA activity and cell invasion and migration ability were measured. p0071 overexpression in the cytoplasm of tumor cell was correlated with lymphatic metastase and poor prognosis of NSCLC. The patients with both abnormal expression of p0071 and E-cadherin (cytoplasmic expression) had a statistically significant shorter survival than the patients without both abnormal expression (P  E-cadherin in NSCLC tissues. p0071 interacted with E-cadherin in the cytoplasm of A549 and SPC cell lines. Treatment with siRNA-p0071 inhibited the invasion and migration ability of NSCLC cells. Above results confirmed that p0071 interacted with E-cadherin in the cytoplasm so as to promote the invasion and metastasis of NSCLC. © 2017 Wiley Periodicals, Inc.

  17. Severe Bilateral Breast Mucinous Carcinoma with Bilateral Lungs and Cutaneous Metastasis: A Case Report and Literature Review

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    Rong Pu

    2018-01-01

    Full Text Available The case of a female who had severe, rare, terminal breast mucinous carcinoma (BMC and failed to receive surgery and chemotherapy was reported. The patient was diagnosed with pure BMC (ER++, PR++, CerbB-2−, and Ki-67 10% accompanied with bilateral lungs, bilateral chest walls with skin ulcer (D = 14 cm, lymph nodes of bilateral armpits, and right supraclavicular metastases. ECOG (Eastern Cooperative Oncology Group and NRS (Numeric Rating Scale pain scores were 4 and 6, respectively. Because the patient refused traditional chemotherapy and radiotherapy on religious grounds, an herbal medicine containing Panax ginseng, Agrimonia pilosa, and white flower Patrinia herb was administered; extensive nursing for tumor debridement was also provided. Quality of Life (QOL improved and pain reduced. Tumor-bearing survival time was prolonged. The present case dictates that herbal extract medicines and supportive treatment can be helpful for uncommon severe BMC as an appropriate alternative treatment.

  18. Mesenchymal Stromal Cell Dependent Regression of Pulmonary Metastasis from Ewing's

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    Andrea Anita Hayes-Jordan

    2014-05-01

    Full Text Available Introduction: Ewing’s sarcoma (ES is the second most common bone tumor in children. Survival has not improved over the last decade and once pulmonary metastatic disease is present, survival is dismal. Mesenchymal stromal cell (MSC therapy has shown potential benefit for Kaposi's sarcoma; however, the role of progenitor cell therapies for cancer remains controversial. MSC treatment of ES or pulmonary metastatic disease has not been demonstrated. We have developed an orthotopic xenograft model of ES in which animals develop spontaneous pulmonary metastases. Within this model, we demonstrate the use of MSCs to target ES lung metastasis. Materials and MethodsHuman ES cells were transfected with luciferase and injected into the rib of nude mice. Development of pulmonary metastases was confirmed by imaging. After flow cytometry based characterization, MSC’s were injected into the tail vein of nude mice with established local ES tumor or pulmonary metastasis. Mice were treated with intravenous MSCs weekly followed by bioluminescent imaging.ResultsThe intravenous injection of MSCs in an ES model decreases the volume of pulmonary metastatic lesions; however, no effect on primary chest wall tumor size is observed. Thus verifying the MSC preferential homing to the lung. MSCs are found to ‘home to’ the pulmonary parenchyma and remain engrafted up to 5 days after delivery. DiscussionMSC treatment of ES slows growth of pulmonary metastasis. MSC’s have more affinity for pulmonary metastasis and can effect a greater decrease in tumor growth in the lungs compared to the primary tumor site

  19. Nasopharyngeal carcinoma with pericardial metastasis

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    Shang-Wen Chen

    2011-07-01

    Full Text Available Nasopharyngeal carcinoma (NPC is prevalent in Taiwan and is characterized by a high frequency of nodal metastasis. The most common organs with distal metastases are the bones, lungs, and liver, with extremely rare cases to the pericardium. Herein, we report a rare case with NPC who presented with dyspnea and orthopnea. Serial studies, including pericardial biopsy, revealed NPC with pericardial metastasis and pericardial effusion. The tumor cells of both the original and metastatic tumors were positive for Epstein–Barr virus by in situ hybridization. This is the first histologically confirmed case of NPC with pericardial metastasis.

  20. [Overexpression of Keap1 inhibits the cell proliferation and metastasis and overcomes the drug resistance in human lung cancer A549 cells].

    Science.gov (United States)

    Weng, X; Yan, Y Y; Tong, Y H; Fan, Y; Zeng, J M; Wang, L L; Lin, N M

    2016-06-23

    To investigate the effect of Keap1-Nrf2 pathway on cell proliferation, metastasis and drug resistance of human lung cancer A549 cell line. A549-Keap1 cell line, constantly expressing wild type Keap1, was established by lentiviral transfection. Real-time RT-PCR and western blot were used to determine the expression of Nrf2 and its target gene in A549 cells. Sulforhodamine B (SRB) assay, flow cytometry, colony formation assay, transwell assay, and cell wound-healing assay were performed to explore the effect of wild type Keap1 expression on the proliferation, invasion, migration and drug resistance of A549 cells. Over-expressed Keap1 decreased the expression of Nrf2 protein and the mRNA level of its downstream target genes and inhibited the ability of cell proliferation and clone formation of A549 cells. Keap1 overexpression induced G0/G1 phase arrest. The percentage of A549-Keap1 cells in G0/G1 phase was significantly higher than that of A549-GFP cells (80.2±5.9)% vs. (67.1±0.9%)(PA549-Keap1 cells (156.33±17.37), the number of invasive A549-GFP cells was significantly higher (306.67±22.19) in a high power field. Keap1 overexpression significantly enhanced the sensitivity of A549 cells to carboplatin and gemcitabine (PA549-Keap1 and A549-GFP cells were (52.1±3.3) μmol/L and (107.8±12.9) μmol/L, respectively. The IC50s of gemcitabine in A549-Keap1 and A549-GFP cells were (6.8±1.2) μmol/L and (9.9±0.5) μmol/L, respectively. Keap1 overexpression significantly inhibits the expression of Nrf2 and its downstream target genes, suppresses tumor cell proliferation and metastasis, and enhances the sensitivity of A549 cells to anticancer drugs.

  1. Comparison of machine learning methods for classifying mediastinal lymph node metastasis of non-small cell lung cancer from 18F-FDG PET/CT images.

    Science.gov (United States)

    Wang, Hongkai; Zhou, Zongwei; Li, Yingci; Chen, Zhonghua; Lu, Peiou; Wang, Wenzhi; Liu, Wanyu; Yu, Lijuan

    2017-12-01

    This study aimed to compare one state-of-the-art deep learning method and four classical machine learning methods for classifying mediastinal lymph node metastasis of non-small cell lung cancer (NSCLC) from 18 F-FDG PET/CT images. Another objective was to compare the discriminative power of the recently popular PET/CT texture features with the widely used diagnostic features such as tumor size, CT value, SUV, image contrast, and intensity standard deviation. The four classical machine learning methods included random forests, support vector machines, adaptive boosting, and artificial neural network. The deep learning method was the convolutional neural networks (CNN). The five methods were evaluated using 1397 lymph nodes collected from PET/CT images of 168 patients, with corresponding pathology analysis results as gold standard. The comparison was conducted using 10 times 10-fold cross-validation based on the criterion of sensitivity, specificity, accuracy (ACC), and area under the ROC curve (AUC). For each classical method, different input features were compared to select the optimal feature set. Based on the optimal feature set, the classical methods were compared with CNN, as well as with human doctors from our institute. For the classical methods, the diagnostic features resulted in 81~85% ACC and 0.87~0.92 AUC, which were significantly higher than the results of texture features. CNN's sensitivity, specificity, ACC, and AUC were 84, 88, 86, and 0.91, respectively. There was no significant difference between the results of CNN and the best classical method. The sensitivity, specificity, and ACC of human doctors were 73, 90, and 82, respectively. All the five machine learning methods had higher sensitivities but lower specificities than human doctors. The present study shows that the performance of CNN is not significantly different from the best classical methods and human doctors for classifying mediastinal lymph node metastasis of NSCLC from PET/CT images

  2. Epigenetic induction of epithelial to mesenchymal transition by LCN2 mediates metastasis and tumorigenesis, which is abrogated by NF-κB inhibitor BRM270 in a xenograft model of lung adenocarcinoma.

    Science.gov (United States)

    Mongre, Raj Kumar; Sodhi, Simrinder Singh; Sharma, Neelesh; Ghosh, Mrinmoy; Kim, Jeong Hyun; Kim, Nameun; Park, Yang Ho; Shin, Young Gyu; Kim, Sung Jin; Jiao, Zhang Jiao; Huynh, Do Luong; Jeong, Dong Kee

    2016-01-01

    Tumor initiating cancer stem-like cells (TICSCs) have recently become the object of intensive study. Human-Lipocalin-2 (hLCN2) acts as a biomarker for cancers. The aim of the present study was to explore new insights regarding the potential role of LCN2 in inducing epithelial to mesenchymal transition (EMT) by transfecting LCN2 into CD133+-A549-TICSCs and its cross-talk with the NF-κB signaling pathway in adenocarcinoma of the lung. Furthermore, EMT was confirmed by transcriptomic analysis, immunoblotting and immunocyto/histochemical analyses. Tumorigenesis and metastasis were confirmed by molecular therapeutics tracer 2DG infrared optical probe in BALB/cSIc-nude mice. It was observed that the CD133+-expressing-LCN2-A549 TICSCs population increased in adenocarcinoma of the lung compared to the normal lung tissue. The expressions of genes involved in stemness, adhesion, motility and drug efflux was higher in these cells than in their non-LCN2 expressing counterparts. The present study revealed that elevated expression of LCN2 significantly induced metastasis via EMT. Overexpression of LCN2 significantly increased stemness and tumor metastasis by modulating NF-κB cellular signaling. BRM270, a novel inhibitor of NF-κB plays a significant role in the EMT reversal. BRM270, a naturaceutical induces cell shrinkage, karyorrhexis and programmed cell death (PCD) which were observed by Hoechst 33342 staining while flow cytometry analysis showed significant (PBRM270 as a novel cancer therapeutic drug to enhance the effect of doxorubicin (Dox)-resistant LCN2 induced metastasis of solid tumors in nude mice.

  3. Effectiveness of accelerated radiotherapy for patients with inoperable non-small cell lung cancer (NSCLC) and borderline prognostic factors without distant metastasis: a retrospective review

    International Nuclear Information System (INIS)

    Nguyen, Linh N.; Komaki, Ritsuko; Allen, Pamela; Schea, Randi A.; Milas, Luka

    1999-01-01

    Purpose: The standard treatment for patients with unresectable or medically inoperable non-small cell lung cancer (NSCLC) and good prognostic factors (e.g., weight loss [WL] ≤5% and Karnofsky performance status [KPS] ≥70) is induction chemotherapy followed by definitive radiotherapy to the primary site at 1.8-2.0 Gy per fraction with a total dose of 60-63 Gy to the target volume. Patients with poor prognostic factors usually receive radiotherapy alone, but the fractionation schedule and total dose have not been standardized. To attempt to optimize irradiation doses and schedule, we compared the effectiveness of accelerated radiotherapy (ACRT) alone to 45 Gy at 3 Gy per fraction with standard radiation therapy (STRT) of 60-66 Gy at 2 Gy per fraction in regard to tumor response, local control, distant metastasis, toxicity, and survival. Methods and Materials: Fifty-five patients treated with radiation for NSCLC at The University of Texas M. D. Anderson Cancer Center between 1990 and 1994 were identified. All 55 patients had node-positive, and no distant metastasis (N+, M0) of NSCLC. Two cohorts were identified. One cohort (26 patients) had borderline poor prognostic factors (KPS less than 70 but higher than 50, and/or WL of more than 5%) and was treated with radiotherapy alone to 45 Gy over 3 weeks at 3 Gy/fraction (ACRT). The second cohort (29 patients) had significantly better prognostic factors (KPS ≥70 and WL ≤5%) and was treated to 60-66 Gy over 6 to 6((1)/(2)) weeks at 2 Gy per fraction (STRT) during the same period. Results: In the first cohort treated by ACRT, the distribution of patients by AJCC stage was IIB 8%, IIIA 19%, and IIIB 73%. Sixty-two percent had KPS 5%. The maximum response rate as determined by chest X-ray was 60% among 45 of 55 patients who were evaluable for response: combined complete responses (20%) and partial responses (40%). Overall survival in these patients was 13% at 2 and 5 years, with a locoregional control rate of 42% and a

  4. Metástases nas leptomeninges da espinal medula num doente com carcinoma de céculas escamosas do pulmão Spinal leptomeningeal metastasis in a patient with squamous cell lung cancer

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    Banu Alicioglu

    2008-12-01

    Full Text Available As metástases nas leptomeninges da espinal medula ocorrem raramente nos tumores sólidos e o prognóstico é bastante reservado. Os adenocarcinomas e os carcinomas de pequenas células são os grupos histológicos mais envolvidos no que se refere aos tumores pulmonares. Um homem de 58 anos com história de carcinoma de células escamosas do pulmão com inversão mediastínica e metástases cerebrais apresenta lombalgias e fraqueza em ambos os membros inferiores. A RMN da coluna vertebral revelou espessamento na espinal medula e múltiplos nódulos do grupo das fibras da cauda equina. Tanto quanto sabemos, trata-se do segundo caso relatado de carcinoma pulmonar de células escamosas que apresenta metástases nas leptomeninges da espinal medula.Spinal leptomeningeal metastasis occurs rarely in solid tumors, and the prognosis is extremely poor. Adenocarcinomas and small-cell carcinomas are the most common histological type detected among lung tumors. A 58-year-old man with a history of squamous-cell lung carcinoma with mediastinal invasion and brain metastasis was examined because of his low back pain and weakness in both lower limbs. Spinal MRI revealed subpial enhancement in the spinal cord; and innumerable nodules with thickening of the cauda equina fibres. To our knowledge, this is the second reported case of squamous cell lung cancer with spinal leptomeningeal metastasis.

  5. Positron emission tomography-computed tomography and 4-hydroxynonenal-histidine immunohistochemistry reveal differential onset of lipid peroxidation in primary lung cancer and in pulmonary metastasis of remote malignancies.

    Science.gov (United States)

    Živković, Nevenka Piskač; Petrovečki, Mladen; Lončarić, Čedna Tomasović; Nikolić, Igor; Waeg, Georg; Jaganjac, Morana; Žarković, Kamelija; Žarković, Neven

    2017-04-01

    The Aim of the study was to reveal if PET-CT analysis of primary and of secondary lung cancer could be related to the onset of lipid peroxidation in cancer and in surrounding non-malignant lung tissue. Nineteen patients with primary lung cancer and seventeen patients with pulmonary metastasis were involved in the study. Their lungs were analyzed by PET-CT scanning before radical surgical removal of the cancer. Specific immunohistochemistry for the major bioactive marker of lipid peroxidation, 4-hydroxynonenal (HNE), was done for the malignant and surrounding non-malignant lung tissue using genuine monoclonal antibody specific for the HNE-histidine adducts. Both the intensity of the PET-CT analysis and the HNE-immunohistochemistry were in correlation with the size of the tumors analyzed, while primary lung carcinomas were larger than the metastatic tumors. The intensity of the HNE-immunohistochemistry in the surrounding lung tissue was more pronounced in the metastatic than in the primary tumors, but it was negatively correlated with the cancer volume determined by PET-CT. The appearance of HNE was more pronounced in non-malignant surrounding tissue than in cancer or stromal cells, both in case of primary and metastatic tumors. Both PET-CT and HNE-immunohistochemistry reflect the size of the malignant tissue. However, lipid peroxidation of non-malignant lung tissue in the vicinity of cancer is more pronounced in metastatic than in primary malignancies and might represent the mechanism of defense against cancer, as was recently revealed also in case of human liver cancer. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  6. Gut metastasis from breast carcinoma

    International Nuclear Information System (INIS)

    Al-Qahtani, Mohammad S.

    2007-01-01

    Breast cancer is the second most common malignancy in women. Common sites of metastases include the liver, lung, bone and the brain. Metastases to the gastrointestinal tract are with patients presenting with small-bowel perforation, intestinal obstruction and gastrointestinal bleeding. Here we report a case of Saudi female presenting with invasive lobular carcinoma and i leo-junction metastasis. (author)

  7. Collagen induced arthritis increases secondary metastasis in MMTV-PyV MT mouse model of mammary cancer

    International Nuclear Information System (INIS)

    Roy, Lopamudra Das; Ghosh, Sriparna; Pathangey, Latha B; Tinder, Teresa L; Gruber, Helen E; Mukherjee, Pinku

    2011-01-01

    Several studies have demonstrated that sites of chronic inflammation are often associated with the establishment and growth of various malignancies. A common inflammatory condition in humans is autoimmune arthritis (AA). Although AA and cancer are different diseases, many of the underlying processes that contribute to the disorders of the joints and connective tissue that characterize AA also affect cancer progression and metastasis. Systemically, AA can lead to cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge being available, there has been minimal research linking breast cancer, arthritis, and metastasis associated with breast cancer. Notably both diseases are extremely prevalent in older post-menopausal women. To establish the novel link between arthritis induced inflammation and secondary metastasis associated with breast cancer, PyV MT mice that spontaneously develop mammary gland carcinoma were injected with Type II collagen (CII) to induce arthritis at 9 and 18 weeks of age for pre-metastatic and metastatic condition. The sites of secondary metastasis and the associated inflammatory microenvironment were evaluated. A significant increase in breast cancer-associated secondary metastasis to the lungs and bones was observed in the arthritic versus the non-arthritic PyV MT mice along with an increase in primary tumor burden. We report significant increases in the levels of interstitial cellular infiltrates and pro-inflammatory cytokines such as interleukin-17 (IL-17), interleukin-6 (IL-6), Pro- Matrix metallopeptidase 9 (Pro-MMP9), insulin like growth factor-II (GF-II) and macrophage colony stimulating factor (M-CSF) in the arthritic lung and bone milieu as well as in the circulation. These pro-inflammatory cytokines along with the inflammatory microenvironment may be the underlying factors facilitating tumor progression and metastasis in

  8. Collagen induced arthritis increases secondary metastasis in MMTV-PyV MT mouse model of mammary cancer

    Directory of Open Access Journals (Sweden)

    Gruber Helen E

    2011-08-01

    Full Text Available Abstract Background Several studies have demonstrated that sites of chronic inflammation are often associated with the establishment and growth of various malignancies. A common inflammatory condition in humans is autoimmune arthritis (AA. Although AA and cancer are different diseases, many of the underlying processes that contribute to the disorders of the joints and connective tissue that characterize AA also affect cancer progression and metastasis. Systemically, AA can lead to cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge being available, there has been minimal research linking breast cancer, arthritis, and metastasis associated with breast cancer. Notably both diseases are extremely prevalent in older post-menopausal women. Methods To establish the novel link between arthritis induced inflammation and secondary metastasis associated with breast cancer, PyV MT mice that spontaneously develop mammary gland carcinoma were injected with Type II collagen (CII to induce arthritis at 9 and 18 weeks of age for pre-metastatic and metastatic condition. The sites of secondary metastasis and the associated inflammatory microenvironment were evaluated. Results A significant increase in breast cancer-associated secondary metastasis to the lungs and bones was observed in the arthritic versus the non-arthritic PyV MT mice along with an increase in primary tumor burden. We report significant increases in the levels of interstitial cellular infiltrates and pro-inflammatory cytokines such as interleukin-17 (IL-17, interleukin-6 (IL-6, Pro- Matrix metallopeptidase 9 (Pro-MMP9, insulin like growth factor-II (GF-II and macrophage colony stimulating factor (M-CSF in the arthritic lung and bone milieu as well as in the circulation. These pro-inflammatory cytokines along with the inflammatory microenvironment may be the underlying factors

  9. Collagen induced arthritis increases secondary metastasis in MMTV-PyV MT mouse model of mammary cancer.

    Science.gov (United States)

    Roy, Lopamudra Das; Ghosh, Sriparna; Pathangey, Latha B; Tinder, Teresa L; Gruber, Helen E; Mukherjee, Pinku

    2011-08-22

    Several studies have demonstrated that sites of chronic inflammation are often associated with the establishment and growth of various malignancies. A common inflammatory condition in humans is autoimmune arthritis (AA). Although AA and cancer are different diseases, many of the underlying processes that contribute to the disorders of the joints and connective tissue that characterize AA also affect cancer progression and metastasis. Systemically, AA can lead to cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge being available, there has been minimal research linking breast cancer, arthritis, and metastasis associated with breast cancer. Notably both diseases are extremely prevalent in older post-menopausal women. To establish the novel link between arthritis induced inflammation and secondary metastasis associated with breast cancer, PyV MT mice that spontaneously develop mammary gland carcinoma were injected with Type II collagen (CII) to induce arthritis at 9 and 18 weeks of age for pre-metastatic and metastatic condition. The sites of secondary metastasis and the associated inflammatory microenvironment were evaluated. A significant increase in breast cancer-associated secondary metastasis to the lungs and bones was observed in the arthritic versus the non-arthritic PyV MT mice along with an increase in primary tumor burden. We report significant increases in the levels of interstitial cellular infiltrates and pro-inflammatory cytokines such as interleukin-17 (IL-17), interleukin-6 (IL-6), Pro- Matrix metallopeptidase 9 (Pro-MMP9), insulin like growth factor-II (GF-II) and macrophage colony stimulating factor (M-CSF) in the arthritic lung and bone milieu as well as in the circulation. These pro-inflammatory cytokines along with the inflammatory microenvironment may be the underlying factors facilitating tumor progression and metastasis in

  10. Oral gingival metastasis: A diagnostic dilemma

    Directory of Open Access Journals (Sweden)

    Nalini Aswath

    2017-01-01

    Full Text Available Oral cavity is a rare target for metastasis with an incidence of 1% among all oral cancers. In 24% of such cases, oral metastasis is the first indication of an undiagnosed primary. Metastatic oral malignancies have been reported in the mandible, tongue, and gingiva. Although gingival metastasis has been reported from lung, prostate, rectal carcinoma in men and carcinoma of breast, adrenal glands, and genitalia in females, gingival metastasis from carcinoma of the penis has not been reported. Herein, a case of metastatic gingival carcinoma that developed after extraction of teeth from primary carcinoma of the penis is presented. An extensive literature search revealed no such similar case reports.

  11. Promotion of experimental liver metastasis by tumor necrosis factor.

    Science.gov (United States)

    Orosz, P; Krüger, A; Hubbe, M; Rüschoff, J; Von Hoegen, P; Männel, D N

    1995-03-16

    Models for experimental metastasis were established to investigate the influence of rmTNF on tumor-colony formation in the liver. Highly metastatic lymphoma tumor cells were either injected i.v. or inoculated s.c. to form spontaneous metastases. In both systems, administration of rmTNF to the animals led to significant enhancement of the number of liver metastases in comparison with control groups. The number of metastatic tumor-cell colonies at an early stage of metastasis was increased, as well as the number of surface metastases in a late stage. Consequently, TNF-treated animals revealed a higher mortality. The optimal time for TNF to exert this metastasis-enhancing effect was found to be 7 days after tumor inoculation. In vitro adhesion of the lymphoma tumor cells to a mouse endothelioma cell line was strongly inhibited by monoclonal antibodies interfering with the interaction of VCAM-1 with VLA-4. These results support and extend earlier results with a fibrosarcoma lung colonization model. In addition, they show that stimulation of the immune system in tumor-bearing hosts activates tumor-promoting pathways, in addition to having possible beneficial effects.

  12. Effects of ultraprotective ventilation, extracorporeal carbon dioxide removal, and spontaneous breathing on lung morphofunction and inflammation in experimental severe acute respiratory distress syndrome.

    Science.gov (United States)

    Güldner, Andreas; Kiss, Thomas; Bluth, Thomas; Uhlig, Christopher; Braune, Anja; Carvalho, Nadja; Quast, Theresa; Rentzsch, Ines; Huhle, Robert; Spieth, Peter; Richter, Torsten; Saddy, Felipe; Rocco, Patricia R M; Kasper, Michael; Koch, Thea; Pelosi, Paolo; de Abreu, Marcelo Gama

    2015-03-01

    To investigate the role of ultraprotective mechanical ventilation (UP-MV) and extracorporeal carbon dioxide removal with and without spontaneous breathing (SB) to improve respiratory function and lung protection in experimental severe acute respiratory distress syndrome. Severe acute respiratory distress syndrome was induced by saline lung lavage and mechanical ventilation (MV) with higher tidal volume (VT) in 28 anesthetized pigs (32.8 to 52.5 kg). Animals (n = 7 per group) were randomly assigned to 6 h of MV (airway pressure release ventilation) with: (1) conventional P-MV with VT ≈6 ml/kg (P-MVcontr); (2) UP-MV with VT ≈3 ml/kg (UP-MVcontr); (3) UP-MV with VT ≈3 ml/kg and SB (UP-MVspont); and (4) UP-MV with VT ≈3 ml/kg and pressure supported SB (UP-MVPS). In UP-MV groups, extracorporeal carbon dioxide removal was used. The authors found that: (1) UP-MVcontr reduced diffuse alveolar damage score in dorsal lung zones (median[interquartile]) (12.0 [7.0 to 16.8] vs. 22.5 [13.8 to 40.8]), but worsened oxygenation and intrapulmonary shunt, compared to P-MVcontr; (2) UP-MVspont and UP-MVPS improved oxygenation and intrapulmonary shunt, and redistributed ventilation towards dorsal areas, as compared to UP-MVcontr; (3) compared to P-MVcontr, UP-MVcontr and UP-MVspont, UP-MVPS yielded higher levels of tumor necrosis factor-α (6.9 [6.5 to 10.1] vs. 2.8 [2.2 to 3.0], 3.6 [3.0 to 4.7] and 4.0 [2.8 to 4.4] pg/mg, respectively) and interleukin-8 (216.8 [113.5 to 343.5] vs. 59.8 [45.3 to 66.7], 37.6 [18.8 to 52.0], and 59.5 [36.1 to 79.7] pg/mg, respectively) in dorsal lung zones. In this model of severe acute respiratory distress syndrome, MV with VT ≈3 ml/kg and extracorporeal carbon dioxide removal without SB slightly reduced lung histologic damage, but not inflammation, as compared to MV with VT = 4 to 6 ml/kg. During UP-MV, pressure supported SB increased lung inflammation.

  13. Metabolomics guided pathway analysis reveals link between cancer metastasis, cholesterol sulfate, and phospholipids

    Directory of Open Access Journals (Sweden)

    Caroline H. Johnson

    2017-10-01

    Full Text Available Abstract Background Cancer cells that enter the metastatic cascade require traits that allow them to survive within the circulation and colonize distant organ sites. As disseminating cancer cells adapt to their changing microenvironments, they also modify their metabolism and metabolite production. Methods A mouse xenograft model of spontaneous tumor metastasis was used to determine the metabolic rewiring that occurs between primary cancers and their metastases. An “autonomous” mass spectrometry-based untargeted metabolomic workflow with integrative metabolic pathway analysis revealed a number of differentially regulated metabolites in primary mammary fat pad (MFP tumors compared to microdissected paired lung metastases. The study was further extended to analyze metabolites in paired normal tissues which determined the potential influence of metabolites from the microenvironment. Results Metabolomic analysis revealed that multiple metabolites were increased in metastases, including cholesterol sulfate and phospholipids (phosphatidylglycerols and phosphatidylethanolamine. Metabolite analysis of normal lung tissue in the mouse model also revealed increased levels of these metabolites compared to tissues from normal MFP and primary MFP tumors, indicating potential extracellular uptake by cancer cells in lung metastases. These results indicate a potential functional importance of cholesterol sulfate and phospholipids in propagating metastasis. In addition, metabolites involved in DNA/RNA synthesis and the TCA cycle were decreased in lung metastases compared to primary MFP tumors. Conclusions Using an integrated metabolomic workflow, this study identified a link between cholesterol sulfate and phospholipids, metabolic characteristics of the metastatic niche, and the capacity of tumor cells to colonize distant sites.

  14. M402, a novel heparan sulfate mimetic, targets multiple pathways implicated in tumor progression and metastasis.

    Directory of Open Access Journals (Sweden)

    He Zhou

    Full Text Available Heparan sulfate proteoglycans (HSPGs play a key role in shaping the tumor microenvironment by presenting growth factors, cytokines, and other soluble factors that are critical for host cell recruitment and activation, as well as promoting tumor progression, metastasis, and survival. M402 is a rationally engineered, non-cytotoxic heparan sulfate (HS mimetic, designed to inhibit multiple factors implicated in tumor-host cell interactions, including VEGF, FGF2, SDF-1α, P-selectin, and heparanase. A single s.c. dose of M402 effectively inhibited seeding of B16F10 murine melanoma cells to the lung in an experimental metastasis model. Fluorescent-labeled M402 demonstrated selective accumulation in the primary tumor. Immunohistological analyses of the primary tumor revealed a decrease in microvessel density in M402 treated animals, suggesting anti-angiogenesis to be one of the mechanisms involved in-vivo. M402 treatment also normalized circulating levels of myeloid derived suppressor cells in tumor bearing mice. Chronic administration of M402, alone or in combination with cisplatin or docetaxel, inhibited spontaneous metastasis and prolonged survival in an orthotopic 4T1 murine mammary carcinoma model. These data demonstrate that modulating HSPG biology represents a novel approach to target multiple factors involved in tumor progression and metastasis.

  15. 3,4-Dihydroxybenzalactone Suppresses Human Non-Small Cell Lung Carcinoma Cells Metastasis via Suppression of Epithelial to Mesenchymal Transition, ROS-Mediated PI3K/AKT/MAPK/MMP and NFκB Signaling Pathways.

    Science.gov (United States)

    Chao, Wei; Deng, Jeng-Shyan; Li, Pei-Ying; Liang, Yu-Chia; Huang, Guan-Jhong

    2017-03-28

    3,4-Dihydroxybenzalactone (DBL) was isolated from Phellinus linteus (PL), which is a folk medicine possessing various physiological effects. In this study, we used highly metastatic A549 cells to investigate efficacy of DBL inhibition of cancer metastasis and possible mechanisms. The results revealed DBL inhibited migratory and invasive abilities of cancer cells at noncytotoxic concentrations. We found DBL suppressed enzymatic activities, protein expression, and RNA levels of matrix metalloproteinase (MMP)-2 and MMP-9. Western blot results showed DBL decreased phosphoinositide 3-kinase (PI3K)/AKT, phosphorylation status of mitogen-activated protein kinases (MAPKs), and focal adhesion kinase (FAK)/paxillin, which correlated with cell migratory ability. DBL also affected epithelial to mesenchymal transition (EMT)-related biomarkers. In addition, DBL enhanced cytoprotective effects through elevated antioxidant enzymes including heme oxygenase 1 (HO-1), catalase, glutathione peroxidase (GPx), and superoxide dismutase (SOD). Moreover, DBL influenced the nuclear translocation of nuclear factor κB (NFκB), nuclear factor erythroid 2-related factor 2 (Nrf2), Snail, and Slug in A549 cells. Taken together, these results suggested that treatment with DBL may act as a potential candidate to inhibit lung cancer metastasis by inhibiting MMP-2 and -9 via affecting PI3K/AKT, MAPKs, FAK/paxillin, EMT/Snail and Slug, Nrf2/antioxidant enzymes, and NFκB signaling pathways.

  16. Mechanisms involved in metastasis enhanced by inflammatory mediators

    OpenAIRE

    Männel, D. N.; Orosz, P.; Hafner, M.; Falk, Werner

    1994-01-01

    The enhancement of tumor metastasis by concurrent inflammatory processes is mainly due to the cytokines TNF and IL-1. In the case of TNF this effect is not restricted to metastasis models as measured by in vivo colony formation but also found in experimental model systems of spontaneous metastasis. Direct effects on the tumor cells or interference with the host NK cell system did not seem to account for the observed TNF effect. Experimental evidence from different test systems rather points t...

  17. Renal Metastasis from Primary Cervical Cancer: A Case Report

    International Nuclear Information System (INIS)

    Jeon, Seong Woo; Kim, See Hyung; Kwon, Sun Young

    2013-01-01

    Metastasis of malignant tumors to the kidney is clinically rare and often discovered by autopsy. Primary lymphoma and lung cancer are known that can metastasize to the kidney. Other malignant tumor metastasis to the kidney is very unusual. Primary cervical cancer metastasis to adjacent pelvic organs and lymph nodes are well known followed by abdominal solid organs such as the liver and adrenal glands. However, reported primary cervical cancer metastasis to the kidney is extremely rare and mostly appeared as bilateral multiple renal masses. We report here on a rare case of unilateral single renal metastasis from primary cervical cancer after concur- rent chemoradiotherapy.

  18. MicroRNA-330-3p promotes cell invasion and metastasis in non-small cell lung cancer through GRIA3 by activating MAPK/ERK signaling pathway

    Directory of Open Access Journals (Sweden)

    Chun-Hua Wei

    2017-06-01

    Full Text Available Abstract Background Brain metastasis (BM is associated with poor prognosis in patients with non-small cell lung cancer (NSCLC. Recent studies demonstrated that microRNA-330-3p (miR-330-3p was involved in NSCLC brain metastasis (BM. However, the exact parts played by miR-330-3p in BM of NSCLC remain unknown. Discovery and development of biomarkers and elucidation of the mechanism underlying BM in NSCLC is critical for effective prophylactic interventions. Here, we evaluated the expression and biological effects of miR-330-3p in NSCLC cells and explored the underlying mechanism of miR-330-3p in promoting cell migration and invasion in NSCLC. Methods Stable over-expression and knockdown of miR-330-3p in NSCLC cells was constructed with lentivirus. Expression levels of miR-330-3p in NSCLC cells were quantified by quantitive real-time PCR (qRT-PCR. The effects of miR-330-3p on NSCLC cells were investigated using assays of cell viability, migration, invasion, cell cycle, apoptosis, western blotting, immunohistochemical, and immunofluorescence staining. A xenograft nude mouse model and in situ brain metastasis model were used to observe tumor growth and brain metastasis. The potential target of miR-330-3p in NSCLC cells was explored using the luciferase reporter assay, qRT-PCR, and western blotting. The miR-330-3p targets were identified using bioinformatics analysis and verified by luciferase reporter assay. The correlation between GRIA3 and DNA methyltransferase (DNMT 1 and DNMT3A was tested by RT-PCR, western blotting, and co-immunoprecipitation (IP. Results miR-330-3p was significantly up-regulated in NSCLC cell lines. MTT assay, transwell migration, and invasion assays showed that miR-330-3p promoted the growth, migration, and invasion of NSCLC cells in vitro and induced tumor growth and metastasis in vivo. Luciferase reporter assays showed that GRIA3 was a target of miR-330-3p. qRT-PCR and western blotting exhibited that miR-330-3p promoted the

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

    Science.gov (United States)

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

    2017-02-01

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

  20. Comparison of 99mTc-3PRGD2 integrin receptor imaging with 99mTc-MDP bone scan in diagnosis of bone metastasis in patients with lung cancer: a multicenter study.

    Science.gov (United States)

    Miao, Weibing; Zheng, Shan; Dai, Haojie; Wang, Feng; Jin, Xiaona; Zhu, Zhaohui; Jia, Bing

    2014-01-01

    99mTc-3PRGD2, a promising tracer targeting integrin receptor, may serve as a novel tumor-specific agent for single photon emission computed tomography (SPECT). A multi-center study was prospectively designed to evaluate the diagnostic accuracy of 99mTc-3PRGD2 imaging for bone metastasis in patients with lung cancer in comparison with the conventional 99mTc-MDP bone scan. The patients underwent whole-body scan and chest tomography successively at both 1 h and 4 h after intravenous injection of 11.1 MBq/Kg 99mTc-3PRGD2. 99mTc-MDP whole-body bone scan was routinely performed within 1 week for comparison. Three experienced nuclear medicine physicians blindly read the 99mTc-3PRGD2 and 99mTc-MDP images. The final diagnosis was established based on the comprehensive assessment of all available data. A total of 44 patients (29 male, 59±10 years old) with suspected lung cancer were recruited from 4 centers. Eighty-nine bone lesions in 18 patients were diagnosed as metastases and 23 bone lesions in 9 patients were benign. In a lesion-based analysis, 99mTc-3PRGD2 imaging demonstrated a sensitivity, specificity, and accuracy of 92.1%, 91.3%, and 92.0%, respectively. The corresponding diagnostic values for 99mTc-MDP bone scan were 87.6%, 60.9%, and 82.1%, respectively in the same patients. 99mTc-MDP bone scan had better contrast in most lesions, whereas the 99mTc-3PRGD2 imaging seemed to be more effective to exclude pseudo-positive lesions and detect bone metastases without osteogenesis. 99mTc-3PRGD2 is a novel tumor-specific agent based on SPECT technology with a promising value in diagnosis of bone metastasis in patients with lung cancer. ClinicalTrials.gov NCT01737112.

  1. Hericium erinaceus (Lion’s Mane) mushroom extracts inhibit metastasis of cancer cells to the lung in CT-26 colon cancer-transplanted mice

    Science.gov (United States)

    We investigated the anti-metastatic activity of four Hericium erinaceus edible mushroom extracts using CT-26 murine colon carcinoma cells as an indicator of inhibition of cell migration to the lung. Hot water (HWE) and microwaved 50% ethanol (MWE) extracts of Hericium erinaceus strongly elicited ca...

  2. Monocyte chemotactic protein-1 attenuates and high-fat diet exacerbates bone loss in mice with pulmonary metastasis of Lewis lung carcinoma

    Science.gov (United States)

    Bone can be adversely affected by obesity and cancer-associated complications including wasting. The objective of this study was to determine whether a high-fat diet and a deficiency in monocyte chemotactic protein-1 (MCP-1) altered bone structural defects found in male C57BL/6 mice with Lewis lung...

  3. Oral melanoma with pulmonary metastasis in a Nigerian local dog ...

    African Journals Online (AJOL)

    Melanomas are the most commonly diagnosed neoplasm of the canine oral cavity accounting for about 7% of all malignant tumours in the dog. Less frequently, metastasis via regional lymph nodes and to the lungs and other organs may occur. A case report of oral melanoma with pulmonary metastasis in a Nigerian local ...

  4. 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

  5. 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.

  6. Nuclear LEF1/TCF4 correlate with poor prognosis but not with nuclear β-catenin in cerebral metastasis of lung adenocarcinomas.

    Science.gov (United States)

    Bleckmann, A; Siam, L; Klemm, F; Rietkötter, E; Wegner, Chr; Kramer, F; Beissbarth, T; Binder, C; Stadelmann, Chr; Pukrop, T

    2013-04-01

    An essential function of the transcription factors LEF1/TCF4 in cerebral metastases of lung adenocarcinomas has been described in mouse models, suggesting a WNT/β-catenin effect as potential mechanism. Their role in humans is still unclear, thus we analyzed LEF1, TCF4, β-catenin, and early stage prognostic markers in 25 adenocarcinoma brain metastases using immunohistochemistry (IHC). IHC revealed nuclear TCF4 in all adenocarcinoma samples, whereas only 36 % depicted nuclear LEF1 and nuclear β-catenin signals. Samples with nuclear LEF1 as well as high TCF4 (++++) expression were associated with a shorter survival (p = 0.01, HR = 6.68), while nuclear β-catenin had no significant impact on prognosis and did not significantly correlate with nuclear LEF1. High proliferation index Ki67 was associated with shorter survival in late-stage disease (p = 0.03, HR 3.27). Additionally, we generated a LEF1/TCF4 as well as an AXIN2 signature, the latter as representative of WNT/β-catenin activity, following a bioinformatics approach with a gene expression dataset of cerebral metastases in lung adenocarcinoma. To analyze the prognostic relevance in primary lung adenocarcinomas, we applied both signatures to a microarray dataset of 58 primary lung adenocarcinomas. Only the LEF1/TCF4 signature was able to separate clusters with impact on survival (p = 0.01, HR = 0.32). These clusters displayed diverging enrichment patterns of the cell cycle pathway. In conclusion, our data show that LEF1/TCF4, but not β-catenin, have prognostic relevance in primary and cerebrally metastasized human lung adenocarcinomas. In contrast to the previous in vivo findings, these results indicate that LEF1/TCF4 act independently of β-catenin in this setting.

  7. Brain metastasis development and poor survival associated with carcinoembryonic antigen (CEA level in advanced non-small cell lung cancer: a prospective analysis

    Directory of Open Access Journals (Sweden)

    Castillo Patricia

    2009-04-01

    Full Text Available Abstract Background Central nervous system is a common site of metastasis in NSCLC and confers worse prognosis and quality of life. The aim of this prospective study was to evaluate the prognostic significance of clinical-pathological factors (CPF, serum CEA levels, and EGFR and HER2 tissue-expression in brain metastasis (BM and overall survival (OS in patients with advanced NSCLC. Methods In a prospective manner, we studied 293 patients with NSCLC in IIIB-IV clinical stage. They received standard chemotherapy. CEA was measured prior to treatment; EGFR and HER2 were evaluated by immunohistochemistry. BM development was confirmed by MRI in symptomatic patients. Results BM developed in 27, and 32% of patients at 1 and 2 years of diagnosis with adenocarcinoma (RR 5.2; 95% CI, 1.002–29; p = 0.05 and CEA ≥ 40 ng/mL (RR 11.4; 95% CI, 1.7–74; p p = 0.048, poor performance status (RR 1.8; 95% CI, 1.5–2.3; p = 0.002, advanced clinical stage (RR 1.44; 95% CI, 1.02–2; p = 0.04, CEA ≥ 40 ng/mL (RR 1.5; 95% CI, 1.09–2.2; p = 0.014 and EGFR expression (RR 1.6; 95% CI, 1.4–1.9; p = 0.012 were independent associated factors to worse OS. Conclusion High CEA serum level is a risk factor for BM development and is associated with poor prognosis in patients with advanced NSCLC. Surface expression of CEA in tumor cells could be the physiopathological mechanism for invasion to CNS.

  8. Giant hepatic metastasis in a patient with coin-like small cell lung carcinoma incidentally diagnosed at autopsy: A case report.

    Science.gov (United States)

    Fodor, Decebal; Gurzu, Simona; Contac, Anca Otilia; Jung, Ioan

    2017-03-01

    Encephalopathy is a rare complication of hepatic metastases. In this paper we present a case of a patient with lung cancer and metastatic-related giant hepatomegaly. A 78-year-old previously healthy male was admitted in the Emergency room in hepatic coma. The abdominal CT scan examination revealed a huge liver filled with solid nodules. No interventions were performed. The patient died at few hours after hospitalization. The autopsy showed a 6.5 kilograms liver with several whitish metastatic nodules and an occult prostate adenocarcinoma. The hilum of both lungs was free of tumor and a 10 mm white nodule was identified surrounding a small bronchus. No peripheral nodules were macroscopically identified. Under microscope, cluster of small cells were observed encasing a small bronchus with multiple minute coin-shaped subpleural foci. A massive intrapulmonary angiolymphatic invasion and metastases from small cell carcinoma in liver, lymph nodes and iliac crest bone marrow were also diagnosed. This case highlights the difficulty of diagnosis of aggressive lung carcinomas and the necessity of checking for metachronous tumors. The encephalopathy might be the result of metastatic damage of the liver parenchyma combined with the paraneoplastic effect of the tumor cells. Few than 25 cases of SCLCs with diffuse liver metastases and fulminant liver failure were reported to December 2016. This is the first reported case with a synchronous prostate cancer and a "coin-like" aspect of the SCLC.

  9. Inhalation chemotherapy for macroscopic primary or metastatic lung tumors: proof of principle using dogs with spontaneously occurring tumors as a model.

    Science.gov (United States)

    Hershey, A E; Kurzman, I D; Forrest, L J; Bohling, C A; Stonerook, M; Placke, M E; Imondi, A R; Vail, D M

    1999-09-01

    This study represents part of an effort to determine the safety and efficacy of inhaled antineoplastic drugs, using pet dogs with spontaneously arising primary and metastatic lung cancers (including sarcoma, carcinoma, and malignant melanoma) as a model. Dogs received new formulations of either paclitaxel (PTX) or doxorubicin (DOX) by the inhalation route every 2 weeks using a specially designed aerosol device. Response was assessed radiographically using the indices of tumor nodule number and volume measurement of discrete pulmonary nodules. Dogs experiencing progressive disease after two consecutive treatments were crossed over to receive the alternate compound. In 24 dogs, 6 (25%) responses were noted including 5 partial responses (PR) and 1 complete response. These include 4 (22.2%) of 18 responses to DOX and 2 (13.3%) of 15 responses to PTX. Responses were noted with osteosarcoma (including three dogs with metastatic osteosarcoma that had failed prior systemic chemotherapy), liposarcoma, hemangiosarcoma, and undifferentiated sarcoma. One dog with mammary carcinoma experienced a 47% reduction in volume after PTX inhalation, just shy of PR criteria. One dog with liposarcoma is experiencing a long-term (>12 months) stabilization of disease on PTX. To date, no systemic toxicities have been observed with either PTX or DOX inhalations. Local (pulmonary) toxicity was not observed with PTX; however, changes consistent with pneumonitis/fibrosis were observed in some dogs receiving DOX. Only one of these dogs showed clinical signs, which were responsive to steroid and antitussive therapy. These data represent "proof of principle" for the avoidance of systemic toxicity while delivering efficacious local drug levels by the inhalation route.

  10. 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.

  11. DCB - Tumor Metastasis Research

    Science.gov (United States)

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

  12. Magnetic Targeting and Delivery of Drug-Loaded SWCNTs Theranostic Nanoprobes to Lung Metastasis in Breast Cancer Animal Model: Noninvasive Monitoring Using Magnetic Resonance Imaging.

    Science.gov (United States)

    Al Faraj, Achraf; Shaik, Asma Sultana; Halwani, Rabih; Alfuraih, Abdulrahman

    2016-06-01

    In this study, we aimed to develop novel therapeutic and diagnostic approaches by improving the targeting of doxorubicin-loaded single-walled carbon nanotubes (SWCNTs) to metastatic regions, and monitor their preferential homing and enhanced therapeutic effect using noninvasive free-breathing magnetic resonance imaging (MRI) and bioluminescence imaging. High-energy flexible magnets were specifically positioned over the metastatic tumor sites in the lungs. SWCNTs biodistribution, tumor progression, and subsequent treatment efficiency were assessed following administration of the magnetically attracted doxorubicin-loaded anti-CD105 conjugated nanocarriers. The use of high-energy magnets offered improved theranostic effect of doxorubicin-loaded nanocarriers, by magnetically targeting them towards metastatic tumor sites in the lungs. MRI allowed sensitive monitoring of nanocarriers biodistribution in the abdominal organs, their preferential homing towards the metastatic sites, and their enhanced therapeutic effect. Combination of noninvasive MRI to localize sensitively the tumor sites, with specific positioning of magnets that can enhance the magnetic targeting of nanocarriers, allowed increasing the treatment efficiency.

  13. Action of hexachlorobenzene on tumor growth and metastasis in different experimental models

    Energy Technology Data Exchange (ETDEWEB)

    Pontillo, Carolina Andrea, E-mail: caroponti@hotmail.com [Laboratorio de Efectos Biológicos de Contaminantes Ambientales, Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires (Argentina); Rojas, Paola, E-mail: parojas2010@gmail.com [Laboratorio de Carcinogénesis Hormonal, Instituto de Biología y Medicina Experimental (IBYME-CONICET), Buenos Aires (Argentina); Chiappini, Florencia, E-mail: florenciachiappini@hotmail.com [Laboratorio de Efectos Biológicos de Contaminantes Ambientales, Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires (Argentina); Sequeira, Gonzalo, E-mail: chicon27_7@hotmail.com [Laboratorio de Carcinogénesis Hormonal, Instituto de Biología y Medicina Experimental (IBYME-CONICET), Buenos Aires (Argentina); Cocca, Claudia, E-mail: cm_cocca@hotmail.com [Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires (Argentina); Crocci, Máximo, E-mail: info@crescenti.com.ar [Instituto de Inmunooncología Crescenti, Buenos Aires (Argentina); Colombo, Lucas, E-mail: lucascol2003@yahoo.com.ar [Instituto de Oncología Angel Roffo, Universidad de Buenos Aires, Buenos Aires,Argentina (Argentina); Lanari, Claudia, E-mail: lanari.claudia@gmail.com [Laboratorio de Carcinogénesis Hormonal, Instituto de Biología y Medicina Experimental (IBYME-CONICET), Buenos Aires (Argentina); and others

    2013-05-01

    Hexachlorobenzene (HCB) is a widespread organochlorine pesticide, considered a possible human carcinogen. It is a dioxin-like compound and a weak ligand of the aryl hydrocarbon receptor (AhR). We have found that HCB activates c-Src/HER1/STAT5b and HER1/ERK1/2 signaling pathways and cell migration, in an AhR-dependent manner in MDA-MB-231 breast cancer cells. The aim of this study was to investigate in vitro the effect of HCB (0.005, 0.05, 0.5, 5 μM) on cell invasion and metalloproteases (MMPs) 2 and 9 activation in MDA-MB-231 cells. Furthermore, we examined in vivo the effect of HCB (0.3, 3, 30 mg/kg b.w.) on tumor growth, MMP2 and MMP9 expression, and metastasis using MDA-MB-231 xenografts and two syngeneic mouse breast cancer models (spontaneous metastasis using C4-HI and lung experimental metastasis using LM3). Our results show that HCB (5 μM) enhances MMP2 expression, as well as cell invasion, through AhR, c-Src/HER1 pathway and MMPs. Moreover, HCB increases MMP9 expression, secretion and activity through a HER1 and AhR-dependent mechanism, in MDA-MB-231 cells. HCB (0.3 and 3 mg/kg b.w.) enhances subcutaneous tumor growth in MDA-MB-231 and C4-HI in vivo models. In vivo, using MDA-MB-231 model, the pesticide (0.3, 3 and 30 mg/kg b.w.) activated c-Src, HER1, STAT5b, and ERK1/2 signaling pathways and increased MMP2 and MMP9 protein levels. Furthermore, we observed that HCB stimulated lung metastasis regardless the tumor hormone-receptor status. Our findings suggest that HCB may be a risk factor for human breast cancer progression. - Highlights: ► HCB enhances MMP2 and MMP9 expression and cell invasion in MDA-MB-231, in vitro. ► HCB-effects are mediated through AhR, HER1 and/or c-Src. ► HCB increases subcutaneous tumor growth in MDA-MB-231 and C4-HI in vivo models. ► HCB activates c-Src/HER1 pathway and increases MMPs levels in MDA-MB-231 tumors. ► HCB stimulates lung metastasis in C4-HI and LM3 in vivo models.

  14. Establishment of Orthotopic Xuanwei Lung Cancer SCID Mouse Model 
and Analysis of Biological Properties

    Directory of Open Access Journals (Sweden)

    Yongchun ZHOU

    2012-08-01

    Full Text Available Background and objective The incidence of Xuanwei lung cancer ranks first in China, and its pathogenesis requires in-depth investigation. This study aims to establish an orthotopic Xuanwei lung cancer severe combined immunodeficiency (SCID mouse model and to provide a basic experimental platform for further study. Methods The Xuanwei lung cancer cell line XWLC-05 was inoculated into the lung tissue of SCID mice in high and low doses. The tumor formation rates, tumor characteristics, spontaneous metastases, and survival times of the mice were observed, taking a subcutaneously transplanted tumor as control. Results The tumor formation rates of the orthotopic transplantation of lung cancer cells in high and low doses were 81% and 83%, respectively, among which mice in the high-dose group appeared cachectic on day 13. Extensive invasion and adhesion were observed in the contralateral lung and thoracic cavity, but no distant metastasis was exhibited. Mice with low-dose cells in the orthotopic transplantation group appeared cachectic and distant metastasis occurred on day 25. The tumor formation rates in the subcutaneous inoculation group by the high and low doses of cells were 100% and 94.5%, respectively, and no distant metastasis was observed. The rate of metastasis within the orthotopic transplantation group and between the orthotopic and subcutaneous inoculation groups showed a significant difference (P<0.05. A significant difference was indicated by the survival rate within and between the groups (P<0.001. Conclusion We successfully established an orthotopic XWLC SCID mouse model, which lays the foundation for a more in-depth study.

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

    International Nuclear Information System (INIS)

    Gong Linlin; Wang, Q.I.; Zhao Lujun; Yuan Zhiyong; Li Ruijian; Wang Ping

    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.

  16. FDG PET/CT and Mediastinal Nodal Metastasis Detection in Stage T1 Non-Small Cell Lung Cancer: Prognostic Implications

    International Nuclear Information System (INIS)

    Shin, Kyung Min; Lee, Kyung Soo; Shim, Young Mog; Kim, Jhin Gook; Kim, Byung Tae; Kwon, O Jung; Park, Keun Chil

    2008-01-01

    We aimed to compare the prognoses of patients with pathologically true negative (P-TN) N2 and PET/CT false negative (FN) results in stage T1 nonsmall cell lung cancer (NSCLC). Our institutional review board approved this retrospective study with a waiver of informed consent. The study included 184 patients (124 men and 60 women; mean age, 59 years) with stage T1 NSCLC who underwent an integrated PET/CT and surgery. After estimating the efficacy of PET/CT for detecting N2 disease, we determined and compared disease-free survival (DFS) rates in three groups (P-TN [n = 161], PET/CT FN [n = 12], and PET/CT true positive [TP, n = 11]) using the Kaplan-Meier analysis and log-rank test. Pathologic N2 disease was observed in 23 (12%) patients. PET/CT had an N2 disease detection sensitivity of 48% (11 of 23 patients), a specificity of 95% (153 of 161), and an accuracy of 89% (164 of 184). The 3-year DFS rate in the PET/CT FN group (31%, 95% confidence interval [CI]; 13.6-48.0%) was similar to that of the TP group (16%, 95% CI; 1.7-29.5%) (p = 0.649), but both groups had significantly shorter DFS rates than the P-TN group (77%, 95% CI; 72.0- 81.2%) (p < 0.001). The PET/CT shows a high specificity, but low sensitivity for detecting N2 disease in stage T1 NSCLC. Patients with PET/CT FN N2 disease have survival rates similar to PET/CT TP N2 disease patients, which are both substantially shorter than the survival rate of P-TN patients

  17. MicroRNAs-from metastasis prediction to metastasis prevention?

    Science.gov (United States)

    Abba, Mohammed; Patil, Nitin; Leupold, Jörg Hendrik; Allgayer, Heike

    2016-03-01

    Recently, we suggested the microRNA (miR) landscape defining metastasis. The first miR-driven network orchestrating invasion, intravasation, and metastasis was confirmed independently across several malignancies, suggesting a rather general principle for metastasis regulation. We hope that our data will stimulate the field in terms of further hypothesis generation, metastasis prediction, and metastasis prevention.

  18. Metastasis of transgenic breast cancer in plasminogen activator inhibitor-1 gene-deficient mice

    DEFF Research Database (Denmark)

    Almholt, Kasper; Nielsen, Boye Schnack; Frandsen, Thomas Leth

    2003-01-01

    of metastasizing breast cancer. In these tumors, the expression pattern of uPA and PAI-1 resembles that of human ductal breast cancer and plasminogen is required for efficient metastasis. In a cohort of 63 transgenic mice that were either PAI-1-deficient or wild-type sibling controls, primary tumor growth......, high levels of PAI-1 as well as uPA are equally associated with poor prognosis in cancer patients. PAI-1 is thought to play a vital role for the controlled extracellular proteolysis during tumor neovascularization. We have studied the effect of PAI-1 deficiency in a transgenic mouse model...... and vascular density were unaffected by PAI-1 status. PAI-1 deficiency also did not significantly affect the lung metastatic burden. These results agree with the virtual lack of spontaneous phenotype in PAI-1-deficient mice and humans and may reflect that the plasminogen activation reaction is not rate...

  19. Spontaneous intracranial epidural hematoma during rivaroxaban treatment

    Energy Technology Data Exchange (ETDEWEB)

    Ruschel, Leonardo Gilmone; Rego, Felipe Marques Monteiro do; Milano, Jeronimo Buzetti; Jung, Gustavo Simiano; Silva Junior, Luis Fernando; Ramina, Ricardo, E-mail: leonardoruschel@yahoo.com.br [Instituto de Neurologia de Curitiba (INC), Curitiba, PR (Brazil)

    2016-11-15

    According to our research, this is the first case described in the literature of spontaneous intracranial epidural hematoma secondary to the use of Xarelto®. Spontaneous intracranial epidural hematomas are rarely described in the literature. They are associated with infectious diseases of the skull, coagulation disorders, vascular malformations of the dura mater and metastasis to the skull. Long-term post-marketing monitoring and independent reports will probably detect the full spectrum of hemorrhagic complications of the use of rivaroxaban. (author)

  20. Spontaneous intracranial epidural hematoma during rivaroxaban treatment.

    Science.gov (United States)

    Ruschel, Leonardo Gilmone; Rego, Felipe Marques Monteiro do; Milano, Jerônimo Buzetti; Jung, Gustavo Simiano; Silva, Luis Fernando; Ramina, Ricardo

    2016-11-01

    According to our research, this is the first case described in the literature of spontaneous intracranial epidural hematoma secondary to the use of Xareltor. Spontaneous intracranial epidural hematomas are rarely described in the literature. They are associated with infectious diseases of the skull, coagulation disorders, vascular malformations of the dura mater and metastasis to the skull. Long-term post-marketing monitoring and independent reports will probably detect the full spectrum of hemorrhagic complications of the use of rivaroxaban.

  1. Experience of treating late cerebral lungcancer metastasis using photodynamic therapy

    Directory of Open Access Journals (Sweden)

    A. I. Ryabova

    2013-01-01

    Full Text Available Treatment outcomes for a patient with solitary brain metastasis after long-term relapse-free follow-up of invasive lung carcinoma were presented. Brain metastasis without other signs of disease progression was diagnosed 10 years after combined modality treatment for stage II lung cancer. Removal of intracerebral metastasis with intraoperative photodynamic therapy was performed. Histology microspecimens of the primary tumor and metastasis were similar. No signs of disease progression in the brain 9 months after surgery were found. This case demonstrates that it is important to increase cancer suspicion for patients with long-term relapse-free follow-up. The use of intraoperative photodynamic therapy with photoditazine as a sensitizer in the treatment of cerebral metastases results in a favorable anti-tumor effect, thus improving life quality of patients

  2. Gastric Metastasis of Triple Negative Invasive Lobular Carcinoma.

    Science.gov (United States)

    Geredeli, Caglayan; Dogru, Osman; Omeroglu, Ethem; Yilmaz, Farise; Cicekci, Faruk

    2015-05-05

    Invasive lobular carcinomas are the second most common type (5% to 15%) of invasive breast carcinomas. The most frequent sites of breast cancer metastasis are the local and distant lymph nodes, brain, lung, liver, and bones; metastasis to the gastrointestinal system, especially to the stomach, is rare. When a mass is detected in an unusual place in a patient with invasive lobular carcinoma, it should be kept in mind that such a mass may be either a second primary carcinoma or the metastasis of an invasive lobular carcinoma. In this report, we present a case of gastric metastasis from triple-negative invasive lobular breast cancer. It is important to make an accurate diagnosis by distinguishing gastric metastasis from breast cancer in order to select the best initial treatment for systemic diseases of breast cancer. Considering our case, healthcare professionals should take into account that cases with invasive lobular breast cancer may experience unusual metastases.

  3. Angiosarcoma of the lung

    Energy Technology Data Exchange (ETDEWEB)

    Grafino, Monica; Alves, Paula; Almeida, Margarida Mendes de; Garrido, Patricia; Hasmucrai, Direndra; Teixeira, Encarnacao; Sotto-Mayor, Renato, E-mail: mgrafino@gmail.com [Centro Hospitalar Lisboa Norte, EPE, Lisboa (Portugal)

    2016-06-01

    Angiosarcoma is a rare malignant vascular tumor. Pulmonary involvement is usually attributable to metastasis from other primary sites, primary pulmonary angiosarcoma therefore being quite uncommon. We report a case of angiosarcoma with pulmonary involvement, probably primary to the lung, which had gone untreated for more than two years. We describe this rare neoplasm and its growth, as well as the extensive local invasion and hematogenous metastasis at presentation. We also discuss its poor prognosis. (author)

  4. Metastasis within a metastasis to the thyroid: A rare phenomenon

    Directory of Open Access Journals (Sweden)

    Yin Ping Wong

    2017-01-01

    Full Text Available Metastatic disease involving the thyroid gland is uncommon. Solitary thyroid metastases from various primary sites particularly kidney, lung, and breast had been previously described. To the best of our knowledge, metastases from two topographically separate primary malignancies to the thyroid have never been documented hitherto. This is the first reported case of cancer-to-cancer metastasis involving an invasive breast carcinoma metastasized within a metastatic renal cell carcinoma in the nonneoplastic thyroid in a 58-year-old woman. Distinguishing a secondary thyroid metastases from a primary thyroid malignancy is utmost crucial as treatment differs. The possibility of tumor metastases from two separated primaries should always be considered in a tumor exhibiting malignant cell populations with two distinctive histomorphological appearances. The role of immunohistochemistry stains in equivocal cases cannot be overemphasized.

  5. Gastric metastasis of triple negative invasive lobular carcinoma

    OpenAIRE

    Caglayan Geredeli; Osman Dogru; Ethem Omeroglu; Farise Yilmaz; Faruk Cicekci

    2015-01-01

    Invasive lobular carcinomas are the second most common type (5% to 15%) of invasive breast carcinomas. The most frequent sites of breast cancer metastasis are the local and distant lymph nodes, brain, lung, liver, and bones; metastasis to the gastrointestinal system, especially to the stomach, is rare. When a mass is detected in an unusual place in a patient with invasive lobular carcinoma, it should be kept in mind that such a mass may be either a second primary carcinoma or the metastasis o...

  6. Mechanism-based inhibition of cancer metastasis with (−)-epigallocatechin gallate

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Atsushi [Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama 362-0806 (Japan); Graduate School of Science and Engineering, Saitama University, Saitama 338-8570 (Japan); Green Tea Laboratory, Saitama Prefectural Agriculture and Forestry Research Center, Saitama 358-0042 (Japan); Watanabe, Tatsuro; Mondal, Anupom; Suzuki, Kaori; Kurusu-Kanno, Miki [Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama 362-0806 (Japan); Li, Zhenghao; Yamazaki, Takashi [Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama 362-0806 (Japan); Graduate School of Science and Engineering, Saitama University, Saitama 338-8570 (Japan); Fujiki, Hirota [Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama 362-0806 (Japan); Suganuma, Masami, E-mail: masami@cancer-c.pref.saitama.jp [Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama 362-0806 (Japan)

    2014-01-03

    Highlights: •EGCG reduced cell motility of highly metastatic human lung cancer cells. •EGCG increased cell stiffness of the cells, indicating the inhibition of phenotypes of EMT. •EGCG inhibited expression of vimentin and Slug in the cells at the leading edge of scratch. •Treatment of MβCD increased cell stiffness, and inhibited cell motility and vimentin expression. •Inhibition of EMT phenotypes with EGCG is a mechanism-based inhibition of cancer metastasis. -- Abstract: Cell motility and cell stiffness are closely related to metastatic activity of cancer cells. (−)-Epigallocatechin gallate (EGCG) has been shown to inhibit spontaneous metastasis of melanoma cell line into the lungs of mice, so we studied the effects of EGCG on cell motility, cell stiffness, and expression of vimentin and Slug, which are molecular phenotypes of epithelial–mesenchymal transition (EMT). Treatments of human non-small cell lung cancer cell lines H1299 and Lu99 with 50 and 100 μM EGCG reduced cell motility to 67.5% and 43.7% in H1299, and 71.7% and 31.5% in Lu99, respectively in in vitro wound healing assay. Studies on cell stiffness using atomic force microscope (AFM) revealed that treatment with 50 μM EGCG increased Young’s modulus of H1299 from 1.24 to 2.25 kPa and that of Lu99 from 1.29 to 2.28 kPa, showing a 2-fold increase in cell stiffness, i.e. rigid elasticity of cell membrane. Furthermore, treatment with 50 μM EGCG inhibited high expression of vimentin and Slug in the cells at a leading edge of scratch. Methyl-β-cyclodextrin, a reagent to deplete cholesterol in plasma membrane, showed inhibition of EMT phenotypes similar that by EGCG, suggesting that EGCG induces inhibition of EMT phenotypes by alteration of membrane organization.

  7. Occurrence and clinical features of brain metastasis after chemoradiotherapy for esophageal carcinoma

    International Nuclear Information System (INIS)

    Kanemoto, Ayae; Hashimoto, Takayuki; Harada, Hideyuki; Asakura, Hirofumi; Ogawa, Hirofumi; Furutani, Kazuhisa; Boku, Narikazu; Nakasu, Yoko; Nishimura, Tetsuo

    2011-01-01

    Brain metastasis from esophageal carcinoma has been considered rare and survival following esophageal carcinoma with distant metastasis is poor. The purpose of this report was to clarify cumulative incidence and risk factors for brain metastasis after chemoradiotherapy for esophageal carcinoma, and to consider recommended treatments for brain metastasis from esophageal carcinoma. We reviewed 391 patients treated with chemoradiotherapy. Median age was 65 years. Clinical stages were I, II, III, and IV in 32, 47, 150, and 162 patients, respectively. Brain imaging was performed usually when patients revealed neurological symptoms. The 3-year cumulative incidence of brain metastasis after chemoradiotherapy was 6.6%. There were 4 patients with single metastasis and 8 with multiple metastases. Initial clinical stages were II, III, and IV in 1, 2, and 9 patients, respectively. Histology included squamous cell carcinoma in 10 patients and others in 2 patients. Univariate analysis demonstrated M factor, distant lymph node relapse, and recurrent lung and liver metastasis as significant risk factors of brain metastasis (P<0.05). Median survival time after diagnosis of brain metastasis was 2.1 months. Brain metastasis was not directly related to cause of mortality. The causes were extracranial tumor deterioration in 8 patients and infection in 4 patients. Brain metastasis may increase in the future with improving survival from esophageal carcinoma. However, considering the poor survival after diagnosis of brain metastasis, short-term palliative therapy for brain metastasis appears preferable to vigorous long-term therapy. (author)

  8. 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.

  9. A single cervical lymph node metastasis of malignant ameloblastoma.

    Science.gov (United States)

    Kim, Yoori; Choi, Sung-Weon; Lee, Jong-Ho; Ahn, Kang-Min

    2014-12-01

    Cervical node metastasis of malignant ameloblastoma is extremely rare. Because of its rarity, there is no standard treatment modality in a single lymph node metastasis in malignant ameloblastoma. Eleven patients of malignant ameloblastoma involving a single cervical lymph node metastasis and one new case were reviewed. Neck treatment was classified into neck dissection and simple excision. Local nodal recurrence, distant metastasis and follow-up periods were investigated. Eight patients were treated with neck dissection (group A) and four patients underwent a simple node excision (group B). Two patients in group A experienced multiple organ metastases such as liver and lung seven months and 13 years after neck dissection respectively. The other patients showed no recurrence and metastasis. In group B, there was no report of a regional neck recurrence and distant metastasis during follow-up of 1-7 years. Multiple nodes metastasis requires a radical neck dissection; however, simple excision with close follow-up may be used in a single node metastasis in malignant ameloblastoma. Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  10. Inhibition of tumor invasion and metastasis by calcium spirulan (Ca-SP), a novel sulfated polysaccharide derived from a blue-green alga, Spirulina platensis.

    Science.gov (United States)

    Mishima, T; Murata, J; Toyoshima, M; Fujii, H; Nakajima, M; Hayashi, T; Kato, T; Saiki, I

    1998-08-01

    We have investigated the effect of calcium spirulan (Ca-SP) isolated from a blue-green alga, Spirulina platensis, which is a sulfated polysaccharide chelating calcium and mainly composed of rhamnose, on invasion of B16-BL6 melanoma, Colon 26 M3.1 carcinoma and HT-1080 fibrosarcoma cells through reconstituted basement membrane (Matrigel). Ca-SP significantly inhibited the invasion of these tumor cells through Matrigel/fibronectin-coated filters. Ca-SP also inhibited the haptotactic migration of tumor cells to laminin, but it had no effect on that to fibronectin. Ca-SP prevented the adhesion of B16-BL6 cells to Matrigel and laminin substrates but did not affect the adhesion to fibronectin. The pretreatment of tumor cells with Ca-SP inhibited the adhesion to laminin, while the pretreatment of laminin substrates did not. Ca-SP had no effect on the production and activation of type IV collagenase in gelatin zymography. In contrast, Ca-SP significantly inhibited degradation of heparan sulfate by purified heparanase. The experimental lung metastasis was significantly reduced by co-injection of B16-BL6 cells with Ca-SP. Seven intermittent i.v. injections of 100 microg of Ca-SP caused a marked decrease of lung tumor colonization of B16-BL6 cells in a spontaneous lung metastasis model. These results suggest that Ca-SP, a novel sulfated polysaccharide, could reduce the lung metastasis of B16-BL6 melanoma cells, by inhibiting the tumor invasion of basement membrane probably through the prevention of the adhesion and migration of tumor cells to laminin substrate and of the heparanase activity.

  11. Comparative proteome analysis of three mouse lung adenocarcinoma CMT cell lines with different metastatic potential by two-dimensional gel electrophoresis and mass spectrometry.

    Science.gov (United States)

    Zhang, Kelan; Wrzesinski, Krzysztof; Stephen, J Fey; Larsen, Peter Mose; Zhang, Xumin; Roepstorff, Peter

    2008-12-01

    Metastasis is a lethal attribute of a cancer and presents a continuing therapeutic challenge. Metastasis is a highly complex process and more knowledge about the mechanisms behind metastasis is highly desirable. Isogenic CMT cell lines were selected from a spontaneous mouse lung adenocarcinoma and characterized in vivo to have different metastatic potential. In this study, the comprehensive protein expression profiles of three of these CMT cell lines at passage 5, 15 and 35 were analyzed by 2-DE separation followed by MS identification. As a result, 82 and 40 unique proteins were found to be significantly up- or down-regulated between cell lines with different metastatic potential at passages 5 and 15, respectively. These proteins were identified by MS and most of them have previously been reported to be related to cancer development and/or metastasis. Bioinformatics analysis indicated that several of the proteins were involved in proteasome, cell-cycle and cell-communication pathways. Among them, some keratins, 14-3-3 proteins and 26S proteasome proteins were identified and their aberrant expression may be directly or indirectly involved in cancer development and metastasis. In conclusion, our comprehensive 2-DE-based proteomics studies revealed some candidate proteins, protein families and signaling pathways, which might be important in cancer development and metastasis.

  12. Leptomeningeal metastasis from hepatocellular carcinoma with other unusual metastases: a case report

    OpenAIRE

    Pan, Zhenyu; Yang, Guozi; Yuan, Tingting; Pang, Xiaochuan; Wang, Yongxiang; Qu, Limei; Dong, Lihua

    2014-01-01

    Background Leptomeningeal metastasis, which results from metastasis of tumors to the arachnoid and pia mater, can lead to the dissemination of tumor cells throughout the subarachnoid space via the cerebral spinal fluid, and frequently with a poor prognosis. The primary tumor in adults is most often breast cancer, lung cancer, or melanoma. Although leptomeningeal metastasis due to cholangiocarcinoma has been reported, to the best of our knowledge there is no cytologically confirmed report of l...

  13. 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)

  14. Spontaneous Splenic Rupture in Melanoma

    Directory of Open Access Journals (Sweden)

    Hadi Mirfazaelian

    2014-01-01

    Full Text Available Spontaneous rupture of spleen due to malignant melanoma is a rare situation, with only a few case reports in the literature. This study reports a previously healthy, 30-year-old man who came with chief complaint of acute abdominal pain to emergency room. On physical examination, abdominal tenderness and guarding were detected to be coincident with hypotension. Ultrasonography revealed mild splenomegaly with moderate free fluid in abdominopelvic cavity. Considering acute abdominal pain and hemodynamic instability, he underwent splenectomy with splenic rupture as the source of bleeding. Histologic examination showed diffuse infiltration by tumor. Immunohistochemical study (positive for S100, HMB45, and vimentin and negative for CK, CD10, CK20, CK7, CD30, LCA, EMA, and chromogranin confirmed metastatic malignant melanoma. On further questioning, there was a past history of a nasal dark skin lesion which was removed two years ago with no pathologic examination. Spontaneous (nontraumatic rupture of spleen is an uncommon situation and it happens very rarely due to neoplastic metastasis. Metastasis of malignant melanoma is one of the rare causes of the spontaneous rupture of spleen.

  15. Diagnosis and treatment of brain metastasis

    International Nuclear Information System (INIS)

    Sajama, Carlos; Lorenzoni, Jose; Tagle, Patricio

    2008-01-01

    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

  16. P53 tumor suppressor gene and protein expression is altered in cell lines derived from spontaneous and alpha-radiation-induced canine lung tumors

    International Nuclear Information System (INIS)

    Tierney, L.A.; Johnson, N.F.; Lechner, J.F.

    1994-01-01

    Mutations in the p53 tumor suppressor gene are the most frequently occurring gene alterations in malignant human cancers, including lung cancer. In lung cancer, common point mutations within conserved exons of the p53 gene result in a stabilized form of mutant protein which is detectable in most cases by immunohistochemistry. In addition to point mutations, allelic loss, rearrangements, and deletions of the p53 gene have also been detected in both human and rodent tumors. It has been suggested that for at least some epithelial neoplasms, the loss of expression of wild-type p53 protein may be more important for malignant transformation than the acquisition of activating mutations. Mechanisms responsible for the loss of expression of wild-type protein include gene deletion or rearrangement, nonsense or stop mutations, mutations within introns or upstream regulatory regions of the gene, and accelerated rates of degradation of the protein by DNA viral oncoproteins

  17. [Pulmonary metastasis from hepatic epithelioid hemangioendothelioma; report of a case].

    Science.gov (United States)

    Ishibashi, Hironori; Ohta, S; Hirose, M; Kokuryu, H; Muro, H

    2007-06-01

    A 30-year-old female complaint of epigastralgia was diagnosed hepatic epitheloid hemangio endothelioma (EHE) by liver biopsy. The multiple nodules in bilateral lungs and liver were revealed on computed tomography (CT). The tumors of the left lung were resected under video-assisted thoracoscopic surgery. Pathologically these lesions were diagnosed as metastasis from EHE of the liver, and the patient was treated with interleukin-2 from hepatic artery for 12 months.

  18. Molecular Mechanisms of Metastasis Suppression in Human Breast Cancer

    Science.gov (United States)

    1997-07-01

    K., Kruse, T., Retief, A., Bale, A., Meo, T., Vergnaud, G., and Warren , S. (1995). The CEPH consortium linkage map of human chromosome 11. Genomics... McCulloch colonization and human fetal lung in SCID mice to et al. [92] propose that the shedding of tumor cells mouse bone marrow or lung, respectively...borne metastases. Ann immunodeficient mice. Invasion Metastasis, 13, Surg, 161, 97-102. 82-91. 92. McCulloch P, Choy A and Martin L, 1995, 73. Clarke

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

    International Nuclear Information System (INIS)

    Kim, Eung Yeop; Lee, Seung Koo; Kim, Dong Joon; Kim, Jin Na; Lee, Kyu Sung; Jung, Woo Hee; Kim, Dong Ik

    2008-01-01

    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

  20. Metastasis of the gastrointestinal tract. FDG-PET imaging

    International Nuclear Information System (INIS)

    Hayasaka, Kazumasa; Nihashi, Takashi; Matsuura, Toshihiro

    2007-01-01

    We assess the usefulness of F-18-fluoro-deoxy-glucose (FDG) positron emission tomography (PET) in the evaluation of gastrointestinal metastases. Four cases (five lesions) in which metastases from three lung cancers and one malignant fibrous histiocytoma (MFH) of the femur were found in the gastrointestinal tract were reviewed (men/women 3:1, age 63-78 years, mean 72 years). The five lesions were duodenal, jejunal metastasis, and two stomach metastases from lung carcinoma, and rectal metastasis from MFH of the femur. FDG-PET was unable to detect small masses, but it was able to detect unforeseen lesions such as gastrointestinal metastases because FDG-PET is a whole-body scan in a single-operation examination. FDG-PET imaging provided valuable information for the diagnosis of gastrointestinal metastasis. (author)

  1. Methylation of the estrogen receptor CpG island distinguishes spontaneous and plutonium-induced tumors from nitrosamine-induced lung tumors

    Energy Technology Data Exchange (ETDEWEB)

    Belinsky, S.A.; Baylin, S.B.; Issa, J.J. [Johns Hopkins Univ., Baltimore, MD (United States)

    1995-12-01

    CpG islands located in the promoter region of genes constitute one mechanism for regulating transcription. These islands are normally free of methylation, regardless of the expression state of the gene. Hypermethylation of CpG islands, the addition of a methyl group to the internal cytosine within CpG dinucleotides, can cause silencing of a gene. Hypermethylation has been detected as an early event at specific chromosome loci during the development of colon cancer and represents one mechanism used by neoplatic cells to inactivate tumor suppressor genes. Recent studies have demonstrated this mechanism in inactivation of the VHL tumor suppressor gene in 19% of sporadic renal tumors and the p16 {sup INK4a} tumor suppressor gene in 30% of non-small cell lung cancers. A recent report indicates that the estrogen receptor gene could also be inactivated through methylation. In addition, estrogen receptor CpG island methylation arises as a direct function of age in normal colonic mucosa and is present in virtually all colonic tumors. In cultured colon cancer cells, methylation-associated loss of expression of the estrogen receptor gene results in deregulated growth, suggesting a role for the estrogen receptor in colon cancer development. These results provide further evidence that gene silencing through methylation could be a predominant epigenetic mechanism underlying the development of many different types of cancer. The purpose of the current investigation was to determine whether estrogen receptor CpG island methylation is involved in the development of lung cancer. The frequency for methylation of the estrogen receptor CpG island in rodent lung tumors is summarized.

  2. Methylation of the estrogen receptor CpG island distinguishes spontaneous and plutonium-induced tumors from nitrosamine-induced lung tumors

    International Nuclear Information System (INIS)

    Belinsky, S.A.; Baylin, S.B.; Issa, J.J.

    1995-01-01

    CpG islands located in the promoter region of genes constitute one mechanism for regulating transcription. These islands are normally free of methylation, regardless of the expression state of the gene. Hypermethylation of CpG islands, the addition of a methyl group to the internal cytosine within CpG dinucleotides, can cause silencing of a gene. Hypermethylation has been detected as an early event at specific chromosome loci during the development of colon cancer and represents one mechanism used by neoplatic cells to inactivate tumor suppressor genes. Recent studies have demonstrated this mechanism in inactivation of the VHL tumor suppressor gene in 19% of sporadic renal tumors and the p16 INK4a tumor suppressor gene in 30% of non-small cell lung cancers. A recent report indicates that the estrogen receptor gene could also be inactivated through methylation. In addition, estrogen receptor CpG island methylation arises as a direct function of age in normal colonic mucosa and is present in virtually all colonic tumors. In cultured colon cancer cells, methylation-associated loss of expression of the estrogen receptor gene results in deregulated growth, suggesting a role for the estrogen receptor in colon cancer development. These results provide further evidence that gene silencing through methylation could be a predominant epigenetic mechanism underlying the development of many different types of cancer. The purpose of the current investigation was to determine whether estrogen receptor CpG island methylation is involved in the development of lung cancer. The frequency for methylation of the estrogen receptor CpG island in rodent lung tumors is summarized

  3. Spontaneous deregulation

    NARCIS (Netherlands)

    Edelman, Benjamin; Geradin, Damien

    Platform businesses such as Airbnb and Uber have risen to success partly by sidestepping laws and regulations that encumber their traditional competitors. Such rule flouting is what the authors call “spontaneous private deregulation,” and it’s happening in a growing number of industries. The authors

  4. Spinal Metastasis Of Wilm's Tumuor: An Unusual Occurrence ...

    African Journals Online (AJOL)

    Background: Metastasis of the Wilm's tumor is usually to surrounding tissue, the lungs and the liver. Rarely is there spread to bone, bone-marrow, spinal canal and other tissues, but this unusual mode of spread sometimes occurs. Objectives: To report a case of Wilm's tumuor complicated by spastic paraplegia consequent to ...

  5. Mesenchymal Stem Cell-Induced DDR2 Mediates Stromal-Breast Cancer Interactions and Metastasis Growth

    Directory of Open Access Journals (Sweden)

    Maria E. Gonzalez

    2017-01-01

    Full Text Available Increased collagen deposition by breast cancer (BC-associated mesenchymal stem/multipotent stromal cells (MSC promotes metastasis, but the mechanisms are unknown. Here, we report that the collagen receptor discoidin domain receptor 2 (DDR2 is essential for stromal-BC communication. In human BC metastasis, DDR2 is concordantly upregulated in metastatic cancer and multipotent mesenchymal stromal cells. In MSCs isolated from human BC metastasis, DDR2 maintains a fibroblastic phenotype with collagen deposition and induces pathological activation of DDR2 signaling in BC cells. Loss of DDR2 in MSCs impairs their ability to promote DDR2 phosphorylation in BC cells, as well as BC cell alignment, migration, and metastasis. Female ddr2-deficient mice homozygous for the slie mutation show inefficient spontaneous BC metastasis. These results point to a role for mesenchymal stem cell DDR2 in metastasis and suggest a therapeutic approach for metastatic BC.

  6. Analysis of spontaneous tumor-specific CD4 T-cell immunity in lung cancer using promiscuous HLA-DR telomerase-derived epitopes: potential synergistic effect with chemotherapy response.

    Science.gov (United States)

    Godet, Yann; Fabre, Elizabeth; Dosset, Magalie; Lamuraglia, Michele; Levionnois, Emeline; Ravel, Patrice; Benhamouda, Nadine; Cazes, Aurélie; Le Pimpec-Barthes, Françoise; Gaugler, Beatrice; Langlade-Demoyen, Pierre; Pivot, Xavier; Saas, Philippe; Maillère, Bernard; Tartour, Eric; Borg, Christophe; Adotévi, Olivier

    2012-05-15

    To investigate the presence and impact of spontaneous telomerase-specific CD4 T-cell responses in cancer patients. A multistep approach was used to design novel pan-HLA-DR-restricted peptides from telomerase. T-cell clones isolated from cancer patients were used to characterize the polarization of telomerase-specific CD4 response. The presence of spontaneous CD4 T-cell response against telomerase was monitored in 84 metastatic non-small cell lung cancer (NSCLC) patients before first-line chemotherapy (CT) using IFN-γ ELISPOT assay. Then we analyzed the impact of the pretherapeutic telomerase-specific CD4 T immunity on clinical outcome in patients according to their respective response to CT. We described four novel telomerase-derived CD4 epitopes referred as universal cancer peptides (UCP) that effectively bind to most commonly found human MHC class II alleles. UCP-specific CD4 T-cell repertoire is present in human and UCP-specific CD4 T-cell clones generated from cancer patients exhibited high avidity and are Th1 polarized. Significant frequency (38%) of naturally occurring UCP-specific T-cell responses were detected before CT in advanced NSCLC but not in healthy volunteers. This response was shown to significantly increase overall survival (OS) of patients responding to CT (Median OS: 53 vs. 40 weeks, P = 0.034). These results show for the first time a potential synergistic effect of telomerase-specific CD4 T-cell response with CT response in NSCLC and underline the potential role of tumor-specific CD4 T-cell response on the efficiency of conventional anticancer therapy. ©2012 AACR.

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

    International Nuclear Information System (INIS)

    Moon, Kyung-Sub; Jung, Shin; Lee, Kyung-Hwa; Hwang, Eu Chang; Kim, In-Young

    2011-01-01

    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. 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. 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. Vaginal metastasis of pancreatic cancer.

    Science.gov (United States)

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

    2015-01-01

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

  9. Multiple metastatic malignant phyllodes tumor of the breast with tonsillar metastasis: a case report.

    Science.gov (United States)

    Sera, Tomohiro; Kashiwagi, Shinichiro; Takashima, Tsutomu; Asano, Yuka; Goto, Wataru; Iimori, Nozomi; Noda, Satoru; Onoda, Naoyoshi; Ohsawa, Masahiko; Hirakawa, Kosei; Ohira, Masaichi

    2017-01-19

    Tonsillar metastasis is very rare and accounts for only 0.8% of tonsillar tumors. And phyllodes tumor of the breast with tonsillar metastasis is very rare. A 57-year-old Japanese woman received surgery (partial mastectomy) of malignant phyllodes tumor. Seven months after initial surgery, pharyngeal pain, swelling, and a feeling of dyspnea developed, and tumor was found in the left palatine tonsil. Computed tomography for further evaluation showed a tonsillar lesion with contrast enhancement, and tonsillar metastasis was suspected. The metastatic lung tumors had not progressed. Laryngoscopic biopsy showed a tonsillar metastasis from the malignant phyllodes tumor. Despite the diagnosis of malignant phyllodes tumor with tonsillar and pulmonary metastases, the patient refused further treatment and died about 1 month later. A patient with a malignant phyllodes tumor of the breast and tonsillar metastasis was reported, along with a discussion of the relevant literature of this very rare pattern of metastasis.

  10. 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.

  11. SIRT7 antagonizes TGF-β signaling and inhibits breast cancer metastasis.

    Science.gov (United States)

    Tang, Xiaolong; Shi, Lei; Xie, Ni; Liu, Zuojun; Qian, Minxian; Meng, Fanbiao; Xu, Qingyang; Zhou, Mingyan; Cao, Xinyue; Zhu, Wei-Guo; Liu, Baohua

    2017-08-22

    Distant metastasis is the main cause of breast cancer-related death; however, effective therapeutic strategies targeting metastasis are still scarce. This is largely attributable to the spatiotemporal intratumor heterogeneity during metastasis. Here we show that protein deacetylase SIRT7 is significantly downregulated in breast cancer lung metastases in human and mice, and predicts metastasis-free survival. SIRT7 deficiency promotes breast cancer cell metastasis, while temporal expression of Sirt7 inhibits metastasis in polyomavirus middle T antigen breast cancer model. Mechanistically, SIRT7 deacetylates and promotes SMAD4 degradation mediated by β-TrCP1, and SIRT7 deficiency activates transforming growth factor-β signaling and enhances epithelial-to-mesenchymal transition. Significantly, resveratrol activates SIRT7 deacetylase activity, inhibits breast cancer lung metastases, and increases survival. Our data highlight SIRT7 as a modulator of transforming growth factor-β signaling and suppressor of breast cancer metastasis, meanwhile providing an effective anti-metastatic therapeutic strategy.Metastatic disease is the major reason for breast cancer-related deaths; therefore, a better understanding of this process and its players is needed. Here the authors report the role of SIRT7 in inhibiting SMAD4-mediated breast cancer metastasis providing a possible therapeutic avenue.

  12. Metformin inhibits the development and metastasis of ovarian cancer.

    Science.gov (United States)

    Wu, Buchu; Li, Shu; Sheng, Lili; Zhu, Jing; Gu, Liying; Shen, Haoran; La, Duanduan; Hambly, Brett D; Bao, Shisan; Di, Wen

    2012-09-01

    The aim of this study was to investigate the role of metformin in the regulation of development and metastasis of ovarian carcinoma cell lines in vitro and ovarian cancer in a nude mouse model in vivo. The effects of metformin on the ability of two high-metastatic potential human ovarian cancer cell lines (SKOV3 and HO8910-PM) to adhere, invade and migrate in vitro were observed by means of a cell adhesion test, cell invasion test and cell migration test. The size and number of the inoculated and metastatic tumours in vivo in a nude mouse were determined following intraperitoneal injection of metformin. Furthermore, the extent of angiogenesis (vWF) and macrophage infiltration in the tumour were determined. Proliferation, migration, invasion and adhesion of ovarian cancer cells were significantly inhibited (Pmetformin inhibited hepatic, intestinal and lung metastasis (Pmetformin inhibits the development and metastasis of ovarian cancer by reducing cellular-ECM interactions, neovascularisation and macrophage infiltration.

  13. Tumorigenicity, invasion and metastasis of the small cell lung cancer cell line NCI-H69 and two derivative lines MOG-H69V and MOG-H69VZ.

    Science.gov (United States)

    Khan, M Z; McNicol, A M; Freshney, R I

    1996-01-01

    Two adherent cell lines MOG-H69V and MOG-H69VZ have been isolated from a continuous cell line, NCI-H69, derived from human small cell lung cancer by Carney et al, [1987]. They have been established and characterised morphologically, biochemically, and for growth characteristics in vitro Khan et al (19). In the present study both the parental and the derivative lines have been investigated for invasiveness in vitro and in vivo. The parental line showed an early invasiveness compared with both the derivative cell lines. All cell lines formed tumours in nude mice with 100% take rate. Xenograft histology of all the cell lines revealed pleomorphic tumours, however the derivative lines showed areas of focal, large, spindle cells containing both acidic and neutral mucin, and spaces between the cells were found filled with alcianophilic, amorphous material. The parental line was invasive and metastatic. Tumours of both the derivative lines were non-metastatic under similar conditions. They were also investigated for neuroendocrine-cell marker expression. These data show that while the behaviour of the parental line was compatible with small cell lung cancer, that of the derivative lines was more indicative of non-small cell lung cancer, both in vitro and in vivo. As previous data suggested a common origin of the parental and the derivative lines, probably from a stem cell subpopulation present in the parental line, these lines represent a useful model for the study of phenotypic changes in lung cancer.

  14. Metastasis inhibition after proton beam, β- and γ-irradiation of melanoma growing in the hamster eye.

    Science.gov (United States)

    Romanowska-Dixon, Bożena; Elas, Martyna; Swakoń, Jan; Sowa, Urszula; Ptaszkiewicz, Marta; Szczygieł, Małgorzata; Krzykawska, Martyna; Olko, Paweł; Urbańska, Krystyna

    2013-01-01

    Standard ocular tumor treatment includes brachytherapy, as well as proton therapy, particularly for large melanoma tumors. However, the effects of different radiation types on the metastatic spread is not clear. We aimed at comparing ruthenium ((106)Ru, emitting β electrons) and iodine ((125)I, γ-radiation) brachytherapy and proton beam therapy of melanoma implanted into the hamster eye on development of spontaneous lung metastases. Tumors of Bomirski Hamster Melanoma (BHM) implanted into the anterior chamber of the hamster eye grew aggressively and completely filled the anterior chamber within 8-10 days. Metastases, mainly in the lung, were found in 100% of untreated animals 30 days after enucleation. Tumors were irradiated at a dose of 3-10 Gy with a (106)Ru plaque and at a dose of 6-14 Gy using a (125)I plaque. The protons were accelerated using the AIC-144 isochronous cyclotron operating at 60 MeV. BHM tumors located in the anterior chamber of the eye were irradiated with 10 Gy, for the depth of 3.88 mm. All radiation types caused inhibition of tumor growth by about 10 days. An increase in the number of metastases was observed for 3 Gy of β-irradiation, whereas at 10 Gy an inhibition of metastasis was found. γ-radiation reduced the metastatic mass at all applied doses, and proton beam therapy at 10 Gy also inhibited the metastastic spread. These results are discussed in the context of recent clinical and molecular data on radiation effects on metastasis.

  15. Inhibition of lung tumor growth and augmentation of radiosensitivity by decreasing peroxiredoxin I expression

    International Nuclear Information System (INIS)

    Chen, M.-F.; Keng, Peter C.; Shau Hungyi; Wu, C.-T.; Hu, Y.-C.; Liao, S.-K.; Chen, W.-C.

    2006-01-01

    Purpose: In this study, we examined the role of peroxiredoxin I (Prx I) in lung cancer cell growth in vitro and in vivo and its influence on these tumor cells' sensitivity to radiotherapy. Methods and materials: We established stable transfectants of A549 (p53+) and H1299 (p53-) lung carcinoma cell lines with Prx I antisense to downregulate their Prx I protein. We then examined their in vitro biologic changes and used nude mice xenografts of these cell lines to compare tumor invasion, spontaneous metastatic capacity, and sensitivity to radiotherapy. Results: The Prx I antisense transfectants of both cell lines showed a significant reduction in Prx I protein production. Prx I antisense transfectants grew more slowly than did the wild type. As xenografts in mice, A549 Prx I antisense transfectants showed a threefold delay in the generation of palpable tumors. The incidence of spontaneous metastasis of Prx I antisense transfectants was significantly less than that of the wild-type cells. Furthermore, irradiation of Prx I antisense transfectants caused more than twice the growth delay compared with the wild type. Conclusion: The results of these studies suggest that inactivation of Prx I may be a promising approach to improve the treatment outcome of patients with lung cancer

  16. Survival after bone metastasis by primary cancer type

    DEFF Research Database (Denmark)

    Svensson, Elisabeth; Christiansen, Christian F; Ulrichsen, Sinna P

    2017-01-01

    OBJECTIVE: In the 10 most common primary types with bone metastases, we aimed to examine survival, further stratifying on bone metastases only or with additional synchronous metastases. METHODS: We included all patients aged 18 years and older with incident hospital diagnosis of solid cancer...... between 1994 and 2010, subsequently diagnosed with BM until 2012. We followed patients from date of bone metastasis diagnosis until death, emigration or 31 December 2012, whichever came first. We computed 1-year, 3-year and 5-year survival (%) and the corresponding 95% CIs stratified on primary cancer...... prostate (34%), breast (22%) and lung (20%). One-year survival after bone metastasis diagnosis was lowest in patients with lung cancer (10%, 95% CI 9% to 11%) and highest in patients with breast cancer (51%, 50% to 53%). At 5 years of follow-up, only patients with breast cancer had over 10% survival (13...

  17. Results of adrenalectomy in lung cancer metastases.

    Science.gov (United States)

    Jalón-Monzón, A; Castanedo-Álvarez, D; Hevia-Suárez, M A; Álvarez-Múgica, M; Medina-González, A; Escaf-Barmadah, S

    2018-03-30

    The aim of this study was to report our centre's experience over the past 15 years with patients with lung carcinoma and adrenal metastases treated sequentially with lung resection and adrenalectomy. We analysed a retrospective series of 19 patients who underwent adrenalectomy for lung carcinoma metastasis. All patients were operated on at the same centre, between October 2000 and October 2015. We performed a descriptive analysis and an overall survival and disease-free survival analysis. The study included 13 men and 6 women. The most common primary lung tumour was adenocarcinoma, 87.5% of which were G3. In 7 patients, the adrenal metastasis was detected synchronously, and in 12 patients it was detected metachronously. The median size of the metastasis was 63mm. Twenty-one percent of the cases presented local recurrence, and 79% presented distant metastasis. The median DFS was 21.5 months, while the DFS at 5 years was calculated at 58.33%. The median overall survival was 37.3 months, while survival at 5 years was calculated at 42.86%. None of the prognostic factors evaluated were statistically significant. Adrenalectomy in cases of isolated lung carcinoma metastasis can offer increased overall survival. Age and the degree of differentiation of the primary lung carcinoma are the factors that most influence poorer survival. Copyright © 2018 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. Vulvar Metastasis from Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Fouad Aoun

    2015-01-01

    Full Text Available Vulvar metastasis of urothelial carcinoma of the bladder is a very rare entity; few cases are reported in the English literature. In this paper, we describe the clinical and pathological characteristics, evolution, and treatment of a patient with vulvar metastasis of urothelial carcinoma of the bladder followed by a brief review of the reported cases in the literature.

  19. 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.

  20. A new semiquantitative method for evaluation of metastasis progression.

    Science.gov (United States)

    Volarevic, A; Ljujic, B; Volarevic, V; Milovanovic, M; Kanjevac, T; Lukic, A; Arsenijevic, N

    2012-01-01

    Although recent technical advancements are directed toward developing novel assays and methods for detection of micro and macro metastasis, there are still no reports of reliable, simple to use imaging software that could be used for the detection and quantification of metastasis in tissue sections. We herein report a new semiquantitative method for evaluation of metastasis progression in a well established 4T1 orthotopic mouse model of breast cancer metastasis. The new semiquantitative method presented here was implemented by using the Autodesk AutoCAD 2012 program, a computer-aided design program used primarily for preparing technical drawings in 2 dimensions. By using the Autodesk AutoCAD 2012 software- aided graphical evaluation we managed to detect each metastatic lesion and we precisely calculated the average percentage of lung and liver tissue parenchyma with metastasis in 4T1 tumor-bearing mice. The data were highly specific and relevant to descriptive histological analysis, confirming reliability and accuracy of the AutoCAD 2012 software as new method for quantification of metastatic lesions. The new semiquantitative method using AutoCAD 2012 software provides a novel approach for the estimation of metastatic progression in histological tissue sections.

  1. Stereotactic radiosurgery for brain metastasis: Pitie-Salpetriere Hospital experience

    International Nuclear Information System (INIS)

    Feuvret, L.; Germain, I.; Cornu, P.; Boisserie, G.; Dormont, D.; Hardiman, C.; Tep, B.; Faillot, T.; Duffau, H.; Simon, J.M.; Dendale, R.; Delattre, J.Y.; Poisson, M.; Marsault, C.; Philippon, J.; Fohanno, D.; Baillet, F.; Mazeron, J.J.

    1998-01-01

    Retrospective analysis of the influence of clinical and technical factors on local control and survival after radiosurgery for brain metastasis. From january 1994 to December 1996, 42 patients presenting with 71 metastases underwent radiosurgery for brain metastasis. The median age was 56 years and the median Karnofsky index 80. Primary sites included: lung (20 patients), kidney (seven), breast (five), colon (two), melanoma (three), osteosarcoma (one) and it was unknown for three patients. Seventeen patients had extracranial metastasis. Twenty-four patients were treated at recurrence which occurred after whole brain irradiation (12 patients), surgical excision (four) or after both treatments (eight). Thirty-six sessions of radiosurgery have been realized for one metastasis and 13 for two, three or four lesions. The median metastasis diameter was 21 mm and the median volume 1.7 cm 3 . The median peripheral dose to the lesion was 14 Gy, and the median dose at the isocenter 20 Gy. Sixty-five metastasis were evaluable for response analysis. The overall local control rate was 82% and the 1-year actuarial rate was 72%. In univariate analysis, theoretical radioresistance (P = 0.001), diameter less than 3 cm (P = 0.039) and initial treatment with radiosurgery (P 0.041) were significantly associated with increased local control. Only the first two factors remained significant in multivariate analysis. No prognostic factor of overall survival was identified. The median survival was 12 months. Six patients had a symptomatic oedema (RTOG grade 2), only one of which requiring a surgical excision. In conclusion, 14 Gy delivered at the periphery of metastasis seems to be a sufficient dose to control most brain metastases, with a minimal toxicity. Better results were obtained for lesions initially treated with radiosurgery, theoretically radioresistant and with a diameter less than 3 cm. (authors)

  2. Choroid metastasis of papillary thyroid carcinoma. Color doppler ultrasound study

    International Nuclear Information System (INIS)

    Ganado, T.; Torre, S. de la; Contreras, E.; Hernandez, J.

    1997-01-01

    The most common causes of intraocular metastases are breast and lung cancers, although many other neoplasms can metastasize to the eye. Most of the metastases are located in the posterior pole and the choroid is more often involved than the retina. We present a case of a choroidal metastasis from a papillary carcinoma of the thyroid, associated with a massive subretinal hemorrhage. Findings with color Doppler ultrasound are emphasized. (Author) 9 refs

  3. Abdominal Wall Metastasis from an Invasive Lobular Carcinoma of the Breast: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hana; Son, Eun Ju; Youk, Ji Hyun; Chung, Jin [Dept. of Radiology, Gangnam Severance Hospital, Yensei University College of Medicine, Seoul (Korea, Republic of); Noh, Song Mi; Jung, Woo Hee [Dept. of Diagnostic Pathology, Gangnam Severance Hospital, Yensei University College of Medicine, Seoul (Korea, Republic of)

    2011-06-15

    Breast cancer is one of the most common malignancies in women. Breast cancer frequently metastasizes to the bones, lungs, and liver. However, the recurrence of distant soft-tissue metastasis except to the chest wall is extremely rare. Here, we describe our experience with a patient in whom invasive lobular carcinoma of the breast with metastasis to the abdominal wall presented as subcutaneous nodules without local recurrence.

  4. Abdominal Wall Metastasis from an Invasive Lobular Carcinoma of the Breast: A Case Report

    International Nuclear Information System (INIS)

    Kim, Hana; Son, Eun Ju; Youk, Ji Hyun; Chung, Jin; Noh, Song Mi; Jung, Woo Hee

    2011-01-01

    Breast cancer is one of the most common malignancies in women. Breast cancer frequently metastasizes to the bones, lungs, and liver. However, the recurrence of distant soft-tissue metastasis except to the chest wall is extremely rare. Here, we describe our experience with a patient in whom invasive lobular carcinoma of the breast with metastasis to the abdominal wall presented as subcutaneous nodules without local recurrence.

  5. Diagnostic study with CT and MR on the metastasis of malignant brain tumors

    International Nuclear Information System (INIS)

    Miyagami, Mitsusuke; Kasahara, Eishi; Tazoe, Makoto; Tsubokawa, Takashi

    1990-01-01

    Forty cases of malignant brain tumors with metastasis which involved 14 malignant gliomas, 15 medulloblastomas and 11 germ cell tumors were studied on CT and MRI. In malignant glioma, transventricular metastasis was seen most frequently, estimating 8 cases (57%) of 14 malignant gliomas with metastasis and showing ependymal-subependymal enhancement on contrast-enhanced CT (CECT). Most of the medulloblastoma with metastasis demonstrated diffuse subarachnoid seeding in the craniospinal space and on image analysis diffuse sulcal-cisternal enhancement was characterized. Trans-ventricular metastasis in medulloblastoma was less than in malignant glioma showing 3 cases (20%) of 15 medulloblastomas, which in most cases showed a nodular tumor in the ventricular wall by metastasis. There were six patients who, on the first admission, were found to have germ cell tumors of the broad infiltrating type with multiple lesions. The tumor sites of metastasis were different from those with malignant gliomas, being frequently localized in the pineal and/or the suprasellar region, on the ventricular wall and in the basal ganglia. Metastasis to a remote area in germ cell tumors was to spinal cords, to the ventricular wall and basal cistern around the brain stem by CSF dissemination, to the lung by hematogenous metastasis and to the peritoneal wall or organs through V-P shunt tube. T 1 -weighted Gd-DTPA MRI was more useful and sensitive than CECT for diagnosis of the leptomeningeal metastasis, particularly for sulcal-cisternal and spinal metastasis. It will be used more often as the first choice for diagnosis of intrathecal metastasis in the future. (author)

  6. A Fatal Complication of Dermatomyositis: Spontaneous Pneumomediastinum

    Directory of Open Access Journals (Sweden)

    Ezgi Demirdöğen Çetinoğlu

    2016-04-01

    Full Text Available Interstitial lung disease (ILD is a negative prognostic factor associated with increased morbidity and mortality in patients with dermatomyositis (DM. Spontaneous pneumomediastinum is a rare complication of DM and it can be fatal. We present a 48-year-old woman with DM and ILD complicated by pneumomediastinum without pneumothorax and subcutaneous emphysema.

  7. Isolated Late Metastasis of a Renal Cell Cancer Treated by Radical Distal Pancreatectomy

    Directory of Open Access Journals (Sweden)

    J. P. Barras

    1996-01-01

    Full Text Available A 53–year-old man underwent right nephrectomy for a locally advanced renal cell carcinoma with concomitant resection of a solitary metastasis in the right lung. Ten years later, he presented with haematochezia caused by a tumour in the tail of pancreas, invading the transverse colon and the greater curvature of the stomach. The tumour was radically resected, and histological examination revealed a solitary metastasis of the previous renal cell carcinoma. This case illustrates a rare indication for pancreatic resection because of pancreatic metastasis.

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

    Science.gov (United States)

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

    2017-04-01

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

  9. Ampullary carcinoma with cutaneous metastasis

    Directory of Open Access Journals (Sweden)

    I-Ting Liu

    2016-06-01

    Full Text Available Carcinoma of the ampulla of Vater is a rare gastrointestinal tumor. Additionally, cutaneous metastasis from such an internal malignancy is also uncommon. We reported the case of a 55-year-old man afflicted with ampullary carcinoma with cutaneous metastasis. The patient did not undergo the standard Whipple procedure but received chemotherapy due to apparent left neck lymph node metastasis noted by initial PET/CT imaging. The skin metastasis presented as a left neck infiltrating purpuric lesion, which was confirmed by skin biopsy approximately one year after the patient's disease was first diagnosed. Thereafter, the patient received further chemotherapy pursuant to his course of medical management. Skin metastasis usually represents a poor patient prognosis. In these cases, treatment of cutaneous metastasis typically includes systemic chemotherapy and local management such as radiation therapy or tumor excision. And when choosing a chemotherapy regimen for the ampullary cancer, the histological subtypes (intestinal or pancreatobiliary should be comprehensively considered. In our review of the literature, the intestinal type seems to have less distant lymph node metastasis, advanced local invasion, as well as recurrence than pancreatobiliary type of ampullary cancer.

  10. Asymptomatic Bladder Metastasis from Breast Cancer

    Directory of Open Access Journals (Sweden)

    Luigi Cormio

    2014-01-01

    Full Text Available Introduction. Breast cancer is the most common nondermatologic cancer in women. Common metastatic sites include lymph nodes, lung, liver, and bone. Metastases to the bladder are extremely rare, with all reported cases presenting with urinary symptoms. Case Report. Herein, we report the first case of completely asymptomatic bladder metastasis from breast cancer, occasionally revealed, 98 months after the initial diagnosis of lobular breast carcinoma, by a follow-up computed tomography scanning showing thickening of left bladder wall and grade II left hydronephrosis. A positive staining for estrogen and progesterone receptors was confirmed by immunohistochemistry. Discussion. The reported case confirms that bladder metastases from breast cancer tend to occur late after the diagnosis of the primary tumor and, for the first time, points out they can be asymptomatic. Conclusion. Such data support the need for careful follow-up and early intervention whenever such clinical situation is suspected.

  11. Epigenetic induction of epithelial to mesenchymal transition by LCN2 mediates metastasis and tumorigenesis, which is abrogated by NF-?B inhibitor BRM270 in a xenograft model of lung adenocarcinoma

    OpenAIRE

    MONGRE, RAJ KUMAR; SODHI, SIMRINDER SINGH; SHARMA, NEELESH; GHOSH, MRINMOY; KIM, JEONG HYUN; KIM, NAMEUN; PARK, YANG HO; SHIN, YOUNG GYU; KIM, SUNG JIN; JIAO, ZHANG JIAO; HUYNH, DO LUONG; JEONG, DONG KEE

    2015-01-01

    Tumor initiating cancer stem-like cells (TICSCs) have recently become the object of intensive study. Human-Lipocalin-2 (hLCN2) acts as a biomarker for cancers. The aim of the present study was to explore new insights regarding the potential role of LCN2 in inducing epithelial to mesenchymal transition (EMT) by transfecting LCN2 into CD133+-A549-TICSCs and its cross-talk with the NF-?B signaling pathway in adenocarcinoma of the lung. Furthermore, EMT was confirmed by transcriptomic analysis, i...

  12. Metástasis hipofisaria Hypophyseal metastasis

    Directory of Open Access Journals (Sweden)

    Miguel Ángel Yanes Quesada

    2009-04-01

    Full Text Available mayoría son lesiones silentes descubiertas accidentalmente en las autopsia. La aparición de metástasis sintomáticas es, en cambio, excepcional. DESARROLLO: se describen aquí los hallazgos clínicos y radiológicos de una paciente femenina de 69 años, con un carcinoma indiferenciado del pulmón, diagnosticado hace 2 años y medio, que comenzó con cefalea y trastornos visuales sin hipopituitarismo ni diabetes insípida. Se le realizó resonancia magnética nuclear y se le diagnosticó una lesión hipofisaria, que fue operada por vía tranesfenoidal, y se informó por anatomía patológica una metástasis del carcinoma del pulmón. CONCLUSIONES: la paciente se encuentra en estos momentos recibiendo quimioterapia, radioterapia y anticuerpo monoclonal con evolución favorable.INTRODUCTION: metastatic tumors of hypophyseal gland are infrequent. Most are silent lesions discovered accidentally in necropsy. Appearance of symptomatic metastasis is however, exceptional. DEVELOPMENT: we describe here clinical and radiological findings in a female patient aged 69, presenting with a non-differential carcinoma of lung, diagnosed two years a half ago, starting with headache and visual disorders without hypopituitarism and insipidus diabetes. We made a nuclear magnetic resonance and diagnosis was a hypophyseal lesion operated on by trans-esphenoidal route, and Pathological Anatomy Service reports a metastasis of lung carcinoma. CONCLUSIONS: patient receives chemotherapy, radiotherapy, and monoclonal antibody with a favorable evolution.

  13. 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.

  14. Neurofibromatosis Type I presenting with Spontaneous Pneumothorax: A Case Report

    International Nuclear Information System (INIS)

    Shin, So Youn; Lee, Young Kyung; Moon, Ah Lim; Sung, Dong Wook

    2010-01-01

    Neurofibromatosis type I is an autosomal dominant disease with variable clinical manifestations related to dermatologic, neurologic, skeletal, and endocrine system. Lung parenchymal involvement such as lung fibrosis and massive bullous emphysema is infrequent. Here, we report on a 36-year-old man with symptoms of dyspnea, and who has a spontaneous pneumothorax, multiple bullae, and pathologically confirmed neurofibromatosis type I

  15. Neurofibromatosis Type I presenting with Spontaneous Pneumothorax: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Shin, So Youn; Lee, Young Kyung; Moon, Ah Lim; Sung, Dong Wook [Kyunghee University College of Medicine, East-West Neo Medical Center, Seoul (Korea, Republic of)

    2010-08-15

    Neurofibromatosis type I is an autosomal dominant disease with variable clinical manifestations related to dermatologic, neurologic, skeletal, and endocrine system. Lung parenchymal involvement such as lung fibrosis and massive bullous emphysema is infrequent. Here, we report on a 36-year-old man with symptoms of dyspnea, and who has a spontaneous pneumothorax, multiple bullae, and pathologically confirmed neurofibromatosis type I

  16. Risk factors for bone metastasis from renal cell cancer.

    Science.gov (United States)

    Chen, Xuan-Yin; Lan, Min; Zhou, Yang; Chen, Wen-Zhao; Hu, Dong; Liu, Jia-Ming; Huang, Shan-Hu; Liu, Zhi-Li; Zhang, Zhi-Hong

    2017-11-01

    The prognosis for renal cell carcinoma (RCC) is related to a high rate of metastasis, including 30% of bone metastasis. In this study, we investigate the correlation between diverse clinical factors and bone metastases secondary from renal cell cancer (RCC), and to identify potential risk factors for bone metastasis in newly diagnosed patients and those who have already received treatment. The clinical data of 372 patients with RCC were reviewed from January 2000 to August 2016. The correlations between age, gender, histopathologic types, alkaline phosphotase (ALP), CEA, AFP, CA-125, CA-153, CA-199, calcium, hemoglobin (HB) and bone metastases were analyzed. And the risk factors for bone metastases in RCC were identified by multivariate logistic regression analysis. The cutoff value, sensitivity and specificity of the independent correlation factors were calculated by receiver operating characteristic (ROC) curve. The bone is the second to the lung as a distant metastasis target site in patients with RCC. Thirty eight individuals were identified with bone metastases. Of these patients, significantly higher levels of ALP, calcium, HB were found than those without bone metastasis (P 0.05, respectively). Multivariate logistic regression analysis indicated that ALP, calcium and HB were independent risk factors correlated with bone metastasis (P factors had comparable accuracy at predicting bone metastasis (AUC were 0.749, 0.633 and 0.665, respectively). The cutoff values of ALP, calcium and HB were 105.5 U/L, 2.615 mmol/L and 111.5 g/L, respectively. The sensitivities of them were 57.9%, 36.8% and 71.1% for predicting bone metastasis, with specificities of 83.5%, 95.2% and 65.3%, respectively. Based on our study, the concentrations of ALP, calcium and HB were potentially risk factors for bone metastasis in patients with RCC. For newly diagnosed patients, if the values of ALP>105.5 U/L, calcium>2.615 mmol/L and HB<111.5 g/L were detected, intensive monitoring and

  17. Angiogenesis Regulates Prostate Cancer Metastasis

    National Research Council Canada - National Science Library

    Pettaway, Curtis

    1999-01-01

    .... We are evaluating the relationship of the expression of the angiogenesis factors bFGF, VEGF, and IL-8 with prostate cancer growth and metastasis, using our orthotopic model of metastatic prostate cancer in nude mice...

  18. A Brief Report of the Status of Central Nervous System Metastasis Enrollment Criteria for Advanced Non-Small Cell Lung Cancer Clinical Trials: A Review of the ClinicalTrials.gov Trial Registry.

    Science.gov (United States)

    McCoach, Caroline E; Berge, Eamon M; Lu, Xian; Barón, Anna E; Camidge, D Ross

    2016-03-01

    Central nervous system (CNS) metastases are common in non-small cell lung cancer (NSCLC), yet clinical trials of new drugs in advanced NSCLC have varying inclusion and exclusion criteria for CNS disease. The true extent of variation in CNS-related enrollment criteria in NSCLC clinical trials has not been documented. We performed a systematic search of the ClinicalTrials.gov website to characterize interventional drug trials enrolling adult patients with advanced NSCLC. Of 413 open trials, 78 (19%) strictly excluded patients with leptomeningeal disease (LMD). Separate from LMD, patients with any history of CNS metastases were strictly excluded in 59 trials (14%), allowed after local treatment in 169 (41%), and allowed with no prior treatment in 106 (26%). No explicit mention of CNS disease was made in 79 trials (19%). In multivariate analysis looking at trial phase, location, sponsor, and treatment type, only sponsor was statistically significant, with pharmaceutical industry-sponsored trials having higher odds of excluding patients with brain metastases than did university or investigator-initiated trials (OR = 2.262, 95% confidence interval: 1.063-4.808, p = 0.0342) CONCLUSIONS: With 14% to 19% of trials excluding any history of LMD or CNS parenchymal metastatic disease and 41% of trials permitting CNS disease only after prior CNS-directed treatment, direct evidence of activity of a treatment on CNS disease cannot be reliably generated in most NSCLC trials. Given the high frequency of CNS disease in NSCLC and only sponsor being associated with specific CNS exclusion criteria, sponsors should consider tailoring trial designs to explore CNS benefit more explicitly. Copyright © 2015 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  19. [The Argument and Consensus of Lymphadenectomy on Lung Cancer Surgery].

    Science.gov (United States)

    Zhang, Lanjun

    2018-03-20

    Lymph node metastasis is an important route of metastasis of lung cancer. Lymphadenectomy has become the standard surgical procedure for lung cancer. The way of intraoperative lymph node assessment also affects the prognosis and treatment strategy of lung cancer. In clinical practice, the way of intraoperative lymph node assessment ranges from selected lymph node biopsy to extended lymph node dissection. The advantages and disadvantages of different lymph node assessment are still controversial. In this article, the argument and consensus of lymphadenectomy on lung cancer operation are summarized.

  20. Burned-out seminoma revealed by solitary rib bone metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Nishisho, Toshihiko; Miyagi, Ryo; Sairyo, Koichi [Tokushima University Graduate School, Department of Orthopedics, Institute of Biomedical Sciences, Tokushima-city, Tokushima (Japan); Sakaki, Mika [Saitama Medical University International Medical Center, Department of Pathology, Hidaka-city, Saitama (Japan); Takao, Shoichiro [Tokushima University Graduate School, Department of Radiology, Institute of Biomedical Sciences, Tokushima-city, Tokushima (Japan)

    2017-10-15

    Burned-out tumor is a rare phenomenon in which a testicular tumor regresses in the primary lesion and progresses in a metastatic lesion. We report the case of a 30-year-old male with burned-out seminoma revealed by open biopsy of solitary 10th rib bone metastasis. He underwent inguinal orchiectomy, which revealed hyalinization, indicating a spontaneously regressed testicular tumor. Chemotherapy for seminoma was administered in three cycles of bleomycin + etoposide + cisplatin therapy. The chemotherapy was effective, and wide resection of the rib was subsequently performed. No postoperative chemotherapy was performed, and there has been no evidence of recurrence for 3 years postoperatively. (orig.)

  1. Silibinin Inhibits NSCLC Metastasis by Targeting the EGFR/LOX Pathway

    Directory of Open Access Journals (Sweden)

    Xiaoying Hou

    2018-02-01

    Full Text Available Tumor metastasis is the most lethal and debilitating process that threatens cancer patients. Among the regulators involved in tumor metastasis, lysyl oxidase (LOX is an important contributor for tumor invasion, migration and the formation of the pre-metastatic niche. Although the relationship between LOX and poor prognosis of lung patients has been preliminary reported, the mechanism remains poorly understood. Here, we found that LOX overexpression is closely related to the survival of lung adenocarcinoma patients but not squamous cell carcinoma patients. Moreover, we confirmed that LOX expression is regulated by the activation of epidermal growth factor receptor (EGFR via the PI3K/AKT, MEK/ERK, and SAPK/JNK signaling pathways in non-small cell lung cancer (NSCLC. Meanwhile, the study also suggested that the traditional anti-fibrosis drug silibinin inhibited NSCLC cell migration in an EGFR/LOX dependent manner. In addition, an orthotopic implantation metastasis model also confirmed that the EGFR inhibitor WZ4002 and silibinin decreased tumor metastasis through the EGFR/LOX pathway. Altogether, this study revealed that LOX expression is regulated by the EGFR pathway and this may account for the anti-cancer metastasis effects of silibinin, indicating LOX as a potentially therapeutic target for NSCLC treatment.

  2. A case series of neuroendocrine (carcinoid) tumor metastasis to the orbit

    Science.gov (United States)

    Turaka, Kiran; Mashayekhi, Arman; Shields, Carol L.; Lally, Sara E.; Kligman, Brad; Shields, Jerry A.

    2011-01-01

    Purpose/Background: To report the clinical and radiographic features and treatment outcome of neuroendocrine tumor (carcinoid) metastasis to the orbit. Materials and Methods: Retrospective chart review of four cases. Results: Mean patient age at the time of diagnosis of the primary neuroendocrine tumor and orbital metastasis was 58 and 66 years, respectively, with a mean duration of 8 years between diagnosis of primary tumor and orbital metastasis. Primary neuroendocrine tumor sites were gastrointestinal tract (n = 2), lung (n = 1), and testicle (n = 1). The most common presenting symptom was diplopia (three cases). Magnetic resonance imaging revealed orbital tumor in all cases. Octreotide scan was positive in one case. Treatment was tumor excision in three cases followed by external beam radiotherapy in two cases and one patient was followed without treatment. Tumor cells showed immunoreactivity to chromogranin, synaptophysin, and neuron-specific enolase in all cases. Mean follow-up after orbital tumor diagnosis was 39 months. Three patients had known systemic extraorbital metastasis before orbital involvement (mean interval of 5.9 years) and one case had immediately after development of orbital metastasis. One patient had multiple recurrences of orbital metastasis and eventually underwent exenteration. Two patients died of disseminated metastasis between 2 and 3 years after diagnosis of orbital metastasis. Conclusion: All four patients with orbital metastasis from neuroendocine tumor had evidence of systemic extraorbital metastasis. Aggressive metastatic neuroendocine tumors of orbit can lead to local recurrence even after surgical excision and radiation. Imaging tests were helpful in allowing early diagnosis and for monitoring after treatment. PMID:22279400

  3. Reactive Astrocytes in Brain Metastasis

    Directory of Open Access Journals (Sweden)

    David Wasilewski

    2017-12-01

    Full Text Available Brain metastasis, the secondary growth of malignant cells within the central nervous system (CNS, exceeds the incidence of primary brain tumors (i.e., gliomas by tenfold and are seemingly on the rise owing to the emergence of novel targeted therapies that are more effective in controlling extracranial disease relatively to intracranial lesions. Despite the fact that metastasis to the brain poses a unmet clinical problem, with afflicted patients carrying significant morbidity and a fatal prognosis, our knowledge as to how metastatic cells manage to adapt to the tissue environment of the CNS remains limited. Answering this question could pave the way for novel and more specific therapeutic modalities in brain metastasis by targeting the specific makeup of the brain metastatic niche. In regard to this, astrocytes have emerged as the major host cell type that cancer cells encounter and interact with during brain metastasis formation. Similarly to other CNS disorders, astrocytes become reactive and respond to the presence of cancer cells by changing their phenotype and significantly influencing the outcome of disseminated cancer cells within the CNS. Here, we summarize the current knowledge on the contribution of reactive astrocytes in brain metastasis by focusing on the signaling pathways and types of interactions that play a crucial part in the communication with cancer cells and how these could be translated into innovative therapies.

  4. Pancreatic acinar cell carcinoma with intracranial metastasis in a dog.

    Science.gov (United States)

    Chang, Shih-Chieh; Liao, Jiunn-Wang; Lin, Yung-Chang; Liu, Cheng-I; Wong, Min-Liang

    2007-01-01

    This report concerns a case of pancreatic carcinoma with widespread metastases to many organs including intracranial metastasis. An eleven-year-old, male, mixed-breed dog showed emaciation, ataxia, and multiple visible tumors within the neck. A MRI examination of the patient was conducted because of ataxia, and it was found that the intracranial invasive growth had resulted in compression of the brain stem. Necropsy was performed after the patient died. Based on gross and microscopic examination, the primary tumor cells were located in the left lobe of the pancreas and widespread metastasis was found into various organs, including the brain, lungs, liver, kidneys, tonsils, serosal surface of the esophagus, and submandibular, pulmonary hilar, mediastinal, and mesenteric lymph nodes. This case indicates that pancreatic adenocarcinoma should be included in the differential diagnosis list when cervical neck masses are detected.

  5. Isolated splenic metastasis of ovaric cancer. Case report and literature review.

    Science.gov (United States)

    Resta, G; Vedana, L; Marino, Silvia; Scagliarini, L; Bandi, M; Anania, G

    2014-01-01

    Splenic metastasis is extremely rare and are usually found in conjunction with metastasis of other organs. In addition, late recurrence even after 10 years of operation is very unusual. The most common sources of splenic metastasis are lung, colonrectal, melanoma, breast and ovarian carcinoma. We present a case of 67 year old woman who was admitted to our department with a solitary splenic metastases after hysterectomy with bilateral salpingo-oophorectomy for ovaric carcinoma 10 years ago. In conclusion, solitary splenic metastasis are very rare and the incidence of the reported cases in the medical literature is increasing. The treatment of choice is laparoscopic splenectomy that must be followed by chemotherapy in order to prevent the development of other possible micrometastases.

  6. Ultrasonography findings of thyroid metastasis in a patient with hepatocellular carcinoma: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kyung Ho; Park, Noh Hyuck; Lim, Jae Hoon; Park, Chan Sub; Seong, Su Ok; Kwon, Tae Jung [Myongji Hospital, Goyang (Korea, Republic of)

    2015-03-15

    Although the thyroid gland is one of the most vascular organs of the body, metastatic disease in the thyroid is encountered infrequently. However, at autopsy, the incidence rate of thyroid metastasis ranges from 1.25% to 24%. The primary sites are the kidney, lung, breast, and gastrointestinal tract. We report a rare case of a hepatocellular carcinoma metastatic to the thyroid gland. The patient had multiple palpable masses in the anterior and left lateral neck along the internal jugular chain on physical examination 9 months after the initial diagnosis of liver tumor. These masses were confirmed as metastasis from hepatocellular carcinoma by ultrasonography-guided 16-G core needle biopsy. We discuss the sonographic findings of thyroid metastasis and their use as an additional aid for differentiating between unknown primary tumor and thyroid metastasis.

  7. Ovarian metastasis from thyroid carcinoma: a case report and literature review.

    Science.gov (United States)

    Corrado, Giacomo; Pomati, Giulia; Russo, Andrea; Visca, Paolo; Vincenzoni, Cristina; Patrizi, Lodovico; Vizza, Enrico

    2014-10-30

    Papillary thyroid carcinoma is rarely associated with metastatic disease. The most common sites of metastasis are the lungs and bones, while only few cases of ovarian metastasis are described in literature. We report the case of a 51 years old woman, treated 9 years before for papillary thyroid carcinoma, presenting to our Institute with a pelvic ovarian mass revealed by ultrasound imaging. After bilateral salpingo-oophorectomy, the histologic examination detected a left ovarian metastasis from papillary thyroid carcinoma. Even if the diagnosis of ovarian metastasis from thyroid carcinoma is often controversial, it should be considered when a woman with an ovarian lesion of unknown origin, has a personal history of malignant thyroid disease. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_193.

  8. Apropos of a case of cutaneous metastasis from laryngeal cancer with review of literature

    Directory of Open Access Journals (Sweden)

    Romeeta Trehan

    2015-01-01

    Full Text Available Cutaneous metastasis from laryngeal carcinoma is a rare occurrence. A 55-year-old male patient with supraglottic cancer was treated with concurrent chemoradiation. Eighteen months later, he presented with ulceroproliferative growth on dorsum of the right hand. Biopsy revealed metastatic squamous cell carcinoma. Further investigations revealed underlying bone destruction with lung metastasis. In view of poor general condition and widespread dissemination of disease, palliative radiotherapy was delivered to the hand of the patient. He achieved satisfactory palliation in form of pain relief, control of bleeding, and discharge. The present report serves to emphasize the importance of properly diagnosing metastatic spread to unusual sites. Such metastasis is rare and is associated with a poor prognosis. Treatment is usually aimed at providing pain relief in these patients with limited life expectancy. Hence, we present a case of extensive cutaneous metastasis from laryngeal carcinoma with review of the literature.

  9. Metastasis of Renal Cell Carcinoma to the Buccal Mucosa 19 Years after Radical Nephrectomy

    Directory of Open Access Journals (Sweden)

    Hernani Gil-Julio

    2012-01-01

    Full Text Available Renal cell carcinoma (RCC has high metastatic potential, which requires early diagnosis to optimize the chance of cure. Metastasis of RCC to the head and neck region is less common and metastasis to the buccal mucosa is extremely rare. This phenomenon occurs mostly in patients with generalized dissemination, especially with lung metastases. In this article we report a case of buccal mucosa metastasis from RCC in a 65-year-old man who presented 19 years after undergoing a left radical nephrectomy for clear cell RCC. Surgical excision of the buccal lesion was performed without evidence of recurrence or new metastatic lesions after 6 years of followup. To our knowledge, this is the first case of metastasis to the buccal mucosa from a RCC reported in the literature.

  10. Thyroid Gland Metastasis from Cancer of the Uterine Cervix: An Extremely Rare Case Report.

    Science.gov (United States)

    Celik, Suleyman Utku; Besli, Dilara; Sak, Serpil Dizbay; Genc, Volkan

    The thyroid gland is a relatively uncommon site for a metastatic disease, although it is richly supplied with blood. The metastases may originate from various primary sites, mainly kidney, lung, head and neck, and breast. Thyroid metastasis from cervical carcinomas is extremely rare; and only a few cases have been previously reported in the literature. In patient with thyroid nodules and an oncological history, the possibility of thyroid metastasis should be seriously considered. Despite the rarity of the metastasis of cervical carcinoma to the thyroid, it is difficult to say appropriate treatment approach for these lesions. When managing such patients, decision-making should balance the possibility of gaining long-term survival against estimation of the aggressiveness of the disease and its possible complications. Here, a case of thyroid metastasis from a squamous cell carcinoma of the uterine cervix presenting with cervical mass and difficulty in swallowing and its treatment is reported.

  11. [Pulmonary Metastasis from a Phyllodes Tumor of the Breast Developing Sixteen Years after Initial Surgery].

    Science.gov (United States)

    Chang, Sung-Soo; Nakano, Takayuki; Okamoto, Taku; Takabatake, Daisuke

    2015-11-01

    We report a case of solitary pulmonary metastasis from a phyllodes tumor of the breast appearing 16 years after initial surgery. The patient was a 56-year-old woman who had undergone surgical extirpation of a left breast tumor diagnosed as phyllodes tumor (borderline malignancy) in 1998, and a right breast tumor diagnosed as fibromatosis in 2000. Sixteen years after the initial operation, she consulted our hospital because of a chest X-ray abnormality detected at a screening examination. Chest computed tomography revealed a well defined nodular shadow in the left upper lobe of the lung. Surgery was done since primary lung cancer was suspected. However, pathological diagnosis was a pulmonary metastasis from the phyllodes tumor of the left breast. Right breast tumor was also diagnosed as a metastasis from the left breast tumor by histopathological re-evaluation.

  12. Adenoid Cystic Carcinoma of the Buccal Mucosa with Rare Delayed Frontal Bone Metastasis: A Case Report

    Directory of Open Access Journals (Sweden)

    Zohreh Dalirsani

    2016-10-01

    Full Text Available Adenoid cystic carcinoma (AdCC is a malignant neoplasm, which accounts for 5-10% of all salivary gland tumors (1. About 50% of these tumors originate from intraoral minor salivary glands usually in the hard palate (1. Three clinically obvious characteristics of AdCC include slow growth rate, perineural invasion and high incidence of distant metastasis (1. The most commonly-affected sites of distant metastasis are bone, liver and brain, followed by lungs (2. Lymph node metastases are rare;  The most common sites  involved by hematogenous spread are lungs (2.  This is a report about a patient with a rare form of AdCC on buccal mucosa with an unusual metastasis to the frontal region after a two-year follow up.

  13. Multiple cystic lung disease

    Directory of Open Access Journals (Sweden)

    Flavia Angélica Ferreira Francisco

    2015-12-01

    Full Text Available Multiple cystic lung disease represents a diverse group of uncommon disorders that can present a diagnostic challenge due to the increasing number of diseases associated with this presentation. High-resolution computed tomography of the chest helps to define the morphological aspects and distribution of lung cysts, as well as associated findings. The combination of appearance upon imaging and clinical features, together with extrapulmonary manifestations, when present, permits confident and accurate diagnosis of the majority of these diseases without recourse to open-lung biopsy. The main diseases in this group that are discussed in this review are lymphangioleiomyomatosis, pulmonary Langerhans cell histiocytosis and folliculin gene-associated syndrome (Birt–Hogg–Dubé; other rare causes of cystic lung disease, including cystic metastasis of sarcoma, are also discussed. Disease progression is unpredictable, and understanding of the complications of cystic lung disease and their appearance during evolution of the disease are essential for management. Correlation of disease evolution and clinical context with chest imaging findings provides important clues for defining the underlying nature of cystic lung disease, and guides diagnostic evaluation and management.

  14. Spontaneous pneumothorax in weightlifters.

    Science.gov (United States)

    Marnejon, T; Sarac, S; Cropp, A J

    1995-06-01

    Spontaneous pneumothorax is infrequently caused by strenuous exertion. To our knowledge there has only been one case of spontaneous pneumothorax associated with weightlifting reported in the medical literature. We describe three consecutive cases of spontaneous pneumothorax associated with weightlifting. We postulate that spontaneous pneumothorax in these patients may be secondary to improper breathing techniques. It is important that physicians and weight trainers be aware of the association between weight lifting and spontaneous pneumothorax and assure that proper instruction is given to athletes who work with weights.

  15. Cisplatin Induces Up-Regulation of KAI1, a Metastasis Suppressor ...

    African Journals Online (AJOL)

    HP

    KAI1 is involved in cell migration, adhesion and synapse formation [7]. Many reports have documented that the KAI1 gene suppresses metastasis in many types of human cancers including breast, pancreatic, lung, bladder, hepatic, gastric, breast, colorectal, ovarian, esophageal, cervical and endometrial [8,9]. The aim of the ...

  16. Nodal metastasis in thyroid cancer

    International Nuclear Information System (INIS)

    Samuel, A.M.

    1999-01-01

    The biological behavior and hence the prognosis of thyroid cancer (TC) depends among other factors on the extent of spread of the disease outside the thyroid bed. This effect is controversial, especially for nodal metastasis of well differentiated thyroid carcinoma (WDC). Nodal metastasis at the time of initial diagnosis behaves differently depending on the histology, age of the patient, presence of extrathyroidal extension, and the sex of the individual. The type of the surgery, administration of 131 I and thyroxin suppression also to some extent influence the rate of recurrence and mortality. Experience has shown that it is not as innocuous as a small intrathyroidal tumor without any invasion outside the thyroid bed and due consideration should be accorded to the management strategies for handling patients with nodal metastasis

  17. Metástase de câncer gástrico simulando neoplasia primária de pulmão: relato de caso e revisão da literatura Gastric cancer metastasis mimicking primary lung cancer: case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Dante Luiz Escuissato

    2002-03-01

    Full Text Available O adenocarcinoma gástrico apresenta, freqüentemente, disseminação por extensão direta para órgãos vizinhos. Metástases para sítios distantes, como o pulmão, são menos freqüentes, sugerindo usualmente outras doenças. O objetivo deste artigo é apresentar o caso de um paciente de 47 anos de idade, cujos exames de imagem (radiografias simples e tomografia computadorizada de tórax apresentaram características sugestivas de neoplasia pulmonar primária e com diagnóstico simultâneo de câncer gástrico evidenciado pela endoscopia digestiva alta. A biópsia, guiada por fibrobroncoscopia, da massa torácica confirmou o diagnóstico de metástase pulmonar de adenocarcinoma gástrico. Além da apresentação do caso, é feita uma revisão do padrão de disseminação do câncer gástrico.Gastric cancer frequently presents intraperitoneal spread. Distant metastases are rare. The authors describe a case of a 47-year-old white man, long-term cigarette smoker, who had a right upper lobe mass seen on plain films and computed tomography of the chest. A gastric adenocarcinoma was concomitantly diagnosed by endoscopic examination. A bronchoscopy guided biopsy showed that the lung mass was in fact a metastasis from gastric adenocarcinoma. In this article, the imaging findings of gastric cancer and the patterns of dissemination to other organs are reviewed.

  18. Solitary splenic metastasis from ovarian carcinosarcoma: a case report

    Directory of Open Access Journals (Sweden)

    Gillespie Thomas

    2011-02-01

    Full Text Available Abstract Introduction Metastatic tumors to the spleen are rare but are usually found in conjunction with metastasis to other organs. The most common sources of splenic metastasis are breast, lung and colorectal cancers as well as melanoma and ovarian carcinoma. A solitary carcinosarcoma metastasis to the spleen of any origin is very rare. To the best of our knowledge, there are fewer than 30 reported cases of ovarian primary tumors with solitary metastasis to the spleen, and only three solitary primary carcinosarcomas to the spleen have been reported, of which one is female. We present what is, to the best of our knowledge, the first case of a solitary metastatic carcinosarcoma to the spleen arising from a primary ovarian carcinsarcoma. Case presentation A 72-year-old Hispanic woman status post-total abdominal hysterectomy for ovarian carcinosarcoma presented with complaints of early satiety and abdominal pain for the past two months with a 30-lb unintentional weight loss. An initial computed tomographic scan of her abdomen and pelvis revealed a 30 cm × 27 cm splenic mass with displacement of the left kidney, stomach and liver. The patient was found to have a solitary metastatic carcinosarcoma of the spleen with biphasic epithelial (carcinomatous and mesenchymal (sarcomatous elements consistent with carcinosarcoma. Conclusion Carcinosarcoma of the spleen is a rare tumor. Carcinosarcomas are a biphasic neoplasm comprising malignant epithelial and mesenchymal components arising from a stem cell capable of differentiation. They can arise anywhere in the female genital tract, most commonly from the endometrium. Even though it is rare, carcinosarcomas can metastasize to the spleen. This unique case of a solitary splenic metastasis from ovarian carcinosarcoma has particular interest in medicine, especially for the specialties of surgical oncology, pathology and hematology/oncology.

  19. Nitric oxide in cancer metastasis.

    Science.gov (United States)

    Cheng, Huiwen; Wang, Lei; Mollica, Molly; Re, Anthony T; Wu, Shiyong; Zuo, Li

    2014-10-10

    Cancer metastasis is the spread and growth of tumor cells from the original neoplasm to further organs. This review analyzes the role of nitric oxide (NO), a signaling molecule, in the regulation of cancer formation, progression, and metastasis. The action of NO on cancer relies on multiple factors including cell type, metastasis stage, and organs involved. Various chemotherapy drugs cause cells to release NO, which in turn induces cytotoxic death of breast, liver, and skin tumors. However, NO has also been clinically connected to a poor cancer prognosis because of its role in angiogenesis and intravasation. This supports the claim that NO can be characterized as both pro-metastatic and anti-metastatic, depending on specific factors. The inhibition of cell proliferation and anti-apoptosis pathways by NO donors has been proposed as a novel therapy to various cancers. Studies suggest that NO-releasing non-steroidal anti-inflammatory drugs act on cancer cells in several ways that may make them ideal for cancer therapy. This review summarizes the biological significance of NO in each step of cancer metastasis, its controversial effects for cancer progression, and its therapeutic potential. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. Maxillofacial metastasis from breast cancer

    Science.gov (United States)

    Namad, Tariq; Benbrahim, Zineb; Najib, Rajae; Mohammed, Afif; Baggar, Soufiane; Bouyahia, Nezar; Arifi, Samia; Mellas, Nawfel

    2014-01-01

    Metastatic tumors to paranasal sinuses are exclusively rare. In this paper, we report acase of breast carcinoma metastasizing to the right maxilla. The metastasis occurred 5 years after radical mastectomy and presented as a primary sinonasalmass. The diagnosis was confirmed with histopathologic andimmunohistochemical examination however the patient died before starting any specific treatment because of tumor bleeding. PMID:25767674

  1. 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...

  2. Breast cancer-associated metastasis is significantly increased in a model of autoimmune arthritis

    Science.gov (United States)

    Das Roy, Lopamudra; Pathangey, Latha B; Tinder, Teresa L; Schettini, Jorge L; Gruber, Helen E; Mukherjee, Pinku

    2009-01-01

    Introduction Sites of chronic inflammation are often associated with the establishment and growth of various malignancies including breast cancer. A common inflammatory condition in humans is autoimmune arthritis (AA) that causes inflammation and deformity of the joints. Other systemic effects associated with arthritis include increased cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge, available for a decade, it has never been questioned if the site of chronic inflammation linked to AA creates a milieu that attracts tumor cells to home and grow in the inflamed bones and lungs which are frequent sites of breast cancer metastasis. Methods To determine if chronic inflammation induced by autoimmune arthritis contributes to increased breast cancer-associated metastasis, we generated mammary gland tumors in SKG mice that were genetically prone to develop AA. Two breast cancer cell lines, one highly metastatic (4T1) and the other non-metastatic (TUBO) were used to generate the tumors in the mammary fat pad. Lung and bone metastasis and the associated inflammatory milieu were evaluated in the arthritic versus the non-arthritic mice. Results We report a three-fold increase in lung metastasis and a significant increase in the incidence of bone metastasis in the pro-arthritic and arthritic mice compared to non-arthritic control mice. We also report that the metastatic breast cancer cells augment the severity of arthritis resulting in a vicious cycle that increases both bone destruction and metastasis. Enhanced neutrophilic and granulocytic infiltration in lungs and bone of the pro-arthritic and arthritic mice and subsequent increase in circulating levels of proinflammatory cytokines, such as macrophage colony stimulating factor (M-CSF), interleukin-17 (IL-17), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and tumor necrosis factor

  3. Breast-cancer-associated metastasis is significantly increased in a model of autoimmune arthritis.

    Science.gov (United States)

    Das Roy, Lopamudra; Pathangey, Latha B; Tinder, Teresa L; Schettini, Jorge L; Gruber, Helen E; Mukherjee, Pinku

    2009-01-01

    Sites of chronic inflammation are often associated with the establishment and growth of various malignancies including breast cancer. A common inflammatory condition in humans is autoimmune arthritis (AA) that causes inflammation and deformity of the joints. Other systemic effects associated with arthritis include increased cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge, available for a decade, it has never been questioned if the site of chronic inflammation linked to AA creates a milieu that attracts tumor cells to home and grow in the inflamed bones and lungs which are frequent sites of breast cancer metastasis. To determine if chronic inflammation induced by autoimmune arthritis contributes to increased breast cancer-associated metastasis, we generated mammary gland tumors in SKG mice that were genetically prone to develop AA. Two breast cancer cell lines, one highly metastatic (4T1) and the other non-metastatic (TUBO) were used to generate the tumors in the mammary fat pad. Lung and bone metastasis and the associated inflammatory milieu were evaluated in the arthritic versus the non-arthritic mice. We report a three-fold increase in lung metastasis and a significant increase in the incidence of bone metastasis in the pro-arthritic and arthritic mice compared to non-arthritic control mice. We also report that the metastatic breast cancer cells augment the severity of arthritis resulting in a vicious cycle that increases both bone destruction and metastasis. Enhanced neutrophilic and granulocytic infiltration in lungs and bone of the pro-arthritic and arthritic mice and subsequent increase in circulating levels of proinflammatory cytokines, such as macrophage colony stimulating factor (M-CSF), interleukin-17 (IL-17), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and tumor necrosis factor-alpha (TNF-alpha) may contribute

  4. 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...... in October 2013 revealed a growing brainstem lesion of 26 mm. Linear accelerator-based radiotherapy and microsurgery were judged contraindicated, why the decision was made to treat the patient with three separate radiosurgical sessions during the course of 1 week, with an 18% tumor volume reduction...

  5. Tissue-Based Microarray Expression of Genes Predictive of Metastasis in Uveal Melanoma and Differentially Expressed in Metastatic Uveal Melanoma

    Directory of Open Access Journals (Sweden)

    Hakan Demirci

    2013-01-01

    Full Text Available Purpose: To screen the microarray expression of CDH1, ECM1, EIF1B, FXR1, HTR2B, ID2, LMCD1, LTA4H, MTUS1, RAB31, ROBO1, and SATB1 genes which are predictive of primary uveal melanoma metastasis, and NFKB2, PTPN18, MTSS1, GADD45B, SNCG, HHIP, IL12B, CDK4, RPLP0, RPS17, RPS12 genes that are differentially expressed in metastatic uveal melanoma in normal whole human blood and tissues prone to metastatic involvement by uveal melanoma. Methods: We screened the GeneNote and GNF BioGPS databases for microarray analysis of genes predictive of primary uveal melanoma metastasis and those differentially expressed in metastatic uveal melanoma in normal whole blood, liver, lung and skin. Results: Microarray analysis showed expression of all 22 genes in normal whole blood, liver, lung and skin, which are the most common sites of metastases. In the GNF BioGPS database, data for expression of the HHIP gene in normal whole blood and skin was not complete. Conclusions: Microarray analysis of genes predicting systemic metastasis of uveal melanoma and genes differentially expressed in metastatic uveal melanoma may not be used as a biomarker for metastasis in whole blood, liver, lung, and skin. Their expression in tissues prone to metastasis may suggest that they play a role in tropism of uveal melanoma metastasis to these tissues.

  6. Isolated clival metastasis as the cause of abducens nerve palsy in a patient of breast carcinoma: A rare case report

    Directory of Open Access Journals (Sweden)

    Akhil Kapoor

    2015-01-01

    Full Text Available Metastatic lesions to the clivus have been reported in various cancers including lung cancer, prostate carcinoma, skin melanoma, and hepatocellular carcinoma. There have been only a few reports of breast cancer presenting with isolated clival metastasis. We report a case of 35-year-old lady, who was known case of breast carcinoma presented with diplopia as the only sign of clival metastasis. The etiology was established by magnetic resonance imaging which showed an enhancing lesion in the clivus. The diagnosis of clival metastasis from breast cancer was confirmed by transsphenoidal biopsy.

  7. Squamous cell lung carcinoma presenting as melena: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Ibrahim Azar

    2017-10-01

    Full Text Available Lung cancer has a predilection to widely metastasize to the liver, bone, brain and adrenal glands. Metastasis of primary lung tumors to the stomach is infrequent, with only sporadic cases reported. Most cases are asymptomatic and diagnosed post-mortem on autopsy. The incidence of symptomatic gastrointestinal metastases is extremely rare. Herein, we describe a case of gastric metastasis by squamous cell lung carcinoma, presenting as melena and diagnosed by esophagogastroduodenoscopy. To the best of our knowledge, only twenty other cases in the English literature have reported symptomatic gastric metastasis of lung cancer diagnosed by endoscopic biopsy. A brief review of the literature shows gastric metastasis of lung cancer to have a predilection to occur most frequently in male smokers with the most common type of tumor likely to be squamous cell carcinoma.

  8. Rewiring of an Epithelial Differentiation Factor, miR-203, to Inhibit Human Squamous Cell Carcinoma Metastasis

    Directory of Open Access Journals (Sweden)

    Nathan Benaich

    2014-10-01

    Full Text Available Metastatic colonization of distant organs underpins the majority of human-cancer-related deaths, including deaths from head and neck squamous cell carcinoma (HNSCC. We report that miR-203, a miRNA that triggers differentiation in multilayered epithelia, inhibits multiple postextravasation events during HNSCC lung metastasis. Inducible reactivation of miR-203 in already established lung metastases reduces the overall metastatic burden. Using an integrated approach, we reveal that miR-203 inhibits metastasis independently of its effects on differentiation. In vivo genetic reconstitution experiments show that miR-203 inhibits lung metastasis by suppressing the prometastatic activities of three factors involved in cytoskeletal dynamics (LASP1, extracellular matrix remodeling (SPARC, and cell metabolism (NUAK1. Expression of miR-203 and its downstream effectors correlates with HNSCC overall survival outcomes, indicating the therapeutic potential of targeting this signaling axis.

  9. Development of a metastatic fluorescent Lewis Lung carcinoma mouse model

    DEFF Research Database (Denmark)

    Rask, Lene; Fregil, Marianne; Høgdall, Estrid

    2013-01-01

    ) and spleen tyrosine kinase (SYK). A modest decrease in Drosha and Dicer mRNA levels was accompanied by significant downregulation of ten microRNAs, including miR-9 and miR-203, in the lung metastatic Lewis Lung carcinoma cell culture. Thus, a tool for cancer metastasis studies has been established...

  10. community acquired pneumonia or βhcg - Producing lung tumor

    African Journals Online (AJOL)

    She developed signs suggestive of βhCG-producing lung tumor with metastasis to the brain and succumbed to the illness before she could be referred for further evaluations and management. Key Words: Community acquired pneumonia, βhCG-producing lung tumor, Paraneoplastic Syndrome, Oculomotor Nerve Palsy.

  11. Choroidal metastases as the initial presentation of lung cancer: A ...

    African Journals Online (AJOL)

    Clinical reports of symptomatic intraocular metastasis as the initial presentation of lung cancer are rare. We report the case of a 49-year-old female patient who presented with loss of vision due to choroidal metastases as the initial manifestation of her disseminated lung cancer. This particular patient was referred to us from ...

  12. Invasive cancer cells and metastasis

    Science.gov (United States)

    Mierke, Claudia Tanja

    2013-12-01

    the biophysical state of the primary tumor cell. To determine the cytoskeletal dynamics they chose magnetic twisting cytometry, where the spontaneous motion of surface bound marker beads was measured, which is a measure for the cytoskeletal remodeling dynamics. The group of Katarina Wolf measured the stiffness of the cell nucleus because it is the largest and stiffest organelle, which may hinder the migration of invasive tumor cells through dense connective tissue [2]. They combined atomic force confocal microscopy for measurement of bulk nuclear stiffness (the inverse of the compressibility) with simultaneous visualization of the cantilever-nucleus contact as well as monitoring of the cell's fate. The dynamics of tissue topology such as the mixing of compartments during cancer invasion and metastasis were theoretically analyzed by Lance L Munn [3]. In particular, he presented a mathematical model of tissue repair and tumor growth based on collective cell migration that simulates a wide range of tumor behaviors using correct tissue compartmentalization and connectivity. In the future, the topological analysis could be helpful for tumor diagnosis or monitoring tumor therapy. The group of Cynthia A Reinhart-King analyzed how the topological guidance of a 3D tumor cell migration at an interface of collagen densities affects cell motility [4]. In particular, they mimicked the heterogeneities in density of the tumor stroma by preparing gels with an interface of high and low density collagen gels and investigated how this affects cell motility. The author's review paper details the effect of focal adhesion proteins such as focal adhesion kinase (FAK) on cell motility and how this effect is driven by mechanical alterations of cells expressing FAK compared to cells with FAK knock-out [5]. In particular, it focused on mechanical properties regulated by FAK in comparison to the mechano-regulating protein vinculin. This article highlights that both focal adhesion proteins

  13. Coherent anti-Stokes Raman scattering imaging of lipids in cancer metastasis

    International Nuclear Information System (INIS)

    Le, Thuc T; Huff, Terry B; Cheng, Ji-Xin

    2009-01-01

    Lipid-rich tumours have been associated with increased cancer metastasis and aggressive clinical behaviours. Nonetheless, pathologists cannot classify lipid-rich tumours as a clinically distinctive form of carcinoma due to a lack of mechanistic understanding on the roles of lipids in cancer development. Coherent anti-Stokes Raman scattering (CARS) microscopy is employed to study cancer cell behaviours in excess lipid environments in vivo and in vitro. The impacts of a high fat diet on cancer development are evaluated in a Balb/c mice cancer model. Intravital flow cytometry and histology are employed to enumerate cancer cell escape to the bloodstream and metastasis to lung tissues, respectively. Cancer cell motility and tissue invasion capability are also evaluated in excess lipid environments. CARS imaging reveals intracellular lipid accumulation is induced by excess free fatty acids (FFAs). Excess FFAs incorporation onto cancer cell membrane induces membrane phase separation, reduces cell-cell contact, increases surface adhesion, and promotes tissue invasion. Increased plasma FFAs level and visceral adiposity are associated with early rise in circulating tumour cells and increased lung metastasis. Furthermore, CARS imaging reveals FFAs-induced lipid accumulation in primary, circulating, and metastasized cancer cells. Lipid-rich tumours are linked to cancer metastasis through FFAs-induced physical perturbations on cancer cell membrane. Most importantly, the revelation of lipid-rich circulating tumour cells suggests possible development of CARS intravital flow cytometry for label-free detection of early-stage cancer metastasis

  14. Spontaneous Tricuspid Valve Chordal Rupture in Idiopathic Pulmonary Hypertension.

    Science.gov (United States)

    Rodrigues, Ana Clara Tude; Afonso, José E; Cordovil, Adriana; Monaco, Claudia; Piveta, Rafael; Cordovil, Rodrigo; Fischer, Claudio H; Vieira, Marcelo; Lira-Filho, Edgar; Morhy, Samira S

    2016-03-01

    Rupture of tricuspid valve is unusual, occurring mainly in the setting of blunt trauma or endomyocardial biopsy. Spontaneous tricuspid valve chordal rupture is particularly rare. We report herein a case of a patient with severe pulmonary hypertension, on the lung transplantation waiting list, who presented with spontaneous chordal rupture, exacerbation of tricuspid insufficiency and worsening of clinical status. Diagnosis and treatment, along with possible mechanisms for this complication, are discussed. © 2015, Wiley Periodicals, Inc.

  15. Brain metastasis from melanoma: the prognostic value of varying sites of extracranial disease.

    Science.gov (United States)

    Bates, James E; Youn, Paul; Usuki, Kenneth Y; Walter, Kevin A; Huggins, Christine F; Okunieff, Paul; Milano, Michael T

    2015-11-01

    Patients with brain metastasis from melanoma have poor outcomes. Radiation is used both for prognostic and symptomatic value. We aimed to further clarify the role of stereotactic radiosurgery (SRS) and whole brain radiotherapy (WBRT) as well as the prognostic implication of various sites of extracranial disease. The records of 73 consecutive patients treated at the University of Rochester Medical Center for brain-metastatic melanoma from January 2004 to October 2013 were reviewed. The median overall survival (OS) was 3.0 months. Patients treated with WBRT alone had decreased OS compared to those treated with SRS alone (HR = 0.38, p = 0.001) or WBRT and SRS (HR = 0.51, p = 0.039). The mean number of brain metastasis differed (p = 0.002) in patients in patients who received WBRT (4.0) compared to those who did not (2.0). Among patients with extracranial disease (n = 63), bone metastasis (HR = 1.86, p = 0.047, n = 15) was a negative prognostic factor; liver (HR = 1.59, p = 0.113, n = 17), lung (HR = 1.51, p = 0.23, n = 51) and adrenal metastasis (HR = 1.70, p = 0.15, n = 10) were not. In patients with concurrent brain and lung metastasis, those with disease limited to those two sites (OS = 8.7 mo, n = 13) had improved OS (HR = 0.44, p = 0.014) compared to those with additional disease (OS = 1.8 mo, n = 50). Based on this hypothesis-generating retrospective analysis, SRS may offer survival benefit compared to WBRT alone in patients with brain metastatic melanoma. Bone metastasis appears to confer a particularly poor prognosis. Those with disease confined to the lung and brain may represent a population with improved prognosis.

  16. Platelets promote tumor growth and metastasis via direct interaction between Aggrus/podoplanin and CLEC-2.

    Directory of Open Access Journals (Sweden)

    Satoshi Takagi

    Full Text Available The platelet aggregation-inducing factor Aggrus, also known as podoplanin, is frequently upregulated in several types of tumors and enhances hematogenous metastasis by interacting with and activating the platelet receptor CLEC-2. Thus, Aggrus-CLEC-2 binding could be a therapeutic molecular mechanism for cancer therapy. We generated a new anti-human Aggrus monoclonal antibody, MS-1, that suppressed Aggrus-CLEC-2 binding, Aggrus-induced platelet aggregation, and Aggrus-mediated tumor metastasis. Interestingly, the MS-1 monoclonal antibody attenuated the growth of Aggrus-positive tumors in vivo. Moreover, the humanized chimeric MS-1 antibody, ChMS-1, also exhibited strong antitumor activity against Aggrus-positive lung squamous cell carcinoma xenografted into NOD-SCID mice compromising antibody-dependent cellular cytotoxic and complement-dependent cytotoxic activities. Because Aggrus knockdown suppressed platelet-induced proliferation in vitro and tumor growth of the lung squamous cell carcinoma in vivo, Aggrus may be involved in not only tumor metastasis but also tumor growth by promoting platelet-tumor interaction, platelet activation, and secretion of platelet-derived factors in vivo. Our results indicate that molecular target drugs inhibiting specific platelet-tumor interactions can be developed as antitumor drugs that suppress both metastasis and proliferation of tumors such as lung squamous cell carcinoma.

  17. Late stage inhibition of hematogenous melanoma metastasis by cystatin C over-expression

    Directory of Open Access Journals (Sweden)

    Cox James L

    2005-05-01

    Full Text Available Abstract Background Tumor metastasis is a frequent cause of treatment failure for cancer patients. A key feature of metastatic cancer cells is their invasive ability. Cysteine proteases contribute to invasive properties of many cancer cell types. To analyze the contribution of cysteine proteases to metastasis we have over-expressed in B16 melanoma cells the natural cysteine protease inhibitor, cystatin C. We measured in vitro invasion of cystatin over-expression clones with Boyden chamber type assays. Tail-vein injections of cells were used to compare lung tumor colonization. Subcutaneous tumor growth and tumor cell metastasis from primary tumors were also analyzed. Apoptosis of tumor cells was measured in lung tissues following melanoma cell injection. Results Results show the in vitro invasion of cystatin C over-expressing cells was dramatically inhibited. Lung tumor colonization was also reduced. Increased tumor cell apoptosis was found to be an important factor and may be related to the reduced tumor burden noted in this system of melanoma metastasis. Conclusion Cysteine proteases therefore, may be a target for future anti-metastatic therapies.

  18. Arachidonic Acid Metabolite as a Novel Therapeutic Target in Breast Cancer Metastasis

    Directory of Open Access Journals (Sweden)

    Thaiz F. Borin

    2017-12-01

    Full Text Available Metastatic breast cancer (BC (also referred to as stage IV spreads beyond the breast to the bones, lungs, liver, or brain and is a major contributor to the deaths of cancer patients. Interestingly, metastasis is a result of stroma-coordinated hallmarks such as invasion and migration of the tumor cells from the primary niche, regrowth of the invading tumor cells in the distant organs, proliferation, vascularization, and immune suppression. Targeted therapies, when used as monotherapies or combination therapies, have shown limited success in decreasing the established metastatic growth and improving survival. Thus, novel therapeutic targets are warranted to improve the metastasis outcomes. We have been actively investigating the cytochrome P450 4 (CYP4 family of enzymes that can biosynthesize 20-hydroxyeicosatetraenoic acid (20-HETE, an important signaling eicosanoid involved in the regulation of vascular tone and angiogenesis. We have shown that 20-HETE can activate several intracellular protein kinases, pro-inflammatory mediators, and chemokines in cancer. This review article is focused on understanding the role of the arachidonic acid metabolic pathway in BC metastasis with an emphasis on 20-HETE as a novel therapeutic target to decrease BC metastasis. We have discussed all the significant investigational mechanisms and put forward studies showing how 20-HETE can promote angiogenesis and metastasis, and how its inhibition could affect the metastatic niches. Potential adjuvant therapies targeting the tumor microenvironment showing anti-tumor properties against BC and its lung metastasis are discussed at the end. This review will highlight the importance of exploring tumor-inherent and stromal-inherent metabolic pathways in the development of novel therapeutics for treating BC metastasis.

  19. Mandibular metastasis of rectum adenocarcinoma: case report

    Directory of Open Access Journals (Sweden)

    Mehmet Ali Çetin

    2018-01-01

    Full Text Available Introduction: Mandibular metastases are quite rare and they constitute less than about %1 of the mandibular malignancies. In mandibular metastatic cases, patients’ complaints generally include bony swelling with pain, tooth pain and tooth loss. Mandibular metastatic lesions mimic periodontal diseases; therefore careful examination is necessary. In differential diagnosis, osteosarcoma, which is a primary bone tumor, primary intraosseous squamous carcinoma, ameloblastoma, and temporomandibular joint diseases should be taken into consideration. Treatment modalities are surgery and chemoradiotherapy. Because of the poor prognosis, the goal of the treatment is only palliative. Case Report: A 51-year-old woman, operated due to rectal adenocarcinoma 3 years previously, was referred to our clinic with a complaint of swelling on the jaw. Cranial magnetic resonance imaging and maxillofacial computed tomography revealed a mass that extended to condyle and lead to bone destruction on the right ramus of the mandible. An incisional biopsy was performed. The histopathology was consistent with colorectal adenocarcinoma metastasis. The patient was referred to a medical oncologist. Conclusion: Differential diagnosis of mandibular lesions should be made carefully, and metastatic tumors should be kept in mind. In patients with history of lung cancer, breast cancer, colorectal carcinoma or similar tumors, oral findings such as tooth pain and tooth loss should be taken into consideration, as these may be the signs of head and neck metastases. Biopsy must be performed after radiological examination.

  20. Non-coding RNAs in cancer brain metastasis

    Science.gov (United States)

    Wu, Kerui; Sharma, Sambad; Venkat, Suresh; Liu, Keqin; Zhou, Xiaobo; Watabe, Kounosuke

    2017-01-01

    More than 90% of cancer death is attributed to metastatic disease, and the brain is one of the major metastatic sites of melanoma, colon, renal, lung and breast cancers. Despite the recent advancement of targeted therapy for cancer, the incidence of brain metastasis is increasing. One reason is that most therapeutic drugs can’t penetrate blood-brain-barrier and tumor cells find the brain as sanctuary site. In this review, we describe the pathophysiology of brain metastases to introduce the latest understandings of metastatic brain malignancies. This review also particularly focuses on non-coding RNAs and their roles in cancer brain metastasis. Furthermore, we discuss the roles of the extracellular vesicles as they are known to transport information between cells to initiate cancer cell-microenvironment communication. The potential clinical translation of non-coding RNAs as a tool for diagnosis and for treatment is also discussed in this review. At the end, the computational aspects of non-coding RNA detection, the sequence and structure calculation and epigenetic regulation of non-coding RNA in brain metastasis are discussed. PMID:26709907

  1. Metastasis to the Thyroid Gland: A Critical Review.

    Science.gov (United States)

    Nixon, Iain J; Coca-Pelaz, Andrés; Kaleva, Anna I; Triantafyllou, Asterios; Angelos, Peter; Owen, Randall P; Rinaldo, Alessandra; Shaha, Ashok R; Silver, Carl E; Ferlito, Alfio

    2017-06-01

    Metastasis to the thyroid gland from nonthyroid sites is an uncommon clinical presentation in surgical practice. The aim of this review was to assess its incidence management and outcomes. A literature review was performed to identify reports of metastases to the thyroid gland. Both clinical and autopsy series were included. Metastases to the gland may be discovered at the time of diagnosis of the primary tumor, after preoperative investigation of a neck mass, or on histologic examination of a thyroidectomy specimen. The most common primary tumors in autopsy studies are from the lung. In clinical series, renal cell carcinoma is most common. For patients with widespread metastases in the setting of an aggressive malignancy, surgery is rarely indicated. However, when patients present with an isolated metastasis diagnosed during follow-up of indolent disease, surgery may achieve control of the central neck and even long-term cure. Other prognosticators include features of the primary tumor, time interval between initial diagnosis and metastasis, and extrathyroid extent of disease. In patients with thyroid metastases, communication among clinicians treating the thyroid and the index primary tumor is essential. The setting is complex, and decisions must be made considering the features of the primary tumor, overall burden of metastases, and comorbidities. Careful balancing of these factors influences individualized approaches.

  2. Novel chemokine-like activities of histones in tumor metastasis.

    Science.gov (United States)

    Chen, Ruochan; Xie, Yangchun; Zhong, Xiao; Fu, Yongmin; Huang, Yan; Zhen, Yixiang; Pan, Pinhua; Wang, Haichao; Bartlett, David L; Billiar, Timothy R; Lotze, Michael T; Zeh, Herbert J; Fan, Xue-Gong; Tang, Daolin; Kang, Rui

    2016-09-20

    Histones are intracellular nucleosomal components and extracellular damage-associated molecular pattern molecules that modulate chromatin remodeling, as well as the immune response. However, their extracellular roles in cell migration and invasion remain undefined. Here, we demonstrate that histones are novel regulators of tumor metastasis with chemokine-like activities. Indeed, exogenous histones promote both hepatocellular carcinoma (HCC) cell migration and invasion through toll-like receptor (TLR)4, but not TLR2 or the receptor for advanced glycosylation end product. TLR4-mediated activation of nuclear factor-κB (NF-κB) by extracellular signal-regulated kinase (ERK) is required for histone-induced chemokine (e.g., C-C motif ligand 9/10) production. Pharmacological and genetic inhibition of TLR4-ERK-NF-κB signaling impairs histone-induced chemokine production and HCC cell migration. Additionally, TLR4 depletion (by using TLR4-/- mice and TLR4-shRNA) or inhibition of histone release/activity (by administration of heparin and H3 neutralizing antibody) attenuates lung metastasis of HCC cells injected via the tail vein of mice. Thus, histones promote tumor metastasis of HCC cells through the TLR4-NF-κB pathway and represent novel targets for treating patients with HCC.

  3. Thyroid mass: Metastasis from nasopharyngeal cancer - an unusual presentation

    Directory of Open Access Journals (Sweden)

    Shirley C Lewis

    2017-01-01

    Full Text Available Thyroid gland is an uncommon site of metastasis, and metastasis to the gland secondary to nasopharyngeal carcinoma is seldom seen. We were only able to identify eight reported cases in the literature. A 61-year-old man, diagnosed case of nasopharyngeal cancer–second primary ( first primary-oropharynx, was found to have a thyroid nodule on routine follow-up positron emission tomography-computed tomography (PET-CT scan. There was no evidence of metastases at any other sites. The thyroid nodule was confirmed as metastatic carcinoma by fine needle aspiration cytology. He was treated with multimodal treatment comprising of surgery followed by reirradiation with concurrent chemotherapy. Subsequently, at the first follow-up (2 months after completion of all treatment, the patient remained asymptomatic, but the response assessment with PET-CT scan was suggestive of lung metastases with no evidence of locoregional disease. Although thyroid parenchymal metastasis is an uncommon occurrence and signifies a poor prognosis, in appropriately selected patients, aggressive therapy with reirradiation and chemotherapy may improve local control and quality of life.

  4. Up-regulation of Rho-associated kinase 1/2 by glucocorticoids promotes migration, invasion and metastasis of melanoma.

    Science.gov (United States)

    Huang, Gao-Xiang; Wang, Yan; Su, Jie; Zhou, Peng; Li, Bo; Yin, Li-Juan; Lu, Jian

    2017-12-01

    Although glucocorticoids (GCs) regulate proliferation, differentiation and apoptosis of tumor cells, their influence on metastasis of tumor cells is poorly understood. Melanoma is a type of skin cancers with high metastasis. We investigated the effect of GCs on metastasis of melanoma cells and its mechanism. We found that GCs significantly promoted the adhesion, migration, invasion of melanoma cells in vitro and lung metastasis in experimental melanoma metastasis mice. Dexamethasone (Dex), a synthetic GC, did not change the RhoA, RhoB and RhoC signalings, but significantly increased the expression and activity of Rho-associated kinase 1/2 (ROCK1/2). The effect of Dex was to increase ROCK1/2 stability mediated by glucocorticoid receptor. Inhibiting ROCK1/2 activity with Y-27632, a ROCK1/2 inhibitor abrogated the pro-migration and pro-metastasis effects of GCs in vitro and in vivo, indicating that ROCK1/2 mediated the pro-metastasis effects of GCs. Activation of PI3K/AKT also contributed to the pro-migration and pro-invasion effects of Dex partially through up-regulating ROCK1/2 expression. Additionally, Dex also down-regulated the expression of tissue inhibitors of matrix metalloproteinase-2. Taken together, our findings provide new data to understand the possible promoting roles and mechanisms of GCs in melanoma metastasis. Copyright © 2017. Published by Elsevier B.V.

  5. Spine Metastases in Lung Cancer

    Directory of Open Access Journals (Sweden)

    O.Yu. Stolyarova

    2015-10-01

    Full Text Available The purpose and the objectives of the study were to determine the incidence of metastatic lesions to various parts of the spine, the assessment of the association with other clinical signs of lung cancer (localization, form, histology, degree of differentiation, staging, nature of extraosseous metastasis, to investigate the effect of these parameters on the survi­val of the patients. Material and methods. The study included 1071 patients with lung cancer aged 24 to 86 years. None of the examined patients has been operated previously for lung cancer, and after arriving at a diagnosis, all patients received radiation therapy, 73 % of them — combined radiochemothe­rapy. Results. Metastasis in the vertebral bodies and vertebral joints occurs in 13 % of patients with lung cancer and in 61 % of patients with bone form of the disease, the ratio of the defeat of thoracic, sacral, lumbar and cervical spine was 6 : 4 : 2 : 1. The development of metastases in the spine is mostly associa­ted with the localization of the tumor in the upper lobe of the lung, the peripheral form of the disease, with non-small cell histologic variants (adenocarcinoma and squamous cell carcinoma. The number of metastases in the spinal column directly correlates with the degree of metastatic involvement of the inguinal lymph nodes, abdominal wall and the liver, has an impact on the invasion of lung tumor into the esophagus and the trachea. The life expectancy of the deceased persons with spine metastases is less than that of other patients with the lung cancer, but the overall survival rate in these groups of patients is not very different. Conclusions. Clinical features of lung cancer with metastases in the spine necessitate the development of medical technology of rational radiochemotherapy in such patients.

  6. Cyclooxygenase-2 inhibition blocks M2 macrophage differentiation and suppresses metastasis in murine breast cancer model.

    Directory of Open Access Journals (Sweden)

    Yi-Rang Na

    Full Text Available Tumor cells are often associated with abundant macrophages that resemble the alternatively activated M2 subset. Tumor-associated macrophages (TAMs inhibit anti-tumor immune responses and promote metastasis. Cyclooxygenase-2 (COX-2 inhibition is known to prevent breast cancer metastasis. This study hypothesized that COX-2 inhibition affects TAM characteristics potentially relevant to tumor cell metastasis. We found that the specific COX-2 inhibitor, etodolac, inhibited human M2 macrophage differentiation, as determined by decreased CD14 and CD163 expressions and increased TNFα production. Several key metastasis-related mediators, such as vascular endothelial growth factor-A, vascular endothelial growth factor-C, and matrix metalloproteinase-9, were inhibited in the presence of etodolac as compared to untreated M2 macrophages. Murine bone marrow derived M2 macrophages also showed enhanced surface MHCII IA/IE and CD80, CD86 expressions together with enhanced TNFα expressions with etodolac treatment during differentiation. Using a BALB/c breast cancer model, we found that etodolac significantly reduced lung metastasis, possibly due to macrophages expressing increased IA/IE and TNFα, but decreased M2 macrophage-related genes expressions (Ym1, TGFβ. In conclusion, COX-2 inhibition caused loss of the M2 macrophage characteristics of TAMs and may assist prevention of breast cancer metastasis.

  7. Spontaneous uterine rupture

    African Journals Online (AJOL)

    ABSTRACT. Rupture of a gravid uterus is a surgical emergency. Predisposing factors include a scarred uterus. Spontaneous rupture of an unscarred uterus during pregnancy is a rare occurrence. We hereby present the case of a spontaneous complete uterine rupture at a gestational age of 34 weeks in a 35 year old patient ...

  8. Spontaneous intracranial hypotension.

    LENUS (Irish Health Repository)

    Fullam, L

    2012-01-31

    INTRODUCTION: Spontaneous\\/primary intracranial hypotension is characterised by orthostatic headache and is associated with characteristic magnetic resonance imaging findings. CASE REPORT: We present a case report of a patient with typical symptoms and classical radiological images. DISCUSSION: Spontaneous intracranial hypotension is an under-recognised cause of headache and can be diagnosed by history of typical orthostatic headache and findings on MRI brain.

  9. Testicular Metastasis from Renal Cell Carcinoma: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Keren Rouvinov

    2017-04-01

    Full Text Available Testicular metastases from renal cell carcinoma (RCC are extremely rare. To the best of our knowledge, only 33 cases have been described in the literature. Most of the reported cases are of unilateral testicular metastasis from RCC. We report a case of metachronous ipsilateral testicular metastasis from RCC in a 78-year-old man 6 years after nephrectomy. Scrotal ultrasonography showed a 4 × 5 cm mass in the right testis. Right inguinal orchiectomy was performed for diagnosis. Computed tomography revealed liver and lung metastases. First-line therapy with sunitinib was started in November 2016 for metastatic RCC.

  10. Isolated Asymptomatic Metastasis in the Myocardium: A Rare Scenario in Case of Carcinoma Penis

    Directory of Open Access Journals (Sweden)

    Santosh Kumar

    2015-01-01

    Full Text Available Penile cancer is a common malignancy in developing countries. It commonly metastasizes to the lymph nodes, lung, liver, and bones. Myocardial metastasis is rare. A 40-year-old male patient presented with ulcerative growth over glans penis. Histologic evaluation of the biopsy sample diagnosed the lesion as squamous cell cancer. Assessment of the stage of the disease revealed cardiac metastasis. Patient received six cycles of chemotherapy. He partially responded, but later succumbed to cardiac failure due to pericardial and pleural effusion.

  11. Vasculogenic mimicry and tumor metastasis.

    Science.gov (United States)

    Zhang, Jingxin; Qiao, Lili; Liang, Ning; Xie, Jian; Luo, Hui; Deng, Guodong; Zhang, Jiandong

    2016-01-01

    Vasculogenic mimicry (VM), a microvascular channel made up of nonendothelial cells, has been accepted as a new model of neovascularization in aggressive tumors, owning to the specific capacity of malignant cells to form vessel-like networks which provide sufficient blood supply for tumor growth. Multiple molecular mechanisms, especially vascular endothelial (VE)-cadherin, erythropoietin-producing hepatocellular receptor A2 (EphA2), phosphatidyl inositol 3-kinase (PI3K), matrix metalloproteinases (MMPs), vascular endothelial growth factor receptor (VEGFR1), and hypoxia inducible factor (HIF)-1a, have been reported to participate in VM formation which is associated with tumor migration and invasion. In addition, hypoxia, cancer stem cells (CSCs) and epithelial-mesenehymal transition (EMT) are regarded as significant factors in VM formation and tumor metastasis. Due to the important effects of VM on tumor progression, a review was carried out in the present study, to synthetically analyze the relationship between VM and tumor metastasis.

  12. 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...

  13. Brain metastasis. Prognostic value of the number of involved extracranial organs

    Energy Technology Data Exchange (ETDEWEB)

    Rades, D. [Luebeck Univ. (Germany). Dept. of Radiation Oncology; Gerdan, L. [Luebeck Univ. (Germany). Dept. of Radiation Oncology; Luebeck Univ. (Germany). Section of Nuclear Medicine; Segedin, B. [Institute of Oncology, Ljubljana (Slovenia). Dept. of Radiation Oncology; Nagy, V. [Oncology Institute Ion Ciricuta, Cluj-Napoca (Romania). Dept. of Radiotherapy; Khoa, M.T. [Hanoi Medical Univ., Hanoi (Viet Nam). Dept. of Nuclear Medicine; Bach Mai Hospital, Hanoi (Viet Nam). Nuclear Medicine and Oncology Center; Trang, N.T. [Bach Mai Hospital, Hanoi (Viet Nam). Nuclear Medicine and Oncology Center; Schild, S.E. [Mayo Clinic, Scottsdale, AZ (United States). Dept. of Radiation Oncology

    2013-12-15

    Background and purpose: This study was performed to evaluate the prognostic role for survival of the number and the type of involved extracranial organs in patients with brain metastasis. Material and methods: The data of 1146 patients who received whole-brain radiotherapy (WBRT) alone for brain metastasis have been retrospectively analyzed. In addition to the number of involved extra cranial organs, seven potential prognostic factors were investigated including WBRT regimen, age, gender, Karnofsky Performance Score (KPS), primary tumor type, number of brain metastases, and the interval from cancer diagnosis to WBRT. Additionally, subgroup analyses were performed for patients with involvement of one (lung vs. bone vs. liver vs. other metastasis) and two (lung + lymph nodes vs. lung + bone vs. lung + liver vs. liver + bone vs. other combinations) extracranial organs. Results: The 6-month survival rates for the involvement of 0, 1, 2, 3, and {>=} 4 extracranial organs were 51, 30, 16, 13, and 10 %, respectively (p < 0.001). On multivariate analysis, the number of involved extracranial organs maintained significance (risk ratio 1.26; 95 % confidence interval 1.18-1.34; p < 0.001). According to the multivariate analysis, age (p < 0.001), gender (p = 0.002), and KPS (p < 0.001) were also independent prognostic factors for survival. In the subgroup analyses of patients with involvement of one and two extracranial organs, survival was not significantly different based on the extracranial organ involved. Conclusion: The number of involved extracranial organs proved to be an independent prognostic factor in patients with brain metastasis, regardless of the organs involved. The number of involved extracranial organs should be considered in future trials designed for patients with brain metastasis. (orig.)

  14. Bone metastasis pattern in initial metastatic breast cancer: a population-based study

    Directory of Open Access Journals (Sweden)

    Xiong Z

    2018-02-01

    Full Text Available Zhenchong Xiong,1–3,* Guangzheng Deng,1–3,* Xinjian Huang,1–3,* Xing Li,1–3 Xinhua Xie,1–3 Jin Wang,1–3 Zeyu Shuang,1–3 Xi Wang1–3 1Department of Breast Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China; 2State Key Laboratory of Oncology in Southern China, Guangzhou, China; 3Collaborative Innovation Center for Cancer Medicine, Guangzhou, China *These authors contributed equally to this work Purpose: Bone is one of the most common sites of breast cancer metastasis, and population-based studies of patients with bone metastasis in initial metastatic breast cancer (MBC are lacking. Materials and methods: From 2010 to 2013, 245,707 breast cancer patients and 8901 patients diagnosed with initial bone metastasis were identified by Surveillance, Epidemiology, and End Results database of the National Cancer Institute. Multivariate logistic and Cox regression were used to identify predictive factors for the presence of bone metastasis and prognosis factors. Kaplan–Meier method and log-rank test were used for survival analysis. Results: Eight thousand nine hundred one patients with initial MBC had bone involvement, accounting for 3.6% of the entire cohort and 62.5% of the patients with initial MBC. Also, 70.5% of patients with bone metastasis were hormone receptor (HR positive (HR+/human epidermal growth factor receptor 2 [HER2]−: 57.6%; HR+/HER2+: 12.9%. Patients with initial bone metastasis had a better 5-year survival rate compared to those with initial brain, liver, or lung metastasis. HR+/HER2− and HR+/HER2+ breast cancer had a propensity of bone metastasis in the entire cohort and were correlated with better prognosis in patients with initial bone metastasis. Local surgery had significantly improved overall survival in initial MBC patients with bone metastasis. Conclusion: Our study has provided population-based estimates of epidemiologic characteristics and prognosis in patients with bone metastasis at the time of

  15. 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.

  16. 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.

  17. Functional and molecular characterisation of EO771.LMB tumours, a new C57BL/6-mouse-derived model of spontaneously metastatic mammary cancer

    Directory of Open Access Journals (Sweden)

    Cameron N. Johnstone

    2015-03-01

    Full Text Available The translation of basic research into improved therapies for breast cancer patients requires relevant preclinical models that incorporate spontaneous metastasis. We have completed a functional and molecular characterisation of a new isogenic C57BL/6 mouse model of breast cancer metastasis, comparing and contrasting it with the established BALB/c 4T1 model. Metastatic EO771.LMB tumours were derived from poorly metastatic parental EO771 mammary tumours. Functional differences were evaluated using both in vitro assays and spontaneous metastasis assays in mice. Results were compared to non-metastatic 67NR and metastatic 4T1.2 tumours of the 4T1 model. Protein and transcript levels of markers of human breast cancer molecular subtypes were measured in the four tumour lines, as well as p53 (Tp53 tumour-suppressor gene status and responses to tamoxifen in vivo and in vitro. Array-based expression profiling of whole tumours identified genes and pathways that were deregulated in metastatic tumours. EO771.LMB cells metastasised spontaneously to lung in C57BL/6 mice and displayed increased invasive capacity compared with parental EO771. By immunohistochemical assessment, EO771 and EO771.LMB were basal-like, as was the 4T1.2 tumour, whereas 67NR had a luminal phenotype. Primary tumours from all lines were negative for progesterone receptor, Erb-b2/Neu and cytokeratin 5/6, but positive for epidermal growth factor receptor (EGFR. Only 67NR displayed nuclear estrogen receptor alpha (ERα positivity. EO771 and EO771.LMB expressed mutant p53, whereas 67NR and 4T1.2 were p53-null. Integrated molecular analysis of both the EO771/EO771.LMB and 67NR/4T1.2 pairs indicated that upregulation of matrix metalloproteinase-3 (MMP-3, parathyroid hormone-like hormone (Pthlh and S100 calcium binding protein A8 (S100a8 and downregulation of the thrombospondin receptor (Cd36 might be causally involved in metastatic dissemination of breast cancer.

  18. Snail acetylation by histone acetyltransferase p300 in lung cancer

    OpenAIRE

    Chang, Rui; Zhang, Yinjie; Zhang, Peng; Zhou, Qinghua

    2017-01-01

    Background Epithelial to mesenchymal transition (EMT) is a complex and dynamic molecular event in lung cancer metastasis that has not yet been thoroughly investigated. EMT transcriptional factors, such as Snail, play a central role in regulation of the EMT process. In this study, we sought to identify an association between p300 and Snail in lung cancer, as well as the engagement of p300 in Snail acetylation. Methods We transfected p300 small interfering RNA into lung cancer cells to detect S...

  19. Construction of radiation - induced metastasis model in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jong Kuk; Jang, Su Jin; Kang, Sung Wook; Kim, Jae Sung; Hwang, Sang Gu; Kang, Joo Hyun [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2011-05-15

    In treatment of cancer, distant metastases are important limiting factor because an estimated 50% of all cancer patients will develop metastases, and the metastases are major causing of cancer treatment failure. Recently a few reports indicated {gamma}-radiation induced an increase of invasiveness of several cancer cells. In this study, we had tried to show the possibility that radiation could also induce metastasis in vivo system. To prove our hypothesis, we constructed primary tumor by using C6-TL transfectant cell line expressing HSV1-tk and firefly luciferase (fLuc), and then {gamma}-radiation was treated to xenografts locally. Treatment of {gamma}-radiation to primary C6-TL xenografts of mice reduced size of xenografts and elongated survival of mice than those of mock control mice. But we also show that {gamma}-radiation treatment was followed by the growth of dormant metastases in various organs including lung and intestine after 2-4 weeks of {gamma}-radiation treatment. When bioluminescence imaging indicated growth of tumor in organs in mice, we sacrificed the mice and repeat acquired bioluminescence imaging after repeatedly. These images presented tumor growth locations exactly in organs. Because metastatic tumor candidates have morphology of foci, biopsies were performed for histological analysis or PCR analysis to confirm metastases. In most foci, histological analysis indicated several features of typical cancer tissue and PCR analysis showed present of fLuc gene in metastases. Detection of fLuc gene in metastases indicated these foci were originated from primary C6-TL xenografts, and the results suggest that {gamma}-radiation could promote metastasis in vivo as well as in vitro system. Although we need to understand changes of intracellular signaling or physiological phenomena of the radiation-induced metastasis yet, these results also imply that {gamma}-radiation treatment only to cancer patients need to pay attention carefully, and development of new

  20. Histopathology of a spontaneously developing mast cell sarcoma in a Wistar rat

    NARCIS (Netherlands)

    Baselmans, A.H.C.; Kuijpers, M.H.M.; Dijk, J.E. van

    1996-01-01

    A case report is given of a very rare spontaneous mast cell tumor in the eyelid of the left eye of a female Wistar rat used in a long-term oral toxicity study. Metastasis of the tumor had occurred in the mandibular lymph nodes and in the liver. Clinically, the animal showed blepharospasm,

  1. Lung Emergencies

    Science.gov (United States)

    ... The Marfan Foundation Marfan & Related Disorders What is Marfan Syndrome? What are Related Disorders? What are the Signs? ... Emergencies Lung Emergencies Surgeries Lung Emergencies People with Marfan syndrome can be at increased risk of sudden lung ...

  2. Cutaneous metastasis to the face from lung adenocarcinoma ...

    African Journals Online (AJOL)

    The patient was 64-year-old man, a heavy smoker; he was referred to our department with a short history of dyspnea, pleuritic pain and loss of weight, as well as a nodule on his left cheek which was noticed simultaneously with the respiratory symptoms. His general condition was good. A chest X-ray revealed a left upper ...

  3. Long noncoding RNA metastasis-associated lung adenocarcinoma ...

    African Journals Online (AJOL)

    Subjects and methods: The relative expression of MALAT1 was determined in 37 human glioblastoma formalin-fixed paraffin embedded (FFPE) tissue samples and 10 FFPE non-neoplastic brain tissues using quantitative reverse transcription polymerase chain reaction (qRT-PCR) technology. Results: The current results ...

  4. Muscular metastasis heralding medullary carcinoma of the thyroid

    Directory of Open Access Journals (Sweden)

    Rawdha Tekaya

    2013-09-01

    Full Text Available Medullary thyroid carcinoma (MTC commonly metastasizes locally to the cervical lymph nodes and distantly to the liver, lungs and bones. Metastatic involvement of the muscles is extremely rare. We reported an unusual case of undiagnosed MTC presenting with symptoms related to metastatic lesions of the brachoradialis and the gluteus medius muscles. A 53-year-old man consulted for a painful mass of the right forearm and atrophy of the quadriceps. Ultrasonography revealed a heterogeneous collection in the forearm. Computed tomographic scan showed a mass in the right lung, an enlargement of mediastinal lymph nodes and solid masses in the right gluteus medius and the left iliopoas muscle extending to the left iliac bone. Pulmonary biopsies displayed findings consistent with metastatic MTC. Fine needle aspiration cytology from the right arm swelling revealed a lesion with the same calcitonin immunostaining patterns as the lung metastasis. The diagnosis of multiple metastases (lung, muscle and bone of MTC is established. The patient has received local radiation therapy and was planned for chemotherapy. Muscular metastases from MTC are rare and although their prognosis is poor, local treatment may be worthwhile.

  5. Slug promotes survival during metastasis through suppression of Puma-mediated apoptosis.

    Science.gov (United States)

    Kim, Seaho; Yao, Jiahong; Suyama, Kimita; Qian, Xia; Qian, Bin-Zhi; Bandyopadhyay, Sanmay; Loudig, Olivier; De Leon-Rodriguez, Carlos; Zhou, Zhen Ni; Segall, Jeffrey; Macian, Fernando; Norton, Larry; Hazan, Rachel B

    2014-07-15

    Tumor cells must overcome apoptosis to survive throughout metastatic dissemination and distal organ colonization. Here, we show in the Polyoma Middle T mammary tumor model that N-cadherin (Cdh2) expression causes Slug (Snai2) upregulation, which in turn promotes carcinoma cell survival. Slug was dramatically upregulated in metastases relative to primary tumors. Consistent with a role in metastasis, Slug knockdown in carcinoma cells suppressed lung colonization by decreasing cell survival at metastatic sites, but had no effect on tumor cell invasion or extravasation. In support of this idea, Slug inhibition by shRNA sensitized tumor cells to apoptosis by DNA damage, resulting in caspase-3 and PARP cleavage. The prosurvival effect of Slug was found to be caused by direct repression of the proapoptotic gene, Puma (Bbc3), by Slug. Consistent with a pivotal role for a Slug-Puma axis in metastasis, inhibition of Puma by RNA interference in Slug-knockdown cells rescued lung colonization, whereas Puma overexpression in control tumor cells suppressed lung metastasis. The survival function of the Slug-Puma axis was confirmed in human breast cancer cells, where Slug knockdown increased Puma expression and inhibited lung colonization. This study demonstrates a pivotal role for Slug in carcinoma cell survival, implying that disruption of the Slug-Puma axis may impinge on the survival of metastatic cells. ©2014 American Association for Cancer Research.

  6. Skull destruction from intracranial metastasis arising from pulmonary squamous cell carcinoma: a case report

    Directory of Open Access Journals (Sweden)

    Kader Imran

    2013-01-01

    Full Text Available Abstract Introduction Squamous cell carcinoma of the lung represents 30% of all non-small cell lung carcinomas. It arises from dysplasia of squamous epithelium of the bronchi and is strongly associated with cigarette smoking. Squamous cell carcinoma of the lung is known to produce metastases in the brain parenchyma. Case presentation We present the case of an 80-year-old indigenous Australian man with an unusual presentation of metastatic carcinoma of the lung. The case demonstrated a squamous cell carcinoma of the lung with an intracranial metastatic lesion destroying the parietal bone and extending into the extracranial soft tissue. A visible deformity as a result of the metastasis was evident on physical examination and computed tomography demonstrated extensive bone destruction. Conclusion The authors were unable to find a case of this occurring from a squamous cell carcinoma of the lung anywhere in the world literature. The case report demonstrates an unusual disease presentation with a rare intracranial metastasis invading through the skull.

  7. Human melanoma metastasis in NSG mice correlates with clinical outcome in patients.

    Science.gov (United States)

    Quintana, Elsa; Piskounova, Elena; Shackleton, Mark; Weinberg, Daniel; Eskiocak, Ugur; Fullen, Douglas R; Johnson, Timothy M; Morrison, Sean J

    2012-11-07

    Studies of human cancer metastasis have been limited by a lack of experimental assays in which cancer cells from patients metastasize in vivo in a way that correlates with clinical outcome. This makes it impossible to study intrinsic differences in the metastatic properties of cancers from different patients. We recently developed an assay in which human melanomas readily engraft in nonobese diabetic/severe combined immunodeficient interleukin-2 receptor-γ chain null (NSG) mice. We show that melanomas from 25 patients exhibited reproducible differences in the rate of spontaneous metastasis after transplantation into NSG mice and that these differences correlated with clinical outcome in the patients. Stage IIIB/C melanomas that formed distant metastases within 22 months in patients also formed tumors that metastasized widely in NSG mice, whereas stage IIIB/C melanomas that did not form distant metastases within 22 to 50 months in patients metastasized more slowly in NSG mice. These differences in the efficiency of metastasis correlated with the presence of circulating melanoma cells in the blood of NSG mice, suggesting that the rate of entry into the blood is one factor that limits the rate of metastasis. The study of NSG mice can therefore yield information about the metastasis of human melanomas in vivo, in this case revealing intrinsic differences among stage III melanomas in their ability to circulate/survive in the blood and to metastasize.

  8. Intracardiac metastasis of immature teratoma after chemotherapy in a patient with testicular mixed germ cell tumor

    Directory of Open Access Journals (Sweden)

    Wei-Chih Chang

    2017-12-01

    Full Text Available Cancer with intra-cardiac metastasis is a rare complication. We herein report a 32-year-old male diagnosed with stage IV mixed germ cell tumor of the testes who received right radical orchiectomy. Initially, he had right lung metastasis and a mediastinal lymph node attached to the right side of the heart. After four cycles of chemotherapy (bleomycin, etoposide, and cisplatin, the patient experienced sudden cardiac arrest. He was later found to have intra-cardiac metastasis with tumor invasion in the right pulmonary artery/veins, left atrium, and left ventricle. The patient subsequently received surgical intervention, and pathology revealed only immature teratoma. This study illustrates the proposition that chemo-resistant residual teratoma can still invade the heart after chemotherapy, and therefore surgical intervention might be needed.

  9. Testicular choriocarcinoma with cutaneous metastasis in a 19-year-old man.

    Science.gov (United States)

    Toberer, Ferdinand; Enk, Alexander; Hartschuh, Wolfgang; Grüllich, Carsten

    2018-04-17

    A 19-year-old man suffering from testicular choriocarcinoma presented to the dermatology department with a cutaneous metastasis on his head. This metastasis was the first sign of disease that led to medical consultation. Histopathology revealed cytotrophoblasts and syncytiotrophoblasts, the later expressing human chorionic gonadotropin antigen. Whole body computed tomography showed multiple metastases of the brain, lung, liver, bone, paraaortic lymph nodes and left uvea, the primary was found in the left testicle. Despite neurosurgical intervention and chemotherapy the patient died nine days after the biopsy of the cutaneous metastasis. Cutaneous metastases of testicular choriocarcinoma are exceptionally rare, with less than a dozen cases reported in the English-language literature. The present case highlights that testicular choriocarcinoma metastatic to the skin should be included in the differential of (poorly differentiated) cutaneous scalp tumors. This article is protected by copyright. All rights reserved.

  10. Anti-S100A4 antibody suppresses metastasis formation by blocking stroma cell invasion

    DEFF Research Database (Denmark)

    Klingelhöfer, Jörg; Grum-Schwensen, Birgitte; Beck, Mette K

    2012-01-01

    microenvironment, making it an attractive target for anti-cancer therapy. In this study, we produced a function-blocking anti-S100A4 monoclonal antibody with metastasis-suppressing activity. Antibody treatment significantly reduced metastatic burden in the lungs of experimental animals by blocking the recruitment......The small Ca-binding protein, S100A4, has a well-established metastasis-promoting activity. Moreover, its expression is tightly correlated with poor prognosis in patients with numerous types of cancer. Mechanistically, the extracellular S100A4 drives metastasis by affecting the tumor...... of T cells to the site of the primary tumor. In vitro studies demonstrated that this antibody efficiently reduced the invasion of T cells in a fibroblast monolayer. Moreover, it was capable of suppressing the invasive growth of human and mouse fibroblasts. We presume therefore that the antibody exerts...

  11. Targeting cytokine signaling checkpoint CIS activates NK cells to protect from tumor initiation and metastasis

    Science.gov (United States)

    Putz, Eva M.; Guillerey, Camille; Kos, Kevin; Stannard, Kimberley; Miles, Kim; Delconte, Rebecca B.; Nicholson, Sandra E.; Huntington, Nicholas D.; Smyth, Mark J.

    2017-01-01

    ABSTRACT The cytokine-induced SH2-containing protein CIS belongs to the suppressor of cytokine signaling (SOCS) protein family. Here, we show the critical role of CIS in suppressing natural killer (NK) cell control of tumor initiation and metastasis. Cish-deficient mice were highly resistant to methylcholanthrene-induced sarcoma formation and protected from lung metastasis of B16F10 melanoma and RM-1 prostate carcinoma cells. In contrast, the growth of primary subcutaneous tumors, including those expressing the foreign antigen OVA, was unchanged in Cish-deficient mice. The combination of Cish deficiency and relevant targeted and immuno-therapies such as combined BRAF and MEK inhibitors, immune checkpoint blockade antibodies, IL-2 and type I interferon revealed further improved control of metastasis. The data clearly indicate that targeting CIS promotes NK cell antitumor functions and CIS holds great promise as a novel target in NK cell immunotherapy. PMID:28344878

  12. Intrathoracic Endotracheal Metastasis from Nasopharyngeal Carcinoma:A First Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Heming Lu

    2010-05-01

    Full Text Available Intrathoracic endotracheal metastasis from a very distant site is extremely rare. We report the first case of such a disease in a 68-year-old man with nasopharyngeal carcinoma who presented with a cough and hemoptysis 34 months after finishing radiotherapy. Prior to tracheal metastasis, he developed a solitary metastasis in the lung and underwent chemotherapy followed by radiotherapy. Computed tomography showed the presence of an enlarged lymph node in the para-aortic arch. Fiberoptic bronchoscopy revealed an endotracheal tumor 1 cm above the carina. Histological and immunohistochemical analyses confirmed its nasopharyngeal origin. He was treated with conventional radiotherapy and three-dimensional conformal radiotherapy; complete tumor remission was achieved. He died of nonmalignant disease with no signs of tumor recurrence 2 years after treatment completion. Radiotherapy may be an appropriate management approach to achieve long-term tumor control for this disease.

  13. Dural Metastasis Mimicking Meningioma: An Interesting Case

    Directory of Open Access Journals (Sweden)

    Hamzaini Abdul Hamid

    2009-01-01

    Full Text Available Dural metastasis is a rare entity in clinical practice. We report a case of dural metastasis secondary to thyroid carcinoma, which on both preoperative CT and MRI and at surgery had the typical appearance of a meningioma. Histopathological findings confirmed metastatic follicular thyroid carcinoma as a primary site. Although rare, dural metastases can mimic a meningioma. Our experience in this case has led us to consider metastasis as a differential diagnosis even when a meningioma is suspected. We believe that reporting of the case of dural metastasis mimicking a meningioma may help clinicians in future.

  14. Laparoscopic partial nephrectomy of thyroid cancer metastasis: case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Cochetti G, Puxeddu E, Del Zingaro M, D’Amico F, Cottini E, Barillaro F, Mearini E

    2013-04-01

    Full Text Available Giovanni Cochetti,1 Efisio Puxeddu,2 Michele Del Zingaro,3 Francesco D’Amico,1 Emanuele Cottini,1 Francesco Barillaro,1 Ettore Mearini11Department of General Surgery and Surgical Specialties, Urological Andrological Surgery and Minimally Invasive Techniques, University of Perugia, Terni, Italy; 2Departmentof Internal Medicine, 3Departmentof Surgical Specialties and PublicHealth, Urological Clinic, Universityof Perugia, Perugia, ItalyBackground: Follicular cell thyroid carcinoma is a quite aggressive form of thyroid cancer. About 10% of follicular thyroid carcinoma shows multiple metastases: lung and bone are the most common sites of metastasis. Renal involvement from thyroid primary cancer is very rare with incidence of 4.5%–5.9%.Purpose: We report the first laparoscopic conservative treatment of renal metastasis from thyroid cancer. This is a new and useful approach in order to delay malignant disease progression and to reduce the surgical discomfort of the patient.Patients and methods: We present the case of a 67-year-old woman, undergoing total thyroidectomy for follicular thyroid cancer with bone and lung metastasis. During adjuvant radiometabolic treatment, renal metastasis was diagnosed. Renal metastasis showed high metabolic activity, reducing the effectiveness of radioiodine therapy for secondary lesions. For this reason, we performed a laparoscopic simple enucleation of the single renal metastasis using extraperitoneal access and a clampless procedure.Results: The excision of the renal lesion improved the effectiveness of adjuvant radioiodine therapy: two months after surgery, the patient underwent adjuvant radiometabolic treatment with iodine-131 (150 mCi and the following whole body scan showed only a small uptaking area at the level of the vertebral metastasis. The lung micrometastases were not detectable. At 36 months follow-up, malignant disease was clinically stable and well controlled.Conclusion: Minimally invasive renal

  15. 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.

  16. Pulmonary metastasis in thyroid cancer

    International Nuclear Information System (INIS)

    Samuel, A.M.; Rajashekharrao, B.; Shah, D.H.

    1999-01-01

    Although thyroid cancer (TC) in its differentiated form is generally associated with a good prognosis and a near normal life expectancy, a subset of patients especially with distant metastatic disease may run an aggressive course leading to poor survival and early death. The clinical presentation and the manner in which the disease progresses differs with the site and type of the metastatic disease. The behaviour and course of skeletal metastasis has been described elsewhere. The biological behaviour and treatment of pulmonary metastatic disease is focussed on

  17. Recurrent spontaneous pneumothoraces and bullous emphysema. A novel mutation causing Birt-Hogg-Dube syndrome.

    Science.gov (United States)

    Burkett, Andrew; Coffey, Niamh; Tomiak, Eva; Voduc, Nha

    2016-01-01

    Birt-Hogg-Dube syndrome (BHDS) is a rare form of classically cystic lung disease that may present with spontaneous pneumothorax. The associated skin manifestations (fibrofolliculomas) are not always present. This article describes a case of spontaneous pneumothorax secondary to bullous emphysema in an otherwise healthy gentleman caused by a novel mutation in the folliculin (FLCN) gene.

  18. Metastasis

    Science.gov (United States)

    ... and Care Surgical Treatment Laparoscopic Surgery Vaccine Radiation Therapy Chemotherapy Clinical Trials Pain Management Nutrition and Exercise Holistic Care Pathology Intraductal Papillary Mucinous Neoplasms Islet Cell ...

  19. Lung density

    DEFF Research Database (Denmark)

    Garnett, E S; Webber, C E; Coates, G

    1977-01-01

    The density of a defined volume of the human lung can be measured in vivo by a new noninvasive technique. A beam of gamma-rays is directed at the lung and, by measuring the scattered gamma-rays, lung density is calculated. The density in the lower lobe of the right lung in normal man during quiet...

  20. Collagenolytic Matrix Metalloproteinases in Chronic Obstructive Lung Disease and Cancer

    Directory of Open Access Journals (Sweden)

    Denzel Woode

    2015-02-01

    Full Text Available Chronic obstructive pulmonary disease (COPD and lung cancer result in significant morbidity and mortality worldwide. In addition to the role of environmental smoke exposure in the development of both diseases, recent epidemiological studies suggests a connection between the development of COPD and lung cancer. Furthermore, individuals with concomitant COPD and cancer have a poor prognosis when compared with individuals with lung cancer alone. The modulation of molecular pathways activated during emphysema likely lead to an increased susceptibility to lung tumor growth and metastasis. This review summarizes what is known in the literature examining the molecular pathways affecting matrix metalloproteinases (MMPs in this process as well as external factors such as smoke exposure that have an impact on tumor growth and metastasis. Increased expression of MMPs provides a unifying link between lung cancer and COPD.

  1. Collagenolytic Matrix Metalloproteinases in Chronic Obstructive Lung Disease and Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Woode, Denzel; Shiomi, Takayuki; D’Armiento, Jeanine, E-mail: jmd12@cumc.columbia.edu [Department of Anesthesiology, Columbia University, College of Physicians and Surgeons, New York, NY 10033 (United States)

    2015-02-05

    Chronic obstructive pulmonary disease (COPD) and lung cancer result in significant morbidity and mortality worldwide. In addition to the role of environmental smoke exposure in the development of both diseases, recent epidemiological studies suggests a connection between the development of COPD and lung cancer. Furthermore, individuals with concomitant COPD and cancer have a poor prognosis when compared with individuals with lung cancer alone. The modulation of molecular pathways activated during emphysema likely lead to an increased susceptibility to lung tumor growth and metastasis. This review summarizes what is known in the literature examining the molecular pathways affecting matrix metalloproteinases (MMPs) in this process as well as external factors such as smoke exposure that have an impact on tumor growth and metastasis. Increased expression of MMPs provides a unifying link between lung cancer and COPD.

  2. 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.

  3. Transformation of a thymic branchial cyst to a carcinoma with pulmonary metastasis in a dog.

    Science.gov (United States)

    Levien, A S; Summers, B A; Szladovits, B; Benigni, L; Baines, S J

    2010-11-01

    A 9-year-old, female neutered Dalmatian was evaluated for acute onset of dyspnoea. Thoracocentesis on presentation yielded 1300 ml sanguineous fluid, while thoracic radiology and ultrasonography showed a mixed-echoic cavitary cranial mediastinal mass, sternal lymph node enlargement and pleural effusion. Surgical exploration of the thorax revealed a multi-lobulated red/brown cranial mediastinal mass and multiple similarly coloured ovoid nodules within several lung lobes. Histopathology revealed thymic branchial cysts with neoplastic transformation and examination of the lung was consistent with metastasis. Despite initially recovering well, acute sepsis and pyothorax resulted in cardiac arrest 8 days postoperatively. This is the first veterinary report of neoplastic transformation of a thymic branchial cyst with pulmonary metastasis. © 2010 British Small Animal Veterinary Association.

  4. Metastatic angiosarcoma of the lung : HRCT findings

    International Nuclear Information System (INIS)

    Kim, Mi Young; Lim, Byung Sung; Oh, Mee Hye; Im, Jung Gi

    1999-01-01

    We describe a case of cavitary metastasis to the lungs from a small angiosarcoma of the scalp, in which the metastatic lesions were complicated by pneumothorax and pulmonary hemorrhage. On high-resolution CT, the lesions simulated the findings of Langerhans cell histiocytosis. Thin-walled cavitary metastatic lesions were similar to those of thin walled air cysts in Langerhans cell histiocytosis. Ground-glass opacity simulated the findings of smoker's respiratory bronchiolitis in Langerhans cell histiocytosis but histologically represented hemorrhage during metastasis of the angiosarcoma

  5. Isolated Pancreatic Metastasis from Malignant Melanoma: Is ...

    African Journals Online (AJOL)

    Thus, pre-operative exhaustive staging is needed to confirm both the absence of local invasion of major vasculature and the absence of distant metastasis. Positron emission tomography scanning seems to have a higher sensitivity and specificity than conventional imaging for detecting metastasis from malignant melanoma.

  6. Hepatic Metastasis of Thymoma: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Jung Hun; Kim, Jang Ho; Shin, Hyun Woong; Lee, Il Ki; Sohn, Kyung Rak [Fatima Hospital, Daegu (Korea, Republic of)

    2005-03-15

    Thymoma is the most common neoplasm in the anterior mediastinum, and extrathoracic involvement is rare. Moreover, cystic liver metastasis is extremely rare; few cases have been reported in the literature to date. We report here on a case of cystic liver metastasis of thymoma treated with surgical resection, describing the ultrasonography, CT and MRI findings

  7. The Effect of Electroacupuncture on Osteosarcoma Tumor Growth and Metastasis: Analysis of Different Treatment Regimens

    Directory of Open Access Journals (Sweden)

    Branden A. Smeester

    2013-01-01

    Full Text Available Osteosarcoma is the most common malignant bone tumor found in children and adolescents and is associated with many complications including cancer pain and metastasis. While cancer patients often seek complementary and alternative medicine (CAM approaches to treat cancer pain and fatigue or the side effects of chemotherapy and treatment, there is little known about the effect of acupuncture treatment on tumor growth and metastasis. Here we evaluate the effects of six different electroacupuncture (EA regimens on osteosarcoma tumor growth and metastasis in both male and female mice. The most significant positive effects were observed when EA was applied to the ST-36 acupoint twice weekly (EA-2X/3 beginning at postimplantation day 3 (PID 3. Twice weekly treatment produced robust reductions in tumor growth. Conversely, when EA was applied twice weekly (EA-2X/7, starting at PID 7, there was a significant increase in tumor growth. We further demonstrate that EA-2X/3 treatment elicits significant reductions in tumor lymphatics, vasculature, and innervation. Lastly, EA-2X/3 treatment produced a marked reduction in pulmonary metastasis, thus providing evidence for EA’s potential antimetastatic capabilities. Collectively, EA-2X/3 treatment was found to reduce both bone tumor growth and lung metastasis, which may be mediated in part through reductions in tumor-associated vasculature, lymphatics, and innervation.

  8. The Roles of Carcinoembryonic Antigen in Liver Metastasis and Therapeutic Approaches

    Science.gov (United States)

    2017-01-01

    Metastasis is a highly complicated and sequential process in which primary cancer spreads to secondary organic sites. Liver is a well-known metastatic organ from colorectal cancer. Carcinoembryonic antigen (CEA) is expressed in most gastrointestinal, breast, and lung cancer cells. Overexpression of CEA is closely associated with liver metastasis, which is the main cause of death from colorectal cancer. CEA is widely used as a diagnostic and prognostic tumor marker in cancer patients. It affects many steps of liver metastasis from colorectal cancer cells. CEA inhibits circulating cancer cell death. CEA also binds to heterogeneous nuclear RNA binding protein M4 (hnRNP M4), a Kupffer cell receptor protein, and activates Kupffer cells to secrete various cytokines that change the microenvironments for the survival of colorectal cancer cells in the liver. CEA also activates cell adhesion-related molecules. The close correlation between CEA and cancer has spurred the exploration of many CEA-targeted approaches as anticancer therapeutics. Understanding the detailed functions and mechanisms of CEA in liver metastasis will provide great opportunities for the improvement of anticancer approaches against colorectal cancers. In this report, the roles of CEA in liver metastasis and CEA-targeting anticancer modalities are reviewed. PMID:28588612

  9. SERPINE2 is a possible candidate promotor for lymph node metastasis in testicular cancer

    Energy Technology Data Exchange (ETDEWEB)

    Nagahara, Akira; Nakayama, Masashi; Oka, Daizo; Tsuchiya, Mutsumi; Kawashima, Atsunari; Mukai, Masatoshi; Nakai, Yasutomo; Takayama, Hitoshi [Department of Urology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita-City, Osaka 565-0871 (Japan); Nishimura, Kazuo [Department of Urology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3 Nakamachi, Higashinari-ku, Osaka, 537-8511 (Japan); Jo, Yoshimasa; Nagai, Atsushi [Department of Urology, Kawasaki Medical University, 577 Matsushima, Kurashiki-City, Okayama 701-0192 (Japan); Okuyama, Akihiko [Department of Urology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita-City, Osaka 565-0871 (Japan); Nonomura, Norio, E-mail: nono@uro.med.osaka-u.ac.jp [Department of Urology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita-City, Osaka 565-0871 (Japan)

    2010-01-22

    Testicular germ cell tumors (TGCTs) commonly metastasize to the lymph node or lung. However, it remains unclear which genes are associated with TGCT metastasis. The aim of this study was to identify gene(s) that promoted human TGCT metastasis. We intraperitoneally administered conditioned medium (CM) from JKT-1, a cell-line from a human testicular seminoma, or JKT-HM, a JKT-1 cell sub-line with high metastatic potential, into mice with JKT-1 xenografts. Administration of CM from JKT-HM significantly promoted lymph node metastasis. A cDNA microarray analysis showed that JKT-HM cells highly expressed the Serpine peptidase inhibitor, clade E, member 2 (SERPINE2), which encodes a secreted protein. Administration of CM from SERPINE2-silenced JKT-HM cells inhibited lymph node metastasis in the xenograft model, compared with administration of CM from JKT-HM cells. There was no significant difference in xenograft volume. Moreover, administration of CM from SERPINE2-over-expressing JKT-1 was likely to promote lymph node metastasis in the xenograft model. There was no difference in the in vitro proliferation or migration of JKT-1 cells cultured with CM from JKT-HM cells, compared to that with CM from JKT-1. There was no promotion of proliferation or lymphangiogenesis in the xenografts, as measured by Ki-67 and LYVE-1 immunohistochemistry, respectively. Although we could not clarify how SERPINE2 promoted lymph node metastasis, it may be a promoter in the development of lymph node metastasis in the human seminoma cells in a mouse xenograft model.

  10. Defining Tumor Cell and Immune Cell Behavior in Vivo during Pulmonary Metastasis of Breast Cancer

    Science.gov (United States)

    2015-09-01

    imaging methodology and its application to the study of metastasis. • March 2015- During this second year of the project I attended the Keystone ...communities at the Keystone Conference on Macrophages and Dendritic Cells, The Photonics West Conference, and The World Molecular Imaging Conference...confocal imaging), we found that cytoplasts became the dominant tumour­cell­derived species within the lung within 15 min (Fig. 1i, j and Extended Data

  11. Metastasis from renal cell carcinoma to thyroid presenting as rapidly growing neck mass

    OpenAIRE

    Mohammadi, Afshin; Toomatari, Seyed Babak Mosavi; Ghasemi-Rad, Mohammad

    2014-01-01

    INTRODUCTION: Renal cell carcinoma (RCC) is commonly known as the “internist's tumor” because of its unpredictable behavior. Metastasis to the thyroid gland is rarely found in clinical practice. PRESENTATION OF CASE: We report a rare case of non-thyroid malignancies NTM from renal cell carcinoma 1.5 years after radical nephrectomy in a 58-year-old man with a rapidly growing neck mass. DISCUSSION: Malignant melanoma, breast carcinoma, lung, and skin cancer are the most common sources of ...

  12. Slug promotes survival during metastasis through suppression of Puma-mediated apoptosis

    OpenAIRE

    Kim, Seaho; Yao, Jiahong; Suyama, Kimita; Qian, Xia; Qian, Bin-Zhi; Bandyopadhyay, Sanmay; Loudig, Olivier; De Leon-Rodriguez, Carlos; Zhou, Zhen Ni; Segall, Jeffrey; Macian, Fernando; Norton, Larry; Hazan, Rachel. B.

    2014-01-01

    Tumor cells must overcome apoptosis to survive throughout metastatic dissemination and distal organ colonization. Here we show in the Polyoma Middle T mammary tumor model that N-cadherin expression causes Slug upregulation, which in turn promotes carcinoma cell survival. Slug was dramatically upregulated in metastases relative to primary tumors. Consistent with a role in metastasis, Slug knockdown in carcinoma cells suppressed lung colonization by decreasing cell survival at metastatic sites,...

  13. Pterostilbene acts through metastasis-associated protein 1 to inhibit tumor growth, progression and metastasis in prostate cancer.

    Directory of Open Access Journals (Sweden)

    Kun Li

    Full Text Available The development of natural product agents with targeted strategies holds promise for enhanced anticancer therapy with reduced drug-associated side effects. Resveratrol found in red wine, has anticancer activity in various tumor types. We reported earlier on a new molecular target of resveratrol, the metastasis-associated protein 1 (MTA1, which is a part of nucleosome remodeling and deacetylation (NuRD co-repressor complex that mediates gene silencing. We identified resveratrol as a regulator of MTA1/NuRD complex and re-activator of p53 acetylation in prostate cancer (PCa. In the current study, we addressed whether resveratrol analogues also possess the ability to inhibit MTA1 and to reverse p53 deacetylation. We demonstrated that pterostilbene (PTER, found in blueberries, had greater increase in MTA1-mediated p53 acetylation, confirming superior potency over resveratrol as dietary epigenetic agent. In orthotopic PCa xenografts, resveratrol and PTER significantly inhibited tumor growth, progression, local invasion and spontaneous metastasis. Furthermore, MTA1-knockdown sensitized cells to these agents resulting in additional reduction of tumor progression and metastasis. The reduction was dependent on MTA1 signaling showing increased p53 acetylation, higher apoptotic index and less angiogenesis in vivo in all xenografts treated with the compounds, and particularly with PTER. Altogether, our results indicate MTA1 as a major contributor in prostate tumor malignant progression, and support the use of strategies targeting MTA1. Our strong pre-clinical data indicate PTER as a potent, selective and pharmacologically safe natural product that may be tested in advanced PCa.

  14. Contiguous spinal metastasis mimicking infectious spondylodiscitis

    International Nuclear Information System (INIS)

    Lee, Chul Min; Lee, Seung Hun; Bae, Ji Yoon

    2015-01-01

    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

  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. Orbital metastasis secondary to pulmonary adenocarcinoma treated with gefitinib: a case report

    Directory of Open Access Journals (Sweden)

    Koma Yasuko

    2012-10-01

    Full Text Available Abstract Introduction Orbital metastases of lung cancer are rare. However, because the number of patients diagnosed with lung cancer is increasing, the probability that a physician will see a patient with an orbital metastasis is also increasing. Unfortunately, the clinical course and response of these patients to cytotoxic chemotherapy are generally poor and keeping a patient’s quality of vision is difficult. In recent years, gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, has brightened the outlook for patients with advanced non-small cell lung cancer, especially for those who carry epidermal growth factor receptor-activating mutations. Case presentation A 62-year-old Japanese man presented with swelling of the eyelid margin and ptosis of his right eye. A physical examination revealed double vision in his right eye and an alteration in elevator muscle mobility. A magnetic resonance image demonstrated a right intra-orbital mass (18 × 16mm. Screening examinations were carried out because this mass was suspected to be a metastasis from another organ. Chest computed tomography revealed a 42 × 37mm mass shadow on the left side of the hilum with mediastinal lymph node metastases. Adenocarcinoma with an epidermal growth factor receptor gene mutation (exon 19 deletion L747-E749; A750P was detected in a transbronchial biopsy specimen; the patient was diagnosed with stage IV (T2N2M1 non-small cell lung cancer. Gefitinib (250mg/day was chosen as first-line chemotherapy because there was no pre-existing interstitial shadow. After two months of treatment, the patient’s right eye opened completely and follow-up magnetic resonance imaging revealed a marked reduction of the intra-orbital mass to 14 × 13mm. Three months after treatment initiation, a follow-up computed tomography showed a marked reduction in the size of the primary lesion to 23 × 20mm. The patient is continuing gefitinib treatment without any adverse effects

  17. Lung Density Changes With Growth and Inflation

    Science.gov (United States)

    Kirk, Gregory; Drummond, M. Bradley; Mitzner, Wayne

    2015-01-01

    BACKGROUND: With body growth from childhood, the lungs can enlarge by either increasing the volume of air in the periphery (as would occur with inspiration) or by increasing the number of peripheral acinar units. In the former case, the lung tissue density would decrease with inflation, whereas in the latter case, the lung density would be relatively constant as the lung grows. To address this fundamental structural issue, we measured the CT scan density in human subjects of widely varying size at two different lung volumes. METHODS: Five hundred one subjects were enrolled in the study. They underwent a chest CT scan at full inspiration and another scan at end expiration. Spirometry, body plethysmography, and diffusing capacity of the lung for carbon monoxide were also measured. RESULTS: There was a strong correlation between the size of the lungs measured at full inspiration on CT scan and the mean lung density (r = −0.72, P = .001). People with larger lungs had significantly lower mean lung density. These density changes among different subjects overlapped the density changes within subjects at different lung volumes. CONCLUSIONS: Lung structure in subjects with larger lungs is different from that in subjects with smaller lungs. Tissue volume does not increase in proportion to lung size, as would be required if larger lungs just had more alveoli. These observations suggest that the growth of the lung into adulthood is not accompanied by new alveoli, but rather by enlargement of existing structures. The presence of greater air spaces in larger lungs could impact the occurrence and pathogenesis of spontaneous pneumothorax or COPD. PMID:25996948

  18. Lung density changes with growth and inflation.

    Science.gov (United States)

    Robert, H Brown; Robert, A Wise; Kirk, Gregory; Drummond, M Bradley; Mitzner, Wayne

    2015-10-01

    With body growth from childhood, the lungs can enlarge by either increasing the volume of air in the periphery (as would occur with inspiration) or by increasing the number of peripheral acinar units. In the former case, the lung tissue density would decrease with inflation, whereas in the latter case, the lung density would be relatively constant as the lung grows. To address this fundamental structural issue, we measured the CT scan density in human subjects of widely varying size at two different lung volumes. Five hundred one subjects were enrolled in the study. They underwent a chest CT scan at full inspiration and another scan at end expiration. Spirometry, body plethysmography, and diffusing capacity of the lung for carbon monoxide were also measured. There was a strong correlation between the size of the lungs measured at full inspiration on CT scan and the mean lung density (r = -0.72, P = .001). People with larger lungs had significantly lower mean lung density. These density changes among different subjects overlapped the density changes within subjects at different lung volumes. Lung structure in subjects with larger lungs is different from that in subjects with smaller lungs. Tissue volume does not increase in proportion to lung size, as would be required if larger lungs just had more alveoli. These observations suggest that the growth of the lung into adulthood is not accompanied by new alveoli, but rather by enlargement of existing structures. The presence of greater air spaces in larger lungs could impact the occurrence and pathogenesis of spontaneous pneumothorax or COPD.

  19. Duodenal metastasis of pulmonary pleomorphic carcinoma: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Sun Hye; Paik, Sang Hyun; Koh, Eun Suk; Shin, Hwa Kyoon; Cha, Jang Gyu; Park, Jai Soung [Soonchunhyang University Bucheon Hospital, Bucheon (Korea, Republic of); Lee, Nam Seok [Purun Radiologic Clinic, Yesan (Korea, Republic of)

    2016-02-15

    Pulmonary pleomorphic carcinoma is an uncommon malignant lesion of the lung. A chest radiograph of 53-year-old man who was suffering from a cough revealed a well-defined mass-like opacity with a broad base on the pleura at the apico-posterior segment of the right upper lobe of the lung. The subsequent chest computed tomography (CT) scan demonstrated an inhomogeneous enhancing mass with central low-attenuation in the right upper lobe. A lobectomy was performed and the mass was determined to be a pleomorphic carcinoma with visceral pleura invasion. Forty days after the operation, the patient complained of melena and an abdominal CT revealed an intraluminal and extraluminal protruding mass around the prepyloric antrum and duodenal bulb. The mass was removed by en-block surgery and diagnosed as metastatic pleomorphic carcinoma from the lung. Previous articles reported a median survival time of 3–10 months for pleomorphic carcinoma, but in this case, the patient has continued to survive, 11 years after surgery. Chest and abdominal CTs have revealed no evidence of tumor recurrence or metastasis.

  20. Pulmonary metastasis after bleomycin-induced endothelial injury and repair

    Energy Technology Data Exchange (ETDEWEB)

    Adamson, I.Y.R.; Young, L.; Orr, F.W.

    1986-03-01

    Injury to the endothelial barrier is thought to enhance the localization and metastasis of circulating tumor cells. This hypothesis was tested by inducing pulmonary endothelial injury in C57bl/6 mice by injecting a single IV dose of bleomycine (120 mg/kg). After 5 days, severe endothelial injury was demonstrated by morphology and by increased levels of protein in lung lavage fluid. When /sup 131/I-iododeoxyuridine labeled syngeneic fibrosarcoma cells were injected IV at this time, a 9 fold increase in their localization was detected 24 hrs later in bleomycin-treated lungs compared to saline controls. By EM, tumor cells were observed at sites of denuded vascular basement membrane. There was also a significant increase in subsequent gross metastases and percentage of lung occupied by tumor in the bleomycin group. Animals examined 10 days after bleomycin showed less endothelial damage and a smaller increase in tumor cell localization and metastases. At 21 days, when endothelial structure and alveolar protein levels had returned to normal, and at 6 weeks, when there was focal fibrosis, no increase in tumor cell localization or metastases was found. It is concluded that damage to the pulmonary endothelium is a key factor in enhancing the trapping of circulating tumor cells and increasing metastatic tumor growth.

  1. Inhibitory mechanism of low-dose, whole-body irradiation with gamma-rays against tumor metastasis

    International Nuclear Information System (INIS)

    Yasuhiro Ohsima; Mitsutoshi Tukimoto; Shuji Kojima

    2007-01-01

    Complete text of publication follows. A lot of beneficial effects of low-dose irradiation are well known. Of them, an inhibitory effect of the radiation on lung metastasis is reported so far. It has been reported that low-dose whole-body irradiation with gamma rays enhanced cytotoxic immune response as one of the mechanisms. In our laboratory, it has been confirmed an enhancement of natural killer activity in mice irradiated with whole-body 0.5Gy gamma-rays. Metastasis is accomplished by multistep process, involving basement membrane destruction, local invasion, intravasation, survival in the bloodstream, extravasation into distant organs, and proliferation at the target site. Besides, a lot of growth factors and proteases are involved in these steps. As to mechanism of inhibition of tumor metastasis induced by low-dose whole-body irradiation, studies from the standpoint of tumor invasion have not been reported. Here, inhibitory effect of 0.5Gy whole-body gamma-ray irradiation on tumor metastasis and its mechanism were examined in pulmonary metastasis model mice injected with B16 melanoma cells. Consequently, 0.5Gy whole-body gamma ray irradiation significantly suppressed colony formation in the lungs. Expression of matrix metalloproteinase- 2 (MMP- 2), a proteinase related to metastasis, in lung tissues was suppressed by the radiation. Alteration of tissue inhibitor of matrix metalloproteinase (TIMP) after the gamma-ray irradiation was examined. Expression of TIMP-1 and TIMP-2 mRNA in the lungs were significantly increased. In order to clarify the inhibitory effect obtained in the in vivo metastatic lung cancer model mice, we studied effects of gamma-rays on cell proliferation, alterations of mRNA and proteins related to tumor metastasis in cultured B16 melanoma cells. Proliferation of B16 melanoma cells was decreased in a dose-dependent manner. MMP-2 mRNA expression was not altered in any doses of gamma-rays. Thought expression of the protein was slightly

  2. Spontaneous Atraumatic Mediastinal Hemorrhage

    Directory of Open Access Journals (Sweden)

    Morkos Iskander BSc, BMBS, MRCS, PGCertMedEd

    2013-04-01

    Full Text Available Spontaneous atraumatic mediastinal hematomas are rare. We present a case of a previously fit and well middle-aged lady who presented with acute breathlessness and an increasing neck swelling and spontaneous neck bruising. On plain chest radiograph, widening of the mediastinum was noted. The bruising was later confirmed to be secondary to mediastinal hematoma. This life-threatening diagnostic conundrum was managed conservatively with a multidisciplinary team approach involving upper gastrointestinal and thoracic surgeons, gastroenterologists, radiologists, intensivists, and hematologists along with a variety of diagnostic modalities. A review of literature is also presented to help surgeons manage such challenging and complicated cases.

  3. GHGKHKNK Octapeptide (P-5m Inhibits Metastasis of HCCLM3 Cell Lines via Regulation of MMP-2 Expression in in Vitro and in Vivo Studies

    Directory of Open Access Journals (Sweden)

    Xun Zhu

    2012-02-01

    Full Text Available P-5m, an octapeptide derived from domain 5 of HKa, was initially found to inhibit the invasion and migration of melanoma cells. The high metastatic potential of melanoma cells was prevented by the HGK motif in the P-5m peptide in vitro and in an experimental lung metastasis model, suggesting that P-5m may play an important role in the regulation of tumor metastasis. The aim of this study was to measure the effect of P-5m on tumor metastasis of human hepatocarcinoma cell line (HCCLM3 in vitro and in vivo in a nude mouse model of hepatocellular carcinoma (HCC, and detect the mechanisms involved in P-5m-induced anti-metastasis. By gelatin zymography, matrix metallo-proteinases 2 (MMP-2 activity in HCCLM3 was dramatically diminished by P-5m peptide. In addition, the migration and metastasis of HCCLM3 cells was also inhibited by the peptide in vitro. In an orthotopic model of HCC in nude mice, P-5m treatment effectively reduced the lung metastasis as well as the expression of MMP-2 in the tumor tissues. Overall, these observations indicate an important role for P-5m peptide in HCC invasion and metastasis, at least partially through modulation MMP-2 expression. These data suggests that P-5m may have therapeutic potential in metastatic human hepatocarcinoma.

  4. Bone scintigraphy for metastasis detection in canine osteosarcoma

    International Nuclear Information System (INIS)

    Forrest, L.J.; Thrall, D.E.

    1994-01-01

    The purpose of this study was to assess the usefulness of serial bone scintigraphy in the detection of skeletal and extraskeletal metastases in dogs with appendicular osteosarcoma. Twenty-six dogs with primary, appendicular osteosarcoma were entered into a limb-sparing protocol. Bone scintigraphy was performed upon presentation, after neoadjuvant therapy but prior to surgery and at selective intervals after limb-sparing surgery to evaluate for the presence of metastasis. Thoracic radiographs, and radiographs of other sites, were also made at the time of each bone scan. All dogs had a complete necropsy. No dog had bone or lung metastases detected prior to treatment. The bone scans, medical records, and radiographs of each dog were reviewed retrospectively. All but one dog developed metastatic disease. Bone metastatic sites were confirmed at necropsy in 12 of the 26 dogs. Seven of these 12 dogs had bone metastatic sites which were not producing clinical signs, i.e. an occult metastasis. In five of the seven dogs, the occult site was the first metastatic site detected. Extraskeletal metastases were identified scintigraphically in six of the 26 dogs, but these were clinically apparent prior to bone scintigraphy in each dog. Suspected malignant scintigraphic lesions were proven benign in six dogs. In five dogs with malignant bone lesions at necropsy the last bone scan prior to euthanasia was normal. The time interval between scintigraphy and necropsy was variable in these five dogs. All dogs without bone metastases at necropsy had normal bone scans. This study validates the usefulness of bone scintigraphy for detection of occult bone metastasis and improved ability for tumor staging in dogs with appendicular osteosarcoma

  5. Intraparenchymal Hemorrhage due to Brain Metastasis of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Rafael Sartori Balbinot

    2017-09-01

    Full Text Available Although extrahepatic metastases from hepatocellular carcinoma (HCC are present in only 5–15% of cases, they are certainly factors associated with poor prognosis. The main sites include lung, lymph nodes, bones, and adrenal glands, in descending order. Metastasis in the central nervous system is extremely rare, and the incidences vary from 0.6 to 1.7%. We report a case of a 54-year-old man previously diagnosed with alcohol-induced cirrhosis of the liver and HCC. The patient was admitted presenting progressive left hemiparesis and headache which started 2 days earlier, with no history of cranioencephalic trauma. After admission, cranial computed tomography revealed an intraparenchymal hemorrhage area with surrounding edema in the right frontal lobe. An angioresonance requested showed a large extra-axial mass lesion located in the right frontal region with well-defined contours and predominantly hypointense signal on T2 sequence. At first, the radiological findings suggested meningioma as the first diagnostic hypothesis. However, the patient underwent surgery. The tumor was completely removed, and the morphological and immunohistochemical findings were consistent with metastatic hepatocarcinoma associated with meningioma. In postoperative care, the patient did not recover from the left hemiparesis and manifested Broca’s aphasia. He had a survival time of 24 weeks, presenting acute liver failure as his cause of death. There is a lack of evidence supporting a specific management of patients with brain metastasis from HCC. Furthermore, there are no studies that evaluate different modalities of therapeutics in brain metastasis of HCC due to the rarity of this condition. Therefore, management must be individualized depending on probable prognostic factors in these patients.

  6. Simultaneous bilateral primary spontaneous pneumothorax

    Directory of Open Access Journals (Sweden)

    Arife Zeybek

    2014-04-01

    Full Text Available Simultaneous bilateral primary pneumothorax is a very rare (1.6 / 100,000 and life-threatening condition. Clinical presentation may vary from mild dyspnea to tension pneumothorax. It may be milder particularly in younger patients, but more severe in patients with advanced age, and tube thoracostomy is a life preserver in the latter group. Since mortality and recurrence rates following tube thoracostomy are high, endoscopic approaches to bilateral hemithorax have been reported in literature. Apical wedge resection and pleural procedures are recommended in video thoracoscopy or mini thoracotomy even if no bulla and/or bleb are detected. Bilateral surgical interventions and additional pleural procedures are associated with increased rate of post-operative complications and longer postoperative hospital-stays. As a first-line approach, the surgical method toward any side of lung with air leakage following a previous tube thoracostomy is considered less invasive, especially in younger patients. Here, we present a case of simultaneous bilateral primary spontaneous pneumothorax (SBPSP in a 21-year old male with no history of smoking and chronic pulmonary disease. A unilateral surgical intervention was performed, and no recurrence was observed during 5-year follow up.

  7. Species-Specific Metastasis of Human Tumor Cells in the Severe Combined Immunodeficiency Mouse Engrafted with Human Tissue

    Science.gov (United States)

    Shtivelman, Emma; Namikawa, Reiko

    1995-05-01

    We have attempted to model human metastatic disease by implanting human target organs into the immunodeficient C.B-17 scid/scid (severe combined immunodeficiency; SCID) mouse, creating SCID-hu mice. Preferential metastasis to implants of human fetal lung and human fetal bone marrow occurred after i.v. injection of human small cell lung cancer (SCLC) cells into SCID-hu mice; the homologous mouse organs were spared. Clinically more aggressive variant SCLC cells metastasized more efficiently to human fetal lung implants than did cells from classic SCLC. Metastasis of variant SCLC to human fetal bone marrow was enhanced in SCID-hu mice exposed to γ-irradiation or to interleukin 1α. These data indicate that the SCID-hu mice may provide a model in which to study species- and tissue-specific steps of the human metastatic process.

  8. 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.

  9. Vascular Targeting of a Gold Nanoparticle to Breast Cancer Metastasis.

    Science.gov (United States)

    Peiris, Pubudu M; Deb, Partha; Doolittle, Elizabeth; Doron, Gilad; Goldberg, Amy; Govender, Priya; Shah, Shruti; Rao, Swetha; Carbone, Sarah; Cotey, Thomas; Sylvestre, Meilyn; Singh, Sohaj; Schiemann, William P; Lee, Zhenghong; Karathanasis, Efstathios

    2015-08-01

    The vast majority of breast cancer deaths are due to metastatic disease. Although deep tissue targeting of nanoparticles is suitable for some primary tumors, vascular targeting may be a more attractive strategy for micrometastasis. This study combined a vascular targeting strategy with the enhanced targeting capabilities of a nanoparticle to evaluate the ability of a gold nanoparticle (AuNP) to specifically target the early spread of metastatic disease. As a ligand for the vascular targeting strategy, we utilized a peptide targeting alpha(v) beta(3) integrin, which is functionally linked to the development of micrometastases at a distal site. By employing a straightforward radiolabeling method to incorporate Technetium-99m into the AuNPs, we used the high sensitivity of radionuclide imaging to monitor the longitudinal accumulation of the nanoparticles in metastatic sites. Animal and histological studies showed that vascular targeting of the nanoparticle facilitated highly accurate targeting of micrometastasis in the 4T1 mouse model of breast cancer metastasis using radionuclide imaging and a low dose of the nanoparticle. Because of the efficient targeting scheme, 14% of the injected AuNP deposited at metastatic sites in the lungs within 60 min after injection, indicating that the vascular bed of metastasis is a viable target site for nanoparticles. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  10. Rho kinase inhibitors block melanoma cell migration and inhibit metastasis.

    Science.gov (United States)

    Sadok, Amine; McCarthy, Afshan; Caldwell, John; Collins, Ian; Garrett, Michelle D; Yeo, Maggie; Hooper, Steven; Sahai, Erik; Kuemper, Sandra; Mardakheh, Faraz K; Marshall, Christopher J

    2015-06-01

    There is an urgent need to identify new therapeutic opportunities for metastatic melanoma. Fragment-based screening has led to the discovery of orally available, ATP-competitive AKT kinase inhibitors, AT13148 and CCT129254. These compounds also inhibit the Rho-kinases ROCK 1 and ROCK 2 and we show they potently inhibit ROCK activity in melanoma cells in culture and in vivo. Treatment of melanoma cells with CCT129254 or AT13148 dramatically reduces cell invasion, impairing both "amoeboid-like" and mesenchymal-like modes of invasion in culture. Intravital imaging shows that CCT129254 or AT13148 treatment reduces the motility of melanoma cells in vivo. CCT129254 inhibits melanoma metastasis when administered 2 days after orthotopic intradermal injection of the cells, or when treatment starts after metastases have arisen. Mechanistically, our data suggest that inhibition of ROCK reduces the ability of melanoma cells to efficiently colonize the lungs. These results suggest that these novel inhibitors of ROCK may be beneficial in the treatment of metastasis. ©2015 American Association for Cancer Research.

  11. Penile metastasis from primary cholangiocarcinoma: the first case report.

    Science.gov (United States)

    Pastore, Antonio Luigi; Palleschi, Giovanni; Manfredonia, Giorgia; Maceroni, Piero; Alvaro, Domenico; De Santis, Domenico; Ferretti, Simone; Porta, Natale; Di Cristofano, Claudio; Della Rocca, Carlo; Fuschi, Andrea; Al Salhi, Yazan; Maggioni, Cristina; Moschese, Davide; Petrozza, Vincenzo; Carbone, Antonio

    2013-10-14

    Metastatic penile carcinoma derived from cholangiocarcinoma (CCA) has not been previously reported in the literature. Common metastatic sites for CCA include the regional lymph nodes and adjacent organs. CCAs are not highly vascularised tumours, making hematogenous metastases uncommon. Hematogenous CCA metastases commonly occur at distant organs such as the lungs, adrenal glands, and bones. Median survival for patients with metastatic disease is generally less than 1 year. A 74-year-old Caucasian man consulted us after having undergone penile ultrasonography for pain and increased thickness at the base of the penis after self-examination. The patient presented with a history of hepatitis C-related cirrhosis and intrahepatic CCA, diagnosed 3 years previously. A biopsy of the corpora cavernosa on both sides revealed a carcinoma harbouring the same histological and immunophenotypical features as the primary hepatic lesion. To date, there is no case of penile or urogenital system metastasis from CCA described in the literature. Therefore, this article represents the first case report of penile metastasis from CCA.

  12. Lobular Carcinoma of the Breast whith an Unusual Metastasis

    Directory of Open Access Journals (Sweden)

    Songül Peltek Özer

    2018-04-01

    Full Text Available Invasive lobular carcinoma is the second most common type of invasive breast cancer accounting for approximately 5-10% of all invasive breast carcinomas. The metastatic patterns of lobular and ductal carcinomas are significantly different. Most series report a greater propensity for lobular carcinoma to metastasize to the gastrointestinal tract, gynecological organs and the peritoneum, while ductal carcinoma most frequently relapses in the liver, lungs and the brain. Gastrointestinal system metastases were observed in 6-18%, the most commonly affected organ is the stomach. We aimed to present a female patient who had been diagnosed with invasive lobular carcinoma of the breast ten years ago and had invasive ductal carcinoma of the other breast three years ago, investigated for excessive ascites and found to have invasive lobular breast carcinoma metastasis to the stomach.

  13. Spontaneous Appendicocutaneous Fistula I

    African Journals Online (AJOL)

    M T0k0de* MB, BS and. Dr 0. A. AWOj0bi+ FMCS (Nig). ABSTRACT. Ruptured appendicitis is not a common cause of spontaneous enterocutaneous fistula. A case of ruptured retrocaecal appendicitis presenting as an enterocutaneous fistula in a Nigerian woman is presented. The literature on this disorder is also reviewed.

  14. [Spontaneous bacterial peritonitis].

    Science.gov (United States)

    Strauss, Edna; Caly, Wanda Regina

    2003-01-01

    Spontaneous bacterial peritonitis occurs in 30% of patients with ascites due to cirrhosis leading to high morbidity and mortality rates. The pathogenesis of spontaneous bacterial peritonitis is related to altered host defenses observed in end-stage liver disease, overgrowth of microorganisms, and bacterial translocation from the intestinal lumen to mesenteric lymph nodes. Clinical manifestations vary from severe to slight or absent, demanding analysis of the ascitic fluid. The diagnosis is confirmed by a number of neutrophils over 250/mm3 associated or not to bacterial growth in culture of an ascites sample. Enterobacteriae prevail and Escherichia coli has been the most frequent bacterium reported. Mortality rates decreased markedly in the last two decades due to early diagnosis and prompt antibiotic treatment. Third generation intravenous cephalosporins are effective in 70% to 95% of the cases. Recurrence of spontaneous bacterial peritonitis is common and can be prevented by the continuous use of oral norfloxacin. The development of bacterial resistance demands the search for new options in the prophylaxis of spontaneous bacterial peritonitis; probiotics are a promising new approach, but deserve further evaluation. Short-term antibiotic prophylaxis is recommended for patients with cirrhosis and ascites shortly after an acute episode of gastrointestinal bleeding.

  15. Spontaneous Grammar Explanations.

    Science.gov (United States)

    Tjoo, Hong Sing; Lewis, Marilyn

    1998-01-01

    Describes one New Zealand university language teacher's reflection on her own grammar explanations to university-level students of Bahasa Indonesian. Examines form-focused instruction through the teacher's spontaneous answers to students' questions about the form of the language they are studying. The teacher's experiences show that it takes time…

  16. EDITORIAL SPONTANEOUS BACTERIAL PERITONITIS ...

    African Journals Online (AJOL)

    hi-tech

    Spontaneous bacterial peritonitis (SBP) frequent]y occurs in patients with liver cirrhosis and ascites. It is defined as an infection of previously sterile ascitic fluid without any demonstrable intrabdominal source of infection. It is now internationally agreed that a polymorphonuclear (PMN) cell count in the ascitic fluid of over 250 ...

  17. Spontaneous dimensional reduction?

    Science.gov (United States)

    Carlip, Steven

    2012-10-01

    Over the past few years, evidence has begun to accumulate suggesting that spacetime may undergo a "spontaneous dimensional reduction" to two dimensions near the Planck scale. I review some of this evidence, and discuss the (still very speculative) proposal that the underlying mechanism may be related to short-distance focusing of light rays by quantum fluctuations.

  18. Combined immunohistochemistry of β-catenin, cytokeratin 7, and cytokeratin 20 is useful in discriminating primary lung adenocarcinomas from metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Tokumoto Noriaki

    2006-02-01

    Full Text Available Abstract Background It is important to discriminate between primary and secondary lung cancer. However, often, the discriminating diagnosis of primary lung acinar adenocarcinoma and lung metastasis of colorectal cancer based on morphological and pathological findings is difficult. The purpose of this study was to evaluate the clinical usefulness of immunohistochemistry of β-catenin, cytokeratin (CK 7, and CK20 for the discriminating diagnosis of lung cancer. Methods We performed immunohistochemistry of β-catenin, CK7, and CK20 in 19 lung metastasis of colorectal cancer samples, 10 corresponding primary colorectal cancer samples and 11 primary lung acinar adenocarcinoma samples and compared the levels of accuracy of the discriminating diagnosis by using antibodies against these antigens. Results Positive staining of β-catenin was observed in all the lung metastasis of colorectal cancer samples as well as in the primary colorectal cancer samples but in none of the primary lung acinar adenocarcinoma samples. Positive staining of CK7 was observed in 90.9% of the primary lung acinar adenocarcinoma samples and in 5.3% of the lung metastasis of colorectal cancer samples, but in none of the primary colorectal cancer samples. Positive staining of CK20 was observed in all the primary colorectal cancer samples and in 84.2% of the lung metastasis of colorectal cancer samples, but in none of the primary lung acinar adenocarcinoma samples. Conclusion Combined immunohistochemistry of β-catenin, CK7, and CK20 is useful for making a discriminating diagnosis between lung metastasis of colorectal cancer and primary lung acinar adenocarcinoma. This method will enable accurate diagnosis of a lung tumor and will be useful for selecting appropriate therapeutic strategies, including chemotherapeutic agents and operation methods.

  19. Inducing of complete necrosis of recurred lung cancer by cryoablation; A case report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sun Hye; Ham, Soo Youn; Hwang, Sung Ho; Oh, Yu Hwan [Dept. of Radiology, Korea University Anam Hospital, College of Medicine, Korea University, Seoul (Korea, Republic of)

    2016-12-15

    Lung cancer is one of the most commonly diagnosed cancers, and the lungs are a common site of metastasis from extrathoracic malignancies. Surgical resection is the gold standard treatment for lung malignancies. However, some of the patients are poor surgical candidates due to various reasons. Currently, image-guided ablation is used as one of the lung cancer treatment modalities. Cryoablation has been adapted as one of the treatments of lung tumors and a growing body of literature has shown that it is a safe and effective option. We report a case of successful cryoablation for a metastatic lesion from surgically resected primary lung cancer.

  20. Lung scintigraphy

    International Nuclear Information System (INIS)

    Dalenz, Roberto.

    1994-01-01

    A review of lung scintigraphy, perfusion scintigraphy with SPECT, lung ventilation SPECT, blood pool SPECT. The procedure of lung perfusion studies, radiopharmaceutical, administration and clinical applications, imaging processing .Results encountered and evaluation criteria after Biello and Pioped. Recommendations and general considerations have been studied about relation of this radiopharmaceutical with other pathologies

  1. Lung transplant

    Science.gov (United States)

    ... transplant surgery include: You are placed on the heart-lung machine. One or both of your lungs are removed. For people who are having a double lung transplant, most or all of the steps from the first side are completed before the second side is ...

  2. Establishment and characterization of a new human pancreatic adenocarcinoma cell line with high metastatic potential to the lung

    International Nuclear Information System (INIS)

    Kalinina, Tatyana; Simon, Ronald; Otto, Benjamin; Dierlamm, Judith; Schwarzenbach, Heidi; Effenberger, Katharina E; Bockhorn, Maximilian; Izbicki, Jakob R; Yekebas, Emre F; Güngör, Cenap; Thieltges, Sabrina; Möller-Krull, Maren; Murga Penas, Eva Maria; Wicklein, Daniel; Streichert, Thomas; Schumacher, Udo; Kalinin, Viacheslav

    2010-01-01

    Pancreatic cancer is still associated with devastating prognosis. Real progress in treatment options has still not been achieved. Therefore new models are urgently needed to investigate this deadly disease. As a part of this process we have established and characterized a new human pancreatic cancer cell line. The newly established pancreatic cancer cell line PaCa 5061 was characterized for its morphology, growth rate, chromosomal analysis and mutational analysis of the K-ras, EGFR and p53 genes. Gene-amplification and RNA expression profiles were obtained using an Affymetrix microarray, and overexpression was validated by IHC analysis. Tumorigenicity and spontaneous metastasis formation of PaCa 5061 cells were analyzed in pfp -/- /rag2 -/- mice. Sensitivity towards chemotherapy was analysed by MTT assay. PaCa 5061 cells grew as an adhering monolayer with a doubling time ranging from 30 to 48 hours. M-FISH analyses showed a hypertriploid complex karyotype with multiple numerical and unbalanced structural aberrations. Numerous genes were overexpressed, some of which have previously been implicated in pancreatic adenocarcinoma (GATA6, IGFBP3, IGFBP6), while others were detected for the first time (MEMO1, RIOK3). Specifically highly overexpressed genes (fold change > 10) were identified as EGFR, MUC4, CEACAM1, CEACAM5 and CEACAM6. Subcutaneous transplantation of PaCa 5061 into pfp -/- /rag2 -/- mice resulted in formation of primary tumors and spontaneous lung metastasis. The established PaCa 5061 cell line and its injection into pfp -/- /rag2 -/- mice can be used as a new model for studying various aspects of the biology of human pancreatic cancer and potential treatment approaches for the disease

  3. The Cancer Cell Oxygen Sensor PHD2 Promotes Metastasis via Activation of Cancer-Associated Fibroblasts

    Directory of Open Access Journals (Sweden)

    Anna Kuchnio

    2015-08-01

    Full Text Available Several questions about the role of the oxygen sensor prolyl-hydroxylase 2 (PHD2 in cancer have not been addressed. First, the role of PHD2 in metastasis has not been studied in a spontaneous tumor model. Here, we show that global PHD2 haplodeficiency reduced metastasis without affecting tumor growth. Second, it is unknown whether PHD2 regulates cancer by affecting cancer-associated fibroblasts (CAFs. We show that PHD2 haplodeficiency reduced metastasis via two mechanisms: (1 by decreasing CAF activation, matrix production, and contraction by CAFs, an effect that surprisingly relied on PHD2 deletion in cancer cells, but not in CAFs; and (2 by improving tumor vessel normalization. Third, the effect of concomitant PHD2 inhibition in malignant and stromal cells (mimicking PHD2 inhibitor treatment is unknown. We show that global PHD2 haplodeficiency, induced not only before but also after tumor onset, impaired metastasis. These findings warrant investigation of PHD2’s therapeutic potential.

  4. Colorectal cancer presenting as bone metastasis

    Directory of Open Access Journals (Sweden)

    M C Suresh Babu

    2017-01-01

    Conclusions: In this study, the patients of colorectal cancer presenting with bone metastasis were of male sex and younger age. The factors that were associated with reduced survival were extraosseous and liver involvement.

  5. Leptomeningeal metastasis mimicking Chronic Subdural Hematoma

    OpenAIRE

    Jain Saurabh

    2017-01-01

    The presentation of Leptomeningeal Metastasis varies widely. It can also present a condition very similar to Chronic Subdural Hematoma. One should have a low threshold for suspicion while diagnosing such conditions to avoid catastrophic events.

  6. Leptomeningeal metastasis mimicking Chronic Subdural Hematoma

    Directory of Open Access Journals (Sweden)

    Jain Saurabh

    2017-12-01

    Full Text Available The presentation of Leptomeningeal Metastasis varies widely. It can also present a condition very similar to Chronic Subdural Hematoma. One should have a low threshold for suspicion while diagnosing such conditions to avoid catastrophic events.

  7. Molecular biology of breast cancer metastasis: Genetic regulation of human breast carcinoma metastasis

    International Nuclear Information System (INIS)

    Welch, Danny R; Steeg, Patricia S; Rinker-Schaeffer, Carrie W

    2000-01-01

    The present is an overview of recent data that describes the genetic underpinnings of the suppression of cancer metastasis. Despite the explosion of new information about the genetics of cancer, only six human genes have thus far been shown to suppress metastasis functionally. Not all have been shown to be functional in breast carcinoma. Several additional genes inhibit various steps of the metastatic cascade, but do not necessarily block metastasis when tested using in vivo assays. The implications of this are discussed. Two recently discovered metastasis suppressor genes block proliferation of tumor cells at a secondary site, offering a new target for therapeutic intervention

  8. MiR-876-5p suppresses epithelial–mesenchymal transition of lung ...

    Indian Academy of Sciences (India)

    Liang Bao

    2017-11-07

    Nov 7, 2017 ... in lung cancer cells and patient tissues. Luciferase activity assay was ... Bone morphogenetic protein 4; epithelial-mesenchymal transition; lung cancer; metastasis; microRNA-876-5p. 1. Introduction ..... -UTR of BMP-4 mRNAs were cloned at the downstream of a luciferase reporter gene (Luci). (C) Levels of ...

  9. Spontaneous healing of spontaneous coronary artery dissection.

    Science.gov (United States)

    Almafragi, Amar; Convens, Carl; Heuvel, Paul Van Den

    2010-01-01

    Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome and sudden cardiac death. It should be suspected in every healthy young woman without cardiac risk factors, especially during the peripartum or postpartum periods. It is important to check for a history of drug abuse, collagen vascular disease or blunt trauma of the chest. Coronary angiography is essential for diagnosis and early management. We wonder whether thrombolysis might aggravate coronary dissection. All types of treatment (medical therapy, percutaneous intervention or surgery) improve the prognosis without affecting survival times if used appropriately according to the clinical stability and the angiographic features of the involved coronary arteries. Prompt recognition and targeted treatment improve outcomes. We report a case of SCAD in a young female free of traditional cardiovascular risk factors, who presented six hours after thrombolysis for ST elevation myocardial infarction. Coronary angiography showed a dissection of the left anterior descending and immediate branch. She had successful coronary artery bypass grafting, with complete healing of left anterior descending dissection.

  10. Spontaneous conventional osteosarcoma transformation of a chondroblastoma: A case report and literature review

    Directory of Open Access Journals (Sweden)

    Prashant Narhari

    2018-01-01

    Full Text Available Chondroblastomas are a primary benign cartilaginous tumor that accounts for approximately 1% of all benign bone tumors. Primarily they are treated by curettage. The patient presented 4 years after a successfully treated chondroblastoma (curettage and Bone cement. Wide resection of the proximal tibia with endoprosthesis replacement was done. Lung CT showed multiple lung metastasis and despite starting chemotherapy, he succumbed to the disease. We discuss regarding the possibilities of “aggressive” chondroblastoma and more recently termed chondroblastoma-like osteosarcoma which is a separate entity from chondroblastoma. Aggressiveness in chondroblastoma can be 1 of 3 types as follows: 1. benign chondroblastoma with lung metastasis. 2. malignant chondroblastoma. 3. subsequent malignant transformation of benign chondroblastoma. We have attempted to review the literature and describe the “aggressive” chondroblastoma and chondroblastoma-like osteosarcoma in this report.

  11. Bilateral Spontaneous Pneumothorax in Chronic Silicosis: A Case Report

    Directory of Open Access Journals (Sweden)

    Pritinanda Mishra

    2014-01-01

    Full Text Available Silicosis is an occupational lung disease caused by inhalation of crystalline silica. People working in occupations like sandblasting, surface drilling, tunneling, silica flour milling, ceramic making, and so forth are predisposed to develop silicosis. Crystalline forms of silica are more fibrogenic than the amorphous forms, highlighting the importance of the physical form in pathogenesis. Lung biopsy is rarely performed for the diagnosis of silicosis as it can easily be detected by occupational history and radiological features. Patients with silicosis can develop complications like tuberculosis, lung cancer, progressive massive fibrosis, cor pulmonale, broncholithiasis, or tracheobronchial compression by lymph nodes. Pleural involvement in silicosis is rare. Spontaneous pneumothorax is a pleural complication that can develop in such patients. Usually in silicosis pneumothorax is unilateral. We hereby report the lung biopsy findings and discuss the mechanism of pneumothorax development in a case of chronic silicosis who, later on died during the course of the disease.

  12. NM23 deficiency promotes metastasis in a UV radiation-induced mouse model of human melanoma.

    Science.gov (United States)

    Jarrett, Stuart G; Novak, Marian; Harris, Nathan; Merlino, Glenn; Slominski, Andrezj; Kaetzel, David M

    2013-01-01

    Cutaneous malignant melanoma is the most lethal form of skin cancer, with 5-year survival rates of melanoma are not well understood, in part due to a paucity of animal models that accurately recapitulate the disease in its advanced forms. We have employed a transgenic mouse strain harboring a tandem deletion of the nm23-m1 and nm23-m2 genes to assess the combined contribution of these genes to suppression of melanoma metastasis. Crossing of the nm23-h1/nm23-h2 knockout in hemizygous-null form ([m1m2](+/-)) to a transgenic mouse strain (hepatocyte growth factor/scatter factor-overexpressing, or HGF(+) strain) vulnerable to poorly-metastatic, UVR-induced melanomas resulted in UVR-induced melanomas with high metastatic potential. Metastasis to draining lymph nodes was seen in almost all cases of back skin melanomas, while aggressive metastasis to lung, thoracic cavity, liver and bone also occurred. Interestingly, no differences were observed in the invasive characteristics of primary melanomas of HGF(+) and HGF(+) × [m1m2](+/-) strains, with both exhibiting invasion into the dermis and subcutis, indicating factors other than simple invasive activity were responsible for metastasis of HGF(+) × [m1m2](+/-) melanomas. Stable cell lines were established from the primary and metastatic melanoma lesions from these mice, with HGF(+) × [m1m2](+/-) lines exhibiting increased single cell migration and genomic instability. These studies demonstrate for the first time in vivo a potent metastasis suppressor activity of NM23 in UVR-induced melanoma, and have provided new tools for identifying molecular mechanisms that underlie melanoma metastasis.

  13. Metastasis of tumor cells is enhanced by downregulation of Bit1.

    Directory of Open Access Journals (Sweden)

    Priya Prakash Karmali

    Full Text Available Resistance to anoikis, which is defined as apoptosis induced by loss of integrin-mediated cell attachment to the extracellular matrix, is a determinant of tumor progression and metastasis. We have previously identified the mitochondrial Bit1 (Bcl-2 inhibitor of transcription protein as a novel anoikis effector whose apoptotic function is independent from caspases and is uniquely controlled by integrins. In this report, we examined the possibility that Bit1 is suppressed during tumor progression and that Bit1 downregulation may play a role in tumor metastasis.Using a human breast tumor tissue array, we found that Bit1 expression is suppressed in a significant fraction of advanced stages of breast cancer. Targeted disruption of Bit1 via shRNA technology in lowly aggressive MCF7 cells conferred enhanced anoikis resistance, adhesive and migratory potential, which correlated with an increase in active Extracellular kinase regulated (Erk levels and a decrease in Erk-directed phosphatase activity. These pro-metastasis phenotypes were also observed following downregulation of endogenous Bit1 in Hela and B16F1 cancer cell lines. The enhanced migratory and adhesive potential of Bit1 knockdown cells is in part dependent on their high level of Erk activation since down-regulating Erk in these cells attenuated their enhanced motility and adhesive properties. The Bit1 knockdown pools also showed a statistically highly significant increase in experimental lung metastasis, with no differences in tumor growth relative to control clones in vivo using a BALB/c nude mouse model system. Importantly, the pulmonary metastases of Bit1 knockdown cells exhibited increased phospho-Erk staining.These findings indicate that downregulation of Bit1 conferred cancer cells with enhanced anoikis resistance, adhesive and migratory properties in vitro and specifically potentiated tumor metastasis in vivo. These results underscore the therapeutic importance of restoring Bit1

  14. Radioimmunoscintigraphy in lung cancer diagnosing

    International Nuclear Information System (INIS)

    Hadjikostova, H.

    1999-01-01

    As the lung cancer is the leading cause of death from cancer at males, the exact staging is essential. Monoclonal antibodies marked with radionuclides like 131 I, 111 In, 99m Tc, etc., allow detecting and staging the small cell lung cancer with sensibility 90%, specificity 45% and accuracy 85%. It is suggested this method to be applied simultaneously with computerized tomography. The diagnostic possibility of radioimmunoscintigraphy (RIS) in earlier detection, recurrence or metastasis as well as follow up the effect of therapy performed at patients with lung cancer are reviewed. RIS is performed with IODOMAB-R-2 (Sorin Biomedica) 131 I antiCEA Mob F(ab') 2 , dose 92.5-185 MBq. Planar images were performed 72 hours after i.v. injection. Four patients with epidermoid squamous cell cancer were examined. Positive results were obtained at 3 patients and one false negative. In general sensitivity of radioimmunoscintigraphy of lung cancer is 75-90%. However there are difficulties at its application linked with necessity of permanent availability of radiolabelled antibodies with high specific activity at the moment of their injection. Despite all radioimmunoscintigraphy is developing as an useful diagnostic method for evaluation and follow up of lung cancer patients

  15. Breast carcinoma metastasis to the lacrimal gland

    DEFF Research Database (Denmark)

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

    2015-01-01

    tomography scans revealed irregular lacrimal gland tumours in the two patients. The two patients had history of breast cancer. The first breast cancer metastasis in the lacrimal gland demonstrated a cribriform growth pattern containing ductal elements. The epithelial tumour cells stained positive...... 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....

  16. A large solitary liver metastasis of thymoma

    International Nuclear Information System (INIS)

    Kang, Si Won; Shinn, Kyung Sub

    1997-01-01

    Extrathoracic metastasis of a thymoma is rare ; we report a case of metastasis to the liver of a large solitary thymoma. Biopsy of the mass showed it to be predominantly lymphocytic and histologically the same as a primary thymoma operated on four years previously. On ultrasound and CT scan, the majority of the metastatic tumor was hemorrhagic, necrotic and/or cystic, with a peripheral, irregularly thick solid component and rather thin, smooth encapsulation

  17. A large solitary liver metastasis of thymoma

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Si Won; Shinn, Kyung Sub [Catholic Univ. College of Medicine, Seoul (Korea, Republic of)

    1997-01-01

    Extrathoracic metastasis of a thymoma is rare ; we report a case of metastasis to the liver of a large solitary thymoma. Biopsy of the mass showed it to be predominantly lymphocytic and histologically the same as a primary thymoma operated on four years previously. On ultrasound and CT scan, the majority of the metastatic tumor was hemorrhagic, necrotic and/or cystic, with a peripheral, irregularly thick solid component and rather thin, smooth encapsulation.

  18. Spontaneous spinal epidural abscess.

    LENUS (Irish Health Repository)

    Ellanti, P

    2011-10-01

    Spinal epidural abscess is an uncommon entity, the frequency of which is increasing. They occur spontaneously or as a complication of intervention. The classical triad of fever, back pain and neurological symptoms are not always present. High index of suspicion is key to diagnosis. Any delay in diagnosis and treatment can have significant neurological consequences. We present the case of a previously well man with a one month history of back pain resulting from an epidural abscess.

  19. Multiple cystic lung disease in an adolescent boy | Sogut | Pan ...

    African Journals Online (AJOL)

    CT scanning of thorax is more sensitive than chest radiography in the detection and the distribution of lung cysts. Patients with cystic lung disease may be asymptomatic or present with nonspecific symptoms, such as chronic cough or shortness of breath. They are at increased risk for spontaneous pneumothorax. Surgical ...

  20. Uterine cervical cancer with brain metastasis as the initial site of presentation.

    Science.gov (United States)

    Sato, Yumi; Tanaka, Kei; Kobayashi, Yoichi; Shibuya, Hiromi; Nishigaya, Yoshiko; Momomura, Mai; Matsumoto, Hironori; Iwashita, Mitsutoshi

    2015-07-01

    Brain metastasis from uterine cervical cancer is rare, with an incidence of 0.5%, and usually occurs late in the course of the disease. We report a case of uterine cervical cancer with brain metastasis as the initial site of presentation. A 50-year-old woman with headache, vertigo, amnesia and loss of appetite was admitted for persistent vomiting. Contrast enhanced computed tomography showed a solitary right frontal cerebral lesion with ring enhancement and uterine cervical tumor. She was diagnosed with uterine cervical squamous cell carcinoma with parametrium invasion and no other distant affected organs were detected. The cerebral lesion was surgically removed and pathologically proved to be metastasis of uterine cervical squamous cell carcinoma. The patient underwent concurrent chemoradiotherapy, followed by cerebral radiation therapy, but multiple metastases to the liver and lung developed and the patient died 7 months after diagnosis of brain metastasis. © 2015 The Authors. Journal of Obstetrics and Gynaecology Research © 2015 Japan Society of Obstetrics and Gynecology.

  1. FOXA2 suppresses the metastasis of hepatocellular carcinoma partially through matrix metalloproteinase-9 inhibition.

    Science.gov (United States)

    Wang, Jian; Zhu, Chang-Peng; Hu, Ping-Fang; Qian, Hui; Ning, Bei-Fang; Zhang, Qing; Chen, Fei; Liu, Jiao; Shi, Bin; Zhang, Xin; Xie, Wei-Fen

    2014-11-01

    The forkhead box transcription factor A2 (FOXA2) is a member of the hepatocyte nuclear factor family and plays an important role in liver development and metabolic homeostasis, but its role in the metastasis of hepatocellular carcinoma (HCC) has not been evaluated. In this study, we found that the expression of FOXA2 was decreased in 68.1% (49/72) of human HCC tissues compared with their paired non-cancerous adjacent tissues. Clinicopathological analysis revealed that reduced FOXA2 expression was correlated with aggressive characteristics (venous invasion, poor differentiation, high tumor node metastasis grade). FOXA2 level was even lower in portal vein tumor thrombus compared with primary tumor tissues and correlated with epithelial-mesenchymal transition in HCC cells. Overexpression of FOXA2 inhibited migration and invasion of Focus cells, whereas knockdown of FOXA2 in HepG2 showed the opposite effect. Moreover, upregulation of FOXA2 suppressed HCC metastasis to bone, brain and lung in two distinct mouse models. Finally, we proved that FOXA2 repressed the transcription of matrix metalloproteinase (MMP)-9 and exerted its antimetastasis effect partially through downregulation of MMP-9. In conclusion, our findings indicate that FOXA2 plays a critical role in HCC metastasis and may serve as a novel therapeutic target for HCC. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. A Rare Thyroid Metastasis from Uveal Melanoma and Response to Immunotherapy Agents

    Directory of Open Access Journals (Sweden)

    Dearbhaile Catherine Collins

    2016-01-01

    Full Text Available Thyroid metastasis is a rare occurrence with cutaneous melanoma and even more uncommon with uveal melanoma. The management of such metastasis is uncertain due to its infrequency and, in the era of immunotherapy, the effect of these novel drugs on uncommon metastasis, such as to the thyroid, is unknown. We report the rare case of a thyroid metastasis in a patient diagnosed with ocular melanoma initially managed with enucleation. Metastatic disease developed in the lung and thyroid gland. The case patient received the immunotherapy ipilimumab with stable disease in the thyroid and progressive disease elsewhere. The patient was then further treated with a second immunotherapy agent, pembrolizumab, and remains with stable disease one year later. We discuss the current literature on thyroid metastases from all causes and the optimal known management strategies. Furthermore, we provide an original report on the response of this disease to the novel immunomodulators, ipilimumab, and pembrolizumab with stable disease four years after initial diagnosis of ocular melanoma.

  3. ADAM15 expression is downregulated in melanoma metastasis compared to primary melanoma

    International Nuclear Information System (INIS)

    Ungerer, Christopher; Doberstein, Kai; Buerger, Claudia; Hardt, Katja; Boehncke, Wolf-Henning; Boehm, Beate; Pfeilschifter, Josef; Dummer, Reinhard; Mihic-Probst, Daniela; Gutwein, Paul

    2010-01-01

    Research highlights: → Strong ADAM15 expression is found in normal melanocytes. → ADAM15 expression is significantly downregulated in patients with melanoma metastasis. → TGF-β can downregulate ADAM15 expression in melanoma cells. → Overexpression of ADAM15 in melanoma cells inhibits migration, proliferation and invasion of melanoma cells. → Conclusion: ADAM15 represents an tumor suppressor protein in melanoma. -- Abstract: In a mouse melanoma metastasis model it has been recently shown that ADAM15 overexpression in melanoma cells significantly reduced the number of metastatic nodules on the lung. Unfortunately, the expression of ADAM15 in human melanoma tissue has not been determined so far. In our study, we characterized the expression of ADAM15 in tissue micro-arrays of patients with primary melanoma with melanoma metastasis. ADAM15 was expressed in melanocytes and endothelial cells of benign nevi and melanoma tissue. Importantly, ADAM15 was significantly downregulated in melanoma metastasis compared to primary melanoma. We further demonstrate that IFN-γ and TGF-β downregulate ADAM15 protein levels in melanoma cells. To investigate the role of ADAM15 in melanoma progression, we overexpressed ADAM15 in melanoma cells. Importantly, overexpression of ADAM15 in melanoma cells reduced the migration, invasion and the anchorage dependent and independent cell growth of melanoma cells. In summary, the downregulation of ADAM15 plays an important role in melanoma progression and ADAM15 act as a tumorsuppressor in melanoma.

  4. ADAM15 expression is downregulated in melanoma metastasis compared to primary melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Ungerer, Christopher; Doberstein, Kai [Pharmazentrum Frankfurt/ZAFES, University Hospital Goethe University Frankfurt, Frankfurt am Main (Germany); Buerger, Claudia; Hardt, Katja; Boehncke, Wolf-Henning [Department of Dermatology, Clinic of the Goethe-University, Theodor-Stern-Kai, Frankfurt (Germany); Boehm, Beate [Division of Rheumatology, Goethe University, Frankfurt am Main (Germany); Pfeilschifter, Josef [Pharmazentrum Frankfurt/ZAFES, University Hospital Goethe University Frankfurt, Frankfurt am Main (Germany); Dummer, Reinhard [Department of Pathology, Institute of Surgical Pathology, University Hospital, Zurich (Switzerland); Mihic-Probst, Daniela [Department of Dermatology, University Hospital Zurich (Switzerland); Gutwein, Paul, E-mail: p.gutwein@med.uni-frankfurt.de [Pharmazentrum Frankfurt/ZAFES, University Hospital Goethe University Frankfurt, Frankfurt am Main (Germany)

    2010-10-22

    Research highlights: {yields} Strong ADAM15 expression is found in normal melanocytes. {yields} ADAM15 expression is significantly downregulated in patients with melanoma metastasis. {yields} TGF-{beta} can downregulate ADAM15 expression in melanoma cells. {yields} Overexpression of ADAM15 in melanoma cells inhibits migration, proliferation and invasion of melanoma cells. {yields} Conclusion: ADAM15 represents an tumor suppressor protein in melanoma. -- Abstract: In a mouse melanoma metastasis model it has been recently shown that ADAM15 overexpression in melanoma cells significantly reduced the number of metastatic nodules on the lung. Unfortunately, the expression of ADAM15 in human melanoma tissue has not been determined so far. In our study, we characterized the expression of ADAM15 in tissue micro-arrays of patients with primary melanoma with melanoma metastasis. ADAM15 was expressed in melanocytes and endothelial cells of benign nevi and melanoma tissue. Importantly, ADAM15 was significantly downregulated in melanoma metastasis compared to primary melanoma. We further demonstrate that IFN-{gamma} and TGF-{beta} downregulate ADAM15 protein levels in melanoma cells. To investigate the role of ADAM15 in melanoma progression, we overexpressed ADAM15 in melanoma cells. Importantly, overexpression of ADAM15 in melanoma cells reduced the migration, invasion and the anchorage dependent and independent cell growth of melanoma cells. In summary, the downregulation of ADAM15 plays an important role in melanoma progression and ADAM15 act as a tumorsuppressor in melanoma.

  5. Role of surgery in breast metastasis from carcinoma of the cervix

    Directory of Open Access Journals (Sweden)

    Parveen Yadav

    2011-01-01

    Full Text Available Carcinoma of the cervix is the most common malignancy among women in India. Although metastatic disease is common, metastasis to breast is rare. A limited number of case reports are published in the world literature. Most of the previous reports of metastatic cervical carcinoma to breast are either autopsy series or widely disseminated disease where no treatment options were available. A rare case of cervical carcinoma presenting as metastasis in breast is reported here where palliative mastectomy improved the general condition of the patient. A female patient aged 58 years was diagnosed and treated for cervical carcinoma, FIGO stage 2B. Four months after the treatment which included both external beam and intracavitory radiotherapy, the patient presented with breast and lung metastasis. Palliative mastectomy was done which improved the general condition of the patient. Metastatic carcinoma of the cervix can present as a case of breast carcinoma. In an appropriate setting, this possibility should be kept in mind. Palliative mastectomy should be offered for patients of cervical carcinoma with metastasis to breast when needed.

  6. Anaplastic carcinoma of thyroid gland with widespread soft tissue metastasis: an unusual presentation.

    Science.gov (United States)

    Hassan, Muhammad; Janjua, Taimoor Khalid; Afridi, Hira Khan; Zahid, Naila Anjum

    2017-07-13

    Anaplastic thyroid cancer is the rarest tumour of the thyroid gland, representing only 2% of clinically recognised thyroid cancers. The most common metastatic sites are lungs, followed by the intrathoracic and neck lymph nodes. We report the case of a 62-year-old woman who presented to our setting with multiple soft tissue nodules, thyroid mass, head swelling and weight loss. Radiological investigation showed a large thyroid mass with widespread metastasis in subcutaneous tissues of both upper limbs, chest and abdomen. Metastasis was also found in lungs, skull and adrenal glands after which the patient was diagnosed with stage IVc anaplastic thyroid carcinoma (ATC). After careful consideration of patient's clinical condition with multiple poor prognostic factors, medical therapy was withheld and she was discharged on hospice care. The patient expired after 1 month. In ATC, metastasis to subcutaneous tissue is an extremely rare occurrence of which there is hardly any evidence in literature. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  7. Dietary supplementation with secoisolariciresinol diglycoside (SDG) reduces experimental metastasis of melanoma cells in mice.

    Science.gov (United States)

    Li, D; Yee, J A; Thompson, L U; Yan, L

    1999-07-19

    We investigated the effect of dietary supplementation with secoisolariciresinol diglycoside (SDG), a lignan precursor isolated from flaxseed, on experimental metastasis of B16BL6 murine melanoma cells in C57BL/6 mice. Four diets were compared: a basal diet (control group) and the basal diet supplemented with SDG at 73, 147 or 293 micromol/kg (equivalent to SDG provided in the 2.5, 5 or 10% flaxseed diet). Mice were fed the diet for 2 weeks before and after an intravenous injection of 0.6 x 10(5) tumor cells. At necropsy, the number and size of tumors that formed in the lungs were determined. The median number of tumors in the control group was 62, and those in the SDG-supplemented groups were 38, 36 and 29, respectively. The last was significantly different from the control (P SDG at 73, 147 and 293 micromol/kg also decreased tumor size (tumor cross-sectional area and volume) in a dose-dependent manner compared with the control values. These results show that SDG reduced pulmonary metastasis of melanoma cells and inhibited the growth of metastatic tumors that formed in the lungs. It is concluded that dietary supplementation with SDG reduces experimental metastasis of melanoma cells in mice.

  8. Junctional adhesion molecule C (JAM-C) dimerization aids cancer cell migration and metastasis.

    Science.gov (United States)

    Garrido-Urbani, Sarah; Vonlaufen, Alain; Stalin, Jimmy; De Grandis, Maria; Ropraz, Patricia; Jemelin, Stéphane; Bardin, Florence; Scheib, Holger; Aurrand-Lions, Michel; Imhof, Beat A

    2018-04-01

    Most cancer deaths result from metastasis, which is the dissemination of cells from a primary tumor to distant organs. Metastasis involves changes to molecules that are essential for tumor cell adhesion to the extracellular matrix and to endothelial cells. Junctional Adhesion Molecule C (JAM-C) localizes at intercellular junctions as homodimers or more affine heterodimers with JAM-B. We previously showed that the homodimerization site (E66) in JAM-C is also involved in JAM-B binding. Here we show that neoexpression of JAM-C in a JAM-C-negative carcinoma cell line induced loss of adhesive property and pro-metastatic capacities. We also identify two critical structural sites (E66 and K68) for JAM-C/JAM-B interaction by directed mutagenesis of JAM-C and studied their implication on tumor cell behavior. JAM-C mutants did not bind to JAM-B or localize correctly to junctions. Moreover, mutated JAM-C proteins increased adhesion and reduced proliferation and migration of lung carcinoma cell lines. Carcinoma cells expressing mutant JAM-C grew slower than with JAM-C WT and were not able to establish metastatic lung nodules in mice. Overall these data demonstrate that the dimerization sites E66-K68 of JAM-C affected cell adhesion, polarization and migration and are essential for tumor cell metastasis. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Paclitaxel-induced hypothermia and hypoperfusion increase breast cancer metastasis and angiogenesis in mice

    Science.gov (United States)

    Ami, Nozomi; Sato, Hideki; Hayakawa, Yoshihiro

    2018-01-01

    Housing temperature has been shown to influence thermoregulation and behavior of preclinical cancer models; and anti-cancer drugs typically reduce peripheral blood flow and body temperature. In the present study, the effects of paclitaxel (PTX)-induced reduction of body temperature and peripheral blood flow on metastatic 4T1 breast cancer was investigated in a mouse model and the modification of these effects by thermoneutral temperature was also assessed. A single dose of PTX decreased the body temperature and peripheral blood flow in mice housed at a standard temperature (23°C). Furthermore, although lung metastasis and angiogenesis of inoculated 4T1 cells increased in mice pretreated with PTX, mice housed at a thermoneutral temperature (30°C) could compensate their body temperature and peripheral blood flow compared with control mice, and also suppressed 4T1 angiogenesis and metastasis to lung. The present results imply that maintenance of body temperature or efficient energy supply for thermogenesis may prevent tumor relapse or metastasis after chemotherapy. PMID:29434941

  10. Invasive ductal carcinoma within fibroadenoma and lung metastases

    Science.gov (United States)

    Abu-Rahmeh, Zuhair; Nseir, William; Naroditzky, Inna

    2012-01-01

    Fibroadenomas are one of the most common benign tumors of the breast. Malignant transformation from fibroadenoma to cancer is rare. We present a case of an invasive ductal carcinoma within an otherwise benign fibroadenoma with lung metastasis in a 69-year-old woman. PMID:22259257

  11. A Rare Cause of Lung Emphysema: Neurofibromatosis

    Directory of Open Access Journals (Sweden)

    Rasih Yazkan

    2012-10-01

    Full Text Available Neurofibromatosis (NF is an autosomal dominant inheritance or spontaneous mutation disease. Skin, eyes, central and peripheral nervous system lesions are characteristic. It is evaluated NF type 1 and NF type 2. NF-1 is the most common type of the disease, and described by von Recklinghausen in 1882. Cutaneous and subcutaneous neurofibromas, kyphoscoliosis, rib deformities, thoracic neoplasms, bullous, emphysematous and fibrotic changes could be seen on chest wall and lung parenchyma. We aimed to report this case with a rare cause of lung emph-ysema and the effects of the involvement of the NF-1 to the lung parenchyma.

  12. Spontaneous Thigh Compartment Syndrome

    Directory of Open Access Journals (Sweden)

    Khan, Sameer K

    2011-02-01

    Full Text Available A young man presented with a painful and swollen thigh, without any history of trauma, illness, coagulopathic medication or recent exertional exercise. Preliminary imaging delineated a haematoma in the anterior thigh, without any fractures or muscle trauma. Emergent fasciotomies were performed. No pathology could be identified intra-operatively, or on follow-up imaging. A review of thigh compartment syndromes described in literature is presented in a table. Emergency physicians and traumatologists should be cognisant of spontaneous atraumatic presentations of thigh compartment syndrome, to ensure prompt referral and definitive management of this limb-threatening condition. [West J Emerg Med. 2011;12(1:134-138].

  13. Lung Radiofrequency Ablation: Potential as a Therapy to Oligometastasis and Oligo-Recurrence

    OpenAIRE

    Hiraki, Takao; Kanazawa, Susumu

    2012-01-01

    The early results (e.g., patient survival) of RFA for the treatment of patients with NSCLC and pulmonary metastasis from various primary lesions including colorectal cancer, lung cancer, hepatocellular carcinoma, renal cell carcinoma, and sarcoma appear encouraging and suggest the potential to offer long-term survival for the patients with oligo-recurrence or oligometastasis of lung cancer. The usefulness of RFA for oligo-recurrence or oligometastasis of lung cancer should be clarified by pro...

  14. Lung radiofrequency ablation: potential as a therapy to oligometastasis and oligorecurrence.

    Science.gov (United States)

    Hiraki, Takao; Kanazawa, Susumu

    2012-01-01

    The early results (e.g., patient survival) of RFA for the treatment of patients with NSCLC and pulmonary metastasis from various primary lesions including colorectal cancer, lung cancer, hepatocellular carcinoma, renal cell carcinoma, and sarcoma appear encouraging and suggest the potential to offer long-term survival for the patients with oligorecurrence or oligometastasis of lung cancer. The usefulness of RFA for oligorecurrence or oligometastasis of lung cancer should be clarified by prospective studies in the future.

  15. Bone metastasis risk factors in breast cancer

    Science.gov (United States)

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

    2017-01-01

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

  16. Colon Mass as a Secondary Metastasis from Cholangiocarcinoma: A Diagnostic and Therapeutic Dilemma

    Science.gov (United States)

    Niazi, Azfar

    2016-01-01

    Cholangiocarcinoma (bile ducts cancer) is a rare and aggressive form of cancer. It metastasizes frequently to liver, peritoneum, and lungs. Colon metastasis is extremely uncommon. We report here a 70-year-old male who was diagnosed with cholangiocarcinoma for which he underwent a Whipple procedure. Fifteen months later, a CT scan revealed mural thickening in the colon; this was supplemented with a PET scan, which confirmed this mass. Histological diagnosis of metastatic cholangiocarcinoma to the colon was made and the patient was treated with chemotherapy. Although rare, cholangiocarcinoma metastasis can be found in the colon. A high index of suspicion is required to diagnose and treat early. More cases need to be reported to find out further about the prognosis of the disease. PMID:27588228

  17. Progression of choroidal metastasis of ovarian serous cystoadenocarcinoma after intravitreal bevacizumab treatment

    Directory of Open Access Journals (Sweden)

    Victor E. Reviglio

    2013-02-01

    Full Text Available A 57-year-old woman presented to her ophthalmologist because of rapid deterioration in vision. Dilated funduscopic examination of the right eye showed an elevated, yellow-orange choroidal mass temporal to the fovea; a complete retinal detachment was present in the left eye. The patient was referred to an oncologist. Computerized tomography of the brain, thorax, abdomen, and pelvis were obtained. They revealed an 11-mm mass in the right parietal lobe, a 30-mm mass in the left temporal lobe, 23-mm mass in the right kidney, and multiple nodules in both lungs. Supported by published experience with intravitreal bevacizumab for choroidal metastasis, the patient was injected into the vitreous through the pars plana of the left eye. The tumor mass did not show signs of regression and the visual acuity was unchanged. The patient suffered from end-state complications tumor metastasis and expired one month after the invitreal injection.

  18. Combined micro CT and histopathology for evaluation of skeletal metastasis in live animals.

    Science.gov (United States)

    Geffre, Christopher P; Pond, Erika; Pond, Gerald D; Sroka, Isis C; Gard, Jaime M; Skovan, Bethany A; Meek, William E; Landowski, Terry H; Nagle, Raymond B; Cress, Anne E

    2015-01-01

    Bone is a favored site for solid tumor metastasis, especially among patients with breast, lung or prostate carcinomas. Micro CT is a powerful and inexpensive tool that can be used to investigate tumor progression in xenograft models of human disease. Many previous studies have relied on terminal analysis of harvested bones to document metastatic tumor activity. The current protocol uses live animals and combines sequential micro CT evaluation of lesion development with matched histopathology at the end of the study. The approach allows for both rapid detection and evaluation of bone lesion progression in live animals. Bone resident tumors are established either by direct (intraosseous) or arterial (intracardiac) injection, and lesion development is evaluated for up to eight weeks. This protocol provides a clinically relevant method for investigating bone metastasis progression and the development of osteotropic therapeutic strategies for the treatment of bone metastases.

  19. Atypical Distant Metastasis of Breast Malignant Phyllodes Tumors: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Tiphaine de Foucher

    2017-01-01

    Full Text Available Malignant phyllodes tumors (MPT are rare breast neoplasms. Preoperative diagnosis is often challenging due to the unspecific clinical, radiological, and histological characteristics of the tumor. Dissemination pathways are local with chest wall invasion, regional with lymph nodes metastasis, and distant, hematogenous, mostly to the lungs, bones, and brain. Distant metastasis (DM can be synchronous or appear months to years after the diagnosis and initial management. The current report describes the case of a 57-year-old woman presenting with a giant/neglected MPT of the breast, with no DM at initial staging, treated by radical modified mastectomy. Motor disorders due to medullar compression by a paravertebral mass appeared at short follow-up, also treated surgically. The patient died from several DM of rapid evolution. To our knowledge, this is the only case described of MPT with metastases to soft tissue causing medullar compression. We present a literature review on unusual metastatic localizations of MPT.

  20. Metastasis from renal cell carcinoma to thyroid presenting as rapidly growing neck mass.

    Science.gov (United States)

    Mohammadi, Afshin; Toomatari, Seyed Babak Mosavi; Ghasemi-Rad, Mohammad

    2014-01-01

    Renal cell carcinoma (RCC) is commonly known as the "internist's tumor" because of its unpredictable behavior. Metastasis to the thyroid gland is rarely found in clinical practice. We report a rare case of non-thyroid malignancies NTM from renal cell carcinoma 1.5 years after radical nephrectomy in a 58-year-old man with a rapidly growing neck mass. Malignant melanoma, breast carcinoma, lung, and skin cancer are the most common sources of non-thyroid malignancies (NTM). Although metastases of NTMs to the thyroid gland are uncommon in clinical practice, it should be considered in patients with a history of prior malignancy and a new thyroid mass. Isolated thyroid metastasis should be considered in patients with a previous history of cancer and newly developing thyroid mass. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. Lung cancer and angiogenesis imaging using synchrotron radiation

    International Nuclear Information System (INIS)

    Liu Xiaoxia; Zhao Jun; Xu, Lisa X; Sun Jianqi; Gu Xiang; Liu Ping; Xiao Tiqiao

    2010-01-01

    Early detection of lung cancer is the key to a cure, but a difficult task using conventional x-ray imaging. In the present study, synchrotron radiation in-line phase-contrast imaging was used to study lung cancer. Lewis lung cancer and 4T1 breast tumor metastasis in the lung were imaged, and the differences were clearly shown in comparison to normal lung tissue. The effect of the object-detector distance and the energy level on the phase-contrast difference was investigated and found to be in good agreement with the theory of in-line phase-contrast imaging. Moreover, 3D image reconstruction of lung tumor angiogenesis was obtained for the first time using a contrast agent, demonstrating the feasibility of micro-angiography with synchrotron radiation for imaging tumor angiogenesis deep inside the body.

  2. Influence of the Different Primary Cancers and Different Types of Bone Metastasis on the Lesion-based Artificial Neural Network Value Calculated by a Computer-aided Diagnostic System,BONENAVI, on Bone Scintigraphy Images

    Directory of Open Access Journals (Sweden)

    TAKURO ISODA

    2017-01-01

    Full Text Available Objective(s: BONENAVI, a computer-aided diagnostic system, is used in bone scintigraphy. This system provides the artificial neural network (ANN and bone scan index (BSI values. ANN is associated with the possibility of bone metastasis, while BSI is related to the amount of bone metastasis. The degree of uptake on bone scintigraphy can be affected by the type of bone metastasis. Therefore, the ANN value provided by BONENAVI may be influenced by the characteristics of bone metastasis. In this study, we aimed to assess the relationship between ANN value and characteristics of bone metastasis. Methods: We analyzed 50 patients (36 males, 14 females; age range: 42–87 yrs, median age: 72.5 yrs with prostate, breast, or lung cancer who had undergone bone scintigraphy and were diagnosed with bone metastasis (32 cases of prostate cancer, nine cases of breast cancer, and nine cases of lung cancer. Those who had received systematic therapy over the past years were excluded. Bone metastases were diagnosed clinically, and the type of bone metastasis (osteoblastic, mildly osteoblastic,osteolytic, and mixed components was decided visually by the agreement of two radiologists. We compared the ANN values (case-based and lesion-based among the three primary cancers and four types of bone metastasis.Results: There was no significant difference in case-based ANN values among prostate, breast, and lung cancers. However, the lesion-based ANN values were the highest in cases with prostate cancer and the lowest in cases of lung cancer (median values: prostate cancer, 0.980; breast cancer, 0.909; and lung cancer, 0.864. Mildly osteoblastic lesions showed significantly lower ANN values than the other three types of bone metastasis (median values: osteoblastic, 0.939; mildly osteoblastic, 0.788; mixed type, 0.991; and osteolytic, 0.969. The possibility of a lesion-based ANN value below 0.5 was 10.9% for bone metastasis in prostate cancer, 12.9% for breast cancer, and 37

  3. Influence of the Different Primary Cancers and Different Types of Bone Metastasis on the Lesion-based Artificial Neural Network Value Calculated by a Computer-aided Diagnostic System, BONENAVI, on Bone Scintigraphy Images.

    Science.gov (United States)

    Isoda, Takuro; BaBa, Shingo; Maruoka, Yasuhiro; Kitamura, Yoshiyuki; Tahara, Keiichiro; Sasaki, Masayuki; Hatakenaka, Masamitsu; Honda, Hiroshi

    2017-01-01

    BONENAVI, a computer-aided diagnostic system, is used in bone scintigraphy. This system provides the artificial neural network (ANN) and bone scan index (BSI) values. ANN is associated with the possibility of bone metastasis, while BSI is related to the amount of bone metastasis. The degree of uptake on bone scintigraphy can be affected by the type of bone metastasis. Therefore, the ANN value provided by BONENAVI may be influenced by the characteristics of bone metastasis. In this study, we aimed to assess the relationship between ANN value and characteristics of bone metastasis. We analyzed 50 patients (36 males,14 females; age range: 87-42 yrs median age:72.5 yrs) with prostate, breast, or lung cancer who had undergone bone scintigraphy and were diagnosed with bone metastasis (32 cases of prostate cancer, nine cases of breast cancer, and nine cases of lung cancer). Those who had received systematic therapy over the past years were excluded. Bone metastases were diagnosed clinically, and the type of bone metastasis (osteoblastic, mildly osteoblastic, osteolytic, and mixed components) was decided visually by the agreement of two radiologists. We compared the ANN values (case-based and lesion-based) among the three primary cancers and four types of bone metastasis. There was no significant difference in case-based ANN values among prostate, breast, and lung cancers. However, the lesion-based ANN values were the highest in cases with prostate cancer and the lowest in cases of lung cancer (median values: prostate cancer, 0.980; breast cancer 0.909; and lung cancer, 0.864). Mildly osteoblastic lesions showed significantly lower ANN values than the other three types of bone metastasis (median values: osteoblastic,; 0.939 mildly osteoblastic; 0.788, mixed type; 0.991, and osteolytic. 0.969) The possibility of a lesion-based ANN value below 0.5 was %10.9 for bone metastasis in prostate cancer, %12.9 for breast cancer, and %37.2 for lung cancer. The corresponding

  4. Spontaneous Tumor Lysis Syndrome

    Directory of Open Access Journals (Sweden)

    Alicia C. Weeks MD

    2015-08-01

    Full Text Available Tumor lysis syndrome (TLS is a known complication of malignancy and its treatment. The incidence varies on malignancy type, but is most common with hematologic neoplasms during cytotoxic treatment. Spontaneous TLS is thought to be rare. This case study is of a 62-year-old female admitted with multisystem organ failure, with subsequent diagnosis of aggressive B cell lymphoma. On admission, laboratory abnormalities included renal failure, elevated uric acid (20.7 mg/dL, and 3+ amorphous urates on urinalysis. Oliguric renal failure persisted despite aggressive hydration and diuretic use, requiring initiation of hemodialysis prior to chemotherapy. Antihyperuricemic therapy and hemodialysis were used to resolve hyperuricemia. However, due to multisystem organ dysfunction syndrome with extremely poor prognosis, the patient ultimately expired in the setting of a terminal ventilator wean. Although our patient did not meet current TLS criteria, she required hemodialysis due to uric acid nephropathy, a complication of TLS. This poses the clinical question of whether adequate diagnostic criteria exist for spontaneous TLS and if the lack of currently accepted guidelines has resulted in the underestimation of its incidence. Allopurinol and rasburicase are commonly used for prevention and treatment of TLS. Although both drugs decrease uric acid levels, allopurinol mechanistically prevents formation of the substrate rasburicase acts to solubilize. These drugs were administered together in our patient, although no established guidelines recommend combined use. This raises the clinical question of whether combined therapy is truly beneficial or, conversely, detrimental to patient outcomes.

  5. The level of serum tumor makers and bone metastases of lung cancer correlation

    International Nuclear Information System (INIS)

    Li Li; Jin Jianhua

    2014-01-01

    Objective: To study the correlation between the level of serum tumor makers and bone metastases of lung cancer. Method: In 128 diagnosed patients with lung cancer, small cell lung cancer were 26 cases, non-small cell lung cancer were 102 cases which included 44 cases of adenocarcinoma, 50 cases of squamous cell carcinoma, 4 cases of large cell carcinoma, 4 cases of squamous adenocarcinoma. 99m Tc-MDP whole-body bone scanning was performed in 128 patients with lung cancer. over the same period, the serum samples were collected in these patients and 30 comparison controls. CEA, CA125, CA199, SCC, NSE, CA15-3, and AFP were measured by ELISA technique. Bone imaging findings analysis used t-test, and serum levels of tumor markers analysis used χ 2 test. Results: The diagnostic of 53 cases of lung cancer with bone metastasis was subject to clinical criteria of lung cancer with bone metastases. The positive ratio of patients with osseous metastasis was confirmed by 99m Tc-MDP whole-body bone scanning was 23.44% (30/128), including 16 cases of lung adenocarcinoma, 9 cases of squamous cell carcinoma, 3 cases of small cell lung cancer , 1 case of large cell lung cancer, 1 case of squamous adenocarcinoma and multiple bone metastases accounted for 66.67% (20/30). The levels of serum CEA, CA125, CA199, SCC, NSE and CA15-3 were higher than the control group (P < O.05). 29 cases of CEA positive and 21 cases of CA125 positive were included in 30 cases of lung cancer with bone metastasis. There was a significant difference between the levels of CEA, CA125, CA199, NSE in lung cancer with bone metastases and without bone metastases (P < 0.05). The sensitivity of 99m Tc-MDP whole-body bone scanning in diagnosis of lung cancer with bone metastasis was 84.91%. Conclusion: The average value of CEA, CA125, and CA199, SCC, NSE and CA15-3 in lung cancer patients were significantly higher than the control group. In addition, there is a significantly correlation between the occurrence of

  6. Feasibility of mesorectal vascular invasion in predicting early distant metastasis in patients with stage T3 rectal cancer based on rectal MRI

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young Chul; Kim, Jai Keun; Lee, Jei Hee [Ajou University School of Medicine, Department of Radiology, Suwon, Gyeonggi-do (Korea, Republic of); Kim, Myeong-Jin [Yonsei University Health system, Department of Diagnostic Radiology, Institute of Gastroenterology, Research Institute of Radiological Science, Seoul (Korea, Republic of); Kim, Young Bae [Ajou University School of Medicine, Department of Pathology, Suwon (Korea, Republic of); Shin, Sung Jae [Ajou University School of Medicine, Department of Gastroenterology, Suwon (Korea, Republic of)

    2016-02-15

    To evaluate the feasibility of mesorectal vascular invasion (MVI) in predicting early distant metastasis developed within 1 year of diagnosis of T3 rectal cancer using magnetic resonance imaging (MRI) Sixty-five patients with T3 rectal cancer (early metastasis, n = 28; non-metastasis, n = 37) were enrolled in this study. Early distant metastases developed in 28 patients (liver, n = 15; lung, n = 9; both, n = 4). Logistic regression was used to determine the independent predictors for early distant metastasis. In univariate analysis, tumour location, carcinoembryonic antigen (CEA), lymphovascular invasion (LVI), MRI-detected MVI, and mesorectal fat infiltration (MFI) (odds ratio [OR], 4.533, 9.583, 5.539, 27.046, and 5.539, respectively) were associated with early distant metastasis. Multivariate analysis demonstrated that MVI (OR, 29.949; P < 0.002) and LVI (OR, 6.684; P = 0.033) were independent factors for early distant metastasis. Specificity and positive predictive value (PPV) of MVI (94.59 %, and 89.47 %, respectively) were significantly higher than those of LVI (64.86 %, and 61.76 %), but sensitivity and negative predictive value were not significantly different between MVI (60.71 %, and 76.09 %) and LVI (75.00 %, and 77.42 %). While sensitivity of MRI-detected MVI was equal to that of CEA in predicting early distant metastasis from T3 rectal cancer, specificity and PPV may be improved by assessing MVI. (orig.)

  7. Lung Cancer

    Science.gov (United States)

    Lung cancer is one of the most common cancers in the world. It is a leading cause of cancer death in men and women in the United States. Cigarette smoking causes most lung cancers. The more cigarettes you smoke per day and ...

  8. Simultaneous Bilateral Spontaneous Pneumothorax Revealed Birt-Hogg-Dubè Syndrome

    Directory of Open Access Journals (Sweden)

    Alessandro Tamburrini

    2015-01-01

    Full Text Available Simultaneous bilateral spontaneous pneumothorax is a very rare clinical event, comprising approximately 1% of all spontaneous pneumothoraces. Clinical signs and symptoms may vary from mild chest pain and dyspnea to severe respiratory failure; nevertheless immediate treatment is mandatory as this condition can deteriorate and progress to tension pneumothorax. An underlying lung disease has been commonly described; in most istances primary or secondary tumors, interstitial diseases, and infectious diseases. Birt-Hogg-Dubè syndrome is a rare inherited disorder clinically characterized by multiple fibrofolliculomas, renal tumors, lung cysts, and, in ~24% of the patients, occurrence of spontaneous pneumothorax. In this case, we firstly report the concurrence of these rare conditions, as a patient presenting a simultaneous bilateral spontaneous pneumothorax was diagnosed with Birt-Hogg-Dubè syndrome based on the typical radiological findings and genetic testing of the folliculin gene located on chromosome 17.

  9. Targeting antisense mitochondrial ncRNAs inhibits murine melanoma tumor growth and metastasis through reduction in survival and invasion factors.

    Science.gov (United States)

    Lobos-González, Lorena; Silva, Verónica; Araya, Mariela; Restovic, Franko; Echenique, Javiera; Oliveira-Cruz, Luciana; Fitzpatrick, Christopher; Briones, Macarena; Villegas, Jaime; Villota, Claudio; Vidaurre, Soledad; Borgna, Vincenzo; Socias, Miguel; Valenzuela, Sebastián; Lopez, Constanza; Socias, Teresa; Varas, Manuel; Díaz, Jorge; Burzio, Luis O; Burzio, Verónica A

    2016-09-06

    We reported that knockdown of the antisense noncoding mitochondrial RNAs (ASncmtRNAs) induces apoptotic death of several human tumor cell lines, but not normal cells, suggesting this approach for selective therapy against different types of cancer. In order to translate these results to a preclinical scenario, we characterized the murine noncoding mitochondrial RNAs (ncmtRNAs) and performed in vivo knockdown in syngeneic murine melanoma models. Mouse ncmtRNAs display structures similar to the human counterparts, including long double-stranded regions arising from the presence of inverted repeats. Knockdown of ASncmtRNAs with specific antisense oligonucleotides (ASO) reduces murine melanoma B16F10 cell proliferation and induces apoptosis in vitro through downregulation of pro-survival and metastasis markers, particularly survivin. For in vivo studies, subcutaneous B16F10 melanoma tumors in C57BL/6 mice were treated systemically with specific and control antisense oligonucleotides (ASO). For metastasis studies, tumors were resected, followed by systemic administration of ASOs and the presence of metastatic nodules in lungs and liver was assessed. Treatment with specific ASO inhibited tumor growth and metastasis after primary tumor resection. In a metastasis-only assay, mice inoculated intravenously with cells and treated with the same ASO displayed reduced number and size of melanoma nodules in the lungs, compared to controls. Our results suggest that ASncmtRNAs could be potent targets for melanoma therapy. To our knowledge, the ASncmtRNAs are the first potential non-nuclear targets for melanoma therapy.

  10. Extraspinal Percutaneous Osteoplasty for the Treatment of Painful Bony Metastasis.

    Science.gov (United States)

    Lee, Jae Heon; Kim, Su Young; Ok, Hwoe Gyeong; Kim, Tae Kyun; Kim, Kyung Hoon

    2018-02-19

    Extraspinal percutaneous osteoplasties (POPs) are novel techniques for the treatment of painful bony metastasis, which is often the cause of both persistent and incidental breakthrough pain. This retrospective study explored the efficacy and complications of extraspinal POPs. The origin of the cancer metastasis, performed POP sites, necessity of adjacent joint injections, pain and Karnofsky Performance Scale (KPS) scores, complications related to the POPs, and life expectancy were evaluated from the medical records from 2009 to 2016. A total of 47 (M/F = 28/19) patients had received 54 POPs, including costoplasty, scapuloplasty, ilioplasty, humeroplasty, ischioplasty, femoroplasty, sternoplasty, and puboplasty, in order of frequency. The most common sites for the origin of the cancer, in order of frequency, were the lung, liver, breast, colon, and kidney. All patients receiving POPs including scapuloplasty, ilioplasty, humeroplasty, and femoroplasty needed adjacent joint injections before or after the POPs. Pain due to metastatic lesions was reduced significantly immediately after the POPs and the reduction was sustained until the end of their lives. The median KPS was increased from 35.4% to 67.7% immediately after the POPs. There were no complications related to the procedures. The mean life expectancy after performing the POPs, for 35 patients which died afterwards, was 99.3 days, ranging from 1 to 767 days. Even though pain in the isolated POP sites may be difficult to measure due to overlapping systemic pain, the POPs provided immediate local pain relief, and the patients showed better physical performance without procedure-related complications. © 2018 The Korean Academy of Medical Sciences.

  11. Lung regeneration by fetal lung tissue implantation in a mouse pulmonary emphysema model.

    Science.gov (United States)

    Uyama, Koh; Sakiyama, Shoji; Yoshida, Mitsuteru; Kenzaki, Koichiro; Toba, Hiroaki; Kawakami, Yukikiyo; Okumura, Kazumasa; Takizawa, Hiromitsu; Kondo, Kazuya; Tangoku, Akira

    2016-01-01

    The mortality and morbidity of chronic obstructive pulmonary disease are high. However, no radical therapy has been developed to date. The purpose of this study was to evaluate whether fetal mouse lung tissue can grow and differentiate in the emphysematous lung. Fetal lung tissue from green fluorescent protein C57BL/6 mice at 16 days' gestation was used as donor material. Twelve-month-old pallid mice were used as recipients. Donor lungs were cut into small pieces and implanted into the recipient left lung by performing thoracotomy under anesthesia. The recipient mice were sacrificed at day 7, 14, and 28 after implantation and used for histological examination. Well-developed spontaneous pulmonary emphysema was seen in 12-month-old pallid mice. Smooth and continuous connection between implanted fetal lung tissue and recipient lung was recognized. Air space expansion and donor tissue differentiation were observed over time. We could clearly distinguish the border zones between injected tissue and native tissue by the green fluorescence of grafts. Fetal mouse lung fragments survived and differentiated in the emphysematous lung of pallid mice. Implantation of fetal lung tissue in pallid mice might lead to further lung regeneration research from the perspective of respiratory and exercise function. J. Med. Invest. 63: 182-186, August, 2016.

  12. Duodenal Metastasis of Malignant Pleural Mesothelioma

    Directory of Open Access Journals (Sweden)

    Huang-Chi Chen

    2008-12-01

    Full Text Available Metastatic malignant mesothelioma of the pleura is uncommon at the time of initial diagnosis. The gastrointestinal lumen is rarely found at autopsy in patients with widespread disease. Here, we describe an extremely rare case of isolated duodenal metastasis of sarcomatoid mesothelioma of the pleura in a 73-year-old man, without memory of any direct exposure to asbestos. The possibility of gastrointestinal tract metastasis should be considered in the presence of anemia or positive occult blood test in patients with malignant pleural mesothelioma.

  13. A Young Man with Bilateral Spontaneous Pneumothorax

    Directory of Open Access Journals (Sweden)

    Liese Lieve Willemien Verhaert

    2011-01-01

    Full Text Available Case. A 33-year-old male nonsmoker presented with sudden onset of dyspnoea and thoracic pain. Chest radiograph showed a left-sided pneumothorax. Few days later he developed a right-sided pneumothorax. He had a positive family history of pneumothorax. High-resolution computed tomography of the chest showed multiple pulmonary cysts predominantly located in the lower lung regions. We suspected Birt-Hogg-Dubé syndrome (BHD. Conclusion. Birt-Hogg-Dubé syndrome is a rare autosomal dominant inherited genodermatosis and characterised by clinical manifestations including hamartomas of the skin, renal tumors, and pulmonary cysts with spontaneous pneumothorax. BHD is probably underdiagnosed because of the wide variability in its clinical expression. It is important to recognize these patients because of the possibility of developing renal cancer.

  14. Ameloblastoma with varied sites of metastasis: report of two cases and literature review.

    Science.gov (United States)

    Lin, Yi; He, Jian-feng; Li, Zhi-yong; Liu, Jian-hua

    2014-07-01

    We report two rare cases of lung metastasis from maxillary ameloblastoma, in order to review its risk and analyse the types of metastases that can present with this disease. A 40-year-old male with multiple recurrences and a 46-year-old female, who had undergone successful surgical treatment of a maxillary ameloblastoma, presented with metastatic lesions. The primary tumour and metastases were benign in both patients. We reviewed and analysed 20 cases of the same condition reported in recent years. Our initial treatment for the primary maxillary lesion was performed more than 10 years before the pulmonary lesions presented. Due to the aggressive nature of this tumour, metastases in the lungs and cervical lymph nodes (male patient) were confirmed. These cases presented a diagnostic challenge due to the multiple and varied sites of recurrence, which indicate the natural behaviour of this tumour. Different routes of metastasis can occur, including implanting, haematogenous, and lymphatic spread. CT-guided percutaneous transthoracic lung biopsy is an important method to confirm metastatic ameloblastoma. Copyright © 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  15. Lung Cancer Screening

    Science.gov (United States)

    ... Treatment Lung Cancer Prevention Lung Cancer Screening Research Lung Cancer Screening (PDQ®)–Patient Version What is screening? Go ... These are called diagnostic tests . General Information About Lung Cancer Key Points Lung cancer is a disease in ...

  16. The metastatic microenvironment: Claudin-1 suppresses the malignant phenotype of melanoma brain metastasis.

    Science.gov (United States)

    Izraely, Sivan; Sagi-Assif, Orit; Klein, Anat; Meshel, Tsipi; Ben-Menachem, Shlomit; Zaritsky, Assaf; Ehrlich, Marcelo; Prieto, Victor G; Bar-Eli, Menashe; Pirker, Christine; Berger, Walter; Nahmias, Clara; Couraud, Pierre-Olivier; Hoon, Dave S B; Witz, Isaac P

    2015-03-15

    Brain metastases occur frequently in melanoma patients with advanced disease whereby the prognosis is dismal. The underlying mechanisms of melanoma brain metastasis development are not well understood. Identification of molecular determinants regulating melanoma brain metastasis would advance the development of prevention and therapy strategies for this disease. Gene expression profiles of cutaneous and brain-metastasizing melanoma variants from three xenograft tumor models established in our laboratory revealed that expression of tight junction component CLDN1 was lower in the brain-metastasizing variants than in cutaneous variants from the same melanoma. The objective of our study was to determine the significance of CLDN1 downregulation/loss in metastatic melanoma and its role in melanoma brain metastasis. An immunohistochemical analysis of human cells of the melanocyte lineage indicated a significant CLDN1 downregulation in metastatic melanomas. Transduction of melanoma brain metastatic cells expressing low levels of CLDN1 with a CLDN1 retrovirus suppressed their metastatic phenotype. CLDN1-overexpressing melanoma cells expressed a lower ability to migrate and adhere to extracellular matrix, reduced tumor aggressiveness in nude mice and, most importantly, eliminated the formation of micrometastases in the brain. In sharp contrast, the ability of the CLDN1-overexpressing cells to form lung micrometastases was not impaired. CLDN1-mediated interactions between these cells and brain endothelial cells constitute the mechanism underlying these results. Taken together, we demonstrated that downregulation or loss of CLDN1 supports the formation of melanoma brain metastasis, and that CLDN1 expression could be a useful prognostic predictor for melanoma patients with a high risk of brain metastasis. © 2014 UICC.

  17. Identification of a myeloid-derived suppressor cell cystatin-like protein that inhibits metastasis

    Science.gov (United States)

    Boutté, Angela M.; Friedman, David B.; Bogyo, Matthew; Min, Yongfen; Yang, Li; Lin, P. Charles

    2011-01-01

    Myeloid-derived suppressor cells (MDSCs) are significantly increased in cancer patients and tumor bearing-animals. MDSCs infiltrate into tumors and promote tumor invasion and metastasis. To identify the mediator responsible for the prometastatic property of MDSCs, we used proteomics. We found neutrophilic granule protein (NGP) was decreased >2-fold in MDSCs from metastatic 4T1 tumor-bearing mice compared to nonmetastatic 67NR controls. NGP mRNA levels were decreased in bone marrow and in tumor-infiltrating MDSCs by 45 and 66%, respectively, in 4T1 tumor-bearing mice compared to 67NR controls. Interestingly, 4T1-conditioned medium reduced myeloid cell NGP expression by ∼40%, suggesting that a secreted factor mediates gene reduction. Sequence analysis shows a putative cystatin domain in NGP, and biochemical analysis confirms NGP a novel cathepsin inhibitor. It inhibited cathepsin B activity by nearly 40% in vitro. NGP expression in 4T1 tumor cells suppressed cell invasion, delayed primary tumor growth, and greatly reduced lung metastasis in vivo. A 2.8-fold reduction of cathepsin activity was found in tumors expressing NGP compared to controls. NGP significantly reduced tumor angiogenesis to 12.6 from 19.6 and lymphangiogenesis to 4.6 from 9.1 vessels/field. Necrosis was detectable only in NGP-expressing tumors, and the number of apoptotic cells increased to 22.4 from 8.3 in controls. Taken together, this study identifies a negative regulator of tumor metastasis in MDSCs, NGP, which is down-regulated in metastatic conditions. The finding suggests that malignant tumors promote invasion/metastasis not only through up-regulation of proteases but also down-regulation of protease inhibitors.—Boutté, A. M., Friedman, D. B., Bogyo, M., Min, Y., Yang, L., Lin, P. C. Identification of a myeloid-derived suppressor cell cystatin-like protein that inhibits metastasis. PMID:21518852

  18. {sup 68}Ga Labeling of DOTMP using Freeze-dried Kit for the Imaging of Bone Metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Dho, So Hee; Choi, Sangmu; Kim, Sooyong; Cho, Eunha; Lee, Soyoung; Jung, Sunghee; Lim, Jaecheong [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2015-10-15

    Bone is a favorable site of metastasis and is invaded common primary tumors such as prostate, breast, and lung. Due to the progressive pain and mortality of the bone metastasis, effort has been focused on the detection of bone metastasis in the field of nuclear medicine (Mitterhauser, Toegel et al. 2007, Mirzaei, Jalilian et al. 2015). In designing suitable imaging agents for bone metastasis, multidentate polyaminophosphonate are regarded as the most promising candidates as carrier ligands owing to their high bone affinity, selective localization in skeletal lesions and ability to form metal chelates with high in-vivo stability (Chakraborty, Das et al. 2008). 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene. Freeze-dried DOTMP kit vial was consist of 400 μ of DOTMP, 19.27 mg of ammonium acetate and 17.62 mg of ascorbic acid. All the preparative steps were carried out under aseptic conditions, and the prepared kit vials were shown in Fig. 3(A). The easy and efficient labeling of this kit with 68Ga make them suitable for preparing 68Ga-DOTMP for imaging of bone metastasis.

  19. TREATMENT USING LAPAROSCOPIC AND THORACOSCOPIC PROCEDURES IN A PATIENT WITH SIGMOID CANCER AND SOLITARY PULMONARY METASTASIS: A CLINICAL CASE

    Directory of Open Access Journals (Sweden)

    A. O. Rasulov

    2014-01-01

    Full Text Available A clinical case of a sigmoid cancer patient with solitary lung metastasis is discussed in this article. Use of minimally invasive surgical technologies allowed to perform a simultaneous combined surgery on abdominal and thoracic cavities and improve rehabilitation time and time to systemic chemotherapy initiation. In presented clinical case patient was comorbid with stage III obesity, which was considered as a contraindication to laparoscopic surgery for a long time.

  20. Abalone visceral extract inhibit tumor growth and metastasis by modulating Cox-2 levels and CD8+ T cell activity

    Directory of Open Access Journals (Sweden)

    II Kim Jae

    2010-10-01

    Full Text Available Abstract Background Abalone has long been used as a valuable food source in East Asian countries. Although the nutritional importance of abalone has been reported through in vitro and in vivo studies, there is little evidence about the potential anti-tumor effects of abalone visceral extract. The aim of the present study is to examine anti-tumor efficacy of abalone visceral extract and to elucidate its working mechanism. Methods In the present study, we used breast cancer model using BALB/c mouse-derived 4T1 mammary carcinoma and investigated the effect of abalone visceral extract on tumor development. Inhibitory effect against tumor metastasis was assessed by histopathology of lungs. Cox-2 productions by primary and secondary tumor were measured by real-time RT-PCR and immunoblotting (IB. Proliferation assay based on [3H]-thymidine incorporation and measurement of cytokines and effector molecules by RT-PCR were used to confirm tumor suppression efficacy of abalone visceral extract by modulating cytolytic CD8+ T cells. The cytotoxicity of CD8+ T cell was compared by JAM test. Results Oral administration of abalone visceral extract reduced tumor growth (tumor volume and weight and showed reduced metastasis as confirmed by decreased level of splenomegaly (spleen size and weight and histological analysis of the lung metastasis (gross analysis and histological staining. Reduced expression of Cox-2 (mRNA and protein from primary tumor and metastasized lung was also detected. In addition, treatment of abalone visceral extract increased anti-tumor activities of CD8+ T cells by increasing the proliferation capacity and their cytolytic activity. Conclusions Our results suggest that abalone visceral extract has anti-tumor effects by suppressing tumor growth and lung metastasis through decreasing Cox-2 expression level as well as promoting proliferation and cytolytic function of CD8+ T cells.

  1. Malignant peripheral nerve sheath tumor associated with neurofibromatosis type 1, with metastasis to the heart: a case report

    Directory of Open Access Journals (Sweden)

    Araki Nobuhito

    2010-01-01

    Full Text Available Abstract A rare case is presented of a 61-year-old man with a malignant peripheral nerve sheath tumor associated with neurofibromatosis type 1, with metastasis to the heart. The primary tumor originated in the right thigh in 1982. Since then, the patient has had repeated local recurrences in spite of repeated surgical treatment and adjuvant chemotherapy. He has developed previous metastases of the lung and heart. The patient died of cardiac involvement.

  2. Molecular Markers of Metastasis in Ductal Mammary Carcinoma

    National Research Council Canada - National Science Library

    Achary, Patnala

    2002-01-01

    .... We have isolated 15 metastasis associated DNA sequences (MADS), of which 3 were found be associated with metastasis in breast cancer patient samples other than the index case that was used in RDA experiments...

  3. Spontaneous Intracranial Hypotension

    International Nuclear Information System (INIS)

    Joash, Dr.

    2015-01-01

    Epidemiology is not only rare but an important cause of new daily persistent headaches among young & middle age individuals. The Etiology & Pathogenesis is generally caused by spinal CSF leak. Precise cause remains largely unknown, underlying structural weakness of spinal meninges is suspected. There are several MR Signs of Intracranial Hypotension that include:- diffuse pachymeningeal (dural) enhancement; bilateral subdural, effusion/hematomas; Downward displacement of brain; enlargement of pituitary gland; Engorgement of dural venous sinuses; prominence of spinal epidural venous plexus and Venous sinus thrombosis & isolated cortical vein thrombosis. The sum of volumes of intracranial blood, CSF & cerebral tissue must remain constant in an intact cranium. Treatment in Many cases can be resolved spontaneously or by use Conservative approach that include bed rest, oral hydration, caffeine intake and use of abdominal binder. Imaging Modalities for Detection of CSF leakage include CT myelography, Radioisotope cisternography, MR myelography, MR imaging and Intrathecal Gd-enhanced MR

  4. Spontaneous wave packet reduction

    International Nuclear Information System (INIS)

    Ghirardi, G.C.

    1994-06-01

    There are taken into account the main conceptual difficulties met by standard quantum mechanics in dealing with physical processes involving macroscopic system. It is stressed how J.A.Wheeler's remarks and lucid analysis have been relevant to pinpoint and to bring to its extreme consequences the puzzling aspects of quantum phenomena. It is shown how the recently proposed models of spontaneous dynamical reduction represent a consistent way to overcome the conceptual difficulties of the standard theory. Obviously, many nontrivial problems remain open, the first and more relevant one being that of generalizing the model theories considered to the relativistic case. This is the challenge of the dynamical reduction program. 43 refs, 2 figs

  5. Iron deficiency anemia as initial presentation of a non-small cell lung carcinoma: A case report

    NARCIS (Netherlands)

    P.V.M. Linsen (Philip V.M.); V.M.J. Linsen (Victor M.J.); G. Buunk (Gerba); D.E. Arnold (Dorothee E.); J.G.J.V. Aerts (Joachim)

    2015-01-01

    textabstractDuodenal metastases secondary to lung cancer are very rare and most of the time asymptomatic. When symptomatic they usually present with bowel obstruction or perforation. We here describe the case of a 68 year-old man with a solitary metastasis in the duodenum from a non-small cell lung

  6. Nanoparticles target early-stage breast cancer metastasis in vivo

    Science.gov (United States)

    Goldman, Evgeniya; Zinger, Assaf; da Silva, Dana; Yaari, Zvi; Kajal, Ashima; Vardi-Oknin, Dikla; Goldfeder, Mor; Schroeder, Josh E.; Shainsky-Roitman, Janna; Hershkovitz, Dov; Schroeder, Avi

    2017-10-01

    Despite advances in cancer therapy, treating cancer after it has metastasized remains an unmet clinical challenge. In this study we demonstrate that 100 nm liposomes target triple-negative murine breast-cancer metastases post intravenous administration. Metastatic breast cancer was induced in BALB/c mice either experimentally, by a tail vein injection of 4T1 cells, or spontaneously, after implanting a primary tumor xenograft. To track their biodistribution in vivo the liposomes were labeled with multi-modal diagnostic agents, including indocyanine green and rhodamine for whole-animal fluorescent imaging, gadolinium for magnetic resonance imaging (MRI), and europium for a quantitative biodistribution analysis. The accumulation of liposomes in the metastases peaked at 24 h post the intravenous administration, similar to the time they peaked in the primary tumor. The efficiency of liposomal targeting to the metastatic tissue exceeded that of a non-liposomal agent by 4.5-fold. Liposomes were detected at very early stages in the metastatic progression, including metastatic lesions smaller than 2 mm in diameter. Surprisingly, while nanoparticles target breast cancer metastasis, they may also be found in elevated levels in the pre-metastatic niche, several days before metastases are visualized by MRI or histologically in the tissue. This study highlights the promise of diagnostic and therapeutic nanoparticles for treating metastatic cancer, possibly even for preventing the onset of the metastatic dissemination by targeting the pre-metastatic niche.

  7. Intracranial Myeloid Sarcoma Metastasis Mimicking Acute Subdural Hematoma

    Directory of Open Access Journals (Sweden)

    Amandip S. Gill

    2017-01-01

    Full Text Available Myeloid sarcoma, a rare consequence of myeloproliferative disorders, is rarely seen in the central nervous system, most commonly in the pediatric population. Although there are a handful of case reports detailing initial presentation of CNS myeloid sarcoma in the adult population, we have been unable to find any reports of CNS myeloid sarcoma presenting as a large mass lesion in a herniating patient. Here, we present the case of a patient transferred to our facility for a very large subdural hematoma. Based on imaging characteristics, it was felt to be a spontaneous hematoma secondary to coagulopathy. No coagulopathy was found. Interestingly, he did have a history of acute myeloid leukemia (AML diagnosed 2 months previously, and intraoperatively he was found to have a confluent white mass invading both the subdural and subarachnoid spaces. There was minimal associated hemorrhage and final pathology showed myeloid sarcoma. This is the first report we are aware of in which CNS myeloid sarcoma presented as a subdural metastasis and also the first report in which we are aware of this etiology causing a herniation syndrome secondary to mass effect.

  8. Seven cases of brain metastasis from papillary thyroid carcinoma

    International Nuclear Information System (INIS)

    Ikekubo, Katsuji; Hino, Megumu; Ito, Hidetomi; Hirao, Kazuyuki; Ueshima, Miho; Tanaka, Tomohiro; Kobayashi, Hiromasa; Ishihara, Takashi; Kurahachi, Hiroyuki

    2000-01-01

    uptake in lung lesions has been alive 15 months after diagnosis of brain metastasis. These results indicate that it is important to detect brain metastasis by imaging techniques and Tg measurements and give treatment as early as possible since the brain is the third most common distant metastatic site and the prognosis is poor. (author)

  9. Spontaneous Pneumothorax in Birt-Hogg-Dube' Syndrome: Two Case Reports

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Hyoung Ju; Woo, Ok Hee; Yong, Hwan Seok; Kang, Eun Young; Kim, Hyun Koo; Choi, Young Ho; Shin, Bong Kyung; Kim, Yoon Kyung [Korea University School of Medicine, Korea University Guro Hospital, Seoul (Korea, Republic of)

    2011-01-15

    Birt-Hogg-Dube'(BHD) syndrome is a rare autosomal dominant inherited disorder that is characterized by skin fibrofolliculomas, renal tumors and multiple lung cysts with or without spontaneous pneumothorax. The disease is caused by germline mutations in the FLCN gene that codes for a protein of unknown function called folliculin. Patients with BHD syndrome do not always have all three manifestations of the skin, kidney and lung. To the best of our knowledge, there has been no case report of the radiologic findings of the lung manifestation in a patient with BHD syndrome in Korea. We report here on two cases of BHD syndrome that presented with spontaneous pneumothorax. The pulmonary abnormalities consisted of multiple thin-walled cysts of various sizes and shapes in both lungs

  10. Spontaneous compactification to homogeneous spaces

    International Nuclear Information System (INIS)

    Mourao, J.M.

    1988-01-01

    The spontaneous compactification of extra dimensions to compact homogeneous spaces is studied. The methods developed within the framework of coset space dimensional reduction scheme and the most general form of invariant metrics are used to find solutions of spontaneous compactification equations

  11. Screening for spontaneous preterm birth

    NARCIS (Netherlands)

    van Os, M.A.; van Dam, A.J.E.M.

    2015-01-01

    Preterm birth is the most important cause of perinatal morbidity and mortality worldwide. In this thesis studies on spontaneous preterm birth are presented. The main objective was to investigate the predictive capacity of mid-trimester cervical length measurement for spontaneous preterm birth in a

  12. Isolated Pancreatic Metastasis from Malignant Melanoma: Is ...

    African Journals Online (AJOL)

    Isolated pancreatic metastasis from malignant melanoma (IPMMM) is rare because most melanoma patients already have a widespread disease at diagnosis. No adjuvant systemic treatment is known to be effi cient in this setting. Experience with pancreatic resection for IPMMM is limited and controversial. We report here ...

  13. A link between inflammation and metastasis

    DEFF Research Database (Denmark)

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

    2015-01-01

    . Intravenously injected S100A4 protein induced expression of SAA proteins and cytokines in an organ-specific manner. In a breast cancer animal model, ectopic expression of SAA1 or SAA3 in tumor cells potently promoted widespread metastasis formation accompanied by a massive infiltration of immune cells...

  14. 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...

  15. Cancer Stem Cells, Tumor Dormancy, And Metastasis

    Directory of Open Access Journals (Sweden)

    Purvi ePatel

    2012-10-01

    Full Text Available Tumor cells can persist undetectably for an extended period of time in primary tumors and in disseminated cancer cells. Very little is known about why and how these tumors persist for extended periods of time and then evolve to malignancy. The discovery of cancer stem cells (CSCs in human tumors challenges our current understanding of tumor recurrence, drug resistance, and metastasis, and opens up new research directions on how cancer cells are capable of switching from dormancy to malignancy. Although overlapping molecules and pathways have been reported to regulate the stem-like phenotype of CSCs and metastasis, accumulated evidence has suggested additional clonal diversity within the stem-like cancer cell subpopulation. This review will describe the current hypothesis linking CSCs and metastasis and summarize mechanisms important for metastatic CSCs to re-initiate tumors in the secondary sites. A better understanding of CSCs’ contribution to clinical tumor dormancy and metastasis will provide new therapeutic revenues to eradicate metastatic tumors and significantly reduce the mortality of cancer patients.

  16. Combination therapy of PKCζ and COX-2 inhibitors synergistically suppress melanoma metastasis.

    Science.gov (United States)

    Zhou, Ping; Qin, Jiaqi; Li, Yuan; Li, Guoxia; Wang, Yinsong; Zhang, Ning; Chen, Peng; Li, Chunyu

    2017-09-02

    Metastatic malignant melanoma is one of the most aggressive malignancies and its treatment remains challenging. Recent studies demonstrate that the melanoma metastasis