Nicaraven reduces cancer metastasis to irradiated lungs by decreasing CCL8 and macrophage recruitment.

Science.gov (United States)

Yan, Chen; Luo, Lan; Urata, Yoshishige; Goto, Shinji; Li, Tao-Sheng

2018-04-01

Radiotherapy for cancer patients damages normal tissues, thereby inducing an inflammatory response and promoting cancer metastasis. We investigated whether nicaraven, a compound with radioprotective and anti-inflammatory properties, could attenuate radiation-induced cancer metastasis to the lungs of mice. Nicaraven and amifostine, another commercial radioprotective agent, had limited effects on both the radiosensitivity of Lewis lung carcinoma cells in vitro and radiation-induced tumor growth inhibition in vivo. Using experimental and spontaneous metastasis models, we confirmed that thorax irradiation with 5 Gy X-rays dramatically increased the number of tumors in the lungs. Interestingly, the number of tumors in the lungs was significantly reduced by administering nicaraven but not by administering amifostine daily after radiation exposure. Furthermore, nicaraven administration effectively inhibited CCL8 expression and macrophage recruitment in the lungs 1 day after thorax irradiation. Our data suggest that nicaraven attenuates radiation-induced lung metastasis, likely by regulating the inflammatory response after radiation exposure. Copyright © 2018 Elsevier B.V. All rights reserved.

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

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

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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

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.)

An Unusual Presentation of Lung Cancer Metastasis: Perianal Abscess

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Murat Kilic

2014-06-01

Full Text Available Lung cancer is one of the most commonly diagnosed cancers in both men and women. Although the most frequent sites of distant metastasis of lung cancers are the pleura, liver, adrenal glands, skeletal system and brain, perianal region has been rarely reported as a metastasis site. A male patient was admitted to our emergency room with a long standing perianal abscess. During abscess drainage, a mass was noticed at the base of the abscess pouch, and thus a biopsy was taken. Pathologically, it was reported as a metastasis of squamous cell carcinoma, therefore some radiological  investigations and endoscopic procedures were performed to determine the primary focus of cancer. A pulmonary mass was revealed in PET/CT, and was considered as primary tumor. Both primary and metastatic perianal tumors can be rarely presented as an abscess formation. In this situation, a biopsy should be performed from the lesion to avoid misdiagnosis.

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.

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

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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.

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

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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.)

Differential diagnosis and cancer staging of a unique case with multiple nodules in the lung - lung adenocarcinoma, metastasis of colon adenocarcinoma, and colon adenocarcinoma metastasizing to lung adenocarcinoma.

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Bai, Yun; Qiu, Jianxing; Shang, Xueqian; Liu, Ping; Zhang, Ying; Wang, Ying; Xiong, Yan; Li, Ting

2015-05-01

Lung cancer is the most common cancer in the world. Despite this, there have been few cases of simultaneous primary and metastatic cancers in the lung reported, let alone coexisting with tumor-to-tumor metastasis. Herein, we describe an extremely unusual case. A 61-year-old man with a history of colon adenocarcinoma was revealed as having three nodules in the lung 11 months after colectomy. The nodule in the left upper lobe was primary lung adenocarcinoma, the larger one in the right upper lobe was a metastasis of colon adenocarcinoma, and the smaller one in the right upper lobe was colon adenocarcinoma metastasizing to lung adenocarcinoma. Our paper focused on the differential diagnosis and cancer staging of this unique case, and discussed the uncommon phenomenon of the lung acting as a recipient in tumor-to-tumor metastasis.

A new semiquantitative method for evaluation of metastasis progression.

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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.

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

2018-04-01

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.

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

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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.

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.

2013-01-01

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. PMID:23526212

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

African Journals Online (AJOL)

We report a rare case of cavitary lung metastasis of a uterine cervix cancer, ... A month later, the patient presented with gynecological bleeding and a pneumothorax. ... Pelvic examination and MRI showed a subsequent local cervix recurrence.

Metastasis to the penis in a patient with adenocarcinoma of lung, case report and literature review.

Science.gov (United States)

Zheng, Fu-Fu; Zhang, Zhong-Yun; Dai, Yu-Ping; Liang, Yue-You; Deng, Chun-Hua; Tao, Yu

2009-01-01

Metastasis of lung cancer to the penis is very rare; it causes various clinical symptoms seriously affecting the quality of life. Early recognition and appropriate management will likely enhance survival in these patients. Here, we report a case of penile metastasis secondary to pulmonary carcinoma along with a review of the literature. One case of penile metastasis secondary to pulmonary carcinoma was detected in a 51-year-old patient who was admitted to the First Affiliated Hospital of Sun Yat-Sen University with persistent cough along with swelling of the perineum and penis. The clinical features, diagnosis, and treatment of this disease along with a relevant literature are reviewed and discussed. A MEDLINE search was performed to identify similar reports in the literature. CT scan revealed lung mass, and a glans penis ulcer and enlargement of inguinal lymph nodes was discovered upon physical examination. CT-guided percutaneous puncture of the lung mass revealed adenocarcinoma of lung, and biopsies of the glans penis ulcer and inguinal lymph nodes confirmed metastatic adenocarcinoma. The patients received chemotherapy and died of acute pulmonary embolism in less than 2 months. Metastasis of lung cancer to the penis is extremely rare. It presents an advanced form of lung cancer, and thus survival is extremely short. Although treatment of penile metastasis is almost always palliative, early recognition may enhance survival for these patients.

Inhibitory effects of silibinin on proliferation and lung metastasis of human high metastasis cell line of salivary gland adenoid cystic carcinoma via autophagy induction

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Jiang C

2016-10-01

Full Text Available Canhua Jiang,1 Shufang Jin,1 Zhisheng Jiang,1 Jie Wang2 1Department of Oral and Maxillofacial Surgery, Xiangya Hospital, 2Department of Immunology, Xiangya School of Medicine, Central South University, Changsha, Hunan, People’s Republic of China Objective: To investigate the possible mechanisms and effects of silibinin (SIL on the proliferation and lung metastasis of human lung high metastasis cell line of salivary gland adenoid cystic carcinoma (ACC-M.Methods: A methyl thiazolyl tetrazolium assay was performed to detect the inhibitory effects of SIL on the proliferation of ACC-M cells in vitro. Fluorescence microscopy and transmission electron microscopy were used to observe the autophagic process. Western blot was performed to detect the expression of microtube-related protein 1 light-chain 3 (LC3. An experimental adenoid cystic carcinoma (ACC lung metastasis model was established in nude mice to detect the impacts of SIL on lung weight and lung cancer nodules. Immunohistochemistry was used to detect the expressions of LC3 in human ACC samples and normal salivary gland tissue samples.Results: SIL inhibited the proliferation of ACC-M cells in a dose- and time-dependent manner, and inductively increased the autophagic bodies in ACC-M cells. Furthermore, SIL could increase the expression of LC3 in ACC-M cells and promote the conversion of LC3-I into LC3-II in a dose- and time-dependent manner. In the ACC lung metastasis model, the lung weight and left and right lung nodules in the SIL-treated group were significantly less than those in the control group (P<0.05. The expressions of LC3-I and LC3-II as well as the positive expression rate of LC3 (80% significantly increased, but the positive expression of LC3 in human ACC (42.22% reduced significantly.Conclusion: SIL could inhibit the proliferation and lung metastasis of ACC-M cells by possibly inducing tumor cells autophagy. Keywords: silibinin, adenoid cystic carcinoma, ACC-M cells, autophagy

Palatine Tonsillar Metastasis of Small-Cell Neuroendocrine Carcinoma from the Lung Detected by FDG-PET/CT After Tonsillectomy: A Case Report

International Nuclear Information System (INIS)

Chen, Xiao-Hong; Bao, Yang-Yang; Zhou, Shui-Hong; Wang, Qin-Ying; Zhao, Kui

2013-01-01

Metastasis from a malignant tumor to the palatine tonsils is rare, accounting for only 0.8% of all tonsillar tumors, with only 100 cases reported in the English-language literature. Various malignant lung carcinomas may metastasize to the tonsils. A few cases of tonsillar metastasis from neuroendocrine lung carcinoma have been reported. A 67-year-old female underwent a right tonsillectomy because of a sore throat and an enlarged right tonsil. The postoperative pathology showed right tonsillar small cell neuroendocrine carcinoma (SCNC). Fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) demonstrated metabolic activity in the lower lobe of the right lung. In addition, hypermetabolic foci were noted in the lymph nodes of the right neck and mediastinum. A needle biopsy of the pulmonary mass showed SCNC. The patient received chemotherapy and died of multiple distant metastases after 6 months. This is the first report using PET/CT to evaluate tonsillar metastasis from lung SCNC

Intermittent hypoxia increases melanoma metastasis to the lung in a mouse model of sleep apnea.

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Almendros, Isaac; Montserrat, Josep M; Torres, Marta; Dalmases, Mireia; Cabañas, Maria L; Campos-Rodríguez, Francisco; Navajas, Daniel; Farré, Ramon

2013-05-01

Obstructive sleep apnea (OSA) has recently been associated with an increased risk of cancer incidence and mortality in humans. Experimental data in mice have also shown that intermittent hypoxia similar to that observed in OSA patients enhances tumor growth. The aim of this study was to test the hypothesis that intermittent hypoxia mimicking OSA enhances lung metastasis. A total of 75 C57BL/6J male mice (10-week-old) were subjected to either spontaneous or induced melanoma lung metastasis. Normoxic animals breathed room air and intermittent hypoxic animals were subjected to cycles of 20s of 5% O2 followed by 40s of room air for 6h/day. Spontaneous and induced lung metastases were studied after subcutaneous and intravenous injection of B16F10 melanoma cells, respectively. Compared with normoxia, intermittent hypoxia induced a significant increase in melanoma lung metastasis. These animal model results suggest that intermittent hypoxia could contribute to cancer metastasis in patients with OSA. Copyright © 2013 Elsevier B.V. All rights reserved.

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

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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.

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 (piRNA......) transcriptomes in relation to lung cancer metastasis. RNA-seq was performed using RNA extracted from formalin-fixed paraffin embedded (FFPE) lung adenocarcinomas (LAC) and brain metastases from 8 patients, and LACs from 8 patients without detectable metastatic disease. Impact on miRNA and piRNA transcriptomes...... was subtle with 9 miRNAs and 8 piRNAs demonstrating differential expression between metastasizing and non-metastasizing LACs. For piRNAs, decreased expression of piR-57125 was the most significantly associated with distant metastasis. Validation by RT-qPCR in a LAC cohort comprising 52 patients confirmed...

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...

Benefit of Adjuvant Chemotherapy After Curative Resection of Lung Metastasis in Colorectal Cancer.

Science.gov (United States)

Park, Hyung Soon; Jung, Minkyu; Shin, Sang Joon; Heo, Su Jin; Kim, Chang Gon; Lee, Min Goo; Beom, Seung Hoon; Lee, Chang Young; Lee, Jin Gu; Kim, Dae Joon; Ahn, Joong Bae

2016-03-01

The survival benefit of adjuvant chemotherapy after colorectal cancer (CRC) lung metastasectomy is uncertain. We enrolled 221 CRC patients who underwent pulmonary metastasectomy between October 2002 and July 2013, including those with previous liver metastasis that had been curatively resected. Disease-free survival (DFS) and overall survival (OS) were calculated from the day of lung metastasectomy. Among all patients, 176 (79.6%) received adjuvant chemotherapy after lung metastasectomy. Median follow-up was 34.7 months from the time of lung metastasectomy [95% confidence interval (95% CI), 7.4-90.9 months]. Patients treated with adjuvant chemotherapy had longer DFS compared with surgery alone (median 32.7 vs 11.2 months respectively, P = 0.076). Multivariate analysis revealed previous liver metastasis, preoperative carcinoembryonic antigen ≥5 ng/mL, disease-free interval chemotherapy as independent risk factors for recurrence. Low-risk patients who had 0-1 risk factors received a significant survival benefit from adjuvant chemotherapy [hazard ratio (HR) 0.54; 95% CI 0.32-0.91, P = 0.020]; however, high-risk patients with ≥2 risk factors did not (HR 1.02; 95% CI 0.48-2.14, P = 0.964). Patients treated with adjuvant chemotherapy showed no OS benefit compared with patients who received surgery alone (median 89.6 vs 86.8 months respectively, P = 0.833). CRC patients received lung metastasectomy could have a DFS benefit from adjuvant chemotherapy, especially in low-risk patients. Larger, prospective studies are needed to evaluate the role of adjuvant chemotherapy after CRC lung metastasectomy.

Cutaneous metastasis reveling lung cancer | Elfatoiki | Pan African ...

African Journals Online (AJOL)

Cutaneous metastasis reveling lung cancer. FZ Elfatoiki, F Hali. Abstract. No Abstract. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about ...

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

Science.gov (United States)

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.

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

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

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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.

Study on blood supply of lung metastasis with trans-pulmonary arterial lipiodol infusion

International Nuclear Information System (INIS)

Zhou Jianqin; Dong Weihua; Dong Weihua; Ouyang Chang; Chang Heng; Xiao Xiangsheng

2008-01-01

Objective: To evaluate the blood supply of pulmonary metastases using small volume of lipiodol through pulmonary arterial infusion. Methods: 10 cases of lung metastasis were enroled including the primary tumors of liver cancer (n=5), renal carcinoma (n=3), chordoma (n=1) and malignant neurofibroma (n=1). Plain CT scan was performed to exclude calcification or ossification within metastasis and then pulmonary arterial DSA was undertaken to evaluate tumor vessels or staining. After pulmonary arteriovenous fistula or other anomalous circulation was excluded by lobar arterial DSA, small volume of lipiodol was infused under fluoroscopy (0.5-1.5 ml for each lobar artery, total volume less than 3.0 ml). CT scan was immediately performed. Blood supply of the pulmonary metastases was assessed according to the accumulation of lipiodol on CT scans. Results: No cases but one experienced cough, expectoration, suffocating or dyspnea. No complication of cerebral or visceral embolism occurred. Totally 27 nodules were studied including 6 nodules with cloudy lipiodol accumulation and 6 nodules with tiny granules of lipiodol accumulation. No enlarged tumor vessel or tumor stain was observed within all 27 nodules on pulmonary arterial DSA. Conclusions: Pulmonary artery supplys only parts of pulmonary metastases, especially those sited at the peripheral region of the lung. Infusion of small volume of lipiodol through pulmonary artery is safe, and the increased density of lung field could return normal after several days. (authors)

Rare occurrence of metastasis from lung cancer to the anus: case report and review of the literature.

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Al-Tarakji, Mohannad; Feilchenfeldt, Jonas; Haidar, Abdulrazzaq; Szabados, Lajos; Abdelaziem, Sherif; Sayed, Ali; Toro, Adriana; Di Carlo, Isidoro

2016-06-08

Anal metastases from lung cancer are infrequent, and there are only 10 published cases. Life expectancy is no longer than 1 year after diagnosis because of the typically advanced stage of disease. Treatment, which is typically inefficient, is administered with the intent to cure or avoid local complications. We report a case of a patient with non-small cell lung cancer presenting with perianal metastasis mimicking an abscess. Because perianal masses may be misdiagnosed, patients with lung and other cancers should be evaluated for metastatic disease.

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

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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

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

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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.

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

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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)

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.

Evaluating human cancer cell metastasis in zebrafish

International Nuclear Information System (INIS)

Teng, Yong; Xie, Xiayang; Walker, Steven; White, David T; Mumm, Jeff S; Cowell, John K

2013-01-01

invasion potential. We also demonstrate, using lung cancers, that the zebrafish model can evaluate the metastatic ability of cancer cells isolated from primary tumors. The zebrafish model described here offers a rapid, robust, and inexpensive means of evaluating the metastatic potential of human cancer cells. Using this model it is possible to critically evaluate whether genetic manipulation of signaling pathways affects metastasis and whether primary tumors contain metastatic cells

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

Research Progress of Lung Cancer with Leptomeningeal Metastasis

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Chunhua MA

2014-09-01

Full Text Available Leptomeningeal metastases is one of the most serious complications of lung cancer, the patients with poor prognosis. Leptomeningeal metastasis in patients with lack specificity of clinical manifestations. The main clinical performance are the damage of cerebral symptoms, cranial nerve and spinal nerve. The diagnosis primarily based on the history of tumor, clinical symptoms, enhance magnetic resnance image (MRI scan and cerebrospinal fluid cytology. In recent years, new ways of detecting clinically, significantly increase the rate of early detection of leptomeningeal metastases. The effect of comprehensive treatments are still sad. The paper make a review of research progress in pathologic physiology, clinical manifestations, diagnosis methods and treatments of lung cancer with leptomeningeal metastases.

Evaluate the Mechanism of Enhanced Metastasis Induced by Arthritis

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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

Protein arginine methyltransferase 5 promotes lung cancer metastasis via the epigenetic regulation of miR-99 family/FGFR3 signaling.

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Jing, Pengyu; Zhao, Nan; Ye, Mingxiang; Zhang, Yong; Zhang, Zhipei; Sun, Jianyong; Wang, Zhengxin; Zhang, Jian; Gu, Zhongping

2018-07-28

Protein arginine methyltransferase 5 (PRMT5) functions as a tumor initiator to regulate several cancer progressions, such as proliferation and apoptosis, by catalyzing the symmetrical dimethylation (me2s) of arginine residues within targeted molecules. However, the exact role of PRMT5-mediated metastasis in lung cancer is not fully understood. Here, we illustrated its potential effects in lung cancer metastasis in vivo and vitro. PRMT5 was frequently overexpressed in lung tumors, and its expression was positively related to tumor stages, lymphatic metastasis and poor outcome. In this model, PRMT5 repressed the transcription of the miR-99 family by symmetrical dimethylation of histone H4R3, which increased FGFR3 expression and in turn activated Erk1/2 and Akt, leading to cell growth and metastasis in lung cancer. Furthermore, loss of PRMT5 exerted anti-metastasis effects on lung cancer progression by blocking histone-modification of miR-99 family. Overall, this study provides new insights into the PRMT5/miR-99 family/FGFR3 axis in regulating lung cancer progression and identifies PRMT5 as a promising prognostic biomarker and therapeutic target. Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.

The value of combined examination of serum CYFRA21-1 levels and bone scan in the diagnosis of bone metastasis in lung cancer

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Yu Jing; Wang Junhong; Zhengping

2007-01-01

Objective: To explore the value of combined examination of serum tumor markers CYFRA21-1 and bone scan in the diagnosis of bone metastasis in lung cancer. Methods: Bone scan and serum CYFRA21-1 levels (with CLIA) determination were performed in 138 patients with lung cancer and 56 patients with benign lung diseases. Results: The serum level of CYFRA21-1 were significantly higher in patients with bone metastasis than those in patients without bone metastasis. The levels were also higher in patients without bone metastasis than those in controls. Most patients with bone metastasis had positive results in bone scan (97.4%), only 2 of the 78 had negative bone scan but positive with CT or MRI. A few patients without bone metastasis and controls had positive bone scan results, caused by previous operation or injury. Conclusion: The combined detection of CYFRA21-1 and bone scan were valuable in the diagnosis of bone metastasis of lung cancer. (authors)

Metastasis features of 546 patients with stage IV non-small cell lung cancer at first visit and the significance in radiotherapy

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Li Fenghu; Lu Bing; Fu Heyi; Han Lei; Li Qingsong; Li Huiqin

2012-01-01

Objective: To investigate the clinical metastasis features and the possibility of 3 dimensional radiotherapy of stage IV non-small cell lung cancer (NSCLC). Methods: The clinical materials of 546 patients with stage IV NSCLC and the relationship b T and N stage and metastasis were retrospectively analyzed. Results In 546 patients with stage IV NSCLC, the number with bone metastasis was 294, the number with brain metastasis was 167, the number with lung metastasis was 137, the number with liver metastasis was 79, the number with adrenal gland metastasis was 66, 37 with lymph node metastasis, 35 with subcutaneous metastasis and 10 with other organ metastasis. The number with single organ metastasis was 379 (69.4%) ,in which 37.7% with bone metastasis, 19.8% with brain metastasis, 16.9% with lung metastasis, 7.4% with liver metastasis, 7.4% with adrenal gland metastasis, 4.5% with lymph node metastasis, 5.5% with subcutaneous metastasis and 0.8% with other organ metastasis. The bone metastasis probability of T 3+4 patient was similar with T 1+2 (69.4%, 30.6%, χ 2 = 7.65, P = 0.067), but N 2+3 patient was more than N 0+1 (69.7%, 30.3%, χ 2 = 7.89, P = 0.044). The brain metastasis probability of T 3+4 patient was more than T 1+2 (70.7%, 29.3%, χ 2 = 10.64, P = 0.018), but N 2+3 patient was similar with N 0+1 (54.5%, 45.5%, χ 2 = 7.14, P = 0.079), and N 1+3+3 patient was more than N 0 (86.8%, 13.2%, χ 2 = 10.26, P = 0.024). Conclusions: In 546 patients with stage IV NSCLC, the most common metastatic organ is bone, the second is brain, the third is lung, the forth is liver, followed by adrenal gland; single organ metastasis is more common than multiple organ metastasis. The later the T stage is, the more severe is the metastasis. Through 3 dimensional radiotherapy, not only the quality of life of some stage IV patients is improved, but also the survival time was prolonged observably. (authors)

Inhibitory effect of magnolol on tumour metastasis in mice.

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Ikeda, Koji; Sakai, Yoshimichi; Nagase, Hisamitsu

2003-09-01

It has previously been reported that magnolol, a phenolic compound isolated from Magnolia obovata, inhibited tumour cell invasion in vitro. The purpose of this study was to investigate the antimetastatic effect of magnolol on tumour metastasis in vivo with experimental and spontaneous metastasis models and to clarify the mechanism. The antimetastatic effects of magnolol were evaluated by an experimental liver and spleen metastasis model using L5178Y-ML25 lymphoma, or an experimental and spontaneous lung metastasis model using B16-BL6 melanoma. Intraperitoneal (i.p.) administration of 2 or 10 mg/kg of magnolol significantly suppressed liver and spleen metastasis or lung metastasis. As for the spontaneous lung metastasis model using B16-BL6 melanoma, multiple i.p. administrations of 10 mg/kg of magnolol after and before tumour inoculation significantly suppressed lung metastasis and primary tumour growth. In addition, magnolol significantly inhibited B16-BL6 cell invasion of the reconstituted basement membrane (Matrigel, MG) without affecting cell growth. These data from the in vivo experiments suggest that magnolol possesses strong antimetastatic ability and that it may be a lead compound for drug development. The antimetastatic action of magnolol is considered to be due to its ability to inhibit tumour cell invasion. Copyright 2003 John Wiley & Sons, Ltd.

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.

Effective treatment with icotinib in lung adenocarcinoma with EGFR and ALK co-alterations and brain metastasis

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Ye CY

2016-10-01

Full Text Available Chenyang Ye,1,* Ji Wang,2,* Shu Zheng,1 Ying Chai3 1Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, National Ministry of Education, Provincial Key Laboratory of Molecular Biology in Medical Sciences, The Second Affiliated Hospital, Zhejiang University School of Medicine, 2Department of Surgical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, 3Department of Thoracic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: We report a rare case of advanced lung cancer with epidermal growth factor receptor and anaplastic lymphoma kinase co-alterations and brain metastasis, in which icotinib treatment was effective for both the primary lung tumor and the brain metastasis. The patient achieved important clinical remission with a progression-free survival for two years. Our treatment strategy appears to be a promising therapeutic approach for this subgroup of patients. Keywords: lung cancer, brain metastasis, EGFR, ALK, icotinib

Late Lung Metastasis of a Primary Eccrine Sweat Gland Carcinoma 10 Years after Initial Surgical Treatment: The First Clinical Documentation

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R. F. Falkenstern-Ge

2013-01-01

Full Text Available Background. Sweat gland carcinoma is a rare malignancy with a high metastatic potential seen more commonly in elderly patients. The scalp is the most common site of occurrence and it usually spreads to regional lymph nodes. Liver, lungs, and bones are the most common sites of distant metastasis. Late lung metastasis of sweat gland adenocarcinoma after a time span of 5 years is extremely rare. Aim. We report a patient with late lung metastasis of a primary sweat gland carcinoma 10 years after initial surgical resection. Conclusion. Sweat gland carcinomas are rare cancers with a poor prognosis. Surgery in the form of wide local excision and lymph node dissection is the mainstay of treatment. Late pulmonary metastases with a latency of 10 years have never been reported in the literature. This is the first clinical documentation of late lung metastasis from sweat gland carcinoma with a latency period of 10 years.

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

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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.

FDG-PET-Detected Extracranial Metastasis in Patients with Non-Small Cell Lung Cancer Undergoing Staging for Surgery or Radical Radiotherapy

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Macmanus, Michael P.; Hicks, Rodney; Fisher, Richard; Rischin, Danny; Michael, Michael; Wirth, Andrew; Ball, David L. [Peter MacCallum Cancer Inst., Melbourne (Australia). Dept. of Radiation Oncology

2003-03-01

The prognostic significance of extracranial distant metastasis detected by positron emission tomography (PET) was investigated in patients with non-small cell lung cancer (NSCLC). Forty-two patients staged with 18F-fluorodeoxyglucose-PET-detected distant metastasis before planned surgery (n=7) or radical radiotherapy (RT)/chemoradiotherapy (n=35) for NSCLC were identified from a prospective database. The influence of metastasis number and other prognostic factors was investigated using Cox's regression analysis. Treatment after PET included surgery (n=2), radical RT (n =5), palliative RT (n=25), chemotherapy (n=8) or supportive care (n=2). All but 4 patients had died by the last follow-up. Median survival was 9 months overall, 12 months for 27 patients with single PET-detected metastasis and 5 months for 15 patients with >1 metastasis (p=0.009). It was found that the Eastern Cooperative Oncology Group performance status (p=0.027) but not pre-PET stage, weight loss or metastasis site correlated with survival. PET-detected metastatic tumor burden appeared to influence survival and should be evaluated as a prognostic factor in NSCLC.

Occipital condyle metastasis: an unusual clinical presentation in carcinoma of the lung

International Nuclear Information System (INIS)

Pasricha, R.; Mohanty, P.P.; Madan, R.C.; Datta, N.R.

2005-01-01

Metastases to the base of the skull and occipital condyle metastases are uncommon as a presenting feature of malignancy. Lung cancers are known for their metastatic potential to various sites, some of which could be the only presenting feature of the underlying malignancy. However, occipital condyle metastases are very rare and to the best of our knowledge, metastases to this site from carcinoma of the lung, as a presenting feature, have never been reported in the literature. The present case report describes the clinical, radiological and the therapeutic interventions that were undertaken in a patient presenting with lung cancer who had solely the features of occipital condyle metastasis

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

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.

Non-metastatic 2 (NME2)-mediated suppression of lung cancer metastasis involves transcriptional regulation of key cell adhesion factor vinculin

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Thakur, Ram Krishna; Yadav, Vinod Kumar; Kumar, Akinchan; Singh, Ankita; Pal, Krishnendu; Hoeppner, Luke; Saha, Dhurjhoti; Purohit, Gunjan; Basundra, Richa; Kar, Anirban; Halder, Rashi; Kumar, Pankaj; Baral, Aradhita; Kumar, MJ Mahesh; Baldi, Alfonso; Vincenzi, Bruno; Lorenzon, Laura; Banerjee, Rajkumar; Kumar, Praveen; Shridhar, Viji; Mukhopadhyay, Debabrata; Chowdhury, Shantanu

2014-01-01

Tumor metastasis refers to spread of a tumor from site of its origin to distant organs and causes majority of cancer deaths. Although >30 metastasis suppressor genes (MSGs) that negatively regulate metastasis have been identified so far, two issues are poorly understood: first, which MSGs oppose metastasis in a tumor type, and second, which molecular function of MSG controls metastasis. Herein, integrative analyses of tumor-transcriptomes (n = 382), survival data (n = 530) and lymph node metastases (n = 100) in lung cancer patients identified non-metastatic 2 (NME2) as a key MSG from a pool of >30 metastasis suppressors. Subsequently, we generated a promoter-wide binding map for NME2 using chromatin immunoprecipitation with promoter microarrays (ChIP-chip), and transcriptome profiling. We discovered novel targets of NME2 which are involved in focal adhesion signaling. Importantly, we detected binding of NME2 in promoter of focal adhesion factor, vinculin. Reduced expression of NME2 led to enhanced transcription of vinculin. In comparison, NME1, a close homolog of NME2, did not bind to vinculin promoter nor regulate its expression. In line, enhanced metastasis of NME2-depleted lung cancer cells was found in zebrafish and nude mice tumor models. The metastatic potential of NME2-depleted cells was remarkably diminished upon selective RNA-i-mediated silencing of vinculin. Together, we demonstrate that reduced NME2 levels lead to transcriptional de-repression of vinculin and regulate lung cancer metastasis. PMID:25249619

Tongue metastasis mimicking an abscess.

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Mavili, Ertuğrul; Oztürk, Mustafa; Yücel, Tuba; Yüce, Imdat; Cağli, Sedat

2010-03-01

Primary tumors metastasizing to the oral cavity are extremely rare. Lung is one of the most common primary sources of metastases to the tongue. Although the incidence of lung cancer is increasing, tongue metastasis as the initial presentation of the tumor remains uncommon. Due to the rarity of tongue metastasis, little is known about its imaging findings. Herein we report the magnetic resonance imaging and clinical findings of a lingual metastasis, mimicking an abscess, from a primary lung cancer.

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

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

Tumour exosome integrins determine organotropic metastasis.

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

2015-11-19

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

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

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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

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

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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.

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

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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.

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)

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

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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.

Increased AAA-TOB3 correlates with lymph node metastasis and advanced stage of lung adenocarcinoma.

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Liu, Yanfeng; Bu, Lina; Li, Wei; Wu, Wei; Wang, Shengyu; Diao, Xin; Zhou, Jing; Chen, Guoan; Yang, Shuanying

2017-07-24

This study was to investigate the differential mitochondrial protein expressions in human lung adenocarcinoma and provide preliminary data for further exploration of the carcinogenic mechanism. Total proteins of A549 and 16HBE mitochondria were extracted through 2D polyacrylamide gel electrophoresis (2-DE). The differential mitochondria proteins were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and were further confirmed by Western blot, immunoelectron microscopy and immunohistochemistry (IHC) in A549 cells as well as lung adenocarcinoma tissues. A total of 41 differentially expressed protein spots were found in A549 mitochondria. Of them, 15 proteins were highly expressed and 26 proteins were lowly expressed in the mitochondria of A549 (by more than 1.5 times). Among the 15 more highly expressed proteins, AAA-TOB3 (by more than 3 times) was highly expressed in the mitochondria of A549 compared with the 16HBE, by LC-MS/MS identification. High electron density and clear circular colloidal gold-marked AAA-TOB3 particles were observed in the A549 cells via immunoelectron microscopy. Besides, AAA-TOB3 was confirmed to be elevated in lung adenocarcinoma by Western blot and IHC. Moreover, increased AAA-TOB3 correlated with lymph node metastasis and advanced stage of lung adenocarcinoma (pAAA-TOB3 was highly expressed in lung adenocarcinoma, and the up-regulation of AAA-TOB3 correlated with lymph node metastasis and advanced stage of lung adenocarcinoma, which suggested that it could serve as a potential molecular marker for lung adenocarcinoma.

[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.

A case of central diabetes insipidus that was caused by pituitary metastasis of lung adenocarcinoma and was controlled by radiation therapy

International Nuclear Information System (INIS)

Izumi, Yusuke; Masuda, Takeshi; Nabeshima, Shinji

2017-01-01

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 four) 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. (author)

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.

Establishment of an orthotopic lung cancer model in nude mice and its evaluation by spiral CT.

Science.gov (United States)

Liu, Xiang; Liu, Jun; Guan, Yubao; Li, Huiling; Huang, Liyan; Tang, Hailing; He, Jianxing

2012-04-01

To establish a simple and highly efficient orthotopic animal model of lung cancer cell line A549 and evaluate the growth pattern of intrathoracic tumors by spiral CT. A549 cells (5×10(6) mL(-1)) were suspended and inoculated into the right lung of BALB/c nude mice via intrathoracic injection. Nude mice were scanned three times each week by spiral CT after inoculation of lung cancer cell line A549. The survival time and body weight of nude mice as well as tumor invasion and metastasis were examined. Tissue was collected for subsequent histological assay after autopsia of mice. The tumor-forming rate of the orthotopic lung cancer model was 90%. The median survival time was 30.7 (range, 20-41) days. The incidence of tumor metastasis was 100%. The mean tumor diameter and the average CT value gradually increased in a time-dependent manner. The method of establishing the orthotopic lung cancer model through transplanting A549 cells into the lung of nude mice is simple and highly successful. Spiral CT can be used to evaluate intrathoracic tumor growth in nude mice vividly and dynamically.

High Salt Intake Attenuates Breast Cancer Metastasis to Lung.

Science.gov (United States)

Xu, Yijuan; Wang, Wenzhe; Wang, Minmin; Liu, Xuejiao; Lee, Mee-Hyun; Wang, Mingfu; Zhang, Hao; Li, Haitao; Chen, Wei

2018-04-04

Diet-related factors are thought to modify the risk of cancers, while the influence of high salt intake remains largely uncharacterized. Breast cancer is the most common cancer in women worldwide. In the present study, we examined the effect of salt intake on breast cancer by using a 4T1 mouse mammary tumor model. Unexpectedly, both the fitness and the survival rate of the tumor-bearing mice were improved by high salt intake. Similarly, high salt intake suppressed the primary tumor growth as well as metastasis to lung in mice. Mechanistically, high salt intake greatly reduced food intake and thus might exert antitumor effect through mimicking calorie restriction. Immunoblotting showed the lower proliferation marker Ki-67 and the higher expression of the tumor suppressor gene p53 in tumors of high salt intake mice. Importantly, high salt intake might induce hyperosmotic stress, which sensitized breast cancer cells to p53-dependent anoikis. Collectively, our findings raise the possibility that endogenous salt deposition might act as the first-line defense system against breast cancer progression as well as metastasis.

Relapsing pattern of brain metastasis after brain irradiation in small cell lung cancer

International Nuclear Information System (INIS)

Murakami, Masao; Kuroda, Yasumasa; Okamoto, Yoshiaki; Kono, Koichi; Yoden, Eisaku; Mori, Takeki

1997-01-01

Many reports concerning radiation therapy for brain metastasis have been published, and which of the various methods urged by these reports provide optional control is still controversial. According to developing diagnosis of metastasis in CNS, therapeutic problems should be referred. We reviewed 67 patients with small cell lung cancer and brain metastasis who underwent brain irradiation (Ave. 47 Gy/5W), and all 15 patients with brain relapse after the irradiation. Relapsing patterns in this clinical setting were divided into local regrowth in the same lesions and re-metastasis (reseeding) in other regions, by reviewing follow up CT and MRI studies. Total survival among 15 patients with brain relapse and 52 without relapse was longer in the former cases than the later: 1-, and 2-year survival (47/19%, 13/8%) and MST (10.8/5.7 months), from the initial brain irradiation. The concerned significant factors limited in younger age, low value of LDH and improvement of NF. Of the 15 patients with brain relapse, 4 developed local regrowth and 11 did re-metastasis. The period of remission since brain irradiation were 172±94.4 and 393±281 days, respectively. Lower number of brain metastasis and lower value of LDH were shown in re-metastasis patients. At the time of brain relapse, 11 patients had recurrence of carcinomatous meningitis. 4 patients were treated with whole brain re-irradiation. All patients died of cancer, including 12 of relapsing CNS diseases and 3 of primary lesion and hepatic metastasis. Leukoencephalopathy developed in 2 patients. Survival since the brain relapse was 2 to 238 days without significant difference in cases of local regrowth and re-metastasis. According to our data on relapsing pattern of brain metastasis after conventional fractionated brain irradiation with an objective dose of 50 Gy, 75% of brain relapse were re-metastasis, we appreciate this irradiation for initial brain metastasis if limited to the brain. (author)

Single Nucleotide Polymorphisms of MMP2 Gene Promoter on the Risk of Development and Metastasis of lung Cancer

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H Keshvary Ravan

2017-04-01

Full Text Available     Background & aim: The high incidence and poor prognosis of the lung cancer makes it aa a major health problem in the last few decades. Determination of frequency of different histopathology types of primary lung cancer has great importance in creating integrated treatment programs and recognized the effective factors causing the disease. Overexpression of MMPs has a direct relation with invasion and metastasis of malignant tumors in different tissues. The aim of this study was to assess the effect of MMP-2 gene promoter polymorphism with lung cancer and metastases in patients with lung cancer and compared with the control groups by the PCR-RFLP method.   Methods: In the present case-control study, The MMP-2 polymorphisms were analyzed by restriction fragment-length polymorphism (RFLP in 50 patients with lung cancer and 77 cohort sample. All samples were taken under supervision of a physician. DNA isolation was performed using DNA extraction kit (Cinnagen, Iran. MMP9 gene was amplified by specific primers and PCR product was digested with FSPBI restriction enzyme. Data were analysis using Chi square by the SPSS software.   Results: The examination of allelic and genotypic distribution in patients with lung cancer and control showed that the allele frequency of C and T in patients with lung cancer were 90 and 10% (P=0.04 and in the control were 80.15 and 30% (P=0.05 respectively. Also genotype frequency of CC, CT and TT in patients with lung cancer were 82, 16 and 2 (P=0.05 and in the control were 69.93, 31.16, 3.1 percentage respectively (P=0.5. No significant difference was seen in comparison of genotype groups in non-metastatic and control. Comparison of homozygous CC genotype and control were confirmed the direct involvement of c allele in metastasis   Conclusion: It seems that individuals with C allele can increase susceptibility to lung cancer. Also these findings indicate that CC genotype as a risk factor facilitating the spread of

Hypophyseal metastasis

International Nuclear Information System (INIS)

Yanes Quesada, Miguel Angel; Yanes Quesada, Marelys; Lopez Arbolay, Omar; Lima Perez, Mayte; Hernandez Yero, Arturo

2009-01-01

Metastatic tumors of hypophyseal gland are infrequent. Most are silent lesions discovered accidentally in necropsy. Appearance of symptomatic metastasis is however, exceptional. 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. (Author)

CT findings of adenocarcinoma of the lung

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Jeon, T. J.; Kim, S. J.; Lee, D. Y.; Ahn, C. M [Yonsei Univ. College of Medicine, Seoul (Korea, Republic of)

1996-03-01

To evaluate CT findings of primary adenocarcinoma of the lung and to assess distant metastasis at the time of diagnosis. CT findings of 150 patients with adenocarcinoma, confirmed by histopathologic methods, were classified as central or peripheral lesion and pattern analysis of typical findings noted in this cancer was carried out. Intra and extrathoracic metastases of adenocarcinoma were also investigated. Of 150 cases of adenocarcinoma of the lung, 121 were found to be of the peripheral type and 29 were of the central type. These peripheral lesions comprised 105 nodules, 11 consolidations, four cavities and one linear lesion, while the central lesions consisted of 19 cases of atelectasis and tens of branchial wall thickening. lung to lung(nine cases), lymphangitic(five cases), and pleural metastasis(16 cases) were presented as intrathoracic metastasis, while bone(17), brain,(six), liver(two) and adrenal metastasis(one case)were presented as extrathoracic metastasis. The most common radiologic finding of adenocarcinoma is a peripheral single mass or nodule but consolidation, cavity or tubular lesions, as well as atelectasis or bronchial wall thickening alone can be presented as unusual findings of adenocarcinoma. As a consequence, it is in many cases difficult to differentially diagnose. Distant metastasis was also noted in many cases of early T-stage lesion, so to successfully manage the patient, careful evaluation of the metastasis is essential.

CT findings of adenocarcinoma of the lung

International Nuclear Information System (INIS)

Jeon, T. J.; Kim, S. J.; Lee, D. Y.; Ahn, C. M

1996-01-01

To evaluate CT findings of primary adenocarcinoma of the lung and to assess distant metastasis at the time of diagnosis. CT findings of 150 patients with adenocarcinoma, confirmed by histopathologic methods, were classified as central or peripheral lesion and pattern analysis of typical findings noted in this cancer was carried out. Intra and extrathoracic metastases of adenocarcinoma were also investigated. Of 150 cases of adenocarcinoma of the lung, 121 were found to be of the peripheral type and 29 were of the central type. These peripheral lesions comprised 105 nodules, 11 consolidations, four cavities and one linear lesion, while the central lesions consisted of 19 cases of atelectasis and tens of branchial wall thickening. lung to lung(nine cases), lymphangitic(five cases), and pleural metastasis(16 cases) were presented as intrathoracic metastasis, while bone(17), brain,(six), liver(two) and adrenal metastasis(one case)were presented as extrathoracic metastasis. The most common radiologic finding of adenocarcinoma is a peripheral single mass or nodule but consolidation, cavity or tubular lesions, as well as atelectasis or bronchial wall thickening alone can be presented as unusual findings of adenocarcinoma. As a consequence, it is in many cases difficult to differentially diagnose. Distant metastasis was also noted in many cases of early T-stage lesion, so to successfully manage the patient, careful evaluation of the metastasis is essential

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.

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)

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

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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.

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

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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.

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

DEFF Research Database (Denmark)

Fabian, Katalin; Gyulai, Marton; Furak, Jozsef

2016-01-01

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

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.

Bone scanning in the evaluation of lung cancer

International Nuclear Information System (INIS)

Jung, Kun Sik; Zeon, Seok Kil; Lee, Hee Jung; Song, Hong Suk

1994-01-01

We studied the diagnostic significance of bone scan in evaluation of bone metastasis by lung cancer, prevalence rate, and the causes of false positive bone scan and soft tissue accumulation of bone seeking agent. This subject include 73 lung cancer patients with bone scan, We analyzed the frequency of the metastasis, its distribution and configuration, and any relationship between bone pain and corresponding region on bone scan. The positive findings of bone scans were compared with simple X-ray film, CT, MRI and other diagnostic modalities. The false positive bone scan and the soft tissue accumulation of bone seeking agent were analyzed. The positive findings on bone scan were noted in 26 cases(36%) and they were coexistent with bone pain in 30%. The correspondence between bone scan and bone X-ray was 38%. False positive bone scans were seen in 12 cases(16%), which include fracture due to thoracotomy and trauma, degenerative bone disease, and bifid rib. Accumulation of bone seeking agent in soft tissue were seen in 13 cases(18%), which included primary tumor, enlarged cervical lymph node, pleural effusion, ascites and pleural thickening. Bone scans should be carefully interpreted in detecting bone metastasis in primary malignancy, because of the 16% false positivity and 18% soft tissue accumulation rate. It is very important to note that the correlation between bone pain and positive findings of bone scans was only 38%

Bone scanning in the evaluation of lung cancer

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Jung, Kun Sik; Zeon, Seok Kil; Lee, Hee Jung; Song, Hong Suk [School of Medicine, Keimyung University, Daegu (Korea, Republic of)

1994-05-15

We studied the diagnostic significance of bone scan in evaluation of bone metastasis by lung cancer, prevalence rate, and the causes of false positive bone scan and soft tissue accumulation of bone seeking agent. This subject include 73 lung cancer patients with bone scan, We analyzed the frequency of the metastasis, its distribution and configuration, and any relationship between bone pain and corresponding region on bone scan. The positive findings of bone scans were compared with simple X-ray film, CT, MRI and other diagnostic modalities. The false positive bone scan and the soft tissue accumulation of bone seeking agent were analyzed. The positive findings on bone scan were noted in 26 cases(36%) and they were coexistent with bone pain in 30%. The correspondence between bone scan and bone X-ray was 38%. False positive bone scans were seen in 12 cases(16%), which include fracture due to thoracotomy and trauma, degenerative bone disease, and bifid rib. Accumulation of bone seeking agent in soft tissue were seen in 13 cases(18%), which included primary tumor, enlarged cervical lymph node, pleural effusion, ascites and pleural thickening. Bone scans should be carefully interpreted in detecting bone metastasis in primary malignancy, because of the 16% false positivity and 18% soft tissue accumulation rate. It is very important to note that the correlation between bone pain and positive findings of bone scans was only 38%.

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)

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

Directory of Open Access Journals (Sweden)

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.

Prognostic Significance of Tumor Size of Small Lung Adenocarcinomas Evaluated with Mediastinal Window Settings on Computed Tomography

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Sakao, Yukinori; Kuroda, Hiroaki; Mun, Mingyon; Uehara, Hirofumi; Motoi, Noriko; Ishikawa, Yuichi; Nakagawa, Ken; Okumura, Sakae

2014-01-01

BACKGROUND: We aimed to clarify that the size of the lung adenocarcinoma evaluated using mediastinal window on computed tomography is an important and useful modality for predicting invasiveness, lymph node metastasis and prognosis in small adenocarcinoma. METHODS: We evaluated 176 patients with small lung adenocarcinomas (diameter, 1-3 cm) who underwent standard surgical resection. Tumours were examined using computed tomography with thin section conditions (1.25 mm thick on high-resolution ...

Establishment of A Novel Chinese Human Lung Adenocarcinoma Cell Line CPA-Yang3 and Its Real Bone Metastasis Clone CPA-Yang3BM in Immunodeficient Mice

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Shunfang YANG

2011-02-01

Full Text Available Background and objective The recurrence and metastasis of lung cancer is a tough problem worldwide. The aim of this study is to establish a novel Chinese lung adenocarcinoma cell line and its real bone-seeking clone sub-line for exploring the molecular mechanism of lung cancer metastasis. Methods The cells came from the pleural effusion of a sixtyfive years old female patient with lung adenocarcinoma and supraclavicular lymph node metastases. The gene expression was detected by real-time quantitative PCR. Intracardiac injection of the cells into nude mice was performed and in vivo imaging was obtained by bone scintigraphy and conventional radiography. Bone metastases were determined on bone scintigraphy and then the lesions were resected under deep anesthesia for bone metastasis cancer cell culture. The process was repeated for four cycles to obtain a real bone-seeking clone. Results The tumorigenesis rate started at 4th passage in immunodeficient mice via subcutaneously and as well as later passages. Approximately 1×106 cancer cells were injected into left cardiac ventricle of immunodeficient mice resulted bone metastasis sites were successfully revealed by bone scintigraphy and pathological diagnosis, the mandible (100%, scapula (33%, humerus (50%, vertebral column (50%, femur (66.7% and accompanied invasion with other organs, the adrenal gland (17%, pulmonary (33%, liver (50%, submaxillary gland (33% in the mice after inoculation two-three weeks. The chromosome karyotype analysis of the cells was subdiploid. Quantitative real-time PCR was used to examined and compared with SPC-A-1 lung adenocarcinoma, ESM1, VEGF-C, IL-6, IL-8, AR, SVIL, FN1 genes were overexpress. The novel cell was named CPA-Yang3. The femur metastasis cell was repeated in vivo-in vitro-in vivo with three cycles and harvested a real bone metastasis clone. It was named CPA-Yang3BM. Conclusion Tne characteristics of novel strain CPAYang3 is a highly metastasis cell line of

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.

Breast metastasis from lung cancer：a report of two cases and literature review

Institute of Scientific and Technical Information of China (English)

Li Wang; Shu-Ling Wang; Hong-Hong Shen; Feng-Ting Niu; Yun Niu

2014-01-01

Breast metastasis from extra-mammary malignancy is rare. An incidence of 0.4% to 1.3% has been reported in literature. hTe primary malignancies that most commonly metastasize to the breast are leukemia, lymphoma, and malignant melanoma. In this report, two cases of pulmonary metastasis to the breast were presented. A 40-year-old female manifested a right breast mass of 2-month duration. Atfer physical examination was performed, a poorly deifned mass was noted in the upper outer quadrant of the right breast. Another 49-year-old female manifested right breast mass of 5-day duration. A poorly deifned mass was noted in the lower inner quadrant of the right breast. Mammography results also revealed breast cancer. hTe patients underwent local excision. Atfer histological and immunohistochemical analyses were conducted, a primary lung carcinoma that metastasized to the breast was diagnosed. An accurate differentiation of metastasis to the breast from primary breast cancer is very important because the treatment and prognosis of the two differ signiifcantly.

Efficacy of icotinib versus traditional chemotherapy as first-line treatment for preventing brain metastasis from advanced lung adenocarcinoma in patients with epidermal growth factor receptor-sensitive mutation.

Science.gov (United States)

Zhao, Xiao; Zhu, Guangqin; Chen, Huoming; Yang, Ping; Li, Fang; Du, Nan

2016-01-01

This study aimed to investigate the potential use of icotinib as first-line treatment to prevent brain metastasis from advanced lung adenocarcinoma. This investigation was designed as a retrospective nonrandomized controlled study. Enrolled patients received either icotinib or traditional chemotherapy as their first-line treatment. The therapeutic efficacy was compared among patients with advanced. (stages IIIB and IV) lung adenocarcinoma with epidermal growth factor receptor (EGFR)-sensitive mutation. The primary endpoint was the cumulative incidence of brain metastasis, whereas, the secondary endpoint was overall survival(OS). Death without brain metastasis was considered a competitive risk to calculate the cumulative risk of brain metastasis. Survival analysis was conducted using the Kaplan-Meier method and statistical significance was determined using the log-rank test. The present study included 396 patients with 131 in the icotinib group and 265 in the chemotherapy group. Among those with EGFR-sensitive mutation, the cumulative risk of brain metastasis was lower in the icotinib group than in the chemotherapy group. However, no significant difference in OS was observed between the two groups. Icotinib can effectively reduce the incidence of brain metastasis and therefore improve prognosis in advanced lung adenocarcinoma patients with EGFR.sensitive mutation.

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.

Cavitary pulmonar metastasis

International Nuclear Information System (INIS)

Marchiori, E.; Matushita, J.P.K.; Azevedo, C.M. de

1984-01-01

Seven cases of cavitary lung metastasis, four from head and neck neoplasma, two from uterine carcinoma and one from hepatoma are reported. The physiopathology and the most common sites of this kind of lesion are discussed. The rarity of the solitary excavated metastasis from hepatoma, not reported previously in the literature reviewed, is emphasized. (Author) [pt

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

Directory of Open Access Journals (Sweden)

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.

Metachronous Lung Cancer: Clinical Characteristics and Effects of Surgical Treatment.

Science.gov (United States)

Rzechonek, Adam; Błasiak, Piotr; Muszczyńska-Bernhard, Beata; Pawełczyk, Konrad; Pniewski, Grzegorz; Ornat, Maciej; Grzegrzółka, Jędrzej; Brzecka, Anna

2018-01-01

The occurrence of a second lung tumor after surgical removal of lung cancer usually indicates a lung cancer metastasis, but sometimes a new lesion proves to be a new primary lung cancer, i.e., metachronous lung cancer. The goal of the present study was to conduct a clinical evaluation of patients with metachronous lung cancer and lung cancer metastasis, and to compare the early and distant outcomes of surgical treatment in both cancer types. There were 26 age-matched patients with lung cancer metastases and 23 patients with metachronous lung cancers, who underwent a second lung cancer resection. We evaluated the histological type of a resected cancer, the extent of thoracosurgery, the frequency of early postoperative complications, and the probability of 5-year survival after the second operation. The findings were that metachronous lung cancer was adenocarcinoma in 52% of patients, with a different histopathological pattern from that of the primary lung cancer in 74% of patients. In both cancer groups, mechanical resections were the most common surgery type (76% of all cases), with anatomical resections such as segmentectomy, lobectomy, or pneumectomy being much rarer conducted. The incidence of early postoperative complications in metachronous lung cancer and lung cancer metastasis (30% vs. 31%, respectively) and the probability of 5-year survival after resection of either cancer tumor (60.7% vs. 50.9%, respectively) were comparable. In conclusion, patients undergoing primary lung cancer surgery require a long-term follow-up due to the risk of metastatic or metachronous lung cancer. The likelihood of metachronous lung cancer and pulmonary lung cancer metastases, the incidence of postoperative complications, and the probability of 5-year survival after resection of metachronous lung cancer or lung cancer metastasis are similar.

Abscess mimicking lung metastasis in a 10-year-old boy – case report

International Nuclear Information System (INIS)

Roik, Danuta; Mosior, Tomasz; Sopyło, Barbara; Małdyk, Jadwiga; Brzewski, Michał

2010-01-01

Malignant pulmonary tumours in children are very rare; the majority are metastases. Nonspecific radiographic findings of these abnormalities are challenging and may delay the final diagnosis and treatment. A 10-year-old boy was admitted to our hospital because of the clinical and radiographic symptoms and signs of pneumonia with abscess formation in the left lower lobe. After initial improvement on antibiotic therapy, a significant deterioration of the patient’s condition was observed, together with progression in radiographic examinations. The patient was treated surgically and transferred to the Haematology and Oncology Department with a final diagnosis of pulmonary metastasis of clear cell sarcoma. Radiographic findings of metastatic diseases may mimic non-neoplastic pulmonary conditions. A lack of specific clinical symptoms and a confusing radiographic pattern in our patient with clear cell sarcoma lung metastasis caused serious diagnostic difficulties

Inhibition of experimental lung metastasis by systemic lentiviral delivery of kallistatin

International Nuclear Information System (INIS)

Shiau, Ai-Li; Wu, Chao-Liang; Lee, Che-Hsin; Teo, Min-Li; Chen, Shin-Yao; Wang, Chrong-Reen; Hsieh, Jeng-Long; Chang, Meng-Ya; Chang, Chih-Jui; Chao, Julie; Chao, Lee

2010-01-01

Angiogenesis plays an important role in the development and progression of tumors. Kallistatin exerts anti-angiogenic and anti-inflammatory activities that may be effective in inhibiting tumor metastasis. We investigated the antitumor effect of lentivirus-mediated kallistatin gene transfer in a syngeneic murine tumor model. Lentiviral vector encoding kallistatin (LV-Kallistatin) was constructed. The expression of kallistatin was verified by enzyme-linked immunosorbent assay (ELISA), and the bioactivity of kallistatin was determined by using cell proliferation, migration, and invasion assays. In addition, antitumor effects of LV-Kallistatin were evaluated by the intravenous injection of virus into tumor-bearing mice. The conditioned medium from LV-Kallistatin-treated cells inhibited the migration and proliferation of endothelial cells. Meanwhile, it also reduced the migration and invasion of tumor cells. In the experimental lung metastatic model, tumor-bearing mice receiving LV-Kallistatin had lower tumor nodules and longer survival than those receiving control virus or saline. Moreover, the microvessel densities, the levels of vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-α, and nuclear factor κB (NF-κB) transcriptional activity were reduced in the LV-Kallistatin-treated mice. Results of this study showed that systemic administration of lentiviral vectors encoding kallistatin inhibited the growth of metastatic tumor and prolonged the survival of tumor-bearing mice. These results suggest that gene therapy using lentiviruses carrying the kallistatin gene, which exerts anti-angiogenic and anti-inflammatory activities, represents a promising strategy for the treatment of lung cancer

Efficacy of icotinib versus traditional chemotherapy as first-line treatment for preventing brain metastasis from advanced lung adenocarcinoma in patients with epidermal growth factor receptor-sensitive mutation

Directory of Open Access Journals (Sweden)

Xiao Zhao

2014-01-01

Full Text Available Objective: This study aimed to investigate the potential use of icotinib as first-line treatment to prevent brain metastasis from advanced lung adenocarcinoma. Patients and Methods: This investigation was designed as a retrospective nonrandomized controlled study. Enrolled patients received either icotinib or traditional chemotherapy as their first-line treatment. The therapeutic efficacy was compared among patients with advanced (stages IIIB and IV lung adenocarcinoma with epidermal growth factor receptor (EGFR-sensitive mutation. The primary endpoint was the cumulative incidence of brain metastasis, whereas the secondary endpoint was overall survival (OS. Death without brain metastasis was considered a competitive risk to calculate the cumulative risk of brain metastasis. Survival analysis was conducted using the Kaplan-Meier method and statistical significance were determined using the log-rank test. Results: The present study included 396 patients with 131 in the icotinib group and 265 in the chemotherapy group. Among those with EGFR-sensitive mutation, the cumulative risk of brain metastasis was lower in the icotinib group than in the chemotherapy group. However, no significant difference in OS was observed between the two groups. Conclusion: Icotinib can effectively reduce the incidence of brain metastasis and therefore improve prognosis in advanced lung adenocarcinoma patients with EGFR-sensitive mutation.

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

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

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

Directory of Open Access Journals (Sweden)

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.

SU-D-207B-03: A PET-CT Radiomics Comparison to Predict Distant Metastasis in Lung Adenocarcinoma

Energy Technology Data Exchange (ETDEWEB)

Coroller, T; Yip, S; Lee, S; Mak, R; Aerts, H [Dana Farber Cancer Institute, Brigham and Women’s Hospital, Havard Medical School, Boston, MA (United States); Kim, J [Brigham and Women’s Hospital, Children’s hospital, Harvard Medical School, Boston, MA (United States)

2016-06-15

Purpose: Early prediction of distant metastasis may provide crucial information for adaptive therapy, subsequently improving patient survival. Radiomic features that extracted from PET and CT images have been used for assessing tumor phenotype and predicting clinical outcomes. This study investigates the values of radiomic features in predicting distant metastasis (DM) in non-small cell lung cancer (NSCLC). Methods: A total of 108 patients with stage II–III lung adenocarcinoma were included in this retrospective study. Twenty radiomic features were selected (10 from CT and 10 from PET). Conventional features (metabolic tumor volume, SUV, volume and diameter) were included for comparison. Concordance index (CI) was used to evaluate features prognostic value. Noether test was used to compute p-value to consider CI significance from random (CI = 0.5) and were adjusted for multiple testing using false rate discovery (FDR). Results: A total of 70 patients had DM (64.8%) with a median time to event of 8.8 months. The median delivered dose was 60 Gy (range 33–68 Gy). None of the conventional features from PET (CI ranged from 0.51 to 0.56) or CT (CI ranged from 0.57 to 0.58) were significant from random. Five radiomics features were significantly prognostic from random for DM (p-values < 0.05). Four were extracted from CT (CI = 0.61 to 0.63, p-value <0.01) and one from PET which was also the most prognostic (CI = 0.64, p-value <0.001). Conclusion: This study demonstrated significant association between radiomic features and DM for patients with locally advanced lung adenocarcinoma. Moreover, conventional (clinically utilized) metrics were not significantly associated with DM. Radiomics can potentially help classify patients at higher risk of DM, allowing clinicians to individualize treatment, such as intensification of chemotherapy) to reduce the risk of DM and improve survival. R.M. has consulting interests with Amgen.

Diffuse Thyroid Metastasis From Lung Cancer Mimicking Thyroiditis on 99mTc-Pertechnetate Scintigraphy.

Science.gov (United States)

Gao, Rui; Gao, Shan; Feng, Jinteng; Wang, Yuanbo; Zhang, Guangjian

2017-09-01

Possible thyroiditis was suspected in a 56-year-old man who initially presented sore throat because laboratory examinations revealed decreased serum thyroid hormone and the Tc-pertechnetate scintigraphy showed no tracer uptake by the thyroid gland. However, subsequent examination demonstrated that the absence of pertechnetate activity in the thyroid was due to complete replacement of thyroid gland by the metastasis from lung adenocarcinoma, which was unknown at the initial presentation.

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...... that B16.F10gp cells were detectable in the lungs as early as 2 hours after intravenous challenge with ≥10(4) tumor cells. When investigating the gene expression as a function of time, we observed a gradual decrease from 2-24 hours post tumor challenge followed by an increase of approximately 2 log10...... 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...

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.

Endobronchial Ultrasound-guided Transbronchial Needle Aspiration 
in the Diagnosis of Intrathoracic Metastasis from Extrapulmonary Malignancy

Directory of Open Access Journals (Sweden)

Jiayuan SUN

2015-05-01

Full Text Available Background and objective Endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA has been widely applied in diagnosing mediastinal and hilar adenopathy. This study is further to evaluate value and safety of EBUS-TBNA in diagnosing intrathoracic metastasis from extrapulmonary malignancy. Methods Prospectively analysis of 41 patients suspected intrathoracic metastasis from previous diagnosed/concurrent extrapulmonary malignancies in Shanghai Chest Hospital, with radiologic findings showing mediastinal/hilar lymph node enlargement or intrapulmonary lesion requiring EBUS-TBNA examination for pathological diagnosis. Results 41 candidate patients enrolled, and 67 mediastinal/hilar lymph nodes and 5 intrapulmonary lesions were aspirated. 14 intrathoracic metastasis, 10 primary lung cancer, 9 reactive lymphadenitis, 4 sarcoid-like reactions, and 1 tuberculosis was diagnosed by EBUS-TBNA. Sensitivity and accuracy of EBUS-TBNA in diagnosing intrathoracic metastasis was 87.50% and 95.12%, respectively. Immunohistochemistry (IHC was performed in 18 malignant tumors to obtain definite type or origin, twelve intrathoracic metastasis and 6 primary lung cancer were further confirmed. Conclusion EBUS-TBNA is a safe, effective method for the diagnosis of intrathoracic metastasis from extrapulmonary malignancy. IHC can provide additional evidence for distinguishing extrapulmonary malignancy from primary lung cancer.

Inhibition of experimental lung metastasis by systemic lentiviral delivery of kallistatin

Directory of Open Access Journals (Sweden)

Chao Julie

2010-05-01

Full Text Available Abstract Background Angiogenesis plays an important role in the development and progression of tumors. Kallistatin exerts anti-angiogenic and anti-inflammatory activities that may be effective in inhibiting tumor metastasis. We investigated the antitumor effect of lentivirus-mediated kallistatin gene transfer in a syngeneic murine tumor model. Methods Lentiviral vector encoding kallistatin (LV-Kallistatin was constructed. The expression of kallistatin was verified by enzyme-linked immunosorbent assay (ELISA, and the bioactivity of kallistatin was determined by using cell proliferation, migration, and invasion assays. In addition, antitumor effects of LV-Kallistatin were evaluated by the intravenous injection of virus into tumor-bearing mice. Results The conditioned medium from LV-Kallistatin-treated cells inhibited the migration and proliferation of endothelial cells. Meanwhile, it also reduced the migration and invasion of tumor cells. In the experimental lung metastatic model, tumor-bearing mice receiving LV-Kallistatin had lower tumor nodules and longer survival than those receiving control virus or saline. Moreover, the microvessel densities, the levels of vascular endothelial growth factor (VEGF, tumor necrosis factor (TNF-α, and nuclear factor κB (NF-κB transcriptional activity were reduced in the LV-Kallistatin-treated mice. Conclusion Results of this study showed that systemic administration of lentiviral vectors encoding kallistatin inhibited the growth of metastatic tumor and prolonged the survival of tumor-bearing mice. These results suggest that gene therapy using lentiviruses carrying the kallistatin gene, which exerts anti-angiogenic and anti-inflammatory activities, represents a promising strategy for the treatment of lung cancer.

Adjuvant chemotherapy versus chemoradiotherapy for small cell lung cancer with lymph node metastasis: a retrospective observational study with use of a national database in Japan

OpenAIRE

Urushiyama, Hirokazu; Jo, Taisuke; Yasunaga, Hideo; Yamauchi, Yasuhiro; Matsui, Hiroki; Hasegawa, Wakae; Takeshima, Hideyuki; Hiraishi, Yoshihisa; Mitani, Akihisa; Fushimi, Kiyohide; Nagase, Takahide

2017-01-01

Background The optimal postoperative treatment strategy for small cell lung cancer (SCLC) remains unclear, especially in patients with lymph node metastasis. We aimed to compare the outcomes of patients with SCLC and lymph node metastasis treated with postoperative adjuvant chemotherapy or chemoradiotherapy. Methods We retrospectively collected data on patients with postoperative SCLC diagnosed with N1 and N2 lymph node metastasis from the Diagnosis Procedure Combination database in Japan, be...

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

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

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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

Discordance of Mutation Statuses of Epidermal Growth Factor Receptor and K-ras between Primary Adenocarcinoma of Lung and Brain Metastasis

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Kun-Ming Rau

2016-04-01

Full Text Available Mutations on epidermal growth factor receptor (EGFR of adenocarcinomas of lung have been found to be associated with increased sensitivity to EGFR tyrosine kinase inhibitors and K-ras mutations may correlate with primary resistance. We aimed to explore the discordant mutation statuses of EGFR and K-ras between primary tumors and matched brain metastases in adenocarcinomas of lung. We used a sensitive Scorpion ARMS method to analyze EGFR mutation, and Sanger sequencing followed by allele-specific real-time polymerase chain reaction to analyze K-ras mutation. Forty-nine paired tissues with both primary adenocarcinoma of lung and matched brain metastasis were collected. Thirteen patients (26.5% were discordant for the status of EGFR between primary and metastatic sites. K-ras gene could be checked in paired specimens from 33 patients, thirteen patients (39.6% were discordant for the status of K-ras. In primary lung adenocarcinoma, there were 14 patients of mutant EGFR had mutant K-ras synchronously. This study revealed that the status of EGFR mutation in lung adenocarcinomas is relatively consistent between primary and metastatic sites compared to K-ras mutation. However, there are still a few cases of adenocarcinoma of lung showing discordance for the status of EGFR mutation. Repeated analysis of EGFR mutation is highly recommended if tissue from metastatic or recurrent site is available for the evaluation of target therapy.

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

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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.

Greater efficacy of chemotherapy plus bevacizumab compared to chemo- and targeted therapy alone on non-small cell lung cancer patients with brain metastasis.

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Tang, Ning; Guo, Jun; Zhang, Qianqian; Wang, Yali; Wang, Zhehai

2016-01-19

Control of non-small-cell lung cancer (NSCLC) with brain metastasis is clinically challenging. This study retrospectively evaluated the efficacy of different adjuvant therapies for 776 cases of advanced NSCLCs with brain metastasis who treated with chemotherapy, chemotherapy plus bevacizumab, tyrosine kinase inhibitor (TKI) alone, or supportive care. The median progression-free survival (mPFS) and median overall survival (mOS) of patients treated with chemotherapy plus bevacizumab were 8.5 and 10.5 months, respectively, which were better than those of patients treated with other three therapies(P chemotherapy plus bevacizumab but was significantly better than that of other therapies. Moreover, for patients with EGFR wild-type NSCLC, the mPFS and mOS after chemotherapy plus bevacizumab were greater than those with other two therapies (P Chemotherapy plus bevacizumab was more effective for NSCLC patients with brain metastasis. Further studies will investigate the benefit of TKI alone for patients with EGFR-mutated. For patients with EGFR wild-type, chemotherapy plus bevacizumab did improve PFS and OS. Furthermore, regimens including pemetrexed led to a greater RR.

Prognostic significance of tumor size of small lung adenocarcinomas evaluated with mediastinal window settings on computed tomography.

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Yukinori Sakao

Full Text Available BACKGROUND: We aimed to clarify that the size of the lung adenocarcinoma evaluated using mediastinal window on computed tomography is an important and useful modality for predicting invasiveness, lymph node metastasis and prognosis in small adenocarcinoma. METHODS: We evaluated 176 patients with small lung adenocarcinomas (diameter, 1-3 cm who underwent standard surgical resection. Tumours were examined using computed tomography with thin section conditions (1.25 mm thick on high-resolution computed tomography with tumour dimensions evaluated under two settings: lung window and mediastinal window. We also determined the patient age, gender, preoperative nodal status, tumour size, tumour disappearance ratio, preoperative serum carcinoembryonic antigen levels and pathological status (lymphatic vessel, vascular vessel or pleural invasion. Recurrence-free survival was used for prognosis. RESULTS: Lung window, mediastinal window, tumour disappearance ratio and preoperative nodal status were significant predictive factors for recurrence-free survival in univariate analyses. Areas under the receiver operator curves for recurrence were 0.76, 0.73 and 0.65 for mediastinal window, tumour disappearance ratio and lung window, respectively. Lung window, mediastinal window, tumour disappearance ratio, preoperative serum carcinoembryonic antigen levels and preoperative nodal status were significant predictive factors for lymph node metastasis in univariate analyses; areas under the receiver operator curves were 0.61, 0.76, 0.72 and 0.66, for lung window, mediastinal window, tumour disappearance ratio and preoperative serum carcinoembryonic antigen levels, respectively. Lung window, mediastinal window, tumour disappearance ratio, preoperative serum carcinoembryonic antigen levels and preoperative nodal status were significant factors for lymphatic vessel, vascular vessel or pleural invasion in univariate analyses; areas under the receiver operator curves were 0

Prognostic Significance of Tumor Size of Small Lung Adenocarcinomas Evaluated with Mediastinal Window Settings on Computed Tomography

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Sakao, Yukinori; Kuroda, Hiroaki; Mun, Mingyon; Uehara, Hirofumi; Motoi, Noriko; Ishikawa, Yuichi; Nakagawa, Ken; Okumura, Sakae

2014-01-01

Background We aimed to clarify that the size of the lung adenocarcinoma evaluated using mediastinal window on computed tomography is an important and useful modality for predicting invasiveness, lymph node metastasis and prognosis in small adenocarcinoma. Methods We evaluated 176 patients with small lung adenocarcinomas (diameter, 1–3 cm) who underwent standard surgical resection. Tumours were examined using computed tomography with thin section conditions (1.25 mm thick on high-resolution computed tomography) with tumour dimensions evaluated under two settings: lung window and mediastinal window. We also determined the patient age, gender, preoperative nodal status, tumour size, tumour disappearance ratio, preoperative serum carcinoembryonic antigen levels and pathological status (lymphatic vessel, vascular vessel or pleural invasion). Recurrence-free survival was used for prognosis. Results Lung window, mediastinal window, tumour disappearance ratio and preoperative nodal status were significant predictive factors for recurrence-free survival in univariate analyses. Areas under the receiver operator curves for recurrence were 0.76, 0.73 and 0.65 for mediastinal window, tumour disappearance ratio and lung window, respectively. Lung window, mediastinal window, tumour disappearance ratio, preoperative serum carcinoembryonic antigen levels and preoperative nodal status were significant predictive factors for lymph node metastasis in univariate analyses; areas under the receiver operator curves were 0.61, 0.76, 0.72 and 0.66, for lung window, mediastinal window, tumour disappearance ratio and preoperative serum carcinoembryonic antigen levels, respectively. Lung window, mediastinal window, tumour disappearance ratio, preoperative serum carcinoembryonic antigen levels and preoperative nodal status were significant factors for lymphatic vessel, vascular vessel or pleural invasion in univariate analyses; areas under the receiver operator curves were 0.60, 0.81, 0

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

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Tei, Mitsuyoshi; Wakasugi, Masaki; Akamatsu, Hiroki

2014-01-01

Choroidal metastasis from colorectal cancer is rare, and there have been no reported cases of such metastasis from early colorectal cancer. We report a case of choroidal metastasis from early rectal cancer. A 61 year-old-man experienced myodesopsia in the left eye 2 years and 6 months after primary rectal surgery for early cancer, and was diagnosed with left choroidal metastasis and multiple lung metastases. Radiotherapy was initiated for the left eye and systemic chemotherapy is initiated for the multiple lung metastases. The patient is living 2 years and 3 months after the diagnosis of choroidal metastasis without signs of recurrence in the left eye, and continues to receive systemic chemotherapy for multiple lung metastases. Current literatures have few recommendations regarding the appropriate treatment of choroidal metastasis from colorectal cancer, but an aggressive multi-disciplinary approach may be effective in local regression. This is the first report of choroidal metastasis from early rectal cancer. We consider it important to enforce systemic chemotherapy in addition to radiotherapy for choroidal metastasis from colorectal cancer. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Complete remission through icotinib treatment in Non-small cell lung cancer epidermal growth factor receptor mutation patient with brain metastasis: A case report

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Wang Tao

2016-01-01

Full Text Available Brain metastasis (BM has been universally recognized as a poor prognostic factor in non-small cell lung cancer (NSCLC. Epidermal growth factor receptor (EGFR tyrosine kinase inhibitors (TKIs have shown efficacy in treating BM with an EGFR mutation. This paper reports a case of BM patient with EGFR-mutated NSCLC. According to the findings, a complete remission (CR of the BM was achieved by icotinib treatment without conducting a radiotherapy, which was followed by a resection of the primary lung cancer lesion and lymph nodes. After one-year follow-up, the disease progressed to liver metastasis and liver lesion biopsy showed a T790M mutation. The patient responded well to the combination treatment of AZD9291 and icotinib after the failure of transcatheter arterial chemoembolization (TACE. This case report suggests that icotinib has a sustainable anticancer response to BM and the combination with icotinib and AZD9291 is effective for liver metastasis with T790M.

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

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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.

Icotinib combined whole brain radiotherapy for patients with brain metastasis from lung adenocarcinoma harboring epidermal growth factor receptor mutation.

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Li, Jin-Rui; Zhang, Ye; Zheng, Jia-Lian

2016-07-01

The brain is a metastatic organ that is most prone to lung adenocarcinoma (LAC). However, the prognosis of patients with brain metastasis remains very poor. In this study, we evaluated the efficacy of icotinib plus whole brain radiation therapy (WBRT) for treating patients with brain metastasis from epidermal growth factor receptor (EGFR)-mutated LAC. All patients received standard WBRT administered to the whole brain in 30 Gy in 10 daily fractions. Each patient was also instructed to take 125 mg icotinib thrice per day beginning from the first day of the WBRT. After completing the WBRT, maintenance icotinib was administered until the disease progressed or intolerable adverse effects were observed. Cranial progression-free survival (CPFS) and overall survival (OS) times were the primary endpoints. A total of 43 patients were enrolled in this study. Two patients (4.7%) presented a complete response (CR), whereas 20 patients (46.5%) presented a partial response (PR). The median CPFS and OS times were 11.0 and 15.0 months, respectively. The one-year CPFS rate was 40.0% for the patients harboring EGFR exon 19 deletion and 16.7% for the patients with EGFR exon 21 L858R (P=0.027). The concurrent administration of icotinib and WBRT exhibited favorable effects on the patients with brain metastasis. EGFR exon 19 deletion was predictive of a long CPFS following icotinib plus WBRT.

Detachment-induced E-cadherin expression promotes 3D tumor spheroid formation but inhibits tumor formation and metastasis of lung cancer cells.

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Powan, Phattrakorn; Luanpitpong, Sudjit; He, Xiaoqing; Rojanasakul, Yon; Chanvorachote, Pithi

2017-11-01

The epithelial-to-mesenchymal transition is proposed to be a key mechanism responsible for metastasis-related deaths. Similarly, cancer stem cells (CSCs) have been proposed to be a key driver of tumor metastasis. However, the link between the two events and their control mechanisms is unclear. We used a three-dimensional (3D) tumor spheroid assay and other CSC-indicating assays to investigate the role of E-cadherin in CSC regulation and its association to epithelial-to-mesenchymal transition in lung cancer cells. Ectopic overexpression and knockdown of E-cadherin were found to promote and retard, respectively, the formation of tumor spheroids in vitro but had opposite effects on tumor formation and metastasis in vivo in a xenograft mouse model. We explored the discrepancy between the in vitro and in vivo results and demonstrated, for the first time, that E-cadherin is required as a component of a major survival pathway under detachment conditions. Downregulation of E-cadherin increased the stemness of lung cancer cells but had an adverse effect on their survival, particularly on non-CSCs. Such downregulation also promoted anoikis resistance and invasiveness of lung cancer cells. These results suggest that anoikis assay could be used as an alternative method for in vitro assessment of CSCs that involves dysregulated adhesion proteins. Our data also suggest that agents that restore E-cadherin expression may be used as therapeutic agents for metastatic cancers. Copyright © 2017 the American Physiological Society.

[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].

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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.

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

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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

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

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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

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

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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.

Predicted extracapsular invasion of hilar lymph node metastasis by fusion positron emission tomography/computed tomography in patients with lung cancer.

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Makino, Takashi; Hata, Yoshinobu; Otsuka, Hajime; Koezuka, Satoshi; Isobe, Kazutoshi; Tochigi, Nobumi; Shiraga, Nobuyuki; Shibuya, Kazutoshi; Homma, Sakae; Iyoda, Akira

2015-09-01

Intraoperative detection of hilar lymph node metastasis, particularly with extracapsular invasion, may affect the surgical procedure in patients with lung cancer, as the preoperative estimation of hilar lymph node metastasis is unsatisfactory. The aim of this study was to investigate whether fusion positron emission tomography/computed tomography (PET/CT) is able to predict extracapsular invasion of hilar lymph node metastasis. Between April, 2007 and April, 2013, 509 patients with primary lung cancer underwent surgical resection at our institution, among whom 28 patients exhibiting hilar lymph node metastasis (at stations 10 and 11) were enrolled in this study. A maximum lymph node standardized uptake value of >2.5 in PET scans was interpreted as positive. A total of 17 patients had positive preoperative PET/CT findings in their hilar lymph nodes, while the remaining 11 had negative findings. With regard to extracapsular nodal invasion, the PET/CT findings (P=0.0005) and the histological findings (squamous cell carcinoma, P=0.05) were found to be significant predictors in the univariate analysis. In the multivariate analysis, the PET/CT findings were the only independent predictor (P=0.0004). The requirement for extensive pulmonary resection (sleeve lobectomy, bilobectomy or pneumonectomy) was significantly more frequent in the patient group with positive compared with the group with negative PET/CT findings (76 vs. 9%, respectively, P=0.01). Therefore, the PET/CT findings in the hilar lymph nodes were useful for the prediction of extracapsular invasion and, consequently, for the estimation of possible extensive pulmonary resection.

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

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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

Complete remission of liver metastasis in a lung cancer patient with epidermal growth factor mutation achieved with Icotinib.

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Zhu, Zhouyu; Chai, Ying

2016-11-01

A 65-year-old Chinese male was referred to our hospital for epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC). Aggressive combined therapy with surgical resection of the right upper lung lesion and chemotherapy was performed. One month later, continued Icotinib treatment was used as magnetic resonance imaging revealed liver metastasis (LM). Interestingly, complete remission of the patient's LM lesions was achieved in six months. To our knowledge, this is the first report documenting a successful case of an NSCLC patient with LM treated with Icotinib after receiving a radical resection for pulmonary carcinoma. Our experience could provide a treatment strategy for patients with similar disease. © 2016 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Time course of development of metastasis in irradiated Lewis lung carcinoma

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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)

Severe pulmonary metastasis in obese and diabetic mice.

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Mori, Akinori; Sakurai, Hiroaki; Choo, Min-Kyung; Obi, Ryosuke; Koizumi, Keiichi; Yoshida, Chiho; Shimada, Yutaka; Saiki, Ikuo

2006-12-15

Although obesity is known as a risk factor for several human cancers, the association of obesity with cancer recurrence and metastasis remains to be characterized. Here, B16-BL6 melanoma and Lewis lung carcinoma cells were intravenously injected into diabetic (db/db) and obese (ob/ob) mice. The number of experimental lung colonies was markedly promoted in these mice when compared with C57BL/6 mice. In contrast, tumor growth at the implanted site was comparable when cells were inoculated orthotopically. The use of B16-BL6 cells stably transfected with the luciferase gene revealed that the increased metastasis reflected a difference mainly within 6 hr after the intravenous inoculation of tumor cells. Administration of recombinant leptin in ob/ob mice abolished the increase in metastasis early on as well as the decrease in the splenic NK cell number. In addition, depletion of NK cells by an anti-asialo-GM1 antibody abrogated the enhanced metastasis in db/db mice. These results demonstrate that metastasis is markedly promoted in diabetic and obese mice mainly because of decreased NK cell function during the early phase of metastasis. Copyright 2006 Wiley-Liss, Inc.

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.

miR-32 inhibits proliferation, epithelial–mesenchymal transition, and metastasis by targeting TWIST1 in non-small-cell lung cancer cells

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Li L

2016-03-01

Full Text Available Lei Li,1,* Dapeng Wu2,* 1Department of Pneumology, 2Department of Radiotherapy, Huaihe Hospital of Henan University, Kaifeng, Henan, People’s Republic of China *These authors contributed equally to this work Background: By analyzing published microRNA microarray studies, miR-32 was found to be markedly reduced in non-small-cell lung cancer (NSCLC tissues compared with that in nontumor tissues. However, little is known about its role and molecular mechanism involved in NSCLC development and progression. Here, we report the effect of miR-32 on NSCLC cell proliferation, epithelial–mesenchymal transition (EMT, and metastasis. Methods: Quantitative real-time PCR was performed to detect the expression level of miR-32 in primary NSCLC cases and cell lines. miR-32-overexpressing H1299 and A549 cells were constructed by lipofection transfection. MTT, transwell chamber, and Western blot assays were used to assess the effect of miR-32 on proliferation, EMT, and metastasis of NSCLC cells, respectively. Target prediction and luciferase reporter assays were performed to investigate the targets of miR-32. Tumor formation assay in vivo was performed to investigate the antitumor effect of miR-32. Results: An inverse correlation existed between miR-32 expression level and NSCLC cell proliferation, EMT, and metastasis, and upregulation of miR-32 repressed NSCLC cell proliferation, EMT, and metastasis. Moreover, we identified and validated that TWIST1 was a direct target of miR-32, and miR-32 regulated NSCLC cell proliferation, EMT, and metastasis, at least in part via modulation of TWIST1. The animal experiments showed that overexpression of miR-32 inhibited the growth of NSCLC tumors in vivo. Keywords: non-small-cell lung cancer, miR-32, TWIST1, proliferation, EMT, nude mice

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

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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

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

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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

Lung Metastases in Neuroblastoma at Initial Diagnosis: A Report from the International Neuroblastoma Risk Group (INRG) Project

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DuBois, Steven G.; London, Wendy B.; Zhang, Yang; Matthay, Katherine K.; Monclair, Tom; Ambros, Peter F.; Cohn, Susan L.; Pearson, Andrew; Diller, Lisa

2009-01-01

Background Neuroblastoma is the most common extracranial pediatric solid cancer. Lung metastasis is rarely detected in children with newly diagnosed neuroblastoma. We aimed to describe the incidence, clinical characteristics, and outcome of patients with lung metastasis at initial diagnosis using a large international database. Procedure The subset of patients from the International Neuroblastoma Risk Group database with INSS stage 4 neuroblastoma and known data regarding lung metastasis at diagnosis was selected for analysis. Clinical and biological characteristics were compared between patients with and without lung metastasis. Survival for patients with and without lung metastasis was estimated by Kaplan-Meier methods. Cox proportional hazards methods were used to determine the independent prognostic value of lung metastasis at diagnosis. Results Of the 2,808 patients with INSS stage 4 neuroblastoma diagnosed between 1990 and 2002, 100 patients (3.6%) were reported to have lung metastasis at diagnosis. Lung metastasis was more common among patients with MYCN amplified tumors, adrenal primary tumors, or elevated lactate dehydrogenase (LDH) levels (p < 0.02 in each case). Five-year overall survival ± standard error for patients with lung metastasis was 34.5% ± 6.8% compared to 44.7% ± 1.3% for patients without lung metastasis (p=0.0002). However, in multivariable analysis, the presence of lung metastasis was not independently predictive of outcome. Conclusions Lung metastasis at initial diagnosis of neuroblastoma is associated with MYCN amplification and elevated LDH levels. Although lung metastasis at diagnosis was not independently predictive of outcome in this analysis, it remains a useful prognostic marker of unfavorable outcome. PMID:18649370

Implantation port-catheter permanent indwelling of pulmonary artery in treating lung metastasis from HCC

International Nuclear Information System (INIS)

Cheng Jiemin; Wang Jianhua; Yan Zhiping; Wang Xiaolin; Gong Gaoquan; Liu Qingxin

2000-01-01

Objective: To observe the efficacy of a percutaneous implantation port-catheter permanent indwelling pulmonary artery for regional chemotherapy of the metastatic lung cancer from HCC. Methods: Between 1995 and 1999, 62 patients (42 males, 20 females; mean age 46 years) suffering from the metastatic lung cancer from HCC underwent percutaneous implantation of port-catheter permanent indwelling pulmonary artery using the right subclavian vein. In 19 patients with metastatic tumor located on one side of the lung, an indwelling catheter was placed into the ipsilateral side pulmonary artery. With metastasis of both sides, the catheter was inserted into the main trunk of pulmonary artery. The regimens of the chemotherapy were 5-FU + CDDP + MMC(FDM) or 5-FU + CDDP + MMC(FDA). Results: The interventional procedure was successfully completed in all 62 cases (100%). The complications occurred in 8% cases, including infections (3.2%), unhealed wound (1.6%) and pneumothorax (3.2%). The treatment effects of 3-months after the procedure were as follows: the obvious decrease of lung tumor size was 35.5%; stable disease (SD) 32.3% and progressive disease (PD) 32.3%. 6 months follow-up: 12 patients were dead (12/62) and the others are still doing well. The response rates were 22.6%, partial response (PR) 32.3%; stable disease (SD) 25.8% and progressive disease (PD) 32.3%. Conclusions: The percutaneous implantation techniques of pulmonary arterial port-catheter could be a good method in the treatment of metastatic lung cancer from HCC because of it is simple, with few complications and positive effect

Adjuvant chemotherapy versus chemoradiotherapy for small cell lung cancer with lymph node metastasis: a retrospective observational study with use of a national database in Japan.

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Urushiyama, Hirokazu; Jo, Taisuke; Yasunaga, Hideo; Yamauchi, Yasuhiro; Matsui, Hiroki; Hasegawa, Wakae; Takeshima, Hideyuki; Hiraishi, Yoshihisa; Mitani, Akihisa; Fushimi, Kiyohide; Nagase, Takahide

2017-09-02

The optimal postoperative treatment strategy for small cell lung cancer (SCLC) remains unclear, especially in patients with lymph node metastasis. We aimed to compare the outcomes of patients with SCLC and lymph node metastasis treated with postoperative adjuvant chemotherapy or chemoradiotherapy. We retrospectively collected data on patients with postoperative SCLC diagnosed with N1 and N2 lymph node metastasis from the Diagnosis Procedure Combination database in Japan, between July 2010 and March 2015. We extracted data on patient age, sex, comorbidities, and TNM classification at lung surgery; operative procedures, chemotherapy drugs, and radiotherapy during hospitalization; and discharge status. Recurrence-free survival was compared between the chemotherapy and chemoradiotherapy groups using multivariable Cox regression analysis. Median recurrence-free survival was 1146 days (95% confidence interval [CI], 885-1407) in the chemotherapy group (n = 489) and 873 days (95% CI, 464-1282) in the chemoradiotherapy group (n = 75). There was no significant difference between these after adjusting for patient backgrounds (hazard ratio, 1.29; 95% CI, 0.91-1.84). There was no significant difference in recurrence-free survival between patients with SCLC and N1-2 lymph node metastasis treated with postoperative adjuvant chemotherapy and chemoradiotherapy. Further randomized clinical trials are needed to address this issue.

Rapid recurrence and bilateral lungs, multiple bone metastasis of malignant solitary fibrous tumor of the right occipital lobe: report of a case and review.

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Wu, Zhengrong; Yang, Hongjun; Weng, Desheng; Ding, Yanqing

2015-07-09

Intracranial malignant solitary fibrous tumor (MSFT) is extremely rare. The authors report a case of MSFT of the right occipital lobe with a rapid recurrence and bilateral lung, multiple bone metastasis. The patient was a 25-year-old male presenting with headache, nausea and visual disturbances without obvious cause. Three times right-side occipital craniotomies were performed and two times postoperative conformal radiotherapy were administered within one year. 4 months after the third time of right-side occipital craniotomy, the patient felt right chest pain and neck pain. Positron emission tomography/computed tomography (PET/CT) showed tumor recurrence of the right occipital lobe and bilateral lung metastasis, multiple bone metastasis including: vertebrae, libs, the left iliac wing, sacrum, the right ischium and upper parts of both femurs. Ultrasound guided puncture biopsy of left-side back of the neck and CT guided puncture biopsy of the third lumbar vertebra were performed. General sample showed grayish white or grayish red with irregular shape. Histopathologically, the tumor was composed of areas of alternating hypercellularity and hypocellularity with spindle-shaped cells, which arranged as fascicular, storiform pattern or patternless pattern, with intervening irregular eosinophilic collagen bundles. Some areas showed hemangiopericytoma-like perivascular pattern and perivascular hyalinization. Tumor cells were pleomorphic with mitotic counts of more than 4 per 10 high power fields and showed coagulative necrosis. Immunohistochemically, tumor cells were diffusely positive for vimentin and CD99, focal positive for CD34, bcl-2 and Actin. Ki-67 labelling index was more than 40%. The final pathological diagnosis was MSFT of the right occipital lobe, metastatic MSFT of left-side back of the neck and the third lumbar vertebra. The MSFT of the right occipital lobe with recurrence and bilateral lung, multiple bone metastasis is extremely rare. Although intracranial

Experience of treating late cerebral lungcancer metastasis using photodynamic therapy

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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

Oral gingival metastasis: A diagnostic dilemma

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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.

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

Diabetes insipidus as the first symptom caused by lung cancer metastasis to the pituitary glands: Clinical presentations, diagnosis, and management

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J F Mao

2011-01-01

Full Text Available Background : Central diabetes insipidus (CDI, secondary to pituitary metastatic lesions, is uncommon; however, lung and breast cancer are the commonest malignancies to have metastases to the pituitary. Early management of systemic chemotherapy and pituitary irradiation might improve the prognosis of patients. Aims : To investigate the clinical features, diagnosis, and management of CDI caused by lung cancer metastasis to the pituitary glands. Materials and Methods : We retrospectively reviewed 10 patients who had CDI as their first symptom before their lung cancers were diagnosed. Their clinical presentations, anterior pituitary gland function, sellar magnetic resonance imaging (MRI, management, and prognosis were described. Settings and Design : This retrospective cross-sectional clinical study was conducted in a medical college hospital. Results : The patient′s mean age was 58.6±7.8 years. Diabetes insipidus was the main complaint when they were referred to our hospital. MRI revealed specific dumbbell-shaped masses in the sella turcica in five patients. In seven patients whose hormones were measured, the levels of hormones from adenohypophysis were abnormally low in six patients. The main treatments included surgery, systemic chemotherapy, and sellar irradiation. Although nine patients had poor prognoses, one patient has survived for more than 3 years, suggesting benefit from early diagnosis and treatment. Conclusions : New-onset CDI might be the only symptom presented by the patients with pituitary metastasis (PM from lung cancer. Dumbbell-shaped sellar masses in MRI are prone to the diagnosis of PM. A thorough examination for primary cancer should be carried out in these aged and elderly patients.

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

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

2010-01-01

significantly reduced the metastatic burden in lungs of PyMT-induced mammary tumors. In S100A4(+/+) PyMT mice, massive leukocyte infiltration at the site of the growing tumor at the stage of malignant transition was associated with increased concentration of extracellular S100A4 in the tumor microenvironment......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...... 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...

Evaluation of solitary pulmonary metastasis of extrathoracic tumor with thin-slice computed tomography

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Shiotani, Seiji; Yamada, Kouzo; Oshita, Fumihiro; Nomura, Ikuo; Noda, Kazumasa; Yamagata, Tatushi; Tajiri, Michihiko; Ishibashi, Makoto; Kameda, Youichi [Kanagawa Cancer Center, Yokohama (Japan)

1995-10-01

Thin-slice computed tomography (CT) images were compared with pathological findings in 9 specimens of solitary pulmonary nodules, which had been pathologically diagnosed as pulmonary metastasis of extrathoracic tumor. The thin-slice CT images were 2 mm-thick images reconstructed using a TCT-900S, HELIX (Toshiba, Tokyo) and examined at two different window and level settings. In every case, the surgical specimens were sliced transversely to correlate with the CT images. According to the image findings, the internal structure was of the solid-density type in every case, and the margin showed spiculation in 22%, notching in 67% and pleural indentation in 89%. Regarding the relationship between the pulmonary vessels and tumors, plural vascular involvement was revealed in every case. Thus, it was difficult to distinguish solitary pulmonary metastasis of extrathoracic tumor from primary lung cancer based on the thin-slice CT images. For some solitary pulmonary metastasis of extrathoracic tumor, a comprehensive diagnostic approach taking both the anamnesis and pathological findings into consideration was required. (author).

PPARGC1A is upregulated and facilitates lung cancer metastasis.

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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.

Peritoneal carcinomatosis, an unusual and only site of metastasis ...

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Isolated peritoneal metastases of lung adenocarcinoma are very rare, even exceptional, occurring most often in the context of a multi-metastatic disease. This report presents a rare clinical case of isolated peritoneal metastasis from lung adenocarcinoma. We report a 56-year-old male who was monitored for lung ...

Preoperative radiological approach for hilar lung cancer

International Nuclear Information System (INIS)

Ohno, Yoshiharu; Higashino, Takanori; Watanabe, Hirokazu; Yoshimura, Masahiro; Sugimura, Kazuro

2003-01-01

Recent advances in CT, MR, and nuclear medicine have made it possible to evaluate morphological and functional information in hilar lung cancer patients more accurately and quantitatively. In this review, we describe recent advances in the radiological approach to hilar lung cancer, focusing on mediastinal invasion, lymph node metastasis, and pulmonary functional imaging. We believe that further basic studies as well as clinical applications of newer MR techniques will play an important role in the management of patients with lung cancer. (author)

Spontaneous lung metastasis formation of human Merkel cell carcinoma cell lines transplanted into scid mice.

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Knips, Jill; Czech-Sioli, Manja; Spohn, Michael; Heiland, Max; Moll, Ingrid; Grundhoff, Adam; Schumacher, Udo; Fischer, Nicole

2017-07-01

Merkel cell carcinoma (MCC) is an aggressive skin cancer entity that frequently leads to rapid death due to its high propensity to metastasize. The etiology of most MCC cases is linked to Merkel cell polyomavirus (MCPyV), a virus which is monoclonally integrated in up to 95% of tumors. While there are presently no animal models to study the role of authentic MCPyV infection on transformation, tumorigenesis or metastasis formation, xenograft mouse models employing engrafted MCC-derived cell lines (MCCL) represent a promising approach to study certain aspects of MCC pathogenesis. Here, the two MCPyV-positive MCC cell lines WaGa and MKL-1 were subcutaneously engrafted in scid mice. Engraftment of both MCC cell lines resulted in the appearance of circulating tumor cells and metastasis formation, with WaGa-engrafted mice showing a significantly shorter survival time as well as increased numbers of spontaneous lung metastases compared to MKL-1 mice. Interestingly, explanted tumors compared to parental cell lines exhibit an upregulation of MCPyV sT-Antigen expression in all tumors, with WaGa tumors showing significantly higher sT-Antigen expression than MKL-1 tumors. RNA-Seq analysis of explanted tumors and parental cell lines furthermore revealed that in the more aggressive WaGa tumors, genes involved in inflammatory response, growth factor activity and Wnt signalling pathway are significantly upregulated, suggesting that sT-Antigen is the driver of the observed differences in metastasis formation. © 2017 UICC.

Isolated Asymptomatic Metastasis in the Myocardium: A Rare Scenario in Case of Carcinoma Penis

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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.

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

International Nuclear Information System (INIS)

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

2014-01-01

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 leptomeningeal metastasis from hepatocellular carcinoma. We herein report a case of leptomeningeal metastasis from hepatocellular carcinoma in a 53-year-old woman with concomitant systemic metastases to the lung, bone, brain, kidney, adrenal gland, subcutaneous tissues, and abdominal pelvis. The neurological symptoms of the patient were relieved after treatment with methotrexate intra-cerebral spinal fluid chemotherapy concurrent with whole brain radiotherapy. To our knowledge this is the first report of leptomeningeal metastasis from hepatocellular carcinoma confirmed by cytology. Treatment with methotrexate intra-cerebral spinal fluid chemotherapy concurrent with whole brain radiotherapy was effective

Diagnostic ability of mediastinal and hilar lymph node metastasis of primary lung cancer

International Nuclear Information System (INIS)

Hwang, Len-Ming

1985-01-01

Preoperative thoracic CT scan and conventional radiologic procedures were performed in 68 primary lung cancer patients who underwent radical operation for intrathoracic lymph nodes. The subjects of this study consisted of 58 males and 10 females. Histologically, squamous cell carcinoma was noted in 28 patients, adenocarcinoma in 31, large cell cancer in 5 and small cell cancer in 4. According to the pTNM factor N classification, n0 was noted in 28 patients, n1 in 13 and n2 in 27. Plain and contrast enhancement CT scan were performed, using GE-made CT 9800, from apex to diaphragm with a 2-second scan time in supine position during full inspiration. As conventional radiologic procedures, posteroanterior and lateral plain roentgenography and posteroanterior and lateral tomography of the thoracic region including the hilum and mediastinum were performed on all patients, and 55 0 oblique tomography and PAG procedures were added, if necessary. Of 68 patients, 40 had metastatic lesions in the mediastinal and hilar lymph nodes, 37 in the ipsilateral hilar lymph nodes and 27 in the mediastinal lymph nodes. Of 37 patients with metastatic lesions in the ipsilateral hilar lymph nodes, 24 had such lesions in the mediastinal lymph nodes as well, and 13 only in the ipsilateral hilar lymph nodes. Three patients had mediastinal metastasis without ipsilateral hilar metastasis. In detecting mediastinal lymph node metastasis, CT showed a sensitivity of 78 %, a specificity of 73 % and an accuracy of 75 % while conventional radiologic procedures had a sensitivity of 41 %, a specificity of 78 %, and an accuracy of 63 %. In the hilum, CT also had a higher sensitivity (73 %, 62 % respectively) and lower specificity (71 %, 77 % respectively) comparing to conventional radiologic procedures. And CT had an accuracy of 72 % while conventional radiologic procedures showed 69 %. (J.P.N.)

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

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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

Lentivirus-mediated knockdown of NLK inhibits small-cell lung cancer growth and metastasis

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Lv MT

2016-11-01

Full Text Available Mutian Lv,1 Yaming Li,1 Xin Tian,2 Shundong Dai,3,4 Jing Sun,5 Guojiang Jin,6 Shenyi Jiang7 1Department of Nuclear Medicine, 2Molecular Oncology Laboratory of Cancer Research Institute, The First Affiliated Hospital of China Medical University, 3Department of Pathology, The First Affiliated Hospital, College of Basic Medical Sciences of China Medical University, 4Department of Pathology, Institute of Pathology and Pathophysiology, 5Department of Immunology and Biotherapy, Liaoning Cancer Hospital and Institute, 6Department of Laboratory Medicine, 7Department of Rheumatology, The First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China Abstract: Nemo-like kinase (NLK, an evolutionarily conserved serine/threonine kinase, has been recognized as a critical regulator of various cancers. In this study, we investigated the role of NLK in human small-cell lung cancer (SCLC, which is the most aggressive form of lung cancer. NLK expression was evaluated by quantitative real-time polymerase chain reaction in 20 paired fresh SCLC tissue samples and found to be noticeably elevated in tumor tissues. Lentivirus-mediated RNAi efficiently suppressed NLK expression in NCI-H446 cells, resulting in a significant reduction in cell viability and proliferation in vitro. Moreover, knockdown of NLK led to cell cycle arrest at the S-phase via suppression of Cyclin A, CDK2, and CDC25A, which could contribute to cell growth inhibition. Furthermore, knockdown of NLK decreased the migration of NCI-H446 cells and downregulated matrix metalloproteinase 9. Treatment with NLK short hairpin RNA significantly reduced SCLC tumor growth in vivo. In conclusion, this study suggests that NLK plays an important role in the growth and metastasis of SCLC and may serve as a potential therapeutic target for the treatment of SCLC. Keywords: NLK, SCLC, RNAi, proliferation, migration

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.

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

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...

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.

A Rare Cause of Testicular Metastasis: Upper Tract Urothelial Carcinoma

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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.

The role of GAGE cancer/testis antigen in metastasis

DEFF Research Database (Denmark)

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

2016-01-01

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

Boron neutron capture therapy (BNCT) as a new approach for clear cell sarcoma (CCS) treatment: Trial using a lung metastasis model of CCS.

Science.gov (United States)

Andoh, Tooru; Fujimoto, Takuya; Suzuki, Minoru; Sudo, Tamotsu; Sakurai, Yoshinori; Tanaka, Hiroki; Fujita, Ikuo; Fukase, Naomasa; Moritake, Hiroshi; Sugimoto, Tohru; Sakuma, Toshiko; Sasai, Hiroshi; Kawamoto, Teruya; Kirihata, Mitsunori; Fukumori, Yoshinobu; Akisue, Toshihiro; Ono, Koji; Ichikawa, Hideki

2015-12-01

Clear cell sarcoma (CCS) is a rare malignant tumor with a poor prognosis. In the present study, we established a lung metastasis animal model of CCS and investigated the therapeutic effect of boron neutron capture therapy (BNCT) using p-borono-L-phenylalanine (L-BPA). Biodistribution data revealed tumor-selective accumulation of (10)B. Unlike conventional gamma-ray irradiation, BNCT significantly suppressed tumor growth without damaging normal tissues, suggesting that it may be a potential new therapeutic option to treat CCS lung metastases. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

Solitary Skull Metastasis as the First Presentation of a Metachronous Primary Lung Cancer in a Survivor from Pancreatic Cancer

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Ali Altalhy

2017-01-01

Full Text Available Skull metastasis from lung cancer is relatively common, yet the first presentation for this malignant disease is a rare occurrence. We herein report a case of a 54-year-old female, who had a good outcome following Whipple procedure for periampullary adenocarcinoma five years before her current presentation. During a routine follow-up, she was found to have a slowly progressive painless right parietal swelling. The systemic screening workup revealed no abdominal disease, but a solitary pulmonary nodule was identified. The presence of these two lesions raised the diagnosis of metastases from a previously treated pancreatic adenocarcinoma. The patient underwent complete excision of the skull lesion and subsequent lung biopsy, both of which proved on histopathological examination to be consistent with a primary lung cancer. This case emphasizes the importance of imaging and histopathological correlation in the diagnosis of solitary skull metastases and their effect on the subsequent management.

Pattern of distant lymph node metastasis in colorectal carcinoma and its correlation with distant organ metastasis: CT evaluation

International Nuclear Information System (INIS)

Cha, Sang Hoon; Park, Cheol Min; Cha, In Ho; Chung, Kyoo Byung; Suh, Won Hyuck

1995-01-01

To evaluate the pattern of distant lymph node metastasis in colorectal carcinoma and its correlation with distant organ metastasis. We retrospectively reviewed abdominal CT scans of 46 patients with pathologically proven colorectal carcinoma. The incidence of distant lymphadenopathy in colorectal carcinoma was 30.4%(14/46). The most commonly involved distant lymph node was the left paraortic lymph node below the renal hilum(9/25). The most common type of distant lymphadenopathy was solitary type(7/14) and all of these lymphadenopathies were noted in the left paraortic lymph node below the renal hilum. Six cases of left sided colorectal carcinoma showed left paraortic lymphadenopathy with solitary type. The incidence of distant organ metastasis was 17.4%(8/46) and markedly increased if distant lymphadenopathy was multiple and confluent, or confluent type(5/7). The incidence of distant lymphadenopathy in colorectal carcinoma was not high and the most common lymphadenopathy was the left paraortic lymph node with solitary type below the renal hilum. The possibility of distant organ metastasis was high if distant lymphadenopathy was multiple and confluent, or confluent type

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.

Value of dual time point F-18 FDG-PET/CT imaging for the evaluation of prognosis and risk factors for recurrence in patients with stage I non-small cell lung cancer treated with stereotactic body radiation therapy

Energy Technology Data Exchange (ETDEWEB)

Satoh, Yoko, E-mail: pecampecam@yahoo.co.jp [PET Center, Kofu Neurosurgical Hospital, ZIP Code 400-0805, Sakaori 1-16-18, Kofu city, Yamanashi Prefecture (Japan); Nambu, Atsushi, E-mail: nambu-a@gray.plala.or.jp [Department of Radiology, University of Yamanashi, ZIP Code 409-3898, Yamanashi University Faculty of Medicine, Shimokato 1110, Chuo City, Yamanashi Prefecture (Japan); Onishi, Hiroshi, E-mail: honishi@yamanashi.ac.jp [Department of Radiology, University of Yamanashi, ZIP Code 409-3898, Yamanashi University Faculty of Medicine, Shimokato 1110, Chuo City, Yamanashi Prefecture (Japan); Sawada, Eiichi, E-mail: e_sawaday_61674@ybb.ne.jp [Department of Radiology, University of Yamanashi, ZIP Code 409-3898, Yamanashi University Faculty of Medicine, Shimokato 1110, Chuo City, Yamanashi Prefecture (Japan); Tominaga, Licht, E-mail: lichtt@gmail.com [Department of Radiology, University of Yamanashi, ZIP Code 409-3898, Yamanashi University Faculty of Medicine, Shimokato 1110, Chuo City, Yamanashi Prefecture (Japan); Kuriyama, Kengo, E-mail: kuriyama@yamanashi.ac.jp [Department of Radiology, University of Yamanashi, ZIP Code 409-3898, Yamanashi University Faculty of Medicine, Shimokato 1110, Chuo City, Yamanashi Prefecture (Japan); Komiyama, Takafumi, E-mail: takafumi-ymu@umin.ac.jp [Department of Radiology, Kofu Municipal Hospital, ZIP Code 400-0832, Masutsubo-cho 366, Kofu City, Yamanashi Prefecture (Japan); Marino, Kan, E-mail: marino-akrf@ych.pref.yamanashi.jp [Department of Radiology, Yamanashi Prefectural Hospital, ZIP Code 400-8506, Fujimi 1-1-1, Kofu City, Yamanashi Prefecture (Japan); Aoki, Shinichi, E-mail: aokis@yamanashi.ac.jp [Department of Radiology, University of Yamanashi, ZIP Code 409-3898, Yamanashi University Faculty of Medicine, Shimokato 1110, Chuo City, Yamanashi Prefecture (Japan); and others

2012-11-15

Purpose: To investigate prognostic and risk factors for recurrence after stereotactic body radiation therapy (SBRT) in patients with stage I non-small cell lung carcinoma (NSCLC), focusing on dual time point [18]F-fluorodeoxyglucose positron emission tomography (FDG PET). Materials and methods: We prospectively evaluated 57 patients with stage I NSCLC (45 T1N0M0 and 12 T2N0M0) who had undergone pretreatment FDG-PET/CT and were subsequently treated with SBRT. All patients received a whole-body PET/CT scan at 60 min and a whole-lung at 120 min after the injection. The maximum standardized uptake value (SUV) and retention index (RI) of the lesions were calculated. Local recurrence, regional lymph node metastasis, distant metastasis, and the recurrence pattern were evaluated. Cox proportional hazard regression analyses were performed to evaluate prognostic factors or risk factors of recurrence. Results: During the median follow-up period of 27 months, local recurrence, regional lymph node metastasis, and distant metastasis were seen in 17 (30%), 12 (21%), and 17 (30%) of the 57 patients, respectively. The 3-year overall survival rate was 63.4%. SUV{sub max} did not affect any recurrence, DFS, OS, or CSS. RI significantly predicted higher distant metastasis (HR 47.546, p = 0.026). In contrast, RI tended to predict lower local recurrence (HR 0.175, p = 0.246) and regional lymph node metastasis (HR 0.109, p = 0.115). Conclusions: SUV{sub max} at staging FDG-PET does not predict any recurrence, DFS, OS or CSS. In contrast, higher RI predicts higher distant metastasis and tended to predict lower local or regional lymph node metastasis.

Enhanced experimental tumor metastasis with age in senescence-accelerated mouse

International Nuclear Information System (INIS)

Shimizu, Kosuke; Kinouchi Shimizu, Naomi; Asai, Tomohiro; Oku, Naoto; Tsukada, Hideo

2008-01-01

Tumor metastasis is affected by the host immune surveillance system. Since aging may attenuate the host immune potential, the experimental tumor metastasis may be enhanced with age. In the present study, we investigated this alteration of experimental tumor metastasis with age. We used senescence-accelerated mice prone 10 (SAMP10) as a model of aged animals. Natural killer cell (NK) activity, as an indicator of immune surveillance potential, in 8-month-old (aged) SAMP10 mice was observed to be much lower than that in 2-month-old (young) mice. When we examined the in vivo trafficking of lung-metastatic K1735M2 melanoma cells in SAMP10 with positron emission tomography (PET), K1735M2 cells labeled with [2- 18 F]2-deoxy-2-fluoro-D-glucose ([ 18 F]FDG) were observed in both young and aged SAMP10 just after injection of the cells, whereas the clearance of 18 F from the lungs was retarded in aged animals. The accumulation of 5-[ 125 I]iodo-2'-deoxyuridine ([ 125 I]IUdR)-labeled K1735M2 cells in the lungs of SAMP10 at 24 h after injection was significantly higher in aged mice. Corresponding to these results, the number of metastatic colonies in the lung was larger in the aged SAMP10 of the experimental tumor metastasis model. The present study demonstrated that the aging process produced a susceptible environment allowing the tumor cells to metastasize due to decrease in the host immune surveillance potential with age. (author)

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.

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 ...

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

ZEB1 induces LOXL2-mediated collagen stabilization and deposition in the extracellular matrix to drive lung cancer invasion and metastasis.

Science.gov (United States)

Peng, D H; Ungewiss, C; Tong, P; Byers, L A; Wang, J; Canales, J R; Villalobos, P A; Uraoka, N; Mino, B; Behrens, C; Wistuba, I I; Han, R I; Wanna, C A; Fahrenholtz, M; Grande-Allen, K J; Creighton, C J; Gibbons, D L

2017-04-06

Lung cancer is the leading cause of cancer-related deaths, primarily due to distant metastatic disease. Metastatic lung cancer cells can undergo an epithelial-to-mesenchymal transition (EMT) regulated by various transcription factors, including a double-negative feedback loop between the microRNA-200 (miR-200) family and ZEB1, but the precise mechanisms by which ZEB1-dependent EMT promotes malignancy remain largely undefined. Although the cell-intrinsic effects of EMT are important for tumor progression, the reciprocal dynamic crosstalk between mesenchymal cancer cells and the extracellular matrix (ECM) is equally critical in regulating invasion and metastasis. Investigating the collaborative effect of EMT and ECM in the metastatic process reveals increased collagen deposition in metastatic tumor tissues as a direct consequence of amplified collagen gene expression in ZEB1-activated mesenchymal lung cancer cells. In addition, collagen fibers in metastatic lung tumors exhibit greater linearity and organization as a result of collagen crosslinking by the lysyl oxidase (LOX) family of enzymes. Expression of the LOX and LOXL2 isoforms is directly regulated by miR-200 and ZEB1, respectively, and their upregulation in metastatic tumors and mesenchymal cell lines is coordinated to that of collagen. Functionally, LOXL2, as opposed to LOX, is the principal isoform that crosslinks and stabilizes insoluble collagen deposition in tumor tissues. In turn, focal adhesion formation and FAK/SRC signaling is activated in mesenchymal tumor cells by crosslinked collagen in the ECM. Our study is the first to validate direct regulation of LOX and LOXL2 by the miR-200/ZEB1 axis, defines a novel mechanism driving tumor metastasis, delineates collagen as a prognostic marker, and identifies LOXL2 as a potential therapeutic target against tumor progression.

Adenylyl cyclase-associated protein 1 in metastasis of squamous cell carcinoma of the head and neck and non-small cell lung cancer

Science.gov (United States)

Kakurina, G. V.; Kolegova, E. S.; Cheremisina, O. V.; Zavyalov, A. A.; Shishkin, D. A.; Kondakova, I. V.; Choinzonov, E. L.

2016-08-01

Progression of tumors and metastasis in particular is one of the main reasons of the high mortality rate among cancer patients. The primary role in developing metastases plays cell locomotion which requires remodeling of the actin cytoskeleton. Form, dynamics, localization and mechanical properties of the actin cytoskeleton are regulated by a variety of actin-binding proteins, which include the adenylyl cyclase-associated protein 1 (CAP1). The study is devoted to the investigation of CAP1 level depending on the presence or absence of metastases in patients with squamous cell carcinoma of the head and neck (SCCHN) and non-small cell lung cancer (NSCLC). The results show the contribution of CAP1 to SCCHN and NSCLC progression. We detected the connection between the tissue protein CAP1 level and the stage of NSCLC and SCCHN disease. Also the levels of the CAP1 protein in tissues of primary tumors and metastases in lung cancer were different. Our data showed that CAP is important in the development of metastases, which suggests further perspectives in the study of this protein for projecting metastasis of NSCLC and SCCHN.

Combined Therapy for Distant Metastasis of Sacral Chordoma

Directory of Open Access Journals (Sweden)

Birol Özkal

2015-01-01

Full Text Available Chordomas are known as rare primary malign tumours that have formed from primitive notochord remains. Sacral chordomas grow slowly but locally and aggressively. Chordomas are locally invasive and have low tendency to metastasis and have a poor prognosis in long-term follow-up. Metastasis may be seen in a rate of 5–40% of the chordomas. Metastasis of chordomas is common in liver, lung, lymph nodes, peritoneum, and brain. The treatment approaches, including surgery, have been discussed in the literature before. Susceptibility to radiotherapy and chemotherapy is controversial in these tumours. The success of surgical treatment affects survival directly. In this report, we will report a sacral chordoma case in which an intraperitoneal distant metastasis occurred and discuss the surgical approach.

[Evaluation and classification of drug therapy for breast cancer with bone-only metastasis].

Science.gov (United States)

Meng, X Y; Song, S T

2017-03-23

Skeleton is one of the most common metastatic organs for breast cancer, which has a better prognosis than visceral metastases. Bone-only metastasis was defined"non-measurable" in the RECIST (Response Evaluation Criteria in Solid Tumors) criteria, and was excluded by clinical trials. However, patients with bone-only metastasis are also in need of effective treatment to prolong survival. Endocrine therapy is the most important treatment for bone metastatic patients. Tumor response of bone metastases can be determined objectively by bone-window CT. Effective treatment should be continued if the symptoms are relieved or osteogenesis is observed. Osteoblastic change in bone-window CT is a sign of improvement after treatment. Endocrine therapy is proper for ER-positive patients. The patients with initial osteoblastic metastasis should not be treated with salvage chemotherapy or anti-HER2 treatment, only if osteolytic metastasis or visceral metastasis is observed. Bishosphonates are just auxiliary drugs in bone metastasis, which should not be abused.

Application of detecting cerebrospinal fluid circulating tumor cells in the diagnosis of meningeal metastasis of non-small cell lung cancer

OpenAIRE

Rong JIANG; Chun-hua MA; Zi-long ZHU; Jin-duo LI; Bin WANG; Li-wei SUN; Yuan LÜ

2014-01-01

Objective To observe a new technology for the detection and enumeration of cerebrospinal fluid (CSF) circulating tumor cells (CTCs) in the diagnosis of non-small cell lung cancer (NSCLC) with meningeal metastasis (MM).  Methods Five cases of NSCLC with MM that were diagnosed by CSF cytology were selected, and 20 ml CSF samples were obtained by lumbar puncture for every patient. The tumor marker immunostaining-fluorescence in situ hybridization (TM-iFISH) technology was adapted to detect...

The concentration of erlotinib in the cerebrospinal fluid of patients with brain metastasis from non-small-cell lung cancer

Science.gov (United States)

DENG, YANMING; FENG, WEINENG; WU, JING; CHEN, ZECHENG; TANG, YICONG; ZHANG, HUA; LIANG, JIANMIAO; XIAN, HAIBING; ZHANG, SHUNDA

2014-01-01

It has been demonstrated that erlotinib is effective in treating patients with brain metastasis from non-small-cell lung cancer. However, the number of studies determining the erlotinib concentration in these patients is limited. The purpose of this study was to measure the concentration of erlotinib in the cerebrospinal fluid of patients with brain metastasis from non-small-cell lung carcinoma. Six patients were treated with the standard recommended daily dose of erlotinib (150 mg) for 4 weeks. All the patients had previously received chemotherapy, but no brain radiotherapy. At the end of the treatment period, blood plasma and cerebrospinal fluid samples were collected and the erlotinib concentration was determined by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The average erlotinib concentration in the blood plasma and the cerebrospinal fluid was 717.7±459.7 and 23.7±13.4 ng/ml, respectively. The blood-brain barrier permeation rate of erlotinib was found to be 4.4±3.2%. In patients with partial response (PR), stable disease (SD) and progressive disease (PD), the average concentrations of erlotinib in the cerebrospinal fluid were 35.5±19.0, 19.1±8.7 and 16.4±5.9 ng/ml, respectively. In addition, the efficacy rate of erlotinib for metastatic brain lesions was 33.3%, increasing to 50% in patients with EGFR mutations. However, erlotinib appeared to be ineffective in cases with wild-type EGFR. In conclusion, a relatively high concentration of erlotinib was detected in the cerebrospinal fluid of patients with brain metastases from non-small-cell lung cancer. Thus, erlotinib may be considered as a treatment option for this patient population. PMID:24649318

Cystic Pulmonary Metastasis in a Patient with Scalp Angiosarcoma: A Case Report

Energy Technology Data Exchange (ETDEWEB)

Kim, Ah Yeong; Lee, Kyung Soo; Han, Jong Ho; Kim, Ho Joong; Kim, Kwhan Mien; Baek, Chung Hwan [Samsugn Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

2011-08-15

It has been well known that angiosarcoma (AS), particularly scalp AS, metastasizes to the lungs with multiple air-filled cystic lesions on chest computed tomography scans. Pneumothorax, due to cystic lesion rupture into the pleural space, is frequent;however, we do not exactly know how rapidly the metastatic lesions spread to the lungs or what the exact pathogenetic mechanism for cystic metastasis is. According to our experience, the speed of disease progression in pulmonary metastasis is relatively fast and the entire lungs may be involved within two or three months. The infiltrating spindle cell tumors in the alveolar walls are tethering the adjacent alveolar spaces in order to form a dilated air-filled cystic lesion.

Experimental melanoma metastasis in lungs of mice with congenital coagulation disorders

NARCIS (Netherlands)

Brüggemann, Lois W.; Versteeg, Henri H.; Niers, Tatjana M.; Reitsma, Pieter H.; Spek, C. Arnold

2008-01-01

Experimental animal studies as well as clinical trials have shown that interventions targeting the blood coagulation cascade inhibit cancer cell metastasis. These data support the hypothesis that congenital prothrombotic disorders, like factor V Leiden, facilitate metastasis whereas bleeding

Pulmonary hilar lymph nodes in lung cancer: assessment with 3D-dynamic contrast-enhanced MR imaging

International Nuclear Information System (INIS)

Hasegawa, Ichiro; Eguchi, Keisuke; Kohda, Ehiichi; Tanami, Yutaka; Mori, Toru; Hatabu, Hiroto; Kuribayashi, Sachio

2003-01-01

Purpose: We performed 3D-dynamic MRI on patients with primary lung cancer to identify its usefulness for detecting hilar adenopathy shown at surgery. Methods and materials: 30 consecutive patients with peripheral lung cancer underwent preoperative 3D-dynamic Gd-DTPA-enhanced MRI. Two thoracic radiologists blinded to histopathologic findings reviewed those studies independently for hilar adenopathy visualization. The results were correlated with surgical and histopathologic findings. Interreader agreement for the detection of hilar adenopathy was assessed by means of the κ statistic. Results: Dynamic MRI demonstrated hilar adenopathy, with or without metastasis revealed at surgery, in all of 15 patients. Adenopathy without metastasis was shown in four patients. Dynamic MRI also revealed metastatic adenopathy in 11 of 12 patients with pathologically proven metastasis. There was only one case with lymph node metastasis that did not have adenopathy either on MRI or even at surgery. The diagnostic accuracy of dynamic MRI for adenopathy with or without metastases revealed at surgery were as follows; sensitivity, 100%; specificity, 100%; positive predictive value, 100%; and negative predictive value, 100%, respectively. The diagnostic accuracy of dynamic MRI for hilar lymph nodes metastasis were as follows; sensitivity, 92%; specificity, 78%; positive predictive value, 73%; and negative predictive value, 93%. Interreader agreement was substantial (κ=0.73) for detection of hilar adenopathy. Conclusion: Hilar adenopathy on 3D-dynamic MRI correlated well with that of surgical finding on patients with primary lung cancer. It may have the potential to make an accurate preoperative evaluation of hilar lymph node metastasis from lung cancer

Significance of serum endostatin levels in patients with primary lung cancer

International Nuclear Information System (INIS)

Peng Qunxin; Ling Chunhua; Ji Cheng

2005-01-01

Objective: To investigate the relationship between the serum level of endostatin and the clinical pathophysiological characteristics in patients with primary lung cancer. Methods: The serum levels of endostatin were detected in 48 patients with primary lung cancer and 50 patients with benign pulmonary diseases by enzyme-linked immunosorbent assay (ELISA) method. Results: Serum endostatin level in patients with primary lung cancer was significantly higher than it in patients with benign pulmonary diseases (P<0.01). It was higher in adenocarcinoma group than that in squamous cell carcinoma and small cell carcinoma group (P<0.05). The level of serum endostatin in lung cancer with TNM stage III + IV was higher than that in patients in stage I + II (P<0.01). And it was also higher in patients suffering from lung cancer with metastasis than that in patients with no metastasis (P<0.05). However, there was not a significant relation between serum endostatin level the location of the tumor and lymph node metastasis. Conclusion: Serum endostatin level in expressed higher in patients with primary lung cancer. There is significant relationship between serum endostatin level, histological classification, TNM stage and metastasis of lung cancer. (authors)

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

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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

Navigated Percutaneous Lung Ablation under High-Frequency Jet Ventilation of a Metastasis from a Wilms’ Tumour: A Paediatric Case Report

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Jacob Freedman

2016-07-01

Full Text Available This is a case report of microwave energy being used to ablate an inoperable metastasis of a Wilms’ tumour in a 6-year-old boy using state-of-the-art navigated computed tomography targeting and high-frequency jet ventilation to reduce organ displacement and the potential risk of procedure-related pneumothorax. After the ablation, the young boy had high-dose chemotherapy followed by an autologous stem cell transplantation with rapid reduction of three recurrent right-sided lung metastases.

Analysis of metastasis of melanoma-bearing hamsters in thermal neutron capture therapy

International Nuclear Information System (INIS)

Ueda, Masataka; Mishima, Yutaka; Ichihashi, Masamitsu

1985-01-01

Melanoma-bearing hamsters were divided into three groups: the MG I was treated with both 10 B 1 -para-boronophenylalanine.HCl ( 10 B 1 -BPA) and neutron capture therapy (NCT); the MG II was treated with NCT alone; and the control group (MG III). The most satisfactory effect on regression was seen in the MG I. When the opposite site to the transplanted tumor site was exposed to thermal neutrons, no enhanced effect on metastasis was seen. Tumor cells of MG I and MG II were transplanted subcutaneously 24 hr after NCT into normal hamsters (MG It and MG IIt), and their growth and metastasis abilities were examined. MG It cells possessed neither growth nor metastasis ability; while MG IIt cells showed normal growth and metastasis abilities. Lethal effects on tumor cells seemed to occur in the MG I at 24 hr after NCT, suggesting no effects of NCT on the metastasis ability of tumor cells. Metastasis was seen in 2 of 8 animals in the MG III; however, inhibitory effects on tumor cells were the same as those in the other groups MG I and MG II. When the cells were exposed to 100 rad and 300 rad of gamma rays to assess effects of gamma rays during NCT, neither tumor growth nor lung metastasis was affected. When the tumor was excised with 5 mm margin, relapse occurred in a high incidence. There was no difference in lung metastasis between NCT and gamma irradiation. (Namekawa, K.)

PAI-1, a target gene of miR-143, regulates invasion and metastasis by upregulating MMP-13 expression of human osteosarcoma.

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Hirahata, Mio; Osaki, Mitsuhiko; Kanda, Yusuke; Sugimoto, Yui; Yoshioka, Yusuke; Kosaka, Nobuyoshi; Takeshita, Fumitaka; Fujiwara, Tomohiro; Kawai, Akira; Ito, Hisao; Ochiya, Takahiro; Okada, Futoshi

2016-05-01

Despite recent improvements in the therapy for osteosarcoma, 30-40% of osteosarcoma patients die of this disease, mainly due to its lung metastasis. We have previously reported that intravenous injection of miR-143 significantly suppresses lung metastasis of human osteosarcoma cells (143B) in a mouse model. In this study, we examined the biological role and mechanism of miR-143 in the metastasis of human osteosarcoma cells. We identified plasminogen activator inhibitor-1 (PAI-1) as a direct target gene of miR-143. To determine the role of PAI-1 in human osteosarcoma cells, siRNA was transfected into 143B cells for knockdown of PAI-1 expression. An in vitro study showed that downregulation of PAI-1 suppressed cell invasion activity, but not proliferation. Moreover, injection of PAI-1 siRNA into a primary lesion in the osteosarcoma mouse model inhibited lung metastasis compared to control siRNA-injected mice, without influencing the proliferative activity of the tumor cells. Subsequent examination using 143B cells revealed that knockdown of PAI-1 expression resulted in downregulation of the expression and secretion of matrix metalloproteinase-13 (MMP-13), which is also a target gene of miR-143 and a proteolytic enzyme that regulates tumor-induced osteolysis. Immunohistochemical analysis using clinical samples showed that higher miR-143 expressing cases showed poor expression of PAI-1 in the primary tumor cells. All such cases belonged to the lung metastasis-negative group. Moreover, the frequency of lung metastasis-positive cases was significantly higher in PAI-1 and MMP-13 double-positive cases than in PAI-1 or MMP-13 single-positive or double-negative cases (P target gene of miR-143, regulates invasion and lung metastasis via enhancement of MMP-13 expression and secretion in human osteosarcoma cells, suggesting that these molecules could be potential therapeutic target genes for preventing lung metastasis in osteosarcoma patients. © 2016 The Authors. Cancer

Inhibitory effect of vitamin C in combination with vitamin K3 on tumor growth and metastasis of Lewis lung carcinoma xenografted in C57BL/6 mice.

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Chen, Ming-Feng; Yang, Chih-Min; Su, Cheng-Ming; Liao, Jiunn-Wang; Hu, Miao-Lin

2011-01-01

Vitamin C in combination with vitamin K3 (vit CK3) has been shown to inhibit tumor growth and lung metastasis in vivo, but the mechanism of action is poorly understood. Herein, C57BL/6 mice were implanted (s.c.) with Lewis lung carcinoma (LLC) for 9 days before injection (i.p.) with low-dose (100 mg vit C/kg + 1 mg vit K3/kg), high-dose (1,000 mg vit C/kg + 10 mg vit K3/kg) vit CK3 twice a week for an additional 28 days. As expected, vit CK3 or cisplatin (6 mg/kg, as a positive control) significantly and dose-dependently inhibited tumor growth and lung metastasis in LLC-bearing mice. Vit CK3 restored the body weight of tumor-bearing mice to the level of tumor-free mice. Vit CK3 significantly decreased activities of plasma metalloproteinase (MMP)-2, -9, and urokinase plasminogen activator (uPA). In lung tissues, vit CK3 1) increased protein expression of tissue inhibitor of metalloproteinase-1 (TIMP-1), TIMP-2, nonmetastatic protein 23 homolog 1 and plasminogen activator inhibitor-1; 2) reduced protein expression of MMP-2 and MMP-9; and 3) inhibited the proliferating cell nuclear antigen (PCNA). These results demonstrate that vit CK3 inhibits primary tumor growth and exhibits antimetastastic potential in vivo through attenuated tumor invasion and proliferation.

Contribution of dynamic contrast MR imaging to the differentiation between dural metastasis and meningioma

International Nuclear Information System (INIS)

Kremer, S.; Grand, S.; Le Bas, J.F.; Remy, C.; Pasquier, B.; Benabid, A.L.; Bracard, S.

2004-01-01

To determine the perfusion-sensitive characteristics of cerebral dural metastases and compare them with the data on meningiomas. Twenty-two patients presenting with dural tumor underwent conventional and dynamic susceptibility-contrast MR imaging: breast carcinoma metastases, two patients; colorectal carcinoma metastasis, one patient; lung carcinoma metastasis, one patient; Merkel carcinoma metastasis, one patient; lymphoma, one patient; meningiomas, 16 patients. The imaging characteristics were analyzed using conventional MR imaging. The cerebral blood volume (CBV) maps were obtained for each patient and the relative CBV (rCBV) in different areas was calculated using the ratio between the CBV in the pathological area (CBVp) and in the contralateral white matter (CBVn). The differentiation between a meningioma and a dural metastasis can be difficult using conventional MR imaging. The rCBVs of lung carcinoma metastasis (1 case: 1.26), lymphoma (1 case: 1.29), breast carcinoma metastasis (2 cases: 1.50,1.56) and rectal carcinoma metastasis (1 case: 3.34) were significantly lower than that of meningiomas (16 cases: mean rCBV = 8.97±4.34, range 4-18). Merkel carcinoma metastasis (1 case: 7.56) showed an elevated rCBV, not different from that of meningiomas. Dural metastases are sometimes indistinguishable from meningiomas using conventional MR imaging. rCBV mapping can provide additional information by demonstrating a low rCBV which may suggest the diagnosis of metastasis. (orig.)

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

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)

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

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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...

Gastric Metastasis of Triple Negative Invasive Lobular Carcinoma.

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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.

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)

[Utility of Multiple Increased Lung Cancer Tumor Markers in Treatment of Patients with Advanced Lung Adenocarcinoma].

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Peng, Yan; Wang, Yan; Hao, Xuezhi; Li, Junling; Liu, Yutao; Wang, Hongyu

2017-10-20

Among frequently-used tumor markers in lung cancer, carcinoembryonic antigen (CEA) and carbohydrate antigen 125 (CA125), cytokeratin 19 (CYFRA21-1) and squamous carcinoma antigen (SCC), neuron specific enolase (NSE) and pro-gastrin-releasing peptide (ProGRP) are respectively expressed highly in lung adenocarcinoma, lung squamous carcinoma and small cell lung cancer. By comparing patients with multiple increased tumor markers (group A) and patients with increase of CEA and/or CA125 (group B), this study aims to investigate the utility of multiple increased tumor markers in therapeutic evaluation and prediction of disease relapsing in patients with advanced lung adenocarcinoma. Patients with stage IV lung adenocarcinoma who receiving the first line chemotherapy in Cancer Hospital, Chinese Academy of Medical Sciences were enrolled and retrospectively analyzed. Clinical characteristic, serum tumor markers before chemotherapy, efficacy evaluation, progression-free survival (PFS) were analyzed. Except CEA and CA125, the highest ratio of increased tumor markersin group A was CYFRA21-1 (93%), then was NSE (36%), SCC (13%) and ProGRP (12%). Patients with multiple increased tumor markers tend to have more distant metastasis (Ptumor markers have high risk of relapse, and maintenance therapy can reduce relapse risk.

Parotid gland as an initial site of metastasis

International Nuclear Information System (INIS)

Borg, Martin F.

2004-01-01

The parotid gland is an uncommon site of metastasis from carcinomas arising outside the head and neck region. Involvement of the parotid gland as an initial site of metastasis or presentation is rare. The present case report is the first, to our knowledge, to describe the management and outcome of an elderly man whose first presentation of an asymptomatic squamous cell carcinoma of the lung was that of a rapidly growing fungating left parotid mass Copyright (2004) Blackwell Publishing Asia Pty Ltd

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

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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.

Micro-pleural Metastasis Without Effusion: CT and US Findings

International Nuclear Information System (INIS)

Na, Hyoung Il; Yoo, Seung Min; Kim, Yang Soo; Lee, Hwa Yeon; Song, In Sup; Shim, Hyung Jin; Kwak, Byung Kook; Shin, Jong Wook

2004-01-01

Pleural metastasis from malignancy is commonly combined with effusion. We report the ultrasonographic and CT findings in a rare case of micro-pleural metastasis without effusion. A 34-year-old male patient with lung cancer underwent video-assisted thoracoscopic surgery (VATS), prior to open thoracotomy. VATS revealed multiple metastatic micronodules on the pleura, which were overlooked on the preoperative CT scan. The HRCT images and chest ultrasonograms showed clear evidence of pleural micro-nodules

Micro-pleural Metastasis Without Effusion: CT and US Findings

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Na, Hyoung Il; Yoo, Seung Min; Kim, Yang Soo; Lee, Hwa Yeon; Song, In Sup; Shim, Hyung Jin; Kwak, Byung Kook; Shin, Jong Wook [Chung-Ang University College of Medicine, Seoul (Korea, Republic of)

2004-09-15

Pleural metastasis from malignancy is commonly combined with effusion. We report the ultrasonographic and CT findings in a rare case of micro-pleural metastasis without effusion. A 34-year-old male patient with lung cancer underwent video-assisted thoracoscopic surgery (VATS), prior to open thoracotomy. VATS revealed multiple metastatic micronodules on the pleura, which were overlooked on the preoperative CT scan. The HRCT images and chest ultrasonograms showed clear evidence of pleural micro-nodules

Pulmonary Metastasis from Pseudomyxoma Peritonei

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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.

Ulcerative Cutaneous Lesions Synchronously Present with the Diagnosis of Primary Lung Cancer

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Khaldoon Shaheen

2013-01-01

Full Text Available The percentage of patients with lung cancer that develop skin metastases is low. The diagnosis is usually made using clinical information and skin biopsy in patients with suspicious skin lesions and history of smoking or lung cancer. The prognosis for patients having lung cancer with skin metastasis is very poor. We describe findings in a 70-year-old man with lung cancer with skin metastases. Interestingly, multiple skin lesions were the first manifestation of the underlying lung cancer. The prognosis for patients having lung cancer with skin metastasis is thus very poor.

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

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

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Nathan Benaich

2014-10-01

Full Text Available Summary: 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. : Benaich et al. have identified miR-203, a microRNA that triggers differentiation in multilayered epithelia, as an inhibitor of lung metastasis in head and neck squamous cell carcinoma (HNSCC cells. They show that miR-203 inhibits metastasis independently of its effects on differentiation. Rather, miR-203 suppresses 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 survival in HNSCC patients.

Gut metastasis from breast carcinoma.

Science.gov (United States)

Al-Qahtani, Mohammed S

2007-10-01

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 rare with patients presenting with small-bowel perforation, intestinal obstruction, and gastrointestinal bleeding. Here we report a case of a Saudi female presenting with invasive lobular carcinoma and ileo-cecal junction metastasis.

Lung cells support osteosarcoma cell migration and survival.

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Yu, Shibing; Fourman, Mitchell Stephen; Mahjoub, Adel; Mandell, Jonathan Brendan; Crasto, Jared Anthony; Greco, Nicholas Giuseppe; Weiss, Kurt Richard

2017-01-25

Osteosarcoma (OS) is the most common primary bone tumor, with a propensity to metastasize to the lungs. Five-year survival for metastatic OS is below 30%, and has not improved for several decades despite the introduction of multi-agent chemotherapy. Understanding OS cell migration to the lungs requires an evaluation of the lung microenvironment. Here we utilized an in vitro lung cell and OS cell co-culture model to explore the interactions between OS and lung cells, hypothesizing that lung cells would promote OS cell migration and survival. The impact of a novel anti-OS chemotherapy on OS migration and survival in the lung microenvironment was also examined. Three human OS cell lines (SJSA-1, Saos-2, U-2) and two human lung cell lines (HULEC-5a, MRC-5) were cultured according to American Type Culture Collection recommendations. Human lung cell lines were cultured in growth medium for 72 h to create conditioned media. OS proliferation was evaluated in lung co-culture and conditioned media microenvironment, with a murine fibroblast cell line (NIH-3 T3) in fresh growth medium as controls. Migration and invasion were measured using a real-time cell analysis system. Real-time PCR was utilized to probe for Aldehyde Dehydrogenase (ALDH1) expression. Osteosarcoma cells were also transduced with a lentivirus encoding for GFP to permit morphologic analysis with fluorescence microscopy. The anti-OS efficacy of Disulfiram, an ALDH-inhibitor previously shown to inhibit OS cell proliferation and metastasis in vitro, was evaluated in each microenvironment. Lung-cell conditioned medium promoted osteosarcoma cell migration, with a significantly higher attractive effect on all three osteosarcoma cell lines compared to basic growth medium, 10% serum containing medium, and NIH-3 T3 conditioned medium (p cell conditioned medium induced cell morphologic changes, as demonstrated with GFP-labeled cells. OS cells cultured in lung cell conditioned medium had increased alkaline

Papillary carcinoma thyroid, metastasis to cheek: First ever reported case in literature

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Aiffa Aiman

2014-01-01

Full Text Available Papillary thyroid carcinoma (PTC metastasis to distant organs is rare and mainly includes lung and bone. Metastasis affecting oral and maxillofacial region is extremely rare. We describe a case of PTC metastasis to cheek. The patient presented with a painless swelling of the left cheek with a history of total thyroidectomy for papillary carcinoma thyroid 5 years back. Cheek metastasis from papillary carcinoma thyroid is extremely rare. To the best of our knowledge, this is the first recorded instance of cheek metastasis from PTC. Common malignancies can metastasize to unusual sites and although infrequent, may be the presenting feature. The successful management of such cases may be achieved by a multidisciplinary approach.

[Clinic significance of nm23, collage IV and PCNA expression in non-small cell lung cancer].

Science.gov (United States)

Yu, Q; Ma, L; Jing, S; Xu, Y; Geng, D

2001-12-20

To study the significance of nm23, collagen IV and PCNA expressions in non-small cell lung cancer. Expressions of the nm23, collagen IV and PCNA in 84 cases of non-small cell lung cancer were examined with SP immunohistochemical technique. Of the 84 cases, there were squamous cell carcinoma 42, adenocarcinoma 42, stage I 27, stage II 24, stage III 24, and stage IV 9. Statistical analysis was performed with Chi-Square test. Expressions of the nm23, collagen IV and PCNA in 84 cases of non-small cell lung cancer were 60. 7% ( 51/ 84) , 75. 0% ( 63/ 84) and 53. 6% ( 45/ 84) respectively. There was negative correlation between the lymph node metastasis and the expressions of nm23 and collagen IV in squamous cell carcinoma, and the expressions of collagen IV and PCNA were associated with tumor differentiation. No correlation was found between TNM stage and expressions of nm23, collagen IV and PCNA. The results indicate that nm23, collagen IV and PCNA participate the modulation of metastasis of non-small cell lung cancer and that they may be used to evaluate the potential of metastasis.

Long-term exposure to hypoxia inhibits tumor progression of lung cancer in rats and mice

International Nuclear Information System (INIS)

Yu, Lunyin; Hales, Charles A

2011-01-01

Hypoxia has been identified as a major negative factor for tumor progression in clinical observations and in animal studies. However, the precise role of hypoxia in tumor progression has not been fully explained. In this study, we extensively investigated the effect of long-term exposure to hypoxia on tumor progression in vivo. Rats bearing transplanted tumors consisting of A549 human lung cancer cells (lung cancer tumor) were exposed to hypoxia for different durations and different levels of oxygen. The tumor growth and metastasis were evaluated. We also treated A549 lung cancer cells (A549 cells) with chronic hypoxia and then implanted the hypoxia-pretreated cancer cells into mice. The effect of exposure to hypoxia on metastasis of Lewis lung carcinoma in mice was also investigated. We found that long-term exposure to hypoxia a) significantly inhibited lung cancer tumor growth in xenograft and orthotopic models in rats, b) significantly reduced lymphatic metastasis of the lung cancer in rats and decreased lung metastasis of Lewis lung carcinoma in mice, c) reduced lung cancer cell proliferation and cell cycle progression in vitro, d) decreased growth of the tumors from hypoxia-pretreated A549 cells, e) decreased Na + -K + ATPase α1 expression in hypoxic lung cancer tumors, and f) increased expression of hypoxia inducible factors (HIF1α and HIF2α) but decreased microvessel density in the lung cancer tumors. In contrast to lung cancer, the growth of tumor from HCT116 human colon cancer cells (colon cancer tumor) was a) significantly enhanced in the same hypoxia conditions, accompanied by b) no significant change in expression of Na + -K + ATPase α1, c) increased HIF1α expression (no HIF2α was detected) and d) increased microvessel density in the tumor tissues. This study demonstrated that long-term exposure to hypoxia repressed tumor progression of the lung cancer from A549 cells and that decreased expression of Na + -K + ATPase was involved in hypoxic

Reduced metastasis of transgenic mammary cancer in urokinase-deficient mice

DEFF Research Database (Denmark)

Almholt, Kasper; Lund, L.R.; Rygaard, Jørgen

2005-01-01

A prominent phenotype of plasmin deficiency in mice is reduced metastasis in the MMTV-PymT transgenic breast cancer model. Proteolytically active plasmin is generated from inactive plasminogen by one of 2 activators, uPA or tPA. We now find that uPA deficiency alone significantly reduces metastasis...... >7-fold in the MMTV-PymT model. We studied a cohort of 55 MMTV-PymT transgenic mice, either uPA-deficient or wild-type controls. Tumor incidence, latency, growth rate and final primary tumor burden were not significantly affected by uPA deficiency. In contrast, average lung metastasis volume...

Impact of the new international association for the study of lung cancer staging system in non-small cell lung cancer: With comparison to the union for international cancer control 6th tumor, node, metastasis edition

International Nuclear Information System (INIS)

Lee, Myung Jae; Lee, So Won; Shim, Sung Shine; Ryu, Yon Ju; Kim, Yoo Kyung

2014-01-01

To investigate the impact of the proposed International Association for the Study of Lung Cancer (IASLC) tumor, node, metastasis (TNM) system on staging and outcome of non small cell lung cancer (NSCLC). With a total of 501 NSCLC patients with staging according to Union for International Cancer Control (UICC), 6th TNM (TNM-6) were reclassified according to the IASLC proposed TNM staging (TNM-7). The impact of TNM-7 in comparison with TNM-6 was evaluated at three levels: change in substage, staging, and outcome. The outcome measure was to compare the stage-specific overall survival of NSCLC between the two groups of patients. A total of 214 (42.7%) patients had changed TNM staging, and 101 (20.2%) patients had changed stage groupings in TNM-7 compared to TNM-6. Among 100 patients showing changed stage grouping, 72 (14.4%) showed upstage and 29 (5.8%) demonstrated downstage. The TNM-7 system resulted in better separation of survival curves among stage-specific NSCLC than TNM-6 system, especially in separation of stage IIA vs. IIB (p 0.023) and stage IIIB vs. IV (p < 0.001). TNM-7 for lung cancer appears to be superior in defining stage-specific survival groups than TNM-6, especially between stage IIA vs. stage IIB and stage IIIB vs. stage IV.

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

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Lamm, Andrew F.; Elaimy, Ameer L.; Mackay, Alexander R.; Fairbanks, Robert K.; Demakas, John J.; Cooke, Barton S.; Lee, Christopher M.; Taylor, Blake S.; Lamoreaux, Wayne T.

2012-01-01

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. PMID:23056973

Genetically engineered endostatin-lidamycin fusion proteins effectively inhibit tumor growth and metastasis

International Nuclear Information System (INIS)

Jiang, Wen-guo; Zhen, Yong-su; Lu, Xin-an; Shang, Bo-yang; Fu, Yan; Zhang, Sheng-hua; Zhou, Daifu; Li, Liang; Li, Yi; Luo, Yongzhang

2013-01-01

Endostatin (ES) inhibits endothelial cell proliferation, migration, invasion, and tube formation. It also shows antiangiogenesis and antitumor activities in several animal models. Endostatin specifically targets tumor vasculature to block tumor growth. Lidamycin (LDM), which consists of an active enediyne chromophore (AE) and a non-covalently bound apo-protein (LDP), is a member of chromoprotein family of antitumor antibiotics with extremely potent cytotoxicity to cancer cells. Therefore, we reasoned that endostatin-lidamycin (ES-LDM) fusion proteins upon energizing with enediyne chromophore may obtain the combined capability targeting tumor vasculature and tumor cell by respective ES and LDM moiety. In this study, we designed and obtained two new endostatin-based fusion proteins, endostatin-LDP (ES-LDP) and LDP-endostatin (LDP-ES). In vitro, the antiangiogenic effect of fusion proteins was determined by the wound healing assay and tube formation assay and the cytotoxicity of their enediyne-energized analogs was evaluated by CCK-8 assay. Tissue microarray was used to analyze the binding affinity of LDP, ES or ES-LDP with specimens of human lung tissue and lung tumor. The in vivo efficacy of the fusion proteins was evaluated with human lung carcinoma PG-BE1 xenograft and the experimental metastasis model of 4T1-luc breast cancer. ES-LDP and LDP-ES disrupted the formation of endothelial tube structures and inhibited endothelial cell migration. Evidently, ES-LDP accumulated in the tumor and suppressed tumor growth and metastasis. ES-LDP and ES show higher binding capability than LDP to lung carcinoma; in addition, ES-LDP and ES share similar binding capability. Furthermore, the enediyne-energized fusion protein ES-LDP-AE demonstrated significant efficacy against lung carcinoma xenograft in athymic mice. The ES-based fusion protein therapy provides some fundamental information for further drug development. Targeting both tumor vasculature and tumor cells by endostatin

The seventh tumour-node-metastasis staging system for lung cancer: Sequel or prequel?

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van Meerbeeck, Jan P; Janssens, Annelies

2013-09-01

Anatomical cancer extent is an important predictor of prognosis and determines treatment choices. In non-small-cell lung cancer (NSCLC) the tumour-node-metastasis (TNM) classification developed by Pierre Denoix replaced in 1968 the Veterans Administration Lung cancer Group (VALG) classification, which was still in use for small-cell lung cancer (SCLC). Clifton Mountain suggested several improvements based on a database of mostly surgically treated United States (US) patients from a limited number of centres. This database was pivotal for a uniform reporting of lung cancer extent by the American Joint Committee of Cancer (AJCC) and the International Union against Cancer (IUCC), but it suffered increasingly from obsolete diagnostic and staging procedures and did not reflect new treatment modalities. Moreover, its findings were not externally validated in large Japanese and European databases, resulting in persisting controversies which could not be solved with the available database. The use of different mediastinal lymph-node maps in Japan, the (US) and Europe facilitated neither the exchange nor the comparison of treatment results. Peter Goldstraw, a United Kingdom (UK) thoracic surgeon, started the process of updating the sixth version in 1996 and brought it to a good end 10 years later. His goals were to improve the TNM system in lung cancer by addressing the ongoing controversies, to validate the modifications and additional descriptors, to validate the TNM for use in staging SCLC and carcinoid tumours, to propose a new uniform lymph-node map and to investigate the prognostic value of non-anatomical factors. A staging committee was formed within the International Association for the Study of Lung Cancer (IASLC) - which supervised the collection of the retrospective data from >100,000 patients with lung cancer - treated throughout the world between 1990 and 2000, analyse them with the help of solid statistics and validate externally with the Surveillance

Endobronchial metastasis: CT findings and its usefulness in bronchoscopic correlation

International Nuclear Information System (INIS)

Ko, Ji Ho; Jung, Gyoo Sik; Kim, Seong Min; Huh Jin Do; Joh, Young Duk; Jang, Tae Weon

2000-01-01

To evaluate the CT findings of bronchial abnormalities in patients with endobronchial metastasis from extrapulmonary tumors, and to correlate these with the bronchoscopic findings. The authors retrospectively reviewed the CT and bronchoscopic findings of 17 patients (M:F =3D 9:8; mean age, 56 years) with histologically proven endobronchial metastasis from extrapulmonary primary tumors. Carcinoma of the uterine cervix (n=3D5) was the most common primary site for endobronchial metastasis. CT findings of bronchial abnormalities with associated peribronchial and lung parenchymal lesions were analyzed and compared with the bronchoscopic findings. Among the 17 patients, 20 sites of bronchial abnormalities were visualized bronchoscopically. CT findings of bronchial abnormalities were smooth narrowing (n=3D11), occlusion (n=3D3), intraluminal mass (n=3D4), and normal (n=3D2). Peribronchial lesions (lymph node enlargement or parenchymal mass) were found in 12 cases. Bronchoscopy revealed bronchial narrowing due to a mucosal nodule or intraluminal polypoid mass in 16 cases, and total obstruction of the bronchus in four. With regard to the identification of bronchial abnormalities, the findings of CT and of bronchoscopy agreed in 17 cases and disagreed in three. While bronchoscopy was advantageous for detecting early mucosal abnormality, CT effectively evaluated the extent of a lesion beyond the stenosis or bronchial obstruction. CT was also useful for predicting the causes of bronchial abnormalities. CT is relatively accurate in evaluating bronchial abnormalities, and in patients with endobronchial metastases may be used as a complementary procedure to bronchoscopy for evaluating the extent of the lesion. (author)

Blocking Surgically Induced Lysyl Oxidase Activity Reduces the Risk of Lung Metastases

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Chen Rachman-Tzemah

2017-04-01

Full Text Available Surgery remains the most successful curative treatment for cancer. However, some patients with early-stage disease who undergo surgery eventually succumb to distant metastasis. Here, we show that in response to surgery, the lungs become more vulnerable to metastasis due to extracellular matrix remodeling. Mice that undergo surgery or that are preconditioned with plasma from donor mice that underwent surgery succumb to lung metastases earlier than controls. Increased lysyl oxidase (LOX activity and expression, fibrillary collagen crosslinking, and focal adhesion signaling contribute to this effect, with the hypoxic surgical site serving as the source of LOX. Furthermore, the lungs of recipient mice injected with plasma from post-surgical colorectal cancer patients are more prone to metastatic seeding than mice injected with baseline plasma. Downregulation of LOX activity or levels reduces lung metastasis after surgery and increases survival, highlighting the potential of LOX inhibition in reducing the risk of metastasis following surgery.

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...

Brain metastasis of small cell lung carcinoma. Comparison of Gd-DTPA enhanced magnetic resonance imaging and enhanced computerized tomography

International Nuclear Information System (INIS)

Nomoto, Yasushi; Yamaguchi, Yutaka; Miyamoto, Tadaaki.

1994-01-01

Small cell carcinoma of the lung (SCLC) frequently metastasizes into the brain, resulting in serious influences upon prognosis. Delayed brain damage caused by prophylactic cranial irradiation (PCI) is also problematic. Gadolinium diethylene triamine pentaacetic acid (Gd-DTPA) enhanced magnetic resonance imaging (MRI) was performed to detect early brain metastasis from SCLC, and its usefulness was compared with contrast computerized tomography (CT). Among 25 SCLC patients, brain metastasis was detected in 11 by MRI and in 10 by CT, although six of them were completely asymptomatic. In the 11 patients, 6.3 and 2.4 lesions were respectively detected on average by MRI and CT. The ability of MRI to detect metastatic lesions of ≥15 mm diameter did not differ from that of CT, but became different as lesions became smaller (P<0.002), and MRI had a decided advantage over CT because as many as 30 lesions of ≤5 mm diameter were detected by MRI, whereas such lesions visualized on CT numbered only one (P<0.0001). MRI was incomparably superior to CT (P<0.0004) for subtentorial lesions since 18 lesions were detected on MRI, but only three, measuring ≥25 mm in diameter, were demonstrated on CT. Gd-DTPA enhanced MRI was determined to be extremely useful in the early diagnosis of SCLC brain metastasis. MRI was thought to reduce delayed brain damage caused by PCI if performed according to an adequate schedule. (author)

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)

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

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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.

Inhibitory effect of BCG cell-wall skeletons (BCG-CWS) emulsified in squalane on tumor growth and metastasis in mice.

Science.gov (United States)

Yoo, Yung Choon; Hata, Katsusuke; Lee, Kyung Bok; Azuma, Ichiro

2002-08-01

The antimetastatic effect of BCG-CWS, which was emulsified in an oil-in-water form with either Drakeol 6VR mineral oil (BCG-CWS/DK) or squalane (BCG-CWS/SQA), on lung metastasis produced by highly metastatic murine tumor cells, Colon26-M3.1 carcinoma cells and B16-BL6 melanoma cells, was investigated in syngeneic mice. An intravenous (i.v.) administration of BCG-CWS (100 mg/mouse) 1 day after tumor inoculation significantly inhibited tumor metastasis of both Colon26-M3.1 carcinoma and B16-BL6 melanoma cells in experimental lung metastasis models. No differences in the antitumor activity of the two oil-based formulations (BCG-CWS/DK and BCG-CWS/SQA) were obverved. However, BCG-CWS/SQA administered through subcutaneous (s.c.) route was shown to be effective only when it was consecutively injected (3 times) after tumor inoculation. An in vivo analysis for tumor-induced angiogenesis showed that a single i.v. administration of BCG-CWS/SQA inhibited the number of tumor-induced blood vessels and suppressed tumor growth. Furthermore, the multiple administration of BCG-CWS/SQA given at on week intervals led to a significant reduction in spontaneous lung metastasis of B16-BL6 melanoma cells in a spontaneous metastasis model. These results suggest that BCG-CWS emulsified with squalane is a potent inhibitory agent of lung metastasis, and that the antimetastatic effect of BCG-CWS is related to the suppression of tumor growth and the inhibition of tumor-induced angiogenesis.

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

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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.

Selective macrophage inhibition abolishes warfarin-induced reduction of metastasis

NARCIS (Netherlands)

Maat, B.

1980-01-01

Warfarin administered to tumor-bearing mice reduces the number of spontaneous lung metastases. Both macrophage inhibitors silica and carrageenan abolish the warfarin-induced decrease in tumour metastasis, which strongly supports the concept that the antitumour effect of coumarin derivatives is

Stage IV pleomorphic carcinoma of the lung without recurrence for 6 years: a case report.

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Miura, Naoko; Mori, Ryo; Takenaka, Tomoyoshi; Yamazaki, Koji; Momosaki, Seiya; Takeo, Sadanori

2017-12-01

Pleomorphic carcinoma is a rare primary lung carcinoma that occurs at a rate of about 0.3%. Even with complete resection, the tumor usually recurs aggressively, resulting in a poor prognosis. Herein, we report a case of advanced pleomorphic carcinoma of the lung who had a long survival time after resection of the primary and metastatic sites. A 48-year-old man was admitted to our hospital due to abdominal pain. Systemic examination revealed a lung mass on the right and a tumor in the jejunum. Surgical resection of both tumors revealed pleomorphic carcinoma of the lung with metastasis to the jejunum. Follow-up after 6 years showed that the patient remained recurrence-free, without the need for additional postoperative treatment. A vigorous treatment strategy that included surgery had the potential to offer long-term survival, despite an advanced pleomorphic carcinoma with distant metastasis to other organs. Reports on more similar cases are needed to evaluate the value of this treatment option.

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

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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.

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

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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.

Bovine Lactoferrin and Lactoferricin, a Peptide Derived from Bovine Lactoferrin, Inhibit Tumor Metastasis in Mice

Science.gov (United States)

Watanabe, Shikiko; Watanabe, Ryosuke; Hata, Katsusuke; Shimazaki, Kei–ichi; Azuma, Ichiro

1997-01-01

We investigated the effect of a bovine milk protein, lactoferrin (LF–B), and a pepsin–generated peptide of LF–B, lactoferricin (Lfcin–B), on inhibition of tumor metastasis produced by highly metastatic murine tumor cells, B16–BL6 melanoma and L5178Y–ML25 lymphoma cells, using experimental and spontaneous metastasis models in syngeneic mice. The subcutaneous (s.c.) administration of bovine apo–lactoferrin (apo–LF–B, 1 mg/mouse) and Lfcin–B (0.5 mg/monse) 1 day after tumor inoculation significantly inhibited liver and lung metastasis of L5178Y–ML25 cells. However, human apo–lactoferrin (apo–LF–H) and bovine holo–lactoferrin (holo–LF–B) at the dose of 1 mg/mouse failed to inhibit tumor metastasis of L5178Y–ML25 cells. Similarly, the s.c. administration of apo–LF–B as well as Lfcin–B, but not apo–LF–H and holo–LF–B, 1 day after tumor inoculation resulted in significant inhibition of lung metastasis of B16–BL6 cells in an experimental metastasis model. Furthermore, in in vivo analysis for tumor–induced angiogenesis, both apo–LF–B and Lfcin–B inhibited the number of tumor–induced blood vessels and suppressed tumor growth on day 8 after tumor inoculation. However, in a long–term analysis of tumor growth for up to 21 days after tumor inoculation, single administration of apo–LF–B significantly suppressed the growth of B16–BL6 cells throughout the examination period, whereas Lfcin–B showed inhibitory activity only during the early period (8 days). In spontaneous metastasis of B16–BL6 melanoma cells, multiple administration of both apo–LF–B and Lfcin–B into tumor–bearing mice significantly inhibited lung metastasis produced by B16–BL6 cells, though only apo–LF–B exhibited an inhibitory effect on tumor growth at the time of primary tumor amputation (on day 21) after tumor inoculation. These results suggest that apo–LF–B and Lfcin–B inhibit tumor metastasis through different

Clinical utility of F-18 FDG PET-CT in the initial evaluation of lung cancer.

Science.gov (United States)

Madsen, Poul Henning; Holdgaard, Paw Christian; Christensen, Janne Buck; Høilund-Carlsen, Poul Flemming

2016-10-01

Positron emission tomography-computed tomography (PET-CT) is a resource-demanding imaging modality with increasing popularity in the workup of patients with suspected or proven lung cancer. To review the clinical usefulness of this imaging modality in the diagnosis, staging, and pre-operative evaluation, we conducted a systematic literature search, review, and quality assessment using the rapid evidence assessment toolkit and the Oxford Centre for Evidence-Based Medicine methodology. The literature search resulted in 4,208 records including 918 reviews, of which 139 met the predefined criteria and were read in full to identify relevant original articles on F-18 FDG PET-CT (1) in the evaluation of solitary pulmonary nodules (n = 14), (2) in curative-intent treatment trials (n = 9), and (3) in planning of invasive procedures (n = 18). We found the following important results from the literature review: 1) PET-CT can rule out malignancy in most solitary pulmonary nodules due to high sensitivity (recommendation level A). 2) PET-CT reduces the number of futile treatment trials (recommendation level A). 3) The sensitivity of PET-CT in general is insufficient to rule out mediastinal lymph node metastasis (recommendation level A). ᅟ 1) With few exceptions, solitary pulmonary nodules can safely be considered benign if the PET-CT scan is negative. Exceptions consist of small (PET-CT scan has excluded occult distant metastases. 3) In general, lymph node metastasis in the mediastinum cannot be ruled out on the basis of a negative PET-CT, and confirmative invasive staging should be performed in most patients before mediastinal metastasis is confirmed or ruled out.

Dosimetric evaluation of the feasibility of stereotactic body radiotherapy for primary lung cancer with lobe-specific selective elective nodal irradiation.

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Komatsu, Tetsuya; Kunieda, Etsuo; Kitahara, Tadashi; Akiba, Takeshi; Nagao, Ryuta; Fukuzawa, Tsuyoshi

2016-01-01

More than 10% of all patients treated with stereotactic body radiotherapy (SBRT) for primary lung cancer develop regional lymph node recurrence. We evaluated the dosimetric feasibility of SBRT with lobe-specific selective elective nodal irradiation (ENI) on dose-volume histograms. A total of 21 patients were treated with SBRT for Stage I primary lung cancer between January 2010 and June 2012 at our institution. The extents of lobe-specific selective ENI fields were determined with reference to prior surgical reports. The ENI fields included lymph node stations (LNS) 3 + 4 + 11 for the right upper lobe tumors, LNS 7 + 11 for the right middle or lower lobe tumors, LNS 5 + 11 for the left upper lobe tumors, and LNS 7 + 11 for the left lower lobe tumors. A composite plan was generated by combining the ENI plan and the SBRT plan and recalculating for biologically equivalent doses of 2 Gy per fraction, using a linear quadratic model. The V20 of the lung, D(1cm3) of the spinal cord, D(1cm3) and D(10cm3) of the esophagus and D(10cm3) of the tracheobronchial wall were evaluated. Of the 21 patients, nine patients (43%) could not fulfill the dose constraints. In all these patients, the distance between the planning target volume (PTV) of ENI (PTVeni) and the PTV of SBRT (PTVsrt) was ≤2.0 cm. Of the three patients who developed regional metastasis, two patients had isolated lymph node failure, and the lymph node metastasis was included within the ENI field. When the distance between the PTVeni and PTVsrt is >2.0 cm, SBRT with selective ENI may therefore dosimetrically feasible. © The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

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

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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.

[A case of brain metastasis discovered after surgery for lung cancer based on changes in CEA, in which long-term survival was obtained by repeated gammaknife irradiation].

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Kakeya, Hiroshi; Inoue, Yuichi; Sawai, Toyomitsu; Ikuta, Yasushi; Ohno, Hideaki; Yanagihara, Katsunori; Higashiyama, Yasuhito; Miyazaki, Yoshitsugu; Soda, Hiroshi; Tashiro, Takayoshi; Kohno, Shigeru

2005-12-01

A 58-year-old man underwent right lower lobectomy for lung adenocarcinoma in June 1998. Since a high level of tumor marker CEA persisted after surgery, chemotherapy was additionally performed, and the CEA level subsequently normalized. However, the CEA level increased in April 1999, and brain metastasis was found in the left occipital lobe, and the first gammaknife irradiation was performed. Multiple brain metastases were found when CEA increased again in August 1999, and the second gammaknife irradiation was performed. Moreover, brain metastases were found in the left frontal and occipital lobes in February 2000, and the third gammaknife irradiation was performed. CEA normalized thereafter, but increased in February 2001. Brain metastasis was found in the right occipital lobe, and the fourth gammaknife irradiation was performed. CEA has remained within the normal range for about 4 years thereafter. Long-term survival was possible by repeated gammaknife irradiation for brain metastases. Monitoring of CEA played an important role in finding recurrent brain metastasis in this patient.

Histone Demethylase RBP2 Is Critical for Breast Cancer Progression and Metastasis

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Jian Cao

2014-03-01

Full Text Available Metastasis is a major clinical challenge for cancer treatment. Emerging evidence suggests that aberrant epigenetic modifications contribute significantly to tumor formation and progression. However, the drivers and roles of such epigenetic changes in tumor metastasis are still poorly understood. Using bioinformatic analysis of human breast cancer gene-expression data sets, we identified histone demethylase RBP2 as a putative mediator of metastatic progression. By using both human breast cancer cells and genetically engineered mice, we demonstrated that RBP2 is critical for breast cancer metastasis to the lung in multiple in vivo models. Mechanistically, RBP2 promotes metastasis as a pleiotropic positive regulator of many metastasis genes, including TNC. In addition, RBP2 loss suppresses tumor formation in MMTV-neu transgenic mice. These results suggest that therapeutic targeting of RBP2 is a potential strategy for inhibition of tumor progression and metastasis.

Src-homology 2 domain-containing tyrosine phosphatase 2 promotes oral cancer invasion and metastasis

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2014-01-01

Background Tumor invasion and metastasis represent a major unsolved problem in cancer pathogenesis. Recent studies have indicated the involvement of Src-homology 2 domain-containing tyrosine phosphatase 2 (SHP2) in multiple malignancies; however, the role of SHP2 in oral cancer progression has yet to be elucidated. We propose that SHP2 is involved in the progression of oral cancer toward metastasis. Methods SHP2 expression was evaluated in paired oral cancer tissues by using immunohistochemical staining and real-time reverse transcription polymerase chain reaction. Isogenic highly invasive oral cancer cell lines from their respective low invasive parental lines were established using a Boyden chamber assay, and changes in the hallmarks of the epithelial-mesenchymal transition (EMT) were assessed to evaluate SHP2 function. SHP2 activity in oral cancer cells was reduced using si-RNA knockdown or enforced expression of a catalytically deficient mutant to analyze migratory and invasive ability in vitro and metastasis toward the lung in mice in vivo. Results We observed the significant upregulation of SHP2 in oral cancer tissues and cell lines. Following SHP2 knockdown, the oral cancer cells markedly attenuated migratory and invasion ability. We observed similar results in phosphatase-dead SHP2 C459S mutant expressing cells. Enhanced invasiveness was associated with significant upregulation of E-cadherin, vimentin, Snail/Twist1, and matrix metalloproteinase-2 in the highly invasive clones. In addition, we determined that SHP2 activity is required for the downregulation of phosphorylated ERK1/2, which modulates the downstream effectors, Snail and Twist1 at a transcript level. In lung tissue sections of mice, we observed that HSC3 tumors with SHP2 deletion exhibited significantly reduced metastatic capacity, compared with tumors administered control si-RNA. Conclusions Our data suggest that SHP2 promotes the invasion and metastasis of oral cancer cells. These results

Advances in Diagnosis and Treatment of Brain Metastases from the Primary Lung Cancer

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Yi LIU

2013-07-01

Full Text Available Lung cancer with brain metastasis was 23% to 65%, and is the most common type in brain metastasis tumors with the poor prognosis. At present, diagnosis and treatment of brain metastases from lung carcinoma and its molecular mechanism have become one hot spot of amount researches. Here, we made a systematic review of the progress of the clinical features, diagnosis and treatment of brain metastases from lung and its molecular mechanism.

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

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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.

Prognostic indicators of outcomes in patients with lung metastases from differentiated thyroid carcinoma during long-term follow-up.

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Sohn, Seo Young; Kim, Hye In; Kim, Young Nam; Kim, Tae Hyuk; Kim, Sun Wook; Chung, Jae Hoon

2018-02-01

Distant metastases, although uncommon, represent maximum disease-related mortality in differentiated thyroid carcinoma (DTC). Lungs are the most frequent sites of metastases. We aimed to evaluate long-term outcomes and identify prognostic factors in metastatic DTC limited to the lungs. This retrospective study included 89 patients with DTC and metastases limited to the lungs, who were treated between 1996 and 2012 at Samsung Medical Center. Progression-free survival (PFS) and cancer-specific survival (CSS) rates were evaluated according to clinicopathologic factors. Cox regression analysis was used to identify independent factors associated with structural progressive disease (PD) and cancer-specific death. With a median follow-up of 84 months, the 5- and 10-year CSS rates were 78% and 73%, respectively. Older age at diagnosis (≥55 years), radioactive iodine (RAI) nonavidity, preoperative or late diagnosis of metastasis and macro-nodular metastasis (≥1 cm) were predictive of decreased PFS and CSS. Multivariate analysis identified older age (P = .002), RAI nonavidity (P = .045) and preoperative (P = .030) or late diagnosis (P = .026) as independent predictors of structural PD. RAI avidity was also independent predictor of cancer-specific death (P = .025). Patients with DTC and metastatic disease limited to the lungs had favourable long-term outcomes. Age, RAI avidity and timing of metastasis were found to be major factors for predicting prognosis. © 2017 John Wiley & Sons Ltd.

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

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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

Clinical outcome for patients of solitary bone only metastasis.

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Hosaka, Seiichi; Katagiri, Hirohisa; Honda, Yosuke; Wasa, Junji; Murata, Hideki; Takahashi, Mitsuru

2016-03-01

Solitary bone only metastasis (SBOM) is a rare condition in which metastasis is limited to a single skeletal lesion originating from a previously treated or controllable primary lesion. The study objective was to evaluate the clinical features and survival regarding this rare condition and to clarify its treatment strategy. A total of 1453 patients with bone metastasis registered in our hospital database were enrolled. To assess the primary and/or metastatic lesion we used plain X-ray images, CT, MRI and FDG-PET scans as well as bone scans. Among the patients, only 27 (1.8%) had SBOM. The primary cancers responsible for SBOM were lung in seven patients, breast in five, kidney in four, prostate in two, uterus in two and other types in seven. Treatment of SBOM involved resection in four patients, radiotherapy only in 17, radiotherapy in combination with zoledronate in six and chemotherapy with zoledronate in one. Local recurrence did not develop in the four cases treated with resection. However, in-field recurrence was found in 4 of 22 (18%) patients who underwent radiotherapy. All three patients who received >40 Gy did not develop in-field recurrence. The overall and event free survival rates at 5 years were 63% and 41%, respectively. Solitary bone only metastasis should be treated with wide resection or long-course radiotherapy at doses 40-50 Gy to achieve long lasting local tumor control. Copyright © 2015 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

Angiosarcoma of the lung

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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)

Long-term survival in bronchogenic carcinoma with a solitary metastasis.

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Shachor, J; Luria, H; Cordova, M; Bernheim, J; Griffel, B; Bruderman, I

1986-03-01

Partial resection of a huge anaplastic large cell carcinoma of the upper lobe of the right lung was performed in a 47-year-old patient in order to relieve symptoms of pulmonary hypertrophic osteoarthropathy. Several months later a solitary metastasis was noted in the muscles of the right forearm. The metastasis was resected and the forearm irradiated. The patient was further treated with injections of autologous tumour cell vaccine and BCG. Today, 7 years later, the patient is alive, without any signs of neoplastic disease.

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 ...

Collagenolytic Matrix Metalloproteinases in Chronic Obstructive Lung Disease and Cancer

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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.

Collagenolytic Matrix Metalloproteinases in Chronic Obstructive Lung Disease and Cancer

International Nuclear Information System (INIS)

Woode, Denzel; Shiomi, Takayuki; D’Armiento, Jeanine

2015-01-01

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

Lower gingival squamous cell carcinoma with brain metastasis during long-term cetuximab treatment: A case report.

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Naruse, Tomofumi; Tokuhisa, Mitsuko; Yanamoto, Souichi; Sakamoto, Yuki; Okuyama, Kohei; Tsuchihashi, Hiroki; Umeda, Masahiro

2018-05-01

Long-term cetuximab treatment can lead to acquired resistance, and tumor progression and/or new lesions often occur. The present report describes a case of lower gingival squamous cell carcinoma with brain metastasis during long-term cetuximab treatment in a 60-year-old man, including findings of an immunohistochemical study. The resected primary tumors, biopsy of the lung metastasis before administration of cetuximab, and brain metastasis specimens mediated by cetuximab were immunohistochemically examined. Histologically, the metastatic brain lesion showed hyperkeratinizing tumor cells with deeply stained irregular nuclei with necrotizing tumor cells, and a decrease in cell density was exhibited in part of the tumor nest. Moreover, the brain lesion was less malignant compared with the primary tumor and metastatic lung lesions. Immunohistochemically, the metastatic brain lesions showed low expression of epidermal growth factor receptor (EGFR) and high expression of N-cadherin compared with the primary tumor and metastatic lung lesions. These results suggest that acquired resistance to cetuximab may be associated with low EGFR expression and increased epithelial-to-mesenchymal transition potential.

Malar Bone Metastasis Revealing a Papillary Thyroid Carcinoma

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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.

Pathologically decreased expression of miR-193a contributes to metastasis by targeting WT1-E-cadherin axis in non-small cell lung cancers

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Junjie Chen

2016-11-01

Full Text Available Abstract Background The metastatic cascade is a complex and multistep process with many potential barriers. Recently, miR-193a has been reported to be a suppressive miRNA in multiple types of cancers, but its underlying anti-oncogenic activity in non-small cell lung cancers (NSCLC is not fully elucidated. Methods The expressions of miR-193a (miR-193a-5p in human lung cancer tissues and cell lines were detected by real-time PCR. Dual-luciferase reporter assay was used to identify the direct target of miR-193a. Cell proliferation, apoptosis, and metastasis were assessed by CCK-8, flow cytometry, and Transwell assay, respectively. Results The expression of miR-193a in lung cancer tissues was decreased comparing to adjacent non-tumor tissues due to DNA hypermethylation in lung cancer tissues. Ectopic expression of miR-193a inhibited cell proliferation, colony formation, migration, and invasion in A549 and H1299 cells. Moreover, overexpression of miR-193a partially reversed tumor growth factor-β1 (TGF-β1-induced epithelial-to-mesenchymal transition (EMT in NSCLC cells. Mechanistically, miR-193a reduced the expression of WT1, which negatively regulated the protein level of E-cadherin, suggesting that miR-193a might prevent EMT via modulating WT1-E-cadherin axis. Importantly, knockdown of WT1 resembled the anti-cancer activity by miR-193a and overexpression of WT1 partially reversed miR-193a-induced anti-cancer activity, indicating that WT1 plays an important role in miR-193a-induced anti-cancer activity. Finally, overexpression of miR-193a decreased the growth of tumor xenografts in mice. Conclusion Collectively, our results have revealed an important role of miR-193a-WT1-E-cadherin axis in metastasis, demonstrated an important molecular cue for EMT, and suggested a therapeutic strategy of restoring miR-193a expression in NSCLC.

Presence of intratumoral platelets is associated with tumor vessel structure and metastasis

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Li, Rong; Zhang, Xu; Zhang, Zhuo; Zhang, Xiao; Ran, Bing; Wu, Jianbo; Ren, Meiping; Chen, Ni; Luo, Mao; Deng, Xin; Xia, Jiyi; Yu, Guang; Liu, Jinbo; He, Bing

2014-01-01

Platelets play a fundamental role in maintaining hemostasis and have been shown to participate in hematogenous dissemination of tumor cells. Abundant platelets were detected in the tumor microenvironment outside of the blood vessel, thus, platelet -tumor cell interaction outside of the bloodstream may play a role in regulating primary tumor growth and metastasis initiation. However, it is unclear that platelet depletion affects tumor vessel structure and dynamics. Using thrombocytopenia induction in two different tumor-bearing mouse models, tumor tissues were performed by Westernblotting and immunohistochemical staining. Vascular permeability was evaluated by determination of intratumoral Evans blue and Miles vascular permeability assay. Furthermore, microdialysis was used to examining the intratumoral extracellular angiogenic growth factors (VEGF, TGF-β) by ELISA. Platelet depletion showed no change in tumor growth and reduced lung metastasis. Platelet depletion led to reduced tumor hypoxia and Met receptor activation and was associated with a decreased release of MMP-2, 9, PAI-1, VEGF, and TGF-β. Tumor vessels in platelet-depleted mice showed impaired vessel density and maturation. Our findings demonstrate that platelets within the primary tumor microenvironment play a critical role in the induction of vascular permeability and initiation of tumor metastasis

Clinical utility of F-18 FDG PET-CT in the initial evaluation of lung cancer

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Madsen, Poul Henning [Vejle Hospital, Department of Medicine, Division of Respiratory Medicine, Vejle (Denmark); Holdgaard, Paw Christian [Vejle Hospital, Department of Nuclear Medicine, Vejle (Denmark); Christensen, Janne Buck [Odense University Hospital/University of Southern Denmark, Department of Quality and Research/HTA, Odense University Hospital and Medical Research Library, Odense (Denmark); Hoeilund-Carlsen, Poul Flemming [Odense University Hospital, Department of Nuclear Medicine, Odense (Denmark)

2016-10-15

Positron emission tomography-computed tomography (PET-CT) is a resource-demanding imaging modality with increasing popularity in the workup of patients with suspected or proven lung cancer. To review the clinical usefulness of this imaging modality in the diagnosis, staging, and pre-operative evaluation, we conducted a systematic literature search, review, and quality assessment using the rapid evidence assessment toolkit and the Oxford Centre for Evidence-Based Medicine methodology. The literature search resulted in 4,208 records including 918 reviews, of which 139 met the predefined criteria and were read in full to identify relevant original articles on F-18 FDG PET-CT (1) in the evaluation of solitary pulmonary nodules (n = 14), (2) in curative-intent treatment trials (n = 9), and (3) in planning of invasive procedures (n = 18). We found the following important results from the literature review: (1) PET-CT can rule out malignancy in most solitary pulmonary nodules due to high sensitivity (recommendation level A). (2) PET-CT reduces the number of futile treatment trials (recommendation level A). (3) The sensitivity of PET-CT in general is insufficient to rule out mediastinal lymph node metastasis (recommendation level A). (1) With few exceptions, solitary pulmonary nodules can safely be considered benign if the PET-CT scan is negative. Exceptions consist of small (<1 cm) and non-solid, solitary pulmonary nodules. These abnormalities should be followed up by CT in a structured programme. (2) No curative-intent treatment should be commenced until a PET-CT scan has excluded occult distant metastases. (3) In general, lymph node metastasis in the mediastinum cannot be ruled out on the basis of a negative PET-CT, and confirmative invasive staging should be performed in most patients before mediastinal metastasis is confirmed or ruled out. (orig.)

Clinical utility of F-18 FDG PET-CT in the initial evaluation of lung cancer

International Nuclear Information System (INIS)

Madsen, Poul Henning; Holdgaard, Paw Christian; Christensen, Janne Buck; Hoeilund-Carlsen, Poul Flemming

2016-01-01

Positron emission tomography-computed tomography (PET-CT) is a resource-demanding imaging modality with increasing popularity in the workup of patients with suspected or proven lung cancer. To review the clinical usefulness of this imaging modality in the diagnosis, staging, and pre-operative evaluation, we conducted a systematic literature search, review, and quality assessment using the rapid evidence assessment toolkit and the Oxford Centre for Evidence-Based Medicine methodology. The literature search resulted in 4,208 records including 918 reviews, of which 139 met the predefined criteria and were read in full to identify relevant original articles on F-18 FDG PET-CT (1) in the evaluation of solitary pulmonary nodules (n = 14), (2) in curative-intent treatment trials (n = 9), and (3) in planning of invasive procedures (n = 18). We found the following important results from the literature review: (1) PET-CT can rule out malignancy in most solitary pulmonary nodules due to high sensitivity (recommendation level A). (2) PET-CT reduces the number of futile treatment trials (recommendation level A). (3) The sensitivity of PET-CT in general is insufficient to rule out mediastinal lymph node metastasis (recommendation level A). (1) With few exceptions, solitary pulmonary nodules can safely be considered benign if the PET-CT scan is negative. Exceptions consist of small (<1 cm) and non-solid, solitary pulmonary nodules. These abnormalities should be followed up by CT in a structured programme. (2) No curative-intent treatment should be commenced until a PET-CT scan has excluded occult distant metastases. (3) In general, lymph node metastasis in the mediastinum cannot be ruled out on the basis of a negative PET-CT, and confirmative invasive staging should be performed in most patients before mediastinal metastasis is confirmed or ruled out. (orig.)

LHX6, An Independent Prognostic Factor, Inhibits Lung Adenocarcinoma Progression through Transcriptional Silencing of β-catenin.

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Yang, Juntang; Han, Fei; Liu, Wenbin; Zhang, Mingqian; Huang, Yongsheng; Hao, Xianglin; Jiang, Xiao; Yin, Li; Chen, Hongqiang; Cao, Jia; Zhang, Huidong; Liu, Jinyi

2017-01-01

Introduction: Our previous study identified LIM homeobox domain 6 (LHX6) as a frequently epigenetically silenced tumor-suppressor gene in lung cancer. However, its clinical value has never been evaluated, and the in-depth anti-tumor mechanism remains unclear. Methods: Public database was used for lung cancer, lung adenocarcinoma and lung squamous carcinoma patients and tissue microarray data was used for lung adenocarcinoma patients to study prognostic outcome of LHX6 expression by Kaplan-Meier and Cox-regression analysis. In vitro proliferation, metastasis and in vivo nude mice model were used to evaluate the anti-tumor effect of LHX6 on lung adenocarcinoma cell lines. The mechanisms were explored using western blot, TOP/FOP flash assays and luciferase reporter assays. LHX6 expression and clinical stages data were collected from The Cancer Genome Atlas database (TCGA). Results: Expression of LHX6 was found to be a favorable independent prognostic factor for overall survival (OS) of total lung adenocarcinoma patients (P=0.014) and patients with negative lymph nodes status (P=0.014) but not related the prognostic outcome of lung squamous cell carcinoma patients. The expression status of LHX6 significantly correlated to histological grade (P<0.01), tumor size (P=0.026), lymph node status (P=0.039) and clinical stages (P<0.01) of lung adenocarcinoma patients. Functionally, LHX6 inhibited the proliferation and metastasis of lung adenocarcinoma cells in vitro and in vivo . Furthermore, LHX6 suppressed the Wnt/β-catenin pathway through transcriptionally silencing the expression of β-catenin, and the promoter region (-1161 bp to +27 bp) was crucial for its inhibitory activity. Conclusions: Our data indicate that the expression of LHX6 may serve as a favorable prognostic biomarker for lung adenocarcinoma patients and provide a novel mechanism of LHX6 involving in the tumorigenesis of lung adenocarcinoma.

Long-Term Survival in Patients With Synchronous, Solitary Brain Metastasis From Non-Small-Cell Lung Cancer Treated With Radiosurgery

International Nuclear Information System (INIS)

Flannery, Todd W.; Suntharalingam, Mohan; Regine, William F.; Chin, Lawrence S.; Krasna, Mark J.; Shehata, Michael K.; Edelman, Martin J.; Kremer, Marnie; Patchell, Roy A.; Kwok, Young

2008-01-01

Purpose: To report the outcome of patients with synchronous, solitary brain metastasis from non-small-cell lung cancer (NSCLC) treated with gamma knife stereotactic radiosurgery (GKSRS). Patients and Methods: Forty-two patients diagnosed with synchronous, solitary brain metastasis from NSCLC were treated with GKSRS between 1993 and 2006. The median Karnofsky performance status (KPS) was 90. Patients had thoracic Stage I-III disease (American Joint Committee on Cancer 2002 guidelines). Definitive thoracic therapy was delivered to 26/42 (62%) patients; 9 patients underwent chemotherapy and radiation, 12 patients had surgical resection, and 5 patients underwent preoperative chemoradiation and surgical resection. Results: The median overall survival (OS) was 18 months. The 1-, 2-, and 5-year actuarial OS rates were 71.3%, 34.1%, and 21%, respectively. For patients who underwent definitive thoracic therapy, the median OS was 26.4 months compared with 13.1 months for those who had nondefinitive therapy, and the 5-year actuarial OS was 34.6% vs. 0% (p < 0.0001). Median OS was significantly longer for patients with a KPS ≥90 vs. KPS < 90 (27.8 months vs. 13.1 months, p < 0.0001). The prognostic factors significant on multivariate analysis were definitive thoracic therapy (p = 0.020) and KPS (p = 0.001). Conclusions: This is one of the largest series of patients diagnosed with synchronous, solitary brain metastasis from NSCLC treated with GKSRS. Definitive thoracic therapy and KPS significantly impacted OS. The 5-year OS of 21% demonstrates the potential for long-term survival in patients treated with GKSRS; therefore, patients with good KPS should be considered for definitive thoracic therapy

Skin metastasis from conventional giant cell tumor of bone: conceptual significance

International Nuclear Information System (INIS)

Tyler, W.; Barrett, T.; Frassica, F.; McCarthy, E.

2002-01-01

A conventional giant cell tumor of the proximal femur recurred twice locally and developed pulmonary nodules. The lung lesions were felt to be an example of ''benign'' metastases. Eight months after the initial presentation, the patient developed a single skin nodule on the contralateral leg. Histologic features of the skin nodule showed conventional giant cell tumor identical to the bone lesion. This nodule is a manifestation of arterial metastasis typical of any malignant tumor and seemingly contradicts the concept of ''benign '' metastasis. (orig.)

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

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)

Prognostic value of lncRNAs in lung carcinoma: a meta-analysis.

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Fan, Fan; Zhu, Zhengqiu; Gao, Chao; Liu, Yun; Wang, Baoqing; Wang, Ziquan; Feng, Jifeng

2017-10-10

Many different long non-coding RNAs (lncRNAs) have been reported to be abnormally expressed in lung carcinoma and may thus serve as prognostic biomarkers for this disease. We conducted this meta-analysis, which included a total of 30 studies identified via searches of PubMed, Embase, Medline, and Web of Science and included 2912 patients from China (28), Germany (1), and Japan (1), to investigate the prognostic value of different lncRNAs in lung carcinoma. The results revealed that lncRNA transcription levels were significantly associated with overall survival in lung cancer patients (HR:1.46, 95% CI: 1.16-1.83, P = 0.000). However, lncRNA transcription levels were not associated with progression-free survival (PFS) (HR: 1.55, 95% CI: 0.50-4.80, P = 0.449). Further analysis showed that high lncRNA transcription levels were significantly associated with tumour-node-metastasis (TNM) stage (III/IV vs I/II: RR = 1.339, 95% CI: 1.046-1.716, P = 0.012), lymph node metastasis (positive vs negative: RR = 1.442, 95% CI: 1.103-1.885, P = 0.007), and distant metastasis (yes vs no: RR = 3.187,95% CI: 1.393-7.294, P = 0.006). Taken together, the results of our present meta-analysis revealed that lncRNAs may be useful prognostic markers for lung carcinoma and may also have value as biomarkers for TNM stage, lymph node metastasis and distant metastasis.

Small cell lung cancer transformation from EGFR-mutated lung adenocarcinoma: A case report and literatures review.

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Liu, Yangyang

2018-06-03

Epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have markedly improved the response of non-small cell lung cancer (NSCLC) with EGFR-mutant patients. However, these patients inevitably come cross acquired resistance to EGFR-TKIs. The transformation of lung adenocarcinoma to small cell lung cancer (SCLC) following treatment with EGFR-TKIs is rare, which leads to resistance to EGFR-TKIs. The present case concerns a case of a 38-year-old man presenting with cough and dyspnea. Radical resection was performed and confirmed an EGFR exon 21 L858R lung adenocarcinoma. However, the patient suffered pleural metastasis after successful treatment with surgery and adjuvant treatment. So, erlotinib was administered with 18 months. Because of enlarged pleural nodule, repeat biopsy identified an SCLC and chemotherapy was started. However, despite the brief success of chemotherapy, our patient suffered brain metastasis. Our case emaphsizes both the profile of transformation from NSCLC to SCLC and the importance of repeat biopsy dealing with drug resistance. We also summarize the clinical characteristics, mechanisms, predictors of SCLC transformation, treatment after transformation and other types of transformation to SCLC.

Possible reduction of hepatoma formation by Smmu 7721 cells in SCID mice and metastasis formation by B16F10 melanoma cells in C57BL/6 mice by Agaricus blazei murill extract.

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Wu, Ming-Fang; Lu, Hsu-Feng; Hsu, Yu-Ming; Tang, Ming-Chu; Chen, Hsueh-Chin; Lee, Ching-Sung; Yang, Yi-Yuan; Yeh, Ming-Yang; Chung, Hsiung-Kwang; Huang, Yi-Ping; Wu, Chih-Chung; Chung, Jing-Gung

2011-01-01

Agaricus blazei Murill extract (ABM) has been reported to possess antitumor effects. In this study, the role of ABM in tumor growth and metastasis in vivo was evaluated in experimental Smmu 7721 hepatoma cells in severe combined immunodeficiency (SCID) mice and B16F10 melanoma cells lung metastasis in C57BL/6 mice. For the tumor growth model, the size of the liver tumor mass was about 10 mm to 20 mm in the control group. In comparison with the control group, the tumor mass seem to grow slowly with ABM treatment, especially at the high dose. For the tumor metastasis model, after a six-week treatment, the survival rates of B6 mice were 0%, 30%, 10% and 50% for control group, low, median and high concentration ABM treatment groups, respectively. The survival rate showed that pretreatment of C57BL/6 (B6) mice with ABM lengthened their lifespan after tumor cell inoculation, which supports the notion that ABM successfully reduced lung metastasis formation by B16F10 melanoma cells. The treatment effect was dependent on the concentration of ABM for tumor growth and metastasis in these models.

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

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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.

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.

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.

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.

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. "9"9"mTc-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 "9"9"mTc-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 "9"9"mTc-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

[A case of group G Streptococcus sepsis, chest wall abscess, and vertebral osteomyelitis mimicking a primary lung cancer with bone metastasis].

Science.gov (United States)

Hayashi, Yumeko; Ishii, Yoshiki; Arai, Ryo; Obara, Kazuki; Kamada, Aya; Takizawa, Hidenori; Hase, Isano; Mashio, Kazuki; Yamada, Issei; Takemasa, Akihiro; Sugiyama, Kumiya; Fukushima, Yasutsugu; Fukuda, Takeshi

2007-01-01

A 73-year-old woman who had been followed in our department of gynecology because of ovarian cancer since 2002, was admitted with liver dysfunction and complaining of back pain and light precordial chest pain. The chest radiograph on admission revealed a tumor in her left upper lung field, and chest CT revealed a tumor adjacent to the chest wall and mediastinum. FDG-positron emission tomography (PET) showed abnormal uptake in the tumor and Th6/7, and the subaortic lymph nodes. On the basis of these findings, primary lung cancer with bone metastasis was suspected. She had a high grade fever on admission, and blood cultures were positive for group G streptococcus. The treatment with intravenous penicillin was started. Percutaneous biopsy of the tumor in her left chest showed an abscess wall in the chest wall, but no evidence of malignancy. Transbronchial lung biopsy and CT-guided biopsy also showed no malignant cells. Since the tumor decreased in size and back pain improved gradually by only antibiotic treatment, a diagnosis of sepsis of group G streptococcus, chest wall abscess, and vertebral osteomyelitis was made. She was treated with intravenous penicillin for 4 weeks and oral amoxicillin for another 4 weeks. After 60 days of antibiotic treatment, the tumor vanished.

The relationship between microvessels density and CT enhancement of the peripheral lung cancer

International Nuclear Information System (INIS)

Liu Shiyuan; Zhou Kangrong; Xiao Xiangsheng; Ye Tingjun; Zhang Zhiyong

1999-01-01

Objective: To investigate the relationship between microvessel density (MVD), clinical prognosis and CT enhancement of the peripheral lung cancer. Methods: 127 cases of peripheral lung cancer were examined with CT (87 cases retrospectively and 40 cases prospectively), and MVD were measured with immunohistochemical method by factor VIII on the specimens of the resected tumors. The results were analyzed and compared with CT enhancement, metastasis and prognosis. Results: The MVD was higher in the peripheral junction zone and interstitial areas than that in the parenchymal areas and necrotic zones of the tumors. Patients with nodal metastasis had higher MVD than those without nodal metastasis (56.9 +- 18.1 versus 43.8 +- 23.6, P 0.05); but the enhancement of the lung cancer correlated well with MVD (r 0.8874). Conclusions: Measurement of the microvessel density of tumor can determine the degree of angiogenesis of neoplasm and predict the metastasis or prognosis of the lung cancer. Angiogenesis not only constitutes the basis of enhancement of the tumor, but also determine the various degrees and patterns of enhancement. Spiral dynamic CT is the technique ideal to demonstrate the enhancement features, which might be helpful in making differential diagnosis of pulmonary nodules

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

Directory of Open Access Journals (Sweden)

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.

[Effect of Spatholobus suberctus on adhesion, invasion, migration and metastasis of melanoma cells].

Science.gov (United States)

Xu, Jian-Ya; Gu, Qin; Xia, Wei-Jun

2010-10-01

To study the effect of Spatholobus suberctus, a kind of Chinese Traditional Medicine which can dissolve the stasis by activating the blood circulation, on invasion, adhesion, migration and metastasis of B16-BL6 metastatic mouse melanoma cells and its mechanism. The proliferation, adhesion, invasion and migration capacity of B16-BL6 metastatic cells was evaluated by MTP assay, adhesion assay and reconstituted basement membrane invasion and migration assay in vitro respectively. Mouse spontaneous motility melanoma model was used to study the effect of Spatholobus suberctus on metastasis in vivo. At the highest innoxious concentration, the extracts of Spatholobus suberctus inhibited the adhesion and invasion capacity of B16-BL6 metastatic cells significantly. In the mouse spontaneous melanoma model, the lung metastatic nodes number and its volume were significantly decreased after continuously treated with the extracts of Spatholobus suberctu. The extracts of Spatholobus suberctu can inhibit the metastasis of of B16-BI6 metastatic mouse melanoma cells and its mechanism may be inhibiting the capability of B16-BL6 cells in adhering to the ECM and invading the basement membrane.

Pulmonary metastasis in osteosarcoma in bone scintigraphy: 2 case reports poster

International Nuclear Information System (INIS)

Grobocopatel, D.; Silva, N.J.; Hunsche, A.; Fernandes, D.D.; Berdichevski, E.H.; Cembrani, L.; Anselmi, C.E.; Anselmi, O.E.

2004-01-01

Full text: Osteosarcoma is considered the most common malignant primary bone tumour in children and adolescents. The lungs are the common sites of metastasis, which, if present, are associated with poor prognosis. Imaging workup includes x-ray, computed tomography, nuclear resonance imaging and bone scintigraphy in order to diagnose, help to choose appropriate treatment and prognosticate this disease. Chemotherapy is used to increase survival rate and to control the occurrence of lung metastasis. CASE 1: ELWS, male, 6 years old. The patient had a left knee trauma followed by increase in size and pain over 15 days. Knee x-ray showed a voluminous lesion and densely calcified tissue in the left knee, with soft tissue involvement. Chest x-ray showed multiple nodular dense lesions diffusely involving the lungs. Left knee MRI showed a neoplasm involving the distal epiphysis of the femur with extension from the bone marrow to the trochanteric region. Biopsy diagnosed small cell osteosarcoma. Chest computed tomography showed multiple opacities in the parenchyma of both lungs, most with calcification, predominantly in the cortical region. Bone scintigraphy showed intense uptake of the radiopharmaceutical in the distal half of the left femur and focal areas of increased uptake in the skull, left humerus, right scapula, thoracic soft tissue (mostly in the right side, in the same place as the pulmonary metastasis seen in the chest computed tomography), 12th thoracic vertebra, 4th lumbar vertebra and in the pelvis. CASE 2: ACD, male 20 years old. The patient presented pain and increase in size of the right knee starting 5 months ago. Right knee x-ray: insufflating bony lesion in the proximal epiphysis of the right tibia compatible with osteosarcoma; increase in volume in soft tissue around the knee. Right knee MRI: voluminous expansive osteoblastic lesion hypointense in T1 and heterogeneous in T2, diffusely enhanced by the use of gadolinium-DTPA; the lesion involved almost

Unusual metastasis of left colon cancer: considerations on two cases.

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Gubitosi, Adelmo; Moccia, Giancarlo; Malinconico, Francesca Antonella; Gilio, Francesco; Iside, Giovanni; Califano, Umberto G A; Foroni, Fabrizio; Ruggiero, Roberto; Docimo, Giovanni; Parmeggiani, Domenico; Agresti, Massimo

2009-04-01

Usually, left colon cancer metastasis concerns liver, abdominal lymph nodes and lungs. Other localizations are quite rare occurrences. In spite of this, some uncommon metastasis sites are reported in literature, such as: peritoneum, ovaries, uterus, kidney testis, bones, thyroid, oral cavity and central nervous system. We report two cases of unusual localizations of left colon cancer metastasis localization, one into the retroperitoneal space and the other at the left axillary lynphnodes and between liver and pancreas. In the first reported case the diffusion pathway may have been the lymphatic mesocolic vessels, partially left in place from the previous surgery. In the second case the alleged metastatic lane may have been through the periumbilical lymph nodes to the parasternal lymph nodes and then to the internal mammary ones, finally reaching the axillary limph nodes.

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

Pituitary metastasis of hepatocellular carcinoma presenting with panhypopituitarism: a case report

International Nuclear Information System (INIS)

Tanaka, Tomoko; Hiramatsu, Katsushi; Nosaka, Takuto; Saito, Yasushi; Naito, Tatsushi; Takahashi, Kazuto; Ofuji, Kazuya; Matsuda, Hidetaka; Ohtani, Masahiro; Nemoto, Tomoyuki; Suto, Hiroyuki; Yamamoto, Tatsuya; Kimura, Hirohiko; Nakamoto, Yasunari

2015-01-01

Metastasis to the pituitary gland is extremely rare and is often detected incidentally by symptoms associated with endocrine dysfunction. Breast and lung cancer are the most common primary metastasizing to pituitary gland. Metastasis from hepatocellular carcinoma to the pituitary gland is extremely rare, with only 10 cases having been previously reported. We present here the first case of pituitary metastasis of hepatocellular carcinoma presenting with panhypopituitarism diagnosed by magnetic resonance imaging. We report the case of an 80-year-old Japanese woman who presented with the sudden onset of hypotension and bradycardia after having previously been diagnosed with hepatocellular carcinoma. Based on low levels of pituitary hormones, she was diagnosed with panhypopituitarism caused by metastasis of the hepatocellular carcinoma to the pituitary gland. Magnetic resonance imaging with arterial spin-labeling was effective in the differential diagnosis of the intrasellar tumor. The patient died despite hormone replacement therapy because of hypovolemic shock. Metastasis to the pituitary gland causes various non-specific symptoms, so it is difficult to diagnose. The present case emphasizes the importance of diagnostic imaging in identifying these metastases. Clinicians should consider the possibility of pituitary metastasis in patients with malignant tumors who demonstrate hypopituitarism

Pituitary metastasis of hepatocellular carcinoma presenting with panhypopituitarism: a case report.

Science.gov (United States)

Tanaka, Tomoko; Hiramatsu, Katsushi; Nosaka, Takuto; Saito, Yasushi; Naito, Tatsushi; Takahashi, Kazuto; Ofuji, Kazuya; Matsuda, Hidetaka; Ohtani, Masahiro; Nemoto, Tomoyuki; Suto, Hiroyuki; Yamamoto, Tatsuya; Kimura, Hirohiko; Nakamoto, Yasunari

2015-11-06

Metastasis to the pituitary gland is extremely rare and is often detected incidentally by symptoms associated with endocrine dysfunction. Breast and lung cancer are the most common primary metastasizing to pituitary gland. Metastasis from hepatocellular carcinoma to the pituitary gland is extremely rare, with only 10 cases having been previously reported. We present here the first case of pituitary metastasis of hepatocellular carcinoma presenting with panhypopituitarism diagnosed by magnetic resonance imaging. We report the case of an 80-year-old Japanese woman who presented with the sudden onset of hypotension and bradycardia after having previously been diagnosed with hepatocellular carcinoma. Based on low levels of pituitary hormones, she was diagnosed with panhypopituitarism caused by metastasis of the hepatocellular carcinoma to the pituitary gland. Magnetic resonance imaging with arterial spin-labeling was effective in the differential diagnosis of the intrasellar tumor. The patient died despite hormone replacement therapy because of hypovolemic shock. Metastasis to the pituitary gland causes various non-specific symptoms, so it is difficult to diagnose. The present case emphasizes the importance of diagnostic imaging in identifying these metastases. Clinicians should consider the possibility of pituitary metastasis in patients with malignant tumors who demonstrate hypopituitarism.

Renal Cell Carcinoma Metastasis to Ipsilateral Parotid and Submandibular Glands: Report of a Case with Sonoelastographic Findings

International Nuclear Information System (INIS)

Balaban, Mehtap; Dogruyol, Sureyya Vudali; Idilman, Ilkay S.; Unal, Ozlem; Ipek, Ali

2016-01-01

Renal cell carcinoma (RCC) – also known as hypernephroma or grawitz tumor – accounts for 3% of the adulthood malignancies. Approximately 30–40% of the patients have metastasis at the time of the diagnosis and most common sites for metastasis are lung, regional lymph nodes, bone and liver. A total of 8–14% of the patients with RCC has head and neck metastasis. However, metastasis to major salivary glands is rarely seen. In this paper, we aimed to report a RCC case with metastasis to parotid and submandibular glands that has the same sonographic and sonoelastographic findings with the primary tumor. 66-year old woman with RCC history was referred to our radiology department for neck ultrasound (US) with painful swelling in the right parotid gland region. A well-defined, 37×21 mm sized hypoechoic heterogeneous solid mass was detected in the superficial-deep lobe of the right parotid gland. The mass was prominently hypervascular in color Doppler ultrasonography scan. Coincidentally, a 13×13 mm hypoechoic lobulated solid mass was detected in the right submandibular gland with similar sonographic findings. Real-time sonoelastography (SEL) was performed to the masses and both of them were blue-green colored that indicates hard tissue. An US and SEL evaluation was also performed to the renal mass (RCC) of the patient. The primary mass was also similar in sonographic and SEL appearance as salivary gland masses. In the patient history, she revealed chemotherapy-radiotherapy treatment 1.5 years ago due to inoperable mass in the mid-lower pole of the left kidney diagnosed as clear cell RCC with vascular invasion, liver, lung and brain metastasis. Because of known primary tumor, the masses in the salivary glands were suspected to be metastatic and a tru-cut biopsy was performed. Pathological result was reported as clear cell RCC metastasis. The etiology of RCC is still unknown and metastatic involvement can be seen at unexpected tissue and organs. Metastatic disease

Isolated splenic metastasis of colon cancer: a case report and literature review

OpenAIRE

Rosa, Nisalda; Martins, Sandra; Lamelas, Javier

2012-01-01

Colorectal cancer (CRC) is a leading cause of death in the elderly and about 20% of these patients present metastasis at diagnosis, most often in the liver. Other common metastatic sites include: lung, bone and brain. Isolated splenic metastases are rare, and they are usually a sign of widespread disease. The authors report a case of the rare occurrence of synchronous isolated splenic metastasis, diagnosed by computed tomography in the preoperative staging of a patient with CRC.O câncer color...

A meta-analysis of 18FDG-PET–CT, 18FDG-PET, MRI and bone scintigraphy for diagnosis of bone metastases in patients with lung cancer

International Nuclear Information System (INIS)

Qu Xinhua; Huang Xiaolu; Yan Weili; Wu Lianming; Dai Kerong

2012-01-01

Background and purpose: Lung cancer is the most common cause of cancer related death among both men and women worldwide. The skeleton is the most common site of cancer metastasis. Early detection is crucial for prognosis. To evaluate and compare the capability for bone metastasis assessment of [ 18 F] fluoro-2-D-glucose positron emission tomography with computed tomography ( 18 FDG-PET–CT), [ 18 F] fluoro-2-D-glucose positron emission tomography ( 18 FDG-PET), magnetic resonance imaging (MRI) and bone scintigraphy (BS) in lung cancer patients, a meta-analysis is preformed. Methods: We searched MEDLINE, OVID, EMBASE and the Cochrane Library for studies evaluating diagnosis validity of 18 FDG-PET–CT, 18 FDG-PET, MRI and BS between January 1990 and August 2010. Meta-analysis methods were used to pool sensitivity, specificity, diagnostic odd ratios (DORs) and to construct a summary receiver-operating characteristic curve (SROC). Results: A total of 17 articles (9 18 FDG-PET–CT studies, 9 18 FDG-PET studies, 6 MRI studies and 16 BS studies) that included 2940 patients who fulfilled all of the inclusion criteria were considered for inclusion in the analysis. The pooled sensitivity for the detection of bone metastasis in lung cancer using 18 FDG-PET–CT, 18 FDG-PET, MRI and BS were 0.92 (95% CI, 0.88–0.95), 0.87 (95% CI, 0.81–0.92), 0.77 (95% CI, 0.65–0.87) and 0.86 (95% CI, 0.82–0.89), respectively. The pooled specificity for the detection of bone metastasis from lung cancer using 18 FDG-PET–CT, 18 FDG-PET, MRI and BS were 0.98 (95% CI, 0.97–0.98), 0.94 (95% CI, 0.92–0.96), 0.92 (95% CI, 0.88–0.95), 0.88 (95% CI, 0.86–0.89), respectively. The pooled DORs estimates for 18 FDG-PET–CT 449.17 were significantly higher than for 18 FDG-PET (118.25, P 18 FDG-PET–CT and 18 FDG-PET were better imaging methods for diagnosing bone metastasis from lung cancer than MRI and BS. 18 FDG-PET–CT has higher diagnostic value (sensitivity, specificity and DORs

From Breast to Bone: Tracking Gene Expression Changes Responsible for Breast Cancer Metastasis in a Humanized Mouse Model with Molecular Imaging

Science.gov (United States)

2015-11-01

metastasis enhancers and 1 GFP as an internal control). Each ORF is associated with a unique nucleic acid “ barcode ” sequence and is identified by...for this screen because BC3-p53KD cells have not yet metastasized robustly to the lungs at this point. Genomic DNA (gDNA) is isolated and submitted...have already identified a potential functional enhancer of metastasis (Fig. 16). The barcode sequence associated with SMOC2 is enriched in lung

Beta1 integrin promotes but is not essential for metastasis of ras-myc transformed fibroblasts

DEFF Research Database (Denmark)

Brakebusch, C; Wennerberg, K; Krell, H W

1999-01-01

To investigate the role of beta1 integrin during tumor metastasis, we established a ras-myc transformed fibroblastoid cell line with a disrupted beta1 integrin gene on both alleles (GERM 11). Stable transfection of this cell line with an expression vector encoding beta1A integrin resulted in beta1A......, tumors induced by the high expressing clones 1A10 and 2F2 were markedly smaller, suggesting an inverse correlation of tumor growth and beta1 integrin expression. The metastasis potential of all three beta1 integrin-expressing GERM 11 sublines tested was significantly higher than that of the beta1......-deficient GERM 11 cells. GERM 116 tumors led in all animals to severe metastasis in lung and liver, while GERM 11 tumors induced only a few metastatic foci in the lung. Stroma of both tumors contained nidogen and high amounts of tenascin C, but only a few very low levels of fibronectin, laminin-1...

Intracerebral metastasis showing restricted diffusion: Correlation with histopathologic findings

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Duygulu, G. [Radiology Department, Ege University Medicine School, Izmir (Turkey); Ovali, G. Yilmaz [Radiology Department, Celal Bayar University Medicine School, Manisa (Turkey)], E-mail: gulgun.yilmaz@bayar.edu.tr; Calli, C.; Kitis, O.; Yuenten, N. [Radiology Department, Ege University Medicine School, Izmir (Turkey); Akalin, T. [Pathology Department, Ege University Medicine School, Izmir (Turkey); Islekel, S. [Neurosurgery Department, Ege University Medicine School, Izmir (Turkey)

2010-04-15

Objective: We aimed to detect the frequency of restricted diffusion in intracerebral metastases and to find whether there is correlation between the primary tumor pathology and diffusion-weighted MR imaging (DWI) findings of these metastases. Material and methods: 87 patients with intracerebral metastases were examined with routine MR imaging and DWI. 11 hemorrhagic metastatic lesions were excluded. The routine MR imaging included three plans before and after contrast enhancement. The DWI was performed with spin-echo EPI sequence with three b values (0, 500 and 1000), and ADC maps were calculated. 76 patients with metastases were grouped according to primary tumor histology and the ratios of restricted diffusion were calculated according to these groups. ADCmin values were measured within the solid components of the tumors and the ratio of metastases with restricted diffusion to that which do not show restricted diffusion were calculated. Fisher's exact and Mann-Whitney U tests were used for the statistical analysis. Results: Restricted diffusion was observed in a total of 15 metastatic lesions (19, 7%). Primary malignancy was lung carcinoma in 10 of these cases (66, 6%) (5 small cell carcinoma, 5 non-small cell carcinoma), and breast carcinoma in three cases (20%). Colon carcinoma and testicular teratocarcinoma were the other two primary tumors in which restricted diffusion in metastasis was detected. There was no statistical significant difference between the primary pathology groups which showed restricted diffusion (p > 0.05). ADCmin values of solid components of the metastasis with restricted diffusion and other metastasis without restricted diffusion also showed no significant statistical difference (0.72 {+-} 0.16 x 10{sup -3} mm{sup 2}/s and 0.78 {+-} 21 x 10{sup -3} mm{sup 2}/s respectively) (p = 0.325). Conclusion: Detection of restricted diffusion on DWI in intracerebral metastasis is not rare, particularly if the primary tumor is lung or breast

Case report on the role of radiofrequency-assisted spleen-preserving surgery for splenic metastasis in the era of check-point inhibitors.

Science.gov (United States)

Mudan, Satvinder; Kumar, Jayant; Mafalda, Neves C; Kusano, Tomokazu; Reccia, Isabella; Zanallato, Artur; Dalgleish, Angus; Habib, Nagy

2017-12-01

An isolated splenic metastasis is a rare phenomenon noted in advanced stage melanoma. We report the role of radiofrequency (RF) -based splenic-preserving splenectomy in a patient with a solitary splenic metastasis from advanced stage melanoma that was managed with checkpoint inhibitors. We report a case of a 60-year-old man who presented with multiple lung metastases and a solitary splenic metastasis with advanced stage melanoma following excision of primary from his trunk 2.3 years back. Considering the diagnosis of advanced stage melanoma with multiple lung metastases and a solitary splenic metastasis, and its ongoing progressive nature. This case was discussed in the tumour board meeting. A decision was made to commence treatment with immunotherapy in the form of PD-1 inhibitor (programmed cell death 1 receptor) pembrolizumab. Follow-up restaging computer tomography (CT) scan of the abdomen and chest showed a significant reduction in the lung and chest wall lesions, but the splenic lesion remained unchanged. Given the lack of response to treatment in the splenic metastasis and the significant decrease in lung metastases, the multidisciplinary team decided that a partial splenectomy combined with continued immunotherapy treatment would be appropriate as the success of immunotherapy was imminent within the splenic preservation. The postoperative recovery was smooth and the patient was discharged from hospital on the sixth postoperative day with normal platelets and white blood cells. The histopathological analysis of the resected specimen showed a metastatic melanoma with negative margins.At 10-month follow-up after the splenic resection the patient had not experienced further tumour recurrences. Spleen-preserving resection for an isolated, solitary splenic metastasis of melanoma is a feasible approach as it not only preserves the ongoing efficacy of checkpoint inhibitors by preserving the physiological T cell milieu, but the immunomodulation properties of RF can

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

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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.

Role of Tumor-Derived Chemokines in Osteolytic Bone Metastasis

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Salvatore J. Coniglio

2018-06-01

Full Text Available Metastasis is the primary cause of mortality and morbidity in cancer patients. The bone marrow is a common destination for many malignant cancers, including breast carcinoma (BC, prostate carcinoma, multiple myeloma, lung carcinoma, uterine cancer, thyroid cancer, bladder cancer, and neuroblastoma. The molecular mechanism by which metastatic cancer are able to recognize, infiltrate, and colonize bone are still unclear. Chemokines are small soluble proteins which under normal physiological conditions mediate chemotactic trafficking of leukocytes to specific tissues in the body. In the context of metastasis, the best characterized role for the chemokine system is in the regulation of primary tumor growth, survival, invasion, and homing to specific secondary sites. However, there is ample evidence that metastatic tumors exploit chemokines to modulate the metastatic niche within bone which ultimately results in osteolytic bone disease. In this review, we examine the role of chemokines in metastatic tumor growth within bone. In particular, the chemokines CCL2, CCL3, IL-8/CXCL8, and CXCL12 are consistently involved in promoting osteoclastogenesis and tumor growth. We will also evaluate the suitability of chemokines as targets for chemotherapy with the use of neutralizing antibodies and chemokine receptor-specific antagonists.

[Establishment of risk evaluation model of peritoneal metastasis in gastric cancer and its predictive value].

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Zhao, Junjie; Zhou, Rongjian; Zhang, Qi; Shu, Ping; Li, Haojie; Wang, Xuefei; Shen, Zhenbin; Liu, Fenglin; Chen, Weidong; Qin, Jing; Sun, Yihong

2017-01-25

To establish an evaluation model of peritoneal metastasis in gastric cancer, and to assess its clinical significance. Clinical and pathologic data of the consecutive cases of gastric cancer admitted between April 2015 and December 2015 in Department of General Surgery, Zhongshan Hospital of Fudan University were analyzed retrospectively. A total of 710 patients were enrolled in the study after 18 patients with other distant metastasis were excluded. The correlations between peritoneal metastasis and different factors were studied through univariate (Pearson's test or Fisher's exact test) and multivariate analyses (Binary Logistic regression). Independent predictable factors for peritoneal metastasis were combined to establish a risk evaluation model (nomogram). The nomogram was created with R software using the 'rms' package. In the nomogram, each factor had different scores, and every patient could have a total score by adding all the scores of each factor. A higher total score represented higher risk of peritoneal metastasis. Receiver operating characteristic (ROC) curve analysis was used to compare the sensitivity and specificity of the established nomogram. Delong. Delong. Clarke-Pearson test was used to compare the difference of the area under the curve (AUC). The cut-off value was determined by the AUC, when the ROC curve had the biggest AUC, the model had the best sensitivity and specificity. Among 710 patients, 47 patients had peritoneal metastasis (6.6%), including 30 male (30/506, 5.9%) and 17 female (17/204, 8.3%); 31 were ≥ 60 years old (31/429, 7.2%); 38 had tumor ≥ 3 cm(38/461, 8.2%). Lauren classification indicated that 2 patients were intestinal type(2/245, 0.8%), 8 patients were mixed type(8/208, 3.8%), 11 patients were diffuse type(11/142, 7.7%), and others had no associated data. CA19-9 of 13 patients was ≥ 37 kU/L(13/61, 21.3%); CA125 of 11 patients was ≥ 35 kU/L(11/36, 30.6%); CA72-4 of 11 patients was ≥ 10 kU/L(11/39, 28

Choroidal Metastases as the Initial Presentation of Lung Cancer: A ...

African Journals Online (AJOL)

We report the case of a 49-year-old female patient who presented with ... nonsmall cell carcinoma of the right lung, which had multiple distant metastases. KEYWORDS: ... metastasis in lung cancer is very low, reported to be ... Kolkata, West Bengal, India. E-mail: .... awareness regarding this rare presentation of lung cancer.

Lymph Node Metastases and Prognosis in Left Upper Division Non-Small Cell Lung Cancers: The Impact of Interlobar Lymph Node Metastasis.

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Hiroaki Kuroda

Full Text Available Left upper division segmentectomy is one of the major pulmonary procedures; however, it is sometimes difficult to completely dissect interlobar lymph nodes. We attempted to clarify the prognostic importance of hilar and mediastinal nodes, especially of interlobar lymph nodes, in patients with primary non-small cell lung cancer (NSCLC located in the left upper division.We retrospectively studied patients with primary left upper lobe NSCLC undergoing surgical pulmonary resection (at least lobectomy with radical lymphadenectomy. The representative evaluation of therapeutic value from the lymph node dissection was determined using Sasako's method. This analysis was calculated by multiplying the frequency of metastasis to the station and the 5-year survival rate of the patients with metastasis to the station.We enrolled 417 patients (237 men, 180 women. Tumors were located in the lingular lobe and at the upper division of left upper lobe in 69 and 348 patients, respectively. The pathological nodal statuses were pN0 in 263 patients, pN1 in 70 patients, and pN2 in 84 patients. Lymph nodes #11 and #7 were significantly correlated with differences in node involvement in patients with left upper lobe NSCLC. Among those with left upper division NSCLC, the 5-year overall survival in pN1 was 31.5% for #10, 39.3% for #11, and 50.4% for #12U. The involvement of node #11 was 1.89-fold higher in the anterior segment than that in the apicoposterior segment. The therapeutic index of estimated benefit from lymph node dissection for #11 was 3.38, #4L was 1.93, and the aortopulmonary window was 4.86 in primary left upper division NSCLC.Interlobar node involvement is not rare in left upper division NSCLC, occurring in >20% cases. Furthermore, dissection of interlobar nodes was found to be beneficial in patients with left upper division NSCLC.

Economic analysis of combined endoscopic and endobronchial ultrasound in the evaluation of patients with suspected non-small cell lung cancer.

LENUS (Irish Health Repository)

Harewood, Gavin C

2010-03-01

Lung cancer remains the most common cause of cancer-related death in the United States. This study evaluated the costs of alternative diagnostic evaluations for patients with suspected non-small cell lung cancer (NSCLC). Researchers used a cost-minimization model to compare various diagnostic approaches in the evaluation of patients with NSCLC. It was less expensive to use an initial endoscopic ultrasound (EUS) with fine needle aspiration (FNA) to detect a mediastinal lymph node metastasis ($18,603 per patient), compared with combined EUS FNA and endobronchial ultrasound (EBUS) with FNA ($18,753). The results were sensitive to the prevalence of malignant mediastinal lymph nodes; EUS FNA remained least costly, if the probability of nodal metastases was <32.9%, as would occur in a patient without abnormal lymph nodes on computed tomography (CT). While EUS FNA combined with EBUS FNA was the most economical approach, if the rate of nodal metastases was higher, as would be the case in patients with abnormal lymph nodes on CT. Both of these strategies were less costly than bronchoscopy or mediastinoscopy. The pre-test probability of nodal metastases can determine the most cost-effective testing strategy for evaluation of a patient with NSCLC. Pre-procedure CT may be helpful in assessing probability of mediastinal nodal metastases.

Evaluation of lung immunity in chimpanzees

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Bice, D.E.; Harris, D.L.; Muggenburg, B.A.; Bowen, J.A.

1980-01-01

The effects of inhaled pollutants on the immune defenses in the lung can be studied in several animal species. To assure that the data obtained can be extrapolated to man, it is essential that the development of lung immunity is similar in the experimental animal selected and in humans. Because of the similarity of immune responses in chimpanzees and in humans, the development of immunity in the chimpanzee after lung immunization was evaluated. The results from the chimpanzees were qualitatively the same as those from previous studies in which single lung lobes of dogs were immunized. It was concluded that immunotoxicology data obtained in dogs can be used to estimate the effects of inhaled pollutants on the immune defense mechanism in the human lung

Image-guided radiotherapy for fifty-eight patients with lung cancer

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Liang Jun; Zhang Tao; Wang Wenqin

2009-01-01

Objective: To study the value of image-guided radiotherapy (IGRT) in lung cancer. Methods: From Mar. 2007 to Dec. 2007,58 patients with lung cancer were treated with IGRT. Set-up errors in each axial direction was calculated based on IGRT images of each patient. The change of GTV was evaluated on both cone-beam CT and CT simulator images. Results: Twenty-two patients with left lung cancer,30 with right lung cancer, 5 with mediastinal lymphanode metastasis and one with vertebra metastasis were included. The set-up error in x, y and z axes was (0.02±0.26) cm, (0.14±0.49) cm and ( -0.13± 0.27) cm, respectively,while the rotary set-up error in each axis was -0.15 degree ± 1.59 degree, -0.01 degree ± 1.50 degree and 0.12 degree ±1.08 degree, respectively. The set-up errors were significantly decreased by using of IGRT. GTV movement was observed in 15 patients (25.9%) ,including 5 with left upper lung cancer. GTV moving to the anterior direction was observed in 9 patients,including 4 with]eft upper lung cancer. GTV reduced in 23 (44.2%) patients during treatment. Asymmetric GTV reduction of 22 lesions was observed,with a mean reductive volume of 4.9 cm 3 . When GTV began to shrink,the irradiation dose was 4 -46 Gy, with 20 -30 Gy in 9 patients. Conclusions: The use of IGRT can significantly reduce set-up errors. GTV movement and reduction are observed in some cases. The time to modify the target volume needs to be further studied. (authors)

Stromal matrix metalloprotease-13 knockout alters Collagen I structure at the tumor-host interface and increases lung metastasis of C57BL/6 syngeneic E0771 mammary tumor cells

International Nuclear Information System (INIS)

Perry, Seth W; Schueckler, Jill M; Burke, Kathleen; Arcuri, Giuseppe L; Brown, Edward B

2013-01-01

Matrix metalloproteases and collagen are key participants in breast cancer, but their precise roles in cancer etiology and progression remain unclear. MMP13 helps regulate collagen structure and has been ascribed largely harmful roles in cancer, but some studies demonstrate that MMP13 may also protect against tumor pathology. Other studies indicate that collagen’s organizational patterns at the breast tumor-host interface influence metastatic potential. Therefore we investigated how MMP13 modulates collagen I, a principal collagen subtype in breast tissue, and affects tumor pathology and metastasis in a mouse model of breast cancer. Tumors were implanted into murine mammary tissues, and their growth analyzed in Wildtype and MMP13 KO mice. Following extraction, tumors were analyzed for collagen I levels and collagen I macro- and micro-structural properties at the tumor-host boundary using immunocytochemistry and two-photon and second harmonic generation microscopy. Lungs were analyzed for metastases counts, to correlate collagen I changes with a clinically significant functional parameter. Statistical analyses were performed by t-test, analysis of variance, or Wilcoxon-Mann–Whitney tests as appropriate. We found that genetic ablation of host stromal MMP13 led to: 1. Increased mammary tumor collagen I content, 2. Marked changes in collagen I spatial organization, and 3. Altered collagen I microstructure at the tumor-host boundary, as well as 4. Increased metastasis from the primary mammary tumor to lungs. These results implicate host MMP13 as a key regulator of collagen I structure and metastasis in mammary tumors, thus making it an attractive potential therapeutic target by which we might alter metastatic potential, one of the chief determinants of clinical outcome in breast cancer. In addition to identifying stromal MMP13 is an important regulator of the tumor microenvironment and metastasis, these results also suggest that stromal MMP13 may protect against

Stromal matrix metalloprotease-13 knockout alters Collagen I structure at the tumor-host interface and increases lung metastasis of C57BL/6 syngeneic E0771 mammary tumor cells.

Science.gov (United States)

Perry, Seth W; Schueckler, Jill M; Burke, Kathleen; Arcuri, Giuseppe L; Brown, Edward B

2013-09-05

Matrix metalloproteases and collagen are key participants in breast cancer, but their precise roles in cancer etiology and progression remain unclear. MMP13 helps regulate collagen structure and has been ascribed largely harmful roles in cancer, but some studies demonstrate that MMP13 may also protect against tumor pathology. Other studies indicate that collagen's organizational patterns at the breast tumor-host interface influence metastatic potential. Therefore we investigated how MMP13 modulates collagen I, a principal collagen subtype in breast tissue, and affects tumor pathology and metastasis in a mouse model of breast cancer. Tumors were implanted into murine mammary tissues, and their growth analyzed in Wildtype and MMP13 KO mice. Following extraction, tumors were analyzed for collagen I levels and collagen I macro- and micro-structural properties at the tumor-host boundary using immunocytochemistry and two-photon and second harmonic generation microscopy. Lungs were analyzed for metastases counts, to correlate collagen I changes with a clinically significant functional parameter. Statistical analyses were performed by t-test, analysis of variance, or Wilcoxon-Mann-Whitney tests as appropriate. We found that genetic ablation of host stromal MMP13 led to: 1. Increased mammary tumor collagen I content, 2. Marked changes in collagen I spatial organization, and 3. Altered collagen I microstructure at the tumor-host boundary, as well as 4. Increased metastasis from the primary mammary tumor to lungs. These results implicate host MMP13 as a key regulator of collagen I structure and metastasis in mammary tumors, thus making it an attractive potential therapeutic target by which we might alter metastatic potential, one of the chief determinants of clinical outcome in breast cancer. In addition to identifying stromal MMP13 is an important regulator of the tumor microenvironment and metastasis, these results also suggest that stromal MMP13 may protect against breast

Establishment and Characterization of a Novel Chinese Human Lung Adenocarcinoma Cell Line CPA-Yang2 in Immunodeficient Mice

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Shunfang YANG

2009-10-01

Full Text Available Background and objective The recurrence, metastasis and multidrug resistance (MDR in lung cancer are the tough problems worldwide. This study was to establish a novel chinese lung adenocarcinoma cell line with high metastasis potential for exploring the mechanism of reccurrence, development and MDR in lung cancer. Methods The cell came from the abdominal dropsy of a fifty-six years old female patient with lung adenocarcinoma and the tumor markers CA125, CYFRA21-1, CEA, NSE were detected to be higher secretion by radioimmunoassay in the abdominal dropsy. Tumorigenicity of immunodeficient mice was confirmed in 8th passage. The cell growth curve was mapped. Analysis of chromosome karyotype was tested. The gene expression was measured by real-time quantitative PCR. Results The tumorigenesis rate started at 8th passage in 3/10 immunodeficient mice via subcutaneously and the fully tumorigenicity was at 11th passage as well as later passages. Under the microscope, the cell showed oval-shap and adherence. The chromosome karyotype analysis of the cells was sub-triploid. Approximately 1×106 and 1.5×106 cancerous cells were injected into left cardiac ventricle and tail vein of immunodeficient mice respectively. The results showed multiorgan metastasis in the mice after three-four weeks, including mandible, scapula, humerus, vertebral column, femur, rib and brain, liver, adrenal gland, pulmonary in the mice after inoculation. The bone metastasis rate was 100% in the tumor bearing mice by bone scintigraphy and pathology. Quantitative real-time PCR was used to examined and compared with SPC-A-1 lung adenocarcinoma, ESM1, VEGF-C, IL-6, IL-8, AR genes were overexpressed. The novel cell was named CPA-Yang2. Conclusion The characteristics of novel strain CPA-Yang2 is a highly metastasis cell line of Chinese lung adenocarcinoma. It has stable traits, highly metastasis ability and maybe is a MDR lung cancerous cell line. Of course, it’s a good experimental

Inhibition of checkpoint kinase 1 sensitizes lung cancer brain metastases to radiotherapy

International Nuclear Information System (INIS)

Yang, Heekyoung; Yoon, Su Jin; Jin, Juyoun; Choi, Seung Ho; Seol, Ho Jun; Lee, Jung-Il

2011-01-01

Research highlights: → The most important therapeutic tool in brain metastasis is radiation therapy. → Radiosensitivity of cancer cells was enhanced with treatment of Chk1 inhibitor. → Depletion of Chk1 in cancer cells showed an enhancement of sensitivity to radiation. → Chk1 can be a good target for enhancement of radiosensitivity. -- Abstract: The most important therapeutic tool in brain metastasis is radiation therapy. However, resistance to radiation is a possible cause of recurrence or treatment failure. Recently, signal pathways about DNA damage checkpoints after irradiation have been noticed. We investigated the radiosensitivity can be enhanced with treatment of Chk1 inhibitor, AZD7762 in lung cancer cell lines and xenograft models of lung cancer brain metastasis. Clonogenic survival assays showed enhancement of radiosensitivity with AZD7762 after irradiation of various doses. AZD7762 increased ATR/ATM-mediated Chk1 phosphorylation and stabilized Cdc25A, suppressed cyclin A expression in lung cancer cell lines. In xenograft models of lung cancer (PC14PE6) brain metastasis, AZD7762 significantly prolonged the median survival time in response to radiation. Depletion of Chk1 using shRNA also showed an enhancement of sensitivity to radiation in PC14PE6 cells. The results of this study support that Chk1 can be a good target for enhancement of radiosensitivity.

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.

Discrepancy of biologic behavior influenced by bone marrow derived cells in lung cancer.

Science.gov (United States)

Zhang, Jie; Niu, Xiao-Min; Liao, Mei-Lin; Liu, Yun; Sha, Hui-Fang; Zhao, Yi; Yu, Yong-Feng; Tan, Qiang; Xiang, Jia-Qing; Fang, Jing; Lv, Dan-Dan; Li, Xue-Bing; Lu, Shun; Chen, Hai-Quan

2010-11-01

Disseminated cancer cells may initially require local nutrients and growth factors to thrive and survive in bone marrow. However, data on the influence of bone marrow derived cells (BMDC, also called bone stromal cells in some publications) on lung cancer cells is largely unexplored. This study explored the mechanism of how bone stromal factors contribute to the bone tropism in lung cancer. The difference among lung cancer cell lines in their abilities to metastasize to bone was found using the SCID animal model. Supernatant of bone marrow aspiration (BM) and condition medium from human bone stromal cells (BSC) were used to study the activity of bone stromal factors. We found bone stromal factors significantly increased the proliferation, invasion, adhesion and expression of angiogenosis-related factors, and inhibited the apoptosis for high bone metastasis H460 lung cancer cells. These biologic effects were not seen in SPC-A1 or A549 cells, which are low bone metastasis lung cancer cells. Adhesion of H460 cells to surface coated with bone stromal cells can activate some signal transduction pathways, and alter the expression of adhesion associated factors, including integrin β 3 and ADAMTS-1, two potential targets related with bone metastasis. We concluded that bone marrow derived cells had a profound effect on biological behavior of lung cancers, therefore favoring the growth of lung cancer cells in bone.

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

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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.

Dual modality CT/PET imaging in lung cancer staging

International Nuclear Information System (INIS)

Diaz, Gabriel A.

2005-01-01

Purpose: To compare the diagnostic capability of PET-HCT image fusion and helical computed tomography (HCT) for nodal and distant metastases detection in patients with lung cancer. Material and methods: Between February, 2003 and March, 2004 sixty-six consecutive lung cancer patients (45 men and 21 women, mean ages: 63 years old, range: 38 to 96 years old) who underwent HCT and PET-HCT fusion imaging were evaluated retrospectively. All patients had histological confirmation of lung cancer and a definitive diagnosis established on the basis of pathology results and/or clinical follow-up. Results: For global nodal staging (hilar and mediastinal) HCT showed a sensitivity, specificity, positive predictive value and negative predictive value of 72%, 47%, 62% and 58% respectively, versus 94%, 77%, 83% and 92% corresponding to PET-HCT examination. For assessment of advanced nodal stage (N3) PET-HCT showed values of 92%, 100%, 100% and 98% respectively. For detection of distant metastasis, HCT alone had values of 67%, 93%, 84% and 83% respectively versus 100%, 98%, 96% and 100% for the PET-HCT fusion imaging. In 20 (30%) patients under-staged or over-staged on the basis of HCT results, PET-HCT allowed accurate staging. Conclusions: PET-HCT fusion imaging was more effective than HCT alone for nodal and distant metastasis detection and oncology staging. (author)

Diabetes Insipidus: An Unusual Presentation of Adenocarcinoma of the Lung in a Patient with no Identifiable Lung Mass.

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Gulati, Shuchi; Kiefer, Christoper; Karim, Nagla Abdel

2015-10-01

Lung cancers are known to metastasize to unusual sites. Despite this knowledge often times the diagnosis of a primary lung cancer gets delayed especially when the patient presents without respiratory symptoms. The patient discussed in our review is a 47-year-old female, smoker who had presented to several hospitals with months of headache, nausea and intermittent episodes of vomiting. She was noted to have hypernatremia due to diabetes insipidus and a pituitary lesion on her magnetic resonance images. The pituitary mass on biopsy was found to represent a metastatic focus from a primary lung adenocarcinoma. Clinicians should be aware of malignancies that are well known to metastasize to the posterior pituitary. Conversely, since not every patient presents with symptoms of metastasis, there is a need to recognize the clinical syndromes (e. g., diabetes insipidus-like symptoms or more subtle symptoms like cranial nerve palsies) associated with potential metastasis to the pituitary.

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

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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

Patterns of metastatic progression after definitive radiation therapy for early-stage and locally advanced non-small cell lung cancer.

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Jensen, Garrett L; Tang, Chad; Hess, Kenneth R; Liao, Zhongxing; Gomez, Daniel R

2017-06-01

Current preclinical models of metastatic disease (particularly oligometastases) suggest that metastases appear in a hierarchical order. We attempted to identify systematic patterns of metastasis in non-small cell lung cancer (NSCLC) after radiation therapy (XRT). We analyzed 1074 patients treated from 12/21/1998 through 8/20/2012 with ≥60 Gy definitive radiation for initially non-metastatic NSCLC. Location and time of metastases were recorded. Regional nodal failure was noted, as was subsequent distal failure. For further analysis, we considered only the five most common sites of metastasis (bone, brain, liver, adrenal, and lung). Metastatic progression over time was defined and patterns elucidated with Chi square tests. Histologic findings were analyzed with Wilcoxon rank sum tests. A significant multistep linear progression was not apparent. Having a first metastasis in lung or bone was associated with respective 16% (median 2.4 months) and 15% likelihoods (median 7.9 months) of secondary brain metastasis. Initial metastasis in the brain led to metastasis in another organ 29.3% of the time, most often in the lung, bone, and liver (medians 3.6, 7.9, and 3.1 months). Adenocarcinoma was more likely than squamous to metastasize to the brain (18 vs. 9%) and any of the five major sites (41 vs. 27%). We did not appreciate dominant patterns suggesting a multi-step hierarchical order of metastasis. Rather, our findings suggest that certain subgroups may develop different patterns of spread depending on a variety of factors.

Natural killer (NK) cells inhibit systemic metastasis of glioblastoma cells and have therapeutic effects against glioblastomas in the brain.

Science.gov (United States)

Lee, Se Jeong; Kang, Won Young; Yoon, Yeup; Jin, Ju Youn; Song, Hye Jin; Her, Jung Hyun; Kang, Sang Mi; Hwang, Yu Kyeong; Kang, Kyeong Jin; Joo, Kyeung Min; Nam, Do-Hyun

2015-12-24

Glioblastoma multiforme (GBM) is characterized by extensive local invasion, which is in contrast with extremely rare systemic metastasis of GBM. Molecular mechanisms inhibiting systemic metastasis of GBM would be a novel therapeutic candidate for GBM in the brain. Patient-derived GBM cells were primarily cultured from surgical samples of GBM patients and were inoculated into the brains of immune deficient BALB/c-nude or NOD-SCID IL2Rgamma(null) (NSG) mice. Human NK cells were isolated from peripheral blood mononucleated cells and expanded in vitro. Patient-derived GBM cells in the brains of NSG mice unexpectedly induced spontaneous lung metastasis although no metastasis was detected in BALB/c-nude mice. Based on the difference of the innate immunity between two mouse strains, NK cell activities of orthotopic GBM xenograft models based on BALB/c-nude mice were inhibited. NK cell inactivation induced spontaneous lung metastasis of GBM cells, which indicated that NK cells inhibit the systemic metastasis. In vitro cytotoxic activities of human NK cells against GBM cells indicated that cytotoxic activity of NK cells against GBM cells prevents systemic metastasis of GBM and that NK cells could be effective cell therapeutics against GBM. Accordingly, NK cells transplanted into orthotopic GBM xenograft models intravenously or intratumorally induced apoptosis of GBM cells in the brain and showed significant therapeutic effects. Our results suggest that innate NK immunity is responsible for rare systemic metastasis of GBM and that sufficient supplementation of NK cells could be a promising immunotherapeutic strategy for GBM in the brain.

Obstructive Small Bowel Metastasis from Uterine Leiomyosarcoma: A Case Report

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Mutahir A. Tunio

2014-01-01

Full Text Available Background. Uterine leiomyosarcoma is a rare and aggressive gynecologic malignancy with an overall poor prognosis. Lungs, bones, and brain are common sites of metastases of uterine leiomyosarcoma. Metastases of uterine leiomyosarcoma to the small bowel are extremely rare, and only four case reports have been published to date. Case presentation. A 55-year-old Saudi woman diagnosed with a case of uterine leiomyosarcoma treated with total abdominal hysterectomy (TAH and bilateral salpingooophorectomy (BSO presented in emergency room after sixteen months with acute abdomen. Subsequent work-up showed a jejunal mass for which resection and end-to-end anastomosis were performed. Biopsy confirmed the diagnosis of small bowel metastasis from uterine leiomyosarcoma. Further staging work-up showed wide spread metastasis in lungs and brain. After palliative cranial irradiation, systemic chemotherapy based on single agent doxorubicin was started. Conclusion. Metastatic leiomyosarcoma of small bowel from uterine leiomyosarcoma is a rare entity and is sign of advanced disease. It should be differentiated from primary leiomyosarcoma of small bowel as both are treated with different systemic chemotherapeutic agents.

High Glucose Promotes Tumor Invasion and Increases Metastasis-Associated Protein Expression in Human Lung Epithelial Cells by Upregulating Heme Oxygenase-1 via Reactive Oxygen Species or the TGF-β1/PI3K/Akt Signaling Pathway

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Xiaowen Kang

2015-02-01

Full Text Available Background: Growing evidence indicates that heme oxygenase-1 (HO-1 is up-regulated in malignancies and subsequently alters tumor aggressiveness and various cancer-related factors, such as high glucose (HG levels. HO-1 expression can be induced when glucose concentrations are above 25 mM; however, the role of HO-1 in lung cancer patients with diabetes remains unknown. Therefore, in this study we investigated the promotion of tumor cell invasion and the expression of metastasis-associated proteins by inducing the up-regulation of HO-1 expression by HG treatment in A549 human lung epithelial cells. Methods: The expression of HO-1and metastasis-associated protein expression was explored by western blot analysis. HO-1 enzymatic activity, reactive oxygen species (ROS production and TGF-β1 production were examined by ELISA. Invasiveness was analyzed using a Transwell chamber. Results: HG treatment of A549 cells induced an increase in HO-1 expression, which was mediated by the HG-induced generation of reactive oxygen species (ROS and transforming growth factor-β1 (TGF-β1 in a concentration- and time-dependent manner. Following the increase in HO-1 expression, the enzymatic activity of HO-1 also increased in HG-treated cells. Pretreatment with N-acetyl-L-cysteine (NAC or with phosphatidylinositol 3-kinase (PI3K/Akt inhibitors attenuated the HG-induced increase in HO-1 expression. HG treatment of A549 cells enhanced the invasion potential of these cells, as shown with a Transwell assay, and increased metastasis-associated protein expression. However, HO-1 siRNA transfection significantly decreased these capabilities. Conclusion: this study is the first to demonstrate that HG treatment of A549 human lung epithelial cells promotes tumor cell invasion and increases metastasis-associated protein expression by up-regulating HO-1 expression via ROS or the TGF-β1/PI3K/Akt signaling pathway.

Feasibility of mesorectal vascular invasion in predicting early distant metastasis in patients with stage T3 rectal cancer based on rectal MRI

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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.)

Metastasis of colon cancer to the thyroid gland: a case diagnosed on fine-needle aspirate by a combined cytological, immunocytochemical, and molecular approach.

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Cozzolino, Immacolata; Malapelle, Umberto; Carlomagno, Chiara; Palombini, Lucio; Troncone, Giancarlo

2010-12-01

Fine-needle aspiration (FNA) with cytological evaluation reliably diagnoses primary and secondary thyroid neoplasms. However, identifying the primary origin of a metastatic process involving the thyroid gland is challenging. In particular, metastasis of colon cancer to the thyroid gland is very rare. In this case report, a right lobe solid thyroid nodule in a 66-year-old male was aspirated. FNA cytology showed necrosis and atypical tall columnar cells; since, the patient at age 60 had undergone surgery for a sigmoid-rectal cancer metastasizing to the liver and subsequently to the lung, a suspicion of metastasis from colon cancer was raised. This was corroborated by cell-block immunocytochemistry showing a cytokeratin (CK) 7 negative/CK20-positive staining pattern; thyreoglobulin and TTF-1 were both negative. Since KRAS codon 12/13 mutations frequently occur in colon cancer, whereas they are extremely uncommon in primary thyroid tumors, DNA was extracted from the aspirated cells, and KRAS mutational analysis was carried out. The codon 12 G12D mutation was found; the same mutation was evident in the primary cancer of the colon and in its liver and lung metastasis. Thus, a combined cytological, immunocytochemical and molecular approach unquestionably correlated metastatic adenocarcinoma cells aspirated from the thyroid to a colo-rectal origin. © 2010 Wiley-Liss, Inc.

A Rare Thyroid Metastasis from Uveal Melanoma and Response to Immunotherapy Agents

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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.

Uterine cervical cancer with brain metastasis as the initial site of presentation.

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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.

An active treatment of lung adenocarcinoma cancer with brain metastases: icotinib

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Zhang Y

2015-06-01

Full Text Available Ying Zhang, Huaping Tang, Jun Li, Meng Li Department of Respiration Medicine, Municipal Hospital, Qingdao, People’s Republic of China Abstract: Lung cancer has the highest mortality rate of all cancers world­wide. A total of 70%–75% of all lung cancers are non-small cell lung cancer (NSCLC with two-thirds presenting with locally advanced or metastatic disease at diagnosis. Brain metastasis is one of the most common problems in the management of NSCLC, worsening the prognosis and quality of life of NSCLC patients. The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs gefitinib and erlotinib have been tested in patients with NSCLC and brain metastasis. Icotinib is a new type of oral EGFR-TKI. In this report, we describe a patient with lung adenocarcinoma cancer with brain metastases who received icotinib treatment and kept satisfactory health-related quality of life for 1 year. Keywords: EGFR, non-small cell lung cancer, tyrosine kinase inhibitor

Bone scintigraphy for metastasis detection in canine osteosarcoma

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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

Spine Metastases in Lung Cancer

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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.

Apigenin inhibits HGF-promoted invasive growth and metastasis involving blocking PI3K/Akt pathway and β4 integrin function in MDA-MB-231 breast cancer cells

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Lee, W.-J.; Chen, W.-K.; Wang, C.-J.; Lin, W.-L.; Tseng, T.-H.

2008-01-01

Hepatocyte growth factor (HGF) and its receptor, Met, known to control invasive growth program have recently been shown to play crucial roles in the survival of breast cancer patients. The diet-derived flavonoids have been reported to possess anti-invasion properties; however, knowledge on the pharmacological and molecular mechanisms in suppressing HGF/Met-mediated tumor invasion and metastasis is poorly understood. In our preliminary study, we use HGF as an invasive inducer to investigate the effect of flavonoids including apigenin, naringenin, genistein and kaempferol on HGF-dependent invasive growth of MDA-MB-231 human breast cancer cells. Results show that apigenin presents the most potent anti-migration and anti-invasion properties by Boyden chamber assay. Furthermore, apigenin represses the HGF-induced cell motility and scattering and inhibits the HGF-promoted cell migration and invasion in a dose-dependent manner. The effect of apigenin on HGF-induced signaling activation involving invasive growth was evaluated by immunoblotting analysis, it shows that apigenin blocks the HGF-induced Akt phosphorylation but not Met, ERK, and JNK phosphorylation. In addition to MDA-MB-231 cells, apigenin exhibits inhibitory effect on HGF-induced Akt phosphorylation in hepatoma SK-Hep1 cells and lung carcinoma A549 cells. By indirect immunofluorescence microscopy assay, apigenin inhibits the HGF-induced clustering of β4 integrin at actin-rich adhesive site and lamellipodia through PI3K-dependent manner. Treatment of apigenin inhibited HGF-stimulated integrin β4 function including cell-matrix adhesion and cell-endothelial cells adhesion in MDA-MB-231 cells. By Akt-siRNA transfection analysis, it confirmed that apigenin inhibited HGF-promoted invasive growth involving blocking PI3K/Akt pathway. Finally, we evaluated the effect of apigenin on HGF-promoted metastasis by lung colonization of tumor cells in nude mice and organ metastasis of tumor cells in chick embryo. By

Role of surgery in breast metastasis from carcinoma of the cervix

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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.

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

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

2008-02-15

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

Observation of the courses of metastasis using PET

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Oku, Naoto; Okada, Shoji

1997-01-01

Positron Emission Computed Tomography (PET), is a nuclear medical diagnostic method by which tomographic images can be obtained non-invasively at a real time. The positron nuclides; 11 C, 13 N, 15 O or 18 F have comparatively high radioactivities which enable to make functional analysis of very small amounts of the cerebral receptors and cellular metabolism. In addition, PET can be used for the determination of blood flow level and thus, it became possible to study the area involved in learning and memory. Several positron-emitting compounds of low molecular weight have been utilized for medical studies and applications. The early courses of metastasis were investigated using (2- 18 F)2-fluoro-2-deoxyglucose ((2- 18 F)FDG). Metastatic cancerous cells labelled with (2- 18 F)FDG were injected into rodents and the radioactivities were monitored by PET, from an aspect of cell adhesion. B16BL6 and MTLn3 cells accumulated highly in the lung of rats in an early stage and gradually disappeared from the organ, whereas RAW 117 cells specifically accumulated in the liver through the early accumulation in the lung. These results indicate that the degree of early accumulation of malignant cells well reflects the feasibility of metastasis. (M.N.)

Alcohol consumption suppresses metastasis of B16-BL6 melanoma in mice.

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Meadows, G G; Elstad, C A; Blank, S E; Gallucci, R M; Pfister, L J

1993-03-01

Female C57BL/6 mice were fed a defined, pelleted diet and given 10% w/v or 20% w/v ethanol in their drinking water. Natural killer (NK) cell cytolytic activity was compared between water-drinking and ethanol-consuming mice and in mice that were also treated with polyinosinic-polycytidylic acid (poly I:C) to augment NK cell activity or with anti-NK1.1 antibody to decrease activity. NK cell cytolytic activity was not altered in mice given 10% ethanol, but was decreased in mice given 20% ethanol compared to water-drinking mice. Poly I:C treatment increased and anti-NK1.1 antibody treatment decreased NK cell activity in both water-drinking and 20% ethanol-consuming mice. Experimental and spontaneous metastases of B16-BL6 melanoma were evaluated as a function of the duration of ethanol consumption before tumor inoculation and as a function of altered NK cell activity. Experimental metastasis was inhibited after 4 and also after 6.5 weeks of ethanol exposure. Poly I:C treatment inhibited tumor lung colonization irrespective of ethanol consumption. Anti-NK1.1 antibody treatment increased metastasis, although to a lesser degree in mice consuming 10% ethanol. Spontaneous metastasis was inhibited in mice consuming 10% ethanol for 4 weeks, and in mice consuming 20% ethanol for 1 and 4 weeks before melanoma inoculation.

Prolonged survival after resection and radiotherapy for solitary brain metastases from non-small-cell lung cancer

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Chee, R. J.; Bydder, S.; Cameron, F.

2007-01-01

Selected patients with brain metastases from non-small-cell lung cancer benefit from aggressive treatment. This report describes three patients who developed solitary brain metastases after previous resection of primary adenocarcinoma of the lung. Each underwent surgical resection of their brain metastasis followed by cranial irradiation and remain disease free 10 or more years later. Two patients developed cognitive impairment approximately 8 years after treatment of their brain metastasis, which was felt to be due to their previous brain irradiation. Here we discuss the treatment of solitary brain metastasis, particularly the value of combined method approaches in selected patients and dose-volume considerations

Rare Case of Duodenal Metastasis From Pulmonary Squamous Cell Carcinoma

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Zain Memon DO

2017-10-01

Full Text Available Pulmonary squamous cell carcinoma is the second most common non–small cell malignancy of the lung. It commonly metastasizes to the adrenal glands, bone, liver, brain, and kidneys. Most occurrences of metastatic squamous cell carcinoma involving the gastrointestinal tract originate from primary lung tumors. Metastasis to the duodenum, however, is exceedingly rare, with very few cases of stomach or duodenal involvement described in the literature. We report the case of a patient with stage IV pulmonary squamous cell carcinoma metastasizing to the duodenum with an uncommon presentation to add to the paucity of literature available regarding this rare finding.

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

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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.

Evaluation of the pain and local tenderness in bone metastasis treated with magnetic resonance-guided focused ultrasound surgery (MRgFUS)

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Namba, Hirofumi; Kawasaki, Motohiro; Kato, Tomonari; Tani, Toshikazu; Ushida, Takahiro; Koizumi, Norihiro

2017-03-01

It has been reported that MRgFUS has pain palliative effects on the local pain in patients with bone metastasis. In general, a severity of pain has been evaluated using only subjective method with numerical rating scale (NRS) or visual analogue scale (VAS). It is important to evaluate local pain-palliative effects of MRgFUS treatment with objective and quantitative method. The aim of this study is to investigate changes in the severity of local pain of bone metastasis before and after MRgFUS treatments, measuring pressure pain threshold (PPT) using pressure algometer, and pain intensity using electrical stimulation device (the Pain Vision system) at most painful site of bone metastasis. We have conducted MRgFUS for pain palliation of bone metastasis for 8 patients, and evaluated the local tenderness quantitatively for 8 patients, and evaluated local pain intensity for 7 patients. Before the treatments, PPTs were 106.3kPa [40.0-431.5] at metastatic site and 344.8 kPa [206.0-667.0] at normal control site, which showed a significant difference. The PPTs at metastatic site shows a significant increase from 106.3 kPa [40.0-431.5] at the baseline to 270.5 kPa [93.5-533.5] at 3 months after the treatment. The NRS score shows a significant decrease from 6.0 [4-8] at baseline to 1 [0-3] at 3 months after the treatment. Similarly, the pain intensity shows a significant decrease 245 [96.3-888.7] at baseline to 55.9 [2.8-292] at 3 months after the treatment. The results of our study illustrate the pain-relieving effects of MRgFUS for the treatment of painful bone metastasis. PPT might be a useful parameter not only for assessing a treatment's effect, but also for the decision of the painful area to treat with MRgFUS. Pain Vision seems to be useful for quantitative and objective evaluation of local pain of painful bone metastasis.

NF-kappaB in Lung Tumorigenesis

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Cai, Zhenjian; Tchou-Wong, Kam-Meng; Rom, William N.

2011-01-01

The development of lung cancer in humans can be divided into three steps initiation, promotion and progression. This process is driven by alterations in related signal transduction pathways. These pathways signal the aberrant activation of NF-kappaB, a transcription factor that regulates the expression of genes important for lung tumorigenesis. Our current knowledge about the role of the NF-kappaB signaling pathway in the development of lung cancer has been bolstered by animal models demonstrating the connection between K-ras and tobacco induced lung transformation with NF-kappaB. Activation of downstream genes leads to cell proliferation, inhibition of apoptosis, angiogenesis, inflammation, invasion, and metastasis

NF-kappaB in Lung Tumorigenesis

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Cai, Zhenjian [Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, New York University School of Medicine, 462 First Avenue, NBV 7N24, New York, NY 10016 (United States); Tchou-Wong, Kam-Meng; Rom, William N., E-mail: william.rom@nyumc.org [Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, New York University School of Medicine, 462 First Avenue, NBV 7N24, New York, NY 10016 (United States); Department of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987 (United States)

2011-12-14

The development of lung cancer in humans can be divided into three steps initiation, promotion and progression. This process is driven by alterations in related signal transduction pathways. These pathways signal the aberrant activation of NF-kappaB, a transcription factor that regulates the expression of genes important for lung tumorigenesis. Our current knowledge about the role of the NF-kappaB signaling pathway in the development of lung cancer has been bolstered by animal models demonstrating the connection between K-ras and tobacco induced lung transformation with NF-kappaB. Activation of downstream genes leads to cell proliferation, inhibition of apoptosis, angiogenesis, inflammation, invasion, and metastasis.

Facial Nerve Palsy: An Unusual Presenting Feature of Small Cell Lung Cancer

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Ozcan Yildiz

2011-01-01

Full Text Available Lung cancer is the second most common type of cancer in the world and is the most common cause of cancer-related death in men and women; it is responsible for 1.3 million deaths annually worldwide. It can metastasize to any organ. The most common site of metastasis in the head and neck region is the brain; however, it can also metastasize to the oral cavity, gingiva, tongue, parotid gland and lymph nodes. This article reports a case of small cell lung cancer presenting with metastasis to the facial nerve.

[The effect of Angelica sinensis on adhesion, invasion, migration and metastasis of melanoma cells].

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Gu, Qin; Xu, Jian-ya; Cheng, Luo-gen; Xia, Wei-jun

2007-03-01

To study the effect of Angelica sinensis on invasion, adhesion, migration and metastasis of B16-BL6 metastatic mouse melanoma cells and discuss its functional mechanism. The proliferation, adhesion, invasion and migration capacity of B16-BL6 metastatic cells was evaluated by MTT assay, adhesion assay and reconstituted basement membrane invasion and migration assay in vitro respectively. Mouse spontaneous melanoma model was used to study the effect of Angelica sinensis on metastasis in vivo. The extract of Angelica sinensis inhibited the proliferation of B16-BL6 metastatic cells and its migration capacity significantly. It regulated bidirectionally the adhesion of B16-BL6 metastatic cells to the basement component laminin while it had no effect on the invasion capacity. In the mouse spotaneous melanoma model, the lung metastatic nodes number and its volume were significantly decreased after continuously treated with the extract of Angelica sinensis at the concentration of 3.67 mg/kg. The extract of Angelica sinensis can inhibit the metastasis of of B16-BL6 metastatic mouse melanoma cells and its mechanism is maybe that Angelica sinensis can inhibit the B16-BL6 cells adhering to the ECM and reduce the migration of B16-BL6 cells.

WIF-1 and Ihh Expression and Clinical Significance in Patients With Lung Squamous Cell Carcinoma and Adenocarcinoma.

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Zhang, Yue; Hu, Chunhong

2016-10-31

This study investigated the expression of wingless-type inhibitory factor-1 (WIF-1) and Ihh protein in tumor tissues and their clinical significance in patients with lung squamous cell carcinoma and adenocarcinoma. The expression of WIF-1 and Ihh protein in 74 squamous cell carcinomas and 76 adenocarcinomas was measured by immunohistochemistry. The percentage of positive WIF-1 protein expression was significantly higher, while positive Ihh protein expression was significantly lower in patients with well-differentiated lung squamous cell carcinoma and adenocarcinoma, tumor node metastasis (TNM) stage I disease, and lymph node metastasis than that in patients with poorly differentiated tumor, TNM stage III disease, and lymph node metastasis (PIhh protein expression survived significantly shorter than patients with negative Ihh protein expression. In contrast, no significant difference in mean survival was observed in patients with lung squamous cell carcinoma and adenocarcinoma with positive and negative WIF-1 protein expression (P>0.05). Ihh is a marker for poor prognosis in patients with lung squamous cell carcinoma and adenocarcinoma. WIF-1 is not a predictive marker for lung cancer.

CT-guided percutaneous conformal cryoablation for lung carcinoma

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Yueyong, Xiao; Bin, Wu; Xiao, Zhang; Hongjun, Li; Da, Yu; Jie, Li; Jun, Li [Department of Radiology, PLA General Hospital, Beijing (China)

2010-02-15

Objective: To investigate the safety, efficacy and feasibility of CT-guided percutaneous conformal cryoablation for lung cancer. Methods: The inclusion criteria were: (1) Poor respiratory function and aged patients who can not bear the thoracic surgical operation. (2) Peripheral lung cancer involving the pleura and chest wall which can not be resected. (3) Residual tumor after other comprehensive treatment. (4) Focal lung cancer but the patient refused surgical resection. The exclusion criteria were: (1) Multifocal lesions. (2) Lesion close to mediastinum with possible risk of vessel injury. (3) Severe impairment of pulmonary functions, the maximum voluntary ventilation is less than 39%. (4) Repeated cough or dyspnea, can not cooperate with the procedure. (5) Poor systemic conditions, cachexia or bleeding. Totally, 76 lung carcinoma lesions on 66 patients were treated by CT-guided percutaneous conformal cryoablation using 17 G cryoprobes. The maximum diameters of the tumors ranged from 1.5 cm to 1.6 cm. For the tumors with the maximum diameter less than 3.0 cm, they were treated by double-needle clamping cryoablation. For those with the maximum diameter between 3.0 and 5.0 cm, they were treated by multiple-needle conformal cryoablation. For those with the maximum diameter larger than 5.0 cm, they were treated with multiple-needle conformal cyroablation, with the needle distance less than 1.5 cm. All the patients were followed-up 6 to 24 months after the procedure using contrast-enhanced CT to evaluate the tumor size and enhancement. Results: For 18 cases with the maximum diameters less than 3.0 cm, CT scan during the procedure showed that the frozen areas extended beyond the edge of the lesions more than 1.0 cm, the lesion attenuated, narrow-band-like encircled translucency around the lesions and 'target sign' with ground-glass density of the peripheral lung tissue. There was no enhancement during the first 1 st, 3 rd month follow-up, only fibrosis scar in 6 th

CT-guided percutaneous conformal cryoablation for lung carcinoma

International Nuclear Information System (INIS)

Xiao Yueyong; Wu Bin; Zhang Xiao; Li Hongjun; Yu Da; Li Jie; Li Jun

2010-01-01

Objective: To investigate the safety, efficacy and feasibility of CT-guided percutaneous conformal cryoablation for lung cancer. Methods: The inclusion criteria were: (1) Poor respiratory function and aged patients who can not bear the thoracic surgical operation. (2) Peripheral lung cancer involving the pleura and chest wall which can not be resected. (3) Residual tumor after other comprehensive treatment. (4) Focal lung cancer but the patient refused surgical resection. The exclusion criteria were: (1) Multifocal lesions. (2) Lesion close to mediastinum with possible risk of vessel injury. (3) Severe impairment of pulmonary functions, the maximum voluntary ventilation is less than 39%. (4) Repeated cough or dyspnea, can not cooperate with the procedure. (5) Poor systemic conditions, cachexia or bleeding. Totally, 76 lung carcinoma lesions on 66 patients were treated by CT-guided percutaneous conformal cryoablation using 17 G cryoprobes. The maximum diameters of the tumors ranged from 1.5 cm to 1.6 cm. For the tumors with the maximum diameter less than 3.0 cm, they were treated by double-needle clamping cryoablation. For those with the maximum diameter between 3.0 and 5.0 cm, they were treated by multiple-needle conformal cryoablation. For those with the maximum diameter larger than 5.0 cm, they were treated with multiple-needle conformal cyroablation, with the needle distance less than 1.5 cm. All the patients were followed-up 6 to 24 months after the procedure using contrast-enhanced CT to evaluate the tumor size and enhancement. Results: For 18 cases with the maximum diameters less than 3.0 cm, CT scan during the procedure showed that the frozen areas extended beyond the edge of the lesions more than 1.0 cm, the lesion attenuated, narrow-band-like encircled translucency around the lesions and 'target sign' with ground-glass density of the peripheral lung tissue. There was no enhancement during the first 1 st, 3 rd month follow-up, only fibrosis scar in 6 th

Mechanisms of RhoGDI2 Mediated Lung Cancer Epithelial-Mesenchymal Transition Suppression

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Huiyan Niu

2014-11-01

Full Text Available Background: The aim of this study was to evaluate the function of RhoGDI2 in lung cancer epithelial-mesenchymal transition (EMT process and to illustrate the underlying mechanisms that will lead to improvement of lung cancer treatment. Methods: The RhoGDI2 knock-down and overexpressing A549 cell lines were first constructed. The influence of RhoGDI2 on cytoskeleton in A549 cells was studied using two approaches: G-LISA-based Rac1 activity measurement and immunostaining-based F-actin distribution. The expression levels of key EMT genes were analyzed using real time quantitative polymerase chain reaction (RT-qPCR, western blot and immunostaining in untreated and RhoGDI2 knock-down or overexpressing A549 cells in both in vivo and in vitro experimental settings. Results: Our study showed that the activity of Rac1, a key gene that is crucial for the initiation and metastasis of human lung adenocarcinoma, causing the redistribution of F-actin with partial loss of cell-cell adhesions and stress fibers, was significantly suppressed by RhoGDI2. RhoGDI2 promoted the expression of EMT marker gene E-cadherin and repressed EMT promoting genes Slug, Snail, α-SMA in both A549 cells and lung and liver organs derived from the mouse models. Knocking-down RhoGDI2 induced abnormal morphology for lung organs. Conclusion: These findings indicate that RhoGDI2 repressed the activity of Rac1 and may be involved in the rearrangement of cytoskeleton in lung cancer cells. RhoGDI2 suppresses the metastasis of lung cancer mediated through EMT by regulating the expression of key genes such as E-cadherin, Slug, Snail and α-SMA in both in vivo and in vitro models.

The Roles of Carcinoembryonic Antigen in Liver Metastasis and Therapeutic Approaches

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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

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

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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.

Testicular choriocarcinoma with cutaneous metastasis in a 19-year-old man.

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Toberer, Ferdinand; Enk, Alexander; Hartschuh, Wolfgang; Grüllich, Carsten

2018-07-01

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 9 days after the biopsy of the cutaneous metastasis. Cutaneous metastases of testicular choriocarcinoma are exceptionally rare, with fewer 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 cutaneous scalp tumors. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

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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.

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

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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.

Comparison of three different methods for the detection of circulating tumor cells in mice with lung metastasis.

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Xu, Weifeng; Wu, Bing; Fu, Lengxi; Chen, Junying; Wang, Zeng; Huang, Fei; Chen, Jinrong; Zhang, Mei; Zhang, Zhenhuan; Lin, Jingan; Lan, Ruilong; Chen, Ruiqing; Chen, Wei; Chen, Long; Hong, Jinsheng; Zhang, Weijian; Ding, Yuxiong; Okunieff, Paul; Lin, Jianhua; Zhang, Lurong

2017-06-01

Circulating tumor cells (CTCs) represent the key step of cancer cell dissemination. The alteration of CTCs correlates with the treatment outcome and prognosis. To enrich and identify CTCs from billions of blood cells renders a very challenging task, which triggers development of several methods, including lysis of RBC plus negative or positive enrichment using antibodies, and filter membrane or spiral microfluidics to capture CTCs. To compare the advantages of different enrichment methods for CTCs, we utilized the 4T1 breast cancer cells transfected with both green fluorescent protein (GFP) and luciferase to trace CTCs in the experimental lung metastasis model. Three methods were used to detect CTCs at the same time: bioluminescence assay, smearing method, and membrane filter method. The in vivo alive mouse imaging was used to dynamically monitor the growth of lung metastases. The sensitivity and accuracy of three detection methods were compared side-by-side. Our results showed that 1) the sensitivity of bioluminescence assay was the highest, but there was no information of CTC morphology; 2) the smearing method and membrane filter method could observe the detail of CTC morphology, such as in single or in cluster, while their sensitivity was lower than bioluminescence assay; 3) A dynamic observation at a 7-day intervals, the lung metastatic cancer grew at a log speed, while CTCs were increased at a low speed. This might be due to the activated immune cells eliminating the CTCs at a speed much faster than CTCs were generated. This comparison of three CTC detection methods in mouse model suggests that bioluminescence assay could be used in quantitative study of the effect of certain agent on the suppression of CTCs, while GFP-based morphological assays could be used to study the dissemination mechanism of CTCs. The combination of both bioluminescence assay and GFP-based assay would generate more information for quantity and quality of CTCs.

[Analysis of the therapeutic effects of different treatment modalities on the outcomes of 87 patients with lung oligometastasis from nasopharyngeal carcinoma after radiotherapy].

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Tang, Q; Hu, Q Y; Piao, Y F; Hua, Y H; Chen, X Z

2016-03-23

The aim of the present study was to evaluate the efficacy of three different modalities in treatment of lung oligometastases from nasopharyngeal carcinoma (NPC) after radiotherapy and to identify a more appropriate treatment modality. The clinical data of 87 cases of lung oligometastases from NPC were analyzed retrospectively. Among them, 33 patients underwent local small-field irradiation+ /- chemotherapy, 28 underwent whole-lung irradiation+ chemotherapy, and 26 underwent simple chemotherapy. The survival rates were calculated using Kaplan-Meier analysis. The differences among the modalities were evaluated using the log-rank test. Cox univariate and multivariate analyses were performed to determine the influencing factors. The 3-year lung metastasis survival (LMS) rates of patients with lung metastasis undergoing the three treatment modalities (local small-field irradiation+ /-chemotherapy, whole-lung irradiation+ chemotherapy and chemotherapy alone) were 89.3%, 72.7%, and 72.4%, respectively, showing a significant difference between the groups (P=0.003). Further subgroup analysis showed that the 5-year LMS rate was significantly higher in the local small-field irradiation+ /-chemotherapy group than that in the whole-lung irradiation+ chemotherapy group and chemotherapy alone group (P=0.001). The 2-year progression-free survival (PFS) rates of the three groups were 57.1%, 25.8% and 3.8%, respectively, showing significant intergroup differences (P=0.002 and P<0.001). Multivariate analysis indicated that compared with the whole lung irradiation group and the chemotherapy alone group, the local irradiation+ /- chemotherapy is an independent favorable prognostic factor for LMS and PFS (P<0.05). Local radiotherapy combined with systemic chemotherapy is the best therapeutic modality for lung oligometastases derived from NPC after radiotherapy, improving the LMS and prolonging the PFS.

Brain imaging before primary lung cancer resection: a controversial topic.

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Hudson, Zoe; Internullo, Eveline; Edey, Anthony; Laurence, Isabel; Bianchi, Davide; Addeo, Alfredo

2017-01-01

International and national recommendations for brain imaging in patients planned to undergo potentially curative resection of non-small-cell lung cancer (NSCLC) are variably implemented throughout the United Kingdom [Hudson BJ, Crawford MB, and Curtin J et al (2015) Brain imaging in lung cancer patients without symptoms of brain metastases: a national survey of current practice in England Clin Radiol https://doi.org/10.1016/j.crad.2015.02.007]. However, the recommendations are not based on high-quality evidence and do not take into account cost implications and local resources. Our aim was to determine local practice based on historic outcomes in this patient cohort. This retrospective study took place in a regional thoracic surgical centre in the United Kingdom. Pathology records for all patients who had undergone lung resection with curative intent during the time period January 2012-December 2014 were analysed in October 2015. Electronic pathology and radiology reports were accessed for each patient and data collected about their histological findings, TNM stage, resection margins, and the presence of brain metastases on either pre-operative or post-operative imaging. From the dates given on imaging, we calculated the number of days post-resection that the brain metastases were detected. 585 patients were identified who had undergone resection of their lung cancer. Of these, 471 had accessible electronic radiology records to assess for the radiological evidence of brain metastases. When their electronic records were evaluated, 25/471 (5.3%) patients had radiological evidence of brain metastasis. Of these, five patients had been diagnosed with a brain metastasis at initial presentation and had undergone primary resection of the brain metastasis followed by resection of the lung primary. One patient had been diagnosed with both a primary lung and a primary bowel adenocarcinoma; on review of the case, it was felt that the brain metastasis was more likely to have

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

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Pontillo, Carolina Andrea; Rojas, Paola; Chiappini, Florencia; Sequeira, Gonzalo; Cocca, Claudia; Crocci, Máximo; Colombo, Lucas; Lanari, Claudia

2013-01-01

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

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

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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.

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)

Evaluation of CT images on metastasis to cervical lymph node in patients with oral cancer

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Fujiki, Tomokazu; Wada, Takurou; Wakasa, Toru; Yanagi, Yoshinobu; Honda, Yasutoshi; Kawai, Noriko; Kishi, Kanji

1998-01-01

There have been many reports about the usefulness of CT in diagnosing cervical lymph node metastasis from oral cancer. With relatively high diagnostic accuracy, various diagnostic criteria have been used. This study evaluated CT images of cervical lymph node metastasis in patients with oral cancer using these criteria. Eighty-nine cases of various oral cancers (132 lymph node groups) were evaluated regarding cervical lymph node metastasis. In patients with nodes measuring over 1 cm in minimal axial diameter, 58.1% were metastatic (metastatic/total=47/74), while 17.2% of patients with nodes measuring less than 1 cm in minimal axial diameter of lymph node were metastatic (10/58). As for other diagnostic criteria, in patients with spherical nodes, 38.7% (metastatic/total=29/75), in patients showing ring enhancement, 70.4% (19/27) and in patients with fusion, 75.0% (3/4) were metastatic. In addition, in patients with spherical nodes measuring over 1 cm in minimal axial diameter, 59.5% (22/37), in patients with nodes measuring over 1 cm in minimal axial diameter and showing ring enhancement, 78.3% (18/23), in patients with spherical nodes showing ring enhancement, 60.0% (9/15) and in patients with spherical nodes measuring over 1 cm in minimal axial diameter and showing ring enhancement, 64.3% (9/14) were metastatic. In case of disappearance of fat layer (1/1), cancer infiltration of the surrounding tissue was seen. In conclusion, over 1 cm in minimal axial diameter, spherical node and ring enhancement were found to be appropriate diagnostic criteria. Furthermore, CT is essential in diagnosing cervical lymph node metastasis from oral cancer. (author)

Lymph Node Metastases and Prognosis in Left Upper Division Non-Small Cell Lung Cancers: The Impact of Interlobar Lymph Node Metastasis

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Kuroda, Hiroaki; Sakao, Yukinori; Mun, Mingyon; Uehara, Hirofumi; Nakao, Masayuki; Matsuura, Yousuke; Mizuno, Tetsuya; Sakakura, Noriaki; Motoi, Noriko; Ishikawa, Yuichi; Yatabe, Yasushi; Nakagawa, Ken; Okumura, Sakae

2015-01-01

Background Left upper division segmentectomy is one of the major pulmonary procedures; however, it is sometimes difficult to completely dissect interlobar lymph nodes. We attempted to clarify the prognostic importance of hilar and mediastinal nodes, especially of interlobar lymph nodes, in patients with primary non-small cell lung cancer (NSCLC) located in the left upper division. Methods We retrospectively studied patients with primary left upper lobe NSCLC undergoing surgical pulmonary resection (at least lobectomy) with radical lymphadenectomy. The representative evaluation of therapeutic value from the lymph node dissection was determined using Sasako’s method. This analysis was calculated by multiplying the frequency of metastasis to the station and the 5-year survival rate of the patients with metastasis to the station. Results We enrolled 417 patients (237 men, 180 women). Tumors were located in the lingular lobe and at the upper division of left upper lobe in 69 and 348 patients, respectively. The pathological nodal statuses were pN0 in 263 patients, pN1 in 70 patients, and pN2 in 84 patients. Lymph nodes #11 and #7 were significantly correlated with differences in node involvement in patients with left upper lobe NSCLC. Among those with left upper division NSCLC, the 5-year overall survival in pN1 was 31.5% for #10, 39.3% for #11, and 50.4% for #12U. The involvement of node #11 was 1.89-fold higher in the anterior segment than that in the apicoposterior segment. The therapeutic index of estimated benefit from lymph node dissection for #11 was 3.38, #4L was 1.93, and the aortopulmonary window was 4.86 in primary left upper division NSCLC. Conclusions Interlobar node involvement is not rare in left upper division NSCLC, occurring in >20% cases. Furthermore, dissection of interlobar nodes was found to be beneficial in patients with left upper division NSCLC. PMID:26247881

Intraparenchymal Hemorrhage due to Brain Metastasis of Hepatocellular Carcinoma

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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.

Mena deficiency delays tumor progression and decreases metastasis in polyoma middle-T transgenic mouse mammary tumors.

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Roussos, Evanthia T; Wang, Yarong; Wyckoff, Jeffrey B; Sellers, Rani S; Wang, Weigang; Li, Jiufeng; Pollard, Jeffrey W; Gertler, Frank B; Condeelis, John S

2010-01-01

The actin binding protein Mammalian enabled (Mena), has been implicated in the metastatic progression of solid tumors in humans. Mena expression level in primary tumors is correlated with metastasis in breast, cervical, colorectal and pancreatic cancers. Cells expressing high Mena levels are part of the tumor microenvironment for metastasis (TMEM), an anatomical structure that is predictive for risk of breast cancer metastasis. Previously we have shown that forced expression of Mena adenocarcinoma cells enhances invasion and metastasis in xenograft mice. Whether Mena is required for tumor progression is still unknown. Here we report the effects of Mena deficiency on tumor progression, metastasis and on normal mammary gland development. To investigate the role of Mena in tumor progression and metastasis, Mena deficient mice were intercrossed with mice carrying a transgene expressing the polyoma middle T oncoprotein, driven by the mouse mammary tumor virus. The progeny were investigated for the effects of Mena deficiency on tumor progression via staging of primary mammary tumors and by evaluation of morbidity. Stages of metastatic progression were investigated using an in vivo invasion assay, intravital multiphoton microscopy, circulating tumor cell burden, and lung metastases. Mammary gland development was studied in whole mount mammary glands of wild type and Mena deficient mice. Mena deficiency decreased morbidity and metastatic dissemination. Loss of Mena increased mammary tumor latency but had no affect on mammary tumor burden or histologic progression to carcinoma. Elimination of Mena also significantly decreased epidermal growth factor (EGF) induced in vivo invasion, in vivo motility, intravasation and metastasis. Non-tumor bearing mice deficient for Mena also showed defects in mammary gland terminal end bud formation and branching. Deficiency of Mena decreases metastasis by slowing tumor progression and reducing tumor cell invasion and intravasation. Mena

Abalone visceral extract inhibit tumor growth and metastasis by modulating Cox-2 levels and CD8+ T cell activity

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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.

Abalone visceral extract inhibit tumor growth and metastasis by modulating Cox-2 levels and CD8+ T cell activity.

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Lee, Choong-Gu; Kwon, Ho-Keun; Ryu, Jae Ha; Kang, Sung Jin; Im, Chang-Rok; Ii Kim, Jae; Im, Sin-Hyeog

2010-10-20

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. 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. 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. 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.

Metástasis hipofisaria Hypophyseal metastasis

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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.

Gigantol Inhibits Epithelial to Mesenchymal Process in Human Lung Cancer Cells

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Thitita Unahabhokha

2016-01-01

Full Text Available Lung cancer remains a leading public health problem as evidenced by its increasing death rate. The main cause of death in lung cancer patients is cancer metastasis. The metastatic behavior of lung cancer cells becomes enhanced when cancer cells undergo epithelial to mesenchymal transition (EMT. Gigantol, a bibenzyl compound extracted from the Thai orchid, Dendrobium draconis, has been shown to have promising therapeutic potential against cancer cells, which leads to the hypothesis that gigantol may be able to inhibit the fundamental EMT process in cancer cells. This study has demonstrated for the first time that gigantol possesses the ability to suppress EMT in non-small cell lung cancer H460 cells. Western blot analysis has revealed that gigantol attenuates the activity of ATP-dependent tyrosine kinase (AKT, thereby inhibiting the expression of the major EMT transcription factor, Slug, by both decreasing its transcription and increasing its degradation. The inhibitory effects of gigantol on EMT result in a decrease in the level of migration in H460 lung cancer cells. The results of this study emphasize the potential of gigantol for further development against lung cancer metastasis.

The diagnostic utility of ultrasonography, CT and PET/CT for the preoperative evaluation of cervical lymph node metastasis inpapillary thyroid cancer patients

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Kim Young Sang; Lee, Tae Hyun; Park, Dong Hee

2016-01-01

To compare the diagnostic utility of ultrasonography (US), CT and positron emission tomography/CT (PET/CT) in the preoperative evaluation of cervical lymph node metastasis in patients with papillary thyroid carcinoma. The study population consisted of 300 patients with pathologically diagnosed papillary thyroid carcinoma after thyroidectomy and neck dissection. Preoperative US, CT, and PET/CT findings were compared with pathologic outcomes after thyroidectomy and neck dissection. Sensitivity in detecting central lymph node metastasis (US 29.9%, CT 27.9%, PET/CT 18.8%) was lower than that for lateral lymph node metastasis (US 56.3%, CT 66.2%, PET/CT 43.7%). Specificity in detecting central lymph node metastasis (US 80.6%, CT 77.7%, PET/CT 83.0%) was lower than that for lateral lymph node metastasis (US 96.8%, CT 80.6%, PET/CT 95.2%). The combination of US and CT had higher specificity (77.3%) and higher sensitivity (33.1%) than US alone. PET/CT has no significant additional benefit over the combination of US and CT. In preoperative evaluations of neck lymph node metastasis, US and CT and PET/CT are more useful in lateral lymph node areas than in central lymph node areas. The combination of US and CT has higher sensitivity than US alone

The diagnostic utility of ultrasonography, CT and PET/CT for the preoperative evaluation of cervical lymph node metastasis inpapillary thyroid cancer patients

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Kim Young Sang; Lee, Tae Hyun; Park, Dong Hee [Dept. of Radiology, Korea Cancer Center Hospital, Seoul (Korea, Republic of)

2016-08-15

To compare the diagnostic utility of ultrasonography (US), CT and positron emission tomography/CT (PET/CT) in the preoperative evaluation of cervical lymph node metastasis in patients with papillary thyroid carcinoma. The study population consisted of 300 patients with pathologically diagnosed papillary thyroid carcinoma after thyroidectomy and neck dissection. Preoperative US, CT, and PET/CT findings were compared with pathologic outcomes after thyroidectomy and neck dissection. Sensitivity in detecting central lymph node metastasis (US 29.9%, CT 27.9%, PET/CT 18.8%) was lower than that for lateral lymph node metastasis (US 56.3%, CT 66.2%, PET/CT 43.7%). Specificity in detecting central lymph node metastasis (US 80.6%, CT 77.7%, PET/CT 83.0%) was lower than that for lateral lymph node metastasis (US 96.8%, CT 80.6%, PET/CT 95.2%). The combination of US and CT had higher specificity (77.3%) and higher sensitivity (33.1%) than US alone. PET/CT has no significant additional benefit over the combination of US and CT. In preoperative evaluations of neck lymph node metastasis, US and CT and PET/CT are more useful in lateral lymph node areas than in central lymph node areas. The combination of US and CT has higher sensitivity than US alone.

Pivotal role of oxidative stress in tumor metastasis under diabetic conditions in mice.

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Ikemura, Mai; Nishikawa, Makiya; Kusamori, Kosuke; Fukuoka, Miho; Yamashita, Fumiyoshi; Hashida, Mitsuru

2013-09-10

Diabetic patients are reported to have a high incidence and mortality of cancer, but little is known about the linkage. In this study, we investigated whether high oxidative stress is involved in the acceleration of tumor metastasis in diabetic mice. Murine melanoma B16-BL6 cells stably labeled with firefly luciferase (B16-BL6/Luc) were inoculated into the tail vein of streptozotocin (STZ)-treated or untreated mice. A luciferase assay demonstrated that tumor cells were present largely in the lung of untreated mice, whereas large numbers of tumor cells were detected in both the lung and liver of STZ-treated mice. Repeated injections of polyethylene glycol-conjugated catalase (PEG-catalase), a long-circulating derivative, reduced the elevated fasting blood glucose levels and plasma lipoperoxide levels of STZ-treated mice, but had no significant effects on these parameters in untreated mice. In addition, the injections significantly reduced the number of tumor cells in the lung and liver in both untreated and STZ-treated mice. Culture of B16-BL6/Luc cells in medium containing over 45 mg/dl glucose hardly affected the proliferation of the cells, whereas the addition of plasma of STZ-treated mice to the medium significantly increased the number of cells. Plasma samples of STZ-treated mice receiving PEG-catalase exhibited no such effect on proliferation. These findings indicate that a hyperglycemia-induced increase in oxidative stress is involved in the acceleration of tumor metastasis, and the removal of systemic hydrogen peroxide by PEG-catalase can inhibit the progression of diabetic conditions and tumor metastasis in diabetes. Copyright © 2013 Elsevier B.V. All rights reserved.

Hypofractionated stereotactic radiotherapy for malignant tumors of the lung

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О. Ю. Аникеева

2015-10-01

Full Text Available Hypofractionated stereotactic radiotherapy was used for 26 patients at medically inoperable stage I of non-small cell lung cancer with dose escalation of 48-54 Gy prescribed at 90 or 95% isodose level in 3-4 fractions. Nine-months local control and cancer-specific survival were 82.0 and 66.8% respectively, with minimal toxicity. For metastatic lung tumors local control was obtained in 92% cases. Hypofractionated stereotactic radiation therapy (SBRT is safe and feasible for the treatment of inoperable primary lung cancer and single lung metastasis.

CXCR4-mediated osteosarcoma growth and pulmonary metastasis is promoted by mesenchymal stem cells through VEGF.

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Zhang, Peng; Dong, Ling; Yan, Kang; Long, Hua; Yang, Tong-Tao; Dong, Ming-Qing; Zhou, Yong; Fan, Qing-Yu; Ma, Bao-An

2013-10-01

Chemokines and chemokine receptor 4 (CXCR4) play an important role in metastasis. CXCR4 is also expressed in the human osteosarcoma cell line 9607-F5M2 (F5M2), which has a high tumorigenic ability and potential for spontaneous pulmonary metastasis. Mesenchymal stem cells (MSCs) contribute to the formation of the tumor stroma and promote metastasis. However, mechanisms underlying the promotion of osteosarcoma growth and pulmonary metastasis by MSCs are still elusive. Our study co-injected the human MSCs and F5M2 cells into the caudal vein of nude mice. The total number of tumor nodules per lung was significantly increased in the F5M2+MSC group compared to the other groups (control, F5M2 cells alone and MSCs alone) at week six. Moreover, a high number of Dil-labeled MSCs was present also at the osteosarcoma metastasis sites in the lung. Using Transwell assays, we found that F5M2 cells migrate towards MSCs, while the CXCR4 inhibitor AMD3100 decreased the migration potential of F5M2 cells towards MSCs. Furthermore, upon treatment with F5M2-conditioned medium, MSCs expressed and secreted higher levels of VEGF as determined by immunohistochemistry, western blotting and ELISA, respectively. Importantly, co-cultured with F5M2 cells, MSCs expressed and secreted higher VEGF levels, while AMD3100 dramatically decreased the VEGF secretion by MSCs. However, CXCR4 expression on F5M2 cells was not significantly increased in the co-culture system. Additionally, VEGF increased the proliferation of both MSCs and F5M2 cells. These findings suggest that CXCR4-mediated osteosarcoma growth and pulmonary metastasis are promoted by MSCs through VEGF.

Appendicitis complicated by appendiceal metastasis via peritoneal dissemination from lung cancer

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Shiota, Naoki; Furonaka, Makoto; Kikutani, Kazuya; Haji, Keiko; Fujisaki, Seiji; Nishida, Toshihiro

2016-01-01

Abstract Peritoneal disseminations from lung cancer are difficult to detect during the patient's clinical course. Therefore, complications of this condition are unclear. We report a case in which peritoneal dissemination from lung cancer complicated appendicitis. A 74?year?old man with lung cancer who was receiving maintenance therapy presented at our hospital because of abdominal pain. It was the seventh day after the 14th cycle of maintenance therapy with bevacizumab. He was diagnosed with ...

Presence of lung metastases in bitches affected by malignant mammary neoplasms in Medellin (Colombia

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Brigitte Gómez J.

2012-08-01

Full Text Available Objective. To define the presence of lung metastasis in bitches with malignant mammary neoplasms. Materials and methods. Thirty female dogs that were attended at Veterinary Hospital (University of Antioquia, Medellin, Colombia were selected for the study. At consultation clinical variables and grade of mammary and inguinal lymph node compromise were registered. Latero-lateral and ventral-dorsal radiographic images of thorax were done for identification of radiographic lesions suggestive of lung metastasis. At surgery biopsies of affected mammary glands were taken for histopathological study and classification of tumors. Data were analyzed by descriptive statistics. Results. The average (± standard error age at clinical diagnosis was 10.87±2.65 year old. French poodle (46.6% cross-breed (13.3% and Schnauzer (10% were the breeds most frequently affected by mammary tumors. The most frequent tumor found was carcinoma (81%, followed by adenoma (8.1%, and other types (10.8%. The most frequently affected mammary glands by tumors were the right and the left inguinal glands (70% and 66.6%, respectively. Five out of 30 bitches (16.6% had lung metastasis according to radiographic examination. From this group of dogs, 4 out of 5 neoplasms (80% were diagnosed as complex carcinoma by histopathology diagnosis. Conclusions. We provide evidence suggesting that complex carcinoma is the most frequent mammary tumor in bitches in our city and it is highly related to lung metastasis.

Metastasis of hepatocellular carcinoma to the heart: unusual patterns in three cases with antemortem diagnosis.

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Lei, M H; Ko, Y L; Kuan, P; Lien, W P; Chen, D S

1992-04-01

Unusual patterns of cardiac metastasis were noted in three cases of hepatocellular carcinoma (HCC): one patient was noted to have a large right ventricular (RV) tumor mass with intracavitary growth and myocardial invasion; the second had massive pulmonary and left atrial (LA) metastasis; and the third patient had a right atrial tumor mass with concomitant RV and LA involvement. Tumor implantation to the RV without right atrial involvement and extensive myocardial invasion is unusual in HCC. The LA involvement is probably related to tumor growth from the pulmonary veins following massive metastasis to the lung, direct invasion of the atrial septum or tumor implantation via a subclinical right-to-left shunt through the patent foramen ovale. To the best of our knowledge, such unusual intracavitary metastases in HCC have not been reported previously. Cardiac metastasis, without local gross recurrence, may be one of the presentations after lobectomy in patients with HCC.

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

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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.

Esophageal Metastasis From Occult Lung Cancer

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Po-Kuei Hsu

2010-06-01

Full Text Available A 66-year-old man with dysphagia was found to have a poorly differentiated esophageal carcinoma by incision biopsy. Following esophagectomy, reconstruction with a gastric tube was performed. Pathological examination and immunohisto-chemistry showed infiltration of adenocarcinoma cells with positive thyroid transcription factor 1-staining in the submucosal layer, which indicated metastatic esophageal carcinoma. Although no pulmonary lesion could be visualized by imaging or bronchoscopy, pulmonary origin was highly suspected as a result of positive thyroid transcription factor 1-staining. To the best of our knowledge, this is the first reported case of metastatic esophageal carcinoma from occult lung cancer (AJCC TNM stage TX.

Modelling pulmonary microthrombosis coupled to metastasis: distinct effects of thrombogenesis on tumorigenesis

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Colin E. Evans

2017-05-01

Full Text Available Thrombosis can cause localized ischemia and tissue hypoxia, and both of these are linked to cancer metastasis. Vascular micro-occlusion can occur as a result of arrest of circulating tumour cells in small capillaries, giving rise to microthrombotic events that affect flow, creating localized hypoxic regions. To better understand the association between metastasis and thrombotic events, we generated an experimental strategy whereby we modelled the effect of microvascular occlusion in metastatic efficiency by using inert microbeads to obstruct lung microvasculature before, during and after intravenous tumour cell injection. We found that controlled induction of a specific number of these microthrombotic insults in the lungs caused an increase in expression of the hypoxia-inducible transcription factors (HIFs, a pro-angiogenic and pro-tumorigenic environment, as well as an increase in myeloid cell infiltration. Induction of pulmonary microthrombosis prior to introduction of tumour cells to the lungs had no effect on tumorigenic success, but thrombosis at the time of tumour cell seeding increased number and size of tumours in the lung, and this effect was strikingly more pronounced when the micro-occlusion occurred on the day following introduction of tumour cells. The tumorigenic effect of microbead treatment was seen even when thrombosis was induced five days after tumour cell injection. We also found positive correlations between thrombotic factors and expression of HIF2α in human tumours. The model system described here demonstrates the importance of thrombotic insult in metastatic success and can be used to improve understanding of thrombosis-associated tumorigenesis and its treatment.

Octamer-binding protein 4 affects the cell biology and phenotypic transition of lung cancer cells involving β-catenin/E-cadherin complex degradation.

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Chen, Zhong-Shu; Ling, Dong-Jin; Zhang, Yang-De; Feng, Jian-Xiong; Zhang, Xue-Yu; Shi, Tian-Sheng

2015-03-01

Clinical studies have reported evidence for the involvement of octamer‑binding protein 4 (Oct4) in the tumorigenicity and progression of lung cancer; however, the role of Oct4 in lung cancer cell biology in vitro and its mechanism of action remain to be elucidated. Mortality among lung cancer patients is more frequently due to metastasis rather than their primary tumors. Epithelial‑mesenchymal transition (EMT) is a prominent biological event for the induction of epithelial cancer metastasis. The aim of the present study was to investigate whether Oct4 had the capacity to induce lung cancer cell metastasis via the promoting the EMT in vitro. Moreover, the effect of Oct4 on the β‑catenin/E‑cadherin complex, associated with EMT, was examined using immunofluorescence and immunoprecipitation assays as well as western blot analysis. The results demonstrated that Oct4 enhanced cell invasion and adhesion accompanied by the downregulation of epithelial marker cytokeratin, and upregulation of the mesenchymal markers vimentin and N‑cadherin. Furthermore, Oct4 induced EMT of lung cancer cells by promoting β‑catenin/E‑cadherin complex degradation and regulating nuclear localization of β‑catenin. In conclusion, the present study indicated that Oct4 affected the cell biology of lung cancer cells in vitro through promoting lung cancer cell metastasis via EMT; in addition, the results suggested that the association and degradation of the β‑catenin/E‑cadherin complex was regulated by Oct4 during the process of EMT.

GHGKHKNK Octapeptide (P-5m Inhibits Metastasis of HCCLM3 Cell Lines via Regulation of MMP-2 Expression in in Vitro and in Vivo Studies

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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.

Novel chemokine-like activities of histones in tumor metastasis.

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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.

Testicular Metastasis from Renal Cell Carcinoma: A Case Report and Review of the Literature

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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.

[Macrophage colony stimulating factor enhances non-small cell lung cancer invasion and metastasis by promoting macrophage M2 polarization].

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Li, Y J; Yang, L; Wang, L P; Zhang, Y

2017-06-23

Objective: To investigate the key cytokine which polarizes M2 macrophages and promotes invasion and metastasis in non-small cell lung cancer (NSCLC). Methods: After co-culture with A549 cells in vitro, the proportion of CD14(+) CD163(+) M2 macrophages in monocytes and macrophage colony stimulating factor (M-CSF) levels in culture supernatant were detected by flow cytometry, ELISA assay and real-time qPCR, respectively. The effects of CD14(+) CD163(+) M2 macrophages on invasion of A549 cells and angiogenesis of HUVEC cells were measured by transwell assay and tubule formation assay, respectively. The clinical and prognostic significance of M-CSF expression in NSCLC was further analyzed. Results: The percentage of CD14(+) CD163(+) M2 macrophages in monocytes and the concentration of M-CSF in the supernatant followed by co-culture was (12.03±0.46)% and (299.80±73.76)pg/ml, respectively, which were significantly higher than those in control group [(2.80±1.04)% and (43.07±11.22)pg/ml, respectively, P macrophages in vitro . M2 macrophages enhanced the invasion of A549 cells (66 cells/field vs. 26 cells/field) and the angiogenesis of HUVEC cells (22 tubes/field vs. 8 tubes/field). The mRNA expression of M-CSF in stage Ⅰ-Ⅱ patients (16.23±4.83) was significantly lower than that in stage Ⅲ-Ⅳ (53.84±16.08; P macrophages, which can further promote the metastasis and angiogenesis of NSCLC. M-CSF could be used as a potential therapeutic target of NSCLC.

Dual-time point scanning of integrated FDG PET/CT for the evaluation of mediastinal and hilar lymph nodes in non-small cell lung cancer diagnosed as operable by contrast-enhanced CT

International Nuclear Information System (INIS)

Kasai, Takami; Motoori, Ken; Horikoshi, Takuro; Uchiyama, Katsuhiro; Yasufuku, Kazuhiro; Takiguchi, Yuichi; Takahashi, Fumiaki; Kuniyasu, Yoshio; Ito, Hisao

2010-01-01

Purpose: To evaluate whether dual-time point scanning with integrated fluorine-18 fluorodeoxyglucose ( 18 F-FDG) positron emission tomography and computed tomography (PET/CT) is useful for evaluation of mediastinal and hilar lymph nodes in non-small cell lung cancer diagnosed as operable by contrast-enhanced CT. Materials and methods: PET/CT data and pathological findings of 560 nodal stations in 129 patients with pathologically proven non-small cell lung cancer diagnosed as operable by contrast-enhanced CT were reviewed retrospectively. Standardized uptake values (SUVs) on early scans (SUVe) 1 h, and on delayed scans (SUVd) 2 h after FDG injection of each nodal station were measured. Retention index (RI) (%) was calculated by subtracting SUVe from SUVd and dividing by SUVe. Logistic regression analysis was performed with seven kinds of models, consisting of (1) SUVe, (2) SUVd, (3) RI, (4) SUVe and SUVd, (5) SUVe and RI, (6) SUVd and RI, and (7) SUVe, SUVd and RI. The seven derived models were compared by receiver-operating characteristic (ROC) analysis. k-Fold cross-validation was performed with k values of 5 and 10. p < 0.05 was considered statistically significant. Results: Model (1) including the term of SUVe showed the largest area under the ROC curve among the seven models. The cut-off probability of metastasis of 3.5% with SUVe of 2.5 revealed a sensitivity of 78% and a specificity of 81% on ROC analysis, and approximately 60% and 80% on k-fold cross-validation. Conclusion: Single scanning of PET/CT is sufficiently useful for evaluating mediastinal and hilar nodes for metastasis.

Regional lung function evaluation with nitrogen-13

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Ahluwalia, B; Brownell, G L; Hales, C; Kazemi, H

1981-10-01

Regional ventilation and perfusion studies are routinely performed with molecular nitrogen-13 (a short-lived positron emitter), a multicrystal positron camera, and a computer. These studies have the advantage of viewing with equal sensitivity all sections of the lung simultaneously. Nitrogen-13 is less soluble than xenon in blood and therefore allows more accurate ventilation imaging. The short half-life of the radiopharmaceutical allows simultaneous ventilation and perfusion scintigraphy of the lung. Unlike other imaging techniques in which the residual radioactivity persists in the lung for hours, nitrogen-13 is rapidly cleared allowing repetitive imaging. Ventilation and perfusion studies are part of the routine preoperative evaluation for lung cancer resection or for bullectomy in patients with chronic obstructive pulmonary disease and for assessment of pulmonary emboli in the presence of chronic obstructive disease.

Advanced Research of Fibroblast Growth Factor Receptor 
in Non-small Cell Lung Cancer

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Dan PU

2013-11-01

Full Text Available Lung cancer is severely threatening human health. In recent years, the treatment for lung adenocarcinoma has made a great progress, targeted therapy has been widely applied in clinic, and benefits amount of patients. However, in squamous cell lung cancer, the incidence of epidermal growth factor receptor (EGFR gene mutant and ALK fusion gene are low,and targeted therapy like Tarceva and crizotinib, can hardly work. Since the fibroblast growth factors (fibroblast growth factor, FGF pathway is considered to be related to tumor cell proliferation, metastasis and angiogenesis, more and more researches proved the amplification of fibroblast growth factor receptor (FGFR in squamous cell lung cancer. Experiments in vivo and in vitro found that blocking FGF pathway could reduce the proliferation of tumor cells and inhibit metastasis. The FGF pathway might be a new target for treatment of squamous cell lung cancer. This article reviews the effect of FGFR in tumorigenesis,as well as the prospect as a therapeutic target in non-small cell lung cancer.

Expression and Clinical Significance of CD147 and MMP-2 
in Squamous Cell Carcinoma and Adenocarcinoma of the Lungs

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Siwen WANG

2011-09-01

Full Text Available Background and objective It has been proven that CD147 was an extracellular matrix metalloproteinase inducer reportedly involved in the invasion and metastasis of malignancies. The aim of this study is to investigate CD147 and MMP-2 expression in squamous cell carcinoma and adenocarcinoma of the lungs and to analyze their clinical significance. Methods Tissue samples from 55 patients with squamous cell carcinoma and adenocarcinoma of the lungs and their corresponding non-cancerous tissues were examined for CD147 and MMP-2 expression using immunohistochemistry. Results The positive expression rates of CD147 and MMP-2 in the squamous cell carcinoma and adenocarcinoma among the lung tissues were significantly higher than those in the corresponding normal lung tissues. Moreover, the CD147 and MMP-2 expression in squamous cell carcinoma and adenocarcinoma of the lungs were related to lymph node metastasis and TNM stages (P<0.05, but not to age, gender and histologic type (P>0.05. MMP-2 expression was highly correlated with CD147 expression. Conclusion CD147 and MMP-2 expression is correlated with the invasion and metastasis of squamous cell carcinoma and adenocarcinoma of the lungs and may be used as objective markers for predicting the behavior of squamous cell carcinoma and adenocarcinoma of the lungs.

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

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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.

Bone metastasis pattern in initial metastatic breast cancer: a population-based study

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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

Evaluation of image-guided helical tomotherapy for the retreatment of spinal metastasis

International Nuclear Information System (INIS)

Mahan, Stephen L.; Ramsey, Chester R.; Scaperoth, Daniel D.; Chase, Daniel J.; Byrne, Thomas E.

2005-01-01

Introduction: Patients with vertebral metastasis that receive radiation therapy are typically treated to the spinal cord tolerance dose. As such, it is difficult to successfully deliver a second course of radiation therapy for patients with overlapping treatment volumes. In this study, an image-guided helical tomotherapy system was evaluated for the retreatment of previously irradiated vertebral metastasis. Methods and Materials: Helical tomotherapy dose gradients and maximum cord doses were measured in a cylindrical phantom for geometric test cases with separations between the planning target volume (PTV) and the spinal cord organ at risk (OAR) of 2 mm, 4 mm, 6 mm, 8 mm, and 10 mm. Megavoltage computed tomography (CT) images were examined for their ability to localize spinal anatomy for positioning purposes by repeat imaging of the cervical spine in an anthropomorphic phantom. In addition to the phantom studies, 8 patients with cord compressions that had received previous radiation therapy were retreated to a mean dose of 28 Gy using conventional fractionation. Results and Discussion: Megavoltage CT images were capable of positioning an anthropomorphic phantom to within ±1.2 mm (2σ) superior-inferiorly and within ±0.6 mm (2σ) anterior-posteriorly and laterally. Dose gradients of 10% per mm were measured in phantom while PTV uniformity indices of less than 11% were maintained. The calculated maximum cord dose was 25% of the prescribed dose for a 10-mm PTV-to-OAR separation and 71% of the prescribed dose for a PTV-to-OAR separation of 2 mm. Eight patients total have been treated without radiation-induced myelopathy or any other adverse effects from treatment. Conclusions: A technique has been evaluated for the retreatment of vertebral metastasis using image-guided helical tomotherapy. Phantom and patient studies indicated that a tomotherapy system is capable of delivering dose gradients of 10% per mm and positioning the patient within 1.2 mm without the use of

{sup 68}Ga Labeling of DOTMP using Freeze-dried Kit for the Imaging of Bone Metastasis

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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.

Serum long non coding RNA MALAT-1 protected by exosomes is up-regulated and promotes cell proliferation and migration in non-small cell lung cancer.

Science.gov (United States)

Zhang, Rui; Xia, Yuhong; Wang, Zhixin; Zheng, Jie; Chen, Yafei; Li, Xiaoli; Wang, Yu; Ming, Huaikun

2017-08-19

Circulating lncRNAs have been defined as a novel biomarker for non-small cell lung cancer (NSCLC), MALAT-1 was first identified lncRNA that was related to lung cancer metastasis. However, the relationship between exosomal lncRNAs and the diagnosis and prognosis of NSCLC was poorly understood. The aim of this study is to evaluate the clinical significance of serum exosomal MALAT-1 as a biomarker in the metastasis of NSCLC. In this study, we firstly isolated the exosomes from healthy subjects and NSCLC patients. Then we measured the expression levels of MALAT-1 contained in exosomes, and found that exosomal MALAT-1 was highly expressed in NSCLC patients, more importantly, the levels of exosomal MALAT-1 were positively associated with tumor stage and lymphatic metastasis. In addition, we decreased MALAT-1 expression by short hairpin RNA and conducted a series of assays including MTT, cell cycle, colony formation, wound-healing scratch and Annexin/V PI by flow cytometry in human lung cancer cell lines. These in vitro studies demonstrated that serum exosome-derived long noncoding RNA MALAT-1 promoted the tumor growth and migration, and prevented tumor cells from apoptosis in lung cancer cell lines. Taken together, this study shed a light on utilizing MALAT-1 in exosomes as a non-invasive serum-based tumor biomarker for diagnosis and prognosis of NSCLC. Copyright © 2017 Elsevier Inc. All rights reserved.

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

A Case Report of Intraocular Metastasis Treated with Radiotherapy

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Kim, Ok Bae; Byun, Sang Jun; Kim, Kwang Soo; Kim, Jin Hee [Keimyung University School of Medicine, Daegu (Korea, Republic of); Lee, Ho Jun [Daegu Catholic University School of Medicine, Daegu (Korea, Republic of)

2009-09-15

Intraocular metastasis is the most common malignancy of the eye. The frequency of intraocular metastasis in all the patients dying of cancer is about 12% and ocular metastases will be detected more frequently in the future because the patients with malignant tumor are now living longer. Intraocular metastasis can cause a serious clinical problem such as blindness. The early recognition and treatment of intraocular metastasis are very important clinical oncologic issues to maintain vision and to maximize the quality of life. However, significance of intraocular metastasis is still under-evaluated for practicing oncologists. External beam radiotherapy is a safe, effective palliative treatment in terms of preserving both the vision and the eye globe.

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....

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.

CT findings of solitary intracranial metastasis

International Nuclear Information System (INIS)

Suh, Dae Chul; Lee, Kyung Soo; Chang, Kee Hyun

1987-01-01

The authors retrospectively reviewed and analyzed CT scans of fifty patients with solitary intracranial lesion selected from 118 patients who had been confirmed to have intracranial metastasis from 1979 to 1985. The results were as follows: 1. The most common primary tumors with solitary metastasis, in order of frequency, were lung cancer, breast cancer, choriocarcinoma, colon cancer, lymphoma and others. 2. Precontrast scans obtained in 35 cases showed cystic very low density in 20%, slightly low density in 9%, isodensity in 20%, high density in 51% when he densities of the lesions were compared with that of the normal brain tissue. 3. After contrast enhancement 43 out of 50 showed one of 4 patterns of enhancement. Homogeneous enhancement without necrosis were found in 26%, homogeneous enhancement with necrosis in 18%, ring-enhancement in 26% and irregular enhancement in 16%. No enhancement was found in 14%. 4. The locations of the metastatic lesions were intra axial in 45 and extra axial in 5. Among the intra axial lesions, the parietal lobe was the most common location. Extra axial metastases were epidural, calvarial and leptomeningeal. 5. Degrees of surrounding edema were mild in 32%, moderate in 19% and severe in 49%

Patterns of Intraosseous Recurrence After Stereotactic Body Radiation Therapy for Coxal Bone Metastasis.

Science.gov (United States)

Ito, Kei; Shimizuguchi, Takuya; Nihei, Keiji; Furuya, Tomohisa; Ogawa, Hiroaki; Tanaka, Hiroshi; Sasai, Keisuke; Karasawa, Katsuyuki

2018-01-01

To analyze the detailed pattern of intraosseous failure after stereotactic body radiation therapy (SBRT) for coxal bone metastasis. Patients treated with SBRT to coxal bone metastasis were identified by retrospective chart review. The SBRT doses were 30 Gy or 35 Gy in 5 fractions. A margin of 5 to 10 mm was added to the gross tumor volume to create the clinical target volume. We evaluated the presence or absence of intraosseous recurrence using magnetic resonance imaging. Intraosseous recurrences were assessed as "in-field" or "marginal/out-of-field." In addition, we measured the distance between the center of the recurrent tumor and the nearest edge of the initial bone metastasis in cases of marginal/out-of-field recurrence. Seventeen patients treated for 17 coxal bone metastases were included. Median age was 64 years (range, 48-79 years). Coxal lesions involved the ilium in 14 cases, pubis in 3, and ischium in 4 (3 lesions crossed over multiple regions). Patients most commonly had renal cell carcinoma (29.4%), followed by lung, hepatic cell, and colorectal cancers (23.5%, 11.8%, and 11.8%, respectively). Median follow-up after SBRT was 13 months (range, 2-44 months). Among all 17 cases, 7 cases developed 8 intraosseous recurrences, including in-field recurrence in 1 case and marginal/out-of-field recurrences in 7 cases. Median time to intraosseous recurrence was 10 months (range, 2-35 months). Among 7 cases with marginal/out-of-field recurrence, mean distance to the center of the recurrent tumor from the nearest edge of the initial bone metastasis was 34 mm (range, 15-55 mm). Most recurrences were observed out-of-field in the same coxal bone. These results suggest that defining the optimal clinical target volume in SBRT for coxal bone metastasis to obtain sufficient local tumor control is difficult. Copyright © 2017 Elsevier Inc. All rights reserved.

Cutaneous metastasis to the face from lung adenocarcinoma ...

African Journals Online (AJOL)

Cutaneous metastases in the facial region occur in less than 0.5% of patients with metastatic cancer, and they usually originate from malignant melanoma. In this report, we describe an unusual case of lung adenocarcinoma metastasizing to his face at the time of initial diagnosis. The patient was 64-year-old man, a heavy ...

Postoperative Radiation Therapy in Resected N2 Stage Non-Small Cell Lung Cancer

International Nuclear Information System (INIS)

Lee, Chang Geol

1993-01-01

A total of forty patients with resected N2 stage non-small cell lung cancer treated with postoperative adjuvant radiation therapy between Jan. 1975 and Dec. 1990 at the Department of Radiation Oncology, Yonsei University College of Medicine, Yonsei Cancer Center were retrospectively analysed to evaluate whether postoperative radiation therapy improves survival. Patterns of failure and prognostic factors affecting survival were also analysed. The 5 year overall and disease free survival rate were 26.3%, 27.3% and median survival 23.5 months. The 5 year survival rates by T-stage were T1 66.7%, T2 25.6% and T3 12.5%. Loco-regional failure rate was 14.3% and distant metastasis rate was 42.9% and both 2.9%. Statistically significant factor affecting distant failure rate was number of positive lymph nodes(>= 4). This retrospective study suggests that postoperative radiation therapy in resected N2 stage non-small cell lung cancer can reduce loco-regional recurrence and may improve survival rate as compared with other studies which were treated by surgery alone. Further study of systemic control is also needed due to high rate of distant metastasis

CD147 deficiency blocks IL-8 secretion and inhibits lung cancer-induced osteoclastogenesis

International Nuclear Information System (INIS)

Wang, Hongkai; Zhuo, Yunyun; Hu, Xu; Shen, Weiwei; Zhang, Ying; Chu, Tongwei

2015-01-01

Bone is a frequent target of lung cancer metastasis, which is associated with significant morbidity and poor prognosis; however, the molecular basis of this process is still unknown. This study investigated the role of extracellular matrix metalloproteinase inducer (also known as cluster of differentiation (CD)147) in osteoclastogenesis resulting from bone metastasis, based on the enrichment of this glycoprotein on the surface of many malignant bone tumors. RNA interference was used to silence CD147 expression in A549 human lung cancer cells. Compared with conditioned medium (CM) from control cells (A549-CM), CM from CD147-deficient cells (A549-si-CM) suppressed receptor activator of nuclear factor κB ligand-stimulated osteoclastogenesis in RAW 264.7 cells and bone marrow-derived macrophages. The mRNA levels of osteoclast-specific genes such as tartrate-resistant acid phosphatase, calcitonin receptor, and cathepsin K were also reduced in the presence of A549-si-CM. CD147 knockdown in A549 cells decreased interleukin (IL)-8mRNA and protein expression. IL-8 is present in large amounts in A549-CM and mimicked its inductive effect on osteoclastogenesis; this was reversed by depletion of IL-8 from the medium. Taken together, these results indicate that CD147 promotes lung cancer-induced osteoclastogenesis by modulating IL-8 secretion, and suggest that CD147 is a potential therapeutic target for cancer-associated bone resorption in lung cancer patients. - Highlights: • Bone loss frequently results from lung cancer metastasis. • Cluster of differentiation (CD)147 was depleted in A549 lung adenocarcinoma cells. • RAW 264.7 cell osteoclastogenesis was blocked by medium from CD147-deficient cells. • Interleukin (IL)-8 level was reduced in the conditioned medium. • Osteoclastogenesis induced by lung tumor cells requires CD147-mediated IL-8 release

CD147 deficiency blocks IL-8 secretion and inhibits lung cancer-induced osteoclastogenesis

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Wang, Hongkai; Zhuo, Yunyun; Hu, Xu; Shen, Weiwei; Zhang, Ying; Chu, Tongwei, E-mail: chtw@sina.com

2015-03-06

Bone is a frequent target of lung cancer metastasis, which is associated with significant morbidity and poor prognosis; however, the molecular basis of this process is still unknown. This study investigated the role of extracellular matrix metalloproteinase inducer (also known as cluster of differentiation (CD)147) in osteoclastogenesis resulting from bone metastasis, based on the enrichment of this glycoprotein on the surface of many malignant bone tumors. RNA interference was used to silence CD147 expression in A549 human lung cancer cells. Compared with conditioned medium (CM) from control cells (A549-CM), CM from CD147-deficient cells (A549-si-CM) suppressed receptor activator of nuclear factor κB ligand-stimulated osteoclastogenesis in RAW 264.7 cells and bone marrow-derived macrophages. The mRNA levels of osteoclast-specific genes such as tartrate-resistant acid phosphatase, calcitonin receptor, and cathepsin K were also reduced in the presence of A549-si-CM. CD147 knockdown in A549 cells decreased interleukin (IL)-8mRNA and protein expression. IL-8 is present in large amounts in A549-CM and mimicked its inductive effect on osteoclastogenesis; this was reversed by depletion of IL-8 from the medium. Taken together, these results indicate that CD147 promotes lung cancer-induced osteoclastogenesis by modulating IL-8 secretion, and suggest that CD147 is a potential therapeutic target for cancer-associated bone resorption in lung cancer patients. - Highlights: • Bone loss frequently results from lung cancer metastasis. • Cluster of differentiation (CD)147 was depleted in A549 lung adenocarcinoma cells. • RAW 264.7 cell osteoclastogenesis was blocked by medium from CD147-deficient cells. • Interleukin (IL)-8 level was reduced in the conditioned medium. • Osteoclastogenesis induced by lung tumor cells requires CD147-mediated IL-8 release.

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.

Evaluation of 18F-FDG PET/CT Parameters for Detection of Lymph Node Metastasis in Cutaneous Melanoma.

Science.gov (United States)

Cha, Jongtae; Kim, Soyoung; Wang, Jiyoung; Yun, Mijin; Cho, Arthur

2018-02-01

The purpose of this study was to investigate the value of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) parameters in the detection of regional lymph node (LN) metastasis in patients with cutaneous melanoma. We evaluated patients with cutaneous melanoma who underwent FDG PET/CT for initial staging or recurrence evaluation. A total of 103 patients were enrolled, and 165 LNs were evaluated. LNs that were confirmed pathologically or by follow-up imaging were included in this study. PET parameters, including maximum standardized uptake value (SUVmax), total lesion glycolysis and tumour-to-liver ratio, were used to determine the presence of metastases, and the results were compared with CT-determined LN metastasis. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off values of the FDG PET parameters. A total of 93 LNs were malignant, and 84 LNs were smaller than 10 mm. In all 165 LNs, an SUVmax of >2.51 showed a sensitivity of 73.1%, a specificity of 88.9%, and an accuracy of 80.0% in detecting metastatic LNs. CT showed a higher specificity (87.3%) and lower accuracy (65.5%). For non-enlarged regional LNs (2.4 showed a high sensitivity (91%) and accuracy (89%) in detecting metastasis in LNs ≥1 cm, and LNs <1 cm with an SUVmax <1.4 were likely to be benign.

[Malignant nonepithelial tumors of the lung].

Science.gov (United States)

Trakhtenberg, A Kh; Biriukov, Iu V; Frank, G A; Kunitsyn, A G; Grigor'eva, S P; Aĭtakov, Z N; Korenev, S V; Efimova, O Iu; Vial'tsev, N V

1990-01-01

The main peculiarities of the clinical course of lung sarcoma were determined from representative material of 134 patients. The main features differentiating malignant nonepithelial tumors from carcinoma of the lung are: younger age (average age 45.5 years), predominantly peripheral clinico-anatomical form (82.8%), and prevalent hematogenic metastasis. Five-year survival in the whole group of patients after surgical treatment was 54%. The size and histological form of the tumor are the main factors of prognosis. The degree of differentiation acquires prognostic significance in tumors measuring more than 3 cm in diameter.

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.

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.

Lung uptake in bone scan - Two case reports

International Nuclear Information System (INIS)

Nahar, N.; Kabir, F.; Islam, N.; Karim, M.A.

2001-01-01

Breast cancer is the 2nd most common cancer in female in our country. When a case of breast cancer is diagnosed a base line bone scan is asked for to exclude skeletal metastasis. This helps for treatment planning and future follow up. Scan pattern in bone metastasis is usually multiple, randomly distributed foci of intensely increased tracer accumulation. Uptake of radio pharmaceutical in breast tissue is frequently observed. Kidneys are another extra skeletal organs through which 99m Tc-MDP is excreted and that's why normal kidneys are faintly visualized in delayed views suggesting normal exertion of tracer. If there is any outflow obstruction in any kidney, it will show hold up of radiotracer on that side. Often radiopharmaceuticals are seen to accumulate in other organs like lungs. Here two cases of breast cancer are discussed where bone scan shows significant uptake of tracer in lungs

DNA polymerase iota (Pol ι) promotes invasion and metastasis of esophageal squamous cell carcinoma.

Science.gov (United States)

Zou, Shitao; Shang, Zeng-Fu; Liu, Biao; Zhang, Shuyu; Wu, Jinchang; Huang, Min; Ding, Wei-Qun; Zhou, Jundong

2016-05-31

DNA polymerase iota (Pol ι) is an error-prone DNA polymerase involved in translesion DNA synthesis (TLS) that contributes to the accumulation of DNA mutations. We recently showed that Pol ι is overexpressed in human esophageal squamous cell cancer (ESCC) tissues which promotes ESCC' progression. The present study was aimed at investigating the molecular mechanisms by which Pol ι enhances the invasiveness and metastasis of ESCC cells. We found that the expression of Pol ι is significantly higher in ESCCs with lymph node metastasis compared to those without lymph node metastasis. Kaplan-Meier analysis revealed an inverse correlation between Pol ι expression and patient prognosis. The expression levels of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), two essential regulators of cells' invasiveness, were positively associated with Pol ι expression in ESCC tissues. Ectopic expression of Pol ι enhanced the motility and invasiveness of ESCC cells as evaluated by wound-healing and transwell assays, respectively. A xenograft nude mouse model showed that Pol ι promotes the colonization of ESCC cells in the liver, lung and kidney. Signaling pathway analysis identified the JNK-AP-1 cascade as a mediator of the Pol ι-induced increase in the expression of MMP-2/9 and enhancement of ESCC progression. These data demonstrate the underlying mechanism by which Pol ι promotes ESCC progression, suggesting that Pol ι is a potential novel prognostic biomarker and therapeutic target for ESCC.

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...

Non-small cell lung cancer brain metastasis screening in the era of positron emission tomography-CT staging: Current practice and outcomes.

Science.gov (United States)

Diaz, Mauricio E; Debowski, Maciej; Hukins, Craig; Fielding, David; Fong, Kwun M; Bettington, Catherine S

2018-05-10

Several clinical guidelines indicate that brain metastasis screening (BMS) should be guided by disease stage in non-small cell lung cancer (NSCLC). We estimate that screening is performed more broadly in practice, and patients undergo brain imaging at considerable cost with questionable benefit. Our aim was to quantify the use and detection rate of BMS in a contemporary cohort staged with 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (PET-CT). We conducted a retrospective review of prospectively collected data from three major lung cancer referral centres in Brisbane between January 2011 and December 2015. Patients included had a new diagnosis of NSCLC and had undergone a PET-CT to stage extra-cranial disease. BMS was defined as dedicated brain imaging with contrast-enhanced computed tomography (CE-CT) or magnetic resonance (MR), in the absence of clinically apparent neurological deficits. A total of 1751 eligible cases were identified and of these 718 (41%) underwent BMS. The majority had CE-CT imaging (n = 703). Asymptomatic brain metastases (BM) were detected in 18 patients (2.5%). Of these patients, 12 had concurrent non-brain metastases. Only six patients (0.8%) had BM alone. The rate of detection increased with N-stage (P = 0.02) and overall stage (P < 0.001). It was 0.5%, 1%, 1.6% and 7.3% for stage I, II, III and IV respectively. The overall screening rate increased with T-stage (P = 0.001), N-Stage (P < 0.001) and overall stage (P < 0.001). Non-small cell lung cancer BMS practices remain at odds with published guidelines. The low number of occult BMs detected supports the existing international recommendations. Rationalising BMS would minimise the burden on patients and the health care system. © 2018 The Royal Australian and New Zealand College of Radiologists.

Quantitative and regional evaluation methods for lung scintigraphs

International Nuclear Information System (INIS)

Fichter, J.

1982-01-01

For the evaluation of perfusion lung scintigraphs with regard to the quantitative valuation and also with regard to the choice of the regions new criteria were presented. In addition to the usual methods of sectioning each lung lobe into upper, middle and lower level and the determination of the per cent activity share of the total activity the following values were established: the median of the activity distribution and the differences of the per cent counting rate as well as of the median of the corresponding regions of the right and left lung. The individual regions should describe the functional structures (lobe and segment structure). A corresponding computer program takes over the projection of lobe and segment regions in a simplified form onto the scintigraph with consideration of individual lung stretching. With the help of a clinical study on 60 patients and 18 control persons with 99mTc-MAA and 133 Xe-gas lung scintigraphs the following results could be determined: depending on the combination of the 32 parameters available for evaluation and the choice of regions between 4 and 20 of the 60 patients were falsely negatively classified and 1 to 2 of the 18 controls were falsely positive. The accuracy of the Tc-scintigraph proved to be better. All together using the best possible parameter combinations comparative results were attained. (TRV) [de

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.

Dual-time point scanning of integrated FDG PET/CT for the evaluation of mediastinal and hilar lymph nodes in non-small cell lung cancer diagnosed as operable by contrast-enhanced CT

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Kasai, Takami, E-mail: takaby@hotmail.co [Department of Radiology, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba-ken 260-8677 (Japan); Motoori, Ken, E-mail: motoorik@faculty.chiba-u.j [Department of Radiology, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba-ken 260-8677 (Japan); Horikoshi, Takuro, E-mail: taku_steelfish@yahoo.co.j [Department of Radiology, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba-ken 260-8677 (Japan); Uchiyama, Katsuhiro, E-mail: ka-uchiyama@nifty.co [Diagnostic PET Imaging Center, Department of Radiology, Sannoh Medical Center, 166-2 Sannohcho, Inage-ku, Chiba City, Chiba-ken 263-0002 (Japan); Yasufuku, Kazuhiro, E-mail: kyasufuku@faculty.chiba-u.j [Department of Thoracic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba-ken 260-8670 (Japan); Takiguchi, Yuichi, E-mail: takiguchi@faculty.chiba-u.j [Department of Respirology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba-ken 260-8670 (Japan); Takahashi, Fumiaki, E-mail: takahashifu@pharm.kitasato-u.ac.j [Division of Biostatistics, Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641 (Japan); Kuniyasu, Yoshio, E-mail: kuniyasu@ace.ocn.ne.j [Diagnostic PET Imaging Center, Department of Radiology, Sannoh Medical Center, 166-2 Sannohcho, Inage-ku, Chiba City, Chiba-ken 263-0002 (Japan); Ito, Hisao, E-mail: hisao@faculty.chiba-u.j [Department of Radiology, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba-ken 260-8677 (Japan)

2010-08-15

Purpose: To evaluate whether dual-time point scanning with integrated fluorine-18 fluorodeoxyglucose ({sup 18}F-FDG) positron emission tomography and computed tomography (PET/CT) is useful for evaluation of mediastinal and hilar lymph nodes in non-small cell lung cancer diagnosed as operable by contrast-enhanced CT. Materials and methods: PET/CT data and pathological findings of 560 nodal stations in 129 patients with pathologically proven non-small cell lung cancer diagnosed as operable by contrast-enhanced CT were reviewed retrospectively. Standardized uptake values (SUVs) on early scans (SUVe) 1 h, and on delayed scans (SUVd) 2 h after FDG injection of each nodal station were measured. Retention index (RI) (%) was calculated by subtracting SUVe from SUVd and dividing by SUVe. Logistic regression analysis was performed with seven kinds of models, consisting of (1) SUVe, (2) SUVd, (3) RI, (4) SUVe and SUVd, (5) SUVe and RI, (6) SUVd and RI, and (7) SUVe, SUVd and RI. The seven derived models were compared by receiver-operating characteristic (ROC) analysis. k-Fold cross-validation was performed with k values of 5 and 10. p < 0.05 was considered statistically significant. Results: Model (1) including the term of SUVe showed the largest area under the ROC curve among the seven models. The cut-off probability of metastasis of 3.5% with SUVe of 2.5 revealed a sensitivity of 78% and a specificity of 81% on ROC analysis, and approximately 60% and 80% on k-fold cross-validation. Conclusion: Single scanning of PET/CT is sufficiently useful for evaluating mediastinal and hilar nodes for metastasis.

Invasive ductal carcinoma within fibroadenoma and lung metastases

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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

SERPINE2 is a possible candidate promotor for lymph node metastasis in testicular cancer

International Nuclear Information System (INIS)

Nagahara, Akira; Nakayama, Masashi; Oka, Daizo; Tsuchiya, Mutsumi; Kawashima, Atsunari; Mukai, Masatoshi; Nakai, Yasutomo; Takayama, Hitoshi; Nishimura, Kazuo; Jo, Yoshimasa; Nagai, Atsushi; Okuyama, Akihiko; Nonomura, Norio

2010-01-01

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.

SERPINE2 is a possible candidate promotor for lymph node metastasis in testicular cancer

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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.

Factors Associated with Life Expectancy in Patients with Metastatic Spine Disease from Adenocarcinoma of the Lung

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Goodwin, C. Rory; Khattab, Mohamed H.; Sankey, Eric W.; Elder, Benjamin D.; Kosztowski, Thomas A.; Sarabia-Estrada, Rachel; Bydon, Ali; Witham, Timothy F.; Wolinsky, Jean-Paul; Gokaslan, Ziya L.; Sciubba, Daniel M.

2015-01-01

Study Design Retrospective study. Objective Our objective was to identify preoperative prognostic factors associated with survival in patients with spinal metastasis from lung carcinoma. Methods A retrospective analysis of 26 patients diagnosed with lung carcinoma metastatic to the spinal column was performed to determine factors associated with survival. We used 3 months survival as the clinical cutoff for whether surgical intervention should be performed. We analyzed patients who survived less than 3 months compared with those who survived more than 3 months. Demographic, preoperative, operative, and postoperative factors including functional scores were collected for analysis. Results The median survival for all patients in our study was 3.5 months. We found a statistically significant difference between the group that survived less than 3 months and the group that survived greater than 3 months in terms of extrathoracic metastasis, visceral metastasis, and average postoperative modified Rankin score. Conclusion Determining which patients with lung cancer spinal metastases will benefit from surgical intervention is often dictated by the patient's predicted life expectancy. Factors associated with poorer prognosis include age, functional status, visceral metastases, and extrathoracic metastases. Although the prognosis for patients with lung cancer spinal metastases is poor, some patients may experience long-term benefit from surgical intervention. PMID:26430597

Bioinformatics analysis of breast cancer bone metastasis related gene-CXCR4

Institute of Scientific and Technical Information of China (English)

Heng-Wei Zhang; Xian-Fu Sun; Ya-Ning He; Jun-Tao Li; Xu-Hui Guo; Hui Liu

2013-01-01

Objective: To analyze breast cancer bone metastasis related gene-CXCR4. Methods: This research screened breast cancer bone metastasis related genes by high-flux gene chip. Results:It was found that the expressions of 396 genes were different including 165 up-regulations and 231 down-regulations. The expression of chemokine receptor CXCR4 was obviously up-regulated in the tissue with breast cancer bone metastasis. Compared with the tissue without bone metastasis, there was significant difference, which indicated that CXCR4 played a vital role in breast cancer bone metastasis. Conclusions: The bioinformatics analysis of CXCR4 can provide a certain basis for the occurrence and diagnosis of breast cancer bone metastasis, target gene therapy and evaluation of prognosis.

Renal cell carcinoma presenting as mandibular metastasis

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Hassan Ahmadnia

2013-01-01

Full Text Available Renal clear cell carcinoma (RCC has different manifestations, including uncommon metastasis and paraneoplastic syndromes. Here we report a rare case of RCC presenting as metastasis to the mandible. A 57-year-old patient with mandibular swelling was referred to the dentist. After necessary evaluations, an incisional biopsy of mandible showed metastatic RCC. The patient was referred to the urologist. The patient underwent right radical nephrectomy. Pathological examination showed clear renal cell carcinoma. Every abnormal bone lesion in the oral cavity should be evaluated carefully and the possibility of a malignant lesion should always be considered.

Utility of preoperative ferumoxtran-10 MRI to evaluate retroperitoneal lymph node metastasis in advanced cervical cancer: Results of ACRIN 6671/GOG 0233

International Nuclear Information System (INIS)

Atri, Mostafa; Zhang, Zheng; Marques, Helga; Gorelick, Jeremy; Harisinghani, Mukesh; Sohaib, Aslam; Koh, Dow-Mu; Raman, Steven; Gee, Michael; Choi, Haesun; Landrum, Lisa; Mannel, Robert; Chuang, Linus; Yu, Jian Qin; McCourt, Carolyn Kay; Gold, Michael

2014-01-01

•We evaluated the added value of a USPIO agent (Ferumoxtran-10) to MRI evaluation of LN metastasis in loco-regionally advanced cervical cancer in a multicenter trial.•There was no significant difference in the accuracy of f-10 MRI as compared to standard MRI to detect LN metastasis in advanced cervical cancer (P > 0.05).•F-10 MRI increased sensitivity of MRI to detect metastasis in small (<8 mm) LNs but at the expense of lower specificity.•Mean size of the largest metastatic focus in the LN on pathology was 13.7 mm in the abdomen and 18.8 mm in the pelvis (P = 0.018). We evaluated the added value of a USPIO agent (Ferumoxtran-10) to MRI evaluation of LN metastasis in loco-regionally advanced cervical cancer in a multicenter trial. There was no significant difference in the accuracy of f-10 MRI as compared to standard MRI to detect LN metastasis in advanced cervical cancer (P > 0.05). F-10 MRI increased sensitivity of MRI to detect metastasis in small (<8 mm) LNs but at the expense of lower specificity. Mean size of the largest metastatic focus in the LN on pathology was 13.7 mm in the abdomen and 18.8 mm in the pelvis (P = 0.018). To assess if ferumoxtran-10 (f-10) improves accuracy of MRI to detect lymph node (LN) metastasis in advanced cervical cancer. F-10 MRI component of an IRB approved HIPAA compliant ACRIN/GOG trial was analyzed. Patients underwent f-10 MRI followed by extra-peritoneal or laparoscopic pelvic and abdominal lymphadenectomy. F-10-sensitive sequences were T2* GRE sequences with TE of 12 and 21. Seven independent blinded readers reviewed f-10-insensitive sequences and all sequences in different sessions. Region correlations were performed between pathology and MRI for eight abdomen and pelvis regions. Sensitivity and specificity were calculated at participant level. Reference standard is based on pathology result of surgically removed LNs. Among 43 women enrolled in the trial between September 2007 and November 2009, 33 women (mean age 49

Combined detection of Twist1, Snail1 and squamous cell carcinoma antigen for the prognostic evaluation of invasion and metastasis in cervical squamous cell carcinoma.

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Yang, Huilun; Hu, Haiyang; Gou, Yanling; Hu, Yuhong; Li, Hui; Zhao, Hongwei; Wang, Beidi; Li, Peiling; Zhang, Zongfeng

2018-04-01

Cervical cancer is one of the most common malignant tumours of the female reproductive system, ranking second only to breast cancer in morbidity worldwide. Essential features of the progression of cervical cancer are invasion and metastasis, which are closely related to disease prognosis and mortality rate. At the present time there is no effective method to evaluate cancer invasion and metastasis before surgery. Here we report our study on molecular changes in biopsy tissue for the prognostic evaluation of cancer invasion and metastasis. Expression of the epithelial-mesenchymal transition-inducing transcription factors Twist1 and Snail1 was detected by immunohistochemistry in 32 normal, 36 low-grade squamous intraepithelial neoplasia (LSIL), 54 high-grade squamous intraepithelial neoplasia (HSIL) and 320 cervical squamous cell carcinoma (CSCC) samples. The correlation between the expression of Twist1, Snail1 and squamous cell carcinoma antigen (SCCA) in CSCC tissues and clinical pathology results was evaluated. A transwell migration and invasion assay was used to explore the roles of Twist1 and Snail1 in the invasion of cancer cells. Lymph node metastasis and lymphovascular space invasion (LVSI) rates for the following groups were analysed: SCCA(+) group, Twist1(+) group, Snail1(+) group, Twist1(+)Snail1(+)group, Twist1(+)SCCA(+)group, Snail1(+)SCCA(+)group and Twist1(+)Snail1(+)SCCA(+) group. The expression of Twist1 and Snail1 was significantly upregulated in HSIL and CSCC (p  0.05). The expression of SCCA was associated with LVSI, lymph node metastasis, FIGO stage and histological grade (p  0.05). Twist1 was an independent factor contributing to the invasion ability of cervical cancer cells. In addition, the positive rate of lymph node metastasis and LVSI was higher in the Twist1(+)Snail1(+)SCCA(+) group than in the SCCA(+) group, Twist1(+) group and Snail1(+) group, respectively (p < 0.05). Combined detection of Twist1 and Snail1 in SCCA-positive biopsy

Comparison of CT and 18F-FDG PET for Detecting Peritoneal Metastasis on the Preoperative Evaluation for Gastric Carcinoma

International Nuclear Information System (INIS)

Lim, Joon Seok; Kim, Myeong Jin; Yun, Mi jin

2006-01-01

The aim of our study was to compare the accuracy of CT and 18 F-FDG PET for detecting peritoneal metastasis in patients with gastric carcinoma. One-hundred-twelve patients who underwent a histologic confirmative exam or treatment (laparotomy, n = 107; diagnostic laparoscopy, n = 4; peritoneal washing cytology, n = 1) were retrospectively enrolled. All the patients underwent CT and 18 F-FDG PET scanning for their preoperative evaluation. The sensitivities, specificities and accuracies of CT and 18 FFDG PET imaging for the detection of peritoneal metastasis were calculated and then compared using Fisher's exact probability test (p 18 F-FDG PET imaging for detecting peritoneal metastasis. Based on the original preoperative reports, CT and 18 F-FDG PET showed sensitivities of 76.5% and 35.3% (p = 0.037), specificities of 91.6% and 98.9% (p = 0.035), respectively, and equal accuracies of 89.3% (p = 1.0). The receptor operating characteristics curve analysis showed a significantly higher diagnostic performance for CT (Az 0.878) than for PET (Az = 0.686) (p 0.004). The interobserver agreement for detecting peritoneal metastasis was good (κ value = 0.684) for CT and moderate ((κ value = 0.460) for PET. For the detection of peritoneal metastasis, CT was more sensitive and showed a higher diagnostic performance than PET, although CT had a relatively lower specificity than did PET

Vertebral metastasis of femur primary osteosarcoma: a case report and literature review

International Nuclear Information System (INIS)

Cioni, Claudia Helena; Oliveira, Andrea Alencar de; Neves, Felipe Trentin

2006-01-01

We present a case of a 21-year-old patient, bearer of femur primary osteosarcoma, who began with pain in the thoracic column. The metastasis of primary osteosarcoma has greater incidence on lungs, rarely affecting vertebras. We reviewed the literature about this disease and emphasized the image's characteristics on the several methods used (traditional radiographic exams, bone scintigraphy, computed tomography, magnetic resonance) and the main differential diagnostics. (author)

Effectiveness of PET Scan in Postoperative Long Term Follow up of Patients with Nonsmall Cell Lung Cancer

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Atilla Pekcolaklar

2012-01-01

Full Text Available Aim: There is very few data about the use of positron emission tomography [PET] in the long term follow up of patients operated for lung cancer. We aimed to evaluate the effectiveness of PET scan in detecting distant metastases in the long term follow up of asymptomatic patients operated for non-small cell lung cancer [NSCLC]. Material and Method: PET scan was performed to sixty five asymptomatic patients. The patients who had a positive PET scan for metastasis underwent MRI and/or biopsy to verify metastasis. Result: : Mean age of the patients was 58.09 8.64 [44-82] years, and 57 [87.7 %] of them were male. Forty eight [73.8%] of the patients had epidermoid cell, 15 [23.1%] had adeno and 2 [%3.1] had large cell carcinoma. Postoperative stage of 1 [1.5%] patient was 1A, 14 [21.5%] of them were stage 1B, 1 [1.5%] of them was stage 2A, 27 [41.5%] of them were stage 2B and 22 [33.8%] of them were stage 3A. PET scan detected metastasis in 7 [10.8%] patients. In one patient PET scan was proven to be false positive. Sites of metastases in PET scan were lung in 3 [4.5%] patients, vertebra in 3 [4.6%] patients and tibia in 1 [1.5%] patient. In detecting distant metastases accuracy rate of PET was calculated as 98%, sensitivity was 100%, and specificity was 98%. Discussion: In asymptomatic patients with NSCLC, PET imaging appears to be useful as an alternative to conventional imaging to rule out unsuspected systemic disease in the postoperative long term follow up.

Radiological evaluation of lung volume among Koreans with silicosis

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Rhee, Byung Chull

1975-01-01

1. Radiological evaluation of lung volumes was carried out thirty Korean males patients with silicosis, and following results were obtained. 2. The mean radiological lung volume among those patients was 7,587 ml. 3. When compared with the group of normal Korean male adults ranging from 31 to 55 years of age, the mean lung volume was increased by 2,346 ml. 4. The lung volume of these patients was even slightly larger than that of the group of Korean athletes of all ages. 5. On the other hand, the vital capacity in patients with silicosis was markedly diminished, the mean vital capacity being 2,909 ml. 6. The patients with silicosis also revealed emphysematous changes in the lung as well as increased residual volumes. The vital capacity was smallest in the latest stage.

Differential expression of bio-markers in primary non-small cell lung cancer and metastatic sites

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Gomez-Roca, C.; Besse, B.; Soria, J.C. [Department of Medicine, Institut Gustave Roussy (IGR), Villejuif (France); Raynaud, Ch.; Morat, L.; Sabatier, L.; Soria, J.C. [Laboratoire de radiobiologie et oncologie, CEA, Fontenay-aux-Roses (France); Penault-Llorca, F. [Department of Pathology Centre Jean Perrin, Institut National de la Sante et de la Recherche Medicale UMR484, Clermont-Ferrand (France); Mercier, O.; Dartevelle, Ph. [Department of Thoracic and Vascular Surgery and Heart-lung Transplantation, Marie Lannelongue Hospital, Le Pleissy-Robinson (France); Commo, F.; Taranchon, E. [Laboratory of Translational Research, IGR, Villejuif (France); Validire, P. [Department of Pathology, Institut Mutualiste Montsouris, Paris (France); Italiano, A. [Department of Medical Oncology, Centre Antoine-Lacassagne - Laboratory of Solid Tumor Genetics, Centre Hospitalier Universitaire de Nice, Nice Cedex (France)

2009-07-01

Introduction: The use of bio-markers to evaluate the presence of a target or to select a specific therapy is increasingly advocated. The correlation of bio-marker expression between the primary tumor and its corresponding metastasis has not yet been well documented and analyzed in patients with non-small cell lung cancer (NSCLC). Methods: The expression of epidermal growth factor receptor (EGFR), excision repair cross-complementing (ERCC1), vascular-endothelial growth factor receptor, and Ki-67 was immuno-histo-chemically analyzed in tumor samples of primary NSCLC and one corresponding metastasis in a population of 49 patients. Results: Sixteen cases (33%) displayed clear discordance in the EGFR status between the primary tumor and the metastasis, with a significant trend toward downregulation of EGFR in the metastasis (p = 0.01). The ERCC1 status was discordant in 20 cases (41%), with a trend toward overexpression in brain and adrenal metastases (p = 0.01 and p = 0.08, respectively). The vascular-endothelial growth factor receptor and Ki-67 statuses were discordant in 13 (27%) and 15 (31%) cases, respectively. No difference in expression was observed between synchronous and metachronous metastasis. Conclusion: bio-marker expression is discordant between the primary tumor and its corresponding metastasis in about one third of patients with NSCLC. These findings should be considered in the setting of clinical trials and further explored using frozen material and high-throughput techniques. (authors)

Remote multiple intracranial hemorrhage in multiple metastatic lung adenocarcinoma following decompression of posterior fossa lesion: Unknown cause

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Subhas Konar

2015-01-01

Full Text Available Cerebral metastasis can present with hemorrhage. However, multiple hemorrhages in metastatic lesions following surgical decompression of a single lesion are never reported. We report a case of cerebral metastasis from lung cancer that developed multiple hemorrhages in supratentorial metastatic lesions following surgical resection of an infratentorial lesion.

Color-Coded Imaging of Syngeneic Orthotopic Malignant Lymphoma Interacting with Host Stromal Cells During Metastasis.

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Matsumoto, Takuro; Suetsugu, Atsushi; Hasegawa, Kosuke; Nakamura, Miki; Aoki, Hitomi; Kunisada, Takahiro; Tsurumi, Hisashi; Shimizu, Masahito; Hoffman, Robert M

2016-04-01

The EL4 cell line was previously derived from a lymphoma induced in a C57/BL6 mouse by 9,10-dimethyl-1,2-benzanthracene. In a previous study, EL4 lymphoma cells expressing red fluorescent protein (EL4-RFP) were established and injected into the tail vein of C57/BL6 green fluorescent protein (GFP) transgenic mice. Metastasis was observed at multiple sites which were also enriched with host GFP-expressing stromal cells. In the present study, our aim was to establish an orthotopic model of EL4-RFP. In the present study, EL4-RFP lymphoma cells were injected in the spleen of C57/BL6 GFP transgenic mice as an orthotopic model of lymphoma. Resultant primary tumor and metastases were imaged with the Olympus FV1000 scanning laser confocal microscope. EL4-RFP metastasis was observed 21 days later. EL4-RFP tumors in the spleen (primary injection site), liver, supra-mediastinum lymph nodes, abdominal lymph nodes, bone marrow, and lung were visualized by color-coded imaging. EL4-RFP metastases in the liver, lymph nodes, and bone marrow in C57/BL6 GFP mice were rich in GFP stromal cells such as macrophages, fibroblasts, dendritic cells, and normal lymphocytes derived from the host animal. Small tumors were observed in the spleen, which were rich in host stromal cells. In the lung, no mass formation of lymphoma cells occurred, but lymphoma cells circulated in lung peripheral blood vessels. Phagocytosis of EL4-RFP lymphoma cells by macrophages, as well as dendritic cells and fibroblasts, were observed in culture. Color-coded imaging of the lymphoma microenvironment suggests an important role of stromal cells in lymphoma progression and metastasis. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.