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Sample records for 1-3 brain metastasis

  1. Whole brain radiotherapy with a conformational external beam radiation boost for lung cancer patients with 1-3 brain metastasis: a multi institutional study

    To determine the outcome of patients with brain metastasis (BM) from lung cancer treated with an external beam radiotherapy boost (RTB) after whole brain radiotherapy (WBRT). A total of 53 BM patients with lung cancer were treated sequentially with WBRT and RTB between 1996 and 2008 according to our institutional protocol. Mean age was 58.8 years. The median KPS was 90. Median recursive partitioning analysis (RPA) and graded prognostic assessment (GPA) grouping were 2 and 2.5, respectively. Surgery was performed on 38 (71%) patients. The median number of BM was 1 (range, 1-3). Median WBRT and RTB combined dose was 39 Gy (range, 37.5 - 54). Median follow-up was 12.0 months. During the period of follow-up, 37 (70%) patients died. The median overall survival (OS) was 14.5 months. Only 13 patients failed in the brain. The majority of patients (n = 29) failed distantly. The 1-year OS, -local control, extracranial failure rates were 61.2%, 75.2% and 60.8%, respectively. On univariate analysis, improved OS was found to be significantly associated with total dose (≤ 39 Gy vs. > 39 Gy; p < 0.01), age < 65 (p < 0.01), absence of extracranial metastasis (p < 0.01), GPA ≥ 2.5 (p = 0.01), KPS ≥ 90 (p = 0.01), and RPA < 2 (p = 0.04). On multivariate analysis, total dose (p < 0.01) and the absence of extracranial metastasis (p = 0.03) retained statistical significance. The majority of lung cancer patients treated with WBRT and RTB progressed extracranially. There might be a subgroup of younger patients with good performance status and no extracranial disease who may benefit from dose escalation after WBRT to the metastatic site

  2. Management ovarian brain metastasis

    Ovarian cancer is the cause of the most frequent mortality and morbidity from gynaecologist malignant diseases. Nowadays, the standard treatment is the optimal debulkization with the following platinum chemotherapy at all the histological subtypes. Even despite the progress in the surgery and chemotherapy, in the last years 5-year-survival at the patients with initially progressive disease has remained relatively low. One of the least favourable situations is the presence of brain metastasis where the survival is limited only to a few weekends. The brain metastases are not very common at ovarian cancer even despite the fact that in the last years there has been in decrease. Brain metastases typically occur metachromically. Our patient had metachromic metastasis in the brain without the presence of extra cranial disease. Radiotherapy in the area of brain metastasis in a monotherapy was secure and well tolerated at the relatively good efficiency. (author)

  3. Microenvironment Determinants of Brain Metastasis

    Zhang Chenyu

    2011-02-01

    Full Text Available Abstract Metastasis accounts for 90% of cancer-related mortality. Brain metastases generally present during the late stages in the natural history of cancer progression. Recent advances in cancer treatment and management have resulted in better control of systemic disease metastatic to organs other than the brain and improved patient survival. However, patients who experience recurrent disease manifest an increasing number of brain metastases, which are usually refractory to therapies. To meet the new challenges of controlling brain metastasis, the research community has been tackling the problem with novel experimental models and research tools, which have led to an improved understanding of brain metastasis. The time-tested "seed-and-soil" hypothesis of metastasis indicates that successful outgrowth of deadly metastatic tumors depends on permissible interactions between the metastatic cancer cells and the site-specific microenvironment in the host organs. Consistently, recent studies indicate that the brain, the major component of the central nervous system, has unique physiological features that can determine the outcome of metastatic tumor growth. The current review summarizes recent discoveries on these tumor-brain interactions, and the potential clinical implications these novel findings could have for the better treatment of patients with brain metastasis.

  4. Microenvironment Determinants of Brain Metastasis

    Zhang Chenyu; Yu Dihua

    2011-01-01

    Abstract Metastasis accounts for 90% of cancer-related mortality. Brain metastases generally present during the late stages in the natural history of cancer progression. Recent advances in cancer treatment and management have resulted in better control of systemic disease metastatic to organs other than the brain and improved patient survival. However, patients who experience recurrent disease manifest an increasing number of brain metastases, which are usually refractory to therapies. To mee...

  5. Concurrent whole brain radiotherapy and bortezomib for brain metastasis

    Survival of patients with brain metastasis particularly from historically more radio-resistant malignancies remains dismal. A phase I study of concurrent bortezomib and whole brain radiotherapy was conducted to determine the tolerance and safety of this approach in patients with previously untreated brain metastasis. A phase I dose escalation study evaluated the safety of bortezomib (0.9, 1.1, 1.3, 1.5, and 1.7 mg/m2) given on days 1, 4, 8 and 11 of whole brain radiotherapy. Patients with confirmed brain metastasis were recruited for participation. The primary endpoint was the dose-limiting toxicity, defined as any ≥ grade 3 non-hematologic toxicity or grade ≥ 4 hematologic toxicity from the start of treatment to one month post irradiation. Time-to-Event Continual Reassessment Method (TITE-CRM) was used to determine dose escalation. A companion study of brain diffusion tensor imaging MRI was conducted on a subset of patients to assess changes in the brain that might predict delayed cognitive effects. Twenty-four patients were recruited and completed the planned therapy. Patients with melanoma accounted for 83% of all participants. The bortezomib dose was escalated as planned to the highest dose of 1.7 mg/m2/dose. No grade 4/5 toxicities related to treatment were observed. Two patients had grade 3 dose-limiting toxicities (hyponatremia and encephalopathy). A partial or minor response was observed in 38% of patients. Bortezomib showed greater demyelination in hippocampus-associated white matter structures on MRI one month after radiotherapy compared to patients not treated with bortezomib (increase in radial diffusivity +16.8% versus 4.8%; p = 0.0023). Concurrent bortezomib and whole brain irradiation for brain metastasis is well tolerated at one month follow-up, but MRI changes that have been shown to predict delayed cognitive function can be detected within one month of treatment

  6. Brain metastasis treated with Cyberknife

    WANG Zhi-zhen; YUAN Zhi-yong; ZHANG Wen-cheng; YOU Jin-qiang; WANG Ping

    2009-01-01

    Background Cyberknife can greatly raise the fractional dose of stereotactic radiosurgery,thus improving its clinical efficacy.We retrospectively analyzed clinical outcomes of brain metastasis treated with Cyberknife.Methods We analyzed 40 cases of brain metastases treated with Cyberknife in the Tianjin Cancer Hospital from August 1,2006 to August 1,2007,for a total of 68 lesions with maximal diameter of 0.4-7.5 cm (average 1.88 cm).Total hypofractional radiated dosage was 18-36 Gy (5-25 Gy/F,1-5 F) by Cyberknife.We evaluated the remission rate of clinical symptoms,correlation factors to new loci,3-month local control rates,and 3-month and 1-year survival rates.All patients were followed up for more than 14 months.Results After 1 week,clinical remission was 90.0% (36/40).After 3 months,the local control rate and therapeutic effective rate were 77.9% (53/68) and 94.1% (64/68),respectively,as observed by cranium augmentation CT or MRI.The three-month,six-month and 1-year survival rates were 97.5% (39/40),82.5% (33/40) and 67.5% (27/40),respectively.Fourteen patients had neopathy outside the original lesion after 3 months.Neopathy was not correlated with age,whole-brain radiotherapy,number of original lesions,maximum diameter of the original lesion,therapeutic dose per fraction,therapeutic frequency or total therapeutic dose.Conclusions Cyberknife got perfect clinical outcomes by higher dosage per fraction.It is an appropriate and valid treatment shortcut for brain metastasis.

  7. Brain Metastasis in Pancreatic Cancer

    Marko Kornmann; Doris Henne-Bruns; Jan Scheele; Christian Rainer Wirtz; Thomas Kapapa; Johannes Lemke

    2013-01-01

    Pancreatic cancer is a fatal disease with a 5-year survival rate below 5%. Most patients are diagnosed at an advanced tumor stage and existence of distant metastases. However, involvement of the central nervous system is rare in pancreatic cancer. We retrospectively analyzed all cases of brain metastases in pancreatic cancer reported to date focusing on patient characteristics, clinical appearance, therapy and survival. Including our own, 12 cases of brain metastases originating from pancreat...

  8. Leptomeningeal metastasis after surgical resection of brain metastases

    Ree, T.C.; Dippel, Diederik; Avezaat, Cees; Vecht, C J; Bent, Martin; Sillevis Smitt, Peter

    1999-01-01

    textabstractOBJECTIVE: To determine the incidence and risk factors for leptomeningeal metastasis after surgery for brain metastasis of solid tumors. METHODS: Review of the records of all patients operated on for brain metastasis between January 1990 and August 1995. RESULTS: In this period 28 patients underwent surgery for brain metastasis, of whom 27 were available for evaluation in this study. Median survival after craniotomy was 11 months. Nine patients (33%) developed leptomeningeal metas...

  9. Neuroradiological aspects of brain metastasis of choriocarcinomas

    Kida, Y.; Kobayashi, T.; Yoshida, J.; Shibuya, N.; Kageyama, N. (Nagoya Univ. (Japan). Faculty of Medicine)

    1981-04-01

    We have had experience with 24 cases of brain metastasis of choriocarcinoma between 1965 to 1979. Twenty-two cases died, while the other two cases survived. Their neuroradiological findings, especially that of CT scan and angiography, are discussed. The angiograms showed a prominent abnormal neovascularization, with a marked tumor stain in the peripheral zone. However, the central zone appeared avascular or hypovascular. A-V fistulas or early venous filling were seen in two among the 6 cases thus examined. CT scans were studied in 9 lesions of 4 patients. Half of them showed a definite high density, even in plain CT's. A central lucency was found in 7 lesions. In plain CT a highly dense area corresponding to tumors is rare; there have, though, been a few such reports in cases of the brain metastasis of malignant melanoma and colon cancer. This was considered to show hemorrhage associated with the tumor. A follow-up study by CT scan is very important for patients with choriocarcinoma, and also for patients with a hydatidiform mole, because of the rapid progress of the symptoms and signs in cases of brain metastasis.

  10. Treatment of Brain Metastasis from Lung Cancer

    Brain metastases are not only the most common intracranial neoplasm in adults but also very prevalent in patients with lung cancer. Patients have been grouped into different classes based on the presence of prognostic factors such as control of the primary tumor, functional performance status, age, and number of brain metastases. Patients with good prognosis may benefit from more aggressive treatment because of the potential for prolonged survival for some of them. In this review, we will comprehensively discuss the therapeutic options for treating brain metastases, which arise mostly from a lung cancer primary. In particular, we will focus on the patient selection for combined modality treatment of brain metastases, such as surgical resection or stereotactic radiosurgery (SRS) combined with whole brain irradiation; the use of radiosensitizers; and the neurocognitive deficits after whole brain irradiation with or without SRS. The benefit of prophylactic cranial irradiation (PCI) and its potentially associated neuro-toxicity for both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) are also discussed, along with the combined treatment of intrathoracic primary disease and solitary brain metastasis. The roles of SRS to the surgical bed, fractionated stereotactic radiotherapy, WBRT with an integrated boost to the gross brain metastases, as well as combining WBRT with epidermal growth factor receptor (EGFR) inhibitors, are explored as well

  11. Genes that mediate breast cancer metastasis to the brain

    Bos, Paula D.; Zhang, Xiang H.-F.; Nadal, Cristina; Shu, Weiping; Gomis, Roger R; Nguyen, Don X.; Minn, Andy J.; Vijver, Marc; Gerald, William; Foekens, John A.; Massagué, Joan

    2009-01-01

    The molecular basis for breast cancer metastasis to the brain is largely unknown1,2. Brain relapse typically occurs years after the removal of a breast tumour2–4, suggesting that disseminated cancer cells must acquire specialized functions to overtake this organ. Here we show that breast cancer metastasis to the brain involves mediators of extravasation through non-fenestrated capillaries, complemented by specific enhancers of blood–brain barrier crossing and brain colonization. We isolated c...

  12. Blood-Brain Barrier Integrity and Breast Cancer Metastasis to the Brain

    Hava Karsenty Avraham; Shalom Avraham; Christopher Sy; Lili Wang; Farheen Arshad

    2011-01-01

    Brain metastasis, an important cause of cancer morbidity and mortality, occurs in at least 30% of patients with breast cancer. A key event of brain metastasis is the migration of cancer cells through the blood-brain barrier (BBB). Although preventing brain metastasis is immensely important for survival, very little is known about the early stage of transmigration and the molecular mechanisms of breast tumor cells penetrating the BBB. The brain endothelium plays an important role in brain meta...

  13. Mixed adenoneuroendocrine carcinoma with brain metastasis

    Xiao-ling YAN

    2015-05-01

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

  14. Radiotherapy for metastasis from breast and lung cancer. Bone and Brain metastasis

    Bone or brain metastasis is the common and serious condition restricting the quality of life (QOL) of the cancer patients and radiotherapy frequently plays an important role in relief of their symptoms. Because radiotherapy is given with palliative intent to the patients with limited, if variable, life expectancy, radiation schedules need to be identified which give maximum patient benefit with minimum associated morbidity and minimum disturbance of the patients' remaining life. We retrospectively analyzed 222 patients with the bone or the brain metastasis from lung or breast cancer to evaluate the effect of radiotherapy on their prognosis and QOL. The 3-year survival rates of the patients with breast and lung cancer were 21% and 3%, respectively (p<0.0001), and breast cancer patients seemed to have better prognosis than lung cancer patients for both bone metastasis (p<0.0001) and brain metastasis (p=0.09). Symptom relief by radiotherapy was obtained 84% for bone metastasis and 64% for brain metastasis and it was not affected by primary lesion (lung or breast). Sixty seven per cent of the bone and the brain metastasis was derived from adenocarcinoma and it had a tendency to give the better prognosis comparing with squamous cell carcinoma. Radiation schedules should be flexibly corresponded to the patients' tumor type (metastatic site, primary disease or histology), even if it is 'just' a palliative therapy, considering their prognosis and QOL. (author)

  15. Differential Reactions of Microglia to Brain Metastasis of Lung Cancer

    He, Bei Ping; Wang, Jian Jun; Zhang, Xian; Wu, Yan; Wang, Miao; Bay, Boon-Huat; Chang, Alex Yuang-Chi

    2006-01-01

    The brain is a common metastatic site for various types of cancers, especially lung cancer. Patients with brain metastases have a poor prognosis in spite of radiotherapy and/or chemotherapy. It is postulated that immune cells in the brain may play a major role in cancer metastasis, dormancy, and relapse. Although microglia may serve as a major component in the brain immune system, the interaction between metastatic cancer cells and microglia is still largely unknown and remains to be elucidat...

  16. The role of radiotherapy in patients with brain metastasis

    Brain metastases are the most frequent metastatic neurologic complication of systemic cancer. Even if the prognosis of brain metastases is grave, with available treatments, most patients experience effective palliation of neurologic symptoms and meaningful extension of life. We evaluated the clinical features and prognostic factors of the patients who were diagnosed as solid tumors with brain metastasis and received radiotherapy for brain metastases. Between January 1987 and January 1998, 71 patients with brain metastases from solid malignancy were included. We reviewed neurologic symptoms and signs of patients and evaluated improvement of neurologic symptoms and signs. Survival durations after brain metastasis were analysed according to several factors such as age, performance status, primary malignancies, the presence of brain metastasis at initial diagnosis of primary tumor, multiplicity of brain metastases, the presence of metastases other than brain, and treatment method. Frequent symptoms associated with brain metastasis were headache (47.9%), motor weakness (40.8%), nausea and vomiting (19.7%) and mental change (19.7%). Palliation of these symptoms was accomplished in 64.9% of cases. The overall median survival time was 16 weeks and 1- and 2-year survival rates were 15.0% and 5.1 % respectively. Patients without extra cranial metastases (n==27) had longer median survival than patients with extracranial metastases (33 weeks vs 10 weeks, P=(WJ18). In patients with single brain metastasis (n=37), the median survival time was longer in patients treated with surgery plus radiotherapy than in patients treated with radiotherapy alone (40 weeks vs 16 weeks, p=O.0438L Patients who has. brain metastases only constitute a prognostically favorable group and they may be benefited from radiotherapy and surgery if indicated

  17. Brain metastasis in breast cancer: a comprehensive literature review.

    Rostami, Rezvan; Mittal, Shivam; Rostami, Pooya; Tavassoli, Fattaneh; Jabbari, Bahman

    2016-05-01

    This comprehensive review provides information on epidemiology, size, grade, cerebral localization, clinical symptoms, treatments, and factors associated with longer survival in 14,599 patients with brain metastasis from breast cancer; the molecular features of breast cancers most likely to develop brain metastases and the potential use of these predictive molecular alterations for patient management and future therapeutic targets are also addressed. The review covers the data from 106 articles representing this subject in the era of modern neuroimaging (past 35 years). The incidence of brain metastasis from breast cancer (24 % in this review) is increasing due to advances in both imaging technologies leading to earlier detection of the brain metastases and introduction of novel therapies resulting in longer survival from the primary breast cancer. The mean age at the time of breast cancer and brain metastasis diagnoses was 50.3 and 48.8 years respectively. Axillary node metastasis was noted in 32.8 % of the patients who developed brain metastasis. The median time intervals between the diagnosis of breast cancer to identification of brain metastasis and from identification of brain metastasis to death were 34 and 15 months, respectively. The most common symptoms experienced in patients with brain metastasis consisted of headache (35 %), vomiting (26 %), nausea (23 %), hemiparesis (22 %), visual changes (13 %) and seizures (12 %). A majority of the patients had multiple metastases (54.2 %). Cerebellum and frontal lobes were the most common sites of metastasis (33 and 16 %, respectively). Of the primary tumors for which biomarkers were recorded, 37 % were estrogen receptor (ER)+, 41 % ER-, 36 % progesterone receptor (PR)+, 34 % PR-, 35 % human epithelial growth factor receptor 2 (HER2)+, 41 % HER2-, 27 % triple negative and 18 % triple positive (TP). Treatment in most patients consisted of a multimodality approach often with two or more of the

  18. Non-coding RNAs in cancer brain metastasis.

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

    2016-01-01

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

  19. Capturing Changes in the Brain Microenvironment during Initial Steps of Breast Cancer Brain Metastasis

    Lorger, Mihaela; Felding-Habermann, Brunhilde

    2010-01-01

    Brain metastases are difficult to treat and mostly develop late during progressive metastatic disease. Patients at risk would benefit from the development of prevention and improved treatments. This requires knowledge of the initial events that lead to brain metastasis. The present study reveals cellular events during the initiation of brain metastasis by breast cancer cells and documents the earliest host responses to incoming cancer cells after carotid artery injection in immunodeficient an...

  20. Screening of brain metastasis through computed tomography in cancer patients

    The screening of brain metastasis through CT was carried out on 338 patients with malignant tumors of various origins before they manifested neurological symptoms. The primary site of the tumors was a lung in 132 cases, a breast in 48, the gastrointestinal tract in 42, the head or neck in 36, and others (80). Silent (asymptomatic) brain metastasis was detected in 10 cases (2.9%). Nine of these cases harboured lung carcinoma (6.9% out of 132 cases), while one harboured carcinoma of the parotid gland metastasizing in the lungs. Multiple intracerebral metastases were detected in 8 of them and a metastasis single in one, while silent meningeal carcinomatosis was diagnosed in the remaining case. The total number of metastatic foci in the brain from the 9 cases was 66. They ranged from 0.4 to 3.0 cm in diameter; 70% of them were less than 1 cm in diameter. A large lesion was usually found in the silent areas of the cerebral hemispheres. Most of the foci were isodense on CT, and the perifocal low density and mass effects were often defective or, when present, slight, so that a post-contrast study was indispensable for their detection. Adequate treatment(whole-brain irradiation, removal, and/or chemotherapy) for brain metastasis was effectively completed in 9 cases, while one patient refused to be treated. The metastatic foci disappeared on CT in 6 cases and decreased in size in 3. Most of them remained asymptomatic in neurological examination until they died 3-7 months later, mainly of systemic metastases outside the CNS. These results indicate the clinical efficacy of the CT screening of brain metastasis for their early detection; this ensures a length of time sufficient to treat them effectively before neurological deficits develop. The timing and interval at which CT screening should be performed are also discussed. (author)

  1. BRAIN METASTASIS FROM HEPATOCELLULAR CARCINOMA: A RARE CASE

    A. Kh. Bekyashev

    2012-01-01

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

  2. Molecular Aspects of Breast Cancer Metastasis to the Brain

    Leonard Da Silva; Simpson, Peter T.; Sunil R. Lakhani; Saunus, Jodi M; Majid Momeny

    2011-01-01

    Our knowledge of the biology underlying the development of brain metastases (BM) from breast cancer has improved over the last decade due to large clinical epidemiological studies, animal models of metastasis, and the use of high-resolution gene expression profiling technologies. However, there are still major gaps in our understanding of the mechanisms utilized by breast cancer cells to colonize the brain microenvironment, thus our arsenal of therapies remains relatively nonspecific, and the...

  3. The vascular basement membrane as "soil" in brain metastasis.

    W Shawn Carbonell

    Full Text Available Brain-specific homing and direct interactions with the neural substance are prominent hypotheses for brain metastasis formation and a modern manifestation of Paget's "seed and soil" concept. However, there is little direct evidence for this "neurotropic" growth in vivo. In contrast, many experimental studies have anecdotally noted the propensity of metastatic cells to grow along the exterior of pre-existing vessels of the CNS, a process termed vascular cooption. These observations suggest the "soil" for malignant cells in the CNS may well be vascular, rather than neuronal. We used in vivo experimental models of brain metastasis and analysis of human clinical specimens to test this hypothesis. Indeed, over 95% of early micrometastases examined demonstrated vascular cooption with little evidence for isolated neurotropic growth. This vessel interaction was adhesive in nature implicating the vascular basement membrane (VBM as the active substrate for tumor cell growth in the brain. Accordingly, VBM promoted adhesion and invasion of malignant cells and was sufficient for tumor growth prior to any evidence of angiogenesis. Blockade or loss of the beta1 integrin subunit in tumor cells prevented adhesion to VBM and attenuated metastasis establishment and growth in vivo. Our data establishes a new understanding of CNS metastasis formation and identifies the neurovasculature as the critical partner for such growth. Further, we have elucidated the mechanism of vascular cooption for the first time. These findings may help inform the design of effective molecular therapies for patients with fatal CNS malignancies.

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

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

    2016-01-01

    The development of brain metastases in patients with advanced stage melanoma is common, but the molecular mechanisms responsible for their development are poorly understood. Melanoma brain metastases cause significant morbidity and mortality and confer a poor prognosis; traditional therapies including whole brain radiation, stereotactic radiotherapy, or chemotherapy yield only modest increases in overall survival (OS) for these patients. While recently approved therapies have significantly improved OS in melanoma patients, only a small number of studies have investigated their efficacy in patients with brain metastases. Preliminary data suggest that some responses have been observed in intracranial lesions, which has sparked new clinical trials designed to evaluate the efficacy in melanoma patients with brain metastases. Simultaneously, recent advances in our understanding of the mechanisms of melanoma cell dissemination to the brain have revealed novel and potentially therapeutic targets. In this review, we provide an overview of newly discovered mechanisms of melanoma spread to the brain, discuss preclinical models that are being used to further our understanding of this deadly disease and provide an update of the current clinical trials for melanoma patients with brain metastases. PMID:27598148

  5. Low incidence of melanoma brain metastasis in the hippocampus

    Aims: ANZMTG 01.07 WBRTMel is a phase 3 randomized trial to address the role of whole brain radiation therapy (WBRT) after local treatment of 1–3 melanoma brain metastases. Modern radiation therapy technologies can now conformally spare the hippocampus during WBRT and therefore potentially reduce the risk of neurocognitive deficit. The aims of this study were to report the prevalence of melanoma metastases within the hippocampal sparing region and to identify variables that correlate with the presence of metastases within the hippocampal sparing region. Methods: The pre-local treatment MRI scans of 77 eligible WBRTMel patients were used to contour the individual metastasis and the hippocampus. The volume, location and closest distance of each metastasis to the hippocampus were recorded. Binary logistic regression was performed to assess the influence of factors on the location of a metastasis within 5 mm of the hippocampus. Results: The median age was 61 and 66% were male. The distribution of the 115 metastases was frontal (50, 43.5%), parietal (23, 20.0%), temporal (13, 11.2%), occipital (18, 15.7%), cerebellum (10, 8.6%) and pineal gland (1, 1.0%). The median aggregate volume of the metastasis was 3516 mm3. None of the metastases were within the hippocampus. Four patients (5.2%) had metastases within 5 mm of the hippocampus. The median distance from metastasis to the nearest hippocampus was 37.2 mm. Only the total volume of metastases was a significant predictor for the risk of a metastasis within the hippocampal sparing region (OR 1.071, 95% CI: 1.003–1.144, p = 0.040). Conclusions: This study confirmed a low incidence of melanoma metastasis in the hippocampal sparing region at diagnosis. Given the lack of randomized data on the safety and benefit of hippocampal sparing WBRT, the current WBRTMel trial provides the opportunity to explore the feasibility of this technique

  6. Treatment of Brain Metastasis from Lung Cancer

    Alexander Chi; Ritsuko Komaki

    2010-01-01

    Brain metastases are not only the most common intracranial neoplasm in adults but also very prevalent in patients with lung cancer. Patients have been grouped into different classes based on the presence of prognostic factors such as control of the primary tumor, functional performance status, age, and number of brain metastases. Patients with good prognosis may benefit from more aggressive treatment because of the potential for prolonged survival for some of them. In this review, we will com...

  7. A rare metastasis from a rare brain tumour

    Aabenhus, Kristine; Hahn, Christoffer Holst

    2014-01-01

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

  8. Radiation therapy for brain metastasis from lung cancer

    The prognosis for patients with brain metastasis from lung cancer following radiation therapy was evaluated. Seventy-eight patients received brain irradiation in the Osaka Prefectural Habikino Hospital between April 1985 and March 1989. Almost all patients had conventional radiotherapy of the whole brain, with a single dose of 2 or 3 Gy. Patients characteristics associated with favorable prognosis were as follows: Performance status of 0∼1, age≤49, female, histology of adenocarcinoma. Patients who received radiotherapy of 56 Gy10 or more, had longer survival time. The findings in the brain CT were evaluated, but the number, size, site of metastases, and mass effect to ventricular system were not related to the prognosis. The overall median survival was 3.5 months and the 1-year survival rate was 9.0%. Further clinical studies are necessary to improve the prognosis in brain metastases. (author)

  9. Solitary hemorrhagic brain metastasis from pulmonary blastoma: a case report

    Lee, Hak Soo; Lee, Seung Ro; Bae, Oh Keun; Park, Doung Woo; Choi, Yo Won; Jeon, Seok Chol; Park, Choong Ki; Hahm, Chang Kok; Lee, Jung Dal [Hanyang Univ. College of Medicine, Seoul (Korea, Republic of)

    1997-02-01

    Pulmonary blastoma is a rare primary lung malignancy consisting of mesenchymal and epithelial components resembling the fetal lung. We report a case of pulmonary blastoma with solitary hemorrhagic brain metastasis in a 32-year-old man. This metastatic lesion was composed mainly of hemorrhagic high density and central necrotic low density areas; on CT it showed partial contrast enhancement and was thus impossible to distinguish from other hemorrhagic lesions.

  10. Solitary hemorrhagic brain metastasis from pulmonary blastoma: a case report

    Pulmonary blastoma is a rare primary lung malignancy consisting of mesenchymal and epithelial components resembling the fetal lung. We report a case of pulmonary blastoma with solitary hemorrhagic brain metastasis in a 32-year-old man. This metastatic lesion was composed mainly of hemorrhagic high density and central necrotic low density areas; on CT it showed partial contrast enhancement and was thus impossible to distinguish from other hemorrhagic lesions

  11. Brain metastasis in two patients with stage IA papillary serous carcinoma of the uterus

    Narasimhulu, Deepa M.; Neekianund Khulpateea; Keith Meritz; Yiquing Xu

    2015-01-01

    We report two cases of brain metastasis in patients initially diagnosed with extremely early stage UPSC after extensive staging surgery. They did not receive either adjuvant chemotherapy or adjuvant pelvic or vaginal cuff radiation. At the same time that these patients were diagnosed with systemic metastasis, they both had a local “drop” metastasis in the vulva or the vaginal cuff. After the initial response to palliative chemotherapy, they both developed brain metastasis. The pattern of recu...

  12. The impact of repeat stereotactic radiosurgery on the management of brain metastasis with maintaining brain function

    We investigated the utility of repeat stereotactic radiosurgery (RSRS), assisted with a careful monitoring by MRI, in the management of brain metastases. Thirty-seven patients harboring brain metastasis received RSRS. RSRS at the same site was performed in 14. The cumulative 5-year survival rate was 29% and the median survival time was 32 months. Cause of death was as follows: 14 uncontrolled extracranial disease and 2 progressed brain metastases. There were no severe adverse events. For 16 patients, neurocognitive function was examined and the most recent results revealed that 88% was not associated with impaired neurocognition. RSRS appears a preferred option to manage brain metastases with maintaining brain function. (author)

  13. Brain metastasis from uterine serous carcinoma: A case report and review of literature

    Tania Sierra; Long Nguyen; Justin Mascitelli; Tamara Kalir; David Fishman

    2015-01-01

    Highlights • Brain metastasis from UPSC is rare, with 9 cases in the literature. • UPSC may resemble other endometrial cancers in regard to brain metastatic behavior. • When appropriate, it seems that multimodal therapy offers the best outcomes.

  14. Serpins Promote Cancer Cell Survival and Vascular Cooption in Brain Metastasis

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

    2014-01-01

    Brain metastasis is an ominous complication of cancer, yet most cancer cells that infiltrate the brain die of unknown causes. Here we identify plasmin from the reactive brain stroma as a defense against metastatic invasion, and plasminogen activator (PA) inhibitory serpins in cancer cells as a shield against this defense. Plasmin suppresses brain metastasis in two ways: by converting membrane-bound astrocytic FasL into a paracrine death signal for cancer cells, and by inactivating the axon pa...

  15. Gamma knife surgery for brain metastasis from hepatocellular carcinoma.

    Qingsheng Xu

    Full Text Available OBJECTIVES: The authors evaluated the results of Gamma knife surgery (GKS for the treatment of metastatic brain tumors from hepatocellular carcinoma (HCC. METHODS AND RESULTS: The authors conducted a retrospective review of the clinical characteristics and treatment outcomes in 14 patients with metastatic brain tumors from HCC who underwent GKS. Twelve (85.7% patients were male. The mean age of the patients was 53±12 years. There were totally 22 brain metastases in 14 patients and 8 patients (57.1% presented with a single brain lesion. Intracranial hemorrhages occurred in 13 (59.1% of the 22 lesions. The mean KPS score was 81±14 (range 50-100. Eleven (78.6% patients were classified as RTOG RPA Class 2. The mean tumor volume was 8.16±8.15 cm(3 (range 0.59-27.0 cm(3. The mean marginal dose prescribed was 18.7±3.2 Gy (range 10.0-22.0 Gy. The mean number of shots administered was 10±9 (range 1-27. The median overall survival time after GKS was 5.0±0.93 months (95% CI 3.2-6.8. No complications related to the radiosurgical treatment were identified. Multivariate analysis showed that the total volume of brain metastases, the RTOG RPA class and serum AFP level were significantly correlated with patients' survival time. CONCLUSIONS: Although survival was extremely poor in patients with brain metastasis (BM from HCC, GKS was shown to lead to prolongation of the survival time. Accordingly, GKS can be considered as a valuable treatment option for proper patients with HCC BM.

  16. Experience on breast cancer with brain metastasis in Kanagawa Cancer Center

    We studied the relationship between clinicopathologic findings and effect of adjuvant therapy on brain metastasis in breast cancer in order to clarify risk factors for brain metastasis in breast cancer patients. We divided patients into a group treated up until December 1999 (Group 1) and a group treated after January 2000 (Group 2), in whom adjuvant therapy was not generalized. Estrogen receptor-negative patients and cases more advanced than T2 showed a high risk of brain metastasis. The time interval to brain metastasis in Group 1 and 2 were 25 and 49.6 months, respectively, showing a significant difference. Taxan derivatives were used in 1.6% of Group 1 and 76% of Group 2. Estrogen receptor negativity, cancer more advanced than T2, and adjuvant therapy are risk factors for brain metastasis. (author)

  17. Risk factors for brain metastasis in small-cell lung cancer after surgery

    Objective: To evaluate clinical risk factors that can predict brain metastasis after complete resection of small cell lung cancer (SCLC) and to assess the role of prophylactic cranial irradiation (PCI) in such kind of patients. Methods: Eighty-eight patients with completely resected stage I - III SCLC from Jan. 2000 to Dec. 2009 in our hospital were retrospectively analyzed. Kaplan-Meier was used to compare the differences in the incidence of metastasis free survival in different groups. Logistic model was used to assess the independent risk factors for brain metastasis. Results: The follow-up rate is 100%, and 37 patients were followed up for more than three years. None of the 3 patients who received PCI developed brain metastasis, while for patients without receiving PCI, 24% developed brain metastases. The incidence of brain metastasis for stage I, II and III SCLC after surgery were 4%, 26% and 29% (χ2 =7.57, P =0.023), respectively. The median survival time and the 3-year survival rate were 18 months and 25% for patients who developed brain metastasis, and 48 months and 59% for those without brain metastasis (χ2 =10.63, P =0.001). Both univariate and multivariate analyses showed that pre-treatment disease stage was independent risk factor for brain metastasis (χ2 =7.57, 8.52; P =0.023, 0.004). Age, sex, tumor location, pathological type, induction chemotherapy, and postoperative chemotherapy/radiotherapy were not significantly correlated with the incidence of brain metastasis (χ2 =0.03, 0.00, 0.00, 2.58, 0.01, 1.23, 0.84; P =0.869, 0.998, 0.992, 0.109, 0.936, 0.266, 0.361, respectively). Conclusions: Pre-treatment disease stage was independent risk factor for brain metastasis in SCLC. PCI may be important for stage II -III SCLC but not for stage I disease. (authors)

  18. Whole brain radiation therapy in management of brain metastasis: results and prognostic factors

    To evaluate the prognostic factors associated with overall survival in patients with brain metastasis treated with whole brain radiotherapy (WBRT) and estimate the potential improvement in survival for patients with brain metastases, stratified by the Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) class. From January 1996 to December 2000, 270 medical records of patients with diagnosis of brain metastasis, who received WBRT in the Hospital do Cancer Sao Paulo A.C. Camargo in the period, were analyzed. The surgery followed by WBRT was used in 15% of patients and 85 % of others patients were submitted at WBRT alone; in this cohort 134 patients (50%) received the fractionation schedule of 30 Gy in 10 fractions. The most common primary tumor type was breast (33%) followed by lung (29%), and solitary brain metastasis was present in 38.1% of patients. The prognostic factors evaluated for overall survival were: gender, age, Karnofsky Performance Status (KPS), number of lesions, localization of lesions, primary tumor site, surgery, chemotherapy, absence extracranial disease, RPA class and radiation doses and fractionation. The OS in 1, 2 and 3 years was 25, 1%, 10, 4% e 4, 3% respectively, and the median survival time was 4.6 months. The median survival time in months according to RPA class after WBRT was: 6.2 class I, 4.2 class II and 3.0 class III (p < 0.0001). In univariate analysis, the significant prognostic factors associated with better survival were: KPS higher than 70 (p < 0.0001), neurosurgery (p < 0.0001) and solitary brain metastasis (p = 0.009). In multivariate analysis, KPS higher than 70 (p < 0.001) and neurosurgery (p = 0.001) maintained positively associated with the survival. In this series, the patients with higher perform status, RPA class I, and treated with surgery followed by whole brain radiotherapy had better survival. This data suggest that patients with cancer and a single metastasis to the brain may be treated

  19. Brain metastasis in two patients with stage IA papillary serous carcinoma of the uterus.

    Narasimhulu, Deepa M; Khulpateea, Neekianund; Meritz, Keith; Xu, Yiquing

    2015-08-01

    We report two cases of brain metastasis in patients initially diagnosed with extremely early stage UPSC after extensive staging surgery. They did not receive either adjuvant chemotherapy or adjuvant pelvic or vaginal cuff radiation. At the same time that these patients were diagnosed with systemic metastasis, they both had a local "drop" metastasis in the vulva or the vaginal cuff. After the initial response to palliative chemotherapy, they both developed brain metastasis. The pattern of recurrence with the lack of adjuvant treatment underscores the urgent need in further evaluation of the potential benefits of adjuvant treatment, including chemotherapy and possibly in combination with radiation in this highly aggressive disease. PMID:26425708

  20. Surgical Treatment for Non-small Cell Lung Cancer Patients with Synchronous Solitary Brain Metastasis

    Bai, Hao; Han, Baohui

    2013-01-01

    Background and objective Brain metastases are common in non-small cell lung cancer. Usual treatments include radiotherapy and chemotherapy. However, these methods result in poor patient prognosis. The aim of this study is to assess the effectiveness of surgical resection in the multimodality management of non-small cell lung cancer patients with synchronous solitary brain metastasis. Methods The clinical data of 46 non-small cell lung cancer patients with synchronous solitary brain metastasis...

  1. Association between brain metastasis from lung cancer and the serum level of myelin basic protein

    Liu, Wei; Zhao, Jing; WEI, YUJUAN

    2015-01-01

    The aim of the present study was to determine the association between the expression of myelin basic protein in the serum and the metastasis of lung cancer to the brain. A total of 68 lung cancer patients, treated in the Department of Respiratory Medicine of the People’s Hospital of Rizhao (Rizhao, China), were divided into two groups, those with brain metastasis (32 cases) and those without brain metastasis (36 cases). The expression levels of myelin basic protein were measured for all the p...

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

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

    2014-01-15

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

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

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

  4. Brain metastasis from prostate cancer. Report of 13 cases and critical analysis of the literature

    Salvati, M.; Frati, A. [INM Neuromed IRCCS, Pozzilli (Italy). Dept. of Neurosurgery; Pavia Univ., Pavia (Italy). IRRCCS Mondino; Russo, N.; Brogna, C.; Piccirilli, M.; Occhiogrosso, G.; Pichierri, A. [Policlinico Umberto 1., Rome (Italy). Dept. of Neurological Sciences-Neurosurgery; D' Andrea, G.; Caroli, E. [Ospedale S. Andrea, Rome (Italy). Dept. of Neurological Sciences-Neurosurgery

    2005-06-15

    Brain metastasis from prostate carcinoma occurs very rarely. We describe 13 patients with single brain metastasis from prostatic cancer. Total removal of the lesions was performed in ten patients. Three patients underwent stereotactic biopsy. All patients were treated with postoperative whole brain radiotherapy (WBRT). Eight patients died for systemic disease after a mean time of 9.2 months with a diagnosis of metastasis. Five patients are still alive at 20, 14, 11, 7 and 6 months, respectively. Even if brain metastasis from prostate cancer is often a terminal event with death occurring within few months from diagnosis, we suggest the same protocol (surgery and/or radiosurgery plus postoperative WBRT) usually adopted to treat brain metastasis from other primitive tumours. A non specific neurological symptomatology and a possible normal dosage of serum specific antigen may contribute to a delay in diagnosis. However, considering the rarity of brain metastasis from prostate carcinoma, standard brain MRI follow-up in men with prostatic cancer does not seem to be necessary yet.

  5. Brain metastasis from prostate cancer. Report of 13 cases and critical analysis of the literature

    Brain metastasis from prostate carcinoma occurs very rarely. We describe 13 patients with single brain metastasis from prostatic cancer. Total removal of the lesions was performed in ten patients. Three patients underwent stereotactic biopsy. All patients were treated with postoperative whole brain radiotherapy (WBRT). Eight patients died for systemic disease after a mean time of 9.2 months with a diagnosis of metastasis. Five patients are still alive at 20, 14, 11, 7 and 6 months, respectively. Even if brain metastasis from prostate cancer is often a terminal event with death occurring within few months from diagnosis, we suggest the same protocol (surgery and/or radiosurgery plus postoperative WBRT) usually adopted to treat brain metastasis from other primitive tumours. A non specific neurological symptomatology and a possible normal dosage of serum specific antigen may contribute to a delay in diagnosis. However, considering the rarity of brain metastasis from prostate carcinoma, standard brain MRI follow-up in men with prostatic cancer does not seem to be necessary yet

  6. Stereotactic irradiation without whole-brain irradiation for single brain metastasis

    Purpose: The effectiveness of stereotactic irradiation (STI) alone without whole-brain irradiation (WBI) for a single metastatic brain tumor was analyzed retrospectively. Methods and Materials: Forty-four patients with this condition were treated using radiosurgery (RS) alone or fractionated stereotactic radiotherapy (FSR) without WBI. Results: The initial response rate was 92% and the overall local control rate was 84% (37 of 44 patients). A total of 39% (18 of 44) of patients experienced intracranial relapse outside the initial target area. Forty-eight percent (21 of 44) of patients required salvage treatment for intracranial relapse. All 7 patients who received WBI as salvage treatment required no further salvage treatment, but 5 of the 14 patients who received salvage STI without WBI required three to four treatments for brain metastasis. Late radiation damage was not seen with initial treatment but was observed with retreatment. The overall median survival time was 261 days, with a standard error of 64 days. Actuarial survival at 12 and 24 months was 34% and 9%, respectively. The actuarial survival rate was significantly affected by the existence of active extracranial disease (p = 0.041). Conclusion: The high response rate and short treatment period of STI alone are advantageous in the treatment of single brain metastasis in patients with active extracranial disease with WBI reserved for relapse. Because of the low complication rate, STI alone may be also useful in patients with good prognosis, without extracranial disease

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

    Forty cases of malignant brain tumors with metastasis which involved 14 malignant gliomas, 15 medulloblastomas and 11 germ cell tumors were studied on CT and MRI. In malignant glioma, transventricular metastasis was seen most frequently, estimating 8 cases (57%) of 14 malignant gliomas with metastasis and showing ependymal-subependymal enhancement on contrast-enhanced CT (CECT). Most of the medulloblastoma with metastasis demonstrated diffuse subarachnoid seeding in the craniospinal space and on image analysis diffuse sulcal-cisternal enhancement was characterized. Trans-ventricular metastasis in medulloblastoma was less than in malignant glioma showing 3 cases (20%) of 15 medulloblastomas, which in most cases showed a nodular tumor in the ventricular wall by metastasis. There were six patients who, on the first admission, were found to have germ cell tumors of the broad infiltrating type with multiple lesions. The tumor sites of metastasis were different from those with malignant gliomas, being frequently localized in the pineal and/or the suprasellar region, on the ventricular wall and in the basal ganglia. Metastasis to a remote area in germ cell tumors was to spinal cords, to the ventricular wall and basal cistern around the brain stem by CSF dissemination, to the lung by hematogenous metastasis and to the peritoneal wall or organs through V-P shunt tube. T1-weighted Gd-DTPA MRI was more useful and sensitive than CECT for diagnosis of the leptomeningeal metastasis, particularly for sulcal-cisternal and spinal metastasis. It will be used more often as the first choice for diagnosis of intrathecal metastasis in the future. (author)

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

    Miyagami, Mitsusuke; Kasahara, Eishi; Tazoe, Makoto; Tsubokawa, Takashi (Nihon Univ., Tokyo (Japan). School of Medicine)

    1990-08-01

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

  9. Miliary brain metastasis presenting with calcification in a patient with lung cancer: a case report

    Inomata Minehiko

    2012-09-01

    Full Text Available Abstract Introduction Miliary brain metastasis is an extremely rare form of brain metastasis which can present with atypical imaging findings. We report the case of a patient with miliary brain metastasis of lung cancer showing calcification in metastatic lesions. Case presentation A 68-year-old Japanese woman was diagnosed with lung adenocarcinoma. Brain computed tomography revealed multiple small calcified lesions in both cerebral hemispheres. Mutation of the epidermal growth factor receptor gene (exon 21, L858R in lung cancer cells was detected, and treatment with gefitinib was initiated. A partial response was observed; however, the patient was readmitted to our hospital because of regrowth of the primary lesion and complaints of nausea, headache, and difficulty walking. Brain magnetic resonance imaging revealed scattered tiny nodules enhanced by gadolinium. A diagnosis of leptomeningeal carcinomatosis was made on the basis of cerebrospinal fluid cytology. The patient’s general status worsened, and she died 356 days after the day of first medical examination. Upon autopsy, the brain was found to be edematous and swollen. Lung carcinoma cells were diffusely disseminated on the meningeal surface. Metastatic foci of small nodular form, accompanied by calcifications, were also found in the brain parenchyma. We diagnosed miliary metastasis of lung carcinoma. Conclusions To the best of our knowledge, this is the third report of calcified miliary brain metastasis confirmed by autopsy. We describe calcified lesions that increased in size during the clinical course of nine months. Brain computed tomography findings that reveal multiple small calcified lesions in patients with malignancy should raise suspicion of miliary brain metastasis.

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

    Sebastiano Cavallaro

    2013-01-01

    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...

  11. In vivo modeling and molecular characterization: a path towards targeted therapy of melanoma brain metastasis

    AvitalGaziel-Sovran

    2013-05-01

    Full Text Available Brain metastasis from melanoma remains mostly incurable and the main cause of death from the disease. Early stage clinical trials and case studies show some promise for targeted therapies in the treatment of melanoma brain metastasis. However, the progression-free survival for currently available therapies, although significantly improved, is still very short. The development of new potent agents to eradicate melanoma brain metastasis relies on the elucidation of the molecular mechanisms that drive melanoma cells to reach and colonize the brain. The discovery of such mechanisms depends heavily on pre-clinical models that enable the testing of candidate factors and therapeutic agents in vivo. In this review we summarize the effects of available targeted therapies on melanoma brain metastasis in the clinic. We provide an overview of existing pre-clinical models to study the disease and discuss specific molecules and mechanisms reported to modulate different aspects of melanoma brain metastasis and finally, by integrating both clinical and basic data, we summarize both opportunities and challenges currently presented to researchers in the field.

  12. The factors that have an impact on the development of brain metastasis in the patients with breast cancer

    Adem Dayan; Dogan Koca; Tulay Akman; Ilhan Oztop; Hulya Ellidokuz; Ugur Yilmaz

    2012-01-01

    Background: To evaluate the factors that have an impact on the development of brain metastasis in patients with breast cancer. Materials and Methods: Among the patients who were followed-up and treated for breast cancer between January 2000 and January 2010, the ones with brain metastasis were included to the analysis. Metastatic breast cancer patients without brain metastasis, which had similar duration of follow-up and median age were included as the control group. Both group were compa...

  13. Brain metastasis from uterine serous carcinoma: A case report and review of literature.

    Sierra, Tania; Nguyen, Long; Mascitelli, Justin; Kalir, Tamara; Fishman, David

    2015-01-01

    Brain metastasis from UPSC is rare, with 9 cases in the literature.•UPSC may resemble other endometrial cancers in regard to brain metastatic behavior.•When appropriate, it seems that multimodal therapy offers the best outcomes. PMID:26076093

  14. The metastatic microenvironment: Claudin-1 suppresses the malignant phenotype of melanoma brain metastasis.

    Izraely, Sivan; Sagi-Assif, Orit; Klein, Anat; Meshel, Tsipi; Ben-Menachem, Shlomit; Zaritsky, Assaf; Ehrlich, Marcelo; Prieto, Victor G; Bar-Eli, Menashe; Pirker, Christine; Berger, Walter; Nahmias, Clara; Couraud, Pierre-Olivier; Hoon, Dave S B; Witz, Isaac P

    2015-03-15

    Brain metastases occur frequently in melanoma patients with advanced disease whereby the prognosis is dismal. The underlying mechanisms of melanoma brain metastasis development are not well understood. Identification of molecular determinants regulating melanoma brain metastasis would advance the development of prevention and therapy strategies for this disease. Gene expression profiles of cutaneous and brain-metastasizing melanoma variants from three xenograft tumor models established in our laboratory revealed that expression of tight junction component CLDN1 was lower in the brain-metastasizing variants than in cutaneous variants from the same melanoma. The objective of our study was to determine the significance of CLDN1 downregulation/loss in metastatic melanoma and its role in melanoma brain metastasis. An immunohistochemical analysis of human cells of the melanocyte lineage indicated a significant CLDN1 downregulation in metastatic melanomas. Transduction of melanoma brain metastatic cells expressing low levels of CLDN1 with a CLDN1 retrovirus suppressed their metastatic phenotype. CLDN1-overexpressing melanoma cells expressed a lower ability to migrate and adhere to extracellular matrix, reduced tumor aggressiveness in nude mice and, most importantly, eliminated the formation of micrometastases in the brain. In sharp contrast, the ability of the CLDN1-overexpressing cells to form lung micrometastases was not impaired. CLDN1-mediated interactions between these cells and brain endothelial cells constitute the mechanism underlying these results. Taken together, we demonstrated that downregulation or loss of CLDN1 supports the formation of melanoma brain metastasis, and that CLDN1 expression could be a useful prognostic predictor for melanoma patients with a high risk of brain metastasis. PMID:25046141

  15. Brain metastasis in two patients with stage IA papillary serous carcinoma of the uterus

    Deepa M. Narasimhulu

    2015-08-01

    Full Text Available We report two cases of brain metastasis in patients initially diagnosed with extremely early stage UPSC after extensive staging surgery. They did not receive either adjuvant chemotherapy or adjuvant pelvic or vaginal cuff radiation. At the same time that these patients were diagnosed with systemic metastasis, they both had a local “drop” metastasis in the vulva or the vaginal cuff. After the initial response to palliative chemotherapy, they both developed brain metastasis. The pattern of recurrence with the lack of adjuvant treatment underscores the urgent need in further evaluation of the potential benefits of adjuvant treatment, including chemotherapy and possibly in combination with radiation in this highly aggressive disease.

  16. Brain metastasis evaluation of lung carcinoma by PET-MRI as a guide therapeutic

    We report a clinical case of a 44 year-old woman with diagnosis of epidermoid lung carcinoma and three brain metastasis treated with surgery and radiation therapy. Three brain PET-MRI studies performed during the follow-up were useful and crucial for the detection of radionecrosis and tumor relapse. Brain PET-MRI is an important diagnostic tool in selected patients with cerebral metastases of lung cancer

  17. Gain of glucose-independent growth upon metastasis of breast cancer cells to the brain

    Chen, Jinyu; Lee, Ho-Jeong; Wu, Xuefeng; Huo, Lei; Kim, Sun-Jin; Xu, Lei; Wang, Yan; He, Junqing; Bollu, Lakshmi Reddy; Gao, Guang; Su, Fei; Briggs, James; Liu, Xiaojing; Melman, Tamar; Asara, John M.

    2014-01-01

    Breast cancer brain metastasis is resistant to therapy and a particularly poor prognostic feature in patient survival. Altered metabolism is a common feature of cancer cells but little is known as to what metabolic changes benefit breast cancer brain metastases. We found that brain-metastatic breast cancer cells evolved the ability to survive and proliferate independent of glucose due to enhanced gluconeogenesis and oxidations of glutamine and branched chain amino acids, which together sustai...

  18. Selective permeabilization of the blood-brain barrier at sites of metastasis

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

    2013-01-01

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

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

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

  20. Short-time focused ultrasound hyperthermia enhances liposomal doxorubicin delivery and antitumor efficacy for brain metastasis of breast cancer

    Wu SK

    2014-09-01

    Full Text Available Sheng-Kai Wu,1 Chi-Feng Chiang,1 Yu-Hone Hsu,1,4 Tzu-Hung Lin,2 Houng-Chi Liou,2 Wen-Mei Fu,2 Win-Li Lin1,3 1Institute of Biomedical Engineering, College of Medicine and College of Engineering, 2Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan; 3Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli, Taiwan; 4Department of Neurosurgery, Cheng-Hsin General Hospital, Taipei, Taiwan Abstract: The blood–brain/tumor barrier inhibits the uptake and accumulation of chemotherapeutic drugs. Hyperthermia can enhance the delivery of chemotherapeutic agent into tumors. In this study, we investigated the effects of short-time focused ultrasound (FUS hyperthermia on the delivery and therapeutic efficacy of pegylated liposomal doxorubicin (PLD for brain metastasis of breast cancer. Murine breast cancer 4T1-luc2 cells expressing firefly luciferase were injected into female BALB/c mice striatum tissues and used as a brain metastasis model. The mice were intravenously injected with PLD (5 mg/kg with/without 10-minute transcranial FUS hyperthermia on day 6 after tumor implantation. The amounts of doxorubicin accumulated in the normal brain tissues and tumor tissues with/without FUS hyperthermia were measured using fluorometry. The tumor growth for the control, hyperthermia, PLD, and PLD + hyperthermia groups was measured using an IVIS spectrum system every other day from day 3 to day 11. Cell apoptosis and tumor characteristics were assessed using immunohistochemistry. Short-time FUS hyperthermia was able to significantly enhance the PLD delivery into brain tumors. The tumor growth was effectively inhibited by a single treatment of PLD + hyperthermia compared with both PLD alone and short-time FUS hyperthermia alone. Immunohistochemical examination further demonstrated the therapeutic efficacy of PLD plus short-time FUS hyperthermia for brain metastasis of breast cancer. The

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

    Song, Qi; Jiao, Shunchang; Li, Fang

    2016-08-20

    Brain metastasis, a common complication of non-small cell lung cancer (NSCLC) with an incidence rate of 30%-50%, significantly affects the patients' quality of life. The prognosis of patients of NSCLC with brain metastasis is extremely poor, the average median survival is only 1 m-2 m without treatment. The targeted therapy based on lung cancer driven gene is a new treatment. Besides, the immunotherapy which can enhance the effect of anti-cancer by simulating the immune system is a new approach. The combination of targeted therapy and immunotherapy can greatly benefit patients in clinical work. PMID:27561803

  2. The factors that have an impact on the development of brain metastasis in the patients with breast cancer

    Adem Dayan

    2012-01-01

    Conclusions: As the prognostic and predictive factors showing the development of brain metastasis in breast cancer patients may be identified, follow-up also including the brain is important in order to take preventive measures.

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

    Nikolaou Marinos; Stamenković Srđan; Stergiou Christos; Skarleas Christos; Torrens Michael

    2015-01-01

    Introduction. Brain metastases from epithelial ovarian cancer (EOC) are rare events. We present a rare case of single ovarian cancer metastasis to the brain treated with gamma-knife radiosurgery (GKRS). Case Outline. A 65-year-old woman with advanced EOC presented with severe neurologic symptoms. A single brain metastasis of 3.2 cm with surrounding edema in the left parietal lobe was detected by brain magnetic resonance imaging (MRI) scan during the work-up...

  4. Focalized external radiotherapy for resected solitary brain metastasis: does the dogma stand?

    Purpose: To investigate whether whole brain irradiation might be replaced by focalized irradiation after resection of a single brain metastasis in patients where extracranial tumor control is deemed to be obtained. Patients and methods: Twelve patients were introduced in a phase I/II prospective study of conformal postoperative external irradiation after resection of a solitary brain metastasis. The radiation treatment consisted of 50.4 Gy (1.8 Gy per fraction, five fractions per week). The planning target volume consisted of the tumor bed and a 2 cm safety margin. All treatments were optimized with head immobilization, dedicated tomodensitometry and computer assisted three-dimensional treatment planning. Results: The median survival was 7.2 months (range 2.4-50.4 months). Eleven of the 12 patients died. Eight of the 12 patients presented intracranial recurrence and seven died as a consequence of intracranial tumor progression. Conclusions: Focalized external irradiation cannot serve as a reasonable alternative to whole brain radiotherapy (WBRT) even for patients with apparently one single resected brain metastasis. The dogma of 'one metastasis=multiple metastases' seems to be confirmed. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  5. Control of the blood-brain barrier function in cancer cell metastasis.

    Blecharz, Kinga G; Colla, Ruben; Rohde, Veit; Vajkoczy, Peter

    2015-10-01

    Cerebral metastases are the most common brain neoplasms seen clinically in the adults and comprise more than half of all brain tumours. Actual treatment options for brain metastases that include surgical resection, radiotherapy and chemotherapy are rarely curative, although palliative treatment improves survival and life quality of patients carrying brain-metastatic tumours. Chemotherapy in particular has also shown limited or no activity in brain metastasis of most tumour types. Many chemotherapeutic agents used systemically do not cross the blood-brain barrier (BBB), whereas others may transiently weaken the BBB and allow extravasation of tumour cells from the circulation into the brain parenchyma. Increasing evidence points out that the interaction between the BBB and tumour cells plays a key role for implantation and growth of brain metastases in the central nervous system. The BBB, as the tightest endothelial barrier, prevents both early detection and treatment by creating a privileged microenvironment. Therefore, as observed in several in vivo studies, precise targetting the BBB by a specific transient opening of the structure making it permeable for therapeutic compounds, might potentially help to overcome this difficult clinical problem. Moreover, a better understanding of the molecular features of the BBB, its interrelation with metastatic tumour cells and the elucidation of cellular mechanisms responsible for establishing cerebral metastasis must be clearly outlined in order to promote treatment modalities that particularly involve chemotherapy. This in turn would substantially expand the survival and quality of life of patients with brain metastasis, and potentially increase the remission rate. Therefore, the focus of this review is to summarise the current knowledge on the role and function of the BBB in cancer metastasis. PMID:26032862

  6. Brain metastasis from hepatocellular carcinoma: the role of surgery as a prognostic factor

    The incidence of brain metastasis from hepatocellular carcinoma (HCC) is expected to increase as a result of prolonged survival due to the recent advances in HCC treatment. However, there is no definite treatment strategy for brain metastasis from HCC mainly due to its rarity and dismal prognosis. To provide helpful recommendations in treatment of brain metastasis from HCC, the authors aimed to identify prognostic factors that influence survival rates with a review of the recently published data. Thirty-three cases of brain metastasis, whose incidence was 0.65%, were selected from a total of 5015 HCC patients and reviewed retrospectively in terms of clinical and radiological features. Median overall survival time after diagnosis of brain metastasis was 10.4 weeks (95% confidence interval [CI], 5.1-15.7 weeks) with 1-, 6- and 12-month survival rates, of 79%, 24% and 6%, respectively. Median survival of the patients treated with surgical resection or surgical resection followed by whole-brain radiation therapy (WBRT) (25.3 weeks; range, 15.8-34.8 weeks) was longer than that of the patients treated with gamma knife surgery (GKS), WBRT, or GKS followed by WBRT (10.4 weeks; range, 7.5-13.3 weeks) as well as that of patients treated with only steroids (1 week; range, 0.0-3.3 weeks) (p < 0.001). Child-Pugh’s classification A group had a longer median survival time than Child-Pugh’s classification B or C group (14.4 weeks vs 8.4 weeks, p = 0.038). RPA class I & II group had also a longer median survival time than RPA class III group did (13.4 weeks vs 2.4 weeks, p = 0.001). Surgical resection (hazard ratio [HR] 0.23, 95% CI 0.08-0.66, p = 0.006) and good liver function at the time of brain metastasis (HR 0.25, 95% CI 0.09-0.69, p = 0.007) were found to be the powerful prognostic factors for favorable survival in the multivariate analysis. In addition, presence of intratumoral hemorrhage was a statistically significant prognostic factor for survival. Although HCC

  7. Clinical Analysis for Brain Tumor-Related Epilepsy during Chemotherapy for Systemic Cancer with Single Brain Metastasis

    Kim, Young Zoon; Lee, Eun Hee; Lee, Kyoung Soo

    2011-01-01

    Purpose The purpose of this prospective observational study was to determine the incidence, patterns, and predisposing factors for brain tumor-related epilepsy (BTRE) during chemotherapy for systemic cancer with single brain metastasis (BM). Materials and Methods Between February 2006 and June 2010, 103 patients who underwent chemotherapy for systemic cancer with single BM were enrolled. We compared the clinical factors of patients and BM between patients with and without BTRE. We determined ...

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

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

  9. Brain metastasis. Prognostic value of the number of involved extracranial organs

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

    2013-12-15

    Background and purpose: This study was performed to evaluate the prognostic role for survival of the number and the type of involved extracranial organs in patients with brain metastasis. Material and methods: The data of 1146 patients who received whole-brain radiotherapy (WBRT) alone for brain metastasis have been retrospectively analyzed. In addition to the number of involved extra cranial organs, seven potential prognostic factors were investigated including WBRT regimen, age, gender, Karnofsky Performance Score (KPS), primary tumor type, number of brain metastases, and the interval from cancer diagnosis to WBRT. Additionally, subgroup analyses were performed for patients with involvement of one (lung vs. bone vs. liver vs. other metastasis) and two (lung + lymph nodes vs. lung + bone vs. lung + liver vs. liver + bone vs. other combinations) extracranial organs. Results: The 6-month survival rates for the involvement of 0, 1, 2, 3, and {>=} 4 extracranial organs were 51, 30, 16, 13, and 10 %, respectively (p < 0.001). On multivariate analysis, the number of involved extracranial organs maintained significance (risk ratio 1.26; 95 % confidence interval 1.18-1.34; p < 0.001). According to the multivariate analysis, age (p < 0.001), gender (p = 0.002), and KPS (p < 0.001) were also independent prognostic factors for survival. In the subgroup analyses of patients with involvement of one and two extracranial organs, survival was not significantly different based on the extracranial organ involved. Conclusion: The number of involved extracranial organs proved to be an independent prognostic factor in patients with brain metastasis, regardless of the organs involved. The number of involved extracranial organs should be considered in future trials designed for patients with brain metastasis. (orig.)

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

    Laura Camacho

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

  11. Brain metastasis. Prognostic value of the number of involved extracranial organs

    Background and purpose: This study was performed to evaluate the prognostic role for survival of the number and the type of involved extracranial organs in patients with brain metastasis. Material and methods: The data of 1146 patients who received whole-brain radiotherapy (WBRT) alone for brain metastasis have been retrospectively analyzed. In addition to the number of involved extra cranial organs, seven potential prognostic factors were investigated including WBRT regimen, age, gender, Karnofsky Performance Score (KPS), primary tumor type, number of brain metastases, and the interval from cancer diagnosis to WBRT. Additionally, subgroup analyses were performed for patients with involvement of one (lung vs. bone vs. liver vs. other metastasis) and two (lung + lymph nodes vs. lung + bone vs. lung + liver vs. liver + bone vs. other combinations) extracranial organs. Results: The 6-month survival rates for the involvement of 0, 1, 2, 3, and ≥ 4 extracranial organs were 51, 30, 16, 13, and 10 %, respectively (p < 0.001). On multivariate analysis, the number of involved extracranial organs maintained significance (risk ratio 1.26; 95 % confidence interval 1.18-1.34; p < 0.001). According to the multivariate analysis, age (p < 0.001), gender (p = 0.002), and KPS (p < 0.001) were also independent prognostic factors for survival. In the subgroup analyses of patients with involvement of one and two extracranial organs, survival was not significantly different based on the extracranial organ involved. Conclusion: The number of involved extracranial organs proved to be an independent prognostic factor in patients with brain metastasis, regardless of the organs involved. The number of involved extracranial organs should be considered in future trials designed for patients with brain metastasis. (orig.)

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

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

    2002-08-01

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

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

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

  14. Gamma Knife Surgery for Brain Metastasis from Hepatocellular Carcinoma

    Qingsheng Xu; Pan Wu; Yiping Feng; Ke Ye; Ying Tong; Yongqing Zhou

    2014-01-01

    OBJECTIVES: The authors evaluated the results of Gamma knife surgery (GKS) for the treatment of metastatic brain tumors from hepatocellular carcinoma (HCC). METHODS AND RESULTS: The authors conducted a retrospective review of the clinical characteristics and treatment outcomes in 14 patients with metastatic brain tumors from HCC who underwent GKS. Twelve (85.7%) patients were male. The mean age of the patients was 53±12 years. There were totally 22 brain metastases in 14 patients and 8 patien...

  15. Outcomes in 12 gynecologic cancer patients with brain metastasis: a single center’s experience

    CÖMERT, Esra ÇABUK; BİLDACI, Tevfik Berk; KARAKAYA, Burcu KISA; TARHAN, Nefise Çağla; Özlem ÖZEN; Gülşen, Salih; Dursun, Polat; Ayhan, Ali

    2012-01-01

    To present 12 gynecologic cancer cases with brain metastasis and a discussion of the relevant literature. Gynecologic malignancy is the second most common cancer in elderly women, following breast cancer. These cancers usually spread locally at first, and common distant metastatic sites are the lungs, liver, spleen, and distant lymph nodes. The brain is not a usual site of metastatic involvement. Materials and methods: The study included 12 cases with various gynecologic malignancies that w...

  16. Brain metastasis from pheochromocytoma in a patient with multiple endocrine neoplasia type 2A.

    Gentile, S; Rainero, I; Savi, L; Rivoiro, C; Pinessi, L

    2001-12-01

    Neurological involvement in multiple endocrine neoplasia (MEN) syndrome is uncommon. Notalgia paresthetica (pruritus localized in an area between D2 and D6 dermatomes) is the neurological symptom more frequently described in patients with MEN 2A. The authors report the unusual case of a MEN 2A patient with a brain metastasis from a pheochromocytoma. PMID:11677427

  17. The fibrinolytic system facilitates tumor cell migration across the blood-brain barrier in experimental melanoma brain metastasis

    Patients with metastatic tumors to the brain have a very poor prognosis. Increased metastatic potential has been associated with the fibrinolytic system. We investigated the role of the fibrinolytic enzyme plasmin in tumor cell migration across brain endothelial cells and growth of brain metastases in an experimental metastatic melanoma model. Metastatic tumors to the brain were established by direct injection into the striatum or by intracarotid injection of B16F10 mouse melanoma cells in C57Bl mice. The role of plasminogen in the ability of human melanoma cells to cross a human blood-brain barrier model was studied on a transwell system. Wild type mice treated with the plasmin inhibitor epsilon-aminocaproic acid (EACA) and plg-/- mice developed smaller tumors and survived longer than untreated wild type mice. Tumors metastasized to the brain of wild type mice treated with EACA and plg-/- less efficiently than in untreated wild type mice. No difference was observed in the tumor growth in any of the three groups of mice. Human melanoma cells were able to cross the human blood-brain barrier model in a plasmin dependent manner. Plasmin facilitates the development of tumor metastasis to the brain. Inhibition of the fibrinolytic system could be considered as means to prevent tumor metastasis to the brain

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

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

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

    Couraud Pierre-Olivier

    2009-07-01

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

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

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

    2012-01-01

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

  1. miR-509 suppresses brain metastasis of breast cancer cells by modulating RhoC and TNF α

    Xing, Fei; Sharma, Sambad; Liu, Yin; Mo, Yin-Yuan; Wu, Kerui; Zhang, Ying-Yu; Pochampally, Radhika; Martinez, Luis A.; Lo, Hui-Wen; Watabe, Kounosuke

    2015-01-01

    The median survival time of breast cancer patients with brain metastasis is less than 6 months, and even a small metastatic lesion often causes severe neurological disabilities. Because of the location of metastatic lesions, a surgical approach is limited and most chemotherapeutic drugs are ineffective due to the blood brain barrier (BBB). Despite this clinical importance, the molecular basis of the brain metastasis is poorly understood. In this study, we have isolated RNA from samples obtain...

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

    Iacoangeli M

    2012-12-01

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

  3. Morphological and functional MRI, MRS, perfusion and diffusion changes after radiosurgery of brain metastasis

    Kang, Tae Wook [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710 (Korea, Republic of)], E-mail: tw227.kang@samsung.com; Kim, Sung Tae [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710 (Korea, Republic of)], E-mail: st7.kim@hotmail.com; Byun, Hong Sik [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710 (Korea, Republic of)], E-mail: hongsik5474.byun@samsung.com; Jeon, Pyoung [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710 (Korea, Republic of)], E-mail: pyoung.jeon@samsung.com; Kim, Keonha [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710 (Korea, Republic of)], E-mail: somatom.kim@samsung.com; Kim, Hyungjin [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710 (Korea, Republic of)], E-mail: hyungjin1219.kim@samsung.com; Lee, Jung II [Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710 (Korea, Republic of)], E-mail: jilee.lee@samsung.com

    2009-12-15

    Radiosurgery is a noninvasive procedure where spatially accurate and highly conformal doses of radiation are targeted at brain lesions with an ablative intent. Recently, radiosurgery has been established as an effective technique for local treatment of brain metastasis. After radiosurgery, magnetic resonance (MR) imaging plays an important role in the assessment of the therapeutic response and of any complications. The therapeutic approach depends on the imaging findings obtained after radiosurgery, which have a role in the decision making to perform additional invasive modalities (repeat resection, biopsy) to obtain a definite diagnosis and to improve the survival of patients. Conventional MR imaging findings are mainly based on morphological alterations of tumors. However, there are variable imaging findings of radiation-induced changes including radiation necrosis in the brain. Radiologists are sometimes confused by radiation-induced injuries, including radiation necrosis, that are seen on conventional MR imaging. The pattern of abnormal enhancement on follow-up conventional MR imaging closely mimics that of a recurrent brain metastasis. So, classifying newly developed abnormal enhancing lesions in follow-up of treated brain metastasis with correct diagnosis is one of the key goals in neuro-oncologic imaging. To overcome limitations of the use of morphology-based conventional MR imaging, several physiological-based functional MR imaging methods have been used, namely diffusion-weighted imaging, perfusion MR imaging, and proton MR spectroscopy, for the detection of hemodynamic, metabolic, and cellular alterations. These imaging modalities provide additional information to allow clinicians to make proper decisions regarding patient treatment.

  4. Tumor-targeting Salmonella typhimurium A1-R arrests growth of breast-cancer brain metastasis

    Zhang, Yong; Miwa, Shinji; Zhang, Nan; Hoffman, Robert M.; Zhao, Ming

    2014-01-01

    Brain metastasis is a morbid, treatment-resistant, end-stage frequent occurrence in breast cancer patients. The aim of this study was to evaluate the efficacy of tumor-targeting Salmonella typhimurium A1-R on breast cancer brain metastases. High brain-metastatic variants of murine 4T1 breast cancer cells expressing red fluorescent protein (RFP) were injected orthotopically in the mammary fat pad in non-transgenic nude mice or in the left ventricle of non-transgenic nude mice and transgenic nu...

  5. Glioblastoma multiforme versus solitary supratentorial brain metastasis. Differentiation based on morphology and magnetic resonance signal characteristics

    Purpose: To evaluate the diagnostic potential of a multi-factor analysis of morphometric parameters and magnetic resonance (MR) signal characteristics of a mass and peritumoral area to distinguish solitary supratentorial metastasis from glioblastoma multiforme (GBM). Materials and Methods: MR examinations of 51 patients with histologically proven GBM and 44 with a single supratentorial metastasis were evaluated. A large variety of morphologic criteria and MR signal characteristics in different sequences were analyzed. The data were subjected to logistic regression to investigate their ability to discriminate between GBM and cerebral metastasis. Receiver-operating characteristic (ROC) analysis was used to select an optimal cut-off point for prediction and to assess the predictive value in terms of sensitivity, specificity, and accuracy of the final model. Results: The logistic regression analysis revealed that the ratio of the maximum diameter of the peritumoral area measured on T2-weighted images (d T2) to the maximum diameter of the enhancing mass area (d T1, post-contrast) is the only useful criterion to distinguish single supratentorial brain metastasis from GBM with a lower ratio favoring GBM (accuracy 68 %, sensitivity 84 % and specificity 45 %). The cut-off point for the ratio d T2/d T1 post-contrast was calculated as 2.35. Conclusion: Measurement of maximum diameters of the peritumoral area in relation to the enhancing mass can be evaluated easily in the clinical routine to discriminate GBM from solitary supratentorial metastasis with an accuracy comparable to that of advanced MRI techniques. (orig.)

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

    Sebastiano Cavallaro

    2013-01-01

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

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

    Paras Nuwal; Ramakant Dixit; Narender Singh Shah; Anil Samaria

    2012-01-01

    Synovial sarcoma is highly malignant tumor of soft tissues, occurring chiefly in the extremities and limb girdle with a propensity for local recurrence and sometimes metastases to the lungs. Primary synovial sarcoma arising in the lungs is rare and brain metastasis as presentation is further uncommon. We report a case of primary monophasic synovial sarcoma lung presenting with brain metastasis in a 35-year-old male patient. The diagnosis was made on percutaneous transthoracic needle aspiratio...

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

    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

    2015-01-01

    Background 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. Methods 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 IL2Rgammanull (NSG) mice. Human NK cells were...

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

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

    2014-06-01

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

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

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

  11. Expression of vascular endothelial growth factor is necessary but not sufficient for production and growth of brain metastasis.

    Yano, S; Shinohara, H; Herbst, R S; Kuniyasu, H; Bucana, C D; Ellis, L M; Davis, D W; McConkey, D J; Fidler, I J

    2000-09-01

    We investigated the molecular mechanisms of angiogenesis in experimental brain metastasis. Cells from six different human cancer cell lines (proven to produce visceral metastasis) were injected into the internal carotid artery of nude mice. Colon carcinoma (KM12SM) and lung adenocarcinoma (PC14PE6 and PC14Br) cells produced large, fast-growing parenchymal brain metastases, whereas lung squamous cell carcinoma (H226), renal cell carcinoma (SN12PM6), and melanoma (TXM13) cells produced only a few slow-growing brain metastases. Rapidly progressing brain metastases contained many enlarged blood vessels. The expression of VEGF mRNA and protein by the tumor cells directly correlated with angiogenesis and growth of brain metastasis. Causal evidence for the essential role of VEGF in this process was provided by transfecting PC14PE6 and KM12SM cells with antisense-VEGF165 gene, which significantly decreased the incidence of brain metastasis. In contrast, transfection of H226 human lung squamous carcinoma cells with sense-VEGF121 or sense-VEGF165 neither enhanced nor inhibited formation of brain metastases. Collectively, the results indicate that VEGF expression is necessary but not sufficient for the production of brain metastasis and that the inhibition of VEGF represents an important therapeutic target. PMID:10987313

  12. Up-regulation of microRNA-10b is associated with the development of breast cancer brain metastasis

    Ahmad, Aamir; Sethi, Seema; Chen, Wei; Ali-Fehmi, Rouba; Mittal, Sandeep; Fazlul H. Sarkar

    2014-01-01

    Brain metastases from primary breast cancer are difficult to treat and associated with poor prognosis. Our understanding of the molecular basis for the development of such cancers is sparse. We hypothesized that the pro-metastatic microRNA-10b (miR-10b) plays a role in breast cancer brain metastasis. The study cohort comprised of twenty patients with breast cancer and brain metastasis as well as ten control patients (age, stage, and follow-up matched) with breast cancer without brain metastas...

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

    Feng Li

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

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

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

  15. Efficacy of XELOX plus Bevacizumab in Brain Metastasis from Rectal Cancer

    Yoichiro Yoshida

    2014-02-01

    Full Text Available Brain metastasis (BM is rare in colorectal cancer (CRC patients. Although BM from CRC is a late-stage phenomenon with an extremely poor prognosis, some subsets of patients would benefit from a multidisciplinary management strategy. The prognosis of patients with BM from CRC was associated with the curability of the therapy for BM and the number of metastatic organs. Metastatic brain tumors are generally treated with radiotherapy because many anticancer drugs cannot cross the blood-brain barrier. Here, we present a case treated with XELOX (capecitabine and oxaliplatin plus bevacizumab for BM from rectal cancer. To our knowledge, this is the first report of a patient who was successfully treated for BM from CRC without radiotherapy. The findings could lead to a paradigm shift in the use of chemotherapy for BM from CRC.

  16. Management of brain metastasis with magnetic resonance imaging and stereotactic irradiation attenuated benefits of prophylactic cranial irradiation in patients with limited-stage small cell lung cancer

    Ozawa, Yuichi; Omae, Minako; Fujii, Masato; Matsui, Takashi; KATO, Masato; Sagisaka, Shinya; Asada, Kazuhiro; Karayama, Masato; Shirai, Toshihiro; Yasuda, Kazumasa; Nakamura, Yutaro; Inui, Naoki; Yamada, Kazunari; Yokomura, Koshi; Suda, Takafumi

    2015-01-01

    Background Magnetic resonance imaging (MRI) enables a more sensitive detection of brain metastasis and stereotactic irradiation (SRI) efficiently controls brain metastasis. In limited-stage small cell lung cancer (LS-SCLC), prophylactic cranial irradiation (PCI) in patients with good responses to initial treatment is recommended based on the survival benefit shown in previous clinical trials. However, none of these trials evaluated PCI effects using the management of brain metastasis with MRI...

  17. Targeting Kv1.3 channels to reduce white matter pathology after traumatic brain injury.

    Reeves, Thomas M; Trimmer, Patricia A; Colley, Beverly S; Phillips, Linda L

    2016-09-01

    Axonal injury is present in essentially all clinically significant cases of traumatic brain injury (TBI). While no effective treatment has been identified to date, experimental TBI models have shown promising axonal protection using immunosuppressants FK506 and Cyclosporine-A, with treatment benefits attributed to calcineurin inhibition or protection of mitochondrial function. However, growing evidence suggests neuroprotective efficacy of these compounds may also involve direct modulation of ion channels, and in particular Kv1.3. The present study tested whether blockade of Kv1.3 channels, using Clofazimine (CFZ), would alleviate TBI-induced white matter pathology in rodents. Postinjury CFZ administration prevented suppression of compound action potential (CAP) amplitude in the corpus callosum of adult rats following midline fluid percussion TBI, with injury and treatment effects primarily expressed in unmyelinated CAPs. Kv1.3 protein levels in callosal tissue extracts were significantly reduced postinjury, but this loss was prevented by CFZ treatment. In parallel, CFZ also attenuated the injury-induced elevation in pro-inflammatory cytokine IL1-β. The effects of CFZ on glial function were further studied using mixed microglia/astrocyte cell cultures derived from P3-5 mouse corpus callosum. Cultures of callosal glia challenged with lipopolysaccharide exhibited a dramatic increase in IL1-β levels, accompanied by reactive morphological changes in microglia, both of which were attenuated by CFZ treatment. These results support a cell specific role for Kv1.3 signaling in white matter pathology after TBI, and suggest a treatment approach based on the blockade of these channels. This therapeutic strategy may be especially efficacious for normalizing neuro-glial interactions affecting unmyelinated axons after TBI. PMID:27302680

  18. Identification and validation of S100A7 associated with lung squamous cell carcinoma metastasis to brain.

    Zhang, Hao; Wang, Yinping; Chen, Yue; Sun, Suozhu; Li, Na; Lv, Dongxia; Liu, Chuanjun; Huang, Lingyun; He, Dacheng; Xiao, Xueyuan

    2007-07-01

    To identify potential markers associated with non-small cell lung cancer (NSCLC) metastasis to brain, comparative proteome analysis on two lung squamous cell carcinoma (SCC) cell lines, NCI-H226 and H226Br (the brain metastatic cell line of NCI-H226), was performed using two-dimensional electrophoresis (2-DE) followed by a tandem mass spectrometer with a matrix-assisted laser desorption/ionization (MALDI) source. Twenty differential proteins were identified, of which 6 proteins were up-regulated in H226Br cell compared with NCI-H226 cells, whereas 14 proteins were down-regulated. S100A7 and 14-3-3sigma, two of candidate proteins significantly upregulated and downregulated in H226Br cell, were selected to verify the liability of the differential proteins by Western blot. The results were in accordance with 2-D data. To determine whether S100A7 overexpression is actually associated with SCC metastasis to brain, S100A7 protein was testified in 10 brain metastasis tissues from NSCLC, 38 primary NSCLC tissues including half matched local positive lymph nodes, 5 primary brain tumors and 2 non-cancer brain tissues by immunohistochemistry. Of particular interest to us was that the positive staining of S100A7 could be found in 3/5 (60%) brain metastases tissue from SCC and 8/21 (38%) the primary lung SCC tissues, while no positive staining was observed in the brain metastases tissue from Ad (n=5), the primary adenocarcinoma (Ad) tissues (n=17), the primary brain tumors (n=5), all local positive lymph nodes from the primary NSCLC (n=19) and non-cancer brain tissues (n=2). These findings suggest that S100A7 expression is closely associated with SCC metastasis to brain and may be a potential biomarker for monitoring the development of SCC. PMID:17418446

  19. A Case of Primary Colon Carcinoma Demonstrated by FDG PET/CT Imaging After Detection of a Solitary Brain Metastasis

    Seval Erhamamcı

    2015-06-01

    Full Text Available The detection of brain metastases as the initial manifestation of colorectal carcinoma without liver or lung involvement is extremely rare. Herein we present a case of a 52-year-old male patient with an unusual presentation of colon cancer, with primary lesions demonstrated by fluorine-18-labeled fluorodeoxyglucose (FDG Positron-emission tomography/computed tomography (PET/CT after detection of a solitary brain metastasis. Brain CT images revealed a brain tumor. Histopathologic evaluation indicated metastatic poorly differentiated adenocarcinoma, while his physical examination was normal. The PET/ CT revealed abnormal intense FDG uptake in the right parietal region and in descending colon, with no other abnormal FDG uptake elsewhere in the body. The histopathologic diagnosis of the descending colon lesion revealed moderately differentiated adenocarcinoma. This case indicates that FDG PET/CT imaging may have a positive impact on the evaluation of patients with brain metastasis from an unknown primary.

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

    Paras Nuwal

    2012-01-01

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

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

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

    2009-01-01

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

  2. The Effectiveness of Bevacizumab in Radionecrosis After Radiosurgery of a Single Brain Metastasis

    Ursino, Stefano; Pasqualetti, Francesco; Pesaresi, Ilaria; Desideri, Ilaria; Cosottini, Mirco; Laliscia, Concetta; Paiar, Fabiola; Fabrini, Maria Grazia

    2015-01-01

    Radionecrosis (RN) of brain tissue is a serious late complication of brain irradiation and historically has been treated with corticos-teroid therapy and alternatively surgical decompression. Recently, bevacizumab has been suggested for treatment of cerebral radiation necrosis. We present a case of a 73-years-old women affected by a primary non-small cell lung cancer with a single brain metastasis treated with radiosurgery. Two years after radiosurgery the patient referred neurological symptoms and a brain magnetic resonance confirmed the presence of RN. The patient refused surgical decompression so underwent at the treatment with bevacizumab 7.5 mg/kg/2 weeks for a total of 4 cycles. After two months of treatment the patient reported strumental and clinical improvement. Ten months after bevacizumab discontinuation the patient experienced a recurrence of RN with evident clinical manifestation and confirmed by radiological imaging. A new treatment with bevacizumab was not performed due to the systemic progression disease and the worsening of clinical status. Despite limited to only one clinical case, our study suggests the efficacy of bevacizumab to treat RN. Future studies are needed to confirm its mechanism and to properly define the optimal scheduling, dosage and duration of therapy. PMID:26788278

  3. The effectiveness of bevacizumab in radionecrosis after radiosurgery of a single brain metastasis

    Durim Delishaj

    2015-12-01

    Full Text Available Radionecrosis (RN of brain tissue is a serious late complication of brain irradiation and historically has been treated with corticosteroid therapy and alternatively surgical decompression. Recently, bevacizumab has been suggested for treatment of cerebral radiation necrosis. We present a case of a 73-years-old women affected by a primary non-small cell lung cancer with a single brain metastasis treated with radiosurgery. Two years after radiosurgery the patient referred neurological symptoms and a brain magnetic resonance confirmed the presence of RN. The patient refused surgical decompression so underwent at the treatment with bevacizumab 7.5 mg/kg/2 weeks for a total of 4 cycles. After two months of treatment the patient reported strumental and clinical improvement. Ten months after bevacizumab discontinuation the patient experienced a recurrence of RN with evident clinical manifestation and confirmed by radiological imaging. A new treatment with bevacizumab was not performed due to the systemic progression disease and the worsening of clinical status. Despite limited to only one clinical case, our study suggests the efficacy of bevacizumab to treat RN. Future studies are needed to confirm its mechanism and to properly define the optimal scheduling, dosage and duration of therapy.

  4. Evaluation of Different Score Index for Predicting Prognosis in Gamma Knife Radiosurgical Treatment for Brain Metastasis

    Purpose: To assess the utility of the Radiation Therapy Oncology Group Recursive Partitioning Analysis (RPA) and Score Index for Radiosurgery (SIR) stratification systems in predicting survival in patients with brain metastasis treated with Gamma Knife radiosurgery (GKRS). Methods and Materials: A total of 185 patients were included in the study. Patients were stratified according to RPA and SIR classes. The RPA and SIR classes, age, Karnofsky Performance Status (KPS), and systemic disease were correlated with survival. Results: Five patients were lost to follow-up. Median survival in patients in RPA Class 1 (30 patients) was 17 months; in Class 2 (140 patients), 10 months; and in Class 3 (10 patients), 3 months. Median survival in patients in SIR Class 1 (30 patients) was 3 months; in Class 2 (135 patients), 8 months; and in Class 3 (15 patients), 20 months. In univariate testing, age younger than 65 years (p = 0.0004), KPS higher than 70 (p = 0.0001), RPA class (p = 0.0078), SIR class (p = 0.0002), and control of the primary tumor (p = 0.02) were significantly associated with improved outcome. In multivariate analysis, KPS (p < 0.0001), SIR class (p = 0.0008), and RPA class (p = 0.03) had statistical value. Conclusions: This study supports the use of GKRS as a single-treatment modality in this selected group of patients. Stratification systems are useful in the estimation of patient eligibility for GKRS. A second-line treatment was necessary in 30% of patients to achieve distal or local brain control. This strategy is useful to control brain metastasis in long-surviving patients.

  5. Whole brain radiotherapy with adjuvant or concomitant boost in brain metastasis: dosimetric comparison between helical and volumetric IMRT technique

    To compare and evaluate the possible advantages related to the use of VMAT and helical IMRT and two different modalities of boost delivering, adjuvant stereotactic boost (SRS) or simultaneous integrated boost (SIB), in the treatment of brain metastasis (BM) in RPA classes I-II patients. Ten patients were treated with helical IMRT, 5 of them with SRS after whole brain radiotherapy (WBRT) and 5 with SIB. MRI co-registration with planning CT was mandatory and prescribed doses were 30 Gy in 10 fractions (fr) for WBRT and 15Gy/1fr or 45Gy/10fr in SRS or SIB, respectively. For each patient, 4 “treatment plans” (VMAT SRS and SIB, helical IMRT SRS and SIB) were calculated and accepted if PTV boost was included in 95 % isodose and dose constraints of the main organs at risk were respected without major deviations. Homogeneity Index (HI), Conformal Index (CI) and Conformal Number (CN) were considered to compare the different plans. Moreover, time of treatment delivery was calculated and considered in the analysis. Volume of brain metastasis ranged between 1.43 and 51.01 cc (mean 12.89 ± 6.37 ml) and 3 patients had double lesions. V95% resulted over 95 % in the average for each kind of technique, but the “target coverage” was inadequate for VMAT planning with two sites. The HI resulted close to the ideal value of zero in all cases; VMAT-SIB, VMAT-SRS, Helical IMRT-SIB and Helical IMRT-SRS showed mean CI of 2.15, 2.10, 2.44 and 1.66, respectively (optimal range: 1.5–2.0). Helical IMRT-SRS was related to the best and reliable finding of CN (0.66). The mean of treatment time was 210 s, 467 s, 440 s, 1598 s, respectively, for VMAT-SIB, VMAT-SRS, Helical IMRT-SIB and Helical IMRT-SRS. This dosimetric comparison show that helical IMRT obtain better target coverage and respect of CI and CN; VMAT could be acceptable in solitary metastasis. SIB modality can be considered as a good choice for clinical and logistic compliance; literature’s preliminary data are confirming

  6. Survival Analysis of Patients with Brain Metastasis by Weighting According to the Primary Tumor Oncotype

    Gwak, Hee Keun; Kim, Woo Chul; Kim, Hun Jung; Park, Jung Hoon; Song, Chang Hoon [Inha University Hospital, Incheon (Korea, Republic of)

    2009-09-15

    This study was performed to retrospectively analyze patient survival by weighting according to the primary tumor oncotype in 160 patients with brain metastasis and who underwent whole brain radiotherapy. A total of 160 metastatic brain cancer patients who were treated with whole brain radiotherapy of 30 Gy between 2002 and 2008 were retrospectively analyzed. The primary tumor oncotype of 20 patients was breast cancer, and that of 103 patients was lung cancer. Except for 18 patients with leptomeningeal seeding, a total of 142 patients were analyzed according to the prognostic factors and the Recursive Partitioning Analysis (RPA) class. Weighted Partitioning Analysis (WPA), with the weighting being done according to the primary tumor oncotype, was performed and the results were correlated with survival and then compared with the RPA Class. The median survival of the patients in RPA Class I (8 patients) was 20.0 months, that for Class II (76 patients) was 10.0 months and that for Class III (58 patients) was 3.0 months (p<0.003). The median survival of patients in WPA Class I (3 patients) was 36 months, that for the patients in Class II (9 patients) was 23.7 months, that for the patients in Class III (70 patients) was 10.9 months and that for the patients in Class IV (60 patients) was 8.6 months (p<0.001). The WPA Class might have more accuracy in assessing survival, and it may be superior to the RPA Class for assessing survival. A new prognostic index, the WPA Class, has more prognostic value than the RPA Class for the treatment of patients with metastatic brain cancer. This WPA Class may be useful to guide the appropriate treatment of metastatic brain lesions.

  7. Survival following gamma knife radiosurgery for brain metastasis from breast cancer

    Breast cancer is the second most common cause of brain metastases in the United States. Although breast cancer induced brain metastases represent an incurable condition, some patients experience prolonged survival. In this retrospective study, we examine a cohort of patients with brain metastases from breast cancer treated with Gamma Knife stereotactic radiosurgery to identify factors that predict better outcomes. A retrospective database of 100 patients treated for brain metastases due to breast cancer via Gamma Knife radiosurgery (GKS) from July 1998 through March 2009 was reviewed. Patients who received radiosurgery as sole treatment, as a planned boost after whole brain radiotherapy or surgical resection, or as salvage after prior whole brain radiation therapy (WBRT) or surgical resection were included. Prognostic factors identified to be significant for survival in previous brain metastasis studies were analyzed for significance by univariate and multivariate Cox analysis. Overall, the median brain progression-free survival time was 7.1 months and the median survival time was 12.3 months. No prognostic variables were significant for brain progression-free survival. For patients treated with a planned GKS after WBRT, GKS as sole treatment, GKS salvage after WBRT, GKS boost after surgery, or GKS for surgical salvage the median survival times (MSTs) were as follows: 12.2 months, 12.4 months, 9.5 months, 27.6 months and 33.4 months respectively. Differences between the groups were not significant (p = 0.06); however, GKS boost after surgery and GKS for salvage after surgery did have a trend toward better overall survival. The MST for patients of age <65 years was 14.5 months, compared to age ≥65 which was 7.7 months (p = 0.06) and remained a significant prognostic factor for overall survival on multivariate analysis. The MST for patients with a single lesion was 16.9 months, not significantly different than the MST of 14.5 months for patients with 2–3 lesions

  8. Automated tracking of nanoparticle-labeled melanoma cells improves the predictive power of a brain metastasis model

    Sundstrom, T.; Daphu, I.; Wendelbo, I.; Hodneland, E.; Lundervold, A.; Immervoll, H.; Skaftnesmo, K. O.; Babič, Michal; Jendelová, Pavla; Syková, Eva; Lund-Johansen, M.; Bjerkvig, R.; Thorsen, F.

    2013-01-01

    Roč. 73, č. 8 (2013), s. 2445-2456. ISSN 0008-5472 R&D Projects: GA ČR(CZ) GAP304/12/1370 Institutional support: RVO:61389013 ; RVO:68378041 Keywords : brain metastasis * MRI * nanoparticles Subject RIV: CD - Macromolecular Chemistry; FD - Oncology ; Hematology (UEM-P) Impact factor: 9.284, year: 2013

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

    Faris Shweikeh

    2014-01-01

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

  10. Radiotherapeutic palliation of brain metastasis: a retrospective quality of life analysis

    PURPOSE/OBJECTIVE: To assess quality of life effects of radiation therapy on patients with brain metastasis. Not only is data on this subject rare, there is also no psychometrically tested brain metastasis symptom scale. We report data using a scale of our own design. MATERIALS and METHODS: Over 200 charts of patients treated for brain metastasis from various primary sites between 1990 and 1995 were reviewed. Seventy-two patients met the criteria for evaluation. They were all treated with radiotherapy and steroids. The majority of patients received a median dose of 30 Gy (Range 20 - 55) to the whole brain. Treatment over 40 Gy was delivered via a boost, either external beam or stereotactic. Pre and post-therapy symptoms of impaired vision, speech, sensation, motor strength, gait, cranial nerves, headache, seizure, lethargy, mentation, and nausea and vomiting were scored. Each symptom was evaluated separately. Following therapy, patients were noted to have improvement, no change, or worsening symptoms. Steroid and anti-seizure medication use pre and post-therapy were also recorded. RESULTS: Patient characteristics: median age is 62 (Range 27 - 82 years); Female: Male 1.4:1; Single: Multiple metastasis = 1:2.3. The primary sites included: lung=56%, breast=15%, unknown=11%, and various=18%. The histologies included: adenocarcinoma=26%, squamous cell carcinoma=21%, small cell carcinoma=15%, infiltrating ductal=14%, and various=24%. All patients had a minimum of one month post-treatment follow up (Range 1 - 24 mths). Sixteen patients are still living. Eighty-nine percent were symptomatic at presentation and 36% presented with only one symptom. The incidence of symptoms before treatment was: altered mentation=26%, decreased motor strength=26%, headache=24%, seizure=21%, altered gait=20%, nausea/vomiting=18%, speech deficit=15%, lethargy=11%, visual change=8%, altered sensation=7%, and cranial nerve deficits=3%. A statistically significant improvement in mentation (p<0

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

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

  12. Dosimetric comparison of Helical Tomotherapy and Gamma Knife Stereotactic Radiosurgery for single brain metastasis

    Linskey Mark E

    2006-08-01

    Full Text Available Abstract Background Helical Tomotherapy (HT integrates linear accelerator and computerized tomography (CT technology to deliver IMRT. Targets are localized (i.e. outlined as gross tumor volume [GTV] and planning target volume [PTV] on the planning kVCT study while daily MVCT is used for correction of patient's set-up and assessment of inter-fraction anatomy changes. Based on dosimetric comparisons, this study aims to find dosimetric equivalency between single fraction HT and Gamma Knife® stereotactic radiosurgery (GKSRS for the treatment of single brain metastasis. Methods The targeting MRI data set from the GKSRS were used for tomotherapy planning. Five patients with single brain metastasis treated with GKSRS were re-planned in the HT planning station using the same prescribed doses. There was no expansion of the GTV to create the PTV. Sub-volumes were created within the PTV and prescribed to the maximum dose seen in the GKSRS plans to imitate the hot spot normally seen in GKSRS. The PTV objective was set as a region at risk in HT planning using the same prescribed dose to the PTV periphery as seen in the corresponding GKSRS plan. The tumor volumes ranged from 437–1840 mm3. Results Conformality indices are inconsistent between HT and GKSRS. HT generally shows larger lower isodose line volumes, has longer treatment time than GKSRS and can treat a much larger lesion than GKSRS. Both HT and GKSRS single fraction dose-volume toxicity may be prohibitive in treating single or multiple lesions depending on the number and the sizes of the lesions. Conclusion Based on the trend for larger lower dose volumes and more constricted higher dose volumes in HT as compared to GKSRS, dosimetric equivalency was not reached between HT and GKSRS.

  13. Dosimetric comparison of Helical Tomotherapy and Gamma Knife Stereotactic Radiosurgery for single brain metastasis

    Helical Tomotherapy (HT) integrates linear accelerator and computerized tomography (CT) technology to deliver IMRT. Targets are localized (i.e. outlined as gross tumor volume [GTV] and planning target volume [PTV]) on the planning kVCT study while daily MVCT is used for correction of patient's set-up and assessment of inter-fraction anatomy changes. Based on dosimetric comparisons, this study aims to find dosimetric equivalency between single fraction HT and Gamma Knife® stereotactic radiosurgery (GKSRS) for the treatment of single brain metastasis. The targeting MRI data set from the GKSRS were used for tomotherapy planning. Five patients with single brain metastasis treated with GKSRS were re-planned in the HT planning station using the same prescribed doses. There was no expansion of the GTV to create the PTV. Sub-volumes were created within the PTV and prescribed to the maximum dose seen in the GKSRS plans to imitate the hot spot normally seen in GKSRS. The PTV objective was set as a region at risk in HT planning using the same prescribed dose to the PTV periphery as seen in the corresponding GKSRS plan. The tumor volumes ranged from 437–1840 mm3. Conformality indices are inconsistent between HT and GKSRS. HT generally shows larger lower isodose line volumes, has longer treatment time than GKSRS and can treat a much larger lesion than GKSRS. Both HT and GKSRS single fraction dose-volume toxicity may be prohibitive in treating single or multiple lesions depending on the number and the sizes of the lesions. Based on the trend for larger lower dose volumes and more constricted higher dose volumes in HT as compared to GKSRS, dosimetric equivalency was not reached between HT and GKSRS

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

    Qiuhong FAN

    2008-06-01

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

  15. Factors associated with tumor response and survival in radiosurgery for brain metastasis

    We reviewed our experience with radiosurgery for brain metastasis and focused on factors associated with tumor response and survival. Our study consists of 19 patients with 25 brain metastases who underwent linear accelerator radiosurgery. There was evidence of extra-central nervous system (CNS) tumors in 15 patients. The maximum diameter of the tumors ranged from 3 to 40 mm with a mean of 20 mm. Tumor doses at the isocenter varied from 16 to 25 Gy with a mean of 21 Gy. Eighteen lesions were treated by radiosurgery alone and 7 lesions received combined radiosurgery with fractionated radiotherapy. Of the 11 patients who experienced CNS failure either in or out of the radiosurgery field, 6 patients had salvage radiotherapy. Median survival was 7 months, and the 1-year actuarial survival rate was 40%. Death was due to extra-CNS tumor manifestations in 11 patients. In 3 patients, CNS failure was the cause of death. One died of local progression, and the other 2 died of newly developed metastases. Poor Karnofsky performance scores and the presence of extra-CNS tumors significantly affected 1-year survival in univariate analysis (p<0.05). Local tumor control was achieved in 80% of the lesions. The 1-year actuarial tumor control rate was 51%. Newly developed brain metastases were observed in 7 patients. The tumor diameter was mostly associated with tumor response in multiple regression analysis (p=0.0031). We concluded that radiosurgery is effective in controlling small brain metastases. Survival benefit is expected for those with good performance status and adequately controlled extra-CNS disease. (author)

  16. BM-26CD15 AND E-SELECTIN MEDIATION OF ADHESION OF NON-SMALL CELL LUNG CANCER CELLS TO BRAIN ENDOTHELIUM IN LUNG-BRAIN METASTASIS

    Pilkington, Geoffrey; Jassam, Samah; Maherally, Zaynah; Smith, James; Fillmore, Helen

    2014-01-01

    BACKGROUND: Lung metastases to the brain are common secondary cancers, representing over 50% of fatal complications of systemic cancer. Metastasis of cancer cells involves multiple steps including intravasation, cancer cell-endothelial rolling and adhesion, extravasation and cerebral colonization. Here, we focused on metastatic Non-Small Cell lung cancer cells adhesion to brain endothelial cells. Specifically, we investigated the role of CD15 in lung cancer and its interaction with E-selectin...

  17. A Rare Case of Solitary Epidural Brain Metastasis of Neuroepithelioma Tumor in A 14 Years Old Man

    R. Barikbin

    2008-01-01

    Full Text Available By definition, a peripheral neuroepithelioma is a primary neuroectodermal tumor (PNET arising from peripheral, nonautonomic neural tissue. PNETs are classified into central and peripheral types. Peripheral PNETs are unusual, often highly aggressive, malignant neoplasms, rarely presenting in the head and neck. Soft tissues PNETs arise from nonautonomic nervous system. In this case, we report a 14-years-old male known case of cervical soft tissue neuroepithelioma presenting with a rare form of metastatic disease as extra axial, epidural metastasis to the brain. On histochemichal analysis of this solitary metastasis, as well as original tumor specimens, markers consistent with PNET tumors were identified.

  18. Comparison of FDG-PET findings of brain metastasis from non-small-cell lung cancer and small-cell lung cancer

    We compared the F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) findings of brain metastasis between patients with non-small-cell lung cancer (NSCLC) and small cell lung cancer (SCLC). A whole-body FDG and a brain PET were performed in 48 patients (31 men, 17 women; 57±9 years, 42 NSCLC, 6 SCLC), who had brain metastasis on magnetic resonance (MR). All primary lung lesions were detected by FDG-PET and confirmed pathologically. We analyzed the PET findings, lesion sizes, and the pathological result of primary lung cancer. Of the 48 patients, 31 (64.6%) showed hypermetabolic lesions on FDG-PET of the brain image, and 14 (29.2%) showed hypometabolic lesions. Three patients (6.3%) had both hypermetabolic and hypometabolic lesions. On the lesion-based analysis, 74 lesions (67.3%) showed hypermetabolism on FDG-PET, and 36 lesions (32.7%) showed hypometabolism. All primary lung lesions were hypermetabolic on FDG-PET. When the FDG findings of metastatic brain lesions were analyzed with the pathological types of primary lung cancer, NSCLC was more frequently associated with hypermetabolic metastatic brain lesions than SCLC (80% and 26.7%, respectively, P<0.01). On comparing the sizes of metastatic lesions between SCLC (1.3±1.2 cm) and NSCLC (1.8±1.2 cm), lesions of <1 cm were more frequent in SCLC than in NSCLC (P=0.012). But no significant relationship was found between the size and PET finding of metastatic lesion (P=0.412). Even when the primary lesion of lung cancer showed hypermetabolism in FDG-PET, FDG accumulation in metastatic brain lesions was variable. One-third of brain metastases from lung cancer showed hypometabolism. NSCLC was more frequently associated with hypermetabolic metastatic brain lesions than SCLC. The PET findings of brain lesions were affected not only by the size of lesion but also by its biological characteristics. (author)

  19. Brain metastasis: an evaluation of the preoperative diagnostic work-up

    This is a retrospective study of the evaluation of various preoperative diagnostic tests in locating the primary lesion in 50 patients with a solitary brain lesion seen on computerized tomography and suspected to be metastatic. These patients underwent craniotomy and 54% had primary tumors 40% metastatic tumors and 6.1% non-neoplastic lesions. Of 20 patients with metastasis, the primary was identified in 19 patients with the following locations: 11 pulmonary, 3 breast, 2 thyroid and 2 colon. In 2 patients, no primary was identified. Using simple conditional probability theory, it was established that the probability of a brain metastatic lesion in patients without a previous history of diagnosed non-nervous system cancer, negative chest x-ray, and normal CEA was 14.7%. However, in patients with a previous history of diagnosed non-nervous system cancer, the probability of having a metastatic lesion is high (88%). Extensive testing preoperatively may be justified in these cases because of its value in surgical decision-making and long-term prognosis. (Author)

  20. Gamma-knife radiosurgery for brain metastasis of renal cell carcinoma. Results in 42 patients

    The present study provides data from clinical experience with gamma-knife radiosurgery (GK) in patients with brain metastasis from renal cell carcinoma (RCC) and shows the value of this less invasive treatment modality. Forty-two patients received GK. Twenty of the 42 cases had multiple brain metastases. Extracranial metastases were observed in the lung (38 cases), bone (12 cases), liver (9 cases), lymph node (5 cases) and skin (6 cases). Neurological symptoms seen in 40 patients were rapidly improved after GK in 32 patients (80%). Magnetic resonance imaging (MRI) evaluation after GK in 32 patients showed the disappearance of brain tumor in 9 patients (28%). Complete response was obtained by GK in tumors up to 30 mm in diameter. Repeated GK for newly developed lesions was conducted in 11 patients. Extracranial tumor resection was conducted in 7 cases (lung: 3, skin: 2, liver: 1, adrenal: 1). Chemoradiotherapy or immunotherapy was effective in 8 cases (lung: 5, liver: 2, bone: 1). The actual one-, two- and three-year survival rates were 44.9%, 16.8%, and 11.2%, respectively. The median survival time was 12.5 months. In univariate analysis, the patients with successfully treated extracranial metastases had significantly better prognosis. In multivariate analysis, the patients with Karnofsky performance scale (KPS)≥80%, who were treated by GK more than once and obtained complete response (CR) or partial response (PR) by GK, had significantly better prognosis. Gamma-knife radiosurgery for RCC is an effective non-invasive modality of treatment. It offers a high local control rate and an improved quality of life and survival rate. (author)

  1. Stereotactic Irradiation of the Postoperative Resection Cavity for Brain Metastasis: A Frameless Linear Accelerator-Based Case Series and Review of the Technique

    Kelly, Paul J., E-mail: pkelly@lroc.harvard.edu [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, MA (United States); Lin Yijie Brittany; Yu, Alvin Y. [Harvard Medical School, Boston, MA (United States); Alexander, Brian M.; Hacker, Fred; Marcus, Karen J.; Weiss, Stephanie E. [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, MA (United States)

    2012-01-01

    Purpose: Whole-brain radiation therapy (WBRT) is the standard of care after resection of a brain metastasis. However, concern regarding possible neurocognitive effects and the lack of survival benefit with this approach has led to the use of stereotactic radiosurgery (SRS) to the resection cavity in place of WBRT. We report our initial experience using an image-guided linear accelerator-based frameless stereotactic system and review the technical issues in applying this technique. Methods and Materials: We retrospectively reviewed the setup accuracy, treatment outcome, and patterns of failure of the first 18 consecutive cases treated at Brigham and Women's Hospital. The target volume was the resection cavity without a margin excluding the surgical track. Results: The median number of brain metastases per patient was 1 (range, 1-3). The median planning target volume was 3.49 mL. The median prescribed dose was 18 Gy (range, 15-18 Gy) with normalization ranging from 68% to 85%. In all cases, 99% of the planning target volume was covered by the prescribed dose. The median conformity index was 1.6 (range, 1.41-1.92). The SRS was delivered with submillimeter accuracy. At a median follow-up of 12.7 months, local control was achieved in 16/18 cavities treated. True local recurrence occurred in 2 patients. No marginal failures occurred. Distant recurrence occurred in 6/17 patients. Median time to any failure was 7.4 months. No Grade 3 or higher toxicity was recorded. A long interval between initial cancer diagnosis and the development of brain metastasis was the only factor that trended toward a significant association with the absence of recurrence (local or distant) (log-rank p = 0.097). Conclusions: Frameless stereotactic irradiation of the resection cavity after surgery for a brain metastasis is a safe and accurate technique that offers durable local control and defers the use of WBRT in select patients. This technique should be tested in larger prospective studies.

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

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

    2013-01-01

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

  3. Tumor necrosis factor receptor superfamily member 9 is upregulated in the endothelium and tumor cells in melanoma brain metastasis

    Patrick N Harter

    2014-12-01

    Full Text Available Aim: The cytokine receptor tumor necrosis factor receptor superfamily member 9 (TNFRSF9 is mainly considered to be a co-stimulatory activation marker in hematopoietic cells. Several preclinical models have shown a dramatic beneficial effect of treatment approaches targeting TNFRSF9 with agonistic antibodies. However, preliminary clinical phase I/II studies were stopped after the occurrence of several severe deleterious side effects. In a previous study, it was demonstrated that TNFRSF9 was strongly expressed by reactive astrocytes in primary central nervous system (CNS tumors, but was largely absent from tumor or inflammatory cells. The aim of the present study was to address the cellular source of TNFRSF9 expression in the setting of human melanoma brain metastasis, a highly immunogenic tumor with a prominent tropism to the CNS. Methods: Melanoma brain metastasis was analyzed in a cohort of 78 patients by immunohistochemistry for TNFRSF9 and its expression was correlated with clinicopathological parameters including sex, age, survival, tumor size, number of tumor spots, and BRAF V600E expression status. Results: Tumor necrosis factor receptor superfamily member 9 was frequently expressed independently on both melanoma and endothelial cells. In addition, TNFRSF9 was also present on smooth muscle cells of larger vessels and on a subset of lymphomonocytic tumor infiltrates. No association between TNFRSF9 expression and patient survival or other clinicopathological parameters was seen. Of note, several cases showed a gradual increase in TNFRSF9 expression on tumor cells with increasing distance from blood vessels, an observation that might be linked to hypoxia-driven TNFRSF9 expression in tumor cells. Conclusion: The findings indicate that the cellular source of TNFRSF9 in melanoma brain metastasis largely exceeds the lymphomonocytic pool, and therefore further careful (re- assessment of potential TNFRSF9 functions in cell types other than

  4. Integrating structure to protein-protein interaction networks that drive metastasis to brain and lung in breast cancer

    Engin, H Billur; G??ney, Emre, 1983-; Keskin, Ozlem; Oliva Miguel, Baldomero; Gursoy, Attila

    2013-01-01

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

  5. [Nursing care for a lung cancer patient with brain metastasis using the family resiliency model].

    Tsai, Chia-Yu; Chen, Shu-Chuan; Jhang, Sin-Yuan; Hong, Ming-Ying

    2014-12-01

    This article describes the experience of the author in providing nursing care to a lung cancer patient with brain metastasis who was unable to care for herself. The period of care ran from July 26th to August 7th, 2012. The focus of the article is on the problems of disease adaptation and the coping strategies of the patient and her primary caregivers. The author used the Family Resiliency Model to collect information via physical examination, observation, and interviews. Five major nursing problems were identified in this case: risk of aspiration, self-care deficits, adjustment disorder, caregiver role strain, and family coping ineffectiveness. Based on these problems, the author constructed an individualized care plan to: 1) improve the self-care ability of the patient, 2) enhance the skills of the primary caregiver, 3) recruit the timely assistance of other family members, 4) and reduce the burden of the primary caregiver. The primary goal of this care plan was to promote the quality of life of the patient and her family. PMID:25464963

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

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

    2015-01-01

    Brain metastasis is a significant unmet clinical problem in breast cancer treatment. It is always associated with poor prognosis and high morbidity. Recently, Slit2/Robo1 pathway has been demonstrated to be involved in the progression of breast carcinoma. However, until present, there are no convincing reports that suggest whether the Slit2/Robo1 axis has any role in brain metastasis of breast cancer. In this study, we investigated the correlation between Slit2/Robo1 signaling and breast canc...

  7. Short-time focused ultrasound hyperthermia enhances liposomal doxorubicin delivery and antitumor efficacy for brain metastasis of breast cancer.

    Wu, Sheng-Kai; Chiang, Chi-Feng; Hsu, Yu-Hone; Lin, Tzu-Hung; Liou, Houng-Chi; Fu, Wen-Mei; Lin, Win-Li

    2014-01-01

    The blood-brain/tumor barrier inhibits the uptake and accumulation of chemotherapeutic drugs. Hyperthermia can enhance the delivery of chemotherapeutic agent into tumors. In this study, we investigated the effects of short-time focused ultrasound (FUS) hyperthermia on the delivery and therapeutic efficacy of pegylated liposomal doxorubicin (PLD) for brain metastasis of breast cancer. Murine breast cancer 4T1-luc2 cells expressing firefly luciferase were injected into female BALB/c mice striatum tissues and used as a brain metastasis model. The mice were intravenously injected with PLD (5 mg/kg) with/without 10-minute transcranial FUS hyperthermia on day 6 after tumor implantation. The amounts of doxorubicin accumulated in the normal brain tissues and tumor tissues with/without FUS hyperthermia were measured using fluorometry. The tumor growth for the control, hyperthermia, PLD, and PLD + hyperthermia groups was measured using an IVIS spectrum system every other day from day 3 to day 11. Cell apoptosis and tumor characteristics were assessed using immunohistochemistry. Short-time FUS hyperthermia was able to significantly enhance the PLD delivery into brain tumors. The tumor growth was effectively inhibited by a single treatment of PLD + hyperthermia compared with both PLD alone and short-time FUS hyperthermia alone. Immunohistochemical examination further demonstrated the therapeutic efficacy of PLD plus short-time FUS hyperthermia for brain metastasis of breast cancer. The application of short-time FUS hyperthermia after nanodrug injection may be an effective approach to enhance nanodrug delivery and improve the treatment of metastatic cancers. PMID:25278753

  8. Short-time focused ultrasound hyperthermia enhances liposomal doxorubicin delivery and antitumor efficacy for brain metastasis of breast cancer

    Wu, Sheng-Kai; Chiang, Chi-Feng; Hsu, Yu-Hone; Lin, Tzu-Hung; Liou, Houng-Chi; Fu, Wen-Mei; Lin, Win-Li

    2014-01-01

    The blood–brain/tumor barrier inhibits the uptake and accumulation of chemotherapeutic drugs. Hyperthermia can enhance the delivery of chemotherapeutic agent into tumors. In this study, we investigated the effects of short-time focused ultrasound (FUS) hyperthermia on the delivery and therapeutic efficacy of pegylated liposomal doxorubicin (PLD) for brain metastasis of breast cancer. Murine breast cancer 4T1-luc2 cells expressing firefly luciferase were injected into female BALB/c mice striatum tissues and used as a brain metastasis model. The mice were intravenously injected with PLD (5 mg/kg) with/without 10-minute transcranial FUS hyperthermia on day 6 after tumor implantation. The amounts of doxorubicin accumulated in the normal brain tissues and tumor tissues with/without FUS hyperthermia were measured using fluorometry. The tumor growth for the control, hyperthermia, PLD, and PLD + hyperthermia groups was measured using an IVIS spectrum system every other day from day 3 to day 11. Cell apoptosis and tumor characteristics were assessed using immunohistochemistry. Short-time FUS hyperthermia was able to significantly enhance the PLD delivery into brain tumors. The tumor growth was effectively inhibited by a single treatment of PLD + hyperthermia compared with both PLD alone and short-time FUS hyperthermia alone. Immunohistochemical examination further demonstrated the therapeutic efficacy of PLD plus short-time FUS hyperthermia for brain metastasis of breast cancer. The application of short-time FUS hyperthermia after nanodrug injection may be an effective approach to enhance nanodrug delivery and improve the treatment of metastatic cancers. PMID:25278753

  9. Medical and health economic assessment of radiosurgery for the treatment of brain metastasis

    von der Schulenburg, Johann-Matthias

    2009-03-01

    Full Text Available Background: Radiotherapy for patients suffering from malignant neoplasms has developed greatly during the past decades. Stereotactic radiosurgery (SRS is one important radiotherapeutic option which is defined by a single and highly focussed application of radiation during a specified time interval. One of its important indications is the treatment of brain metastases. Objectives: The objective of this HTA is to summarise the current literature concerning the treatment of brain metastasis and to compare SRS as a single or additional treatment option to alternative treatment options with regard to their medical effectiveness/efficacy, safety and cost-effectiveness as well as their ethical, social and legal implications. Methods: A structured search and hand search of identified literature are performed from January 2002 through August 2007 to identify relevant publications published in English or German. Studies targeting patients with single or multiple brain metastases are included. The methodological quality of included studies is assessed according to quality criteria, based on the criteria of evidence based medicine. Results: Of 1,495 publications 15 medical studies meet the inclusion criteria. Overall study quality is limited and with the exception of two randomized controlleed trials (RCT and two meta-analyses only historical cohort studies are identified. Reported outcome measures are highly variable between studies. Studies with high methodological quality provide evidence, that whole-brain radiotherapy (WBRT in addition to SRS and SRS in addition to WBRT is associated with improved local tumour control rates and neurological function. However, only in patients with single brain metastasis, RPA-class 1 (RPA = Recursive partitioning analysis and certain primary tumour entities, this combination of SRS and WBRT is associated with superior survival compared to WBRT alone. Studies report no significant differences in adverse events between

  10. Inhibition of Type I Insulin-Like Growth Factor Receptor Signaling Attenuates the Development of Breast Cancer Brain Metastasis

    Saldana, Sandra M.; Lee, Heng-Huan; Lowery, Frank J; Khotskaya, Yekaterina B.; Xia, Weiya; Zhang, Chenyu; Chang, Shih-Shin; Chou, Chao-Kai; Steeg, Patricia S; Yu, Dihua; Hung, Mien-Chie

    2013-01-01

    Brain metastasis is a common cause of mortality in cancer patients, yet potential therapeutic targets remain largely unknown. The type I insulin-like growth factor receptor (IGF-IR) is known to play a role in the progression of breast cancer and is currently being investigated in the clinical setting for various types of cancer. The present study demonstrates that IGF-IR is constitutively autophosphorylated in brain-seeking breast cancer sublines. Knockdown of IGF-IR results in a decrease of ...

  11. 1,3-Dinitrobenzene Induces Age- and Region-Specific Oxidation to Mitochondria-Related Proteins in Brain

    Kubik, Laura L.; Landis, Rory W.; Remmer, Henriette; Bergin, Ingrid L; Philbert, Martin A.

    2015-01-01

    Regions of the brain with high energy requirements are especially sensitive to perturbations in mitochondrial function. Hence, neurotoxicant exposures that target mitochondria in regions of high energy demand have the potential to accelerate mitochondrial damage inherently occurring during the aging process. 1,3-Dinitrobenzene (DNB) is a model neurotoxicant that selectively targets mitochondria in brainstem nuclei innervated by the eighth cranial nerve. This study investigates the role of age...

  12. SNPs in the TGF-β signaling pathway are associated with increased risk of brain metastasis in patients with non-small-cell lung cancer.

    Qianxia Li

    Full Text Available PURPOSE: Brain metastasis (BM from non-small cell lung cancer (NSCLC is relatively common, but identifying which patients will develop brain metastasis has been problematic. We hypothesized that genotype variants in the TGF-β signaling pathway could be a predictive biomarker of brain metastasis. PATIENTS AND METHODS: We genotyped 33 SNPs from 13 genes in the TGF-β signaling pathway and evaluated their associations with brain metastasis risk by using DNA from blood samples from 161 patients with NSCLC. Kaplan-Meier analysis was used to assess brain metastasis risk; Cox hazard analyses were used to evaluate the effects of various patient and disease characteristics on the risk of brain metastasis. RESULTS: The median age of the 116 men and 45 women in the study was 58 years; 62 (39% had stage IIIB or IV disease. Within 24 months after initial diagnosis of lung cancer, brain metastasis was found in 60 patients (37%. Of these 60 patients, 16 had presented with BM at diagnosis. Multivariate analysis showed the GG genotype of SMAD6: rs12913975 and TT genotype of INHBC: rs4760259 to be associated with a significantly higher risk of brain metastasis at 24 months follow-up (hazard ratio [HR] 2.540, 95% confidence interval [CI] 1.204-5.359, P = 0.014; and HR 1.885, 95% CI 1.086-3.273, P = 0.024, compared with the GA or CT/CC genotypes, respectively. When we analyzed combined subgroups, these rates showed higher for those having both the GG genotype of SMAD6: rs12913975 and the TT genotype of INHBC: rs4760259 (HR 2.353, 95% CI 1.390-3.985, P = 0.001. CONCLUSIONS: We found the GG genotype of SMAD6: rs12913975 and TT genotype of INHBC: rs4760259 to be associated with risk of brain metastasis in patients with NSCLC. This finding, if confirmed, can help to identify patients at high risk of brain metastasis.

  13. Incidence, symptoms, treatment, and prognosis in 113 patients with brain/meningeal metastasis from breast cancer. Screening in accordance with hormone receptor and HER2/neu

    In 113 of 422 patients with metastatic/recurrent breast cancer (MBC who were treated in our hospital after 2001, brain/meningeal metastasis was detected. In 240 patients who died, the overall incidence of brain/meningeal metastasis was 36.3% (n=87). With respect to hormone receptor (HR) and HER2 presence, metastasis was detected in 32 (58.2%) of 55 patients showing HR(-) and HER2(+), 17 (39.5%) of 43 patients showing HR(-) and HER2(-), 19 (31.5%) of 54 patients showing HR(+) and HER2(+), and 17 (20%) of 85 patients showing HR(+) and HER2(-) (brain metastasis was detected in 2 of 3 patients in whom HR or HER2 was unclear); the incidence was significantly higher in HR(-) or HER2(+) patients. Of our series including surviving patients, asymptomatic brain metastasis was detected using contrast-enhanced MRI in 24 HER2(+) patients. In the above 113 patients, the median survival time (MST) after diagnosis was 10 months. However, it was 17 months in 24 patients who underwent screening. For treatment, whole brain radiotherapy (WBRT) or stereotactic radiosurgery (SRS) mainly with a gamma knife was performed. During a follow-up of more than 12 months, 1 to 4 sessions of treatment (mean: 2.39, median: 2) were required. In 50% of the patients, both WBRT and SRS were performed. There were no HR- or HER2- related differences in survival after brain metastasis. However, the MST was 34 months in 7 patients in whom the 1st relapse site involved the brain. In the future, the usefulness of early treatment via brain metastasis screening should be reviewed in HR(-) and HER2(+) patients. (author)

  14. Opposing Effects of Pigment Epithelium-Derived Factor on Breast Cancer Cell versus Neuronal Survival: Implication for Brain Metastasis and Metastasis-Induced Brain Damage

    Fitzgerald, Daniel P.; Subramanian, Preeti; Deshpande, Monika; Graves, Christian; Gordon, Ira; Qian, Yongzhen; Snitkovsky, Yeva; Liewehr, David J.; Steinberg, Seth M.; Paltán-Ortiz, José D.; Herman, Mary M.; Camphausen, Kevin; Palmieri, Diane; BECERRA, S. PATRICIA; Steeg, Patricia S

    2012-01-01

    Brain metastases are a significant cause of cancer patient morbidity and mortality, yet preventative and therapeutic options remain an unmet need. The cytokine PEDF is downregulated in resected human brain metastases of breast cancer compared to primary breast tumors, suggesting that restoring its expression might limit metastatic spread. Here we show that outgrowth of large experimental brain metastases from human 231-BR or murine 4T1-BR breast cancer cells was suppressed by PEDF expression,...

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

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

    2016-03-01

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

  16. The evaluation of the radiation therapy of brain metastasis from lung cancer by means of computed tomography

    We studied the effect of radiation therapy (RT) on 132 patients with brain metastasis from lung cancer between April 1978 and May 1987; evaluation was done by means of computed tomography (CT) scans. The CT findings of brain metastasis had some relationship to the histological types of lung cancer. Besides, the response to RT on CT images correlated with the histological diagnosis and the CT findings, both solid-contrast enhancement (S type) and ring-contrast enhancement (R type), of metastatic lesions. The results were as follows. A shrinkage of the brain metastases following RT was observed in 98.3% for small-cell carcinoma, in 75.0% for adenocarcinoma, and in 72.7% for squamous-cell carcinoma. The S type showed a better response to RT than did the R type, irrespective of their histological type, during RT. During RT, a decrease in tumor size was observed in the S type, while a decrease in the thickness of the ring wall, without any remarkable change in tumor size, was observed in the R type. In cases with small-cell carcinoma and squamous-cell carcinoma, smaller metastatic lesions had greater effects than larger ones. After the completion of RT, a delayed effect was found on the follow-up CT in the cases with adenocarcinoma and squamous-cell carcinoma. Adenocarcinoma in the S type and squamous-cell carcinoma in the R type showed the best delayed effect. (author)

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

    丁维军; 杨伟芳; 于长辉

    2012-01-01

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

  18. STAT3 pathway regulates lung-derived brain metastasis initiating cell capacity through miR-21 activation.

    Singh, Mohini; Garg, Neha; Venugopal, Chitra; Hallett, Robin; Tokar, Tomas; McFarlane, Nicole; Mahendram, Sujeivan; Bakhshinyan, David; Manoranjan, Branavan; Vora, Parvez; Qazi, Maleeha; Arpin, Carolynn C; Page, Brent; Haftchenary, Sina; Rosa, David A; Lai, Ping-Shan; Gómez-Biagi, Rodolfo F; Ali, Ahmed M; Lewis, Andrew; Geletu, Mulu; Murty, Naresh K; Hassell, John A; Jurisica, Igor; Gunning, Patrick T; Singh, Sheila K

    2015-09-29

    Brain metastases (BM) represent the most common tumor to affect the adult central nervous system. Despite the increasing incidence of BM, likely due to consistently improving treatment of primary cancers, BM remain severely understudied. In this study, we utilized patient-derived stem cell lines from lung-to-brain metastases to examine the regulatory role of STAT3 in brain metastasis initiating cells (BMICs). Annotation of our previously described BMIC regulatory genes with protein-protein interaction network mapping identified STAT3 as a novel protein interactor. STAT3 knockdown showed a reduction in BMIC self-renewal and migration, and decreased tumor size in vivo. Screening of BMIC lines with a library of STAT3 inhibitors identified one inhibitor to significantly reduce tumor formation. Meta-analysis identified the oncomir microRNA-21 (miR-21) as a target of STAT3 activity. Inhibition of miR-21 displayed similar reductions in BMIC self-renewal and migration as STAT3 knockdown. Knockdown of STAT3 also reduced expression of known downstream targets of miR-21. Our studies have thus identified STAT3 and miR-21 as cooperative regulators of stemness, migration and tumor initiation in lung-derived BM. Therefore, STAT3 represents a potential therapeutic target in the treatment of lung-to-brain metastases. PMID:26314961

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

    Inderjit Daphu

    2014-05-01

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

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

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

  1. Neurobiological study of fish brains gives insights into the nature of Gonadotropin-releasing hormone 1-3 neurons.

    YoshitakaOka

    2013-11-01

    Full Text Available Accumulating evidence suggests that up to three different molecular species of GnRH peptides encoded by different paralogs of gnrh genes are expressed by anatomically distinct groups of GnRH neurons in the brain of one vertebrate species. They are called gnrh1, gnrh2, and gnrh3. Recent evidence from molecular, anatomical, and physiological experiments strongly suggests that each GnRH system functions differently. Here, we review recent advancement in the functional studies of the three different GnRH neuron systems, mainly focusing on the electrophysiological analysis of the GnRH-green fluorescent protein (GFP transgenic animals. The introduction of GFP transgenic animals for the electrophysiological analysis of GnRH neurons greatly advanced our knowledge on their anatomy and electrophysiology, especially of gnrh1 neurons, which has long defied detailed electrophysiological analysis of single neurons because of their small size and scattered distribution. Based on the results of recent studies, we propose that different electrophysiological properties, especially the spontaneous patterns of electrical activities and their time-dependent changes, and the axonal projections characterize the different functions of GnRH1-3 neurons; GnRH1 neurons act as hypophysiotropic neuroendocrine regulators, and GnRH2 and GnRH3 neurons act as neuromodulators in wide areas of the brain.

  2. Relevance of PTEN loss in brain metastasis formation in breast cancer patients.

    Wikman, Harriet; Lamszus, Katrin; Detels, Niclas; Uslar, Liubov; Wrage, Michaela; Benner, Christian; Hohensee, Ina; Ylstra, Bauke; Eylmann, Kathrin; Zapatka, Marc; Sauter, Guido; Kemming, Dirk; Glatzel, Markus; Müller, Volkmar; Westphal, Manfred

    2012-01-01

    Introduction With the improvement of therapeutic options for the treatment of breast cancer, the development of brain metastases has become a major limitation to life expectancy in many patients. Therefore, our aim was to identify molecular markers associated with the development of brain metastases in breast cancer. Methods Patterns of chromosomal aberrations in primary breast tumors and brain metastases were compared with array-comparative genetic hybridization (CGH). The most significant r...

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

    Dmytriyeva, Oksana; Pankratova, Stanislava; Owczarek, Sylwia;

    2012-01-01

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

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

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

    2011-11-15

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

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

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

  6. A Study Evaluating INIPARIB in Combination With Chemotherapy to Treat Triple Negative Breast Cancer Brain Metastasis

    2016-02-17

    Estrogen Receptor Negative (ER-Negative) Breast Cancer; Progesterone Receptor Negative (PR-Negative) Breast Cancer; Human Epidermal Growth Factor Receptor 2 Negative (HER2-Negative) Breast Cancer; Brain Metastases

  7. Patent foramen ovale as a preferential mechanism for increasing the likelihood of brain tumor metastasis

    Rigatelli, Gianluca; Rossi, Andrea; Dell'Avvocata, Fabio; Cardaioli, Paolo

    2011-01-01

    Metastases are the most common tumors of the central nervous system which may lie dormant behind the brain blood- barrier sheltering from chemiotherapeutic drugs, and whose presence usually indicates a poor prognosis. Development of brain metastases includes the intravasation of the cancer cells through the tumor blood vessels, their circulation within the venous system, passing through the pulmonary filter thus reaching the systemic circulation. Patent foramen ovale (PFO) is a natural commun...

  8. Breast cancer surface receptors predict risk for developing brain metastasis and subsequent prognosis

    Grewal, Jai; Kesari, Santosh

    2008-01-01

    Determining the status of breast cancer surface receptors (estrogen receptor, progesterone receptor, HER2/neu) has become routine in the care of patients with this disease and has proven to be helpful in guiding treatment. For this reason, breast cancer has become a model for molecularly guided therapy in solid tumors. Emerging data support that these receptors are associated with risk for developing brain metastases. Additionally, once brain metastases have occurred these receptors may also ...

  9. A multi-institutional outcome and prognostic factor analysis of radiosurgery (RS) for resectable single brain metastasis

    PURPOSE: Recent randomized trials comparing resection of single brain metastasis (BM) in selected patients (pts) followed by whole brain radiotherapy (WBRT) to WBRT alone demonstrated statistically significant survival advantage for surgery (Patchell, 1990 and Noordijk, 1994). This multi-institutional retrospective study was performed in similar pts who were treated with RS and WBRT to provide a baseline for comparison for a future randomized trial. MATERIALS AND METHODS: The RS databases of four institutions were reviewed to identify all pts who met the following criteria: single BM; age > 18; surgically resectable lesion; independently functional (KPS ≥ 70); non-radiosensitive histology (small cell, lymphoma, myeloma, germ cell excluded); no prior cranial surgery or WBRT. 122 of 533 pts with BM treated with RS met these criteria. Pts were categorized by: (a) status of the primary: 'absent' = complete resection, 26 pts; 'controlled' locally controlled with radiotherapy or chemotherapy, 70 pts; 'under treatment' = undergoing radiotherapy, 15 pts; 'active' = no definitive or successful treatment of the primary, 11 pts; (b) status of non-CNS metastasis: present=64 pts, absent=58 pts; (c) age: median=61, range 23-83; (d) KPS : KPS 70/80/90/100=20/26/44/32 pts; (e) histology: lung=58, melanoma=16, breast=13, renal=12,colon=9, other=10, unknown primary=4; (f) time from primary to BM: median=12 months, range=1-252 months; (g) gender: male=64, female=58; (h) tumor volume: median=2.68 cc, range=0.13-27.2 cc. RS was performed with a linear accelerator based technique (peripheral dose 10-27 Gy, median 17 Gy). WBRT was performed in all but 5 pts who refused it (range 25 - 40 Gy, median 37.5 Gy). RESULTS: The potential median follow-up for all pts is 123 weeks (wks). The overall local response rate is 59% (complete response = 25%, partial response = 34%). In field progression occurred in 17 patients (14%), with overall local control of 86%. Local control was highest for

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

    Jinhyun Choi

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

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

    Choi, Jinhyun; Kim, Jun Won; Keum, Yo Sup; Lee, Ik Jae

    2016-01-01

    Purpose To analyze the clinical features and prognostic factors associated with the survival of patients with a very rare occurrence of brain metastasis (BM) from differentiated thyroid cancer (DTC). Methods and Materials A total of 37 patients with DTC who were diagnosed with BM between 1995 and 2014 were included. We reviewed the clinical characteristics, treatment modalities, and image findings of BM. Factors associated with survival were evaluated, and the patients were divided into three prognostic groups (Groups A, B, and C) for comparative analysis. Results The median age at BM was 63 years, and the median time from initial thyroid cancer diagnosis to BM was 3.8 years. The median survival and the 1-year actuarial survival rate after BM were 8.8 months and 47%, respectively. According to univariate and multivariate analyses, four good prognostic factors (GPFs) were identified including age ≤ 60 years, PS ≤ ECOG 2, ≤ 3 BM sites, and without extracranial metastasis prior to BM. Three prognostic groups were designed based on age and number of remaining GPFs: patients ≤ 60 years of age with at least 2 GPFs (Group A) had the most favorable prognosis with a median survival of 32.8 months; patients ≤ 60 years of age with fewer than 2 GPFs and those > 60 years of age with at least 2 GPFs (Group B) had an intermediate prognosis with a median survival of 9.4 months; and patients > 60 years of age with fewer than 2 GPFs (Group C) had the least favorable prognosis with a median survival of 1.5 months. Conclusions The survival of patients with BM form DTC differed among the prognostic groups based on the total number of good prognostic factors. PMID:27128487

  12. Assessment of the Molecular Expression and Structure of Gangliosides in Brain Metastasis of Lung Adenocarcinoma by an Advanced Approach Based on Fully Automated Chip-Nanoelectrospray Mass Spectrometry

    Zamfir, Alina D.; Serb, Alina; Vukeli, Željka; Flangea, Corina; Schiopu, Catalin; Fabris, Dragana; Kalanj-Bognar, Svjetlana; Capitan, Florina; Sisu, Eugen

    2011-12-01

    Gangliosides (GGs), sialic acid-containing glycosphingolipids, are known to be involved in the invasive/metastatic behavior of brain tumor cells. Development of modern methods for determination of the variations in GG expression and structure during neoplastic cell transformation is a priority in the field of biomedical analysis. In this context, we report here on the first optimization and application of chip-based nanoelectrospray (NanoMate robot) mass spectrometry (MS) for the investigation of gangliosides in a secondary brain tumor. In our work a native GG mixture extracted and purified from brain metastasis of lung adenocarcinoma was screened by NanoMate robot coupled to a quadrupole time-of-flight MS. A native GG mixture from an age-matched healthy brain tissue, sampled and analyzed under identical conditions, served as a control. Comparative MS analysis demonstrated an evident dissimilarity in GG expression in the two tissue types. Brain metastasis is characterized by many species having a reduced N-acetylneuraminic acid (Neu5Ac) content, however, modified by fucosylation or O-acetylation such as Fuc-GM4, Fuc-GM3, di- O-Ac-GM1, O-Ac-GM3. In contrast, healthy brain tissue is dominated by longer structures exhibiting from mono- to hexasialylated sugar chains. Also, significant differences in ceramide composition were discovered. By tandem MS using collision-induced dissociation at low energies, brain metastasis-associated GD3 (d18:1/18:0) species as well as an uncommon Fuc-GM1 (d18:1/18:0) detected in the normal brain tissue could be structurally characterized. The novel protocol was able to provide a reliable compositional and structural characterization with high analysis pace and at a sensitivity situated in the fmol range.

  13. In vivo MRI of cancer cell fate at the single-cell level in a mouse model of breast cancer metastasis to the brain.

    Heyn, Chris; Ronald, John A; Ramadan, Soha S; Snir, Jonatan A; Barry, Andrea M; MacKenzie, Lisa T; Mikulis, David J; Palmieri, Diane; Bronder, Julie L; Steeg, Patricia S; Yoneda, Toshiyuki; MacDonald, Ian C; Chambers, Ann F; Rutt, Brian K; Foster, Paula J

    2006-11-01

    Metastasis (the spread of cancer from a primary tumor to secondary organs) is responsible for most cancer deaths. The ability to follow the fate of a population of tumor cells over time in an experimental animal would provide a powerful new way to monitor the metastatic process. Here we describe a magnetic resonance imaging (MRI) technique that permits the tracking of breast cancer cells in a mouse model of brain metastasis at the single-cell level. Cancer cells that were injected into the left ventricle of the mouse heart and then delivered to the brain were detectable on MR images. This allowed the visualization of the initial delivery and distribution of cells, as well as the growth of tumors from a subset of these cells within the whole intact brain volume. The ability to follow the metastatic process from the single-cell stage through metastatic growth, and to quantify and monitor the presence of solitary undivided cells will facilitate progress in understanding the mechanisms of brain metastasis and tumor dormancy, and the development of therapeutics to treat this disease. PMID:17029229

  14. TTF-1 may not be a Reliable Marker for Differentiating Metastasis from Brain Tumors

    Betül ÜNAL

    2014-09-01

    Full Text Available Objective: TTF-1 is widely used as an immunohistochemical marker of lung and thyroid tumors. However, TTF-1 expression has been described in tumors from other sites. The presence of TTF-1 expression in primary brain tumors is largely unclear and has not been clearly specified yet. We characterized expression of two TTF-1 clones in primary brain tumors with relevance to tumor types and grades. Material and Method: We studied immunohistochemistry with tissue micro-array, using both clones (8G7G3/1 and SPT24 in 45 primary brain tumors of different types and grades. Our cases consisted of 1 grade I, 7 grade II, 4 grade III, 20 grade IV astrocytic tumors; 9 meningiomas, 2 oligodendrogliomas, 1 schwannoma and 1 medulloblastoma. Results: We have found TTF-1 nuclear staining using the SPT24 clone in 4 cases (3 cases were grade IV and 1 was grade III. Focal and weak staining was seen in three cases and moderate-strong and diffuse staining was seen in one case. All the tumors were negative with clone 8G7G3/1. Clone SPT24 was more sensitive but less specific. Conclusion: TTF-1 can also be expressed in primary brain tumors, particularly grade III to IV tumors. TTF-1 expression was a rare finding in previous studies, however strong and diffuse staining was not observed until today. We think that TTF-1 nuclear expression in high-grade astrocytic tumors cannot rule out primaries even when diffuse and strong staining. Clinical and pathological parameters should be evaluated together.

  15. Medical and health economic assessment of radiosurgery for the treatment of brain metastasis

    von der Schulenburg, Johann-Matthias; Willich, Stefan N.; Vauth, Christoph; Ernst, Iris; Schwarzbach, Christoph; Bockelbrink, Angelina; Müller-Riemenschneider, Falk

    2009-01-01

    Background Radiotherapy for patients suffering from malignant neoplasms has developed greatly during the past decades. Stereotactic radiosurgery (SRS) is one important radiotherapeutic option which is defined by a single and highly focussed application of radiation during a specified time interval. One of its important indications is the treatment of brain metastases . Objectives The objective of this HTA is to summarise the current literature concerning the treatment of b...

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

    Brain metastases (BM) represent one of the most frequent complications related to cancer, and their treatment continues to evolve. We have evaluated the activity, toxicity and the impact on Quality of Life (QoL) of a concomitant treatment with whole brain radiotherapy (WBRT) and Temozolomide (TMZ) in patients with brain metastases from solid tumors in a prospective Simon two stage study. Fifty-nine patients were enrolled and received 30 Gy WBRT with concomitant TMZ (75 mg/m2/day) for ten days, and subsequently TMZ (150 mg/m2/day) for up to six cycles. The primary end points were clinical symptoms and radiologic response. Five patients had a complete response, 21 patients had a partial response, while 18 patients had stable disease. The overall response rate (45%) exceeded the target activity per study design. The median time to progression was 9 months. Median overall survival was 13 months. The most frequent toxicities included grade 3 neutropenia (15%) and anemia (13%), and only one patient developed a grade 4 thrombocytopenia. Age, Karnofsky performance status, presence of extracranial metastases and the recursive partitioning analysis (RPA) were found to be predictive factors for response in patients. Overall survival (OS) and progression-free survival (PFS) were dependent on age and on the RPA class. We conclude that this treatment is well tolerated, with an encouraging objective response rate, and a significant improvement in quality of life (p < 0.0001) demonstrated by FACT-G analysis. All patients answered the questionnaires and described themselves as 'independent' and able to act on their own initiatives. Our study found a high level of satisfaction for QoL, this provides useful information to share with patients in discussions regarding chemotherapy treatment of these lesions

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

    Wang Tao; Wang Ruimin; Dong Zhouhuan; Liang Naichao; Chang Ping

    2016-01-01

    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 prima...

  18. Brain Metastasis is Predetermined in Early-Stages of Cutaneous Melanoma by CD44v6 Expression through Epigenetic Regulation of the Spliceosome

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

    2014-01-01

    Melanoma brain metastasis (MBM) is frequent and has a very poor prognosis with no current predictive factors or therapeutic molecular targets. Our study unravels the molecular alterations of cell-surface glycoprotein CD44 variants during melanoma progression to MBM. High expression of CD44 splicing variant 6 (CD44v6) in primary melanoma (PRM) and regional lymph node metastases from AJCC Stage IIIC patients significantly predicts MBM-development. The expression of CD44v6 also enhances the migr...

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

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

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

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

    2015-07-15

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

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

    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 T3+4 patient was similar with T1+2 (69.4%, 30.6%, χ2 = 7.65, P = 0.067), but N2+3 patient was more than N0+1 (69.7%, 30.3%, χ2 = 7.89, P = 0.044). The brain metastasis probability of T3+4 patient was more than T1+2 (70.7%, 29.3%, χ2 = 10.64, P = 0.018), but N2+3 patient was similar with N0+1 (54.5%, 45.5%, χ2 = 7.14, P = 0.079), and N1+3+3 patient was more than N0 (86.8%, 13.2%, χ2 = 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)

  2. 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

    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.

  3. Pharmacologic Inhibition of MLK3 Kinase Activity Blocks the In Vitro Migratory Capacity of Breast Cancer Cells but Has No Effect on Breast Cancer Brain Metastasis in a Mouse Xenograft Model

    Rhoo, Kun Hyoe; Granger, Megan; Sur, Joynita; Feng, Changyong; Gelbard, Harris A.; Dewhurst, Stephen; Polesskaya, Oksana

    2014-01-01

    Brain metastasis of breast cancer is an important clinical problem, with few therapeutic options and a poor prognosis. Recent data have implicated mixed lineage kinase 3 (MLK3) in controlling the in vitro migratory capacity of breast cancer cells, as well as the metastasis of MDA-MB-231 breast cancer cells from the mammary fat pad to distant lymph nodes in a mouse xenograft model. We therefore set out to test whether MLK3 plays a role in brain metastasis of breast cancer cells. To address thi...

  4. Radiotherapy for asymptomatic brain metastasis in epidermal growth factor receptor mutant non-small cell lung cancer without prior tyrosine kinase inhibitors treatment: a retrospective clinical study

    Non-small cell lung cancer (NSCLC) with brain metastasis (BM) harboring an epidermal growth factor receptor (EGFR) mutation shows good response to tyrosine kinase inhibitors (TKIs). This study is to assess the appropriate timing of brain radiotherapy (RT) for asymptomatic BM in EGFR mutant NSCLC patients. There were 628 patients diagnosed with EGFR mutant NSCLC between October 2005 and December 2011. Treatment outcomes had been retrospectively evaluated in 96 patients with asymptomatic BM without prior TKI treatment. 39 patients received first-line brain RT, 23 patients received delayed brain RT, and 34 patients did not receive brain RT. With a median follow-up of 26 months, the 2-year OS was 40.6 %. Univariate analyses revealed that ECOG performance status (p = 0.006), other distant metastases (p = 0.002) and first line systemic treatment (p = 0.032) were significantly associated with overall survival (OS). Multivariate analyses revealed that other sites of distant metastases (p = 0.030) were prognostic factor. The timing of brain RT was not significantly related to OS (p = 0.246). The 2-year BM progression-free survival (PFS) was 26.9 %. Brain RT as first-line therapy failed to demonstrate a significant association with BM PFS (p = 0.643). First-line brain RT failed to improve long-term survival in TKI-naïve EGFR mutant NSCLC patients with asymptomatic BM. Prospective studies are needed to validate these clinical findings

  5. Radiosurgical treatment of previously irradiated primary brain tumors and brain metastasis: final report of radiation therapy oncology group (RTOG) protocol 90-05

    Purpose/Objective: To determine the maximum single radiosurgical dose that can be given to patients (pts) with recurrent primary brain tumors (1 deg. BT) or brain metastasis (BM) who had received prior fractionated external beam radiation therapy (FEBRT). Materials/Methods: The treated tumor had to be ≤40 mm in maximum diameter. Dose was prescribed to the periphery of the tumor (without margin) based on diameter, to the 50% to 90% isodose line. Initial doses were: Arm 1--≤20 mm, 18 Gy; Arm 2--21 to 30 mm, 15 Gy; and Arm 3--31 to 40 mm, 12 Gy. Dose was then escalated in 3 Gy increments, providing that unacceptable neurologic toxicity (grade 3,4, or 5 using the RTOG Central Nervous System (CNS) Toxicity Criteria) occurred in 3, 5977 mm3, and 18,202 mm3 for tumors ≤20 mm, 21-30 mm, and 31-40 mm in maximum diameter, respectively. Thirty-one pts were treated on a Gamma Knife and 125 on a linear accelerator. The table below summarizes the toxicity results of the study: Analysis of variables contributing to toxicity demonstrated that tumors with a maximum diameter of 21-40 mm had a 1.2 times greater chance of developing unacceptable neurologic toxicity than tumors ≤20 mm in diameter. Local failure (in the radiosurgical treatment volume) occurred in 37 pts (24%). The most significant variable contributing to local failure was tumor type. 1 deg. BT were twice as likely to develop local failure than BM. Twenty-one pts (14%) underwent reoperation. Pathologic findings were as follows: tumor only--38%, tumor + necrosis--33%, necrosis only--19%, and non-diagnostic--10%. Conclusions: In previously irradiated patients with recurrent 1 deg. BT and BM, the maximum safe dose of single fraction radiosurgery was 24 Gy for tumors ≤20 mm in maximum diameter, 21 Gy for 21-30 mm tumors, and 15 Gy for tumors 31-40 mm

  6. Brain-derived neurotrophic factor modulation of Kv1.3 channel is disregulated by adaptor proteins Grb10 and nShc

    Marks David R

    2009-01-01

    Full Text Available Abstract Background Neurotrophins are important regulators of growth and regeneration, and acutely, they can modulate the activity of voltage-gated ion channels. Previously we have shown that acute brain-derived neurotrophic factor (BDNF activation of neurotrophin receptor tyrosine kinase B (TrkB suppresses the Shaker voltage-gated potassium channel (Kv1.3 via phosphorylation of multiple tyrosine residues in the N and C terminal aspects of the channel protein. It is not known how adaptor proteins, which lack catalytic activity, but interact with members of the neurotrophic signaling pathway, might scaffold with ion channels or modulate channel activity. Results We report the co-localization of two adaptor proteins, neuronal Src homology and collagen (nShc and growth factor receptor-binding protein 10 (Grb10, with Kv1.3 channel as demonstrated through immunocytochemical approaches in the olfactory bulb (OB neural lamina. To further explore the specificity and functional ramification of adaptor/channel co-localization, we performed immunoprecipitation and Western analysis of channel, kinase, and adaptor transfected human embryonic kidney 293 cells (HEK 293. nShc formed a direct protein-protein interaction with Kv1.3 that was independent of BDNF-induced phosphorylation of Kv1.3, whereas Grb10 did not complex with Kv1.3 in HEK 293 cells. Both adaptors, however, co-immunoprecipitated with Kv1.3 in native OB. Grb10 was interestingly able to decrease the total expression of Kv1.3, particularly at the membrane surface, and subsequently eliminated the BDNF-induced phosphorylation of Kv1.3. To examine the possibility that the Src homology 2 (SH2 domains of Grb10 were directly binding to basally phosphorylated tyrosines in Kv1.3, we utilized point mutations to substitute multiple tyrosine residues with phenylalanine. Removal of the tyrosines 111–113 and 449 prevented Grb10 from decreasing Kv1.3 expression. In the absence of either adaptor protein

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

    Wang Tao

    2016-02-01

    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.

  8. Stereotactic Irradiation of the Postoperative Resection Cavity for Brain Metastasis: A Frameless Linear Accelerator-Based Case Series and Review of the Technique

    Purpose: Whole-brain radiation therapy (WBRT) is the standard of care after resection of a brain metastasis. However, concern regarding possible neurocognitive effects and the lack of survival benefit with this approach has led to the use of stereotactic radiosurgery (SRS) to the resection cavity in place of WBRT. We report our initial experience using an image-guided linear accelerator-based frameless stereotactic system and review the technical issues in applying this technique. Methods and Materials: We retrospectively reviewed the setup accuracy, treatment outcome, and patterns of failure of the first 18 consecutive cases treated at Brigham and Women’s Hospital. The target volume was the resection cavity without a margin excluding the surgical track. Results: The median number of brain metastases per patient was 1 (range, 1–3). The median planning target volume was 3.49 mL. The median prescribed dose was 18 Gy (range, 15–18 Gy) with normalization ranging from 68% to 85%. In all cases, 99% of the planning target volume was covered by the prescribed dose. The median conformity index was 1.6 (range, 1.41–1.92). The SRS was delivered with submillimeter accuracy. At a median follow-up of 12.7 months, local control was achieved in 16/18 cavities treated. True local recurrence occurred in 2 patients. No marginal failures occurred. Distant recurrence occurred in 6/17 patients. Median time to any failure was 7.4 months. No Grade 3 or higher toxicity was recorded. A long interval between initial cancer diagnosis and the development of brain metastasis was the only factor that trended toward a significant association with the absence of recurrence (local or distant) (log-rank p = 0.097). Conclusions: Frameless stereotactic irradiation of the resection cavity after surgery for a brain metastasis is a safe and accurate technique that offers durable local control and defers the use of WBRT in select patients. This technique should be tested in larger prospective

  9. Brain metastasis of gynecologic tumors. Experience in the laboratory of neuropathology in a period of 5 years (1998-2003). Clinical Hospital Dr. Manuel Quintela, Montevideo Uruguay

    Intracranial metastases occur in 13.5 to 37% of patients with cancer spread, the most common primary sites lung, breast, kidney and gastrointestinal tract. Gynecologic malignancies rarely give brain metastases, with the exception of choriocarcinoma. The incidence of metastasis ovarian carcinomas brain varies between 0.9 and 3.3%, although figures are increasing due to improved survival with treatment chemotherapy and early detection of lesions. Secondly, figures of between 0.4 and 1.2% are metastases cervix. They are usually poorly differentiated tumors with disease advanced locoregional and disseminated systemic disease. carcinomas endometrium are less common, with an incidence of 0.3%. Generally have widely disseminated disease.The purpose of this study is to document the occurrence of brain metastases gynecologic origin in the Laboratory of Neuropathology of the Clinical Hospital between 1998 and 2003 In this period 273 cases were studied brain metastases of whom 4.7% (n = 13) had a primitive gynecological. Of these 38.4% were for ovarian primitive, 30.7% a primitive cervical and 30.7% to a primitive endometrium. Analyzed clinical features, the topography of the lesions and histological type. While metastases from gynecologic tumors are rare, should be considered patients with one or more brain mass, even in those cases where primary disease is unknown

  10. Increased survival with the combination of stereotactic radiosurgery and gefitinib for non-small cell lung cancer brain metastasis patients: a nationwide study in Taiwan

    Whole brain irradiation (WBRT) either with or without resection has historically been the treatment for brain metastases from non-small cell lung cancer (NSCLC). The effect of gamma knife (GK) radiosurgery, chemotherapy, or the combination remains incompletely defined. In this study, we assessed the outcome of brain metastases from non-small cell lung cancer treated by WBRT followed by GK, gefitinib, or the combination of GK and gefitinib. We retrieved the records of NSCLC patients with brain metastases from the National Health Insurance Research Database (NHIRD) of Taiwan from 2004 to 2010. WBRT either with or without resection was the first line treatment for nearly all patients. The decision to add GK and/or gefitinib treatment was at the discretion of the treating physician and based upon a patient’s medical records and imaging data. These patients were classified into four groups including WBRT, WBRT + gefitinib, WBRT + GK, WBRT + gefitinib + GK. These data was evaluated for difference in survival and factors that portended an extended survival from the time of brain metastasis diagnosis. Of the 60194 patients with newly diagnosed NSCLC, 23874 (39.6 %) developed brain metastases. The distribution of patients for the groups was WBRT for 20241, WBRT + gefitinib for 3379, WBRT + GK for 155, and WBRT+ gefitinib + GK for 99 patients. The median survival for the time of brain metastasis diagnosis for WBRT, WBRT+ gefitinib, WBRT+ GK, WBRT+ gefitinib + GK groups was 0.53, 1.01, 1.46, and 2.25 years, respectively (p < 0.0001). The hazard ratio (95 % CI) for survival was 1, 0.56, 0.43, and 0.40, respectively (p < 0.001). The adjusted hazard ratio (95 % CI) by age, sex and Charlson comorbidity index (CCI) was 1, 0.73, 0.49, and 0.42, respectively (p < 0.001). Patients with brain metastases from NSCLC receiving GK or gefitinib demonstrated extended survival. The improved survival seen with GK and gefitinib suggests a survival benefit in selected patients receiving the

  11. Radiotherapy in different doses for non-small cell lung cancer patients with brain metastasis-phase I-II study

    Objective: To observe the tolerance, effectiveness and prognostic factors of three different doses for non-small cell lung cancer (NSCLC) patients with brain metastasis. Methods: Seventy-five NSCLC patients with known brain metastasis were irradiated in the following protocols. Group A whole brain irradiation to 30 Gy/10 fractions over 2 weeks then boosted to 45 Gy/15 fractions over 3 weeks for patients with only one lesion in the brain without any extracranial involvement (14 cases). Group B whole irradiation to 39 Gy/13 fractions over 2.5 weeks for patients with more than one lesion in the brain also without any extracranial involvement (29 cases). Group C whole irradiation to 30 Gy/10 fractions over 2 weeks for patients with both extracranial and brain lesions (32 cases). Results: The incidence of symptom relief (pain, nausea and vomiting) was 100% in all groups. The incidences of neurological sign relief in groups A,B,C were 100%(7/7), 86%(12/14), 93%(14/15). The overall median local control duration was 7.6 months (0.8-52.7 months). The overall 1-and 2-year local control rates were 46% and 23%. The 1-and 2-year local control rates of groups A, B, C were 55% and 38%, 52% and 26%, 33% and 10%, respectively. The overall median survival was 9.6 months (0.8-52.8 months). The overall 1-and 2-year survival rates were 49% and 26%. The 1-and 2-year survival rates of groups A, B, C were 53% and 49%, 50% and 23%, 45% and 9%, respectively. Side effects: None of these patients showed serious acute side effects except one in group A who developed gastrointestinal bleeding and one in group C who had epileptic seizures during the second session of irradiation. Late effects: Two patients in group B showed impairment in thought coherence and behavior though without any tumor in the brain after 23, 17 months of irradiation. The results of Cox regression in local control suggested that higher dose may give better local control duration (P=0.003). And another result of Cox

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

    Kun Hyoe Rhoo

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

  13. Differentiation of local tumor recurrence from radiation-induced changes after stereotactic radiosurgery for treatment of brain metastasis: case report and review of the literature

    Structural follow-up magnetic resonance imaging (MRI) after stereotactic radiosurgery (SRS) for brain metastases frequently displays local changes in the area of applied irradiation, which are often difficult to interpret (e.g., local tumor recurrence, radiation-induced changes). The use of stereotactic biopsy for histological assessment of these changes has a high diagnostic accuracy and can be considered as method of choice. In order to solve this relevant clinical problem non-invasively, advanced MRI techniques and amino acid positron-emission-tomography (PET) are increasingly used. We report the long-term follow-up of a patient who had been treated with linear accelerator based SRS for cerebral metastases of a lung cancer. Fifty-eight months after SRS, the differentiation of local recurrent brain metastasis from radiation-induced changes using structural MRI was difficult. For further differentiation, perfusion-weighted MRI (PWI), proton magnetic resonance spectroscopy (MRS), and 11C-methyl-L-methionine (MET) PET was performed. Due to artifacts and technical limitations, PWI MRI and MRS findings were not conclusive. In contrast, MET PET findings were suggestive for radiation-induced changes. Finally, a stereotactic biopsy for histological assessment of these changes demonstrated clearly a radiation-induced necrosis and the absence of vital tumor. The use of stereotactic biopsy for histological assessment of indistinguishable lesions on structural MRI after SRS for treatment of brain metastasis represents a highly reliable method to differentiate local tumor recurrence from radiation-induced changes. In this field, results of studies with both advanced MRI techniques and amino acid PET suggest encouraging results. However, artifacts and technical limitations (e.g., lesion size) are still a problem and comparative studies are needed to investigate the relationship, diagnostic performance, and complementary character of advanced MRI techniques and amino acid PET

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

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

    2014-06-15

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

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

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

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

    Ro Jungsil

    2012-07-01

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

  17. In vitro release of 1,3-bis (2-chloroethyl)-1-nitrosourea sustained-release microspheres and the distribution in rat brain tissues

    Xia Li; Liping Guo; Qin Li

    2006-01-01

    BACKGROUND: The implantation of released chemotherapeutic drugs, which takes biodegradable polymer as vector, into the tumor site can get high concentration and release the drug for a long time, it can directly act on the tumor cells, and reduce the general toxicity.OBJECTIVE: To explore the in vitro and in vivo course of 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) sustained-release from BCNU-loaded polylactide (PLA) microspheres (MS) and location in rat brain tissue.DESIGN: A repetitive measurement.SETTING: Central Pharmacy, General Hospital of Chinese People's Armed Police Forces.MATERIALS: Thirty male SD rats were used. PLA (Mr5000, batch number: KSL8377) was produced by Wako Pure Chemical Inc.,Ltd. (Japan); BCNU (batch number: 021121) by Tianjin Jinyao Amino Acid Co., Ltd.;BCNU-PLA-MS was prepared by the method of solvent evaporation and pressed into tablets (10 mg/tablet).High-performance liquid chromatography (HPLC) Agilent 1100 (USA); LS9800 liquid-scintillation radiometric apparatus (Beckman). Chromatographic conditions: Elite Hypersil ODS2 C18 chromatographic column (5 μm,4.6 mm ×150 mm); Mobile phase: methanol: water (50:50), flow rate was 1.0 mL per minute, wave length of ultraviolet detection was 237 nm, and the inlet amount of samples was 10 μL.METHODS: The experiments were carried out in the experimental animal center of the General Hospital of Chinese Armed Police from May 2004 to July 2005. ① In vitro BCNU-PLA-MS release test: BCNU-PLA-MS was prepared by the method of solvent evaporation, then placed in 0.1 mol/L phosphate buffered solution (PBS, pH 7.4, 37 ℃), part of MS were taken out at 1, 2, 3, 7, 10 and 15 days respectively, and the rest amount of BCNU in MS was determined by HPLC, then the curve of BCNU-PLA-MS release was drawn. ②In vivo BCNU-PLA-MS release and distribution test: The rats were anesthetized, then BCNU-PLA-MS were implanted to the site 1 mm inferior to the cortex of frontal lobe. Five rats were killed postoperatively

  18. Palbociclib in Treating Patients With Metastatic HER-2 Positive or Triple-Negative Breast Cancer With Brain Metastasis

    2016-05-13

    Breast Carcinoma Metastatic in the Brain; Estrogen Receptor Negative; HER2/Neu Negative; HER2/Neu Positive; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma

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

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

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

    Rau, Kun-Ming; Chen, Han-Ku; Shiu, Li-Yen; Chao, Tsai-Ling; Lo, Yi-Ping; Wang, Chin-Chou; Lin, Meng-Chih; Huang, Chao-Cheng

    2016-01-01

    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. PMID:27070580

  1. Factors influencing the survival of rat brain tumor cells after in vitro treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea

    Wheeler, K.T.; Tel, N.; Williams, M.E.; Sheppard, S.; Levin, V.A.; Kara, P.M.

    1975-06-01

    The shape of dose-response curves obtained for asynchronous, exponential growing 9L rat brain tumor cells treated in vitro with 1,3-bis(2-chloroethyl)-l-nitrosourea changed as a function of the drug exposure time. For short treatment times (<1 hr), the dose-response curves had shoulders, indicating that the cells may accumulate sublethal damage; however, after longer treatments (>1 hr), little if any shoulder was apparent. The slope of the exponential portion of the dose-response curve increased progressively with treatment periods from 15 min to 2 hr. Longer exposure times (up to 24 hr) produced no further changes in the cell-kill kinetics. Cell survival was directly related to the BCNU exposure dose and to the amount of bound BCNU per cell. Extrapolation of the curves for these two variables indicated that some BCNU damage accumulates before death occurs. The amount of serum and cell products available in the medium to bind BCNU affected the level of survival; however, there was no evidence that extracellular spontaneous breakdown products or chemical transformation products were involved in the cell-killing mechanism. (auth)

  2. Brain metastasis of Wilms tumor with diffuse anaplasia and complex cytogenetic phenotype in a child with neurofibromatosis Type 1.

    Shvartsbeyn, Marianna; Bassani, Luigi; Mikolaenko, Irina; Wisoff, Jeffrey H

    2011-10-01

    The authors report the first case of a Wilms tumor (WT) with diffuse anaplasia metastatic to the brain in a 13-year-old girl with a history of neurofibromatosis Type 1. At presentation, the metastatic tumor had radiological features that suggested a meningioma. Histologically it was characterized by striking anaplasia and features similar to the patient's previously resected WT with diffuse anaplasia. PMID:21961578

  3. Secondary Analysis of RTOG 9508, a Phase 3 Randomized Trial of Whole-Brain Radiation Therapy Versus WBRT Plus Stereotactic Radiosurgery in Patients With 1-3 Brain Metastases; Poststratified by the Graded Prognostic Assessment (GPA)

    Sperduto, Paul W., E-mail: psperduto@mropa.com [Metro-Minnesota CCOP and Minneapolis Radiation Oncology, Minneapolis, Minnesota (United States); Shanley, Ryan [Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota (United States); Luo, Xianghua [Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota (United States); Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota (United States); Andrews, David [Thomas Jefferson University, Department of NeuroOncology, Philadelphia, Pennsylvania (United States); Werner-Wasik, Maria [Thomas Jefferson University, Department of Radiation Oncology, Philadelphia, Pennsylvania (United States); Valicenti, Richard [UC Davis Medical Center, Department of Radiation Oncology, Sacramento, California (United States); Bahary, Jean-Paul [CHUM Hospital Notre Dame, Quebec (Canada); Souhami, Luis [McGill University, Montreal, Quebec (Canada); Won, Minhee [NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania (United States); Mehta, Minesh [University of Maryland Medical System, Baltimore, Maryland (United States)

    2014-11-01

    Purpose: Radiation Therapy Oncology Group (RTOG) 9508 showed a survival advantage for patients with 1 but not 2 or 3 brain metastasis (BM) treated with whole-brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) versus WBRT alone. An improved prognostic index, the graded prognostic assessment (GPA) has been developed. Our hypothesis was that if the data from RTOG 9508 were poststratified by the GPA, the conclusions may vary. Methods and Materials: In this analysis, 252 of the 331 patients were evaluable by GPA. Of those, 211 had lung cancer. Breast cancer patients were excluded because the components of the breast GPA are not in the RTOG database. Multiple Cox regression was used to compare survival between treatment groups, adjusting for GPA. Treatment comparisons within subgroups were performed with the log-rank test. A free online tool ( (brainmetgpa.com)) simplified GPA use. Results: The fundamental conclusions of the primary analysis were confirmed in that there was no survival benefit overall for patients with 1 to 3 metastases; however, there was a benefit for the subset of patients with GPA 3.5 to 4.0 (median survival time [MST] for WBRT + SRS vs WBRT alone was 21.0 versus 10.3 months, P=.05) regardless of the number of metastases. Among patients with GPA 3.5 to 4.0 treated with WBRT and SRS, the MST for patients with 1 versus 2 to 3 metastases was 21 and 14.1 months, respectively. Conclusions: This secondary analysis of predominantly lung cancer patients, consistent with the original analysis, shows no survival advantage for the group overall when treated with WBRT and SRS; however, in patients with high GPA (3.5-4), there is a survival advantage regardless of whether they have 1, 2, or 3 BM. This benefit did not extend to patients with lower GPA. Prospective validation of this survival benefit for patients with multiple BM and high GPA when treated with WBRT and SRS is warranted.

  4. Short-time focused ultrasound hyperthermia enhances liposomal doxorubicin delivery and antitumor efficacy for brain metastasis of breast cancer

    Wu SK; Chiang CF; Hsu YH; Lin TH; Liou HC; Fu WM; Lin WL

    2014-01-01

    Sheng-Kai Wu,1 Chi-Feng Chiang,1 Yu-Hone Hsu,1,4 Tzu-Hung Lin,2 Houng-Chi Liou,2 Wen-Mei Fu,2 Win-Li Lin1,3 1Institute of Biomedical Engineering, College of Medicine and College of Engineering, 2Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan; 3Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli, Taiwan; 4Department of Neurosurgery, Cheng-Hsin General Hospital, Taipei, Taiwan Abstract: The blood&nd...

  5. Metastasis Suppressor Genes

    Yan, Jinchun; Yang, Qin; Huang, Qihong

    2013-01-01

    Metastasis is a major cause of cancer mortality. Metastasis is a complex process that requires the regulation of both metastasis-promoting and metastasis suppressor genes. The discovery of metastasis suppressor genes contributes significantly to our understanding of metastasis mechanisms and provides prognostic markers and therapeutic targets in clinical cancer management. In this review, we summarize the methods that have been used to identify metastasis suppressors and the potential clinica...

  6. Consecutive acquisition of time-resolved contrast-enhanced MR angiography and perfusion MR imaging with added dose of gadolinium-based contrast agent Aids diagnosis of suspected brain metastasis

    Time-resolved contrast-enhanced magnetic resonance (MR) angiography (TCMRA) and perfusion MR imaging (PWI) have been used to assess the hemodynamics of brain tumors. We assessed the feasibility and value of consecutive performance of these techniques to evaluate suspected brain metastasis following supplementary injection of gadolinium-based contrast medium. In 69 patients with suspected brain metastasis, we obtained precontrast MR images followed by TCMRA and postcontrast T1-weighted images after administration of 0.1 mmol/kg gadoteridol. When findings were negative or equivocal, we injected an additional 0.1-mmol/kg dose of gadoteridol and obtained PWI and second postcontrast T1-weighted images. We used a 3-point scale to grade perfusion maps and TCMRA and assessed whether these techniques added information to conventional MR imaging in the differential diagnosis. We also evaluated whether the second contrast injection improved the conspicuity and/or number of enhancing lesions and used a 4-point scoring system to quantitatively analyze diagnostic yield of TCMRA and PWI. We could assess tumor hemodynamics on PWI maps and TCMRA images in all 69 patients. In 14 cases (20%), PWI and/or TCMRA added information to conventional MR findings. After second injection of contrast medium, lesion conspicuity improved in 58 of the 69 cases (84%), and the number of detected lesions increased in 11 of 31 cases diagnosed with metastatic disease (36%). Quantitative analysis revealed TCMRA and PWI provided significant additional diagnostic information (Kruskal-Wallis test, P<0.0001). Consecutive acquisition of TCMRA and PWI using supplementary contrast injection can facilitate differential diagnosis of suspected brain metastasis and improve the number and conspicuity of detected lesions. (author)

  7. Mixed Inhibition of Adenosine Deaminase Activity by 1,3-Dinitrobenzene: A Model for Understanding Cell-Selective Neurotoxicity in Chemically-Induced Energy Deprivation Syndromes in Brain

    Wang, Yipei; Liu, Xin; Schneider, Brandon; Zverina, Elaina A.; Russ, Kristen; Wijeyesakere, Sanjeeva J.; Fierke, Carol A.; Richardson., Rudy J.; Philbert, Martin A.

    2011-01-01

    Astrocytes are acutely sensitive to 1,3-dinitrobenzene (1,3-DNB) while adjacent neurons are relatively unaffected, consistent with other chemically-induced energy deprivation syndromes. Previous studies have investigated the role of astrocytes in protecting neurons from hypoxia and chemical injury via adenosine release. Adenosine is considered neuroprotective, but it is rapidly removed by extracellular deaminases such as adenosine deaminase (ADA). The present study tested the hypothesis that ...

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

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

    2014-03-15

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

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

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

  10. Distribution and ontogeny of 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid-sensitive and quisqualate-insensitive [3H]glutamate binding sites in the rat brain.

    Wright, R A; McDonald, J W; Schoepp, D D

    1994-09-01

    Displacement of [3H]glutamate by 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid and quisqualate (in the presence of saturating concentrations of ionotropic glutamate receptor agonists) was used to characterize optimal ionic conditions, distribution, and the ontogeny of glutamate receptor binding sites in rat brain. Using rat forebrain membranes or receptor autoradiography, optimal 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid-sensitive [3H]glutamate binding was found in the presence of 100 mM bromide ions and in the absence of calcium ions. Under these conditions, [3H]glutamate binding was relatively quisqualate insensitive. In regions of the neonatal (11-day-old) and adult rat brain, this [3H]glutamate binding was highest in forebrain (striatum, cerebral cortex, and hippocampus) and hypothalamus/mid-brain but was lower in the cerebellum, olfactory bulb, and pons/medulla regions. 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid-sensitive and quisqualate-insensitive [3H]glutamate binding was present in the rat forebrain at 1 day of age and gradually increased more than twofold by day 50 (adult). Thus, in the presence of bromide ions and in the absence of calcium ions, [3H]glutamate labels a subpopulation of metabotropic glutamate receptors that are sensitive to 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid but insensitive to quisqualate. Expression of [3H]glutamate binding under these conditions was both regionally and developmentally regulated in rat brain, suggesting that [3H]glutamate is labeling a distinct population of metabotropic glutamate receptors. PMID:7914226

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

    Tomohiro Okuda; Sakura Yamamoto; Seiki Matsuo; Hisashi Kataoka; Jo Kitawaki

    2016-01-01

    We report a case of pregnancy-associated breast cancer with metastasis to the brain, likely resulting from hereditary breast and ovarian cancer (HBOC). A 35-year-old woman (gravida 2, para 0-1-0-1) underwent a right mastectomy and right axillary dissection after a cesarean section at 30 years of age; her mother died at 47 years of age due to breast cancer. Histopathological examination indicated an invasive ductal carcinoma with triple-negative cancer (cancer stage 2B [pT3N0M0]). The patient ...

  12. AEG-1与CXCR4对乳腺癌脑转移的影响%Effect of AEG-1 and CXCR4 Gene on Breast Cancer Brain Metastasis

    曲明阳; 李森; 赵胜男; 邢光明

    2011-01-01

    目的 探讨AEG-1与CXCR4基因表达对乳腺癌脑转移的影响.方法 对1997~2007年收治的乳腺癌患者进行随访,以发生脑转移的33例患者作为病例组,以未发生脑转移的45例患者作为对照组.通过免疫组化法,对照分析AEG-1及CXCR4对脑转移的影响.结果 脑转移组中AEG-1及CXCR4的阳性表达率分别为63.6%和60.6%,与其在对照组中表达(31.1%和33.3%)差异显著(P<0.05).logistic回归分析结果显示,AEG-1和CXCR4回归系数分别为1.242和1.545.结论 AEG-1和CXCR4阳性表达是乳腺癌发生脑转移的独立危险因子,AEG-1及CXCR4有望成为针对乳腺癌脑转移的高特异性早期诊断指标及基因治疗靶点.%Objective Explore the effect of AEG-1 and CXCR4 gene on brain metastasis in breast cancer. Methods 33 breast cancer patients with brain metastasis and 45 patients without brain metastasis in our hospital from 1997 to 2007 were chosen randomly for the case control study by immunohisto chemical method. Results the expression rate for AEG-land CXCR4 in the two groups were 63. 6% ,60. 6% and 31. 1% ,33. 3% respectively,with a notebly difference be observed, the regression coefficient for AEG-1 and CXCR4 was 1. 242 and 1. 545. Conclusion AEG-1 and CXCR4 were independent risk factors and may be specific diagnosis index and gene treatment taget for brain metastasis in breast cancer.

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

    Tomohiro Okuda

    2016-01-01

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

  14. Brain

    ... will return after updating. Resources Archived Modules Updates Brain Cerebrum The cerebrum is the part of the ... the outside of the brain and spinal cord. Brain Stem The brain stem is the part of ...

  15. A phase II multi-institutional study assessing simultaneous in-field boost helical tomotherapy for 1-3 brain metastases

    Rodrigues George

    2012-03-01

    Full Text Available Abstract Background Our research group has previously published a dosimetric planning study that demonstrated that a 60 Gy/10 fractions intralesional boost with whole-brain radiotherapy (WBRT to 30 Gy/10 fractions was biologically equivalent with a stereotactic radiosurgery (SRS boost of 18 Gy/1 fraction with 30 Gy/10 fractions WBRT. Helical tomotherapy (HT was found to be dosimetrically equivalent to SRS in terms of target coverage and superior to SRS in terms of normal tissue tolerance. A phase I trial has been now completed at our institution with a total of 60 enrolled patients and 48 evaluable patients. The phase II dose has been determined to be the final phase I cohort dose of 60 Gy/10 fractions. Methods/Design The objective of this clinical trial is to subject the final phase I cohort dose to a phase II assessment of the endpoints of overall survival, intracranial control (ICC and intralesional control (ILC. We hypothesize HT would be considered unsuitable for further study if the median OS for patients treated with the HT SIB technique is degraded by 2 months, or the intracranial progression-free rates (ICC and ILC are inferior by 10% or greater compared to the expected results with treatment by whole brain plus SRS as defined by the RTOG randomized trial. A sample size of 93 patients was calculated based on these parameters as well as the statistical assumptions of alpha = 0.025 and beta = 0.1 due to multiple statistical testing. Secondary assessments of toxicity, health-related quality-of-life, cognitive changes, and tumor response are also integrated into this research protocol. Discussion To summarize, the purpose of this phase II trial is to assess this non-invasive alternative to SRS in terms of central nervous system (CNS control when compared to SRS historical controls. A follow-up phase III trial may be required depending on the results of this trial in order to definitively assess non-inferiority/superiority of this approach

  16. A phase II multi-institutional study assessing simultaneous in-field boost helical tomotherapy for 1-3 brain metastases

    Our research group has previously published a dosimetric planning study that demonstrated that a 60 Gy/10 fractions intralesional boost with whole-brain radiotherapy (WBRT) to 30 Gy/10 fractions was biologically equivalent with a stereotactic radiosurgery (SRS) boost of 18 Gy/1 fraction with 30 Gy/10 fractions WBRT. Helical tomotherapy (HT) was found to be dosimetrically equivalent to SRS in terms of target coverage and superior to SRS in terms of normal tissue tolerance. A phase I trial has been now completed at our institution with a total of 60 enrolled patients and 48 evaluable patients. The phase II dose has been determined to be the final phase I cohort dose of 60 Gy/10 fractions. The objective of this clinical trial is to subject the final phase I cohort dose to a phase II assessment of the endpoints of overall survival, intracranial control (ICC) and intralesional control (ILC). We hypothesize HT would be considered unsuitable for further study if the median OS for patients treated with the HT SIB technique is degraded by 2 months, or the intracranial progression-free rates (ICC and ILC) are inferior by 10% or greater compared to the expected results with treatment by whole brain plus SRS as defined by the RTOG randomized trial. A sample size of 93 patients was calculated based on these parameters as well as the statistical assumptions of alpha = 0.025 and beta = 0.1 due to multiple statistical testing. Secondary assessments of toxicity, health-related quality-of-life, cognitive changes, and tumor response are also integrated into this research protocol. To summarize, the purpose of this phase II trial is to assess this non-invasive alternative to SRS in terms of central nervous system (CNS) control when compared to SRS historical controls. A follow-up phase III trial may be required depending on the results of this trial in order to definitively assess non-inferiority/superiority of this approach. Ultimately, the purpose of this line of research is to

  17. 非小细胞肺癌脑转移122例预后因素分析%Analysis of prognostic factors in 122 non-small-cell lung cancer patients with brain metastasis

    蒋鹏; 吴阳; 辛勇; 姚元虎; 章龙珍

    2015-01-01

    Objective To explore the prognostic factors of non-small-cell lung cancer (NSCLC) patients with brain metastasis. Methods 122 NSCLC patients with brain metastasis from Jan 2007 to Dec 2012 were incorporated, and followed with death as the end. The influence factors of prognosis were retrospective analyzed. Kaplan-Meier method was used for survival analysis, the Log-rank test for single factor analysis,and Cox regression model for multiple factors analysis. Results The single-factor and multi-factor analysis showed that the influence factors of prognosis were age, pathological type, number of intracranial metastasis, presence of extracranial metastasis, treatment, Karnofsky score, the original site control situation (P0.05). The average survival times of patients with palliative symptomatic treatment, simple whole brain radiotherapy, whole brain radiotherapy local lesion plus the amount of radiation, whole brain radiotherapy local lesion plus the amount of radiation combined with chemotherapy were (2.14 ±0.19) months, (7.28 ±0.60) months, (16.90 ±1.35) months, (17.7±1.12) months, 1 year survival rates were 0, 8.5%, 71.0%, 93.3%. Survival analysis showed that there was statistical significance among the four groups (P= 0.000). Conclusion The age, pathological type, number of intracranial metastasis, presence of extracranial metastasis, treatment, Karnofsky score, the original site control situation are the prognosis factors in NSCLC patients with brain metastasis, therefore the treatment of these patients should be comprehensively analyzed.%目的:探讨非小细胞肺癌(NSCLC)脑转移患者预后的影响因素。方法回顾性分析2007年1月至2012年12月收治的122例NSCLC脑转移患者临床及随访资料,以死亡为结局,NSCLC脑转移患者预后的影响因素。以Kaplan-Meier方法进行生存分析,Log-rank检验进行单因素分析,Cox回归模型进行多因素分析。结果经单因素及多因素分析显示影响NSCLC脑

  18. 转移性乳腺癌出现脑转移相关危险因素分析%Analysis of the risk factors for brain metastasis among patients with metastatic breast cancer

    李瑞霞; 魏素菊

    2013-01-01

    Objective This study aimed at retrospective analysis of some metastatic breast cancer cases,investigated the recurrence of brain metastases of metastatic breast cancer in patients with risk factors,and provided a reference for the implementation of prevention strategies in the treatment plan and a reasonable choice.Methods A total of 796 breast cancer cases was visited,of whom 456 patients with recurrent metastatic breast cancer,in which 61 patients were with brain metastasis.The follow-up data were analyzed with SPSS13.0 software.x2 was used to test the age,estrogen receptor (ER),progesterone receptor (PR),cerbB-2 expression,lymph node metastasis,and brain metastasis.The COX proportional hazard model was used to analyze the recurrence and metastasis in patients with single-factor,multi-factor analysis,in order to obtain the independent prognostic factors.Results The x2 tests that group age ≤ 35 years,hormone receptor-negative,CerbB-2 (2 +)/(3 +) has a higher risk than another group (x2 =24.92,8.28,4.02,P <0.01 orP <0.05).COX univariate analysis showed that patient age,tumor size,ER and PR expression,CerbB-2 expression,lung metastases were looked.as the first metastatic site and hormone therapy.Those were significant factors whether the patient suffered from brain metastasis (P < 0.05).COX multivariate analysis showed that age,ER and PR expression,CerbB-2 expression,and lung metastases were looked as the first metastatic site acted as an independent prognostic factor for brain metastasis (P <0.05).Conclusions Age,ER and PR expression,CerbB-2 expression,lung metastases as the first metastatic site are the independent prognostic factors for brain metastasis.%目的 对转移性乳腺癌病例进行回顾性分析,探讨其再发生脑转移的危险因素,以便于预防策略的实施和合理治疗计划的选择.方法 随访的796例乳腺癌患者中有456例出现转移,其中再出现脑转移者61例.将随访资料录入SPSS 13.0软

  19. Unusual Presentation of Renal Cell Carcinoma: Gluteal Metastasis

    Yunus Emre Goger; Mehmet Mesut Piskin; Mehmet Balasar; Mehmet Kilinc

    2013-01-01

    Renal cell carcinoma (RCC) has widespread and unpredictable metastatic potential. The most common sites of metastatic RCC are the lungs, lymph nodes, bones, liver, and brain; however the soft tissue metastasis is rare (2,3). Here we report a 76-year-old male patient who had renal cell carcinoma presented with gluteal metastasis. To our knowledge this is the first renal cell cancer case with gluteal metastasis at the initial diagnosis.

  20. Decoding Melanoma Metastasis

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

  1. Decoding Melanoma Metastasis

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

    2010-12-30

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

  2. Pathobiology of brain metastases

    Nathoo, N; Chahlavi, A; Barnett, G. H.; Toms, S A

    2005-01-01

    Brain metastasis is a major cause of systemic cancer morbidity and mortality. Many factors participate in the development and maintenance of brain metastases. The survival of the metastasis depends upon crucial interactions between tumour cells and the brain microenvironment during its development at the new site. This review focuses on the pathobiological mechanisms involved in the establishment and regulation of brain metastases. Developments in molecular biology have vastly expanded our kn...

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

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

  4. GAMMA KNIFE RADIOSURGERY OF BRAIN METASTASIS FROM MALIGNANT PLEURAL MESOTHELIOMA – REPORT OF THREE CASES WITH AUTOPSY STUDY IN A CASE –

    Kobayashi, Tatsuya; TSUGAWA, TAKAHIKO; Hashizume, Chisa; Toriyama, Takanobu; Asai, Masami; Mori, Yoshimasa; Shibamoto, Yuta

    2014-01-01

    ABSTRACT The median survival time of malignant pleural mesothelioma (MPM) has been 9 months. Given the short survival, there have been only few cases in which brain metastases have been diagnosed and treated before death. Three cases of brain metastases treated by gamma knife radiosurgery (GKR) are reported. Case 1 showed a metastatic lesion in the right frontal lobe which was treated by GKR two years after diagnosis of MPM. The lesion markedly reduced and the symptoms were improved, But the ...

  5. Cerebral metastasis from malignant pleural mesothelioma

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

    2013-01-01

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

  6. Astrocytes Directly Influence Tumor Cell Invasion and Metastasis In Vivo

    Wang, Ling; Cossette, Stephanie M.; Rarick, Kevin R.; Gershan, Jill; Michael B Dwinell; Harder, David R.; Ramchandran, Ramani

    2013-01-01

    Brain metastasis is a defining component of tumor pathophysiology, and the underlying mechanisms responsible for this phenomenon are not well understood. Current dogma is that tumor cells stimulate and activate astrocytes, and this mutual relationship is critical for tumor cell sustenance in the brain. Here, we provide evidence that primary rat neonatal and adult astrocytes secrete factors that proactively induced human lung and breast tumor cell invasion and metastasis capabilities. Among wh...

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

    Kamel, Mahmoud Hamdy

    2012-02-03

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

  8. 1-3个肺癌脑转移灶患者放疗疗效及预后分析%Whole brain radiation with 3D-CRT/IMRT boost for patients with 1-3 brain metastases from lung cancer

    李月敏; 张玉海; 朱建华; 张娜; 曲怡梅; 武勇; 何宇锋; 夏火生; 韩守云

    2010-01-01

    目的:探讨 1-3个肺癌脑转移灶患者行全脑放疗后病灶局部适形/调强放疗加量的疗效和耐受性.方法: 回顾性分析2008年1月至2010年3月对76例1-3个脑转移灶肺癌患者进行全脑放疗后病灶局部放疗加量的疗效和副反应.生存分析采用Kaplan-Meier法,多因素COX回归分析影响患者预后的因素,各亚组之间的差异比较采用Logrank检验.结果: 全组随访1.4-51个月,平均18.6个月,临床缓解率为73%,临床获益率92%.1年生存率34%,2年生存率20%.中位生存时间为9.6月,仅1个颅内转移灶的患者中位生存时间为11.4个月,2-3个转移灶的患者中位生存时间为7.8个月.无III-IV级血液学以外的副反应出现.结论: 适形/调强放疗技术肿瘤局部加量配合全脑放疗疗效确切,患者有很好的耐受性,可以延长患者寿命,提高生存质量.

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

    Kun-Ming Rau; Han-Ku Chen; Li-Yen Shiu; Tsai-Ling Chao; Yi-Ping Lo; Chin-Chou Wang; Meng-Chih Lin; Chao-Cheng Huang

    2016-01-01

    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-spec...

  10. Differentiation of local tumor recurrence from radiation-induced changes after stereotactic radiosurgery for treatment of brain metastasis: case report and review of the literature

    Kickingereder, Philipp; Dorn, Franziska; Blau, Tobias; Schmidt, M.; Kocher, Martin; Galldiks, Norbert; Ruge, Maximilian I.

    2013-01-01

    Background Structural follow-up magnetic resonance imaging (MRI) after stereotactic radiosurgery (SRS) for brain metastases frequently displays local changes in the area of applied irradiation, which are often difficult to interpret (e.g., local tumor recurrence, radiation-induced changes). The use of stereotactic biopsy for histological assessment of these changes has a high diagnostic accuracy and can be considered as method of choice. In order to solve this relevant clinical problem non-in...

  11. Cavitary pulmonar metastasis

    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)

  12. Spinal subdural metastasis

    A case of metastasis to the thoracic spinal subdural space is reported. Metrizamide myelography showed narrowing of the upper thoracic subarachnoid space. A tumor in the spinal subdural space is unusual; only a few cases have been reported. The myelographic appearance is not specific; and epidural metastasis can produce the same myelographic picture. (orig.)

  13. Labeling by [3H]1,3-di(2-tolyl)guanidine of two high affinity binding sites in guinea pig brain: Evidence for allosteric regulation by calcium channel antagonists and pseudoallosteric modulation by sigma ligands

    Equilibrium binding studies with the sigma receptor ligand [3H]1,3-di(2-tolyl)guanidine ([3H]DTG) demonstrated two high affinity binding sites in membranes prepared from guinea pig brain. The apparent Kd values of DTG for sites 1 and 2 were 11.9 and 37.6 nM, respectively. The corresponding Bmax values were 1045 and 1423 fmol/mg of protein. Site 1 had high affinity for (+)-pentazocine, haloperidol, (R)-(+)-PPP, carbepentane, and other sigma ligands, suggesting a similarity with the dextromethorphan/sigma 1 binding site described by Musacchio et al. [Life Sci. 45:1721-1732 (1989)]. Site 2 had high affinity for DTG and haloperidol (Ki = 36.1 nM) and low affinity for most other sigma ligands. Kinetic experiments demonstrated that [3H]DTG dissociated in a biphasic manner from both site 1 and site 2. DTG and haloperidol increased the dissociation rate of [3H]DTG from site 1 and site 2, demonstrating the presence of pseudoallosteric interactions. Inorganic calcium channel blockers such as Cd2+ selectively increased the dissociation rate of [3H]DTG from site 2, suggesting an association of this binding site with calcium channels

  14. Effects of 1,3-diphenyl-1,3-propanedione on neurotransmitter contents of brain in mice administered with cocaine%1,3-二苯-1,3-丙二酮对可卡因致小鼠神经递质含量变化的影响

    陈娟; 王一超; 崔蓉; 刘晓晓; 张宝旭

    2016-01-01

    Objective:To investigate the possible reversal effects of 1 ,3-diphenyl-1 ,3-propanedione (DPPD)for cocaine-induced content changes of neurotransmitters of brain in mice.Methods:In this study,36 healthy ICR male mice were randomly divided into control group,cocaine group,three DPPD pretreatment groups (200,400,and 800 mg/kg)and DPPD alone group (800 mg/kg).The mice in control group were administered intragastrically with 1 % Tween 80 for 3 d,and the mice in cocaine group were administered intragastrically with 1 % Tween 80 for 2 d before cocaine was injected subcutaneously on the 3rd day.The mice in the three DPPD pretreatment groups were administered intragastrically (DPPD 200,400,and 800 mg/kg)for 3 d before cocaine was injected subcutaneously 30 min after the administration on the 3rd day.The mice in DPPD alone group were administered intragastrically with DPPD at dose of 800 mg/kg for 3 d.The mice were sacrificed 20 minutes after cocaine injection.The contents of dopamine (DA)and 5-hydroxytryptamin (5-HT)in the mice brain were determined by high performance liquid chromatography (HPLC)-fluorescence detector,the contents of glutamic acid (Glu) and γ-aminobutyric acid (GABA)in the mice brain were determined by HPLC-ultraviolet detector,and the neurotransmitter levels were compared between the groups.Results:The results showed that as com-pared with the control group,DA and GABA contents in cocaine group increased significantly (P <0.01 and P <0.05),while Glu content decreased (P <0.05).As compared with cocaine group,the DA levels in the three DPPD pretreatment groups (200,400,and 800 mg/kg)all decreased significantly (P <0.01 ).In DPPD 200 mg/kg pre-administration group,GABA content decreased (P <0.05),and the contents of the four kinds of neurotransmitters had no statistical differences with those of the control group.Conclusion:DPPD may have potential reversal effects of the content changes of neurotransmitters in mice brain induced by cocaine at a lower dose

  15. Brain metastases from colorectal cancer

    Vagn-Hansen, Chris Aksel; Rafaelsen, Søren Rafael

    2001-01-01

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

  16. Targeting Breast Cancer Metastasis

    Xin Jin; Ping Mu

    2015-01-01

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

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

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

    2010-08-01

    Small-cell lung cancer is a highly aggressive carcinoma, with poorer prognosis in patients with brain metastases. We present the case of a 49-year-old woman diagnosed with a cerebellar tumour which, following surgery, was revealed to be a metastatic small-cell lung carcinoma. Subsequent CT and PET scanning showed a small, isolated 8 mm nodule in the upper lobe of the right lung. The patient was suffering from schizophrenia and has been treated with clozapine for 17 years. Because of the unusual presentation, there was no therapy given for the primary tumour at the time, and systemic therapy or surgery was discussed. However, 18 months later, the nodule was slightly larger (14 mm), and surgery was performed. On pathology examination, the tumour was presented as a typical small-cell carcinoma. Standard chest irradiation with systemic chemotherapy was given. At the time of writing, 39 months after diagnosis of metastatic small-cell carcinoma, the patient is disease free. However, this case is unusual in that a long-term observation of a small stable primary tumour in the lung took place without any therapy being given. This case strongly supports the thesis that small-cell lung cancer may comprise a heterogeneous group of tumours with different biological properties. The proapoptotic effect of clozapine may be also taken into account. PMID:20537425

  18. Cerebral metastasis from malignant pleural mesothelioma

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

    2013-01-01

    Malignant mesothelioma is an uncommon, highly invasive tumor derived from the mesothelial cells of pleura or peritoneum characterized by poor outcome. Mesothelioma was thought to metastasize locally only via direct invasion and not have distant spread. Distant metastases were discovered mostly on post-mortem examination. The authors present a case of 62-year-old man with pleural mesothelioma and brain metastasis. PMID:24963909

  19. Metastatic neuroblastoma in the brain parenchyma; a case report

    During childhood, neuroblastoma is a relatively common malignant neoplasm which commonly metastasizes to other organs. Metastasis to the central nervous system from an extracranial neuroblastoma is rare, however, and brain parenchymal metastasis is very rare. We describe a case of brain parenchymal metastasis from primary abdominal neuroblastoma, and review the literature

  20. Sudden hearing loss due to internal auditory canal metastasis of Her2-positive gastric cancer: A case report

    Kim, Chang-Hee; Shin, Jung Eun; Roh, Hong Gee; LEE, JONG SIK; Yoon, So Young

    2014-01-01

    Internal auditory canal (IAC) metastasis due to leptomeningeal carcinomatosis (LMC) from gastric cancer (GC) has rarely been reported. Early manifestation of symptoms, such as hearing loss, vertigo and facial paralysis, in cases of IAC metastasis due to LMC may facilitate the early detection of brain metastasis. To the best of our knowledge, the present study is the first to report IAC metastasis due to LMC in human epidermal growth factor receptor 2 (Her2)-positive GC. This study reports a c...

  1. Lung Metastasis Mimicking Fingertip Infection

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

    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.

  2. Genomics screens for metastasis genes

    Yan, Jinchun; Huang, Qihong

    2012-01-01

    Metastasis is responsible for most cancer mortality. The process of metastasis is complex, requiring the coordinated expression and fine regulation of many genes in multiple pathways in both the tumor and host tissues. Identification and characterization of the genetic programs that regulate metastasis is critical to understanding the metastatic process and discovering molecular targets for the prevention and treatment of metastasis. Genomic approaches and functional genomic analyses can syst...

  3. Astrocytes directly influence tumor cell invasion and metastasis in vivo.

    Ling Wang

    Full Text Available Brain metastasis is a defining component of tumor pathophysiology, and the underlying mechanisms responsible for this phenomenon are not well understood. Current dogma is that tumor cells stimulate and activate astrocytes, and this mutual relationship is critical for tumor cell sustenance in the brain. Here, we provide evidence that primary rat neonatal and adult astrocytes secrete factors that proactively induced human lung and breast tumor cell invasion and metastasis capabilities. Among which, tumor invasion factors namely matrix metalloprotease-2 (MMP-2 and MMP-9 were partly responsible for the astrocyte media-induced tumor cell invasion. Inhibiting MMPs reduced the ability of tumor cell to migrate and invade in vitro. Further, injection of astrocyte media-conditioned breast cancer cells in mice showed increased invasive activity to the brain and other distant sites. More importantly, blocking the preconditioned tumor cells with broad spectrum MMP inhibitor decreased the invasion and metastasis of the tumor cells, in particular to the brain in vivo. Collectively, our data implicate astrocyte-derived MMP-2 and MMP-9 as critical players that facilitate tumor cell migration and invasion leading to brain metastasis.

  4. Computed tomographic evaluation of intracranial metastasis

    Hong, Jin Kyo; Eun, Chung Kie; Kim, Soon Yong [Kyung Hee University Hospital, Seoul (Korea, Republic of)

    1982-09-15

    Computed tomography was proved to be the most accurate diagnostic tool in the analysis of brain metastasis than any other classical methods. The authors studied CT findings of intracranial metastasis in 31 cases proven clinically and histologically. The results were as follows: 1. Age distribution of the cases was 15 males and 16 females with peak age of 6th decade in males and 4th decade in female. 2. Metastic lesions were multiple in 18 cases and single in 13 cases. 3. The most common degree of edema was grade III, 43% of total metastatic foci. Marked edematous low densities with relatively small nodular high densities in precontrast scan and variable contrast enhancement of the nodular densities were the most frequent CT findings. 4. No specific characteristics according to the primary cancer was noted. All four cases of choriocarcinoma showed hemorrhagic tendency.

  5. Radiosurgery without whole brain radiotherapy in melanoma brain metastases

    To evaluate the effectiveness of radiosurgery without whole brain radiotherapy in the palliative treatment of melanoma brain metastases, we retrospectively assessed the results in 35 patients: 4 with a solitary brain metastasis, 13 with a single brain metastasis and metastases elsewhere and 18 with multiple brain metastases. The local control rate was 98.2% (55/56 metastases) at 3 months. Median survival was 22 months in patients with a solitary brain metastasis, 7.5 months in patients with a single brain metastasis and metastases elsewhere, and 4 months in patients with multiple brain metastases. Complications were unusual and surgery was required in 2 of 35 patients. These results show for the first time that melanoma patients with a unique brain metastasis with or without metastases elsewhere clearly benefit from tumour control easily obtained by radiosurgery. Although the comparison of radiosurgery with surgery and/or whole brain radiotherapy cannot be adequately addressed, radiosurgery alone seems to provide similar results with lower morbidity and impact on quality of life. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  6. Cathepsins mediate tumor metastasis

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

    2013-01-01

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

  7. Adaptive hypofractionated gamma knife radiosurgery for a large brainstem metastasis

    Georges Sinclair; Jiri Bartek; Heather Martin; Pierre Barsoum; Ernest Dodoo

    2016-01-01

    Background: To demonstrate how adaptive hypofractionated radiosurgery by gamma knife (GK) can be successfully utilized to treat a large brainstem metastasis - a novel approach to a challenging clinical situation. Case Description: A 42-year-old woman, diagnosed with metastatic nonsmall cell lung cancer in July 2011, initially treated with chemotherapy and tyrosine kinase inhibitors, developed multiple brain metastases March 2013, with subsequent whole brain radiotherapy , after which a ma...

  8. Hemidystonia as an Initial Manifestation of Leptomeningeal Metastasis

    Hyun-Jung Jung; Seong-Min Choi; Byeong-Chae Kim

    2009-01-01

    A 76-year-old woman gradually developed action dystonia of the left hand and foot. Leptomeningeal metastasis of the right fronto-parietal area associated with gastric adenocarcinoma was found on the brain magnetic resonance imaging (MRI) and positron emission tomography (PET) studies. We discuss the mechanisms involved in the development of secondary hemidystonia and review dystonia associated with cortical lesions.

  9. Leptomeningeal metastasis from squamous cell carcinoma of oesophagus with unusual presentation

    Akhavan, Ali; Navabii, Hossein

    2012-01-01

    Oesophageal cancer rarely metastasis to the brain but advances in brain imaging and increasing survival of these patients has led to more detection of this condition. Although oesophageal cancer is common in the north of Iran it is less frequent in the central parts such as Yazd. Leptomeningeal metastasis is very uncommon in oesophageal cancer. This paper presents a 73-year-old man with leptomeningeal carcinomatosis from squamous cell carcinoma of oesophagus presented by hoarseness due to tru...

  10. AMELANOTIC MELANOMA WITH ATYPICAL CLINICAL PRESENTATION AND MULTIPLE METASTASIS

    Revathy

    2014-11-01

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

  11. Isolated omental metastasis of renal cell carcinoma after extraperitoneal open partial nephrectomy: A case report

    Acar, Ömer; Mut, Tuna; Sağlıcan, Yeşim; Sag, Alan Alper; Falay, Okan; Selcukbiricik, Fatih; Tabak, Levent; Esen, Tarık

    2016-01-01

    Introduction Metachronous metastatic spread of clinically localized renal cell carcinoma (RCC) affects almost 1/3 of the patients. They occur most frequently in lung, liver, bone and brain. Isolated omental metastasis of RCC has not been reported so far. Case presentation A 62-year-old patient previously diagnosed and treated due to pulmonary sarcoidosis has developed an omental metastatic lesion 13 years after having undergone open extraperitoneal partial nephrectomy for T1 clear-cell RCC. Constitutional symptoms and imaging findings that were attributed to the presence of a sarcomatoid paraneoplastic syndrome triggered by the development this metastatic focus complicated the diagnostic work-up. Biopsy of the [18F]-fluorodeoxyglucose (+) lesions confirmed the diagnosis of metastatic RCC and the patient was managed by the resection of the omental mass via near-total omentectomy followed by targeted therapy with a tyrosine kinase inhibitor. Discussion Late recurrence of RCC has been reported to occur in 10–20% of the patients within 20 years. Therefore lifelong follow up of RCC has been advocated by some authors. Diffuse peritoneal metastases have been reported in certain RCC subtypes with adverse histopathological features. However, isolated omental metastasis without any sign of peritoneal involvement is an extremely rare condition. Conclusion To our knowledge, this is the first reported case of metachronously developed, isolated omental metastasis of an initially T1 clear-cell RCC. Constitutional symptoms, despite a long interval since nephrectomy, should raise the possibility of a paraneoplastic syndrome being associated with metastatic RCC. Morphological and molecular imaging studies together with histopathological documentation will be diagnostic. PMID:26874583

  12. Retinoblastoma presenting as metastasis

    Objective: The purpose of this study was to evaluate the frequency of metastatic retinoblastoma on initial presentation. Design: Prospective study. Place and duration of study: Supra Regional Centre for Retinoblastoma, Department of Ophthalmology, Khyber Teaching Hospital Peshawar Pakistan from July 1, 1999 to January 31, 2003. Methods: Data was collected from 80 registered Retinoblastoma patients admitted and examined under anaesthesia for tumours assessment. Diagnosis was supported with the help of CT scan and confirmed by histopathology of the enucleated specimen for evidence of optic nerve invasion by the tumour. Results: Twenty (25%) patients were presenting as Metastasis on initial presentation. Mean age was 3.5 years, range was 7 months to 12 years. Out of these 20 patients with metastasis, 10 were male and 10 were female. Eighteen (90%) of them were from lower socio-economic group. Conclusion: Failure in early diagnosis of retinoblastoma, advance age and unilateral disease are associated with extraocular spread; this tragic scenario can be prevented best be early detection and prompt treatment plan implementation. (author)

  13. CT与MRI图像融合对脑转移瘤三维适形放疗靶区的影响%The influence of target volume by CT/MRI image fusion on brain metastasis's three-dimensional conformal radiotherapy

    陈苏玮; 袁锋; 林志仁; 王伟锋

    2012-01-01

    Objective To improve the accuracy of delineating three-dimensional conformal radiotherapy target volume by comparing the difference between computed tomography(CT)/magnetic resonance imaging (MRI) image fusion on brain metastasis area and CT's target area. Methods CT's images and MRI's images collected from 25 cases with brain metastasis in the same period were transmitted to image processing workstation and fused into CT/MRI images, and then 41 pairs of gross tumor volume (GTV) were delineated in CT and CT/MRI, and finally difference was compared between the two group. Results The value of GTVCT in 41 pairs from 25 cases was (31.75±9.93) cm3 and in GTVCT/MRI was (28.92±8.25) cm3. Among 41 control groups, the number of the accuracy of GTVCT lower than that of GTVCT/MRI was 18, GTCCT higher than that of GTVCT/MRI was 23. Conclusion The improving accuracy of brain metastasis's target volume sketched by CT/MRI image fusion is more suitable for three-dimensional conformal radiotherapy.%目的 研究CT与MRI图像融合的脑转移瘤靶区与CT图像靶区的不同,提高三维适形放疗靶区勾画的准确性.方法 同期采集25例脑转移瘤患者的CT和MRI图像,传送至图像处理工作站融合成CT/MRI图像,分别在CT及CT/MRI融合图像勾画41组GTV,比较两种图像勾画的GTV的差别.结果 25例患者共41组靶区的GTVcr为(31.75±9.93)cm3,GTVCT/MRI为(28.92±8.25)cm3.41个对照组中,GTVCr <GTVCT/MRI为18个,GTVCT >GTVCT/MRI为23个.结论 采用CT/MRI融合后图像勾画的脑转移瘤靶区精确度提高,更适合于三维立体适形放疗.

  14. Extraneural Glioblastoma Multiforme Vertebral Metastasis

    Goodwin, C. Rory; Liang, Lydia; Abu-Bonsrah, Nancy; Hdeib, Alia; Elder, Benjamin D.; Kosztowski, Thomas; Bettegowda, Chetan; Laterra, John; Burger, Peter; Sciubba, Daniel M.

    2016-01-01

    Glioblastoma multiforme (GBM) is the most common malignant central nervous system tumor; however, extraneural metastasis is uncommon. Of those that metastasize extraneurally, metastases to the vertebral bodies represent a significant proportion. We present a review of 28 cases from the published literature of GBM metastasis to the vertebra. The mean age at presentation was 38.4 years with an average overall survival of 26 months. Patients were either asymptomatic with metastasis discovered at autopsy or presented with varying degrees of pain, weakness of the extremities, or other neurologic deficits. Of the cases that included the time to spinal metastasis, the average time was 26.4 months with a reported survival of 10 months after diagnosis of vertebral metastasis. A significant number of patients had no treatments for their spinal metastasis, although the intracranial lesions were treated extensively with surgery and/or adjuvant therapy. With increasing incremental gains in the survival of patients with GBM, clinicians will encounter patients with extracranial metastasis. As such, this review presents timely information concerning the presentation and outcomes of patients with vertebral metastasis. PMID:26704201

  15. Current Concepts of Metastasis Formation

    Peter Gassman

    2011-07-01

    Full Text Available The development of secondary distant organ and lymph node metastasis has an extraordinary impact on the prognosis of patients with solid cancer. In most cases the advent of metastatic growth represents the turning point from a local, potentially curable, disease to a systemic non-curable situation. As a highly regulated process, metastasis formation follows a distinct, non-random pattern characteristic for each tumor entity. Metastasis formation and strategies to prevent this lethal event in the progression of cancer is of fundamental interest for cancer science and patient care. In this special issue of Cancers, papers highlighting cellular mechanisms of metastasis formation, genetic and epigenetic aspects associated with organ and tumor specific metastasis formation, as well as papers outlining experimental and clinical therapeutic concepts for anti-metastatic treatment are included.

  16. Is Selenium a Potential Treatment for Cancer Metastasis?

    Yu-Chi Chen

    2013-04-01

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

  17. Role of the nervous system in cancer metastasis.

    Li, Sha; Sun, Yanlai; Gao, Dongwei

    2013-04-01

    The notion that tumors lack innervation was proposed several years ago. However, nerve fibers are irregulatedly found in some tumor tissues. Their terminals interaction with cancer cells are considered to be neuro-neoplastic synapses. Moreover, neural-related factors, which are important players in the development and activity of the nervous system, have been found in cancer cells. Thus, they establish a direct connection between the nervous system and tumor cells. They modulate the process of metastasis, including degradation of base membranes, cancer cell invasion, migration, extravasation and colonization. Peripheral nerve invasion provides another pathway for the spread of cancer cells when blood and lymphatic metastases are absent, which is based on the interactions between the microenvironments of nerve fibers and tumor cells. The nervous system also modulates angiogenesis, the tumor microenvironment, bone marrow, immune functions and inflammatory pathways to influence metastases. Denervation of the tumor has been reported to enhance cancer metastasis. Stress, social isolation and other emotional factors may increase distant metastasis through releasing hormones from the brain, the hypothalamic-pituitary-adrenal axis and autonomic nervous system. Disruption of circadian rhythms will also promote cancer metastasis through direct and indirect actions of the nervous system. Therefore, the nervous system plays an important role in cancer metastasis. PMID:23599747

  18. Papillary thyroid microcarcinoma presenting as skull base metastasis

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

    2010-01-01

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

  19. Unusual splenic metastasis from oesophageal cancer.

    Murthy S; Prabhakaran P; Rao S; Kumar R

    1991-01-01

    The most common visceral metastasis from oesophageal carcinomas are lungs and liver. A case of splenic metastasis from a squamous carcinoma of oesophagus is reported. To our knowledge, splenic metastasis without any nodal disease has not been described previously. The pattern of reported metastasis is summarised.

  20. Synthesis and in vivo studies of a specific monoamine oxidase B inhibitor: 5-[4-(benzyloxy)phenyl]-3-(2-cyanoethyl)-1,3,4-oxadiazol-[11C]-2(3H)-one. Biodistribution in the rat and positron emission tomography studies in the baboon brain

    We report the radiochemical synthesis of a specific MAO B inhibitor, namely 5-[4-(benzyloxy)phenyl]-3-(2-cyanoethyl)-1,3,4-oxadiazol-[11C]-2(3H)-one (2b) (in vitro IC50=4nM and selectivity over 71000 for MAO B), by cyclization of its hydrazide precursor 1 with [11C]phosgene. The reaction occurred within 2 min. The product obtained after HPLC purification, 2b, had a high specific activity (11.1-22.2 GBq/μmol), allowing its use in experiments as a radiotracer in vivo. Biodistribution of 2b in the CNS and in the peripheral organs of the rat, and positron emission tomography (PET) studies in the living baboon brain, pretreated or not with L-depdenyl (1 mg/kg, 1 h), an irreversible MAO B-specific inhibitor, were undertaken. The results showed a good uptake of 2b in all organs of the rate, with a rapid clearance from the blood (10 min). Metabolite analyses in plasma and in the diencephalon of the rat showed tha 2b was the only radioactive compound in brain structure whereas in plasma three other radioactive products appeared. PET experiments show that in the L-deprenyl-pretreated baboon brain, specific binding of 2b represents around 70% of total radioactivity, whereas in the blood and plasma the radioactivity cleared rapidly (15 min). (orig.)

  1. Synthesis and in vivo studies of a specific monoamine oxidase B inhibitor: 5-[4-(benzyloxy)phenyl]-3-(2-cyanoethyl)-1,3,4-oxadiazol-[{sup 11}C]-2(3H)-one. Biodistribution in the rat and positron emission tomography studies in the baboon brain

    Bernard, S. [Service Hospitalier Frederic Joliot, DRIPP, CEA, 91 - Orsay (France)]|[Lab. de Chimie Organique Medicale, Unite de Recherche Chimie et Pharmacologie, Faculte de Medecine Xavier Bichat, Paris-7 Univ., 75 (France); Fuseau, C. [Service Hospitalier Frederic Joliot, DRIPP, CEA, 91 - Orsay (France); Schmid, L. [Service Hospitalier Frederic Joliot, CNRS URA, CEA, 91 - Orsay (France); Milcent, R. [Lab. de Chimie Organique Medicale, Unite de Recherche Chimie et Pharmacologie, Faculte de Medecine Xavier Bichat, Paris-7 Univ., 75 (France); Crouzel, C. [Service Hospitalier Frederic Joliot, DRIPP, CEA, 91 - Orsay (France)

    1996-02-01

    We report the radiochemical synthesis of a specific MAO B inhibitor, namely 5-[4-(benzyloxy)phenyl]-3-(2-cyanoethyl)-1,3,4-oxadiazol-[{sup 11}C]-2(3H)-one (2b) (in vitro IC{sub 50}=4nM and selectivity over 71000 for MAO B), by cyclization of its hydrazide precursor 1 with [{sup 11}C]phosgene. The reaction occurred within 2 min. The product obtained after HPLC purification, 2b, had a high specific activity (11.1-22.2 GBq/{mu}mol), allowing its use in experiments as a radiotracer in vivo. Biodistribution of 2b in the CNS and in the peripheral organs of the rat, and positron emission tomography (PET) studies in the living baboon brain, pretreated or not with L-depdenyl (1 mg/kg, 1 h), an irreversible MAO B-specific inhibitor, were undertaken. The results showed a good uptake of 2b in all organs of the rate, with a rapid clearance from the blood (10 min). Metabolite analyses in plasma and in the diencephalon of the rat showed tha 2b was the only radioactive compound in brain structure whereas in plasma three other radioactive products appeared. PET experiments show that in the L-deprenyl-pretreated baboon brain, specific binding of 2b represents around 70% of total radioactivity, whereas in the blood and plasma the radioactivity cleared rapidly (15 min). (orig.)

  2. Cutaneous metastasis in anorectal adenocarcinoma

    Krishnendra Varma

    2015-01-01

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

  3. Endobronchial metastasis in breast cancer.

    Albertini, R E; Ekberg, N L

    1980-01-01

    Ten patients with endobronchial metastasis from primary breast cancer were found among 1200 fibreoptic bronchoscopies. Six of these patients had radiological signs suggesting bronchial obstruction. The diagnosis was verified in nine cases by means of bronchoscopic biopsy or cytology and in one by thoracotomy. Endobronchial metastasis should be considered when symptoms or chest films suggest endobronchial disease in a patient with a history of breast cancer.

  4. Choroidal and cutaneous metastasis from gastric adenocarcinoma

    2013-01-01

    Choroidal or cutaneous metastasis of gastric cancer is rare. Gastrointestinal cancer was found in only 4% in patients with uveal metastasis. Choroidal metastasis from gastric cancer was reported in two cases in earlier literature. The frequency of gastric cancer as a primary lesion was 6% in cutaneous metastasis of men, and cutaneous metastasis occurs in 0.8% of all gastric cancers. We report a patient with gastric adenocarcinoma who presented with visual disorder in his left eye and skin pai...

  5. Gallbladder metastasis from renal cell carcinoma mimicking acute cholecystitis

    Sand M

    2009-02-01

    Full Text Available Abstract Renal cell carcinoma constitutes about 3% of adult malignancies. It has a high metastatic potential associated with synchronous or metachronous metastatic disease. Further, it is known to metastasize mainly to the lung, bone, brain, liver, or adrenal glands. In very rare cases it can metastasize to the gallbladder mimicking acute cholecystitis on clinical exam. In this case we present a patient who developed a gallbladder metastasis five years after a renal cell carcinoma mimicking acute cholecystitis.

  6. Hemidystonia as an Initial Manifestation of Leptomeningeal Metastasis

    Hyun-Jung Jung

    2009-10-01

    Full Text Available A 76-year-old woman gradually developed action dystonia of the left hand and foot. Leptomeningeal metastasis of the right fronto-parietal area associated with gastric adenocarcinoma was found on the brain magnetic resonance imaging (MRI and positron emission tomography (PET studies. We discuss the mechanisms involved in the development of secondary hemidystonia and review dystonia associated with cortical lesions.

  7. CT findings of solitary intracranial metastasis

    Suh, Dae Chul; Lee, Kyung Soo; Chang, Kee Hyun [Collge of Medicine, Seoul National University, Seoul (Korea, Republic of)

    1987-04-15

    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%.

  8. [Leptomeningeal Dissemination in Patients with Pituitary Metastasis from Breast Cancer].

    Hayashi, Nakamasa; Mitsuya, Koichi; Harada, Hideyuki; Watanabe, Junichiro; Nishimura, Tetsuo; Nakasu, Yoko

    2016-05-01

    Pituitary metastases are uncommon complications of systemic cancer and account for only 1% of pituitary lesions. Breast cancer is one of the most common tumors to metastasize to the pituitary gland. A multidisciplinary approach that calls for close collaboration among oncologists, neurosurgeons, radiologists, and endocrinologists is mandatory for diagnosis and treatment of pituitary metastasis. From 2002 through 2013, 6 patients with pituitary metastases were treated at Shizuoka Cancer Center Hospital. The patients' age at presentation ranged from 45 to 75 years(average 59 years). Five of 6 patients had symptoms: anterior pituitary insufficiency in 4, diabetes insipidus in 3, and visual deficits in 2 patients. Five patients had other metastases at the time of presentation. Local irradiation to the metastatic lesion was adopted in 4, and whole brain irradiation was in 2 patients. In all cases, local control was achieved after irradiation, however, the pituitary insufficiency did not recover. Two of 4 patients treated with local irradiation suffered from meningeal dissemination within 5 months after treatment, and died at 8 and 11 months after diagnosis of pituitary metastasis, respectively. The patients treated with whole brain irradiation had longer survival periods. Early diagnosis, endocrinological management, and radiation therapy improve the quality of life in patients suffering from pituitary metastasis. Whole brain irradiation may be favorable in order to prevent meningeal dissemination. PMID:27166841

  9. Isolated Uterine Metastasis of Invasive Ductal Carcinoma

    Deniz Arslan

    2013-01-01

    Full Text Available Introduction. Most common metastasis sites of breast cancer are the lungs, bones, liver, and brain, whereas uterine involvement by metastatic breast disease is rare. Metastatic carcinoma of the uterus usually originates from other genital sites, most commonly being from the ovaries. Invasive lobular carcinoma spreads to gynecologic organs more frequently than invasive ductal carcinoma. Case Report. A 57-year-old postmenopausal woman was diagnosed with breast carcinoma 2 years ago and modified radical mastectomy was performed. Pathological examination of tumor revealed invasive ductal carcinoma, stage IIIc. She presented with abdominal pain and distension. Diagnostic workup and gynecologic examination revealed lesions that caused diffuse thickening of the uterus wall. Endometrial sampling was performed for confirmation of the diagnosis. She underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. Breast carcinoma metastases in endometrium and myometrium were confirmed histopathologically and immunohistochemically. Conclusion. We herein report the first case of isolated uterine patient who had invasive ductal carcinoma of breast.

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

    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

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

    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

  12. Intra-cranial metastasis of gastrointestinal stromal tumor

    WONG Chun-sing; CHU Yiu-ching

    2011-01-01

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

  13. An open cohort study of bone metastasis incidence following surgery in breast cancer patients

    Yoshimoto Masataka

    2010-07-01

    Full Text Available Abstract Background To help design clinical trials of adjuvant bisphosphonate therapy for breast cancer, the temporal incidence of bone metastasis was investigated in a cohort of patients. We have tried to draw the criteria to use adjuvant bisphosphonate. Methods Consecutive breast cancer patients undergoing surgery between 1988 and 1998 (5459 patients were followed up regarding bone metastasis until December 2006. Patients' characteristics at the time of surgery were analyzed by Cox's method, with bone metastasis as events. Patient groups were assigned according to Cox's analysis, and were judged either to require the adjuvant bisphosphonate or not, using the tentative criteria: high risk (>3% person-year, medium risk (1-3%, and low risk ( Results Bone metastasis incidence was constant between 1.0 and 2.8% per person-year more than 10 years. Non-invasive cancer was associated with a very low incidence of bone metastasis (1/436. Multivariate Cox's analysis indicated important factors for bone metastasis were tumor grade (T, nodal grade (pN, and histology. Because T and pN were important factors for bone metastasis prediction, subgroups were made by pTNM stage. Patients at stages IIIA, IIIB and IV had an incidence of >3% per person-year, patients with stage I Conclusions Bone metastasis incidence remained constant for many years. Using pN, T, and histopathology, patients could be classified into high, medium, and low risk groups.

  14. Brain angiogenesis: Mechanism and Therapeutic Intervention in Brain Tumors

    Kim, Woo-Young; Lee, Ho-Young

    2009-01-01

    Formation of new blood vessels is required for growth and metastasis of all solid tumors. New blood vessels are established in tumors mainly through angiogenesis. Brain tumors in particular are highly angiogenic. Therefore, interventions designed to prevent angiogenesis may be effective at controlling brain tumors. Indeed, many recent findings from preclinical and clinical studies of antiangiogenic therapy for brain tumors showed that it is a promising approach to managing this deadly disease...

  15. Role of the Blood-Brain Barrier in the Formation of Brain Metastases

    Krizbai, István A.; János Haskó; Csilla Fazakas; Judit Molnár; Imola Wilhelm

    2013-01-01

    The majority of brain metastases originate from lung cancer, breast cancer and malignant melanoma. In order to reach the brain, parenchyma metastatic cells have to transmigrate through the endothelial cell layer of brain capillaries, which forms the morphological basis of the blood-brain barrier (BBB). The BBB has a dual role in brain metastasis formation: it forms a tight barrier protecting the central nervous system from entering cancer cells, but it is also actively involved in protecting ...

  16. Metastasis genetics, epigenetics, and the tumor microenvironment

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

  17. Penile metastasis from rectal carcinoma

    Murhekar K

    2007-01-01

    Full Text Available Penile metastases are infrequent and often originate from genitor-urinary organs including bladder and prostate. In the present communication, we report an unusual case of penile metastasis from rectal adenocarcinoma. Though uncommon, this presentation is not unknown. A review of literature of penile metastases in colorectal cancers is also summarized here.

  18. Pulmonary Metastasis from Pseudomyxoma Peritonei

    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.

  19. Gingival Metastasis from Gallbladder Cancer

    Te-Sheng Chang

    2002-08-01

    Full Text Available Gallbladder cancer is generally diagnosed at an advanced stage. The liver is the mostcommonly invaded organ by direct extension and/or metastasis, followed by regional lymphnodes. Oral soft tissue metastasis is extremely unusual. This report describes the case of a62-year-old woman diagnosed with advanced metastatic gallbladder cancer, who initiallypresented with abdominal pain. Diagnosis of gallbladder cancer was made about 3 monthsafter her symptoms developed, when a laparoscopic cholecystectomy was performedbecause of the suspicion of gallstones. Liver metastasis was also discovered during surgery.A postoperative investigation revealed additional lung and bone metastases. A visible leftgingival tumor was found on physical examination and was confirmed as gallbladder cancermetastasis by compatible histopathology 1 month after surgery. The patient responded poorlyto chemotherapy and unfortunately died 5 months after the diagnosis. The clinical presentationof gallbladder cancer was relatively typical, apart from the unusual gingival metastasis.The medical literature contains quite a few examples of metastatic lesions locatedstrictly in the oral soft tissue, however no case of gallbladder cancer metastasizing to theoral soft tissue has been previously reported.

  20. Brain Metastases from Colorectal Cancer: Microenvironment and Molecular Mechanisms

    Yi-Wen Zang; Xiao-Dong Gu; Jian-Bin Xiang; Zong-You Chen

    2012-01-01

    Colorectal cancer is one of the most common digestive tract malignancies in the world. Owing to the newer and more effective systemic therapies, the life of colorectal cancer patients can be remarkably prolonged, and the incidence of brain metastases is increasing. However, little is known about the underlying mechanisms of brain metastasis from colorectal cancer. Here we review the tumor microenvironment and metastasis associated molecules in brain metastases from colorectal cancer. A furthe...

  1. Anal metastasis as the sentinel and isolated presentation of invasive ductal breast carcinoma.

    Rengifo, C; Titi, S; Walls, J

    2016-05-01

    Breast cancer currently affects 1 in 8 women in the UK during their lifetime. Common sites for breast cancer metastasis include the axillary lymph nodes, bones, lung, liver, brain, soft tissue and adrenal glands. There is well documented evidence detailing breast metastasis to the gastrointestinal tract but anal metastasis is exceptionally rare. We present the case of a 78-year-old woman with an anal metastasis as the sentinel and isolated presentation of an invasive ductal breast carcinoma. As advances in the treatment of breast cancer improve, and with an ageing and expanding population, there will be an increasing number of cancer survivors, and more of these unusual presentations may be encountered in the future. PMID:27087339

  2. Hand1 overexpression inhibits medulloblastoma metastasis.

    Asuthkar, Swapna; Guda, Maheedhara R; Martin, Sarah E; Antony, Reuben; Fernandez, Karen; Lin, Julian; Tsung, Andrew J; Velpula, Kiran K

    2016-08-19

    Medulloblastoma (MB) is the most frequent malignant pediatric brain tumor. Current treatment includes surgery, radiation and chemotherapy. However, ongoing treatment in patients is further classified according to the presence or absence of metastasis. Since metastatic medulloblastoma are refractory to current treatments, there is need to identify novel biomarkers that could be used to reduce metastatic potential, and more importantly be targeted therapeutically. Previously, we showed that ionizing radiation-induced uPAR overexpression is associated with increased accumulation of β-catenin in the nucleus. We further demonstrated that uPAR protein act as cytoplasmic sequestration factor for a novel basic helix-loop-helix transcription factor, Hand1. Among the histological subtypes classical and desmoplastic subtypes account for the majority while large cell/anaplastic variant is most commonly associated with metastatic disease. In this present study using immunohistochemical approach and patient data mining for the first time, we demonstrated that Hand1 expression is observed to be downregulated in all the subtypes of medulloblastoma. Previously we showed that Hand1 overexpression regulated medulloblastoma angiogenesis and here we investigated the role of Hand1 in the context of Epithelial-Mesenchymal Transition (EMT). Moreover, UW228 and D283 cells overexpressing Hand1 demonstrated decreased-expression of mesenchymal markers (N-cadherin, β-catenin and SOX2); metastatic marker (SMA); and increased expression of epithelial marker (E-cadherin). Strikingly, human pluripotent stem cell antibody array showed that Hand1 overexpression resulted in substantial decrease in pluripotency markers (Nanog, Oct3/4, Otx2, Flk1) suggesting that Hand1 expression may be essential to attenuate the EMT and our findings underscore a novel role for Hand1 in medulloblastoma metastasis. PMID:27297109

  3. Pedunculated hepatocellular carcinoma and splenic metastasis

    Mao-Lin Yan; Yao-Dong Wang; Zhi-De Lai; Yi-Feng Tian; Hong-Biao Chen; Fu-Nan Qiu; Song-Qiang Zhou

    2009-01-01

    Only a few cases of pedunculated hepatocellular carcinoma (P-HCC) have been reported in the literature. The common sites of extrahepatic metastases in patients with HCC are the lungs, regional lymph nodes,kidney, bone marrow and adrenals. Metastasis to spleen is mostly via hematogenous metastasis, direct metastasis to spleen was very rare. We report a case of P-HCC presenting as a left upper abdominal lesions which involved the spleen that was actually a P-HCC with splenic metastasis. This case is unique as P-HCC directly involved the spleen which is not via hematogenous metastasis.

  4. OVARIAN METASTASIS IN PATIENT WITH ENDOMETRIAL CARCINOMA

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

    2005-01-01

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

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

    To assess treatment toxicity and patients' survival/quality of life (QoL) after volumetric modulated arc therapy (VMAT) with simultaneous in-field boost (SIB) for cancer patients with 1 - 4 brain metastases (BM) treated with or without surgery. Between March and December 2010, 29 BM patients (total volume BM, < 40 cm3) aged < 80 years, KPS ≥ 70, RPA < III were included in this prospective trial. Whole brain VMAT (30 Gy) and a SIB to the BM (40 Gy) was delivered in 10 fraction. Mean age was 62.1 ± 8.5 years. Fifteen (51.7%) underwent surgery. KPS and MMSE were prospectively assessed. A self-assessed questionnaire was used to assess the QoL (EORTC QLQ-C30 with -BN20 module). As of April 2011 and after a mean FU of 5.4 ± 2.8 months, 14 (48.3%) patients died. The 6-month overall survival was 55.1%. Alopecia was only observed in 9 (31%) patients. In 3-month survivors, KPS was significantly (p = 0.01) decreased. MMSE score remained however stable (p = 0.33). Overall, QoL did decrease after VMAT. The mean QLQ-C30 global health status (p = 0.72) and emotional functional (p = 0.91) scores were decreased (low QoL). Physical (p = 0.05) and role functioning score (p = 0.01) were significantly worse and rapidly decreased during treatment. The majority of BN20 domains and single items worsened 3 months after VMAT except headaches (p = 0.046) and bladder control (p = 0.26) which improved. The delivery of 40 Gy in 10 fractions to 1 - 4 BM using VMAT was achieved with no significant toxicity. QoL, performance status, but not MMSE, was however compromised 3 months after treatment in this selected cohort of BM patients

  6. A Case of Lung Cancer with Brain Metastases Diagnosed After Epileptic Seizure

    Murat Eroglu

    2014-03-01

    Full Text Available    Epileptic seizures can accompany benign diseases, also can be the first sign of malign tumors. In brain metastasis, epileptic seizures can be seen before the symptoms of the primary lesion. Brain metastasis is bad prognostic factor in all malignancies and it is determined that lung cancers are the most metastatic tumors to the brain. Especially in new onset epileptic seizures in elderly patients, metastatic brain tumors are frequent in etiology. We aimed to present a lung cancer patient with brain metastasis who admitted emergency department with first epileptic seizure.

  7. Pericytes limit tumor cell metastasis

    Xian, Xiaojie; Håkansson, Joakim; Ståhlberg, Anders;

    2006-01-01

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

  8. A review of penile metastasis

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

    2012-01-01

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

  9. Raman spectroscopy of bone metastasis

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

    2012-02-01

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

  10. Tissue Dissociation for Metastasis Studies.

    Kabeer, Farhia; Podsypanina, Katrina

    2016-01-01

    The main requirement for most metastasis-related applications is the conversion of solid tissue into a single-cell suspension. In theory, this suspension represents the diversity of cells present in the tissue, whether malignant or benign. We have found that cell viability, as measured by trypan blue staining or fluorescence-activated cell sorting (FACS), is critical for evaluating the success of the tissue-dissociation procedure. The recommended goal is at least 70% cell viability. PMID:26832679

  11. Complications of vertebral metastasis surgery

    Pascal-Moussellard, H.; Broc, G.; Pointillart, V.; Siméon, F.; Vital, J. M.; Sénégas, J.

    1998-01-01

    The authors report their experience concerning complications of spinal metastasis surgery. The purpose of this study was to assess the frequency of such complications and analyse the factors influencing their occurrence. The records of 145 patients treated between 1982 and 1991 for metastatic disease of the spine were retrospectively reviewed for intra- and postoperative complications. Other factors such as radiation therapy, emergent nature of surgery, and neurologic deficits were analysed f...

  12. Imaging of ocular melanoma metastasis.

    Balasubramanya, Rashmi; Selvarajan, Santosh Kumar; Cox, Mougnyan; Joshi, Ganesh; Deshmukh, Sandeep; Mitchell, Donald G; O'Kane, Patrick

    2016-09-01

    Ocular melanoma is the most common adult primary intraocular tumour. Although helpful for detecting liver lesions. In particular, newer hepatobiliary contrast agents which offer an additional hepatobiliary phase of excretion help in the detection of even tiny liver metastases. Diffusion-weighted imaging is helpful when an i.v. contrast cannot be administered. Treated lesions are also better evaluated with MRI. CT is useful for evaluating lung nodules, large liver metastasis or in patients in whom MRI is medically contraindicated. The disadvantage lies in its inability to detect small liver metastasis and the radiation dose involved. The lesions treated with iodized oil as part of chemoembolization procedures can be followed on CT. Ultrasound can be used only for detecting hepatic metastases. However, it is heavily operator dependent, technically challenging and time consuming especially in patients who are large. Extrahepatic metastasis cannot be seen on ultrasound. Its utility is primarily for the biopsy of liver lesions. Positron emission tomography (PET)-CT can detect lung nodules and large liver lesions but is insensitive to small liver lesions. Moreover, the high radiation dose is a major disadvantage. PMID:27168029

  13. Late onset leptomeningeal and whole spine metastasis from supratentorial Glioblastoma multiforme: An uncommon manifestation of a common tumor.

    Sharma, Divyam; Gupta, Anshul; Dhillon, Gurupal S; Chhabra, Satnam Singh

    2016-01-01

    Glioblastoma multiforme (GBM) is one of the most common and aggressive primary brain tumors, composing 12-20% of all the intracranial tumors in adults with a highly malignant course and average life expectancy of approximately 12-14 months following initial diagnosis. Leptomeningeal or intramedullary metastasis from primary GBM is a rare phenomenon with a poor prognosis. We present a rare case of GBM with late onset intramedullary, extramedullary, as well as leptomeningeal spinal metastasis. PMID:27217661

  14. Late onset leptomeningeal and whole spine metastasis from supratentorial Glioblastoma multiforme: An uncommon manifestation of a common tumor

    Divyam Sharma; Anshul Gupta; Gurupal S Dhillon; Satnam Singh Chhabra

    2016-01-01

    Glioblastoma multiforme (GBM) is one of the most common and aggressive primary brain tumors, composing 12-20% of all the intracranial tumors in adults with a highly malignant course and average life expectancy of approximately 12-14 months following initial diagnosis. Leptomeningeal or intramedullary metastasis from primary GBM is a rare phenomenon with a poor prognosis. We present a rare case of GBM with late onset intramedullary, extramedullary, as well as leptomeningeal spinal metastasis.

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

    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.

  16. MicroRNAs in Brain Metastases: Potential Role as Diagnostics and Therapeutics

    Samer Alsidawi; Ehsan Malek; Driscoll, James J.

    2014-01-01

    Brain metastases remain a daunting adversary that negatively impact patient survival. Metastatic brain tumors affect up to 45% of all cancer patients with systemic cancer and account for ~20% of all cancer-related deaths. A complex network of non-coding RNA molecules, microRNAs (miRNAs), regulate tumor metastasis. The brain micro-environment modulates metastatic tumor growth; however, defining the precise genetic events that promote metastasis in the brain niche represents an important, unres...

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

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

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

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

    2011-01-15

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

  19. 1,3,5-trinitroso- and 1,3,5-trinitrohexahydro-1,3,5-triazine-2H6

    Perdeuteration of 1,3,5-trinitrosohexahydro-1,3,5-triazine was brought about by treatment with potassium alkoxide in CH3O2H(99.5%). The important high energy compound, 1,3,5-trinitrohexahydro-1,3,5-triazine (RDX), was obtained in its perdeuterated modification (>99% 2H) by oxidation of the perdeuterated trinitrosamine with a mixture of nitric acid (100%) and hydrogen peroxide (30%). (author)

  20. Protocadherin-7 induces bone metastasis of breast cancer

    Li, Ai-Min [Department of Orthopedics, The 5th Central Hospital of Tianjin, Tianjin (China); Tian, Ai-Xian [Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Zhang, Rui-Xue [Department of Clinical Laboratory Diagnosis, Tianjin Medical University, Tianjin (China); Ge, Jie [Department of Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Sun, Xuan [Department of Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Cao, Xu-Chen, E-mail: caoxuch@126.com [Department of Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China)

    2013-07-05

    Highlights: •PCDH7 is overexpression in high bone metastatic MDA-MB-231 cells. •PCDH7 is up-regulation in bone metastatic breast cancer tissues. •Suppression of PCDH7 inhibits cell proliferation, migration, and invasion in vitro. •PCDH7 induces breast cancer bone metastasis in vivo. -- Abstract: Breast cancer had a propensity to metastasize to bone, resulting in serious skeletal complications associated with poor outcome. Previous study showed that Protocadherin-7 (PCDH7) play an important role in brain metastatic breast cancer, however, the role of PCDH7 in bone metastatic breast cancer has never been explored. In the present study, we found that PCDH7 expression was up-regulation in bone metastatic breast cancer tissues by real-time PCR and immunohistochemistry assays. Furthermore, suppression of PCDH7 inhibits breast cancer cell proliferation, migration, and invasion in vitro by MTT, scratch, and transwell assays. Most importantly, overexpression of PCDH7 promotes breast cancer cell proliferation and invasion in vitro, and formation of bone metastasis in vivo. These data provide an important insight into the role of PCDH7 in bone metastasis of breast cancer.

  1. Protocadherin-7 induces bone metastasis of breast cancer

    Highlights: •PCDH7 is overexpression in high bone metastatic MDA-MB-231 cells. •PCDH7 is up-regulation in bone metastatic breast cancer tissues. •Suppression of PCDH7 inhibits cell proliferation, migration, and invasion in vitro. •PCDH7 induces breast cancer bone metastasis in vivo. -- Abstract: Breast cancer had a propensity to metastasize to bone, resulting in serious skeletal complications associated with poor outcome. Previous study showed that Protocadherin-7 (PCDH7) play an important role in brain metastatic breast cancer, however, the role of PCDH7 in bone metastatic breast cancer has never been explored. In the present study, we found that PCDH7 expression was up-regulation in bone metastatic breast cancer tissues by real-time PCR and immunohistochemistry assays. Furthermore, suppression of PCDH7 inhibits breast cancer cell proliferation, migration, and invasion in vitro by MTT, scratch, and transwell assays. Most importantly, overexpression of PCDH7 promotes breast cancer cell proliferation and invasion in vitro, and formation of bone metastasis in vivo. These data provide an important insight into the role of PCDH7 in bone metastasis of breast cancer

  2. BM-25PRONEURAL TRANSCRIPTION FACTOR Atoh1 DRIVES LEPTOMENINGEAL METASTASIS OF THE SONIC HEDGEHOG SUBGROUP OF MEDULLOBLASTOMA

    Picotte, Katie; Li, Li; Zhao, Haotian

    2014-01-01

    Medulloblastoma, the most common malignant pediatric brain tumor, arises from the cerebellum and spreads throughout the cerebrospinal fluid to the leptomeninges, covering the brain and spinal cord. Leptomeningeal metastasis, a frequent finding at diagnosis and recurrence, is a significant indicator of poor prognosis. Treatment of affected children includes irradiation of the developing brain and spine, and chemotherapy, which cause debilitating neurological complications. Despite the grave co...

  3. [Jawbone metastasis masquerading as dental pain].

    Goldman, Y; Yarom, N

    2016-01-01

    Metastases to the oral cavity are rare. However, in 25% of cases, oral symptoms will be the first sign of metastatic disease. The incidence of jaws metastases is twice as high as the incidence of metastases to the soft tissues of the oral cavity. In some cases, jaws metastases can mimic dental or periodontal pain. We report a case of a 67 year old female who was referred to our clinic because of severe pain on her left posterior mandible which was not relieved by endodontic treatment of the first and second molar. She was diagnosed with breast cancer in 2005 and had been treated with surgery, chemotherapy and radiotherapy. Seven years later, lung metastases were found and she was treated with chemotherapy. Later on, brain metastases developed which had been treated with radiotherapy. On presentation, she complained of pain on the posterior left mandible which was accompanied by a burning sensation of the lower left lip and chin. CT scan revealed a soft tissue mass perforating the lingual and buccal plates of the posterior left mandible, which was compatible with a diagnosis of metastasis. Radiotherapy rapidly relieved the pain. Unfortunately, the patient passed away one month later. Dentists should be able to recognize the signs and symptoms associated with metastases to the jaws and should include it in the differential diagnosis, especially in patients with oncologic background. PMID:27295929

  4. Solitary pulmonary metastasis from prostate sarcomatoid cancer

    Oyamada Yoshitaka; Maeshima Arafumi; Goto Taichiro; Kato Ryoichi

    2010-01-01

    Abstract Background Pulmonary metastasis from prostate cancer is considered to be a late event, and patients can be treated with chemotherapy or hormonal manipulation. However, there has been only a few reports on surgical resection for pulmonary metastasis from prostate cancer. Case Presentation We present a surgical case of solitary pulmonary metastasis from prostate cancer. A 73-year-old man underwent pelvic evisceration for prostate cancer. Histopathological examination revealed a poorly ...

  5. Metastasis-Initiating Cells in Renal Cancer

    Khan, Mohammed I.; Czarnecka, Anna M; Duchnowska, Renata; Kukwa, Wojciech; Szczylik, Cezary

    2013-01-01

    Metastasis is a complex process that propagates cells from the primary or initial site of the cancer occurrence to distant parts of the body. Cancer cells break from the cancer site and circulate through the bloodstream or lymph vessels, allowing them to reach nearly all parts of the body. These circulating tumour cells (CTCs) contain specialized metastasis-initiating cells (MICs) that reside in the biological heterogeneous primary tumour. Researchers have hypothesized that metastasis of rena...

  6. CT diagnosis of peritoneal metastasis tumor

    Objective: To study the CT findings and diagnosis of peritoneal metastasis. Methods: The CT findings of 17 cases with surgical- pathologically proved peritoneal metastasis were analyzed retrospectively. Results The CT findings of peritoneal metastasis included: (1)ascites (12 cases ); (2)the aternation of parietal peritoneum including broad band thickening (7 cases), nodular sign (2 cases), and massive thickening (1 cases); (3) the involved omentum and mesenterium: 'smut' appearances (7 cases), nodular sign (2 cases), 'omental cake' (5 cases); (4) the invlovement of mesenteric vessels; (5) single-or multi-cystic lesions within peritoneum (1 case) . Conclusion: CT scan is the first choice for metastasis of peritoneum. (authors)

  7. Prostate cancer and metastasis initiating stem cells

    Kathleen Kelly; Juan Juan Yin

    2008-01-01

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

  8. 5 CFR 1.3 - Definitions.

    2010-01-01

    ... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Definitions. 1.3 Section 1.3 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE RULES COVERAGE AND DEFINITIONS (RULE I) § 1.3 Definitions. As used in the rules in this subchapter: (a) Competitive service shall have the...

  9. 50 CFR 1.3 - Service.

    2010-10-01

    ... 50 Wildlife and Fisheries 1 2010-10-01 2010-10-01 false Service. 1.3 Section 1.3 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR GENERAL PROVISIONS DEFINITIONS § 1.3 Service. Service means the United States Fish and Wildlife Service, Department of the Interior....

  10. Management of solitary and multiple brain metastases from breast cancer

    Addison Willett; J Ben Wilkinson; Chirag Shah; Mehta, Minesh P.

    2015-01-01

    As local and systemic control of breast cancer improves, metastasis to the brain remains a common event requiring a specialized management approach. Women diagnosed with breast cancer who develop brain metastases have superior overall survival compared to patients with other forms of metastatic carcinoma. This article summarizes some of the unique aspects of care for patients with breast cancer metastases to the brain.

  11. Successful treatment of a brain-metastasized renal cell carcinoma

    Johnston, Kim W.; Walid, M. Sami

    2009-01-01

    Renal cell carcinoma is an uncommon type of cancer that rarely metastasizes to the brain. The prognosis after discovering brain metastasis has traditionally been dismal. We are presenting a case of renal cell carcinoma with multiple brain metastases that was successfully treated with multimodal therapy including a new type of medication.

  12. A review of penile metastasis

    Luigi Mearini

    2012-06-01

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

  13. Oral metastasis of chondroblastic osteosarcoma

    Rakesh Kumar Dumpala

    2012-01-01

    Full Text Available Osteosarcoma is the most common primary malignant mesenchymal tumor, accounting for approximately 20% of sarcomas, with 5% incidence in the jaws. They present various clinical and histological aspects as well as variable disease prognosis and outcome. About 50% of all osteosarcomas are osteoblastic, 25% fibroblastic, 25% chondroblastic. Metastasis of osteosarcoma in the oral cavity is rare, and very few cases have been described so far in the literature. This article presents a metastatic case of chondroblastic osteosarcoma in the mandibular right-attached gingiva arising from 4 th rib. This case report further suggests that chondroblastic osteosarcoma has poor prognosis.

  14. Pulmonary metastasis in thyroid cancer

    Although thyroid cancer (TC) in its differentiated form is generally associated with a good prognosis and a near normal life expectancy, a subset of patients especially with distant metastatic disease may run an aggressive course leading to poor survival and early death. The clinical presentation and the manner in which the disease progresses differs with the site and type of the metastatic disease. The behaviour and course of skeletal metastasis has been described elsewhere. The biological behaviour and treatment of pulmonary metastatic disease is focussed on

  15. Brain metastases of breast cancer.

    Palmieri, Diane; Smith, Quentin R; Lockman, Paul R; Bronder, Julie; Gril, Brunilde; Chambers, Ann F; Weil, Robert J; Steeg, Patricia S

    Central nervous system or brain metastases traditionally occur in 10-16% of metastatic breast cancer patients and are associated with a dismal prognosis. The development of brain metastases has been associated with young age, and tumors that are estrogen receptor negative, Her-2+ or of the basal phenotype. Treatment typically includes whole brain irradiation, or either stereotactic radiosurgery or surgery with whole brain radiation, resulting in an approximately 20% one year survival. The blood-brain barrier is a formidable obstacle to the delivery of chemotherapeutics to the brain. Mouse experimental metastasis model systems have been developed for brain metastasis using selected sublines of human MDA-MB-231 breast carcinoma cells. Using micron sized iron particles and MRI imaging, the fate of MDA-MB-231BR cells has been mapped: Approximately 2% of injected cells form larger macroscopic metastases, while 5% of cells remain as dormant cells in the brain. New therapies with permeability for the blood-brain barrier are needed to counteract both types of tumor cells. PMID:17473372

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

    Naushad A. B. Ahamed

    2015-01-01

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

  17. Toe metastasis: A rare pattern of cervical cancer spread ☆

    Ciccone, Marcia A.; Conturie, Charlotte L.; Lee, Cassie M.; Matsuo, Koji

    2014-01-01

    Highlights • Toe metastasis is a rare pattern of cervical cancer spread. • Enlarged erythematous toe is an important sign suggesting bone metastasis. • Toe metastasis represents a grave prognostic indicator of cervical cancer.

  18. Intradural extramedullary metastasis from papillary carcinoma of thyroid

    Akhavan, Ali; Mehrabaniyan, Mohammad Reza; Jarahi, Mohammadreza; Navabii, Hossein

    2012-01-01

    Although spinal metastasis is a common finding in malignancies, however intradural extramedullary metastasis is very rare. This paper presents a 71-year-old woman, known case of papillary carcinoma of thyroid with intradural extramedullary metastasis in thoracic spine.

  19. MicroRNA and Metastasis.

    Ma, L

    2016-01-01

    Noncoding RNAs are important regulatory molecules of cellular processes. MicroRNAs (miRNAs) are small noncoding RNAs that bind to complementary sequences in the 3' untranslated region of target mRNAs, leading to degradation of the target mRNAs and/or inhibition of their translation. Some miRNAs are essential for normal animal development; however, many other miRNAs are dispensable for development but play a critical role in pathological conditions, including tumorigenesis and metastasis. miRNA genes often reside at fragile chromosome sites and are deregulated in cancer. Some miRNAs function as oncogenes or tumor suppressors, collectively termed "oncomirs." Specific metastasis-regulating miRNAs, collectively termed "metastamirs," govern molecular processes and pathways in malignant progression in either a tumor cell-autonomous or a cell-nonautonomous manner. Recently, exosome-transferred miRNAs have emerged as mediators of the tumor-stroma cross talk. In this chapter, we focus on the functions, mechanisms of action, and therapeutic potential of miRNAs, particularly oncomirs and metastamirs. PMID:27613133

  20. The Current and Future Treatment of Brain Metastases

    Hardesty, Douglas A.; Nakaji, Peter

    2016-01-01

    Brain metastases are the most common intracranial malignancy, accounting for significant morbidity and mortality in oncology patients. The current treatment paradigm for brain metastasis depends on the patient’s overall health status, the primary tumor pathology, and the number and location of brain lesions. Herein, we review the modern management options for these tumors, including surgical resection, radiotherapy, and chemotherapy. Recent operative advances, such as fluorescence, confocal microscopy, and brachytherapy, are highlighted. With an increased understanding of the pathophysiology of brain metastasis come increased future therapeutic options. Therapy targeted to specific tumor molecular pathways, such as those involved in blood–brain barrier transgression, cell–cell adhesion, and angiogenesis, are also reviewed. A personalized plan for each patient, based on molecular characterizations of the tumor that are used to better target radiotherapy and chemotherapy, is undoubtedly the future of brain metastasis treatment. PMID:27252942

  1. Metastasis Suppressors and Their Roles in Breast Carcinoma

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

    2007-01-01

    Metastasis remains the most deadly aspect of cancer and still evades direct treatment. Clinically and experimentally, primary tumor development and metastasis are distinct processes—locally growing tumors can progress without the development of metastases. The discovery of endogenous molecules that exclusively inhibit metastasis suggests that metastasis is an amenable therapeutic target. By definition, metastasis suppressors inhibit metastasis without inhibiting tumorigenicity and are thus di...

  2. Supratentorial metastasis of medulloblastoma in adults.

    Kumar, Sushil; Handa, Amit; Jha, Deepak K; Choudhary, Ajay

    2016-01-01

    Two adults, 31 and 20 years of age, developed supratentorial metastasis 3½ years and 11 months, respectively, after gross total removal of their posterior fossa medulloblastoma. The first case developed spinal metastasis as well. Both had undergone craniospinal irradiation. Case 1 underwent laminectomy and case 2 underwent craniotomy because their presenting symptoms required so. PMID:27366282

  3. Nearly Complete Response of Brain Metastases from HER2 Overexpressing Breast Cancer with Lapatinib and Capecitabine after Whole Brain Irradiation

    Esin Oktay

    2013-01-01

    Full Text Available Trastuzumab treatment does not prevent intracranial seeding and is largely ineffective for established central nervous system metastasis in HER2 overexpressing breast cancer patients. Combination therapy of lapatinib and capecitabine may be an effective treatment option for brain metastasis of HER2-positive breast cancer. We report a patient with breast cancer overexpressing HER-2 where brain metastases were successfully treated with radiation and a combination of lapatinib and capecitabine.

  4. Palmar cutaneous metastasis from carcinoma cervix

    Elamurugan T

    2011-01-01

    Full Text Available Carcinoma of the uterine cervix is the most common gynecological malignancy in developing countries. However, its cutaneous metastasis is a rare entity. The reported incidence of cutaneous metastasis ranges from 0.1 to 2%. Frequent sites of cutaneous metastasis in decreasing order are: abdominal wall, vulva and anterior chest wall. To the best of our knowledge, only three cases of cutaneous metastasis to the upper extremity have been reported in the world. We report a case of a 74-year-old postmenopausal lady diagnosed to have carcinoma cervix (stage IIIB who presented with cutaneous metastasis to palm and thigh, 10 months after radical radiotherapy. At presentation, the primary disease had resolved completely. She had a small nodular growth in the left palm and left thigh. Fine needle aspirate cytology and core needle biopsy from both the nodular lesions were positive for squamous cell carcinoma.

  5. Contiguous spinal metastasis mimicking infectious spondylodiscitis

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

    2015-12-15

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

  6. Pazopanib Inhibits the Activation of PDGFRβ-Expressing Astrocytes in the Brain Metastatic Microenvironment of Breast Cancer Cells

    Gril, Brunilde; Palmieri, Diane; Qian, Yongzhen; Anwar, Talha; Liewehr, David J.; Steinberg, Seth M.; Andreu, Zoraida; Masana, Daniel; Fernández, Paloma; Steeg, Patricia S; Vidal-Vanaclocha, Fernando

    2013-01-01

    Brain metastases occur in more than one-third of metastatic breast cancer patients whose tumors overexpress HER2 or are triple negative. Brain colonization of cancer cells occurs in a unique environment, containing microglia, oligodendrocytes, astrocytes, and neurons. Although a neuroinflammatory response has been documented in brain metastasis, its contribution to cancer progression and therapy remains poorly understood. Using an experimental brain metastasis model, we characterized the brai...

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

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

    2014-01-01

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

  8. MR imaging of leptomeningeal metastasis

    Seven patients with CNS neoplasia and leptomeningeal metastases on contrast-enhanced CT were evaluated with MR imaging. Diffuse sulcal and cisternal tumor seeding was not apparent on T1- or T2-weighted images. In two of three patients, MR imaging demonstrated fewer nodular or focal cisternal masses than did the CT study. Ependymal and subependymal metastases were indistinguishable from periventricular abnormalities associated with radiation therapy and/or hydrocephalus. The findings suggest that leptomeningeal metastasis may be very subtle or not apparent on MR imaging, and therefore contrast-enhanced CT and MR imaging should be considered complementary techniques in the initial diagnosis and follow-up of tumors which may metastasize to the leptomeninges

  9. Drug Development for Metastasis Prevention.

    Fontebasso, Yari; Dubinett, Steven M

    2015-01-01

    Metastatic disease is responsible for 90% of death from solid tumors. However, only a minority of metastasis-specific targets has been exploited therapeutically, and effective prevention and suppression of metastatic disease is still an elusive goal. In this review, we will first summarize the current state of knowledge about the molecular features of the disease, with particular focus on steps and targets potentially amenable to therapeutic intervention. We will then discuss the reasons underlying the paucity of metastatic drugs in the current oncological arsenal and potential ways to overcome this therapeutic gap. We reason that the discovery of novel promising targets, an increased understanding of the molecular features of the disease, the effect of disruptive technologies, and a shift in the current preclinical and clinical settings have the potential to create more successful drug development endeavors. PMID:27279241

  10. Status and prognosis of lymph node metastasis in patients with cardia cancer – A systematic review

    Okholm, Cecilie; Svendsen, Lars Bo; Achiam, Michael P

    2014-01-01

    BACKGROUND: Adenocarcinoma of the gastroesophageal junction (GEJ) has a poor prognosis and survival rates significantly decreases if lymph node metastasis is present. An extensive lymphadenectomy may increase chances of cure, but may also lead to further postoperative morbidity and mortality....... Therefore, the optimal treatment of cardia cancer remains controversial. A systematic review of English publications dealing with adenocarcinoma of the cardia was conducted to elucidate patterns of nodal spread and prognostic implications. METHODS: A systematic literature search based on PRISMA guidelines...... identifying relevant studies describing lymph node metastasis and the associated prognosis. Lymph node stations were classified according to the Japanese Gastric Cancer Association guidelines. RESULTS: The highest incidence of metastasis is seen in the nearest regional lymph nodes, station no. 1-3 and...

  11. Biodegradation of Hexahydro-1,3,5-Trinitro-1,3,5-Triazine

    McCormick, N G; Cornell, J H; Kaplan, A M

    1981-01-01

    Biodegradation of the explosive hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) occurs under anaerobic conditions, yielding a number of products, including: hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine, hexahydro-1,3-dinitroso-5-nitro-1,3,5-triazine, hexahydro-1,3,5-trinitroso-1,3,5-triazine, hydrazine, 1,1-dimethyl-hydrazine, 1,2-dimethylhydrazine, formaldehyde, and methanol. A scheme for the biodegradation of RDX is proposed which proceeds via successive reduction of the nitro groups to a p...

  12. Lymph Node Metastasis of Gastric Cancer

    Akagi, Tomonori, E-mail: tomakagi@med.oita-u.ac.jp [Oita University Faculty of Medicine, Department of Gastroenterological Surgery, 1-1 Idaigaoka, Hasama-machi, Oita 879-5593 (Japan); Shiraishi, Norio [Surgical division, Center for community medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Oita 879-5593 (Japan); Kitano, Seigo [Oita University Faculty of Medicine, Department of Gastroenterological Surgery, 1-1 Idaigaoka, Hasama-machi, Oita 879-5593 (Japan)

    2011-04-26

    Despite a decrease in incidence in recent decades, gastric cancer is still one of the most common causes of cancer death worldwide [1]. In areas without screening for gastric cancer, it is diagnosed late and has a high frequency of nodal involvement [1]. Even in early gastric cancer (EGC), the incidence of lymph node (LN) metastasis exceeds 10%; it was reported to be 14.1% overall and was 4.8 to 23.6% depending on cancer depth [2]. It is important to evaluate LN status preoperatively for proper treatment strategy; however, sufficient results are not being obtained using various modalities. Surgery is the only effective intervention for cure or long-term survival. It is possible to cure local disease without distant metastasis by gastrectomy and LN dissection. However, there is no survival benefit from surgery for systemic disease with distant metastasis such as para-aortic lymph node metastasis [3]. Therefore, whether the disease is local or systemic is an important prognostic indicator for gastric cancer, and the debate continues over the importance of extended lymphadenectomy for gastric cancer. The concept of micro-metastasis has been described as a prognostic factor [4-9], and the biological mechanisms of LN metastasis are currently under study [10-12]. In this article, we review the status of LN metastasis including its molecular mechanisms and evaluate LN dissection for the treatment of gastric cancer.

  13. Lymph Node Metastasis of Gastric Cancer

    Despite a decrease in incidence in recent decades, gastric cancer is still one of the most common causes of cancer death worldwide [1]. In areas without screening for gastric cancer, it is diagnosed late and has a high frequency of nodal involvement [1]. Even in early gastric cancer (EGC), the incidence of lymph node (LN) metastasis exceeds 10%; it was reported to be 14.1% overall and was 4.8 to 23.6% depending on cancer depth [2]. It is important to evaluate LN status preoperatively for proper treatment strategy; however, sufficient results are not being obtained using various modalities. Surgery is the only effective intervention for cure or long-term survival. It is possible to cure local disease without distant metastasis by gastrectomy and LN dissection. However, there is no survival benefit from surgery for systemic disease with distant metastasis such as para-aortic lymph node metastasis [3]. Therefore, whether the disease is local or systemic is an important prognostic indicator for gastric cancer, and the debate continues over the importance of extended lymphadenectomy for gastric cancer. The concept of micro-metastasis has been described as a prognostic factor [4-9], and the biological mechanisms of LN metastasis are currently under study [10-12]. In this article, we review the status of LN metastasis including its molecular mechanisms and evaluate LN dissection for the treatment of gastric cancer

  14. Imaging of bone metastasis: An update

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

    2015-01-01

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

  15. Screening candidate metastasis-associated genes in three-dimensional HCC spheroids with different metastasis potential

    Chen, Rongxin; Dong, Yinying; Xie, Xiaoying; Chen, Jie; Gao, Dongmei; Liu, Yinkun; Ren, Zhenggang; Cui, Jiefeng

    2014-01-01

    Purpose: Previously, we have established a tissue-like HCC spheroid which better mirrors the biological features of tumorigenesis and metastasis. This study was to find out metastasis-associated genes between two 3D HCC spheroids with different metastasis potential using comparative PCR arrays. Materials and Methods: Two HCC spheroids derived from high-metastatic MHCC97H cells and low-metastatic Hep3B cells were formed respectively in a rotating wall vessel bioreactor after 3D culture for 15 ...

  16. Influence of CT/MRI Fusion Image on Target Volume and 3-D Conformal Radiotherapy in Non-small Cell Lung Cancer with Brain Metastasis%CT/MRI诊断影像融合对非小细胞肺癌脑转移瘤靶区及三维适形治疗影响

    杨金山; 魏永兵; 侯超; 李静; 朱瑞霞

    2014-01-01

    目的:比较CT图像和CT/MRI融合图像来源的肺癌脑转移肿瘤靶区,评价CT/MRI融合靶区容积应用于三维适形放射治疗时,对治疗剂量的影响。方法:将20例非小细胞肺癌脑转移患者的增强CT和MRI扫描的图像传送至图像处理工作站,在CT和CT/MRI融合图像上分别勾画GTV和周围重要的器官。每个病例分别在CT图像和CT/MRI融合图像都做1个三维适形放射治疗计划。肿瘤的处方剂量为60 Gy,比较2个治疗计划中肿瘤靶区的95%容积(D95)受照平均剂量、周围正常组织的5%容积(D5)受照平均剂量。结果:CT/MRI融合图像上的肿瘤靶区平均比CT上的肿瘤靶区大21.32%。用CT上勾画的靶区有一部分肿瘤处于低剂量区,CT/MRI融合图像上的靶区D95剂量分布较好,但在周围重要器官的剂量分布较高。结论:CT/MRI融合图像有助于靶区的确定,在三维适形放射治疗计划上的肿瘤靶区剂量分布足够,能提高靶区勾画的准确性,更利于精确放疗的实施。%Objective:To compare the CT images and CT/MRI images fusion sources of lung cancer with brain metastasis tumor target,and to evaluae the effects of dose for treatment on target volume CT/MRI fusion for three-dimensional conformal radiotherapy. Method:The enhancement CT and MRI scan image of 20 patients with brain metastases from non-small cell lung cancer was transfer to image processing workstation,GTV and surrounding vital organs on CT and CT/MRI images fusion was delineated respectively. A three-dimensional conformal radiotherapy plan was done in CT images and CT/MRI fusion images of ach case. Tumor prescription dose was 60 Gy. Compared the average dose of the 95%volume(D95)tumor target,the average dose of the 5%of the normal tissue around of the two treatment plans. Result:The tumor targets of the CT/MRI images fusion was greater than those of the CT tumor targets on average 21.32%. A part of the tumor was

  17. Molecular biology of breast cancer metastasis: Genetic regulation of human breast carcinoma metastasis

    The present is an overview of recent data that describes the genetic underpinnings of the suppression of cancer metastasis. Despite the explosion of new information about the genetics of cancer, only six human genes have thus far been shown to suppress metastasis functionally. Not all have been shown to be functional in breast carcinoma. Several additional genes inhibit various steps of the metastatic cascade, but do not necessarily block metastasis when tested using in vivo assays. The implications of this are discussed. Two recently discovered metastasis suppressor genes block proliferation of tumor cells at a secondary site, offering a new target for therapeutic intervention

  18. Isolated malignant melanoma metastasis to the pancreas

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

    2013-01-01

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

  19. Stereotactic body radiotherapy for solitary spine metastasis

    Lee, Sun Young [Dept. of Radiation Oncology, Sun Medical Center, Daejeon (Korea, Republic of); Chun, Mison [Dept. of Radiation Oncology, Ajou University School of Medicine, Suwon (Korea, Republic of); Lee, Mi Jo [Dept. of Radiation Oncology, Eulji Universtiy School of Medicine, Daejeon (Korea, Republic of)

    2013-12-15

    A clear consensus has not been established regarding the best treatment for solitary bone metastasis. Here, we reviewed the medical records of patients with a controlled primary malignancy who had only solitary spine metastasis without metastasis to the extraspinal bone or viscera and underwent treatment between April 2007 and December 2012 with stereotactic body radiosurgery using CyberKnife, with a total dose of 24 Gy in three to four fractions. During that time, there were only four cases. This was effective in each case, and all the four patients had no local failure and remained alive at a median follow-up of 68 months (range, 64 to 80 months). Although our experience is limited, this study suggests that stereotactic body radiotherapy could be a feasible, safe, effective, and noninvasive alternative treatment for solitary spine metastasis in patients who are medically inoperable or unsuitable for surgery.

  20. Silencing FAT10 inhibits metastasis of osteosarcoma.

    Ma, Chengbin; Zhang, Zhiyu; Cui, Yan; Yuan, Hongmou; Wang, Feng

    2016-08-01

    Metastasis is the main challenge of osteosarcoma treatment. Herein, we first reveal the oncogenic role of FAT10 in metastasis of osteosarcoma. FAT10 was upregulated in osteosarcoma, especially in metastatic osteosarcoma. High level of FAT10 was associated with poorer prognosis of osteosarcoma patients. Moreover, Transwell and Matrigel assays revealed that silencing FAT10 significantly inhibited the invasive and migratory abilities of osteosarcoma cells. Metastasis assay in vivo showed that silencing FAT10 decreased the number of mice with distant metastasis. We also found that FAT10 may act its oncogenic functions through regulating HOXB9. Collectively, the results suggested that FAT10 may be a novel therapeutic target for osteosarcoma patients. PMID:27279480

  1. HANSF 1.3.2 User's Manual

    The HANSF analysis tool is an integrated model considering phenomena inside a multi-canister overpack (MCO) spent nuclear fuel container such as fuel oxidation, convective and radiative heat transfer, and the potential for fission product release. This manual reflects the HANSF version 1.3.2, a revised version of 1.3.1. HANSF 1.3.2 was written to correct minor errors and to allow modeling of condensate flow on the MCO inner surface. HANSF 1.3.2 is intended for use on personal computers such as IBM-compatible machines with Intel processors running under Lahey TI or digital Visual FORTRAN, Version 6.0, but this does not preclude operation in other environments

  2. HANSF 1.3 user's manual

    The HANSF analysis tool is an integrated model considering phenomena inside a multi-canister overpack (MCO) spent nuclear fuel container such as fuel oxidation, convective and radiative heat transfer, and the potential for fission product release. It may be used for all phases of spent fuel disposition including cold vacuum drying, transportation, and storage. This manual reflects HANSF version 1.3, a revised version of version 1.2a. HANSF 1.3 was written to add new models for axial nodalization, add new features for ease of usage, and correct errors. HANSF 1.3 is intended for use on personal computers such as IBM-compatible machines with Intel processors running under a DOS-type operating system. HANSF 1.3 is known to compile under Lahey TI and Digital Visual FORTRAN, Version 6.0, but this does not preclude operation in other environments

  3. Molecular mechanisms of metastasis in prostate cancer

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

    2009-01-01

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

  4. Tracheal metastasis of small cell lung cancer

    De, Sajal

    2009-01-01

    Endotracheal metastases of primary lung cancer are rare. Only one case of tracheal metastasis from small cell lung cancer has been reported in literature. Here, we report a rare case of a 45-year-old woman who was admitted for sudden-onset breathlessness with respiratory failure and required ventilatory support. Endotracheal growth was identified during bronchoscopy, and biopsy revealed endotracheal metastasis of small cell lung cancer.

  5. Three-dimensional context regulation of metastasis

    Erler, Janine Terra; Weaver, Valerie M

    2009-01-01

    stroma to promote transformation, tumor growth, motility and invasion, enhance cancer cell survival, enable metastatic dissemination, and facilitate the establishment of tumor cells at distant sites. Matrix degradation can additionally promote malignant progression and metastasis. Tumor hypoxia...... is functionally linked to altered stromal-epithelial interactions. Hypoxia additionally induces the expression of pro-migratory, survival and invasion genes, and up-regulates expression of ECM components and modifying enzymes, to enhance tumor progression and metastasis. Synergistic interactions between matrix...

  6. Leptomeningeal metastasis of spinal cord

    Ten patients with leptomeningeal metastases of spinal cord were studied with a 1.5-T MR imager. Six patients had primary central nervous system (CNS) tumors, and the other four had their primary tumor outside of the CNS. All patients had positive CSF cytologic findings, and cervical cords were generally examined. MR findings on T1-weighted images before and after gadolinium-DTPA administration were divided into three types. Type 1, the diffuse form (four cases), was characterized by (1) increased CSF intensity, (2) poor cord-CSF interface, and (3) perimedullary enhancement; type 2, the nodular form (one case) by discrete nodules adherent to the cord surface; and type 3, predominance of intramedullary metastases (three cases), by localized cord swelling with central enhancement. In two cases, no significant findings were found. In conclusion, T1-weighted images with Gd-DTPA enhancement were valuable in the MR imaging of spinal meningeal metastasis. The main route of intramedullary tumor spread is believed to be via arterial seeding, but the authors study suggests that intramedullary metastases resulting from direct extension from the CSF were not infrequent

  7. Synthesis of Some New Derivatives of 1,3-Dichloro-1,1,3,3-tetraphenyldisilazane

    2001-01-01

    The reactive properties of 1,3-dichloro-1,1,3,3-tetraphenyldisilazane (DCTPS) with water, methanol, phenylamine and lithium salt of hexamethylcyclotrisilazane (D3NLi) were investigated, and four new derivatives were obtained.

  8. Cutaneous metastasis as a first presentation for lung adenocarcinoma

    Yazan Abdeen

    2016-01-01

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

  9. Late Bilateral Renal Metastasis of Choriocarcinoma: A Case Report

    M. Tahmasebi

    2008-01-01

    Full Text Available Introduction: Late bilateral renal metastasis of chori-ocarcinoma is a rare condition. Herein we report a case of late renal metastasis of choriocarcinoma."nCase Presentation: A 28 years old woman presented with gross hematuria since three months ago. A mo-bile palpable mass in her right flank was detected. She was not pregnant but had a history of abortion at six weeks of gestation in seven years age. Her gyneco-logic examination was normal. She had severe anemia (Hb=7.2, elevated ESR (52 with normal renal and liver function testes. Ultrasonography showed bilat-eral large kidney masses by solid-cystic components, with predominant solid parts. Bilateral lobulated het-erogeneous renal masses were found at non-enhancing axial CT-Scan, with notable enhancement of solid parts after administration of contrast agent. Angiography revealed bilateral hypovascular renal masses. Right radical nephrectomy performed for the patient and pathology reported choriocarcinoma of kidney. Finally, she was referred for chemotherapy of contralateral renal mass, but she delayed that for three months. She died following a seizure attack and cardiopulmonary arrest without response to prompt cardio-pulmonary resuscitation. Autopsy not permit-ted by relevants. "nConclusion: Late metastases of choriocarcinoma may appear in kidney or brain after a long time following the primary source of malignancy, when the primary lesion has disappeared.

  10. Radiosurgery for brain metastases and cerebral edema.

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

    2015-03-01

    The objective of this study was to assess reduction in cerebral edema following linear accelerator radiosurgery (LINAC) as first line therapy for brain metastasis. We reviewed the medical records of all patients who underwent LINAC radiosurgery for brain metastasis at our institution during 2010-2012, and who had not previously undergone either surgery or whole brain radiotherapy. Data were analyzed for 55 brain metastases from 46 patients (24 males), mean age 59.9 years. During the 2 months following LINAC radiosurgery, the mean steroid dose decreased from 4.8 to 2.6 mg/day, the mean metastasis volume decreased from 3.79±4.12 cc to 2.8±4.48 cc (p=0.001), and the mean edema volume decreased from 16.91±30.15 cc to 12.85±24.47 cc (p=0.23). The 17 patients with reductions of more than 50% in brain edema volume had single metastases. Edema volume in the nine patients with two brain metastases remained stable in five patients (volume change 10%, 2-14 cc). In a subanalysis of eight metastases with baseline edema volume greater than 40 cc, edema volume decreased from 77.27±37.21 cc to 24.84±35.6 cc (p=0.034). Reductions in brain edema were greater in metastases for which non-small-cell lung carcinoma and breast cancers were the primary diseases. Overall, symptoms improved in most patients. No patients who were without symptoms or who had no signs of increased intracranial pressure at baseline developed signs of intracranial pressure following LINAC radiosurgery. In this series, LINAC stereotactic radiosurgery for metastatic brain lesions resulted in early reduction in brain edema volume in single metastasis patients and those with large edema volumes, and reduced the need for steroids. PMID:25533053

  11. Detection of cancer before distant metastasis

    To establish a distant metastasis (DM) cells must disseminate from the primary tumor and overcome a series of obstacles, the metastatic cascade. In this study we develop a mathematical model for this cascade to estimate the tumor size and the circulating tumor cell (CTC) load before the first metastasis has formed from a primary breast cancer tumor. The metastatic cascade is described in discrete steps: 1. local tumor growth; 2. dissemination into circulation; 3. survival in circulation; 4. extravasation into tissue; and 5. growth into a metastasis. The model was built using data and relationships described in the literature to predict the relationship between tumor size and probability of distant metastasis for 38715 patients with surgically removed TXNXM0 primary breast cancer from the Netherlands Cancer Registry. The model was calibrated using primary tumor size, probability of distant metastasis and time to distant metastasis for 1489 patients with stage T1BNXM0 (25% of total patients with T1BNXM0). Validation of the model was done with data for all patients. From the time to distant metastasis of these 38715 breast cancer patients, we determined a tumor doubling time of 1.7 ± 0.9 months. Fitting the data for 25% of T1B patients estimates a metastatic efficiency of 1 metastasis formed per 60 million disseminated tumor cells. Validation of the model to data of patients in all T-stages shows good agreement between model and epidemiological data. To reduce the 5-year risk of distant metastasis for TXNXM0 from 9.2% to 1.0%, the primary tumor needs to be detected and removed before it reaches a diameter of 2.7 ± 1.6 mm. At this size, the model predicts that there will be 9 ± 6 CTC/L blood. To reduce the rate of distant metastasis in surgically treated TXNXM0 breast cancer to 1%, imaging technology will need to be able to detect lesions of 2.7 mm in diameter or smaller. Before CTC detection can be applied in the early disease setting, sensitivity will need to be

  12. Computed tomography in brain metastases of colorectal cancer

    Metastatic brain tumors from colorectal cancers are relatively rare. In previous reports, the incidence ranged from 3 to 5 percent of all metastatic brain tumors. We report 7 cases of metastatic brain tumors from colorectal cancers. The time interval from the diagnosis of the primary tumors to the brain metastasis was 3 years on the average. Metastasis to the lung and liver were also found in 6 cases at the time of the diagnosis of the brain metastasis. The CEA levels in the serum were highly elevated in all cases. Solitary metastasis was found in all cases; cancers tend to metastasize in the deep area of the cerebrum or cerebellum. On a plain CT scan, tumors were demonstrated as ring-type, with a high-density mass, and ring-like enhancement was seen in 6 cases. Prognosis was very poor in most cases. The median survival time from diagnosis of brain metastasis was 4.5 months in the 2 cases with surgery and 3.5 months in the 4 cases without surgery. (author)

  13. On D=2 (1/3,1/3) supersymmetric theories 2

    Denoting by D=2 (1/3,1/3) superalgebra; the off critical symmetry of the Φ5/7,5/7 perturbation of the C=6/7 conformal theory, we build a new superspace solution of the (1/3,1/3)- subalgebra generated by spin ±1/3 charge operators extending the usual (1/2,1/2) supersymmetry generated by spin ±1/2 charges. This solution is based on the use of two Grassmann variables instead of one parafermionic variable θ±1/3 satisfying the cubic nilpotency condition (θ±1/3)3=0. Known results on the C=6/7 tricritical Potts model are recovered as special features. A relation with N=2 Landau-Ginzburg models is also discussed. (author). 17 refs, 1 tab

  14. Brain Basics

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

  15. Brain Basics

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

  16. Brain Basics

    Full Text Available ... Brain Basics provides information on how the brain works, how mental illnesses are disorders of the brain, ... learning more about how the brain grows and works in healthy people, and how normal brain development ...

  17. Bis(1,3-dithiole) Compounds

    Andersen, Jan Rud; Engler, E. M.; Green, D. C.; Patel, V. V.

    1977-01-01

    There is described the preparation of bis-1,3-dithiole compounds (I) which are key synthetic precursors for the preparation of new polymeric metal bis(dithiolene) (i.e., II) and tetrathiafulvalene compounds (i.e., III): (Image Omitted)...

  18. 17 CFR 1.3 - Definitions.

    2010-04-01

    .... Editorial Note: For Federal Register citations affecting § 1.3, see the List of CFR Sections Affected, which... terms have the same meaning and refer to a customer trading in any commodity named in the definition of..., That an account owned by any shareholder or member of a cooperative association of producers,...

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

    Marvaso, Giulia; BARONE, AGNESE; VACCARO, CATERINA; Bruzzaniti, Vicente; GRESPI, SILVIA; SCOTTI, VALERIO; Bianco, Cataldo

    2013-01-01

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

  20. Toward determining the lifetime occurrence of metastatic brain tumors estimated from 2007 United States cancer incidence data

    Davis, Faith G; Dolecek, Therese A.; McCarthy, Bridget J.; Villano, John L.

    2012-01-01

    Few population estimates of brain metastasis in the United States are available, prompting this study. Our objective was to estimate the expected number of metastatic brain tumors that would subsequently develop among incident cancer cases for 1 diagnosis year in the United States. Incidence proportions for primary cancer sites known to develop brain metastasis were applied to United States cancer incidence data for 2007 that were retrieved from accessible data sets through Centers for Diseas...

  1. Molecular characterization of the 1,3-propanediol (1,3-PD) operon of Clostridium butyricum

    Raynaud, Céline; Sarçabal, Patricia; Meynial-Salles, Isabelle; Croux, Christian; Soucaille, Philippe

    2003-01-01

    The genes encoding the 1,3-propanediol (1,3-PD) operon of Clostridium butyricum VPI1718 were characterized from a molecular and a biochemical point of view. This operon is composed of three genes, dhaB1, dhaB2, and dhaT. When grown in a vitamin B12-free mineral medium with glycerol as carbon source, Escherichia coli expressing dhaB1, dhaB2, and dhaT produces 1,3-PD and high glycerol dehydratase and 1,3-PD dehydrogenase activities. dhaB1 and dhaB2 encode, respectively, a new type of glycerol d...

  2. The benefit of whole brain reirradiation in patients with multiple brain metastases

    To assess the outcomes, symptom palliation and survival rates in patients who received repeat whole brain radiotherapy (WBRT). Twenty-eight patients who had progression of brain metastasis received a second course of WBRT. Univariate log-rank testing and multivariate Cox regression analysis were used to determine the factors for death among several variables (cumulative BED [BEDcumulative], primary tumor site, Karnofsky performance scale [KPS], previous SRS, number of metastases and absence of extracranial metastases). Correlations between variables and treatment response were evaluated with the Chi-squared test. The median KPS was 60 (range 50 to 100) at the initiation of reirradiation. The median time interval between the two courses of WBRT was 9.5 months (range 3–27 months). The median doses of the first course and the second course of WBRT were 30 Gy (range 20 to 30 Gy) and 25 Gy (range 20 to 30 Gy), respectively. The mean BEDcumulative was 129.5 Gy (range 110 to 150 Gy). Severe or unexpected toxicity was not observed. Symptomatic response was detected in 39% of the patients. The median overall survival following reirradiation was 3 months (range 1 to 12 months, 95% CI 1.82-4.118). Survival was significantly better in responders (median 10 months, 95% CI 3.56-16.43) compared with non-responders (median 2 months, 95% CI 1.3-2.64) (p = 0.000). In multivariate analysis, patients that had lung cancer (p = 0.01), initial KPS ≥60 (p = 0.03) or longer intervals to reirradiation (p = 0.01) had significantly better survival rates. A careful second course of whole brain irradiation might provide a symptomatic and survival benefit in patients with good performance status and longer cranial progression-free intervals

  3. Breast metastasis from carcinoma of gall bladder

    Ajaz Ahmad Malik

    2013-01-01

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

  4. Hematogenous Gastric Metastasis of Pancreatic Cancer

    Sasajima, Junpei; Okamoto, Kotaro; Taniguchi, Masato

    2016-01-01

    While the gastric involvement of pancreatic cancer is occasionally observed as the result of direct invasion, hematogenous gastric metastasis is rare. A 72-year-old Japanese male presented with general fatigue, pollakiuria, and thirst. Computed tomography revealed a 4.6-cm solid mass in the pancreatic tail and a 4.2-cm multilocular cystic mass in the pancreatic head with multiple liver and lymphatic metastasis. Notably, two solid masses were detected in the gastric wall of the upper body and the antrum; both were separated from the primary pancreatic cancer and seemed to be located in the submucosal layer. Esophagogastroduodenoscopy revealed a submucosal tumor with a normal mucosa in the posterior wall of the upper body of the stomach, suggesting the gastric hematogenous metastasis of pancreatic cancer. The suspected diagnosis was unresectable pancreatic cancer with multiple metastases that was concomitant with the intraductal papillary mucinous neoplasm of the pancreas.

  5. Breast Cancer Pathology, Receptor Status, and Patterns of Metastasis in a Rural Appalachian Population

    Linda Vona-Davis

    2014-01-01

    Full Text Available Breast cancer patients in rural Appalachia have a high prevalence of obesity and poverty, together with more triple-negative phenotypes. We reviewed clinical records for tumor receptor status and time to distant metastasis. Body mass index, tumor size, grade, nodal status, and receptor status were related to metastatic patterns. For 687 patients, 13.8% developed metastases to bone (n=42 or visceral sites (n=53. Metastases to viscera occurred within five years, a latent period which was shorter than that for bone (P=0.042. More women with visceral metastasis presented with grade 3 tumors compared with the bone and nonmetastatic groups (P=0.0002. There were 135/574 women (23.5% with triple-negative breast cancer, who presented with lymph node involvement and visceral metastases (68.2% versus 24.3%; P=0.033. Triple-negative tumors that metastasized to visceral sites were larger (P=0.007. Developing a visceral metastasis within 10 years was higher among women with triple-negative tumors. Across all breast cancer receptor subtypes, the probability of remaining distant metastasis-free was greater for brain and liver than for lung. The excess risk of metastatic spread to visceral organs in triple-negative breast cancers, even in the absence of positive nodes, was combined with the burden of larger and more advanced tumors.

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

    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.

  7. Gd-DTPA-enhanced MR imaging for metastatic brain tumors

    The present series consists of 24 patients with brain metastasis smaller than 10 mm in diameter demonstrated on Gd-DTPA enhanced MR imaging (Gd-MRI). All patients underwent contrast-enhanced (CE) CT to be compared with Gd-MRI in size, number and detectability. The primary lesions of the series included 18 patients with lung cancer (9 with adenocarcinoma, 4 with small cell cancer, 3 with squamous cell cancer and 2 with large cell cancer), 4 with breast cancer, and each 1 with parotid cancer and renal cell carcinoma. All 24 patients except one who underwent surgery were treated with radiation therapy. In 13 patients examined by Gd-MRI and CE-CT both before and after the brain irradiation, therapeutic effect was estimated on each diagnostic imaging comparatively. In regard to size of brain metastases of 24 patients, 91 lesions smaller than 5 mm in diameter were detected by Gd-MRI but only 15 by CE-CT. Three of all patients, no brain metastasis was found on CE-CT. In 6 patients estimated as CR (complete remission) by CE-CT after brain irradiation, Gd-MRI evidenced tumor residues in 5 patients to alter the score of therapeutic effect as PR (partial remission). The difference in therapeutic effects confirmed by Gd-MRI was noted according to histological results and size of metastasis. The most radiosensitive tumor was small cell lung cancer, of which brain metastases smaller than 5 mm in diameter completely disappeared after 20∼50 Gy irradiation. Prophylactic whole brain irradiation has been an alternative indication for small cell lung cancer when CT showed no evidence of brain metastasis. However, our data strongly suggest that the small or tiny brain metastases negative on CE-CT will become new subjects of 'radical' radiotherapy. The higher sensitivity of Gd-MRI for detecting brain metastasis may propose new clinical prospects in staging, planning of therapy and estimation of therapeutic effect. (author)

  8. 2-Nitro-1,3-dinitrooxypropane

    Damon A. Parrish

    2013-03-01

    Full Text Available The title compound, C3H5N3O8, was synthesized by reacting 2-nitropropane-1,3-diol with acetyl nitrate. The molecule is bisected by a crystallograpic mirror plane. In the crystal, the molecules pack in a ribbon-like fashion along the c axis, with the central nitro groups pointing in the same direction. C—H...O contacts apparently provide some additional packing stabilization.

  9. Industrial emissions of 1,3-butadiene.

    Mullins, J A

    1990-01-01

    Sources of industrial emissions of 1,3-butadiene are discussed both by process (production, consumers) and type (equipment leaks, point sources). Quantification of the emissions are presented, as reported by the U.S. Environmental Protection Agency in 1986. The reported emissions attributed to equipment leaks (also known as fugitive emissions) range from about 50 to 95% of the total, depending on the specific production process used. The methods by which these emissions were estimated are dis...

  10. Cranial computed tomographic abnormalities in leptomeningeal metastasis

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

  11. Renal cell carcinoma presenting as mandibular metastasis

    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.

  12. 1-3 piezocomposite SmartPanels

    Fiore, Daniel; Gentilman, Richard L.; Pham-Nguyen, Hong; Serwatka, William J.; McGuire, Patrick T.; Near, Craig D.; Bowen, Leslie J.

    1997-05-01

    Piezocomposite SmartPanelsTM, consisting of 1-3 actuators and pressure sensors and net-shape-molded PZT accelerometers in a large area low profile panel, have been fabricated at Materials Systems Inc. and evaluated at the Naval Research Laboratory. Single layer and two-layer 100 X 100 mm SmartPanels have been tested for sensor sensitivities, actuator authority, surface displacement uniformity, and sensor-actuator coupling. Multilayer GRP circuits boards are used both as stiff faceplates and to provide electrical connections and ground planes. The SmartPanel technology has recently been scaled up to 250 X 250 mm devices. SmartPanels draw upon PZT (lead zirconate titanate) ceramic injection molding technology, which is used to produce cost-effective and robust 1-3 piezoelectric ceramic-polymer composite materials. The 1-3 materials are used extensively for SonoPanelTM transducers in a number of sensor and actuator applications. SonoPanels have been qualified for US Navy applications, based on successful completion of pressure and shock tests, and are currently being scaled up from 250 X 250 mm to 750 X 750 mm panels. Several applications for SmartPanels and SonoPanels are described, including conformable transducers, multielement arrays, pressure sensors, and velocity sensors.

  13. Cod glycopeptide with picomolar affinity to galectin-3 suppresses T-cell apoptosis and prostate cancer metastasis

    Guha, Prasun; Kaptan, Engin; Bandyopadhyaya, Gargi; Kaczanowska, Sabina; Davila, Eduardo; Thompson, Keyata; Martin, Stuart S.; Dhananjaya V Kalvakolanu; Vasta, Gerardo R; Ahmed, Hafiz

    2013-01-01

    Cancer metastasis and immune suppression are critical issues in cancer therapy. Here, we show that a β-galactoside–binding lectin [galectin-3 (gal3)] that recognizes the Thomsen-Friedenreich disaccharide (TFD, Galβ1,3GalNAc) present on the surface of most cancer cells is involved in promoting angiogenesis, tumor-endothelial cell adhesion, and metastasis of prostate cancer cells, as well as evading immune surveillance through killing of activated T cells. To block gal3-mediated interactions, w...

  14. Brain herniation

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

  15. Unusual presentation of oesophageal carcinoma with adrenal metastasis

    Adrenal gland is a common site of metastasis in many cancers but it is very rare in oesophageal carcinoma. We report one such case found to have adrenal metastasis on follow-up PET/computed tomography scan

  16. Popliteal lymph node metastasis of tibial osteoblastic osteosarcoma

    Yalın Dirik

    2014-01-01

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

  17. Invasive cancer cells and metastasis

    Mierke, Claudia Tanja

    2013-12-01

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

  18. Para-recurrent lymph node metastasis was a significant predictor for cervical lymph nodes metastasis in thoracic esophageal carcinoma

    Objective: To evaluate correlation factors of cervical lymph nodes metastasis in thoracic esophageal carcinoma. Methods: Local-regional metastasis of lymph node for 126 cases with esophageal squamous cell cancer after surgery from 2004 to 2009 were reviewed. Risk factors of cervical lymph nodes metastasis were examined by multiple Logistic regression analysis. Results: In 126 cases, supraclavicular lymph node metastasis rate was 43.7% (55/126). By logistic regression, none of the primary site, T stage, N stage, histological grade, lymph node metastasis rate, lymph node metastasis degree and number of lymph nodes metastatic field was not the high risk of cervical lymph nodes metastasis. In addition, multivariate analysis found that lymph node metastasis in mediastinum region 1 was high risk factor for lymph node metastasis of region 1 (χ2 =12.14, 9.27, P =0.000, 0.002), lymph node metastasis in region III and region 2 were high risk factors for lymph node metastasis of region IIa (χ2 =14.56, 8.27, 8.02, 3.93, P =0.000, 0.004, 0.005, 0.047). Conclusion: Mediastinal para-recurrent nerve lymph node metastasis is a significant predictor for cervical lymph nodes metastasis. (authors)

  19. CT evaluation of choriocarcinoma with brain metastases

    It is well established that the computed tomography(CT) is an essential part not only in screening primary brain tumors, but also in staging known malignancy. This paper reports various CT findings demonstrated in 12 cases of choriocarcinoma with brain metastasis. The CT findings such as the number, location and density of the metastatic lesions, the degree of brain edema, mass effect and effect of contrast enhancement are reviewed as well as the episode of stroke syndrome and survival duration after neurologic symptom attacks. The results were as follows: 1. The of these cases showed solitary metastatic lesion and remaining 2 cases were multiple lesions. 2. One was isodense density and the others were hemorrhagic increased density by CT. 3. All of these showed mass effect to the surrounding structures along with moderate to marked brain edema. 4. The position of the metastatic lesion were located at the supratentorially in all cases. Most of them were at the unilateral frontal or parietal area or both of them. One which noted multiple metastatic foci showed at the bilateral occipital regions. 5. Nine cases showed ring enhancement after contrast infusion. One which noted isodense density on the noninfusion scan showed also ring enhancement after contrast infusion. 6. Nine cases showed positive stroke syndrome. One of them was performed emergency craniotomy. The remaining 3 cases noted progressive neurologic symptoms. 7. Two cases were noted only brain metastasis but the others also had various degree of pulmonary metastasis and 2 of latter had hepatic metastasis, too. 8. Most of the cases were treated with CHAMOCA regimen, and one of them was taken whole brain irradiation (3000 rads/2 weeks). Another on case revealed marked regression of not only metastatic brain lesion but the pulmonary lesion after the 8th course of CHAMOCA regimen and still alive for over 460 days

  20. CT evaluation of choriocarcinoma with brain metastases

    Yoon, Sei Chul; Kim, Choon Yul; Kwon, Hyung Chul; Bahk, Young Whee; Kim, Seung Jo [Catholic Medical College, Seoul (Korea, Republic of)

    1984-03-15

    It is well established that the computed tomography(CT) is an essential part not only in screening primary brain tumors, but also in staging known malignancy. This paper reports various CT findings demonstrated in 12 cases of choriocarcinoma with brain metastasis. The CT findings such as the number, location and density of the metastatic lesions, the degree of brain edema, mass effect and effect of contrast enhancement are reviewed as well as the episode of stroke syndrome and survival duration after neurologic symptom attacks. The results were as follows: 1. The of these cases showed solitary metastatic lesion and remaining 2 cases were multiple lesions. 2. One was isodense density and the others were hemorrhagic increased density by CT. 3. All of these showed mass effect to the surrounding structures along with moderate to marked brain edema. 4. The position of the metastatic lesion were located at the supratentorially in all cases. Most of them were at the unilateral frontal or parietal area or both of them. One which noted multiple metastatic foci showed at the bilateral occipital regions. 5. Nine cases showed ring enhancement after contrast infusion. One which noted isodense density on the noninfusion scan showed also ring enhancement after contrast infusion. 6. Nine cases showed positive stroke syndrome. One of them was performed emergency craniotomy. The remaining 3 cases noted progressive neurologic symptoms. 7. Two cases were noted only brain metastasis but the others also had various degree of pulmonary metastasis and 2 of latter had hepatic metastasis, too. 8. Most of the cases were treated with CHAMOCA regimen, and one of them was taken whole brain irradiation (3000 rads/2 weeks). Another on case revealed marked regression of not only metastatic brain lesion but the pulmonary lesion after the 8th course of CHAMOCA regimen and still alive for over 460 days.

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

    Guldner, Ian H.; Yang, Lin; Cowdrick, Kyle R.; Wang, Qingfei; Alvarez Barrios, Wendy V.; Zellmer, Victoria R.; Zhang, Yizhe; Host, Misha; Liu, Fang; Chen, Danny Z.; Zhang, Siyuan

    2016-04-01

    Metastatic microenvironments are spatially and compositionally heterogeneous. This seemingly stochastic heterogeneity provides researchers great challenges in elucidating factors that determine metastatic outgrowth. Herein, we develop and implement an integrative platform that will enable researchers to obtain novel insights from intricate metastatic landscapes. Our two-segment platform begins with whole tissue clearing, staining, and imaging to globally delineate metastatic landscape heterogeneity with spatial and molecular resolution. The second segment of our platform applies our custom-developed SMART 3D (Spatial filtering-based background removal and Multi-chAnnel forest classifiers-based 3D ReconsTruction), a multi-faceted image analysis pipeline, permitting quantitative interrogation of functional implications of heterogeneous metastatic landscape constituents, from subcellular features to multicellular structures, within our large three-dimensional (3D) image datasets. Coupling whole tissue imaging of brain metastasis animal models with SMART 3D, we demonstrate the capability of our integrative pipeline to reveal and quantify volumetric and spatial aspects of brain metastasis landscapes, including diverse tumor morphology, heterogeneous proliferative indices, metastasis-associated astrogliosis, and vasculature spatial distribution. Collectively, our study demonstrates the utility of our novel integrative platform to reveal and quantify the global spatial and volumetric characteristics of the 3D metastatic landscape with unparalleled accuracy, opening new opportunities for unbiased investigation of novel biological phenomena in situ.

  2. Metastasis and bone loss: Advancing treatment and prevention

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

    2010-01-01

    Tumor metastasis to the skeleton affects over 400,000 individuals in the United States annually, more than any other site of metastasis, including significant proportions of patients with breast, prostate, lung and other solid tumors. Research on the bone microenvironment and its role in metastasis suggests a complex role in tumor growth. Parallel preclinical and clinical investigations into the role of adjuvant bone-targeted agents in preventing metastasis and avoiding cancer therapy-induced...

  3. The electroencephalogram in metastatic brain tumors

    P. Pinto Pupo

    1967-12-01

    Full Text Available Sixty cases of intracranial metastatic tumors diagnosed either clinically or by neurosurgery (28 operative cases, 26 with radiological contrast examinations and 6 with clinical diagnosis only are reported. The EEG tests had been made previously to the diagnosis of metastasis. The EEG results are analysed according to the previous impression gained from this test and are presented in 5 tables, on which the cases are divided as per the brain topography of the metastasis. The positive EEG data are analysed and the possibility of topographic diagnosis discussed. The results agree with those presented in the literature. The AA. reach the following conclusions: 1 in patients with suspect brain metastasis the normal EEG allows with great probability to exclude the possibility; 2 in patients with malignant tumor the EEG signs of involvement of the nervous parenchyma are the most important elements for positive diagnosis of brain metastasis; 3 in the cases of metastasis developing at the posterior fossa, either there were indicative signs of the process at that level or the EEG was normal; 4 the EEG signs of an irritant process at the brain cortex were less frequent and, in the majority of cases, appeared in the temporal and parietal areas; 5 the signs of involvement of the mesodiencephalic structures in tumors of the brain hemispheres appeared only when the tumor was located in the median part of the hemisphere (temporal or parietal lobes; 6 signs of depression of the basal electric brain activity in the affected areas appeared rarely and in cases of parietal or occipital tumors; 7 the electric brain activity of other areas of the involved hemisphere or in the opposite hemisphere was normal in the majority of the cases observed. Considering the results of the literature and their own the AA. believe that the EEG could be a semiological method to be used at the preoperative examinations of patients with malignant tumors, with a view at establishing the

  4. Management of solitary and multiple brain metastases from breast cancer

    Addison Willett

    2015-01-01

    Full Text Available As local and systemic control of breast cancer improves, metastasis to the brain remains a common event requiring a specialized management approach. Women diagnosed with breast cancer who develop brain metastases have superior overall survival compared to patients with other forms of metastatic carcinoma. This article summarizes some of the unique aspects of care for patients with breast cancer metastases to the brain.

  5. Optical fine-needle imaging biopsy of the brain

    Kim, Jun Ki; Choi, Jin Woo; Yun, Seok H.

    2013-01-01

    We demonstrate optical fine-needle imaging biopsy (FNIB), combining a fine needle (22 gauge) and a high-resolution side-view probe (350-μm diameter) for minimally invasive interrogation of brain tissue in situ. We apply this technique to examine pathogenesis in murine models of neurodegeneration, brain metastasis of melanoma, and arterial occlusion, respectively. The demonstrated ability to obtain cellular images in the deep brain without craniotomy may be useful in the longitudinal studies o...

  6. Utility of Brain PET-MRI in the restaging of a colorectal cancer with brain metastases

    We report a case of a 47 year-old male diagnosed with carcinoma of sigmoid who presented initially with lung metastases and later with a single brain metastasis which was surgically removed. During follow up, brain tumor recurrence was detected by FDG PET-MRI scan up to 4 times using radiosurgery and /or stereotactic radiotherapy for salvage. The FDG PET-MRI study was useful and crucial for the detection of brain metastases and to guide treatment. Brain re-irradiation is useful to improve symptoms and survival, but may also have toxic affects so its indication must be cautious and applied in selected patients

  7. Nasopharyngeal carcinoma with bone marrow metastasis.

    Zen, H G; Jame, J M; Chang, A Y; Li, W Y; Law, C K; Chen, K Y; Lin, C Z

    1991-02-01

    Five of 23 patients with recurrent nasopharyngeal carcinoma (NPC) were diagnosed to have bone marrow metastasis. They all had advanced local-regional disease, and were treated with neoadjuvant chemotherapy and definitive radiotherapy after the initial diagnosis. Bone marrow metastasis developed 4-24 months later. The clinical features were anemia (5 of 5), leukopenia (3 of 5), thrombocytopenia (4 of 5), sepsis (3 of 5), tenderness of the sternum (3 of 5), and fever (4 of 5). Patients frequently had elevation of serum lactic dehydrogenase (LDH), alkaline phosphatase (ALK-P), and IgG and IgA antibody titers to Epstein-Barr viral capsid antigen when bone marrow involvement was diagnosed. However, clinical manifestations and laboratory tests were not specific. It is important that three patients had normal bone scans. All five patients had a rapid downhill course; four patients died within 23 days, and the fifth 3 months after the diagnosis of bone marrow metastasis. We concluded that bone marrow was a common metastatic site in NPC patients. Bone marrow metastasis adversely affected patients' survival and required a high index of suspicion for diagnosis. We suggested that bone marrow biopsy should be considered as a routine staging procedure in NPC patients and indicated especially when patients presented with abnormal blood counts, sepsis, bone pain, or tenderness of the sternum. It may be positive in the face of a normal bone scan. PMID:1987743

  8. Leptomeningeal metastasis: a CT and MRI study

    We evaluated 35 patients with leptomeningeal metastasis (LM) that was proved by repeated positive cytology (33 patients) and/or autopsy (10 patients) with T1-weighted Gadolinium-DTPA-enhanced MRI and contrast-enhanced CT. The patients (20 women and 15 men) ranged in age from 5-77 years (mean 56 years). Tumour histology included 26 carcinomas, 1 sarcoma, 6 leucaemias, 1 medulloblastoma and 1 primary CNS lymphoma. Intracranial abnormalities were noted in 58% of cases by CT and 88% by MRI, and included hydrocephalus, meningeal or ependymal enhancement, subarachnoidal or intraparenchymal nodules. Leptomeningeal metastasis was detected by MRI in 13 of 17 examined patients, including the three cases with a positive CT. It was proved that MRI is equal or superior to CT in demonstrating meningeal or ependymal enhancement and quantifying enhanced subarachnoidal or parenchymal nodules. However, in the evaluation of leptomeningeal metastasis both modalities had a high incidence of false-negative studies, 89% (31 of 35) by CT and 24% (4 of 17) by MRI. In contrast, two patients with initially negative cytology had pathological MRI findings. Our data indicate that Gadolinium-enhanced MRI is the preferred imaging modality in leptomeningeal metastasis, and suggest that CT does not add significant additional information. However, LM is primarily a histological diagnosis by detecting tumour cells in the cerebrospinal fluid. (orig.)

  9. Cancer Stem Cells, Tumor Dormancy, And Metastasis

    Purvi ePatel

    2012-10-01

    Full Text Available Tumor cells can persist undetectably for an extended period of time in primary tumors and in disseminated cancer cells. Very little is known about why and how these tumors persist for extended periods of time and then evolve to malignancy. The discovery of cancer stem cells (CSCs in human tumors challenges our current understanding of tumor recurrence, drug resistance, and metastasis, and opens up new research directions on how cancer cells are capable of switching from dormancy to malignancy. Although overlapping molecules and pathways have been reported to regulate the stem-like phenotype of CSCs and metastasis, accumulated evidence has suggested additional clonal diversity within the stem-like cancer cell subpopulation. This review will describe the current hypothesis linking CSCs and metastasis and summarize mechanisms important for metastatic CSCs to re-initiate tumors in the secondary sites. A better understanding of CSCs’ contribution to clinical tumor dormancy and metastasis will provide new therapeutic revenues to eradicate metastatic tumors and significantly reduce the mortality of cancer patients.

  10. A link between inflammation and metastasis

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

    2015-01-01

    S100A4 is implicated in metastasis and chronic inflammation, but its function remains uncertain. Here we establish an S100A4-dependent link between inflammation and metastatic tumor progression. We found that the acute-phase response proteins serum amyloid A (SAA) 1 and SAA3 are transcriptional t...

  11. Altered tumor cell glycosylation promotes metastasis

    LuborBorsig

    2014-02-01

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

  12. A new protein Girdin in tumor metastasis

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

    2010-01-01

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

  13. Inguinal lymph node metastasis of colon cancer

    Sloane McGraw

    2011-01-01

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

  14. Diagnosis of bone metastasis from thyroid carcinoma

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

    2015-01-01

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

  15. Leptomeningeal metastasis: a CT and MRI study

    Oschmann, P. [Dept. of Neurology, Univ. of Giessen (Germany); Bauer, T. [Dept. of Radiology, Univ. of Giessen (Germany); Kaps, M. [Dept. of Neurology, Univ. of Giessen (Germany); Trittmacher, S. [Dept. of Radiology, Univ. of Giessen (Germany); Dorndorf, W. [Dept. of Neurology, Univ. of Giessen (Germany)

    1994-08-01

    We evaluated 35 patients with leptomeningeal metastasis (LM) that was proved by repeated positive cytology (33 patients) and/or autopsy (10 patients) with T1-weighted Gadolinium-DTPA-enhanced MRI and contrast-enhanced CT. The patients (20 women and 15 men) ranged in age from 5-77 years (mean 56 years). Tumour histology included 26 carcinomas, 1 sarcoma, 6 leucaemias, 1 medulloblastoma and 1 primary CNS lymphoma. Intracranial abnormalities were noted in 58% of cases by CT and 88% by MRI, and included hydrocephalus, meningeal or ependymal enhancement, subarachnoidal or intraparenchymal nodules. Leptomeningeal metastasis was detected by MRI in 13 of 17 examined patients, including the three cases with a positive CT. It was proved that MRI is equal or superior to CT in demonstrating meningeal or ependymal enhancement and quantifying enhanced subarachnoidal or parenchymal nodules. However, in the evaluation of leptomeningeal metastasis both modalities had a high incidence of false-negative studies, 89% (31 of 35) by CT and 24% (4 of 17) by MRI. In contrast, two patients with initially negative cytology had pathological MRI findings. Our data indicate that Gadolinium-enhanced MRI is the preferred imaging modality in leptomeningeal metastasis, and suggest that CT does not add significant additional information. However, LM is primarily a histological diagnosis by detecting tumour cells in the cerebrospinal fluid. (orig.)

  16. (2-Methoxy-1,3-phenylenediboronic acid

    Janusz Serwatowski

    2008-02-01

    Full Text Available The molecular structure of the title compound, 2-CH3O—C6H3-1,3-[B(OH2]2 or C7H10B2O5, features two intramolecular O—H...O hydrogen bonds of different strengths. One of the boronic acid groups is almost coplanar with the aromatic ring, whereas the second is significantly twisted. Molecules are linked by intermolecular O—H...O hydrogen bonds, generating infinite chains cross-linked to form a two-dimensional sheet structure aligned parallel to the (01overline{1} plane.

  17. Molecular characterization of the 1,3-propanediol (1,3-PD) operon of Clostridium butyricum

    Raynaud, Céline; Sarçabal, Patricia; Meynial-Salles, Isabelle; Croux, Christian; Soucaille, Philippe

    2003-01-01

    The genes encoding the 1,3-propanediol (1,3-PD) operon of Clostridium butyricum VPI1718 were characterized from a molecular and a biochemical point of view. This operon is composed of three genes, dhaB1, dhaB2, and dhaT. When grown in a vitamin B12-free mineral medium with glycerol as carbon source, Escherichia coli expressing dhaB1, dhaB2, and dhaT produces 1,3-PD and high glycerol dehydratase and 1,3-PD dehydrogenase activities. dhaB1 and dhaB2 encode, respectively, a new type of glycerol dehydratase and its activator protein. The deduced proteins DhaB1 and DhaB2, with calculated molecular masses of 88,074 and 34,149 Da, respectively, showed no homology with the known glycerol dehydratases that are all B12 dependent but significant similarity with the pyruvate formate lyases and pyruvate formate lyases activating enzymes and their homologues. The 1,158-bp dhaT gene codes for a 1,3-PD dehydrogenase with a calculated molecular mass of 41,558 Da, revealing a high level of identity with other DhaT proteins from natural 1,3-PD producers. The expression of the 1,3-PD operon in C. butyricum is regulated at the transcriptional level, and this regulation seems to involve a two-component signal transduction system DhaAS/DhaA, which may have a similar function to DhaR, a transcriptional regulator found in other natural 1,3-PD producers. The discovery of a glycerol dehydratase, coenzyme B12 independent, should significantly influence the development of an economical vitamin B12-free biological process for the production of 1,3-PD from renewable resources. PMID:12704244

  18. Brain Basics

    Full Text Available ... Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses magnetic fields to take pictures of the brain's structure, studies show that brain growth in children with autism ...

  19. Evaluating human cancer cell metastasis in zebrafish

    In vivo metastasis assays have traditionally been performed in mice, but the process is inefficient and costly. However, since zebrafish do not develop an adaptive immune system until 14 days post-fertilization, human cancer cells can survive and metastasize when transplanted into zebrafish larvae. Despite isolated reports, there has been no systematic evaluation of the robustness of this system to date. Individual cell lines were stained with CM-Dil and injected into the perivitelline space of 2-day old zebrafish larvae. After 2-4 days fish were imaged using confocal microscopy and the number of metastatic cells was determined using Fiji software. To determine whether zebrafish can faithfully report metastatic potential in human cancer cells, we injected a series of cells with different metastatic potential into the perivitelline space of 2 day old embryos. Using cells from breast, prostate, colon and pancreas we demonstrated that the degree of cell metastasis in fish is proportional to their invasion potential in vitro. Highly metastatic cells such as MDA231, DU145, SW620 and ASPC-1 are seen in the vasculature and throughout the body of the fish after only 24–48 hours. Importantly, cells that are not invasive in vitro such as T47D, LNCaP and HT29 do not metastasize in fish. Inactivation of JAK1/2 in fibrosarcoma cells leads to loss of invasion in vitro and metastasis in vivo, and in zebrafish these cells show limited spread throughout the zebrafish body compared with the highly metastatic parental cells. Further, knockdown of WASF3 in DU145 cells which leads to loss of invasion in vitro and metastasis in vivo also results in suppression of metastasis in zebrafish. In a cancer progression model involving normal MCF10A breast epithelial cells, the degree of invasion/metastasis in vitro and in mice is mirrored in zebrafish. Using a modified version of Fiji software, it is possible to quantify individual metastatic cells in the transparent larvae to correlate with

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

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

    2016-01-01

    The aberrant activity of Wnt signaling is an early step in the transformation of normal intestinal cells to malignant tissue, leading to more aggressive tumors, and eventually metastases. In colorectal cancer (CRC), metastasis accounts for about 90% of patient deaths, representing the most lethal event during the course of the disease and is directly linked to patient survival, critically limiting successful therapy. This review focuses on our studies of the metastasis-inducing gene S100A4, w...

  1. Progression of choroidal metastasis of ovarian serous cystoadenocarcinoma after intravitreal bevacizumab treatment

    Victor E. Reviglio

    2013-02-01

    Full Text Available A 57-year-old woman presented to her ophthalmologist because of rapid deterioration in vision. Dilated funduscopic examination of the right eye showed an elevated, yellow-orange choroidal mass temporal to the fovea; a complete retinal detachment was present in the left eye. The patient was referred to an oncologist. Computerized tomography of the brain, thorax, abdomen, and pelvis were obtained. They revealed an 11-mm mass in the right parietal lobe, a 30-mm mass in the left temporal lobe, 23-mm mass in the right kidney, and multiple nodules in both lungs. Supported by published experience with intravitreal bevacizumab for choroidal metastasis, the patient was injected into the vitreous through the pars plana of the left eye. The tumor mass did not show signs of regression and the visual acuity was unchanged. The patient suffered from end-state complications tumor metastasis and expired one month after the invitreal injection.

  2. Brain metastases from esophageal cancers. Clinical features and treatment results

    Metastatic brain tumors from esophageal cancer are relatively rare. We analyzed the clinical features and results of treatment in 14 cases of brain metastases from esophageal carcinoma. The average time to diagnosis of brain metastases in the 11 patients with metachronous lesions was 13 months. The average age of patients at the diagnosis of brain metastasis was 65 years. Most patients had T4 or N1 disease at the time of diagnosis of esophageal cancer. Performance status of grade 3 was most frequent at the time of diagnosis of brain metastasis. Treatment for brain metastases was surgery followed by radiation in five cases, radiotherapy alone in seven cases, and conservative treatment in two cases. The median survival time of all patients from the treatment of brain metastases was 2 months, with only one patient alive after more than one year. Improvement in neurological symptoms was demonstrated in 42% of cases. These extremely poor treatment results reflect the fact that most patients at the time of diagnosis of brain metastasis had poor performance status and the presence of extracerebral metastases. Therefore, a short-course, high-dose-per-fraction treatment for brain metastases from esophageal cancer should be selected from the viewpoint of quality of life. (author)

  3. The reactions of the hydroxymethyl radical with 1,3-dimethyluracil and 1,3-dimethylthymine

    Hydroxymethyl radicals .(period on line)CH2OH, generated by the radiolysis of methanol (0.5 mol dm-3) in N2O-saturated aqueous solutions, were reacted with 1,3-dimethyluracil or 1,3-dimethylthymine (10-3 mol dm-3). The products were identified and their G values determined. It has been concluded that in 1,3-dimethyluracil .(period on line)CH2OH attack occurs only at C(6) while in 1,3-dimethylthymine there is partitioning between addition (two-thirds) and H-abstraction from the C(5)-methyl group (one-third). A rate constant for CH2OH addition to 1,3-dimethyluracil of about 104 dm3 mol-1 s-1 is estimated. Complexities that may arise in the radiolysis of pyrimidines such as 1,3-dimethylthymine, apparently as a consequence of the formation of 5-alkylidenepyrimidines, are discussed. A value of 0.15 has been estimated for the disproportionation/combination ratio for the hydroxymethyl radical self-termination reaction. (author)

  4. Achievement report on research and development of medical and welfare equipment technology. Unit {sup 13}C-MRS for noninvasive measurement of brain metabolism; Iryo fukushi kiki gijutsu kenkyu kaihatsu seika hokokusho. Mushinshuteki no taisha keisokuyo {sup 1}3C-MRS sochi

    NONE

    1999-11-01

    The effort is to develop technologies of conducting highly sensitive, uninterrupted observation of metabolism in the brain by use of the {sup 13}C-MRS unit, for which some carbon chain compounds (glucose, amino acids, etc.), which assume an important part in metabolism, are labelled by a stable isotope {sup 13}C and then administered to living things. A multi-slice HSQC (heteronuclear single quantum coherence) method is developed for the achievement of sensitivity enhanced 16 folds, excellent compound isolating capability, and high localizing capability, and these contribute to the specification of an optimum pulse sequence. A double tuning coil is developed for transmission, and a 6-channel multi-surface coil for reception, these two providing a 3-fold increase in detection probe sensitivity. The nonlinear least-square method is applied for the processing of spectral data, which enables excellent isolation of compounds. It also enables the generation of an inclined magnetic field quick to rise and of a sequence high in amplitude/phase accuracy. New methods are developed for the synthesis of {sup 13}C-labelled glucose, dopa, glutamine, glutamic acid, and GABA (gamma-aminobutyric acid) which are expected to be useful in brain metabolism measurement, and the products are administered to animals for evaluation. (NEDO)

  5. 1-3-7 minute intravenous urography

    Bahk, Yong Whee; Yoon, Sei Chul; Lee, Myung Hee [Catholic Medical College, Seoul (Korea, Republic of)

    1980-12-15

    Intravenous urography (IVU) as it is used widely today was probably started in early 1950's after the introduction of triiodobenzoic acid compounds as contrast media. This long cherished traditional method consists of taking radiograms at 5, 15 and 25 minutes after the injection of contrast medium. There are a few modifications of this standard urographic examination such as five minute IVU (Woodruff, 1959), minute-sequence pyelogram (Maxwell et al., 1964), drip infusion pyelography (Schencker, 1964) and nephrotomography (Evans et al., 1955). The present study has been undertaken to test if the conventional standard IVU can be more rapidly performed without losing essential informational contents of urograms. In this new clinical trial, urograms were taken at the end of 1, 3 and 7 minutes instead of 5, 15 and 25 minutes after the intravenous injection of contrast medium. We injected 40 ml of meglumine diatrizoate solution within 30 seconds using an 18G iv needle. (The amount of injected contrast medium has been reduced recently to ordinary single dose of 20 ml for subjects weighing less than 8 kg). Upon viewing the 7 minute film in front of an automatic processor, the examination was terminated after obtaining an upright view unless any further radiogram was indicated. As shown in Tables and Figures, our new 1-3-7 minute method has been proven to provide us with as much essential and useful information as conventional 5-15-25 minute urography. Thus, we were able to finish one examination within 10 minutes without losing any necessary diagnostic information. In some of patients with obstructive uropathy such as stone the examination was extended as long as it was desired. Side reactions were occasional nausea, flushing and rare mild vomiting which never prevented the examination.

  6. Role of the Blood-Brain Barrier in the Formation of Brain Metastases

    István A. Krizbai

    2013-01-01

    Full Text Available The majority of brain metastases originate from lung cancer, breast cancer and malignant melanoma. In order to reach the brain, parenchyma metastatic cells have to transmigrate through the endothelial cell layer of brain capillaries, which forms the morphological basis of the blood-brain barrier (BBB. The BBB has a dual role in brain metastasis formation: it forms a tight barrier protecting the central nervous system from entering cancer cells, but it is also actively involved in protecting metastatic cells during extravasation and proliferation in the brain. The mechanisms of interaction of cancer cells and cerebral endothelial cells are largely uncharacterized. Here, we provide a comprehensive review on our current knowledge about the role of junctional and adhesion molecules, soluble factors, proteolytic enzymes and signaling pathways mediating the attachment of tumor cells to brain endothelial cells and the transendothelial migration of metastatic cells. Since brain metastases represent a great therapeutic challenge, it is indispensable to understand the mechanisms of the interaction of tumor cells with the BBB in order to find targets of prevention of brain metastasis formation.

  7. Hysteretic behavior of proprotein convertase 1/3 (PC1/3.

    Marcelo Y Icimoto

    Full Text Available The proprotein convertases (PCs are calcium-dependent proteases responsible for processing precursor proteins into their active forms in eukariotes. The PC1/3 is a pivotal enzyme of this family that participates in the proteolytic maturation of prohormones and neuropeptides inside the regulated secretory pathway. In this paper we demonstrate that mouse proprotein convertase 1/3 (mPC1/3 has a lag phase of activation by substrates that can be interpreted as a hysteretic behavior of the enzyme for their hydrolysis. This is an unprecedented observation in peptidases, but is frequent in regulatory enzymes with physiological relevance. The lag phase of mPC1/3 is dependent on substrate, calcium concentration and pH. This hysteretic behavior may have implications in the physiological processes in which PC1/3 participates and could be considered an additional control step in the peptide hormone maturation processes as for instance in the transformation of proinsulin to insulin.

  8. Radionuclide therapy for thyroid cancer with nervous system metastasis

    Differentiated thyroid cancer is 85% of all thyroid cancer, and is known to have good prognosis with proper surgery and radioiodine therapy. But 4% of papillary carcinoma and 36% of follicular carcinoma present with distant metastasis. Even if the patient had distant metastasis, total thyroidectomy and radioiodine therapy show good response. Forty seven percent of bone metastases are found in the initial diagnosis, in which vertebral metastases is 29%, pelvic metastases 22%. The metastases to vertebrae often combine spinal cord compression, making it difficult to deliver enough radiation dose to the lesion with radioiodine or external beam irradiation. Brain metastases is found in less than 1% of thyroid cancer, and is also difficult to cure. In Korea Cancer Center Hospital, from 1997 to 2002, we analyzed 437 patients with thyroid cancer who were treated with radioiodine after total thyroidectomy. There were four patients with brain metastases, and 32 patients with vertebral metastases. In four patients with brain metastases, one patient, who also had bone metastases, received high dose radioiodine therapy after total thyroidectomy, and is alive for more than 15 months. Another patients received total thyroidectomy, radioiodine therapy and external irradiation therapy, and survived 22 months. Two patients refused further treatment and died in one month. I-131 uptake in the metastatic lesion in brain is reported to be 17%, and multimodality therapy with surgery, radioiodine therapy, external irradiation and chemotherapy may improve the prognosis. In 32 patients with vertebral metastases, 19 patients (59.4%) showed I-131 uptake after high dose radioiodine therapy, and 5 year survival rate was 65.8%. 13 patients without I-131 uptake after radioiodine therapy had 26.9% of 5 year survival rate. In 11 patients with spinal cord compression, 7 patients received high dose radioiodine therapy and external irradiation after total thyroidectomy and spinal surgery, and six

  9. Recent development of LiNi1/3Co1/3Mn1/3O2 as cathode material of lithium ion battery.

    Zhu, Ji-Ping; Xu, Quan-Bao; Yang, Hong-Wei; Zhao, Jun-Jie; Yang, Guang

    2011-12-01

    Layered LiNi1/3Co1/3Mn1/3O2, owing to its excellent electrochemical properties, has been used as cathode material for lithium-ion batteries, especially for hybrid electric vehicles. It has many merits such as high capacity, long cycle life, low cost and little harm to environment. Therefore, LiNi1/3Co1/3Mn1/3O2 has become a great concern by scholars on energy and material fields. However, the electronic conductivity and the charge-discharge capacity at high current should be enhanced before any materials modifications. Here, this paper summarizes the main synthetic technologies of LiNi1/3Co1/3Mn1/3O2 in recent years, including synthesis methods, doping, surface coating modification, and the future development trends discussed. PMID:22408910

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

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

    2008-01-01

    BACKGROUND: Brain metastasis is a common complication and a major cause of morbidity and mortality in human malignancies. We investigated whether the proliferating cell index of surgically treated single brain metastasis would predict the relapse at a location remote from the initial resection site...... subsequently by radiotherapy to the whole brain were stained by immunohistochemistry for the marker CDC47 and the proliferation index was calculated. The index was then analysed with respect to clinical parameters, including the incidence of brain relapse within 2 months of the first resection, the timing of...... the patients with lesions which had not relapsed or which had relapsed more than 2 months after first craniotomy (n = 12). The synchronous brain metastasis (that is, those occurring before or within 2 months of the primary cancer diagnosis) had a significantly higher proliferation index than the...

  11. 1,3-Dinitrobenzene neurotoxicity - Passage effect in immortalized astrocytes.

    Maurer, Laura L; Latham, Jackelyn D; Landis, Rory W; Song, Dong Hoon; Epstein, Tamir; Philbert, Martin A

    2016-03-01

    Age-related disturbances in astrocytic mitochondrial function are linked to loss of neuroprotection and decrements in neurological function. The immortalized rat neocortical astrocyte-derived cell line, DI-TNC1, provides a convenient model for the examination of cellular aging processes that are difficult to study in primary cell isolates from aged brain. Successive passages in culture may serve as a surrogate of aging in which time-dependent adaptation to culture conditions may result in altered responses to xenobiotic challenge. To investigate the hypothesis that astrocytic mitochondrial homeostatic function is decreased with time in culture, low passage DI-TNC1 astrocytes (LP; #2-8) and high passage DI-TNC1 astrocytes (HP; #17-28) were exposed to the mitochondrial neurotoxicant 1,3-dinitrobenzene (DNB). Cells were exposed in either monoculture or in co-culture with primary cortical neurons. Astrocyte mitochondrial membrane potential, morphology, ATP production and proliferation were monitored in monoculture, and the ability of DI-TNC1 cells to buffer K(+)-induced neuronal depolarization was examined in co-cultures. In HP DI-TNC1 cells, DNB exposure decreased proliferation, reduced mitochondrial membrane potential and significantly decreased mitochondrial form factor. Low passage DI-TNC1 cells effectively attenuated K(+)-induced neuronal depolarization in the presence of DNB whereas HP counterparts were unable to buffer K(+) in DNB challenge. Following DNB challenge, LP DI-TNC1 cells exhibited greater viability in co-culture than HP. The data provide compelling evidence that there is an abrupt phenotypic change in DI-TNC1 cells between passage #9-16 that significantly diminishes the ability of DI-TNC1 cells to compensate for neurotoxic challenge and provide neuroprotective spatial buffering. Whether or not these functional changes have an in vivo analog in aging brain remains to be determined. PMID:26769196

  12. Nanoradiopharmaceuticals for Bone Cancer Metastasis Imaging.

    Coelho, Bianca Feliciano; de Souza Albernaz, Marta; Iscaife, Alexandre; Moreira Leite, Katia Ramos; de Souza Junqueira, Mara; Bernardes, Emerson Soares; da Silva, Emerson Oliveira; Santos-Oliveira, Ralph

    2015-01-01

    Drug delivery systems are under intense investigation all around the world, especially in oncology research. Indeed, in some cases, like bone metastasis, nanodrugs may represent the last and best choice for both treatment and imaging of early cancer foci. Nuclear medicine has been using MDP labelled with 99mTc as radiopharmaceuticals for many years; however, their use as nanoradiopharmaceuticals is very innovative and creates a new way to establish radiopharmacy in this new scenario offered by nanotechnology. In this study we developed and tested nano-MDP-labelled with 99mTc in rats induced with bone cancer metastasis and the results showed that it may work in patients. However, some further experiments are required in order to initiate protocols in humans. PMID:25847010

  13. [Thyroid's metastasis of tonsillar squamous cell carcinoma].

    Scanelli, Giovanni; Aimoni, Claudia; Marchetti, Elisabetta; Geminiani, Matteo; Pastore, Antonio

    2005-09-01

    The authors describe the case of a 58 years old man, affected by squamous cell carcinoma of the tonsil, who underwent left tonsillectomy with bilateral neck dissection, followed by radiotherapy. After a 6 months period, the patient began to suffer from dysphonia, dysphagia and loss of weight: a painless neoformation was detected at the right lobe of the tyhroid, resulted a metastasis of the tonsillar neoplasm. The search for intranodular thyroglobulin was negative; the patient underwent thyroidectomy which showed a massive infiltration of the right cricothyroid space, cricoid and thyroid wing cartilage necrosis and intralaryngeal tumor infiltration. The authors describe the thyroid metastasis treatment, present an up-to-date review of the literature and suggest a thyroid careful clinical evaluation in every patient with a previous history of oropharyngeal cancer. PMID:16229323

  14. Visfatin Mediates SCLC Cells Migration across Brain Endothelial Cells through Upregulation of CCL2

    Tingting Liu

    2015-05-01

    Full Text Available Small-cell lung cancer (SCLC is characterized as an aggressive tumor with brain metastasis. Although preventing SCLC metastasis to the brain is immensely important for survival, the molecular mechanisms of SCLC cells penetrating the blood–brain barrier (BBB are largely unknown. Recently, visfatin has been considered as a novel pro-inflammatory adipocytokine involved in various cancers. Herein, we present evidence that elevated levels of visfatin in the serum of SCLC patients were associated with brain metastasis, and visfain was increased in NCI-H446 cells, a SCLC cell line, during interacting with human brain microvascular endothelial cells (HBMEC. Using in vitro BBB model, we found that visfatin could promote NCI-H446 cells migration across HBMEC monolayer, while the effect was inhibited by knockdown of visfatin. Furthermore, our findings indicated that CC chemokine ligand 2 (CCL2 was involved in visfatin-mediated NCI-H446 cells transendothelial migtation. Results also showed that the upregulation of CCL2 in the co-culture system was reversed by blockade of visfatin. In particular, visfatin-induced CCL2 was attenuated by specific inhibitor of PI3K/Akt signaling in NCI-H446 cells. Taken together, we demonstrated that visfatin was a prospective target for SCLC metastasis to brain, and understanding the molecular mediators would lead to effective strategies for inhibition of SCLC brain metastasis.

  15. Intramuscular metastasis from malignant melanoma: MR findings

    We present a rare case of intramuscular metastasis from malignant melanoma. The lesion showed intermediate to high signal intensity on T1-weighted magnetic resonance (MR) images and mixed signal intensities containing high and low signals on T2-weighted images. The signal intensity on T1-weighted images, which is due to the paramagnetic effect of melanin, is a characteristic MR finding of this entity. (orig.)

  16. Isolated penile metastasis from bladder carcinoma

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

    1999-10-01

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

  17. Cancer stem cells, tumor dormancy, and metastasis

    EmilyChen

    2012-01-01

    Tumor cells can persist undetectably for an extended period of time in primary tumors and in disseminated cancer cells. Very little is known about why and how these tumors persist for extended periods of time and then evolve to malignancy. The discovery of cancer stem cells (CSCs) in human tumors challenges our current understanding of tumor recurrence, drug resistance, and metastasis, and opens up new research directions on how cancer cells are capable of switching from dormancy to malignanc...

  18. Isolated penile metastasis from bladder carcinoma

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

  19. Wnt and Wnt inhibitors in bone metastasis

    Sottnik, Joseph L; Christopher L. Hall; Zhang, Jian; Evan T. Keller

    2012-01-01

    Bone metastasis is a clinically devastating development of progressive cancers including prostate carcinoma, breast carcinoma and multiple myeloma. Bone metastases are typically painful, lead to adverse skeletal-related events, such as fracture, and are highly resistant to therapy. A major contribution to the ability of cancers to successfully establish bone metastases is their ability to exploit mechanisms of normal bone remodeling. Wnts are a large family of morphogenic proteins that are cr...

  20. Carcinoma cervix presenting with clivus metastasis

    Arpitha S Rao

    2015-01-01

    Full Text Available We present an unusual case of a large metastatic lesion from carcinoma cervix located in the clivus. Patient presented with severe headache and vomiting, mimicking an intracranial pathology. Radiological imaging suggested metastatic origin of the lesion and later on investigations revealed primary in the uterine cervix. The anatomic importance of extradural neural axis component in the process of metastasis of carcinoma cervix to the clivus is highlighted in this case report.

  1. Stress Proteins and Pancreatic Cancer Metastasis

    Cano, Carla E.; Iovanna, Juan L.

    2010-01-01

    Tumor metastasis is challenged by its resistance to microenvironmental stress infringed during escape from the primary tumor and the colonization of a foreign secondary tissue. Because of its great metastatic potential and its strong resistance to anticancer drugs, pancreatic cancer is regarded as a paradigm of the adaptation of cancer cells to microenvironmental stress. Thus, to understand how pancreatic cancer cells adapt to the different endogenous and therapy-related stresses is crucial f...

  2. Mandibular metastasis of cholangiocarcinoma: A case report

    You, Tae Min; Kim, Kee-Deog; Jeong, Ho-Gul; Park, Wonse

    2015-01-01

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

  3. Breast carcinoma metastasis to the lacrimal gland

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

    2015-01-01

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

  4. Intracranial metastasis of spinal intramedullary anaplastic astrocytoma

    Kataria, Rashim; Bhasme, Vishal; Chopra, Sanjeev; V D Sinha; Singhvi, Shashi

    2011-01-01

    Meningeal spread of spinal intramedullary astrocytoma into the cranium is rare. Only few case reports are available so far in the literature. We report a case of intramedullary high grade astrocytoma of the conus, developing intracranial metastasis after three months of partial excision of the spinal mass. The need for radical surgery, entire neuroaxis radiation, and adjuvant chemotherapy is suggested in the management of malignant spinal cord astrocytoma to prevent dissemination.

  5. Microenvironmental regulation of tumor progression and metastasis

    Quail, DF; Joyce, JA

    2013-01-01

    Cancers develop in complex tissue environments, which they depend upon for sustained growth, invasion and metastasis. Unlike tumor cells, stromal cell types within the tumor microenvironment (TME) are genetically stable, and thus represent an attractive therapeutic target with reduced risk of resistance and tumor recurrence. However, specifically disrupting the pro-tumorigenic TME is a challenging undertaking, as the TME has diverse capacities to induce both beneficial and adverse consequence...

  6. Pancreatic Metastasis from a Solitary Fibrous Tumor of the Central Nervous System

    Takahiro Osuga

    2014-01-01

    Full Text Available Context Solitary fibrous tumor of the central nervous system is uncommon, with only around 200 reported cases. Further, extracranial metastasis is extremely rare, and only 5 cases of hematogenous metastases have been reported so far. To the best of our knowledge, there have been no reports of solitary fibrous tumor of the central nervous system metastasizing to the pancreas. Case report A 62-year-old woman was referred for evaluation of a pancreatic mass, which was strongly suspected to be a neuroendocrine tumor. However, the histological findings and immunohistochemical profile indicated the presence of a solitary fibrous tumor. Because the medical history revealed previous transcranial resection for intracranial meningioma 16 years ago, we conducted a pathological review of the brain specimen obtained by the first operation and found that it had the same histology and immunohistochemical profile as the current endoscopic ultrasound-guided fineneedle aspiration specimen. Consequently, the final diagnosis, on the basis of the brain specimen, was changed from meningioma to solitary fibrous tumor of the central nervous system, and the pancreatic mass was diagnosed as metastasis from solitary fibrous tumor of the central nervous system. The patient underwent middle pancreatectomy; the pancreatic specimen also had the same histology and immunohistochemical profile as the brain specimen. Conclusion Histological findings and immunohistochemical profile obtained by EUS-FNA are invaluable for the correct diagnosis to avoid excessive surgical procedures.

  7. Synthesis of New 2-(1,3-Dithianylphenols and Hexakis-[p-(1,3-dithian-2-ylphenoxy]cyclotriphosphazene

    Prónayová Nadezda

    1997-01-01

    Full Text Available 2-Chloro-1,3-dithiane was obtained by the chlorination of 1,3-dithiane with N-chlorosuccinimide. Reactions of 2-chloro-1,3-dithiane with various substituted phenols lead to 2-(1,3-dithianylphenols (3. Hexakis-[p-(1,3-dithian-2-ylphenoxy]cyclotriphosphazene (6 was obtained by reaction with hexachlorotriazacyclotriphosphazene (5.

  8. Hexahydro-1,3,5-trinitro-1,3,5-triazine translocation in poplar trees

    Thompson, P.L. [Seattle Univ., WA (United States). Dept. of Civil and Environmental Engineering; Ramer, L.A.; Schnoor, J.L. [Univ. of Iowa, Iowa City, IA (United States). Dept. of Civil and Environmental Engineering

    1999-02-01

    This article evaluates the translocation of the explosive hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) in hybrid poplar trees (Populus deltoides x nigra, DN34) grown in hydroponic solutions. Mass balances with [U-{sup 14}C]RDX were used to assess RDX translocation. Up to 60% of the RDX uptaken by the tree accumulated in leaf tissues. Analysis of plant extracts by high-performance liquid chromatography equipped with radiochemical detection indicated that RDX was not significantly transformed during exposure periods of up to 7 d. The bioaccumulation of RDX may be an important concern for phytoremediation efforts.

  9. Therapy for bone metastasis from different cancers

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

    2016-01-01

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

  10. Bone Metastasis from Renal Cell Carcinoma

    Chen, Szu-Chia; Kuo, Po-Lin

    2016-01-01

    About one-third of patients with advanced renal cell carcinoma (RCC) have bone metastasis that are often osteolytic and cause substantial morbidity, such as pain, pathologic fracture, spinal cord compression and hypercalcemia. The presence of bone metastasis in RCC is also associated with poor prognosis. Bone-targeted treatment using bisphosphonate and denosumab can reduce skeletal complications in RCC, but does not cure the disease or improve survival. Elucidating the molecular mechanisms of tumor-induced changes in the bone microenvironment is needed to develop effective treatment. The “vicious cycle” hypothesis has been used to describe how tumor cells interact with the bone microenvironment to drive bone destruction and tumor growth. Tumor cells secrete factors like parathyroid hormone-related peptide, transforming growth factor-β and vascular endothelial growth factor, which stimulate osteoblasts and increase the production of the receptor activator of nuclear factor κB ligand (RANKL). In turn, the overexpression of RANKL leads to increased osteoclast formation, activation and survival, thereby enhancing bone resorption. This review presents a general survey on bone metastasis in RCC by natural history, interaction among the immune system, bone and tumor, molecular mechanisms, bone turnover markers, therapies and healthcare burden. PMID:27338367

  11. Surgical Brain Metastases: Management and Outcome Related to Prognostic Indexes: A Critical Review of a Ten-Year Series

    Caroli, Manuela; Di Cristofori, Andrea; Lucarella, Francesca; Raneri, Fabio Angelo; Portaluri, Francesco; Gaini, Sergio Maria

    2011-01-01

    Brain metastasis are the most common neoplastic lesions of the nervous system. Many cancer patients are diagnosed on the basis of a first clinical presentation of cancer on the basis of a single or multiple brain lesions. Brain metastases are manifestations of primary disease progression and often determine a poor prognosis. Not all patients with a brain metastases undergo surgery: many are submitted to alternative or palliative treatments. Management of patients with brain metastases is stil...

  12. Outcome of surgical resection for brain metastases and radical treatment of the primary tumor in Chinese non–small-cell lung cancer patients

    Li, Zhenye; Zhang, Xiangheng; Jiang, Xiaobing; Guo, Chengcheng; Sai, Ke; Yang, Qunying; He, Zhenqiang; Wang, Yang; Chen, Zhongping; Li, Wei; Mou, Yonggao

    2015-01-01

    Purpose Brain metastasis is the most common complication of brain cancer; nevertheless, primary lung cancer accounts for approximately 20%–40% of brain metastases cases. Surgical resection is the preferred treatment for brain metastases. However, no studies have reported the outcome of surgical resection of brain metastases from non–small-cell lung cancer (NSCLC) in the People’s Republic of China. Moreover, the optimal treatment for primary NSCLC in patients with synchronous brain metastases ...

  13. Anti-tumor activities of luteolin and silibinin in glioblastoma cells: overexpression of miR-7-1-3p augmented luteolin and silibinin to inhibit autophagy and induce apoptosis in glioblastoma in vivo.

    Chakrabarti, Mrinmay; Ray, Swapan K

    2016-03-01

    Glioblastoma is the deadliest brain tumor in humans. High systemic toxicity of conventional chemotherapies prompted the search for natural compounds for controlling glioblastoma. The natural flavonoids luteolin (LUT) and silibinin (SIL) have anti-tumor activities. LUT inhibits autophagy, cell proliferation, metastasis, and angiogenesis and induces apoptosis; while SIL activates caspase-8 cascades to induce apoptosis. However, synergistic anti-tumor effects of LUT and SIL in glioblastoma remain unknown. Overexpression of tumor suppressor microRNA (miR) could enhance the anti-tumor effects of LUT and SIL. Here, we showed that 20 µM LUT and 50 µM SIL worked synergistically for inhibiting growth of two different human glioblastoma U87MG (wild-type p53) and T98G (mutant p53) cell lines and natural combination therapy was more effective than conventional chemotherapy (10 µM BCNU or 100 µM TMZ). Combination of LUT and SIL caused inhibition of growth of glioblastoma cells due to induction of significant amounts of apoptosis and complete inhibition of invasion and migration. Further, combination of LUT and SIL inhibited rapamycin (RAPA)-induced autophagy, a survival mechanism, with suppression of PKCα and promotion of apoptosis through down regulation of iNOS and significant increase in expression of the tumor suppressor miR-7-1-3p in glioblastoma cells. Our in vivo studies confirmed that overexpression of miR-7-1-3p augmented anti-tumor activities of LUT and SIL in RAPA pre-treated both U87MG and T98G tumors. In conclusion, our results clearly demonstrated that overexpression of miR-7-1-3p augmented the anti-tumor activities of LUT and SIL to inhibit autophagy and induce apoptosis for controlling growth of different human glioblastomas in vivo. PMID:26573275

  14. Renal cell carcinoma presenting as a solitary cutaneous facial metastasis: case report and review of the literature

    Porter, Neil A; Anderson, Helen L; Al-Dujaily, Saad

    2006-01-01

    Background Renal cell carcinoma is well known for its frequency to metastasise, particularly to lungs, liver, bones and brain. Metastasis to the skin is much less common. Presentation as a result of the skin lesion is even more unusual, with only 14 previously reported cases in the English literature. The majority of these cases have been reported in patients with recurrent disease or with other metastases. Case presentation We present only the second case of non-recurrent renal cell carcinom...

  15. A Review of the Clinical Outcomes for Patients Diagnosed with Brainstem Metastasis and Treated with Stereotactic Radiosurgery

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

    2013-01-01

    Only 3%–5% of all brain metastases are located in the brainstem. We present a comprehensive review of the clinical outcomes from modern studies that treated patients with brainstem metastasis using either a Gamma Knife or a linear accelerator-based stereotactic radiosurgery. The median survival time of patients was compared to better understand what clinical or treatment factors are predictive of improved survival. This information can then be utilized to optimize patient care. The data sugge...

  16. Pancreatic solitary and synchronous metastasis from breast cancer: a case report and systematic review of controversies in diagnosis and treatment

    Molino, Carlo; Mocerino, Carmela; Braucci, Antonio; Riccardi, Ferdinando; Trunfio, Martino; Carrillo, Giovanna; Vitale, Maria Giuseppa; Cartenì, Giacomo; De Sena, Guido

    2014-01-01

    Background Metastases from breast cancer cause the frequent involvement of lung, bone, liver, and brain, while the occurrence of metastases to the gastrointestinal tract is rare, and more frequently discovered after a primary diagnosis of breast cancer. Solitary pancreatic metastases from breast cancer, without widespread disease, are actually unusual, and only 19 cases have been previously described; truly exceptional is a solitary pancreatic metastasis becoming evident together with the pri...

  17. Brain Tumors

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

  18. Brain Basics

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

  19. Brain Tumors

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

  20. Brain Fingerprinting

    ravi kumar

    2012-12-01

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

  1. Rational Operation for Primary Gastric Carcinoma with Liver Metastasis

    Caigang Liu; Ping Lu; Jinsong Gu; Junqing Chen

    2007-01-01

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

  2. Brain metastatic cancer cells release microRNA-181c-containing extracellular vesicles capable of destructing blood–brain barrier

    Tominaga, Naoomi; Kosaka, Nobuyoshi; Ono, Makiko; Katsuda, Takeshi; Yoshioka, Yusuke; Tamura, Kenji; Lötvall, Jan; Nakagama, Hitoshi; Ochiya, Takahiro

    2015-01-01

    Brain metastasis is an important cause of mortality in breast cancer patients. A key event during brain metastasis is the migration of cancer cells through blood–brain barrier (BBB). However, the molecular mechanism behind the passage through this natural barrier remains unclear. Here we show that cancer-derived extracellular vesicles (EVs), mediators of cell–cell communication via delivery of proteins and microRNAs (miRNAs), trigger the breakdown of BBB. Importantly, miR-181c promotes the de...

  3. Treatment strategies for lung cancer brain metastases

    Forty-one patients suffered initial relapses with brain metastasis after surgery for non-small lung cancer at our hospital between 1978 and 1995. These patients were a total of 8.4% of all cases of surgical removal, and had an average relapse period of 8.6 months ± 8.0 months after surgery on the primary lesions. Of these, surgical removal of metastasized lesions was performed on 18 patients (43%), in which the 5-year post-operative survival rate was 35.7%, and the median survival time was good at 28 months. It was found that the survival period was significantly extended in the group whose relapse period was less than one year after surgery on the primary lesions, and in the group who received cranial irradiation post-operatively on the metastasized brain lesion. Following surgery on the metastasized lesion, second relapses occurred in nine patients, and six patients suffered from second relapses in the brain, of which four did not receive cranial irradiation post-operatively. Cases of radiotherapy in patients of 70 years of age or more frequently manifested post-radiotherapy subacute neuropathy. From the above, it is thought that the following procedures should be adopted: Periodic examination for brain metastasis during the 24 months following surgery for non-small cell lung carcinoma for purposes of early detection; in cases where brain metastasis is detected, if no metastasis is identified in other organs, a policy of surgical removal should be adopted where possible; and, in cases of 70 years of age or less following surgery on the metastasized lesion, cranial irradiation should be considered. (author)

  4. Radiosurgery for brain metastases: is whole brain radiotherapy necessary?

    Purpose: Because whole brain radiotherapy (WBRT) may cause dementia in long-term survivors, selected patients with brain metastases may benefit from initial treatment with radiosurgery (RS) alone reserving WBRT for salvage as needed. We reviewed results of RS ± WBRT in patients with newly diagnosed brain metastasis to provide background for a prospective trial. Methods and Materials: Patients with single or multiple brain metastases managed initially with RS alone vs. RS + WBRT (62 vs. 43 patients) from 1991 through February 1997 were retrospectively reviewed. The use of upfront WBRT depended on physician preference and referral patterns. Survival, freedom from progression (FFP) endpoints, and brain control allowing for successful salvage therapy were measured from the date of diagnosis of brain metastases. Actuarial curves were estimated using the Kaplan-Meier method. Analyses to adjust for known prognostic factors were performed using the Cox proportional hazards model (CPHM) stratified by primary site. Results: Survival and local FFP were the same for RS alone vs. RS + WBRT (median survival 11.3 vs. 11.1 months and 1-year local FFP by patient 71% vs. 79%, respectively). Brain FFP (scoring new metastases and/or local failure) was significantly worse for RS alone vs. RS + WBRT (28% vs. 69% at 1 year; CPHM adjusted p = 0.03 and hazard ratio = 0.476). However, brain control allowing for successful salvage of a first failure was not significantly different for RS alone vs. RS + WBRT (62% vs. 73% at 1 year; CPHM adjusted p = 0.56). Conclusions: The omission of WBRT in the initial management of patients treated with RS for up to 4 brain metastases does not appear to compromise survival or intracranial control allowing for salvage therapy as indicated. A randomized trial of RS vs. RS + WBRT is needed to assess survival, quality of life, and cost in good-prognosis patients with newly diagnosed brain metastases

  5. High Voltage and High Capacity Characteristics of LiNi1/3Co1/3Mn1/3O2 Cathode for Lithium Battery Applications

    P.Periasamy, N.Kalaiselvi, H.S.-Kim

    2007-09-01

    Full Text Available Possibility of synthesizing LiNi1/3Co1/3Mn1/3O2 cathode via., soft chemistry based Gelatin Assisted Combustion [GAC] approach has been examined through the present study. GAC method with a calcination temperature as high as 750°C for a period of 24h. was found to be essential to prepare LiNi1/3Co1/3Mn1/3O2 powders with good hexagonal ordering and better cycling performance. The intensity ratio of (003 and (104 bragg peaks is greater than unity, which is an indication for the absence of cation mixing. The observed CV peaks confirm the presence of Ni, Co and Mn ions in their +3 oxidation state. A maximum discharge capacity of ~180mAh/g has been exhibited by the synthesized LiNi1/3Co1/3Mn1/3O2 cathode, when charged up to 4.6V. Hence, it is demonstrated that the LiNi1/3Co1/3Mn1/3O2 cathode synthesized through the present study could be exploited both as a high voltage and high capacity cathode material for use in rechargeable lithium battery applications.

  6. Brain Basics

    Full Text Available ... The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are the basic working unit of the ... distant nerve cells (via axons) to form brain circuits. These circuits control specific body functions such as ...

  7. Brain Basics

    Full Text Available ... than ever before. Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses magnetic fields to take pictures of the brain's structure, studies ...

  8. Brain Basics

    Full Text Available ... Brain Basics provides information on how the brain works, how mental illnesses are disorders of the brain, ... others live with symptoms of mental illness every day. They can be moderate, or serious and cause ...

  9. Brain Basics

    Full Text Available ... helps Sarah to better cope with her feelings. Brain Research Modern research tools and techniques are giving scientists ... the treatment for a person's specific conditions. Such brain research help increase the understanding of how the brain ...

  10. Brain Basics

    Full Text Available ... little dopamine or problems using dopamine in the thinking and feeling regions of the brain may play ... than ever before. Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses ...

  11. Brain Basics

    Full Text Available ... as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are the basic working unit of the brain ... specialized for the function of conducting messages. A neuron has three basic parts: Cell body which includes ...

  12. Brain Malformations

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

  13. Brain Basics

    Full Text Available ... brain's structure, studies show that brain growth in children with autism appears to peak early. And as ... grow there are differences in brain development in children who develop bipolar disorder than children who do ...

  14. Brain Basics

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

  15. Brain Basics

    Full Text Available ... understanding of the brain than ever before. Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses magnetic fields to take pictures ...

  16. Brain Basics

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

  17. Brain surgery

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

  18. Radiosurgery for brain metastases: is whole brain radiation therapy necessary?

    Purpose: Because whole brain radiotherapy (WBRT) carries a significant risk of dementia in long-term survivors, it is desirable to determine if some patients with brain metastases may be managed with radiosurgery (RS) alone, reserving WBRT for salvage therapy as needed. To begin to approach this problem, we retrospectively reviewed freedom from brain failure/progression (Brain FFP) and survival of patients with newly-diagnosed solitary or multiple brain metastases treated with Gamma Knife RS ± WBRT. Materials and Methods: All patients treated at our institution with Gamma Knife RS for newly-diagnosed solitary or multiple (2-8) brain metastases from September 1991 through December 1995 were reviewed. Whether or not WBRT was given depended on physician preference and referral patterns. Brain FFP was measured from the date of RS until development of a new brain metastasis or progression of a treated metastasis, with censoring at the time of the last imaging study. Survival was measured from the date of RS until death or last clinical follow-up. Actuarial curves were estimated using the Kaplan-Meier method and compared with the log rank test. Multivariate analyses to adjust for known prognostic variables (age, KPS, history of extracranial metastases, and total target volume) were performed using the Cox proportional hazards model. Results: From September 1991-December 1995, 90 patients with newly-diagnosed brain metastases underwent RS. Three patients treated palliatively to a small component of their intracranial disease were excluded, leaving 54 treated with RS alone and 33 treated with RS + WBRT. Age ranged from 31-83 years (median, 59 years), KPS from 60-100 (median, 90), and total target volume from 0.15-26.1 cm3 (median, 5.5 cm3). Fifty patients had a history of extracranial metastases. Results are shown below. In the RS alone group, (22(54)) patients (41%) had a brain failure and (20(54)) (37%) died without evidence of brain failure. In the RS + WBRT group, (12

  19. A prospective study on concurrent chemotherapy and thoracic three - dimensional radiotherapy for stage IV non - small cell lung cancer (2) - The impact of different metastasis organs on survival

    Objective: To prospectively evaluate the survival of different metastasis organs with concurrent chemotherapy and thoracic three-dimensional radiotherapy (CCTTRT) for stage IV non-small cell lung cancer (NSCLC). Methods: Two hundred and one patients of stage IV NSCLC were enrolled from January, 2003 to July, 2010. Of the 182 patients eligible for analysis, The number of patients with single-organ metastasis or multiple-organ metastasis was 107 and 75, respectively. Patients were treated by platinum-based chemotherapy, the median number of cycle was 4. The median dose to planning target volume of primary tumor (DTPTV) was 63 Gy. Survival was calculated by Kaplan-Meier method and compared using the Logrank. Results: The follow-up rate of 201 patients was 97.5%. with 201, 170 and 134 patients finished 2 =10.10, P =0.001), respectively; compared with multi-organ metastasis, the 1-, 2-, and 3-year OS rate and MST of patients with bone, lung metastasis only was 58%, 25%, 16% and 14 months (χ2 =10.42, P=0.001) and 49%, 21%, 21% and 11 months (χ2 =6.39, P=0.011) respectively;patients with brain metastasis only did not show advantage of survival comparing with patients with multi-organ metastasis (49%, 8%, 0% and 12 months and 29%, 12%, 0% and 8 months,respectively; χ2 =0.71, P =0.401); the 1-, 2-, and 3-year OS rate and MST was 63%, 23%, 19% and 15 months and 42%, 15%, 0% and 10 months,respectively for patients with single-organ metastasis and multi-organ metastasis patients who accepted 4 - 5 cycles of chemotherapy (χ2 =6.47, P =0.011); for patients under the same metastasis and 4 - 5 cycles of chemotherapy, no matter whether single-organ or multiple-organ metastases, the 1 -, 2-, 3-year OS rate and MST of patients with enough radiotherapy on DTPTV ≥63 Gy were better than patients without enough radiotherapy (DTPTV 2 =4.73, P =0.030; 54%, 21%, 0% and 14.3 months and 29%, 10%, 0% and 7.6 months, respectively, χ2 =8.16, P =0.004). The MST of liver metastases was 6

  20. Pituitary metastasis of lung neuroendocrine carcinoma: case report and literature review.

    de Siqueira, Pedro Freire; Mathez, Andréia Latanza Gomes; Pedretti, Denize Borges; Abucham, Julio

    2015-12-01

    Metastasis to the pituitary gland is an unusual situation in clinical practice, but the frequency thereof is increasing due to the increased survival of cancer patients, and greater availability of imaging. In most cases, they are found between the sixth and seventh decades of life, as determined in image examination of patients with known malignant neoplasm, but, generally, asymptomatic with respect to pituitary involvement. The most common primary sites are breast in women and lung in men. We present the case of a 64-year-old patient with clinical visual changes, polyuria, polydipsia, and decreased level of consciousness whose tests showed pan-hypopituitarism, hypernatremia and low urine specific gravity, and extensive mass in sellar region. Diabetes insipidus was confirmed and treated, corticotrophic and thyroid deficits were corrected and then the patient underwent resection by transsphenoidal surgery. The histopathological and immunohistochemistry analysis revealed pituitary metastasis of lung neuroendocrine tumor. Subsequently, a chest CT scan showed pulmonary mass consistent with primary neoplasm. Despite the water and electrolyte correction and intravenous glucocorticoid replacement, the patient continued to show decreased level of consciousness due to compression of the brain stem by the pituitary mass, evolving to death. The purpose is to call attention to the differential diagnosis of invasive lesions of the sellar region, mainly in individuals over 50 years and/or when associated with diabetes insipidus, as it may be a case of metastasis, although there is no known primary neoplasm. PMID:26677090

  1. Brain mapping

    Blaž Koritnik

    2004-01-01

    Cartography of the brain ("brain mapping") aims to represent the complexities of the working brain in an understandable and usable way. There are four crucial steps in brain mapping: (1) acquiring data about brain structure and function, (2) transformation of data into a common reference, (3) visualization and interpretation of results, and (4) databasing and archiving. Electrophysiological and functional imaging methods provide information about function of the human brain. A prere...

  2. MicroRNA regulation network in colorectal cancer metastasis

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

    2014-01-01

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

  3. Molecular Mechanism Underlying Lymphatic Metastasis in Pancreatic Cancer

    Zhiwen Xiao

    2014-01-01

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

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

    Tashnin Rahman

    2015-01-01

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

  5. ARPP-19 promotes proliferation and metastasis of human glioma.

    Jiang, Tao; Zhao, Bing; Li, Xiaocan; Wan, Jinghai

    2016-09-01

    Glioma is the most common and aggressive type of human primary brain tumor with a poor outcome. The molecular mechanisms underlying glioma development and progression are still poorly understood. Recent studies have reported a novel role of ARPP-19 in the regulation of cell mitosis and cancer progression. However, no study has been carried out to determine the role of ARPP-19 in human glioma cells and assess the expression and clinical significance of ARPP-19 in human glioma. In this study, we systematically examined the role of ARPP-19 in glioma A172 cells and examined the expression of ARPP-19 and CD147 in 81 cases of human glioma tissue specimens and correlated them to clinicopathological parameters and patient survival. We found that ARPP-19 promoted both proliferation and metastasis of human glioma cells and the expression of ARPP-19 and CD147 in high-grade glioma was significantly higher than that in the low-grade glioma. Patients whose tumors were positive for expression of ARPP-19 or CD147 showed lower relapse-free survival and overall survival than patients whose tumors were negative for ARPP-19 or CD147, respectively. Pearson correlation analysis indicated that there was a statistically significant correlation between ARPP-19 and CD147. Expressions of ARPP-19 and CD147 may serve as biomarkers for high-grade glioma and poor patient survival. PMID:27380244

  6. Spinal Leptomeningeal Metastasis from Gastric Cancer: Case Report

    Çokmert, Suna; Doğanay, Latife; Paköz, Burak; Yüksel, Alper; Gezer, Emrah; Alakavuklar, Mehmet Niyazi

    2015-01-01

    Leptomeninges are a rare region for metastasis in solid tumors. The most common causes of leptomeningeal metastasis are breast cancer, lung cancer, melanoma and leukemia-lymphomas. Leptomeningeal metastasis associated with gastric cancer is an exceedingly rare condition but it is rapidly progressive and poor prognosis. The diagnosis is confirmed by examination of the cerebrospinal fluid and imaging methods. There are several treatment options for patients with LMC, including intrathecal chemo...

  7. Steps in Prostate Cancer Progression that lead to Bone Metastasis

    Jin, Jung-Kang; Dayyani, Farshid; Gallick, Gary E.

    2011-01-01

    Prostate cancer is a complex disease in which metastasis to the bone is the main cause of death. Initial stages of metastasis are generally similar to those for most solid tumors; however, the mechanisms that underlie the homing of prostate tumor cells to the bone remain incompletely understood. Prostate cancer bone metastasis is also a microenvironment-driven disease, involving bi-directional interactions between the tumor and the bone microenvironment. In this review, we discuss the current...

  8. Intraneural metastasis of gastric carcinoma leads to sciatic nerve palsy

    Ichikawa Jiro; Matsumoto Seiichi; Shimoji Takashi; Tanizawa Taisuke; Gokita Tabu; Hayakawa Keiko; Aoki Kaoru; Ina Saori; Kanda Hiroaki

    2012-01-01

    Abstract Background Soft tissue metastases, in particular intraneural metastasis, from any carcinomas seldom occur. To our knowledge, no case of sciatic nerve palsy due to intraneural metastasis of gastric carcinoma is reported in the literature. Case presentation A case is reported of a 82-year old woman with sciatic nerve palsy with intraneural metastasis of gastric carcinoma. Although she had undergone partial gastrectomy with T2b, N0, M0 two years ago and primary site was cured, she devel...

  9. Patrolling Monocytes Control Tumor Metastasis to the Lung

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

    2015-01-01

    The immune system plays an important role in regulating tumor growth and metastasis. For example, classical monocytes promote tumorigenesis and cancer metastasis; however, how nonclassical “patrolling” monocytes interact with tumors is unknown. Here we show that patrolling monocytes are enriched in the microvasculature of the lung and reduce tumor metastasis to lung in multiple mouse metastatic tumor models. Nr4a1-deficient mice, which specifically lack patrolling monocytes, showed increased ...

  10. Endothelial nitric oxide synthase mediates lymphangiogenesis and lymphatic metastasis

    Lahdenranta, Johanna; Hagendoorn, Jeroen; Padera, Timothy P; Hoshida, Tohru; Nelson, Gregory; Kashiwagi, Satoshi; Jain, Rakesh K.; Fukumura, Dai

    2009-01-01

    Lymphatic metastasis is a critical determinant of cancer prognosis. Recently, several lymphangiogenic molecules such as vafscular endothelial growth factor (VEGF)-C and -D were identified. However, the mechanistic understanding of lymphatic metastasis is still in infancy. Nitric oxide (NO) plays a crucial role in regulating blood vessel growth and function as well as lymphatic vessel function. NOS expression correlates with lymphatic metastasis. However, causal relationship between NOS and ly...

  11. trans-Bis(1,3-diphenylpropane-1,3-dionato(methanoloxidovanadium(IV methanol disolvate

    Carla Pretorius

    2012-12-01

    Full Text Available In the title compound, [V(C15H11O22O(CH3OH]·2CH3OH, the VIV atom is coordinated by two 1,3-diphenylpropane-1,3-dionate ligands and an oxide ligand in an axial position. The sixth position is occupied by the O atom of a methanol group bonded trans to the oxide atom. The octahedral geometry is significantly distorted, with the VIV atom lying 0.330 (3 Å above the equatorial plane formed by the O atoms of the two β-diketonate ligands. In the crystal, O—H...O hydrogen bonds between the coordinating methanol group in the complex and the two methanol solvent molecules lead to the formation of polymeric chains along the c-axis direction. Weak C—H...O contacts are also observed.

  12. Crystal structure of 2-(1,3-dioxoindan-2-ylisoquinoline-1,3,4-trione

    Raza Murad Ghalib

    2015-01-01

    Full Text Available In the title isoquinoline-1,3,4-trione derivative, C18H9NO5, the five-membered ring of the indane fragment adopts an envelope conformation with the nitrogen-substituted C atom being the flap. The planes of the indane benzene ring and the isoquinoline-1,3,4-trione ring make a dihedral angle of 82.06 (6°. In the crystal, molecules are linked into chains extending along the bc plane via C—H...O hydrogen-bonding interactions, enclosing R22(8 and R22(10 loops. The chains are further connected by π–π stacking interations, with centroid-to-centroid distances of 3.9050 (7 Å, forming layers parallel to the b axis.

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

    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.

  14. Is inositol (1,3,4,5)-tetrakisphosphate a new second messenger

    Hansen, C.A.; Williamson, J.R.

    1986-05-01

    Hormone-stimulated hydrolysis of inositol (Ins) lipids results in the rapid formation of Ins(1,4,5)P/sub 3/, the second messenger for intracellular Ca/sup 2 +/ mobilization. Recently, a more polar inositol phosphate, Ins(1,3,4,5)P/sub 4/ as well as its probable hydrolysis product Ins(1,3,4)P/sub 3/ have been reported to accumulate in carbachol-stimulated brain slices. Vasopressin addition to hepatocytes prelabeled with (/sup 3/H)-Ins also showed a rapid increase of Ins(1,3,4,5)P/sub 4/, which was similar to that of Ins(1,4,5)P/sub 3/, while the accumulation of Ins(1,3,4)P/sub 3/ was slower. In order to examine whether Ins(1,3,4,5)P/sub 4/ has any functional effects on Ca/sup 2 +/ homeostasis, it was synthesized enzymatically from (/sup 3/H)-Ins(1,4,5)P/sub 3/ using a partially purified phosphoinositol kinase activity from rat brain cortex. (/sup 3/H)-labeled inositol phosphates were separated by anion exchange chromatography and analyzed by HPLC using ammonium formate/phosphoric acid gradient elution. Preliminary experiments indicate that Ins(1,3,4,5)P/sub 4/ up to 10 ..mu..M does not release Ca/sup 2 +/ from vesicular pools in saponin-permeabilized hepatocytes. It has a slight inhibitory effect on Ins(1,4,5)P/sub 3/-induced Ca/sup 2 +/ release. The effect of Ins(1,3,4,5)P/sub 4/ on plasma membrane Ca/sup 2 +/ fluxes are presently being investigated.

  15. Prostatic adenocarcinoma with and without metastasis to bone in dogs

    The signalment, clinical signs, and histologic tumor pattern were compared retrospectively in 12 dogs having primary prostatic adenocarcinoma with (5 cases) and without metastasis (7 cases) to bone. Weight loss and lumbar pain were observed more frequently in dogs having prostatic adenocarcinoma with metastasis to bone. A distinctive histologic pattern was not associated with prostatic adenocarcinoma that had metastasized to bone. The alveolar papillary pattern was the predominant histologic type observed in both groups. Metastasis to extra pelvic bony sites included the scapulas, ribs, and digits. The results of this study indicate that skeletal metastasis was not uncommon in dogs having prostatic adenocarcinoma

  16. The Impact of the Size of Nodal Metastases on Recurrence Risk in Breast Cancer Patients With 1-3 Positive Axillary Nodes After Mastectomy

    Harris, Eleanor E.R., E-mail: Eleanor.harris@moffitt.org [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Freilich, Jessica [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Lin, Hui-Yi [Biostatistics Core, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Chuong, Michael [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Acs, Geza [Department of Anatomic Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States)

    2013-03-01

    Purpose: Use of postmastectomy radiation therapy (PMRT) in breast cancer patients with 1-3 positive nodes is controversial. The objective of this study was to determine whether the size of nodal metastases in this subset could predict who would benefit from PMRT. Methods and Materials: We analyzed 250 breast cancer patients with 1-3 positive nodes after mastectomy treated with contemporary surgery and systemic therapy at our institution. Of these patients, 204 did not receive PMRT and 46 did receive PMRT. Local and regional recurrence risks were stratified by the size of the largest nodal metastasis measured as less than or equal to 5 mm or greater than 5 mm. Results: The median follow-up was 65.6 months. In the whole group, regional recurrences occurred in 2% of patients in whom the largest nodal metastasis measured 5 mm or less vs 6% for those with metastases measuring greater than 5 mm. For non-irradiated patients only, regional recurrence rates were 2% and 9%, respectively. Those with a maximal nodal size greater than 5 mm had a significantly higher cumulative incidence of regional recurrence (P=.013). The 5-year cumulative incidence of a regional recurrence in the non-irradiated group was 2.7% (95% confidence interval [CI], 0.7%-7.2%) for maximal metastasis size of 5 mm or less, 6.9% (95% CI, 1.7%-17.3%) for metastasis size greater than 5 mm, and 16% (95% CI, 3.4%-36.8%) for metastasis size greater than 10 mm. The impact of the maximal nodal size on regional recurrences became insignificant in the multivariable model. Conclusions: In patients with 1-3 positive lymph nodes undergoing mastectomy without radiation, nodal metastasis greater than 5 mm was associated with regional recurrence after mastectomy, but its effect was modified by other factors (such as tumor stage). The size of the largest nodal metastasis may be useful to identify high-risk patients who may benefit from radiation therapy after mastectomy.

  17. Outcome of surgical resection for brain metastases and radical treatment of the primary tumor in Chinese non–small-cell lung cancer patients

    Li Z

    2015-04-01

    Full Text Available Zhenye Li,1,3,* Xiangheng Zhang,1,* Xiaobing Jiang,1 Chengcheng Guo,1 Ke Sai,1 Qunying Yang,1 Zhenqiang He,1 Yang Wang,1 Zhongping Chen,1 Wei Li,2 Yonggao Mou1 1Department of Neurosurgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 2Department of Anesthesiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 3Beijing Neurosurgical Institute, Capital Medical University, Beijing, People’s Republic of China *These authors have contributed equally to this work Purpose: Brain metastasis is the most common complication of brain cancer; nevertheless, primary lung cancer accounts for approximately 20%–40% of brain metastases cases. Surgical resection is the preferred treatment for brain metastases. However, no studies have reported the outcome of surgical resection of brain metastases from non–small-cell lung cancer (NSCLC in the People’s Republic of China. Moreover, the optimal treatment for primary NSCLC in patients with synchronous brain metastases is hitherto controversial. Patients and methods: We retrospectively analyzed the cases of NSCLC patients with brain metastases who underwent neurosurgical resection at the Sun Yat-sen University Cancer Center, and assessed the efficacy of surgical resection and the necessity of aggressive treatment for primary NSCLC in synchronous brain metastases patients. Results: A total of 62 patients, including 47 men and 15 women, with brain metastases from NSCLC were enrolled in the study. The median age at the time of craniotomy was 54 years (range 29–76 years. At the final follow-up evaluation, 50 patients had died. The median OS time was 15.1 months, and the survival rates were 70% and 37% at 1 and 2 years, respectively. The median OS

  18. Thermochemistry of 1,1,3,3-tetramethylguanidine and 1,1,3,3-tetramethylguanidinium nitrate

    Graphical abstract: - Highlights: • The enthalpy of formation of 1,1,3,3-tetramethylguanidinium nitrate was determined by combustion calorimetry. • The cohesive energy of liquid 1,1,3,3-tetramethylguanidinium nitrate was evaluated. • The crystal structure of 1,1,3,3-tetramethylguanidinium nitrate was determined by single crystal X-ray diffraction. • ΔfHmo (l/g) of 1,1,3,3-tetramethylguanidine (tmg) were obtained by solution and Calvet calorimetry. • ΔfHmo (g) calculated by the W1-F12 procedure was in excellent agreement with the corresponding experimental value. - Abstract: Considerable efforts have recently been made to investigate how the structure of protic ionic liquids determines some of their most important properties for technological applications (e.g. low vapour pressure, conductivity). In contrast, the assessment of cohesive energies (which are also linked to those properties) based on thermodynamic results is still practically unexplored. This problem is addressed here for 1,1,3,3-tetramethylguanidinium nitrate, [Htmg][NO3], through a combination of experimental and computational chemistry results at the reference temperature of 298.15 K. The standard molar enthalpies of formation, ΔfHmo([Htmg][NO3],cr)=-(311.8±2.3)kJ·mol-1, and fusion, ΔfusHmo([Htmg][NO3])=16.2±3.8kJ·mol-1, of solid 1,1,3,3-tetramethylguanidinium nitrate (form I polymorph) were obtained by combustion and differential scanning calorimetry, respectively. From these results ΔfHmo([Htmg][NO3],l)=-(295.6±4.4)kJ·mol-1 could be derived. Also determined were the standard molar enthalpies of formation, ΔfHmo(tmg, l)=7.7±2.8kJ·mol-1, and vaporisation, ΔvapHmo(tmg,l)=50.0±1.2kJ·mol-1, of 1,1,3,3-tetramethylguanidine, by reaction solution and Calvet-drop microcalorimetry, respectively, leading to ΔfHmo(tmg,g)=57.7±3.0kJ·mol-1. This result is in excellent agreement with ΔfHmo(tmg,g)=58.4±4.0kJ·mol-1, obtained from the ab initio calculation of the standard molar

  19. Synthesis of 14C-labeled hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX)

    14C-labeled hexahydro-1,3,5-trinitro-1,3,5-triazine (2, RDX) was prepared by nitrolysis of hexahydro-1,3,5-tripropionyl-1,3,5-triazine (1) for bioenvironmental studies. 1 was synthesized from paraformaldehyde and propionitrile by a modified method reported earlier. (Author)

  20. Identification of a seasonal pattern to brain metastases

    Sakellakis M

    2016-03-01

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

  1. Contemporary approaches for imaging skeletal metastasis

    David Ulmert; Lilja Solnes; Daniel LJ Thorek

    2015-01-01

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

  2. Choriocarcinoma: a rare case of stomach metastasis

    Raju Agarwal

    2014-06-01

    Full Text Available Choriocarcinoma is a rare form of cancer which commonly occurs in women of reproductive age, rarely in post-menopausal women and in women under 20 years of age. We report a rare case of uterine choriocarcinoma with stomach metastasis in a 29 year-old woman who presented with upper gastrointestinal symptoms. The presented case report emphasizes the need for innovative treatment approach and appropriate diagnostic technology to enable early diagnosis and correct treatment. Furthermore the case highlights the need for healthcare workers to consider rare causes of gastrointestinal signs and symptoms. [Int J Reprod Contracept Obstet Gynecol 2014; 3(3.000: 787-789

  3. Choroidal metastasis of a breast carcinoma

    The case of a 55-year-old woman with diagnosis of multinodular Grade II ductal infiltrating carcinoma in left breast was presented in this article. She presented with temporal visual field defect in her left eye. A choroidal metastatic tumor was diagnosed by indirect binocular ophthalmoscopy, confirmed by ocular echography. The primary tumor was removed by surgery and the choroidal lesion was treated with systemic chemotherapy, hormonal therapy and external beam radiation therapy. Six months after the treatment, the choroidal metastasis showed complete regression, and the best visual acuity of 20/20 was recovered, which was the initial value at the diagnosis of disease

  4. Monoclonal Antibody Testing for Cancer Metastasis

    1993-01-01

    Malignant cells are characterized by the ability to invade surrounding normal tissues. Tumor invasion is abetted by proteolytic enzymes that have been correlated with recurrent disease and metastasis. These enzymes are involved in a cascade of proteolytic interactions with other enzymes and inhibitors which allow cancer cells to dissolve surrounding extracellular matrix, thereby enabling the cells to rapidly invade adjacent tissues and migrate to metastatic sites distant from the primary tumor. Among these proteases are the plasminogen activators (PA), collagenase IV, faminase, and in some cases cathepsin D, which together mediate key steps in the invasion process of metastasis. Cells which have the selective advantage for invasion and metastasis are those capable of regulating their proteolytic activity and proliferation. Cells in the process of invasion would be probably down-regulated for proliferation, but subsequent to attachment and adhesion at a distant site, would then be in a proliferative mode, up-regulating DNA replication. Urokinase (uPA) can be present in the tissues in several molecular forms. The inactive proenzyme is a single chain protein (scuPA) that is cleaved at Lys. 158 to form the double chain, high molecular weight active form (HMW-uPA) of 54 kD. A low molecular weight form (LMW-uPA) can also be produced by cleavage of the HMW-U PA at Lys. 135 - Lys. 136 giving a 35 kD active enzyme. Recently, it has been shown that the HMW active form of urokinase, bound to the tumor cell membrane, is responsible for the local lysis of the extracellular matrix, hence the tissue invasion mechanism for metastasis (Andreasen et al, 19861. Receptor- (membrane) bound uPA is twice as efficient (catalytically) as free fluid-phase uPA. Tho unbound uPA and the LMW form is not responsible for most of the local dissolution of extracellular matrix in the immediate vicinity of the metastatic tumor cell. High levels of urokinase (greater than 3.49 ng/mg of total protein

  5. Preparation of layered oxide Li(Co1/3Ni1/3Mn1/3)O2 via the sol-gel process

    ZHANG Wen; LIU Hanxing; HU Chen; ZHU Xianjun; LI Yanxi

    2008-01-01

    To obtain homogenous layered oxide Li(Co1/3Ni1/3Ni1/3Mn1/3)O2 as a lithium insertion positive electrode material,the sol-gel process using citric acid as a chelating agent was applied.The material Li(Co1/3,Ni1/3Mn1/3)O2 was synthesized at different calcination temperatures.XRD experiment indicated that the hyered Li(Co1/3Ni1/3Mn1/3)O2material could he synthesized at a lower temperature of 800℃,and the oxidation state of Co,Ni,and Mn in the cathode confirmed by XPS were +3,+2,and +4,respectively.SEM observations showed that the synthesized material could form homogenous particle morphology with the particle size of about 200nm In spite of different calcination temperatures,the charge-discharge curves of all the samples for the initial cycle were similar,and the cathode synthesized at 900℃ showed a small irreversible capacity loss of 11.24% and a high discharge capacity of 212.2 mAh.g-1 in the voltage range of 2.9-4.6 V.

  6. Multikinase inhibitor regorafenib inhibits the growth and metastasis of colon cancer with abundant stroma.

    Takigawa, Hidehiko; Kitadai, Yasuhiko; Shinagawa, Kei; Yuge, Ryo; Higashi, Yukihito; Tanaka, Shinji; Yasui, Wataru; Chayama, Kazuaki

    2016-05-01

    Interaction between tumor cells and stromal cells plays an important role in the growth and metastasis of colon cancer. We previously found that carcinoma-associated fibroblasts (CAFs) expressed platelet-derived growth factor receptor-β (PDGFR-β) and that PDGFR targeted therapy using imatinib or nilotinib inhibited stromal reaction. Bone marrow-derived mesenchymal stem cells (MSCs) migrate to tumor stroma and differentiate into CAFs. A novel oral multikinase inhibitor regorafenib inhibits receptor tyrosine kinases expressed on stromal cells (vascular endothelial growth factor receptor 1-3, TIE2, PDGFR-β, and fibroblast growth factors) and tumor cells (c-KIT, RET, and BRAF). These molecules are involved in tumor growth, angiogenesis, lymphangiogenesis, and stromal activation. Therefore, we examined whether regorafenib impaired the tumor-promoting effect of CAFs/MSCs. KM12SM human colon cancer cells alone or KM12SM cells with MSCs were transplanted into the cecal wall of nude mice. Co-implantation of KM12SM cells with MSCs into the cecal wall of nude mice produced tumors with abundant stromal component and promoted tumor growth and lymph node metastasis. Single treatment with regorafenib inhibited tumor growth and metastasis by inhibiting both tumor cells and stromal reaction. This tumor-inhibitory effect of regorafenib was more obvious in tumors developed by co-implanting KM12SM cells with MSCs. Our data suggested that targeting of the tumor microenvironment with regorafenib affected tumor cell-MSC interaction, which in turn inhibited the growth and metastasis of colon cancer. PMID:26865419

  7. Brain Basics

    Full Text Available ... in Real Life Brain Research Glossary Brain Basics (PDF, 10 pages) Introduction Watch the Brain Basics video ... early brain development, and may also assist in learning and memory. ... rise to disabilities or diseases. neural circuit —A network of neurons ...

  8. Brain Basics

    Full Text Available ... than ever before. Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses magnetic fields to take pictures of the brain's structure, studies show that brain growth in children with autism appears to peak early. And as ...

  9. Brain Basics

    Full Text Available ... Research Modern research tools and techniques are giving scientists a more detailed understanding of the brain than ever before. Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses magnetic fields to take pictures of the brain's structure, studies ...

  10. Brain Basics

    Full Text Available ... Welcome. Brain Basics provides information on how the brain works, how mental illnesses are disorders of the brain, ... highly developed area at the front of the brain that, in humans, plays a role in executive functions such as ...

  11. Brain mapping

    Blaž Koritnik

    2004-08-01

    Full Text Available Cartography of the brain ("brain mapping" aims to represent the complexities of the working brain in an understandable and usable way. There are four crucial steps in brain mapping: (1 acquiring data about brain structure and function, (2 transformation of data into a common reference, (3 visualization and interpretation of results, and (4 databasing and archiving. Electrophysiological and functional imaging methods provide information about function of the human brain. A prerequisite for multisubject, multidimensional and multimodal mapping is transformation of individual images to match a standard brain template. To produce brain maps, color, contours, and other visual cues are used to differentiate metabolic rates, electrical field potentials, receptor densities, and other attributes of structure or function. Databases are used to organize and archive data records. By relating the maps to cognitive functions and psychological models, brain mapping offers a prerequisite for the understanding of organizational principles of the human brain.

  12. Quantitation of glial fibrillary acidic protein in human brain tumours

    Rasmussen, S; Bock, E; Warecka, K;

    1980-01-01

    The glial fibrillary acidic protein (GFA) content of 58 human brain tumours was determined by quantitative immunoelectrophoresis, using monospecific antibody against GFA. Astrocytomas, glioblastomas, oligodendrogliomas, spongioblastomas, ependymomas and medulloblastomas contained relatively high...... amounts of GFA, up to 85 times the concentration in parietal grey substance of normal human brain. GFA was not found in neurinomas, meningiomas, adenomas of the hypophysis, or in a single case of metastasis of adenocarcinoma. Non-glial tumours of craniopharyngioma and haemangioblastoma were infiltrated by...

  13. Cancer-associated fibroblasts promote hepatocellular carcinoma metastasis through chemokine-activated hedgehog and TGF-β pathways.

    Liu, Jiao; Chen, Sheng; Wang, Wei; Ning, Bei-Fang; Chen, Fei; Shen, Weifeng; Ding, Jin; Chen, Wansheng; Xie, Wei-Fen; Zhang, Xin

    2016-08-28

    Fibroblasts are rich in the surrounding microenvironment of hepatocellular carcinoma (HCC) because most HCCs occur in fibrotic or cirrhotic livers. However, the role of cancer-associated fibroblasts (CAFs) in HCC metastasis remains obscure. Here, we reported that CAFs promote the migration and invasion of HCC cells in vitro and facilitate the HCC metastasis to the bone, brain and lung in NOD/SCID mice. The RayBio human chemokine antibody array revealed that CAFs secret higher levels of CCL2, CCL5, CCL7 and CXCL16 than peri-tumor fibroblasts. CCL2 and CCL5 increase the migration but not the invasion of HCC cells, while CCL7 and CXCL16 promote both migration and invasion of HCC cells. Moreover, CCL2 and CCL5 stimulate the activation of the hedgehog (Hh) pathway, while CCL7 and CXCL16 enhance the activity of the transforming growth factor-β (TGF-β) pathway in HCC cells. The neutralizing antibodies of chemokines notably attenuate the effect of CAFs on HCC metastasis and compromised the activation of Hh and TGF-β pathways in HCC cells. In summary, CAF-secreted CCL2, CCL5, CCL7 and CXCL16 promote HCC metastasis through the coordinate activation of Hh and TGF-β pathways in HCC cells. PMID:27216982

  14. Synthesis and characterization of layered Li(Ni1/3Mn1/3Co1/3)O2 cathode materials by spray-drying method

    LIU Zhi-min; HU Guo-rong; PENG Zhong-dong; DENG Xin-rong; LIU Ye-xiang

    2007-01-01

    Spherical Li(Ni1/3Mn1/3Co1/3)O2 was prepared via the homogenous precursors produced by solution spray-drying method. The precursors were sintered at different temperatures between 600 and 1 000 ℃ for 10 h. The impacts of different sintering temperatures on the structure and electrochemical performances of Li(Ni1/3Mn1/3Co1/3)O2 were compared by means of X-ray diffractometry(XRD), scanning electron microscopy(SEM), and charge/discharge test as cathode materials for lithium ion batteries. The experimental results show that the spherical morphology of the spray-dried powers maintains during the subsequent heat treatment and the specific capacity increases with rising sintering temperature. When the sintering temperature rises up to 900 ℃, Li(Ni1/3Mn1/3Co1/3)O2 attains a reversible capacity of 153 mA·h/g between 3.00 and 4.35 V at 0.2C rate with excellent cyclability.

  15. Water quality criteria for hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX)

    Etnier, E.L.

    1989-04-01

    The occurrence of the munitions compound hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) in groundwater surrounding Army ammunition plants may result in contamination of local drinking water supplies. RDX exerts its primary toxic effect in humans on the central nervous system, but also involves gastrointestinal and renal effects. Symptomatic effects following acute exposure include hyperirritability, nausea, vomiting, generalized epileptiform seizures, and prolonged postictal confusion and amnesia. Health effects data were analyzed for RDX, and although no controlled human studies exist concerning the acute or chronic toxic effects of exposure to RDX, sufficient animal toxicity data are available to derive an ambient water quality criterion for the protection of human health. This paper summarizes the available literature on metabolism of RDX and human and animal toxicity. Based on noncarcinogenic mammalian toxicity data, and following the methodologies of the U.S. Environmental Protection Agency, an ambient water quality criterion for the protection of human health of 103 micrograms/liter is proposed for ingestion of drinking water and aquatic foodstuffs. A criterion of 105 micrograms/liter is proposed for ingestion of drinking water alone.54 references.

  16. Oxidation reactions of 1,3-diphenylpropane-1,3-dione

    Medha Rele; B S Patro; S Adhikari; G P Kalena; S Chattopadhyay; T Mukherjee

    2002-12-01

    The free radical scavenging properties and possible antioxidant activity of 1,3-diphenylpropane-1,3-dione (1) are reported. Pulse radiolysis technique was employed to study the one-electron oxidation of 1 with various radicals viz. CCl3O$_{2}^{\\bullet}$, N$_{3}^{\\bullet}$ and ${}^{\\bullet}$OH in homogeneous aqueous solution. All these radicals reacted with 1 under ambient conditions at almost diffusion controlled rates producing transient species with an absorption maximum around 420 nm that decayed at first order rates. The transient absorption peak was shifted in the case of CCl3OO$^{\\bullet}$ radical reaction with 1 due to change in the polarity of the medium. Formation of a stable product with a broad absorption band starting from 400 nm and cut off at 230 nm was observed in the oxidation of 1 with ${}^{\\bullet}$OH and ${}^{\\bullet}$N3 radicals. In a biological system also, 1 showed significant inhibitory activity against Fe2+-mediated lipid peroxidation. Based on these observations, a suitable mechanism for the oxidation of 1 has been proposed.

  17. Global secretome analysis identifies novel mediators of bone metastasis

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

    2012-01-01

    Bone is the one of the most common sites of distant metastasis of solid tumors.Secreted proteins are known to influence pathological interactions between metastatic cancer cells and the bone stroma.To comprehensively profile secreted proteins associated with bone metastasis,we used quantitative and non-quantitative mass spectrometry to globally analyze the secretomes of nine cell lines of varying bone metastatic ability from multiple species and cancer types.By comparing the secretomes of parental cells and their bone metastatic derivatives,we identified the secreted proteins that were uniquely associated with bone metastasis in these cell lines.We then incorporated bioinformatic analyses of large clinical metastasis datasets to obtain a list of candidate novel bone metastasis proteins of several functional classes that were strongly associated with both clinical and experimental bone metastasis.Functional validation of selected proteins indicated that in vivo bone metastasis can be promoted by high expression of (1) the salivary cystatins CST1,CST2,and CST4; (2) the plasminogen activators PLAT and PLAU; or (3) the collagen functionality proteins PLOD2 and COL6A1.Overall,our study has uncovered several new secreted mediators of bone metastasis and therefore demonstrated that secretome analysis is a powerful method for identification of novel biomarkers and candidate therapeutic targets.

  18. A Case of Sphenoid Sinus Metastasis in Hepatocellular Carcinoma.

    Lee, Tae Hoon; Rangan, Vikram; Khallafi, Hicham

    2016-06-01

    Sphenoid sinus metastasis from hepatocellular carcinoma (HCC) has been reported only rarely. We present a case of solitary sphenoid sinus metastasis of a 2.7 × 2.3 cm single HCC lesion. (Hepatology 2016;63:2050-2053). PMID:26928869

  19. Solitary Metastasis of Gastric Cancer to Fibula: A Case Report

    Gastric cancer is one of the most common and most fatal neoplasms in human. Its skeletal metastasis is less frequent, particularly when solitary. The objective of this article is to represent a case of solitary fibular metastasis from this cancer not reported before based on Medline search

  20. Hypoxia-induced metastasis model in embryonic zebrafish

    Rouhi, Pegah; Jensen, Lasse D.; Cao, Ziquan;

    2010-01-01

    early events of tumor cell invasion and dissemination in living animals. We recently developed a zebrafish metastasis model to dissect the detailed events of hypoxia-induced tumor cell invasion and metastasis in association with angiogenesis at the single-cell level. In this model, fluorescent Di...

  1. Global secretome analysis identifies novel mediators of bone metastasis.

    Blanco, Mario Andres; LeRoy, Gary; Khan, Zia; Alečković, Maša; Zee, Barry M; Garcia, Benjamin A; Kang, Yibin

    2012-09-01

    Bone is the one of the most common sites of distant metastasis of solid tumors. Secreted proteins are known to influence pathological interactions between metastatic cancer cells and the bone stroma. To comprehensively profile secreted proteins associated with bone metastasis, we used quantitative and non-quantitative mass spectrometry to globally analyze the secretomes of nine cell lines of varying bone metastatic ability from multiple species and cancer types. By comparing the secretomes of parental cells and their bone metastatic derivatives, we identified the secreted proteins that were uniquely associated with bone metastasis in these cell lines. We then incorporated bioinformatic analyses of large clinical metastasis datasets to obtain a list of candidate novel bone metastasis proteins of several functional classes that were strongly associated with both clinical and experimental bone metastasis. Functional validation of selected proteins indicated that in vivo bone metastasis can be promoted by high expression of (1) the salivary cystatins CST1, CST2, and CST4; (2) the plasminogen activators PLAT and PLAU; or (3) the collagen functionality proteins PLOD2 and COL6A1. Overall, our study has uncovered several new secreted mediators of bone metastasis and therefore demonstrated that secretome analysis is a powerful method for identification of novel biomarkers and candidate therapeutic targets. PMID:22688892

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

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

    2008-01-01

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

  3. Cod glycopeptide with picomolar affinity to galectin-3 suppresses T-cell apoptosis and prostate cancer metastasis.

    Guha, Prasun; Kaptan, Engin; Bandyopadhyaya, Gargi; Kaczanowska, Sabina; Davila, Eduardo; Thompson, Keyata; Martin, Stuart S; Kalvakolanu, Dhananjaya V; Vasta, Gerardo R; Ahmed, Hafiz

    2013-03-26

    Cancer metastasis and immune suppression are critical issues in cancer therapy. Here, we show that a β-galactoside-binding lectin [galectin-3 (gal3)] that recognizes the Thomsen-Friedenreich disaccharide (TFD, Galβ1,3GalNAc) present on the surface of most cancer cells is involved in promoting angiogenesis, tumor-endothelial cell adhesion, and metastasis of prostate cancer cells, as well as evading immune surveillance through killing of activated T cells. To block gal3-mediated interactions, we purified a glycopeptide from cod (designated TFD100) that binds gal3 with picomolar affinity. TFD100 blocks gal3-mediated angiogenesis, tumor-endothelial cell interactions, and metastasis of prostate cancer cells in mice at nanomolar levels. Moreover, apoptosis of activated T cells induced by either recombinant gal3 or prostate cancer patient serum-associated gal3 was inhibited at nanomolar concentration of TFD100. Because the gal3-TFD interaction is a key factor driving metastasis in most epithelial cancers, this high-affinity TFD100 should be a promising antimetastatic agent for the treatment of various cancers, including prostate adenocarcinoma. PMID:23479624

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

    NamPhongNguyen

    2013-11-01

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

  5. Seward, Alaska 1/3 arc-second DEM

    National Oceanic and Atmospheric Administration, Department of Commerce — The 1/3-second Seward Alaska Elevation Grid provides bathymetric data in ASCII raster format of 1/3-second resolution in geographic coordinates. This grid is...

  6. Guam 1/3 arc-second DEM

    National Oceanic and Atmospheric Administration, Department of Commerce — The 1/3-second Guam Elevation Grid provides bathymetric data in ASCII raster format of 1/3-second resolution in geographic coordinates. This grid is strictly for...

  7. Newport, Oregon 1/3 arc-second DEM

    National Oceanic and Atmospheric Administration, Department of Commerce — The 1/3-second Newport, Oregon Elevation Grid provides bathymetric data in ASCII raster format of 1/3-second resolution in geographic coordinates. This grid is...

  8. Southwestern Washington 1/3 arc-second DEM

    National Oceanic and Atmospheric Administration, Department of Commerce — The 1/3-second Southwest Washington Elevation Grid provides bathymetric data in ASCII raster format of 1/3-second resolution in geographic coordinates. This grid is...

  9. Seaside, Oregon 1/3 arc-second DEM

    National Oceanic and Atmospheric Administration, Department of Commerce — The 1/3-second Seaside Oregon Elevation Grid provides bathymetric data in ASCII raster format of 1/3-second resolution in geographic coordinates. This grid is...

  10. San Diego, California 1/3 arc-second DEM

    National Oceanic and Atmospheric Administration, Department of Commerce — The 1/3-second San Diego, California Elevation Grid provides bathymetric data in ASCII raster format of 1/3-second resolution in geographic coordinates. This grid...

  11. Choroid Melanoma Metastasis to Spine: A Rare Case Report

    Hiren Mandaliya

    2016-01-01

    Full Text Available Metastatic choroid melanoma is a highly malignant disease with a limited life expectancy. The liver is the most common site for metastasis of uveal melanoma followed by lung, bone, skin, and subcutaneous tissue. Metastasis from choroidal melanoma usually occurs within the first five years of treatment for primary tumours. Metastatic choroid melanoma to the spine/vertebrae is extremely rare. We report the first case of spinal metastasis from choroid melanoma in a 61-year-old man who had been treated for primary ocular melanoma three years earlier with radioactive plaque brachytherapy. Synchronously, at the time of metastasis, he was also diagnosed as having a new primary lung adenocarcinoma as well. The only other case reported on vertebral metastasis from malignant melanoma of choroid in literature in which primary choroid melanoma was enucleated.

  12. Angiosarcoma of the Thyroid and Regional Lymph Node Metastasis

    Lutfi Dogan

    2013-10-01

    Full Text Available Thyroid angiosarcomas are typically infiltrative and large tumors with very similar clinical findings of anaplastic carcinoma of thyroid. Early hematogenous metastasis is very frequent, but regional lymph node metastasis is quite rare. We present a case of angiosarcoma of the thyroid gland in a 68 years old man with regional lymph node metastasis. Total thyroidectomy with right modified radical neck dissection was applied. Four out of 19 lymph nodes dissected were seen to contain metastasis. Metastatic tumor was composed of sarcomatous areas containing large numbers of blood filled clefts. There after the surgery PET-CT was performed and multiple metastatic involvements were reported. Thyroid angiosarcomas are completely different tumors from angiomatoid anaplastic carcinomas. Longer survival with these tumors is only possible with agressive surgery and in case of regional LN metastasis, neck dissection should be done.

  13. Application of Proteomics in the Study of Tumor Metastasis

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

    2004-01-01

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

  14. Inflammation and Tumor Microenvironment in Lymph Node Metastasis

    In nearly all human cancers, the presence of lymph node (LN) metastasis increases clinical staging and portends worse prognosis (compared to patients without LN metastasis). Herein, principally reviewing experimental and clinical data related to malignant melanoma, we discuss diverse factors that are mechanistically involved in LN metastasis. We highlight recent data that link tumor microenvironment, including inflammation (at the cellular and cytokine levels) and tumor-induced lymphangiogenesis, with nodal metastasis. Many of the newly identified genes that appear to influence LN metastasis facilitate general motility, chemotactic, or invasive properties that also increase the ability of cancer cells to disseminate and survive at distant organ sites. These new biomarkers will help predict clinical outcome and point to novel future therapies in metastatic melanoma as well as other cancers

  15. 10 CFR 1.3 - Sources of additional information.

    2010-01-01

    .../cfr/. Final opinions made in the adjudication of cases are published in “Nuclear Regulatory Commission... 10 Energy 1 2010-01-01 2010-01-01 false Sources of additional information. 1.3 Section 1.3 Energy NUCLEAR REGULATORY COMMISSION STATEMENT OF ORGANIZATION AND GENERAL INFORMATION Introduction § 1.3...

  16. Production of α1,3-Galactosyltransferase–Deficient Pigs

    Phelps, Carol J.; Koike, Chihiro; Vaught, Todd D.; Boone, Jeremy; Wells, Kevin D.; Chen, Shu-Hung; Ball, Suyapa; Specht, Susan M.; Polejaeva, Irina A.; Monahan, Jeff A.; Jobst, Pete M.; Sharma, Sugandha B.; Lamborn, Ashley E.; Garst, Amy S.; Moore, Marilyn; Demetris, Anthony J.; Rudert, William A.; Bottino, Rita; Bertera, Suzanne; Trucco, Massimo; Starzl, Thomas E.; Dai, Yifan; Ayares, David L.

    2011-01-01

    The enzyme α1,3-galactosyltransferase (α1,3GT or GCTA1) synthesizes α1,3-galactose (α1,3Gal) epitopes (Galα1,3Galβ1,4GlcNAc-R), which are the major xenoantigens causing hyperacute rejection in pig-to-human xenotransplantation. Complete removal of α1,3Gal from pig organs is the critical step toward the success of xenotransplantation. We reported earlier the targeted disruption of one allele of the α1,3GT gene in cloned pigs. A selection procedure based on a bacterial toxin was used to select for cells in which the second allele of the gene was knocked out. Sequencing analysis demonstrated that knockout of the second allele of the α1,3GT gene was caused by a T-to-G single point mutation at the second base of exon 9, which resulted in inactivation of the α1,3GT protein. Four healthy α1,3GT double-knockout female piglets were produced by three consecutive rounds of cloning. The piglets carrying a point mutation in the α1,3GT gene hold significant value, as they would allow production of α1,3Gal-deficient pigs free of antibiotic-resistance genes and thus have the potential to make a safer product for human use. PMID:12493821

  17. FEATURES OF BILATERAL BREAST CANCER NODAL METASTASIS

    Ye. A. Fesik

    2014-01-01

    Full Text Available This article focuses on issues related to the identification and investigation of the lymph node metastases with bilateral breast cancer. The presence of metastases in the lymph nodes determines the stage of the disease, and introducing a form of tumor progression, characterizes the course and prognosis for the future in a specific patient. Thus, the identification of possible morphological and immunohistochemical characteristics of the tumor tissue and their comparison with the frequency and severity of regional lymph nodes would help to solve the problem of the identification of prognostic factors and markers associated with the risk of nodal metastasis in bilateral breast cancer. This work is relevant due to the fact that the literature on this issue to date are treated ambiguously, and answers to many questions, unfortunately, no.The authors performed a morphological study of the tumor tissue from 600 patients suffering from unilateral and bilateral breast cancer. To avoid false results were studied only cases corresponding to the histological type of invasive carcinoma of non-specific type. The study found that a greater number and a greater percentage of the affected lymph node metastases were observed in patients with bilaterally synchronous tumors. The patients of this group of metastatic lymph nodes was detected more frequently in the presence of infiltrative component of three or more types of structures with the presence of these discrete groups of tumor cells, and the observed maximum degree of inflammatory infiltration of the tumor stroma. In the group of patients with unilateral breast cancer nodal metastasis often detects when triple negative molecular genetic type of the lesion, with large amounts of tumor site, in the presence of infiltrative component of three or more types of structures with the obligatory presence of these microalveolar structures and discretely spaced groups of tumor cells and the highest severity of

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

    A. A. Tryakin

    2014-07-01

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

  19. Ten-Year Survival of a Patient Treated with Stereotactic Gamma Knife Radiosurgery for Brain Metastases from Colon Cancer with Ovarian and Lymph Node Metastases: A Case Report

    Morinaga, Nobuhiro; Tanaka, Naritaka; Shitara, Yoshinori; Ishizaki, Masatoshi; Yoshida, Takatomo; Kouga, Hideaki; Wakabayashi, Kazuki; Fukuchi, Minoru; Tsunoda, Yoshiyuki; Kuwano, Hiroyuki

    2016-01-01

    Brain metastasis from colorectal cancer is infrequent and carries a poor prognosis. Herein, we present a patient alive 10 years after the identification of a first brain metastasis from sigmoid colon cancer. A 39-year-old woman underwent sigmoidectomy for sigmoid colon cancer during an emergency operation for pelvic peritonitis. The pathological finding was moderately differentiated adenocarcinoma. Eleven months after the sigmoidectomy, a metastatic lesion was identified in the left ovary. De...

  20. Fractionated stereotactic radiotherapy for recurrent small cell lung cancer brain metastases after whole brain radiotherapy

    Objective: Evaluation the Fractionated Stereotactic Radiotherapy (FSRT) for the patients with small-cell lung cancer (SCLC) after the whole brain radiotherapy (WBRT) failure. Methods: We retrospectively analyzed 35 patients with brain metastases from small-cell lung cancer treated with linear accelerator FSRT after the WBRT failure. Multivariate analysis was used to determine significant prognostic factor related to survival. Results: The following-up rate was 100%. The median following-up time was 11 months. The median over-all survival (OS) time was 10.3(1 -30) months after FSRT. Controlled extra cranial disease was the only identified significant predictor of increased median OS time (χ2 =4.02, P =0.045 ). The median OS time from the diagnosis of brain metastasis was 22 (6 - 134 ) months. 14 patients died from brain metastasis, 14 from extra-cranial progression, 1 from leptomeningeal metastases, and 3 from other causes. Local control at 6 months and 12 months was 91% and 76%, respectively. No significant late complications. New brain metastases outside of the treated area developed in 17% of patients at a median time of 4(2 -20) months; all patients had received previous WBRT. Conclusions: Fractionated stereotactic radiotherapy was safe and effective treatment for recurrent small-cell lung carcinoma brain metastases. (authors)