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Sample records for leptomeningeal metastasis treated

  1. Cranial computed tomographic abnormalities in leptomeningeal metastasis

    SciTech Connect

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

    1984-11-01

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

  2. Anaplastic extramedullary cervical ependymoma with leptomeningeal metastasis.

    PubMed

    Pomeraniec, I J; Dallapiazza, R F; Sumner, H M; Lopes, M B; Shaffrey, C I; Smith, J S

    2015-12-01

    We present a rare extramedullary ependymoma with diffuse spinal metastatic disease, and review the previous reports of extramedullary spinal ependymomas. Ependymomas are the most common intramedullary spinal cord tumor in adults. These tumors rarely present as extramedullary masses. We treated a 23-year-old man with a history of progressive neck, shoulder and arm pain, with sensory and motor symptoms in the C7 dermatome. MRI of the cervical spine demonstrated a ventral contrast-enhancing lesion with evidence of enhancement along the dura and spinal cord of the upper cervical spine, thoracic spine, and cauda equina. He underwent a tumor debulking procedure without complications. Following surgery, he received craniospinal radiation to treat the remaining tumor and diffuse leptomeningeal disease. The final pathology of the tumor revealed that is was a World Health Organization Grade III anaplastic ependymoma. At the 1 year follow-up, the patient had stable imaging and had returned to his preoperative functional status. Of the 19 reported patients with primary intradural, extramedullary spinal ependymomas, two had extradural components and seven had anaplastic grades. Only one tumor with an anaplastic grade resulted in metastatic disease, but without spinal recurrence. To our knowledge, this is the first report of an intradural, extramedullary spinal ependymoma with an anaplastic grade, presenting with concomitant diffuse, nodular leptomeningeal metastasis involving the upper cervical spine, thoracic spine, conus medullaris, and cauda equina. Similar to the treatment of intramedullary ependymomas with metastasis, this patient underwent an aggressive debulking procedure followed by radiation therapy to the entire neuroaxis.

  3. Durable response of breast cancer leptomeningeal metastasis to capecitabine monotherapy

    PubMed Central

    Rogers, Lisa R.; Remer, Sandra E.; Tejwani, Sheela

    2004-01-01

    We report a durable (12-month) response to capecitabine monotherapy, shown clinically, by MRI, and by cerebrospinal fluid analysis, in a patient with leptomeningeal metastasis from breast cancer. PMID:14769142

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

    PubMed

    Stark, Andreas M; Mehdorn, H Maximilian

    2013-08-01

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

  5. Leptomeningeal metastasis from gynecologic cancers diagnosed by brain MRI.

    PubMed

    Toyoshima, Masafumi; Tsuji, Keita; Shigeta, Shogo; Tokunaga, Hideki; Ito, Kiyoshi; Watanabe, Yoh; Yoshinaga, Kosuke; Otsuki, Takeo; Niikura, Hitoshi; Yaegashi, Nobuo

    Leptomeningeal metastasis (LM) is rarely observed in gynecologic cancers. As gadolinium-enhanced magnetic resonance imaging (Gd-MRI) is highly effective for diagnosing LM, the aim of this study is to describe the clinical behaviors and outcomes of LM patients who were diagnosed by Gd-MRI. After securing institutional review board approvals, we retrospectively reviewed patient records. Eight patients were found to have LM from gynecological malignancies. Primary tumors included three ovarian cancers, one tubal cancer, one peritoneal cancer, two endometrial cancers, and one cervical cancer. Gd-MRI of the brain and the spine is indicated as the high-priority inspection for the diagnosis of this devastating complication.

  6. Cranial and spinal leptomeningeal dissemination in esthesioneuroblastoma: Two reports of distant central nervous system metastasis and rationale for treatment

    PubMed Central

    Sivakumar, Walavan; Oh, Nathan; Cutler, Aaron; Colman, Howard; Couldwell, William T.

    2015-01-01

    Background: Esthesioneuroblastoma is a locally aggressive cancer of the nasal cavity. While systemic metastasis can occur in 10-30% of patients, there are only six reported cases of distal metastasis from leptomeningeal dissemination. Case Description: The authors report two cases of esthesioneuroblastoma treated previously with multimodal therapy in which distal metastatic recurrence was found and describe their treatment protocol, which has resulted in long-term success. Conclusion: Understanding the drivers of leptomeningeal dissemination in more prevalent primary neuroectodermal tumors may hold the key to developing successful treatment algorithms for this disease. PMID:26682087

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

    PubMed Central

    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 true vocal cord plegia. PMID:23174999

  8. Diagnosis and treatment patterns for patients with leptomeningeal metastasis from solid tumors across Europe.

    PubMed

    Le Rhun, Emilie; Rudà, Roberta; Devos, Patrick; Hoang-Xuan, Khê; Brandsma, Dieta; Pérez Segura, Pedro; Soffietti, Riccardo; Weller, Michael

    2017-06-01

    Leptomeningeal metastases are a late manifestation of systemic cancer which affects up to 10% of patients with solid tumors. Prognosis is poor, and overall survival at 1 year is only approximately 10%. Management depends mainly on general and neurological condition, primary tumor, and patterns of metastasis, notably absence or presence of concurrent systemic or solid brain metastases. Here we set out to characterize current practice patterns of diagnosis and treatment of patients with leptomeningeal metastasis in Europe. We prepared a web-based survey including 25 simple or multiple choices questions on best practice supplemented by eight case vignettes with various diagnosis and management options. The survey was sent to the membership of the European Association of Neuro-Oncology and the European Organisation for Research and Treatment of Cancer Brain Tumor Group. Between April 7, 2016 and August 8, 2016, 224 colleagues from 26 countries initiated the survey, 115 colleagues completed the whole survey. There were major differences both in the general diagnostic and therapeutic approach, e.g., regarding the use of cerebrospinal fluid (CSF) flow studies, intra-CSF chemotherapy, various types of radiotherapy, and even more so when selecting decisions on diagnostic and therapeutic measures for single case vignettes. Diagnosis and treatment decisions for patients with leptomeningeal metastasis from solid tumors vary widely across Europe. Standardization of diagnosis and evaluation tools as well as controlled studies to improve the level of evidence for all therapeutic approaches to LM are required.

  9. Nimotuzumab treatment and outcome analysis in patients with leptomeningeal metastasis from nonsmall cell lung cancer.

    PubMed

    Ju, Yanfang; Wang, Jinliang; Sun, Shengjie; Jiao, Shunchang

    2016-12-01

    Leptomeningeal metastasis (LM) leades a devastating consequence in patients with nonsmall cell lung cancer(NSCLC). Treatment is very limited for patients with LM. We introduced to use nimotuzumab (also known as h-R3) combined with methotrexate for treating LM in NSCLC patients. In the present report, twenty patients with LM of NSCLC were included, and the clinicopathology information and outcomes after treatment were analyzed. All the twenty patients with LM were lung adenocarcinoma. Thirteen patients had poor Eastern Cooperative Oncology Group performance status (≥ 3) before treatment, fifteen patients received combined administration of h-R3 and methotrexate, and another five patients received h-R3 treatment alone. The median survival time after the diagnosis of LM was 5 months (range, 2.4-7.6 months) for these twenty patients. The mean cerebrospinal fluid opening pressure was 270mmH2O before treatment and decreased significantly after treatment (140 mmH2O) (P < 0.001). Associated symptoms were relieved quickly after one or two cycles of intrathecal therapy. These findings indicated that nimotuzumab might be a potential drug for treatment of LM in NSCLC patients.

  10. ATOH1 Promotes Leptomeningeal Dissemination and Metastasis of Sonic Hedgehog Subgroup Medulloblastomas.

    PubMed

    Grausam, Katie B; Dooyema, Samuel D R; Bihannic, Laure; Premathilake, Hasitha; Morrissy, A Sorana; Forget, Antoine; Schaefer, Amanda M; Gundelach, Justin H; Macura, Slobodan; Maher, Diane M; Wang, Xin; Heglin, Alex H; Ge, Xijin; Zeng, Erliang; Puget, Stephanie; Chandrasekar, Indra; Surendran, Kameswaran; Bram, Richard J; Schüller, Ulrich; Talyor, Michael D; Ayrault, Olivier; Zhao, Haotian

    2017-07-15

    Medulloblastoma arising from the cerebellum is the most common pediatric brain malignancy, with leptomeningeal metastases often present at diagnosis and recurrence associated with poor clinical outcome. In this study, we used mouse medulloblastoma models to explore the relationship of tumor pathophysiology and dysregulated expression of the NOTCH pathway transcription factor ATOH1, which is present in aggressive medulloblastoma subtypes driven by aberrant Sonic Hedgehog/Patched (SHH/PTCH) signaling. In experiments with conditional ATOH1 mouse mutants crossed to Ptch1(+/-) mice, which develop SHH-driven medulloblastoma, animals with Atoh1 transgene expression developed highly penetrant medulloblastoma at a young age with extensive leptomeningeal disease and metastasis to the spinal cord and brain, resembling xenografts of human SHH medulloblastoma. Metastatic tumors retained abnormal SHH signaling like tumor xenografts. Conversely, ATOH1 expression was detected consistently in recurrent and metastatic SHH medulloblastoma. Chromatin immunoprecipitation sequencing and gene expression profiling identified candidate ATOH1 targets in tumor cells involved in development and tumorigenesis. Among these targets specific to metastatic tumors, there was an enrichment in those implicated in extracellular matrix remodeling activity, cytoskeletal network and interaction with microenvironment, indicating a shift in transcriptomic and epigenomic landscapes during metastasis. Treatment with bone morphogenetic protein or SHH pathway inhibitors decreased tumor cell proliferation and suppressed metastatic tumor growth, respectively. Our work reveals a dynamic ATOH1-driven molecular cascade underlying medulloblastoma metastasis that offers possible therapeutic opportunities. Cancer Res; 77(14); 3766-77. ©2017 AACR. ©2017 American Association for Cancer Research.

  11. Concurrent intrathecal methotrexate and liposomal cytarabine for leptomeningeal metastasis from solid tumors: a retrospective cohort study.

    PubMed

    Scott, Brian J; van Vugt, Vincent A; Rush, Toni; Brown, Tiffany; Chen, Clark C; Carter, Bob S; Schwab, Richard; Fanta, Paul; Helsten, Teresa; Bazhenova, Lyudmila; Parker, Barbara; Pingle, Sandeep; Saria, Marlon G; Brown, Bradley D; Piccioni, David E; Kesari, Santosh

    2014-09-01

    Leptomeningeal metastasis (LM) from solid tumors is typically a late manifestation of systemic cancer with limited survival. Randomized trials comparing single agent intrathecal methotrexate to liposomal cytarabine have shown similar efficacy and tolerability. We hypothesized that combination intrathecal chemotherapy would be a safe and tolerable option in solid tumor LM. We conducted a retrospective cohort study of combination IT chemotherapy in solid tumor LM at a single institution between April 2010 and July 2012. In addition to therapies directed at active systemic disease, each subject received IT liposomal cytarabine plus IT methotrexate with dexamethasone premedication. Patient characteristics, survival outcomes and toxicities were determined by systematic chart review. Thirty subjects were treated during the study period. The most common cancer types were breast 15 (50 %), glioblastoma 6 (20 %), and lung 5 (17 %). Cytologic clearance was achieved in 6 (33 %). Median non-glioblastoma overall survival was 30.2 weeks (n = 18; range 3.9-73.4), and did not differ significantly by tumor type. Median time to neurologic progression was 7 weeks (n = 8; range 0.9-57), with 10 subjects (56 %) experiencing death from systemic disease without progression of LM. Age less than 60 was associated with longer overall survival (p = 0.01). Six (21 %) experienced grade III toxicities during treatment, most commonly meningitis 2 (7 %). Combination IT chemotherapy was feasible in this small retrospective cohort. Prospective evaluation is necessary to determine tolerability, the impact on quality of life and neurocognitive outcomes or any survival benefit when compared to single agent IT chemotherapy.

  12. Leptomeningeal metastasis in breast cancer – a systematic review

    PubMed Central

    Scott, Brian J.; Oberheim-Bush, Nancy A.; Kesari, Santosh

    2016-01-01

    Background There is limited data on the impact of specific patient characteristics, tumor subtypes or treatment interventions on survival in breast cancer LM. Methods A systematic review was conducted to assess the impact of hormone receptor and HER-2 status on survival in breast cancer LM. A search for clinical studies published between 1/1/2007 and 7/1/2012 and all randomized-controlled trials was performed. Survival data from all studies are reported by study design (prospective trials, retrospective cohort studies, case studies). Results A total of 36 studies with 851 LM breast cancer subjects were identified. The majority (87%) were treated with intrathecal chemotherapy. Pooled median overall survival ranged from 14.9-18.1 weeks depending on study type. Breast cancer LM survival (15 weeks) was longer than other solid tumor LM 8.3 weeks and lung cancer LM 8.7 weeks, but shorter than LM lymphoma (15.4 versus 24.2 weeks). The impact of hormone receptor and HER-2 status on survival could not be determined. Conclusions A median overall survival of 15 weeks in prospective studies of breast cancer LM provides a historical comparison for future LM breast cancer trials. Other outcomes including the impact of molecular status on survival could not be determined based on available studies. PMID:26543235

  13. Diagnostic Value of CYFRA 21-1 in the Cerebrospinal Fluid for Leptomeningeal Metastasis

    PubMed Central

    Zhang, Zhen; Shi, Qiang; Hao, Jing; Zhao, Na; Liu, Zhijie

    2017-01-01

    Cerebrospinal fluid (CSF) cytology has low sensitivity for leptomeningeal metastasis (LM); thus, new markers are needed to improve the diagnostic accuracy of LM. We measured carcinoembryonic antigen (CEA) and cytokeratin 19 fragments (CYFRA 21-1) in paired samples of CSF and serum from patients with LM and patients with nonmalignant neurological diseases (NMNDs) as controls. Receiver operating curve analysis was performed to assess their diagnostic accuracy for LM. In patients with NMNDs, CEA and CYFRA 21-1 levels in the CSF were significantly lower than the serum levels. In patients with LM, there was no significant difference between the CSF and serum CEA levels, whereas the CYFRA 21-1 levels were significantly higher in the CSF than the serum. CSF/serum quotients of CYFRA 21-1 were higher than those of CEA in patients with LM and patients with NMNDs. CSF CYFRA 21-1 and CSF/serum quotient of CYFRA 21-1 had high accuracy for differentiating LM from NMNDs that was similar to CSF CEA and CSF/serum quotient of CYFRA 21-1, whereas serum CYFRA 21-1 is of poor diagnostic value. Measurement of CSF CYFRA 21-1 should not be overlooked in patients with suspected LM, even if the serum CYFRA 21-1 level is within normal limits. PMID:28298807

  14. Potential of F-18 PET/CT in the Detection of Leptomeningeal Metastasis.

    PubMed

    Short, Ryan G; Bal, Susan; German, John P; Poelstra, Raymond J; Kardan, Arash

    2014-12-01

    Leptomeningeal metastasis (LM) is a rare but increasingly common condition in which malignant cells migrate to the meninges. The gold standard for diagnosing LM is detection of cancer cells in the cerebrospinal fluid (CSF). Contrast enhanced-magnetic resonance imaging (CE-MRI) is also used to diagnose LM. We describe a case of LM in which CE-MRI of the neuroaxis was initially negative for meningeal enhancement but F-18 fluorodeoxyglucose positron-emission tomography/computed tomography (F-18 FDG PET/CT) revealed hypermetabolism within the lumbar spinal canal. Positive F-18 FDG PET findings have rarely been reported in LM and, to our knowledge, have never been reported in the context of initially negative CE-MRI scanning of the neuroaxis. F-18 FDG PET/CT may represent an alternative modality for diagnosing LM in patients who are unable to undergo CE-MRI and/or LP or in patients for whom initial CE-MRI and/or LP are negative for LM.

  15. Rare cell capture technology for the diagnosis of leptomeningeal metastasis in solid tumors

    PubMed Central

    Nayak, Lakshmi; Fleisher, Martin; Gonzalez-Espinoza, Rita; Lin, Oscar; Panageas, Katherine; Reiner, Anne; Liu, Chhui-Mei; DeAngelis, Lisa M.

    2013-01-01

    Objective: To evaluate the utility of rare cell capture technology (RCCT) in the diagnosis of leptomeningeal metastasis (LM) from solid tumors through identification of circulating tumor cells (CTCs) in the CSF. Methods: In this pilot study, CSF samples from 60 patients were analyzed. The main patient cohort consisted of 51 patients with solid tumors undergoing lumbar puncture for clinical suspicion of LM. Those patients underwent initial MRI evaluation and had CSF analyzed through conventional cytology and for the presence of CTCs using RCCT, based on immunomagnetic platform enrichment utilizing anti–epithelial cell adhesion molecule antibody-covered magnetic nanoparticles. An additional 9 patients with CSF pleocytosis but without solid tumors were separately analyzed to ensure accurate differentiation between CTCs and leukocytes. Results: Among the 51 patients with solid tumors, 15 patients fulfilled criteria for LM. CSF CTCs were found in 16 patients (median 20.7 CTCs/mL, range 0.13 to >150), achieving a sensitivity of 100% as compared with 66.7% for conventional cytology and 73.3% for MRI. One patient had a false-positive CSF CTC result (specificity = 97.2%); however, that patient eventually met LM criteria 6 months after the tap. CSF CTCs were not found in any of the additional 9 patients with CSF pleocytosis. Conclusion: RCCT is an accurate, novel method for the detection of LM in solid tumors, potentially providing earlier diagnostic confirmation and sparing patients from repeat lumbar punctures. PMID:23553479

  16. Leptomeningeal metastasis as initial manifestation of signet ring colorectal adenocarcinoma: a case report with review of literature

    PubMed Central

    Assi, Rita; Hamieh, Lana; Mukherji, Deborah; Haydar, Ali; Temraz, Sally; El-Dika, Imane

    2015-01-01

    Leptomeningeal carcinomatosis (LMC) is an exceedingly rare event especially as a first manifestation of an occult primary colorectal cancer and even when there is a known history of malignancy. Sensorineural hearing loss is by itself an unusual isolated presentation of LMC with unsolved pathophysiology in this setting. In this paper, we report such a case and review the literature for similar cases, focusing on postulated mechanisms of spread. In view of the poor prognosis they carry, we highly recommend that physicians be aware of the risk of rare metastasis from colorectal adenocarcinoma in order to establish an early confirmative diagnosis. PMID:26697206

  17. Risk of Leptomeningeal Disease in Patients Treated With Stereotactic Radiosurgery Targeting the Postoperative Resection Cavity for Brain Metastases

    SciTech Connect

    Atalar, Banu; Modlin, Leslie A.; Choi, Clara Y.H.; Adler, John R.; Gibbs, Iris C.; Chang, Steven D.; Harsh, Griffith R.; Li, Gordon; Nagpal, Seema; Hanlon, Alexandra; Soltys, Scott G.

    2013-11-15

    Purpose: We sought to determine the risk of leptomeningeal disease (LMD) in patients treated with stereotactic radiosurgery (SRS) targeting the postsurgical resection cavity of a brain metastasis, deferring whole-brain radiation therapy (WBRT) in all patients. Methods and Materials: We retrospectively reviewed 175 brain metastasis resection cavities in 165 patients treated from 1998 to 2011 with postoperative SRS. The cumulative incidence rates, with death as a competing risk, of LMD, local failure (LF), and distant brain parenchymal failure (DF) were estimated. Variables associated with LMD were evaluated, including LF, DF, posterior fossa location, resection type (en-bloc vs piecemeal or unknown), and histology (lung, colon, breast, melanoma, gynecologic, other). Results: With a median follow-up of 12 months (range, 1-157 months), median overall survival was 17 months. Twenty-one of 165 patients (13%) developed LMD at a median of 5 months (range, 2-33 months) following SRS. The 1-year cumulative incidence rates, with death as a competing risk, were 10% (95% confidence interval [CI], 6%-15%) for developing LF, 54% (95% CI, 46%-61%) for DF, and 11% (95% CI, 7%-17%) for LMD. On univariate analysis, only breast cancer histology (hazard ratio, 2.96) was associated with an increased risk of LMD. The 1-year cumulative incidence of LMD was 24% (95% CI, 9%-41%) for breast cancer compared to 9% (95% CI, 5%-14%) for non-breast histology (P=.004). Conclusions: In patients treated with SRS targeting the postoperative cavity following resection, those with breast cancer histology were at higher risk of LMD. It is unknown whether the inclusion of whole-brain irradiation or novel strategies such as preresection SRS would improve this risk or if the rate of LMD is inherently higher with breast histology.

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

    PubMed Central

    2012-01-01

    About 20% to 40% of patients with non-small cell lung cancer (NSCLC) will develop brain metastases during the natural course of their disease. The prognosis for such patients is very poor with limited survival. In addition to the standard whole brain radiation therapy (WBRT), some studies have shown that chemotherapy drugs and/or epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) can improve the outcome of these patients. Here, we report a stage IIIA patient who developed multiple brain metastases one year after operation. Oral gefitinib with concurrent WBRT were given as first-line therapy. Complete response and a 50-month progression-free survival (PFS) were obtained. Double dosage of gefitinib (500 mg per day) together with pemetrexed were given as the second-line therapy after the patient developed new brain lesions and leptomeningeal metastasis during the maintenance therapy of gefitinib. The PFS for the second-line therapy was six months. In total, the patient obtained an overall survival of 59 months since the first diagnosis of brain metastases. Mutational analysis showed a 15-nucleotide deletion and a missense mutation in exon 19 of the EGFR gene, and a missense mutation at codon 12 of the K-ras gene. These underlying genetic changes might partially explain the long-term survival of this patient after brain metastases when treated with concurrent or sequential therapies of EGFR-TKI, radiotherapy and chemotherapy. PMID:23134665

  19. Development of a new method for identification and quantification in cerebrospinal fluid of malignant cells from breast carcinoma leptomeningeal metastasis

    PubMed Central

    2012-01-01

    Background The diagnosis of leptomeningeal metastasis (LM) in patients with solid tumors remains difficult. The usual diagnostic methods of cytomorphological assessment of cerebro-spinal fluid (CSF) and gadolinium enhanced MRI of the entire neuraxis lack both specificity and sensitivity. The Veridex CellSearch® technology has been designed for the detection of circulating tumor cells (CTC) in blood from cancer patients and validated for the follow-up and prognosis of breast, prostate, colorectal, and lung cancer. Our aim was to adapt this technology for the detection and the enumeration of tumor cells in the CSF of breast cancer patients presenting with LM. Methods On the occasion of a randomized phase III study evaluating the role of the intrathecal treatment in LM from breast cancer (DEPOSEIN, EudraCT N°: 2010-023134-23), the CellSearch® technology was adapted to direct enrichment, enumeration and visualization of tumor cells in 5 mL CSF samples, collected on CellSave® Preservative Tubes and analyzed within 3 days after CSF sampling. Results Sixteen CSF of 8 patients with primary breast cancer presenting with LM were studied. EpCAM+/cytokeratin + cells with typical morphology could be observed and enumerated sequentially with reproducible results in low or elevated numbers in 8 patients. Conclusion This methodology, established on a limited volume of sample and allowing delayed processing, could prove of great interest in the diagnosis and follow-up of cancer patients with LM, especially to appreciate the efficacy of chemotherapy. PMID:23145812

  20. Experimental Treatments for Leptomeningeal Metastases From Solid Malignancies.

    PubMed

    Sahebjam, Solmaz; Forsyth, Peter A; Smalley, Keiran S; Tran, Nam D

    2017-01-01

    Leptomeningeal metastasis is a consequence of advanced solid malignancies and has limited treatment options. It is possible that it is becoming more common as the leptomeninges act as a sanctuary site for recurrence from systemic cancer. Potential targeted and immunotherapy agents for the most common types of solid-tumor leptomeningeal metastasis are reviewed, as are their dosing/delivery strategies and novel, immunological approaches. Historically, patients with leptomeningeal metastasis have been excluded from clinical trials, and data on the management of leptomeningeal metastasis come from single case reports and retrospective analyses. For the first time ever, published reports suggest the tide may be turning in this challenging disease.

  1. Detection of Leptomeningeal Metastasis by Contrast-Enhanced 3D T1-SPACE: Comparison with 2D FLAIR and Contrast-Enhanced 2D T1-Weighted Images

    PubMed Central

    Gil, Bomi; Hwang, Eo-Jin; Lee, Song; Jang, Jinhee; Jung, So-Lyung; Ahn, Kook-Jin; Kim, Bum-soo

    2016-01-01

    Introduction To compare the diagnostic accuracy of contrast-enhanced 3D(dimensional) T1-weighted sampling perfection with application-optimized contrasts by using different flip angle evolutions (T1-SPACE), 2D fluid attenuated inversion recovery (FLAIR) images and 2D contrast-enhanced T1-weighted image in detection of leptomeningeal metastasis except for invasive procedures such as a CSF tapping. Materials and Methods Three groups of patients were included retrospectively for 9 months (from 2013-04-01 to 2013-12-31). Group 1 patients with positive malignant cells in CSF cytology (n = 22); group 2, stroke patients with steno-occlusion in ICA or MCA (n = 16); and group 3, patients with negative results on MRI, whose symptom were dizziness or headache (n = 25). A total of 63 sets of MR images are separately collected and randomly arranged: (1) CE 3D T1-SPACE; (2) 2D FLAIR; and (3) CE T1-GRE using a 3-Tesla MR system. A faculty neuroradiologist with 8-year-experience and another 2nd grade trainee in radiology reviewed each MR image- blinded by the results of CSF cytology and coded their observations as positives or negatives of leptomeningeal metastasis. The CSF cytology result was considered as a gold standard. Sensitivity and specificity of each MR images were calculated. Diagnostic accuracy was compared using a McNemar’s test. A Cohen's kappa analysis was performed to assess inter-observer agreements. Results Diagnostic accuracy was not different between 3D T1-SPACE and CSF cytology by both raters. However, the accuracy test of 2D FLAIR and 2D contrast-enhanced T1-weighted GRE was inconsistent by the two raters. The Kappa statistic results were 0.657 (3D T1-SPACE), 0.420 (2D FLAIR), and 0.160 (2D contrast-enhanced T1-weighted GRE). The 3D T1-SPACE images showed the highest inter-observer agreements between the raters. Conclusions Compared to 2D FLAIR and 2D contrast-enhanced T1-weighted GRE, contrast-enhanced 3D T1 SPACE showed a better detection rate of

  2. [Radiotherapy for Alleviation of Paraparesis due to Leptomeningeal and Cauda Equina Metastasis of HER2-Positive Breast Cancer: A Case Report].

    PubMed

    Fujimoto, Shutaro; Iwasaki, Motoyuki; Ito, Masaki; Niiya, Yoshimasa; Itosaka, Hiroyuki; Mabuchi, Shouji; Nishioka, Takeshi; Echizenya, Hayato; Kasai, Kiyoshi

    2015-09-01

    Leptomeningeal metastasis is a rare entity and its diagnosis is often difficult. Moreover, evidence-based therapeutic strategies have not yet been established. A 52-year-old woman presented with high fever and was diagnosed with bacterial meningitis at first examination;although her fever was alleviated, she experienced motor weakness in both of her lower extremities. Ga scintigraphy highlighted the hot-spot areas of the disease in the cranial bone. She was then transferred to our department. Open biopsy of the skull showed metastasis of the cancer. Chest CT results indicated right breast cancer and Gd-DTPA imaging showed obvious enhancement of the pia mater around the conus medullaris and cauda equina. However, cerebrospinal fluid(CSF)cytological examination did not show the presence of any positive cells;consequently, mastectomy was performed in the thoracic surgical department. The severity of paraparesis and pain in her legs increased;however, repeat MRI 1 month later showed no evidence of any change. Therefore, we performed biopsy of the cauda equina and arachnoid lesions. The pathological diagnosis was metastasis of breast cancer with positive human epidermal growth factor receptor 2(HER2)immunological staining. The results of a repeat cytological examination of the CSF during the surgery were negative. Local radiotherapy(25 Gy/5 Fr)as a monotherapy was selected for the patient, because her family did not approve of the combination of radiotherapy and chemotherapy. The severity of both paraparesis and limb pain decreased immediately after the radiotherapy.

  3. Treatment of Leptomeningeal Carcinomatosis in a Patient With Metastatic Cholangiocarcinoma

    PubMed Central

    McNeill, Katharine; Volpicelli, Frank M.; Warltier, Karin; Iturrate, Eduardo; Okamura, Charles; Adler, Nicole; Smith, Joshua; Sigmund, Alana; Mednick, Aron; Wertheimer, Benjamin; Hochman, Katherine

    2014-01-01

    A 49-year-old woman with cholangiocarcinoma metastatic to the lungs presented with new-onset unrelenting headaches. A lumbar puncture revealed malignant cells consistent with leptomeningeal metastasis from her cholangiocarcinoma. Magnetic resonance imaging (MRI) of the brain revealed leptomeningeal enhancement. An intrathecal (IT) catheter was placed and IT chemotherapy was initiated with methotrexate. Her case is notable for the rarity of cholangiocarcinoma spread to the leptomeninges, the use of IT chemotherapy with cytologic and potentially symptomatic response, and a possible survival benefit in comparison to previously reported cases of leptomeningeal carcinomatosis secondary to cholangiocarcinoma. PMID:26157901

  4. Chest Wall Pain as the Presenting Symptom of Leptomeningeal Carcinomatosis

    PubMed Central

    Sim, Kyoung Bo; Lee, Ho Jun; Park, Jin-Woo; Ryu, Gi Hyeong; Chang, Jihea; Kwon, Bum Sun

    2014-01-01

    Leptomeningeal metastasis (LMM), also referred to as leptomeningeal carcinomatosis, results from diffuse infiltration of the leptomeninges by malignant cells originating from extra-meningeal primary tumors. It occurs in approximately 5%-10% of patients with solid tumor. Among solid tumors, the most common types leading to infiltration of the leptomeninges are breast cancer, lung cancer, and melanoma. Patients with LMM may present various signs and symptoms. Herein, we report a rare case with initial presentation of isolated chest wall pain. Computed tomography of the chest with contrast revealed a 2.5-cm nodule over the left upper lung. Biopsy confirmed the diagnosis of adenocarcinoma. Later, cerebrospinal fluid cytology exam also confirmed leptomeningeal seeding. It is rare for leptomeningeal carcinomatosis patients to present with chest wall pain. Therefore, a high index of suspicion is mandatory for accurate and prompt diagnosis. PMID:25566489

  5. Leptomeningeal metastases in the MRI era(Podcast)(CME)

    PubMed Central

    Clarke, J.L.; Perez, H.R.; Jacks, L.M.; Panageas, K.S.; DeAngelis, L.M.

    2010-01-01

    Background: Diagnosis of leptomeningeal metastasis (LM) has become increasingly frequent. The diagnostic gold standard has been CSF cytology, but MRI is now used routinely for diagnosis. Diagnosis and prognosis of LM has not been studied in the MRI era. Methods: Patients with LM from 2002 through 2004 were identified through a neurology database, as well as by reviewing all abnormal CSF cytologies from a pathology database. Diagnosis was made by malignant cytology or imaging; suspicious cases treated as LM were also included. Results: A total of 187 patients with LM were analyzed in this retrospective review. Of these, 150 had solid and 37 had hematopoietic malignancies. Median age was 56.4 years, and median Karnofsky performance status (KPS) was 70. The most common types of solid tumor were breast (65 patients), lung (47), gastrointestinal (11), and melanoma (9). Of the hematopoietic tumors, 21 were lymphoma and 15 were leukemia. Fifty-three percent of patients were diagnosed by imaging, 23% by cytology, and 24% by both. Treatment included radiation therapy in 55%, intrathecal chemotherapy in 29%, and systemic chemotherapy in 18%; 21% received supportive care alone. Median overall survival was 2.4 (95% confidence interval 1.9–3.1) months. Median survival for patients with hematopoietic tumors was 4.7 months and for solid tumors was 2.3 months (p = 0.0006). In multivariate analysis, initial KPS and tumor type (solid vs hematopoietic) were significant predictors of survival. Conclusions: Despite enhanced diagnosis with MRI, prognosis remains poor in leptomeningeal metastasis. Those with hematopoietic tumors continue to fare better than those with solid tumors. GLOSSARY CI = confidence interval; ICP = intracranial pressure; KPS = Karnofsky performance status; LM = leptomeningeal metastasis; VP = ventriculoperitoneal. PMID:20439847

  6. Palliation of Painful Perineal Metastasis Treated with Radiofrequency Thermal Ablation

    SciTech Connect

    Thanos, L. Mylona, S.; Kalioras, V.; Pomoni, M.; Batakis, N.

    2005-04-15

    We report a case of painful perineal metastasis from urinary bladder carcinoma in a 73-years-old woman, treated with CT-guided radiofrequency ablation (RFA). The pain was immediately relieved and follow-up at 1 and 6 months showed total necrosis of the mass. One year later, the patient has no pain and her quality of life is improved.

  7. Complete response in HER2+ leptomeningeal carcinomatosis from breast cancer with intrathecal trastuzumab.

    PubMed

    Oliveira, Mafalda; Braga, Sofia; Passos-Coelho, José Luís; Fonseca, Ricardo; Oliveira, João

    2011-06-01

    Trastuzumab, a monoclonal antibody against the HER2 receptor, is a major breakthrough in the treatment of HER2+ breast cancer. However, its high molecular weight precludes it from crossing the intact blood-brain barrier, making the central nervous system a sanctuary to HER2+ breast cancer metastases. We prospectively assessed functional outcome and toxicity of administering trastuzumab directly into the cerebrospinal fluid of a patient with leptomeningeal carcinomatosis (LC) and brain metastases from HER2+ breast cancer that had already been treated with other intrathecal chemotherapy, with no benefit. Upon signed informed consent, weekly lumbar puncture with administration of trastuzumab 25 mg was begun to a 44 year-old women with metastatic breast cancer (lymph node, bone, lung, and liver involvement) previously treated with tamoxifen, letrozole, anthracyclines, taxanes, capecitabine, intravenous trastuzumab, and lapatinib. She received 67 weekly administrations of intrathecal trastuzumab with marked clinical improvement and no adverse events. She survived 27 months after LC diagnosis. A complete leptomeningeal response, with no evidence of leptomeningeal metastasis at necropsy, was achieved. We believe that intrathecal trastuzumab administration should be prospectively evaluated to confirm clinical activity and optimize dose, schedule, and duration of treatment.

  8. Primary leptomeningeal melanocytosis--a case report with an autopsy diagnosis.

    PubMed

    Nikola, Zivković; Dragan, Mihailović; Mijović, Zaklina; Milentijević, Maja Jovicić

    2012-07-01

    Primary melanocytosis of the leptomeninges is a rare tumor, most likely originating from the melanocytes in the leptomeninges. The average survival is only about 5 months. A 61-years-old woman presented with headache, amaurosis and hallucinations lasted for two months, and she had been treated at the Clinic for Psychiatry and Clinic for Infectious Diseases. The cerebrospinal fluid analysis showed a lower level of glucose and a higher level of proteins. Small shaded areas of basal leptomeninges and hydrocephalus were found by computed tomography and magnetic resonance imaging. The autopsy showed a dark brown mass on basal leptomeninges with blurred boundaries. No pigmented skin lesions were found. Histopathological analysis revealed a primary leptomeningeal melanocytosis. Primary leptomeningeal melanocytosis is a rare tumor, difficult to diagnose. This case is being presented for its specificity, since this diagnosis is not frequently seen in practice.

  9. Cardiac metastasis from renal cell carcinoma successfully treated with pazopanib: impact of TKIs' antiangiogenic activity.

    PubMed

    Schinzari, Giovanni; Monterisi, Santa; Signorelli, Diego; Cona, Silvia; Cassano, Alessandra; Danza, Francesco; Barone, Carlo

    2014-01-01

    Cardiac metastasis from renal cell carcinoma, especially without neoplastic thrombosis of the vena cava, is extremely rare. The prognosis of patients with metastatic renal cell carcinoma has been radically influenced by the introduction of tyrosine kinase inhibitors, but very few reports in the literature have described their activity in heart metastasis. We report the case of a woman with a left ventricle metastasis from kidney cancer without renal vein involvement, who was treated with pazopanib. The patient achieved a prolonged partial response, with clear signs of metastasis devascularization and a favorable toxicity profile.

  10. Metastasis

    MedlinePlus

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

  11. Current Approaches of Photothermal Therapy in Treating Cancer Metastasis with Nanotherapeutics

    PubMed Central

    Zou, Lili; Wang, Hong; He, Bin; Zeng, Lijuan; Tan, Tao; Cao, Haiqiang; He, Xinyu; Zhang, Zhiwen; Guo, Shengrong; Li, Yaping

    2016-01-01

    Cancer metastasis accounts for the high mortality of many types of cancer. Owing to the unique advantages of high specificity and minimal invasiveness, photothermal therapy (PTT) has been evidenced with great potential in treating cancer metastasis. In this review, we outline the current approaches of PTT with respect to its application in treating metastatic cancer. PTT can be used alone, guided with multimodal imaging, or combined with the current available therapies for effective treatment of cancer metastasis. Numerous types of photothermal nanotherapeutics (PTN) have been developed with encouraging therapeutic efficacy on metastatic cancer in many preclinical animal experiments. We summarize the design and performance of various PTN in PTT alone and their combinational therapy. We also point out the lacking area and the most promising approaches in this challenging field. In conclusion, PTT or their combinational therapy can provide an essential promising therapeutic modality against cancer metastasis. PMID:27162548

  12. Intrathecal Trastuzumab Treatment in Patients with Breast Cancer and Leptomeningeal Carcinomatosis

    PubMed Central

    Park, Won-Young; Kim, Han-Jo; Kim, Kyoungha; Bae, Sang-Byung; Lee, Namsu; Lee, Kyu-Taek; Won, Jong-Ho; Park, Hee-Sook; Lee, Sang-Cheol

    2016-01-01

    Leptomeningeal carcinomatosis is a fatal manifestation of metastatic breast cancer. Investigation of intrathecal (IT) trastuzumab for leptomeningeal carcinomatosis is currently underway; however, there has been no consensus. We report on two cases of human epidermal growth factor receptor 2 positive (HER2+) breast cancer following IT trastuzumab for leptomeningeal carcinomatosis. The first patient was treated with weekly IT 15 mg methotrexate plus IT 50 mg trastuzumab for 7 months, followed by IT trastuzumab (50 mg > 25 mg) for 18 months. The other patient received IT trastuzumab with systemic chemotherapy (trastuzumab and/or paclitaxel) for 13 months. Good control of leptomeningeal disease was achieved with IT trastuzumab in both patients, with survival durations of 20 and 29 months, respectively. We suggest that IT trastuzumab is a promising treatment for patients with HER2+ breast cancer and leptomeningeal carcinomatosis. PMID:25761487

  13. A case report of pancreatic metastasis from synovial sarcoma successfully treated by metastasectomy with adjuvant chemotherapy

    PubMed Central

    Makino, Yuki; Shigekawa, Minoru; Kegasawa, Tadashi; Suda, Takahiro; Yoshioka, Teppei; Iwahashi, Kiyoshi; Ikezawa, Kenji; Sakamori, Ryotaro; Yakushijin, Takayuki; Kajihara, Jun; Tomimaru, Yoshito; Eguchi, Hidetoshi; Imura, Yoshinori; Outani, Hidetatsu; Naka, Norifumi; Honma, Keiichiro; Morii, Eiichi; Tatsumi, Tomohide; Hiramatsu, Naoki; Takehara, Tetsuo

    2016-01-01

    Abstract Introduction: Synovial sarcoma is a malignant soft tissue sarcoma which arises near joints. The most frequent metastasis sites of synovial sarcoma are the lungs, lymph nodes, and bone. Pancreatic metastasis is quite rare; only 3 cases have been reported worldwide to date. We herein present the 4th case of pancreatic metastasis from synovial sarcoma. Methods and Results: A 32-year-old man underwent extended excision of synovial sarcoma in the left pelvis and femur in 2009. In 2013, follow-up contrast-enhanced computed tomography revealed a 35-mm heterogeneously enhanced mass in the pancreas body. Endoscopic ultrasound-guided fine needle aspiration of the mass revealed a diffuse proliferation of atypical spindle cells in a fascicular arrangement. Because the histology was quite similar to the resected specimen of synovial sarcoma in 2009, the mass was suspected to be a metastasis from synovial sarcoma. Laparoscopic distal pancreatectomy with adjuvant adriamycin/ifosfamide chemotherapy was subsequently performed. Synovial sarcoma-specific SS18-SSX1 (synovial sarcoma translocation, chromosome 18-synovial sarcoma X1) or SS18-SSX2 chimera mRNA was detected in the resected specimen, confirming the diagnosis of metastasis from synovial sarcoma. The patient did well for 30 months without recurrence. Conclusion: This case suggests that pancreatic metastasis from synovial sarcoma can be successfully treated by metastasectomy with adjuvant chemotherapy. PMID:27684804

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

    PubMed

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

    2014-01-01

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

  15. Carcinomatous meningitis: Leptomeningeal metastases in solid tumors

    PubMed Central

    Le Rhun, Emilie; Taillibert, Sophie; Chamberlain, Marc C.

    2013-01-01

    Leptomeningeal metastasis (LM) results from metastatic spread of cancer to the leptomeninges, giving rise to central nervous system dysfunction. Breast cancer, lung cancer, and melanoma are the most frequent causes of LM among solid tumors in adults. An early diagnosis of LM, before fixed neurologic deficits are manifest, permits earlier and potentially more effective treatment, thus leading to a better quality of life in patients so affected. Apart from a clinical suspicion of LM, diagnosis is dependent upon demonstration of cancer in cerebrospinal fluid (CSF) or radiographic manifestations as revealed by neuraxis imaging. Potentially of use, though not commonly employed, today are use of biomarkers and protein profiling in the CSF. Symptomatic treatment is directed at pain including headache, nausea, and vomiting, whereas more specific LM-directed therapies include intra-CSF chemotherapy, systemic chemotherapy, and site-specific radiotherapy. A special emphasis in the review discusses novel agents including targeted therapies, that may be promising in the future management of LM. These new therapies include anti-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors erlotinib and gefitinib in nonsmall cell lung cancer, anti-HER2 monoclonal antibody trastuzumab in breast cancer, anti-CTLA4 ipilimumab and anti-BRAF tyrosine kinase inhibitors such as vermurafenib in melanoma, and the antivascular endothelial growth factor monoclonal antibody bevacizumab are currently under investigation in patients with LM. Challenges of managing patients with LM are manifold and include determining the appropriate patients for treatment as well as the optimal route of administration of intra-CSF drug therapy. PMID:23717798

  16. Bone metastasis in breast cancer is treated by high-dose tamoxifen.

    PubMed

    Stathopoulos, George P; Trafalis, Dimitrios; Kaparelou, Maria

    2016-01-01

    Bone metastases in breast cancer are quite common, and some patients may have no other site of metastasis. An effective treatment is often endocrine agents administration (tamoxifen or antiaromatases), given mainly to postmenopausal women. Radiation treatment is also effective, although difficult to perform in cases of extensive skeletal disease. Chemotherapy does not help. The purpose of this study was to investigate the effectiveness of high-dose tamoxifen in female patients with breast cancer and bone metastasis. 28 patients with breast cancer were treated with high-dose tamoxifen. All of them had been pretreated with hormonal therapy including low-dose tamoxifen. The results were extremely positive with clinical amelioration and also disappearance of osteolysis in some patients. Twenty six out of 28 patients responded to the treatment, the criteria being mainly pain reduction and body mobilization (an amelioration which lasted 8 months-4 years). Tamoxifen is efficient when readministered at high dose to breast cancer patient with bone metastasis.

  17. A rare case of leptomeningeal carcinomatosis in a patient with uveal melanoma: case report and review of literature.

    PubMed

    Fedorenko, Inna V; Evernden, Brittany; Kenchappa, Rajappa S; Sahebjam, Solmaz; Ryzhova, Elena; Puskas, John; McIntosh, Linda; Caceres, Gisela; Magliocco, Anthony; Etame, Arnold; Harbour, J William; Smalley, Keiran S M; Forsyth, Peter A

    2016-10-01

    Uveal melanoma is a rare subtype of melanoma, accounting for only 3-5% of all melanoma cases in the USA. Although fewer than 4% of uveal melanoma patients present with metastasis at diagnosis, approximately half will develop metastasis, more than 90% of which disseminate to the liver. Infrequently, a number of malignancies can lead to leptomeningeal metastases, a devastating and terminal complication. In this case report, we present an exceedingly rare case of a patient with uveal melanoma who developed leptomeningeal carcinomatosis as the sole site of metastasis. After conventional methods to diagnose leptomeningeal carcinomatosis fell short, a diagnosis was confirmed on the basis of identification and genomic analysis of melanoma circulating tumor cells in the cerebrospinal fluid.

  18. Neurological and cytological response as potential early predictors of time-to-progression and overall survival in patients with leptomeningeal carcinomatosis treated with intrathecal liposomal cytarabine: a retrospective cohort study.

    PubMed

    Fusco, Juan P; Castañón, Eduardo; Carranza, Omar E; Zubiri, Leire; Martín, Patricia; Espinós, Jaime; Rodríguez, Javier; Santisteban, Marta; Aramendía, José M; Gil-Bazo, Ignacio

    2013-12-01

    Interesting neurological and cytological response rates after intrathecal (i.t) liposomal cytarabine have been observed in patients with leptomeningeal carcinomatosis (LMC) from solid tumors. However, the potential use of those responses as early predictors of time-to-progression (TTP) and overall survival (OS) is unexplored. 27 consecutive patients with LMC treated with 50 mg i.t liposomal cytarabine under compassionate drug use were retrospectively studied. All patients received i.t treatment every 2 weeks during induction and every 4 weeks during maintenance periods. Neurological and cytological responses were assessed before every liposomal cytarabine cycle. Most of the patients were female (17/27) diagnosed with breast cancer (15/27). A complete neurological response was seen among 11 % of the patients; partial response in 22 % of the patients; stable disease in 30 % of the patients and progressive disease in 37 % of them. Cytological assessment was available in 11/27 patients showing a 26 % complete response rate. The median time to neurological and cytological response was 15 days and 14 days, respectively. Patients showing a combined neurological and cytological response showed a significantly longer median TTP (122 vs. 3 days; p = 0.001) and OS (141 vs. 3 days; p = 0.002) compared to those showing both neurological and cytological progression. No grade 4 toxicities were recorded. According to these preliminary results, early neurological and cytological responses may be further studied as early predictors of TTP and OS in patients receiving i.t liposomal cytarabine for LMC.

  19. Stereotactic Radiosurgery as Part of Multimodal Treatment in a Bulky Leptomeningeal Recurrence of Breast Cancer

    PubMed Central

    Burton, Eric C; Shaughnessy, Joseph N

    2016-01-01

    Breast cancer metastatic to the brain and/or leptomeningeal spread of disease is a frequently encountered clinical situation, especially given the extended course of disease in these patients. Systemic therapies can often effectively prolong extracranial disease control, making effective strategies to control central nervous system-based disease even more critical. We present a case of bulky leptomeningeal relapse of breast cancer in the setting of prior whole brain radiation therapy. In order to treat the patient’s bulky disease and leptomeningeal spread while avoiding the potential toxicities of repeat whole brain radiation, the patient was treated with frameless stereotactic radiosurgery and intrathecal chemotherapy. This is the first report of this treatment approach for leptomeningeal relapse of breast cancer. The patient had an excellent response to treatment and durable intracranial control. PMID:27081584

  20. Hepatocellular carcinoma with gastric metastasis treated by simultaneous hepatic and gastric resection: report of a case.

    PubMed

    Haruki, Koichiro; Misawa, Takeyuki; Gocho, Takeshi; Saito, Ryota; Shiba, Hiroaki; Akiba, Tadashi; Yanaga, Katsuhiko

    2016-10-01

    Hepatocellular carcinoma (HCC) with gastric metastasis is extremely rare. There have been few reports on curative surgical resection for gastric metastasis of HCC. We herein report such a case successfully treated by simultaneous surgical resection. A 73-year-old male was admitted for evaluation and treatment of a liver tumor. Computed tomography showed an exophytic tumor of 170 mm in diameter located in the left lobe of the liver with poor delineation to the gastric wall. Upper gastrointestinal endoscopy revealed a submucosal tumor with ulceration in the antrum of the stomach. With a diagnosis of HCC with invasion to the gastric wall, an en bloc resection was planned, and the patient underwent laparotomy. The patients underwent left hemihepatectomy with partial resection of the stomach for adhesion and distal gastrectomy for the tumor. Pathological examination of the liver tumor revealed poorly differentiated HCC, and pathological diagnosis of the tumor in the submucosal and muscular layer of the stomach was compatible with metastasis from HCC, which was separate from the liver tumor. Therefore, we diagnosed the tumor as HCC with hematogenous gastric metastasis. The patient remains well with no evidence of tumor recurrence as of 13 months after resection.

  1. Prognostic factors in patients with brain metastasis from non-small cell lung cancer treated with whole-brain radiotherapy.

    PubMed

    Harada, Hideyuki; Asakura, Hirofumi; Ogawa, Hirofumi; Mori, Keita; Takahashi, Toshiaki; Nakasu, Yoko; Nishimura, Tetsuo

    2016-01-01

    The purpose of this study was to evaluate the prognostic factors associated with overall survival (OS) in nonsmall cell lung cancer (NSCLC) patients with brain metastasis who received whole-brain radiotherapy (WBRT). This study included 264 consecutive NSCLC patients with brain metastasis who received WBRT. Patients with leptomeningeal metastasis and those who underwent craniotomy or stereotactic radiotherapy before WBRT were excluded. The evaluated prognostic factors for OS included gender, neurological deficit, histology, epidermal growth factor receptor (EGFR) mutation status, previous cytotoxic chemotherapy, previous EGFR-tyrosine kinase inhibitor treatment, recursive partitioning analysis (RPA) class, and diagnosis-specific graded prognostic assessment (DS-GPA) score. All factors with a P < 0.05 in univariate analysis were entered into multivariate analysis using Cox regression and a confidence interval of 99%. Two hundred thirty patients had died, 14 patients were alive, and 20 patients were lost to follow-up. The median follow-up time was 20.9 months. The median survival time was 5.5 months (95% confidence interval; 4.8-6.3). Univariate analysis showed that gender, neurological deficit, histology, EGFR mutation status, RPA class, and DS-GPA score were significant prognostic factors for OS. In multivariate analysis, RPA class and histology were found to be significant prognostic factors for OS, with P values of 0.0039 and 0.0014, respectively. RPA Class I or II (Karnofsky Performance Status ≥70) and adenocarcinoma histology were associated with longer OS. These factors should be taken into account when considering indication for WBRT.

  2. Symmetrical Curvilinear Cytotoxic Edema Along the Surface of the Brain Stem: A Probable New Magnetic Resonance Imaging Finding of Leptomeningeal Carcinomatosis

    PubMed Central

    Khil, Eun Kyung; Lee, A Leum; Chang, Kee-Hyun; Yun, Tae Jin; Hong, Hyun Sook

    2015-01-01

    Abstract Lung cancer is one of the most common neoplasms to appear leptomeningeal metastasis (LM). Contrast-enhanced magnetic resonance imaging (MRI) is better diagnostic choice for LM and usually shows focal nodular or diffuse linear enhancement on the leptomeninges along the sulci and tentorium in the brain. We experienced atypical 2 cases of lung cancer in patients who showed unusual brain MRI finding of symmetrical curvilinear or band-like, nonenhancing cytotoxic edema along the surface of the brain stem. This finding is unique and different from the general findings of leptomeningeal metastasis. This unique imaging finding of symmetric curvilinear nonenhancing cytotoxic edema along the brainstem is extremely rare and represents a new presentation of leptomeningeal carcinomatosis. PMID:26200611

  3. [Leptomeningeal spread of an intramedullary cervical pilocytic astrocytoma: case report and literature review].

    PubMed

    Jusué-Torres, I; Alcázar-Vaquerizo, L; Gómez-Angulo, J C; Navarro-Torres, R; López-Serrano, R; García-Miralles, N

    2011-10-01

    BACKGROUND. The rarest location of pilocytic astrocytoma is intramedullary. Gliomas represent up to 24 - 30% of intramedullary tumors in adulthood and are second only after ependymomas. Leptomeningeal dissemination through cerebrospinal fluid is unusual and occurs predominantly in medulloblastomas, ependymoblastomas, central neuroblastomas, ependymomas, germ cell tumors and high-grade gliomas. The majority of spinal cord gliomas reporting metastasis were anaplastic astrocytomas or glioblastomas multiforme and relatively few were low-grade gliomas. The incidence of leptomeningeal spread of low-grade tumors is rare. A rare cranial extension of brain leptomeningeal dissemination in an intramedullary pilocytic astrocytoma during adulthood is reported. CASE REPORT. A 51 year-old-man with a recurrent intramedullary mass at C5-C7 level operated 4 times with all pathological anatomy reports describing the lesion as Pilocytic Astrocytoma developed, after 15 years from the diagnosis, visual hallucinations and his level of consciousness worsened to Glasgow coma score 13/15. The MRI showed highly enhanced cranial and spinal leptomeninges and paquimeninges with a micro nodular-granulomatous aspect associated with intense affectation of basal cisterns, subarachnoid spaces and convexity of both cerebral hemispheres suggestive of leptomeningeal spread of the spinal mass. The patient expired after three days. CONCLUSION. Leptomeningeal spread is a rare phenomenon and when it happens usually doesn't change the primary tumor's behavior. In our case the aggressiveness could be explained by a potential malignization of the primary tumor that it was not documented because of the partial resections from the lasts surgeries or instead the tumor was actually a monomorphous pilomyxoid tumor.

  4. Treating cancer stem cells and cancer metastasis using glucose-coated gold nanoparticles

    PubMed Central

    Hu, Chenxia; Niestroj, Martin; Yuan, Daniel; Chang, Steven; Chen, Jie

    2015-01-01

    Cancer ranks among the leading causes of human mortality. Cancer becomes intractable when it spreads from the primary tumor site to various organs (such as bone, lung, liver, and then brain). Unlike solid tumor cells, cancer stem cells and metastatic cancer cells grow in a non-attached (suspension) form when moving from their source to other locations in the body. Due to the non-attached growth nature, metastasis is often first detected in the circulatory systems, for instance in a lymph node near the primary tumor. Cancer research over the past several decades has primarily focused on treating solid tumors, but targeted therapy to treat cancer stem cells and cancer metastasis has yet to be developed. Because cancers undergo faster metabolism and consume more glucose than normal cells, glucose was chosen in this study as a reagent to target cancer cells. In particular, by covalently binding gold nanoparticles (GNPs) with thio-PEG (polyethylene glycol) and thio-glucose, the resulting functionalized GNPs (Glu-GNPs) were created for targeted treatment of cancer metastasis and cancer stem cells. Suspension cancer cell THP-1 (human monocytic cell line derived from acute monocytic leukemia patients) was selected because it has properties similar to cancer stem cells and has been used as a metastatic cancer cell model for in vitro studies. To take advantage of cancer cells’ elevated glucose consumption over normal cells, different starvation periods were screened in order to achieve optimal treatment effects. Cancer cells were then fed using Glu-GNPs followed by X-ray irradiation treatment. For comparison, solid tumor MCF-7 cells (breast cancer cell line) were studied as well. Our irradiation experimental results show that Glu-GNPs are better irradiation sensitizers to treat THP-1 cells than MCF-7 cells, or Glu-GNPs enhance the cancer killing of THP-1 cells 20% more than X-ray irradiation alone and GNP treatment alone. This finding can help oncologists to design

  5. Seed migration to the spinal canal after postresection brachytherapy to treat a large brain metastasis.

    PubMed

    Hirschfeld, Cole B; Schwartz, Theodore H; Parashar, Bhupesh; Wernicke, A Gabriella

    2016-01-01

    Seed migration after interstitial prostate brachytherapy has been well documented in the literature. However, there have been no detailed reports of seed migration after permanent interstitial brachytherapy to treat cerebral malignancies. In this article, the authors report a rare case of seed migration after adjuvant cesium-131 ((131)Cs) brachytherapy was used to treat a large paraventricular brain metastasis. The patient was a 63-year-old man with a 5.8-cm right frontal metastasis abutting the right lateral ventricle and causing severe edema and mass effect. The patient was enrolled in an ongoing clinical trial at our institution to receive permanent intraoperative (131)Cs brachytherapy in an effort to prevent tumor recurrence in the resection cavity. Stranded seeds were covered with Surgicel, and the cavity was filled with Tisseel to prevent seed migration. Imaging obtained at 54 days postsurgery showed no seed migration, but imaging obtained at 158 days revealed 12 brachytherapy seeds in the spinal canal from T11 to S2. The seeds were left in place because they were inactive at this time due to the short half-life of (131)Cs (9.7 days); they remained stable on followup imaging, and the patient was asymptomatic. Although the clinical consequences remain unclear, the migration of inactive seeds is not currently considered to be a complication of intracerebral brachytherapy and we do not believe that additional measures must be taken to prevent it. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  6. [A case of long-term survival of liver metastasis of breast cancer successfully treated with chemotherapy and endocrine therapy].

    PubMed

    Shiba, E; Koyama, H; Sasaki, Y; Iwanaga, T; Terasawa, T; Wada, A

    1985-09-01

    A 42-year-old woman was diagnosed as having hepatic metastasis two years after radical mastectomy for breast cancer. She was initially treated with oophorectomy and cytotoxic chemotherapy, which resulted in complete regression of the lesion within two years after the start of the treatment. She remained free of the disease until the fifth year thereafter, when she again developed a metastatic lesions in her liver. Since then, she has been treated sequentially with various kinds of chemotherapy and endocrine therapy with a certain degree of response to each treatment. She has survived 12 years and three months after the development of liver metastasis. This patient is the longest survivor of hepatic metastasis from breast cancer in the Japaneses literature.

  7. Robustness of the neurological prognostic score in brain metastasis patients treated with Gamma Knife radiosurgery.

    PubMed

    Serizawa, Toru; Higuchi, Yoshinori; Nagano, Osamu; Matsuda, Shinji; Aoyagi, Kyoko; Ono, Junichi; Saeki, Naokatsu; Iwadate, Yasuo; Hirai, Tatsuo; Takemoto, Shinya; Shibamoto, Yuta

    2016-12-02

    OBJECTIVE The neurological prognostic score (NPS) was recently proposed as a means for predicting neurological outcomes, such as the preservation of neurological function and the prevention of neurological death, in brain metastasis patients treated with Gamma Knife radiosurgery (GKRS). NPS consists of 2 groups: Group A patients were expected to have better neurological outcomes, and Group B patients were expected to have poorer outcomes. NPS robustness was tested in various situations. METHODS In total, 3040 patients with brain metastases that were treated with GKRS were analyzed. The cumulative incidence of the loss of neurological function independence (i.e., neurological deterioration) was estimated using competing risk analysis, and NPS was compared between Groups A and B by employing Gray's model. NPS was tested to determine if it can be applied to 5 cancer categories-non-small cell lung cancer, small cell lung cancer, gastrointestinal tract cancer, breast cancer, and other cancers-as well as if it can be incorporated into the 5 major grading systems: recursive partitioning analysis (RPA), score index for stereotactic radiosurgery (SIR), basic score for brain metastases (BSBM), graded prognostic assessment (GPA), and modified-RPA (M-RPA). RESULTS There were 2263 patients in NPS Group A and 777 patients in Group B. Neurological deterioration was observed in 586 patients (19.2%). The cumulative incidences of neurological deterioration were 9.5% versus 21.0%, 14.1% versus 25.4%, and 17.6% versus 27.8% in NPS Groups A and B at 1, 2, and 5 years, respectively. Significant differences were detected between the NPS groups in all cancer categories. There were significant differences between NPS Groups A and B for all classes in terms of the BSBM, GPA, and M-RPA systems, but the differences failed to reach statistical significance in terms of RPA Class I and SIR Class 0 to 3. CONCLUSIONS The NPS was verified as being highly applicable to all cancer categories and

  8. APOBEC3B expression in human leptomeninges and meningiomas

    PubMed Central

    Johnson, Mahlon D.; Reeder, Jay E.; O'Connell, Mary

    2016-01-01

    Nucleic acid-editing enzymes of the apolipoprotein B mRNA-editing enzyme (APOBEC) family have been associated with somatic mutation in cancer. However, the role of APOBEC catalytic subunit 3B (APOBEC3B) editing in the pathogenesis of base substitutions in meningiomas is unknown. In the present study, the expression of APOBEC3B was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analyses in five fetal and one adult human leptomeninges and 38 meningiomas. Genomic DNA was sequenced using the Illumina Tru-Seq Cancer Panel. Three meningioma primary cultures were also established and treated with cerebrospinal fluid form patients without neurological disease or platelet-derived growth factor-BB (PDGF-BB), prior to evaluation of APOBEC3B expression. By western blotting, APOBEC3B was revealed to be present in 100% of the fetal leptomeninges, and in 88% of World Health Organization grade I, 100% of grade II and 83% of grade III meningiomas tested, but was not different between grades. RT-qPCR revealed no difference in the mRNA expression of APOBEC3B between grades. Sequencing revealed no elevated levels of the C>T mutations that are characteristic of APOBEC3B editing of genomic DNA. Treatment with cerebrospinal fluid and PDGF-BB had no effect on APOBEC3B protein expression in the leptomeningeal or meningioma cells. These findings suggest that the mutations associated with increased APOBEC3B expression may not be central to the pathogenesis of meningiomas. PMID:28101245

  9. Biochemical failure as a determinant of distant metastasis and death in prostate cancer treated with radiotherapy.

    PubMed

    Pollack, Alan; Hanlon, Alexandra L; Movsas, Benjamin; Hanks, Gerald E; Uzzo, Robert; Horwitz, Eric M

    2003-09-01

    Biochemical failure (BF), defined by a rising prostate-specific antigen (PSA) profile, is an early surrogate of treatment failure. However, little evidence is available to show that BF is associated with death for patents with prostate cancer treated with radiotherapy. We examined the relationship between BF and death from prostate cancer. A total of 942 patients were treated between 1987 and 1998 with external beam radiotherapy who had sufficient PSA determinations in follow-up for the analyses described. The median radiation dose was 72 Gy, median PSA was 9.9 ng/mL, and median follow-up was 73 months. The American Society for Therapeutic Radiology and Oncology consensus definition was used to define BF. Kaplan-Meier calculations were from the start of radiotherapy. Cox proportional hazards regression multivariate analyses were used to investigate the association of BF (time-dependent variable) and other factors to distant metastasis (DM), cause-specific death (CSD), and overall death (OD). The year of treatment was included in some of the multivariate analyses to correct for potential unknown factors that may have occurred during the years of the study, such as stage migration. BF was observed in 316 patients (34%), and 66 (7%) experienced DM, 32 (3%) died of prostate cancer, and 230 (24%) died overall during the study period. The Kaplan-Meier 5-year rate estimates from the start of treatment for BF, DM, CSD, and OD were 38%, 6%, 3%, and 13%, respectively. All patients with DM had BF. In multivariate analyses, BF was associated with DM and CSD, but not OD. The inclusion of the year of treatment did not alter these relationships. BF, as a time-dependent covariate, was the strongest determinant of DM and was also very significantly related to CSD. The inclusion of the year of treatment had little effect on these associations. Longer follow-up is needed to determine conclusively the relationship of BF to OD.

  10. Isolated Liver Metastasis in Hürthle Cell Thyroid Cancer Treated with Microwave Ablation.

    PubMed

    Segkos, Konstantinos; Schmidt, Carl; Nabhan, Fadi

    2017-01-01

    Hürthle cell thyroid cancer (HCTC) is a less common form of differentiated thyroid cancer. It rarely metastasizes to the liver, and when it does, the metastasis is almost never isolated. Here we report a 62-year-old male with widely invasive Hürthle cell thyroid cancer, who underwent total thyroidectomy and received adjuvant treatment with I-131 with posttreatment scan showing no evidence of metastatic disease. His thyroglobulin however continued to rise after that and eventually an isolated liver metastasis was identified. He underwent laparoscopic microwave ablation of the liver metastasis, with dramatic decline in thyroglobulin and no structural disease identified to date. This case highlights the rare occurrence of isolated liver metastasis from HCTC and also illustrates the utility of thermoablation as an alternative to surgical resection in the treatment of small isolated liver metastases from HCTC.

  11. Isolated Liver Metastasis in Hürthle Cell Thyroid Cancer Treated with Microwave Ablation

    PubMed Central

    2017-01-01

    Hürthle cell thyroid cancer (HCTC) is a less common form of differentiated thyroid cancer. It rarely metastasizes to the liver, and when it does, the metastasis is almost never isolated. Here we report a 62-year-old male with widely invasive Hürthle cell thyroid cancer, who underwent total thyroidectomy and received adjuvant treatment with I-131 with posttreatment scan showing no evidence of metastatic disease. His thyroglobulin however continued to rise after that and eventually an isolated liver metastasis was identified. He underwent laparoscopic microwave ablation of the liver metastasis, with dramatic decline in thyroglobulin and no structural disease identified to date. This case highlights the rare occurrence of isolated liver metastasis from HCTC and also illustrates the utility of thermoablation as an alternative to surgical resection in the treatment of small isolated liver metastases from HCTC. PMID:28163939

  12. Intrathecal trastuzumab for leptomeningeal carcinomatosis in patients with human epidermal growth factor receptor 2 positive breast cancer

    PubMed Central

    Gulia, Seema; Gupta, Sudeep; Singh, Ashish

    2016-01-01

    There has been recent increase in incidence of leptomeningeal carcinomatosis, possibly due to widespread use of adjuvant trastuzumab and its known poor CNS penetration. Currently there are limited therapeutic options for these patients and outcome is poor. We report two cases of women with HER2 positive breast cancer who developed leptomeningeal carcinomatosis for which they were treated with intrathecal trastuzumab in combination with systemic therapy. Both patients had rapid symptomatic benefit and radiological response and remained progression free for at least seven months. Intrathecal trastuzumab can be considered a reasonable therapeutic option for these difficult to treat patients. PMID:27688614

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

    PubMed Central

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

    2014-01-01

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

  14. Leptomeningeal rheumatoid nodules: diagnosis and failed therapeutics.

    PubMed

    Nesbitt, Cassie; Willshire, Luke; Quan, Doreen; Shaw, Cameron; Batchelor, Peter

    2015-02-01

    A 67-year-old woman presented with recurrent transient ischaemic attack-like episodes over a 2 year period. Nodular enhancing leptomeningeal changes were detected on MRI and were consistent with meningeal rheumatoid nodules on biopsy. The patient's nodular disease continued to progress and regress clinically and radiologically irrespective of disease modifying agents and peripheral and serological rheumatoid arthritis control. This patient's unique presentation and diagnostic work-up is discussed alongside the dilemma of therapeutic management of meningeal rheumatoid nodules.

  15. Metastasis-Induced Acute Pancreatitis Successfully Treated with Chemotherapy and Radiotherapy in a Patient with Small Cell Lung Cancer

    PubMed Central

    Okutur, Kerem; Bozkurt, Mustafa; Korkmaz, Taner; Karaaslan, Ercan; Guner, Levent; Goksel, Suha; Demir, Gokhan

    2015-01-01

    Although involvement of pancreas is a common finding in small cell lung cancer (SCLC), metastasis-induced acute pancreatitis (MIAP) is very rare. A 50-year-old female with SCLC who had limited disease and achieved full response after treatment presented with acute pancreatitis during her follow-up. The radiologic studies revealed a small area causing obliteration of the pancreatic duct without mass in the pancreatic neck, and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) confirmed the metastasis of SCLC. The patient was treated successfully with systemic chemotherapy and radiotherapy delivered to pancreatic field. In SCLC, cases of MIAP can be encountered with conventional computed tomography with no mass image, and positron emission tomography and EUS-FNA can be useful for diagnosis of such cases. Aggressive systemic and local treatment can prolong survival, especially in patients with good performance status. PMID:26075124

  16. Osimertinib administration via nasogastric tube in an EGFR-T790M-positive patient with leptomeningeal metastases.

    PubMed

    Takeda, Takayuki; Itano, Hideki; Takeuchi, Mayumi; Nishimi, Yurika; Saitoh, Masahiko; Takeda, Sorou

    2017-07-01

    Patients with an epidermal growth factor receptor (EGFR) mutation are usually administered EGFR-tyrosine kinase inhibitors (TKIs) as standard-of-care treatment. However, acquired resistance occurs between 9 and 13 months. The T790M-resistant mutations are the most common, and osimertinib has been found to be effective in treating EGFR-T790M-positive patients. A 73-year-old female lung cancer patient with an EGFR-sensitizing mutation was receiving fourth-line chemotherapy when she complained of anorexia, headache, and irritability. A lumbar puncture showed adenocarcinoma in the cerebrospinal fluid (CSF), which led to the diagnosis of leptomeningeal metastasis. Her performance status (PS) deteriorated quickly and she also developed dysphagia. The EGFR mutation testing of the CSF demonstrated L858R+T790M double mutations, and an osimertinib suspension was subsequently administered through a nasogastric tube. The PS improved to 1, oral intake became possible after 20 days, and further improvements were observed by gadolinium-enhanced magnetic resonance imaging. The patient remains progression-free for 10 months after osimertinib administration.

  17. Numb chin syndrome secondary to leptomeningeal carcinomatosis from gastric adenocarcinoma

    PubMed Central

    Riesgo, Vincent J.; Poveda, Julio; Rammohan, Kottil

    2015-01-01

    Numb chin syndrome (NCS) can be a sign of malignancy. Its association with gastric adenocarcinoma is rare. We report a case of a 27-year-old Hispanic female that presented with complaint of left sided headache associated with numbness of the left side of chin and lower gingiva. Initial brain MRI, whole body gallium scan, high resolution CT of chest and elevated protein in the CSF were suggestive of sarcoidosis. She was treated with IV steroids with transient clinical improvement. Two weeks later, her symptoms worsened and further evaluation revealed the diagnosis of a poorly differentiated metastatic gastric adenocarcinoma with leptomeningeal involvement. This case report aims to emphasize the importance of identifying NCS as a possible indication of an underlying malignant condition. Reported cases of NCS associated with metastatic gastric adenocarcinoma are very rare. PMID:25830044

  18. Primary intracranial solitary leptomeningeal glioma: a report of 3 cases.

    PubMed

    Wakabayashi, K; Shimura, T; Mizutani, N; Koide, A; Yamagiwa, O; Mori, F; Nishiyama, K; Tanaka, R; Takahashi, H

    2002-01-01

    Primary intracranial solitary leptomeningeal gliomas are exceedingly rare. We, therefore, performed a detailed clinical, radiological and pathological analysis to better characterize these tumors in 3 patients (33- and 72-year-old men and a 72-year-old woman). Two of the tumors were located in the frontal region and 1 in the temporal region. Magnetic resonance imaging revealed a well circumscribed large lesion (maximal diameter 4 - 6 cm) with peritumoral edema, mixed low- and isosignal intensity on T1-weighted images, hypersignal intensity on T2-weighted images and non-homogeneous contrast enhancement. External carotid angiography demonstrated a vascular supply to these tumors via branches of the middle meningeal artery. Gross total resection was achieved in all patients. The pathological diagnosis was glioblastoma in 2 patients and oligodendroglioma in 1. The MIB-1 nuclear labeling index ranged from 11.8% - 23.6% (mean 18.2%). Local tumor recurrence was documented in 2 patients after 8 and 11 months, respectively. The other patient with glioblastoma developed a metastasis to the femur 39 months after craniotomy. A definitive diagnosis can be made by careful radiological assessment and histopathological examination.

  19. Ventriculoperitoneal shunting versus endoscopic third ventriculostomy in the treatment of patients with hydrocephalus related to metastasis

    PubMed Central

    Gonda, David D.; Kim, Teddy E.; Warnke, Peter C.; Kasper, Ekkehard M.; Carter, Bob S.; Chen, Clark C.

    2012-01-01

    Background: Between 2005 and 2010, we treated patients with hydrocephalus related to cerebral metastases, who were not good candidates for surgical resection by either endoscopic third ventriculostomy (ETV) or ventriculoperitoneal shunting (VPS). Patients were excluded from ETV if they had a clinical history suggestive of non-obstructive hydrocephalus, including: (1) history of infection or ventricular hemorrhage and (2) leptomeningeal carcinomatosis. The rest of the patients were treated with VPS. Methods: We analyzed the clinical outcome of these patient cohorts, to determine whether the efficacy of VPS was compromised due to a history of infection, ventricular hemorrhage, or leptomeningeal carcinomatosis, and compared these results to those patients who underwent ETV. Results: Sixteen patients were treated with ETV and 36 patients were treated with VPS. The overall efficacy of symptomatic palliation was comparable in the ETV and VPS patients (ETV = 69%, VPS = 75%). In both groups, patients with more severe hydrocephalic symptoms such as nausea, vomiting, and lethargy were more likely to benefit from the procedure. The overall complication rate for the two groups was comparable (ETV = 12.6%, VPS = 19.4%), although the spectrum of complications differed. The overall survival, initial Karnofsky performance status (KPS), and three-month KPS, were similarly comparable (median survival: ETV 3 months, VPS 5.5 months; initial KPS: ETV = 66 ± 7, VPS = 69 ± 12; 3 months KPS: ETV = 86 ± 7, KPS = 84 ± 12). Conclusion: VPS remains a reasonable option for poor RPA grade metastasis patients with hydrocephalus, even in the setting of a previous infection, hemorrhage, or in those with leptomeningeal disease. Optimal treatment of this population will involve the judicious consideration of the relative merits of VPS and ETV. PMID:23061013

  20. Melanoma and pigmentation of the leptomeninges in Ugandan Africans

    PubMed Central

    Lewis, M. G.

    1969-01-01

    A case of leptomeningeal melanoma in an African child of 7 years is presented together with a survey of pigmentation in the normal African brain. There is a direct relationship between the depth of pigment of the leptomeninges and the skin in Ugandan Africans, suggesting that similar factors operate in the control of melanocytes in these two sites. Images PMID:5776549

  1. [A case of liver metastasis from sigmoid colon cancer treated effectively by second-line chemotherapy].

    PubMed

    Gokita, Kentaro; Ami, Katsunori; Matsunaga, Yutaro; Fujiya, Keiichi; Ohshima, Nana; Amagasa, Hidetoshi; Ganno, Hideaki; Imai, Kenichiro; Fukuda, Akira; Nagahama, Takeshi; Ando, Masayuki; Akita, Hidetaka; Tei, Shikofumi; Okada, Youichi; Arai, Kuniyoshi

    2014-11-01

    A case of successful chemotherapy for a metachronous liver metastasis following resection for sigmoid colon cancer is presented. A 51-year-old man underwent sigmoidectomy, ileocecal resection, and descending colon colostomy for sigmoid colon cancer with ileum invasion. Six courses of FOLFOX4 were performed as adjuvant chemotherapy. One year after sigmoidectomy, a liver metastasis was detected on computed tomography (CT) examination. Chemotherapy with FOLFOX+bevacizumab was restarted. Three courses were administered, but hepatic dysfunction occurred after the second and third courses, and FOLFOX was discontinued. Subsequent chemotherapy was reinitiated with FOLFIRI+bevacizumab. After 9 courses, the carcinoembryonic antigen level was normalized and appeared to be decreased by imaging studies. Upon the patient's request, only oral S-1 was administered. After 2 courses, CT revealed that the diameter of the tumor had increased by 2 cm. Therefore, right lobectomy of the liver, colostomy closure, and anastomosis were performed. During these procedures, a nodule was found in the omentum and was removed. Rapid intra-operative diagnosis revealed peritoneal dissemination. The pathological diagnosis was liver metastasis of sigmoid colon cancer, with necrosis and fibrosis seen in approximately one-half of specimens. The surgical margins were negative. Neither metastatic cancer nor dissemination were found in the resected greater omentum.

  2. Orbital metastasis secondary to pulmonary adenocarcinoma treated with gefitinib: a case report.

    PubMed

    Koma, Yasuko; Goto, Keiko; Yoshida, Chihiro; Kimura, Kengo; Matsumoto, Yusuke; Koyama, Midori; Nakashima, Nariyasu; Masuya, Daiki; Matsuoka, Hirofumi; Yoshimatsu, Harukazu; Azumi, Atsushi; Suzuki, Yujiro

    2012-10-18

    Orbital metastases of lung cancer are rare. However, because the number of patients diagnosed with lung cancer is increasing, the probability that a physician will see a patient with an orbital metastasis is also increasing. Unfortunately, the clinical course and response of these patients to cytotoxic chemotherapy are generally poor and keeping a patient's quality of vision is difficult. In recent years, gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, has brightened the outlook for patients with advanced non-small cell lung cancer, especially for those who carry epidermal growth factor receptor-activating mutations. A 62-year-old Japanese man presented with swelling of the eyelid margin and ptosis of his right eye. A physical examination revealed double vision in his right eye and an alteration in elevator muscle mobility. A magnetic resonance image demonstrated a right intra-orbital mass (18 × 16mm). Screening examinations were carried out because this mass was suspected to be a metastasis from another organ. Chest computed tomography revealed a 42 × 37mm mass shadow on the left side of the hilum with mediastinal lymph node metastases. Adenocarcinoma with an epidermal growth factor receptor gene mutation (exon 19 deletion L747-E749; A750P) was detected in a transbronchial biopsy specimen; the patient was diagnosed with stage IV (T2N2M1) non-small cell lung cancer.Gefitinib (250mg/day) was chosen as first-line chemotherapy because there was no pre-existing interstitial shadow. After two months of treatment, the patient's right eye opened completely and follow-up magnetic resonance imaging revealed a marked reduction of the intra-orbital mass to 14 × 13mm. Three months after treatment initiation, a follow-up computed tomography showed a marked reduction in the size of the primary lesion to 23 × 20mm. The patient is continuing gefitinib treatment without any adverse effects noted on computed tomography, physical, or laboratory

  3. Orbital metastasis secondary to pulmonary adenocarcinoma treated with gefitinib: a case report

    PubMed Central

    2012-01-01

    Introduction Orbital metastases of lung cancer are rare. However, because the number of patients diagnosed with lung cancer is increasing, the probability that a physician will see a patient with an orbital metastasis is also increasing. Unfortunately, the clinical course and response of these patients to cytotoxic chemotherapy are generally poor and keeping a patient’s quality of vision is difficult. In recent years, gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, has brightened the outlook for patients with advanced non-small cell lung cancer, especially for those who carry epidermal growth factor receptor-activating mutations. Case presentation A 62-year-old Japanese man presented with swelling of the eyelid margin and ptosis of his right eye. A physical examination revealed double vision in his right eye and an alteration in elevator muscle mobility. A magnetic resonance image demonstrated a right intra-orbital mass (18 × 16mm). Screening examinations were carried out because this mass was suspected to be a metastasis from another organ. Chest computed tomography revealed a 42 × 37mm mass shadow on the left side of the hilum with mediastinal lymph node metastases. Adenocarcinoma with an epidermal growth factor receptor gene mutation (exon 19 deletion L747-E749; A750P) was detected in a transbronchial biopsy specimen; the patient was diagnosed with stage IV (T2N2M1) non-small cell lung cancer. Gefitinib (250mg/day) was chosen as first-line chemotherapy because there was no pre-existing interstitial shadow. After two months of treatment, the patient’s right eye opened completely and follow-up magnetic resonance imaging revealed a marked reduction of the intra-orbital mass to 14 × 13mm. Three months after treatment initiation, a follow-up computed tomography showed a marked reduction in the size of the primary lesion to 23 × 20mm. The patient is continuing gefitinib treatment without any adverse effects noted on computed

  4. Outcome of Patients With Pilocytic Astrocytoma and Leptomeningeal Dissemination

    SciTech Connect

    Mazloom, Ali; Hodges, Joseph C.; Teh, Bin S.; Chintagumpala, Murali; Paulino, Arnold C.

    2012-10-01

    Purpose: To determine the patient, tumor, and treatment characteristics of patients with pilocytic astrocytoma (PA) and leptomeningeal dissemination (LMD). Methods and Materials: A PubMed search of English-language studies pertaining to PA with LMD was performed using a combination of keywords that included juvenile pilocytic astrocytoma, low-grade astrocytoma, low-grade glioma, leptomeningeal dissemination, neuraxis spread, and radiotherapy. We found 26 studies with 58 patients between 1976 and 2005 that met these criteria. Results: The median survival for PA patients with LMD was 65 months. The 1-, 2-, and 5-year overall survival (OS) rate after the diagnosis of LMD was 81.1%, 75.7%, and 55.5%. The 1-, 2-, and 5-year progression-free survival (PFS) rate after the diagnosis of LMD was 69.3%, 66.5%, and 34.6%, respectively. Age, gender, primary site location, timing of LMD presentation (synchronous vs. metachronous), and LMD location did not significantly influence OS or PFS. No statistically significant difference was found in OS or PFS between the chemotherapy and radiotherapy groups. Likewise, no difference was found in OS or PFS according to the use of craniospinal irradiation vs. less extensive RT fields. Conclusions: Approximately one-half of PA patients were alive 5 years after the diagnosis of LMD. Both chemotherapy and radiotherapy have efficacy against LMD. Although the use of craniospinal irradiation did not have an effect on PFS, the patient numbers were small and a larger number treated with craniospinal irradiation is needed to determine its efficacy.

  5. Changes Mimicking New Leptomeningeal Disease After Intensity-Modulated Radiotherapy for Medulloblastoma

    SciTech Connect

    Muscal, Jodi A.; Jones, Jeremy Y.; Paulino, Arnold C.; Bertuch, Alison A.; Su, Jack; Woo, Shiao Y.; Mahoney, Donald H.; Chintagumpala, Murali

    2009-01-01

    Purpose: Acute and late changes in magnetic resonance imaging of the pediatric brain have been described after radiotherapy (RT). We report the post-RT neuroimaging changes in the posterior fossa after intensity-modulated RT (IMRT) in children with medulloblastoma and contrast them with those of leptomeningeal disease. Methods and Materials: We performed a retrospective review of 53 consecutive children with medulloblastoma who were treated with craniospinal RT followed by IMRT to the posterior fossa and chemotherapy between 1997 and 2006. Results: After IMRT to the posterior fossa, 8 (15%) of 53 patients developed increased fluid-attenuated inversion-recovery signal changes in the brainstem or cerebellum and patchy, multifocal, nodular contrast enhancement at a median of 6 months. The enhancement superficially resembled leptomeningeal disease. However, the enhancement resolved without intervention at a median of 6 months later. The accompanying fluid-attenuated inversion-recovery signal changes occasionally preceded the enhancement, were often parenchymal in location, and resolved or persisted to a lesser degree. All 8 patients with transient magnetic resonance imaging changes in the posterior fossa were alive at last follow-up. In contrast, leptomeningeal disease occurred in 8 (15%) of our 53 patients at a median of 19.5 months after IMRT completion. Of these 8 patients, 7 demonstrated initial nodular enhancement outside the conformal field, and 7 patients died. Conclusion: Magnetic resonance imaging changes can occur in the posterior fossa of children treated with IMRT for medulloblastoma. In our experience, these transient changes occur at a characteristic time and location after RT, allowing them to be distinguished from leptomeningeal disease.

  6. Mutations in g protein encoding genes and chromosomal alterations in primary leptomeningeal melanocytic neoplasms.

    PubMed

    Küsters-Vandevelde, Heidi V N; van Engen-van Grunsven, Ilse A C H; Coupland, Sarah E; Lake, Sarah L; Rijntjes, Jos; Pfundt, Rolph; Küsters, Benno; Wesseling, Pieter; Blokx, Willeke A M; Groenen, Patricia J T A

    2015-04-01

    Limited data is available on the genetic features of primary leptomeningeal melanocytic neoplasms (LMNs). Similarities with uveal melanoma were recently suggested as both entities harbor oncogenic mutations in GNAQ and GNA11. Whether primary LMNs share additional genetic alterations with uveal melanoma including copy number variations is unknown. Twenty primary LMNs ranging from benign and intermediate-grade melanocytomas to melanomas were tested by direct sequencing for hotspot mutations in the genes GNA11, GNAQ, BRAF, NRAS and HRAS. Furthermore, the lesions were tested for copy number variations of chromosomes frequently present in uveal melanoma (1p, 3, 6 and 8q) by multiplex ligation-dependent probe amplification (MLPA). Genome-wide analyses of copy number alterations of two leptomeningeal melanocytic neoplasms were performed using the OncoScan SNP-array. GNAQ(Q209) mutations were present in eleven LMNs, while two of 20 cases carried a GNA11(Q209) mutation. No BRAF, HRAS or NRAS hotspot mutations were detected. Monosomy 3 and gain of 8q were present in one leptomeningeal melanoma, and one intermediate-grade melanocytoma harbored a gain of chromosome 6. With MLPA, the melanocytomas did not show any further gross chromosomal variations. Our data shows that primary LMNs, like uveal melanoma, harbor oncogenic mutations in GNAQ and GNA11 but lack mutations in BRAF, NRAS and HRAS. This finding may help in the differential diagnosis between a primary LMN and a metastasis from a cutaneous melanoma to the central nervous system. Copy number variations in some aggressive LMNs resemble those present in uveal melanoma but their prognostic significance is unclear.

  7. A Review of the Clinical Outcomes for Patients Diagnosed with Brainstem Metastasis and Treated with Stereotactic Radiosurgery

    PubMed Central

    Lamm, Andrew F.; Elaimy, Ameer L.; Lamoreaux, Wayne T.; Mackay, Alexander R.; Fairbanks, Robert K.; Demakas, John J.; Cooke, Barton S.; 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 suggests that higher prescribed marginal dose and the associated greater local control of brainstem lesions are associated with longer patient survival. Further research is necessary to better describe the most effective dose for individual brainstem lesions and to tailor optimum therapy to specific patient subgroups. PMID:23691365

  8. Pulsatile Erlotinib in EGFR-Positive Non-Small-Cell Lung Cancer Patients With Leptomeningeal and Brain Metastases: Review of the Literature.

    PubMed

    How, Joan; Mann, Janelle; Laczniak, Andrew N; Baggstrom, Maria Q

    2017-07-01

    Patients with epidermal growth factor receptor (EGFR)-positive (EGFR(+)) non-small-cell lung cancer (NSCLC) show improved response rates when treated with tyrosine kinase inhibitors (TKIs) such as erlotinib. However, standard daily dosing of erlotinib often does not reach therapeutic concentrations within the cerebrospinal fluid (CSF), resulting in progression of central nervous system (CNS) disease. Intermittent, high-dose administration of erlotinib reaches therapeutic concentrations within the CSF and is well tolerated in patients. Experience with "pulsatile" dosing, however, is limited. We review the literature on the pharmacology and clinical outcomes of pulsatile erlotinib in the treatment of EGFR(+) NSCLC with brain and leptomeningeal metastases, and include available data on the use of next-generation TKIs in CNS progression. We also provide our institution's experience with patients treated with pulsatile erlotinib for CNS metastasis, and propose clinical criteria for its use. Pulsatile erlotinib is a reasonable alternative in EGFR(+) patients with new or worsening CNS disease, without evidence of systemic progression, and without confirmed T790M resistance mutations within the CNS. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Efficacy of the Irreversible ErbB Family Blocker Afatinib in Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor (TKI)–Pretreated Non–Small-Cell Lung Cancer Patients with Brain Metastases or Leptomeningeal Disease

    PubMed Central

    Tufman, Amanda; Wehler, Thomas; Pelzer, Theo; Wiewrodt, Rainer; Schütz, Martin; Serke, Monika; Stöhlmacher-Williams, Jan; Märten, Angela; Maria Huber, Rudolf; Dickgreber, Nicolas J.

    2015-01-01

    Introduction: Afatinib is an effective first-line treatment in patients with epidermal growth factor receptor (EGFR)-mutated non–small-cell lung cancer (NSCLC) and has shown activity in patients progressing on EGFR-tyrosine kinase inhibitors (TKIs). First-line afatinib is also effective in patients with central nervous system (CNS) metastasis. Here we report on outcomes of pretreated NSCLC patients with CNS metastasis who received afatinib within a compassionate use program. Methods: Patients with NSCLC progressing after at least one line of chemotherapy and one line of EGFR-TKI treatment received afatinib. Medical history, patient demographics, EGFR mutational status, and adverse events including tumor progression were documented. Results: From 2010 to 2013, 573 patients were enrolled and 541 treated with afatinib. One hundred patients (66% female; median age, 60 years) had brain metastases and/or leptomeningeal disease with 74% having documented EGFR mutation. Median time to treatment failure for patients with CNS metastasis was 3.6 months, and did not differ from a matched group of 100 patients without CNS metastasis. Thirty-five percent (11 of 31) of evaluable patients had a cerebral response, five (16%) responded exclusively in brain. Response duration (range) was 120 (21–395) days. Sixty-six percent (21 of 32) of patients had cerebral disease control on afatinib. Data from one patient with an impressive response showed an afatinib concentration in the cerebrospinal fluid of nearly 1 nMol. Conclusion: Afatinib appears to penetrate into the CNS with concentrations high enough to have clinical effect on CNS metastases. Afatinib may therefore be an effective treatment for heavily pretreated patients with EGFR-mutated or EGFR–TKI-sensitive NSCLC and CNS metastasis. PMID:25247337

  10. Leptomeningeal carcinomatosis as the primary presentation of relapse in breast cancer

    PubMed Central

    Sacco, Keith; Muhammad, Aun; Saleem, Waqar; Alshaker, Heba; Monzon, Leonardo; Islam, Mohammad Rafiqul; Pchejetski, Dmitri

    2016-01-01

    Leptomeningeal metastasis (LM) is an uncommon presentation of relapse in breast cancer, which is associated with poor clinical outcomes and poor prognosis. Notably, LM most commonly occurs in breast cancer. The aim of the present review was to investigate the occurrence of LM as the primary presentation of relapse following remission in breast cancer patients and to determine whether specific histological subtypes are predisposed to meningeal metastases. In addition, the present review evaluated whether patients presenting with LM as the primary site of relapse exhibit differences in survival when compared with patients exhibiting metastasis to other sites. Cross-sectional studies have demonstrated that LM is commonly associated with other sites of distant metastasis including lung, liver and bone metastases. The histological breast cancer subtype most commonly associated with LM was invasive lobular carcinoma, while triple-negative breast cancer patients appear to be predisposed to the development of LM when considering the overall prevalence of histological breast cancer subtypes. At present, data regarding LM as the primary site of relapse are limited due to its rarity as the first site of metastasis in breast cancer. Case-controlled studies are required to investigate the incidence of LM as the primary site of recurrence in breast cancer patients as this would enable treatment standardization and identification of prognostic factors for improved survival. PMID:27446350

  11. Extensive cortical involvement in leptomeningeal carcinomatosis.

    PubMed

    Ayzenberg, I; Börnke, C; Tönnes, C; Ziebarth, W; Lavrov, A; Lukas, C

    2012-12-01

    We present a 77-year-old previously well patient with facial asymmetry and progressive weakness of the lower extremities. An initial MRI revealed slight contrast enhancement of the meninges. Three consecutive cerebrospinal fluid examinations demonstrated low glucose concentration, marked elevation of total protein and moderate pleocytosis. No tumor cells, fungi, acid-fast bacilli or mycobacterial DNA were found. The patient's level of consciousness deteriorated dramatically, and follow-up MRI showed widespread extensive cortical hyperintensities. The lesions showed restricted diffusion on diffusion-weighted images as well as low values on the corresponding apparent diffusion coefficient maps, the changes consistent with diffuse cytotoxic edema. Neuropathological examination findings were of leptomeningeal carcinomatosis (LMC) with diffuse continuous infiltration of the cerebral cortex, cerebellum and spinal cord. The autopsy revealed a subcentimetre adenocarcinoma of the lung. To our knowledge, this is the first report demonstrating extensive cortical involvement in adenocarcinomatous LMC.

  12. Treatment of leptomeningeal metastases in a rat model using a recombinant adenovirus containing the HSV-tk gene.

    PubMed

    Vincent, A J; Esandi, M D; van Someren, G; Noteboom, J L; Avezaat, C J; Vecht, C; Smitt, P A; van Bekkum, D W; Valerio, D; Hoogerbrugge, P M; Bout, A

    1996-10-01

    The authors constructed recombinant adenoviral vectors to investigate their potential for gene therapy treatment of leptomeningeal metastases. Several human cell lines that were derived from tumors occurring as leptomeningeal metastases and that were infected in vitro with major late promoter recombinant adenovirus containing the luciferase (luc) gene (IG.Ad.MLP.luc) showed high levels of expression. When these human tumor cell lines were infected in vitro with recombinant adenovirus harboring the herpes simplex virus-thymidine kinase (HSV-tk) gene (IG.Ad.MLP.TK), they were highly sensitive to the killing effects of ganciclovir (GCV). Transduction efficiency of leptomeningeal tumor cells in vivo was assessed by injecting 9-L rat brain tumor cells into the cerebrospinal fluid of Fischer rats via the cisterna magna. After 3 days, recombinant adenovirus containing the lacZ reporter gene (IG.Ad.MLP.lacZ) was injected via the same route. Six days after tumor cell injection, expression of the reporter gene was observed in tumor cells along the total neural axis. Subsequently, rats with leptomeningeal metastases were treated 3 days after tumor cell injection with HSV-tk. Beginning on the next day, GCV was injected intraperitoneally for 10 days. The rats that developed neurological symptoms were killed immediately. The symptom-free latency of every rat was determined. The rats treated with HSV-tk and subsequent GCV had significantly longer (p < 0.01) symptom-free latency than all control groups. This study demonstrates the feasibility and efficacy of this therapeutic approach in a rat model. Clinically, it should be used in the palliative treatment of patients with leptomeningeal metastases.

  13. Fractionated Wide-Field Radiation Therapy Followed by Fractionated Local-Field Irradiation for Treating Widespread Painful Bone Metastasis

    SciTech Connect

    Ki, Yongkan; Kim, Wontaek; Nam, Jiho; Kim, Donghyun; Jeon, Hosang; Park, Dahl; Kim, Dongwon

    2011-01-01

    Purpose: Wide-field radiation therapy (WFRT) is an effective treatment for widespread bone metastasis. We evaluated local-field irradiation (LFI) after fractionated WFRT (f-WFRT) for treating the patients with multiple painful bone lesions. Methods and Materials: From 1998 to 2007, 32 patients with multiple bone metastases were treated with fractionated LFI (f-LFI) after f-WFRT. All patients initially received 15 Gy in 5 fractions to a wide field, followed by LFI (9-15 Gy in 3 Gy fractions). Response was assessed by evaluating the degree of pain relief using a visual analog scale before radiotherapy, after f-WFRT, and after f-LFI. Results: Fractionated LFI following f-WFRT yielded an overall relief rate of 93.8% and a complete relief rate of 43.8%. The rate of the appearance of new disease was 6.3% for the patients with complete relief, 20.5% for the patients with a partial relief, and 50% for the patients with no relief. Conclusion: Fractionated LFI after f-WFRT is a well-tolerated and effective treatment for multiple metastatic bone disease.

  14. Preclinical Modeling and Therapeutic Avenues for Cancer Metastasis to the Central Nervous System.

    PubMed

    Singh, Mohini; Bakhshinyan, David; Venugopal, Chitra; Singh, Sheila K

    2017-01-01

    Metastasis is the dissemination of cells from the primary tumor to other locations within the body, and continues to be the predominant cause of death among cancer patients. Metastatic progression within the adult central nervous system is 10 times more frequent than primary brain tumors. Metastases affecting the brain parenchyma and leptomeninges are associated with grave prognosis, and even after successful control of the primary tumor the median survival is a dismal 2-3 months with treatment options typically limited to palliative care. Current treatment options for brain metastases (BM) and disseminated brain tumors are scarce, and the improvement of novel targeted therapies requires a broader understanding of the biological complexity that characterizes metastatic progression. In this review, we provide insight into patterns of BM progression and leptomeningeal spread, outlining the development of clinically relevant in vivo models and their contribution to the discovery of innovative cancer therapies. In vivo models paired with manipulation of in vitro methods have expanded the tools available for investigators to develop agents that can be used to prevent or treat metastatic disease. The knowledge gained from the use of such models can ultimately lead to the prevention of metastatic dissemination and can extend patient survival by transforming a uniformly fatal systemic disease into a locally controlled and eminently more treatable one.

  15. Leptomeningeal metastases: a RANO proposal for response criteria.

    PubMed

    Chamberlain, Marc; Junck, Larry; Brandsma, Dieta; Soffietti, Riccardo; Rudà, Roberta; Raizer, Jeffrey; Boogerd, Willem; Taillibert, Sophie; Groves, Morris D; Le Rhun, Emilie; Walker, Julie; van den Bent, Martin; Wen, Patrick Y; Jaeckle, Kurt A

    2017-04-01

    Leptomeningeal metastases (LM) currently lack standardization with respect to response assessment. A Response Assessment in Neuro-Oncology (RANO) working group with expertise in LM developed a consensus proposal for evaluating patients treated for this disease. Three basic elements in assessing response in LM are proposed: a standardized neurological examination, cerebral spinal fluid (CSF) cytology or flow cytometry, and radiographic evaluation. The group recommends that all patients enrolling in clinical trials undergo CSF analysis (cytology in all cancers; flow cytometry in hematologic cancers), complete contrast-enhanced neuraxis MRI, and in instances of planned intra-CSF therapy, radioisotope CSF flow studies. In conjunction with the RANO Neurological Assessment working group, a standardized instrument was created for assessing the neurological exam in patients with LM. Considering that most lesions in LM are nonmeasurable and that assessment of neuroimaging in LM is subjective, neuroimaging is graded as stable, progressive, or improved using a novel radiological LM response scorecard. Radiographic disease progression in isolation (ie, negative CSF cytology/flow cytometry and stable neurological assessment) would be defined as LM disease progression. The RANO LM working group has proposed a method of response evaluation for patients with LM that will require further testing, validation, and likely refinement with use. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  16. Cerebral Metastasis of a Malignant Pleural Mesothelioma: A Case Report and Review of the Literature

    PubMed Central

    Kolias, Angelos G; Allinson, Kieren; Santarius, Thomas

    2015-01-01

    Background: Malignant pleural mesothelioma (MPM) is an aggressive malignant neoplasm that was thought to be a localised disease with limited metastatic capability. However, recent post-mortem studies have identified metastases to the central nervous system (CNS) in about 3% of cases. Case Description: We present the case of a 65-year-old with a solitary supratentorial metastatic deposit of MPM treated with surgical resection and adjuvant whole brain radiotherapy. Despite a good surgical outcome with symptomatic recovery, the patient died of cardiopulmonary compromise five months postoperatively. Conclusions: Although rare, CNS metastasis of MPM is a condition that neurosurgeons should be aware of. CNS metastases may occur via three distinct mechanisms, namely perineural spread, leptomeningeal carcinomatosis and, most commonly, haematogenous spread leading to parenchymal deposits. Surgical resection of these deposits can lead to symptomatic improvement, and together with radiotherapy, to local disease control. However, the overall survival remains poor. PMID:26180665

  17. Placental-site trophoblastic tumor with PET scan-detected surgically treated lung metastasis.

    PubMed

    Nieves, Lucybeth; Hoffman, James; Allen, Gretchen; Currie, John; Sorosky, Joel I

    2008-06-01

    Metastatic placental-site trophoblastic tumor (PSTT) continues to be a diagnostic and management dilemma due to its relative resistance to chemotherapy and the difficulties in diagnosing such a rare tumor. We describe a 35-year-old woman with PSTT presenting with irregular bleeding and a mass in the lung. Dilation and curettage provided the diagnosis of PSTT by frozen section of the specimen. Subsequently, a total abdominal hysterectomy was performed and the patient received three cycles of EMA-CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine) Positron emission tomography (PET) scan confirmed a persistent lung nodule that was treated with wedge resection. She is currently in clinical remission. Surgery may have a role in salvaging a patient with persistent PET-positive disease after chemotherapy.

  18. Management of cervical lymph node metastasis in tonsillar squamous cell carcinoma: Is it necessary to treat node-negative contralateral neck?

    PubMed

    Cho, Kwang Jae; Joo, Young Hoon; Sun, Dong Il; Kim, Min Sik

    2011-08-01

    To investigate the appropriate management of cervical lymph node metastasis in patients with tonsillar squamous cell carcinoma (SCC). The medical records of 49 patients that were surgically treated for tonsillar SCC were evaluated. Preoperative and postoperative stages, clinical factors affecting the nodal metastasis, and its relationship with survival were examined. Among 49 ipsilateral neck dissection (ND) specimens, 34 neck specimens (69%) were pN+. Out of 17 cases that underwent ipsilateral elective NDs, 4 cases (24%) were found to have pN+ necks. The disease-specific survival of the 34 patients with pN+ necks and 4 patients with occult metastases was worse than that of the remaining patients with pN0 necks and without occult metastasis, respectively (p=0.049 and p=0.023, respectively). All cases (100%) that underwent contralateral therapeutic NDs had pN+ findings. Two out of the 21 cases (less than 10%) that underwent contralateral elective NDs turned out to have pN+ necks and did not show any difference in survival compared to the 19 cases with pN0 necks. The degree of differentiation was associated with contralateral nodal metastasis. Patients with tonsillar SCC require thorough ipsilateral neck treatment because of the high probability of nodal metastasis and the close association between lymph node metastasis and survival. The contralateral cN+ neck should also be treated; however, the contralateral cN0 neck might be preserved with caution on the cases with poorly differentiated primary tumors and/or ipsilateral cN+ necks. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  19. Cyberknife Radiosurgery and Concurrent Intrathecal Chemotherapy for Leptomeningeal Metastases: Case Report of Prolonged Survival of a HER-2+ Breast Cancer Patient Status-Post Craniospinal Irradiation.

    PubMed

    Lekovic, Gregory; Drazin, Doniel; Mak, Albert C; Schwartz, Marc S

    2016-01-07

    Leptomeningeal disease (LMD) from breast cancer is usually a rapidly fatal condition, with median overall survival reported to be 15 weeks. Conventional treatment for LMD includes craniospinal irradiation and intrathecal (IT) methotrexate. However, the role of stereotactic radiation for leptomeningeal disease remains poorly defined. This case report describes our experience using Cyberknife radiosurgery to treat a 49-year-old female with HER-2+ breast cancer and focal/nodular leptomeningeal metastases that were refractory to craniospinal irradiation and concurrent IT chemotherapy. This combined approach--i.e., craniospinal irradiation, IT chemotherapy, and Cyberknife Radiosurgery for local, recurrent metastases--resulted in survival of 46 months with controlled disease. Based on our experience with this patient, we believe further consideration of radiosurgery for LMD is warranted.

  20. Cyberknife Radiosurgery and Concurrent Intrathecal Chemotherapy for Leptomeningeal Metastases: Case Report of Prolonged Survival of a HER-2+ Breast Cancer Patient Status-Post Craniospinal Irradiation

    PubMed Central

    Lekovic, Gregory; Mak, Albert C; Schwartz, Marc S

    2016-01-01

    Leptomeningeal disease (LMD) from breast cancer is usually a rapidly fatal condition, with median overall survival reported to be 15 weeks. Conventional treatment for LMD includes craniospinal irradiation and intrathecal (IT) methotrexate. However, the role of stereotactic radiation for leptomeningeal disease remains poorly defined. This case report describes our experience using Cyberknife radiosurgery to treat a 49-year-old female with HER-2+ breast cancer and focal/nodular leptomeningeal metastases that were refractory to craniospinal irradiation and concurrent IT chemotherapy. This combined approach--i.e., craniospinal irradiation, IT chemotherapy, and Cyberknife Radiosurgery for local, recurrent metastases--resulted in survival of 46 months with controlled disease. Based on our experience with this patient, we believe further consideration of radiosurgery for LMD is warranted.  PMID:26918221

  1. Primary diffuse leptomeningeal gliomatosis mimicking meningeal tuberculosis.

    PubMed

    Ruiz-Ares, Gerardo; Collantes-Bellido, Elena; Rodriguez de Rivera, Francisco; Medina-Báez, Josmarlin; Palomo-Ferrer, Farnando; Morales-Bastos, Carmen; Arpa, Javier

    2011-05-01

    Primary diffuse leptomeningeal gliomatosis (PDLG) is a rare condition, with only 45 cases recorded to date, characterized by infiltration of the meninges by glial cells without evidence of primary tumor in the brain or spinal cord parenchyma. Here, we describe a patient with PDLG who was managed with tuberculostatic drugs owing to multiple findings that were suggestive of tuberculous meningitis. A 19-year-old woman presented with headaches and behavioral changes. A sudden decrease in visual acuity with papilledema, bilateral sixth nerve palsies, and neck stiffness developed. Lumbar puncture showed elevated opening pressure (50 cm H2O). Cerebrospinal fluid (CSF) analysis showed glucose 30 mg/dL, protein 26.5 mg/dL, white blood cell count 150 (60% lymphocytes, 40% neutrophils). The second sample of CSF provided adenosine deaminase activity 21.9 U/L. Polymerase chain reaction for Koch's bacillus was positive in the third CSF sample. Magnetic resonance imaging revealed meningeal thickening of the quadrigeminal cistern, tentorium cerebelli, cerebral convexity, and spinal cord, with gadolinium enhancement in nodular lesions. The patient died 22 weeks after symptom onset owing to brainstem infarction. Postmortem pathologic studies revealed PDLG. This entity should be included in the differential diagnosis of tuberculous meningitis that does not respond to treatment with antituberculous drugs. Surgical biopsy should be considered in contrast-enhanced areas in magnetic resonance imaging.

  2. Olaparib treatment for BRCA-mutant ovarian cancer with leptomeningeal disease.

    PubMed

    Bangham, Madeleine; Goldstein, Robert; Walton, Henry; Ledermann, Jonathan A

    2016-11-01

    Leptomeningeal disease occurs more commonly in BRCA-mutated ovarian cancer.•A clinically significant dose of olaprib is able to penetrate the leptomeninges.•Leptomeningeal metastases in a BRCA-mutated ovarian cancer responded to olaparib.

  3. [A case of complete response for advanced gastric cancer with liver metastasis treated with combination chemotherapy of weekly paclitaxel and doxifluridine].

    PubMed

    Okabe, Toshio; Ohya, Toshihiro; Matsumoto, Hiroshi; Tago, Ken-Ichi; Totsuka, Osamu; Numaga, Yuki; Higuchi, Toru; Iesato, Hiroshi; Yokomori, Tadahiro; Kawate, Susumu; Takeyoshi, Izumi

    2009-01-01

    A 68-year-old man underwent total gastrectomy for Type 3 gastric cancer with liver metastasis. The final finding was T3(SE), N1, H1, P0, CY0(class IV), Stage IV, Cur C. After surgery, he was treated with combination chemotherapy of weekly paclitaxel(PTX)/doxifluridine(5'-DFUR). Paclitaxel was administered at a dose of 80 mg/m(2) on day 1, 8 and 15, and doxifluridine was orally administered at a dose of 533 mg/m(2) day for five days followed by withdrawal for two days. This regimen was repeated every four weeks. After 2 courses, the tumor marker level normalized, and the size of the liver metastasis was remarkably decreased. After 5 courses, a CT scan revealed the liver metastasis had disappeared, and he has now survived without recurrence after the disappearance of the liver metastasis. No severe adverse reactions were observed, and the man can be treated as an outpatient. This therapy may thus be effective in the treatment of advanced gastric cancer following non-curative operation.

  4. Primary Diffuse Leptomeningeal Gliomatosis: Radiological/Pathological Features

    PubMed Central

    Mohamed, Mohamed

    2016-01-01

    We present the case of a 43-year-old lady who presented with headaches, visual impairment, and seizures, progressing rapidly over the course of a few weeks. Extensive workup excluded an inflammatory or infectious cause. Imaging studies revealed diffuse thickening of the leptomeninges and serial CSF analysis showed raised opening pressures and increased protein levels. A diagnostic biopsy of the lower thoracic dura confirmed the diagnosis of primary diffuse leptomeningeal gliomatosis (PDGL). She was managed supportively for her symptoms and unfortunately she passed away a few weeks later. PMID:27891270

  5. Cancerous leptomeningitis and familial congenital hypopituitarism.

    PubMed

    Vujovic, S; Vujosevic, S; Kavaric, S; Sopta, J; Ivovic, M; Saveanu, A; Brue, T; Korbonits, M; Popovic, V

    2016-05-01

    People are at higher risk of cancer as they get older or have a strong family history of cancer. The potential influence of environmental and behavioral factors remains poorly understood. Earlier population and case control studies reported that upper quartile of circulating IGF-I is associated with a higher risk of developing cancer suggesting possible involvement of the growth hormone (GH)/IGF system in initiation or progression of cancer. Since GH therapy increases IGF-1 levels, there have been concerns that GH therapy in hypopituitarism might increase the risk of cancer. We report a 42-year-old female patient who presented with subacute onset of symptoms of meningitis and with the absence of fever which resulted in death 70 days after the onset of symptoms. The patient together with her younger brother was diagnosed at the age of 5 years with familial congenital hypopituitarism, due to homozygous mutation c.150delA in PROP1 gene. Due to evolving hypopituitarism, she was replaced with thyroxine (from age 5), hydrocortisone (from age 13), GH (from age 13 until 17), and sex steroids in adolescence and adulthood. Her consanguineous family has a prominent history of malignant diseases. Six close relatives had malignant disease including her late maternal aunt with breast cancer. BRCA 1 and BRCA 2 mutational analysis in the patient's mother was negative. Histology after autopsy disclosed advanced ovarian cancer with multiple metastases to the brain, leptomeninges, lungs, heart, and adrenals. Low circulating IGF-1 did not seem to protect this patient from cancer initiation and progression in the context of strong family history of malignancies.

  6. Sanctuary site leptomeningeal metastases in HER-2 positive breast cancer: A review in the era of trastuzumab.

    PubMed

    Kordbacheh, T; Law, W Y; Smith, I E

    2016-04-01

    The development of trastuzumab and other targeted systemic therapies has transformed the management of HER-2 positive breast cancers. However, as patients live longer and systemic therapies may not cross the blood brain barrier a rising number of patients are developing leptomeningeal metastases and brain metastases as a sanctuary site of disease. Intrathecal trastuzumab has been reported to treat these. We describe a breast cancer patient with HER-2 positive leptomeningeal disease in the spinal cord successfully treated with intrathecal trastuzumab and methotrexate, alongside systemic anti-HER-2 therapy and radiotherapy. We also review the literature to date on the efficacy and safety of intrathecal trastuzumab, and recent evidence suggesting that intrathecal trastuzumab passes via the blood brain barrier into the serum to achieve intravenous concentrations similar to that seen with systemic therapy alone. Overall, intrathecal trastuzumab appears to be a safe and often effective treatment for leptomeningeal metastases in HER-2 positive breast cancer. Ongoing phase I and II studies are required to determine optimum dosing schedules, validate CSF and CSF-to-serum pharmacokinetics, determine efficacy, and to assess the added benefits or disadvantages of prior radiotherapy and concomitant systemic therapy.

  7. Inferior mesenteric artery lymph node metastasis in rectal cancer treated with neoadjuvant chemoradiotherapy: Incidence, prediction and prognostic impact.

    PubMed

    Sun, Y; Chi, P; Lin, H; Lu, X; Huang, Y; Xu, Z; Huang, S; Wang, X

    2017-01-01

    To assess the effect of neoadjuvant chemoradiotherapy (nCRT) on inferior mesenteric artery (IMA) nodal metastasis and identify predictors for IMA nodal metastasis in locally advanced rectal cancer (LARC) after nCRT. Propensity score matching of 1167 patients with LARC was performed. Clinicopathological predictors and survival rates were analyzed using univariate and multivariate analyses. Compared to surgery alone, nCRT reduced the incidence of IMA nodal metastasis (before matching, 4.8% vs 9.1%, p = 0.004; after matching, 4.3% vs 10.1%, p = 0.002). Logistic regression analysis revealed that poorly differentiated (OR = 5.955, p < 0.001), tumors located above the peritoneal reflection (OR = 3.513, p = 0.005), and preoperative CEA levels ≧10 ng/ml (OR = 4.774, p = 0.005) were associated with IMA nodal metastasis. Time intervals to surgery ≧6 weeks were associated with fewer IMA nodal metastasis (OR = 0.274, p = 0.009).Over a median 40-month follow-up, the 3-year overall survival and disease-free survival rates were 63.0% and 43.1% in IMA-positive patients, respectively, which were significantly lower than the corresponding 89.0% and 82.4% rates in IMA-negative patients. Cox regression analysis revealed that IMA nodal metastasis was independently associated with unfavorable 3-year DFS. nCRT reduced the incidence of IMA node metastasis. Tumors located above the peritoneal reflection, poorly differentiated, and higher preoperative CEA levels were associated with IMA nodal metastasis after nCRT. IMA lymph node dissection is beneficial to certain patients with IMA nodal metastases, and the oncologic benefit may be improved if IMA nodal metastasis can be predicted. Copyright © 2016 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  8. Isolated pachymeningeal metastasis from breast cancer: Clinical features and prognostic factors.

    PubMed

    Heo, Mi Hwa; Cho, Yoo Jin; Kim, Hee Kyung; Kim, Ji-Yeon; Park, Yeon Hee

    2017-10-01

    To evaluate the clinical features and prognoses of patients with isolated pachymeningeal metastasis (IPM) from breast cancer. We reviewed the medical records of all patients with metastatic breast cancer (MBC) treated from January 2009 to August 2016. Eligibility criteria included diagnosis of pachymeningeal metastasis based on brain magnetic resonance imaging and histologic diagnosis of primary breast cancer. We excluded patients with concomitant parenchymal or leptomeningeal metastases. Thirty-eight patients who matched our inclusion criteria were included in this study. The incidence of IPM in breast cancer was 1.5% of all patients with MBC. The molecular subtype distribution was: triple negative, 29.0%; ER+/HER2-, 44.7%; ER+/HER2+, 18.4%; and ER-/HER2+, 7.9%. All isolated pachymeningeal involvement resulted from the direct extension of skull metastases. The median time to IPM from systemic metastasis was 28.6 (95% CI: 23.6-33.6) months. The median time to IPM from skull metastasis was 5.2 (95% CI: 0-10.9) months. The median overall survival (OS) from IPM was 4.0 (95% CI: 2.5-5.5) months. In patients who received chemotherapy the OS was longer than for those who received radiotherapy or supportive care only [median OS 8.9 (95% CI: 0.0-18.4), 2.8 (95% CI: 0.5-5.0), and 0.8 (95% CI: 0.6-1.1) months, respectively (p = 0.006)]. Multivariate analysis revealed that good performance status and chemotherapy were associated with better survival outcomes. Stratified evaluation is required for patients with skull metastasis from breast cancer, as pachymeningeal involvement can develop and be associated with unsuspected outcomes. Copyright © 2017. Published by Elsevier Ltd.

  9. Significance of establishing collateral circulation by leptomeningeal anastomoses in the occlusion of arteriae cerebri mediae.

    PubMed

    Kulenović, Amela; Dilberović, Faruk

    2004-05-01

    We have investigated establishment of collateral circulation in patients with cerebral circulation disorder. Thirty angiograms of patients treated at Neurological Department of Hospital Centre in Sarajevo suffering from arteriae cerebri mediae occlusion were used for this study. Cerebral anastomoses that included connections between arteriae cerebri anterior and arteriae cerebri mediae over leptomeningeal anastomoses occurred in some patients suffering from occlusion of this arteriae. It was concluded that the majority of anastomoses existed between big leptomeningeal branches of postcommunicant segment of a. cerebri anterior and branches of cerebri mediae. These collaterals are of great significance as their functional ability is sometimes of a high degree in cases of occlusion of one or the other artery. It can be concluded that anastomosing of the blood vessels increases their volume in the whole and therefore more blood can be provided, although physiological factors should not be neglected, as functional effectiveness of collateral circulation in postocclusive states depends also on the state of the whole cerebrovascular system, then on the speed of creation of occlusion (thrombosis or embolism), systemic arterial pressure, volume and viscosity of the blood.

  10. PTP4A3 Independently Predicts Metastasis and Survival in Upper Tract Urothelial Carcinoma Treated with Radical Nephroureterectomy.

    PubMed

    Yeh, Hsin-Chih; Li, Ching-Chia; Huang, Chun-Nung; Hour, Tzyh-Chyuan; Yeh, Bi-Wen; Li, Wei-Ming; Liang, Peir-In; Chang, Lin-Li; Li, Chien-Feng; Wu, Wen-Jeng

    2015-11-01

    Increasing evidence has shown that protein tyrosine phosphatases have dominant roles in setting the levels of tyrosine phosphorylation and promoting oncogenic processes. PTP4A3 has been implicated in cancer metastasis but to our knowledge the role of PTP4A3 in upper tract urothelial carcinoma is unknown. The aim of this study was to investigate the association of PTP4A3 with disease characteristics, distant metastasis and prognosis of upper tract urothelial carcinoma. The importance of PTP4A3 was initially examined in paired normal urothelium, noninvasive upper tract urothelial carcinoma, invasive upper tract urothelial carcinoma and nodal metastatic tissue. The PTP4A3 transcript level was assessed in another 20 upper tract urothelial carcinoma samples by real-time reverse transcriptase-polymerase chain reaction. PTP4A3 protein expression was determined by immunohistochemistry using the H-score in 340 upper tract urothelial carcinoma samples. It was further correlated with clinicopathological factors, and disease specific and metastasis-free survival. The expression of PTP4A3 significantly increased from normal urothelium, noninvasive upper tract urothelial carcinoma and invasive upper tract urothelial carcinoma to nodal metastatic tissue (p <0.001). The PTP4A3 transcript level was also markedly up-regulated in higher stage upper tract urothelial carcinoma (p = 0.002). Over expression of PTP4A3 protein was significantly associated with advanced pT status, nodal metastasis, lymphovascular invasion and perineural invasion (each p <0.001) as well as with inferior disease specific and metastasis-free survival on multivariate analysis (each p <0.0001). In addition, it predicted metastasis in patients with pTa, pT1 and pT2 upper tract urothelial carcinoma. Results imply that PTP4A3 has a role in the carcinogenesis of upper tract urothelial carcinoma. PTP4A3 over expression independently predicted the metastasis and outcome of upper tract urothelial carcinoma, which was

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

    SciTech Connect

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

    2008-09-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2017-03-01

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

  13. Serial lumbar and ventricular cerebrospinal fluid biochemical marker measurements in patients with leptomeningeal metastases from solid and hematological tumors.

    PubMed

    Twijnstra, A; Ongerboer de Visser, B W; van Zanten, A P; Hart, A A; Nooyen, W J

    1989-05-01

    This study presents results of investigations of lumbar and ventricular cerebrospinal fluid (CSF) biochemical markers (Beta-glucuronidase (B-gluc), Beta-2-microglobulin (B2-m), and carcinoembrionic antigen (CEA] in 28 patients with five different tumor types with leptomeningeal metastasis diagnosed by CSF cytology and/or autopsy. All received methotrexate and radiotherapy at some stage. Decadron or other symptomatic treatments were not used. Measurements of the concentrations of B-gluc, B2-m and CEA were evaluated with the aim of correlating the results of these measurements to site of disease, of monitoring response and early relapse of leptomeningeal disease, and of establishing the duration of survival. In almost all our patients the results of ventricular CSF B-gluc, B2-m and CEA measurements were lower than those obtained from lumbar CSF. The markers did not correlate with site of disease or CSF cytology. A clear relationship was found between pretreatment lumbar CSF B2-m and CEA levels, response to therapy and survival. The markers are also useful for monitoring response. The findings of this study indicate that B2-m and CEA levels have a prognostic value with regard to response to therapy and time of survival.

  14. Pulmonary metastasis as sole manifestation of relapse in previously treated localised prostate cancer: three exceptional case reports

    PubMed Central

    Gago, Joaquim Peres; Câmara, Gabriela; Dionísio, Jorge; Opinião, Ana

    2016-01-01

    Metastatic prostate cancer recurrence after definitive local therapy can occur in any tissue. Usually, the first affected site is the bone. Lung metastases without bone or lymph node involvement are extremely rare in patients with prostate cancer, and only a handful of cases are reported in the literature. In several other malignancies, such as breast cancer, sarcomas, colorectal cancer, and renal cell carcinoma, long-term disease-free survival has been reported after resection of solitary pulmonary metastases. We present three unusual cases of isolated pulmonary recurrence of prostate cancer after initial definitive local therapy. One of the patients underwent resection of the lung metastasis, resulting in a long-term disease-free survival. Both surgical excision of solitary and oligometastatic lung secondary lesions and systemic therapy can play an important role in long-term disease control. Surgery should be considered for selected and well-informed patients with pulmonary metastasis after primary localised treatment for prostate cancer. PMID:27350790

  15. [Choroidal metastasis from a lung adenocarcinoma treated by intravitreal injection of anti-VEGF and external beam radiotherapy: A case report].

    PubMed

    Menoux, I; Guihard, S; Antoni, D; Bijon, J-C; Noël, G

    2017-03-23

    Choroidal metastases of lung cancer are very uncommon. This localization should be suspected on blurred vision and confirmed with an ophthalmological examination. Its treatment is not entirely codified. We report a case of blurred vision secondary to bilateral choroidal metastasis in a patient with choroidal metastases from a lung adenocarcinoma, treated by intravitreal anti-vascular endothelial growth factor (VEGF) injection and external beam radiotherapy. According to a literature review, we analyzed the place of the targeted treatments used alone or combined with the radiotherapy.

  16. Expression of HER-2 in rectal cancers treated with preoperative radiotherapy: a potential biomarker predictive of metastasis.

    PubMed

    Yao, Yun-Feng; Du, Chang-Zheng; Chen, Nan; Chen, Pengju; Gu, Jin

    2014-05-01

    Evidence suggests HER-2 overexpression may be predictive of prognosis in colorectal cancer patients, though this remains controversial. This study was performed to assess the prognostic value of HER-2 expression in locally advanced rectal cancer patients after preoperative radiotherapy. HER-2 expression was evaluated based on immunohistochemical (IHC) staining of resected specimens from 142 mid-to-low rectal cancer patients. Fluorescence in situ hybridization (FISH) was performed to confirm HER-2 overexpression in samples with an IHC score of 2+. Tumor regression grading (TRG) of the primary tumors was determined semiquantitatively using a tumor regression grading scheme advocated in the AJCC Cancer Staging Manual 7 edition. When the total staining intensity was evaluated, 106 samples (74.6%) showed barely-perceptible positivity (0-1+; HER-2--negative), 15 samples (10.6%) showed moderate positivity (2+) and 21 samples (14.8%) showed strong positivity (3+, HER-2 positive). FISH confirmed that 2 cases showing moderate HER-2 positivity (2+) overexpressed HER2. There was no significant difference between the HER-2 positive and -negative groups with respect to age, gender, TRG, TNM stage, downstaging status, lymphovascular invasion or tumor differentiation. A significant correlation was found between HER-2 overexpression and the incidence of distant metastasis (p = 0.005). Subgroup analysis revealed this correlation was not significant (p = 0.247) in the radiation-insensitive (TRG0-2) subgroup, whereas a significant correlation (p = 0.026) between HER-2 overexpression and distant metastasis was found in the radiation-resistant (TRG3) subgroup. Multivariate analysis identified ypN stage (OR = 0.473, p = 0.002)and overexpression of HER-2 (OR = 3.704, p = 0.008) as independent risk factors for distant metastasis. There was no correlation between HER-2 overexpression and disease-free survival or overall survival among the study population. We reported that HER-2

  17. NRAS(Q61K) mutated primary leptomeningeal melanoma in a child: case presentation and discussion on clinical and diagnostic implications.

    PubMed

    Angelino, Giulia; De Pasquale, Maria Debora; De Sio, Luigi; Serra, Annalisa; Massimi, Luca; De Vito, Rita; Marrazzo, Antonio; Lancella, Laura; Carai, Andrea; Antonelli, Manila; Giangaspero, Felice; Gessi, Marco; Menchini, Laura; Scarciolla, Laura; Longo, Daniela; Mastronuzzi, Angela

    2016-07-20

    Primary melanocytic neoplasms are rare in the pediatric age. Among them, the pattern of neoplastic meningitis represents a peculiar diagnostic challenge since neuroradiological features may be subtle and cerebrospinal fluid analysis may not be informative. Clinical misdiagnosis of neoplastic meningitis with tuberculous meningitis has been described in few pediatric cases, leading to a significant delay in appropriate management of patients. We describe the case of a child with primary leptomeningeal melanoma (LMM) that was initially misdiagnosed with tuberculous meningitis. We review the clinical and molecular aspects of LMM and discuss on clinical and diagnostic implications. A 27-month-old girl with a 1-week history of vomiting with mild intermittent strabismus underwent Magnetic Resonance Imaging, showing diffuse brainstem and spinal leptomeningeal enhancement. Cerebrospinal fluid analysis was unremarkable. Antitubercular treatment was started without any improvement. A spinal intradural biopsy was suggestive for primary leptomeningeal melanomatosis. Chemotherapy was started, but general clinical conditions progressively worsened and patient died 11 months after diagnosis. Molecular investigations were performed post-mortem on tumor tissue and revealed absence of BRAF(V600E), GNAQ(Q209) and GNA11(Q209) mutations but the presence of a NRAS(Q61K) mutation. Our case adds some information to the limited experience of the literature, confirming the presence of the NRAS(Q61K) mutation in children with melanomatosis. To our knowledge, this is the first case of leptomeningeal melanocytic neoplasms (LMN) without associated skin lesions to harbor this mutation. Isolated LMN presentation might be insidious, mimicking tuberculous meningitis, and should be suspected if no definite diagnosis is possible or if antitubercular treatment does not result in dramatic clinical improvement. Leptomeningeal biopsy should be considered, not only to confirm diagnosis of LMN but also to

  18. Solitary cerebral metastasis from transitional cell carcinoma after a 14-year remission of urinary bladder cancer treated with gemcitabine: Case report and literature review

    PubMed Central

    Sarmiento, J. Manuel; Wi, Matt S.; Piao, Zhe; Stiner, Eric S.

    2012-01-01

    Background: Brain metastases are the most common adult brain tumors, frequently arising from primary tumors in the lung, breast, skin, kidneys, and colon. Transitional cell carcinoma (TCC), the most common type of urinary bladder cancer, is a rare cause of brain metastasis with an ominous prognosis. Case Description: A 68-year-old female presented with right-sided paresis and focal motor seizures of her right upper and lower extremities 14 years after being diagnosed and treated for primary TCC of the urinary bladder with gemcitabine-based chemotherapy. MRI imaging revealed a 3.1 × 3.1 × 2.7 cm heterogeneously enhancing mass located along the posterior aspect of the left frontal convexity. The lesion was accessed using a transsulcal approach and was surgically debulked along the motor cortex with motor strip mapping, followed by adjuvant whole-brain radiation therapy. Pathological examination confirmed metastatic carcinoma with features of TCC, a rare entity among metastatic brain tumors. Conclusion: Brain metastases may present several years later in patients with TCC of the urinary bladder who have been treated with surgery and chemotherapy. Chemotherapeutic agents that penetrate the blood–brain barrier, such as gemcitabine, may delay development of cerebral metastasis from primary TCC of the urinary bladder. PMID:22937482

  19. Extrahepatic Bile Duct Obstruction and Erosive Disruption by Cavitating Porta Hepatis Nodal Metastasis, Treated by Uncovered Wallstent

    SciTech Connect

    Trambert, Jonathan J. Frost, Andrei; Malasky, Charlotte

    2004-08-15

    A 45-year-old woman with advanced gastric carcinoma presented with obstructive jaundice. Percutaneous transhepatic cholangiography (PTC) revealed erosive disruption of the extrahepatic bile ducts by a cavitating metastasis in the porta hepatis, as well as a biliary-duodenal fistula. External-internal biliary drainage via the fistula was plagued by recurrent drain occlusion by necrotic debris. This was ultimately alleviated by successful catheterization of the distal common bile duct (CBD) through the cavity, and linking the common hepatic duct (CHD) and CBD with a Wallstent, across the cavity. This succeeded in improving internal biliary drainage and isolating the exfoliating debris of the cavity from the bile ducts.

  20. A Case on Streptococcal Pneumonia Associated with Leptomeningitis, Osteomyelitis and Epidural Abscess in a Patient with AIDS

    PubMed Central

    Jeon, Jae Woong; Kim, Joo Seok; Ryu, Il Hwan; Choi, Ji Wook; Kim, Min Gyu; Na, Young Min; Yun, Hyeon Jeong

    2014-01-01

    Patients with acquired immunodeficiency syndrome (AIDS) are at higher risks of bacterial pneumonia than the general population, and the pathogen is the most commonly involved Streptococcus pneumoniae. We hereby report a case of pneumococcal pneumonia associated with leptomeningitis, osteomyelitis and epidural abscess in a patient with AIDS. He is being successfully treated with ampicillin/sulbactam and clindamycin. And because the pneumococcal infection is usually associated with morbidity and mortality rates in the setting of AIDS, we should consider for pneumococcal vaccinations among the AIDS populations. PMID:24624217

  1. Intestinal metastasis causing intussusception in a patient treated for osteosarcoma with history of multiple metastases: a case report.

    PubMed

    Hung, G Y; Chiou, T; Hsieh, Y L; Yang, M H; Chen, W Y

    2001-04-01

    Intestinal intussusception caused by metastatic tumors is a very rare condition. Preoperative diagnosis is not easy because of the condition's rarity and because of mild abdominal physical presentation. We report on a patient with osteosarcoma who suffered from abdominal pain and emesis during the period of autologous peripheral blood stem cell transplantation. He had undergone tumor excision and radiotherapy several times prior to autologous peripheral blood stem cell transplantation because of multiple metastases. Intestinal metastasis was suspected initially by computed tomographic scan and sonogram and was proved by surgical resection and pathological findings. Clinicians caring for pediatric patients with osteosarcoma with a history of multiple metastases should consider the possibility of intestinal metastases when equivocal abdominal symptoms develop after intensive chemotherapy.

  2. [A case of possible retroperitoneal metastasis of breast cancer successfully treated with oral S-1 and cyclophosphamide therapy after TC therapy].

    PubMed

    Yoneyama, Kimiyasu; Takeshita, Toshio; Suzuki, Hiroshi; Morise, Masaki; Suzuki, Tetsutarou; Kishi, Shinya; Tsutsui, Atsuko; Matsumoto, Akiko

    2011-03-01

    We report a case of possible retroperitoneal metastasis of breast cancer successfully treated with oral S-1 and cyclophosphamide therapy after docetaxel and cyclophosphamide (TC) therapy. A 57-year-old woman with a history of bilateral breast cancer showed an increase in tumor markers during treatment with oral anastrozole as postoperative adjuvant therapy 4 years after her second cancer surgery. After careful examination, the patient was diagnosed as having multiple bone metastases and her medication was changed to oral letrozole. After 3 months, the patient developed left back pain and was referred to our hospital. CT scanning showed an enhanced mass in the region from the left perirenal and posterior pararenal spaces to the left psoas major muscle and the anterior aspect of the left iliacus muscle, suggesting retroperitoneal metastasis. TC therapy was performed and, as a result, tumor markers decreased and the mass disappeared on CT imaging. After discontinuation of TC therapy, the tumor markers increased again, following which oral S-1 and cyclophosphamide therapy were administered, and the tumor markers decreased. At the time of this writing, the patient is still undergoing therapy, and no recurrence has been observed. We concluded that oral S-1 and cyclophosphamide therapy were useful in the present case and were associated with few adverse effects.

  3. Baseline Serum Lactate Dehydrogenase Levels for Patients Treated With Intensity-Modulated Radiotherapy for Nasopharyngeal Carcinoma: A Predictor of Poor Prognosis and Subsequent Liver Metastasis

    SciTech Connect

    Zhou Guanqun; Tang Linglong; Mao Yanping; Chen Lei; Li Wenfei; Sun Ying; Liu Lizhi; Li Li; Lin Aihua; Ma Jun

    2012-03-01

    Purpose: To evaluate the prognostic value of baseline serum lactate dehydrogenase (LDH) levels in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). Methods and Materials: Cases of NPC (n = 465) that involved treatment with IMRT with or without chemotherapy were retrospectively analyzed. Results: The mean ({+-}SD) and median baseline serum LDH levels for this cohort were 172.77 {+-} 2.28 and 164.00 IU/L, respectively. Levels of LDH were significantly elevated in patients with locoregionally advanced disease (p = 0.016). Elevated LDH levels were identified as a prognostic factor for rates of overall survival (OS), disease-free survival (DFS), and distant metastasis-free survival (DMFS), with p values <0.001 in the univariate analysis and p < 0.001, p = 0.004, and p = 0.003, respectively, in the multivariate analysis. Correspondingly, the prognostic impact of patient LDH levels was found to be statistically significant for rates of OS, DFS, and DMFS (p = 0.028, 0.024, and 0.020, respectively). For patients who experienced subsequent liver failure after treatment, markedly higher pretreatment serum LDH levels were detected compared with patients experiencing distant metastasis events at other sites (p = 0.032). Conclusions: Elevated baseline LDH levels are associated with clinically advanced disease and are a poor prognosticator for OS, DFS, and DMFS for NPC patients. These results suggest that elevated serum levels of LDH should be considered when evaluating treatment options.

  4. T-cell primary leptomeningeal lymphoma in cerebellopontine angle

    PubMed Central

    Briongos-Figuero, Laisa Socorro; Gómez-Traveso, Tamara; Pérez-Castrillon, José Luis

    2015-01-01

    Primary meningeal lymphomas are very rare and those derived from T cells are even more infrequent (less than 5% of primary central nervous system lymphomas). Cerebellopontine angle involvement in the primary T-cell lymphoma is exceptional. Clinical presentation depends on the type of lesions, and histological diagnosis is needed. We present a rare case of a 50-year-old woman who presented with clinical cerebellar syndrome with posterior opsoclonus-myoclonus syndrome. Necropsy evaluation revealed primary diffuse leptomeningeal non-Hodgkin's T-cell lymphoma. PMID:25750225

  5. Safety-net versus private hospital setting for brain metastasis patients treated with radiosurgery alone: Disparities in follow-up care and outcomes.

    PubMed

    Diao, Kevin; Sun, Yanqing; Yoo, Stella K; Yu, Cheng; Ye, Jason C; Trakul, Nicholas; Jennelle, Richard L; Kim, Paul E; Zada, Gabriel; Gruen, John P; Chang, Eric L

    2017-09-13

    Stereotactic radiosurgery (SRS) alone is an increasingly accepted treatment for brain metastases, but it requires adherence to frequently scheduled follow-up neuroimaging because of the risk of distant brain metastasis. The effect of disparities in access to follow-up care on outcomes after SRS alone is unknown. This retrospective study included 153 brain metastasis patients treated consecutively with SRS alone from 2010 through 2016 at an academic medical center and a safety-net hospital (SNH) located in Los Angeles, California. Outcomes included neurologic symptoms, hospitalization, steroid use and dependency, salvage SRS, salvage whole-brain radiotherapy, salvage neurosurgery, and overall survival. Ninety-three of the 153 patients were private hospital (PH) patients, and 60 were SNH patients. The median follow-up time was 7.7 months. SNH patients received fewer follow-up neuroimaging studies (1.5 vs 3; P = .008). In a multivariate analysis, the SNH setting was a significant risk factor for salvage neurosurgery (hazard ratio [HR], 13.65; P < .001), neurologic symptoms (HR, 3.74; P = .002), and hospitalization due to brain metastases (HR, 6.25; P < .001). More clinical visits were protective against hospitalizations due to brain metastases (HR, 0.75; P = .002), whereas more neuroimaging studies were protective against death (HR, 0.65; P < .001). SNH patients with brain metastases treated with SRS alone had fewer follow-up neuroimaging studies and were at higher risk for neurologic symptoms, hospitalization for brain metastases, and salvage neurosurgery in comparison with PH patients. Clinicians should consider the practice setting and patient access to follow-up care when they are deciding on the optimal strategy for the treatment of brain metastases. Cancer 2017;. © 2017 American Cancer Society. © 2017 American Cancer Society.

  6. Metastasis-free survival is associated with overall survival in men with PSA-recurrent prostate cancer treated with deferred androgen deprivation therapy

    PubMed Central

    Schweizer, M. T.; Zhou, X. C.; Wang, H.; Yang, T.; Shaukat, F.; Partin, A. W.; Eisenberger, M. A.; Antonarakis, E. S.

    2013-01-01

    Background Clinical trials in men with biochemically recurrent prostate cancer (BRPC) have been hampered by long survival times, making overall survival (OS) a difficult end point to reach. Intermediate end points are needed in order to conduct such trials within a more feasible time frame. Patients and methods This is a retrospective analysis of 450 men with BRPC following prostatectomy treated at a single institution between 1981 and 2010, of which 140 developed subsequent metastases. Androgen deprivation therapy (ADT) was deferred until after the development of metastases. Cox regression models were developed to investigate factors influencing OS. Results Median metastasis-free survival (MFS) was 10.2 years [95% confidence interval (CI) 7.6–14.0 years]; median OS after metastasis was 6.6 years (95%CI 5.8–8.4 years). Multivariable Cox regressions identified four independently prognostic variables for OS: MFS (HR 0.77; 95% CI 0.63–0.94), number of metastases (≤3 versus ≥4; HR 0.50; 95% CI 0.29–0.85), pain (absent versus present; HR 0.43; 95% CI 0.25–0.72), and bisphosphonate use (yes versus no; HR 0.60; 95% CI 0.37–0.98). Conclusions MFS emerged as an independent predictor of OS in men with BRPC treated with deferred ADT after the development of metastases. MFS may be a reasonable intermediate end point in future clinical trials. This observation requires prospective validation. PMID:23946329

  7. Addition of Anti-Angiogenetic Therapy with Bevacizumab to Chemo- and Radiotherapy for Leptomeningeal Metastases in Primary Brain Tumors

    PubMed Central

    Burger, Michael C.; Zeiner, Pia S.; Jahnke, Kolja; Wagner, Marlies; Mittelbronn, Michel; Steinbach, Joachim P.

    2016-01-01

    Leptomeningeal dissemination of a primary brain tumor is a condition which is challenging to treat, as it often occurs in rather late disease stages in highly pretreated patients. Its prognosis is dismal and there is still no accepted standard of care. We report here a good clinical effect with a partial response in three out of nine patients and a stable disease with improvement on symptoms in two more patients following systemic anti-angiogenic treatment with bevacizumab (BEV) alone or in combination with chemo- and/or radiotherapy in a series of patients with leptomeningeal dissemination from primary brain tumors (diffuse astrocytoma WHO°II, anaplastic astrocytoma WHO°III, anaplastic oligodendroglioma WHO°III, primitive neuroectodermal tumor and glioblastoma, both WHO°IV). This translated into effective symptom control in five out of nine patients, but only moderate progression-free and overall survival times were reached. Partial responses as assessed by RANO criteria were observed in three patients (each one with anaplastic oligodendroglioma, primitive neuroectodermal tumor and glioblastoma). In these patients progression-free survival (PFS) intervals of 17, 10 and 20 weeks were achieved. In three patients (each one with diffuse astrocytoma, anaplastic astrocytoma and primitive neuroectodermal tumor) stable disease was observed with PFS of 13, 30 and 8 weeks. Another three patients (all with glioblastoma) were primary non-responders and deteriorated rapidly with PFS of 3 to 4 weeks. No severe adverse events were seen. These experiences suggest that the combination of BEV with more conventional therapy schemes with chemo- and/or radiotherapy may be a palliative treatment option for patients with leptomeningeal dissemination of brain tumors. PMID:27253224

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

    PubMed Central

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

    2012-01-01

    The prognosis of patients diagnosed with stage IV nonsmall cell lung cancer that have brain and brainstem metastasis is very poor, with less than a third surviving a year past their initial date of diagnosis. We present the rare case of a 57-year-old man who is a long-term survivor of brainstem and recurrent brain metastasis, after aggressive treatment. He is now five and a half years out from diagnosis and continues to live a highly functional life without evidence of disease. Four separate Gamma Knife stereotactic radiosurgeries in conjunction with two craniotomies were utilized since his initial diagnosis to treat recurrent brain metastasis while chemoradiation therapy and thoracic surgery were used to treat his primary disease in the right upper lung. In his situation, Gamma Knife radiosurgery proved to be a valuable, safe, and effective tool for the treatment of multiply recurrent brain metastases within critical normal structures. PMID:23056973

  9. Cucurbitacin I blocks cerebrospinal fluid and platelet derived growth factor-BB stimulation of leptomeningeal and meningioma DNA synthesis

    PubMed Central

    2013-01-01

    Background Currently, there are no consistently effective chemotherapies for recurrent and inoperable meningiomas. Recently, cucurbitacin I (JSI-124), a naturally occurring tetracyclic triterpenoid compound used as folk medicines has been found to have cytoxic and anti-proliferative properties in several malignancies thru inhibition of activator of transcription (STAT3) activation. Previously, we have found STAT3 to be activated in meningiomas, particularly higher grade tumors. Methods Primary leptomeningeal cultures were established from 17, 20 and 22 week human fetuses and meningioma cell cultures were established from 6 World Health Organization (WHO) grade I or II meningiomas. Cells were treated with cerebrospinal fluid from patients without neurologic disease. The effects of cucurbitacin I on cerebrospinal fluid stimulation of meningioma cell DNA synthesis phosphorylation/activation of JAK1, STAT3, pMEK1/2, p44/42MAPK, Akt, mTOR, Rb and caspase 3 activation were analyzed in human leptomeningeal and meningioma cells. Results Cerebrospinal fluid significantly stimulated DNA synthesis in leptomeningeal cells. Co-administration of cucurbitacin I (250 nM) produces a significant blockade of this effect. Cucurbitacin I alone also produced a significant reduction in basal DNA synthesis. In grade I and II meningiomas, cerebrospinal fluid also significantly stimulated DNA synthesis. Co-administration of cucurbitacin I (250 nM) blocked this effect. In the leptomeningeal cultures, cerebrospinal fluid stimulated STAT3 phosphorylation but not p44/42MAPK, Akt or mTOR. Cucurbitacin I had no effect on basal STAT3 phosphorylation but co-administration with cerebrospinal fluid blocked cerebrospinal fluid stimulation of STAT3 phosphorylation in each. In the grade I meningiomas, cerebrospinal fluid stimulated phosphorylation of STAT3 and decreased MEK1/2 and cucurbitacin I had no effect on basal STAT3, p44/42MAPK, Akt, JAK1, mTOR, or Rb phosphorylation. In the grade II

  10. Periodate-treated, non-anticoagulant heparin-carrying polystyrene (NAC-HCPS) affects angiogenesis and inhibits subcutaneous induced tumour growth and metastasis to the lung

    PubMed Central

    Ono, K; Ishihara, M; Ishikawa, K; Ozeki, Y; Deguchi, H; Sato, M; Hashimoto, H; Saito, Y; Yura, H; Kurita, A; Maehara, T

    2002-01-01

    Periodate-treated, non-anticoagulant heparin-carrying polystyrene consists of about ten periodate-oxidized, alkaline-degraded low molecular weight-heparin chains linked to a polystyrene core and has a markedly lower anti-coagulant activity than heparin. In this study, we evaluated the effect of non-anticoagulant heparin-carrying polystyrene on tumour growth and metastasis. Non-anticoagulant heparin-carrying polystyrene has a higher activity to inhibit vascular endothelial growth factor-165-, fibroblast growth factor-2- or hepatocyte growth factor-induced human microvascular endothelial cell growth than heparin, ten periodate-oxidized-heparin and ten periodate-oxidized-low molecular weight-heparin, which is probably due to the heparin-clustering effect of non-anticoagulant heparin-carrying polystyrene. Non-anticoagulant heparin-carrying polystyrene inhibited human microvascular endothelial cell, B16 melanoma and Lewis lung cancer cell adhesion to Matrigel-coated plates. Non-anticoagulant heparin-carrying polystyrene also showed strong inhibitory activities in the tubular formation of endothelial cells on Matrigel and B16-melanoma and Lewis lung cancer cell invasion in a Matrigel-coated chamber assay. In vivo studies showed that growth of subcutaneous induced tumours and lung metastasis of B16-melanoma and Lewis lung cancer cells were more effectively inhibited by non-anticoagulant heparin-carrying polystyrene than ten periodate-oxidized-heparin and ten periodate-oxidized-low molecular weight-heparin. Furthermore, non-anticoagulant heparin-carrying polystyrene markedly reduced the number of CD34-positive vessels in subcutaneous Lewis lung cancer tumours, indicating a strong inhibition of angiogenesis. These results suggest that non-anticoagulant heparin-carrying polystyrene has an inhibitory activity on angiogenesis and tumour invasion and may be very useful in cancer therapy. British Journal of Cancer (2002) 86, 1803–1812. doi:10.1038/sj.bjc.6600307 www

  11. [A patient with hepatic metastasis of breast cancer successfully treated with combined chemoendocrine therapy using epirubicin, tegafur and tamoxifen].

    PubMed

    Rai, Y; Emi, Y; Nishijima, N; Kai, S; Kano, T

    1999-09-01

    A solitary 1 cm sized metastatic lesion was found in the S5 region of the liver on a postoperative ultrasound screening of a 52-year-old breast cancer patient. It was confirmed by CT, MRI and hepatic angiography. At first, she was successfully treated with trans-arterial pirarubicin and lipiodol infusion but a metastatic lesion of similar size was found 6 months later in the same region. We then administered a triple 20 mg dose of epirubicin intravenously, and 450 mg of UFT and 30 mg of tamoxifen daily. Six months later the lesion had disappeared on US and CT scans and a complete remission has persisted for 18 months.

  12. Dysphagia and anorexia as presentations of leptomeningeal carcinomatosis.

    PubMed

    Aiyer, Rohit; Engelman, Ester; Xue, Wei; Yu, Edward

    2016-04-12

    A 61-year-old woman presented to the emergency department, with a 4-day history of isolated oropharyngeal dysphagia associated with anorexia and weight loss over the previous 4 weeks. She had no other focal neurological symptoms and no deficits on examination. She had been in a 4-year remission of breast cancer postmastectomy and chemoradiation. Neuroimaging showed enhancement of cranial nerves VII, VIII, cisternal segment of cranial V, dorsal and ventral surfaces of the cervical and thoracic cord as well as enhancement of the cauda equina. Cerebrospinal fluid analysis revealed carcinomatous cells. The patient was diagnosed as having leptomeningeal carcinomatosis secondary to lobular breast cancer and was started on radiation therapy, antihormonal treatments and intrathecal methotrexate.

  13. Diagnosis of lymphomatous leptomeningitis by cerebrospinal fluid lymphocyte cell surface markers.

    PubMed

    Goodson, J D; Strauss, G M

    1979-06-01

    We present a patient with metastatic lymphomatous leptomeningitis in whom the diagnosis was made on the basis of cerebrospinal fluid lymphocyte surface markers and later confirmed by cerebrospinal fluid cytology. The diagnosis of metastatic leptomeningitis can be elusive, and the differential includes a wide variety of infectious and noninfectious processes. We propose that lymphocyte surface marker studies can be a useful technique in expediting the evaluation of certain patients with lymphoma who have evidence of central nervous sytem involvement.

  14. Leptomeningeal neurons are a common finding in infants and are increased in sudden infant death syndrome.

    PubMed

    Rickert, Christian H; Gros, Oliver; Nolte, Kay W; Vennemann, Mechtild; Bajanowski, Thomas; Brinkmann, Bernd

    2009-03-01

    Developmental abnormalities of the brain, in particular, the brainstem potentially affecting centers for breathing, circulation and sleep regulation, are thought to be involved in the etiology of sudden infant death syndrome (SIDS). In order to investigate whether leptomeningeal neurons could serve as morphological indicators for a developmental failure or retardation in cerebral maturation, we evaluated the density of isolated leptomeningeal neurons (without associated glia) in 15 brain regions of 24 SIDS and 8 control cases, representing part of the German Study on sudden infant death. Leptomeningeal neurons were encountered in 79% of SIDS and 68% of control cases. More leptomeningeal neurons in SIDS versus control cases were found in lower pons (p = 0.002), upper pons (p = 0.016), cerebellar hemispheres (p = 0.012), lower medulla oblongata (p = 0.039), and temporal lobe (p = 0.041). Summarizing the data according to gross anatomical region of origin (i.e., brainstem, cerebellum or cerebrum), higher numbers of leptomeningeal neurons in SIDS cases were only found in the brainstem (p = 0.006 vs. 0.13 and 0.19, respectively). Our data show that single leptomeningeal neurons are present in most normal infantile brains. The age-dependent increase of leptomeningeal neurons among SIDS cases may either (a) represent a delayed maturation or retardation, i.e., a later or slower reduction of neurons or a delayed peak in occurrence (shift toward an older age), or (b) may be interpreted as a generally increased occurrence of leptomeningeal neurons among SIDS cases as a result of a diffuse developmental abnormality during central nervous system maturation.

  15. Cranial dural arteriovenous shunts. Part 4. Clinical presentation of the shunts with leptomeningeal venous drainage.

    PubMed

    Baltsavias, Gerasimos; Spiessberger, Alex; Hothorn, Torsten; Valavanis, Anton

    2015-04-01

    Cranial dural arteriovenous fistulae have been classified into high- and low-risk lesions mainly based on the pattern of venous drainage. Those with leptomeningeal venous drainage carry a higher risk of an aggressive clinical presentation. Recently, it has been proposed that the clinical presentation should be considered as an additional independent factor determining the clinical course of these lesions. However, dural shunts with leptomeningeal venous drainage include a very wide spectrum of inhomogeneous lesions. In the current study, we correlated the clinical presentation of 107 consecutive patients harboring cranial dural arteriovenous shunts with leptomeningeal venous drainage, with their distinct anatomic and angiographic features categorized into eight groups based on the "DES" (Directness and Exclusivity of leptomeningeal venous drainage and features of venous Strain) concept. We found that among these groups, there are significant angioarchitectural differences, which are reflected by considerable differences in clinical presentation. Leptomeningeal venous drainage of dural sinus shunts that is neither direct nor exclusive and without venous strain manifested only benign symptoms (aggressive presentation 0%). On the other end of the spectrum, the bridging vein shunts with direct and exclusive leptomeningeal venous drainage and venous strain are expected to present aggressive symptoms almost always and most likely with bleeding (aggressive presentation 91.5%). Important aspects of the above correlations are discussed. Therefore, the consideration of leptomeningeal venous drainage alone, for prediction of the clinical presentation of these shunts appears insufficient. Angiographic analysis based on the above concept, offers the possibility to distinguish the higher- from the lower-risk types of leptomeningeal venous drainage. In this context, consideration of the clinical presentation as an additional independent factor for the prediction of their clinical

  16. Effector T-cell trafficking between the leptomeninges and the cerebrospinal fluid.

    PubMed

    Schläger, Christian; Körner, Henrike; Krueger, Martin; Vidoli, Stefano; Haberl, Michael; Mielke, Dorothee; Brylla, Elke; Issekutz, Thomas; Cabañas, Carlos; Nelson, Peter J; Ziemssen, Tjalf; Rohde, Veit; Bechmann, Ingo; Lodygin, Dmitri; Odoardi, Francesca; Flügel, Alexander

    2016-02-18

    In multiple sclerosis, brain-reactive T cells invade the central nervous system (CNS) and induce a self-destructive inflammatory process. T-cell infiltrates are not only found within the parenchyma and the meninges, but also in the cerebrospinal fluid (CSF) that bathes the entire CNS tissue. How the T cells reach the CSF, their functionality, and whether they traffic between the CSF and other CNS compartments remains hypothetical. Here we show that effector T cells enter the CSF from the leptomeninges during Lewis rat experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. While moving through the three-dimensional leptomeningeal network of collagen fibres in a random Brownian walk, T cells were flushed from the surface by the flow of the CSF. The detached cells displayed significantly lower activation levels compared to T cells from the leptomeninges and CNS parenchyma. However, they did not represent a specialized non-pathogenic cellular sub-fraction, as their gene expression profile strongly resembled that of tissue-derived T cells and they fully retained their encephalitogenic potential. T-cell detachment from the leptomeninges was counteracted by integrins VLA-4 and LFA-1 binding to their respective ligands produced by resident macrophages. Chemokine signalling via CCR5/CXCR3 and antigenic stimulation of T cells in contact with the leptomeningeal macrophages enforced their adhesiveness. T cells floating in the CSF were able to reattach to the leptomeninges through steps reminiscent of vascular adhesion in CNS blood vessels, and invade the parenchyma. The molecular/cellular conditions for T-cell reattachment were the same as the requirements for detachment from the leptomeningeal milieu. Our data indicate that the leptomeninges represent a checkpoint at which activated T cells are licensed to enter the CNS parenchyma and non-activated T cells are preferentially released into the CSF, from where they can reach areas of antigen

  17. Metronomic Capecitabine Effectively Blocks Leptomeningeal Carcinomatosis From Breast Cancer: A Case Report and Literature Review

    PubMed Central

    Maur, Michela; Omarini, Claudia; Piacentini, Federico; Fontana, Annalisa; Pettorelli, Elisa; Cascinu, Stefano

    2017-01-01

    Patient: Female, 57 Final Diagnosis: Meningeal carcinomatosis from breast cancer Symptoms: Seizures Medication: — Clinical Procedure: — Specialty: Oncology Objective: Unusual clinical course Background: Meningeal carcinomatosis is a rare complication in breast cancer patients. At present, there are no defined guidelines for its management. The efficacy of systemic treatment seems to depend on its ability to cross the blood-brain-barrier and its interaction with tumor vasculature. Metronomic chemotherapy is a known modality of drug administration able to inhibit tumor angiogenesis. Case Report: We present a case of symptomatic leptomeningeal carcinomatosis from breast cancer successfully treated with capecitabine. Based on the hypothesis that angiogenesis contributes to neoplastic meningitis, the patient was treated with a metronomic schedule that provided long-term clinical benefit with a very low toxicity profile. Conclusions: To assess the real impact of metronomic chemotherapy in patients with meninges involvement, a phase II study will be starting soon in our institution. A review of the literature concerning the management of meningeal carcinomatosis is also presented. PMID:28242865

  18. Outcome Evaluation of Patients with Limited Brain Metastasis From Malignant Melanoma, Treated with Surgery, Radiation Therapy, and Targeted Therapy.

    PubMed

    Pessina, Federico; Navarria, Pierina; Tomatis, Stefano; Cozzi, Luca; Franzese, Ciro; Di Guardo, Lorenza; Ascolese, Anna Maria; Reggiori, Giacomo; Franceschini, Davide; Del Vecchio, Michele; Bello, Lorenzo; Scorsetti, Marta

    2017-09-01

    The incidence of brain metastases from melanoma is increasing. Several effective treatment options are now available but what can be considered the optimal therapeutic strategy is not yet defined. We evaluated the outcome of patients with brain metastatic melanoma in terms of local control rate, brain distant progression, and overall survival. The present retrospective study includes only patients with limited brain metastases (≤4) who underwent surgery plus stereotactic radiosurgery (SRS), or SRS alone. Surgical resection was performed in patients with good Karnofsky performance score, single large brain lesions, controlled extracranial disease, and SRS alone in all other cases. Supramargical resection was performed in all patients. The prescribed radiotherapy doses were 24 Gy/1 fraction and 30 Gy in 3-5 fractions for lesions >2.5 cm. Clinical outcome was evaluated by brain magnetic resonance imaging performed 2 months after radiotherapy and then every 3 months. From April 2011 to October 2015, 53 patients were treated. The median age was 54 years (range, 29-82 years). Most of patients had 1-2 brain metastases (86.8%). Twelve patients (22.6%) underwent surgical resection followed by SRS on the tumor bed, and 41 (77.4%) received SRS alone. The median follow-up time was 20.9 months (range, 5.7-61.3 months). The median, 1-, 2-, 3-year overall survival were 11.8 months, 47.2%, 28%, and 21.8%, respectively. Factors recorded as influencing survival were the number of brain metastases, the melanoma-specific graded prognostic assessment score, and BRAF mutated status. Our data identifier a subset of patients with a more favorable outcome who could take advantage of a more aggressive local approach followed by targeted therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Posterior cervical lymph node metastasis as the valuable prognostic factor for stage IVA/IVB nasopharyngeal carcinoma treated with induction chemotherapy followed by concurrent chemo-radiotherapy.

    PubMed

    Thephamongkhol, Kullathorn; Setakornnukul, Jiraporn; Rojwatkarnjana, Sunanta; Chansilpa, Yaowalak

    2014-12-09

    To evaluate the prognostic properties of retropharyngeal lymph node (RP), posterior cervical lymph node (PCN), and supraclavicular lymph node (SPC), in stage IVA/IVB nasopharyngeal carcinoma (NPC) patients in setting of induction chemotherapy. We performed a retrospective study including 43 patients with stage IVA/IVB NPC (7th AJCC) treated with induction chemotherapy followed by concurrent chemo-radiotherapy. We analyzed prognosis with the multivariate Cox regression model and p-value from the Wald's test, using the backward elimination method (by likelihood ratio test and percent change of coefficient factors). Overall, 24 patients (55.8%) were in stage IVA and 19 (44.2%) in stage IVB. After a median follow-up time of 30 months, the 2-year overall survival (OS) was 79.1%, while the 2-year progression free survival (PFS) and distant metastasis free survival (DMFS) were 59.8% and 69.1%, respectively. In multivariate analysis for predicting DMFS, SPC involvement was not statistically significant (HR 3.39; 95% CI 0.76-15.07; p=0.1), whereas RP involvement was statistically significant (HR 5.81; 95% CI 1.08-31.16; p=0.04). Moreover, and more importantly, PCN involvement was the only nodal factor to predict all of DMFS, PFS, and OS (respectively HR 5.57, 95% CI 1.12-27.71, p=0.036; HR 16.05, 95% CI 1.93-133.65, p=0.01; and HR 28.02, 95% CI 2.74-286.22, p=0.005). PCN involvement is the only independent prognostic factor of stage IVA/IVB NPC patients treated by induction chemotherapy that predicts DMFS and turns this effect to PFS and OS. PCN involvement is a highly accurate predictor for failure of conventional chemo-radiotherapy. Therefore, patients with PCN involvement should be defined at high-risk, as to be investigated for a new staging system.

  20. Obesity is associated with castration-resistant disease and metastasis in men treated with androgen deprivation therapy after radical prostatectomy: results from the SEARCH database

    PubMed Central

    Keto, Christopher J.; Aronson, William J.; Terris, Martha K.; Presti, Joseph C.; Kane, Christopher J.; Amling, Christopher L.; Freedland, Stephen J.

    2012-01-01

    OBJECTIVE To investigate whether obesity predicts poor outcomes in men starting androgen deprivation therapy (ADT) before metastasis, since previous studies found worse outcomes after surgery and radiation for obese men. METHODS A retrospective review was carried out of 287 men in the SEARCH database treated with radical prostatectomy between 1988 and 2009.Body mass index (BMI) was categorized to <25, 25–29.9 and ≥30 kg/m2.Proportional hazards models were used to test the association between BMI and time to castration-resistant prostate cancer (PC), metastases and PC-specific mortality adjusting for demographic and clinicopathological data. RESULTS During a median 73-month follow-up after radical prostatectomy, 403 men (14%) received early ADT.Among 287 men with complete data, median BMI was 28.3 kg/m2.Median follow-up from the start of ADT was 52 months during which 44 men developed castration-resistant PC, 34 developed metastases and 24 died from PC.In multivariate analysis, higher BMI was associated with a trend for greater risk of progression to castration-resistant PC (P = 0.063), a more than threefold increased risk of developing metastases (P = 0.027) and a trend toward worse PC-specific mortality (P = 0.119).Prognostic biomarkers did not differ between BMI groups. CONCLUSIONS Among men treated with early ADT, our results suggest that obese men may have increased risk of PC progression.These data support the general hypothesis that obesity is associated with aggressive PC, although validation of these findings and further study of the mechanisms linking obesity and poor PC outcomes are required. PMID:22094083

  1. Permeability of the arachnoid and pia mater. The role of ion channels in the leptomeningeal physiology.

    PubMed

    Filippidis, Aristotelis S; Zarogiannis, Sotirios G; Ioannou, Maria; Gourgoulianis, Konstantinos; Molyvdas, Paschalis-Adam; Hatzoglou, Chrissi

    2012-04-01

    The purpose of this paper is to study the ionic permeability of the leptomeninges related to the effect of ouabain (sodium-potassium-ATPase inhibitor) and amiloride (epithelial sodium channel (ENaC) inhibitor) on the tissue, as well as identify the presence of ion channels. Cranial leptomeningeal samples from 26 adult sheep were isolated. Electrophysiological measurements were performed with Ussing system and transmembrane resistance values (R(TM) in Ω*cm(2)) obtained over time. Experiments were conducted with the application of ouabain 10(-3) M or amiloride 10(-5) M at the arachnoidal and pial sides. Immunohistochemical studies of leptomeningeal tissue were prepared with alpha-1 sodium-potassium-ATPase (ATP1A1), beta-ENaC, and delta-ENaC subunit antibodies. The application of ouabain at the arachnoidal side raised the transmembrane resistance statistically significantly and thus decreased its ionic permeability. The addition of ouabain at the pial side led also to a significant but less profound increment in transmembrane resistance. The addition of amiloride at the arachnoidal or pial side did not produce any statistical significant change in the R(TM) from controls (p > 0.05). Immunohistochemistry confirmed the presence of the ATP1A1 and beta- and delta-ENaC subunits at the leptomeninges. In summary, leptomeningeal tissue possesses sodium-potassium-ATPase and ENaC ion channels. The application of ouabain alters the ionic permeability of the leptomeninges thus reflecting the role of sodium-potassium-ATPase. Amiloride application did not alter the ionic permeability of leptomeninges possibly due to localization of ENaC channels towards the subarachnoid space, away from the experimental application sites. The above properties of the tissue could potentially be related to cerebrospinal fluid turnover at this interface.

  2. Ki-67 Is an Independent Predictor of Metastasis and Cause-Specific Mortality for Prostate Cancer Patients Treated on Radiation Therapy Oncology Group (RTOG) 94-08

    SciTech Connect

    Verhoven, Bret; Yan, Yan; Ritter, Mark; Khor, Li-Yan; Hammond, Elizabeth; Jones, Christopher; Amin, Mahul; Bahary, Jean-Paul; Zeitzer, Kenneth; Pollack, Alan

    2013-06-01

    Purpose: The association of Ki-67 staining index (Ki67-SI) with overall survival (OS), disease-specific mortality (DSM), distant metastasis (DM), and biochemical failure (BF) was examined in men with favorable- to intermediate-risk prostate cancer receiving radiation therapy (RT) alone or with short-term androgen deprivation (ADT) in Radiation Therapy Oncology Group (RTOG) 94-08. Methods and Materials: 468 patients (23.6%) on RTOG 94-08 had sufficient tissue for Ki67-SI analysis. The median follow-up time was 7.9 years. Ki67-SI was determined by immunohistochemistry and quantified manually and by image analysis. Correlative analysis versus clinical outcome was performed using the third quartile (≥Q3) cutpoint. A proportional hazards multivariable analysis (MVA) dichotomized covariates in accordance with trial stratification and randomization criteria. Results: In MVAs adjusted for all treatment covariates, high Ki67-SI (≥Q3) was correlated with increased DSM (hazard ratio [HR] 2.48, P=.03), DM (HR 3.5, P=.002), and BF (HR 3.55, P<.0001). MVA revealed similar Ki67-associated hazard ratios in each separate treatment arm for DSM, DM, and BF; these reached significance only for DM in the RT-alone arm and for BF in both arms. Ki67-SI was not a significant predictor of intraprostatic recurrence assessed by repeated biopsy 2 years after treatment. Patients with a high or low Ki67-SI seemed to experience a similar relative benefit from the addition of ADT to radiation. Conclusions: High Ki67-SI independently predicts for increased DSM, DM, and protocol BF in primarily intermediate-risk prostate cancer patients treated with RT with or without ADT on RTOG 94-08 but does not predict for local recurrence or for increased relative benefit from ADT. This and prior studies lend support for the use of Ki67-SI as a stratification factor in future trials.

  3. Age-dependent responses of glial cells and leptomeninges during systemic inflammation.

    PubMed

    Wu, Zhou; Tokuda, Yukie; Zhang, Xin-Wen; Nakanishi, Hiroshi

    2008-12-01

    Systemic inflammation causes the age-dependent differential glial responses, but little is known about how age influences the barrier function of leptomeninges during systemic inflammation. This study was conducted to elucidate the relationship between the glial responses and the levels of tight junction proteins, occludin and ZO-1, in adjuvant arthritis (AA) rats. In young AA rats, microglia and astrocytes localized to the proximity of the leptomeninges expressed interleukin (IL)-10 and transforming growth factor (TGF)-beta1. The level of occludin significantly increased. In middle-aged AA rats, however, glial cells expressed IL-1beta and prostaglandin E(2) (PGE(2))-synthesizing enzymes. Furthermore, occludin and ZO-1 significantly decreased, resulting in the increased permeability of leptomeninges. In the cultured leptomeningeal cells, IL-1beta and PGE(2) caused a marked loss of occludin and ZO-1, respectively. Pretreatment with IL-10 and TGF-beta1 significantly antagonized their effects. These findings establish that age strongly influences the barrier functions of the leptomeninges through the age-dependent differential glial responses during systemic inflammation.

  4. Leptomeningeal dissemination of pilocytic astrocytoma in a 17-year-old boy.

    PubMed

    Jandaghi, Ali BabaeI; Bidabadi, Elham; Saadat, Seyed; Alijani, Babak; Daliri, Saeid; Reyhanian, Zoheir; Mashouf, Mehryar

    2014-01-01

    Pilocytic astrocytoma with leptomeningeal dissemination is a rare phenomenon and can be associated with obstructive hydrocephalus and an unfavorable prognosis. Herein, we report a seventeen-year-old boy with a history of ventriculo-peritoneal shunt insertion due to severe hydrocephalus who presented with progressive headache and vomiting together with ocular and cerebellar signs and symptoms. Neuroimaging confirmed the presence of multiple intracranial masses in the cerebellum and thalamus. Intracranial dissemination of tumor to the the leptomeninges was seen during neuroendoscopy. Simultaneous biopsy and endoscopic third ventriculostomy were performed and the diagnosis of low-grade pilocytic astrocytoma with leptomeningeal dissemination was made by histological examination. The patient underwent chemotherapy in combination with radiotherapy to reduce the risk of reoccurrence of the primary tumor and was followed for one year.

  5. Disseminated oligodendroglial-like leptomeningeal tumor with anaplastic progression and presumed extraneural disease: case report.

    PubMed

    Kessler, Brice A; Bookhout, Christine; Jaikumar, Sivakumar; Hipps, John; Lee, Yueh Z

    2015-01-01

    We report the neuroimaging and histopathologic findings of a 12-year-old female patient with a disseminated oligodendroglial-like leptomeningeal tumor with anaplastic progression and presumed extraneural metastatic disease. These tumors may represent distinct pathology primarily seen in pediatric patients. Neuroimaging demonstrates diffuse, progressive enhancement of the leptomeninges often with interval development of intraparenchymal lesions on follow-up. Disease is typically confined to the central nervous system, though diffuse peritoneal disease was seen in our case, possibly through metastatic seeding of the abdomen via ventriculoperitoneal shunt.

  6. Aspirin, lysine, mifepristone and doxycycline combined can effectively and safely prevent and treat cancer metastasis: prevent seeds from gemmating on soil.

    PubMed

    Wan, Liyuan; Dong, Haiyan; Xu, Huo; Ma, Ji; Zhu, Yewei; Lu, Yusheng; Wang, Jichuang; Zhang, Ting; Li, Tao; Xie, Jingjing; Xu, Bo; Xie, Fangwei; Gao, Yu; Shao, Jingwei; Tu, Xiaohuang; Jia, Lee

    2015-11-03

    Recent scientific advances have increased our understanding of the cancer metastatic complexities and provided further impetus for new combination therapies to prevent cancer metastasis. Here, we demonstrated that a combination (HAMPT) of aspirin, lysine, mifepristone and doxycycline can effectively and safely prevent cancer metastasis. The pharmaceutically-formulated HAMPT inhibited adhesion of cancer cells to either endothelial cells or extracellular matrix via down-regulating cell adhesion molecules ICAM-1 and α4-integrin. HAMPT inhibited the cloak effect by activated platelets on cancer cells, thereby interfering adhesion and invasion of cancer cells to the underlying stroma. At the effective concentration, HAMPT induced cancer cells into dormancy with minor inhibition on cell viability. Four-day pretreatment followed by 30-day oral administration of HAMPT (33.5-134 mg/kg) to the mice inoculated with cancer cells produced significant inhibition on cancer metastasis dose-dependently without marked side effects. Fifty-day rat toxicity study with HAMPT at doses (335-1340 mg/kg) 20-fold higher than its therapeutic dose produced no significant toxicity. Interestingly, the acute toxic death could not be reached at the maximum administrable dose (5 g/kg). This proof-of-concept study provides the first conceptual evidence that cancer metastasis can be controlled by using affordable old drugs to restrain circulating tumor cells from gemmating on the metastatic soil without the need for cytotoxicity.

  7. Aspirin, lysine, mifepristone and doxycycline combined can effectively and safely prevent and treat cancer metastasis: prevent seeds from gemmating on soil

    PubMed Central

    Xu, Huo; Ma, Ji; Zhu, Yewei; Lu, Yusheng; Wang, Jichuang; Zhang, Ting; Li, Tao; Xie, Jingjing; Xu, Bo; Xie, Fangwei; Gao, Yu; Shao, Jingwei; Tu, Xiaohuang; Jia, Lee

    2015-01-01

    Recent scientific advances have increased our understanding of the cancer metastatic complexities and provided further impetus for new combination therapies to prevent cancer metastasis. Here, we demonstrated that a combination (HAMPT) of aspirin, lysine, mifepristone and doxycycline can effectively and safely prevent cancer metastasis. The pharmaceutically-formulated HAMPT inhibited adhesion of cancer cells to either endothelial cells or extracellular matrix via down-regulating cell adhesion molecules ICAM-1 and α4-integrin. HAMPT inhibited the cloak effect by activated platelets on cancer cells, thereby interfering adhesion and invasion of cancer cells to the underlying stroma. At the effective concentration, HAMPT induced cancer cells into dormancy with minor inhibition on cell viability. Four-day pretreatment followed by 30-day oral administration of HAMPT (33.5-134 mg/kg) to the mice inoculated with cancer cells produced significant inhibition on cancer metastasis dose-dependently without marked side effects. Fifty-day rat toxicity study with HAMPT at doses (335-1340 mg/kg) 20-fold higher than its therapeutic dose produced no significant toxicity. Interestingly, the acute toxic death could not be reached at the maximum administrable dose (5 g/kg). This proof-of-concept study provides the first conceptual evidence that cancer metastasis can be controlled by using affordable old drugs to restrain circulating tumor cells from gemmating on the metastatic soil without the need for cytotoxicity. PMID:26459390

  8. SU-E-J-256: Predicting Metastasis-Free Survival of Rectal Cancer Patients Treated with Neoadjuvant Chemo-Radiotherapy by Data-Mining of CT Texture Features of Primary Lesions

    SciTech Connect

    Zhong, H; Wang, J; Shen, L; Hu, W; Wan, J; Zhou, Z; Zhang, Z

    2015-06-15

    Purpose: The purpose of this study is to investigate the relationship between computed tomographic (CT) texture features of primary lesions and metastasis-free survival for rectal cancer patients; and to develop a datamining prediction model using texture features. Methods: A total of 220 rectal cancer patients treated with neoadjuvant chemo-radiotherapy (CRT) were enrolled in this study. All patients underwent CT scans before CRT. The primary lesions on the CT images were delineated by two experienced oncologists. The CT images were filtered by Laplacian of Gaussian (LoG) filters with different filter values (1.0–2.5: from fine to coarse). Both filtered and unfiltered images were analyzed using Gray-level Co-occurrence Matrix (GLCM) texture analysis with different directions (transversal, sagittal, and coronal). Totally, 270 texture features with different species, directions and filter values were extracted. Texture features were examined with Student’s t-test for selecting predictive features. Principal Component Analysis (PCA) was performed upon the selected features to reduce the feature collinearity. Artificial neural network (ANN) and logistic regression were applied to establish metastasis prediction models. Results: Forty-six of 220 patients developed metastasis with a follow-up time of more than 2 years. Sixtyseven texture features were significantly different in t-test (p<0.05) between patients with and without metastasis, and 12 of them were extremely significant (p<0.001). The Area-under-the-curve (AUC) of ANN was 0.72, and the concordance index (CI) of logistic regression was 0.71. The predictability of ANN was slightly better than logistic regression. Conclusion: CT texture features of primary lesions are related to metastasisfree survival of rectal cancer patients. Both ANN and logistic regression based models can be developed for prediction.

  9. Bone morphogenetic protein-4 and 7 and receptors regulate vascular endothelial growth factor and receptors in human fetal leptomeninges.

    PubMed

    Johnson, Mahlon D; Reeder, Jay E; O'Connell, Mary

    2015-10-08

    Bone morphogenetic proteins (BMP) 4 and 7 have important roles in neuronal differentiation and cortical development in the murine brain. However BMP4 and BMP7 expression and functions in the developing human brain are unknown. In this study, frozen tissue human fetal leptomeninges, formalin-fixed tissue and primary fetal leptomeningeal cell cultures were studied. By western blot, BMP4, BMP7 and BMPRIa were demonstrated in 15, 17 20, 23 week (wk) human leptomeninges. BMP receptor II was detected at 15 and 17 wks. Immunohistochemically, BMP4 immunoreactivity was also found in 20 to 39 wk human leptomeninges. BMP4 significantly reduced basal DNA synthesis at 22 wks. BMP7 100 and 300 ng/ml stimulated basal DNA synthesis in the 15, 17 and 22 wk leptomeninges. BMP4 and BMP7 increased phosphorylation of SMAD-1, 5, 8 in most cells and had no effect on phosphorylation of p-38MAPK, or p44/42MAPK. BMP4 and BMP7 produced a decrease in VEGF RNA expression in 2 of 4 leptomeninges. BMP4 and BMP7 increased VEGFR1 RNA in 2 or 3 of 4 leptomeningeal cultures respectively. BMP4 produced a decrease in VEGFR2 RNA in 2 of 4 and BMP7 in 3 of 4 while BMP7 reduced VEGFR2 protein in the leptomeninges. The findings show, for the first time, BMP4, BMP7 and receptors are expressed and active in the human fetal leptomeninges. They suggest these BMPs influence vascular development in this tissue by regulating VEGF and its receptors. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  10. A case of brain and leptomeningeal metastases from urothelial carcinoma of the bladder.

    PubMed

    Erhamamcı, S; Reyhan, M; Altinkaya, N

    2014-01-01

    Brain metastases are unusual from urethelial carcinoma of bladder and particularly the occurrence of leptomeningeal metastases is extremely rare, with few cases described in the literature. We present a case of a 45-year-old man with a rare brain metastases as the first metastatic manifestation secondary to urethelial carcinoma of bladder followed by leptomeningeal metastases without any other organ involvement. Eleven months after the diagnosis of high-grade urethelial carcinoma of bladder (T2N0M0), the patient was detected having brain metastases by MRI. FDG PET/CT images for the metastatic evaluation showed no abnormal FDG uptake elsewhere in the body except the brain. Histopathology examination from brain lesion demonstrated the cerebral lesion to be a metastatic urothelial carcinoma. Two months later, the patient was diagnosed to have leptomeningeal metastases by MRI. Our patient's condition gradually worsened, and he died 3 months after the diagnosis of leptomeningeal metastases. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

  11. Chronic Leptomeningitis and Spinal Intradural Mass Secondary to Alternaria Infection in a Patient with Ventriculoperitoneal Shunt

    PubMed Central

    Thompson, Russell; Jandial, Rahul; Tegtmeier, Bernard; Chen, Mike Yue

    2016-01-01

    Fungal infection following placement of ventriculostomy or ventriculoperitoneal (VP) shunt is uncommon. We report the first case of Alternaria related central nervous system (CNS) shunt infection in a patient with CNS ependymoma manifesting as leptomeningitis and a spinal intradural mass. This case illustrates the diagnostic and management challenges. PMID:27840750

  12. Leptomeningeal dissemination of a low-grade lumbar paraganglioma: case report.

    PubMed

    Thomson, Nick; Pacak, Karel; Schmidt, Meic H; Palmer, Cheryl A; Salzman, Karen L; Champine, Marjan; Schiffman, Joshua D; Cohen, Adam L

    2017-01-27

    Leptomeningeal dissemination of paraganglioma is rare, with only 2 prior cases in the literature. The authors present the case of a metastatic low-grade lumbar paraganglioma via leptomeningeal dissemination. This report emphasizes the utility of 3,4-dihydroxy-6-(18)F-fluoro-l-phenylalanine ((18)F-FDOPA) PET scanning for diagnosis, as well as the combination of radiation therapy and alkylating chemotherapeutic agents for the treatment of this rare phenomenon. The patient was a 61-year-old woman who presented with low-back pain and was found to have an isolated L-3 intrathecal tumor on MRI. Sixteen months after gross-total en bloc resection of the paraganglioma, the patient again became symptomatic with new neurological symptoms. MRI findings revealed enhancing leptomeningeal nodules throughout the spine. (18)F-FDOPA PET/CT scanning was used to confirm the diagnosis of disseminated paraganglioma. Intrathecal thiotepa, radiation therapy, and systemic therapy with capecitabine and temozolomide have been used sequentially over a 2-year period, with each able to stabilize tumor growth for several months. The authors also summarize the 2 other reports of leptomeningeal dissemination of paragangliomas in the literature and compare the course and management of the 3 cases.

  13. Managing leptomeningeal melanoma metastases in the era of immune and targeted therapy

    PubMed Central

    Smalley, Keiran S.M.; Fedorenko, Inna V.; Kenchappa, Rajappa; Sahebjam, Solmaz; Forsyth, Peter A.

    2016-01-01

    Melanoma frequently metastasizes to the brain, with CNS involvement being clinically evident in ~30% of patients (as high as 75% at autopsy). In ~5% cases melanoma cells also metastasize to the leptomeninges, the sub-arachnoid space and cerebrospinal fluid (CSF). Patients with leptomeningeal melanoma metastases (LMM) have the worst prognosis and are characterized by rapid disease progression (mean survival 8-10 weeks) and a death from neurological causes. The recent years have seen tremendous progress in the development of targeted and immune therapies for melanoma that has translated into an increased survival benefit. Despite these gains, the majority of patients fail therapy and there is a suspicion that the brain and the leptomeninges are a “sanctuary” sites for melanoma cells that escape both targeted therapy and immunologic therapies. Emerging evidence suggests that 1) Cancer cells migrating to the CNS may have unique molecular properties and 2) the CNS/leptomeningeal microenvironment represents a pro-survival niche that influences therapeutic response. In this Mini-Review we will outline the clinical course of LMM development and will describe how the intracranial immune and cellular microenvironments offer both opportunities and challenges for the successful management of this disease. We will further discuss the latest data demonstrating the potential use of BRAF inhibitors and immune therapy in the management of LMM, and will review future potential therapeutic strategies for the management of this most devastating complication of advanced melanoma. PMID:27084046

  14. Novel stem/progenitor cells with neuronal differentiation potential reside in the leptomeningeal niche

    PubMed Central

    Bifari, Francesco; Decimo, Ilaria; Chiamulera, Christian; Bersan, Emanuela; Malpeli, Giorgio; Johansson, Jan; Lisi, Veronica; Bonetti, Bruno; Fumagalli, Guido; Pizzolo, Giovanni; Krampera, Mauro

    2009-01-01

    Stem cells capable of generating neural differentiated cells are recognized by the expression of nestin and reside in specific regions of the brain, namely, hippocampus, subventricular zone and olfactory bulb. For other brain structures, such as leptomeninges, which contribute to the correct cortex development and functions, there is no evidence so far that they may contain stem/precursor cells. In this work, we show for the first time that nestin-positive cells are present in rat leptomeninges during development up to adulthood. The newly identified nestin-positive cells can be extracted and expanded in vitro both as neurospheres, displaying high similarity with subventricular zone–derived neural stem cells, and as homogeneous cell population with stem cell features. In vitro expanded stem cell population can differentiate with high efficiency into excitable cells with neuronal phenotype and morphology. Once injected into the adult brain, these cells survive and differentiate into neurons, thus showing that their neuronal differentiation potential is operational also in vivo. In conclusion, our data provide evidence that a specific population of immature cells endowed of neuronal differentiation potential is resident in the leptomeninges throughout the life. As leptomeninges cover the entire central nervous system, these findings could have relevant implications for studies on cortical development and for regenerative medicine applied to neurological disorders. PMID:19228261

  15. Diffuse Spinal Leptomeningeal Spread of a Pilocytic Astrocytoma in a 3-year-old Child.

    PubMed

    Alyeldien, Ameer; Teuber-Hanselmann, Sarah; Cheko, Azad; Höll, Tanja; Scholz, Martin; Petridis, Athanasios K

    2016-03-25

    Pilocytic astrocytomas correspond to low-grade gliomas and therefore metastasize exceedingly rare. However, pilocytic astrocytomas are able to and leptomeningeal dissemination may be seen. What are the treatment options of these cases? We present a case report of a 3-year-old child with a pilocytic astrocytoma of the optic chiasm with leptomeningeal dissemination of the spinal meninges. Partial resection of the cerebral tumor has been performed. Since the leptomeningeal dissemination was seen all over the spinal meninges, the child did not undergo further surgical treatment. A wait and watch strategy were followed. Chemotherapy was initiated, if a 25% tumor growth was seen. Leptomeningeal dissemination of a pilocytic astrocytoma is seen so infrequently that no standard therapy is established. Since these metastases may occur even up to 2 decades after primary tumor resection, long-term follow-up is indicated. In case of spinal metastases, surgical treatment should be performed if feasible. Otherwise observation should be possessed and/or chemotherapy should be initiated.

  16. Diffuse Spinal Leptomeningeal Spread of a Pilocytic Astrocytoma in a 3-year-old Child

    PubMed Central

    Alyeldien, Ameer; Teuber-Hanselmann, Sarah; Cheko, Azad; Höll, Tanja; Scholz, Martin; Petridis, Athanasios K.

    2016-01-01

    Pilocytic astrocytomas correspond to low-grade gliomas and therefore metastasize exceedingly rare. However, pilocytic astrocytomas are able to and leptomeningeal dissemination may be seen. What are the treatment options of these cases? We present a case report of a 3-year-old child with a pilocytic astrocytoma of the optic chiasm with leptomeningeal dissemination of the spinal meninges. Partial resection of the cerebral tumor has been performed. Since the leptomeningeal dissemination was seen all over the spinal meninges, the child did not undergo further surgical treatment. A wait and watch strategy were followed. Chemotherapy was initiated, if a 25% tumor growth was seen. Leptomeningeal dissemination of a pilocytic astrocytoma is seen so infrequently that no standard therapy is established. Since these metastases may occur even up to 2 decades after primary tumor resection, long-term follow-up is indicated. In case of spinal metastases, surgical treatment should be performed if feasible. Otherwise observation should be possessed and/or chemotherapy should be initiated. PMID:27162602

  17. Managing leptomeningeal melanoma metastases in the era of immune and targeted therapy.

    PubMed

    Smalley, Keiran S M; Fedorenko, Inna V; Kenchappa, Rajappa S; Sahebjam, Solmaz; Forsyth, Peter A

    2016-09-15

    Melanoma frequently metastasizes to the brain, with CNS involvement being clinically evident in ∼30% of patients (as high as 75% at autopsy). In ∼5% cases melanoma cells also metastasize to the leptomeninges, the sub-arachnoid space and cerebrospinal fluid (CSF). Patients with leptomeningeal melanoma metastases (LMM) have the worst prognosis and are characterized by rapid disease progression (mean survival 8-10 weeks) and a death from neurological causes. The recent years have seen tremendous progress in the development of targeted and immune therapies for melanoma that has translated into an increased survival benefit. Despite these gains, the majority of patients fail therapy and there is a suspicion that the brain and the leptomeninges are a "sanctuary" sites for melanoma cells that escape both targeted therapy and immunologic therapies. Emerging evidence suggests that (1) Cancer cells migrating to the CNS may have unique molecular properties and (2) the CNS/leptomeningeal microenvironment represents a pro-survival niche that influences therapeutic response. In this Mini-Review, we will outline the clinical course of LMM development and will describe how the intracranial immune and cellular microenvironments offer both opportunities and challenges for the successful management of this disease. We will further discuss the latest data demonstrating the potential use of BRAF inhibitors and immune therapy in the management of LMM, and will review future potential therapeutic strategies for the management of this most devastating complication of advanced melanoma.

  18. Nobiletin attenuates metastasis via both ERK and PI3K/Akt pathways in HGF-treated liver cancer HepG2 cells.

    PubMed

    Shi, Ming-Der; Liao, Yi-Chen; Shih, Yuan-Wei; Tsai, Li-Yu

    2013-06-15

    Hepatocyte growth factor (HGF), and its receptor, c-Met activation has recently been shown to play important roles in cancer invasion and metastasis in a wide variety of tumor cells. We use HGF as an invasive inducer of human HepG2 cells to investigate the effect of four flavones including apigenin, tricetin, tangeretin, and nobiletin on HGF/c-Met-mediated tumor invasion and metastasis. Among them, nobiletin markedly inhibited HGF-induced the abilities of the adhesion, invasion, and migration by cell-matrix adhesion assay and transwell-chamber invasion/migration assay under non-cytotoxic concentrations. Data also showed nobiletin inhibited HGF-induced cell scattering and cytoskeleton changed such as filopodia and lamellipodia. Furthermore, nobiletin could inhibit HGF-induced the membrane localization of phosphorylated c-Met, ERK2, and Akt, but not phosphorylated JNK1/2 and p38. Next, nobiletin significantly decreased the levels of phospho-ERK2 and phospho-Akt in ERK2 or Akt siRNA-transfected cells concomitantly with a marked reduction on cell invasion and migration. In conclusion, nobiletin attenuates HGF-induced HepG2 cells metastasis involving both ERK and PI3K/Akt pathways and are potentially useful as anti-metastatic agents for the treatment of hepatoma.

  19. Intramedullary metastasis.

    PubMed

    Moffie, D; Stefanko, S Z

    1980-01-01

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

  20. IMAGING DIAGNOSIS--MAGNETIC RESONANCE IMAGING OF DIFFUSE LEPTOMENINGEAL OLIGODENDROGLIOMATOSIS IN A DOG WITH "DURAL TAIL SIGN".

    PubMed

    Lobacz, Monika Anna; Serra, Fabienne; Hammond, Gawain; Oevermann, Anna; Haley, Allison C

    2016-11-04

    A case of diffuse leptomeningeal oligodendrogliomatosis affecting the brain and spinal cord of a dog is presented. A 7.5-year old, male neutered Staffordshire bull terrier presented for evaluation of a chronic history of tetraparesis and seizures, with a multifocal neuroanatomical localization was determined. Extra-axial intradural lesions with an atypical presentation of a dural tail sign were seen on MRI. Histologically, the lesions were consistent with leptomeningeal oligodendrogliomatosis. To the authors' knowledge, a dural tail sign has not previously been reported as an MRI characteristic of diffuse leptomeningeal oligodendrogliomatosis in dogs.

  1. Older Age Predicts Decreased Metastasis and Prostate Cancer-Specific Death for Men Treated With Radiation Therapy: Meta-Analysis of Radiation Therapy Oncology Group Trials

    SciTech Connect

    Hamstra, Daniel A.; Bae, Kyounghwa; Pilepich, Miljenko V.; Hanks, Gerald E.; Grignon, David J.; McGowan, David G.; Roach, Mack; Lawton, Colleen; Lee, R. Jeffrey; Sandler, Howard

    2011-12-01

    Purpose: The impact of age on prostate cancer (PCa) outcome has been controversial; therefore, we analyzed the effect of age on overall survival (OS), distant metastasis, prostate cancer-specific death (PCSD), and nonprostate cancer death (NPCD) on patients with locally advanced PCa. Methods and Materials: Patients who participated in four Radiation Therapy Oncology Group (RTOG) phase III trials, 8531, 8610, 9202, and 9413, were studied. Cox proportional hazards regression was used for OS analysis, and cumulative events analysis with Fine and Gray's regression was used for analyses of metastasis, PCSD, and NPCD. Results: Median follow-up of 4,128 patients with median age of 70 (range, 43-88 years) was 7.3 years. Most patients had high-risk disease: cT3 to cT4 (54%) and Gleason scores (GS) of 7 (45%) and 8 to 10 (27%). Older age ({<=}70 vs. >70 years) predicted for decreased OS (10-year rate, 55% vs. 41%, respectively; p < 0.0001) and increased NPCD (10-year rate, 28% vs. 46%, respectively; p < 0.0001) but decreased metastasis (10-year rate, 27% vs. 20%, respectively; p < 0.0001) and PCSD (10-year rate, 18% vs. 14%, respectively; p < 0.0001). To account for competing risks, outcomes were analyzed in 2-year intervals, and age-dependent differences in metastasis and PCSD persisted, even in the earliest time periods. When adjusted for other covariates, an age of >70 years remained associated with decreased OS (hazard ratio [HR], 1.56 [95% confidence interval [CI], 1.43-1.70] p < 0.0001) but with decreased metastasis (HR, 0.72 [95% CI, 0.63-0.83] p < 0.0001) and PCSD (HR, 0.78 [95% CI, 0.66-0.92] p < 0.0001). Finally, the impact of the duration of androgen deprivation therapy as a function of age was evaluated. Conclusions: These data support less aggressive PCa in older men, independent of other clinical features. While the biological underpinning of this finding remains unknown, stratification by age in future trials appears to be warranted.

  2. Leptomeningeal Cells Transduce Peripheral Macrophages Inflammatory Signal to Microglia in Reponse to Porphyromonas gingivalis LPS

    PubMed Central

    Zhang, Xinwen; Ni, Junjun; Yu, Weixian; Nakanishi, Hiroshi

    2013-01-01

    We report here that the leptomeningeal cells transduce inflammatory signals from peripheral macrophages to brain-resident microglia in response to Porphyromonas gingivalis (P.g.) LPS. The expression of Toll-like receptor 2 (TLR2), TLR4, TNF-α, and inducible NO synthase was mainly detected in the gingival macrophages of chronic periodontitis patients. In in vitro studies, P.g. LPS induced the secretion of TNF-α and IL-1β from THP-1 human monocyte-like cell line and RAW264.7 mouse macrophages. Surprisingly, the mean mRNA levels of TNF-α and IL-1β in leptomeningeal cells after treatment with the conditioned medium from P.g. LPS-stimulated RAW264.7 macrophages were significantly higher than those after treatment with P.g. LPS alone. Furthermore, the mean mRNA levels of TNF-α and IL-1β in microglia after treatment with the conditioned medium from P.g. LPS-stimulated leptomeningeal cells were significantly higher than those after P.g. LPS alone. These observations suggest that leptomeninges serve as an important route for transducing inflammatory signals from macrophages to microglia by secretion of proinflammatory mediators during chronic periodontitis. Moreover, propolis significantly reduced the P.g. LPS-induced TNF-α and IL-1 β production by leptomeningeal cells through inhibiting the nuclear factor-κB signaling pathway. Together with the inhibitory effect on microglial activation, propolis may be beneficial in preventing neuroinflammation during chronic periodontitis. PMID:24363500

  3. Is Kiva implant advantageous to balloon kyphoplasty in treating osteolytic metastasis to the spine? Comparison of 2 percutaneous minimal invasive spine techniques: a prospective randomized controlled short-term study.

    PubMed

    Korovessis, Panagiotis; Vardakastanis, Konstantinos; Vitsas, Vasilios; Syrimpeis, Vasilios

    2014-02-15

    Prospective, parallel-group, controlled, comparative randomized study. To compare cement leakage rate and efficacy for vertebral body restoration of balloon kyphoplasty (BK) versus Kiva novel implant with polymethylmethacrylate (PMMA) for treating osteolytic vertebral body metastasis. Minimally invasively vertebral augmentation techniques with PMMA are mostly performed for treating osteoporotic compression fractures. The Kiva implant with PMMA offers better vertebral body restoration and less PMMA leakage than BK in osteoporotic fractures. No previous study compared leakage rate and efficacy for vertebral body restoration in traditional BK and Kiva with PMMA in osteolytic vertebral body metastases. This study examined 23 patients (71 ± 13 yr) with 41 osteolytic vertebral bodies, who received Kiva with low viscosity PMMA and 24 patients (70 ± 11 yr) with 43 vertebral body osteolyses, who were reinforced with BK and high viscosity PMMA. All osteolyses were graded as Tomita 1 to 3. Anterior vertebral body height ratio (AVBHr), posterior vertebral body height ratio (PVBHr), and middle vertebral body height ratio (MVBHr), Gardner kyphotic deformity, PMMA leakage and were measured and compared between the groups. Visual analogue scale and Oswestry Disability Index were used for functional outcome evaluation. No patient survived after 3 months. Asymptomatic PMMA leakage occurred in 4 (9.3%) vertebrae in the BK group solely (2 to the spinal canal, in Tomita grade 3 osteolysis) Anterior, posterior and middle vertebral body height ratio, Gardner angle improved insignificantly in both groups. Visual anlogue scale and Oswestry Disability Index improved postoperatively similarly in both groups (P < 0.001). BK and Kiva provided equally significant spinal pain relief in patients with cancer with osteolytic metastasis. The absence of cement leakage in the Kiva group and absence of neurological complication in the BK group leakages reflects the safety of both augmentation

  4. Creation of a Prognostic Index for Spine Metastasis to Stratify Survival in Patients Treated With Spinal Stereotactic Radiosurgery: Secondary Analysis of Mature Prospective Trials

    SciTech Connect

    Tang, Chad; Hess, Kenneth; Bishop, Andrew J.; Pan, Hubert Y.; Christensen, Eva N.; Yang, James N.; Tannir, Nizar; Amini, Behrang; Tatsui, Claudio; Rhines, Laurence; Brown, Paul; Ghia, Amol

    2015-09-01

    Purpose: There exists uncertainty in the prognosis of patients following spinal metastasis treatment. We sought to create a scoring system that stratifies patients based on overall survival. Methods and Materials: Patients enrolled in 2 prospective trials investigating stereotactic spine radiation surgery (SSRS) for spinal metastasis with ≥3-year follow-up were analyzed. A multivariate Cox regression model was used to create a survival model. Pretreatment variables included were race, sex, age, performance status, tumor histology, extent of vertebrae involvement, previous therapy at the SSRS site, disease burden, and timing of diagnosis and metastasis. Four survival groups were generated based on the model-derived survival score. Results: Median follow-up in the 206 patients included in this analysis was 70 months (range: 37-133 months). Seven variables were selected: female sex (hazard ratio [HR] = 0.7, P=.02), Karnofsky performance score (HR = 0.8 per 10-point increase above 60, P=.007), previous surgery at the SSRS site (HR = 0.7, P=.02), previous radiation at the SSRS site (HR = 1.8, P=.001), the SSRS site as the only site of metastatic disease (HR = 0.5, P=.01), number of organ systems involved outside of bone (HR = 1.4 per involved system, P<.001), and >5 year interval from initial diagnosis to detection of spine metastasis (HR = 0.5, P<.001). The median survival among all patients was 25.5 months and was significantly different among survival groups (in group 1 [excellent prognosis], median survival was not reached; group 2 reached 32.4 months; group 3 reached 22.2 months; and group 4 [poor prognosis] reached 9.1 months; P<.001). Pretreatment symptom burden was significantly higher in the patient group with poor survival than in the group with excellent survival (all metrics, P<.05). Conclusions: We developed the prognostic index for spinal metastases (PRISM) model, a new model that identified patient subgroups with poor and excellent prognoses.

  5. Impending Atypical Femoral Fracture in Patients With Medullary Thyroid Cancer With Skeletal Metastasis Treated With Long-term Bisphosphonate and Denosumab.

    PubMed

    Koizumi, Mitsuru; Gokita, Tabu; Toda, Kazuhisa

    2017-02-24

    Atypical femoral fractures (AFFs) occur in osteoporosis patients receiving long-term bisphosphonate. Atypical femoral fractures also occur in cancer patients receiving long-term bisphosphonate or denosumab, but the prevalence is low. We describe a 53-year-old woman with a history of medullary thyroid cancer and skull metastasis who was prescribed bisphosphonate for 6 years and denosumab for 1.5 years, consecutively. Bone scintigraphy performed because of spontaneous groin pain showed uptake in the lateral aspect of the left femur, which was confirmed as impending AFF. In oncological patients receiving long-term bisphosphonate or denosumab, AFF should be included as a differential diagnosis with focal femoral findings.

  6. Atypical choroid plexus papilloma: spontaneous resolution of diffuse leptomeningeal contrast enhancement after primary tumor removal in 2 pediatric cases.

    PubMed

    Scala, Marcello; Morana, Giovanni; Milanaccio, Claudia; Pavanello, Marco; Nozza, Paolo; Garrè, Maria Luisa

    2017-09-01

    Atypical choroid plexus papillomas can metastasize in the form of leptomeningeal seeding. Postoperative chemotherapy is the recommended first-line treatment when gross-total removal is not achieved or in cases of disseminated disease. Here the authors report on 2 children with atypical choroid plexus papillomas and MRI findings of diffuse leptomeningeal enhancement at diagnosis, later presenting with spontaneous resolution of the leptomeningeal involvement after removal of the primary lesions. Observations in this report expand our knowledge about the natural history and biological behavior of these tumors and highlight the role of close neuroimaging surveillance in the management of atypical choroid plexus papillomas in cases with MRI evidence of diffuse leptomeningeal enhancement at presentation.

  7. Using association rules mining to explore pattern of Chinese medicinal formulae (prescription) in treating and preventing breast cancer recurrence and metastasis

    PubMed Central

    2012-01-01

    Background Chinese herbal medicine is increasingly widely used as a complementary approach for control of breast cancer recurrence and metastasis. In this paper, we examined the implicit prescription patterns behind the Chinese medicinal formulae, so as to explore the Chinese medicinal compatibility patterns or rules in the treatment or control of breast cancer recurrence and metastasis. Methods This study was based on the herbs recorded in Pharmacopoeia of the People’s Republic of China, and the literature sources from Chinese Journal Net and China Master Dissertations Full-text Database (1990 – 2010) to analyze the compatibility rule of the prescription. Each Chinese herb was listed according to the selected medicinal formulae and the added information was organized to establish a database. The frequency and the association rules of the prescription patterns were analyzed using the SPSS Clenmentine Data Mining System. An initial statistical analysis was carried out to categorize the herbs according to their medicinal types and dosage, natures, flavors, channel tropism, and functions. Based on the categorization, the frequencies of occurrence were computed. Results The main prescriptive features from the selected formulae of the mining data are: (1) warm or cold herbs in the Five Properties category; sweet or bitter herbs in the Five Flavors category and with affinity to the liver meridian are the most frequently prescribed in the 96 medicinal formulae; (2) herbs with tonifying and replenishing, blood-activating and stasis-resolving, spleen-strengthening and dampness-resolving or heat-clearing and detoxicating functions that are frequently prescribed; (3) herbs with blood-tonifying, yin-tonifying, spleen-strengthening and dampness-resolving, heat-clearing and detoxicating, and blood-activating with stasis-resolving functions that are interrelated and prescribed in combination with qi-tonifying herbs. Conclusions The results indicate that there is a close

  8. High-grade invasive urothelial carcinoma of the ureter with systematic lymph node metastasis successfully treated by nephroureterectomy followed by chemotherapy

    PubMed Central

    Liu, Zhu-Qing; Zhang, Xi; Xu, Qing

    2015-01-01

    We report a case of high-grade invasive urothelial carcinoma with squamous differentiation of the urinary tract. A 72-year-old woman was referred to our hospital because of asymptomatic gross hematuria. A right-sided laparoscopic radical nephroureterectomy with bladder cuff removal and right-sided pelvic lymphadenectomy were performed at our institution. Postoperative pathological examination showed high-grade urothelial carcinoma with squamous differentiation. Five months later, CT scan of the neck diagnosed it as lymph nodes metastasis. Following the laparoscopic radical nephroureterectomy, chemotherapy with gemcitabine and cisplatin or nedaplatin was carried out. After several cycles’ chemotherapy, nearly all the enlarged lymph node disappeared. Seven years and five years passed, urothelial carcinoma has not recurred after the surgery and all the lymph node disappeared respectively. PMID:25932275

  9. Pancreatic adenocarcinoma presenting with sudden onset bilateral deafness secondary to metastatic leptomeningeal infiltration.

    PubMed

    Blows, Samuel Joseph; Morgan, Richard; Dhariwal, Umeet; Petts, Gemma; Roncaroli, Frederico

    2012-11-01

    Deafness is a very common problem in older persons. We present a case of metastatic adenocarcinoma of the pancreas with deafness being the patient's only reason for seeking medical attention. The patient had bilateral vestibulocochlear nerve palsies with associated lower motor neurone facial nerve palsies and a bulbar palsy. Magnetic resonance imaging of his brain was unremarkable. It was only on post-mortem histology that tumour infiltrating the leptomeninges was demonstrated. Leptomeningeal metastases are rarely associated with adenocarcinoma of the pancreas. A review of the literature reveals only two other case reports of mestatic pancreatic carcinoma presenting with deafness but both had demonstrable temporal bone lesions on MRI as opposed to the meninges.

  10. Genetic variations in the PI3K-PTEN-AKT-mTOR pathway are associated with distant metastasis in nasopharyngeal carcinoma patients treated with intensity-modulated radiation therapy

    PubMed Central

    Guo, Qiaojuan; Lu, Tianzhu; Chen, Yan; Su, Ying; Zheng, Yuhong; Chen, Zeng; Chen, Chao; Lin, Shaojun; Pan, Jianji; Yuan, Xianglin

    2016-01-01

    Distant metastasis is the primary failure pattern of nasopharyngeal carcinoma(NPC) in intensity-modulated radiation therapy(IMRT) era. This study was conducted to find the impact of genetic variations in the phosphatidylinositol 3-kinase(PI3K)/phosphatase and tensin homologue(PTEN)/v-akt murine thymoma viral oncogene homologue(AKT)/mammalian target of rapamycin(mTOR) pathway on the risk of distant metastasis in NPC. We genotyped 16 single-nucleotide polymorphisms(SNPs) in five core genes in this pathway from 496 patients treated by IMRT with or without chemotherapy. The relationships between genetic polymorphisms and distant progression were evaluated. We observed that two loci in the AKT1 gene(rs3803300 and rs2494738 alone or combined) were associated with prognosis, with patients carrying at least one variant allele had significantly reduced risk of distant failure, especially in N2-3 group. In addition, we found that genetic variation may had some joint effect with N classification in recursive-partitioning analysis(RPA) analysis, with which patients were stratified into four different risk subgroups (RPA model): RPA1(low risk), RPA2(moderate risk), RPA3(high risk) and RPA4(highest risk). Our findings suggested that genetic variations within the PI3K signaling pathway modulate the development and invasion of NPC patients. Further research is needed to replicate the study in other centers and races, and to unravel the functional significance of these polymorphisms. PMID:27876891

  11. Physiology of the intrathecal bolus: the leptomeningeal route for macromolecule and particle delivery to CNS.

    PubMed

    Papisov, Mikhail I; Belov, Vasily V; Gannon, Kimberley S

    2013-05-06

    Presently, there are no effective treatments for several diseases involving the CNS, which is protected by the blood-brain, blood-CSF, and blood-arachnoid barriers. Traversing any of these barriers is difficult, especially for macromolecular drugs and particulates. However, there is significant experimental evidence that large molecules can be delivered to the CNS through the cerebrospinal fluid (CSF). The flux of the interstitial fluid in the CNS parenchyma, as well as the macro flux of CSF in the leptomeningeal space, are believed to be generally opposite to the desirable direction of CNS-targeted drug delivery. On the other hand, the available data suggest that the layer of pia mater lining the CNS surface is not continuous, and the continuity of the leptomeningeal space (LMS) with the perivascular spaces penetrating into the parenchyma provides an unexplored avenue for drug transport deep into the brain via CSF. The published data generally do not support the view that macromolecule transport from the LMS to CNS is hindered by the interstitial and CSF fluxes. The data strongly suggest that leptomeningeal transport depends on the location and volume of the administered bolus and consists of four processes: (i) pulsation-assisted convectional transport of the solutes with CSF, (ii) active "pumping" of CSF into the periarterial spaces, (iii) solute transport from the latter to and within the parenchyma, and (iv) neuronal uptake and axonal transport. The final outcome will depend on the drug molecule behavior in each of these processes, which have not been studied systematically. The data available to date suggest that many macromolecules and nanoparticles can be delivered to CNS in biologically significant amounts (>1% of the administered dose); mechanistic investigation of macromolecule and particle behavior in CSF may result in a significantly more efficient leptomeningeal drug delivery than previously thought.

  12. Disruption of the leptomeningeal blood barrier in neuromyelitis optica spectrum disorder

    PubMed Central

    Flanagan, Eoin P.; Fujihara, Kazuo; Kim, Ho Jin; Skejoe, Hanne P.; Wuerfel, Jens; Kuroda, Hiroshi; Kim, Su Hyun; Maillart, Elisabeth; Marignier, Romain; Pittock, Sean J.; Paul, Friedemann; Weinshenker, Brian G.

    2017-01-01

    Objective: To describe leptomeningeal blood-barrier impairment reflected by MRI gadolinium-enhanced lesions in patients with aquaporin-4 immunoglobulin G (AQP4-IgG)–positive neuromyelitis optica spectrum disorder (NMOSD). Methods: A retrospective case series of 11 AQP4-IgG–positive NMOSD patients with leptomeningeal enhancement (LME) were collected from 5 centers. External neuroradiologists, blinded to the clinical details, evaluated MRIs. Results: LME was demonstrated on postcontrast T1-weighted and fluid-attenuated inversion recovery images as a sign of leptomeningeal blood-barrier disruption and transient leakage of contrast agent into the subarachnoid space in 11 patients, 6 in the brain and 6 in the spinal cord. The patterns of LME were linear or extensive and were accompanied by periependymal enhancement in 5 cases and intraparenchymal enhancement in all cases. The location of LME in the spinal cord was adjacent to intraparenchymal contrast enhancement with involvement of a median number of 12 (range 5–17) vertebral segments. At the time of LME on MRI, all patients had a clinical attack such as encephalopathy (36%) and/or myelopathy (70%) with median interval between symptom onset and LME of 12 days (range 2–30). LME occurred in association with an initial area postrema attack (44%), signs of systemic infection (33%), or AQP4-IgG in CSF (22%) followed by clinical progression. LME was found at initial clinical presentation in 5 cases and at clinical relapses leading to a diagnosis of NMOSD in 6 cases. Conclusion: This study suggests that altered leptomeningeal blood barrier may be accompanied by intraparenchymal blood-brain barrier breakdown in patients with AQP4-IgG–positive NMOSD during relapses. PMID:28451627

  13. Spinal Meningeal Melanocytoma with Benign Histology Showing Leptomeningeal Spread: Case Report

    PubMed Central

    Kim, Seon Jeong; Choo, Hye Jung; Lee, Sun Joo; Lee, In Sook; Kim, Ji Yeon; Kim, Hoon

    2013-01-01

    Meningeal melanocytoma is a rare benign tumor with relatively good prognosis. However, local aggressive behavior of meningeal melanocytoma has been reported, especially in cases of incomplete surgical resection. Malignant transformation was raised as possible cause by prior reports to explain this phenomenon. We present an unusual case of meningeal melanocytoma associated with histologically benign leptomeningeal spread and its subsequent aggressive clinical course, and describe its radiological findings. PMID:23690716

  14. Leptomeningeal failure in patients with breast cancer receiving stereotactic radiosurgery for brain metastases.

    PubMed

    Wang, Edina C; Huang, Andrew J; Huang, Karen E; McTyre, Emory R; Lo, Hui-Wen; Watabe, Kounosuke; Metheny-Barlow, Linda; Laxton, Adrian W; Tatter, Stephen B; Strowd, Roy E; Chan, Michael D; Page, Brandi R

    2017-09-01

    Prior studies suggest a high incidence of leptomeningeal failure (LMF) in breast cancer metastatic to brain. This study examines breast cancer-specific variables affecting development of LMF and survival after Gamma-Knife Radiosurgery (GKS). Between 2000-2010, 149 (breast) and 658 other-histology patients were treated with GKS. Hormone/HER2, age, local/distant brain failure, prior craniotomy, and prior whole-brain radiotherapy (WBRT) were assessed. Median follow-up was 54months (range, 0-106). Serial MRI determined local and distant-brain failure and LMF. Statistical analysis with categorical/continuous data comparisons were done with Fisher's-exact, Wilcoxon rank-sum, log-rank tests, and Cox-Proportional Hazard models. Of 149 patients, 21 (14%) developed LMF (median time of 11.9months). None of the following predicted for LMF: Her2-status (HR=0.49, p=0.16), hormone-receptor status (HR=1.15, p=0.79), prior craniotomy (HR=1.58, p=0.42), prior WBRT (HR=1.36, p=0.55). Non-significant factors between patients that did (n=21) and did not (n=106) develop LMF included neurologic death (p=0.34) and median survival (8.6 vs 14.2months, respectively). Breast patients who had distant-failure after GKS (65/149; 43.6%) were more likely to later develop LMF (HR 4.2, p=0.005); including 15/65 (23%) patients who had distant-failure and developed LMF. Median time-to-death for patients experiencing LMF was 6.1months (IQR 3.4-7.8) from onset of LMF. Median survival from LMF to death was much longer in breast (6.1months) than in other (1.7months) histologies CONCLUSION: Breast cancer patients had a longer survival after diagnosis of LMF versus other histologies. Neither ER/PR/HER2 status, nor prior surgery or prior WBRT predicted for development of LMF in breast patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Decrease in leptomeningeal ivy sign on fluid-attenuated inversion recovery images after cerebral revascularization in patients with Moyamoya disease.

    PubMed

    Kawashima, M; Noguchi, T; Takase, Y; Nakahara, Y; Matsushima, T

    2010-10-01

    The "ivy" sign that is identified on FLAIR images in patients with Moyamoya disease is considered to be leptomeningeal collaterals. The aim of our study was to evaluate the correlation between postoperative decrease in ivy sign and cerebral hemodynamic status in the bypass-established hemisphere. Twenty-two patients with Moyamoya disease were enrolled. Postoperative changes in the ivy sign on FLAIR images were examined in each patient after bypass surgery. The correlation between postoperative changes in the ivy sign and hemodynamic status was examined in 10 patients by using SPECT. Of the 22 preoperative ivy-positive patients, 21 showed decreased ivy signs on the operative side. Average intervals between the operation day and the date when the decreased or vanished ivy sign was first recognized were 157.6 days in patients who underwent direct bypass and 212.2 days in patients who underwent indirect bypass. A postoperative decrease in ivy signs was found to be significantly correlated with an improved hemodynamic status of the surgically treated hemisphere, resulting in a postoperative increase in regional vascular reserve and a decreased proportion of the misery perfusion area (P < .01). Postoperative changes in the ivy sign can be used as a marker for identifying improved hemodynamics and also for testing the effectiveness of cerebral revascularization.

  16. A rat glioblastoma model with diffuse leptomeningeal gliomatosis induced by intracarotid injection of C6 glioma cells.

    PubMed

    Wasita, Brian; Kamitani, Hideki; Kinoshita, Yusuke; Mamun, Mahabub Hasan; Watanabe, Takashi

    2009-06-01

    A reproducible brain tumor model using experimental animals is required to study biological behavior and develop more potent antineoplastic drugs and effective therapeutic modalities. In this work, we attempted to establish diffuse leptomeningeal gliomatosis in the rat by intracarotid injection of C6 glioma cells. Intracarotid injection of 1 x 10(7) C6 glioma cells in Wistar rats was performed to establish a primary diffuse leptomeningeal gliomatosis model. Ki-67 and matrix metalloproteinases (MMPs) immunohistochemistry staining were used to study the biological behavior of the developed tumor. Methodology, physical findings and histopathological features were also discussed. Leptomeningeal gliomas grew in all Wistar rats after the administration of 1 x 10(7) C6 glioma cells. Intracranial hypertension, weight loss and cachexia developed, and the median survival time was 18.0 +/- 2.9 days. The glioma mass distributed throughout the ventricles, the leptomeningeal regions in the brain and the brainstem, with typical pathological features of glioblastoma. The immunohistochemistry stainings showed high Ki-67 labeling index (42.1 +/- 10.3%), and concomitant overexpression of MMP-2 and MMP-9 suggested proliferation, invasion and angiogenesis potential. The advantage of the intracarotid injection route is the absence of an operative scar in the cranium. This established animal model is a novel model of primary diffuse leptomeningeal gliomatosis. This model probably can be used for pre-clinical testing in the progression of glioblastoma.

  17. Clinical outcome and efficacy of current anti-leukemic therapy for leptomeningeal involvement in acute myeloid leukemia.

    PubMed

    Kwon, Ji Hyun; Koh, Young-Il; Yoon, Sung-Soo; Park, Seonyang; Kim, Inho

    2016-11-01

    We investigated risk factors and outcome in acute myeloid leukemia (AML) patients with leptomeningeal involvement. Medical records of patients with non-promyelocytic AML at Seoul National University Hospital from January of 2000 to November of 2013 were reviewed. Leptomeningeal involvement was defined as the presence of atypical or malignant hematopoietic cells in the cerebrospinal fluid. Among 775 patients with AML, 141 patients (18.2 %) underwent cerebrospinal fluid examination. Leptomeningeal involvement of AML, confirmed in 38 patients (4.9 %), was associated with high white blood cell count and high level of lactic. There were seven patients in the favorable risk group (19.4 %), 21 in the intermediate risk group (58.3 %), and eight in the adverse risk group (22.2 %). Twenty-eight patients (85.7 %) developed leptomeningeal involvement during relapse status or refractory status. Thirty-one patients (81.6 %) received intrathecal chemotherapy, and whole-brain and/or craniospinal radiotherapy was conducted in 10 patients (27.0 %). The rate of complete remission after induction chemotherapy was 63.2 %. Median overall survival was 9.9 months. Radiotherapy and complete remission after the first induction chemotherapy were associated with longer overall survival. Leptomeningeal involvement in acute myeloid leukemia is rare, but relatively common in relapsed status or refractory status. Craniospinal radiotherapy and complete remission after induction chemotherapy were found to favorable prognostic factors.

  18. DCB - Tumor Metastasis Research

    Cancer.gov

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

  19. Minimally Invasive Muscle Sparing Posterior-Only Approach for Lumbar Circumferential Decompression and Stabilization to Treat Spine Metastasis--Technical Report.

    PubMed

    Donnelly, Dustin J; Abd-El-Barr, Muhammad M; Lu, Yi

    2015-11-01

    Palliative tumor resection and subsequent stabilization are important for maximizing function and quality of life for patients suffering from spinal metastases. However, traditional operative techniques for spinal metastases with vertebral body destruction involve extensive soft tissue dissection. In the lumbar spine, open 2-staged spine procedures are routinely required with an anterior retroperitoneal approach for corpectomy and cage insertion and posterior decompression and stabilization with pedicle screws and rods. Both stages require extensive soft tissue dissection that results in significant surgical morbidity, long recovery time, and subsequent delay in initiating postoperative chemoradiotherapy, as well as initially hampering patients' overall quality of life. A minimally invasive approach is desirable for achieving spinal stability, pain control, functional recovery, rapid initiation of adjuvant therapies, and overall patient satisfaction, especially in patients whose medical and surgical therapies are aimed at palliation rather than cure. A 59-year-old man with renal cell carcinoma and a known L1 vertebral body metastasis presented with severe progressive low back pain and was found to have a pathologic L1 vertebral body fracture with focal kyphosis. Here, we describe a minimally invasive muscle-sparing, posterior-only approach for L1 transpedicular hemicorpectomy and expandable cage placement, L1 laminectomy, and T11-L3 posterior instrumented stabilization. The surgical corridor was achieved through the Wiltse muscle plane between the multifidus and longissimus muscles so that minimal muscle detachment was required to achieve transpedicular access to the anterior and middle spinal columns. The L1 nerve root was completely skeletonized to allow adequate lumbar hemicorpectomy, tumor resection, and expandable titanium cage insertion. Lastly, percutaneous pedicle screws and rods were inserted from T11 to L3 for stabilization. The patient tolerated the

  20. Symptomatic intracranial metastasis in penile carcinoma

    PubMed Central

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

    2010-01-01

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

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

    PubMed

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

    2011-10-01

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

  2. Infarction Distribution Pattern in Acute Stroke May Predict the Extent of Leptomeningeal Collaterals

    PubMed Central

    Verma, Rajeev Kumar; Gralla, Jan; Klinger-Gratz, Pascal Pedro; Schankath, Adrian; Jung, Simon; Mordasini, Pasquale; Zubler, Christoph; Arnold, Marcel; Buehlmann, Monika; Lang, Matthias F.

    2015-01-01

    Objective The aim of this study was to evaluate whether the distribution pattern of early ischemic changes in the initial MRI allows a practical method for estimating leptomeningeal collateralization in acute ischemic stroke (AIS). Methods Seventy-four patients with AIS underwent MRI followed by conventional angiogram and mechanical thrombectomy. Diffusion restriction in Diffusion weighted imaging (DWI) and correlated T2-hyperintensity of the infarct were retrospectively analyzed and subdivided in accordance with Alberta Stroke Program Early CT score (ASPECTS). Patients were angiographically graded in collateralization groups according to the method of Higashida, and dichotomized in 2 groups: 29 subjects with collateralization grade 3 or 4 (well-collateralized group) and 45 subjects with grade 1 or 2 (poorly-collateralized group). Individual ASPECTS areas were compared among the groups. Results Means for overall DWI-ASPECTS were 6.34 vs. 4.51 (well vs. poorly collateralized groups respectively), and for T2-ASPECTS 9.34 vs 8.96. A significant difference between groups was found for DWI-ASPECTS (p<0.001), but not for T2-ASPECTS (p = 0.088). Regarding the individual areas, only insula, M1-M4 and M6 showed significantly fewer infarctions in the well-collateralized group (p-values <0.001 to 0.015). 89% of patients in the well-collateralized group showed 0–2 infarctions in these six areas (44.8% with 0 infarctions), while 59.9% patients of the poor-collateralized group showed 3–6 infarctions. Conclusion Patients with poor leptomeningeal collateralization show more infarcts on the initial MRI, particularly in the ASPECTS areas M1 to M4, M6 and insula. Therefore DWI abnormalities in these areas may be a surrogate marker for poor leptomeningeal collaterals and may be useful for estimation of the collateral status in routine clinical evaluation. PMID:26327519

  3. Molecular Targeted Therapies for the Treatment of Leptomeningeal Carcinomatosis: Current Evidence and Future Directions

    PubMed Central

    Lee, Dae-Won; Lee, Kyung-Hun; Kim, Jin Wook; Keam, Bhumsuk

    2016-01-01

    Leptomeningeal carcinomatosis (LMC) is the multifocal seeding of cerebrospinal fluid and leptomeninges by malignant cells. The incidence of LMC is approximately 5% in patients with malignant tumors overall and the rate is increasing due to increasing survival time of cancer patients. Eradication of the disease is not yet possible, so the treatment goals of LMC are to improve neurologic symptoms and to prolong survival. A standard treatment for LMC has not been established due to low incidences of LMC, the rapidly progressing nature of the disease, heterogeneous populations with LMC, and a lack of randomized clinical trial results. Treatment options for LMC include intrathecal chemotherapy, systemic chemotherapy, and radiation therapy, but the prognoses remain poor with a median survival of <3 months. Recently, molecular targeted agents have been applied in the clinic and have shown groundbreaking results in specific patient groups epidermal growth factor receptor (EGFR)-targeted therapy or an anaplastic lymphoma kinase (ALK) inhibitor in lung cancer, human epidermal growth factor receptor 2 (HER2)-directed therapy in breast cancer, and CD20-targeted therapy in B cell lymphoma). Moreover, there are results indicating that the use of these agents under proper dose and administration routes can be effective for managing LMC. In this article, we review molecular targeted agents for managing LMC. PMID:27399673

  4. Leptomeningeal carcinomatosis and sensorineural hearing loss: correlation of labyrinthine enhancement patterns with symptoms.

    PubMed

    Goyault, G; Kremer, S; Martin, E; Riehm, S; Dietemann, J-L; Veillon, F

    2009-05-01

    The purpose of this study was to investigate the correlation between hearing loss and inner ear enhancement in patients suffering from leptomeningeal carcinomatosis (LC) involving the internal acoustic canal (IAC). Previous studies have only reported an association between IAC enhancement and sensorineural deafness. In a prospective study conducted from 2005 to 2007, 14 patients with LC involving the IAC underwent high-resolution MRI and otolaryngology examination. MRI images were analyzed by two experienced radiologists who were blinded to audiologic investigation results. Three (21%) patients had IAC and inner ear enhancement on gadolinium-weighted MRI. All three had a sensorineural hearing loss. Eleven (79%) patients had IAC enhancement without inner ear enhancement. Nine of these 11 patients were free of sensorineural hearing loss. Only two of them had sensorineural deafness. These findings are suggestive of a relation between hearing loss and inner ear enhancement in leptomeningeal carcinomatosis, as previously reported for bacterial meningitis. However, further investigations, including radiopathological correlation and a larger number of patients, are warranted to confirm these preliminary results.

  5. Macrophages related to leptomeninges and ventral nerve roots. An ultrastructural study.

    PubMed Central

    Fraher, J P; McDougall, R D

    1975-01-01

    In immature rats active macrophages were frequently seen projecting into the subarachnoid space from the surface of the leptomeninges. They also occurred between the layers of the pia and within the nerve roots. They were most frequent during the first two weeks after birth, which is a period of rapid neural growth and myelination in ventral roots. In contrast, they were much fewer at later stages. The ultrastructural characteristics of these cells are described. It is suggested that these cells take part in tissue growth and remodelling by the removal of material which degenerates or becomes redundant during development. For example, they may ingest effete leptomeningeal cells or fragments of them. Those within the ventral roots may phagocytose abnormal Schwann cells, or the myelin of sheaths which have failed to develop normally. It is also suggested that macrophages may be involved in the excavation of the subarachnoid space. Another possible function in which they may be involved is the ingestion of material, possibly of a protein nature, from the cerebrospinal fluid. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:1213953

  6. Leptomeningeal contrast enhancement and blood-CSF barrier dysfunction in aseptic meningitis

    PubMed Central

    Eisele, Philipp; Ebert, Anne D.; Griebe, Martin; Engelhardt, Britta; Szabo, Kristina; Hennerici, Michael G.; Gass, Achim

    2015-01-01

    Objective: To investigate the blood-CSF barrier (BCSFB) dysfunction in aseptic meningitis. Methods: In our case series of 14 patients with acute aseptic meningitis, we compared MRI characteristics with CSF findings. Results: Contrast enhancement in the sulcal space in a leptomeningeal pattern was visualized in 7 patients with BCSFB dysfunction categorized as moderate to severe as evidenced by the CSF/serum albumin ratio (Qalb) but was not present in those with mild or no barrier disturbance (p = 0.001). The Qalb as a marker for the leakiness of the BCSFB and, more indirectly, of the blood-brain barrier (BBB) was positively correlated with the incidence of leptomeningeal contrast enhancement seen on postcontrast fluid-attenuated inversion recovery (FLAIR) MRI (p = 0.003). Patients with a more pronounced brain barrier dysfunction recovered more slowly and stayed longer in the hospital. Conclusions: The severity of meningeal BBB disturbance can be estimated on postcontrast FLAIR MRI, which may be of diagnostic value in patients with aseptic meningitis. PMID:26516629

  7. Leptomeningeal cyst due to vacuum extraction delivery in a twin infant.

    PubMed

    Bobinski, L; Boström, S; Zsigmond, P; Theodorsson, A

    2007-03-01

    A rare case of a leptomeningeal cyst is reported in a twin male neonate delivered using a vacuum extractor, who presented a huge, non-pulsating, oedematous mass overlying the frontal fontanelle after birth. The mass was initially diagnosed as a cephalo haematoma. Ultrasonography indicated intracranial bleeding and a subsequent CT scan revealed an intraparenchymal bleeding above the left frontal horn, combined with a thin, left-sided, subdural haematoma and subarachnoid haemorrhage in the left Sylvian fissure. Apart from a bulging soft and round formation (2 x 2 x 3 cm) next to the anterior fontanel growing since birth, the neurological development of the infant was normal. MRI examination at the age of 7 months revealed that it consisted of a cystic mass (leptomeningeal cyst) connected to the left frontal horn, stretching right through the brain and also penetrating the dura mater. No signs of the perinatal haematomas were observed at this time. Surgical treatment, with fenestration of the cyst into the frontal horn and a watertight duraplasty with a periosteal flap and thrombin glue covered by small bone chips, was performed at 9 months of age. Due to a residual skull bone defect a second cranioplasty with autologous skull bone was performed three and half years later. During a follow-up period of 12 years the neurological and psychological development of the boy has been indistinguishable to that of his twin brother, indicating the satisfactory outcome of the treatment.

  8. Primary leptomeningeal melanoma of the cervical spine mimicking a meningioma-a case report.

    PubMed

    Marx, Sascha; Fleck, Steffen K; Manwaring, Jotham; Vogelgesang, Silke; Langner, Soenke; Schroeder, Henry W S

    2014-08-01

    Background and Importance Primary leptomeningeal melanoma (PLM) is highly malignant and exceedingly rare. Due to its rarity, diagnostic and treatment paradigms have been slow to evolve. We report the first case of a PLM that mimics a cervical spine meningioma and then discuss the current clinical, radiologic, and pathologic diagnostic methodologies as well as expected outcomes related to this disease. Clinical Presentation A 54-year-old woman presented a dural-based extramedullary solid mass ventral to the C2-C3 spinal cord causing spinal cord compression without cord signal changes, characteristic of meningioma. Intraoperative microscopic inspection revealed numerous black spots littering the surface of the dura; the tumor itself was yellow in appearance and had a soft consistency. Pathologic analysis of the specimen revealed a malignant melanin-containing tumor. No primary site was found, so a diagnosis of primary leptomeningeal melanoma was made, and the patient subsequently received interferon therapy. To date (2 years postoperatively), no local or systemic recurrence of the tumor has been identified. Conclusion As with most rare tumors, case reports constitute the vast majority of references to PLM. Only an increased awareness and an extensive report of each individual case can help diagnose and clarify the nature of PLM. Clinicians need to be aware of such malignant conditions when diagnosing benign tumoral lesions of the spine such as meningiomas.

  9. Primary Leptomeningeal Melanoma of the Cervical Spine Mimicking a Meningioma—A Case Report

    PubMed Central

    Marx, Sascha; Fleck, Steffen K.; Manwaring, Jotham; Vogelgesang, Silke; Langner, Soenke; Schroeder, Henry W.S.

    2014-01-01

    Background and Importance Primary leptomeningeal melanoma (PLM) is highly malignant and exceedingly rare. Due to its rarity, diagnostic and treatment paradigms have been slow to evolve. We report the first case of a PLM that mimics a cervical spine meningioma and then discuss the current clinical, radiologic, and pathologic diagnostic methodologies as well as expected outcomes related to this disease. Clinical Presentation A 54-year-old woman presented a dural-based extramedullary solid mass ventral to the C2–C3 spinal cord causing spinal cord compression without cord signal changes, characteristic of meningioma. Intraoperative microscopic inspection revealed numerous black spots littering the surface of the dura; the tumor itself was yellow in appearance and had a soft consistency. Pathologic analysis of the specimen revealed a malignant melanin-containing tumor. No primary site was found, so a diagnosis of primary leptomeningeal melanoma was made, and the patient subsequently received interferon therapy. To date (2 years postoperatively), no local or systemic recurrence of the tumor has been identified. Conclusion As with most rare tumors, case reports constitute the vast majority of references to PLM. Only an increased awareness and an extensive report of each individual case can help diagnose and clarify the nature of PLM. Clinicians need to be aware of such malignant conditions when diagnosing benign tumoral lesions of the spine such as meningiomas. PMID:25083399

  10. Unusual Metastasis from Carcinoma Cervix.

    PubMed

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

    2016-10-01

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

  11. Integrins and metastasis

    PubMed Central

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

    2013-01-01

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

  12. Cholesterol granuloma associated with otitis media and leptomeningitis in a cat due to a Streptococcus canis infection.

    PubMed

    Van der Heyden, Sara; Butaye, Patrick; Roels, Stefan

    2013-01-01

    Cholesterol granuloma in the middle ear is a pathological condition often associated with otitis media in humans. Cholesterol granulomas in cats are rarely described. To our knowledge, this is the first report of middle ear cholesterol granuloma in a cat, associated with otitis media and leptomeningitis due to a Streptococcus canis septicemia.

  13. Proteins Involved in HER2 Signalling Pathway, Their Relations and Influence on Metastasis-Free Survival in HER2-Positive Breast Cancer Patients Treated with Trastuzumab in Adjuvant Setting

    PubMed Central

    Adamczyk, Agnieszka; Grela-Wojewoda, Aleksandra; Domagała-Haduch, Małgorzata; Ambicka, Aleksandra; Harazin-Lechowska, Agnieszka; Janecka, Anna; Cedrych, Ida; Majchrzyk, Kaja; Kruczak, Anna; Ryś, Janusz; Niemiec, Joanna

    2017-01-01

    Aim: Resistance to trastuzumab (which is a standard therapy for breast cancer patients with HER2 overexpression) is associated with higher risk of progression or cancer death, and might be related to activation of signalling cascades (PI3K/AKT/mTOR, Ras/Raf/MAPK) and decreased level of their inhibitors. Material and methods: Formalin-fixed paraffin-embedded tumour specimens from 118 HER2-overexpressing breast cancer patients treated with radical local therapy and trastuzumab in adjuvant setting were used for the assessment of: (1) PIK3CA gene mutations (p.H1047R and p.E545K) by qPCR, and (2) expression of Ki-67, EGFR, MUC4, HER3 and PTEN by immunohistochemistry. Results: Lower Ki-67LI was observed in EGFR-immunonegative and in PTEN-immunopositive tumours. MUC4-immunonegative tumours more frequently were PTEN- and HER3-immunonegative. Favourable metastasis-free survival was observed in patients with tumours characterized by Ki-67LI≤50% (p=0.027), HER3 immunonegativity or PTEN immunopositivity (vs. tumours with HER3 expression and lack of PTEN expression, p=0.043), additionally, the trend was observed for patients with pN0+pN1 pathological tumour stage (vs. pN2+pN3) (p=0.086). Cox model revealed that independent negative prognostic factors were: (i) Ki-67LI>50% (p=0.014, RR=4.6, 95% CI 1.4-15.4), (ii) HER3 immunopositivity together with PTEN immunonegativity (p=0.034, RR=3.7, 95% CI 1.1-12.5). Conclusion: The results of our study suggest that combined analysis of HER3 and PTEN expression might bring information on trastuzumab sensitivity in the group of HER2-positive breast cancer patients treated with trastuzumab in adjuvant setting. PMID:28123607

  14. Beyond Axillary Lymph Node Metastasis, BMI and Menopausal Status Are Prognostic Determinants for Triple-Negative Breast Cancer Treated by Neoadjuvant Chemotherapy

    PubMed Central

    Bonsang-Kitzis, Hélène; Chaltier, Léonor; Belin, Lisa; Savignoni, Alexia; Rouzier, Roman; Sablin, Marie-Paule; Lerebours, Florence; Bidard, François-Clément; Cottu, Paul; Sastre-Garau, Xavier; Laé, Marick; Pierga, Jean-Yves; Reyal, Fabien

    2015-01-01

    Background Triple-negative breast cancers (TNBC) are a specific subtype of breast cancers with a particularly poor prognosis. However, it is a very heterogeneous subgroup in terms of clinical behavior and sensitivity to systemic treatments. Thus, the identification of risk factors specifically associated with those tumors still represents a major challenge. A therapeutic strategy increasingly used for TNBC patients is neoadjuvant chemotherapy (NAC). Only a subset of patients achieves a pathologic complete response (pCR) after NAC and have a better outcome than patients with residual disease. Purpose The aim of this study is to identify clinical factors associated with the metastatic-free survival in TNBC patients who received NAC. Methods We analyzed 326 cT1-3N1-3M0 patients with ductal infiltrating TNBC treated by NAC. The survival analysis was performed using a Cox proportional hazard model to determine clinical features associated with prognosis on the whole TNBC dataset. In addition, we built a recursive partitioning tree in order to identify additional clinical features associated with prognosis in specific subgroups of TNBC patients. Results We identified the lymph node involvement after NAC as the only clinical feature significantly associated with a poor prognosis using a Cox multivariate model (HR = 3.89 [2.42–6.25], p<0.0001). Using our recursive partitioning tree, we were able to distinguish 5 subgroups of TNBC patients with different prognosis. For patients without lymph node involvement after NAC, obesity was significantly associated with a poor prognosis (HR = 2.64 [1.28–5.55]). As for patients with lymph node involvement after NAC, the pre-menopausal status in grade III tumors was associated with poor prognosis (HR = 9.68 [5.71–18.31]). Conclusion This study demonstrates that axillary lymph node status after NAC is the major prognostic factor for triple-negative breast cancers. Moreover, we identified body mass index and menopausal status as

  15. Metastasis and AKT activation.

    PubMed

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

    2009-03-01

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

  16. Cutaneous Metastasis From Sacral Chordoma.

    PubMed

    Gleghorn, Kristyna; Goodwin, Brandon; Sanchez, Ramon

    2017-04-01

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

  17. Prognostic value of PIK3CA mutation status, PTEN and androgen receptor expression for metastasis-free survival in HER2-positive breast cancer patients treated with trastuzumab in adjuvant setting.

    PubMed

    Adamczyk, Agnieszka; Niemiec, Joanna; Janecka, Anna; Harazin-Lechowska, Agnieszka; Ambicka, Aleksandra; Grela-Wojewoda, Aleksandra; Domagała-Haduch, Małgorzata; Cedrych, Ida; Majchrzyk, Kaja; Kruczak, Anna; Ryś, Janusz; Jakubowicz, Jerzy

    2015-06-01

    Resistance to trastuzumab in patients with HER2-overexpressing breast cancer is associated with higher risk of progression or cancer death, and might be related to activation of PI3K/AKT/mTOR and Ras/Raf/MAPK signaling cascades and a decreased level of their inhibitor (PTEN). HER2-overexpressing breast cancer patients (n=75) treated with radical local therapy and trastuzumab in adjuvant setting were included into the study. Deoxyribonucleic acid isolated from paraffin sections was used to assess mutational status of the PIK3CA gene (p.H1047R and p.E545K mutations) by the quantitative polymerase chain reaction technique. Expression of selected proteins (ER, PgR, AR, Ki-67, EGFR) was assessed using immunohistochemistry. In the studied group we found significantly higher Ki-67LI in EGFR-positive carcinomas (p=0.048). Moreover, EGFR immunonegativity was observed more frequently in low-grade (G1/G2) carcinomas as well as in estrogen/progesterone and androgen receptor immunopositive tumors (p=0.042, p=0.016, p=0.044, respectively). Favorable metastasis-free survival was observed in patients with pN0 and pN1 (vs. pN2+3) stage (p=0.040) and with tumors characterized by low Ki-67LI (≤50% vs. >50%) (p=0.014). Patients with tumor androgen receptor immunonegativity (weak or lack of expression) or strong PTEN expression survived 3 years without metastases (p=0.007). The results of our study suggest that androgen receptor and PTEN status might be considered as indicators of trastuzumab sensitivity.

  18. Symptomatic spinal metastasis: A systematic literature review of the preoperative prognostic factors for survival, neurological, functional and quality of life in surgically treated patients and methodological recommendations for prognostic studies

    PubMed Central

    Nater, Anick; Martin, Allan R.; Sahgal, Arjun; Choi, David

    2017-01-01

    Purpose While several clinical prediction rules (CPRs) of survival exist for patients with symptomatic spinal metastasis (SSM), these have variable prognostic ability and there is no recognized CPR for health related quality of life (HRQoL). We undertook a critical appraisal of the literature to identify key preoperative prognostic factors of clinical outcomes in patients with SSM who were treated surgically. The results of this study could be used to modify existing or develop new CPRs. Methods Seven electronic databases were searched (1990–2015), without language restriction, to identify studies that performed multivariate analysis of preoperative predictors of survival, neurological, functional and HRQoL outcomes in surgical patients with SSM. Individual studies were assessed for class of evidence. The strength of the overall body of evidence was evaluated using GRADE for each predictor. Results Among 4,818 unique citations, 17 were included; all were in English, rated Class III and focused on survival, revealing a total of 46 predictors. The strength of the overall body of evidence was very low for 39 and low for 7 predictors. Due to considerable heterogeneity in patient samples and prognostic factors investigated as well as several methodological issues, our results had a moderately high risk of bias and were difficult to interpret. Conclusions The quality of evidence for predictors of survival was, at best, low. We failed to identify studies that evaluated preoperative prognostic factors for neurological, functional, or HRQoL outcomes in surgical patients with SSM. We formulated methodological recommendations for prognostic studies to promote acquiring high-quality evidence to better estimate predictor effect sizes to improve patient education, surgical decision-making and development of CPRs. PMID:28225772

  19. Cognitive decline in an elderly hospitalized patient with primary leptomeningeal melanomatosis.

    PubMed

    Bobba, Ravi; Arsura, Edward

    2004-11-01

    Delirium is one of the most common disorders in hospitalized patients. The authors present the case of an elderly male patient with postoperative cognitive decline that did not resolve with the conventional treatment. The diagnosis was only established on autopsy. A 75-year-old man was evaluated after a fall. Initial evaluation revealed voluntary guarding in the right epigastric region, and free air was detected under the right hemidiaphragm on abdominal radiography. An exploratory laparotomy revealed a perforation that had apparently sealed off. After surgery, he had initial improvement toward baseline; however, after several days, his postoperative course was complicated by a progressive deterioration in mental status, recurrent seizures, and aspiration pneumonia. Computed tomographic scan of the brain showed communicating hydrocephalus. Examination of the cerebrospinal fluid revealed an elevated opening pressure and elevated protein. His mental status continued to deteriorate, and he died. Autopsy revealed the pathologic diagnosis of primary leptomeningeal melanomatosis.

  20. Can leptomeningeal myelomatosis be predicted in patients with IgD multiple myeloma?

    PubMed

    Velasco, R; Petit, J; Llatjós, R; Juan, A; Bruna, J

    2010-08-01

    Involvement of the central nervous system (CNS) by multiple myeloma (MM) is rare. Immunoglobulin D (IgD) MM represents only 1% to 2% of all MM patients. Previous reports show a disproportionate number of patients with IgD MM with leptomeningeal myelomatosis (LMM). Several biological markers have been associated with LMM. The development of LMM in a woman with IgD MM is reported. Our patient should be considered as having a high-risk of CNS disease based on: (i) presence of IgD-lambda MM; (ii) high myeloma burden (stage III); (iii) additional extramedullary disease; (iv) presence of circulating plasma cells, some with plasmablastic morphology; and (v) CD56-negative immunophenotype. The association between these features of MM reported previously and a high risk of LMM is reviewed. Studies including patients with these features are warranted to confirm their attributed LMM risk and to investigate the role of prophylactic chemoradiotherapy in this clinical setting.

  1. Proteomic Biomarker Identification in Cerebrospinal Fluid for Leptomeningeal Metastases with Neurological Complications.

    PubMed

    Galicia, Norma; Díez, Paula; Dégano, Rosa M; Guest, Paul C; Ibarrola, Nieves; Fuentes, Manuel

    2017-01-01

    Leptomeningeal metastases (LM) from solid tumours, lymphoma and leukaemia are characterized by multifocal neurological deficits with a high mortality rate. Early diagnosis and initiation of treatment are essential to kerb neurological deterioration. However, this is not always possible as 25% of cerebrospinal fluid samples produce false-negative results at first cytological examination. The identification of biomarkers that allow stratification of individuals according to risk for developing LM would be a major benefit. Proteomic-based approaches are now in increasing use for this purpose, and these are reviewed in this chapter with a focus on cerebrospinal fluid (CSF) analyses. The construction of a CSF proteome disease database would also facilitate analysis of other neurological disorders.

  2. Leptomeningeal Dissemination of a Low-Grade Lumbar Paraganglioma: Case Report and Review of the Literature

    PubMed Central

    Thomson, Nick; Pacak, Karel; Palmer, Cheryl A.; Salzman, Karen; Champine, Marjan; Schiffman, Josh; Schmidt, Meic; Cohen, Adam L.

    2016-01-01

    Paragangliomas are rare extra-adrenal neuroendocrine tumors that are derived from embryonic neural crest cells. They are classified as functioning or nonfunctioning based on their ability to produce catecholamines. If nonfunctional, they are mostly asymptomatic and typically discovered as incidental lesions. If functional, they may secrete catecholamines, leading to clinical presentations similar to adrenal pheochromocytomas, including episodic headaches, hypertension, sweating and tachycardia. Most paragangliomas are benign, however, 15 to 35 percent may eventually become metastatic.1 Standard treatment for paraspinal paragangliomas below the neck is surgical resection with adjuvant radiation therapy on an individualized basis. In spite of complete excision, 20 percent of patients with primary extra-adrenal paragangliomas below the neck may develop recurrence.2 Leptomeningeal dissemination is a rare phenomenon, seen only in a small number of cases worldwide.3 PMID:28128698

  3. Differences in cerebrospinal fluid inflammatory cell reaction of patients with leptomeningeal involvement by lymphoma and carcinoma.

    PubMed

    Illán, Julia; Simo, Marta; Serrano, Cristina; Castañón, Susana; Gonzalo, Raquel; Martínez-García, María; Pardo, Javier; Gómez, Lidia; Navarro, Miguel; Altozano, Javier Pérez; Alvarez, Ruth; Bruna, Jordi; Subirá, Dolores

    2014-12-01

    Dissemination of neoplastic cells into the cerebrospinal fluid (CSF) and leptomeninges is a devastating complication in patients with epithelial cell neoplasia (leptomeningeal carcinomatosis [LC]) and lymphomas (lymphomatous meningitis [LyM]). Information about the surrounding inflammatory cell populations is scarce. In this study, flow cytometry immunophenotyping was used to describe the distribution of the main leukocyte populations in the CSF of 83 patients diagnosed with neoplastic meningitis (LC, n = 65; LyM, n = 18). These data were compared with those obtained in the CSF from 55 patients diagnosed with the same groups of neoplasia without meningeal involvement (solid tumors, n = 36; high-grade lymphoma, n = 19). Median (interquartile) rates of lymphocytes, monocytes, and polymorphonuclear (PMN) cells were 59.7% (range, 35-76.6%), 24% (range, 16-53%), and 1.5% (range, 0-7.6%) in LC, respectively, and 98.5% (range, 70.8-100%), 1.5% (range, 0-29.3%), and 0% in LyM, respectively (P < 0.001). No difference was observed between patients with breast adenocarcinoma (n = 30) and lung adenocarcinoma (n = 21), nor with different rates of malignant CSF involvement. Patients with lymphoma (with or without LyM) had a similar CSF leukocyte distribution, but cancer patients with LC and without LC had a distinctive PMN cell rate (P = 0.002). These data show that CSF samples from patients with LC have a greater number of inflammatory cells and a different leukocyte distribution than seen in the CSF from patients with LyM. Description of PMN cells is a distinctive parameter of patients with LC, compared with the CSF from patients with LyM and patients with cancer but without LC.

  4. SU-E-J-254: Evaluating the Role of Mid-Treatment and Post-Treatment FDG-PET/CT in Predicting Progression-Free Survival and Distant Metastasis of Anal Cancer Patients Treated with Chemoradiotherapy

    SciTech Connect

    Zhang, H; Wang, J; Chuong, M; D’Souza, W; Choi, W; Lu, W; Latifi, K; Hoffe, S; Moros, E; Saeed, Nadia; Tan, S; Shridhar, R

    2015-06-15

    Purpose: To evaluate the role of mid-treatment and post-treatment FDG-PET/CT in predicting progression-free survival (PFS) and distant metastasis (DM) of anal cancer patients treated with chemoradiotherapy (CRT). Methods: 17 anal cancer patients treated with CRT were retrospectively studied. The median prescription dose was 56 Gy (range, 50–62.5 Gy). All patients underwent FDG-PET/CT scans before and after CRT. 16 of the 17 patients had an additional FDG-PET/CT image at 3–5 weeks into the treatment (denoted as mid-treatment FDG-PET/CT). 750 features were extracted from these three sets of scans, which included both traditional PET/CT measures (SUVmax, SUVpeak, tumor diameters, etc.) and spatialtemporal PET/CT features (comprehensively quantify a tumor’s FDG uptake intensity and distribution, spatial variation (texture), geometric property and their temporal changes relative to baseline). 26 clinical parameters (age, gender, TNM stage, histology, GTV dose, etc.) were also analyzed. Advanced analytics including methods to select an optimal set of predictors and a model selection engine, which identifies the most accurate machine learning algorithm for predictive analysis was developed. Results: Comparing baseline + mid-treatment PET/CT set to baseline + posttreatment PET/CT set, 14 predictors were selected from each feature group. Same three clinical parameters (tumor size, T stage and whether 5-FU was held during any cycle of chemotherapy) and two traditional measures (pre- CRT SUVmin and SUVmedian) were selected by both predictor groups. Different mix of spatial-temporal PET/CT features was selected. Using the 14 predictors and Naive Bayes, mid-treatment PET/CT set achieved 87.5% accuracy (2 PFS patients misclassified, all local recurrence and DM patients correctly classified). Post-treatment PET/CT set achieved 94.0% accuracy (all PFS and DM patients correctly predicted, 1 local recurrence patient misclassified) with logistic regression, neural network or

  5. Targeting Breast Cancer Metastasis

    PubMed Central

    Jin, Xin; Mu, Ping

    2015-01-01

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

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

    PubMed

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

    2011-11-01

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

  7. Targeting Prostate Cancer Metastasis

    DTIC Science & Technology

    2015-09-01

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

  8. [Liposomal cytarabine for the treatment of leptomeningeal dissemination of central nervous system tumours in children and adolescents].

    PubMed

    Moreno, Lucas; García Ariza, Miguel Angel; Cruz, Ofelia; Calvo, Carlota; Fuster, Jose Luis; Salinas, Jose Antonio; Moscardo, Cristina; Portugal, Raquel; Merino, Jose Manuel; Madero, Luis

    2016-11-01

    Leptomeningeal dissemination in paediatric central nervous system (CNS) tumours is associated with a poor outcome, and new therapeutic strategies are desperately needed. One of the main difficulties in the treatment of CNS tumours is blood brain barrier penetration. Intrathecal therapy has shown to be effective in several paediatric tumours. The aim of this article is to review the data available on the use of liposomal cytarabine for paediatric patients with leptomeningeal dissemination of CNS tumours, including the pharmacology, administration route, safety and efficacy data. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  9. Hyperintense ipsilateral cortical sulci on FLAIR imaging in carotid stenosis: ivy sign equivalent from enlarged leptomeningeal collaterals.

    PubMed

    Hacein-Bey, Lotfi; Mukundan, Govind; Shahi, Kavian; Chan, Hung; Tajlil, Ali T

    2014-01-01

    Fluid-attenuated inversion recovery (FLAIR) imaging provides high contrast between hyperintense lesions and normal tissue. Hyperintense structures in convexity sulci are commonly linked to abnormal cerebrospinal fluid composition, whether blood, protein, or infection. A patient with hemispheric transient ischemic attacks from severe carotid stenosis had hyperintense convexity sulci on FLAIR magnetic resonance imaging, interpreted as possible prior hemorrhage, making the patient ineligible for carotid stent reconstruction. Retrospective analysis revealed that hyperintense sulci were dilated leptomeningeal collaterals. In severe arterial disease causing cerebral hypoperfusion, dilated leptomeningeal vessels should be considered a cause for serpiginous hyperintense structures on FLAIR imaging, similar to the "ivy sign" described in moya-moya patients. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. [18F]Fluorothymidine PET imaging in the diagnosis of leptomeningeal involvement with diffuse large B-cell lymphoma

    PubMed Central

    Thorp, Kristin; Leann Smith, M.; Kedzierska, Katarzyna; Fung, Kar-Ming A.; Chacko, George; Swisher, Karen; Epstein, Robert; Gumerlock, Mary K.

    2011-01-01

    Abstract The diagnosis of leptomeningeal carcinomatosis remains difficult despite improvement in central nervous system (CNS) imaging and cytologic examination of the cerebral spinal fluid. False-negative results are common, providing obstacles in assessing both prophylactic and therapeutic efforts. As a result of increased survival of patients with a variety of systemic neoplasms it is likely that central nervous involvement will need to be addressed more often. This article presents a patient with a diffuse large B-cell lymphoma with polymorphic features. Imaging using 18F-labeled fluorodeoxythymidine (FLT) proved useful in demonstrating both parenchymal and leptomeningeal CNS involvement. The potential for FLT to identify proliferative tissue may make it uniquely suitable for detection of CNS malignant disease. PMID:22004872

  11. Panax notoginseng saponins (PNS) inhibits breast cancer metastasis.

    PubMed

    Wang, Peiwei; Cui, Jingang; Du, Xiaoye; Yang, Qinbo; Jia, Chenglin; Xiong, Minqi; Yu, Xintong; Li, Li; Wang, Wenjian; Chen, Yu; Zhang, Teng

    2014-07-03

    Panax notoginseng (Burkill) F.H. Chen (Araliaceae) has been extensively used as a therapeutic agent to treat a variety of diseases. Panax notoginseng saponins (PNS) consist of major therapeutically active components of Panax notoginseng. PNS inhibit the growth of a variety of tumor cells in vitro and in vivo. The aim of the study is to investigate the effects and underlying mechanisms of PNS on breast cancer metastasis. 4T1 cell, a highly metastatic mouse breast carcinoma cell line, was utilized for in vitro and in vivo assays. In vitro assays were first performed to examine the effects of PNS on 4T1 cell viability, migration and invasion, respectively. Real-time PCR analyses were also performed to examine the effects of PNS on the expression of genes associated with tumor metastasis. The effect of PNS on 4T1 tumor cell metastasis was further assessed in spontaneous and experimental metastasis models in vivo. PNS treatment exhibited a dose-dependent effect on impairing 4T1 cell viability in vitro. However, when examined at a lower dose that did not affect cell viability, the migration and invasion of 4T1 cell was remarkably inhibited in vitro. Meanwhile, PNS treatment led to upregulated expression of genes known to inhibit metastasis and downregulated expression of genes promoting metastasis in cultured 4T1 cells. These results suggested a selective effect of PNS on 4T1 migration and invasion. This hypothesis was further addressed in 4T1 metastasis models in vivo. The results showed that the lung metastasis was significantly inhibited by PNS treatment in both spontaneous and experimental metastasis models. Taken together, our results demonstrated an inhibitory effect of PNS on 4T1 tumor metastasis, warranting further evaluation of PNS as a therapeutic agent for treating breast cancer metastasis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. First description of cervical intradural thymoma metastasis.

    PubMed

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

    2015-11-16

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

  13. First description of cervical intradural thymoma metastasis

    PubMed Central

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

    2015-01-01

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

  14. [Biology of cancer metastasis].

    PubMed

    Robert, Jacques

    2013-04-01

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

  15. Long-term survival after a favorable response to anti-EGFR antibody plus chemotherapy to treat bone marrow metastasis: a case report of KRAS-wildtype rectal cancer

    PubMed Central

    Nakamura, Sho; Fukui, Tadahisa; Suzuki, Shuhei; Takeda, Hiroyuki; Watanabe, Kaname; Yoshioka, Takashi

    2017-01-01

    Bone marrow metastasis is a rare consequence of colorectal cancer that results in a poor prognosis; few reports describe a favorable response to doublet chemotherapy combined with targeted therapy, which is currently the standard treatment. We experienced a case where anti-epidermal growth factor receptor (EGFR) antibody produced a marked anti-tumor response to bone marrow metastasis that led to long-term survival. A 51-year-old man was diagnosed with a primary KRAS-wildtype rectal cancer with multiple metastases, including the bone marrow. Disease control was achieved for 10.8 months following chemotherapy with a modified FOLFOX6 regimen combined with an anti-EGFR antibody. He died of cancer 22.7 and 16.6 months after disease onset and first-line chemotherapy, respectively. This case shows that early tumor shrinkage and deepness of response to the anti-EGFR antibody were observed even in a patient with bone marrow metastasis. Anti-EGFR antibody therapy should therefore be considered even when a patient’s medical condition appears to be poor owing to bone marrow metastasis. Moreover, tumors that are likely to be sensitive to chemotherapy, such as RAS-wildtype colorectal cancers, can be considered for anti-EGFR antibody therapy even if the patient is considered unfit for chemotherapy. PMID:28260928

  16. Autophagy in Cancer Metastasis

    PubMed Central

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

    2016-01-01

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

  17. Hypoxia-mediated metastasis.

    PubMed

    Chang, Joan; Erler, Janine

    2014-01-01

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

  18. Genomics screens for metastasis genes

    PubMed Central

    Yan, Jinchun; Huang, Qihong

    2014-01-01

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

  19. Choroid Melanoma Metastasis to Spine: A Rare Case Report

    PubMed Central

    Mandaliya, Hiren; Singh, Nandini; George, Sanila; George, Mathew

    2016-01-01

    Metastatic choroid melanoma is a highly malignant disease with a limited life expectancy. The liver is the most common site for metastasis of uveal melanoma followed by lung, bone, skin, and subcutaneous tissue. Metastasis from choroidal melanoma usually occurs within the first five years of treatment for primary tumours. Metastatic choroid melanoma to the spine/vertebrae is extremely rare. We report the first case of spinal metastasis from choroid melanoma in a 61-year-old man who had been treated for primary ocular melanoma three years earlier with radioactive plaque brachytherapy. Synchronously, at the time of metastasis, he was also diagnosed as having a new primary lung adenocarcinoma as well. The only other case reported on vertebral metastasis from malignant melanoma of choroid in literature in which primary choroid melanoma was enucleated. PMID:26989537

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

    PubMed

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

    2011-01-01

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

  1. Usefulness of Flow Cytometric Analysis for Detecting Leptomeningeal Diseases in Non-Hodgkin Lymphoma

    PubMed Central

    Shin, Sang-Yong; Kim, Hee-Jin; Oh, Young Lyun; Kim, Seok Jin; Kim, Won Seog

    2016-01-01

    Background The clinical usefulness of flow cytometry (FCM) for the diagnosis of leptomeningeal diseases (LMD) in non-Hodgkin lymphomas has been suggested in previous studies but needs to be further validated. With this regards, we evaluated the use of FCM for LMD in a series of Korean patients with non-Hodgkin lymphoma. Methods FCM and cytomorphology were conducted using samples obtained from clinically suspected LMD patients, follow-up LMD patients, and those with high risk of developing tumorigenic diseases. We then compared results of FCM and cytomorphology. In total, 55 and 47 CSF samples were analyzed by FCM and cytomorphology, respectively. Results Of the samples analyzed, 25.5% (14/55) and 12.8% (6/47) were positive by FCM and cytomorphology, respectively. No samples were determined as negative by FCM but positive by cytomorphology. Seven patients were positive only by FCM and negative by cytomorphology, and six among them were clinically confirmed to have LMD either by follow-up cytomorphology or imaging study. Conclusions We observed a high detection rate of tumor cells by FCM compared with cytomorphology. FCM study can be useful in early sensitive detection of LMD. PMID:26915608

  2. Leptomeningeal metastases presenting exclusively with ocular disturbance in 34 patients: A tertiary care cancer hospital experience.

    PubMed

    Mayer, Rory Richard; Frankfort, Benjamin Jay; Strickland, Ben A; Debnam, James Matthew; McCutcheon, Ian E; Groves, Morris D; Weinberg, Jeffrey S

    2017-05-01

    Leptomeningeal disease (LMD) represents disseminated intracranial metastatic disease that requires early detection and initiation of therapy. Patients with LMD typically present with a variety of neurologic problems, including ocular disturbances. However, little is reported on LMD presenting exclusively with ocular-related disturbances in the absence of any other central nervous system (CNS) dysfunction. Our goal was to describe the workup for ocular disturbances in the setting of known cancer diagnosis. Retrospective case study utilizing prospectively collected database at a tertiary cancer care center for all patients with diagnosis of LMD between 2001 and 2009. Main outcome was descriptive analysis of ocular findings by primary or admitting service with or without formal ophthalmology exam in workup for LMD. 34 patients demonstrated ocular disturbances without any other CNS manifestations. Our findings demonstrate that 71% of ocular disturbances were detected by the primary admitting services. Formal consultation with ophthalmology resulted in the detection of the remaining cases. The most common findings were cranial nerve deficits, papilledema, and optic disc or retinal infiltration by tumor. These findings supported a further work-up for CNS disease. Therefore, it is appropriate to refer cancer patients with visual complaints or findings on exam to ophthalmology to evaluate for evidence suggestive of LMD that may support a further work-up. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Overview of recent trends in diagnosis and management of leptomeningeal multiple myeloma.

    PubMed

    Yellu, Mahender R; Engel, Jessica M; Ghose, Abhimanyu; Onitilo, Adedayo A

    2016-03-01

    Neurological complications related to multiple myeloma (MM) are not uncommon; however, direct involvement of the central nervous system (CNS) is extremely rare and represents a diagnostic and therapeutic challenge. Significant survival difference has been noted with the introduction of novel therapy in patients with MM, but their effect on the incidence and their use for management of leptomeningeal myeloma (LMM) is uncertain. Analysis of published data demonstrates its recent increased incidence, median time to CNS presentation, and slight improvement in median survival after diagnosis of LMM. Less common MM isotypes have been overrepresented in LMM. CNS relapse occurred mostly in patients with Durie-Salmon stage III MM. Despite treatments, standard or experimental, the survival rates of LMM remain dismal. Monitoring high risk patients closely, even after achieving complete remission, may be useful in early detection of LMM. As we gain better understanding of LMM, we recommend that future research and clinical care focus on earlier diagnosis and development of more efficient CNS-directed therapy to improve survival in this patient population.

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

    PubMed

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

    2014-12-01

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

  5. Muc1 promotes migration and lung metastasis of melanoma cells

    PubMed Central

    Wang, Xiaoli; Lan, Hongwen; Li, Jun; Su, Yushu; Xu, Lijun

    2015-01-01

    Early stages of melanoma can be successfully treated by surgical resection of the tumor, but there is still no effective treatment once it is progressed to metastatic phases. Although growing family of both melanoma metastasis promoting and metastasis suppressor genes have been reported be related to metastasis, the molecular mechanisms governing melanoma metastatic cascade are still not completely understood. Therefore, defining the molecules that govern melanoma metastasis may aid the development of more effective therapeutic strategies for combating melanoma. In the present study, we found that muc1 is involved in the metastasis of melanoma cells and demonstrated that muc1 disruption impairs melanoma cells migration and metastasis. The requirement of muc1 in the migration of melanoma cells was further confirmed by gene silencing in vitro. In corresponding to this result, over-expression of muc1 significantly promoted the migratory of melanoma cells. Moreover, down-regulation of muc1 expression strikingly inhibits melanoma cellular metastasis in vivo. Finally, we found that muc1 promotes melanoma migration through the protein kinase B (Akt) signaling pathway. To conclude, our findings suggest a novel mechanism underlying the metastasis of melanoma cells which might serve as a new intervention target for the treatment of melanoma. PMID:26609470

  6. Vaginal metastasis of pancreatic cancer.

    PubMed

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

    2015-01-01

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

  7. Breast Cancer Metastasis

    PubMed Central

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

    2014-01-01

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

  8. Solitary skull metastasis as initial manifestation of hepatocellular carcinoma.

    PubMed

    Shim, Yu Shik; Ahn, Jung Yong; Cho, Jun Hyung; Lee, Kyu Sung

    2008-06-21

    A solitary skull metastasis from hepatocellular carcinoma (HCC) prior to diagnosis of the primary tumor without liver dysfunction is a very rare event. A 71-year-old male, without known liver disease, presented to our institution with a palpable occipital scalp mass. On brain magnetic resonance imaging (MRI), a highly enhanced and osteolytic skull tumor was observed. The histological diagnosis obtained from the percutaneous needle biopsy was a cranial metastasis from HCC. The metastatic tumor was removed via occipital craniectomy, and the two primary liver mass lesions were subsequently treated by transarterial chemoembolization. An isolated skull metastasis may be the sole initial presentation of HCC. Early diagnosis is essential in order to treat the primary disease. A skull metastasis from HCC should be considered in the differential diagnosis in patients with subcutaneous scalp mass and osteolytic defects on X-ray.

  9. Cutaneous metastasis revealing a relapse of gastric linitis: Another case

    PubMed Central

    Kairouani, Mouna; Perrin, Julie; Dietemann-Barabinot, Anne; Diab, Rafiq; Ruck, Stephane

    2012-01-01

    INTRODUCTION Cutaneous metastasis from gastric cancer is a rare occurrence. The linitis gastric carcinoma accounts only 8.7% of all gastric cancers. PRESENTATION OF CASE We report a case of female patient who was followed for linits cancer with peritoneal metastasis treated by six cycles of chemotherapy. After seventeen months of control, the relapse of the disease revealed by occurrence of cutaneous metastatsis. DISCUSSION Cutaneous metastasis from linit gastric is rare and the prognostic remains poor. The treatment is palliative. CONCLUSION This rare presentation should encourage the practitioners to biopsy any suspicion skin lesion. PMID:23276763

  10. Cutaneous metastasis revealing a relapse of gastric linitis: Another case.

    PubMed

    Kairouani, Mouna; Perrin, Julie; Dietemann-Barabinot, Anne; Diab, Rafiq; Ruck, Stephane

    2013-01-01

    Cutaneous metastasis from gastric cancer is a rare occurrence. The linitis gastric carcinoma accounts only 8.7% of all gastric cancers. We report a case of female patient who was followed for linits cancer with peritoneal metastasis treated by six cycles of chemotherapy. After seventeen months of control, the relapse of the disease revealed by occurrence of cutaneous metastatsis. Cutaneous metastasis from linit gastric is rare and the prognostic remains poor. The treatment is palliative. This rare presentation should encourage the practitioners to biopsy any suspicion skin lesion. Copyright © 2012 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

  11. Targeting Neuromimicry in Prostate Cancer Metastasis

    DTIC Science & Technology

    2016-10-01

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

  12. Murine models of breast cancer bone metastasis

    PubMed Central

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

    2016-01-01

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

  13. Gallbladder metastasis: spectrum of imaging findings.

    PubMed

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

    2011-12-01

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

  14. Integrative radiogenomic analysis for genomic signatures in glioblastomas presenting leptomeningeal dissemination

    PubMed Central

    You, Hye Jin; Park, Ho-Young; Kim, Jinkuk; Lee, In-Hee; Seol, Ho Jun; Lee, Jung-Il; Kim, Sung Tae; Kong, Doo-Sik; Nam, Do-Hyun

    2016-01-01

    Abstract Despite therapeutic advances, the prognosis for glioblastoma (GBM) remains poor. In particular, leptomeningeal dissemination (LMD) has a dismal prognosis. The aim of this study was to identify tumor molecular phenotype, which has a great propensity to develop LMD. Between May 2004 and December 2012, a total of 145 GBM tumor samples were obtained from data registry. A total of 20 of the 145 patients with GBM were found to develop LMD. A specialized radiologist confirmed the diagnosis of LMD on magnetic resonance imaging. To clarify the genomic signatures in GBM with LMD, we performed integrative analysis of whole transcriptome sequencing and copy number alteration in the radiological features indicating LMD phenotypes in GBM. Eleven newly diagnosed patients with GBM with LMD had worse prognosis than those without LMD (median 5.55 vs. 12.94 months, P < 0.0001). Integrating analysis using gene expression based on the change of copy number revealed that SPOCK1, EHD2, SLC2A3, and ANXA11 were highly expressed with the gain of copy number, compared with the gene expression in the non-LMD group. In addition, it was demonstrated that NME2, TMEM100, and SIVA1 were downregulated with the loss of copy number. We also found that mesenchymal subtype accounted for 50% in LMD group, whereas mesenchymal subtype consisted of 29% in non-LMD group, even though there was no statistical significance (P = 0.06). Through this radiogenomic analysis, we suggested the possibility of finding candidate genes associated with LMD and highlighted the significance of integrating approach to clarify the molecular characteristics in LMD. PMID:27399113

  15. Permeability Imaging as a Biomarker of Leptomeningeal Collateral Flow in Patients with Intracranial Arterial Stenosis.

    PubMed

    Chen, Hui; Wu, Bing; Zhu, Guangming; Wintermark, Max; Wu, Xinhuai; Su, Zihua; Xu, Xiao; Tian, Chenglin; Ma, Lin; Zhang, Weiwei; Lou, Xin

    2015-04-01

    Different methods of angiography are of great clinical utility; however, it still remains unstandardized as which method would be suitable to determine cerebral collateral circulation. Here we compared digital subtraction angiography (DSA), computer tomography angiography (CTA) and dynamic contrast-enhanced T1-weighted imaging magnetic resonance imaging (MRI) findings in seven patients with severe intracranial arterial stenosis, and determine whether volume transfer constant (K(trans)) maps of permeability imaging could be used as the biomarkers of cerebral collateral circulation. We retrospectively reviewed seven adult patients with severe intracranial arterial stenosis or occlusion with a complete parenchymal and vascular imaging work-up. DSA, CTA source imaging (CTA-SI), arterial spin labeling (ASL), and K(trans) maps were used to assess their collateral flow. Cohen's Kappa coefficient was calculated to test the consistency of their collateral scores. A reasonable agreement was found between DSA and K(trans) maps (Kappa = 0.502, P < 0.001) when all 15 regional vascular sites were included, and a better agreement found after exclusion of perforating artery territories (N = 10 sites, Kappa = 0.766, P < 0.001). The agreement between CTA-SI and DSA was moderate on all 15 sites (Kappa = 0.413, P < 0.001) and 10 sites (Kappa = 0.329, P < 0.001). The agreement between ASL and DSA was least favorable, no matter for all 15 sites (Kappa = 0.270, P < 0.001) or 10 sites (Kappa = 0.205, P = 0.002). K(trans) maps are useful and promising for leptomeningeal collateral assessment, when compared to CTA-SI or ASL. Further studies are requited for verify its validity in a large registry of patients.

  16. Intracranial Meningioma with Leptomeningeal Dissemination : Retrospective Study with Review of the Literature

    PubMed Central

    Park, Ki-Su; Kim, Ki-Hong; Park, Seong-Hyun; Lee, Dong-Hyun

    2015-01-01

    Objective The purposes of this article are to present 5 cases of intracranial meningioma with leptomeningeal dissemination (LD) and investigate the characteristics of this disease. Methods We present a retrospective case series of 5 females at our institutions (age ranged 21-72 years, mean 54.6 years) diagnosed with LD of an intracranial meningioma after surgery between 1998 and 2013. A database search revealed 45 cases with LD of meningioma in the English literature. Characteristic features were analyzed and compared. Results The incidence rate at our institutions of LD of meningioma was 0.9% (5/534). World Health Organization (WHO) grade was distributed as follows: I : 2, II : 2, and III : 1. Time to LD ranged from 2.5 months to 6.9 years; the patient with WHO grade III had the shortest interval to LD. The patient with an intraventricular meningioma (WHO grade II) had the second shortest interval to LD (1.7 years), and simultaneously revealed both LD and extraneuronal metastases. Four of 5 patients showed a disease progression, with the survival ranging from 1 month to 3.8 years after LD. Based on the literature, the initial tumor was an intraventricular meningioma in 9 patients, and their time to LD was shorter on average (mean 1.9 years). Histologically, 26 of 45 (58%) were initially diagnosed with a WHO grade II or III meningioma, and 6 of 19 patients (32%) with WHO grade I revealed malignant transformation. Conclusion This study shows that intraventricular location and histologically aggressive features seem to increase the chance of LD of meningioma. PMID:25932292

  17. [Cervical lymph node metastasis in medullary thyroid carcinoma].

    PubMed

    Yan, Dangui; Zhang, Bin; Li, Zhengjiang; Wu, Yuehuang; Liu, Shaoyan; Liu, Wensheng; Xu, Zhengang; Tang, Pingzhang

    2015-04-01

    To study the patterns of cervical lymph node metastasis of medullary thyroid carcinoma. Ninety-one patients with medullary thyroid carcinoma first treated between January 1999 and October 2014 were analyzed retrospectively. Of 91 patients, 39 cases presented with clinical negative node (cN0) and 52 cases with clinical positive node (cN+). Central compartment dissection was performed in all cases. Lateral neck dissection was performed in 52 cN+ cases (71 sides). All neck dissection specimens were obtained and analyzed for lymph node (LN) involvement with respect to neck levels. The distribution of LN with metastasis was studied in cN+ patients and the following factors were used to study the predictive value of central compartment LN metastasis: sex, age, family history, tumor size, bilateral tumor, multifocality of the tumor, extracapsular spread, and remote metastasis. Univariate analysis with the χ(2) test was used to analyze the statistical correlation between central compartment LN metastasis and other clinical factors. Multiple logistic regression analysis was used to identify the factors related to central compartment metastasis. Neck and bilateral neck metastasis rates were 73.6%, 19.8% respectively. Metastasis rates in central compartment and superior mediastinal region were 68.1% and 27.5% respectively. The central compartment metastasis rate was 33.3% in cN0 patients and 94.2% in cN+ patients. The superior mediastinal metastasis rate was 2.6% in cN0 patients and 46.2% in cN+ patients. Extracapsular spread was an independent predictive factor for central compartment metastasis (χ(2)=15.592, P=0.000, OR=12.876). The incidences of LN metastases at level II, III, IV, V were 62.9%,84.5%,83.1%,50.0% in cN+ patient, respectively. Multi-sites were involved. The possibility of lateral neck metastasis was higher when preoperative value of calcitonin was higher than 300 ng/L (66.7% vs 28.6%, χ(2)=5.771, P=0.016). Cervical lymph node metastasis of medullary

  18. Metastasis to the pancreas and the spleen: an increasing diagnostic and therapeutic challenge

    PubMed Central

    Jesús Fernández-Aceñero, M.; Abengózar Muela, Marta; Chaves Portela, Sara; Wolfgang Vorwald, Peter

    2011-01-01

    We have reviewed the electronic biopsies database files of the Department of Surgical Pathology, Fundación Jiménez Díaz in Madrid (Spain). In this time period (1998–2010) we have found 3 pancreatic metastasis and 5 splenic metastasis. Two of the pancreatic metastases were originated in clear cell renal cell carcinomas. The last pancreatic metastasis was from a malignant cutaneous melanoma diagnosed and treated 8 years before. As for splenic metastasis, three of them were diagnosed during the abdominal surgery for primary therapy of the tumour (2 ovaries and one endometrium), while the remaining 2 corresponded to metastasis from a lung primary diagnosed 1 year before and a colonic primary diagnosed 6 years before. The patients with splenic metastasis died on the short term with progression of the disease despite resection of the splenic lesions, while the patients with pancreatic metastasis have survived longer. PMID:24765305

  19. Solitary midbrain metastasis.

    PubMed

    Ongerboer de Visser, B W; Moffie, D

    1981-01-01

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

  20. Tumour progression and metastasis

    PubMed Central

    Arvelo, Francisco; Sojo, Felipe; Cotte, Carlos

    2016-01-01

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

  1. Metastasis and AKT activation.

    PubMed

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

    2008-10-01

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

  2. Tumour progression and metastasis.

    PubMed

    Arvelo, Francisco; Sojo, Felipe; Cotte, Carlos

    2016-01-01

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

  3. Primary diffuse leptomeningeal gliosarcomatosis with a sphenoid/sellar mass: confirmation of the ectopic glial tissue theory?

    PubMed

    Dimou, James; Tsui, Alpha; Maartens, Nicholas F; King, James A J

    2011-05-01

    Gliosarcoma is a rare glioblastoma variant, classically arising in the cerebral hemispheres. We report a patient with primary diffuse leptomeningeal gliomatosis (PDLG) with a sphenoid sinus and sellar mass. An 84-year-old woman presented with progressive headache and right-sided visual failure, associated with ipsilateral oculomotor nerve palsy and left temporal field loss. Neuraxial MRI showed a large lesion within the sphenoid sinus and sella resulting in chiasmal compression, and diffuse cranial and spinal leptomeningeal enhancement. Endoscopic transphenoidal biopsy and debulking of the sphenosellar lesion was performed, and gliosarcoma was diagnosed on histopathological examination. The patient was palliated due to poor performance status. To our knowledge, this is the only report of gliosarcoma within the paranasal sinuses and the second report of PDLG where the histological analysis has confirmed gliosarcoma. We believe this adds significant weight to the theory that heterotopic nests of glial tissue, in this instance within the sphenoid or sella, are the putative origin of PDLG. Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.

  4. Association of cutaneous red-to-purple hemangiomas with leptomeningeal hemangiomas. a clinical study of two patients.

    PubMed

    Pascual-Castroviejo, I; Pascual-Pascual, S I; Velazquez-Fragua, R; García-Guereta, L; López-Gutiérrez, J-C; Olivares, P; Tovar, J

    2010-02-01

    Cutaneous hemangioma is a benign vascular tumor of infancy with an initial proliferating period that appears between 1 to 2 weeks of life, extends during 18 months to 2 years of life, and then slowly regresses during several years until it disappears completely. They are characterized by endothelial cell proliferation followed by diminishing hyperplasia and progressive fibrosis. Vascular malformations are present at birth, grow commensurately with the child, and are characterized histologically by a normal rate of endothelial cell turnover, flat endothelium, thin (normal) basal membrane and normal mast cells. These cutaneous anomalies are commonly associated with cerebellar malformations, main cerebral arteries anomalies, congenital cardiac anomalies and/or coarctation of the aorta and persistence of embryonic arteries. Cutaneous hemangiomas can be associated with intracranial or extracranial hemangiomas that regress at the same time as the cutaneous hemangiomas. Cutaneous hemangiomas may show different types of color. Cutaneous red-to-purple hemangiomas are uncommon and their bright-red color is evident from the first weeks of life and remains unaltered until the hemangioma disappears. The intracranial angiographic studies in our series of more than 50 cases with facial hemangioma showed that patients with red-to-purple hemangiomas are commonly associated with localized leptomeningeal hemangiomas either in the ipsilateral or contralateral side. These leptomingeal hemangiomas were visualized only by MR enhanced with gadolinium. Involution of the cutaneous and leptomeningeal hemangiomas seems to occur simultaneously as in other types of external and internal hemangiomas.

  5. High sensitivity of flow cytometry improves detection of occult leptomeningeal disease in acute lymphoblastic leukemia and lymphoblastic lymphoma.

    PubMed

    Del Principe, Maria Ilaria; Buccisano, Francesco; Cefalo, Mariagiovanna; Maurillo, Luca; Di Caprio, Luigi; Di Piazza, Fabio; Sarlo, Chiara; De Angelis, Gottardo; Irno Consalvo, Maria; Fraboni, Daniela; De Santis, Giovanna; Ditto, Concetta; Postorino, Massimiliano; Sconocchia, Giuseppe; Del Poeta, Giovanni; Amadori, Sergio; Venditti, Adriano

    2014-09-01

    Conventional cytology (CC) of cerebrospinal fluid (CSF) fails to demonstrate malignant cells in up to 45 % of patients with acute lymphoblastic leukemia or lymphoblastic lymphoma (ALL/LL) in whom occult leptomeningeal disease is present. Flow cytometry (FCM) is considered more sensitive than CC, but clinical implications of CC negativity/CC positivity are not yet established. CSF samples from 38 adult patients with newly diagnosed ALL/LL were examined. Five (13 %) and nine (24 %) specimens were CC positive-FC positive (FCM(pos)/CC(pos)) and CC negative-FC positive (CC(neg)/FCM(pos)), respectively. The remaining 24 (63 %) samples were double negative (CC(neg)/FCM(neg)) (p = 0.001). CC(neg)/FCM(pos) patients showed a significantly shorter overall survival (OS) compared to CC(neg)/FCM(neg) ones. In multivariate analysis, the status of single FCM positivity was demonstrated to affect independently duration of OS (p = 0.005). In conclusion, FCM significantly improves detection of leptomeningeal occult localization in ALL/LL and appears to anticipate an adverse outcome. Further prospective studies on larger series are needed to confirm this preliminary observation.

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

    PubMed

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

    2012-01-01

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

  7. Development of Individualized Anti-Metastasis Strategies by Engineering Nanomedicines

    PubMed Central

    He, Qianjun; Guo, Shengrong; Qian, Zhiyong; Chen, Xiaoyuan

    2015-01-01

    Metastasis is deadly and also tough to treat as it is much more complicated than the primary tumour. Anti-metastasis approaches available so far are far from being optimal. A variety of nanomedicine formulas provide a plethora of opportunities for developing new strategies and means for tackling metastasis. It should be noted that individualized anti-metastatic nanomedicines are different from common anti-cancer nanomedicines as they specifically target different populations of malignant cells. This review briefly introduces the features of the metastatic cascade, and proposes a series of nanomedicine-based anti-metastasis strategies aiming to block each metastatic step. Moreover, we also concisely introduce the advantages of several promising nanoparticle platforms and their potential for constructing state-of-the-art individualized anti-metastatic nanomedicines. PMID:26056688

  8. Development of individualized anti-metastasis strategies by engineering nanomedicines.

    PubMed

    He, Qianjun; Guo, Shengrong; Qian, Zhiyong; Chen, Xiaoyuan

    2015-10-07

    Metastasis is deadly and also tough to treat as it is much more complicated than the primary tumour. Anti-metastasis approaches available so far are far from being optimal. A variety of nanomedicine formulae provide a plethora of opportunities for developing new strategies and means for tackling metastasis. It should be noted that individualized anti-metastatic nanomedicines are different from common anti-cancer nanomedicines as they specifically target different populations of malignant cells. This review briefly introduces the features of the metastatic cascade, and proposes a series of nanomedicine-based anti-metastasis strategies aiming to block each metastatic step. Moreover, we also concisely introduce the advantages of several promising nanoparticle platforms and their potential for constructing state-of-the-art individualized anti-metastatic nanomedicines.

  9. Melanoma metastasis to the spleen: Laparoscopic approach

    PubMed Central

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

    2009-01-01

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

  10. Microenvironmental regulation of tumor progression and metastasis

    PubMed Central

    Quail, DF; Joyce, JA

    2014-01-01

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

  11. Renal Clear Cell Carcinoma and Tonsil Metastasis

    PubMed Central

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

    2013-01-01

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

  12. Renal clear cell carcinoma and tonsil metastasis.

    PubMed

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

    2013-01-01

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

  13. Cell-free and concentrated ascites reinfusion therapy (CART) for management of massive malignant ascites in gastric cancer patients with peritoneal metastasis treated with intravenous and intraperitoneal paclitaxel with oral S-1.

    PubMed

    Yamaguchi, H; Kitayama, J; Emoto, S; Ishigami, H; Ito, T; Hanafusa, N; Watanabe, T

    2015-07-01

    Massive malignant ascites originating from peritoneal metastasis of gastric cancer is difficult to control and resistant to chemotherapy. Cell-free and Concentrated Ascites Reinfusion Therapy (CART) is one of the types of apheresis therapy, by which filtered and concentrated ascites containing albumin and globulin is reinfused intravenously to patients. We retrospectively studied the feasibility of intraperitoneal (IP) chemotherapy combined with CART in gastric cancer patients with massive malignant ascites. Paclitaxel (PTX) was administered via an IP access port implanted in the subcutaneous space. If patient had massive ascites at the start of treatment, paracentesis was performed through a percutaneous IP catheter and then CART was performed. PTX was administered through the catheter until the ascites diminished. A total of 127 CART procedures in 30 patients were analyzed. The average volume of processed ascites was 3.1 L, which was concentrated to 0.33 L containing 85.5 g protein on average. Significant increases in urine volume, serum total protein and albumin level were found after the CART. Increase in body temperature (0.3°C), decrease in platelet count (3.8 × 10(4)/μl), and changes in blood pressure (2 mm Hg) were found after the CART procedure, but no clinically significant adverse event was experienced. The median survival time and 1-year survival of 30 patients who received IP chemotherapy combined with the CART procedure was 10.2 months and 43.3% respectively. IP chemotherapy combined with CART might be a promising strategy for patients with massive malignant ascites originating from peritoneal metastasis of gastric cancer. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Tocotrienol and cancer metastasis.

    PubMed

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

    2016-01-01

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

  15. Syndecan-1 and Metastasis Dormancy

    DTIC Science & Technology

    2015-09-01

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

  16. Molecular Mechanisms of Bone Metastasis.

    PubMed

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

    2016-01-01

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

  17. Pretreatment [{sup 18}F]-fluoro-2-deoxy-glucose Positron Emission Tomography Maximum Standardized Uptake Value as Predictor of Distant Metastasis in Early-Stage Non-Small Cell Lung Cancer Treated With Definitive Radiation Therapy: Rethinking the Role of Positron Emission Tomography in Personalizing Treatment Based on Risk Status

    SciTech Connect

    Nair, Vimoj J.; MacRae, Robert; Sirisegaram, Abby; Pantarotto, Jason R.

    2014-02-01

    Purpose: The aim of this study was to determine whether the preradiation maximum standardized uptake value (SUV{sub max}) of the primary tumor for [{sup 18}F]-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) has a prognostic significance in patients with Stage T1 or T2N0 non-small cell lung cancer (NSCLC) treated with curative radiation therapy, whether conventional or stereotactic body radiation therapy (SBRT). Methods and Materials: Between January 2007 and December 2011, a total of 163 patients (180 tumors) with medically inoperable histologically proven Stage T1 or T2N0 NSCLC and treated with radiation therapy (both conventional and SBRT) were entered in a research ethics board approved database. All patients received pretreatment FDG-PET / computed tomography (CT) at 1 institution with consistent acquisition technique. The medical records and radiologic images of these patients were analyzed. Results: The overall survival at 2 years and 3 years for the whole group was 76% and 67%, respectively. The mean and median SUV{sub max} were 8.1 and 7, respectively. Progression-free survival at 2 years with SUV{sub max} <7 was better than that of the patients with tumor SUV{sub max} ≥7 (67% vs 51%; P=.0096). Tumors with SUV{sub max} ≥7 were associated with a worse regional recurrence-free survival and distant metastasis-free survival. In the multivariate analysis, SUV{sub max} ≥7 was an independent prognostic factor for distant metastasis-free survival. Conclusion: In early-stage NSCLC managed with radiation alone, patients with SUV{sub max} ≥7 on FDG-PET / CT scan have poorer outcomes and high risk of progression, possibly because of aggressive biology. There is a potential role for adjuvant therapies for these high-risk patients with intent to improve outcomes.

  18. Hepatic metastasis complicated by abscess formation.

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2009-06-01

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

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

    PubMed

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

    2015-04-15

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

  2. Characteristics and Treatments of Large Cystic Brain Metastasis: Radiosurgery and Stereotactic Aspiration

    PubMed Central

    Kim, Moinay; Cheok, Stephanie; Chung, Lawrance K.; Ung, Nolan; Thill, Kimberly; Voth, Brittany; Kwon, Do Hoon; Kim, Jeong Hoon; Kim, Chang Jin; Tenn, Stephen; Lee, Percy

    2015-01-01

    Brain metastasis represents one of the most common causes of intracranial tumors in adults, and the incidence of brain metastasis continues to rise due to the increasing survival of cancer patients. Yet, the development of cystic brain metastasis remains a relatively rare occurrence. In this review, we describe the characteristics of cystic brain metastasis and evaluate the combined use of stereotactic aspiration and radiosurgery in treating large cystic brain metastasis. The results of several studies show that stereotactic radiosurgery produces comparable local tumor control and survival rates as other surgery protocols. When the size of the tumor interferes with radiosurgery, stereotactic aspiration of the metastasis should be considered to reduce the target volume as well as decreasing the chance of radiation induced necrosis and providing symptomatic relief from mass effect. The combined use of stereotactic aspiration and radiosurgery has strong implications in improving patient outcomes. PMID:25977901

  3. Meaningful prevention of breast cancer metastasis: candidate therapeutics, preclinical validation, and clinical trial concerns.

    PubMed

    Zimmer, Alexandra S; Steeg, Patricia S

    2015-01-01

    The development of drugs to treat breast and other cancers proceeds through phase I dose finding, phase II efficacy, and phase III comparative studies in the metastatic setting, only then asking if metastasis can be prevented in adjuvant trials. Compounds without overt cytotoxic activity, such as those developed to inhibit metastatic colonization, will likely fail to shrink established lesions in the metastatic setting and never be tested in a metastasis prevention scenario where they were preclinically validated. We and others have proposed phase II primary and secondary metastasis prevention studies to address this need. Herein, we have asked whether preclinical metastasis prevention data agrees with the positive adjuvant setting trials. The data are limited but complimentary. We also review fundamental pathways involved in metastasis, including Src, integrins, focal adhesion kinase (FAK), and fibrosis, for their clinical progress to date and potential for metastasis prevention. Issues of inadequate preclinical validation and clinical toxicity profiles are discussed.

  4. Intracranial Leptomeningeal Carcinomatosis in Three Cases from Breast Cancer Demonstrated on F-18 Fluorodeoxyglucose Positron Emission Tomography/Computerized Tomography.

    PubMed

    Ortapamuk, Hulya; Demir, Mustafa Kemal

    2017-01-01

    Leptomeningeal carcinomatosis (LC) is an uncommon late manifestation of non-central nervous system (CNS) solid tumors. With prolonged survival in solid tumors, an increased frequency of metastases is noted in these tumors too. The detection of tumor cells in the cerebrospinal fluid remains the gold standard. Noninvasively, magnetic resonance imaging is frequently used for the diagnosis of LC. Although its low sensitivity of F-18 fluorodeoxyglucose positron emission tomography/computerized tomography (F-18 FDG PET/CT) on demonstrating CNS lesions, it could be useful in identifying the possibility of LC of breast carcinoma by giving high attention to the meninges. We discuss here three cases all of them having intracranial LC; where (18)F-FDG PET/CT study helped us in the diagnosis of LC. To our knowledge, this is the second report about intracranial LC from breast cancer demonstrating on (18)F-FDG PET/CT.

  5. Intracranial Leptomeningeal Carcinomatosis in Three Cases from Breast Cancer Demonstrated on F-18 Fluorodeoxyglucose Positron Emission Tomography/Computerized Tomography

    PubMed Central

    Ortapamuk, Hulya; Demir, Mustafa Kemal

    2017-01-01

    Leptomeningeal carcinomatosis (LC) is an uncommon late manifestation of non-central nervous system (CNS) solid tumors. With prolonged survival in solid tumors, an increased frequency of metastases is noted in these tumors too. The detection of tumor cells in the cerebrospinal fluid remains the gold standard. Noninvasively, magnetic resonance imaging is frequently used for the diagnosis of LC. Although its low sensitivity of F-18 fluorodeoxyglucose positron emission tomography/computerized tomography (F-18 FDG PET/CT) on demonstrating CNS lesions, it could be useful in identifying the possibility of LC of breast carcinoma by giving high attention to the meninges. We discuss here three cases all of them having intracranial LC; where 18F-FDG PET/CT study helped us in the diagnosis of LC. To our knowledge, this is the second report about intracranial LC from breast cancer demonstrating on 18F-FDG PET/CT. PMID:28242978

  6. Molecular insights into tumour metastasis: tracing the dominant events.

    PubMed

    Jin, Ke; Li, Tong; van Dam, Hans; Zhou, Fangfang; Zhang, Long

    2017-04-01

    Metastasis of malignant cells to vital organs remains the major cause of mortality in many types of cancers. The tumour invasion-metastasis cascade is a stepwise and multistage process whereby tumour cells disseminate from primary sites and spread to colonize distant sites through the systemic haematogenous or lymphatic circulations. The general steps of metastasis may be similar in almost all tumour types, but metastasis to different tissues seems to require distinct sets of regulators and/or an 'educated' microenvironment which may facilitate the infiltration and colonization of tumour cells to specific tissues. Moreover, interactions of tumour cells with stromal cells, endothelial cells, and immune cells that they encounter will also aid them to gain survival advantages, evade immune surveillance, and adapt to the new host microenvironment. Due to the high correlation between tumour metastasis and survival rate of patients, a deeper understanding of the molecular participants and processes involved in metastasis could pave the way towards novel, more effective and targeted approaches to prevent and treat tumour metastasis. In this review, we provide an update on the regulation networks orchestrated by the dominant regulators of different stages throughout the metastatic process including, but not limited to, epithelial-mesenchymal transition in local invasion, resistance to anoikis during migration, and colonization of different distant sites. We also put forward some suggestions and problems concerning the treatment of tumour metastasis that should be solved and/or improved for better therapies in the near future. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  7. Endothelial nitric oxide synthase mediates lymphangiogenesis and lymphatic metastasis

    PubMed Central

    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 lymphatic metastasis has not been documented. To this end, we first show that both VEGF receptor-2 and -3 stimulation activate eNOS in lymphatic endothelial cells and that NO donors induce proliferation and/or survival of cultured lymphatic endothelial cells in a dose dependent manner. We find that an NOS inhibitor L-NMMA blocked regeneration of lymphatic vessels. Using intravital microscopy that allows us to visualize the steps of lymphatic metastasis, we show that genetic deletion of eNOS as well as NOS blockade attenuates peritumor lymphatic hyperplasia of VEGF-C-overexpressing T241 fibrosarcomas and decreases the delivery of metastatic tumor cells to the draining lymph nodes. Genetic deletion of eNOS in the host also leads to a decrease in T241 tumor cell dissemination to the lymph nodes and macroscopic lymph node metastasis of B16F10 melanoma. These findings indicate that eNOS mediates VEGF-C induced lymphangiogenesis and, consequently, plays a critical role in lymphatic metastasis. Our findings explain the correlation between NOS and lymphatic metastasis seen in a number of human tumors and open the door for potential therapies exploiting NO signaling to treat diseases of the lymphatic system. PMID:19318557

  8. Differentiation of Leptomeningeal and Vascular Enhancement on Post-contrast FLAIR MRI Sequence: Role in Early Detection of Infectious Meningitis

    PubMed Central

    Ahmad, Armeen; Azad, Sheenam

    2015-01-01

    Objective: To qualitatively and quantitatively differentiate leptomeningeal and vascular enhancement on Post-contrast Fluid Attenuated Inversion Recovery (PCFLAIR) sequence compared to post-contrast T1-weighted (PCT1W) sequence with fat suppression (FS) and evaluate its role in early detection of infectious meningitis. Materials and Methods: Thirty-one patients with diagnosis of meningitis were evaluated with pre and post-contrast FLAIR and T1-weighted sequences with fat suppression (FS). Qualitative assessment was done by two observers for presence, absence or equivocal status of leptomeningeal enhancement. Further, quantitative estimation of single pixel signal intensities (SPSI) for meningeal and vascular enhancement was undertaken. A statistical comparison was performed using Kappa coefficient and t-test. Results: The overall qualitative accuracy was 90.3% for PCFLAIR compared to 54.8% for PCT1W with FS sequence. PCFLAIR was found to be 100% accurate in the detection of tubercular and pyogenic meningitis and 70% accurate in the detection of viral meningitis while PCT1W with FS sequence showed the corresponding accuracy to be 76.2% and 0% respectively. Both observers rated PCFLAIR images better than PCT1W with FS at detecting meningitis (p<0.05). The quantitative assessment revealed that the SPSI difference between the average meningeal and vascular enhancement on PCFLAIR was significantly greater than that on PCT1W with FS sequence (t= 6.31, p<0.01). Conclusion: PCFLAIR sequence has insignificant component of vascular enhancement compared to meningeal enhancement. This makes meningeal inflammation easily discernable and aids in early detection of infectious meningitis. PMID:25738054

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

    PubMed

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

    2017-04-01

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

  10. Isolated Pancreatic Metastasis from Malignant Melanoma: Is Pancreatectomy Worthwile?

    PubMed Central

    Birnbaum, David Jérémie; Moutardier, Vincent; Turrini, Olivier; Gonçalves, Anthony; Delpero, Jean Robert

    2013-01-01

    Isolated pancreatic metastasis from malignant melanoma (IPMMM) is rare because most melanoma patients already have a widespread disease at diagnosis. No adjuvant systemic treatment is known to be efficient in this setting. Experience with pancreatic resection for IPMMM is limited and controversial. We report here the case of an IPMMM patient successfully treated by pancreaticoduodenectomy with a prolonged survival of 6 years. PMID:24741425

  11. Long noncoding RNA MALAT1 promotes brain metastasis by inducing epithelial-mesenchymal transition in lung cancer.

    PubMed

    Shen, Liqin; Chen, Lei; Wang, Yongsheng; Jiang, Xiaochun; Xia, Hongping; Zhuang, Zhixiang

    2015-01-01

    Brain metastasis often has a poor prognosis in patients with advanced non-small cell lung cancer (NSCLC). Therefore, it is urgent to identify factors associated with lung cancer brain metastasis. Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) also known as noncoding nuclear-enriched abundant transcript 2 is a long noncoding RNA, which is highly conserved amongst mammals. It has been shown to be increased in a variety of tumors including NSCLC and regulate the expression of metastasis-associated genes. However, the role of MALAT1 in lung cancer brain metastasis has not been investigated. In this study, we examined the level of MALAT1 in 78 cases of NSCLC samples with 19 brain metastasis and 59 non-brain metastasis by qRT-PCR. We observed that the level of MALAT1 was significantly higher in brain metastasis than that of non brain metastasis samples (P < 0.001). The level of MALAT1 was associated with patients' survival. To investigate the role of MALAT1 in brain metastasis, we established a highly invasive and metastatic cell subline using the brain metastasis lung cancer cell H1915. We found that MALAT1 is increased in highly invasive subline of brain metastasis lung cancer cells. Further functional studies indicate that silencing MALAT1 inhibits highly invasive subline of brain metastasis lung cancer cell migration and metastasis by inducing epithelial-mesenchymal transition (EMT). Therefore, increased level of long noncoding RNA MALAT1 promotes lung cancer brain metastasis by inducing EMT, which may be a promising prognosis factor and therapeutic target to treat lung cancer brain metastasis in future.

  12. Emerging Biological Principles of Metastasis.

    PubMed

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

    2017-02-09

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

  13. Treating metastatic cancer with nanotechnology.

    PubMed

    Schroeder, Avi; Heller, Daniel A; Winslow, Monte M; Dahlman, James E; Pratt, George W; Langer, Robert; Jacks, Tyler; Anderson, Daniel G

    2011-12-23

    Metastasis accounts for the vast majority of cancer deaths. The unique challenges for treating metastases include their small size, high multiplicity and dispersion to diverse organ environments. Nanoparticles have many potential benefits for diagnosing and treating metastatic cancer, including the ability to transport complex molecular cargoes to the major sites of metastasis, such as the lungs, liver and lymph nodes, as well as targeting to specific cell populations within these organs. This Review highlights the research, opportunities and challenges for integrating engineering sciences with cancer biology and medicine to develop nanotechnology-based tools for treating metastatic disease.

  14. Novel Aptamers to Target Metastasis

    DTIC Science & Technology

    2012-11-01

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

  15. Therapeutic management of intracranial dural arteriovenous shunts with leptomeningeal venous drainage: report of 53 consecutive patients with emphasis on transarterial embolization with acrylic glue.

    PubMed

    Guedin, Pierre; Gaillard, Stephan; Boulin, Anne; Condette-Auliac, Stephanie; Bourdain, Frederic; Guieu, Stephanie; Dupuy, Michel; Rodesch, Georges

    2010-03-01

    There is a strong correlation between the venous drainage pattern of intracranial dural arteriovenous shunts (ICDAVSs) and the affected patients' clinical presentation. The ICDAVSs that have cortical venous reflux (CVR) (retrograde leptomeningeal drainage: Borden Type 2 and 3 lesions) are very aggressive and have a poor natural history. Although the necessity of treatment remains debatable in ICDAVSs that drain exclusively into a sinus (Borden Type 1), lesions with CVR must be treated because of the negative effects of the retrograde venous drainage. Surgery, radiosurgery, and embolization have been proposed for management of these lesions, but endovascular therapy is considered the most appropriate therapeutic strategy in ICDAVSs. New embolic materials, such as Onyx, have been recently developed and are considered to represent a kind of "gold standard" for embolization of these lesions. The purpose of this study is to emphasize the importance of transarterial embolization using acrylic glue in the therapeutic management of ICDAVSs with CVR, and to compare the results the authors obtained using this treatment with those reported in the literature for Onyx treatment of the same type of dural shunts. The clinical and radiological records of 53 consecutive patients suffering from ICDAVSs with CVR (Borden Types 2 or 3) were reviewed. All cases were managed with the same angiographic and therapeutic protocol. Localization of the lesions, their clinical symptoms, their angioarchitecture, their therapeutic management, and the results were analyzed. Fourteen ICDAVSs were located at the superior sagittal sinus and/or convexity veins, 13 at the transverse and sigmoid sinuses, 10 at the tentorium, 5 in the anterior cranial fossa, 4 at the foramen magnum, 3 at the torcula, 2 at the straight sinus, and 1 at the vein of Galen. One patient presented with an infantile form of ICDAVS with multiple shunts. Hemorrhage had occurred in 36% of cases. Forty-three patients underwent

  16. Lysyl oxidase is essential for hypoxia-induced metastasis.

    PubMed

    Erler, Janine T; Bennewith, Kevin L; Nicolau, Monica; Dornhöfer, Nadja; Kong, Christina; Le, Quynh-Thu; Chi, Jen-Tsan Ashley; Jeffrey, Stefanie S; Giaccia, Amato J

    2006-04-27

    Metastasis is a multistep process responsible for most cancer deaths, and it can be influenced by both the immediate microenvironment (cell-cell or cell-matrix interactions) and the extended tumour microenvironment (for example vascularization). Hypoxia (low oxygen) is clinically associated with metastasis and poor patient outcome, although the underlying processes remain unclear. Microarray studies have shown the expression of lysyl oxidase (LOX) to be elevated in hypoxic human tumour cells. Paradoxically, LOX expression is associated with both tumour suppression and tumour progression, and its role in tumorigenesis seems dependent on cellular location, cell type and transformation status. Here we show that LOX expression is regulated by hypoxia-inducible factor (HIF) and is associated with hypoxia in human breast and head and neck tumours. Patients with high LOX-expressing tumours have poor distant metastasis-free and overall survivals. Inhibition of LOX eliminates metastasis in mice with orthotopically grown breast cancer tumours. Mechanistically, secreted LOX is responsible for the invasive properties of hypoxic human cancer cells through focal adhesion kinase activity and cell to matrix adhesion. Furthermore, LOX may be required to create a niche permissive for metastatic growth. Our findings indicate that LOX is essential for hypoxia-induced metastasis and is a good therapeutic target for preventing and treating metastases.

  17. Pattern of cervical lymph node metastasis in tonsil cancer: predictive factor analysis of contralateral and retropharyngeal lymph node metastasis.

    PubMed

    Chung, Eun-Jae; Oh, Jeong-In; Choi, Kyu-Young; Lee, Dong-Jin; Park, Il-Seok; Kim, Jin-Hwan; Rho, Young-Soo

    2011-08-01

    The purpose of this study was to determine the pattern of cervical lymph node metastasis in tonsil cancer including the retropharyngeal (RPLN) nodal metastasis. Seventy-six tonsillar squamous cell carcinoma patients who underwent surgery-based treatment were retrospectively analyzed. Most patients had advanced stage (stages III and IV: 81.6%) tonsil cancer. Sixteen patients were treated with surgery only. Postoperative radiotherapy was performed to 38 patients, and chemoradiation to 22 patients. Seventy-one therapeutic neck dissections and 27 elective neck dissections were performed. Thirty-four patients underwent RPLN dissection based on the preoperative inclusion criteria. There was a statistically significant metastasis in level I or V nodes, when the ipsilateral multilevel, or contralateral nodes were positive. The rate of contralateral occult cases was 28.6%. T3-4 stages, primary lesions close to the midline, or ipsilateral multilevel involvement were significantly associated with contralateral metastasis. Ipsilateral multilevel involvement was the independent factor with multivariate analysis. RPLN metastasis was confirmed in 9 of the 34 (26.5%) subjects. Disease-specific survival rate was significantly different according to RPLN status (82.1% vs. 55.6%; p=0.021). Positive pre-operative image, posterior pharyngeal wall invasion, more than N2 stage, contralateral node metastasis, or ipsilateral multilevel involvement were correlated with RPLN metastasis. Bilateral neck dissection is mandatory for primary lesions close to the midline and advanced ipsilateral nodal disease. Elective RPLN dissection should be considered for patients with advanced neck and primary tumor, particularly for tumors with posterior pharyngeal wall invasion. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. Orbital metastasis of endocervical stromal sarcoma: a rare tumor and an uncommon metastasis.

    PubMed

    Seker, Mehmet Metin; Uslu, Ali Ugur; Ozer, Hatice; Seker, Ayse; Kacan, Turgut; Babacan, Nalan; Aker, Handan; Elagoz, Sahande

    2014-12-01

    Endocervical stromal sarcoma (ECSS) is a very rare uterine sarcoma. The most common presentation is pelvic mass and vaginal bleeding. The mainstay of treatment is surgery. There is no consensus on the adjuvant treatment. Relapses are usually in the pelvic and abdominal regions. To a lesser extent, lung, liver and bone metastases may be seen. A 46-year-old woman had total abdominal hysterectomy (TAH) with bilateral salpingo-oophorectomy (BSO) performed due to endometrial polyp and leiomyoma. Six months after the TAH-BSO, she was admitted to the hospital with cough and hemoptysis. A thoracic mass was detected, and a biopsy was done. The diagnosis was low-grade ECSS metastasis. One week after thoracotomy, she was admitted to the hospital with loss of vision in the left eye. An orbital mass was detected with magnetic resonance imaging. Endometrial and cervical pathology preparations were reassessed and were compatible with ECSS. We performed mammography, thorax, and abdomen and cranial imaging to rule out other malignancies that may cause lung and orbital metastasis. Partial remission was achieved with systemic chemotherapy and orbital radiotherapy. Orbital metastasis may be seen in ECSS patients. Although we have less knowledge about the choice of chemotherapeutic agents, ifosfamide and doxorubicin are effective in treating ECSS.

  19. Orbital metastasis of endocervical stromal sarcoma: a rare tumor and an uncommon metastasis

    PubMed Central

    Uslu, Ali Ugur; Ozer, Hatice; Seker, Ayse; Kacan, Turgut; Babacan, Nalan; Aker, Handan; Elagoz, Sahande

    2014-01-01

    Endocervical stromal sarcoma (ECSS) is a very rare uterine sarcoma. The most common presentation is pelvic mass and vaginal bleeding. The mainstay of treatment is surgery. There is no consensus on the adjuvant treatment. Relapses are usually in the pelvic and abdominal regions. To a lesser extent, lung, liver and bone metastases may be seen. A 46-year-old woman had total abdominal hysterectomy (TAH) with bilateral salpingo-oophorectomy (BSO) performed due to endometrial polyp and leiomyoma. Six months after the TAH-BSO, she was admitted to the hospital with cough and hemoptysis. A thoracic mass was detected, and a biopsy was done. The diagnosis was low-grade ECSS metastasis. One week after thoracotomy, she was admitted to the hospital with loss of vision in the left eye. An orbital mass was detected with magnetic resonance imaging. Endometrial and cervical pathology preparations were reassessed and were compatible with ECSS. We performed mammography, thorax, and abdomen and cranial imaging to rule out other malignancies that may cause lung and orbital metastasis. Partial remission was achieved with systemic chemotherapy and orbital radiotherapy. Orbital metastasis may be seen in ECSS patients. Although we have less knowledge about the choice of chemotherapeutic agents, ifosfamide and doxorubicin are effective in treating ECSS. PMID:26327880

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

    PubMed

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

    2014-10-01

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

  1. TEL2 suppresses metastasis by down-regulating SERPINE1 in nasopharyngeal carcinoma.

    PubMed

    Sang, Yi; Chen, Ming-Yuan; Luo, Donghua; Zhang, Ru-Hua; Wang, Li; Li, Mei; Luo, Rongzhen; Qian, Chao-Nan; Shao, Jian-Yong; Zeng, Yi-Xin; Kang, Tiebang

    2015-10-06

    Metastasis is the major cause of treatment failure in patients with nasopharyngeal carcinoma (NPC). However, the molecular mechanisms of NPC metastasis are poorly understood. Here, using our customized gene microarray containing all of the known human transcription factors and the current markers for epithelial-mesenchymal transition, we report that TEL2 was down-regulated in highly metastatic NPC cells and the metastatic tissues in lymph node. Mechanistically, TEL2 inhibits the cell migration and invasion in vitro and metastasis in vivo by directly suppressing the SERPINE1 promoter in NPC. Consistently, an inverse correlation was observed between the protein levels of TEL2 and SERPINE1 using clinical NPC samples. Collectively, we have provided the first evidence that TEL2 plays a key role in NPC metastasis by directly down-regulating SERPINE1, and that this novel axis of TEL2 / SERPINE1 may be valuable to develop new strategies for treating NPC patients with metastasis.

  2. Clinicopathological factors are predictors of distant metastasis from major salivary gland carcinomas.

    PubMed

    Mariano, F V; da Silva, S D; Chulan, T C; de Almeida, O P; Kowalski, L P

    2011-05-01

    The risk of distant metastasis of salivary gland cancers has usually been associated with histological type, tumour size, and site. The aim of this study was to evaluate a series of patients with major salivary gland carcinomas in order to identify potential risk factors associated with distant metastasis. 255 patients treated for major salivary gland carcinoma in Brazil from 1953 to 2004 were reviewed. Clinical and treatment data were obtained from the medical records and histological features reviewed. 57 (22%) of 255 patients had distant metastasis. The lungs were the most common metastatic site (40 cases, 65%) and adenoid cystic carcinoma the most frequent histological type involved (27 cases, 47%). The percentage of tumours in the submandibular, parotid, and sublingual glands that presented distant metastasis was 42%, 20%, and 17%, respectively. These results provide evidences that clinicopathological factors (tumour site and histology) are significant predictors of distant metastasis in patients with major salivary gland carcinomas.

  3. Carcinoma ex pleomorphic adenoma of parotid gland with hepatic metastasis: clinic-radiological case report.

    PubMed

    Dhillon, Manu; Tomar, Divya; Sharma, Manu; Goel, Samta; Srivastava, Siddharth

    2014-04-01

    Pleomorphic adenoma originally called the mixed tumour is a neoplasm commonly involving major salivary glands. The spectrum of malignancy in pleomorphic adenoma comprises three distinct entities - Carcinoma ex pleomorphic adenoma, carcinosarcoma and benign metastasising pleomorphic adenoma. Carcinoma ex pleomorphic adenoma consists of pleomorphic adenoma with a malignant epithelial component. Occasionally, carcinomas ex pleomorphic adenoma develops metastasis. Here we are reporting here a case of benign pleomorphic adenoma arising in parotid gland which turned into malignancy after four years. The patient developed facial nerve paralysis suggesting malignant transformation. Along the course of the disease, the patient developed regional metastasis to lymph nodes and neck and distant metastasis to liver. This case report emphasises the role of advanced imaging modalities in the early diagnosis of the condition and evaluation of metastasis. The patients with this condition should be treated early for favorable outcome and investigated for distant metastasis.

  4. The effect of bone morphogenetic protein-2 on osteosarcoma metastasis

    PubMed Central

    Gill, Jonathan; Connolly, Patrick; Roth, Michael; Chung, So Hak; Zhang, Wendong; Piperdi, Sajida; Hoang, Bang; Yang, Rui; Guzik, Hillary; Gorlick, Richard; Geller, David S.

    2017-01-01

    Purpose Bone Morphogenetic Protein-2 (BMP-2) may offer the potential to enhance allograft-host osseous union in limb-salvage surgery following osteosarcoma resection. However, there is concern regarding the effect of locally applied BMP-2 on tumor recurrence and metastasis. The purpose of this project was to evaluate the effect of exogenous BMP-2 on osteosarcoma migration and invasion across a panel of tumor cell lines in vitro and to characterize the effect of BMP-2 on pulmonary osteosarcoma metastasis within a xenograft model. Experimental design The effect of BMP-2 on in vitro tumor growth and development was assessed across multiple standard and patient-derived xenograft osteosarcoma cell lines. Tumor migration capacity, invasion, and cell proliferation were characterized. In addition, the effect on metastasis was measured using a xenograft model following tail-vein injection. The effect of exogenous BMP-2 on the development of metastases was measured following both single and multiple BMP-2 administrations. Results There was no significant difference in migration capacity, invasion, or cell proliferation between the BMP-2 treated and the untreated osteosarcoma cell lines. There was no significant difference in pulmonary metastases between either the single-dose or multi-dose BMP-2 treated animals and the untreated control animals. Conclusions In the model systems tested, the addition of BMP-2 does not increase osteosarcoma proliferation, migration, invasion, or metastasis to the lungs. PMID:28264040

  5. The effect of bone morphogenetic protein-2 on osteosarcoma metastasis.

    PubMed

    Gill, Jonathan; Connolly, Patrick; Roth, Michael; Chung, So Hak; Zhang, Wendong; Piperdi, Sajida; Hoang, Bang; Yang, Rui; Guzik, Hillary; Morris, Jonathan; Gorlick, Richard; Geller, David S

    2017-01-01

    Bone Morphogenetic Protein-2 (BMP-2) may offer the potential to enhance allograft-host osseous union in limb-salvage surgery following osteosarcoma resection. However, there is concern regarding the effect of locally applied BMP-2 on tumor recurrence and metastasis. The purpose of this project was to evaluate the effect of exogenous BMP-2 on osteosarcoma migration and invasion across a panel of tumor cell lines in vitro and to characterize the effect of BMP-2 on pulmonary osteosarcoma metastasis within a xenograft model. The effect of BMP-2 on in vitro tumor growth and development was assessed across multiple standard and patient-derived xenograft osteosarcoma cell lines. Tumor migration capacity, invasion, and cell proliferation were characterized. In addition, the effect on metastasis was measured using a xenograft model following tail-vein injection. The effect of exogenous BMP-2 on the development of metastases was measured following both single and multiple BMP-2 administrations. There was no significant difference in migration capacity, invasion, or cell proliferation between the BMP-2 treated and the untreated osteosarcoma cell lines. There was no significant difference in pulmonary metastases between either the single-dose or multi-dose BMP-2 treated animals and the untreated control animals. In the model systems tested, the addition of BMP-2 does not increase osteosarcoma proliferation, migration, invasion, or metastasis to the lungs.

  6. Optic Neuritis as Isolated Manifestation of Leptomeningeal Carcinomatosis: A Case Report and Systematic Review of Ocular Manifestations of Neoplastic Meningitis

    PubMed Central

    Basilico, Paola; Trezzi, Ilaria; Borellini, Linda; Franco, Giulia; Civelli, Vittorio; Bresolin, Nereo; Baron, Pierluigi

    2013-01-01

    Introduction. Leptomeningeal carcinomatosis occurs in about 5% of cancer patients. Ocular involvement is a common clinical manifestation and often the presenting clinical feature. Materials and Methods. We report the case of a 52-year old lady with optic neuritis as isolated manifestation of neoplastic meningitis and a review of ocular involvement in neoplastic meningitis. Ocular symptoms were the presenting clinical feature in 34 patients (83%) out of 41 included in our review, the unique manifestation of meningeal carcinomatosis in 3 patients (7%). Visual loss was the presenting clinical manifestation in 17 patients (50%) and was the most common ocular symptom (70%). Other ocular signs were diplopia, ptosis, papilledema, anisocoria, exophthalmos, orbital pain, scotomas, hemianopsia, and nystagmus. Associated clinical symptoms were headache, altered consciousness, meningism, limb weakness, ataxia, dizziness, seizures, and other cranial nerves involvement. All patients except five underwent CSF examination which was normal in 1 patient, pleocytosis was found in 11 patients, increased protein levels were observed in 16 patients, and decreased glucose levels were found in 8 patients. Cytology was positive in 29 patients (76%). Conclusion. Meningeal carcinomatosis should be considered in patients with ocular symptoms even in the absence of other suggestive clinical symptoms. PMID:24223306

  7. Efficiency of silencing RNA for removal of transthyretin V30M in a TTR leptomeningeal animal model.

    PubMed

    Gonçalves, Paula; Martins, Helena; Costelha, Susete; Maia, Luis F; Saraiva, Maria Joao

    2016-12-01

    Some TTR mutants target the central nervous system (CNS). Familial amyloid polyneuropathy (FAP) with leptomeningeal involvement has been described in 9% of transthyretin (TTR) mutations and in valine for methionine at position 30 (V30M) patients. These individuals present dementia, ataxia, brain hemorrhages and focal neurological episodes (FNEs). FNEs occurred also in V30M FAP patients with longer disease duration, who have undergone liver transplant to remove the source of plasma mutant TTR as a form of treatment. It is thus to expect that as better treatments for FAP emerge and prolong survival, meningeal-vascular CNS deposition will increase and need special therapies. Recently, we detected TTR meningeal-vascular deposition in a V30M TTR transgenic mouse model, opening new avenues of research to investigate selective treatments of this condition. Since pre-clinical studies with TTR siRNA therapeutics were shown to promote clearance of TTR non-fibrillar deposits in several organs and tissues, we investigated its effect on TTR meningeal-vascular deposition. We show that systemically administered TTR siRNA promoted TTR clearance in the extracellular matrix of meninges and brain blood vessels. Surprisingly, despite the striking decline of blood TTR, cerebrospinal fluid TTR levels were unaffected. Though this is reassuring because siRNA will not interfere with the neuroprotective role of TTR in the CNS, it raises new questions on therapeutical approaches for CNS ATTR.

  8. [Amyloid beta-related angiitis: brain lesions showing leptomeningeal gadolinium enhancement on MRI and characteristic surgical pathologic features].

    PubMed

    Koike, Yuka; Ouchi, Haruka; Sato, Tomoe; Shimbo, Junsuke; Sato, Aki; Sasaki, Osamu; Shibuya, Hiroyuki; Okamoto, Kouichirou; Kakita, Akiyoshi; Igarashi, Shuichi

    2013-06-01

    Amyloid-β-related angiitis (ABRA) of the CNS occurs in association with vasculitis of small-and medium-sized leptomeningeal arteries. Here, we describe the clinicopathological features of a 76-year-old man with ABRA. The patient suffered progressive truncal oscillation, aphasia, and recent memory disturbance with a subacute disease onset. His cerebrospinal fluid showed a mild increase in protein levels (101 mg/dL) and pleocytosis (8/mm(3)). High-intensity brain lesion were detected on T(2)-weighted and FLAIR MRI scans, and prominent spread of gadolinium enhancement spreading was observed through the sulci of the left occipital and temporal lobes and left cerebellar hemisphere. A biopsy of the left temporal lesion showed a granulomatous and angiodestructive inflammation with infiltration of many CD4(+) T-lymphocytes and multinucleated giant cells and with fibrinoid necrosis of the arterial walls in the subarachnoid space. Immunolabeling for Aβ(1-40) revealed the abundant deposition of this protein in the affected arteries. On the basic of the diagnosis of ABRA, immunosuppressive therapy was conducted, and it ameliorated the clinical course.

  9. Brain Stem and Entire Spinal Leptomeningeal Dissemination of Supratentorial Glioblastoma Multiforme in a Patient during Postoperative Radiochemotherapy

    PubMed Central

    Kong, Xiangyi; Wang, Yu; Liu, Shuai; Chen, Keyin; Zhou, Qiangyi; Yan, Chengrui; He, Huayu; Gao, Jun; Guan, Jian; Yang, Yi; Li, Yongning; Xing, Bing; Wang, Renzhi; Ma, Wenbin

    2015-01-01

    Abstract Glioblastoma multiforme (GBM) is the most common primary malignancy of the central nervous system in adults. Macroscopically evident and symptomatic spinal metastases occur rarely. Autopsy series suggest that approximately 25% of patients with intracranial GBM have evidence of spinal subarachnoid seeding, although the exact incidence is not known as postmortem examination of the spine is not routinely performed.1–3 Herein, we present a rare case of symptomatic brain stem and entire spinal dissemination of GBM in a 36-year-old patient during postoperative adjuvant radiochemotherapy with temozolomide and cisplatin. Visual deterioration, intractable stomachache, and limb paralysis were the main clinical features. The results of cytological and immunohistochemical tests on the cerebrospinal fluid cells were highly suggestive of spinal leptomeningeal dissemination. After 1 month, the patient's overall condition deteriorated and succumbed to his disease. To the best of our knowledge, this is the first reported case of GBM dissemination presenting in this manner. Because GBM extracranial dissemination is rare, we also reviewed pertinent literature regarding this uncommon entity. Although metastases to spinal cord from GBM are uncommon, it is always important to have in mind when patients with a history of GBM present with symptoms that do not correlate with the primary disease pattern. PMID:26091464

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

    PubMed Central

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

    2013-01-01

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

  11. Metastasis to a spinal meningioma.

    PubMed

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

    2017-01-01

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

  12. The challenge of targeting metastasis.

    PubMed

    Fidler, Isaiah J; Kripke, Margaret L

    2015-12-01

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

  13. Individualized optimal surgical extent of the lateral neck in papillary thyroid cancer with lateral cervical metastasis.

    PubMed

    Park, Jae-Yong; Koo, Bon Seok

    2014-06-01

    Despite an excellent prognosis, cervical lymph node (LN) metastases are common in patients with papillary thyroid cancer (PTC). The presence of metastasis is associated with an increased risk of locoregional recurrence, which significantly impairs quality of life and may decrease survival. Therefore, it has been an important determinant of the extent of lateral LN dissection in the initial treatment of PTC patients with lateral cervical metastasis. However, the optimal extent of therapeutic lateral neck dissection (ND) remains controversial. Optimizing the surgical extent of LN dissection is fundamental for balancing the surgical morbidity and oncological benefits of ND in PTC patients with lateral neck metastasis. We reviewed the currently available literature regarding the optimal extent of lateral LN dissection in PTC patients with lateral neck metastasis. Even in cases with suspicion of metastatic LN at the single lateral level or isolated metastatic lateral LN, the application of ND including all sublevels from IIa and IIb to Va and Vb may be overtreatment, due to the surgical morbidity. When there is no suspicion of LN metastasis at levels II and V, or when multilevel aggressive neck metastasis is not found, sublevel IIb and Va dissection may not be necessary in PTC patients with lateral neck metastasis. Thus consideration of the individualized optimal surgical extent of lateral ND is important when treating PTC patients with lateral cervical metastasis.

  14. Mitochondria in relation to cancer metastasis.

    PubMed

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

    2012-12-01

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

  15. γ knife radiosurgery of brain metastasis from breast cancer.

    PubMed

    Padovani, Laetitia; Muracciole, Xavier; Régis, Jean

    2012-01-01

    The incidence of brain metastasis in patients with metastatic breast cancer ranges from 14 to 16%.Age, number of metastatic sites, short disease-free survival and molecular subtypes are associated with the occurrence of brain metastasis. Patients classified in the triple-negative group more frequently presented brain metastasis as the first site (26%) than those in the human epidermal growth factor receptor 2 (HER2)-positive (6%) or luminal (12%) subtypes. Whole brain radiation therapy (WBRT) is still the standard treatment for breast cancer patients with brain metastasis. The 1- and 2-year survival rates of patients with brain metastasis were 25 and 10%, respectively, with a median survival of 6 months. In selected patients with single brain metastasis, majority of lung cancer, three randomized controlled trials underlined the significant survival benefit in adding local treatment such as surgery or stereotactic radio surgery to WBRT. Similarly, the upfront stereotactic radiosurgery (SRS) alone did not affect survival rate in three other randomized studies and represents an alternative treatment for patients with stage 1-4. Metastatic breast cancer patients with Karnofsky Performance Scale ≥70, single or oligometastatic brain metastases and well-controlled extracranial disease or favorable disease-specific graded prognostic assessment group presented a median overall survival of 16 months. Delaying WBRT could spare patients of neurocognitive toxicity due to full-dose whole brain irradiation. Nevertheless, the real WBRT neurocognitive impact is still unclear. These patients should be followed with serial magnetic resonance image every 3 months and treated with WBRT or additional SRS at recurrence to control brain disease.

  16. Metastasis genetics, epigenetics, and the tumor microenvironment

    USDA-ARS?s Scientific Manuscript database

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

  17. [The inhibitory effect of nafamostat mesilate (FUT-175) on liver metastasis].

    PubMed

    Kimura, T; Fuchimoto, S; Iwagaki, H; Orita, K

    1993-01-01

    Basic investigation of inhibitory effect on metastasis of nafamostat mesilate (FUT-175) which is a kind of serine protease inhibitors, was performed. Colon 26 cells were injected to the portal vein of CDF1 mice. FUT-175 at doses of 0.3, 1.0, 3.0, 10.0 mg/kg was injected intravenously every 7 day. Mice were sacrificed on day 21, and metastasis of liver surface were measured. The dose dependent reduction of metastasis was observed and reduction of metastasis of mice treated at a dose of 10.0 mg/kg was significant. FUT-175 showed no cytotoxicity at doses of 10(-5) M or less in vitro, and blood concentration of mice, treated at a dose of 10.0 mg/kg, was 2.67 x 10(-7) M. The results showed that inhibitory effect of FUT-175 on metastasis was not caused by direct cytotoxicity. FUT-175 at 2.67 x 10(-7) M in vitro can inhibit only thrombin and plasmin at nearly 50%, and can not inhibit platelet aggregation and collagenase directly. Possible mechanism of inhibition of metastasis is that FUT-175 inhibited both thrombin-mediated platelet aggregation and plasmin-mediated collagenase activation, that arrest and extravasation in cancer cells were inhibited. If protease inhibitor is administered continuously and immediately after surgery, liver metastasis may be prevented.

  18. Right ventricular metastasis of leiomyosarcoma.

    PubMed

    Dencker, Magnus; Valind, Sven; Stagmo, Martin

    2009-05-05

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

  19. Intracranial tuberculoma mimicking brain metastasis.

    PubMed

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

    2015-01-01

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

  20. Global Gene Expression Profiles Identify Metastasis Regulatory Networks | Center for Cancer Research

    Cancer.gov

    Metastasis is a systemic disease in which cancer cells break away from a tumor and migrate to other parts of the body, usually via the blood or lymphatic systems, to form new tumors. Metastatic tumors are difficult to treat and account for the majority of cancer-related deaths. Susceptibility to metastasis is known to have a genetic component, with some individuals more predisposed than others. However, because of the complex interchange between random genomic and epigenetic events that contribute to the disease, characterization of individual genes or small numbers of genes is not sufficient to understand the processes leading up to metastasis.

  1. Late occurrence of drop metastasis to the spine in a case of esthesioneuroblastoma.

    PubMed

    Rao, Abigail J; Gultekin, S Humayun; Neuwelt, Edward A; Cintrón-Colón, Hector R; Ragel, Brian T

    2011-11-01

    Esthesioneuroblastoma is an aggressive neuroectodermal tumor that originates from the olfactory mucosa and often recurs locally. Distant metastasis of esthesioneuroblastoma has been described, but there are few reports of drop metastasis to the spinal cord. Here, we report a case of multiple drop metastases to the cervical, thoracic, and lumbar regions of the spinal cord that occurred 18 years after resection and radiotherapy of the original anterior cranial fossa lesion. There was no evidence of local recurrence. The symptomatic lesion was treated with resection and adjuvant chemotherapy. The options available for treatment of this disease are summarized with a review of the few reported cases of spinal metastasis of esthesioneuroblastoma.

  2. Metastasis of genitourinary tumors to the head and neck region.

    PubMed

    Ogunyemi, Ore; Rojas, A; Hematpour, K; Rogers, D; Head, C; Bennett, C

    2010-02-01

    The objective of the present study is to characterize genitourinary tumors (GU) metastatic to the head and neck and to determine long-term prognoses. Using a retrospective chart review of 734 patients treated between January 1995 and May 2005 with an ICD-9 code pertaining to a metastatic head and neck cancer, we found 37 patients with primary GU tumors. There were 24 cases of prostate cancer, 10 cases of renal cell carcinoma, and 4 cases of transitional cell carcinoma. Sixteen of 24 patients (67%) with prostate cancer had a cranial metastasis while 6 of 9 (67%) patients with renal cell carcinoma had cerebral metastasis. We concluded that prolonged survival is possible in prostate cancer patients treated aggressively with radiation and chemotherapy, indicating that early detection and aggressive screening are important in these patients.

  3. Survivin Is a Potential Mediator of Prostate Cancer Metastasis

    SciTech Connect

    Zhang Min; Coen, John J.; Khor, Li-Yan; Pollack, Alan; Zhang Yifen; Zietman, Anthony L.; Shipley, William U.

    2010-11-15

    Purpose: We examined whether Survivin expression is associated with an increased risk of metastasis in prostate cancer. Methods and Materials: A total of 205 patients with T1 (23%) and T2 (77%) prostate cancer were treated with conventional external beam radiation therapy from 1991 to 1993 at the Massachusetts General Hospital. Of the patients, 62 had adequate and suitable-stained tumor material for Survivin analysis. Median follow-up was 102 months (range, 5-127 months). Distant failure was determined on the basis of clinical criteria. In preclinical studies, replication-deficient adenovirus encoding phosphorylation-defective Survivin Thr34{yields}Ala dominant-negative mutant pAd-S(T34A) or short hairpin RNA (shRNA) was used to inhibit Survivin in prostate cancer models, and the cell motility, morphology, and metastasis were investigated. Results: Our correlative data on men with early-stage (T1/T2) prostate cancers treated at Massachusetts General Hospital by definitive radiotherapy indicated that overexpression of Survivin (positive staining in {>=}10% cells) was associated with a significantly increased risk for the subsequent development of distant metastasis (p = 0.016) in the univariate analysis. In the multivariate analysis, overexpression of Survivin remained an independent predictor of distant metastasis (p = 0.008). The inhibition of Survivin dramatically inhibited invasiveness of prostate cancer cells in the in vitro invasion assay and spontaneous metastasis in the Dunning prostate cancer in vivo model. Furthermore, attenuation of Survivin resulted in changes in the microtubule cytoskeleton, loss of cellular polarity, and loss of motility. Conclusions: This study suggests that Survivin may be a potentially important prognostic marker and promising therapeutic target in metastatic prostate cancer.

  4. Palliative Surgery for Rare Cases of Anterior Urethral Metastasis in Prostate Cancer

    PubMed Central

    Gómez Gómez, Enrique; Carrasco Aznar, Jose Carlos; Moreno Rodríguez, Maria del Mar; Valero Rosa, José; Requena Tapia, Maria José

    2014-01-01

    Penis metastasis from prostate cancer is very rare, and its management varies from case to case as there are very few cases reported in the literature. We describe a patient with prostate cancer treated with radiotherapy and androgen deprivation therapy who presented with urethral bleeding as a symptom of anterior urethral metastasis during followup. We propose a way to manage this and review the literature. PMID:25161796

  5. Ureteroiliac fistula secondary to radiotherapy in a patient with single renal metastasis of colon adenocarcinoma

    PubMed Central

    Dormeus, Sarah; Hernández, Erick A.; Nicolazzi, Mickaël; Barba, Javier F.; Algarra, Rubén; Tienza, Antonio; Pascual, Juan I.; Berián, José M.; Zudaire, Juan J.

    2013-01-01

    We report the case of a 61-year-old man diagnosed in 2001 with rectal cancer (stage T3N1M0). The patient was treated with surgery, adjuvant chemotherapy and radiotherapy. In 2009, he was admitted to the urology department with a complaint of right hemiabdominal pain. The anatomopathological investigation reported renal metastasis of colon adenocarcinoma. After surgery, he received adjuvant chemotherapy. No tumour recurrence or metastasis was reported at the 22-month follow-up. PMID:23671507

  6. Regenerative Stem Cell Therapy for Breast Cancer Bone Metastasis

    DTIC Science & Technology

    2015-11-01

    mice challenged with CAGhep cells. Similarly, significant bone destruction was observed in the spine, particularly the L4 bone of the lumbar region...However, images of bone 3D reconstruction for cohorts treated with OPG therapy showed intact tibia and lumbar spinal bone with bone density and...ological fractures, nerve compression syndromes, and hypercal- cemia (2). Current therapies for bone metastasis in breast cancer patients are limited and are

  7. Breast Cancer Metastasis to Bone Affects Osteoblast Differentiation

    DTIC Science & Technology

    2005-05-01

    osteoblasts cultured with conditioned medium from NIH 3T3 fibroblasts did not affect cell number. b. Task lb-le: These aims were not pursued. Because...not affected by NIH 3T3 fibroblast conditioned medium or vehicle control medium. Cells were examined at various times up to 35 days of culture. Tasks...Understanding how breast cancer cells affect osteoblasts following skeletal metastasis will be instrumental in finding new drug targets to not only treat

  8. MicroRNAs in gastric cancer metastasis.

    PubMed

    Shi, Zhaoqi; Wei, Qingxia; She, Junjun

    2014-01-01

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

  9. MET copy number gain is associated with gefitinib resistance in leptomeningeal carcinomatosis of EGFR-mutant lung cancer.

    PubMed

    Nanjo, Shigeki; Arai, Sachiko; Wang, Wei; Takeuchi, Shinji; Yamada, Tadaaki; Hata, Akito; Katakami, Nobuyuki; Okada, Yasunori; Yano, Seiji

    2017-01-30

    Leptomeningeal carcinomatosis (LMC) occurs frequently in EGFR-mutant lung cancer, and develops acquired resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs). This study aimed to clarify the mechanism of EGFR-TKI resistance in LMC and seek for a novel therapeutic strategy. We examined EGFR mutations, including the T790M gatekeeper mutation, in 32 re-biopsy specimens from 12 LMC and 20 extracranial lesions of EGFR-mutant lung cancer patients who became refractory to EGFR-TKI treatment. All the 32 specimens had the same baseline EGFR mutations, but the T790M mutation was less frequent in LMC specimens than in extracranial specimens (8% vs. 55%, p<0.01). To study molecular mechanisms of acquired EGFR-TKI resistance in LMC, we utilized our previously developed mouse model of LMC with the EGFR-mutant lung cancer cell line PC-9/ffluc cells, in which acquired resistance to gefitinib was induced by continuous oral treatment. Compared with subcutaneously inoculated gefitinib-resistant tumors, the T790M mutation was less frequent in LMC that acquired resistance to gefitinib. PC-9/LMC-GR cells were established from the gefitinib-resistant LMC model, and they were found to be intermediately resistant to gefitinib and osimertinib (third generation EGFR-TKI). Although EGFR-T790M was negative, gefitinib resistance of PC-9/LMC-GR cells was related to MET copy number gain with MET activation. Moreover, combined use of EGFR-TKI and crizotinib, a MET inhibitor, dramatically regressed LMC with acquired resistance to gefitinib or osimertinib. These findings suggest that combination therapy with MET inhibitors may be promising for controlling LMC that acquires resistance to EGFR-TKIs.

  10. Signet Cell in the Brain: A Case Report of Leptomeningeal Carcinomatosis as the Presenting Feature of Gastric Signet Cell Cancer

    PubMed Central

    Khan, Muhammad Talha; Idrisov, Evgeny A; Maqsood, Aadil; Asad-Ur-Rahman, FNU; Abusaada, Khalid

    2017-01-01

    Malignant infiltration of pia and arachnoid mater, referred to as leptomeningeal carcinomatosis (LMC), is a rare complication of gastric carcinoma. The most common underlying malignancy in patients with LMC are leukemia, breast cancer, lymphoma, and lung cancer. We report a case of gastric adenocarcinoma that presented with LMC in the absence of overt gastrointestinal signs or symptoms. A 56-year-old Hispanic woman presented to the hospital with a three-week history of intermittent headaches and visual blurring. An initial brain imaging showed infarction in the distribution of right posterior inferior cerebellar artery (PICA) along with communicating hydrocephalus. She underwent ventriculoperitoneal (VP) shunt placement with improvement in her symptoms. Two months later she presented again with deterioration in her mental status. Imaging studies and cerebrospinal fluid (CSF) analysis confirmed the diagnosis of LMC. Further studies determined the primary tumor to be signet ring cell gastric adenocarcinoma. However, she did not have any preceding gastrointestinal symptoms. In light of the poor prognosis, the patient's family proceeded with comfort care measures. Our case portrays a rare presentation of gastric adenocarcinoma with LMC without other distant organ metastatic involvement. It also illustrates the occult nature of gastric carcinoma and signifies the importance of neurologic assessment of patients, with or at risk of gastric carcinoma. ​It also raises a theoretical concern for VP shunt as a potential conduit of malignant cells from the abdomen to the central nervous system, which may serve as an important susbtrate for future research. PMID:28405535

  11. A New Paradigm for Mechanobiological Mechanisms in Tumor Metastasis

    PubMed Central

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

    2012-01-01

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

  12. [Jawbone metastasis masquerading as dental pain].

    PubMed

    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.

  13. Schisandrin B Attenuates Cancer Invasion and Metastasis Via Inhibiting Epithelial-Mesenchymal Transition

    PubMed Central

    Liu, Kun; Ding, Zonghui; Hu, Xun

    2012-01-01

    Background Metastasis is the major cause of cancer related death and targeting the process of metastasis has been proposed as a strategy to combat cancer. Therefore, to develop candidate drugs that target the process of metastasis is very important. In the preliminary studies, we found that schisandrin B (Sch B), a naturally-occurring dibenzocyclooctadiene lignan with very low toxicity, could suppress cancer metastasis. Methodology BALB/c mice were inoculated subcutaneously or injected via tail vein with murine breast cancer 4T1 cells. Mice were divided into Sch B-treated and control groups. The primary tumor growth, local invasion, lung and bone metastasis, and survival time were monitored. Tumor biopsies were examined immuno- and histo-pathologically. The inhibitory activity of Sch B on TGF-β induced epithelial-mesenchymal transition (EMT) of 4T1 and primary human breast cancer cells was assayed. Principal Findings Sch B significantly suppressed the spontaneous lung and bone metastasis of 4T1 cells inoculated s.c. without significant effect on primary tumor growth and significantly extended the survival time of these mice. Sch B did not inhibit lung metastasis of 4T1 cells that were injected via tail vein. Delayed start of treatment with Sch B in mice with pre-existing tumors did not reduce lung metastasis. These results suggested that Sch B acted at the step of local invasion. Histopathological evidences demonstrated that the primary tumors in Sch B group were significantly less locally invasive than control tumors. In vitro assays demonstrated that Sch B could inhibit TGF-β induced EMT of 4T1 cells and of primary human breast cancer cells. Conclusions Sch B significantly suppresses the lung and bone metastasis of 4T1 cells via inhibiting EMT, suggesting its potential application in targeting the process of cancer metastasis. PMID:22848381

  14. Significance of lymph node metastasis on survival of women with uterine adenosarcoma.

    PubMed

    Machida, Hiroko; Nathenson, Michael J; Takiuchi, Tsuyoshi; Adams, Crystal L; Garcia-Sayre, Jocelyn; Matsuo, Koji

    2017-03-01

    Uterine adenosarcoma (UAS) is a rare gynecologic malignancy and the significance of lymph node metastasis on survival has not been well studied. A retrospective study was performed utilizing the Surveillance, Epidemiology, End Results Program to examine UAS (n=994), endometrial stromal sarcoma (ESS, n=2910), and uterine leiomyosarcoma (LMS, n=5506) diagnosed between 1973 and 2013. The impact of lymph node metastasis on cause-specific survival (CSS) was cross-compared by multivariable analysis. Systematic literature review was conducted to examine the impact of nodal metastasis on progression-free survival (PFS) in UAS. UAS had the lowest incidence of lymph node metastasis among the sarcoma subtypes examined (UAS 2.9%, LMS 3.4%, and ESS 6.6%, P<0.001). Lymph node metastasis was independently associated with decreased CSS in all three tumor types (all, P<0.01); however, magnitudes of statistical significance of lymph node metastasis for CSS were similar across the three tumor types: adjusted-hazard ratio (aHR) for UAS 2.34, ESS 2.43, and LMS 2.10. Systematic literature review identified 230 unique cases of surgically treated UAS. On multivariable analysis, lymph node metastasis (aHR 4.72) had the greatest degree of significance for PFS compared to other tumor factors including sarcomatous overgrowth (aHR 2.88), heterologous elements (aHR 2.08), and deep myometrial invasion (aHR 1.51). Large tumor, deep myometrial invasion, and sarcomatous overgrowth were associated with increased risk of lymph node metastasis (all, P<0.05). While uterine adenosarcoma had a low incidence of lymph node metastasis, the impact of lymph node metastasis on survival was comparable to ESS or LMS. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. The role of radiofrequency ablation for treatment of metachronous isolated hepatic metastasis from colorectal cancer.

    PubMed

    Lee, Byoung Chul; Lee, Hyun Gu; Park, In Ja; Kim, So Yeon; Kim, Ki-Hun; Lee, Jae Hoon; Kim, Chan Wook; Lee, Jong Lyul; Yoon, Yong Sik; Lim, Seok-Byung; Yu, Chang Sik; Kim, Jin Cheon

    2016-09-01

    We investigated recurrence pattern and oncologic outcomes after treatment of metachronous isolated liver metastases from colorectal cancer according to treatment modality.We retrospectively analyzed 123 patients treated with hepatic resection and 82 patients treated with radiofrequency ablation (RFA) for metachronous isolated hepatic metastasis from colorectal cancer (HMCRC). We compared clinicopathological data, recurrence pattern, and recurrence-free survival (RFS) rates after the treatment of hepatic metastasis between patients treated with RFA and resection.The patients in the 2 groups were similar in gender, location of primary tumor, disease-free interval to hepatic metastasis, pathologic stage of primary tumor, and number of hepatic metastasis. The age was older in RFA group but it was not statistically different. The mean diameter of the largest hepatic mass was greater in the resection group than in the RFA group (3.1 vs 1.9 cm, P < 0.001). Chemotherapy after the treatment of hepatic metastasis was more commonly given in hepatic resection group (76.4% vs 62.2%, P = 0.04). Recurrence after the treatment of hepatic metastasis was not significantly different between the 2 groups (54.5% vs 65.9% in the resection and RFA groups). However, intrahepatic recurrence without extra-hepatic metastases was more common in the RFA group than in the resection group (47.5% vs 12.1%, P < 0.001). The RFS rate after the treatment of hepatic metastasis was significantly higher in resection group (48.6% vs 33.7%, P = 0.015). The size and number of hepatic metastasis, primary tumor stage, disease-free interval to hepatic metastasis, and the modality of treatment (RFA vs resection) for hepatic metastasis were confirmed as associated factors with re-recurrence after the treatment of hepatic metastasis. Among patients with solitary hepatic metastases of ≤3 cm, marginal recurrence was higher in the RFA group (3% vs 17.2%) and re-RFA was performed to achieve comparable

  16. The role of radiofrequency ablation for treatment of metachronous isolated hepatic metastasis from colorectal cancer

    PubMed Central

    Lee, Byoung Chul; Lee, Hyun Gu; Park, In Ja; Kim, So Yeon; Kim, Ki-Hun; Lee, Jae Hoon; Kim, Chan Wook; Lee, Jong Lyul; Yoon, Yong Sik; Lim, Seok-Byung; Yu, Chang Sik; Kim, Jin Cheon

    2016-01-01

    Abstract We investigated recurrence pattern and oncologic outcomes after treatment of metachronous isolated liver metastases from colorectal cancer according to treatment modality. We retrospectively analyzed 123 patients treated with hepatic resection and 82 patients treated with radiofrequency ablation (RFA) for metachronous isolated hepatic metastasis from colorectal cancer (HMCRC). We compared clinicopathological data, recurrence pattern, and recurrence-free survival (RFS) rates after the treatment of hepatic metastasis between patients treated with RFA and resection. The patients in the 2 groups were similar in gender, location of primary tumor, disease-free interval to hepatic metastasis, pathologic stage of primary tumor, and number of hepatic metastasis. The age was older in RFA group but it was not statistically different. The mean diameter of the largest hepatic mass was greater in the resection group than in the RFA group (3.1 vs 1.9 cm, P < 0.001). Chemotherapy after the treatment of hepatic metastasis was more commonly given in hepatic resection group (76.4% vs 62.2%, P = 0.04). Recurrence after the treatment of hepatic metastasis was not significantly different between the 2 groups (54.5% vs 65.9% in the resection and RFA groups). However, intrahepatic recurrence without extra-hepatic metastases was more common in the RFA group than in the resection group (47.5% vs 12.1%, P < 0.001). The RFS rate after the treatment of hepatic metastasis was significantly higher in resection group (48.6% vs 33.7%, P = 0.015). The size and number of hepatic metastasis, primary tumor stage, disease-free interval to hepatic metastasis, and the modality of treatment (RFA vs resection) for hepatic metastasis were confirmed as associated factors with re-recurrence after the treatment of hepatic metastasis. Among patients with solitary hepatic metastases of ≤3 cm, marginal recurrence was higher in the RFA group (3% vs 17.2%) and re-RFA was performed to achieve

  17. Animal Models of Bone Metastasis

    PubMed Central

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

    2015-01-01

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

  18. [Bone metastasis of gastric cancer].

    PubMed

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

    2006-08-01

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

  19. [Uterine metastasis revealing gastric adenocarcinoma].

    PubMed

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

    1995-01-01

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

  20. Dissecting and Targeting Latent Metastasis

    DTIC Science & Technology

    2013-09-01

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

  1. Dissecting and Targeting Latent Metastasis

    DTIC Science & Technology

    2015-09-01

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

  2. Colorectal hepatic metastasis: Evolving therapies

    PubMed Central

    Macedo, Francisco Igor B; Makarawo, Tafadzwa

    2014-01-01

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

  3. Raman spectroscopy of bone metastasis

    NASA Astrophysics Data System (ADS)

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

    2012-02-01

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

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

    NASA Astrophysics Data System (ADS)

    Chambers, Ann

    2010-03-01

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

  5. Cancer stem cells and metastasis.

    PubMed

    Sampieri, Katia; Fodde, Riccardo

    2012-06-01

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

  6. Metastasis: an early event in cancer progression.

    PubMed

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

    2017-05-01

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

  7. Regulation of the metastasis of murine ocular melanoma by natural killer cells.

    PubMed

    Harning, R; Koo, G C; Szalay, J

    1989-09-01

    In the current study we examine parameters affecting the metastasis of ocular tumors of in vivo derived B16F10 melanoma. In C57BL/6J beige (bg/bg) mice, with low NK activity, metastasis to the lungs was increased and survival time decreased. In C57BL/6J normal (+/+) mice treatment with PK136, a highly specific monoclonal anti-NK antibody (Ab), caused a depletion of NK cytotoxic activity, as demonstrated using a standard 51Cr release assay. In animals bearing ocular tumors, treatment with PK136 Ab resulted in significantly increased pulmonary metastasis and an altered pattern of metastasis. The effect of combined treatment protocols using LS2616 (linomide) and cyclophosphamide (Cy) was examined in enucleated and unenucleated animals. Treatment with LS2616 and Cy resulted in a significant decrease in mean pulmonary metastases (MPM), a decreased frequency of metastasis to the submandibular lymph nodes and an increase in mean survival time. In enucleated mice this combined treatment protocol resulted in apparent cures, the lowest MPM and the longest survival time observed. When tumor-bearing mice were treated with either silica, carrageenan or sublethal gamma irradiation, no effect on metastasis or survival was observed. This study demonstrates the importance of the NK cell as a primary effector cell for the control of metastasis from in vivo derived ocular B16F10 melanoma.

  8. TNFα-activated mesenchymal stromal cells promote breast cancer metastasis by recruiting CXCR2(+) neutrophils.

    PubMed

    Yu, P F; Huang, Y; Han, Y Y; Lin, L Y; Sun, W H; Rabson, A B; Wang, Y; Shi, Y F

    2017-01-26

    Mesenchymal stromal cells (MSCs) tend to infiltrate into tumors and form a major component of the tumor microenvironment. Our previous work demonstrated that tumor necrosis factor α (TNFα)-activated MSCs significantly promoted tumor growth. However, the role of TNFα-treated MSCs in tumor metastasis remains elusive. Employing a lung metastasis model of murine breast cancer, we found that TNFα-activated MSCs strikingly enhanced tumor metastasis compared with normal MSCs. We analyzed the chemokine profiles and found that the expression of CCL5, CCR2 and CXCR2 ligands were enhanced in TNFα-activated MSCs. Using genetic or pharmacological strategies to inhibit CCL5 or CCR2, we demonstrated that CCL5 and CCR2 ligands were indispensable in supporting TNFα-activated MSCs to promote tumor metastasis. Analysis of immune cells revealed that CXCR2 ligands (CXCL1, CXCL 2 and CXCL5) expressed by TNFα-activated MSCs efficiently recruited CXCR2(+) neutrophils into tumor. These neutrophils were responsible for the pro-metastatic effect of MSCs since inhibition of this chemotaxis abolished increased neutrophil recruitment and tumor metastasis. The interaction between neutrophils and tumor cells resulted in markedly elevated metastasis-related genes by tumor cells, including CXCR4, CXCR7, MMP12, MMP13, IL-6 and TGFβ. Importantly, in IL8(high) human breast cancer samples, we also observed similar alterations of gene expression. Collectively, our findings demonstrate that TNFα-activated MSCs promote tumor metastasis via CXCR2(+) neutrophil recruitment.

  9. Renal cell carcinoma metastasis to the parathyroid gland: A very rare occurrence.

    PubMed

    Ofo, Enyinnaya; Mandavia, Rishi; Jeannon, Jean-Pierre; Odell, Edward; Simo, Ricard

    2014-01-01

    Metastases to the parathyroid gland are very uncommon. Although renal cell carcinoma metastasis to the head and neck region is well recognised, with a predilection for unpredictable metastasis to unusual sites such as the thyroid gland, nose, paranasal sinuses, and cranial bones, there are no reports of parathyroid gland involvement. We describe an unusual case of renal cell carcinoma metastasis to a parathyroid gland in a 69-year-old male who had been treated 8 years previously for a pT3b N0 M1 clear cell carcinoma of the right kidney with a right nephrectomy, and interferon immunotherapy for 18 months. The patient had originally presented to the plastic surgeons with a rapidly enlarging 3cm superficial lesion on the ventral aspect of the left forearm, which was excised with histology revealing metastatic renal (clear) cell carcinoma. Renal cell carcinoma has a reputation for unpredictable patterns of metastasis, and our case highlights this, with the first description in the literature of parathyroid gland metastasis. Despite the poor prognosis associated with metastatic renal cell carcinoma, our patient is still alive 10 years following original presentation, despite having metastasis to two different extra-renal sites and a shortened course of initial adjuvant systemic therapy. In parathyroid gland metastasis, metastectomy can offer excellent local long term local control. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Investigation of the roles of exosomes in colorectal cancer liver metastasis.

    PubMed

    Wang, Xia; Ding, Xiaoling; Nan, Lijuan; Wang, Yiting; Wang, Jing; Yan, Zhiqiang; Zhang, Wei; Sun, Jihong; Zhu, Wei; Ni, Bing; Dong, Suzhen; Yu, Lei

    2015-05-01

    The leading cause of death among cancer patients is tumor metastasis. Tumor-derived exosomes are emerging as mediators of metastasis. In the present study, we demonstrated that exosomes play a pivotal role in the metastatic progression of colorectal cancer. First, a nude mouse model of colorectal cancer liver metastasis was established and characterized. Then, we demonstrated that exosomes from a highly liver metastatic colorectal cancer cell line (HT-29) could significantly increase the metastatic tumor burden and distribution in the mouse liver of Caco-2 colorectal cancer cells, which ordinarily exhibit poor liver metastatic potential. We further investigated the mechanisms by which HT-29-derived-exosomes influence the liver metastasis of colorectal cancer and found that mice treated with HT-29-derived exosomes had a relatively higher level of CXCR4 in the metastatic microenvironment, indicating that exosomes may promote colorectal cancer metastasis by recruiting CXCR4-expressing stromal cells to develop a permissive metastatic microenvironment. Finally, the migration of Caco-2 cells was significantly increased following treatment with HT-29-derived exosomes in vitro, further supporting a role for exosomes in modulating colorectal tumor-derived liver metastasis. The data from the present study may facilitate further translational medicine research into the prevention and treatment of colorectal cancer liver metastasis.

  11. The Host Microenvironment Influences Prostate Cancer Invasion, Systemic Spread, Bone Colonization, and Osteoblastic Metastasis

    PubMed Central

    Ganguly, Sourik S.; Li, Xiaohong; Miranti, Cindy K.

    2014-01-01

    Prostate cancer (PCa) is the second leading cause of cancer death in men worldwide. Most PCa deaths are due to osteoblastic bone metastases. What triggers PCa metastasis to the bone and what causes osteoblastic lesions remain unanswered. A major contributor to PCa metastasis is the host microenvironment. Here, we address how the primary tumor microenvironment influences PCa metastasis via integrins, extracellular proteases, and transient epithelia-mesenchymal transition (EMT) to promote PCa progression, invasion, and metastasis. We discuss how the bone-microenvironment influences metastasis; where chemotactic cytokines favor bone homing, adhesion molecules promote colonization, and bone-derived signals induce osteoblastic lesions. Animal models that fully recapitulate human PCa progression from primary tumor to bone metastasis are needed to understand the PCa pathophysiology that leads to bone metastasis. Better delineation of the specific processes involved in PCa bone metastasize is needed to prevent or treat metastatic PCa. Therapeutic regimens that focus on the tumor microenvironment could add to the PCa pharmacopeia. PMID:25566502

  12. Adrenal Metastasis from Uterine Papillary Serous Carcinoma

    PubMed Central

    Lubana, Sandeep Singh; Singh, Navdeep; Tuli, Sandeep S.; Seligman, Barbara

    2016-01-01

    Patient: Female, 60 Final Diagnosis: UPSC with adrenal metastasis Symptoms: Post menopausal bleeding Medication: — Clinical Procedure: Adrenalectomy Specialty: Oncology Objective: Rare disease Background: Uterine papillary serous carcinoma (UPSC) is a highly malignant form of endometrial cancer with a high propensity for metastases and recurrences even when there is minimal or no myometrial invasion. It usually metastasizes to the pelvis, retroperitoneal lymph nodes, upper abdomen, and peritoneum. However, adrenal metastases from UPSC is extremely rare. Here, we present a case of UPSC with adrenal metastasis that occurred 6 years after the initial diagnosis. Case Report: A 60-year-old woman previously diagnosed with uterine papillary serous carcinoma at an outside facility presented in September of 2006 with postmenopausal bleeding. She underwent comprehensive surgical staging with FIGO (International Federation of Gynecology and Obstetrics) stage 2. Post-operatively, the patient was treated with radiation and chemotherapy. The treatment was completed in April of 2007. The patient had no evidence of disease until July 2009 when she was found to have a mass highly suspicious for malignancy. Subsequently, she underwent right upper lobectomy. The morphology of the carcinoma was consistent with UPSC. She refused chemotherapy due to a previous history of chemotherapy-induced neuropathy. The patient was followed up with regular computed tomography (CT) scans. In October 2012 a new right adrenal nodule was seen on CT, which showed intense metabolic uptake on positron emission tomography (PET)/CT scan. The patient underwent right adrenalectomy. Pathology of the surgical specimen was consistent with UPSC. Conclusions: UPSC is an aggressive variant of endometrial cancer associated with high recurrence rate and poor prognoses. Long-term follow-up is needed because there is a possibility of late metastases, as in this case. PMID:27117594

  13. Diagnosis of leptomeningeal disease in diffuse large B-cell lymphomas of the central nervous system by flow cytometry and cytopathology.

    PubMed

    Schroers, Roland; Baraniskin, Alexander; Heute, Christoph; Vorgerd, Matthias; Brunn, Anna; Kuhnhenn, Jan; Kowoll, Annika; Alekseyev, Andriy; Schmiegel, Wolff; Schlegel, Uwe; Deckert, Martina; Pels, Hendrik

    2010-12-01

    Reliable detection of leptomeningeal disease has the potential of facilitating the diagnosis of central nervous system (CNS) lymphoma and is important for therapeutic considerations. Currently, the standard diagnostic procedure for the detection of lymphoma in the cerebrospinal fluid is cytopathology. To improve the limited specificity and sensitivity of cytopathology, flow cytometry has been suggested as an alternative. Here, we evaluated multi-parameter flow cytometry in combination with conventional cytopathology in cerebrospinal fluid (CSF) samples from 30 patients with primary CNS lymphoma and seven patients with secondary CNS lymphoma. Overall, in 11 of 37 (29.7%) patients with CNS lymphoma, lymphoma cells were detected in CSF by flow cytometry, while cytopathology was less sensitive displaying unequivocally malignant CSF cells in only seven of all 37 (18.9%) patients. Six (16.2%) patients showed cytopathological results suspicious of lymphoma; however, in only one of these patients, the diagnosis of CSF lymphoma cells could be confirmed by flow cytometry. In primary CNS lymphomas (PCNSL), seven of 30 (23.3%) patients were positive for CSF lymphoma cells in flow cytometry, in contrast to four (13.3%) patients with PCNSL with definitely positive cytopathology. In summary, our results suggest that multi-parameter flow cytometry increases the sensitivity and specificity of leptomeningeal disease detection in CNS lymphomas. Both methods should be applied concurrently for complementary diagnostic assessment in patients with CNS lymphoma. © 2010 John Wiley & Sons A/S.

  14. The leptomeningeal "ivy sign" on fluid-attenuated inversion recovery MR imaging in Moyamoya disease: a sign of decreased cerebral vascular reserve?

    PubMed

    Mori, N; Mugikura, S; Higano, S; Kaneta, T; Fujimura, M; Umetsu, A; Murata, T; Takahashi, S

    2009-05-01

    Moyamoya disease is an idiopathic occlusive cerebrovascular disorder with abnormal microvascular proliferation. We investigated the clinical utility of leptomeningeal high signal intensity (ivy sign) sometimes seen on fluid-attenuated inversion recovery images in Moyamoya disease. We examined the relationship between the degree of the ivy sign and the severity of the ischemic symptoms in 96 hemispheres of 48 patients with Moyamoya disease. We classified each cerebral hemisphere into 4 regions from anterior to posterior. In 192 regions of 24 patients, we examined the relationship between the degree of the ivy sign and findings of single-photon emission CT, including the resting cerebral blood flow (CBF) and cerebral vascular reserve (CVR). The degree of the ivy sign showed a significant positive relationship with the severity of the ischemic symptoms (P < .001). Of the 4 regions, the ivy sign was most frequently and prominently seen in the anterior part of the middle cerebral artery region. The degree of the ivy sign showed a negative relationship with the resting CBF (P < .0034) and a more prominent negative relationship with the CVR (P < .001). The leptomeningeal ivy sign indicates decreased CVR in Moyamoya disease.

  15. Development and external validation of nomograms to predict the risk of skeletal metastasis at the time of diagnosis and skeletal metastasis-free survival in nasopharyngeal carcinoma.

    PubMed

    Yang, Lin; Xia, Liangping; Wang, Yan; He, Shasha; Chen, Haiyang; Liang, Shaobo; Peng, Peijian; Hong, Shaodong; Chen, Yong

    2017-09-06

    The skeletal system is the most common site of distant metastasis in nasopharyngeal carcinoma (NPC); various prognostic factors have been reported for skeletal metastasis, though most studies have focused on a single factor. We aimed to establish nomograms to effectively predict skeletal metastasis at initial diagnosis (SMAD) and skeletal metastasis-free survival (SMFS) in NPC. A total of 2685 patients with NPC who received bone scintigraphy (BS) and/or 18F-deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and 2496 patients without skeletal metastasis were retrospectively assessed to develop individual nomograms for SMAD and SMFS. The models were validated externally using separate cohorts of 1329 and 1231 patients treated at two other institutions. Five independent prognostic factors were included in each nomogram. The SMAD nomogram had a significantly higher c-index than the TNM staging system (training cohort, P = 0.005; validation cohort, P < 0.001). The SMFS nomogram had significantly higher c-index values in the training and validation sets than the TNM staging system (P < 0.001 and P = 0.005, respectively). Three proposed risk stratification groups were created using the nomograms, and enabled significant discrimination of SMFS for each risk group. The prognostic nomograms established in this study enable accurate stratification of distinct risk groups for skeletal metastasis, which may improve counseling and facilitate individualized management of patients with NPC.

  16. Acridine orange inhibits pulmonary metastasis of mouse osteosarcoma.

    PubMed

    Satonaka, Haruhiko; Kusuzaki, Katsuyuki; Akeda, Koji; Tsujii, Masaya; Iino, Takahiro; Uemura, Takeshi; Matsubara, Takao; Nakamura, Tomoki; Asanuma, Kunihiro; Matsumine, Akihiko; Sudo, Akihiro

    2011-12-01

    Although the survival of patients with osteosarcoma has improved following development of chemotherapy and surgery, the presence of pulmonary metastases indicate a poor prognosis. We developed photodynamic and radiodynamic therapies with acridine orange (AO-PDT and AO-RDT) for minimally invasive surgery to treat musculoskeletal sarcomas and reported a good clinical outcome of local control and limb function. We investigated the effect of AO-PDT using flash-wave light (FWL) on pulmonary metastasis of mouse osteosarcoma. In in vitro and in vivo studies, AO alone and AO-PDT significantly inhibited cell invasion and the growth of pulmonary metastases from primary mouse osteosarcoma. AO may have a specific metastasis-inhibitory effect, different from the effect of AO-PDT. The fluorovisualization effect on pulmonary metastases following intravenous AO administration showed that pulmonary metastases localized on the lung surface were recognized as brilliant green lesions. In conclusion, AO-PDT using FWL inhibited cell invasion and pulmonary metastases in mouse osteosarcoma; therefore, this treatment modality might be applicable for treating pulmonary metastasis from malignant musculoskeletal tumors in humans.

  17. Atrial natriuretic peptide prevents cancer metastasis through vascular endothelial cells.

    PubMed

    Nojiri, Takashi; Hosoda, Hiroshi; Tokudome, Takeshi; Miura, Koichi; Ishikane, Shin; Otani, Kentaro; Kishimoto, Ichiro; Shintani, Yasushi; Inoue, Masayoshi; Kimura, Toru; Sawabata, Noriyoshi; Minami, Masato; Nakagiri, Tomoyuki; Funaki, Soichiro; Takeuchi, Yukiyasu; Maeda, Hajime; Kidoya, Hiroyasu; Kiyonari, Hiroshi; Shioi, Go; Arai, Yuji; Hasegawa, Takeshi; Takakura, Nobuyuki; Hori, Megumi; Ohno, Yuko; Miyazato, Mikiya; Mochizuki, Naoki; Okumura, Meinoshin; Kangawa, Kenji

    2015-03-31

    Most patients suffering from cancer die of metastatic disease. Surgical removal of solid tumors is performed as an initial attempt to cure patients; however, surgery is often accompanied with trauma, which can promote early recurrence by provoking detachment of tumor cells into the blood stream or inducing systemic inflammation or both. We have previously reported that administration of atrial natriuretic peptide (ANP) during the perioperative period reduces inflammatory response and has a prophylactic effect on postoperative cardiopulmonary complications in lung cancer surgery. Here we demonstrate that cancer recurrence after curative surgery was significantly lower in ANP-treated patients than in control patients (surgery alone). ANP is known to bind specifically to NPR1 [also called guanylyl cyclase-A (GC-A) receptor]. In mouse models, we found that metastasis of GC-A-nonexpressing tumor cells (i.e., B16 mouse melanoma cells) to the lung was increased in vascular endothelium-specific GC-A knockout mice and decreased in vascular endothelium-specific GC-A transgenic mice compared with control mice. We examined the effect of ANP on tumor metastasis in mice treated with lipopolysaccharide, which mimics systemic inflammation induced by surgical stress. ANP inhibited the adhesion of cancer cells to pulmonary arterial and micro-vascular endothelial cells by suppressing the E-selectin expression that is promoted by inflammation. These results suggest that ANP prevents cancer metastasis by inhibiting the adhesion of tumor cells to inflamed endothelial cells.

  18. Atrial natriuretic peptide prevents cancer metastasis through vascular endothelial cells

    PubMed Central

    Nojiri, Takashi; Hosoda, Hiroshi; Tokudome, Takeshi; Miura, Koichi; Ishikane, Shin; Otani, Kentaro; Kishimoto, Ichiro; Shintani, Yasushi; Inoue, Masayoshi; Kimura, Toru; Sawabata, Noriyoshi; Minami, Masato; Nakagiri, Tomoyuki; Funaki, Soichiro; Takeuchi, Yukiyasu; Maeda, Hajime; Kidoya, Hiroyasu; Kiyonari, Hiroshi; Shioi, Go; Arai, Yuji; Hasegawa, Takeshi; Takakura, Nobuyuki; Hori, Megumi; Ohno, Yuko; Miyazato, Mikiya; Mochizuki, Naoki; Okumura, Meinoshin; Kangawa, Kenji

    2015-01-01

    Most patients suffering from cancer die of metastatic disease. Surgical removal of solid tumors is performed as an initial attempt to cure patients; however, surgery is often accompanied with trauma, which can promote early recurrence by provoking detachment of tumor cells into the blood stream or inducing systemic inflammation or both. We have previously reported that administration of atrial natriuretic peptide (ANP) during the perioperative period reduces inflammatory response and has a prophylactic effect on postoperative cardiopulmonary complications in lung cancer surgery. Here we demonstrate that cancer recurrence after curative surgery was significantly lower in ANP-treated patients than in control patients (surgery alone). ANP is known to bind specifically to NPR1 [also called guanylyl cyclase-A (GC-A) receptor]. In mouse models, we found that metastasis of GC-A–nonexpressing tumor cells (i.e., B16 mouse melanoma cells) to the lung was increased in vascular endothelium-specific GC-A knockout mice and decreased in vascular endothelium-specific GC-A transgenic mice compared with control mice. We examined the effect of ANP on tumor metastasis in mice treated with lipopolysaccharide, which mimics systemic inflammation induced by surgical stress. ANP inhibited the adhesion of cancer cells to pulmonary arterial and micro-vascular endothelial cells by suppressing the E-selectin expression that is promoted by inflammation. These results suggest that ANP prevents cancer metastasis by inhibiting the adhesion of tumor cells to inflamed endothelial cells. PMID:25775533

  19. Incidence of brain metastasis from esophageal cancer.

    PubMed

    Welch, G; Ross, H J; Patel, N P; Jaroszewski, D E; Fleischer, D E; Rule, W G; Paripati, H R; Ramirez, F C; Ashman, J B

    2017-09-01

    We investigated whether the incidence of brain metastasis (BM) from primary esophageal and esophagogastric cancer is increasing. A single-institution retrospective review identified 583 patients treated from January 1997 to January 2016 for stages I through IV cancer of the esophagus and esophagogastric junction (follow-up, ≥3 months). Collected data included demographic information, date and staging at primary diagnosis, histologic subtype, treatment regimen for primary lesion, date of BM diagnosis, presence or absence of central nervous system symptoms, presence or absence of extracranial disease, treatment regimen for intracranial lesions, and date of death. The overall cohort included 495 patients (85%) with adenocarcinoma and 82 (14%) with squamous cell carcinoma (492 [84%] were male; median age at diagnosis, 68 years [range: 26-90 years]). BM was identified in 22 patients (3.8%) (median latency after primary diagnosis, 11 months). Among patients with BM, the primary histology was adenocarcinoma in 21 and squamous cell carcinoma in 1 (P = 0.30). BM developed in 12 who were initially treated for locally advanced disease and in 10 stage IV patients who presented with distant metastases. Overall survival (OS) after BM diagnosis was 18% at 1 year (median, 4 months). No difference in OS after BM diagnosis was observed in patients initially treated for localized disease compared to patients who presented with stage IV disease; however, OS was superior for patients who initially had surgical resection compared to patients treated with whole brain radiotherapy or stereotactic radiosurgery alone (1-year OS, 67% vs. 0%; median OS, 13.5 vs. 3 months; P = 0.003). The incidence of BM is low in patients with esophageal cancer. Outcomes were poor overall for patients with BM, but patients who underwent neurosurgical resection had improved survival. © The Authors 2017. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus

  20. Mucinous breast cancer with solitary metastasis to humeral head: a case report.

    PubMed

    Aljarrah, Adil; Al-Hashmi, Maryam; Malik, Kamran Ahmad; Sukhpal, Sawhney; Hussein, Samir; Al-Riyami, Marwa; Al-Moundhri, Mansour

    2013-09-01

    Breast cancer is the most common cause of metastatic deposits in the skeleton, and bone is the most common site of recurrence of breast cancer. Breast cancer metastasis most commonly affects the spine, ribs, pelvis, and proximal long bones; however, only 3.5% of breast cancer patients develop long-bone metastases. The humerus is the most common upper-extremity site for bony metastasis, and pathologic fractures can result. The patient in the current study presented with breast cancer and discovered to have humeral head metastasis during initial workup. The dilemma was in investigation the modality to confirm humeral head metastasis as there are many differential diagnoses with similar findings. After staging workup, the patient was treated with neoadjuvant chemotherapy followed by modified radical mastectomy and radiotherapy of the chest wall and the shoulder. The lesion in humerus was well healed.

  1. Metastasis of osteosarcoma to stomach made clinically evident by hematemesis: a case report

    PubMed Central

    2013-01-01

    Background Gastric metastasis from osteosarcoma is very rare and its clinical features are not well recognized. Case presentation A 73-year-old man was diagnosed with osteosarcoma and treated with four cycles of preoperative chemotherapy with ifosfamide and doxorubicin followed by wide resection. Two cycles of postoperative chemotherapy with ifosfamide and doxorubicin and ten cycles of chemotherapy with carboplatin and etoposide were administered. Eleven months after the surgery, he vomited fresh blood. Unusual progression of anemia was observed with the hematemesis. A biopsy was performed by gastrointestinal endoscopy, and the stomach tumor was diagnosed as metastasis of osteosarcoma. Conclusions Even though gastric metastasis from osteosarcoma is very rare, all three previous reports and our case showed the presence of ulcer on the surface of the gastric lesion. We should consider the possibility of gastric metastasis in patients with osteosarcoma in whom progression of anemia or gastric hemorrhage is observed. PMID:23442337

  2. Unusual late extrapulmonary metastasis in osteosarcoma.

    PubMed

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

    1999-01-01

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

  3. Heart failure resulting from giant left atrial synovial sarcoma metastasis.

    PubMed

    Winkler, B; Grapow, M; Seeberger, M; Matt, P; Aulitzky, W; Eckstein, F

    2012-02-01

    Synovial sarcoma metastasis affecting the heart and infiltrating the mitral valve is a very rare pathology. We report the case of a 44-year-old male treated with chemotherapy for atypical synovial sarcoma of the oral mucosa who presented to our clinic after cardiac decompensation with a presumptive diagnosis of myxoma of the left atrium. A large necrotic tumour positive for CK 22, EMA, CD 99 and BCL-2 but negative for translocation in COBRA-FISH analysis by break-apart probe could be excised and revealed a very rare subtype of synovial sarcoma metastasis arising from the endocard of the left atrium. The tumour was resected and the mitral valve reconstructed through ring annuloplasty. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  4. Patterns of lymph node metastasis of parotid cancer.

    PubMed

    Shinomiya, Hitomi; Otsuki, Naoki; Yamashita, Daisuke; Nibu, Ken-Ichi

    2016-08-01

    To define the incidence and pattern of spread of lymph node metastasis from parotid cancers and to clarify the risk factors and appropriate extent of neck dissection (ND) for individual patient with parotid cancer. A total of 72 patients with parotid gland cancer treated by surgery between 1994 and 2013 were analyzed retrospectively by reference to medical records. In line with our protocol, patients with clinically positive lymph nodes and/or cT3/T4 disease were generally selected to undergo ND. Pathological examinations revealed mucoepidermoid carcinoma in 23 patients, carcinoma ex pleomorphic adenoma in 11, adenoid cystic carcinoma in 9, salivary duct carcinoma in 9, acinic cell carcinoma in 8, squamous cell carcinoma in 5, adenocarcinoma NOS in 4, epithelial myoepithelial carcinoma in 2, and basal cell carcinoma in 1. Thirty-three patients underwent neck dissection: modified radical ND (MRND) in 13, and elective ND (END) in 20. Postoperative RT (PORT) was performed in 33 patients. Among 13 cN+ patients, 10 were pN+ and lymph node metastasis was distributed mainly in levels I, II, III and V. Among 59 cN- patients, clinical T1, T2, T3 and T4 classifications accounted for 10, 24, 10 and 15 patients, respectively. The incidence of occult lymph node metastasis was 22%. Occult lymph node metastasis was mostly seen in the intraparotid, levels I and II of patients with cT4 disease. Among the ND group, 12 necks were pathologically negative for cancer (pN0). Relapse of neck lymph node metastasis occurred only in two patients treated by MRND with pathologically positive lymph nodes (pN+). These patients developed local and distant metastasis within 1 year after neck lymph node recurrence, and subsequently died of the cancer. pN+ was found in 19/30 high grade (63%), 1/10 intermediate grade (10%), and 3/32 low grade (9.4%). Among 33 patients who received PORT, only 1 patient relapsed neck lymph node. For patients with clinically positive lymph nodes, ipsilateral modified

  5. The leptomeningeal ivy sign on fluid-attenuated inversion recovery images in moyamoya disease: positron emission tomography study.

    PubMed

    Kaku, Yasuyuki; Iihara, Koji; Nakajima, Norio; Kataoka, Hiroharu; Fukushima, Kazuhito; Iida, Hidehiro; Hashimoto, Nobuo

    2013-01-01

    score and decreases in CBF/CBV (p < 0.001). We evaluated the correlation between ivy sign proliferation and the findings of 15O gas PET. We suggested that ivy sign proliferation was associated with both dilated pial vasculature and the slow flow of developed leptomeningeal collaterals in patients with MMD. Copyright © 2013 S. Karger AG, Basel.

  6. The Level of Squamous Cell Carcinoma Antigen and Lymph Node Metastasis in Locally Advanced Cervical Cancer.

    PubMed

    Lekskul, Navamol; Charakorn, Chuenkamon; Lertkhachonsuk, Arb-Aroon; Rattanasiri, Sasivimol; Israngura Na Ayudhya, Nathpong

    2015-01-01

    This study aimed to determine the utility and a cut-off level of serum squamous cell carcinoma antigen (SCC-Ag) to predict lymph node metastasis in locally advanced cervical cancer cases. We also investigated the correlation between SCC-Ag level and lymph node status. From June 2009 to June 2014, 232 patients with cervical cancer stage IB2-IVA, who were treated at Ramathibodi Hospital, were recruited. Receiver operating characteristic (ROC) curves were used to identify the best cut-off point of SCC-Ag level to predict lymph node metastasis. Quantile regression was performed to evaluate the correlation between SCC-Ag levels and pelvic lymph node metastasis, paraaortic lymph node metastasis, and parametrial involvement as well as tumor size. Pelvic lymph node metastasis and paraaortic lymph node metastasis were diagnosed in 46.6% and 20.1% of the patients, respectively. The median SCC-Ag level was 6 ng/mL (range, 0.5 to 464.6 ng/ mL). The areas under ROC curves between SCC-Ag level and pelvic lymph node metastasis, paraaotic lymph node metastasis, parametrial involvements were low. SCC-Ag level was significantly correlated with paraaortic lymph node status (p=0.045) but not with pelvic lymph node status and parametrial involvement. SCC-Ag level was also related to the tumor diameter (p<0.05). SCC-Ag level is not a good predictor for pelvic and paraaortic lymph node metastasis. However, it is still beneficial to assess the tumor burden of squamous cell carcinoma of the cervix.

  7. 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

    SciTech Connect

    Hashimoto, Kenji; Narita, Yoshitaka; Miyakita, Yasuji; Ohno, Makoto; Sumi, Minako; Mayahara, Hiroshi; Kayama, Takamasa; Shibui, Soichiro

    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.

  8. Zosteriform skin metastasis of lung cancer.

    PubMed

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

    2012-12-01

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

  9. Roles of Fyn in pancreatic cancer metastasis.

    PubMed

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

    2010-02-01

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

  10. Endocannabinoids as Guardians of Metastasis

    PubMed Central

    Tegeder, Irmgard

    2016-01-01

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

  11. A review of penile metastasis

    PubMed Central

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

    2012-01-01

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

  12. Immune cell promotion of metastasis

    PubMed Central

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

    2015-01-01

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

  13. Ovarian Cancer Development and Metastasis

    PubMed Central

    Lengyel, Ernst

    2010-01-01

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

  14. Intramedullary spinal metastasis of a carcinoid tumor.

    PubMed

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

    2015-12-01

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

  15. Heparanase Mechanisms in Melanoma Brain Metastasis

    DTIC Science & Technology

    2014-08-01

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

  16. Thyroid Mass: Metastasis from Nasopharyngeal Cancer - An Unusual Presentation

    PubMed Central

    Lewis, Shirley C; D'cruz, Anil K; Joshi, Amit; Kumar, Rajiv; Kane, Shubhada V; Laskar, Sarbani Ghosh

    2017-01-01

    Thyroid gland is an uncommon site of metastasis, and metastasis to the gland secondary to nasopharyngeal carcinoma is seldom seen. We were only able to identify eight reported cases in the literature. A 61-year-old man, diagnosed case of nasopharyngeal cancer–second primary ( first primary-oropharynx), was found to have a thyroid nodule on routine follow-up positron emission tomography-computed tomography (PET-CT) scan. There was no evidence of metastases at any other sites. The thyroid nodule was confirmed as metastatic carcinoma by fine needle aspiration cytology. He was treated with multimodal treatment comprising of surgery followed by reirradiation with concurrent chemotherapy. Subsequently, at the first follow-up (2 months after completion of all treatment), the patient remained asymptomatic, but the response assessment with PET-CT scan was suggestive of lung metastases with no evidence of locoregional disease. Although thyroid parenchymal metastasis is an uncommon occurrence and signifies a poor prognosis, in appropriately selected patients, aggressive therapy with reirradiation and chemotherapy may improve local control and quality of life. PMID:28216872

  17. Physician preferences for bone metastasis drug therapy in Canada

    PubMed Central

    Arellano, J.; González, J.M.; Qian, Y.; Habib, M.; Mohamed, A.F.; Gatta, F.; Hauber, A.B.; Posner, J.; Califaretti, N.; Chow, E.

    2015-01-01

    Background Currently in Canada, several bone-targeted agents (btas) with varying characteristics are available for the prevention of skeletal-related events (sres) in patients with bone metastasis secondary to solid tumours. In the present study, we evaluated the preferences of physicians in Canada for the various attributes of the available btas. Methods Physicians treating patients with bone metastasis from solid tumours were invited to complete an online discrete-choice experiment. Respondents were asked to choose between pairs of hypothetical medications for virtual patients. Each hypothetical medication was described based on predefined key attributes: time until first sre, time until worsening of pain, medication-related annual risk of osteonecrosis of the jaw (onj), medication-related annual risk of renal impairment, and mode of administration. A random-parameters logit model was used to analyze the choices between hypothetical medications and thus infer physician preferences for medication attributes. Results Responses from the 200 physicians who completed the discrete-choice experiment suggested that months until first sre, risk of renal impairment, and months until worsening of pain were considered the most important attributes affecting choice of bta. The annual risk of onj was considered the least important attribute. Conclusions When making treatment decisions about the choice of bta for patients with bone metastasis from solid tumours, delaying sres and worsening of pain, and reducing the risk of renal impairment are primary considerations for physicians in Canada. PMID:26628874

  18. EGFR and HER2 signaling in breast cancer brain metastasis

    PubMed Central

    Sirkisoon, Sherona R.; Carpenter, Richard L.; Rimkus, Tadas; Miller, Lance; Metheny-Barlow, Linda; Lo, Hui-Wen

    2016-01-01

    Breast cancer occurs in approximately 1 in 8 women and 1 in 37 women with breast cancer succumbed to the disease. Over the past decades, new diagnostic tools and treatments have substantially improved the prognosis of women with local diseases. However, women with metastatic disease still have a dismal prognosis without effective treatments. Among different molecular subtypes of breast cancer, the HER2-enriched and basal-like subtypes typically have higher rates of metastasis to the brain. Basal-like metastatic breast tumors frequently express EGFR. Consequently, HER2- and EGFR-targeted therapies are being used in the clinic and/or evaluated in clinical trials for treating breast cancer patients with brain metastases. In this review, we will first provide an overview of the HER2 and EGFR signaling pathways. The roles that EGFR and HER2 play in breast cancer metastasis to the brain will then be discussed. Finally, we will summarize the preclinical and clinical effects of EGFR- and HER2-targeted therapies on breast cancer metastasis. PMID:26709660

  19. Novel chemokine-like activities of histones in tumor metastasis

    PubMed Central

    Chen, Ruochan; Xie, Yangchun; Zhong, Xiao; Fu, Yongmin; Huang, Yan; Zhen, Yixiang; Pan, Pinhua; Wang, Haichao; Bartlett, David L.; Billiar, Timothy R.; Lotze, Michael T.; Zeh, Herbert J.; Fan, Xue-Gong; Tang, Daolin; Kang, Rui

    2016-01-01

    Histones are intracellular nucleosomal components and extracellular damage-associated molecular pattern molecules that modulate chromatin remodeling, as well as the immune response. However, their extracellular roles in cell migration and invasion remain undefined. Here, we demonstrate that histones are novel regulators of tumor metastasis with chemokine-like activities. Indeed, exogenous histones promote both hepatocellular carcinoma (HCC) cell migration and invasion through toll-like receptor (TLR)4, but not TLR2 or the receptor for advanced glycosylation end product. TLR4-mediated activation of nuclear factor-κB (NF-κB) by extracellular signal-regulated kinase (ERK) is required for histone-induced chemokine (e.g., C-C motif ligand 9/10) production. Pharmacological and genetic inhibition of TLR4-ERK-NF-κB signaling impairs histone-induced chemokine production and HCC cell migration. Additionally, TLR4 depletion (by using TLR4−/− mice and TLR4-shRNA) or inhibition of histone release/activity (by administration of heparin and H3 neutralizing antibody) attenuates lung metastasis of HCC cells injected via the tail vein of mice. Thus, histones promote tumor metastasis of HCC cells through the TLR4-NF-κB pathway and represent novel targets for treating patients with HCC. PMID:27623211

  20. Tumor satellite in predicting occult nodal metastasis of tongue cancer.

    PubMed

    Yang, Tsung-Lin; Lou, Pei-Jen; Chang, Yih-Leong; Wu, Chen-Tu; Wang, Cheng-Ping; Ko, Jenq-Yuh

    2011-10-01

    Tongue cancer is well known to have a high potential for locoregional metastasis. However, controversy about electively treating the neck in early-stage tongue cancer remains. Although many risk factors related to cervical occult nodal metastasis (ONM) have been investigated, the ability of the tumor to spread, a phenomenon that results from the intrinsic property of the tumor and its interaction with the surrounding environment, has seldom been addressed. Retrospective case series with chart review. Tertiary referral hospital of university. Patients with early-stage squamous cell carcinoma of the oral tongue. In 71 eligible enrolled patients, ONM was detected in 19 (27%) patients, while the results were negative (ONM(-)) in 52 (73%) patients. The average tumor satellite distance (TSD) in the ONM(+) group was 4.1 ± 4.3 mm, in contrast to that in the ONM(-) group (1.0 ± 1.5 mm; P < .001). When stratified by increased TSD values, the significance of the difference between the 2 groups increased. For clinical applications, the optimal TSD threshold for determining the ONM probability was 3.5 mm. Multivariate analyses demonstrated that TSD was an independent prognosticator. The results indicate that TSD is a feasible pathological parameter that is useful for determining the status of cervical nodal metastasis. It can be used as an indicator of potential cervical subclinical disease and as a guideline for deciding the necessity and modality of neck treatment.

  1. Suppression of breast cancer metastasis through the inactivation of ADP-ribosylation factor 1

    PubMed Central

    Xie, Xiayang; Tang, Shou-Ching; Cai, Yafei; Pi, Wenhu; Deng, Libin; Wu, Guangyu; Chavanieu, Alain; Teng, Yong

    2016-01-01

    Metastasis is the major cause of cancer-related death in breast cancer patients, which is controlled by specific sets of genes. Targeting these genes may provide a means to delay cancer progression and allow local treatment to be more effective. We report for the first time that ADP-ribosylation factor 1 (ARF1) is the most amplified gene in ARF gene family in breast cancer, and high-level amplification of ARF1 is associated with increased mRNA expression and poor outcomes of patients with breast cancer. Knockdown of ARF1 leads to significant suppression of migration and invasion in breast cancer cells. Using the orthotopic xenograft model in NSG mice, we demonstrate that loss of ARF1 expression in breast cancer cells inhibits pulmonary metastasis. The zebrafish-metastasis model confirms that the ARF1 gene depletion suppresses breast cancer cells to metastatic disseminate throughout fish body, indicating that ARF1 is a very compelling target to limit metastasis. ARF1 function largely dependents on its activation and LM11, a cell-active inhibitor that specifically inhibits ARF1 activation through targeting the ARF1-GDP/ARNO complex at the Golgi, significantly impairs metastatic capability of breast cancer cell in zebrafish. These findings underline the importance of ARF1 in promoting metastasis and suggest that LM11 that inhibits ARF1 activation may represent a potential therapeutic approach to prevent or treat breast cancer metastasis. PMID:27517156

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

    PubMed

    Meng, X Y; Song, S T

    2017-03-23

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

  3. The effect of midline crossing of lateral supraglottic cancer on contralateral cervical lymph node metastasis.

    PubMed

    Yılmaz, Taner; Süslü, Nilda; Atay, Gamze; Günaydın, Rıza Önder; Bajin, Münir Demir; Özer, Serdar

    2015-05-01

    The degree of midline crossing of lateral supraglottic cancer does not significantly change its rate of contralateral cervical metastasis. The rate of occult metastasis is too high to take the risk of contralateral regional recurrence. We support routine bilateral neck dissection even in lateral supraglottic cancers with no or minimal midline crossing. Data on the rate of contralateral cervical metastasis of laterally located supraglottic cancer, the effect of its degree of midline crossing on contralateral cervical metastasis, and its treatment are still controversial. This was a retrospective cohort, chart review involving 305 surgically treated patients with T1-3 squamous cell carcinoma of the supraglottic larynx. In all, 184 patients had bilateral neck dissection; 86 N0 contralateral necks were followed up. Thirty-five patients who needed postoperative radiation therapy because of the primary tumor or ipsilateral neck dissection specimen also received radiation therapy to the contralateral neck. The degree of midline crossing at the epiglottis was measured on a laryngectomy specimen with a ruler and expressed as 'no,' '<5 mm' or '≥5 mm.' The rates of occult and overall contralateral metastasis in our series were 16% and 28%, respectively. There was no statistically significant difference between contralateral neck metastasis and recurrence rates in the neck dissection, follow-up, and irradiation groups according to the degree of midline crossing.

  4. Transcutaneous carbon dioxide induces mitochondrial apoptosis and suppresses metastasis of oral squamous cell carcinoma in vivo.

    PubMed

    Takeda, Daisuke; Hasegawa, Takumi; Ueha, Takeshi; Imai, Yusuke; Sakakibara, Akiko; Minoda, Masaya; Kawamoto, Teruya; Minamikawa, Tsutomu; Shibuya, Yasuyuki; Akisue, Toshihiro; Sakai, Yoshitada; Kurosaka, Masahiro; Komori, Takahide

    2014-01-01

    Squamous cell carcinoma (SCC) is the main histological type of oral cancer. Its growth rate and incidence of metastasis to regional lymph nodes is influenced by various factors, including hypoxic conditions. We have previously reported that transcutaneous CO2 induces mitochondrial apoptosis and decreases lung metastasis by reoxygenating sarcoma cells. However, previous studies have not determined the sequential mechanism by which transcutaneous CO2 suppresses growth of epithelial tumors, including SCCs. Moreover, there is no report that transcutaneous CO2 suppresses lymphogenous metastasis using human cell lines xenografts. In this study, we examined the effects of transcutaneous CO2 on cancer apoptosis and lymphogenous metastasis using human SCC xenografts. Our results showed that transcutaneous CO2 affects expressions of PGC-1α and TFAM and protein levels of cleavage products of caspase-3, caspase-9 and PARP, which relatives mitochondrial apoptosis. They also showed that transcutaneous CO2 significantly inhibits SCC tumor growth and affects expressions of HIF-1α, VEGF, MMP-2 and MMP-9, which play essential roles in tumor angiogenesis, invasion and metastasis. In conclusion, transcutaneous CO2 suppressed tumor growth, increased mitochondrial apoptosis and decreased the number of lymph node metastasis in human SCC by decreasing intra-tumoral hypoxia and suppressing metastatic potential with no observable effect in vivo. Our findings indicate that transcutaneous CO2 could be a novel therapeutic tool for treating human SCC.

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

    PubMed

    Shoji, Sunao; Tang, Xian Yang; Sato, Haruhiro; Usui, Yukio; Uchida, Toyoaki; Terachi, Toshiro

    2010-09-01

    Cancer metastasis is a leading cause of death in cancer patients and is a multistep process involving complex interactions between tumor and host cells. To metastasize, tumor cells must invade or migrate from the primary tumor and be transported to close or distant secondary sites. A tumor cell should successfully accomplish each step of the pathway or metastasis may not develop. KiSS-1 is a human metastasis suppressor gene that inhibits metastasis of human melanomas and breast carcinomas without affecting tumorigenicity. KiSS-1 encodes a carboxy-terminally amidated peptide with 54 amino-acid residues. The peptide was isolated from human placenta as the endogenous ligand of an orphan G-protein-coupled receptor and termed 'metastin'. The literature reports metastin related to human carcinoma, such as melanoma, thyroid cancer, esophageal squamous cell carcinoma (ESCC), hepatocellular carcinoma, pancreatic carcinoma, as well as breast, ovarian, bladder and kidney cancer. These malignancies are difficult to treat and, even in early-stage cancer, a number of patients develop metastasis shortly after surgery. Studies have suggested that metastin inhibits tumor invasion or migration through focal adhesion kinase, paxillin, MAP kinase or Rho A. Additionally, metastin may be a biomarker in ESCC, pancreatic carcinoma and bladder cancer. Metastin has potential as a suitable biomarker in the identification of tumors with high metastatic potential and as a novel effective treatment modality for patients with metastasis.

  6. Lymph node metastasis in t4 maxillary sinus squamous cell carcinoma: incidence and treatment outcome.

    PubMed

    Homma, Akihiro; Hayashi, Ryuichi; Matsuura, Kazuto; Kato, Kengo; Kawabata, Kazuyoshi; Monden, Nobuya; Hasegawa, Yasuhisa; Onitsuka, Tetsuro; Fujimoto, Yasushi; Iwae, Shigemichi; Okami, Kenji; Matsuzuka, Takashi; Yoshino, Kunitoshi; Nibu, Ken-Ichi; Kato, Takakuni; Nishino, Hiroshi; Asakage, Takahiro; Ota, Ichiro; Kitamura, Morimasa; Kubota, Akira; Ueda, Tsutomu; Ikebuchi, Kaichiro; Watanabe, Akihito; Fujii, Masato

    2014-05-01

    The purpose of this study was to evaluate the incidence of lymph node metastasis among patients with T4 maxillary sinus squamous cell carcinoma (MS-SCC) as well as the delayed metastasis rate and the treatment outcome for untreated N0 neck in patients with T4 MS-SCC. Consecutive series of all patients (n = 128) with previously untreated T4 maxillary sinus SCC between 2006 and 2007 were obtained from 28 institutions belonging to or cooperating in the Head and Neck Cancer Study Group of the Japan Clinical Oncology Group. Of the 128 patients, 28 (21.9 %) had lymph node metastasis, and six patients (4.7 %) had distant metastasis at diagnosis. Among the 111 patients who were treated with curative intent, 98 had clinically N0 neck disease and did not receive prophylactic neck irradiation. A total of 11 patients (11.2 %) subsequently developed evidence of lymph node metastasis, of whom eight were among the 83 patients with an N0 neck and had not received elective neck treatment. There were 15 patients who received an elective neck dissection as part of the initial treatment, of whom three had pathologically positive for lymph node metastases. Of 11 patients, six patients with nonlateral retropharyngeal lymph node metastasis without primary or distant disease were successfully salvaged. This study identified the incidence of lymph node metastasis among patients with T4 MS-SCC as well as the delayed metastasis rate and the treatment outcome for untreated N0 neck in patients with T4 MS-SCC. These results will be of assistance in selecting treatment strategy for T4 MS-SCC in the future.

  7. [Ocular Metastasis in Lung Cancer: a Retrospective Analysis in a Single Chinese Hospital and Literature Review].

    PubMed

    Xu, Yan; Sun, Yiduo; Zhao, Jing; Chen, Minjiang; Jiangde, Lina; Li, Longyun; Zhong, Wei; Wang, Mengzhao

    2017-05-20

    Eye is a rare site of lung cancer metastasis, and ocular metastasis is one of the largest challenges to cancer patients' quality of life (QOL). Here we present our experience on ocular metastasis of lung cancer and review relevant literature in an attempt to investigate the clinical features, treatment, and prognosis of these tumors. The records of 9 patients with ocular metastasis of lung cancer treated at our hospital were analyzed. A literature review identified 42 cases reported in the last 10 years and their medical records were retrospectively estimated. The median age of our patients was 51 years (range 41-61). Diagnosis of lung cancer included non-small cell lung carcinoma (NSCLC) in 7 patients, in which adenocarcinoma (ADC) were recorded in 6 patients, small cell lung carcinoma (SCLC) in 1 patient, and unknown in 1 patient. The site of ocular metastasis included choroid (n=8) and iris (n=1). In the literature review, SCLC constituted 21.4% (n=9) and ADC constituted 47.6% (n=20). Choroid presented to be the most common site for eye metastasis (66.7%, n=28). As for disease control rate, systemic chemotherapy for lung cancer patients with ocular metastasis presented to be only 28%. Meanwhile, combination of systemic treatment with ocular treatment could improve patients' eye symptoms effectively. The most common lung cancer that metastasizes to the eye is ADC. The choroid is the most common site for ocular metastasis. Ocular treatment can improve patients' eye symptoms, while the effect of systemic chemotherapy treatment is limited.

  8. ERBB3 is required for metastasis formation of melanoma cells

    PubMed Central

    Tiwary, S; Preziosi, M; Rothberg, P G; Zeitouni, N; Corson, N; Xu, L

    2014-01-01

    Melanoma is curable when it is at an early phase but is lethal once it becomes metastatic. The recent development of BRAFV600E inhibitors (BIs) showed great promise in treating metastatic melanoma, but resistance developed quickly in the treated patients, and these inhibitors are not effective on melanomas that express wild-type BRAF. Alternative therapeutic strategies for metastatic melanoma are urgently needed. Here we report that ERBB3, a member of the epidermal growth factor receptor family, is required for the formation of lung metastasis from both the BI-sensitive melanoma cell line, MA-2, and the BI-resistant melanoma cell line, 451Lu-R. Further analyses revealed that ERBB3 does not affect the initial seeding of melanoma cells in lung but is required for their further development into overt metastases, indicating that ERBB3 might be essential for the survival of melanoma cells after they reach the lung. Consistent with this, the ERBB3 ligand, NRG1, is highly expressed in mouse lungs and induces ERBB3-depdnent phosphorylation of AKT in both MA-2 and 451Lu-R cells in vitro. These findings suggest that ERBB3 may serve as a target for treating metastatic melanomas that are resistant to BIs. In support of this, administration of the pan-ERBB inhibitor, canertinib, significantly suppresses the metastasis formation of BI-resistant melanoma cell lines. PMID:25000258

  9. Non-small cell lung carcinoma metastasis to the anus.

    PubMed

    Dhandapani, Ramya Gowri; Anosike, Chinedum; Ganguly, Akash

    2016-04-29

    A 70-year-old man presenting with a lung mass was investigated and treated with pneumonectomy for adenocarcinoma of the lung. He re-presented 3 months later with a large perianal abscess and mass. Subsequent investigations and biopsies showed disseminated metastases from the lung primary. Immunohistochemical staining confirmed the nature of the anal metastasis from the lung adenocarcinoma. Lung cancer is notorious for metastases, hence it is important to be aware of the uncommon modes of spread, which will help obtain early diagnosis and optimise treatment. 2016 BMJ Publishing Group Ltd.

  10. Femoral Metastasis from Penile Carcinoma: Report of 2 Cases.

    PubMed

    Braumann, Laura; Tsagozis, Panagiotis; Wedin, Rikard; Brosjö, Otte

    2015-01-01

    Purpose. Penile cancer rarely gives symptomatic skeletal metastases. Methods. We present 2 patients with squamous carcinoma of the penis who were surgically treated for metastases in the femur. Results. Both patients had pathological fractures and were operated on. In one case, the skeletal metastasis preceded any lymphatic spread of the disease, suggesting early haematogenous dissemination. Conclusions. Endoprosthetic reconstruction resulted in pain relief and restored the ambulatory capacity. Clinicians should be aware of the possibility for symptomatic bone metastases with a risk for pathological fracture in patients with penile cancer.

  11. Isolated splenic metastasis from colon cancer: Case report

    PubMed Central

    Abdou, Jiddou; Omor, Youssef; Boutayeb, Saber; Elkhannoussi, Basma; Errihani, Hassan

    2016-01-01

    Isolated splenic metastases from colorectal cancer are very rare clinical entities and when they are present, they usually manifest widely disseminated disease. In this paper we report a case of metachronous solitary isolated splenic metastasis from colon cancer in a 64-year-old woman who was successfully treated by laparoscopic splenectomy. We discuss the pathological and clinical aspects of this condition. We furthermore comment on the diagnostic and therapeutic options of this rare entity through our observation of the case and consideration of the 31 case reports published in the literature. PMID:27182171

  12. Treatment of brain metastasis from lung cancer.

    PubMed

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

    2012-01-01

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

  13. Metastasis-associated protein 2 (MTA2) promotes the metastasis of non-small-cell lung cancer through the inhibition of the cell adhesion molecule Ep-CAM and E-cadherin.

    PubMed

    Zhang, Bin; Zhang, Hao; Shen, Gang

    2015-08-01

    metastasis-associated protein 2 might be a potential therapeutic target for treating the metastasis of non-small-cell lung cancer. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Port-site recurrence after thoracoscopic resection of pulmonary metastasis owing to osteogenic sarcoma.

    PubMed

    Sartorelli, K H; Partrick, D; Meagher, D P

    1996-10-01

    Video-assisted thoracic surgery (VATS) is being used increasingly to evaluate and treat intrathoracic pathology. Port-site seeding is a rare but feared complication when minimally invasive surgical techniques are used in the evaluation and treatment of malignancies. The authors report a case of port-site seeding after thoracoscopic resection of pulmonary metastasis from an osteogenic sarcoma.

  15. Warfarin inhibits metastasis of Mtln3 rat mammary carcinoma without affecting primary tumour growth.

    PubMed Central

    McCulloch, P.; George, W. D.

    1989-01-01

    Coumarin anticoagulants inhibit metastasis in several animal models, but the mechanism of this effect is uncertain. In order to determine the role of cytotoxic and/or cytostatic actions of coumarins on the tumour cells, we have studied the effects of warfarin on tumour cell growth in a model in which tumour metastasis is inhibited by this drug. Clonogenic assay, growth curve analysis and thymidine labelling index revealed that warfarin had no effects on Mtln3 mammary carcinoma cell growth in vitro at concentrations below 1 mM. The growth rate of subcutaneously implanted Mtln3 tumour deposits in female F344 rats, assessed by weight and by stathmokinetic analysis of the tumour tissue, was identical in warfarin-treated and control animals. Spontaneous metastasis from such tumours to the lungs was, however, significantly reduced in warfarin-treated animals (median 0 pulmonary tumours per animal in warfarin treated, eight tumours per animal in control animals; P less than 0.05, Mann-Whitney). The mean plasma warfarin concentration in warfarin treated rats was 1.63 microM. These results suggest that warfarin treatment of the host animal can inhibit tumour metastasis without having any direct or indirect effect on the growth rate of the tumour cells. PMID:2930682

  16. Detection of meningioma metastasis to liver and lung using somatostatin receptor scintigraphy.

    PubMed

    Lanfranchi, Michael; Nikpoor, Nayer

    2013-08-01

    Extracranial meningioma metastasis is rare. We report a case of a 74-year-old Caucasian man with intracranial recurrence of atypical meningioma treated with a combination of surgical resection and gamma knife radiotherapy over a 4-year period. Somatostatin receptor scintigraphy using (111)In pentreotide for surveillance of tumor recurrence showed multiple pulmonary and hepatic metastases.

  17. Mechanisms of Ovarian Cancer Metastasis: Biochemical Pathways

    PubMed Central

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

    2012-01-01

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

  18. Imaging of bone metastasis: An update.

    PubMed

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

    2015-08-28

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

  19. Metaplastic Breast Carcinoma With Multiple Muscle Metastasis

    PubMed Central

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

    2015-01-01

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

  20. Breast cancer metastasis to the pituitary gland.

    PubMed

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

    2014-11-01

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

  1. Thyroid metastasis as initial presentation of clear cell renal carcinoma

    PubMed Central

    Ramírez-Plaza, César Pablo; Domínguez-López, Marta Elena; Blanco-Reina, Francisco

    2015-01-01

    Introduction Metastatic tumors account for 1.4–2.5% of thyroid malignancies. About 25–30% of patients with clear cell renal carcinoma (CCRC) have distant metastasis at the time of diagnosis, being the thyroid gland a rare localization [5%]. Presentation of the case A 62-year woman who underwent a cervical ultrasonography and a PAAF biopsy reporting atypical follicular proliferation with a few intranuclear vacuoles “suggestive” of thyroid papillary cancer in the context of a multinodular goiter was reported. A total thyroidectomy was performed and the histology of a clear cell renal carcinoma (CCRC) was described in four nodules of the thyroid gland. A CT scan was performed and a renal giant right tumor was found. The patient underwent an eventful radical right nephrectomy and the diagnosis of CCRC was confirmed. Discussion Thyroid metastasis (TM) from CCRC are usually apparent in a metachronic context during the follow-up of a treated primary (even many years after) but may sometimes be present at the same time than the primary renal tumor. Our case is exceptional because the TM was the first evidence of the CCRC, which was subsequently diagnosed and treated. Conclusion The possibility of finding of an incidental metastatic tumor in the thyroid gland from a previous unknown and non-diganosed primary (as CCRC in our case was) is rare and account only for less than 1% of malignancies. Nonetheless, the thyroid gland is a frequent site of metastasis and the presence of “de novo” thyroid nodules in oncologic patients must be always considered and studied. PMID:25827295

  2. Treating Infertility

    MedlinePlus

    ... Education & Events Advocacy For Patients About ACOG Treating Infertility Home For Patients Search FAQs Treating Infertility Page ... Treating Infertility FAQ137, March 2015 PDF Format Treating Infertility Gynecologic Problems What is infertility? What treatment options ...

  3. Invasion and metastasis in pancreatic cancer.

    PubMed

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

    2003-01-22

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

  4. Ovarian carcinoma presenting as cutaneous nasal metastasis*

    PubMed Central

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

    2016-01-01

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

  5. Organotropic metastasis: role of tumor exosomes.

    PubMed

    Liu, Yang; Cao, Xuetao

    2016-02-01

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

  6. Three-dimensional context regulation of metastasis.

    PubMed

    Erler, Janine T; Weaver, Valerie M

    2009-01-01

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

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

    PubMed

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

    2017-08-22

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

  8. Heparanase Mechanisms in Melanoma Brain Metastasis

    DTIC Science & Technology

    2015-10-01

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

  9. Metastasis Suppressors and the Tumor Microenvironment

    PubMed Central

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

    2011-01-01

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

  10. Prediction of Metastasis Using Second Harmonic Generation

    DTIC Science & Technology

    2016-07-01

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

  11. Cardiac metastasis of oral squamous cell carcinoma.

    PubMed

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

    2015-09-09

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

  12. Gastric metastasis by lung small cell carcinoma

    PubMed Central

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

    2006-01-01

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

  13. Lysyl oxidase mediates hypoxic control of metastasis.

    PubMed

    Erler, Janine T; Giaccia, Amato J

    2006-11-01

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

  14. C-type lectins facilitate tumor metastasis

    PubMed Central

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

    2017-01-01

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

  15. Magnetic Resonance Imaging of Liver Metastasis.

    PubMed

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

    2016-12-01

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

  16. C-type lectins facilitate tumor metastasis.

    PubMed

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

    2017-01-01

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

  17. Galectin-3 binding and metastasis.

    PubMed

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

    2012-01-01

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

  18. Ion Channels in Brain Metastasis

    PubMed Central

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

    2016-01-01

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

  19. Tumor-targeting Salmonella typhimurium A1-R inhibits human prostate cancer experimental bone metastasis in mouse models.

    PubMed

    Toneri, Makoto; Miwa, Shinji; Zhang, Yong; Hu, Cameron; Yano, Shuya; Matsumoto, Yasunori; Bouvet, Michael; Nakanishi, Hayao; Hoffman, Robert M; Zhao, Ming

    2015-10-13

    Bone metastasis is a frequent occurrence in prostate cancer patients and often is lethal. Zoledronic acid (ZOL) is often used for bone metastasis with limited efficacy. More effective models and treatment methods are required to improve the outcome of prostate cancer patients. In the present study, the effects of tumor-targeting Salmonella typhimurium A1-R were analyzed in vitro and in vivo on prostate cancer cells and experimental bone metastasis. Both ZOL and S. typhimurium A1-R inhibited the growth of PC-3 cells expressing red fluorescent protien in vitro. To investigate the efficacy of S. typhimurium A1-R on prostate cancer experimental bone metastasis, we established models of both early and advanced stage bone metastasis. The mice were treated with ZOL, S. typhimurium A1-R, and combination therapy of both ZOL and S. typhimurium A1-R. ZOL and S. typhimurium A1-R inhibited the growth of solitary bone metastases. S. typhimurium A1-R treatment significantly decreased bone metastasis and delayed the appearance of PC-3 bone metastases of multiple mouse models. Additionally, S. typhimurium A1-R treatment significantly improved the overall survival of the mice with multiple bone metastases. The results of the present study indicate that S. typhimurium A1-R is useful to prevent and inhibit prostate cancer bone metastasis and has potential for future clinical use in the adjuvant setting.

  20. Management of differentiated thyroid carcinoma with bone metastasis: a case report and review of the Chinese literature.

    PubMed

    Zhang, Wei-dong; Liu, Da-ren; Feng, Cheng-cheng; Zhou, Chuan-biao; Zhan, Chen-ni; Que, Ri-sheng; Chen, Li

    2014-12-01

    Differentiated thyroid carcinoma (DTC) is a common malignancy. The general treatments are thyroidectomy of the affected lobe along with lymphadenectomy. However, bone metastasis is rare in DTC compared with other malignancies and the management of metastasis foci is still controversial. Here we present a case of follicular thyroid carcinoma with the 6th cervical vertebra body metastasis successfully treated by total thyroidectomy, cervical corpectomy, and internal fixation, followed by hormone replacement therapy and radioiodine therapy. Eleven additional patients diagnosed as thyroid carcinoma with bone metastasis collected from Chinese literature between January 1996 and December 2013 were also reviewed. The mean age of the 12 patients at presentation was (53.9±9.2) years (rang, 42-72 years) and the male to female ratio was 1:2. Nine cases received total/near-total thyroidectomy or lobectomy while the other three patients refused for personal reasons. The interventions for bone metastasis were one-stage operation (9/12), I(131) adjuvant therapy (3/12), chemotherapy (1/12), and no intervention (1/12). During the follow-up, two patients died of metastatic carcinoma recurrence, one died of multiple organ metastasis, and one with an unknown reason. We conclude that the management of thyroid carcinoma with bone metastasis needs multidisciplinary cooperation. Surgical resection is still the first choice for cure, while the combined one-stage operation on the primary and metastatic sites followed by hormone replacement therapy and radioiodine therapy is an applicable treatment.

  1. Tumor-targeting Salmonella typhimurium A1-R inhibits human prostate cancer experimental bone metastasis in mouse models

    PubMed Central

    Toneri, Makoto; Miwa, Shinji; Zhang, Yong; Hu, Cameron; Yano, Shuya; Matsumoto, Yasunori; Bouvet, Michael; Nakanishi, Hayao; Hoffman, Robert M.; Zhao, Ming

    2015-01-01

    Bone metastasis is a frequent occurrence in prostate cancer patients and often is lethal. Zoledronic acid (ZOL) is often used for bone metastasis with limited efficacy. More effective models and treatment methods are required to improve the outcome of prostate cancer patients. In the present study, the effects of tumor-targeting Salmonella typhimurium A1-R were analyzed in vitro and in vivo on prostate cancer cells and experimental bone metastasis. Both ZOL and S. typhimurium A1-R inhibited the growth of PC-3 cells expressing red fluorescent protien in vitro. To investigate the efficacy of S. typhimurium A1-R on prostate cancer experimental bone metastasis, we established models of both early and advanced stage bone metastasis. The mice were treated with ZOL, S. typhimurium A1-R, and combination therapy of both ZOL and S. typhimurium A1-R. ZOL and S. typhimurium A1-R inhibited the growth of solitary bone metastases. S. typhimurium A1-R treatment significantly decreased bone metastasis and delayed the appearance of PC-3 bone metastases of multiple mouse models. Additionally, S. typhimurium A1-R treatment significantly improved the overall survival of the mice with multiple bone metastases. The results of the present study indicate that S. typhimurium A1-R is useful to prevent and inhibit prostate cancer bone metastasis and has potential for future clinical use in the adjuvant setting. PMID:26431498

  2. High incidence of prostate cancer metastasis in Afro-Brazilian men with low educational levels: a retrospective observational study.

    PubMed

    de Souza, Alexandre Barbosa Câmara; Guedes, Hugo Gonçalo; Oliveira, Victor Carbone Bernardes; de Araújo, Fábio Aires; Ramos, Carlos Cesar Oliveira; Medeiros, Karina Carla Paula; Araújo, Raimundo Fernandes

    2013-06-04

    This study investigated factors related to ethnicity and educational level, their correlation with tumor stage at the time of diagnosis, and their influence on treatment outcomes in patients with prostate cancer. In this retrospective observational study, we analyzed the medical records of 1,349 male patients treated for prostatic adenocarcinoma. We collected information about sociodemographic variables, including educational level and self-reported skin color. We also classified the disease according whether it was to more likely to present with metastasis and measured the tumor response to treatment. Less-educated (<8 years of education) individuals were 4.8 times more likely to develop metastasis than those with more education (>11 years of education; p < 0.001). Similarly, patients with a self-reported black skin color had a 300% increased risk of metastasis at diagnosis (p = 0.001). Distant metastasis was independently correlated with worse outcomes, such that individuals with distant metastasis were 10 times more likely to die than were those without distant metastasis. Patients with self-reported black skin color and <8 years of education were more likely to display advanced disease at the time of diagnosis compared with their counterparts. Only the presence of metastasis was independently associated with mortality or progressive disease.

  3. microRNA-214 promotes epithelial-mesenchymal transition and metastasis in lung adenocarcinoma by targeting the suppressor-of-fused protein (Sufu)

    PubMed Central

    Chen, Junying; Xiang, Tong; Li, Qijing; Diao, Xinwei; Zhu, Bo

    2015-01-01

    Distant metastasis is the major cause of cancer-related deaths in patients with lung adenocarcinoma (LAD). Emerging evidence reveals that miRNA is critical for tumor metastasis. miR-214 expression has been associated with LAD progression. However, whether and how miR-214 is involved in the development and metastasis of LAD remain unaddressed. Here, we found that the expression of miR-214 was elevated in LAD and correlated positively with LAD metastasis and epithelial-mesenchymal transition (EMT). In addition, we found that miR-214 enhanced the molecular program controlling the EMT of LAD cells and promoted LAD cell metastasis both in vitro and in vivo. This study thus provides the first evidence to show that the miR-214 expression by LAD cells contributes to the EMT and metastasis of LAD. Mechanistically, Sufu was identified as an important miR-214 functional target for the EMT and metastasis of LAD, ectopic expression of Sufu alleviated miR-214 promoted EMT and metastasis. Importantly, the expression of Sufu inversely correlated with the expression of miR-214 and vimentin and positively associated with the expression of E-cadherin in the tumor cells from human LAD patients. Collectively, this study uncovers a previously unappreciated miR-214-Sufu pathway in controlling EMT and metastasis of LAD and suggests that interfering with miR-214 and Sufu could be a viable approach to treat late stage metastatic LAD patients. PMID:26462018

  4. Preventive Effects of Zoledronic Acid on Bone Metastasis in Mice Injected with Human Breast Cancer Cells

    PubMed Central

    Jeong, Joon; Lee, Kyung Sun; Choi, Yang-Kyu; Oh, Young Ju

    2011-01-01

    Bisphosphonates are used routinely to reduce bone-related events in breast cancer patients with bone metastasis. We evaluated the effects of zoledronic acid, a third generation, nitrogen-containing bisphosphonate, to prevent bone metastasis in breast cancer. Zoledronic acid or vehicle alone was administered to nude mice either simultaneously or after intracardiac injection of human breast cancer MDA-MB-231 cells. Nude mice treated with zoledronic acid at early time points showed a lower incidence of bone metastases than did vehicle-treated nude mice, but these differences were not statistically significant. Only 37.5% of mice treated with zoledronic acid at the time of tumor cell inoculation developed bone metastases compared to over 51.8% of mice receiving vehicle alone (P = 0.304). Cell count of apoptosis confirmed by immunohistochemical staining in metastatic bone tissue significantly increased in the zoledronic acid-treated groups compared to non-treated group (1,018.3 vs 282.0; P = 0.046). However, metastatic tumor cells, which invade soft tissue around the bone, did not show extensive apoptosis; there were no differences between the zoledronic acid-treated and control groups. These results suggest that zoledronic acid increases apoptosis of metastatic breast tumor cells in the bone and could therefore reduce metastatic tumor burden. These results support the use of zoledronic acid to reduce the incidence of bone metastasis in breast cancer. PMID:22147993

  5. Pulmonary metastasis of a meningioma presenting as a solitary pulmonary nodule: 2 case reports.

    PubMed

    Leemans, J; Van Calenbergh, F; Sciot, R; Debiec-Rychter, M; Decaluwe, H; Nackaerts, K

    2016-04-01

    Distant metastases of meningioma are rare, especially in grade 1 meningiomas. In a recent literature review, only 115 cases were found. In almost all published cases, the meningioma was treated several years before the metastasis was diagnosed. The lungs are the most frequent site of metastasis. We describe two patients treated for meningioma (one case grade 1, the other grade 3) who were referred to the Respiratory Oncology Unit because of the incidental finding of a pulmonary nodule on routine chest radiography. Both had undergone several neurosurgical procedures but the last operation was more than 7 years before in both cases. Positron emission tomography scan was suggestive of a malignant lung tumour. The lesions were surgically removed. Pathology confirmed meningioma in both cases with the same WHO grade, immunohistochemical and genetic profiles as the original meningioma. Both patients recovered well from thoracic surgery. The patient with grade 3 meningioma died three years later from intracranial recurrence. When a patient previously treated for meningioma develops a nodular lung lesion, metastasis of the meningioma should be in the differential diagnosis list. Because of the occurrence of distant metastasis even in grade I meningiomas, we suggest that the grading system should take into account genetic changes in the meningioma. Chromosome 1p and 14q losses possibly explain the aggressive behaviour of the grade 1 meningioma.

  6. Aminomethylphosphonic acid inhibits growth and metastasis of human prostate cancer in an orthotopic xenograft mouse model

    PubMed Central

    Parajuli, Keshab Raj; Zhang, Qiuyang; Liu, Sen; You, Zongbing

    2016-01-01

    Aminomethylphosphonic acid (AMPA) has been shown to inhibit prostate cancer cell growth in vitro. The purpose of the present study was to determine if AMPA could inhibit growth and metastasis of prostate cancer in vivo. Human prostate cancer PC-3-LacZ-luciferase cells were implanted into the ventral lateral lobes of the prostate in 39 athymic Nu/Nu nude male mice. Seven days later, mice were randomized into the control group (n = 14, treated intraperitoneally with phosphate buffered saline), low dose group (n = 10, treated intraperitoneally with AMPA at 400 mg/kg body weight/day), and high dose group (n = 15, treated intraperitoneally with AMPA at 800 mg/kg body weight/day). Tumor growth and metastasis were examined every 4-7 days by bioluminescence imaging of live mice. We found that AMPA treatment significantly inhibited growth and metastasis of orthotopic xenograft prostate tumors and prolonged the survival time of the mice. AMPA treatment decreased expression of BIRC2 and activated caspase 3, leading to increased apoptosis in the prostate tumors. AMPA treatment decreased expression of cyclin D1. AMPA treatment also reduced angiogenesis in the prostate tumors. Taken together, these results demonstrate that AMPA can inhibit prostate cancer growth and metastasis, suggesting that AMPA may be developed into a therapeutic agent for the treatment of prostate cancer. PMID:26840261

  7. Aminomethylphosphonic acid inhibits growth and metastasis of human prostate cancer in an orthotopic xenograft mouse model.

    PubMed

    Parajuli, Keshab Raj; Zhang, Qiuyang; Liu, Sen; You, Zongbing

    2016-03-01

    Aminomethylphosphonic acid (AMPA) has been shown to inhibit prostate cancer cell growth in vitro. The purpose of the present study was to determine if AMPA could inhibit growth and metastasis of prostate cancer in vivo. Human prostate cancer PC-3-LacZ-luciferase cells were implanted into the ventral lateral lobes of the prostate in 39 athymic Nu/Nu nude male mice. Seven days later, mice were randomized into the control group (n = 14, treated intraperitoneally with phosphate buffered saline), low dose group (n = 10, treated intraperitoneally with AMPA at 400 mg/kg body weight/day), and high dose group (n = 15, treated intraperitoneally with AMPA at 800 mg/kg body weight/day). Tumor growth and metastasis were examined every 4-7 days by bioluminescence imaging of live mice. We found that AMPA treatment significantly inhibited growth and metastasis of orthotopic xenograft prostate tumors and prolonged the survival time of the mice. AMPA treatment decreased expression of BIRC2 and activated caspase 3, leading to increased apoptosis in the prostate tumors. AMPA treatment decreased expression of cyclin D1. AMPA treatment also reduced angiogenesis in the prostate tumors. Taken together, these results demonstrate that AMPA can inhibit prostate cancer growth and metastasis, suggesting that AMPA may be developed into a therapeutic agent for the treatment of prostate cancer.

  8. Prognostic Factors After Extraneural Metastasis of Medulloblastoma

    SciTech Connect

    Mazloom, Ali; Zangeneh, Azy H.; Paulino, Arnold C.

    2010-09-01

    Purpose: To review the existing literature regarding the characteristics, prognostic factors, treatment, and survival of patients with medulloblastoma, who develop extraneural metastasis (ENM). Methods and Materials: A PubMed search of English language articles from 1961 to 2007 was performed, yielding 47 articles reporting on 119 patients. Factors analyzed included age, time interval to development of ENM, ENM location, central nervous system (CNS) involvement, treatment, and outcome. Results: Sites of ENM included bone in 84% of patients, bone marrow in 27% of patients, lymph nodes in 15% of patients, lung in 6% of patients, and liver in 6% of patients. Median survival was 8 months after diagnosis of ENM. The 1-, 2-, and 5-year overall survival (OS) rates after diagnosis of ENM were 41.9%, 31.0%, and 26.0%, respectively. The 1-, 2-, and 5-year progression-free survival (PFS) rates after diagnosis of ENM were 34.5%, 23.2%, and 13.4%, respectively. For patients without CNS involvement at the time of ENM diagnosis, the 1-, 2-, and 5-year OS rates for those treated with and without radiotherapy (RT) were 82.4%, 64.8%, and 64.8% vs. 51.0%, 36.6%, and 30.5%, respectively (p = 0.03, log-rank test). RT did not significantly improve OS or PFS rates for those with CNS involvement. Concurrent CNS involvement, ENM in the lung or liver, a time interval of <18 months to development of ENM, and a patient age of <16 years at ENM diagnosis were found to be negative prognostic factors for both OS and PFS. Conclusions: Several prognostic factors were identified for patients with ENM from medulloblastoma. Patients without concurrent CNS involvement, who received RT after ENM diagnosis had an OS and PFS benefit compared to those who did not receive RT.

  9. Brain metastasis in sarcoma: Does metastasectomy or aggressive multi-disciplinary treatment improve survival outcomes.

    PubMed

    Chua, Clarinda; Raaj, Jeevan; Pan, Summer; Farid, Mohamad; Lee, Jin Fu Marcus; Ho, Zhen Chong; Sairi, Alisa; Sittampalam, Kesavan; Tao, Miriam; Tay, Kevin; Lim, Soon Thye; Chin, Francis; Teo, Melissa; Quek, Richard

    2016-03-01

    Brain metastasis is rare in sarcoma. Prognostic factors, optimal management strategies and therapeutic outcomes of such patients are not well studied. We aimed to evaluate the incidence, clinical characteristics and treatment outcomes of parenchymal brain metastasis in sarcoma patients. This is a single center retrospective analysis. Overall survival (OS) was calculated from the time of diagnosis of brain metastasis to time of death. Sixteen patients (2.1%) with complete electronic medical records treated at our institution from 2002 to 2010 were identified. Median age was 52 years; 88% had additional sites of metastases. Eight different subtypes of soft tissue and bone sarcoma were identified. Eighty-one percent of the patients developed metachronous brain metastasis at a median of 14 months after initial sarcoma diagnosis. Thirty-eight percent of patients had solitary brain metastasis and 44% underwent aggressive therapy for brain metastasis, defined as either surgical resection or multimodality treatment. The remaining 56% received conservative treatment (either whole brain radiation alone, chemotherapy alone or best supportive care). Median OS for the entire cohort was 3.5 months (95% CI 1.1-6.3 months). A trend toward improved OS was observed with an aggressive treatment approach, 3.7 months versus 1.2 months (P = 0.077) and the usage of chemotherapy (P = 0.071). Brain metastasis in sarcoma is rare, usually coexists with significant systemic disease and is associated with a grave prognosis. Use of chemotherapy and an aggressive treatment approach in well-selected patients may be associated with improved survival. Prospective studies are needed to confirm these findings. © 2013 Wiley Publishing Asia Pty Ltd.

  10. Antibody-mediated p53 protein therapy prevents liver metastasis in vivo.

    PubMed

    Hansen, James E; Fischer, Laurice K; Chan, Grace; Chang, Sophia S; Baldwin, Scott W; Aragon, Robert J; Carter, Jacqueline J; Lilly, Michael; Nishimura, Robert N; Weisbart, Richard H; Reeves, Mark E

    2007-02-15

    To evaluate the clinical efficacy of monoclonal antibody (mAb) 3E10 Fv antibody-mediated p53 protein therapy, an Fv-p53 fusion protein produced in Pichia pastoris was tested on CT26.CL25 colon cancer cells in vitro and in vivo in a mouse model of colon cancer metastasis to the liver. In vitro experiments showed killing of CT26.CL25 cells by Fv-p53 but not Fv or p53 alone, and immunohistochemical staining confirmed that Fv was required for transport of p53 into cells. Prevention of liver metastasis in vivo was tested by splenic injection of 100 nmol/L Fv-p53 10 min and 1 week after injection of CT26.CL25 cancer cells into the portal vein of BALB/c mice. Mice were sacrificed 1 week after the second injection of Fv-p53 and assigned a quantitative metastasis score. Control mice had an average metastasis score of 3.3 +/- 1.3, whereas mice treated with Fv-p53 had an average metastasis score of 0.8 +/- 0.4 (P = 0.004). These results indicate that Fv-p53 treatment had a profound effect on liver metastasis and represent the first demonstration of effective full-length p53 protein therapy in vivo. mAb 3E10 Fv has significant clinical potential as a mediator of intracellular and intranuclear delivery of p53 for prevention and treatment of cancer metastasis.

  11. Race Is a Risk for Lymph Node Metastasis in Patients With Gastric Cancer.

    PubMed

    Ikoma, Naruhiko; Blum, Mariela; Chiang, Yi-Ju; Estrella, Jeannelyn S; Roy-Chowdhuri, Sinchita; Fournier, Keith; Mansfield, Paul; Ajani, Jaffer; Badgwell, Brian D

    2017-04-01

    The frequency of lymph node metastasis in each T stage of gastric cancer has not been as well described for Western populations as it has for Asian populations. This study aimed to determine these frequencies and to investigate risk factors associated with lymph node metastases in a racially diverse U.S. A prospectively maintained database of 8260 patients with gastric or gastroesophageal junction adenocarcinoma treated at our institution from 1995 to 2013 was reviewed to identify those who underwent surgical resection without preoperative therapy. Associations between clinicopathologic variables and lymph node metastasis were tested with uni- and multivariate analyses. The study identified 218 patients with a pathologic diagnosis of gastric adenocarcinoma who underwent upfront gastrectomy. These study subjects included 115 white (53 %), 19 black (9 %), and 41 Asian (19 %) patients. At least 15 lymph nodes were examined in 148 (68 %) of the patients. The lymph node metastasis rates were 10 % for stage T1a, 34 % for stage T1b, 44 % for stage T2, 73 % for stage T3, and 95 % for stage T4 tumors. Univariate analysis showed that submucosal invasion, race, 15 or more lymph nodes examined, and lymphovascular invasion were associated with lymph node metastasis in T1 and T2 tumors. The multivariate analysis showed all but lymphovascular invasion to be independent risk factors for nodal metastasis. The rates of lymph node metastasis observed in this study were higher than those reported in Asian reports. Race was an independent risk factor for lymph node metastasis. Caution is therefore needed when evidence from Asian countries is extrapolated to more racially diverse Western countries.

  12. Novel roles of DC-SIGNR in colon cancer cell adhesion, migration, invasion, and liver metastasis.

    PubMed

    Na, Heya; Liu, Xiaoli; Li, Xiaomeng; Zhang, Xinsheng; Wang, Yu; Wang, Zhaohui; Yuan, Menglang; Zhang, Yu; Ren, Shuangyi; Zuo, Yunfei

    2017-01-21

    Tumor metastasis is an essential cause of the poor prognosis of colon cancer. DC-SIGNR is a C-type lectin that is frequently found on human liver sinusoidal endothelial cells. LSECtin, which is a homologue of DC-SIGNR, has been demonstrated to participate in colon cancer liver metastasis. Due to the similarities in the expression pattern and structure of the two proteins, we speculated that DC-SIGNR could also be involved in this process. Colon cancer cells were treated with the DC-SIGNR protein or control IgG, after which cell migration, invasion, and morphology were assayed. Xenograft mouse models were used to determine the role of DC-SIGNR in colon cancer liver metastasis in vivo. In addition, a human gene expression array was used to detect differential gene expression in colon cancer cells stimulated with the DC-SIGNR protein. The serum level of DC-SIGNR was examined in colon cancer patients by ELISA, and the significance of DC-SIGNR was determined. In our research, we investigated whether DC-SIGNR promotes colon cancer cell adhesion, migration, and invasion. Knocking down mouse DC-SIGNR decreased the liver metastatic potency of colon cancer cells and increased survival time. Expressing human DC-SIGNR enhanced colon cancer liver metastasis. Furthermore, DC-SIGNR conferred metastatic capability on cancer cells by upregulating various metallothionein isoforms. To validate the above results, we also found that the serum DC-SIGNR level was statistically higher in colon cancer patients with liver metastasis compared with those without metastasis. These results imply that DC-SIGNR may promote colon carcinoma hepatic metastasis and could serve as a promising therapeutic target for anticancer treatment.

  13. Immunohistochemical markers of distant metastasis in laryngeal and hypopharyngeal squamous cell carcinomas.

    PubMed

    Rodrigo, Juan P; Martínez, Patricia; Allonca, Eva; Alonso-Durán, Laura; Suárez, Carlos; Astudillo, Aurora; García-Pedrero, Juana María

    2014-03-01

    Metastasis remains a major cause of mortality in head and neck squamous cell carcinoma (HNSCC). Current clinicopathological features have shown limited predictability for the risk of distant metastasis in individual patients, and therefore more accurate and reliable markers are needed. The aim of this study was to investigate the ability of various molecular markers present in primary tumors to predict the risk of developing distant metastasis. Restrictive clinical criteria were applied for patient selection in order to carry out a case-control study with comparable clinical features on a group-wide basis and a similar risk of metastasis. All patients were surgically treated (with postoperative radiotherapy when appropriate) and classified as stage IV disease. Immunohistochemical analysis was performed for a panel of proteins known to participate in cellular processes relevant to metastatic dissemination (E-cadherin, annexin A2, cortactin, FAK, EGFR, p53, and p-AKT). Results showed that the loss of E-cadherin expression was significantly correlated with the risk of distant metastasis (P = 0.002; log-rank test), while the loss of annexin A2 expression was nearly statistically significant (P = 0.06). None of the other protein markers assessed were associated with the development of distant metastasis. Therefore, according to our data the loss of epithelial adhesion seems to play a central role in the development of metastasis in HNSCC, and more importantly, immunohistochemical assessment of key proteins involved in cell adhesion regulation, such as E-cadherin could represent a useful tool to evaluate easily and routinely the metastatic potential of these carcinomas.

  14. Ewing's sarcoma with metachronous pulmonary metastasis after successful treatment of osteosarcoma in a child.

    PubMed

    Stebnicky, Milan; Belak, Jozef; Bohus, Peter; Gmitter, Frantisek; Jenco, Igor; Tkacova, Ruzena

    2009-01-01

    A rare case of duplicate tumor, osteosarcoma and Ewing's sarcoma, complicated by metachronous pulmonary metastasis in a child is reported. A nine-year-old girl's osteosarcoma was treated by neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy. Four years later, resection of the chest wall to remove an Ewing's sarcoma had to be performed, followed by chemotherapy and radiotherapy. At the age of 17, the girl underwent a metastasectomy of Ewing's sarcoma metastasis to the lung. Five years later, the patient is free from any recognizable malignant disease. We conclude that after the complete surgical removal of two primary tumors, metastasectomy is an optimal treatment procedure in case of a solitary pulmonary metastasis.

  15. A switch from CD44+ cell to EMT cell drives the metastasis of prostate cancer

    PubMed Central

    Shang, Zhiqun; Cai, Qiliang; Zhang, Minghao; Zhu, Shimiao; Ma, Yuan; Sun, Libin; Jiang, Ning; Tian, Jing; Niu, Xiaodan; Chen, Jiatong; Sun, Yinghao; Niu, Yuanjie

    2015-01-01

    Epithelial–mesenchymal transition (EMT) has been linked to cancer stem-like (CD44+) cell in the prostate cancer (PCa) metastasis. However, the molecular mechanism remains elusive. Here, we found EMT contributed to metastasis in PCa patients failed in androgen deprivation therapy (ADT). Castration TRAMP model also proved PCa treated with ADT promoted EMT with increased CD44+ stem-like cells. Switched CD44+ cell to EMT cell is a key step for luminal PCa cell metastasis. Our results also suggested ADT might go through promoting TGFβ1-CD44 signaling to enhance swift to EMT. Targeting CD44 with salinomycin and siRNA could inhibit cell transition and decrease PCa invasion. Together, cancer stem-like (CD44+) cells could be the initiator cells of EMT modulated by TGFβ1-CD44 signaling. Combined therapy of ADT with anti-CD44 may become a new potential therapeutic approach to battle later stage PCa. PMID:25483103

  16. Transpupillary thermotherapy in the treatment of choroidal metastasis from breast carcinoma.

    PubMed

    Vianna, Raul N G; Pena, Rafael; Muralha, Acácio; Muralha, Lília; Muranaka, Eduardo

    2004-01-01

    Most patients who develop metastatic carcinoma to the choroid are managed by local radiation or chemotherapy. Since transpupillary thermotherapy (TTT) is currently gaining attention as an optional treatment for choroidal melanomas and hemangiomas, we sought to determine whether TTT is suitable for treatment of solitary choroidal metastasis at the posterior pole. We report on a patient with decreased vision due to a serous macular detachment in a eye with a solitary choroidal metastasis from breast carcinoma, who was managed by TTT. After two months of follow up, total re-absorption of the serous macular detachment was achieved and the patient recovered full visual acuity in the treated eye. The choroidal mass became atrophic and hyperpigmentation of the retinal pigment epithelium and retinal folds in the macular region were observed. After six months of TTT, the ocular picture remained unchanged. TTT can be considered an acceptable therapeutic option for solitary choroidal metastasis associated with serous retinal detachment.

  17. The KISS1 metastasis suppressor: A good night kiss for disseminated cancer cells

    PubMed Central

    Beck, Benjamin H.; Welch, Danny R.

    2013-01-01

    Re-expression of KISS1 in tumor cell lines allows all antecedent steps of metastasis, but prevents colonization of secondary sites. Because tumor cells have already disseminated by the time of cancer diagnosis, KISS1 may represent a new opportunity for therapeutic intervention. Moreover, numerous clinical reports demonstrate that a loss or reduction of KISS1 expression in different human cancers inversely correlates with tumor progression, metastasis, and survival. Taken together, these observations compel the hypothesis that KISS1 could be of tremendous utility in controlling metastasis in a therapeutic context. In this review, we highlight some key findings from preclinical and clinical studies and discuss strategies whereby KISS1 may be exploited clinically to treat metastases. PMID:20303258

  18. Procollagen Lysyl Hydroxylase 2 is Essential for Hypoxia-Induced Breast Cancer Metastasis

    PubMed Central

    Gilkes, Daniele; Bajpai, Saumendra; Wong, Carmen Chak-Lui; Chaturvedi, Pallavi; Hubbi, Maimon E.; Wirtz, Denis; Semenza, Gregg L.

    2013-01-01

    Metastasis is the leading cause of death among patients who have breast cancer. Understanding the role of the extracellular matrix in the metastatic process may lead to the development of improved therapies to treat cancer patients. Intratumoral hypoxia, found in the majority of breast cancers, is associated with an increased risk of metastasis and mortality. We found that in hypoxic breast cancer cells, HIF-1 activates transcription of the PLOD1 and PLOD2 genes encoding procollagen lysyl hydroxylases that are required for the biogenesis of collagen, which is a major constituent of the extracellular matrix. High PLOD2 expression in breast cancer biopsies is associated with increased risk of mortality. We demonstrate that PLOD2 is critical for fibrillar collagen formation by breast cancer cells, increases tumor stiffness, and is required for metastasis to lymph nodes and lungs. PMID:23378577

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

    PubMed Central

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

    2015-01-01

    Cognitive impairment is a common symptom in patients with brain metastasis, and significant cognitive dysfunction is prevalent in a majority of patients who are still able to engage in basic self-care activities. In the current study, the neurocognitive performance of 32 patients with brain metastasis and 32 demographically-matched controls was examined using a battery of standardized neuropsychological tests, with the goal of comprehensively examining the cognitive functioning of newly diagnosed brain metastasis patients. The cognition of all patients was assessed within 1 week of beginning treatment for brain metastasis. Results indicated impairments in verbal memory, attention, executive functioning, and language in relation to healthy controls. Performance in relation to appropriate normative groups was also examined. Overall, cognitive deficits were prevalent and memory was the most common impairment. Given that cognitive dysfunction was present in this cohort of patients with largely minimal functional impairment, these results have implications for patients, caregivers and health care providers treating patients with brain metastasis. PMID:25035099

  20. Impact of middle and lower jugular neck dissection on supraclavicular lymph node metastasis from endometrial carcinoma

    PubMed Central

    2012-01-01

    Supraclavicular lymph node metastasis from endometrial carcinoma is considerably rarer than metastasis from uterine cervical cancer. To date, there have been no reported cases regarding systematic neck dissection as a salvage treatment. In this report, we describe the neck dissection procedure carried out on a 74-year-old woman with supraclavicular lymph node metastasis. Our objective was to histologically determine the origin of the metastasis while simultaneously providing appropriate treatment. The patient’s past medical history included two prior cases of cancer: rectal cancer 7 years earlier and endometrial adenocarcinoma 4 years earlier. We determined that middle and lower jugular neck dissection was appropriate in treating this case based on the results of our preoperative FDG-PET and tumor markers. This surgery provided histological evidence that metastasis occurred from endometrial carcinoma. Middle and lower jugular neck dissection was expected to improve the patient’s prognosis without impacting the patient’s active daily life. We have continued to monitor the patient closely over an extended period. PMID:22788987

  1. Identifying risk factors for brain metastasis in breast cancer patients: Implication for a vigorous surveillance program.

    PubMed

    Chow, Lorraine; Suen, Dacita; Ma, Kwok Kuen; Kwong, Ava

    2015-10-01

    Brain metastasis occurs in 10-15% of metastatic breast cancer patients and is associated with poor prognosis. This study aims to identify tumor characteristics of primary breast cancer, which are related to brain metastases in Hong Kong Chinese patients. A retrospective study of patients with invasive breast cancer receiving treatment in a university hospital from January 2001 to December 2008 was performed. The clinicopathological factors of patients with brain metastases were analyzed and compared with those who had no brain metastasis. Risk factors for brain metastasis were identified by univariate analysis first and then by multivariate analysis. A total of 912 patients with invasive breast cancer were treated during the study period. Of these, 30 patients were found to have distant metastases to brain. Patients with brain metastases had more breast tumors of higher histological grade (Grade III, 78.9% vs. 30.2%; p = 0.001). Their tumors also had a significantly higher rate of negative estrogen receptors (78.9% vs. 30.2%, p = 0.001). On multivariate analysis, only high tumor grading was found to be predictive of developing brain metastasis. Chinese breast cancer patients with brain metastasis were more likely to have high-grade tumors and negative estrogen receptor status. A more vigorous surveillance program for the central nervous system should be considered for this group of patients. Copyright © 2015. Published by Elsevier Taiwan.

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

    PubMed

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

    2017-01-02

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

  3. Cerebral Metastasis from Breast Cancer in a Male Patient with HIV

    PubMed Central

    Badke, Guilherme Lellis; de Aguiar, Guilherme Brasileiro; Silva, João Miguel de Almeida; Paiva, Aline Lariessy Campos; da Silva, Eduardo Urbano; Veiga, José Carlos Esteves

    2015-01-01

    Context. Breast cancer (BC) in men is a rare condition, corresponding to 1% of all neoplasms in this gender. Some studies show that up to 93% of BC cases in men are advanced disease. If its occurrence constitutes an uncommon fact, the appearance of a metastasis to the central nervous system (CNS) is extremely rare. The objective of the present study is to present the case of a male patient, bearer of HIV infection, who presented with BC and later metastasis to the CNS. We also include a brief review of the literature. Case Report. We describe a case of a male patient, 59 years old, with HIV infection and a history of BC treated 4 years earlier, which progressed into headache and vertigo. Neuroimaging exams showed lesions suggestive of cerebral metastasis and a stereotaxic biopsy confirmed BC metastasis. Conclusion. Breast cancer in men with metastasis to the CNS is a rare condition and similar reports were not found in the available databases. It should be pointed out that even though rare, it should be considered among the differential diagnoses for SNC metastases in men, although HIV infection favors the appearance of some types of cancer. PMID:25694836

  4. Thymoquinone inhibits cancer metastasis by downregulating TWIST1 expression to reduce epithelial to mesenchymal transition

    PubMed Central

    Khan, Md. Asaduzzaman; Tania, Mousumi; Wei, Chunli; Mei, Zhiqiang; Fu, Shelly; Cheng, Jingliang; Xu, Jianming; Fu, Junjiang

    2015-01-01

    Proteins that promote epithelial to mesenchymal transition (EMT) are associated with cancer metastasis. Inhibition of EMT regulators may be a promising approach in cancer therapy. In this study, Thymoquinone (TQ) was used to treat cancer cell lines to investigate its effects on EMT-regulatory proteins and cancer metastasis. We show that TQ inhibited cancer cell growth, migration and invasion in a dose-dependent manner. At the molecular level, TQ treatment decreased the transcriptional activity of the TWIST1 promoter and the mRNA expression of TWIST1, an EMT-promoting transcription factor. Accordingly, TQ treatment also decreased the expression of TWIST1-upregulated genes such as N-Cadherin and increased the expression of TWIST1-repressed genes such as E-Cadherin, resulting in a reduction of cell migration and invasion. TQ treatment also inhibited the growth and metastasis of cancer cell-derived xenograft tumors in mice but partially attenuated the migration and invasion in TWIST1-overexpressed cell lines. Furthermore, we found that TQ treatment enhanced the promoter DNA methylation of the TWIST1 gene in BT 549 cells. Together, these results demonstrate that TQ treatment inhibits TWIST1 promoter activity and decreases its expression, leading to the inhibition of cancer cell migration, invasion and metastasis. These findings suggest TQ as a potential small molecular inhibitor of cancer growth and metastasis. PMID:26023736

  5. The anthraquinone derivative Emodin inhibits angiogenesis and metastasis through downregulating Runx2 activity in breast cancer.

    PubMed

    Ma, Junchao; Lu, Hong; Wang, Shan; Chen, Bin; Liu, Zhaojie; Ke, Xiaoqin; Liu, Ting; Fu, Jianjiang

    2015-04-01

    Emodin (EMD) is an anthraquinone derivative extracted from the root and rhizome of Rheum palmatum L. which exhibits a range of activities, including anti-bacterial, antitumor, diuretic and vasorelaxant effects. The ability to inhibit metastasis and angiogenesis was shown in previous pharmacological studies, but clear information to address EMD affecting angiogenesis and metastasis in human breast cancer is still lacking. In the present study, we evaluated a possible role for EMD in angiogenesis and metastasis induced by breast cancer cells. It was revealed here that EMD attenuated tumor cell-induced metastasis and angiogenesis both in vitro and in vivo. Furthermore, it was found that these inhibitory effects were caused by MMPs and VEGFR-2 inhibition in metastatic breast cancer cells and endothelial cells, respectively. Western blot analysis showed reduction of Runx2 activation in the EMD-treated cells. ELISA based Runx2 transcription factor assay showed that the interaction between Runx2 and target sequences was inhibited by EMD. Our findings suggested that the inhibitory effects of EMD on tumor-induced metastasis and angiogenesis were caused by MMPs and VEGFR-2 inhibition, which may be associated with the downregulation of Runx2 transcriptional activity.

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

    PubMed

    Ci, Yingqian; Qiao, Jinping; Han, Mei

    2016-12-17

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

  7. Epithelial-mesenchymal transition in colorectal cancer metastasis: A system review.

    PubMed

    Cao, Hui; Xu, Enping; Liu, Hong; Wan, Ledong; Lai, Maode

    2015-08-01

    Tumor metastasis is a multi-step process by which tumor cells disseminate from their primary site and form secondary tumors at a distant site. And metastasis is the major cause of death in the vast majority of cancer patients. However, the mechanisms underlying each step remain obscure. In the past decade, a developmental program epithelial-to-mesenchymal transition (EMT) has been increasingly recognized to play pivotal and intricate roles in promoting carcinoma invasion and metastasis. The EMT process is very complex and controlled by various families of transcriptional regulators through different signaling pathways. In this system review, we focus on the molecular network of the EMT program and its malignant phenotypes associated with metastasis in colorectal cancer (CRC), including cancer stem cells, tumor budding, circulating tumor cells and drug resistance. A better understanding of the molecular regulation of the dynamic EMT program during tumor metastasis will help to provide much-needed therapeutic interventions to target this program when treating metastatic CRC. Copyright © 2015 Elsevier GmbH. All rights reserved.

  8. Blockade of FLT4 suppresses metastasis of melanoma cells by impaired lymphatic vessels.

    PubMed

    Lee, Ji Yoon; Hong, Seok-Ho; Shin, Minsang; Heo, Hye-Ryeon; Jang, In Ho

    2016-09-16

    The metastatic spread of tumor cells via lymphatic vessels affects the relapse of tumor patients. New lymphatic vessel formation, including lymphangiogenesis, is promoted in the tumor environment. The lymphangiogenic factor VEGF-C can mediate lymphatic vessel formation and induce tumor metastasis by binding with FLT4. In melanoma, metastasis via lymphatics such as lymph nodes is one of the main predictors of poor outcome. Thus, we investigated whether blockade of FLT4 can reduce metastasis via the suppression of lymphatic capillaries. Proliferative lymphatic capillaries in melanoma were estimated by immunohistochemistry using FLT4 antibody after the injection of the FLT4 antagonist MAZ51. The numbers of tumor modules in metastasised lungs were calculated by gross examination and lymphatic related factors were examined by qRT-PCR. MAZ51 injection resulted in the suppression of tumor size and module number and the inhibition of proliferative lymphatic vessels in the intratumoral region in the lung and proliferating melanoma cells in the lung compared to those of untreated groups. Additionally, high FLT4 and TNF-alpha were detected in melanoma-induced tissue, while lymphatic markers such as VEGF-C, FLT4 and Prox-1 were significantly decreased in MAZ51 treated groups, implying that anti-lymphangiogenesis by MAZ51 may provide a potential strategy to prevent tumor metastasis in melanoma and high number of lymphatic capillaries could be used diagnosis for severe metastasis. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    PubMed Central

    Zhao, Min; Li, Zhe; Qu, Hong

    2015-01-01

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

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

    PubMed

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

    2012-02-01

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

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

    PubMed

    Zhao, Min; Li, Zhe; Qu, Hong

    2015-10-21

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

  12. Mitochondrial metabolism in cancer metastasis

    PubMed Central

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

    2012-01-01

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

  13. Spinal metastasis in head and neck cancer

    PubMed Central

    2012-01-01

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

  14. Tumour exosome integrins determine organotropic metastasis

    PubMed Central

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

    2015-01-01

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

  15. Tumour exosome integrins determine organotropic metastasis

    SciTech Connect

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

    2015-10-28

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

  16. Tumour exosome integrins determine organotropic metastasis

    DOE PAGES

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

    2015-10-28

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

  17. Tumour exosome integrins determine organotropic metastasis.

    PubMed

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

    2015-11-19

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

  18. Surgical treatment of brain metastasis: a review.

    PubMed

    Mut, Melike

    2012-01-01

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

  19. Bone metastasis risk factors in breast cancer

    PubMed Central

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

    2017-01-01

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

  20. Brain metastasis: Unique challenges and open opportunities.

    PubMed

    Lowery, Frank J; Yu, Dihua

    2017-01-01

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

  1. Features and prognostic impact of distant metastasis in patients with stage IV lung adenocarcinoma harboring EGFR mutations: importance of bone metastasis.

    PubMed

    Fujimoto, Daichi; Ueda, Hiroyuki; Shimizu, Ryoko; Kato, Ryoji; Otoshi, Takehiro; Kawamura, Takahisa; Tamai, Koji; Shibata, Yumi; Matsumoto, Takeshi; Nagata, Kazuma; Otsuka, Kyoko; Nakagawa, Atsushi; Otsuka, Kojiro; Katakami, Nobuyuki; Tomii, Keisuke

    2014-06-01

    Mutated epidermal growth factor receptor (EGFR) and signaling pathways were associated with multiple brain and intra-pulmonary metastases, oncogenic progression and metastasis. However, features of metastasis to other organs and the independent prognostic influence of metastatic lesions were not elucidated in patients with lung cancer harboring EGFR mutations. Between January 2007 and April 2012, we treated 277 patients diagnosed with stage IV lung adenocarcinoma. Studied were 246 patients with available tumor EGFR mutation data who also underwent radiographic evaluation of lung, abdominal, brain, and bone metastases. The EGFR mutated group (N = 98) had significantly more metastatic lesions in the brain and bone than the wild-type group (N = 148): brain, 3 (1-93) versus 2 (1-32) median (range), P = 0.023; bone, 3 (1-43) versus 2 (1-27), P = 0.035, respectively. In addition, EGFR mutations were significantly more frequent in patients with multiple than non-multiple lung metastases (24/40 vs. 12/42, P = 0.004). Multivariate analysis showed that bone metastasis was a significant independent negative predictive factor of overall survival (OS) in patients with mutated [hazard ratio (HR) 2.04; 95 % confidence interval (CI) 1.17-3.64; P = 0.011] and wild-type EGFR (HR 2.09; 95 % CI 1.37-3.20; P < 0.001). In conclusion, patients with mutated EGFR had more lung, brain, and bone metastases, and bone metastasis was an independent negative predictor of OS.

  2. Terminal processes of serotonin neurons in the caudal spinal cord of the molly, Poecilia latipinna, project to the leptomeninges and urophysis.

    PubMed

    Cohen, S L; Kriebel, R M

    1989-03-01

    The caudal neurosecretory complex of poeciliids has previously been shown to be innervated by extranuclear and intrinsic serotonergic projections. In the present study, immunohistochemical techniques were used to characterize fibers originating from serotonin neurons intrinsic to the caudal spinal cord. Bipolar and multipolar neurons were oriented ventromedially, and contained numerous large granular vesicles. Three types of serotonergic fibers were distinguished based on their distribution and morphology. Intrinsic Type-A fibers branched into varicose segments near the ventrolateral surface of the spinal cord and contacted the basal lamina beneath the leptomeninges. Type-B fibers coursed longitudinally to enter the urophysis, where they diverged and terminated around fenestrated capillaries. Labelled vesicles in Type-A and Type-B terminals were the same size as those in labelled cells and in unlabelled neurosecretory terminals in the urophysis. Type-C small varicose fibers branched within the neuropil of the caudal neurosecretory complex. Serotonin may be secreted into the submeningeal cerebrospinal fluid, the urophysis, and the caudal vein by Type-A and Type-B fibers, whereas, Type-C fibers may be processes of serotonergic interneurons in the neuroendocrine nucleus. The possibility that urotensins I and II or arginine vasotocin were colocalized in the processes of the intrinsic serotonin neurons was investigated immunohistochemically. The negative results of these experiments suggest that serotonin-containing neurons may represent a neurochemically distinct subpopulation in the caudal neurosecretory complex.

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

    PubMed Central

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

    2015-01-01

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

  4. Radiofrequency ablation of hepatic metastasis: results of treatment in forty patients.

    PubMed

    Rath, G K; Julka, P K; Thulkar, S; Sharma, D N; Bahl, Amit; Bhatnagar, S

    2008-01-01

    To evaluate the local control of hepatic metastasis with radiofrequency ablation treatment. We did a retrospective analysis in 40 patients treated with radiofrequency ablation for hepatic metastasis. The tumors ablated included up to two metastatic liver lesions, with primaries in breast, gastrointestinal tract, cervix, etc. Radiofrequency ablation was performed under general anesthesia in all cases, using ultrasound guidance. Radionics Cool-Tip RF System was used to deliver the treatment. The median age of patients treated was 49 years. There were 13 female and 27 male patients. The median tumor size ablated was 1.5 cm (0.75-4.0 cm). A total of 52 radiofrequency ablation cycles were delivered. Successful ablation was achieved in all patients with hepatic metastasis less than 3 cm in size. Pain was the most common complication seen (75%). One patients developed skin burns. At 2-year follow-up 7.5% of patients had locally recurrent disease. Radiofrequency ablation is a minimally invasive treatment modality. It can be useful in a select group of patients with solitary liver metastasis of less than 3 cm size.

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

    PubMed

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

    2015-03-01

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

  6. Pterostilbene acts through metastasis-associated protein 1 to inhibit tumor growth, progression and metastasis in prostate cancer.

    PubMed

    Li, Kun; Dias, Steven J; Rimando, Agnes M; Dhar, Swati; Mizuno, Cassia S; Penman, Alan D; Lewin, Jack R; Levenson, Anait S

    2013-01-01

    The development of natural product agents with targeted strategies holds promise for enhanced anticancer therapy with reduced drug-associated side effects. Resveratrol found in red wine, has anticancer activity in various tumor types. We reported earlier on a new molecular target of resveratrol, the metastasis-associated protein 1 (MTA1), which is a part of nucleosome remodeling and deacetylation (NuRD) co-repressor complex that mediates gene silencing. We identified resveratrol as a regulator of MTA1/NuRD complex and re-activator of p53 acetylation in prostate cancer (PCa). In the current study, we addressed whether resveratrol analogues also possess the ability to inhibit MTA1 and to reverse p53 deacetylation. We demonstrated that pterostilbene (PTER), found in blueberries, had greater increase in MTA1-mediated p53 acetylation, confirming superior potency over resveratrol as dietary epigenetic agent. In orthotopic PCa xenografts, resveratrol and PTER significantly inhibited tumor growth, progression, local invasion and spontaneous metastasis. Furthermore, MTA1-knockdown sensitized cells to these agents resulting in additional reduction of tumor progression and metastasis. The reduction was dependent on MTA1 signaling showing increased p53 acetylation, higher apoptotic index and less angiogenesis in vivo in all xenografts treated with the compounds, and particularly with PTER. Altogether, our results indicate MTA1 as a major contributor in prostate tumor malignant progression, and support the use of strategies targeting MTA1. Our strong pre-clinical data indicate PTER as a potent, selective and pharmacologically safe natural product that may be tested in advanced PCa.

  7. Pterostilbene Acts through Metastasis-Associated Protein 1 to Inhibit Tumor Growth, Progression and Metastasis in Prostate Cancer

    PubMed Central

    Rimando, Agnes M.; Dhar, Swati; Mizuno, Cassia S.; Penman, Alan D.; Lewin, Jack R.; Levenson, Anait S.

    2013-01-01

    The development of natural product agents with targeted strategies holds promise for enhanced anticancer therapy with reduced drug-associated side effects. Resveratrol found in red wine, has anticancer activity in various tumor types. We reported earlier on a new molecular target of resveratrol, the metastasis-associated protein 1 (MTA1), which is a part of nucleosome remodeling and deacetylation (NuRD) co-repressor complex that mediates gene silencing. We identified resveratrol as a regulator of MTA1/NuRD complex and re-activator of p53 acetylation in prostate cancer (PCa). In the current study, we addressed whether resveratrol analogues also possess the ability to inhibit MTA1 and to reverse p53 deacetylation. We demonstrated that pterostilbene (PTER), found in blueberries, had greater increase in MTA1-mediated p53 acetylation, confirming superior potency over resveratrol as dietary epigenetic agent. In orthotopic PCa xenografts, resveratrol and PTER significantly inhibited tumor growth, progression, local invasion and spontaneous metastasis. Furthermore, MTA1-knockdown sensitized cells to these agents resulting in additional reduction of tumor progression and metastasis. The reduction was dependent on MTA1 signaling showing increased p53 acetylation, higher apoptotic index and less angiogenesis in vivo in all xenografts treated with the compounds, and particularly with PTER. Altogether, our results indicate MTA1 as a major contributor in prostate tumor malignant progression, and support the use of strategies targeting MTA1. Our strong pre-clinical data indicate PTER as a potent, selective and pharmacologically safe natural product that may be tested in advanced PCa. PMID:23469203

  8. [Sacral metastasis simulating aneurysmal bone cyst].

    PubMed

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

    2014-01-01

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

  9. Control of Metastasis by NK Cells.

    PubMed

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

    2017-08-14

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

  10. Brain abscess mimicking brain metastasis in breast cancer.

    PubMed

    Khullar, Pooja; Datta, Niloy R; Wahi, Inderjeet Kaur; Kataria, Sabeena

    2016-03-01

    61 year old female presented with chief complaints of headache for 30 days, fever for 10 days, altered behavior for 10 days and convulsion for 2 days. She was diagnosed and treated as a case of carcinoma of left breast 5 years ago. MRI brain showed a lobulated lesion in the left frontal lobe. She came to our hospital for whole brain radiation as a diagnosed case of carcinoma of breast with brain metastasis. Review of MRI brain scan, revealed metastasis or query infective pathology. MR spectroscopy of the lesion revealed choline: creatinine and choline: NAA (N-Acetylaspartate) ratios of ∼1.6 and 1.5 respectively with the presence of lactate within the lesion suggestive of infective pathology. She underwent left fronto temporal craniotomy and evacuation of abscess and subdural empyema. Gram stain showed gram positive cocci. After 1 month of evacuation and treatment she was fine. This case suggested a note of caution in every case of a rapidly evolving space-occupying lesion independent of the patient's previous history. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  11. Distant metastasis of rectal adenocarcinoma in a temporary tracheostoma

    PubMed Central

    Sifrer, Robert; Strojan, Primoz; Zidar, Nina; Zargi, Miha; Groselj, Ales; Krajinovic, Milena

    2014-01-01

    Background The temporary tracheostoma’s metastases of head and neck cancer had already been reported in the literature. So far, they had been considered as regional dissemination of the malignant disease. We report a case of temporary tracheostoma’s metastasis of carcinoma from non-head-and-neck primary site, what has not been reported in the literature, yet. Therefore, it is the first reported case of the systemic dissemination of malignant tumour into temporary tracheostoma. Case report. Fifty-four-year-old female patient, previously treated for a rectal adenocarcinoma, reported in our office with exophytic pink tissue masses around the temporary tracheostoma. The biopsy and immunohistochemistry findings were consistent with temporary tracheostoma’s metastasis of the rectal adenocarcinoma. The patient received palliative radiotherapy and died of systemic progression of the disease. Conclusions The patients with history of primary cancer of any origin and exophytic proliferating changes around the tracheostoma require an appropriate diagnostic work-up including a biopsy. The type of treatment depends on the extent of the disease, previous therapy and general condition of the patient. PMID:25435853

  12. Vertebral hemangioma coincident with metastasis of colon adenocarcinoma.

    PubMed

    Zapałowicz, Krzysztof; Bierzyńska-Macyszyn, Grażyna; Stasiów, Bartłomiej; Krzan, Aleksandra; Wierzycka, Beata; Kopycka, Anna

    2016-03-01

    The authors report on colon cancer metastasis to the L-3 vertebra, which had been previously found to be involved by an asymptomatic hemangioma. A 61-year-old female patient was admitted after onset of lumbar axial pain and weakness of the right quadriceps muscle. Her medical history included colon cancer that had been diagnosed 3 years earlier and was treated via a right hemicolectomy followed by chemotherapy. Presurgical imaging revealed an asymptomatic hemangioma in the L-3 vertebral body. Computed tomography and MRI of the spine were performed after admission and revealed a hemangioma in the L-3 vertebral body as well as a soft-tissue mass protruding from the L-3 vertebral body to the spinal canal. Treatment consisted of vertebroplasty of the hemangioma, left L-3 hemilaminectomy, and removal of the pathological mass from the spinal canal and the L-3 vertebral body. Histopathological examination revealed the presence of colon cancer metastasis and a hemangioma in the same vertebra.

  13. Neuroendocrine carcinoma of the pancreas with soft tissue metastasis.

    PubMed

    Chen, Jie; Zheng, Qi; Yang, Zhe; Huang, Xin-Yu; Yuan, Zhou; Tang, Juan

    2012-12-07

    Neuroendocrine carcinoma (NEC) of the pancreas is rare. We report the case of a 34-year-old man with pancreatic NEC with soft tissue metastasis. The patient presented with right upper abdominal discomfort. Computed tomography revealed a low-density heterogeneous mass in the tail and body of the pancreas that encroached on the greater curvature of the stomach and spleen. We performed exploratory laparotomy and total pancreatectomy with splenectomy and total gastrectomy. Histopathological analysis showed spindle-shaped cells with scanty cytoplasm and hyperchromatic nuclei, confirming a primary pancreatic NEC. One month after the surgery, the patient experienced leg swelling. Positron emission tomography-computed tomography revealed high uptake of fludeoxyglucose in the left leg, and the leg was amputated. Histopathological analysis confirmed metastasis of pancreatic NEC. The patient was followed up and received chemotherapy (etoposide and cisplatin). One month after amputation, the level of tumor marker neuron-specific enolase was 142.70 μg/L and computed tomography scan revealed an aggravated metastatic lesion. The patient suffered from unbearable pain and we treated him with odynolysis. Four months postoperatively, the patient died of respiratory failure.

  14. Distant metastasis of rectal adenocarcinoma in a temporary tracheostoma.

    PubMed

    Sifrer, Robert; Strojan, Primoz; Zidar, Nina; Zargi, Miha; Groselj, Ales; Krajinovic, Milena

    2014-12-01

    The temporary tracheostoma's metastases of head and neck cancer had already been reported in the literature. So far, they had been considered as regional dissemination of the malignant disease. We report a case of temporary tracheostoma's metastasis of carcinoma from non-head-and-neck primary site, what has not been reported in the literature, yet. Therefore, it is the first reported case of the systemic dissemination of malignant tumour into temporary tracheostoma. Fifty-four-year-old female patient, previously treated for a rectal adenocarcinoma, reported in our office with exophytic pink tissue masses around the temporary tracheostoma. The biopsy and immunohistochemistry findings were consistent with temporary tracheostoma's metastasis of the rectal adenocarcinoma. The patient received palliative radiotherapy and died of systemic progression of the disease. The patients with history of primary cancer of any origin and exophytic proliferating changes around the tracheostoma require an appropriate diagnostic work-up including a biopsy. The type of treatment depends on the extent of the disease, previous therapy and general condition of the patient.

  15. Sentinel lymph node metastasis in anal melanoma: a case report.

    PubMed

    Tien, Huey Y; McMasters, Kelly M; Edwards, Michael J; Chao, Celia

    2002-01-01

    Anal melanoma represents only 1% of all melanomas. Owing to delayed diagnosis and early metastasis, the prognosis is uniformly poor. Sentinel lymph node (SLN) biopsy has become the preferred method of nodal staging method for cutaneous melanoma. The role of SLN biopsy for staging of anal melanoma remains unclear. We report a 39-yr-old Caucasian woman who presented with a history of chronic hemorrhoidal pain. She noted a pedunculated peri-anal mass associated with bleeding. Upon biopsy, the lesion was found to be a 6-mm thick primary anal melanoma. There was no evidence of metastatic disease on preoperative imaging studies. She underwent wide local excision of the peri-anal site of the primary melanoma and intra-operative lymphatic mapping with both isosulfan blue and filtered technetium sulfur colloid. With the guidance a lymphoscintigram, ipsilateral inguinal sentinel lymphadenectomy identified five nodes, all of which were both "hot" and blue. One node was found to have a 1-mm metastatic deposit. Subsequently, the patient was treated with adjuvant radiation therapy to the primary site as well as to the superficial and deep inguinal nodal basins. She also received four cycles of biochemotherapy. SLN biopsy appears feasible for staging the superficial inguinal lymph nodes in patients with anal melanoma. However, the impact of SLN biopsy, early detection of occult metastasis, and adjuvant systemic and radiation therapy on the long-term survival of patients with anal melanoma is uncertain.

  16. Rectal carcinoid tumor metastasis to a skull base meningioma

    PubMed Central

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

    2016-01-01

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

  17. Osteosarcoma metastasis causing ileo-ileal intussusception.

    PubMed

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

    2013-08-12

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

  18. Crossing the endothelial barrier during metastasis.

    PubMed

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

    2013-12-01

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

  19. [Surgical managment of colorectal liver metastasis].

    PubMed

    Prot, Thomas; Halkic, Nermin; Demartines, Nicolas

    2007-06-27

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

  20. The Multiple Roles of Exosomes in Metastasis

    PubMed Central

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

    2016-01-01

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

  1. Surviving at a distance: organ specific metastasis

    PubMed Central

    Obenauf, Anna C.; Massagué, Joan

    2015-01-01

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

  2. Metastasis from oral cancer: an overview.

    PubMed

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

    2012-01-01

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

  3. The Multiple Roles of Exosomes in Metastasis.

    PubMed

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

    2017-01-02

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

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

    PubMed

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

    2015-06-01

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

  5. FN14 and GRP94 expression are prognostic/predictive biomarkers of brain metastasis outcome that open up new therapeutic strategies.

    PubMed

    Martínez-Aranda, Antonio; Hernández, Vanessa; Guney, Emre; Muixí, Laia; Foj, Ruben; Baixeras, Núria; Cuadras, Daniel; Moreno, Víctor; Urruticoechea, Ander; Gil, Miguel; Oliva, Baldo; Moreno, Ferran; González-Suarez, Eva; Vidal, Noemí; Andreu, Xavier; Seguí, Miquel A; Ballester, Rosa; Castella, Eva; Sierra, Angels

    2015-12-29

    Brain metastasis is a devastating problem in patients with breast, lung and melanoma tumors. GRP94 and FN14 are predictive biomarkers over-expressed in primary breast carcinomas that metastasized in brain. To further validate these brain metastasis biomarkers, we performed a multicenter study including 318 patients with breast carcinomas. Among these patients, there were 138 patients with metastasis, of whom 84 had brain metastasis. The likelihood of developing brain metastasis increased by 5.24-fold (95%CI 2.83-9.71) and 2.55- (95%CI 1.52-4.3) in the presence of FN14 and GRP94, respectively. Moreover, FN14 was more sensitive than ErbB2 (38.27 vs. 24.68) with similar specificity (89.43 vs. 89.55) to predict brain metastasis and had identical prognostic value than triple negative patients (p < 0.0001). Furthermore, we used GRP94 and FN14 pathways and GUILD, a network-based disease-gene prioritization program, to pinpoint the genes likely to be therapeutic targets, which resulted in FN14 as the main modulator and thalidomide as the best scored drug. The treatment of mice with brain metastasis improves survival decreasing reactive astrocytes and angiogenesis, and down-regulate FN14 and its ligand TWEAK. In conclusion our results indicate that FN14 and GRP94 are prediction/prognosis markers which open up new possibilities for preventing/treating brain metastasis.

  6. FN14 and GRP94 expression are prognostic/predictive biomarkers of brain metastasis outcome that open up new therapeutic strategies

    PubMed Central

    Martínez-Aranda, Antonio; Hernández, Vanessa; Guney, Emre; Muixí, Laia; Foj, Ruben; Baixeras, Núria; Cuadras, Daniel; Moreno, Víctor; Urruticoechea, Ander; Gil, Miguel; Oliva, Baldo; Moreno, Ferran; González-Suarez, Eva; Vidal, Noemí; Andreu, Xavier; Seguí, Miquel A.; Ballester, Rosa; Castella, Eva; Sierra, Angels

    2015-01-01

    Brain metastasis is a devastating problem in patients with breast, lung and melanoma tumors. GRP94 and FN14 are predictive biomarkers over-expressed in primary breast carcinomas that metastasized in brain. To further validate these brain metastasis biomarkers, we performed a multicenter study including 318 patients with breast carcinomas. Among these patients, there were 138 patients with metastasis, of whom 84 had brain metastasis. The likelihood of developing brain metastasis increased by 5.24-fold (95%CI 2.83–9.71) and 2.55- (95%CI 1.52–4.3) in the presence of FN14 and GRP94, respectively. Moreover, FN14 was more sensitive than ErbB2 (38.27 vs. 24.68) with similar specificity (89.43 vs. 89.55) to predict brain metastasis and had identical prognostic value than triple negative patients (p < 0.0001). Furthermore, we used GRP94 and FN14 pathways and GUILD, a network-based disease-gene prioritization program, to pinpoint the genes likely to be therapeutic targets, which resulted in FN14 as the main modulator and thalidomide as the best scored drug. The treatment of mice with brain metastasis improves survival decreasing reactive astrocytes and angiogenesis, and down-regulate FN14 and its ligand TWEAK. In conclusion our results indicate that FN14 and GRP94 are prediction/prognosis markers which open up new possibilities for preventing/treating brain metastasis. PMID:26497551

  7. Invasive cancer cells and metastasis

    NASA Astrophysics Data System (ADS)

    Mierke, Claudia Tanja

    2013-12-01

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

  8. Low-dose methotrexate inhibits lung metastasis and lengthens survival in rat osteosarcoma.

    PubMed

    Tomoda, Ryota; Seto, Masashi; Hioki, Yasunari; Sonoda, Jun; Matsumine, Akihiko; Kusuzaki, Katsuyuki; Uchida, Atsumasa

    2005-01-01

    Lung metastasis is the most crucial event affecting the treatment of osteosarcoma and is dependent on tumor angiogenesis. To improve the prognosis for patients with osteosarcoma, prevention of lung metastasis is essential. Low-dose methotrexate is a useful drug for treating a variety of diseases. Low-dose methotrexate reportedly plays a role in antiangiogenesis for the synovial blood vessels in rheumatoid arthritis. However, whether low-dose methotrexate is correlated with tumor angiogenesis and metastasis is unclear. We investigated the inhibitory effect of methotrexate on lung metastasis in a rat osteosarcoma cell line with high metastatic potential, S-SLM. Two weeks after inoculation of S-SLM cells into male Fischer 344 rats, low-dose methotrexate (1.2 mg/kg once or twice a week) or saline was intraperitonealy injected for 4 weeks and the antimetastatic effect was evaluated. Low-dose methotrexate significantly reduced the number of lung metastatic nodules and the wet weight of the lungs. Immunohistochemical staining showed a decrease in microvessel density in the metastatic nodules. We also evaluated the effect of methotrexate on the proliferation of endothelial cells and S-SLM osteosarcoma cells in vitro. Methotrexate significantly inhibited the proliferation of endothelial cells at a lower concentration than that of S-SLM osteosarcoma cells. These data suggest that low-dose methotrexate inhibited lung metastasis of osteosarcoma through its antiangiogenic activity. Our results indicate that low-dose methotrexate is a promising drug for tumor dormancy therapy in patients with osteosarcoma and lung metastasis.

  9. Atorvastatin inhibits RhoC function and limits head and neck cancer metastasis

    PubMed Central

    Islam, Mozaffarul; Sharma, Smita; Kumar, Bhavna; Teknos, Theodoros N.

    2015-01-01

    SUMMARY Objective RhoC oncogene is a well characterized marker of metastasis in a majority of invasive cancers, including HNSCC. Elevated RhoC expression has been found to be associated with distant metastasis. Statins are a class of drugs that are used to reduce cholesterol levels by inhibiting HMG-CoA reductase activity which in turns prevents mevalonate synthesis, which is a precursor for synthesis of cholesterol and prenylation. Interestingly, the proper function of Rho proteins depends on prenylation. Significantly, it has been reported that metastasis in human melanoma can be reduced by atorvastatin which inhibits RhoC activity by preventing its geranylgeranylation. Given that RhoC is a key oncogene involved in metastasis, we hypothesized Atorvastatin can reduce head and neck metastasis by inhibiting RhoC activity. Methods In vitro and in vivo studies were carried out to evaluate the ability of Atorvastatin to inhibit RhoC function and HNSCC metastasis. Cell motility, proliferation, cell invasion, and colony formation assays were performed according to the standard protocols. Results Atorvastatin treatment significantly reduced the active form of RhoC in vitro and diminished cell motility, invasion, proliferation and colony formation. Importantly, we observed a significant decrease in p-ERK1/2 and p-STAT3 in Atorvastatin treated cell lines. In vivo experiments revealed inhibition of angiogenesis and lung metastases with Atorvastatin therapy. Conclusions This study is the first of its kind to establish a potential role of Atorvastatin in head and neck cancer therapy. These findings suggest that Atorvastatin can be a potential low risk adjuvant therapy to minimize metastases in aggressive forms of HNSCC. PMID:23648017

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

    PubMed

    Mendt, Mayela; Cardier, Jose E

    2017-08-01

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

  11. Port site metastasis after robotic-assisted laparoscopic hysterectomy for uterine cervical cancer: a case report and literature review.

    PubMed

    Kim, Bokyong; Huh, Seung Jae; Kim, Byoung-Gie

    2013-12-01

    The incidence of port site metastasis after robotic-assisted laparoscopic surgery for cervical cancer is not well known. According to recent studies of gynecological malignancies, the reported incidence is low and comparable to the results of conventional laparoscopic surgery. Here, we report the case of a patient who suffered port site metastasis after robotic-assisted laparoscopic hysterectomy for stage IB1 uterine cervical cancer. The current case is, as we know, only the third episode of port site metastasis after robotic-assisted laparoscopic surgery for cervical cancer documented in the medical literature. Following diagnosis of the port site metastasis, the patient was treated with concurrent chemoradiotherapy (CRT) and experienced a remarkable early response. We reviewed the patient's medical chart and imaging studies, and searched the Medline database to evaluate the incidence, prognosis and treatment outcomes of such cases of port site metastasis in uterine cervical cancer patients. CRT resulted in a rapid decrease in tumor size and relief of abdominal pain in our patient. CRT might be considered as a salvage or palliative modality in patients with port site metastasis and/or locoregional recurrence. Copyright © 2013. Published by Elsevier B.V.

  12. Alectinib for choroidal metastasis in a patient with crizotinib-resistant ALK rearranged positive non-small cell lung cancer.

    PubMed

    Okuma, Yusuke; Tanaka, Yuichiro; Kamei, Tina; Hosomi, Yukio; Okamura, Tatsuru

    2015-01-01

    Choroidal metastasis is rare in cancer patients. Small molecules of molecular targeted agents for lung cancer with actionable mutations were reported to be palliated for symptoms caused by choroidal metastasis. Visual disturbance by choroidal metastasis significantly decreases quality of life during the patient's remaining lifespan; therefore, radiotherapy or laser photocoagulation is proposed with consensus. However, improvement in survival with matched molecular targeted agents for oncogenic driver mutations reminds us to also be concerned with late treatment toxicities. A 30-year-old female patient previously treated with crizotinib harboring ALK rearranged non-small cell lung cancer complained of visual disturbance, fever, and bone pains undergoing anti-PD-1 antibody treatment. A decreased proportion of ALK fusion was demonstrated by fluorescence in situ hybridization in liver metastasis compared to the primary site in a chemo-naïve state. She was diagnosed with low vision, choroidal metastasis and retinal detachment. Therefore, she started alectinib treatment and both her ocular and systemic symptoms were palliated in a week. Later, she temporarily discontinued alectinib because of skin rash although the choroidal metastasis and retinal detachment resolved and she regained low vision completely at 2 weeks. She obtained partial response with alectinib for more than 5 months after recovering from skin rash.

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

    PubMed Central

    Jiang, Canhua; Jin, Shufang; Jiang, Zhisheng; Wang, Jie

    2016-01-01

    Objective To investigate the possible mechanisms and effects of silibinin (SIL) on the proliferation and lung metastasis of human lung high metastasis cell line of salivary gland adenoid cystic carcinoma (ACC-M). Methods A methyl thiazolyl tetrazolium assay was performed to detect the inhibitory effects of SIL on the proliferation of ACC-M cells in vitro. Fluorescence microscopy and transmission electron microscopy were used to observe the autophagic process. Western blot was performed to detect the expression of microtube-related protein 1 light-chain 3 (LC3). An experimental adenoid cystic carcinoma (ACC) lung metastasis model was established in nude mice to detect the impacts of SIL on lung weight and lung cancer nodules. Immunohistochemistry was used to detect the expressions of LC3 in human ACC samples and normal salivary gland tissue samples. Results SIL inhibited the proliferation of ACC-M cells in a dose- and time-dependent manner, and inductively increased the autophagic bodies in ACC-M cells. Furthermore, SIL could increase the expression of LC3 in ACC-M cells and promote the conversion of LC3-I into LC3-II in a dose- and time-dependent manner. In the ACC lung metastasis model, the lung weight and left and right lung nodules in the SIL-treated group were significantly less than those in the control group (P<0.05). The expressions of LC3-I and LC3-II as well as the positive expression rate of LC3 (80%) significantly increased, but the positive expression of LC3 in human ACC (42.22%) reduced significantly. Conclusion SIL could inhibit the proliferation and lung metastasis of ACC-M cells by possibly inducing tumor cells autophagy. PMID:27822066

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

    PubMed

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

    2012-11-01

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

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

    PubMed

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

    2009-03-01

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

  16. Metastasis Suppressors and Their Roles in Breast Carcinoma

    PubMed Central

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

    2007-01-01

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

  17. Bioluminescence imaging of bone metastasis in rodents.

    PubMed

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

    2012-01-01

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

  18. Opening a Chromatin Gate to Metastasis

    PubMed Central

    Minna, John D.; Johnson, Jane E.

    2017-01-01

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

  19. Opening a Chromatin Gate to Metastasis.

    PubMed

    Minna, John D; Johnson, Jane E

    2016-07-14

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

  20. Stereotactic radiosurgery of brain metastasis from melanoma.

    PubMed

    Marchan, Edward M; Sheehan, Jason

    2012-01-01

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

  1. Presumed choroidal metastasis of Merkel cell carcinoma

    SciTech Connect

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

    1990-05-01

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

  2. Cerebral metastasis from malignant pleural mesothelioma.

    PubMed

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

    2013-09-26

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

  3. Breast cancer metastasis and the lymphatic system

    PubMed Central

    RAHMAN, MUNAZZAH; MOHAMMED, SULMA

    2015-01-01

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

  4. Altered Tumor-Cell Glycosylation Promotes Metastasis

    PubMed Central

    Häuselmann, Irina; Borsig, Lubor

    2014-01-01

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

  5. Neural Regulation of Breast Cancer Metastasis

    DTIC Science & Technology

    2009-10-01

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

  6. Three-dimensional context regulation of metastasis

    PubMed Central

    Erler, Janine T.; Weaver, Valerie M.

    2009-01-01

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

  7. Rapamycin Promotes Mouse 4T1 Tumor Metastasis that Can Be Reversed by a Dendritic Cell-Based Vaccine.

    PubMed

    Lin, Tien-Jen; Liang, Wen-Miin; Hsiao, Pei-Wen; M S, Pradeep; Wei, Wen-Chi; Lin, Hsin-Ting; Yin, Shu-Yi; Yang, Ning-Sun

    2015-01-01

    Suppression of tumor metastasis is a key strategy for successful cancer interventions. Previous studies indicated that rapamycin (sirolimus) may promote tumor regression activity or enhance immune response against tumor targets. However, rapamycin also exhibits immunosuppressant effects and is hence used clinically as an organ transplantation drug. We hypothesized that the immunosuppressive activities of rapamycin might also negatively mediate host immunity, resulting in promotion of tumor metastasis. In this study, the effects of rapamycin and phytochemical shikonin were investigated in vitro and in vivo in a 4T1 mouse mammary tumor model through quantitative assessment of immunogenic cell death (ICD), autophagy, tumor growth and metastasis. Tumor-bearing mice were immunized with test vaccines to monitor their effect on tumor metastasis. We found that intraperitoneal (ip) administration of rapamycin after a tumor-resection surgery drastically increased the metastatic activity of 4T1 tumors. Possible correlation of this finding to human cancers was suggested by epidemiological analysis of data from Taiwan's National Health Insurance Research Database (NHIRD). Since our previous studies showed that modified tumor cell lysate (TCL)-pulsed, dendritic cell (DC)-based cancer vaccines can effectively suppress metastasis in mouse tumor models, we assessed whether such vaccines may help offset this rapamycin-promoted metastasis. We observed that shikonin efficiently induced ICD of 4T1 cells in culture, and DC vaccines pulsed with shikonin-treated TCL (SK-TCL-DC) significantly suppressed rapamycin-enhanced metastasis and Treg cell expansion in test mice. In conclusion, rapamycin treatment in mice (and perhaps in humans) promotes metastasis and the effect may be offset by treatment with a DC-based cancer vaccine.

  8. Chondrosarcoma metastasis in the thyroid gland: a case report

    PubMed Central

    2014-01-01

    Introduction Chondrosarcoma metastases in the thyroid gland are exceptional. To the best of our knowledge, only two cases have been previously reported in the literature. Here we report the third case. Case presentation We report the case of a 51-year-old Arab woman who presented in 2011 with a diaphyseal chondrosarcoma of her right tibia treated by surgery. In the last quarter of 2013, she presented a hard mass in her thyroid gland with dyspnea and a right laryngeal paresis. She underwent a debulking surgery with tracheostomy in order to prevent difficulty in respiration. The final pathology revealed the diagnosis of a chondrosarcoma metastasis within her thyroid gland. She died several days later. Conclusions Even if primary and metastatic chondrosarcomas of the thyroid gland are exceptional, they should be considered in the differential diagnosis of thyroid gland masses. The prognosis is poor but surgery may help preserve quality of life. PMID:24886665

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

    PubMed

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

    2013-12-01

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

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

    PubMed Central

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

    2016-01-01

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

  11. Colon Mass as a Secondary Metastasis from Cholangiocarcinoma: A Diagnostic and Therapeutic Dilemma.

    PubMed

    Niazi, Azfar; Saif, Muhammad W

    2016-07-22

    Cholangiocarcinoma (bile ducts cancer) is a rare and aggressive form of cancer. It metastasizes frequently to liver, peritoneum, and lungs. Colon metastasis is extremely uncommon. We report here a 70-year-old male who was diagnosed with cholangiocarcinoma for which he underwent a Whipple procedure. Fifteen months later, a CT scan revealed mural thickening in the colon; this was supplemented with a PET scan, which confirmed this mass. Histological diagnosis of metastatic cholangiocarcinoma to the colon was made and the patient was treated with chemotherapy. Although rare, cholangiocarcinoma metastasis can be found in the colon. A high index of suspicion is required to diagnose and treat early. More cases need to be reported to find out further about the prognosis of the disease.

  12. Lymphangiogenesis and Lymphatic Metastasis in Breast Cancer

    PubMed Central

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

    2009-01-01

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

  13. Genomic Alteration During Metastasis of Lung Adenocarcinoma.

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2011-01-01

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

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

    PubMed

    Kawaguchi, Takanori

    2016-01-01

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

  16. Selective activator protein-1 inhibitor T-5224 prevents lymph node metastasis in an oral cancer model.

    PubMed

    Kamide, Daisuke; Yamashita, Taku; Araki, Koji; Tomifuji, Masayuki; Tanaka, Yuya; Tanaka, Shingo; Shiozawa, Shunichi; Shiotani, Akihiro

    2016-05-01

    Activator protein-1 (AP-1) is a transcriptional factor that regulates the expression of various genes associated with tumor invasion and migration. The purpose of our study was to assess the therapeutic effects of a novel selective AP-1 inhibitor, T-5224, in preventing lymph node metastasis in head and neck squamous cell carcinoma (HNSCC) in an orthotopic mouse model. We assessed the effect of T-5224 on HNSCC cell invasion, migration, proliferation, and MMP activity by carrying out an in vitro study using an invasion assay, scratch assay, WST-8 assay, and gelatin zymography. We also observed morphological changes in HNSCC cells by time-lapse microscopy. Furthermore, cervical lymph node metastasis was assessed using an orthotopic tumor model of human oral squamous cell carcinoma cells (HSC-3-M3) injected in the tongue of a BALB/c nude mouse. T-5224 (150 mg/kg) or vehicle was given orally every day for 4 weeks. Animals were killed and assessed for lymph node metastasis by H&E staining of resected lymph nodes. T-5224 significantly inhibited the invasion, migration, and MMP activity of HNSCC cells in a dose-dependent manner; there was no significant influence on cell proliferation. The antimetastatic effect of T-5224 was also confirmed in our animal study. The rate of cervical lymph node metastasis in the model was 40.0% in the T-5224-treated group (n = 30) versus 74.1% in the vehicle-treated group (n = 27; P < 0.05). In conclusion, T-5224 inhibited the invasion and migration of HNSCC cells in vitro, and prevented lymph node metastasis in head and neck cancer in an animal model. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  17. Tamoxifen inhibits ER-negative breast cancer cell invasion and metastasis by accelerating Twist1 degradation.

    PubMed

    Ma, Gang; He, Jianjun; Yu, Yang; Xu, Yixiang; Yu, Xiaobin; Martinez, Jarrod; Lonard, David M; Xu, Jianming

    2015-01-01

    Twist1 is a transcription factor driving epithelial-mesenchymal transition, invasion and metastasis of breast cancer cells. Mice with germ-line Twist1 knockout are embryonic lethal, while adult mice with inducible Twist1 knockout have no obvious health problems, suggesting that Twist1 is a viable therapeutic target for the inhibition of invasion and metastasis of breast cancer in adult patients. In this study, we expressed a luciferase protein or a Twist1-luciferase fusion protein in HeLa cells as part of a high throughput system to screen 1280 compounds in the Library of Pharmacologically Active Compounds (LOPAC) from Sigma-Aldrich for their effects on Twist1 protein expression. One of the most interesting compounds identified is tamoxifen, a selective estrogen receptor (ER) modulator used to treat ER-positive breast cancer. Tamoxifen treatment significantly accelerated Twist1 degradation in multiple cell lines including HEK293 human kidney cells, 4T1 and 168FARN mouse mammary tumor cells with either ectopically or endogenously expressed Twist1. Tamoxifen-induced Twist1 degradation could be blocked by the MG132 proteasome inhibitor, suggesting that tamoxifen induces Twist1 degradation through the ubiquitination-proteasome pathway. However, tamoxifen-induced Twist1 degradation was independent of Twist1 mRNA expression, estrogen signaling and MAPK-mediated Twist1 phosphorylation in these cells. Importantly, tamoxifen also significantly inhibited invasive behavior in Matrigel and lung metastasis in SCID-bg mice of ER-negative 4T1 mammary tumor cells, which depend on endogenous Twist1 to invade and metastasize. These results indicate that tamoxifen can significantly accelerate Twist1 degradation to suppress cancer cell invasion and metastasis, suggesting that tamoxifen can be used not only to treat ER-positive breast cancers but also to reduce Twist1-mediated invasion and metastasis in ER-negative breast cancers.

  18. Boron neutron capture therapy for recurrent oral cancer and metastasis of cervical lymph node.

    PubMed

    Kimura, Y; Ariyoshi, Y; Shimahara, M; Miyatake, S; Kawabata, S; Ono, K; Suzuki, M; Maruhashi, A

    2009-07-01

    We treated 6 patients with recurrent oral cancer and metastasis to the cervical lymph nodes after conventional treatments in 5 and non-conventional in 1 using BNCT, and herein report our results. The clinical response in our patients ranged from CR to PD. In 5 cases, spontaneous pain decreased immediately after BNCT. Three of the 6 are alive at the time of writing and we found that BNCT contributed to QOL improvement in all.

  19. The Role of Crk Adaptor Proteins in Breast Tumorigenesis and Bone Metastasis

    DTIC Science & Technology

    2012-09-01

    signature and the basal molecular subtypes found within breast cancer cell lines. Heatmap of the Crk signature in the Neve breast cancer cell line...metastasis to bone. Cancer Cell 2003, 3:537-549. 16. Minn AJ, Gupta GP, Siegel PM, Bos PD , Shu W, Giri DD, Viale A, Olshen AB, Gerald WL, Massague J...prognosis using molecular profiling in estrogen receptor-positive breast cancer treated with tamoxifen. BMC Genomics 2008, 9:239. 27. Neve RM, Chin K

  20. Melatonin decreases breast cancer metastasis by modulating Rho-associated kinase protein-1 expression.

    PubMed

    Borin, Thaiz Ferraz; Arbab, Ali Syed; Gelaleti, Gabriela Bottaro; Ferreira, Lívia Carvalho; Moschetta, Marina Gobbe; Jardim-Perassi, Bruna Victorasso; Iskander, A S M; Varma, Nadimpalli Ravi S; Shankar, Adarsh; Coimbra, Verena Benedick; Fabri, Vanessa Alves; de Oliveira, Juliana Garcia; Zuccari, Debora Aparecida Pires de Campos

    2016-01-01

    The occurrence of metastasis, an important breast cancer prognostic factor, depends on cell migration/invasion mechanisms, which can be controlled by regulatory and effector molecules such as Rho-associated kinase protein (ROCK-1). Increased expression of this protein promotes tumor growth and metastasis, which can be restricted by ROCK-1 inhibitors. Melatonin has shown oncostatic, antimetastatic, and anti-angiogenic effects and can modulate ROCK-1 expression. Metastatic and nonmetastatic breast cancer cell lines were treated with melatonin as well as with specific ROCK-1 inhibitor (Y27632). Cell viability, cell migration/invasion, and ROCK-1 gene expression and protein expression were determined in vitro. In vivo lung metastasis study was performed using female athymic nude mice treated with either melatonin or Y27832 for 2 and 5 wk. The metastases were evaluated by X-ray computed tomography and single photon emission computed tomography (SPECT) and by immunohistochemistry for ROCK-1 and cytokeratin proteins. Melatonin and Y27632 treatments reduced cell viability and invasion/migration of both cell lines and decreased ROCK-1 gene expression in metastatic cells and protein expression in nonmetastatic cell line. The numbers of 'hot' spots (lung metastasis) identified by SPECT images were significantly lower in treated groups. ROCK-1 protein expression also was decreased in metastatic foci of treated groups. Melatonin has shown to be effective in controlling metastatic breast cancer in vitro and in vivo, not only via inhibition of the proliferation of tumor cells but also through direct antagonism of metastatic mechanism of cells rendered by ROCK-1 inhibition. When Y27632 was used, the effects were similar to those found with melatonin treatment.

  1. Melatonin decreases breast cancer metastasis by modulating Rho-associated kinase protein-1 expression

    PubMed Central

    Borin, Thaiz Ferraz; Arbab, Ali Syed; Gelaleti, Gabriela Bottaro; Ferreira, Lívia Carvalho; Moschetta, Marina Gobbe; Jardim-Perassi, Bruna Victorasso; Iskander, ASM; Varma, Nadimpalli Ravi S.; Shankar, Adarsh; Coimbra, Verena Benedick; Fabri, Vanessa Alves; de Oliveira, Juliana Garcia; de Campos Zuccari, Debora Aparecida Pires

    2016-01-01

    The occurrence of metastasis, an important breast cancer prognostic factor, depends on cell migration/invasion mechanisms, which can be controlled by regulatory and effector molecules such as Rho-associated kinase protein (ROCK-1). Increased expression of this protein promotes tumor growth and metastasis, which can be restricted by ROCK-1 inhibitors. Melatonin has shown oncostatic, antimetastatic, and anti-angiogenic effects and can modulate ROCK-1 expression. Metastatic and nonmetastatic breast cancer cell lines were treated with melatonin as well as with specific ROCK-1 inhibitor (Y27632). Cell viability, cell migration/invasion, and ROCK-1 gene expression and protein expression were determined in vitro. In vivo lung metastasis study was performed using female athymic nude mice treated with either melatonin or Y27832 for 2 and 5 wk. The metastases were evaluated by X-ray computed tomography and single photon emission computed tomography (SPECT) and by immunohistochemistry for ROCK-1 and cytokeratin proteins. Melatonin and Y27632 treatments reduced cell viability and invasion/migration of both cell lines and decreased ROCK-1 gene expression in metastatic cells and protein expression in nonmetastatic cell line. The numbers of ‘hot’ spots (lung metastasis) identified by SPECT images were significantly lower in treated groups. ROCK-1 protein expression also was decreased in metastatic foci of treated groups. Melatonin has shown to be effective in controlling metastatic breast cancer in vitro and in vivo, not only via inhibition of the proliferation of tumor cells but also through direct antagonism of metastatic mechanism of cells rendered by ROCK-1 inhibition. When Y27632 was used, the effects were similar to those found with melatonin treatment. PMID:26292662

  2. Calvarial metastasis from endometrial carcinoma: Case report and review of the literature

    PubMed Central

    Cecchi, Paolo C.; Kluge, Reinhard; Schwarz, Andreas

    2014-01-01

    Hematogenous bone metastases from endometrial carcinoma are not frequent and their treatment is a matter of debate. We describe an extremely rare case of calvarial metastasis from endometrial carcinoma in an 80-year-old woman treated by means of one-step surgical radical resection and heterologous cranioplasty, along with a review of the literature regarding epidemiology, clinico-radiological features, prognosis, and management of skull metastases. PMID:25685234

  3. Superselective Internal Radiation With Yttrium-90 Microspheres in the Management of a Chemorefractory Testicular Liver Metastasis

    SciTech Connect

    Sideras, Panagiotis A.; Sofocleous, Constantinos T. Brody, Lynn A.; Siegelbaum, Robert H.; Shah, Rajesh P.; Taskar, Neeta-Pandit

    2012-04-15

    We treated a patient with biopsy-proven, chemotherapy-resistant testicular cancer liver metastasis using Y-90 selective internal radiation treatment. We chose yttrium-90 rather than surgery and ablation due to tumor location and size as well as the patient's clinical history. The result was marked tumor response by positron emission tomography and computed tomography as well as significant improvement of the patient's quality of life accompanied by a substantial decrease of his tumor markers.

  4. The effect of human tissue factor pathway inhibitor-2 on the growth and metastasis of fibrosarcoma tumors in athymic mice.

    PubMed

    Chand, Hitendra Singh; Du, Xin; Ma, Duan; Inzunza, Hector David; Kamei, Shintaro; Foster, Donald; Brodie, Steven; Kisiel, Walter

    2004-02-01

    Human tissue factor pathway inhibitor-2 (TFPI-2) is a matrix-associated Kunitz inhibitor that inhibits the plasmin- and trypsin-mediated activation of zymogen matrix metalloproteinases involved in tumor progression, invasion, and metastasis. To directly assess its role in tumor growth and metastasis in vivo, we stably transfected HT-1080 fibrosarcoma cells expressing either fully active wild-type human TFPI-2 (WT) or inactive R24Q TFPI-2 (QT) and examined their ability to form tumors and metastasize in athymic mice in comparison to mock-transfected cells (MT). MT and QT fibrosarcoma tumors grew 2 to 3 times larger than WT tumors. Tumor metastasis was confined to the lung and was observed in 75% of mice treated with either MT or QT cells, whereas only 42% of mice treated with WT cells developed lung metastases. Real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analyses of each tumor group revealed 3- to 6-fold lower levels of murine vascular endothelial growth factor gene expression in WT tumors in relation to either MT or QT tumors. Comparative tumor gene expression analysis revealed that several human genes implicated in oncogenesis, invasion, metastasis, apoptosis, and angiogenesis had significantly altered levels of expression in WT tumors. Our collective data demonstrate that secretion of inhibitory TFPI-2 by a highly metastatic tumor cell markedly inhibits its growth and metastasis in vivo by regulating pericellular extracellular matrix (ECM) remodeling and angiogenesis.

  5. Brain metastasis in pediatric extracranial solid tumors: survey and literature review.

    PubMed

    Kebudi, Rejin; Ayan, Inci; Görgün, Omer; Ağaoğlu, Fulya Yaman; Vural, Sema; Darendeliler, Emin

    2005-01-01

    Brain is a rare site of metastasis in most extracranial pediatric solid tumors. The aim of this study is to investigate the incidence, treatment, prognosis of brain metastasis in extracranial pediatric malignant tumors in a single institution and to review the literature. From September 1989 to December 2002, 1100 children treated in the Division of Pediatric Oncology, Oncology Institute, Istanbul University. Patients with parenchymal metastases in the brain were assessed. Sixteen (10 female, 6 male) of 1100 patients (1.45%) with extracranial solid tumors developed brain metastases. The median age of the patients was 10.5 (1-16) years. The diagnosis was sarcomas in 12 patients: 5 osteosarcomas, 4 Ewing's sarcoma family tumors, 1 rhabdomyosarcoma, 1 clear cell sarcoma of the soft tissue, 1 alveolar soft part sarcoma. Two patients had Wilms' tumor and two had germ cell tumors. Four patients (25%) had brain metastasis at diagnosis. Twelve (75%) developed brain metastasis during therapy or relapse at a median duration of 16 (1-70) months from initial diagnosis. All patients had metastases to various sites, mostly lung, at the time the brain metastases were detected. Treatment included surgery, followed by postoperative radiotherapy (RT) and chemotherapy (CT) in 1, S and RT in 1, S in 1, RT and CT in 6, RT in 1, CT in 1 and no treatment in 5. Only one patient with alveolar soft part sarcoma is alive with disease 20 months from diagnosis of brain metastasis. All other patients died at a median time of 2 months (2 days-6 months) from the time of brain metastasis. Children with metastatic cancer who develop headaches or any other neurologic symptom should be investigated for possible brain metastasis. Although, the outcome for these patients is dismal in this series and in the literature; reports of long term survival in a few cases with Wilms' tumor, osteosarcoma and alveolar soft

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

    PubMed

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

    2017-09-01

    Current therapy for rheumatoid arthritis (RA) relies on global suppression of the immune response or specific blockade of inflammatory cytokines. However, it is unclear how immunosuppressants affect patients w