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Sample records for metastatic brain cancers

  1. Metastatic Cancer

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    Metastatic cancer is cancer that spreads from its site of origin to another part of the body. Learn how cancer spreads, possible symptoms, common sites where cancer spreads, and how to find out about treatment options.

  2. Gene expression profiles help identify the Tissue of Origin for metastatic brain cancers

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    VandenBerg Scott R

    2010-04-01

    Full Text Available Abstract Background Metastatic brain cancers are the most common intracranial tumor and occur in about 15% of all cancer patients. In up to 10% of these patients, the primary tumor tissue remains unknown, even after a time consuming and costly workup. The Pathwork® Tissue of Origin Test (Pathwork Diagnostics, Redwood City, CA, USA is a gene expression test to aid in the diagnosis of metastatic, poorly differentiated and undifferentiated tumors. It measures the expression pattern of 1,550 genes in these tumors and compares it to the expression pattern of a panel of 15 known tumor types. The purpose of this study was to evaluate the performance of the Tissue of Origin Test in the diagnosis of primary sites for metastatic brain cancer patients. Methods Fifteen fresh-frozen metastatic brain tumor specimens of known origins met specimen requirements. These specimens were entered into the study and processed using the Tissue of Origin Test. Results were compared to the known primary site and the agreement between the two results was assessed. Results Fourteen of the fifteen specimens produced microarray data files that passed all quality metrics. One originated from a tissue type that was off-panel. Among the remaining 13 cases, the Tissue of Origin Test accurately predicted the available diagnosis in 12/13 (92.3% cases. Discussion This study demonstrates the accuracy of the Tissue of Origin Test when applied to predict the tissue of origin of metastatic brain tumors. This test could be a very useful tool for pathologists as they classify metastatic brain cancers.

  3. A lung cancer case with numerous calcified metastatic nodules of the brain

    International Nuclear Information System (INIS)

    Fukuda, Y.; Homma, T.; Kohga, H.; Uki, J.; Shisa, H.

    1988-01-01

    A case of pulmonary adenocarcinoma with numerous calcified metastatic nodules of the brain is reported. Autopsy revealed about 400 metastatic nodules in the central nervous system, most of which were calcified. (orig.)

  4. Risk factors for brain metastases in patients with metastatic colorectal cancer

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    Christensen, Troels Dreier; Palshof, Jesper Andreas; Larsen, Finn Ole

    2017-01-01

    BACKGROUND: Brain metastases (BM) from colorectal cancer (CRC) are rare, but the incidence is suspected to rise as treatment of metastatic (m) CRC improves. The aim of this study was to identify possible biological and clinical characteristics at initial presentation of mCRC that could predict......, the risk of developing BM was significantly increased in patients with rectal cancer (HR = 3.9; 95% CI = 1.2-13.3), metachronous metastatic disease (HR = 2.3; 95% CI = 1.2-4.4) and lung metastases (HR = 4.2; 95% CI = 2.2-7.9). On multivariate cox regression analysis only lung metastases were significantly...... associated BM (HR = 3.5; 95% CI = 1.8-6.8). None of the investigated mutations were associated with BM. CONCLUSION: The incidence of BM was 8.8% in patients with mCRC who received third-line therapy. The most important risk factor for developing BM was lung metastases. Furthermore, rectal cancer...

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

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    M. Suzuki

    2014-01-01

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

  6. Brain metastases in patients who receive trastuzumab-containing chemotherapy for HER2-overexpressing metastatic breast cancer

    International Nuclear Information System (INIS)

    Ono, Makiko; Ando, Masashi; Yunokawa, Mayu

    2009-01-01

    Recently, a high rate of brain metastases has been reported among patients with human epidermal growth factor receptor (HER2)-overexpressing metastatic breast cancer who were treated with trastuzumab. The present study examined risk factors for the development of brain metastasis in patients with HER2-overexpressing breast cancer who were treated with trastuzumab. We retrospectively reviewed 204 patients with HER-2-overexpressing breast cancer who were treated with a trastuzumab-containing regimen between 1999 and 2006. Patients with clinical symptoms were diagnosed as having brain metastases when brain magnetic resonance imaging (MRI) or a computed tomography (CT) scan revealed positive findings for brain metastases. The median follow-up time of this cohort was 53.6 months. Among the patients who received a trastuzumab-containing regimen, 74 patients (36.3%) developed brain metastases. The median survival from the diagnosis of brain metastases was 13.5 months (95% confidence interval [CI], 12.2-14.7 months). The median time interval between the beginning of trastuzumab treatment and the diagnosis of brain metastases was 13.6 months (range, 0.0-45.8 months). Among patients with brain metastases, the median overall survival period was 39 months. A multivariate logistic regression analysis showed that age (≤50 years), recurrent breast cancer, and liver metastases were significant risk factors for the development of brain metastases. Patients with HER2-overexpressing breast cancer treated with trastuzumab had a high incidence of brain metastases (36.3%). Routine screening for brain metastases 1 year after the start of trastuzumab treatment, may be warranted in younger patients (≤50 years) who had recurrent breast cancer with liver metastases. (author)

  7. Treatment of metastatic brain lesion

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    A. M. Zaytsev

    2015-01-01

    Full Text Available Objective. Increasing survival in patients with secondary brain damage, and identifying the factors of favorable and adverse prognosis.Material and method. In P. A. Hertsen Moscow Oncology Research Institute from 2007 to 2013 there were treated 268 patients with brain metastases. The mean age was 55.8 years (from 24 to 81 years. Metastases of colorectal cancer identified in 7.8%, cases of lung cancer in 34%, melanoma 9.3 %, breast cancer in 26%, kidney cancer in 11%, with non-identified primary tumor in 4.5%, other tumors accounted for 6.7%. Solitary metastasis was diagnosed in 164 (61,19% patients, oligometastasis (2-3 - 72 (26,87% patients with polymetastasis (more than 3 – 32 (11,94% patients. In 106 (39,55% of patients with brain metastases it was the only manifestation of the generalization process. To control the radical removal of the tumor in 93 (34,7% patients we used the method of fluorescence navigation (FN with the drug Alasens. In 66 (24,6% patients intraoperatively was held a session of photodynamic therapy (PDT. In 212 (79,1% cases, the removal of metastasis performed totally, 55 (20,9% patients stated Subtotal removal.Results. The observation period for the patients ranged from 3 to 79 months. Survival median among the entire group of patients with metastatic brain lesion was 12 months. Overall survival was significantly dependent on RPA class, the volume of postoperative treatment, histological type of primary tumor, number of intracerebral metastases and the timing of the relapse-free period.Conclusions. Factors that affects the overall survival are the features of the histology of the primary lesion, multiplicity of metastatic lesions, RPA class and the synchronous nature of the metastasis. The median of overall survival of patients who did not receive after surgical treatment of a particular type of therapy was only 4 months. If to use the combined treatment (surgical treatment with the irradiation of the whole brain median

  8. Targeting metastatic breast cancer with ANG1005, a novel peptide-paclitaxel conjugate that crosses the blood-brain-barrier (BBB

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    Fei Li

    2017-03-01

    Full Text Available We devoted this short interview piece with Dr Shou-Ching Tang at Augusta University to feature some promising results from a clinical phase II trial on a novel brain-penetrating peptide-paclitaxel-conjugate, ANG1005, in treating brain metastatic breast cancer. These results were presented by Dr. Tang at the recent annual meeting of the European Society for Medical Oncology (ESMO 2016 Congress. This development heralds an important step forward towards the development of effective chemotherapeutic agents, which can cross the blood-brain-barrier and effectively treat and prevent the brain metastatic cancers.

  9. The roles of microglia/macrophages in tumor progression of brain cancer and metastatic disease.

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    Wu, Shih-Ying; Watabe, Kounosuke

    2017-06-01

    Malignant brain tumors and brain metastases are highly aggressive diseases that are often resistant to treatment. Consequently, the current prognosis of patients with brain tumors and metastases is dismal. Activated microglia and macrophages are often observed in close proximity to or within the malignant tumor masses, suggesting that microglia/macrophages play an important role in brain tumor progression. Microglia, being resident macrophages of the central nervous system, form a major component of the brain immune system. They exhibit anti-tumor functions by phagocytosis and the release of cytotoxic factors. However, these microglia/macrophages can be polarized into becoming tumor-supportive and immunosuppressive cells by certain tumor-derived soluble factors, thereby promoting tumor maintenance and progression. The activated microglia/macrophages also participate in the process of tumor angiogenesis, metastasis, dormancy, and relapse. In this review, we discuss the recent literature on the dual roles of microglia/macrophages in brain tumor progression. We have also reviewed the effect of several well-known microglia/macrophages-derived molecules and signals on brain tumor progression and further discussed the potential therapeutic strategies for targeting the pro-tumor and metastatic functions of microglia/macrophages.

  10. Olaparib In Metastatic Breast Cancer

    Science.gov (United States)

    2017-12-17

    Metastatic Breast Cancer; Invasive Breast Cancer; Somatic Mutation Breast Cancer (BRCA1); Somatic Mutation Breast Cancer (BRCA2); CHEK2 Gene Mutation; ATM Gene Mutation; PALB2 Gene Mutation; RAD51 Gene Mutation; BRIP1 Gene Mutation; NBN Gene Mutation

  11. Have Changes in Systemic Treatment Improved Survival in Patients with Breast Cancer Metastatic to the Brain?

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    Carsten Nieder

    2008-01-01

    Full Text Available Newly developed systemic treatment regimens might lead to improved survival also in the subgroup of breast cancer patients that harbour brain metastases. In order to examine this hypothesis, a matched pairs analysis was performed that involved one group of patients, which were treated after these new drugs were introduced, and one group of patients, which were treated approximately 10 years earlier. The two groups were well balanced for the known prognostic factors age, KPS, extracranial disease status, and recursive partitioning analysis class, as well as for the extent of brain treatment. The results show that the use of systemic chemotherapy has increased over time, both before and after the diagnosis of brain metastases. However, such treatment was performed nearly exclusively in those patients with brain metastases that belonged to the prognostically more favourable groups. Survival after whole-brain radiotherapy has remained unchanged in patients without further active treatment. It has improved in prognostically better patients and especially patients that received active treatment, where the 1-year survival rates have almost doubled. As these patient groups were small, confirmation of the results in other series should be attempted. Nevertheless, the present results are compatible with the hypothesis that improved systemic therapy might contribute to prolonged survival in patients with brain metastases from breast cancer.

  12. Mystery of the brain metastatic disease in breast cancer patients: improved patient stratification, disease prediction and targeted prevention on the horizon?

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    Polivka, Jiri; Kralickova, Milena; Polivka, Jiri; Kaiser, Christina; Kuhn, Walther; Golubnitschaja, Olga

    2017-06-01

    The breast cancer (BC) diagnosis currently experiences the epidemic evolution with more than half of million deaths each year. Despite screening programmes applied and treatments available, breast cancer patients frequently develop distant metastases. The brain is one of the predominant sites of the metastatic spread recorded for more than 20% of BC patients, in contrast to the general population, where brain tumours are rarely diagnosed. Although highly clinically relevant, the brain tumour mystery in the cohort of breast cancer patients has not been yet adequately explained. This review summarises currently available information on the risk factors predicting brain metastases in BC patients to motivate the relevant scientific areas to explore the data/facts available and elucidate disease-specific mechanisms that are of a great clinical utility.

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

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    2016-03-01

    addition, we have streamlined and optimized tissue-clearing pipeline . We are able to multiplex staining multiple tissue markers in situ, including...8 3 1. Introduction…………………………………………………………. Among all breast cancer metastatic replaces , 30% of breast cancer-associated...continue develop our imaging platform to obtain insight on molecular mechanisms of metabolic shifting. We aim to achieve the following goals: 1

  14. MR findings of metastatic brain tumors

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    Ahn, Joong Mo; Chang, Kee Hyun; Han, Moon Hee; Cha, Sang Hoon; Ryoo, Jae Wook [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1993-05-15

    The purpose of this study is to describe the magnetic resonance imaging (MR) findings of metastatic brain tumors with emphasis on the signal intensities of the lesion on MR. Thirty four patients with intracranial metastases were studies with MR imaging. The diagnosis was established on the basis of either brain biopsy or combination of brain MR findings and the presence of primary tumors. The primary tumors include lung cancer (n=18), breast cancer (n=3), stomach cancer (n=3), rectal cancer (n=1), renal cell carcinoma (n=1), hepatocellular carcinoma (n=1), ovarian cancer (n=1), thyroid cancer (n=1), melanoma (n=1) and unknown primary sites (n=4). The parenchymal lesion were solitary in 35% (12/34) and multiple in 65% (22/34). The size of lesions was variable, ranging from several millimetes to 5 cm in diameter. The corticomedullar junction of the cerebral hemispheres was the most common location of the lesions (68%). The signal intensity of solid portion of the lesions was usually either isointense (44%) or hypointense (29%) on T1-weighted images, whereas it appeared in isointense (47%), hypointense (8%) or hypointense (11%) on protion density-weighted or T2-weighted images. The remaining cases showed mixed signal intensities. The enhancement patterns were variable including nodular (<1 cm) (6%), homogeneous (19%), heterogeneous (10%), ring-like enhancement (22%) or mixed pattern (43%). The size of surrounding edema was larger than the tumor diameter in 76%. In conclusion, although there are no specific MR findings of intracranial metastasis except multiplicity, intracranial metastasis should be included in differential diagnosis with high priority, when a solitary mass showing isointensity on body T1- and T2-weighted images with massive surrounding edema, especially in the corticomedullary junction of the cerebral hemispheres is encountered.

  15. MR findings of metastatic brain tumors

    International Nuclear Information System (INIS)

    Ahn, Joong Mo; Chang, Kee Hyun; Han, Moon Hee; Cha, Sang Hoon; Ryoo, Jae Wook

    1993-01-01

    The purpose of this study is to describe the magnetic resonance imaging (MR) findings of metastatic brain tumors with emphasis on the signal intensities of the lesion on MR. Thirty four patients with intracranial metastases were studies with MR imaging. The diagnosis was established on the basis of either brain biopsy or combination of brain MR findings and the presence of primary tumors. The primary tumors include lung cancer (n=18), breast cancer (n=3), stomach cancer (n=3), rectal cancer (n=1), renal cell carcinoma (n=1), hepatocellular carcinoma (n=1), ovarian cancer (n=1), thyroid cancer (n=1), melanoma (n=1) and unknown primary sites (n=4). The parenchymal lesion were solitary in 35% (12/34) and multiple in 65% (22/34). The size of lesions was variable, ranging from several millimetes to 5 cm in diameter. The corticomedullar junction of the cerebral hemispheres was the most common location of the lesions (68%). The signal intensity of solid portion of the lesions was usually either isointense (44%) or hypointense (29%) on T1-weighted images, whereas it appeared in isointense (47%), hypointense (8%) or hypointense (11%) on protion density-weighted or T2-weighted images. The remaining cases showed mixed signal intensities. The enhancement patterns were variable including nodular (<1 cm) (6%), homogeneous (19%), heterogeneous (10%), ring-like enhancement (22%) or mixed pattern (43%). The size of surrounding edema was larger than the tumor diameter in 76%. In conclusion, although there are no specific MR findings of intracranial metastasis except multiplicity, intracranial metastasis should be included in differential diagnosis with high priority, when a solitary mass showing isointensity on body T1- and T2-weighted images with massive surrounding edema, especially in the corticomedullary junction of the cerebral hemispheres is encountered

  16. Measuring the metastatic potential of cancer cells

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    Morrison, Dennis R.; Gratzner, Howard; Atassi, M. Z.

    1993-01-01

    Cancer cells must secrete proteolytic enzymes to invade adjacent tissues and migrate to a new metastatic site. Urokinase (uPA) is a key enzyme related to metastasis in cancers of the lung, colon, gastric, uterine, breast, brain, and malignant melanoma. A NASA technology utilization project has combined fluorescence microscopy, image analysis, and flow cytometry, using fluorescent dyes, and urokinase-specific antibodies to measure uPA and abnormal DNA levels (related to cancer cell proliferation) inside the cancer cells. The project is focused on developing quantitative measurements to determine if a patient's tumor cells are actively metastasizing. If a significant number of tumor cells contain large amounts of uPA (esp. membrane-bound) then the post-surgical chemotherapy or radiotherapy can be targeted for metastatic cells that have already left the primary tumor. These analytical methods have been applied to a retrospective study of biopsy tissues from 150 node negative, stage 1 breast cancer patients. Cytopathology and image analysis has shown that uPA is present in high levels in many breast cancer cells, but not found in normal breast. Significant amounts of uPA also have been measured in glioma cell lines cultured from brain tumors. Commercial applications include new diagnostic tests for metastatic cells, in different cancers, which are being developed with a company that provides a medical testing service using flow cytometry for DNA analysis and hormone receptors on tumor cells from patient biopsies. This research also may provide the basis for developing a new 'magic bullet' treatment against metastasis using chemotherapeutic drugs or radioisotopes attached to urokinase-specific monoclonal antibodies that will only bind to metastatic cells.

  17. Chemotherapy of metastatic colon cancer

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    M. Yu. Fedyanin

    2012-01-01

    Full Text Available Colorectal cancer is one of the leading causes of cancer incidence and mortality. In 2008 inRussian Federation55 719 new cases of colorectal cancer were diagnosed and 37 911 patients died of this disease. A significant progress was achieved in metastatic colorectal cancer treatment during the last decades. A lot of treatment options became available: from 5-fluoruracil monotherapy to combined treatment treatment schemes including surgery. A group of patients with isolated liver metastases was distinguished, who can achieve 5-year survival rate of 40 % after systemic treatment and surgery. Today, based on clinical data and molecular analysis, we come close to individualized treatment of this patient group. In this literature review results of metastatic colorectal cancer chemotherapy are being analyzed and rational treatment tactic is proposed based on therapy goals. 

  18. Radiosurgery for metastatic brain tumors

    International Nuclear Information System (INIS)

    Serizawa, Toru

    2009-01-01

    Stereotactic radiosurgery (SRS) precisely delivers high-dose radiation to a small target (usually less than 3-4 cm in diameter), in a single session with steep dose-fall, employing various radiation methods. SRS provides good tumor control for small brain metastases from various primary cancers, with minimal untoward effects on surrounding normal brain. This excellent tumor control prevents neurological death and maintains good activity of daily life. Although surgery with whole-brain radiation therapy (WBRT) remains an important option for patients with a solitary brain metastasis, SRS with or without WBRT should be considered in patients with a limited number of small tumors and a good prognosis. Many reports, as well as both retrospective and prospective reviews, have shown WBRT before or after SRS to improve local control and reduce new distant lesion emergence. However, upfront WBRT does not improve survival. There are two major delivery techniques, Gamma Knife (GK; Elekta AB, Stockholm, Sweden) SRS and linear accelerator (LINIAC)-based SRS. They are based on quite different concepts, and have different techniques and clinical applications. These differences complicate the discussion of the limitations of and indications for SRS and the necessity for prophylactic WBRT. This review discusses numerous aspects of SRS, its value as compared with other treatment modalities, the necessity for prophylactic WBRT with SRS, the limitations of and indications for SRS, and the difference between GK and LINIAC SRS, based on the literature and our experience, and proposes a new strategy for the treatment of brain metastases in view of the available clinical data and experience. (author)

  19. Supplementation with selenium-enriched yeast attenuates brain metastatic growth.

    Science.gov (United States)

    Wrobel, Jagoda K; Seelbach, Melissa J; Chen, Lei; Power, Ronan F; Toborek, Michal

    2013-01-01

    Metastases are the leading cause of cancer mortality and their development may be affected by diet. The aim of this study was to compare the effects of dietary supplementation with different selenium (Se) compounds on the dynamics of brain metastasis development in a novel mouse model. Mice were fed experimental diets enriched (1 mg/kg) with sodium selenite (Se-S), seleno-1-methionine (Se-Meth), a yeast-derived organic form of selenium (Se-Yeast), or a control diet (Se brain vasculature. The development of brain metastatic tumors was monitored for 2 wk following injection. Mice bearing brain metastatic tumors and fed Se-Yeast- or Se-S-enriched diets displayed a higher survival rate compared with other experimental and control groups. Importantly, Se-Yeast supplementation decreased the growth of brain metastatic tumors as determined by the measurement of the intensity of the bioluminescent signal emitted by K1735-Luc cells upon reaction with luciferin. Different chemical forms of Se have distinct effects on the development of brain metastases. Organic Se in the form of Se-Yeast may be a valuable agent in suppression of brain metastatic disease.

  20. Cisplatin With or Without Veliparib in Treating Patients With Recurrent or Metastatic Triple-Negative and/or BRCA Mutation-Associated Breast Cancer With or Without Brain Metastases

    Science.gov (United States)

    2018-03-12

    Breast Carcinoma Metastatic in the Brain; Deleterious BRCA1 Gene Mutation; Deleterious BRCA2 Gene Mutation; Estrogen Receptor Negative; HER2/Neu Negative; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Stage IV Breast Cancer AJCC v6 and v7; Triple-Negative Breast Carcinoma

  1. A case of primary lung cancer lesion demonstrated by F-18 FDG positron emission tomography/computed tomography (PET/CT) one year after the detection of metastatic brain tumor.

    Science.gov (United States)

    Ozeki, Yuichi; Abe, Yoshiyuki; Kita, Hideyuki; Tamura, Katsumi; Sakata, Ikuko; Ishida, Jiro; Machida, Kikuo

    2011-07-01

    Cancer of unknown primary origin (CUP) is an aggressive disease with a poor prognosis. Metastatic brain tumors occur in approximately 15% of all cancer patients. F-18 2'-deoxy-2fluoro-D-glucose (FDG) positron emission tomography (PET) combined with computed tomography (PET/CT) contributes to the evaluation of cancer staging, although the benefits of PET/CT for detection of CUP origins has yet to be determined. In this study, we present a 37-year-old man with a brain tumor detected by magnetic resonance imaging. Surgical biopsy indicated a metastatic undifferentiated carcinoma, while clinical examination and a CT scan did not detect any abnormalities, with the exception of brain metastases. PET/CT did not reveal abnormal FDG uptake. PET/CT revealed abnormal intense FDG uptake in a small nodular lesion in the right lung 1 year following the detection of brain metastasis, and no other abnormal FDG uptake was observed elsewhere in the body. Right upper lobectomy and dissection of mediastinal lymph nodes were performed. The pathological diagnosis was poorly differentiated adenocarcinoma, which was similar to the brain metastatic lesion, and there was no lymph node metastasis. This case revealed an extremely rare lung cancer with primary lesions demonstrated by PET/CT 1 year after the detection of brain metastasis. This case reveals that F-18 FDG PET/CT imaging of CUP origin is capable of positively impacting on the identification of small primary tumor foci.

  2. Pattern of brain metastatic disease according to HER-2 and ER receptor status in breast cancer patients.

    Science.gov (United States)

    Lekanidi, K; Evans, A L; Shah, J; Jaspan, T; Baker, L; Evans, A J

    2013-10-01

    To document the type, location, extent, and complications of brain metastases in patients with breast cancer and identify associations with oestrogen receptor (ER) negative and human epidermal growth factor receptor 2 (HER-2) receptor expression. Breast cancer patients with known brain metastases were included in this retrospective study, if cross-sectional imaging of the brain [computed tomography (CT)] was available to review and HER-2 and ER status was known. Two neuroradiologists, who were blinded to the receptor status, separately and for each patient, documented on a proforma the location, number, and dimensions of the deposits and the presence or absence of hydrocephalus. Adjudication was sought where there was discrepancy between the two reports. ER status, HER-2 receptor status, and patient age were also documented. The results were analysed using two-sided Fisher's exact tests with Lancaster's mid-P correction and associations were sought between the tumour characteristics and the pattern of brain disease. Sixty patients were included in the study. There was an association between young age (brain stem metastases [11 of 18 (61%) versus three of 26 (11.5%); p = 0.035], more frequent occurrence of hydrocephalus [7 of 12 (36.8%) versus three of 26 (11.5%); p = 0.049], and a higher incidence of occipital metastases [12 of 18 (66.7%) versus eight of 26 (30.8%); p = 0.029]. ER-negative HER-2-positive women are more likely to present with a larger number of lesions, more brain stem/occipital metastases, and hydrocephalus, which may predispose them to unfavourable outcomes following treatment. Copyright © 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  3. Biological Therapy in Treating Patients With Metastatic Cancer

    Science.gov (United States)

    2013-02-21

    Breast Cancer; Colorectal Cancer; Extrahepatic Bile Duct Cancer; Gallbladder Cancer; Gastric Cancer; Head and Neck Cancer; Liver Cancer; Lung Cancer; Metastatic Cancer; Ovarian Cancer; Pancreatic Cancer; Testicular Germ Cell Tumor

  4. Vectors for Treatment of Metastatic Breast Cancer

    National Research Council Canada - National Science Library

    Deisseroth, Albert B

    2005-01-01

    The objective is to design, build and study vectors which would be able to break tolerance to breast cancer associated TAA and be used to suppress the recurrence of metastatic breast cancer following surgical resection...

  5. Vectors for Treatment of Metastatic Breast Cancer

    National Research Council Canada - National Science Library

    Deisseroth, Albert

    2004-01-01

    The objective is to design, build and study vectors which would be able to break tolerance to breast cancer associated TAA and be used to suppress the recurrence of metastatic breast cancer following surgical resection...

  6. Current treatment of metastatic endometrial cancer.

    Science.gov (United States)

    Temkin, Sarah M; Fleming, Gini

    2009-01-01

    Endometrial cancer is the most common gynecologic malignancy. The majority of patients have disease confined to the uterus and have an excellent overall prognosis. However, subgroups of patients have advanced primary disease or recurrences following primary treatment. The management of metastatic disease is variable, depending on factors such as comorbidities, tumor grade, performance status, and prior treatments. Management options include hormonal therapy and cytotoxic chemotherapy, as well as targeted therapies that inhibit angiogenesis and the cellular signaling pathways involved in cell growth and proliferation. A comprehensive review of these treatments for metastatic endometrial cancer was conducted and is discussed. Hormonal therapy and cytotoxic chemotherapy have traditionally been used in the treatment of metastatic endometrial cancer. Advances in molecular biology have led to multiple potential targeted therapies to be used in the treatment of metastatic endometrial cancer. While several treatment modalities are now available to treat patients who present with metastatic endometrial cancer, overall prognosis remains poor.

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

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    Ong John M

    2007-03-01

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

  8. A case of primary lung cancer lesion demonstrated by F-18 FDG positron emission tomography/computed tomography (PET/CT) one year after the detection of metastatic brain tumor

    OpenAIRE

    OZEKI, YUICHI; ABE, YOSHIYUKI; KITA, HIDEYUKI; TAMURA, KATSUMI; SAKATA, IKUKO; ISHIDA, JIRO; MACHIDA, KIKUO

    2011-01-01

    Cancer of unknown primary origin (CUP) is an aggressive disease with a poor prognosis. Metastatic brain tumors occur in approximately 15% of all cancer patients. F-18 2′-deoxy-2fluoro-D-glucose (FDG) positron emission tomography (PET) combined with computed tomography (PET/CT) contributes to the evaluation of cancer staging, although the benefits of PET/CT for detection of CUP origins has yet to be determined. In this study, we present a 37-year-old man with a brain tumor detected by magnetic...

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

    Science.gov (United States)

    2017-03-01

    anatomical location is completely random, this observation is not completely unexpected. After multiple attempts and careful consider the risk and...metastases in their metastatic niche, technical barriers have impeded efforts to dissect the contri - bution of diverse spatial components of the metastatic...www.nature.com/srep Competing financial interests: The authors declare no competing financial interests. How to cite this article: Guldner, I. H

  10. A pilot study to determine the timing and effect of bevacizumab on vascular normalization of metastatic brain tumors in breast cancer

    International Nuclear Information System (INIS)

    Chen, Bang-Bin; Lu, Yen-Shen; Lin, Ching-Hung; Chen, Wei-Wu; Wu, Pei-Fang; Hsu, Chao-Yu; Yu, Chih-Wei; Wei, Shwu-Yuan; Cheng, Ann-Lii; Shih, Tiffany Ting-Fang

    2016-01-01

    To determine the appropriate time of concomitant chemotherapy administration after antiangiogenic treatment, we investigated the timing and effect of bevacizumab administration on vascular normalization of metastatic brain tumors in breast cancer patients. Eight patients who participated in a phase II trial for breast cancer-induced refractory brain metastases were enrolled and subjected to 4 dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) examinations that evaluated Peak, Slope, iAUC 60 , and Ktrans before and after treatment. The treatment comprised bevacizumab on Day 1, etoposide on Days 2–4, and cisplatin on Day 2 in a 21-day cycle for a maximum of 6 cycles. DCE-MRI was performed before treatment and at 1 h, 24 h, and 21 days after bevacizumab administration. Values of the 4 DCE-MRI parameters reduced after bevacizumab administration. Compared with baseline values, the mean reductions at 1 and 24 h were −12.8 and −24.7 % for Peak, −46.6 and −65.8 % for Slope, −27.9 and −55.5 % for iAUC 60 , and −46.6 and −63.9 % for Ktrans, respectively (all P < .05). The differences in the 1 and 24 h mean reductions were significant (all P < .05) for all the parameters. The generalized estimating equation linear regression analyses of the 4 DCE-MRI parameters revealed that vascular normalization peaked 24 h after bevacizumab administration. Bevacizumab induced vascular normalization of brain metastases in humans at 1 and 24 h after administration, and the effect was significantly higher at 24 h than at 1 h. ClinicalTrials.gov, identifier NCT01281696, registered prospectively on December 24, 2010

  11. Brain metastases from colorectal cancer

    DEFF Research Database (Denmark)

    Vagn-Hansen, Chris Aksel; Rafaelsen, Søren Rafael

    2001-01-01

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

  12. Abiraterone Improves Survival in Metastatic Prostate Cancer

    Science.gov (United States)

    A multinational phase III trial found that the drug abiraterone acetate prolonged the median survival of patients with metastatic castration-resistant prostate cancer by 4 months compared with patients who received a placebo.

  13. Changing Natural History of HER2-Positive Breast Cancer Metastatic to the Brain in the Era of New Targeted Therapies.

    Science.gov (United States)

    Mounsey, Louisa A; Deal, Allison M; Keith, Kevin C; Benbow, Julia M; Shachar, Shlomit S; Zagar, Timothy; Dees, E Claire; Carey, Lisa A; Ewend, Matthew G; Anders, Carey K

    2018-02-01

    Given the wide adoption of human epidermal growth factor receptor 2 (HER2)-targeted therapies for advanced HER2-positive breast cancer, we studied the natural history of patients with HER2-positive breast cancer brain metastases (BCBM) over time. Patients with HER2-positive BCBM identified from a prospectively maintained database at the University of North Carolina were divided into 3 cohorts by year of BCBM diagnosis. Cohorts were selected by year of HER2-targeted therapy US Food and Drug Administration approval. Overall survival (OS), time to first metastasis, time to BCBM, and BCBM survival were estimated by the Kaplan-Meier method. Associations between OS after BCBM and clinical variables were assessed by Cox proportional hazards regression models. One hundred twenty-three patients were identified. Median age was 51 years, and 58% were white and 31% African American. OS from initial breast cancer diagnosis improved over time: 3.6 years (95% confidence interval [CI], 2.8-6.1) in the 1998-2007 cohort, 6.6 years (95% CI, 4.5-8.6) in the 2008-2012 cohort, and 7.6 years (95% CI, 4.4-9.6) in the 2013-2015 cohort (P = .05). While time from initial diagnosis to first metastasis did not differ (P = .12), time to BCBM increased over time (2.6 years [95% CI, 1.3-3.5] for 1998-2007; 2.6 years [95% CI, 2.1-4.3] for 2008-2012, and 3.3 years [95% CI, 2.2-6] for 2013-2015; P = .05). Although OS from BCBM did not significantly differ by cohort, patients who received HER2-targeted therapy after BCBM had a prolonged OS (2.1 years [95% CI, 1.6-2.6] vs. 0.65 years [95% CI, 0.4-1.3]; P = .001). OS from initial breast cancer diagnosis significantly improved over time for patients with HER2-positive breast cancer who develop BCBM, now exceeding 7 years; survival from BCBM diagnosis may now exceed 2 years. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Breast cancer metastatic to the kidney with renal vein involvement.

    Science.gov (United States)

    Nasu, Hatsuko; Miura, Katsutoshi; Baba, Megumi; Nagata, Masao; Yoshida, Masayuki; Ogura, Hiroyuki; Takehara, Yasuo; Sakahara, Harumi

    2015-02-01

    The common sites of breast cancer metastases include bones, lung, brain, and liver. Renal metastasis from the breast is rare. We report a case of breast cancer metastatic to the kidney with extension into the renal vein. A 40-year-old woman had undergone left mastectomy for breast cancer at the age of 38. A gastric tumor, which was later proved to be metastasis from breast cancer, was detected by endoscopy. Computed tomography performed for further examination of the gastric tumor revealed a large left renal tumor with extension into the left renal vein. It mimicked a primary renal tumor. Percutaneous biopsy of the renal tumor confirmed metastasis from breast cancer. Surgical intervention of the stomach and the kidney was avoided, and she was treated with systemic chemotherapy. Breast cancer metastatic to the kidney may present a solitary renal mass with extension into the renal vein, which mimics a primary renal tumor.

  15. Advances in diagnosis and treatment of metastatic cervical cancer

    Science.gov (United States)

    2016-01-01

    Cervical cancer is one of the most common cancers in women worldwide. The outcome of patients with metastatic cervical cancer is poor. We reviewed the relevant literature concerning the treatment and diagnosis of metastatic cervical cancer. There are two types of metastasis related to different treatments and survival rates: hematogenous metastasis and lymphatic metastasis. Patients with hematogenous metastasis have a higher risk of death than those with lymphatic metastasis. In terms of diagnosis, fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) and PET-computed tomography are effective tools for the evaluation of distant metastasis. Concurrent chemoradiotherapy and subsequent chemotherapy are well-tolerated and efficient for lymphatic metastasis. As for lung metastasis, chemotherapy and/or surgery are valuable treatments for resistant, recurrent metastatic cervical cancer and chemoradiotherapy may be the optimal choice for stage IVB cervical cancer. Chemotherapy and bone irradiation are promising for bone metastasis. A better survival is achieved with multimodal therapy. Craniotomy or stereotactic radiosurgery is an optimal choice combined with radiotherapy for solitary brain metastases. Chemotherapy and palliative brain radiation may be considered for multiple brain metastases and other organ metastases. PMID:27171673

  16. Brain metastasis in patients with metastatic breast cancer in the real world: a single-institution, retrospective review of 12-year follow-up.

    Science.gov (United States)

    Matsuo, Satomi; Watanabe, Junichiro; Mitsuya, Koichi; Hayashi, Nakamasa; Nakasu, Yoko; Hayashi, Mitsuhiro

    2017-02-01

    The data of 589 metastatic breast cancer (MBC) patients in a single institution were reviewed to determine the outcomes of patients with brain metastasis (BM) and assess the efficacy of BM screening. The patients with BM among the 589 MBC patients who underwent treatment at Shizuoka Cancer Center (Shizuoka, Japan) from 09/2002 to 03/2014 were retrospectively analyzed. During the study period, BM developed in 187 (31.7%) patients. The tumor subtypes were as follows: luminal (hormone receptor [HR]+, HER2-), 44.9%; luminal-HER2 (HR+, HER2+), 14.9%; HER2 (HR-, HER2+), 21.3%; and triple-negative (TN), 16.0%. BM was detected in 48.6% of the patients by screening MRI. While 137 of 187 patients underwent local therapy, whole-brain irradiation was the most frequently applied therapy (63.5%). The median overall survival from the diagnosis of BM was as follows: luminal, 7.0 months (M); luminal-HER2, 13.3 M; HER2, 17.7 M; TN, 4.2 M. The HER2 status (hazard ratio [HR]: 0.58, 95% confidence interval [CI] 0.38-0.88) and nonprogressive extracranial lesion(s) (HR: 0.45, 95% CI 0.29-0.71) were identified as prognostic factors in a multivariate analysis. When limited to HER2-overexpressed MBC patients, the multivariate analysis revealed that non-progressive extracranial lesion(s) (HR: 0.20, 95% CI 0.088-0.47) and stereotactic irradiation (STI) as an initial treatment (HR: 0.18, 95% CI 0.061-0.56) were prognostic factors. Our retrospective review showed that early detection of BM by screening MRI, followed by STI, improved the prognosis of HER2-overexpressed MBC patients with BM. A further prospective randomized study is needed to confirm our findings.

  17. Enzalutamide in metastatic prostate cancer before chemotherapy

    DEFF Research Database (Denmark)

    Beer, Tomasz M; Armstrong, Andrew J; Rathkopf, Dana E

    2014-01-01

    BACKGROUND: Enzalutamide is an oral androgen-receptor inhibitor that prolongs survival in men with metastatic castration-resistant prostate cancer in whom the disease has progressed after chemotherapy. New treatment options are needed for patients with metastatic prostate cancer who have...... the most common clinically relevant adverse events associated with enzalutamide treatment. CONCLUSIONS: Enzalutamide significantly decreased the risk of radiographic progression and death and delayed the initiation of chemotherapy in men with metastatic prostate cancer. (Funded by Medivation and Astellas...... skeletal-related event (hazard ratio, 0.72), a complete or partial soft-tissue response (59% vs. 5%), the time until prostate-specific antigen (PSA) progression (hazard ratio, 0.17), and a rate of decline of at least 50% in PSA (78% vs. 3%) (P

  18. Targeting breast to brain metastatic tumours with death receptor ligand expressing therapeutic stem cells.

    Science.gov (United States)

    Bagci-Onder, Tugba; Du, Wanlu; Figueiredo, Jose-Luiz; Martinez-Quintanilla, Jordi; Shah, Khalid

    2015-06-01

    Characterizing clinically relevant brain metastasis models and assessing the therapeutic efficacy in such models are fundamental for the development of novel therapies for metastatic brain cancers. In this study, we have developed an in vivo imageable breast-to-brain metastasis mouse model. Using real time in vivo imaging and subsequent composite fluorescence imaging, we show a widespread distribution of micro- and macro-metastasis in different stages of metastatic progression. We also show extravasation of tumour cells and the close association of tumour cells with blood vessels in the brain thus mimicking the multi-foci metastases observed in the clinics. Next, we explored the ability of engineered adult stem cells to track metastatic deposits in this model and show that engineered stem cells either implanted or injected via circulation efficiently home to metastatic tumour deposits in the brain. Based on the recent findings that metastatic tumour cells adopt unique mechanisms of evading apoptosis to successfully colonize in the brain, we reasoned that TNF receptor superfamily member 10A/10B apoptosis-inducing ligand (TRAIL) based pro-apoptotic therapies that induce death receptor signalling within the metastatic tumour cells might be a favourable therapeutic approach. We engineered stem cells to express a tumour selective, potent and secretable variant of a TRAIL, S-TRAIL, and show that these cells significantly suppressed metastatic tumour growth and prolonged the survival of mice bearing metastatic breast tumours. Furthermore, the incorporation of pro-drug converting enzyme, herpes simplex virus thymidine kinase, into therapeutic S-TRAIL secreting stem cells allowed their eradication post-tumour treatment. These studies are the first of their kind that provide insight into targeting brain metastasis with stem-cell mediated delivery of pro-apoptotic ligands and have important clinical implications. © The Author (2015). Published by Oxford University Press on

  19. Prognosis of metastatic breast cancer: are there differences between patients with de novo and recurrent metastatic breast cancer?

    NARCIS (Netherlands)

    Lobbezoo, D.J.; Kampen, R.J. van; Voogd, A.C.; Dercksen, M.W.; Berkmortel, F. van den; Smilde, T.J.; Wouw, A.J. van de; Peters, F.P.; Riel, J.M. van; Peters, N.A.; Boer, M. de; Peer, P.G.M.; Tjan-Heijnen, V.C.

    2015-01-01

    BACKGROUND: We aimed to determine the prognostic impact of time between primary breast cancer and diagnosis of distant metastasis (metastatic-free interval, MFI) on the survival of metastatic breast cancer patients. METHODS: Consecutive patients diagnosed with metastatic breast cancer in 2007-2009

  20. Cetuximab in treatment of metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Guren, Tormod Kyrre; Thomsen, Maria Morandi; Kure, Elin H

    2017-01-01

    BACKGROUND: The NORDIC-VII study is a randomised phase III trial of cetuximab plus continuous or intermittent fluorouracil, folinic acid, and oxaliplatin (Nordic FLOX) vs FLOX alone in first-line treatment of metastatic colorectal cancer. The present report presents an updated and final survival...

  1. Sorafenib makes headway on metastatic thyroid cancer.

    Science.gov (United States)

    2013-07-01

    In a randomized phase III clinical trial, patients with metastatic differentiated cancer of the thyroid who were treated with sorafenib achieved median progression-free survival of 10.8 months, compared with 5.8 months among patients treated with placebo.

  2. Ziv-aflibercept in metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Patel A

    2013-12-01

    Full Text Available Anuj Patel, Weijing Sun Division of Hematology-Oncology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Abstract: The combination of cytotoxic chemotherapy and antiangiogenic agents has become a conventional treatment option for patients with metastatic colorectal cancer. Ziv-aflibercept is a fusion protein which acts as a decoy receptor for vascular endothelial growth factor (VEGF-A, VEGF-B, and placental growth factor (PlGF; it was approved in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI for the treatment of patients with metastatic colorectal cancer that is resistant to or has progressed after an oxaliplatin-containing fluoropyrimidine-based regimen. Herein we review the role of tumor angiogenesis as the rationale for antiangiogenic therapy, the clinical data associated with ziv-aflibercept, and its current role as a treatment option compared to other antiangiogenic agents, such as bevacizumab and regorafenib. Keywords: aflibercept, angiogenesis, colorectal cancer

  3. Surgical management of metastatic differentiated thyroid cancer

    International Nuclear Information System (INIS)

    Fakih, A.R.; Mistry, R.C.

    1999-01-01

    The differentiated management of metastatic differentiated thyroid cancer (DTC) with lymph node and/or systemic metastases is very much a treatable cancer. Interaction between the surgeon and the nuclear medicine specialist is essential to ensure quality survival in these patient. This review is confined to surgical aspects and is based on experience with 417 patients who were operated for DTC at the Tata Memorial Hospital between 1971 and 1985

  4. Paclitaxel and doxorubicin in metastatic breast cancer

    DEFF Research Database (Denmark)

    Gehl, J; Boesgaard, M; Paaske, T

    1996-01-01

    For the past decades the anthracyclines have been regarded as among the most active drugs for the treatment of metastatic breast cancer. However, the 5-year survival rate in patients with stage IV breast cancer continues to be below 20%, and new active drugs and drug combinations clearly must...... be explored. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has been demonstrated to be highly effective in treating patients with advanced breast cancer, including those with anthracycline-resistant breast cancer, a fact that has led to efforts to combine paclitaxel and anthracyclines...

  5. Two Domains of Vimentin Are Expressed on the Surface of Lymph Node, Bone and Brain Metastatic Prostate Cancer Lines along with the Putative Stem Cell Marker Proteins CD44 and CD133

    Energy Technology Data Exchange (ETDEWEB)

    Steinmetz, Nicole F. [Case Western Reserve University, Department of Biomedical Engineering, 10900 Euclid Ave, Cleveland, OH 44106 (United States); Maurer, Jochen [Sanford-Burnham, Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037 (United States); Sheng, Huiming [Torrey Pines Institute for Molecular Studies, Division of Immune Regulation, 3550 General Atomics Court, San Diego, CA 92121 (United States); Bensussan, Armand [INSERM U976, Hôpital Saint Louis, F-75475 Paris (France); Department of Immunology, Dermatology and Oncology, Univ Paris Diderot, Sorbonne Paris Cité, UMRS976 F-75475 Paris (France); Maricic, Igor; Kumar, Vipin [Torrey Pines Institute for Molecular Studies, Laboratory of Autoimmunity, 3550 General Atomics Court, San Diego, CA 92121 (United States); Braciak, Todd A., E-mail: tbraciak@tpims.org [Torrey Pines Institute for Molecular Studies, Division of Immune Regulation, 3550 General Atomics Court, San Diego, CA 92121 (United States)

    2011-07-13

    Vimentin was originally identified as an intermediate filament protein present only as an intracellular component in many cell types. However, this protein has now been detected on the surface of a number of different cancer cell types in a punctate distribution pattern. Increased vimentin expression has been indicated as an important step in epithelial-mesenchymal transition (EMT) required for the metastasis of prostate cancer. Here, using two vimentin-specific monoclonal antibodies (SC5 and V9 directed against the coil one rod domain and the C-terminus of the vimentin protein, respectively), we examined whether either of these domains would be displayed on the surface of three commonly studied prostate cancer cell lines isolated from different sites of metastases. Confocal analysis of LNCaP, PC3 and DU145 prostate cancer cell lines (derived from lymph node, bone or brain prostate metastases, respectively) demonstrated that both domains of vimentin are present on the surface of these metastatic cancer cell types. In addition, flow cytometric analysis revealed that vimentin expression was readily detected along with CD44 expression but only a small subpopulation of prostate cancer cells expressed vimentin and the putative stem cell marker CD133 along with CD44. Finally, Cowpea mosaic virus (CPMV) nanoparticles that target vimentin could bind and internalize into tested prostate cancer cell lines. These results demonstrate that at least two domains of vimentin are present on the surface of metastatic prostate cancer cells and suggest that vimentin could provide a useful target for nanoparticle- or antibody- cancer therapeutic agents directed against highly invasive cancer and/or stem cells.

  6. Theranostics Targeting Metastatic Breast Cancer

    Science.gov (United States)

    2016-10-01

    Clinical Cancer Res 2009;15(10):3574–3582. 37. de Bruin M, Miyake K, Litman T, Robey R, Bates SE. Reversal of resistance by GF120918 in cell lines...receptor type alpha in relation to cell type, malignancy, and differentiation in ovary, uterus, and cervix . Cancer Epidemiol Biomarkers Prev 1999;8(9... cancer . Steroids 2014. 242. Zafrani B, Aubriot MH, Mouret E, De Cremoux P, De Rycke Y, Nicolas A, Boudou E, Vincent- Salomon A, Magdelenat H, Sastre

  7. Immunotherapy for metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Ellebaek, Eva; Andersen, Mads Hald; Svane, Inge Marie

    2012-01-01

    Although no immunotherapeutic treatment is approved for colorectal cancer (CRC) patients, promising results from clinical trials suggest that several immunotherapeutic strategies may prove efficacious and applicable to this group of patients. This review describes the immunogenicity of CRC...... and presents the most interesting strategies investigated so far: cancer vaccination including antigen-defined vaccination and dendritic cell vaccination, chemo-immunotherapy, and adoptive cell transfer. Future treatment options as well as the possibility of combining existing therapies will be discussed along...

  8. Immunotherapy in metastatic prostate cancer

    Directory of Open Access Journals (Sweden)

    Susan F Slovin

    2016-01-01

    Full Text Available Introduction: Prostate cancer remains a challenge as a target for immunological approaches. The approval of the first cell-based immune therapy, Sipuleucel-T for prostate cancer introduced prostate cancer as a solid tumor with the potential to be influenced by the immune system. Methods: We reviewed articles on immunological management of prostate cancer and challenges that lie ahead for such strategies. Results: Treatments have focused on the identification of novel cell surface antigens thought to be unique to prostate cancer. These include vaccines against carbohydrate and blood group antigens, xenogeneic and naked DNA vaccines, and pox viruses used as prime-boost or checkpoint inhibitors. No single vaccine construct to date has resulted in a dramatic antitumor effect. The checkpoint inhibitor, anti-CTLA-4 has resulted in several long-term remissions, but phase III trials have not demonstrated an antitumor effect or survival benefit. Conclusions: Multiple clinical trials suggest that prostate cancer may not be optimally treated by single agent immune therapies and that combination with biologic agents, chemotherapies, or radiation may offer some enhancement of benefit.

  9. Radioisotopes in management of metastatic prostate cancer.

    Science.gov (United States)

    Raval, Amar; Dan, Tu D; Williams, Noelle L; Pridjian, Andrew; Den, Robert B

    2016-01-01

    Metastatic prostate cancer continues to be a leading cause of morbidity and mortality in men with prostate cancer. Over the last decade, the treatment landscape for patients with castrate-resistant disease has drastically changed, with several novel agents demonstrating an improvement in overall survival in large, multi-institutional randomized trials. Traditional treatment with radioisotopes has largely been in the palliative setting. However, the first in class radiopharmaceutical radium-223 has emerged as the only bone-directed treatment option demonstrating an improvement in overall survival. Medline publications from 1990 to 2016 were searched and reviewed to assess the use of currently approved radioisotopes in the management of prostate cancer including emerging data regarding integration with novel systemic therapies. New positron emission tomography-based radiotracers for advanced molecular imaging of prostate cancer were also queried. Radioisotopes play a crucial role in the diagnosis and treatment of prostate cancer in the definitive and metastatic setting. Molecular imaging of prostate cancer and theranostics are currently being investigated in the clinical arena. The use of modern radioisotopes in selected patients with mCRPC is associated with improvements in overall survival, pain control, and quality of life.

  10. Metastatic Breast Cancer and Hormonal Receptor Status among a ...

    African Journals Online (AJOL)

    disease. Many studies show that metastatic lesions frequently lodge in bones, lung and liver. Tumour hormone receptor status correlates with site of metastatic lesions and survival among breast cancer patients. Objective: To determine the sites of metastatic breast lesions and how they relate to the hormonal receptor status.

  11. Study of metastatic foci by CT in autopsied lung cancer

    International Nuclear Information System (INIS)

    Koga, Mitsuru; Nobe, Yoshifumi; Fujii, Kyoichi.

    1983-01-01

    The authors reexamined all of the image diagnoses made during whole hospitalization in 11 lung cancer cases with autopsy. Of 39 metastatic foci observed at autopsy in the liver, kidney, pancreas, adrenal and brain, 12 had been diagnosed on transverse CT images before death. Three foci were missed at initial readings. The period from CT to autopsy was less than 3 months for 9 of 12 correctly diagnosed foci. For 13 of 27 foci undetected by CT, CT was conducted more than 3 months before death. (Chiba, N)

  12. Metastatic Breast Cancer and Hormonal Receptor Status among a ...

    African Journals Online (AJOL)

    Background: Breast cancer is the third commonest cancer in women in Uganda. The majority of breast cancer patients in Uganda present with advanced disease. Many studies show that metastatic lesions frequently lodge in bones, lung and liver. Tumour hormone receptor status correlates with site of metastatic lesions and ...

  13. Peritumoral hemorrhage immediately after radiosurgery for metastatic brain tumor

    International Nuclear Information System (INIS)

    Uchino, Masafumi; Kitajima, Satoru; Miyazaki, Chikao; Otsuka, Takashi; Seiki, Yoshikatsu; Shibata, Iekado

    2003-01-01

    We report a case of a 44-year-old woman with metastatic brain tumors who suffered peri-tumoral hemorrhage soon after stereotactic radiosurgery (SRS). She had been suffering from breast cancer with multiple systemic metastasis. She started to have headache, nausea, dizziness and speech disturbance 1 month before admission. There was no bleeding tendency in the hematological examination and the patient was normotensive. Neurological examination disclosed headache and slightly aphasia. Magnetic resonance imaging showed a large round mass lesion in the left temporal lobe. It was a well-demarcated, highly enhanced mass, 45 mm in diameter. SRS was performed on four lesions in a single session (Main mass: maximum dose was 30 Gy in the center and 20 Gy in the margin of the tumor. Others: maximum 25 Gy margin 20 Gy). After radiosurgery, she had severe headache, nausea and vomiting and showed progression of aphasia. CT scan revealed a peritumoral hemorrhage. Conservative therapy was undertaken and the patient's symptoms improved. After 7 days, she was discharged, able to walk. The patient died of extensive distant metastasis 5 months after SRS. Acute transient swelling following conventional radiotherapy is a well-documented phenomenon. However, the present case indicates that such an occurrence is also possible in SRS. We have hypothesized that acute reactions such as brain swelling occur due to breakdown of the fragile vessels of the tumor or surrounding tissue. (author)

  14. Asymptomatic brain metastases in patients with cutaneous metastatic malignant melanoma

    DEFF Research Database (Denmark)

    Zukauskaite, Ruta; Schmidt, Henrik; Asmussen, Jon Thor

    2013-01-01

    The aim of the study was to identify the frequency of asymptomatic brain metastases detected by computed tomography (CT) scans in patients with metastatic cutaneous melanoma referred to first-line systemic treatment. Between 1995 and 2009, 697 Danish patients were screened with a contrast......-enhanced CT scan of the brain before the start of interleukin-2 (IL-2)-based immunotherapy. Among the 697 patients, 80 had asymptomatic brain metastases (12%). Patients' characteristics did not differ significantly between groups with and without brain metastases. Patients received systemic treatment (IL-2...

  15. Characterization of KRAS Rearrangements in Metastatic Prostate Cancer

    Science.gov (United States)

    Wang, Xiao-Song; Shankar, Sunita; Dhanasekaran, Saravana M.; Ateeq, Bushra; Sasaki, Atsuo T.; Jing, Xiaojun; Robinson, Daniel; Cao, Qi; Prensner, John R.; Yocum, Anastasia K.; Wang, Rui; Fries, Daniel F.; Han, Bo; Asangani, Irfan A.; Cao, Xuhong; Li, Yong; Omenn, Gilbert S.; Pflueger, Dorothee; Gopalan, Anuradha; Reuter, Victor E.; Kahoud, Emily Rose; Cantley, Lewis C.; Rubin, Mark A.; Palanisamy, Nallasivam; Varambally, Sooryanarayana; Chinnaiyan, Arul M.

    2011-01-01

    Using an integrative genomics approach called Amplification Breakpoint Ranking and Assembly (ABRA) analysis, we nominated KRAS as a gene fusion with the ubiquitin-conjugating enzyme UBE2L3 in the DU145 cell line, originally derived from prostate cancer metastasis to the brain. Interestingly, analysis of tissues revealed that 2 of 62 metastatic prostate cancers harbored aberrations at the KRAS locus. In DU145 cells, UBE2L3-KRAS produces a fusion protein, specific knock-down of which, attenuates cell invasion and xenograft growth. Ectopic expression of the UBE2L3-KRAS fusion protein exhibits transforming activity in NIH 3T3 fibroblasts and RWPE prostate epithelial cells in vitro and in vivo. In NIH 3T3 cells, UBE2L3-KRAS attenuates MEK/ERK signaling, commonly engaged by oncogenic mutant KRAS, and instead signals via AKT and p38 MAPK pathways. This is the first report of a gene fusion involving Ras family suggesting that this aberration may drive metastatic progression in a rare subset of prostate cancers. PMID:22140652

  16. Vascular Functional Imaging and Physiological Environment of Hyperplasia, Non-Metastatic and Metastatic Breast Cancer

    National Research Council Canada - National Science Library

    Bhujwalla, Zaver

    1999-01-01

    .... In year 3 we have used the significant technical developments implemented in year 2 to determine the vascular characteristics of human breast cancer cells preselected for differences in invasive and metastatic behavior...

  17. Vascular Functional Imaging and Physiological Environment of Hyperplasia, Non-Metastatic and Metastatic Breast Cancer

    National Research Council Canada - National Science Library

    Bhujwalla, Zaver

    1998-01-01

    Our research proposal consists of the following three closely related aims directed towards understanding the role of vascular, physiological and metabolic properties in the metastatic dissemination of breast cancer. Aim 1...

  18. Molecularly targeted drugs for metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Cheng YD

    2013-11-01

    Full Text Available Ying-dong Cheng, Hua Yang, Guo-qing Chen, Zhi-cao Zhang Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China Abstract: The survival rate of patients with metastatic colorectal cancer (mCRC has significantly improved with applications of molecularly targeted drugs, such as bevacizumab, and led to a substantial improvement in the overall survival rate. These drugs are capable of specifically targeting the inherent abnormal pathways in cancer cells, which are potentially less toxic than traditional nonselective chemotherapeutics. In this review, the recent clinical information about molecularly targeted therapy for mCRC is summarized, with specific focus on several of the US Food and Drug Administration-approved molecularly targeted drugs for the treatment of mCRC in the clinic. Progression-free and overall survival in patients with mCRC was improved greatly by the addition of bevacizumab and/or cetuximab to standard chemotherapy, in either first- or second-line treatment. Aflibercept has been used in combination with folinic acid (leucovorin–fluorouracil–irinotecan (FOLFIRI chemotherapy in mCRC patients and among patients with mCRC with wild-type KRAS, the outcomes were significantly improved by panitumumab in combination with folinic acid (leucovorin–fluorouracil–oxaliplatin (FOLFOX or FOLFIRI. Because of the new preliminary studies, it has been recommended that regorafenib be used with FOLFOX or FOLFIRI as first- or second-line treatment of mCRC chemotherapy. In summary, an era of new opportunities has been opened for treatment of mCRC and/or other malignancies, resulting from the discovery of new selective targeting drugs. Keywords: metastatic colorectal cancer (mCRC, antiangiogenic drug, bevacizumab, aflibercept, regorafenib, cetuximab, panitumumab, clinical trial, molecularly targeted therapy

  19. Peritumoral hemorrhage after radiosurgery for metastatic brain tumor

    International Nuclear Information System (INIS)

    Motozaki, Takahiko; Ban, Sadahiko; Yamamoto, Toyoshiro; Hamasaki, Masatake.

    1994-01-01

    An unusual case of peritumoral hemorrhage after radiosurgery for the treatment of metastatic brain tumor is reported. This 64-year-old woman had a history of breast cancer and underwent right mastectomy in 1989. She remained well until January 1993, when she started to have headache, nausea and speech disturbance, and was hospitalized on February 25, 1993. Neurological examination disclosed right hemiparesis and bilateral papilledema. CT scan and MR imaging showed a solitary round mass lesion in the left basal ganglia region. It was a well-demarcated, highly enhanced mass, 37 mm in diameter. Cerebral angiography confirmed a highly vascular mass lesion in the same location. She was treated with radiosurgery on March 8 (maximum dose was 20 Gy in the center and 10 Gy in the peripheral part of the tumor). After radiosurgery, she had an uneventful course and clinical and radiosurgical improvement could be detected. Her neurological symptoms and signs gradually improved and reduction of the tumor size and perifocal edema could be seen one month after radiosurgery. However, 6 weeks after radiosurgery, she suddenly developed semicoma and right hemiplegia. CT scan disclosed a massive peritumoral hemorrhage. Then, emergency craniotomy, evacuation of the hematoma and total removal of the tumor were performed on April 24. Histopathological diagnosis was adenocarcinoma. It was the same finding as that of the previous breast cancer. Histopathological examination revealed necrosis without tumor cells in the center and residual tumor cells in the peripheral part of the tumor. It is postulated that peritumoral hemorrhage was caused by hemodynamic changes in the vascular-rich tumor after radiosurgery and breakdown of the fragile abnormal vessels in the peripheral part of the tumor. (author)

  20. LIGHT: A Novel Immunotherapy for Primary and Metastatic Prostate Cancer

    Science.gov (United States)

    2015-11-01

    1  AD_________________ Award Number: W81XWH-11-1-0518 TITLE: LIGHT: A Novel Immunotherapy for Primary and Metastatic Prostate Cancer...COVERED 1 Sep 2011 - 31 Aug 2015 4. TITLE AND SUBTITLE LIGHT: A Novel Immunotherapy for Primary and Metastatic Prostate Cancer 5a. CONTRACT NUMBER...prostate, immunotherapy may be the only way to treat it [6, 7]. A majority of clinical trials for the immunotherapy of prostate cancer have yielded

  1. Reconstructing metastatic seeding patterns of human cancers

    Science.gov (United States)

    Reiter, Johannes G.; Makohon-Moore, Alvin P.; Gerold, Jeffrey M.; Bozic, Ivana; Chatterjee, Krishnendu; Iacobuzio-Donahue, Christine A.; Vogelstein, Bert; Nowak, Martin A.

    2017-01-01

    Reconstructing the evolutionary history of metastases is critical for understanding their basic biological principles and has profound clinical implications. Genome-wide sequencing data has enabled modern phylogenomic methods to accurately dissect subclones and their phylogenies from noisy and impure bulk tumour samples at unprecedented depth. However, existing methods are not designed to infer metastatic seeding patterns. Here we develop a tool, called Treeomics, to reconstruct the phylogeny of metastases and map subclones to their anatomic locations. Treeomics infers comprehensive seeding patterns for pancreatic, ovarian, and prostate cancers. Moreover, Treeomics correctly disambiguates true seeding patterns from sequencing artifacts; 7% of variants were misclassified by conventional statistical methods. These artifacts can skew phylogenies by creating illusory tumour heterogeneity among distinct samples. In silico benchmarking on simulated tumour phylogenies across a wide range of sample purities (15–95%) and sequencing depths (25-800 × ) demonstrates the accuracy of Treeomics compared with existing methods. PMID:28139641

  2. Enzalutamide Improves Survival in Patients with Metastatic Prostate Cancer

    Science.gov (United States)

    A summary of results from an international phase III trial that compared enzalutamide (Xtandi®) and placebo for the treatment of metastatic prostate cancer that had progressed during treatment with androgen deprivation therapy.

  3. Cytoreductive surgery for men with metastatic prostate cancer

    Directory of Open Access Journals (Sweden)

    Nikolas Katelaris

    2016-09-01

    Conclusions: This data supports recent findings demonstrating that radical prostatectomy for metastatic prostate cancer is feasible. Further studies are needed to explore the role of cytoreductive surgery with regards to the potential oncological benefit.

  4. Outcomes of colon resection in patients with metastatic colon cancer.

    Science.gov (United States)

    Moghadamyeghaneh, Zhobin; Hanna, Mark H; Hwang, Grace; Mills, Steven; Pigazzi, Alessio; Stamos, Michael J; Carmichael, Joseph C

    2016-08-01

    Patients with advanced colorectal cancer have a high incidence of postoperative complications. We sought to identify outcomes of patients who underwent resection for colon cancer by cancer stage. The National Surgical Quality Improvement Program database was used to evaluate all patients who underwent colon resection with a diagnosis of colon cancer from 2012 to 2014. Multivariate logistic regression analysis was performed to investigate patient outcomes by cancer stage. A total of 7,786 colon cancer patients who underwent colon resection were identified. Of these, 10.8% had metastasis at the time of operation. Patients with metastatic disease had significantly increased risks of perioperative morbidity (adjusted odds ratio [AOR]: 1.44, P = .01) and mortality (AOR: 3.72, P = .01). Patients with metastatic disease were significantly younger (AOR: .99, P colon cancer have metastatic disease. Postoperative morbidity and mortality are significantly higher than in patients with localized disease. Published by Elsevier Inc.

  5. Utility and limitation of radiosurgery for metastatic brain tumors

    International Nuclear Information System (INIS)

    Kagawa, Kota; Kiya, Katsuzo; Satoh, Hideki; Mizoue, Tatsuya; Matsushige, Toshinori; Araki, Hayato; Akimitsu, Tomohide

    2003-01-01

    The purpose of this study was to evaluate the utility and limitations of radiosurgery for metastatic brain lesions, and to compare the clinical results of stereotactic radiosurgery (SRS) with those of whole-brain radiation therapy (WBRT) in 45 patients with metastatic brain tumors. The patients were divided into two groups: the SRS group (22 patients) and the WBRT group (23 patients). Mean survival was not significantly different between the two groups. However, in patients with 6 or more lesions, both survival time and recurrence-free time in the SRS group were inferior to those in the WBRT group. The main complication in the SRS group was perifocal edema, while dementia was seen in the WBRT group. The bedridden period was longer in the WBRT group than in the SRS group. Death caused by brain lesions was rare in both groups. From these results, SRS preserves high quality of life longer than WBRT, but SRS should be cautiously used in patients with 6 or more lesions. (author)

  6. First line chemotherapy plus trastuzumab in metastatic breast cancer ...

    African Journals Online (AJOL)

    Breast cancer is the most common malignant disease and among the most frequent causes of cancer mortality in females worldwide. Metastatic breast cancer (MBC) is conventionally considered to be incurable. In first-line treatment of HER-2 positive MBC, randomized trials have demonstrated that trastuzumab when ...

  7. Targeting Siah2 as Novel Therapy for Metastatic Prostate Cancer

    Science.gov (United States)

    2015-10-01

    metastasis and responses to curcumin 19 Goals: This proposal tests the hypothesis that chemokine biomarkers that predict biochemical recurrence of...prostate cancer regulate metastatic progression of the cancer and curcumin can inhibit metastasis of prostate cancer by antagonizing inflammatory signaling

  8. Predicting survival of de novo metastatic breast cancer in Asian women: systematic review and validation study.

    Directory of Open Access Journals (Sweden)

    Hui Miao

    Full Text Available BACKGROUND: In Asia, up to 25% of breast cancer patients present with distant metastases at diagnosis. Given the heterogeneous survival probabilities of de novo metastatic breast cancer, individual outcome prediction is challenging. The aim of the study is to identify existing prognostic models for patients with de novo metastatic breast cancer and validate them in Asia. MATERIALS AND METHODS: We performed a systematic review to identify prediction models for metastatic breast cancer. Models were validated in 642 women with de novo metastatic breast cancer registered between 2000 and 2010 in the Singapore Malaysia Hospital Based Breast Cancer Registry. Survival curves for low, intermediate and high-risk groups according to each prognostic score were compared by log-rank test and discrimination of the models was assessed by concordance statistic (C-statistic. RESULTS: We identified 16 prediction models, seven of which were for patients with brain metastases only. Performance status, estrogen receptor status, metastatic site(s and disease-free interval were the most common predictors. We were able to validate nine prediction models. The capacity of the models to discriminate between poor and good survivors varied from poor to fair with C-statistics ranging from 0.50 (95% CI, 0.48-0.53 to 0.63 (95% CI, 0.60-0.66. CONCLUSION: The discriminatory performance of existing prediction models for de novo metastatic breast cancer in Asia is modest. Development of an Asian-specific prediction model is needed to improve prognostication and guide decision making.

  9. Brain cancer spreads

    DEFF Research Database (Denmark)

    Perryman, Lara; Erler, Janine Terra

    2014-01-01

    The discovery that ~20% of patients with brain cancer have circulating tumor cells breaks the dogma that these cells are confined to the brain and has important clinical implications (Müller et al., this issue).......The discovery that ~20% of patients with brain cancer have circulating tumor cells breaks the dogma that these cells are confined to the brain and has important clinical implications (Müller et al., this issue)....

  10. Ixabepilone: a new chemotherapeutic option for refractory metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Shannon Puhalla

    2008-09-01

    Full Text Available Shannon Puhalla, Adam BrufskyUPMC Magee-Womens Cancer Program, University of Pittsburgh, Pittsburgh, Pennsylvania, USAAbstract: Taxane therapy is commonly used in the treatment of metastatic breast cancer. However, most patients will eventually become refractory to these agents. Ixabepilone is a newly approved chemotherapeutic agent for the treatment of metastatic breast cancer. Although it targets microtubules similarly to docetaxel and paclitaxel, ixabepilone has activity in patients that are refractory to taxanes. This review summarizes the pharmacology of ixapebilone and clinical trials with the drug both as a single agent and in combination. Data were obtained using searches of PubMed and abstracts of the annual meetings of the American Society of Clinical Oncology and the San Antonio Breast Cancer Symposium from 1995 to 2008. Ixapebilone is a semi-synthetic analog of epothilone B that acts to induce apoptosis of cancer cells via the stabilization of microtubules. Phase I clinical trials have employed various dosing schedules ranging from daily to weekly to 3-weekly. Dose-limiting toxicites included neuropathy and neutropenia. Responses were seen in a variety of tumor types. Phase II studies verified activity in taxane-refractory metastatic breast cancer. The FDA has approved ixabepilone for use as monotherapy and in combination with capecitabine for the treatment of metastatic breast cancer. Ixabepilone is an efficacious option for patients with refractory metastatic breast cancer. The safety profile is similar to that of taxanes, with neuropathy and neutropenia being dose-limiting. Studies are ongoing with the use of both iv and oral formulations and in combination with other chemotherapeutic and biologic agents.Keywords: ixabepilone, epothilone, metastatic breast cancer, taxane-refractory

  11. Targeting Siah2 as Novel Therapy for Metastatic Prostate Cancer

    Science.gov (United States)

    2017-12-01

    AWARD NUMBER: W81XWH-14-1-0553 TITLE: Targeting Siah2 as Novel Therapy for Metastatic Prostate Cancer PRINCIPAL INVESTIGATOR: Martin Gleave...Siah2 as Novel Therapy for Metastatic Prostate Cancer 5b. GRANT NUMBER W81XWH-14-1-0553 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Martin Gleave 5d...goal of this project was to develop a novel means to inhibit prostate cancer development and progression. The development of Siah1/2 inhibitors to the

  12. Comparison of survival of patients with metastases from known versus unknown primaries: survival in metastatic cancer.

    Science.gov (United States)

    Riihimäki, Matias; Thomsen, Hauke; Hemminki, Akseli; Sundquist, Kristina; Hemminki, Kari

    2013-01-28

    Cancer of unknown primary site (CUP) is considered an aggressive metastatic disease but whether the prognosis differs from metastatic cancers of known primary site is not known. Such data may give insight into the biology of CUP and the metastatic process in general. 6,745 cancer patients, with primary metastatic cancer at diagnosis, were identified from the Swedish Cancer Registry, and were compared with 2,881 patients with CUP. Patients were diagnosed and died between 2002 and 2008. The influence of the primary site, known or unknown, on survival in patients with metastases at specific locations was investigated. Hazard ratios (HRs) of death were estimated for several sites of metastasis, where patients with known primary sites were compared with CUP patients. Overall, patients with metastatic cancers with known primary sites had decreased hazards of death compared to CUP patients (HR = 0.69 [95% CI = 0.66-0.72]). The exceptions were cancer of the pancreas (1.71 [1.54-1.90]), liver (1.58 [1.36-1.85]), and stomach (1.16 [1.02-1.31]). For individual metastatic sites, patients with liver or bone metastases of known origin had better survival than those with CUP of the liver and bone. Patients with liver metastases of pancreatic origin had an increased risk of death compared with patients with CUP of the liver (1.25 [1.06-1.46]). The median survival time of CUP patients was three months. Patients with CUP have poorer survival than patients with known primaries, except those with brain and respiratory system metastases. Of CUP sites, liver metastases had the worst prognosis. Survival in CUP was comparable to that in metastatic lung cancer. The aggressive behavior of CUP may be due to initial immunosuppression and immunoediting which may allow accumulation of mutations. Upon escape from the suppressed state an unstoppable tumor spread ensues. These novel data on the epidemiology of the metastatic process at the population level demonstrated large survival differences

  13. Comparison of survival of patients with metastases from known versus unknown primaries: survival in metastatic cancer

    Directory of Open Access Journals (Sweden)

    Riihimäki Matias

    2013-01-01

    Full Text Available Abstract Background Cancer of unknown primary site (CUP is considered an aggressive metastatic disease but whether the prognosis differs from metastatic cancers of known primary site is not known. Such data may give insight into the biology of CUP and the metastatic process in general. Methods 6,745 cancer patients, with primary metastatic cancer at diagnosis, were identified from the Swedish Cancer Registry, and were compared with 2,881 patients with CUP. Patients were diagnosed and died between 2002 and 2008. The influence of the primary site, known or unknown, on survival in patients with metastases at specific locations was investigated. Hazard ratios (HRs of death were estimated for several sites of metastasis, where patients with known primary sites were compared with CUP patients. Results Overall, patients with metastatic cancers with known primary sites had decreased hazards of death compared to CUP patients (HR = 0.69 [95% CI = 0.66–0.72]. The exceptions were cancer of the pancreas (1.71 [1.54–1.90], liver (1.58 [1.36–1.85], and stomach (1.16 [1.02–1.31]. For individual metastatic sites, patients with liver or bone metastases of known origin had better survival than those with CUP of the liver and bone. Patients with liver metastases of pancreatic origin had an increased risk of death compared with patients with CUP of the liver (1.25 [1.06–1.46]. The median survival time of CUP patients was three months. Conclusions Patients with CUP have poorer survival than patients with known primaries, except those with brain and respiratory system metastases. Of CUP sites, liver metastases had the worst prognosis. Survival in CUP was comparable to that in metastatic lung cancer. The aggressive behavior of CUP may be due to initial immunosuppression and immunoediting which may allow accumulation of mutations. Upon escape from the suppressed state an unstoppable tumor spread ensues. These novel data on the epidemiology of the

  14. RO4929097 and Whole-Brain Radiation Therapy or Stereotactic Radiosurgery in Treating Patients With Brain Metastases From Breast Cancer

    Science.gov (United States)

    2015-01-22

    Estrogen Receptor-negative Breast Cancer; Extensive Stage Small Cell Lung Cancer; HER2-negative Breast Cancer; HER2-positive Breast Cancer; Male Breast Cancer; Recurrent Breast Cancer; Recurrent Melanoma; Recurrent Non-small Cell Lung Cancer; Recurrent Small Cell Lung Cancer; Stage IV Breast Cancer; Stage IV Melanoma; Stage IV Non-small Cell Lung Cancer; Tumors Metastatic to Brain; Unspecified Adult Solid Tumor, Protocol Specific

  15. An unusual cause of dysphagia in ductal breast cancer due to submucosal oropharyngeal metastatic spread: a case report

    OpenAIRE

    Gujral, Dorothy M; Quante, Mara; Simcock, Richard AJ

    2009-01-01

    Introduction Invasive ductal and lobular carcinomas represent 67.9% and 6.3% of breast carcinoma, respectively. Metastatic breast cancer typically involves the lungs, bones, brain, and liver. Studies have shown differing patterns of metastatic spread between ductal and lobular carcinoma. Lobular carcinoma is more likely to metastasise to the gastrointestinal tract. Case presentation We report the case of a 49 year old white woman with invasive ductal carcinoma with lobular differentiation who...

  16. Clinicopathologic factors associated with de novo metastatic breast cancer.

    Science.gov (United States)

    Shen, Tiansheng; Siegal, Gene P; Wei, Shi

    2016-12-01

    While breast cancers with distant metastasis at presentation (de novo metastasis) harbor significantly inferior clinical outcomes, there have been limited studies analyzing the clinicopathologic characteristics in this subset of patients. In this study, we analyzed 6126 breast cancers diagnosed between 1998 and 2013 to identify factors associated with de novo metastatic breast cancer. When compared to patients without metastasis at presentation, race, histologic grade, estrogen/progesterone receptor (ER/PR) and HER2 statuses were significantly associated with de novo metastasis in the entire cohort, whereas age, histologic grade, PR and HER2 status were the significant parameters in the subset of patients with locally advanced breast cancer (Stage IIB/III). The patients with de novo metastatic breast cancer had a significant older mean age and a lower proportion of HER2-positive tumors when compared to those with metastatic recurrence. Further, the HER2-rich subtype demonstrated a drastically higher incidence of de novo metastasis when compared to the luminal and triple-negative breast cancers in the entire cohort [odds ratio (OR)=5.68 and 2.27, respectively] and in the patients with locally advanced disease (OR=4.02 and 2.12, respectively), whereas no significant difference was seen between de novo metastatic cancers and those with metastatic recurrence. Moreover, the luminal and HER2-rich subtypes showed bone-seeking (OR=1.92) and liver-homing (OR=2.99) characteristics, respectively, for the sites of de novo metastasis, while the latter was not observed in those with metastatic recurrence. Our data suggest that an algorithm incorporating clinicopathologic factors, especially histologic grade and receptor profile, remains of significant benefit during decision making in newly diagnosed breast cancer in the pursuit of precision medicine. Copyright © 2016 Elsevier GmbH. All rights reserved.

  17. Surgical resection of synchronously metastatic adrenocortical cancer.

    Science.gov (United States)

    Dy, Benzon M; Strajina, Veljko; Cayo, Ashley K; Richards, Melanie L; Farley, David R; Grant, Clive S; Harmsen, William S; Evans, Doug B; Grubbs, Elizabeth G; Bible, Keith C; Young, William F; Perrier, Nancy D; Que, Florencia G; Nagorney, David M; Lee, Jeffrey E; Thompson, Geoffrey B

    2015-01-01

    Metastatic adrenocortical carcinoma (ACC) is rapidly fatal, with few options for treatment. Patients with metachronous recurrence may benefit from surgical resection. The survival benefit in patients with hematogenous metastasis at initial presentation is unknown. A review of all patients undergoing surgery (European Network for the Study of Adrenal Tumors) stage IV ACC between January 2000 and December 2012 from two referral centers was performed. Kaplan-Meier estimates were analyzed for disease-free and overall survival (OS). We identified 27 patients undergoing surgery for stage IV ACC. Metastases were present in the lung (19), liver (11), and brain (1). A complete resection (R0) was achieved in 11 patients. The median OS was improved in patients undergoing R0 versus R2 resection (860 vs. 390 days; p = 0.02). The 1- and 2-year OS was also improved in patients undergoing R0 versus R2 resection (69.9 %, 46.9 % vs. 53.0 %, 22.1 %; p = 0.02). Patients undergoing neoadjuvant therapy (eight patients) had a trend towards improved survival at 1, 2, and 5 years versus no neoadjuvant therapy (18 patients) [83.3 %, 62.5 %, 41.7 % vs. 56.8 %, 26.6 %, 8.9 %; p = 0.1]. Adjuvant therapy was associated with improved recurrence-free survival at 6 months and 1 year (67 %, 33 % vs. 40 %, 20 %; p = 0.04) but not improved OS (p = 0.63). Sex (p = 0.13), age (p = 0.95), and location of metastasis (lung, p = 0.51; liver, p = 0.67) did not correlate with OS after operative intervention. Symptoms of hormonal excess improved in 86 % of patients. Operative intervention, especially when an R0 resection can be achieved, following systemic therapy may improve outcomes, including OS, in select patients with stage IV ACC. Response to neoadjuvant chemotherapy may be of use in defining which patients may benefit from surgical intervention. Adjuvant therapy was associated with decreased recurrence but did not improve OS.

  18. Glycoprotein non-metastatic b (GPNMB: A metastatic mediator and emerging therapeutic target in cancer

    Directory of Open Access Journals (Sweden)

    Maric G

    2013-07-01

    Full Text Available Gordana Maric,1,2 April AN Rose,3 Matthew G Annis,1,2 Peter M Siegel1,2,4,5 1Goodman Cancer Research Centre, 2Department of Medicine, 3Faculty of Medicine, 4Department of Biochemistry, 5Department of Anatomy and Cell Biology, McGill University, Montréal, Québec, Canada Abstract: Molecularly targeted therapies are rapidly growing with respect to their clinical development and impact on cancer treatment due to their highly selective anti-tumor action. However, many aggressive cancers such as triple-negative breast cancer (TNBC currently lack well-defined therapeutic targets against which such agents can be developed. The identification of tumor-associated antigens and the generation of antibody drug-conjugates represent an emerging area of intense interest and growth in the field of cancer therapeutics. Glycoprotein non-metastatic b (GPNMB has recently been identified as a gene that is over-expressed in numerous cancers, including TNBC, and often correlates with the metastatic phenotype. In breast cancer, GPNMB expression in the tumor epithelium is associated with a reduction in disease-free and overall survival. Based on these findings, glembatumumab vedotin (CDX-011, an antibody-drug conjugate that selectively targets GPNMB, is currently being investigated in clinical trials for patients with metastatic breast cancer and unresectable melanoma. This review discusses the physiological and potential pathological roles of GPNMB in normal and cancer tissues, respectively, and details the clinical advances and challenges in targeting GPNMB-expressing malignancies. Keywords: GPNMB, osteoactivin, breast cancer, antibody-drug conjugates, CDX-011

  19. Nanomedicine as an emerging platform for metastatic lung cancer therapy.

    Science.gov (United States)

    Landesman-Milo, Dalit; Ramishetti, Srinivas; Peer, Dan

    2015-06-01

    Metastatic lung cancer is one of the most common cancers leading to mortality worldwide. Current treatment includes chemo- and pathway-dependent therapy aiming at blocking the spread and proliferation of these metastatic lesions. Nanomedicine is an emerging multidisciplinary field that offers unprecedented access to living cells and promises the state of the art in cancer detection and treatment. Development of nanomedicines as drug carriers (nanocarriers) that target cancer for therapy draws upon principles in the fields of chemistry, medicine, physics, biology, and engineering. Given the zealous activity in the field as demonstrated by more than 30 nanocarriers already approved for clinical use and given the promise of recent clinical results in various studies, nanocarrier-based strategies are anticipated to soon have a profound impact on cancer medicine and human health. Herein, we will detail the latest innovations in therapeutic nanomedicine with examples from lipid-based nanoparticles and polymer-based approaches, which are engineered to deliver anticancer drugs to metastatic lung cells. Emphasis will be placed on the latest and most attractive delivery platforms, which are developed specifically to target lung metastatic tumors. These novel nanomedicines may open new avenues for therapeutic intervention carrying new class of drugs such as RNAi and mRNA and the ability to edit the genome using the CRISPER/Cas9 system. Ultimately, these strategies might become a new therapeutic modality for advanced-stage lung cancer.

  20. [Role of surgery for metastatic breast cancer at diagnosis].

    Science.gov (United States)

    Vlastos, Georges; Rapiti, Elisabetta; Verkooijen, Helena M; Bouchardy, Christine

    2007-10-24

    Metastatic breast cancer is considered as incurable. Treatments of choice are systemic and palliative. Surgery of the primary tumor is usually indicated for palliation of local complications. However recently published studies seem to demonstrate that the surgical excision of the primary tumor increase survival, in particular for patients with negative surgical margins or with only bone metastases. As these studies have been adjusted for factors that may induce biais, only a prospective clinical randomized trial may confirm the role of surgery in the management of metastatic breast cancer.

  1. Chemotherapeutic Treatment of Priapism in Metastatic Rectal Cancer

    Directory of Open Access Journals (Sweden)

    Y. Kitai

    2008-12-01

    Full Text Available A 65-year-old man was admitted with penile tenderness and dysuria due to priapism. Enhanced computed tomography revealed metastatic tumors in the liver, lung, sacrum and lymph nodes. Advanced rectal cancer, detected by colonoscopy as a primary tumor, was treated with chemotherapy (FOLFOX4. Although the rectal cancer showed no change, five months of chemotherapy improveid the priapism, suggesting that chemotherapy can improve rare symptoms of rectal cancer.

  2. Mast Cell Infiltration in Human Brain Metastases Modulates the Microenvironment and Contributes to the Metastatic Potential

    Directory of Open Access Journals (Sweden)

    Ananya Roy

    2017-06-01

    Full Text Available Metastatic brain tumors continue to be a clinical problem, despite new therapeutic advances in cancer treatment. Brain metastases (BMs are among the most common mass lesions in the brain that are resistant to chemotherapies, have a very poor prognosis, and currently lack any efficient diagnostic tests. Predictions estimate that about 40% of lung and breast cancer patients will develop BM. Despite this, very little is known about the immunological and genetic aberrations that drive tumorigenesis in BM. In this study, we demonstrate the infiltration of mast cells (MCs in a large cohort of human BM samples with different tissues of origin for primary cancer. We applied patient-derived BM cell models to the study of BM cell–MC interactions. BM cells when cocultured with MCs demonstrate enhanced growth and self-renewal capacity. Gene set enrichment analyses indicate increased expression of signal transduction and transmembrane proteins related genes in the cocultured BM cells. MCs exert their effect by release of mediators such as IL-8, IL-10, matrix metalloprotease 2, and vascular endothelial growth factor, thereby permitting metastasis. In conclusion, we provide evidence for a role of MCs in BM. Our findings indicate MCs’ capability of modulating gene expression in BM cells and suggest that MCs can serve as a new target for drug development against metastases in the brain.

  3. Cold atmospheric plasma for selectively ablating metastatic breast cancer cells.

    Science.gov (United States)

    Wang, Mian; Holmes, Benjamin; Cheng, Xiaoqian; Zhu, Wei; Keidar, Michael; Zhang, Lijie Grace

    2013-01-01

    Traditional breast cancer treatments such as surgery and radiotherapy contain many inherent limitations with regards to incomplete and nonselective tumor ablation. Cold atmospheric plasma (CAP) is an ionized gas where the ion temperature is close to room temperature. It contains electrons, charged particles, radicals, various excited molecules, UV photons and transient electric fields. These various compositional elements have the potential to either enhance and promote cellular activity, or disrupt and destroy them. In particular, based on this unique composition, CAP could offer a minimally-invasive surgical approach allowing for specific cancer cell or tumor tissue removal without influencing healthy cells. Thus, the objective of this research is to investigate a novel CAP-based therapy for selectively bone metastatic breast cancer treatment. For this purpose, human metastatic breast cancer (BrCa) cells and bone marrow derived human mesenchymal stem cells (MSCs) were separately treated with CAP, and behavioral changes were evaluated after 1, 3, and 5 days of culture. With different treatment times, different BrCa and MSC cell responses were observed. Our results showed that BrCa cells were more sensitive to these CAP treatments than MSCs under plasma dose conditions tested. It demonstrated that CAP can selectively ablate metastatic BrCa cells in vitro without damaging healthy MSCs at the metastatic bone site. In addition, our study showed that CAP treatment can significantly inhibit the migration and invasion of BrCa cells. The results suggest the great potential of CAP for breast cancer therapy.

  4. Cold atmospheric plasma for selectively ablating metastatic breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Mian Wang

    Full Text Available Traditional breast cancer treatments such as surgery and radiotherapy contain many inherent limitations with regards to incomplete and nonselective tumor ablation. Cold atmospheric plasma (CAP is an ionized gas where the ion temperature is close to room temperature. It contains electrons, charged particles, radicals, various excited molecules, UV photons and transient electric fields. These various compositional elements have the potential to either enhance and promote cellular activity, or disrupt and destroy them. In particular, based on this unique composition, CAP could offer a minimally-invasive surgical approach allowing for specific cancer cell or tumor tissue removal without influencing healthy cells. Thus, the objective of this research is to investigate a novel CAP-based therapy for selectively bone metastatic breast cancer treatment. For this purpose, human metastatic breast cancer (BrCa cells and bone marrow derived human mesenchymal stem cells (MSCs were separately treated with CAP, and behavioral changes were evaluated after 1, 3, and 5 days of culture. With different treatment times, different BrCa and MSC cell responses were observed. Our results showed that BrCa cells were more sensitive to these CAP treatments than MSCs under plasma dose conditions tested. It demonstrated that CAP can selectively ablate metastatic BrCa cells in vitro without damaging healthy MSCs at the metastatic bone site. In addition, our study showed that CAP treatment can significantly inhibit the migration and invasion of BrCa cells. The results suggest the great potential of CAP for breast cancer therapy.

  5. Treatment of initially metastatic small-cell lung cancer

    International Nuclear Information System (INIS)

    Kohutek, F.; Bystricky, B.; Tamasova, M.

    2013-01-01

    Lung cancer (LC) is the most common cause of death associated with neoplasms. The incidence of LC in 2007 was 71.3/100,000 men and 18.6/100,000 women in Slovakia. Small-cell lung cancer (SCLC) includes 15 - 18% of all cases. The diagnosis of LC is based on patient's history, physical examination, basic laboratory tests, x-ray imaging and computed tomography (CT) imaging and histology. The material required for histology can be obtained by means of endoscopy or surgery. Ultrasonography (USG) and/or CT of abdomen is commonly performed as a part of staging process, along with CT or MRI of brain. Bone scan is performed in case of suspicion of bone involvement. According to TNM classification, seventh edition, the same classification can be used for SCLC and non-small cell lung cancer (NSCLC). Chemotherapy and radiotherapy are available for treatment of initially metastatic SCLC. First-line chemotherapy regimen should be based on combination of cisplatin or carboplatin with etoposide (PE). Alternatively, CAV regimen (cyclophosphamide, doxorubicin, vincristine) can be used. Newer regimens did not provide benefit when compared to standard regimens. If progression occurs later than 3 months after finishing first-line chemotherapy, the same regimen may be used in second-line chemotherapy. If progression occurs earlier than 3 months after finishing first-line chemotherapy, topotecan-based regimen is an option for second-line line chemotherapy. Despite promising outcomes of amrubicin-based second-line chemotherapy in Japan, amrubicin is not available in countries of E U. Standard therapy schedules do not include radiotherapy targeted on primary tumor and affected lymph-nodes. According to American and European guidelines, prophylactic cranial irradiation is recommended for patients with extensive disease-SCLC with good performance status after achieving complete or partial response to first-line chemotherapy. (author)

  6. Actomyosin tension as a determinant of metastatic cancer mechanical tropism

    Science.gov (United States)

    McGrail, Daniel J.; Kieu, Quang Minh N.; Iandoli, Jason A.; Dawson, Michelle R.

    2015-04-01

    Despite major advances in the characterization of molecular regulators of cancer growth and metastasis, patient survival rates have largely stagnated. Recent studies have shown that mechanical cues from the extracellular matrix can drive the transition to a malignant phenotype. Moreover, it is also known that the metastatic process, which results in over 90% of cancer-related deaths, is governed by intracellular mechanical forces. To better understand these processes, we identified metastatic tumor cells originating from different locations which undergo inverse responses to altered matrix elasticity: MDA-MB-231 breast cancer cells that prefer rigid matrices and SKOV-3 ovarian cancer cells that prefer compliant matrices as characterized by parameters such as tumor cell proliferation, chemoresistance, and migration. Transcriptomic analysis revealed higher expression of genes associated with cytoskeletal tension and contractility in cells that prefer stiff environments, both when comparing MDA-MB-231 to SKOV-3 cells as well as when comparing bone-metastatic to lung-metastatic MDA-MB-231 subclones. Using small molecule inhibitors, we found that blocking the activity of these pathways mitigated rigidity-dependent behavior in both cell lines. Probing the physical forces exerted by cells on the underlying substrates revealed that though force magnitude may not directly correlate with functional outcomes, other parameters such as force polarization do correlate directly with cell motility. Finally, this biophysical analysis demonstrates that intrinsic levels of cell contractility determine the matrix rigidity for maximal cell function, possibly influencing tissue sites for metastatic cancer cell engraftment during dissemination. By increasing our understanding of the physical interactions of cancer cells with their microenvironment, these studies may help develop novel therapeutic strategies.

  7. Metastatic breast cancer - age has a significant effect on survival

    African Journals Online (AJOL)

    1991-03-02

    Mar 2, 1991 ... tic breast cancer seen in the same period were included in the analysis as a comparative group. Factors taken into consideration included: age group, asso- ciated disease (other medical disorder resulting in little or severe disability),5 hormone receptor stams, performance stams, dominant metastatic site ...

  8. FCGR polymorphisms and cetuximab efficacy in chemorefractory metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Geva, Ravit; Vecchione, Loredana; Kalogeras, Konstantinos T

    2015-01-01

    OBJECTIVE: We aimed to better clarify the role of germline variants of the FCG2 receptor, FCGR2A-H131R and FCGR3A-V158F, on the therapeutic efficacy of cetuximab in metastatic colorectal cancer (mCRC). A large cohort with sufficient statistical power was assembled. DESIGN: To show a HR advantage...

  9. Continuous vs. intermittent androgen deprivation therapy for metastatic prostate cancer

    NARCIS (Netherlands)

    Langenhuijsen, J.F.; Badhauser, D.; Schaaf, B.; Kiemeney, L.A.L.M.; Witjes, J.A.; Mulders, P.F.A.

    2013-01-01

    OBJECTIVES: To analyze the predictive value of PSA for progression and the role of testosterone for quality of life (QOL) in patients with androgen deprivation therapy (ADT) for metastatic prostate cancer. MATERIALS AND METHODS: PSA and testosterone data were used from a phase III trial randomizing

  10. Cost-Effectiveness Analysis of Regorafenib for Metastatic Colorectal Cancer.

    Science.gov (United States)

    Goldstein, Daniel A; Ahmad, Bilal B; Chen, Qiushi; Ayer, Turgay; Howard, David H; Lipscomb, Joseph; El-Rayes, Bassel F; Flowers, Christopher R

    2015-11-10

    Regorafenib is a standard-care option for treatment-refractory metastatic colorectal cancer that increases median overall survival by 6 weeks compared with placebo. Given this small incremental clinical benefit, we evaluated the cost-effectiveness of regorafenib in the third-line setting for patients with metastatic colorectal cancer from the US payer perspective. We developed a Markov model to compare the cost and effectiveness of regorafenib with those of placebo in the third-line treatment of metastatic colorectal cancer. Health outcomes were measured in life-years and quality-adjusted life-years (QALYs). Drug costs were based on Medicare reimbursement rates in 2014. Model robustness was addressed in univariable and probabilistic sensitivity analyses. Regorafenib provided an additional 0.04 QALYs (0.13 life-years) at a cost of $40,000, resulting in an incremental cost-effectiveness ratio of $900,000 per QALY. The incremental cost-effectiveness ratio for regorafenib was > $550,000 per QALY in all of our univariable and probabilistic sensitivity analyses. Regorafenib provides minimal incremental benefit at high incremental cost per QALY in the third-line management of metastatic colorectal cancer. The cost-effectiveness of regorafenib could be improved by the use of value-based pricing. © 2015 by American Society of Clinical Oncology.

  11. Intraarterial infusion chemotherapy for the treatment of metastatic liver cancer

    International Nuclear Information System (INIS)

    Arai, Yasuaki; Kido, Choichiro

    1987-01-01

    Some techniques of the most recent interventional radiology are very useful for the treatment of metastatic liver cancer and changing the style of hepatic infusion chemotherapy. This report shows our latest results and methods of hepatic infusion chemotherapy for metastatic liver cancer. 1. For the catheter placement, a new catheterization route via the left subclavian artery into the hepatic artery was developed and performed in 132 cases. Superselective catheterization succeeded in 123 cases (93.2 %). This procedure is less invasive than laparotomy and less troublesome than other percutaneous routes. 2. For useful infusion system, an implantable injection port ''Reservoir'' was developed and it was used in 87 cases. This method makes arterial infusion chemotherapy easy, and imploves their quality of life. 3. To acquire adequate drug delivery, arterial redistribution by steel coils was done, and 109 arteries in 80 cases were occluded. This method is very useful to make multiple hepatic artery single and it is important to avoid gasroduodenal complications. 4. Now, using these techniques, the phase II study of 5FU, ADM, MMC combined hepatic infusion in patients with non-resectable metastatic liver cancer is done. Up to this time, such a phase study on arterial infusion chemotherapy was difficult because of technical problems, but these new techniques make it possible. In conclusion, these new methods change the style and conception of hepatic infusion, and these make much progress on the treatment of patients with metastatic liver cancer. (author)

  12. Optimal duration of systemic treatment in metastatic colorectal cancer

    NARCIS (Netherlands)

    Simkens, Lieke H. J.; Koopman, Miriam; Punt, Cornelis J. A.

    2014-01-01

    With the currently available cytotoxic and targeted drugs, metastatic colorectal cancer (mCRC) may be controlled by systemic treatment for a significant period of time. However, many questions remain about the optimal use of drugs and duration of treatment. We reviewed the data from clinical trials

  13. Metastatic breast cancer - age has a significant effect on survival ...

    African Journals Online (AJOL)

    The data on 217 elderly (aged ≥ 65 years) and 209 middleaged postmenopausal patients with metastatic breast cancer treated in the Department of Medical Oncology, University of Pretoria, from 1976 to 1985 were analysed to determine the effect of age on survival. When considered as a group, the elderly have a more ...

  14. Proton pumps, angiogenesis, and metastatic breast cancer

    Science.gov (United States)

    Rojas, Jose D.; Sanka, Shankar C.; Luo, Defeng; Busch, Christian; Martinez, Gloria M.; Hendrix, Mary J. C.; Martinez-Zaguilan, Raul

    2000-04-01

    We have previously shown the relationship between metastatic potential and plasmalemmal V-H+-ATPase (pmV-ATPase) expression in tumor cells. This led us to hypothesize that pmV-ATPase activity is involved in invasion. Angiogenesis involves invasion of adjacent tissues by microvascular endothelial cells, thus we hypothesized that pmV-ATPases contribute to pHin regulation and invasion in microvascular endothelial cells.

  15. The E1 copper binding domain of full-length amyloid precursor protein mitigates copper-induced growth inhibition in brain metastatic prostate cancer DU145 cells

    Energy Technology Data Exchange (ETDEWEB)

    Gough, Mallory, E-mail: m.gough1@lancaster.ac.uk; Blanthorn-Hazell, Sophee, E-mail: s.blanthorn-hazell@lancaster.ac.uk; Delury, Craig, E-mail: c.delury@lancaster.ac.uk; Parkin, Edward, E-mail: e.parkin@lancaster.ac.uk

    2014-10-31

    Highlights: • Copper levels are elevated in the tumour microenvironment. • APP mitigates copper-induced growth inhibition of DU145 prostate cancer (PCa) cells. • The APP intracellular domain is a prerequisite; soluble forms have no effect. • The E1 CuBD of APP is also a prerequisite. • APP copper binding potentially mitigates copper-induced PCa cell growth inhibition. - Abstract: Copper plays an important role in the aetiology and growth of tumours and levels of the metal are increased in the serum and tumour tissue of patients affected by a range of cancers including prostate cancer (PCa). The molecular mechanisms that enable cancer cells to proliferate in the presence of elevated copper levels are, therefore, of key importance in our understanding of tumour growth progression. In the current study, we have examined the role played by the amyloid precursor protein (APP) in mitigating copper-induced growth inhibition of the PCa cell line, DU145. A range of APP molecular constructs were stably over-expressed in DU145 cells and their effects on cell proliferation in the presence of copper were monitored. Our results show that endogenous APP expression was induced by sub-toxic copper concentrations in DU145 cells and over-expression of the wild-type protein was able to mitigate copper-induced growth inhibition via a mechanism involving the cytosolic and E1 copper binding domains of the full-length protein. APP likely represents one of a range of copper binding proteins that PCa cells employ in order to ensure efficient proliferation despite elevated concentrations of the metal within the tumour microenvironment. Targeting the expression of such proteins may contribute to therapeutic strategies for the treatment of cancers.

  16. Microenvironment -Programmed Metastatic Prostate Cancer Stem Cells (mPCSCs)

    Science.gov (United States)

    2016-10-01

    mPCSCs)” PI : Dean Tang 1. INTRODUCTION: The main goal of this IDEA project is to help elucidate the cellular and molecular mechanisms underlying...metastatic prostate cancer stem cells 3. ACCOMPLISHMENTS: Dr. Tang, the PI of this grant, together with most lab members, moved from the M.D...repressing CD44. Nat Med 17, 211-215 (2011). 5. Qin, J. et al. The PSA -/lo prostate cancer cell population harbors self-renewing long-term tumor

  17. Non-coding RNAs in cancer brain metastasis

    Science.gov (United States)

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

    2017-01-01

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

  18. Medical image of the week: metastatic testicular cancer

    Directory of Open Access Journals (Sweden)

    Debo M

    2014-06-01

    Full Text Available A 30 year-old man with metastatic embryonal testicular cancer was admitted to the hospital with severe abdominal pain. A contrast enhanced CT of the abdomen demonstrated large metastatic burden throughout the liver and the left adrenal gland (Figures 1 and 2. The mass arising from the left adrenal gland caused significant mass effect. The left kidney was compressed, though without hydronephrosis, and the spleen was displaced laterally. Renal and hepatic functions were preserved. His pain was controlled with opioids and oral steroids with significant improvement.

  19. Promising oncolytic agents for metastatic breast cancer treatment

    Directory of Open Access Journals (Sweden)

    Cody JJ

    2015-06-01

    Full Text Available James J Cody,1 Douglas R Hurst2 1ImQuest BioSciences, Frederick, MD, 2Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA Abstract: New therapies for metastatic breast cancer patients are urgently needed. The long-term survival rates remain unacceptably low for patients with recurrent disease or disseminated metastases. In addition, existing therapies often cause a variety of debilitating side effects that severely impact quality of life. Oncolytic viruses constitute a developing therapeutic modality in which interest continues to build due to their ability to spare normal tissue while selectively destroying tumor cells. A number of different viruses have been used to develop oncolytic agents for breast cancer, including herpes simplex virus, adenovirus, vaccinia virus, measles virus, reovirus, and others. In general, clinical trials for several cancers have demonstrated excellent safety records and evidence of efficacy. However, the impressive tumor responses often observed in preclinical studies have yet to be realized in the clinic. In order for the promise of oncolytic virotherapy to be fully realized for breast cancer patients, effectiveness must be demonstrated in metastatic disease. This review provides a summary of oncolytic virotherapy strategies being developed to target metastatic breast cancer. Keywords: oncolytic virus, virotherapy, breast cancer, metastasis 

  20. Metastatic brain tumour in pregnancy: A case report

    Directory of Open Access Journals (Sweden)

    Pantović Sveto

    2012-01-01

    Full Text Available Introduction. Malignant tumours of the central nervous system in pregnancy are rare and are most frequently diagnosed in the second part of pregnancy Of all malignant tumours which may occur in pregnancy, intracranial tumours bear the highest risk of maternal and foetal morbidity and mortality. Case Outline. A 29-year-old primipara was admitted to our hospital as an emergency in the twenty-ninth week of pregnancy due to headache, right eye sight disorders (double vision, nausea and vomiting. The patient had a total thyroidectomy and a dissection of lymph glands of the neck at the age of seven years due to papillary carcinoma of the thyroid glands. The clinical and sonographic test revealed regular foetal growth and morphology. The MRI showed expansive changes in the brain parenchyma corresponding to metastatic lesion with the subtentorial herniation of the uncus of the hippocampus by compressive effect onto the right cerebral peduncle of the mesencephalon. Emergent neurosurgical intervention was indicated. Having in mind the age at pregnancy, it was decided to perform a caesarean operation. Alive female child was born weighing 1,370 grams. The post-operative procedure was normal. The patient was transferred to the neurosurgery department on the first post-operative day, where she underwent emergent surgery. Immunohistochemistry confirmed the metastatic tumour originating from the primary papillary adenocarcinoma of the thyroid gland. Conclusion. Neurosurgical diseases in pregnancy simultaneously jeopardize two lives and represent both medical and ethical problem. Upon confirming the presence of intracranial malignancy in pregnancy, further procedure is very individual and it implies cooperation of gynaecologists, neurologists, neurosurgeons, oncologists, anaesthesiologists and neonatologists.

  1. Cell-Free DNA in Metastatic Colorectal Cancer

    DEFF Research Database (Denmark)

    Spindler, Karen-Lise G; Boysen, Anders K; Pallisgård, Niels

    2017-01-01

    -analysis of the prognostic value of total cfDNA in patients with metastatic colorectal cancer (mCRC) treated with chemotherapy. In addition, we report on the overall performance of cfDNA as source for KRAS mutation detection. MATERIALS AND METHODS: A systematic literature search of PubMed and Embase was performed by two...... therapy. Small fragments of circulating cell-free DNA (cfDNA) can be measured in a simple blood sample. This report presents the first meta-analysis of the prognostic value of total cfDNA measurement in patients with metastatic colorectal cancer. Data from 1,076 patients confirmed that patients...... with the lowest pre-treatment levels of cfDNA had a significantly higher chance of longer survival than those with higher levels. Cell-free DNA analysis can also be used for detection of tumor-specific mutations, and hold potential as a valuable tool in colorectal cancer treatment....

  2. Promising oncolytic agents for metastatic breast cancer treatment

    Science.gov (United States)

    Cody, James J; Hurst, Douglas R

    2015-01-01

    New therapies for metastatic breast cancer patients are urgently needed. The long-term survival rates remain unacceptably low for patients with recurrent disease or disseminated metastases. In addition, existing therapies often cause a variety of debilitating side effects that severely impact quality of life. Oncolytic viruses constitute a developing therapeutic modality in which interest continues to build due to their ability to spare normal tissue while selectively destroying tumor cells. A number of different viruses have been used to develop oncolytic agents for breast cancer, including herpes simplex virus, adenovirus, vaccinia virus, measles virus, reovirus, and others. In general, clinical trials for several cancers have demonstrated excellent safety records and evidence of efficacy. However, the impressive tumor responses often observed in preclinical studies have yet to be realized in the clinic. In order for the promise of oncolytic virotherapy to be fully realized for breast cancer patients, effectiveness must be demonstrated in metastatic disease. This review provides a summary of oncolytic virotherapy strategies being developed to target metastatic breast cancer. PMID:27512671

  3. Unusual presentation of metastatic gall bladder cancer

    Directory of Open Access Journals (Sweden)

    Piyush Shukla

    2014-01-01

    Full Text Available To report the first case of rare isolated breast metastasis from carcinoma gall bladder. Single patient case report. A 35-year-old pre-menopausal female presented with 2 FNx01 2 cm right upper outer quadrant breast lump. Post-mastectomy, histology confirmed it to be metastatic adenocarcinoma positive for both Cytokeratin (CK 7 and CK20. Past history as told by the patient revealed that 2 years back, cholecystectomy was performed for gall stones, of which no histology reports were present; she had a port site scar recurrence which showed it to be adenocarcinoma. Adjuvant chemotherapy and radiotherapy was advised which the patient did not complete. This is probably the first case reported of isolated breast metastasis from gall bladder carcinoma, diagnosed retrospectively. It also highlights the importance of adjuvant treatment in gall bladder malignancy.

  4. Cytoreductive prostatectomy in metastatic prostate cancer

    DEFF Research Database (Denmark)

    Becker, Joachim Aidt; Berg, Kasper Drimer; Røder, Martin Andreas

    2017-01-01

    The impact of cytoreductive radical prostatectomy on oncological outcome in patients with prostate cancer and limited number of bone metastases is unclear. Data from cancer registries, multi-institutional databases and a single institutional case-control study indicate a possible benefit...

  5. Targeted treatment of advanced and metastatic breast cancer with lapatinib

    Directory of Open Access Journals (Sweden)

    Brendan Corkery

    2008-09-01

    Full Text Available Brendan Corkery1,2, Norma O’Donovan2, John Crown1,21St. Vincent’s University Hospital, Dublin, Ireland; 2National Institute for Cellular Biotechnology, Dublin City University, Dublin, IrelandAbstract: Improved molecular understanding of breast cancer in recent years has led to the discovery of important drug targets such as HER-2 and EGFR. Lapatinib is a potent dual inhibitor of HER-2 and EGFR. Preclinical and phase I studies have shown activity with lapatinib in a number of cancers, including breast cancer, and the drug is well tolerated. The main known drug interactions are with paclitaxel and irinotecan. The most significant side-effects of lapatinib are diarrhea and adverse skin events. Rates of cardiotoxicity compare favorably with trastuzumab, a monoclonal antibody against HER-2. This paper focuses on lapatinib in advanced and metastatic breast cancer, which remains an important therapeutic challenge. Phase II and III studies show activity as monotherapy, and in combination with chemotherapy or hormonal agents. Results from these studies suggest that the main benefit from lapatinib is in the HER-2 positive breast cancer population. Combinations of lapatinib and trastuzumab are also being studied and show encouraging results, particularly in trastuzumab-refractory metastatic breast cancer. Lapatinib may have a specific role in treating HER-2 positive CNS metastases. The role of lapatinib as neoadjuvant therapy and in early breast cancer is also being evaluated.Keywords: HER-2, EGFR, erbB, lapatinib, Tykerb®, tyrosine kinase

  6. Combination Drug Delivery Approaches in Metastatic Breast Cancer

    Directory of Open Access Journals (Sweden)

    Jun H. Lee

    2012-01-01

    Full Text Available Disseminated metastatic breast cancer needs aggressive treatment due to its reduced response to anticancer treatment and hence low survival and quality of life. Although in theory a combination drug therapy has advantages over single-agent therapy, no appreciable survival enhancement is generally reported whereas increased toxicity is frequently seen in combination treatment especially in chemotherapy. Currently used combination treatments in metastatic breast cancer will be discussed with their challenges leading to the introduction of novel combination anticancer drug delivery systems that aim to overcome these challenges. Widely studied drug delivery systems such as liposomes, dendrimers, polymeric nanoparticles, and water-soluble polymers can concurrently carry multiple anticancer drugs in one platform. These carriers can provide improved target specificity achieved by passive and/or active targeting mechanisms.

  7. Metastatic Breast Cancer or Multiple Myeloma? Camouflage by Lytic Lesions

    Directory of Open Access Journals (Sweden)

    Bruce Hough

    2010-01-01

    Full Text Available We report a case of a female with stage I infiltrating ductal carcinoma who received adjuvant therapy including trastuzumab. One year later she developed lytic lesions and was retreated with trastuzumab that was held after she developed symptomatic heart failure. Lytic lesions were attributed to relapse of breast cancer, and cardiac failure attributed to prior trastuzumab therapy. After complications necessitated multiple hospitalizations, a further workup revealed that the lytic lesions were not metastatic breast cancer but multiple myeloma. Her advanced multiple myeloma was associated with systemic amyloidosis involving gut and heart, which ultimately led to her demise. This report addresses the pitfalls of overlapping symptoms and the question of which patients with suspected metastatic disease should undergo a biopsy.

  8. Extreme hypothyroidism associated with sunitinib treatment for metastatic renal cancer.

    Science.gov (United States)

    Del Fabbro, Egidio; Dev, Rony; Cabanillas, Maria E; Busaidy, Naifa L; Rodriguez, EdenMae C; Bruera, Eduardo

    2012-08-01

    Although thyroid abnormalities are reported with the use of tyrosine kinase inhibitors, patients rarely require replacement therapy. The initial multicentre studies of sunitinib for metastatic renal cancer did not report hypothyroidism in fatigued patients, and thyroid tests were not routinely monitored. More recent studies, however, suggest that up to 70% of patients develop thyroid test abnormalities during treatment with sunitinib. Despite these concerns, the clinical relevance of sunitinib-induced hypothyroidism is uncertain since thyroid gland recovery is the norm in most patients. We report a case of a patient with metastatic papillary renal cell cancer on combination anti-angiogenic therapy with sunitinib, who developed unusually high thyroid stimulating hormone levels and severe symptoms despite receiving L-thyroxine. Our case also illustrates the complexity of managing sunitinib-associated thyroid dysfunction, which may be accompanied by transient thyroiditis, hyperthyroidism, and profound hypothyroidism.

  9. Lung cancer: atypical brain metastases mimicking neurocysticercosis.

    Science.gov (United States)

    Mota, Patrícia Caetano; Reis, Carina; Pires, Nuno Filipe; Sousa, Graça; Chamadoira, Clara; Guimarães, Marcos; Castro, Lígia; Marques, Margarida; Gomes, Isabel

    2011-12-01

    The authors describe a case of a 47-year-old male smoker with a 3-month history of hearing loss, tinnitus and dizziness. Physical examination revealed neurosensory hearing loss. Small rounded hypodensities without mass effect were evident in a computed tomography scan of the head, confirmed by brain magnetic resonance imaging as multiple cystic lesions in both cerebral and cerebellar hemispheres, without perilesional edema or gadolinium enhancement, suggestive of neurocysticercosis. Extraparenchymal involvement was also noted. Albendazole and dexamethasone were started. As a chest radiograph showed a bilateral reticulonodular pattern, a bronchoscopy was performed showing normal results. However, transbronchial biopsy revealed lung adenocarcinoma. Thoracoabdominopelvic computed tomography scan showed secondary lung and bone lesions. Since brain lesions were not suggestive of secondary tumor lesions, a brain biopsy was performed confirming metastatic disease. This case illustrates some peculiar imagiological features of brain metastases in lung cancer, indicating that sometimes invasive procedures are required to establish a definitive diagnosis.

  10. Targeting Mitochondrial Inhibitors for Metastatic Castrate Resistant Prostate Cancer

    Science.gov (United States)

    2017-09-01

    niclosamide and 7 hydroxy-β-Lapachone (7OH β-Lap) analog lipophilic mitochondria toxins (MT) to human serum albumin (HSA) via a PSA specific peptide... human serum albumin (HSA) via a PSA specific peptide linker sequence to systemically deliver these novel agents via the blood so that these cell...effect”. Keywords Metastatic castration resistant prostate cancer, mitochondria toxins, human serum albumin , PSA-activated prodrugs Accomplishments

  11. Visualising and quantifying angiogenesis in metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Hansen, Torben Frøstrup; Nielsen, Boye Schnack; Jakobsen, Anders

    2013-01-01

    Angiogenesis plays an important role in tumour growth and dissemination. We have recently shown that blood vessel density, determined by image analysis based on microRNA-126 (miRNA-126) in situ hybridization (ISH) in the primary tumours of metastatic colorectal cancers (mCRC), is predictive of ch...... of chemotherapy response. Here, we evaluated whether more general approaches to determine vessel density in primary tumours are equally predictive of chemotherapy response....

  12. Salvage Lenvatinib Therapy in Metastatic Anaplastic Thyroid Cancer.

    Science.gov (United States)

    Iñiguez-Ariza, Nicole M; Ryder, Mabel M; Hilger, Crystal R; Bible, Keith C

    2017-07-01

    Historical anaplastic thyroid cancer (ATC) outcomes have been terrible, with a median survival of only five months and <20% one-year survival. Improved outcomes are now achieved with aggressive initial therapy in stages IVA and IVB disease, but patients with distant metastatic disease (stage IVC) still do poorly; improved therapies are sorely needed. Kinase inhibitors have emerged as promising agents in the therapy of advanced medullary and differentiated thyroid cancer, but there are limited data regarding the use of lenvatinib in ATC. The aim of this study was to delineate clinical outcomes in a series of patients with advanced ATC in response to lenvatinib therapy. A retrospective analysis was conducted involving all lenvatinib-treated Mayo Clinic ATC patients in 2015. Of 28 distinct ATC patients seen in 2015, three (11%) with metastatic disease of ECOG performance status 2-3 were treated with lenvatinib. Two patients were male; age range at ATC diagnosis was 57-84 years. All three patients attained successful local control of their disease with surgery and/or combined chemoradiotherapy. Lenvatinib was offered as the second, third, or fourth line of therapy at the time of metastatic disease progression. Two patients incurred minor responses to therapy, with structural regression of distant metastatic tumor disease soon after starting lenvatinib treatment (at one to two months), while one patient achieved stable disease, but no Response Evaluation Criteria In Solid Tumors partial responses resulted. Overall survival after starting lenvatinib was two, six, and seven months. Fatigue and hypertension were prominent, and one patient developed pulmonary emboli while on lenvatinib. This initial single-institution experience suggests that lenvatinib may have some disease-modifying activity in metastatic ATC that is otherwise refractory to cytotoxic chemotherapy. Unfortunately, observed benefits were transient, and toxicities were prominent. Clinical trials are required

  13. Gene Delivery for Metastatic Prostate Cancer Cells

    National Research Council Canada - National Science Library

    Pang, Shen

    2001-01-01

    .... Enhanced by the bystander effect, the specific expression of the DTA gene causes significant cell death in prostate cancer cell cultures, with very low background cell eradication in control cell lines...

  14. Roles of the Cyclooxygenase 2 Matrix Metalloproteinase 1 Pathway in Brain Metastasis of Breast Cancer*

    Science.gov (United States)

    Wu, Kerui; Fukuda, Koji; Xing, Fei; Zhang, Yingyu; Sharma, Sambad; Liu, Yin; Chan, Michael D.; Zhou, Xiaobo; Qasem, Shadi A.; Pochampally, Radhika; Mo, Yin-Yuan; Watabe, Kounosuke

    2015-01-01

    Brain is one of the major sites of metastasis in breast cancer; however, the pathological mechanism of brain metastasis is poorly understood. One of the critical rate-limiting steps of brain metastasis is the breaching of blood-brain barrier, which acts as a selective interface between the circulation and the central nervous system, and this process is considered to involve tumor-secreted proteinases. We analyzed clinical significance of 21 matrix metalloproteinases on brain metastasis-free survival of breast cancer followed by verification in brain metastatic cell lines and found that only matrix metalloproteinase 1 (MMP1) is significantly correlated with brain metastasis. We have shown that MMP1 is highly expressed in brain metastatic cells and is capable of degrading Claudin and Occludin but not Zo-1, which are key components of blood-brain barrier. Knockdown of MMP1 in brain metastatic cells significantly suppressed their ability of brain metastasis in vivo, whereas ectopic expression of MMP1 significantly increased the brain metastatic ability of the cells that are not brain metastatic. We also found that COX2 was highly up-regulated in brain metastatic cells and that COX2-induced prostaglandins were directly able to promote the expression of MMP1 followed by augmenting brain metastasis. Furthermore, we found that COX2 and prostaglandin were able to activate astrocytes to release chemokine (C-C motif) ligand 7 (CCL7), which in turn promoted self-renewal of tumor-initiating cells in the brain and that knockdown of COX2 significantly reduced the brain metastatic ability of tumor cells. Our results suggest the COX2-MMP1/CCL7 axis as a novel therapeutic target for brain metastasis. PMID:25691572

  15. miR-345 in Metastatic Colorectal Cancer

    DEFF Research Database (Denmark)

    Schou, Jakob V; Rossi, Simona; Jensen, Benny V

    2014-01-01

    for overall survival (OS) in patients with metastatic colorectal cancer (mCRC) treated with cetuximab and irinotecan. METHODS: From 138 patients with mCRC in 3rd line therapy with cetuximab and irinotecan in a prospective phase II study, 738 pretreatment miRNAs were isolated and profiled from whole blood......INTRODUCTION: MicroRNAs (miRNAs) have important regulatory functions in cellular processes and have shown promising potential as prognostic markers for disease outcome in patients with cancer. The aim of the present study was to find miRNA expression profiles in whole blood that were prognostic...

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

    Directory of Open Access Journals (Sweden)

    Couraud Pierre-Olivier

    2009-07-01

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

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

    International Nuclear Information System (INIS)

    Khaitan, Divya; Sankpal, Umesh T; Weksler, Babette; Meister, Edward A; Romero, Ignacio A; Couraud, Pierre-Olivier; Ningaraj, Nagendra S

    2009-01-01

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

  18. Automatic metastatic brain tumor segmentation for stereotactic radiosurgery applications

    Science.gov (United States)

    Liu, Yan; Stojadinovic, Strahinja; Hrycushko, Brian; Wardak, Zabi; Lu, Weiguo; Yan, Yulong; Jiang, Steve B.; Timmerman, Robert; Abdulrahman, Ramzi; Nedzi, Lucien; Gu, Xuejun

    2016-12-01

    The objective of this study is to develop an automatic segmentation strategy for efficient and accurate metastatic brain tumor delineation on contrast-enhanced T1-weighted (T1c) magnetic resonance images (MRI) for stereotactic radiosurgery (SRS) applications. The proposed four-step automatic brain metastases segmentation strategy is comprised of pre-processing, initial contouring, contour evolution, and contour triage. First, T1c brain images are preprocessed to remove the skull. Second, an initial tumor contour is created using a multi-scaled adaptive threshold-based bounding box and a super-voxel clustering technique. Third, the initial contours are evolved to the tumor boundary using a regional active contour technique. Fourth, all detected false-positive contours are removed with geometric characterization. The segmentation process was validated on a realistic virtual phantom containing Gaussian or Rician noise. For each type of noise distribution, five different noise levels were tested. Twenty-one cases from the multimodal brain tumor image segmentation (BRATS) challenge dataset and fifteen clinical metastases cases were also included in validation. Segmentation performance was quantified by the Dice coefficient (DC), normalized mutual information (NMI), structural similarity (SSIM), Hausdorff distance (HD), mean value of surface-to-surface distance (MSSD) and standard deviation of surface-to-surface distance (SDSSD). In the numerical phantom study, the evaluation yielded a DC of 0.98  ±  0.01, an NMI of 0.97  ±  0.01, an SSIM of 0.999  ±  0.001, an HD of 2.2  ±  0.8 mm, an MSSD of 0.1  ±  0.1 mm, and an SDSSD of 0.3  ±  0.1 mm. The validation on the BRATS data resulted in a DC of 0.89  ±  0.08, which outperform the BRATS challenge algorithms. Evaluation on clinical datasets gave a DC of 0.86  ±  0.09, an NMI of 0.80  ±  0.11, an SSIM of 0.999  ±  0.001, an HD of 8

  19. A Recombinant Platform for Prioritizing Aerolysin Molecular Grenades for Metastatic Prostate Cancer

    Science.gov (United States)

    2016-12-01

    AWARD NUMBER: W81XWH-14-1-0377 TITLE: A Recombinant Platform for Prioritizing Aerolysin Molecular Grenades for Metastatic Prostate Cancer ...2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER A Recombinant Platform for Prioritizing Aerolysin Molecular Grenades for Metastatic Prostate Cancer 5b...progression of prostate cancer (PCa) to castrate resistant metastatic disease is an ominous diagnosis. To overcome tumor cell heterogeneity based

  20. Carbohydrate antigen 549 in metastatic breast cancer during cytostatic treatment and follow-up

    DEFF Research Database (Denmark)

    Sölétormos, G; Nielsen, D; Schiøler, V

    1992-01-01

    This study was designed to investigate whether the serum tumour marker CA 549 gave early and reliable information about disease activity among metastatic breast cancer patients during cytostatic treatment and follow-up. 50 females with metastatic breast cancer were monitored clinically...... among 91% by marker progression. Clinical progression was excluded among 93% without marker progression. In conclusion, monitoring of metastatic breast cancer patients could include CA 549 if standardised criteria for marker evaluation are used....

  1. Unusual aggressive breast cancer: metastatic malignant phyllodes tumor.

    Science.gov (United States)

    Singer, Adam; Tresley, Jonathan; Velazquez-Vega, Jose; Yepes, Monica

    2013-02-01

    For the year of 2012, it has been estimated that breast cancer will account for the greatest number of newly diagnosed cancers and the second highest proportion of cancer related deaths among women. Breast cancer, while often lumped together as one disease, represents a diverse group of malignancies with different imaging findings, histological appearances and behavior. While most invasive primary breast cancers are epithelial derived adenocarcinomas, rare neoplasms such as the phyllodes tumor may arise from mesenchymal tissue. Compared to the breast adenocarcinoma, the phyllodes tumor tends to affect a younger population, follows a different clinical course, is associated with different imaging and histological findings and is managed distinctively. There may be difficulty in differentiating the phyllodes tumor from a large fibroadenoma, but the mammographer plays a key role in reviewing the clinical and imaging data in order to arrive at the correct diagnosis. Early diagnosis with proper surgical management can often cure non-metastatic phyllodes tumors. However, in rare cases where metastasis occurs, prognosis tends to be poor. This report describes the presentation, imaging findings and management of a metastatic malignant phyllodes tumor.

  2. Phytochemicals potently inhibit migration of metastatic breast cancer cells†

    Science.gov (United States)

    Ham, Stephanie Lemmo; Nasrollahi, Samila; Shah, Kush N.; Soltisz, Andrew; Paruchuri, Sailaja; Yun, Yang H.; Luker, Gary D.; Bishayee, Anupam; Tavana, Hossein

    2017-01-01

    Cell migration is a major process that drives metastatic progression of cancers, the major cause of cancer death. Existing chemotherapeutic drugs have limited efficacy to prevent and/or treat metastasis, emphasizing the need for new treatments. We focus on triple negative breast cancer (TNBC), the subtype of breast cancer with worst prognosis and no standard chemotherapy protocols. Here we demonstrate that a group of natural compounds, known as phytochemicals, effectively block migration of metastatic TNBC cells. Using a novel cell micropatterning technology, we generate consistent migration niches in standard 96-well plates where each well contains a cell-excluded gap within a uniform monolayer of cells. Over time, cells migrate into and occupy the gap. Treating TNBC cells with non-toxic concentrations of phytochemicals significantly blocks motility of cells. Using a molecular analysis approach, we show that anti-migratory property of phytochemicals is partly due to their inhibitory effects on phosphorylation of ERK1/2. This study provides a framework for future studies to understand molecular targets of phytochemicals and evaluate their effectiveness in inhibiting metastasis in animal models of cancer. PMID:26120051

  3. Metastatic Organotropism: An Intrinsic Property of Breast Cancer Molecular Subtypes.

    Science.gov (United States)

    Wei, Shi; Siegal, Gene P

    2017-03-01

    It has long been known that some cancers have the propensity to metastasize to certain organs thus creating a nonrandom distribution of sites for distant relapse, a phenomenon known as "metastatic organotropism." Some of these examples include ovary primary to abdominal cavity, prostate primary to bone, and pancreas primary to liver. In contrast, other tumor types, such as mammary and renal cell carcinoma, can relapse in multiple organs although approximately half of advanced breast cancers metastasize to bone. On the other hand gene expression profiling studies have identified various breast cancer classes with prognostic significance. Recent studies have revealed that breast cancer subtypes differ not only in primary tumor characteristics but also in their metastatic behavior. In particular, the luminal tumors are remarkable for their significant bone-seeking phenotype; the HER2 subtype demonstrates a significant liver-homing characteristic; whereas so-called triple-negative breast cancers predispose to lung metastases. These findings suggest that this knowledge could potentially be utilized in the development of effective disease surveillance strategies in the pursuit of precision medicine, thus necessitating further investigation.

  4. Targeting metastatic colorectal cancer – present and emerging treatment options

    Directory of Open Access Journals (Sweden)

    Ciombor KK

    2014-07-01

    Full Text Available Kristen K Ciombor,1 Jordan Berlin21Division of Medical Oncology, Department of Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA; 2Division of Hematology/Oncology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Nashville, TN, USAAbstract: Metastatic colorectal cancer is a significant cause of morbidity and mortality in the US and around the world. While several novel cytotoxic and biologic therapies have been developed and proven efficacious in the past two decades, their optimal use in terms of patient selection, drug combinations, and regimen sequences has yet to be defined. Recent investigations regarding anti-epidermal growth factor receptor therapies include the comparison of single-agent panitumumab and cetuximab, the benefit of adding cetuximab to chemotherapy in the conversion therapy setting, the comparison of cetuximab and bevacizumab when added to first-line chemotherapy, and predictive biomarkers beyond KRAS exon 2 (codons 12 and 13 mutations. With respect to anti-vascular endothelial growth factor therapies, new data on continuing bevacizumab beyond disease progression on a bevacizumab-containing chemotherapy regimen, the addition of bevacizumab to triplet chemotherapy in the first-line setting, maintenance therapy with bevacizumab plus either capecitabine or erlotinib, the addition of aflibercept to chemotherapy, and regorafenib as monotherapy have emerged. Recent scientific and technologic advances in the field of metastatic colorectal cancer promise to elucidate the biological underpinnings of this disease and its therapies for the goal of improving personalized treatments for patients with metastatic colorectal cancer.Keywords: cetuximab, panitumumab, bevacizumab, aflibercept, regorafenib, biomarker

  5. Prognostic value of serum tetranectin in patients with metastatic breast cancer

    DEFF Research Database (Denmark)

    Høgdall, C K; Sölétormos, G; Nielsen, D

    1993-01-01

    To evaluate serum tetranectin as a prognostic marker before first-line chemotherapy, serum levels were studied in 67 patients with metastatic breast cancer. In the Cox analyses, the relative risk (RR) for death of cancer varied with the cut-off level of serum tetranectin. A maximal RR of 5...... prognostic factor in metastatic breast cancer....

  6. Pembrolizumab and Ruxolitinib Phosphate in Treating Patients With Metastatic Stage IV Triple Negative Breast Cancer

    Science.gov (United States)

    2018-03-05

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

  7. Photo-nano immunotherapy for metastatic cancers (Conference Presentation)

    Science.gov (United States)

    Zhou, Feifan

    2016-03-01

    We constructed a multifunction nano system SWNT-GC and investigated the synergize photothermal and immunological effects. Here, we improve the SWNT-GC nano system and design a new synergistic nano-particle, both have the photothermal effects and immunological effects. We investigate the therapeutic effects and detect the immune response with metastatic mouse tumor models. We also study the therapeutic mechanism after treatment in vitro and in vivo. With the enhancement of nano-materials on photothermal effects, laser treatment could destroy primary tumor and protect normal tissue with low dose laser irradiation. With the immunological effects of nano-materials, the treatment could trigger specific antitumor immune response, to eliminate the metastasis tumor. It is providing a promising treatment modality for the metastatic cancers.

  8. Tumour heterogeneity promotes collective invasion and cancer metastatic dissemination.

    Science.gov (United States)

    Hallou, Adrien; Jennings, Joel; Kabla, Alexandre J

    2017-08-01

    Heterogeneity within tumour cell populations is commonly observed in most cancers. However, its impact on metastatic dissemination, one of the primary determinants of the disease prognosis, remains poorly understood. Working with a simplified numerical model of tumour spheroids, we investigated the impact of mechanical heterogeneity on the onset of tumour invasion into surrounding tissues. Our work establishes a positive link between tumour heterogeneity and metastatic dissemination, and recapitulates a number of invasion patterns identified in vivo , such as multicellular finger-like protrusions. Two complementary mechanisms are at play in heterogeneous tumours. A small proportion of stronger cells are able to initiate and lead the escape of cells, while collective effects in the bulk of the tumour provide the coordination required to sustain the invasive process through multicellular streaming. This suggests that the multicellular dynamics observed during metastasis is a generic feature of mechanically heterogeneous cell populations and might rely on a limited and generic set of attributes.

  9. Metastatic pancreatic cancer presenting as linitis plastica of the stomach.

    Science.gov (United States)

    Garg, Shivani; Mulki, Ramzi; Sher, Daniel

    2016-03-08

    Metastatic disease from pancreatic carcinoma involving the stomach is an unusual event, and the pattern of spread in the form of linitis plastica, to our knowledge, has not been reported previously. Local recurrence after curative resection for pancreatic cancer is the most common pattern of disease. We report a case of metastatic pancreatic adenocarcinoma presenting as linitis plastica of the stomach 4 years after curative resection. A 52-year-old man presented with epigastric pain and melaena 4 years after undergoing a Whipple's procedure for a poorly-differentiated pancreatic adenocarcinoma, stage IB; T2N0M0. CT imaging of the abdomen revealed thickening of the gastric wall, and subsequent oesophagogastroduodenoscopy (OGD) revealed diffuse friable erythaematous tissue. The biopsy specimen obtained during the OGD revealed a poorly differentiated adenocarcinoma, with similar appearance to the prior specimen obtained from the pancreas. 2016 BMJ Publishing Group Ltd.

  10. Combination of TB lymphadenitis and metastatic LAP in breast cancer

    Directory of Open Access Journals (Sweden)

    Abdolhassan Talaiezadeh

    2015-06-01

    Full Text Available Tuberculosis (TB may present as pulmonary and extra-pulmonary. TB lymphadenitis is the most common presentation of extra-pulmonary TB. TB lymphadenitis should be taken into account in the differential diagnosis of different disorders such as metastatic lymphadenopathy. The reported patient was a 65-year-old lady with breast cancer and conglomerated and matted axillary lymphadenopathy who received chemotherapy. She presented with more extensive axillary LAP contrary to our expectation. Modified radical mastectomy was done and pathology analysis reported TB lymphadenitis associated with metastatic LAP. Under cover of anti-TB therapy adjuvant chemoradiation therapy was started. Accordingly, we recommend TB be ruled out in every patient who needs chemotherapy in the endemic region because chemotherapy may cause the extension of TB in the body.

  11. Mutational analysis and clinical correlation of metastatic colorectal cancer.

    Science.gov (United States)

    Russo, Andrea L; Borger, Darrell R; Szymonifka, Jackie; Ryan, David P; Wo, Jennifer Y; Blaszkowsky, Lawrence S; Kwak, Eunice L; Allen, Jill N; Wadlow, Raymond C; Zhu, Andrew X; Murphy, Janet E; Faris, Jason E; Dias-Santagata, Dora; Haigis, Kevin M; Ellisen, Leif W; Iafrate, Anthony J; Hong, Theodore S

    2014-05-15

    Early identification of mutations may guide patients with metastatic colorectal cancer toward targeted therapies that may be life prolonging. The authors assessed tumor genotype correlations with clinical characteristics to determine whether mutational profiling can account for clinical similarities, differences, and outcomes. Under Institutional Review Board approval, 222 patients with metastatic colon adenocarcinoma (n = 158) and rectal adenocarcinoma (n = 64) who underwent clinical tumor genotyping were reviewed. Multiplexed tumor genotyping screened for >150 mutations across 15 commonly mutated cancer genes. The chi-square test was used to assess genotype frequency by tumor site and additional clinical characteristics. Cox multivariate analysis was used to assess the impact of genotype on overall survival. Broad-based tumor genotyping revealed clinical and anatomic differences that could be linked to gene mutations. NRAS mutations were associated with rectal cancer versus colon cancer (12.5% vs 0.6%; P colon cancer (13% vs 3%; P = .024) and older age (15.8% vs 4.6%; P = .006). TP53 mutations were associated with rectal cancer (30% vs 18%; P = .048), younger age (14% vs 28.7%; P = .007), and men (26.4% vs 14%; P = .03). Lung metastases were associated with PIK3CA mutations (23% vs 8.7%; P = .004). Only mutations in BRAF were independently associated with decreased overall survival (hazard ratio, 2.4; 95% confidence interval, 1.09-5.27; P = .029). The current study suggests that underlying molecular profiles can differ between colon and rectal cancers. Further investigation is warranted to assess whether the differences identified are important in determining the optimal treatment course for these patients. © 2014 American Cancer Society.

  12. A review on metastatic breast cancer in Iran

    Directory of Open Access Journals (Sweden)

    Hamidreza Alizadeh Otaghvar

    2015-06-01

    Full Text Available Metastatic breast cancer is a disease of early breast cancer that usually occurs several years after the early breast cancer. Breast cancer is the most common cancer among Iranian women. According to the new statistics in Iran 6160 breast cancers are diagnosed in the country each year and 1063 cases lead to death. In this paper, epidemiology, diagnosis and treatment have been investigated. In this study, case–control clinical trials and open studies with adequate data were collected. Due to the higher risk of age group 40–49 years and the advent of advanced breast cancer in Iranian women, the early diagnosis and determination of the exact size of the tumor before surgery is important in choosing a therapy plan. The decision on the therapy of invasive breast cancer depends on several factors such as cancer stage, tumor size and type, pathological and cytological status of the tumor, the patient's opinion, the presence or absence of estrogen and progesterone receptors in the cytoplasm of tumor cells and so on.

  13. Hormone therapy in metastatic prostate cancer

    Directory of Open Access Journals (Sweden)

    Jebelameli P

    1997-09-01

    Full Text Available Only orchiectomy is still commonly used today either as a single therapy or in combination regimens. Hypophysectomy & adrenalectomy showed such devastating effects on the endocrine equilibrium as to be inconsistent with an acceptable quality of life or even with survival. Chemical adrenalectomy was also tried with drugs (eg. aminoglutethmide, spironolactone leading to consequences superimposable to those of surgical adrenalectomy. Along with orchiectomy, three groups of substances are commonly used today for the hormonal therapy of prostate cancer: estrogens, LHRH agonists & anti androgens. Bilateral orchiectomy removes 90-95% of circulating testosterone. Clinical studies document 60-80% of positive responders to castration, on continued evaluation, relapse occurs usually within 6-24 months in responders, with a death rate of 50% within 6 months. The androgenic activity still remaining after castration may explain the partial & progressively decreasing effectiveness of this & other testosterone reducing therapies. Antiandrogens define substances that act directly at the target site, where interacting with steroid hormone receptors, they impede the binding of androgens. A trend towards the combination of testosterone-reducing & androgen-blocking treatment is developing in modern therapy of prostate cancer. This is due to the complementary characteristics of the two different pharmacological mechanisms that are involved. In this study castration+antiandrogen is compared to castration alone. The results demonstrate a significantly greater percentage of positive objective & subjective responses with antiandrogen than with placebo. In addition survival time was increased in patients treated with castration+antiandrogen than castration+placebo.

  14. Functionalization of nanotextured substrates for enhanced identification of metastatic breast cancer cells

    Science.gov (United States)

    Mansur, Nuzhat; Raziul Hasan, Mohammad; Kim, Young-tae; Iqbal, Samir M.

    2017-09-01

    Metastasis is the major cause of low survival rates among cancer patients. Once cancer cells metastasize, it is extremely difficult to contain the disease. We report on a nanotextured platform for enhanced detection of metastatic cells. We captured metastatic (MDA-MDB-231) and non-metastatic (MCF-7) breast cancer cells on anti-EGFR aptamer modified plane and nanotextured substrates. Metastatic cells were seen to change their morphology at higher rates when captured on nanotextured substrates than on plane substrates. Analysis showed statistically different morphological behaviors of metastatic cells that were very pronounced on the nanotextured substrates. Several distance matrices were calculated to quantify the dissimilarity of cell shape change. Nanotexturing increased the dissimilarity of the metastatic cells and as a result the contrast between metastatic and non-metastatic cells increased. Jaccard distance measurements found that the shape change ratio of the non-metastatic and metastatic cells was enhanced from 1:1.01 to 1:1.81, going from plane to nanotextured substrates. The shape change ratio of the non-metastatic to metastatic cells improved from 1:1.48 to 1:2.19 for the Hausdorff distance and from 1:1.87 to 1:4.69 for the Mahalanobis distance after introducing nanotexture. Distance matrix analysis showed that nanotexture increased the shape change ratios of non-metastatic and metastatic cells. Hence, the detectability of metastatic cells increased. These calculated matrices provided clear and explicit measures to discriminate single cells for their metastatic state on functional nanotextured substrates.

  15. Cytogenomic profiling of breast cancer brain metastases reveals potential for repurposing targeted therapeutics.

    Science.gov (United States)

    Bollig-Fischer, Aliccia; Michelhaugh, Sharon K; Wijesinghe, Priyanga; Dyson, Greg; Kruger, Adele; Palanisamy, Nallasivam; Choi, Lydia; Alosh, Baraa; Ali-Fehmi, Rouba; Mittal, Sandeep

    2015-06-10

    Breast cancer brain metastases remain a significant clinical problem. Chemotherapy is ineffective and a lack of treatment options result in poor patient outcomes. Targeted therapeutics have proven to be highly effective in primary breast cancer, but lack of molecular genomic characterization of metastatic brain tumors is hindering the development of new treatment regimens. Here we contribute to fill this void by reporting on gene copy number variation (CNV) in 10 breast cancer metastatic brain tumors, assayed by array comparative genomic hybridization (aCGH). Results were compared to a list of cancer genes verified by others to influence cancer. Cancer gene aberrations were identified in all specimens and pathway-level analysis was applied to aggregate data, which identified stem cell pluripotency pathway enrichment and highlighted recurring, significant amplification of SOX2, PIK3CA, NTRK1, GNAS, CTNNB1, and FGFR1. For a subset of the metastatic brain tumor samples (n = 4) we compared patient-matched primary breast cancer specimens. The results of our CGH analysis and validation by alternative methods indicate that oncogenic signals driving growth of metastatic tumors exist in the original cancer. This report contributes support for more rapid development of new treatments of metastatic brain tumors, the use of genomic-based diagnostic tools and repurposed drug treatments.

  16. Thyroid Cancer Presenting with Concomitant Metastatic Breast Cancer in the Thyroid

    Directory of Open Access Journals (Sweden)

    Chung-Chen Wang

    2014-12-01

    Full Text Available The thyroid is an unusual site to find cancer metastasis. When it does occur, such cancer spread is often manifested in multiple metastases and generally suggests a poor prognosis. We presented here a 49-year-old woman recently diagnosed with thyroid cancer, who had been treated for stage IIA breast cancer 8 years ago. After radical right thyroidectomy and left subtotal thyroidectomy, her pathological report showed papillary thyroid carcinoma, right thyroid, with concomitant metastatic breast carcinoma. This is the first case of which we are aware involving coexisting thyroid cancer and metastatic breast cancer in the ipsilateral lobe. Moreover, the circumstances of this case show a very unique clinical course compared with previous studies. Given the unusual circumstances of our case, we further discuss the relationship between thyroid cancer and breast cancer.

  17. Photodynamic therapy for metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    E. V. Horanskaya

    2014-01-01

    Full Text Available Results of treatment for cutaneous metastasis of breast cancer with photjdynamic therapy are represented. The study included 46 patients, the total number of treated cutaneous metastases was 535. For photodynamic therapy photosensitizer photolon given intravenously at a dose of 0.9–1.6 mg/kg body weight 3 h before treatment session (wave length 661±1 nm, плотность мощности 0,11–0,56 J/cm2, мощность на выходе волокна 0,3–2,0 Wt, light dose 50–600 J/cm2. Complete regression of metastasis was obtained in 33.6% of cases, partial – in 39.4%, stabilization – in 22.6%, progression of disease was in 4.3% of cases. The results show the perspectiveness of photodynamic therapy for metastasis as one of the step of treatment. 

  18. Radioembolization for primary and metastatic liver cancer.

    Science.gov (United States)

    Memon, Khairuddin; Lewandowski, Robert J; Kulik, Laura; Riaz, Ahsun; Mulcahy, Mary F; Salem, Riad

    2011-10-01

    The incidence of hepatocellular carcinoma is increasing. Most patients present beyond potentially curative options and are usually affected by underlying cirrhosis. In this scenario, transarterial therapies, such as radioembolization, are rapidly gaining acceptance as a potential therapy for hepatocellular carcinoma and liver metastases. Radioembolization is a catheter-based liver-directed therapy that involves the injection of micron-sized embolic particles loaded with a radioisotope by use of percutaneous transarterial techniques. Cancer cells are preferentially supplied by arterial blood and normal hepatocytes by portal venous blood; therefore, radioembolization specifically targets tumor cells with a high dose of lethal radiation and spares healthy hepatocytes. The antitumor effect mostly comes from radiation rather than embolization. The most commonly used radioisotope is yttrium-90. The commercially available devices are TheraSphere (glass based; MDS Nordion, Ottawa, Canada) and SIR-Sphere (resin based; Sirtex, Lane Cove, Australia). The procedure is performed on an outpatient basis. The incidence of complications is comparatively less than other locoregional therapies and may include nausea, fatigue, abdominal pain, hepatic dysfunction, biliary injury, fibrosis, radiation pneumonitis, gastrointestinal ulcers, and vascular injury. However, these complications can be avoided by meticulous pretreatment assessment, careful patient selection, and adequate dosimetry. This article focuses on both the technical and clinical aspects of radioembolization with emphasis on patient selection, uses and complications. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Depression in older women with metastatic breast cancer.

    Science.gov (United States)

    D'Ambruoso, Sarah F

    2014-12-01

    Depressive symptoms are common in older women with late-stage breast cancer, and some of these patients meet criteria for major depressive disorder. Significant overlap exists among many of the most prevalent physical signs and symptoms of depression in older adults (e.g., weight loss, fatigue) and the physical signs and symptoms of malignancy or treatment for malignancy, which may contribute to ongoing underdiagnosis and undertreatment of depression in this population. The National Comprehensive Cancer Network and evidence-based geriatric nursing guidelines call for routine screening for depression with valid and reliable screening instruments among high-risk groups at every encounter. Geriatrics, oncology, and palliative care nurses are encouraged to regularly screen older women with metastatic breast cancer for depressive symptoms and maintain a low threshold for initiation of behavioral and/or psychopharmacological interventions. Copyright 2014, SLACK Incorporated.

  20. Third-line therapy for metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Gundgaard, M.G.; Ehrnrooth, E.; Sørensen, Jens Benn

    2008-01-01

    , panitumumab. As a result, third-line treatment is now a necessary step in the optimal treatment of patients with metastatic colorectal cancer (MCRC). MATERIALS AND METHODS: We conducted a literature review of English language publications on third-line therapy for MCRC from January 2000 to April 2007. Data......BACKGROUND: The past years' therapy for colorectal cancer has evolved rapidly with the introduction of novel cytotoxic agents such as irinotecan, capecitabine and oxaliplatin. Further advances have been achieved with the integration of targeted agents such as bevacizumab, cetuximab and recently......OS of 16 months. With irinotecan and 5-FU, mOS around 8 months were reported and with cetuximab combined with irinotecan, the highest mOS was 9.8 months. CONCLUSION: Third-line therapy in advanced colorectal cancer may improve mOS for patients with MCRC. Therefore, randomized studies should be conducted...

  1. Treatment of metastatic colorectal cancer: focus on panitumumab

    International Nuclear Information System (INIS)

    Tay, Rebecca Y; Wong, Rachel; Hawkes, Eliza A

    2015-01-01

    Targeted agents are an important therapeutic option in the treatment of metastatic colorectal cancer (mCRC). Panitumumab is a recombinant, fully humanized, immunoglobulin G2 monoclonal antibody that targets the epidermal growth factor receptor (EGFR) with efficacy in mCRC as monotherapy and in combination with chemotherapy. Kirsten rat sarcoma (KRAS) mutation status has emerged as an important biomarker to predict response to anti-EGFR therapy. Optimal timing for panitumumab use in the mCRC treatment algorithm has not been established. This review discusses the mechanism of action, predictive biomarkers, and role of panitumumab in the treatment of mCRC

  2. A study of perifocal low-density area in metastatic brain tumor

    International Nuclear Information System (INIS)

    Suzuki, Ryuta; Okada, Kodai; Hiratsuka, Hideo; Inaba, Yutaka; Tsuyumu, Matsutaira.

    1980-01-01

    It is well known that vasogenic brain edema often develops in brain tumors, head injuries, and inflammatory brain lesions. In order to investigate the development and resolution of vasogenic brain edema, some CT findings of metastatic brain tumors were studied in detail. 20 cases of metastatic brain tumors of the past three years were examined by means of a CT scan. In almost all the cases there was a perifocal low-density area (PFL) in the CT findings. In the tumors which were cystic and/or located in the infratentorial space, PFL was not present or, if present, only slightly so. On the contrary, in the tumors which were nodular and/or in the supratentorial space, PFL was present extensively. In the supratentorial metastasis, PFL seemed to be restricted within the white matter and not to involve the gray matter nor such midline structures as basal ganglia and corpus callosum. Besides, PFL was always in contact with the lateral ventricular wall. These results show that PFL in the metastatic tumors resembles in shape the experimental cold-induced brain edema in cats. PFL is presumed to represent vasogenic brain edema; these findings support the hypothesis that the main mechanism of the resolution of vasogenic brain edema is the drainage of the edema fluid into the ventricular CSF. (author)

  3. Profile of palbociclib in the treatment of metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Ehab M

    2016-05-01

    treatment of postmenopausal women with ERα+/HER2− locally advanced or metastatic breast cancer. In this review, we discuss the potential role of CDK inhibition in breast cancer treatment, and focus on palbociclib progress from preclinical studies to clinical trials with mentioning the most recent ongoing as well as planned Phase II and Phase III trials of palbociclib in advanced breast cancer.Keywords: cyclin-dependent kinases, cell cycle, metastatic breast cancer, PD0332991

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

    Science.gov (United States)

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

    2015-03-15

    Brain metastases occur frequently in melanoma patients with advanced disease whereby the prognosis is dismal. The underlying mechanisms of melanoma brain metastasis development are not well understood. Identification of molecular determinants regulating melanoma brain metastasis would advance the development of prevention and therapy strategies for this disease. Gene expression profiles of cutaneous and brain-metastasizing melanoma variants from three xenograft tumor models established in our laboratory revealed that expression of tight junction component CLDN1 was lower in the brain-metastasizing variants than in cutaneous variants from the same melanoma. The objective of our study was to determine the significance of CLDN1 downregulation/loss in metastatic melanoma and its role in melanoma brain metastasis. An immunohistochemical analysis of human cells of the melanocyte lineage indicated a significant CLDN1 downregulation in metastatic melanomas. Transduction of melanoma brain metastatic cells expressing low levels of CLDN1 with a CLDN1 retrovirus suppressed their metastatic phenotype. CLDN1-overexpressing melanoma cells expressed a lower ability to migrate and adhere to extracellular matrix, reduced tumor aggressiveness in nude mice and, most importantly, eliminated the formation of micrometastases in the brain. In sharp contrast, the ability of the CLDN1-overexpressing cells to form lung micrometastases was not impaired. CLDN1-mediated interactions between these cells and brain endothelial cells constitute the mechanism underlying these results. Taken together, we demonstrated that downregulation or loss of CLDN1 supports the formation of melanoma brain metastasis, and that CLDN1 expression could be a useful prognostic predictor for melanoma patients with a high risk of brain metastasis. © 2014 UICC.

  5. Serum HER-2: Sensitivity, specificity, and predictive values for detecting metastatic recurrence in breast cancer patients

    DEFF Research Database (Denmark)

    Sørensen, Patricia Diana; Jakobsen, Erik Hugger; Madsen, Jonna Skov

    2013-01-01

    The aim of this study was to determine the sensitivity, specificity, and predictive values of serum HER-2 for detecting metastatic recurrence in breast cancer patients.......The aim of this study was to determine the sensitivity, specificity, and predictive values of serum HER-2 for detecting metastatic recurrence in breast cancer patients....

  6. MRI for discriminating metastatic ovarian tumors from primary epithelial ovarian cancers

    OpenAIRE

    Xu, Yanhong; Yang, Jia; Zhang, Zaixian; Zhang, Guixiang

    2015-01-01

    Aims To find specific magnetic resonance imaging (MRI) features to differentiate metastatic ovarian tumors from primary epithelial ovarian cancers. Methods Eleven cases with metastatic ovarian tumors and 26 cases with primary malignant epithelial ovarian cancers were retrospectively studied. All features such as patient characteristics, MRI findings and biomarkers were evaluated. The differences including laterality, configuration, uniformity of locules, diffusion weighted imaging (DWI) signa...

  7. Challenges in providing culturally-competent care to patients with metastatic brain tumours and their families.

    Science.gov (United States)

    Longo, Lianne; Slater, Serena

    2014-01-01

    Being diagnosed with a metastatic brain tumour can be devastating as it is characterized by very low cure rates, as well as significant morbidity and mortality. Given the poor life expectancy and progressive disability that ensues, patients and family members experience much turmoil, which includes losses that bring about changes to family roles, routines and relationships. Crisis and conflict are common during such major disruptions to a family system, as individual members attempt to make sense of the illness experience based on cultural and spiritual beliefs, past experiences and personal philosophies. It is imperative health care providers strive towards increased awareness and knowledge of how culture affects the overall experience of illness and death in order to help create a mutually satisfactory care plan. Providing culturally-competent care entails the use of proper communication skills to facilitate the exploration of patient and family perspectives and allows for mutual decision making. A case study will illustrate the challenges encountered in providing culturally-competent care to a woman with brain cancer and her family. As the patient's health declined, the family entered into a state of crisis where communication between family members and health care professionals was strained; leading to conflict and sub-optimal outcomes. This paper will address the ethical dilemma of providing culturally-competent care when a patient's safety is at risk, and the nursing implications of upholding best practices in the context of differing beliefs and priorities.

  8. [A case of metastatic gastric cancer originating from transverse colon cancer].

    Science.gov (United States)

    Nushijima, Youichirou; Nakano, Katsutoshi; Sugimoto, Keishi; Nakaguchi, Kazunori; Kan, Kazuomi; Maruyama, Hirohide; Doi, Sadayuki; Okamura, Shu; Murata, Kohei

    2014-11-01

    Metastatic gastric cancer is uncommon, and metastasis of colorectal cancer to the stomach is extremely rare. We report a case of metastatic gastric cancer that originated from transverse colon cancer. A 52-year-old woman underwent a left hemicolectomy and D3 lymph node dissection based on a diagnosis of transverse colon cancer. The pathology results were as follows: mucinous adenocarcinoma, type 2, 6 × 11 cm, ss, ly1 v1, pm (-), dm (-), n1 (+), P0, H0, M0, Stage IIIa. The patient received XELOX as postoperative adjuvant therapy for 6 months. One year and 3 months after the left hemicolectomy, gastroscopy revealed a submucosal tumor in the lower body of the stomach and an incipient cancer in the cardia of the stomach, and a colonoscopy revealed an incipient cancer in the transverse colon. An endoscopic ultrasonography fine needle aspiration biopsy of the submucosal tumor in the lower body of the stomach was performed. Histology showed that this tumor was a mucinous adenocarcinoma similar to the primary transverse colon cancer, which led to a diagnosis of metastatic gastric cancer originating from transverse colon cancer. Distant metastasis was not detected. Endoscopic submucosal dissection of the incipient gastric cancer was performed, as were distal gastrectomy and partial colectomy. Peritoneal dissemination and para-aortic lymph node recurrence were detected 7 months after the second surgery.

  9. Stromal Gene Expression is Predictive for Metastatic Primary Prostate Cancer.

    Science.gov (United States)

    Mo, Fan; Lin, Dong; Takhar, Mandeep; Ramnarine, Varune Rohan; Dong, Xin; Bell, Robert H; Volik, Stanislav V; Wang, Kendric; Xue, Hui; Wang, Yuwei; Haegert, Anne; Anderson, Shawn; Brahmbhatt, Sonal; Erho, Nicholas; Wang, Xinya; Gout, Peter W; Morris, James; Karnes, R Jeffrey; Den, Robert B; Klein, Eric A; Schaeffer, Edward M; Ross, Ashley; Ren, Shancheng; Sahinalp, S Cenk; Li, Yingrui; Xu, Xun; Wang, Jun; Wang, Jian; Gleave, Martin E; Davicioni, Elai; Sun, Yinghao; Wang, Yuzhuo; Collins, Colin C

    2018-04-01

    Clinical grading systems using clinical features alongside nomograms lack precision in guiding treatment decisions in prostate cancer (PCa). There is a critical need for identification of biomarkers that can more accurately stratify patients with primary PCa. To identify a robust prognostic signature to better distinguish indolent from aggressive prostate cancer (PCa). To develop the signature, whole-genome and whole-transcriptome sequencing was conducted on five PCa patient-derived xenograft (PDX) models collected from independent foci of a single primary tumor and exhibiting variable metastatic phenotypes. Multiple independent clinical cohorts including an intermediate-risk cohort were used to validate the biomarkers. The outcome measurement defining aggressive PCa was metastasis following radical prostatectomy. A generalized linear model with lasso regularization was used to build a 93-gene stroma-derived metastasis signature (SDMS). The SDMS association with metastasis was assessed using a Wilcoxon rank-sum test. Performance was evaluated using the area under the curve (AUC) for the receiver operating characteristic, and Kaplan-Meier curves. Univariable and multivariable regression models were used to compare the SDMS alongside clinicopathological variables and reported signatures. AUC was assessed to determine if SDMS is additive or synergistic to previously reported signatures. A close association between stromal gene expression and metastatic phenotype was observed. Accordingly, the SDMS was modeled and validated in multiple independent clinical cohorts. Patients with higher SDMS scores were found to have worse prognosis. Furthermore, SDMS was an independent prognostic factor, can stratify risk in intermediate-risk PCa, and can improve the performance of other previously reported signatures. Profiling of stromal gene expression led to development of an SDMS that was validated as independently prognostic for the metastatic potential of prostate tumors. Our

  10. Comparison of 1H-MRS-detected metabolic characteristics in single metastatic brain tumors of different origin

    International Nuclear Information System (INIS)

    Chernov, M.F.; Ono, Yuko; Kubo, Osami; Hori, Tomokatsu

    2006-01-01

    Various types of intracranial metastases exhibit different growth patterns, which can be reflected in their metabolic characteristics and investigated noninvasively by proton magnetic resonance spectroscopy ( 1 H-MRS). The objective of the present study was comparison of the 1 H-MRS-detected metabolic parameters in brain metastases of different origin. Twenty-five patients (15 men and 10 women; mean age, 62.0 years) with single, previously nontreated metastatic brain tumors were investigated by long-echo single-voxel volume-selected 1 H-MRS. The primary cancer was located in the lungs (10 cases), colon and rectum (8 cases), breast (3 cases), kidney (2 cases), prostate (1 case), and cardiac muscle (1 case). Comparison of clinical and radiological variables, including type of tumor contrast enhancement and extension of peritumoral edema, did not disclose statistically significant differences in metastatic brain tumors of different origin. At the same time, comparison of 1 H-MRS-detected metabolic characteristics revealed that metastases of colorectal carcinoma have greater content of mobile lipids (Lip) compared to other neoplasms. In conclusion, high Lip content in the viable brain metastases of colorectal carcinoma can be used as an additional diagnostic clue for noninvasive identification of these tumors and should be taken into consideration in cases of 1 H-MRS-based differentiation of their recurrence and radiation-induced necrosis after radiosurgical or radiotherapeutic treatment. (author)

  11. Metastatic Progression of Breast Cancer by Allelic Loss on Chromosome 18q21

    National Research Council Canada - National Science Library

    Thiagalingam, Sam

    2004-01-01

    ... and VEGF in breast cancer. Additionally, our preliminary data also provides evidence for the synergistic activation of pro-angiogenic/ metastatic effects by TGFbeta in the presence of defective SMAD4 in breast cancer...

  12. Changes in the gastric potential difference during chemotherapy in patients with metastatic breast cancer

    DEFF Research Database (Denmark)

    Fabrin, B; Højgaard, L; Mouridsen, H T

    1991-01-01

    Nausea and vomiting are frequent side-effects of intravenous cancer chemotherapy. How these complications were related to the gastric mucosal function was investigated by measuring the gastric mucosal potential difference (PD). Eight patients with metastatic breast cancer receiving chemotherapy...

  13. Radical prostatectomy for locally advanced and metastatic prostate cancer.

    Science.gov (United States)

    Veeratterapillay, R; Goonewardene, S S; Barclay, J; Persad, R; Bach, C

    2017-04-01

    The management of advanced prostate cancer remains challenging. Traditionally, radical prostatectomy was discouraged in patients with locally advanced or node positive disease owing to the increased complication rate and treatment related morbidity. However, technical advances and refinements in surgical techniques have enabled the outcomes for patients with high risk prostate cancer to be improved. More recently, the concept of cytoreductive prostatectomy has been described where surgery (often Combined with an extended lymph node dissection) is performed in the setting of metastatic disease. Indirect evidence suggests an advantage using the cytoreductive approach. Hypothetical explanations for this observed benefit include decreased tumour burden, immune modulation, improved response to secondary treatment and avoidance of secondary complications attributable to local tumour growth. Nevertheless, prospective trials are required to investigate this further.

  14. Unsupported off-label chemotherapy in metastatic colon cancer

    Directory of Open Access Journals (Sweden)

    de Souza Jonas A

    2012-12-01

    Full Text Available Abstract Background Newer systemic therapies have the potential to decrease morbidity and mortality from metastatic colorectal cancer, yet such therapies are costly and have side effects. Little is known about their non-evidence-based use. Methods We conducted a retrospective cohort study using commercial insurance claims from UnitedHealthcare, and identified incident cases of metastatic colon cancer (mCC from July 2007 through April 2010. We evaluated the use of three regimens with recommendations against their use in the National Comprehensive Cancer Center Network Guidelines, a commonly used standard of care: 1 bevacizumab beyond progression; 2 single agent capecitabine as a salvage therapy after failure on a fluoropyridimidine-containing regimen; 3 panitumumab or cetuximab after progression on a prior epidermal growth factor receptor antibody. We performed sensitivity analyses of key assumptions regarding cohort selection. Costs from a payer perspective were estimated using the average sales price for the entire duration and based on the number of claims. Results A total of 7642 patients with incident colon cancer were identified, of which 1041 (14% had mCC. Of those, 139 (13% potentially received at least one of the three unsupported off-label (UOL therapies; capecitabine was administered to 121 patients and 49 (40% likely received it outside of clinical guidelines, at an estimated cost of $718,000 for 218 claims. Thirty-eight patients received panitumumab and six patients (16% received it after being on cetuximab at least two months, at an estimated cost of $69,500 for 19 claims. Bevacizumab was administered to 884 patients. Of those, 90 (10% patients received it outside of clinical guidelines, at an estimated costs of $1.34 million for 636 claims. Conclusions In a large privately insured mCC cohort, a substantial number of patients potentially received UOL treatment. The economic costs and treatment toxicities of these therapies warrant

  15. Increased Expression and Aberrant Localization of Mucin 13 in Metastatic Colon Cancer

    Science.gov (United States)

    Gupta, Brij K.; Maher, Diane M.; Ebeling, Mara C.; Sundram, Vasudha; Koch, Michael D.; Lynch, Douglas W.; Bohlmeyer, Teresa; Watanabe, Akira; Aburatani, Hiroyuki; Puumala, Susan E.; Jaggi, Meena

    2012-01-01

    MUC13 is a newly identified transmembrane mucin. Although MUC13 is known to be overexpressed in ovarian and gastric cancers, limited information is available regarding the expression of MUC13 in metastatic colon cancer. Herein, we investigated the expression profile of MUC13 in colon cancer using a novel anti-MUC13 monoclonal antibody (MAb, clone ppz0020) by immunohistochemical (IHC) analysis. A cohort of colon cancer samples and tissue microarrays containing adjacent normal, non-metastatic colon cancer, metastatic colon cancer, and liver metastasis tissues was used in this study to investigate the expression pattern of MUC13. IHC analysis revealed significantly higher (pcolon cancer samples compared with faint or very low expression in adjacent normal tissues. Interestingly, metastatic colon cancer and liver metastasis tissue samples demonstrated significantly (pcolon cancer and adjacent normal colon samples. Moreover, cytoplasmic and nuclear MUC13 expression correlated with larger and poorly differentiated tumors. Four of six tested colon cancer cell lines also expressed MUC13 at RNA and protein levels. These studies demonstrate a significant increase in MUC13 expression in metastatic colon cancer and suggest a correlation between aberrant MUC13 localization (cytoplasmic and nuclear expression) and metastatic colon cancer. PMID:22914648

  16. Australian contemporary management of synchronous metastatic colorectal cancer.

    Science.gov (United States)

    Malouf, Phillip; Gibbs, Peter; Shapiro, Jeremy; Sockler, Jim; Bell, Stephen

    2018-01-01

    This article outlines the current Australian multidisciplinary treatment of synchronous metastatic colorectal adenocarcinoma and assesses the factors that influence patient outcome. This is a retrospective analysis of the prospective 'Treatment of Recurrent and Advanced Colorectal Cancer' registry, describing the patient treatment pathway and documenting the extent of disease, resection of the colorectal primary and metastases, chemotherapy and biological therapy use. Cox regression models for progression-free and overall survival were constructed with a comprehensive set of clinical variables. Analysis was intentionn-ton-treat, quantifying the effect of treatment intent decided at the multidisciplinary team meeting (MDT). One thousand one hundred and nine patients presented with synchronous metastatic disease between July 2009 and November 2015. Median follow-up was 15.8 months; 4.4% (group 1) had already curative resections of primary and metastases prior to MDT, 22.2% (group 2) were considered curative but were referred to MDT for opinion and/or medical oncology treatment prior to resection and 70.2% were considered palliative at MDT (group 3). Overall, 83% received chemotherapy, 55% had their primary resected and 23% had their metastases resected; 13% of resections were synchronous, 20% were staged with primary resected first and 62% had only the colorectal primary managed surgically. Performance status, metastasis resection (R0 versus R1 versus R2 versus no resection), resection of the colorectal primary and treatment intent determined at MDT were the most significant factors for progression-free and overall survival. This is the largest Australian series of synchronous metastatic colorectal adenocarcinoma and offers insight into the nature and utility of contemporary practice. © 2016 Royal Australasian College of Surgeons.

  17. Targeted Therapies for Brain Metastases from Breast Cancer

    Directory of Open Access Journals (Sweden)

    Vyshak Alva Venur

    2016-09-01

    Full Text Available The discovery of various driver pathways and targeted small molecule agents/antibodies have revolutionized the management of metastatic breast cancer. Currently, the major targets of clinical utility in breast cancer include the human epidermal growth factor receptor 2 (HER2 and epidermal growth factor receptor (EGFR, vascular endothelial growth factor (VEGF receptor, mechanistic target of rapamycin (mTOR pathway, and the cyclin-dependent kinase 4/6 (CDK-4/6 pathway. Brain metastasis, however, remains a thorn in the flesh, leading to morbidity, neuro-cognitive decline, and interruptions in the management of systemic disease. Approximately 20%–30% of patients with metastatic breast cancer develop brain metastases. Surgery, whole brain radiation therapy, and stereotactic radiosurgery are the traditional treatment options for patients with brain metastases. The therapeutic paradigm is changing due to better understanding of the blood brain barrier and the advent of tyrosine kinase inhibitors and monoclonal antibodies. Several of these agents are in clinical practice and several others are in early stage clinical trials. In this article, we will review the common targetable pathways in the management of breast cancer patients with brain metastases, and the current state of the clinical development of drugs against these pathways.

  18. Changes in cytoskeletal dynamics and nonlinear rheology with metastatic ability in cancer cell lines

    International Nuclear Information System (INIS)

    Coughlin, Mark F; Fredberg, Jeffrey J

    2013-01-01

    Metastatic outcome is impacted by the biophysical state of the primary tumor cell. To determine if changes in cancer cell biophysical properties facilitate metastasis, we quantified cytoskeletal biophysics in well-characterized human skin, bladder, prostate and kidney cell line pairs that differ in metastatic ability. Using magnetic twisting cytometry with optical detection, cytoskeletal dynamics was observed through spontaneous motion of surface bound marker beads and nonlinear rheology was characterized through large amplitude forced oscillations of probe beads. Measurements of cytoskeletal dynamics and nonlinear rheology differed between strongly and weakly metastatic cells. However, no set of biophysical parameters changed systematically with metastatic ability across all cell lines. Compared to their weakly metastatic counterparts, the strongly metastatic kidney cancer cells exhibited both increased cytoskeletal dynamics and stiffness at large deformation which are thought to facilitate the process of vascular invasion. (paper)

  19. STUDY ON ADHERENCE TO CAPECITABINE AMONG PATIENTS WITH COLORECTAL CANCER AND METASTATIC BREAST CANCER

    Directory of Open Access Journals (Sweden)

    Adiel Goes de FIGUEIREDO JUNIOR

    2014-09-01

    Full Text Available Context Capecitabine, an oral drug, is as effective as traditional chemotherapy drugs. Objectives To investigate the adhesion to treatment with oral capecitabine in breast and colorectal cancer, and to determine any correlation with changes in patient’s quality of life. Methods Patients with colorectal cancer or breast cancer using capecitabine were included. The patients were asked to bring any medication left at the time of scheduled visits. The QLQ-C30 questionnaire was applied at the first visit and 8-12 weeks after treatment. Results Thirty patients were evaluated. Adherence was 88.3% for metastatic colon cancer, 90.4% for non-metastatic colon cancer, 94.3% for rectal cancer and 96.2% for metastatic breast cancer. No strong correlation between adherence and European Organisation for Research and Treatment of Cancer QLQ-C30 functional or symptom scale rates had been found. There was no statistically significant correlation between compliance and the functional and symptom scales of the questionnaire before and after chemotherapy, with the exception of dyspnea. Conclusions Although no absolute adherence to oral capecitabine treatment had been observed, the level of adherence was good. Health professionals therefore need a greater focus in the monitoring the involvement of patients with oral treatment regimens. Patients with lesser degrees of dyspnea had greater compliance.

  20. Options for Second-Line Treatment in Metastatic Colorectal Cancer.

    Science.gov (United States)

    Lee, James J; Sun, Weijing

    2016-01-01

    Colorectal cancer (CRC) remains a major public health problem in the United States and worldwide. The majority of patients who have CRC eventually present with metastatic disease. The overall therapeutic goals for most patients with metastatic CRC (mCRC) are to control the disease, prolong life span, and maximize quality of life. Therefore, the ratio of efficacy to toxicity is one of the most important factors in choosing among treatment options and sequencing regimens. In addition, the choice of first-line systemic therapy will affect the options for second-line treatment. Several newer cytotoxic agents for the treatment of mCRC have been approved during the past 2 decades by the US Food and Drug Administration (FDA), including irinotecan, oxaliplatin, and capecitabine. The combination of a fluoropyrimidine (5-fluorouracil or capecitabine) with either oxaliplatin or irinotecan has been widely accepted as standard cytotoxic chemotherapy for either the first- or second-line treatment of mCRC. The FDA has approved several pathway-targeting agents for the treatment of mCRC; these include agents that target the vascular endothelial growth factor receptor pathway (bevacizumab, ziv-aflibercept, and ramucirumab) and those that target the epidermal growth factor receptor pathway (cetuximab and panitumumab). Here, we review the current clinical options for the second-line treatment of mCRC and the rationales for their use.

  1. Updated options for liver-limited metastatic colorectal cancer.

    Science.gov (United States)

    Alberts, Steven R

    2008-12-01

    Liver metastases from colorectal cancer (CRC) are common in patients presenting with an initial diagnosis of metastatic disease or at the time of recurrence. Without treatment, patients with metastatic disease have a poor prognosis. Surgical resection of the metastases might provide long-term benefit.; however, the size, number, or location of the metastases can limit the ability to perform a resection. The use of chemotherapy, both systemic and via hepatic artery infusion, in patients undergoing surgery for liver metastases from CRC has augmented the long-term survival benefits and even the cure obtained in some patients with surgery. Chemotherapy might also convert a portion of patients with initially unresectable liver metastases to resectable. A growing body of literature is helping to define the role of chemotherapy for potentially resectable liver metastases and for initially unresectable liver metastases. The introduction of newer agents such as oxaliplatin and irinotecan, and targeted agents such as cetuximab and bevacizumab, has led to meaningful improvements in response rates and survival over those previously achieved with 5-fluorouracil. Further trials are needed to refine the use of chemotherapy and targeted agents in the management of patients with liver metastases.

  2. Metastatic Melanoma Patient Had a Complete Response with Clonal Expansion after Whole Brain Radiation and PD-1 Blockade.

    Science.gov (United States)

    Haymaker, Cara L; Kim, DaeWon; Uemura, Marc; Vence, Luis M; Phillip, Ann; McQuail, Natalie; Brown, Paul D; Fernandez, Irina; Hudgens, Courtney W; Creasy, Caitlin; Hwu, Wen-Jen; Sharma, Padmanee; Tetzlaff, Michael T; Allison, James P; Hwu, Patrick; Bernatchez, Chantale; Diab, Adi

    2017-02-01

    We report here on a patient with metastatic melanoma who had extensive brain metastases. After being treated with the sequential combination of whole brain radiation therapy followed by the PD-1-inhibitory antibody, pembrolizumab, the patient had a durable complete response. Retrospective laboratory studies of T cells revealed that, after treatment with anti-PD-1 commenced, effector CD8 + T cells in the blood expanded and the ratio of CD8 + :Treg T cells increased. A CD8 + T-cell clone present in the initial brain metastases was expanded in the blood after anti-PD-1 treatment, which suggested an antitumor role for this clone. Immunohistochemical analysis confirmed the presence of CD8 + T cells and low PD-L1 expression in the brain metastases before immunotherapy initiation. This sequence of therapy may provide an option for melanoma patients with unresponsive brain metastases. Cancer Immunol Res; 5(2); 100-5. ©2017 AACR. ©2017 American Association for Cancer Research.

  3. Automated extraction of metastatic liver cancer regions from abdominal contrast CT images

    International Nuclear Information System (INIS)

    Yamakawa, Junki; Matsubara, Hiroaki; Kimura, Shouta; Hasegawa, Junichi; Shinozaki, Kenji; Nawano, Shigeru

    2010-01-01

    In this paper, automated extraction of metastatic liver cancer regions from abdominal contrast X-ray CT images is investigated. Because even in Japan, cases of metastatic liver cancers are increased due to recent Europeanization and/or Americanization of Japanese eating habits, development of a system for computer aided diagnosis of them is strongly expected. Our automated extraction procedure consists of following four steps; liver region extraction, density transformation for enhancement of cancer regions, segmentation for obtaining candidate cancer regions, and reduction of false positives by shape feature. Parameter values used in each step of the procedure are decided based on density and shape features of typical metastatic liver cancers. In experiments using practical 20 cases of metastatic liver tumors, it is shown that 56% of true cancers can be detected successfully from CT images by the proposed procedure. (author)

  4. Metastatic gastric cancer – focus on targeted therapies

    Directory of Open Access Journals (Sweden)

    Meza-Junco J

    2012-06-01

    Full Text Available Judith Meza-Junco, Michael B SawyerDepartment of Oncology, Cross Cancer Institute, Edmonton, Alberta, CanadaAbstract: Gastric cancer (GC is currently the second leading cause of cancer death worldwide; unfortunately, most patients will present with locally advanced or metastatic disease. Despite recent progress in diagnosis, surgery, chemotherapy, and radiotherapy, prognosis remains poor. A better understanding of GC biology and signaling pathways is expected to improve GC therapy, and the integration of targeted therapies has recently become possible and appears to be promising. This article focuses on anti-Her-2 therapy, specifically trastuzumab, as well as other epidermal growth factor receptor antagonists such as cetuximab, panitumub, matuzumab, nimotzumab, gefitinib, and erlotinib. Additionally, drugs that target angiogenesis pathways are also under investigation, particulary bevacizumab, ramucirumab, sorafenib, sunitinib, and cediranib. Other targeted agents in preclinical or early clinical development include mTOR inhibitors, anti c-MET, polo-like kinase 1 inhibitors, anti-insulin-like growth factor, anti-heat shock proteins, and small molecules targeting Hedgehog signaling.Keywords: gastric cancer, targeted therapy, antiangiogenesis drugs, anti-EGFR drugs

  5. Psychological interventions for women with non-metastatic breast cancer.

    Science.gov (United States)

    Jassim, Ghufran A; Whitford, David L; Hickey, Anne; Carter, Ben

    2015-05-28

    Breast cancer is the most common cancer affecting women worldwide. It is a distressing diagnosis and, as a result, considerable research has examined the psychological sequelae of being diagnosed and treated for breast cancer. Breast cancer is associated with increased rates of depression and anxiety and reduced quality of life. As a consequence, multiple studies have explored the impact of psychological interventions on the psychological distress experienced after a diagnosis of breast cancer. To assess the effects of psychological interventions on psychological morbidities, quality of life and survival among women with non-metastatic breast cancer. We searched the following databases up to 16 May 2013: the Cochrane Breast Cancer Group Specialised Register, CENTRAL, MEDLINE, EMBASE, CINAHL and PsycINFO; and reference lists of articles. We also searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) search portal and ClinicalTrials.gov for ongoing trials in addition to handsearching. Randomised controlled trials that assessed the effectiveness of psychological interventions for non-metastatic breast cancer in women. Two review authors independently appraised and extracted data from eligible trials. Any disagreement was resolved by discussion. Extracted data included information about participants, methods, the intervention and outcome. Twenty-eight randomised controlled trials comprising 3940 participants were included. The most frequent reasons for exclusion were non-randomised trials and the inclusion of women with metastatic disease. A wide range of interventions were evaluated, with 24 trials investigating a cognitive behavioural therapy and four trials investigating psychotherapy compared to control. Pooled standardised mean differences (SMD) from baseline indicated less depression (SMD -1.01, 95% confidence interval (CI) -1.83 to -0.18; P = 0.02; 7 studies, 637 participants, I(2) = 95%, low quality evidence), anxiety

  6. Invasive ductal breast cancer metastatic to the sigmoid colon

    Directory of Open Access Journals (Sweden)

    Zhou Xiao-cong

    2012-11-01

    Full Text Available Abstract The most common sites of breast cancer metastasis are the bone, lung, liver and brain. However, colonic metastases from breast cancer are very rare in the clinic. We describe an unusual case of sigmoid colonic metastasis from invasive ductal breast cancer. With this report, we should increase the clinical awareness that any patient with a colorectal lesion and a history of malignancy should be considered to have a metastasis until proven otherwise. Early diagnosis is very important, which enables prompt initiation of systemic treatment, such as chemotherapy, endocrine therapy or both, thus avoiding unnecessary radical surgical resection and improving the prognosis.

  7. Can urologists introduce the concept of “oligometastasis” for metastatic bladder cancer after total cystectomy?

    OpenAIRE

    Ogihara, Koichiro; Kikuchi, Eiji; Watanabe, Keitaro; Kufukihara, Ryohei; Yanai, Yoshinori; Takamatsu, Kimiharu; Matsumoto, Kazuhiro; Hara, Satoshi; Oyama, Masafumi; Monma, Tetsuo; Masuda, Takeshi; Hasegawa, Shintaro; Oya, Mototsugu

    2017-01-01

    We investigated whether the concept of oligometastasis may be introduced to the clinical management of metastatic bladder cancer patients. Our study population comprised 128 patients diagnosed with metastatic bladder cancer after total cystectomy at our 6 institutions between 2004 and 2014. We extracted independent predictors for identifying a favorable. Occurrence that fulfilled all 4 criteria which were independently associated with cancer-specific death was defined as oligometastasis: a so...

  8. Re-irradiation for metastatic brain tumors with whole-brain radiotherapy

    International Nuclear Information System (INIS)

    Akiba, Takeshi; Kunieda, Etsuo; Kogawa, Asuka; Komatsu, Tetsuya; Tamai, Yoshifumi; Ohizumi, Yukio

    2012-01-01

    The objective of this study was to determine whether second whole-brain irradiation is beneficial for patients previously treated with whole-brain irradiation. A retrospective analysis was done for 31 patients with brain metastases who had undergone re-irradiation. Initial whole-brain irradiation was performed with 30 Gy/10 fractions for 87% of these patients. Whole-brain re-irradiation was performed with 30 Gy/10 fractions for 42% of these patients (3-40 Gy/1-20 fractions). Three patients underwent a third whole-brain irradiation. The median interval between the initial irradiation and re-irradiation was 10 months (range: 2-69 months). The median survival time after re-irradiation was 4 months (range: 1-21 months). The symptomatic improvement rate after re-irradiation was 68%, and the partial and complete tumor response rate was 55%. Fifty-two percent of the patients developed Grade 1 acute reactions. On magnetic resonance imaging, brain atrophy was observed in 36% of these patients after the initial irradiation and 74% after re-irradiation. Grade ≥2 encephalopathy or cognitive disturbance was observed in 10 patients (32%) after re-irradiation. Based on univariate analysis, significant factors related to survival after re-irradiation were the location of the primary cancer (P=0.003) and the Karnofsky performance status at the time of re-irradiation (P=0.008). A Karnofsky performance status ≥70 was significant based on multivariate analysis (P=0.050). Whole-brain re-irradiation for brain metastases placed only a slight burden on patients and was effective for symptomatic improvement. However, their remaining survival time was limited and the incidence of cognitive disturbance was rather high. (author)

  9. Assessment of cognitive function in patients with metastatic cancer

    DEFF Research Database (Denmark)

    Kurita, Geana Paula; Sandvad, Marlene; Lundorff, Lena

    2018-01-01

    OBJECTIVE: This study aimed at analyzing the validity and reliability of the continuous reaction time (CRT) test, the finger-tapping test (FTT), the Digit Span Test (DST), the Trail Making Test - part B (TMTB), and the Mini-Mental State Examination (MMSE) in patients with metastatic cancer. METHOD...... for the MMSE because of a skewed response distribution. For discriminant validity, patients were slower on two measures of the CRT (p = 0.00483, p = 0.00030) and FTT dominant hand (p = 0.00306). Regarding sensitivity and specificity, only the DST and TMTB seemed to predict cognitive deficit; however, the ROC...... curve areas were ≤ 0.73. In terms of criterion validity, there were few significant correlations between the tests and the sociodemographic and clinical variables, and for the most part were very weak. Reliability was deemed to be adequate for the TMTB, DST, and FTT. SIGNIFICANCE OF RESULTS...

  10. 'Tablet burden' in patients with metastatic breast cancer.

    Science.gov (United States)

    Milic, Marina; Foster, Anna; Rihawi, Karim; Anthoney, Alan; Twelves, Chris

    2016-03-01

    The implications for patients with cancer, of the 'tablet burden' resulting from increasing use of oral anticancer drugs and medication for co-morbidities have not previously been well explored. We sought to (i) quantify tablet burden in women with metastatic breast cancer (MBC), (ii) establish which groups of drug contribute most to this burden and (iii) gain insight into patients' attitudes towards oral anti-cancer treatment. One hundred patients with MBC anonymously completed a questionnaire describing their medication histories and attitudes towards their tablets. The patients (mean age 60, range 31-95) were all female and taking a median of six tablets (range 0-31) daily; 37 patients were taking >10 tablets. Oral anticancer treatment constituted the category of treatment taken by the highest proportion of patients, followed by symptomatic cancer treatments, proton pump inhibitors and cardiovascular medication. Numerically, however, symptomatic drugs accounted for 44% of all tablets and specific anti-cancer treatment for 15%; medication not directly related to the cancer accounted for the remaining 40% of tablets. A quarter of patients reported inconvenience in taking their tablets, the main reason being tablet size and one third reported forgetting their tablets at least once a week. Nearly two thirds of patients expressing a preference favoured oral anticancer treatment, the commonest reason being greater convenience. Tablet burden is considerable for many patients with MBC and can be problematic. A significant proportion of tablets represent treatment for co-morbidities, the significance of which may be questionable in women with MBC. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Chemotherapy for bladder cancer: treatment guidelines for neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and metastatic cancer

    DEFF Research Database (Denmark)

    Sternberg, Cora N; Donat, S Machele; Bellmunt, Joaquim

    2007-01-01

    with the use of Medline; additional cited works not detected on the initial search regarding neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and chemotherapy for patients with metastatic urothelial cancer were reviewed. Evidence-based recommendations for diagnosis and management...... the published literature on chemotherapy for patients with locally advanced bladder cancer. This article reports the development of international guidelines for the treatment of patients with locally advanced bladder cancer with neoadjuvant and adjuvant chemotherapy. Bladder preservation is also discussed......, as is chemotherapy for patients with metastatic urothelial cancer. The conference panel consisted of 10 medical oncologists and urologists from 3 continents who are experts in this field and who reviewed the English-language literature through October 2004. Relevant English-language literature was identified...

  12. Brain metastasis from colorectal cancer

    International Nuclear Information System (INIS)

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

    2007-01-01

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

  13. Collecting and Studying Blood and Tissue Samples From Patients With Locally Recurrent or Metastatic Prostate or Bladder/Urothelial Cancer

    Science.gov (United States)

    2017-12-04

    Healthy Control; Localized Urothelial Carcinoma of the Renal Pelvis and Ureter; Metastatic Malignant Neoplasm in the Bone; Metastatic Malignant Neoplasm in the Soft Tissues; Metastatic Urothelial Carcinoma of the Renal Pelvis and Ureter; Recurrent Bladder Carcinoma; Recurrent Prostate Carcinoma; Recurrent Urothelial Carcinoma of the Renal Pelvis and Ureter; Stage IV Bladder Cancer; Stage IV Bladder Urothelial Carcinoma; Stage IV Prostate Cancer

  14. Tailored treatment of metastatic colorectal cancer: clinical and pre-clinical developments

    NARCIS (Netherlands)

    Kuijpers, A.M.J.

    2015-01-01

    Colorectal cancer is the third leading cause of cancer-related death in males and females in developed countries. Metastases in distant organs, which develop in 50% of colorectal cancer patients, are responsible for the majority of colorectal cancer deaths. Treatment of metastatic disease should

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

    Directory of Open Access Journals (Sweden)

    Xiong Z

    2018-02-01

    Full Text Available Zhenchong Xiong,1–3,* Guangzheng Deng,1–3,* Xinjian Huang,1–3,* Xing Li,1–3 Xinhua Xie,1–3 Jin Wang,1–3 Zeyu Shuang,1–3 Xi Wang1–3 1Department of Breast Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China; 2State Key Laboratory of Oncology in Southern China, Guangzhou, China; 3Collaborative Innovation Center for Cancer Medicine, Guangzhou, China *These authors contributed equally to this work Purpose: Bone is one of the most common sites of breast cancer metastasis, and population-based studies of patients with bone metastasis in initial metastatic breast cancer (MBC are lacking. Materials and methods: From 2010 to 2013, 245,707 breast cancer patients and 8901 patients diagnosed with initial bone metastasis were identified by Surveillance, Epidemiology, and End Results database of the National Cancer Institute. Multivariate logistic and Cox regression were used to identify predictive factors for the presence of bone metastasis and prognosis factors. Kaplan–Meier method and log-rank test were used for survival analysis. Results: Eight thousand nine hundred one patients with initial MBC had bone involvement, accounting for 3.6% of the entire cohort and 62.5% of the patients with initial MBC. Also, 70.5% of patients with bone metastasis were hormone receptor (HR positive (HR+/human epidermal growth factor receptor 2 [HER2]−: 57.6%; HR+/HER2+: 12.9%. Patients with initial bone metastasis had a better 5-year survival rate compared to those with initial brain, liver, or lung metastasis. HR+/HER2− and HR+/HER2+ breast cancer had a propensity of bone metastasis in the entire cohort and were correlated with better prognosis in patients with initial bone metastasis. Local surgery had significantly improved overall survival in initial MBC patients with bone metastasis. Conclusion: Our study has provided population-based estimates of epidemiologic characteristics and prognosis in patients with bone metastasis at the time of

  16. Activity of Nanobins Loaded with Cisplatin and Arsenic Trioxide in Primary and Metastatic Breast Cancer

    Science.gov (United States)

    Swindell, Elden Peter, III

    Despite recent advances in breast cancer screening and detection, the disease is still a leading cause of death for women of all ages. Young, African-American women are disproportionally affected with a type of breast cancer, triple-negative breast cancer, which is particularly difficult to treat and has the worst prognosis of any breast cancer subtype. These tumors often spread to the lungs, liver, bones and brains of patients, which is ultimately fatal. This dissertation presents results from a series of in vivo and in vitro experiments that investigate the clinical utility of a novel nanoparticulate formulation of cisplatin and arsenic trioxide, NB(Pt,As) for treating primary and metastatic triple-negative breast cancer. These nanobins consist of a solid, crystalline metal nanoparticle surrounded by a lipid bilayer with 80-90 nm diameter. This drug payload is extremely stable, and so NB(Pt,As) is extremely well tolerated in mice. Furthermore, NB(Pt,As) is effective in two different mouse models of breast cancer, one of primary tumor growth an another of lung metastases. A discovery presented here, that thiol containing compounds are required for drug release, may explain these seemingly incongruous results. The large amount of intracellular thiol can trigger drug release, while the low concentration of free thiols in blood is insufficient to cause drug release. To improve the treatment of brain tumors with this unique drug, we added transferrin to the surface of the nanobin using copper-catalyzed "click" chemistry, which preserves protein activity. The addition of transferrin to the nanobins enables 10 fold greater uptake in the brains of mice treated with the transferrin-targeted nanobins Tf-NB(Pt,A) compared to NB(Pt,As). By penetrating the blood brain barrier, the Tf-NB(Pt,As) was able to reduce breast cancer metastases in the brains of mice, whereas NB(Pt,As) had no effect. Taken together, these results demonstrate the intricate balance of drug release

  17. Peritumoral hemorrhage after radiosurgery for metastatic brain tumor; A case report

    Energy Technology Data Exchange (ETDEWEB)

    Motozaki, Takahiko (Nishinomiya City General Hospital, Hyogo (Japan)); Ban, Sadahiko; Yamamoto, Toyoshiro; Hamasaki, Masatake

    1994-08-01

    An unusual case of peritumoral hemorrhage after radiosurgery for the treatment of metastatic brain tumor is reported. This 64-year-old woman had a history of breast cancer and underwent right mastectomy in 1989. She remained well until January 1993, when she started to have headache, nausea and speech disturbance, and was hospitalized on February 25, 1993. Neurological examination disclosed right hemiparesis and bilateral papilledema. CT scan and MR imaging showed a solitary round mass lesion in the left basal ganglia region. It was a well-demarcated, highly enhanced mass, 37 mm in diameter. Cerebral angiography confirmed a highly vascular mass lesion in the same location. She was treated with radiosurgery on March 8 (maximum dose was 20 Gy in the center and 10 Gy in the peripheral part of the tumor). After radiosurgery, she had an uneventful course and clinical and radiosurgical improvement could be detected. Her neurological symptoms and signs gradually improved and reduction of the tumor size and perifocal edema could be seen one month after radiosurgery. However, 6 weeks after radiosurgery, she suddenly developed semicoma and right hemiplegia. CT scan disclosed a massive peritumoral hemorrhage. Then, emergency craniotomy, evacuation of the hematoma and total removal of the tumor were performed on April 24. Histopathological diagnosis was adenocarcinoma. It was the same finding as that of the previous breast cancer. Histopathological examination revealed necrosis without tumor cells in the center and residual tumor cells in the peripheral part of the tumor. It is postulated that peritumoral hemorrhage was caused by hemodynamic changes in the vascular-rich tumor after radiosurgery and breakdown of the fragile abnormal vessels in the peripheral part of the tumor. (author).

  18. Disseminated breast cancer cells acquire a highly malignant and aggressive metastatic phenotype during metastatic latency in the bone.

    Directory of Open Access Journals (Sweden)

    Carolyn G Marsden

    Full Text Available BACKGROUND: Disseminated tumor cells (DTCs in the bone marrow may exist in a dormant state for extended periods of time, maintaining the ability to proliferate upon activation, engraft at new sites, and form detectable metastases. However, understanding of the behavior and biology of dormant breast cancer cells in the bone marrow niche remains limited, as well as their potential involvement in tumor recurrence and metastasis. Therefore, the purpose of this study was to investigate the tumorigenicity and metastatic potential of dormant disseminated breast cancer cells (prior to activation in the bone marrow. METHODOLOGY/PRINCIPAL FINDINGS: Total bone marrow, isolated from mice previously injected with tumorspheres into the mammary fat pad, was injected into the mammary fat pad of NUDE mice. As a negative control, bone marrow isolated from non-injected mice was injected into the mammary fat pad of NUDE mice. The resultant tumors were analyzed by immunohistochemistry for expression of epithelial and mesenchymal markers. Mouse lungs, livers, and kidneys were analyzed by H+E staining to detect metastases. The injection of bone marrow isolated from mice previously injected with tumorspheres into the mammary fat pad, resulted in large tumor formation in the mammary fat pad 2 months post-injection. However, the injection of bone marrow isolated from non-injected mice did not result in tumor formation in the mammary fat pad. The DTC-derived tumors exhibited accelerated development of metastatic lesions within the lung, liver and kidney. The resultant tumors and the majority of metastatic lesions within the lung and liver exhibited a mesenchymal-like phenotype. CONCLUSIONS/SIGNIFICANCE: Dormant DTCs within the bone marrow are highly malignant upon injection into the mammary fat pad, with the accelerated development of metastatic lesions within the lung, liver and kidney. These results suggest the acquisition of a more aggressive phenotype of DTCs during

  19. Bevacizumab increases the incidence of cardiovascular events in patients with metastatic breast or colorectal cancer

    Directory of Open Access Journals (Sweden)

    Ioannis Kapelakis

    2017-05-01

    Conclusions: The addition of bevacizumab to conventional chemotherapy for metastatic breast or colorectal cancer increases the incidence of cardiovascular events, which is mainly due to the increased prevalence of myocardial infarction and thromboembolic events.

  20. Increased survival in men with metastatic prostate cancer receiving chemo and hormone therapy

    Science.gov (United States)

    Men with hormone-sensitive metastatic prostate cancer who received the chemotherapy drug docetaxel given at the start of standard hormone therapy lived longer than patients who received hormone therapy alone, according to early results from a NIH-supporte

  1. The clinical significance of circulating tumor cells in non-metastatic colorectal cancer - A review

    DEFF Research Database (Denmark)

    Thorsteinsson, M; Jess, Per

    2011-01-01

    BACKGROUND: Finding a clinical tool to improve the risk stratification and identifying those colorectal cancer patients with an increased risk of recurrence is of great importance. The presence of circulating tumor cells (CTC) in peripheral blood can be a strong marker of poor prognosis in patients...... with metastatic disease, but the prognostic role of CTC in non-metastatic colorectal cancer is less clear. The aim of this review is to examine the possible clinical significance of circulating tumor cells in non-metastatic colorectal cancer (TNM-stage I-III) with the primary focus on detection methods...... and prognosis. METHODS: The PubMed and Cochrane database and reference lists of relevant articles were searched for scientific literature published in English from January 2000 to June 2010. We included studies with non-metastatic colorectal cancer (TNM-stage I-III) and CTC detected pre- and/or post...

  2. The Role of Osteoblast-Derived Inflammatory Cytokines in Bone Metastatic Breast Cancer

    National Research Council Canada - National Science Library

    Bussard, Karen M

    2008-01-01

    Breast cancer (BC) has a predilection for bone metastases. While the mechanism for directional metastasis is unknown, the bone microenvironment likely provides a fertile soil for metastatic BC cells...

  3. Collagenases in Breast Cancer Cell-Induced Metastatic Tumor Growth and Progression

    National Research Council Canada - National Science Library

    Selvamurugan, Nagarajan

    2003-01-01

    .... Transforming growth factor (TGF)-Beta1 is a crucial molecule in metastatic breast cancer. It can potentially disrupt the normal balance between osteoclast- and osteoblast-derived matrix metalloproteinase (MMP...

  4. Assessment on zoledronic acid use in patients with bone metastatic breast cancer

    International Nuclear Information System (INIS)

    Soriano Garcia, Jorge L; Batista Albuerne, Noyde; Lima Perez, Mayte

    2010-01-01

    The biphosphonates are the cornerstone in the bone metastases treatment. In present paper the effectiveness and safety of the zoledronic acid (ZA) use in patients with bone metastatic breast cancer (MBC)

  5. The clinical value of hybrid sentinel lymphoscintigraphy to predict metastatic sentinel lymph nodes in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Na, Cang Ju; Kim, Jeong Hun; Choi, Se Hun; Han, Yeon Hee; Jeong, Hwan Jeong; Sohn, Myung Hee; Youn, Hyun Jo; Lim, Seok Tae [Chonbuk National University Medical School and Hospital, Jeonju (Korea, Republic of)

    2015-03-15

    Hybrid imaging techniques can provide functional and anatomical information about sentinel lymph nodes in breast cancer. Our aim in this study was to evaluate which imaging parameters on hybrid sentinel lymphoscintigraphy predicted metastatic involvement of sentinel lymph nodes (SLNs) in patients with breast cancer. Among 56 patients who underwent conventional sentinel lymphoscintigraphy, 45 patients (age, 53.1 ± 9.5 years) underwent hybrid sentinel lymphoscintigraphy using a single-photon emission computed tomography (SPECT)/computed tomography (CT) gamma camera. On hybrid SPECT/CT images, we compared the shape and size (long-to-short axis [L/S] ratio) of the SLN, and SLN/periareolar injection site (S/P) count ratio between metastatic and non-metastatic SLNs. Metastatic involvement of sentinel lymph nodes was confirmed by pathological biopsy. Pathological biopsy revealed that 21 patients (46.7 %) had metastatic SLNs, while 24 (53.3 %) had non-metastatic SLNs. In the 21 patients with metastatic SLNs, the SLN was mostly round (57.1 %) or had an eccentric cortical rim (38.1 %). Of 24 patients with non-metastatic SLNs, 13 patients (54.1 %) had an SLN with a C-shape rim or eccentric cortex. L/S ratio was 2.04 for metastatic SLNs and 2.38 for non-metastatic SLNs. Seven (33 %) patients had T1 primary tumors and 14 (66 %) had T2 primary tumors in the metastatic SLN group. In contrast, 18 (75 %) patients had T1 primary tumors and six (25 %) had T2 tumors in the non-metastatic SLN group. S/P count ratio was significantly lower in the metastatic SLN group than the non-metastatic SLN group for those patients with a T1 primary tumor (p = 0.007). Hybrid SPECT/CT offers the physiologic data of SPECT together with the anatomic data of CT in a single image. This hybrid imaging improved the anatomic localization of SLNs in breast cancer patients and predicted the metastatic involvement of SLNs in the subgroup of breast cancer patients with T1 primary tumors.

  6. Patient considerations in metastatic colorectal cancer – role of panitumumab

    Directory of Open Access Journals (Sweden)

    Rogers JE

    2017-04-01

    Full Text Available Jane E Rogers Pharmacy Clinical Programs, University of Texas MD Anderson Cancer Center, Houston, TX, USA Abstract: Epidermal growth factor receptor (EGFR is overexpressed in many malignancies, including colorectal cancer (CRC, making EGFR an attractive treatment option. Panitumumab and cetuximab, monoclonal antibodies (mAbs directed at EGFR, are both currently utilized in the management of metastatic CRC (mCRC. Through the development of these agents in mCRC, key issues surrounding each mAbs use have been revealed. These key issues include negative patient outcome avoidance when determining use, the economic burden with high-cost medication, predictive biomarkers, tumor location, patient geographic location, patient quality of life, and the prevention of debilitating adverse effects. CRC remains a common malignancy, with many of these patients expected to receive targeted therapy, including EGFR mAb therapy. Oncologists must recognize these EGFR mAb factors in order to improve outcomes. This review aims to provide a chronological timeline on the development of panitumumab, clinical pearls, and guidance on the current use of panitumumab in mCRC. Keywords: receptor, epidermal growth factor, antineoplastic agent, antibodies, monoclonal, colorectal neoplasms

  7. MRI for discriminating metastatic ovarian tumors from primary epithelial ovarian cancers.

    Science.gov (United States)

    Xu, Yanhong; Yang, Jia; Zhang, Zaixian; Zhang, Guixiang

    2015-08-28

    To find specific magnetic resonance imaging (MRI) features to differentiate metastatic ovarian tumors from primary epithelial ovarian cancers. Eleven cases with metastatic ovarian tumors and 26 cases with primary malignant epithelial ovarian cancers were retrospectively studied. All features such as patient characteristics, MRI findings and biomarkers were evaluated. The differences including laterality, configuration, uniformity of locules, diffusion weighted imaging (DWI) signal of solid components and enhancement of solid portions between metastatic ovarian tumors and primary epithelial ovarian cancers were compared by Fisher's exact test. Median age of patients, the maximum diameter of lesions and biomarkers were compared by the Mann-Whitney test. Patients with metastatic ovarian tumors were younger than patients with primary epithelial ovarian cancers in the median age (P = 0.015). Patients with bilateral tumors in metastatic ovarian tumors were more than those of primary epithelial ovarian cancers (P = 0.032). The maximum diameter of lesions in metastatic ovarian tumors was smaller than that of primary epithelial ovarian cancers (P = 0.005). The locules in metastatic ovarian tumors were more uniform than those of primary epithelial ovarian cancers (P = 0.024). The enhancement of solid portions in metastatic ovarian tumors showed more moderate than that of primary epithelial ovarian cancers (P = 0.037). There was no statistically significant difference between the two groups in configuration, DWI signal of solid components and ascites. Biomarkers such as CA125 and human epididymis protein 4 (HE4) in metastatic ovarian tumors showed less elevated than that of primary epithelial ovarian cancers. Significant differences between metastatic ovarian tumors and primary epithelial ovarian cancers were found in the median age of patients, laterality, the maximum diameter of lesions, uniformity of locules, enhancement patterns of solid portions and

  8. Computed tomographic brain scanning in the diagnosis of metastatic neoplasms

    Energy Technology Data Exchange (ETDEWEB)

    Ringelstein, E.B.; Zeumer, H.; Hacke, W.; Keulers, P.

    1981-11-20

    Clinical investigations and computed brain scanning were done in 305 patients with primary extracerebral malignant tumours. One third of the patients had cerebral metastases. In most patients with brain metastases extracerebral secondary tumours were known already. Silent brain metastases were present in only 0.6% of all investigated tumour patients. All other patients had either objective neurologic-psychiatric defects or at least symptoms (headache, vomiting). Use of cranial computed tomography in all tumour patients as a pure screening method is thus not justified. The indication for the investigation is dependent on the clinical symptomatology. However, not only objective neurologic-psychiatric defects must be taken into account, but also occurrence of new symptoms.

  9. Computed tomographic brain scanning in the diagnosis of metastatic neoplasms

    International Nuclear Information System (INIS)

    Ringelstein, E.B.; Zeumer, H.; Hacke, W.; Keulers, P.

    1981-01-01

    Clinical investigations and computed brain scanning were done in 305 patients with primary extracerebral malignant tumours. One third of the patients had cerebral metastases. In most patients with brain metastases extracerebral secondary tumours were known already. Silent brain metastases were present in only 0.6% of all investigated tumour patients. All other patients had either objective neurologic-psychiatric defects or at least symptoms (headache, vomiting). Use of cranial computed tomography in all tumour patients as a pure screening method is thus not justified. The indication for the investigation is dependent on the clinical symptomatology. However, not only objective neurologic-psychiatric defects must be taken into account, but also occurrence of new symptoms. (orig.) [de

  10. Intracerebral haemorrhage in primary and metastatic brain tumours.

    Science.gov (United States)

    Salmaggi, Andrea; Erbetta, Alessandra; Silvani, Antonio; Maderna, Emanuela; Pollo, Bianca

    2008-09-01

    Intracerebral haemorrhage may both be a presenting manifestation in unrecognised brain tumour or--more frequently--take place in the disease course of known/suspected brain tumour due to diagnostic/therapeutic procedures, including biopsy, locoregional treatments and anti-angiogenic therapies. Apart from the difficulties inherent to accurate neuroradiological diagnosis in selected cases with small tumour volume, the main clinical problem that neurologists face is represented by decision making in prophylaxis/treatment of venous thromboembolism in these patients. These points are briefly discussed and available evidence on the last point is commented on.

  11. Biofluid-Based Detection of the Migration Switch in Prostate Cancer to Predict Metastatic Disease

    Science.gov (United States)

    2016-09-01

    AWARD NUMBER: W81XWH-15-1-0416 TITLE: Biofluid-Based Detection of the Migration Switch in Prostate Cancer to Predict Metastatic Disease PRINCIPAL...Aug 2016 Sep.20164. TITLE AND SUBTITLE Biofluid-Based Detection of the Migration Switch in Prostate Cancer to Predict Metastatic Disease 5a...accurately and non-invasively monitor localized disease longitudinally will allow patients to avoid the side effects and morbidity of definitive treatment

  12. Estramustine phosphate versus placebo as second line treatment after orchiectomy in patients with metastatic prostate cancer

    DEFF Research Database (Denmark)

    Iversen, P; Rasmussen, F; Asmussen, C

    1997-01-01

    We compared the effect of 560 mg. estramustine phosphate daily to placebo as a supplement to standard palliative therapy in patients with progressive disease after bilateral orchiectomy as first line therapy for metastatic prostate cancer.......We compared the effect of 560 mg. estramustine phosphate daily to placebo as a supplement to standard palliative therapy in patients with progressive disease after bilateral orchiectomy as first line therapy for metastatic prostate cancer....

  13. Bevacizumab plus chemotherapy in elderly patients with previously untreated metastatic colorectal cancer: single center experience

    Directory of Open Access Journals (Sweden)

    Ocvirk Janja

    2016-06-01

    Full Text Available Metastatic colorectal cancer (mCRC is mainly a disease of elderly, however, geriatric population is underrepresented in clinical trials. Patient registries represent a tool to assess and follow treatment outcomes in this patient population. The aim of the study was with the help of the patients’ register to determine the safety and efficacy of bevacizumab plus chemotherapy in elderly patients who had previously untreated metastatic colorectal cancer.

  14. CURRENT POSSIBILITIES OF TREATMENT FOR VISCERAL METASTASES IN PATIENTS WITH METASTATIC CASTRATION-REFRACTORY PROSTATE CANCER

    Directory of Open Access Journals (Sweden)

    A. V. Govorov

    2014-07-01

    Full Text Available Medications increasing the survival of patients with metastatic castration-refractory prostate cancer (CRPC are lacking today. In the past 3 years, in the pharmaceutical market there have been a few novel drugs to treat progressive prostate cancer. Abiraterone acetate is an androgen synthesis inhibitor, which is also used to increase the survival of patients with metastatic CRPC that progresses after chemotherapy. The results of treatment for metastatic CRPC depend on a number of factors. Visceral metastases are poor predictors of the course of the disease. The results of abiraterone acetate treatment were analyzed in CRPC patients with visceral metastases.

  15. Can urologists introduce the concept of "oligometastasis" for metastatic bladder cancer after total cystectomy?

    Science.gov (United States)

    Ogihara, Koichiro; Kikuchi, Eiji; Watanabe, Keitaro; Kufukihara, Ryohei; Yanai, Yoshinori; Takamatsu, Kimiharu; Matsumoto, Kazuhiro; Hara, Satoshi; Oyama, Masafumi; Monma, Tetsuo; Masuda, Takeshi; Hasegawa, Shintaro; Oya, Mototsugu

    2017-12-19

    We investigated whether the concept of oligometastasis may be introduced to the clinical management of metastatic bladder cancer patients. Our study population comprised 128 patients diagnosed with metastatic bladder cancer after total cystectomy at our 6 institutions between 2004 and 2014. We extracted independent predictors for identifying a favorable. Occurrence that fulfilled all 4 criteria which were independently associated with cancer-specific death was defined as oligometastasis: a solitary metastatic organ; number of metastatic lesions of 3 or less; the largest diameter of metastatic foci of 5cm or less; and no liver metastasis. We evaluated differences in clinical outcomes between patients with oligometastasis (oligometastasis group) and those without oligometastasis (non-oligometastasis group). Overall, there were 43 patients in the oligometastasis group. The 2-year cancer-specific survival rate in the oligometastasis group was 53.3%, which was significantly higher than that in the non-oligometastasis group (16.1%, poligometastasis (poligometastasis group. The 2-year cancer-specific survival rate in the oligometastasis group was 55.0%, which was significantly higher than that in the non-oligometastasis group (22.0%, p=0.005). Non-oligometastasis (p=0.009) was the only independent risk factor for cancer-specific death. We presented that urothelial carcinoma with oligometastasis had a favorable prognosis and responded to systemic chemotherapy. Oligometastasis may be treated as a separate entity in the field of metastatic urothelial carcinoma.

  16. Can urologists introduce the concept of “oligometastasis” for metastatic bladder cancer after total cystectomy?

    Science.gov (United States)

    Ogihara, Koichiro; Kikuchi, Eiji; Watanabe, Keitaro; Kufukihara, Ryohei; Yanai, Yoshinori; Takamatsu, Kimiharu; Matsumoto, Kazuhiro; Hara, Satoshi; Oyama, Masafumi; Monma, Tetsuo; Masuda, Takeshi; Hasegawa, Shintaro; Oya, Mototsugu

    2017-01-01

    We investigated whether the concept of oligometastasis may be introduced to the clinical management of metastatic bladder cancer patients. Our study population comprised 128 patients diagnosed with metastatic bladder cancer after total cystectomy at our 6 institutions between 2004 and 2014. We extracted independent predictors for identifying a favorable. Occurrence that fulfilled all 4 criteria which were independently associated with cancer-specific death was defined as oligometastasis: a solitary metastatic organ; number of metastatic lesions of 3 or less; the largest diameter of metastatic foci of 5cm or less; and no liver metastasis. We evaluated differences in clinical outcomes between patients with oligometastasis (oligometastasis group) and those without oligometastasis (non-oligometastasis group). Overall, there were 43 patients in the oligometastasis group. The 2-year cancer-specific survival rate in the oligometastasis group was 53.3%, which was significantly higher than that in the non-oligometastasis group (16.1%, poligometastasis (poligometastasis group. The 2-year cancer-specific survival rate in the oligometastasis group was 55.0%, which was significantly higher than that in the non-oligometastasis group (22.0%, p=0.005). Non-oligometastasis (p=0.009) was the only independent risk factor for cancer-specific death. We presented that urothelial carcinoma with oligometastasis had a favorable prognosis and responded to systemic chemotherapy. Oligometastasis may be treated as a separate entity in the field of metastatic urothelial carcinoma. PMID:29340094

  17. Targeting brain tumors by intra-arterial delivery of cell-penetrating peptides: a novel approach for primary and metastatic brain malignancy.

    Science.gov (United States)

    Joshi, Shailendra; Cooke, Johann R N; Ellis, Jason A; Emala, Charles W; Bruce, Jeffrey N

    2017-12-01

    Computational modeling shows that intra-arterial delivery is most efficient when the delivered drugs rapidly and avidly bind to the target site. The cell-penetrating peptide trans-activator of transcription (TAT) is a candidate carrier molecule that could mediate such specificity for brain tumor chemotherapeutics. To test this hypothesis we first performed in vitro studies testing the uptake of TAT by one primary and three potentially metastatic brain cancer cell lines (9L, 4T-1, LLC, SKOV-3). Then we performed in vivo studies in a rat model where TAT was delivered either intra-arterially (IA) or intravenously (IV) to 9L brain tumors. We observed robust uptake of TAT by all tumor cell lines in vitro. Flow cytometry and confocal microscopy revealed a rapid uptake of fluorescein-labeled TAT within 5 min of exposure to the cancer cells. IA injections done under transient cerebral hypoperfusion (TCH) generated a four-fold greater tumor TAT concentration compared to conventional IV injections. We conclude that it is feasible to selectively target brain tumors with TAT-linked chemotherapy by the IA-TCH method.

  18. Rationale for the Use of Upfront Whole Brain Irradiation in Patients with Brain Metastases from Breast Cancer

    Directory of Open Access Journals (Sweden)

    Agnes V. Tallet

    2014-05-01

    Full Text Available Breast cancer is the second most common cause of brain metastases and deserves particular attention in relation to current prolonged survival of patients with metastatic disease. Advances in both systemic therapies and brain local treatments (surgery and stereotactic radiosurgery have led to a reappraisal of brain metastases management. With respect to this, the literature review presented here was conducted in an attempt to collect medical evidence-based data on the use of whole-brain radiotherapy for the treatment of brain metastases from breast cancer. In addition, this study discusses here the potential differences in outcomes between patients with brain metastases from breast cancer and those with brain metastases from other primary malignancies and the potential implications within a treatment strategy.

  19. Cabozantinib-S-Malate in Treating Patients With Recurrent or Metastatic Endometrial Cancer

    Science.gov (United States)

    2017-11-20

    Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Mixed Adenocarcinoma; Endometrial Serous Adenocarcinoma; Metastatic Endometrioid Adenocarcinoma; Recurrent Uterine Corpus Carcinoma; Stage IV Uterine Corpus Cancer AJCC v7; Stage IVA Uterine Corpus Cancer AJCC v7; Stage IVB Uterine Corpus Cancer AJCC v7; Uterine Corpus Carcinosarcoma

  20. Molecular profiling of 6,892 colorectal cancer samples suggests different possible treatment options specific to metastatic sites.

    Science.gov (United States)

    El-Deiry, Wafik S; Vijayvergia, Namrata; Xiu, Joanne; Scicchitano, Angelique; Lim, Bora; Yee, Nelson S; Harvey, Harold A; Gatalica, Zoran; Reddy, Sandeep

    2015-01-01

    Metastatic colorectal cancer (mCRC) carries a poor prognosis with an overall 5-year survival of 13.1%. Therapies guided by tumor profiling have suggested benefit in advanced cancer. We used a multiplatform molecular profiling (MP) approach to identify key molecular changes that may provide therapeutic options not typically considered in mCRC. We evaluated 6892 mCRC referred to Caris Life Sciences by MP including sequencing (Sanger/NGS), immunohistochemistry (IHC) and in-situ hybridization (ISH). mCRC metastases to liver, brain, ovary or lung (n = 1507) showed differential expression of markers including high protein expression of TOPO1 (52%) and/or low RRM1 (57%), TS (71%) and MGMT (39%), suggesting possible benefit from irinotecan, gemcitabine, 5FU/capecitabine and temozolomide, respectively. Lung metastases harbored a higher Her2 protein expression than the primary colon tumors (4% vs. 1.8%, p = 0.028). Brain and lung metastases had higher KRAS mutations than other sites (65% vs 59% vs 47%, respectively, p = 0.07, cancer versus colon cancer (10% and 3.3%, respectively). MP of 6892 CRCs identified significant differences between primary and metastatic sites and among BRAF/KRAS sub-types. Our findings are hypothesis generating and need to be examined in prospective studies. Specific therapies may be considered for different actionable targets in mCRC as revealed by MP.

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

    International Nuclear Information System (INIS)

    Sueyama, Hiroo; Yamanoi, Tadayoshi; Uematu, Takayoshi

    2001-01-01

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

  2. m-RNA mammaglobin expression in metastatic breast cancer patient at Medan city, Indonesia

    Science.gov (United States)

    Rimbun, S.; Siregar, Y.

    2018-03-01

    Breast cancer is the most common causes of women’s death in the world. Metastatic spread presents a major clinical problem in about 30% of the patients. The study aims to investigate the clinical reliability of mammaglobin mRNA as a marker of circulating cancer cells in breast cancer patients. The positivity of blood was analyzed in relation to clinical and pathological characteristics. This study was on 29 breast cancer patients (13 metastatic, 16 non- metastatic patients), where28 were invasive intraductal carcinoma type and 1 was invasive lobular carcinoma type. Breast cancer patients were according to the histologic grade into grade I (7 patients),grade II (6 patients) and grade III (15 patients). All individuals included in this study were subjected to detection of mammaglobin m-RNA of circulating tumor cells in peripheral blood using RT-PCR technique. Positivity for mammaglobin in blood samples was in 38% of patients with metastatic but not in the non-metastatic patients. The presence of mammaglobin correlated with metastatic tumor (P = 0.011). Mammaglobin overexpression in breast tissue was significantly positive in low-grade tumors (I and II).

  3. [Study on medical economic evaluation methods for metastatic brain tumors therapy].

    Science.gov (United States)

    Takura, Tomoyuki; Hayashi, Motohiro; Muragaki, Yoshihiro; Iseki, Hiroshi; Uetsuka, Yoshio

    2010-07-01

    Treatment design for metastatic brain tumors is required to firstly care about the life and function for which the patient hopes because it is terminal care. Therefore, to discuss the value of the therapy, a viewpoint of the QOL and the socioeconomic factors other than the survival rate is important. However, examination that applies these factors to the therapy needs to be carried out more thoroughly. With this in mind, we discuss cost effectiveness of therapy for metastatic brain tumor, through a pilot study on gamma knife therapy. We studied 18 patients (mean age 61.6 years old) undergoing therapy for metastatic brain tumors. The health rate QOL was assessed by the profile-type measure SF-36 (Short-Form 36-Item Ver1.2) and the preference-based measure EQ-5D (EuroQoL-5D), before and six months after gamma knife therapy. Cost-utility-analysis (yen/Qaly) was carried out from quality adjusted life years (Qalys) and medical fee claims. In addition, we made a correlation analysis of the irradiation procedure and the gains attained. The observation by SF-36 for six months was useful for metastatic brain tumor. As a result, the QOL indicators showed increased mental health (MH: p=0.040) and role emotional (RE: p=0.029) with significant difference. In the measurement of EQ-5D, it was added only for one month based on the significant difference (p=0.022) from the pre-therapy QOL. The utilities that were analyzed became 0.052+/-0.175SD (score), and Qalys were 0.135. Because the cost was 721.4+/-5.2SD (thousand yen), the performance of cost-utility-analysis was estimated as 5, 330, 000 (yen/Qaly). In addition, positive correlation (r=0.845/p=0.034) was found between the EQ-5D utility score and the tumor irradiation energy (mJ), etc. We established a new value over and above mere survival rate concerning metastatic brain tumor therapy. The socioeconomics and efficacy of therapy are more difficult to discuss in this disease than in other diseases. We did this by clarifying

  4. Metastatic Brain Tumors: A Retrospective Review in East Azarbyjan (Tabriz

    Directory of Open Access Journals (Sweden)

    Zinat Miabi

    2011-02-01

    Full Text Available A set of one hundred and twenty nine patients with known primary malignancy and suspected brain metastasis was reviewed in present study. The patients were selected among patients presented to the MRI section of Imam Khomeini Hospital or a private MRI center in Tabriz (Iran. Primary tumor site, clinical manifestations, number and site of lesions were identified in this patient population. The primary tumor site was breast in 55 patients (42.6%, followed by lung (40.3%, kidney (7.7%, colorectal (4.6%, lymphoma (3.1% and melanoma (1.5%. Most patients were presented with features of increased intracranial pressure (headaches and vomiting, seizures and focal neurologic signs. Single brain metastasis occurred in 16.3% of patients, while multiple lesions accounted for 83.7% of patients. Ninety seven patients had supratentorial metastases (75.2%. Twenty cases (15.5% had metastases in both compartments. Infratentorial lesions were observed only in twelve patients (9.3%.

  5. Determinants of Last-line Treatment in Metastatic Breast Cancer.

    Science.gov (United States)

    Cinausero, Marika; Gerratana, Lorenzo; De Carlo, Elisa; Iacono, Donatella; Bonotto, Marta; Fanotto, Valentina; Buoro, Vanessa; Basile, Debora; Vitale, Maria Grazia; Rihawi, Karim; Fasola, Gianpiero; Puglisi, Fabio

    2017-07-14

    In metastatic breast cancer (MBC) patients, the identification of factors helping clinicians in the choice between active therapy versus best supportive care is needed clinically. The aim of the present study was to identify the clinicopathologic factors that could improve the prognostic valuation of MBC patients and clinical decision-making at the end of life. The present study analyzed data from a retrospective series of 522 MBC patients treated at the oncology department (University Hospital of Udine) from January 2004 to June 2014. The association between clinicopathologic features and death within 30 or 90 days since last-line treatment prescription was explored. Differences between lightly (≤ 3 lines) and heavily (> 3 lines) pretreated patients and the factors affecting treatment choice were investigated. The event "death" occurred in 410 patients. The median last-line survival was 100 days. The median number of therapeutic lines was 3. On multivariate analysis, worse Eastern Cooperative Oncology Group performance status was significantly associated with death within 90 and 30 days since last-line treatment prescription. Among the heavily pretreated patients, liver function impairment and evaluation by a breast cancer specialist were significantly associated with a greater and lower risk of death within 30 days, respectively. Among the lightly pretreated patients with luminal disease, age < 70 years, luminal B-like disease, and number of previous lines were associated with a greater chance of receiving chemotherapy. In the present study, the Eastern Cooperative Oncology Group performance status was the most robust independent factor driving the last-line therapeutic choice for MBC patients. In addition, the molecular subtype and oncologist subspecialization also influenced the decision-making process. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Pretargeted radioimmunotherapy in rapidly progressing, metastatic, medullary thyroid cancer.

    Science.gov (United States)

    Kraeber-Bodéré, Françoise; Salaun, Pierre-Yves; Oudoux, Aurore; Goldenberg, David M; Chatal, Jean-François; Barbet, Jacques

    2010-02-15

    Medullary thyroid cancer (MTC) patients with localized residual disease and/or distant metastases may survive for several years or rapidly progress and die of their disease. Thus, highly reliable prognostic factors are needed for an early distinction between high-risk patients who need to be treated and low-risk patients who warrant a watch-and-wait approach. Calcitonin doubling time is an independent predictor of survival, with a high predictive value in a population of patients who have not normalized their calcitonin, even after repeated surgery. Several imaging methods should be proposed for patients with abnormal residual calcitonin levels persisting after complete surgery: ultrasonography and computed tomography (CT) for neck exploration, and CT for chest, abdomen, and pelvis. Magnetic resonance imaging (MRI) appears to have an advantage over CT for the detection of liver metastases from endocrine tumors. Moreover, MRI appears to be a sensitive imaging technique for detecting the spread of MTC to bone/bone marrow. 2-Fluoro-2-deoxy-D-glucose positron emission tomography/CT could be used for staging patients with progressive MTC, with possible prognostication by standard uptake value quantification. For systemic treatment of patients with rapidly progressing metastatic MTC, chemotherapy is not considered a valid therapeutic option. It is too early to evaluate the potential effectiveness of multikinase inhibitors, although interesting results of phase 2 studies have shown a transient stabilization in 30% to 50% of patients. Pretargeted radioimmunotherapy has been the only innovative treatment modality convincingly showing some survival benefit when compared with a historical untreated control group. (c) 2010 American Cancer Society.

  7. Sudden hemorrhage in metastatic thyroid carcinoma of the brain during treatment with 131I

    International Nuclear Information System (INIS)

    Holmquest, D.L.; Lake, P.

    1976-01-01

    A patient with papillary--follicular carcinoma of the thyroid, with metastases to the lungs, skeleton, and brain, was treated 5 weeks after thyroidectomy with 135 mCi of 131 I. Although preliminary studies with 1 mCi had not shown any iodine uptake by the brain metastasis, this lesion showed intense concentration at the time of the larger therapeutic dose. Four days later, acute hemorrhage of the tumor occurred, requiring surgical removal. Although 131 I therapy would seem an unlikely cause of acute necrosis and hemorrhage in these lesions, the association of therapeutic radioiodine and hemorrhage is interesting. Since recent reports suggest that brain metastasis may be somewhat more common than previously suspected, we suggest that brain imaging be included in the workup prior to radioiodine therapy of patients with advanced metastatic disease or neurologic symptoms

  8. Enhanced Metastatic Recurrence Via Lymphatic Trafficking of a High-Metastatic Variant of Human Triple-Negative Breast Cancer After Surgical Resection in Orthotopic Nude Mouse Models.

    Science.gov (United States)

    Yano, Shuya; Takehara, Kiyoto; Tazawa, Hiroshi; Kishimoto, Hiroyuki; Kagawa, Shunsuke; Bouvet, Michael; Fujiwara, Toshiyoshi; Hoffman, Robert M

    2017-03-01

    We previously developed and characterized a highly invasive and metastatic triple-negative breast cancer (TNBC) variant by serial orthotopic implantation of MDA-MB-231 human breast cancer cells in nude mice. Eventually, a highly invasive and metastatic variant of human TNBC was isolated after lymph node metastases was harvested and orthotopically re-implanted into the mammary gland of nude mice for two cycles. The variant thereby isolated is highly invasive in the mammary gland and metastasized to lymph nodes in 10 of 12 mice compared to 2 of 12 of the parental cell line. In the present report, we observed that high-metastatic MDA-MB-231H-RFP cells produced significantly larger subcutaneous tumors compared with parental MDA-MB-231 cells in nude mice. Extensive lymphatic trafficking by high-metastatic MDA-MB-231 cells was also observed. High-metastatic MDA-MB-231 developed larger recurrent tumors 2 weeks after tumor resection compared with tumors that were not resected in orthotopic models. Surgical resection of the MDA-MB-231 high-metastatic variant primary tumor in orthotopic models also resulted in rapid and enhanced lymphatic trafficking of residual cancer cells and extensive lymph node and lung metastasis that did not occur in the non-surgical mice. These results suggest that surgical resection of high metastatic TNBC can greatly increase the malignancy of residual cancer. J. Cell. Biochem. 118: 559-569, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  9. Consistent expression of guanylyl cyclase-C in primary and metastatic gastrointestinal cancers.

    Directory of Open Access Journals (Sweden)

    Hadi Danaee

    Full Text Available The transmembrane receptor guanylate cyclase-C (GCC has been found to be expressed in colorectal cancers. However, limited data are available on GCC protein expression in non-colorectal gastrointestinal tumors and few studies have reported whether GCC protein expression was consistently preserved in synchronous primary and metastatic cancer tissues.GCC protein status was assessed by immunohistochemistry in tumor specimens from individuals (n = 627 with gastrointestinal tumors, including esophageal (n = 130, gastric (n = 276, pancreatic (n = 136, and colorectal (n = 85 primary and metastatic tumors. Tissue specimens consisted of tissue microarrays containing esophageal, gastric, pancreatic tumors, and whole-slide tissue sections from colorectal cancer patients with matching primary and metastatic tumors.Among the evaluated esophageal, gastric, and pancreatic tumors, the frequency of GCC positivity at the protein level ranged from 59% to 68%. GCC was consistently expressed in primary and matched/synchronous metastatic lesions of colorectal cancer tissues derived from the same patients.This observational study demonstrated the protein expression of GCC across various gastrointestinal malignancies. In all cancer histotypes, GCC protein localization was observed predominantly in the cytoplasm compared to the membrane region of tumor cells. Consistent immunohistochemistry detection of GCC protein expression in primary colorectal cancers and in their matched liver metastases suggests that the expression of GCC is maintained throughout the process of tumor progression and formation of metastatic disease.

  10. Elevated cyclin A associated kinase activity promotes sensitivity of metastatic human cancer cells to DNA antimetabolite drug.

    Science.gov (United States)

    Wang, Jin; Yin, Hailin; Panandikar, Ashwini; Gandhi, Varsha; Sen, Subrata

    2015-08-01

    Drug resistance is a major obstacle in successful systemic therapy of metastatic cancer. We analyzed the involvement of cell cycle regulatory proteins in eliciting response to N (phosphonoacetyl)-L-aspartate (PALA), an inhibitor of de novo pyrimidine synthesis, in two metastatic variants of human cancer cell line MDA-MB-435 isolated from lung (L-2) and brain (Br-1) in nude mouse, respectively. L-2 and Br-l cells markedly differed in their sensitivity to PALA. While both cell types displayed an initial S phase delay/arrest, Br-l cells proliferated but most L-2 cells underwent apoptosis. There was distinct elevation in cyclin A, and phosphorylated Rb proteins concomitant with decreased expression of bcl-2 protein in the PALA treated L-2 cells undergoing apoptosis. Markedly elevated cyclin A associated and cdk2 kinase activities together with increased E2F1-DNA binding were detected in these L-2 cells. Induced ectopic cyclin A expression sensitized Br-l cells to PALA by activating an apoptotic pathway. Our findings demonstrate that elevated expression of cyclin A and associated kinase can activate an apoptotic pathway in cells exposed to DNA antimetabolites. Abrogation of this pathway can lead to resistance against these drugs in metastatic variants of human carcinoma cells.

  11. Metabolic management of brain cancer.

    Science.gov (United States)

    Seyfried, Thomas N; Kiebish, Michael A; Marsh, Jeremy; Shelton, Laura M; Huysentruyt, Leanne C; Mukherjee, Purna

    2011-06-01

    Malignant brain tumors are a significant health problem in children and adults. Conventional therapeutic approaches have been largely unsuccessful in providing long-term management. As primarily a metabolic disease, malignant brain cancer can be managed through changes in metabolic environment. In contrast to normal neurons and glia, which readily transition to ketone bodies (β-hydroxybutyrate) for energy under reduced glucose, malignant brain tumors are strongly dependent on glycolysis for energy. The transition from glucose to ketone bodies as a major energy source is an evolutionary conserved adaptation to food deprivation that permits the survival of normal cells during extreme shifts in nutritional environment. Only those cells with a flexible genome and normal mitochondria can effectively transition from one energy state to another. Mutations restrict genomic and metabolic flexibility thus making tumor cells more vulnerable to energy stress than normal cells. We propose an alternative approach to brain cancer management that exploits the metabolic flexibility of normal cells at the expense of the genetically defective and metabolically challenged tumor cells. This approach to brain cancer management is supported from recent studies in mice and humans treated with calorie restriction and the ketogenic diet. Issues of implementation and use protocols are presented for the metabolic management of brain cancer. Copyright © 2010. Published by Elsevier B.V.

  12. Knee pain and swelling: An atypical presentation of metastatic colon cancer to the patella

    Directory of Open Access Journals (Sweden)

    Bethany Gasagranda, DO

    2014-01-01

    Full Text Available Knee pain is a common reason for a patient to seek medical evaluation. Of the many causes of knee pain, malignancy is one of the least common. When malignancy is the etiology of the pain, it is usually due to a primary tumor of the osseous structures or soft tissues of the knee joint. Metastatic disease involving the knee joint is uncommon, with few cases reported in the literature. Of these reported cases, metastatic colon cancer is exceedingly rare. However, in a patient with new onset knee pain and the proper clinical history, metastatic disease should be considered as a potential explanation of symptoms. We report a case of knee pain and swelling due to metastatic colon cancer to the patella.

  13. PIK3CA mutations may be discordant between primary and corresponding metastatic disease in Breast Cancer

    DEFF Research Database (Denmark)

    Dupont Jensen, Jeanette; Laenkholm, Anne-Vibeke; Knoop, Ann

    2011-01-01

    PURPOSE: PIK3CA mutations are frequent in breast cancer and activate the PI3K/Akt pathway. Unexpectedly, PIK3CA mutation appears in general to be associated with better outcome. In a cohort of patients where both primary and metastatic lesions were available the objective was to assess changes...... recurrence than wild type cases (p=0.03). CONCLUSIONS: PIK3CA mutations occur at high frequency in primary and metastatic breast cancer; these may not necessarily confer increased aggressiveness as mutants had a longer time to recurrence. Because PIK3CA status quite frequently changes between primary...... metastatic breast tumors. Samples were analysed for PIK3CA mutations (exon 9 and 20) as well as immunohistochemical evaluation for PTEN, pAKT, Ki67, ER and HER2. RESULTS: PIK3CA mutation was detected in 45 % of the primary tumors. Overall there was a net gain in mutation in metastatic disease, to 53...

  14. Halofuginone Inhibits Angiogenesis and Growth in Implanted Metastatic Rat Brain Tumor Model-an MRI Study

    Directory of Open Access Journals (Sweden)

    Rinat Abramovitch

    2004-09-01

    Full Text Available Tumor growth and metastasis depend on angiogenesis; therefore, efforts are made to develop specific angiogenic inhibitors. Halofuginone (HF is a potent inhibitor of collagen type α1(I. In solid tumor models, HF has a potent antitumor and antiangiogenic effect in vivo, but its effect on brain tumors has not yet been evaluated. By employing magnetic resonance imaging (MRI, we monitored the effect of HF on tumor progression and vascularization by utilizing an implanted malignant fibrous histiocytoma metastatic rat brain tumor model. Here we demonstrate that treatment with HF effectively and dose-dependently reduced tumor growth and angiogenesis. On day 13, HF-treated tumors were fivefold smaller than control (P < .001. Treatment with HF significantly prolonged survival of treated animals (142%; P = .001. In HF-treated rats, tumor vascularization was inhibited by 30% on day 13 and by 37% on day 19 (P < .05. Additionally, HF treatment inhibited vessel maturation (P = .03. Finally, in HF-treated rats, we noticed the appearance of a few clusters of satellite tumors, which were distinct from the primary tumor and usually contained vessel cores. This phenomenon was relatively moderate when compared to previous reports of other antiangiogenic agents used to treat brain tumors. We therefore conclude that HF is effective for treatment of metastatic brain tumors.

  15. The ketogenic diet and hyperbaric oxygen therapy prolong survival in mice with systemic metastatic cancer.

    Science.gov (United States)

    Poff, Angela M; Ari, Csilla; Seyfried, Thomas N; D'Agostino, Dominic P

    2013-01-01

    Abnormal cancer metabolism creates a glycolytic-dependency which can be exploited by lowering glucose availability to the tumor. The ketogenic diet (KD) is a low carbohydrate, high fat diet which decreases blood glucose and elevates blood ketones and has been shown to slow cancer progression in animals and humans. Abnormal tumor vasculature creates hypoxic pockets which promote cancer progression and further increase the glycolytic-dependency of cancers. Hyperbaric oxygen therapy (HBO₂T) saturates tumors with oxygen, reversing the cancer promoting effects of tumor hypoxia. Since these non-toxic therapies exploit overlapping metabolic deficiencies of cancer, we tested their combined effects on cancer progression in a natural model of metastatic disease. We used the firefly luciferase-tagged VM-M3 mouse model of metastatic cancer to compare tumor progression and survival in mice fed standard or KD ad libitum with or without HBO₂T (2.5 ATM absolute, 90 min, 3x/week). Tumor growth was monitored by in vivo bioluminescent imaging. KD alone significantly decreased blood glucose, slowed tumor growth, and increased mean survival time by 56.7% in mice with systemic metastatic cancer. While HBO₂T alone did not influence cancer progression, combining the KD with HBO₂T elicited a significant decrease in blood glucose, tumor growth rate, and 77.9% increase in mean survival time compared to controls. KD and HBO₂T produce significant anti-cancer effects when combined in a natural model of systemic metastatic cancer. Our evidence suggests that these therapies should be further investigated as potential non-toxic treatments or adjuvant therapies to standard care for patients with systemic metastatic disease.

  16. The ketogenic diet and hyperbaric oxygen therapy prolong survival in mice with systemic metastatic cancer.

    Directory of Open Access Journals (Sweden)

    Angela M Poff

    Full Text Available INTRODUCTION: Abnormal cancer metabolism creates a glycolytic-dependency which can be exploited by lowering glucose availability to the tumor. The ketogenic diet (KD is a low carbohydrate, high fat diet which decreases blood glucose and elevates blood ketones and has been shown to slow cancer progression in animals and humans. Abnormal tumor vasculature creates hypoxic pockets which promote cancer progression and further increase the glycolytic-dependency of cancers. Hyperbaric oxygen therapy (HBO₂T saturates tumors with oxygen, reversing the cancer promoting effects of tumor hypoxia. Since these non-toxic therapies exploit overlapping metabolic deficiencies of cancer, we tested their combined effects on cancer progression in a natural model of metastatic disease. METHODS: We used the firefly luciferase-tagged VM-M3 mouse model of metastatic cancer to compare tumor progression and survival in mice fed standard or KD ad libitum with or without HBO₂T (2.5 ATM absolute, 90 min, 3x/week. Tumor growth was monitored by in vivo bioluminescent imaging. RESULTS: KD alone significantly decreased blood glucose, slowed tumor growth, and increased mean survival time by 56.7% in mice with systemic metastatic cancer. While HBO₂T alone did not influence cancer progression, combining the KD with HBO₂T elicited a significant decrease in blood glucose, tumor growth rate, and 77.9% increase in mean survival time compared to controls. CONCLUSIONS: KD and HBO₂T produce significant anti-cancer effects when combined in a natural model of systemic metastatic cancer. Our evidence suggests that these therapies should be further investigated as potential non-toxic treatments or adjuvant therapies to standard care for patients with systemic metastatic disease.

  17. Metastatic breast cancer in a Nigerian tertiary hospital | Adisa ...

    African Journals Online (AJOL)

    limited countries with attendant poor outcome. Objective: To describe the pattern of clinical presentation and challenges of treating patients presenting with metastatic breast carcinoma in a Nigerian hospital. Method: Clinical records of all patients ...

  18. [Metastatic breast cancer to the stomach: An uncommon evolution of breast carcinoma].

    Science.gov (United States)

    Hild, C; Talha-Vautravers, A; Hoefler, P; Zirabe, S; Bellocq, J-P; Mathelin, C

    2014-01-01

    Breast carcinoma exceptionally leads to metastatic linitis plastica. Distinguishing a breast cancer metastasis to the stomach from a primary gastric cancer on the basis of clinical and radiological signs is very challenging. Thanks to being cognizant of the previous history of invasive lobular carcinoma and the gastric biopsy followed by immunohistochemical analysis, gastric metastasis can be diagnosed. Despite the use of chemotherapy and hormonal therapy, gastric metastasis remains often associated with poor prognosis. We present a case where gastric biopsy allowed a metastatic breast cancer to the stomach to be diagnosed and we discuss its clinical, diagnostic, pathological and therapeutic particularities. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  19. Advanced new strategies for metastatic cancer treatment by therapeutic stem cells and oncolytic virotherapy

    OpenAIRE

    Park, Geon-Tae; Choi, Kyung-Chul

    2016-01-01

    The field of therapeutic stem cell and oncolytic virotherapy for cancer treatment has rapidly expanded over the past decade. Oncolytic viruses constitute a promising new class of anticancer agent because of their ability to selectively infect and destroy tumor cells. Engineering of viruses to express anticancer genes and specific cancer targeting molecules has led to the use of these systems as a novel platform of metastatic cancer therapy. In addition, stem cells have a cancer specific migra...

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

    Directory of Open Access Journals (Sweden)

    Sebastiano Cavallaro

    2013-01-01

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

  1. Metastatic Squamous Neck Cancer with Occult Primary Treatment (PDQ®)—Health Professional Version

    Science.gov (United States)

    Metastatic squamous neck cancer with occult primary in adults occurs when squamous cell cancer spreads to lymph nodes in the neck from an undetectable primary tumor. Treatment includes surgery and radiation therapy. Learn about the diagnosis, survival, staging, and treatment of these tumors.

  2. Updated 2016 EAU Guidelines on Muscle-invasive and Metastatic Bladder Cancer

    NARCIS (Netherlands)

    Witjes, J.A.; Lebret, T.; Comperat, E.M.; Cowan, N.C.; Santis, M. de; Bruins, H.M.; Hernandez, V.; Espinos, E.L.; Dunn, J.; Rouanne, M.; Neuzillet, Y.; Veskimae, E.; Heijden, A.G. van der; Gakis, G.; Ribal, M.J.

    2017-01-01

    CONTEXT: Invasive bladder cancer is a frequently occurring disease with a high mortality rate despite optimal treatment. The European Association of Urology (EAU) Muscle-invasive and Metastatic Bladder Cancer (MIBC) Guidelines are updated yearly and provides information to optimise diagnosis,

  3. Metastatic ovarian carcinoma to the brain: an approach to identification and classification for neuropathologists.

    Science.gov (United States)

    Nafisi, Houman; Cesari, Matthew; Karamchandani, Jason; Balasubramaniam, Gayathiri; Keith, Julia Lee

    2015-04-01

    Brain metastasis is an uncommon but increasing manifestation of ovarian epithelial carcinoma and neuropathologists' collective experience with these tumors is limited. We present clinicopathological characteristics of 13 cases of brain metastases from ovarian epithelial carcinoma diagnosed at two academic institutions. The mean ages at diagnosis of the ovarian carcinoma and their subsequent brain metastases were 58.7 and 62.8 years, respectively. At the time of initial diagnosis of ovarian carcinoma the majority of patients had an advanced stage and none had brain metastases as their first manifestation of malignancy. Brain metastases tended to be multiple with ring-enhancing features on neuroimaging. Primary tumors and their brain metastases were all high-grade histologically and the histologic subtypes were: nine high-grade serous carcinoma (HGSC) cases, two clear cell carcinoma (CCC) cases and a single case each of carcinosarcoma and high-grade adenocarcinoma. A recommended histo- and immunopathological approach to these tumours are provided to aid neuropathologists in the recognition and classification of metastatic ovarian carcinoma to the brain. © 2014 Japanese Society of Neuropathology.

  4. Metastatic gastric cancer presenting with shoulder-hand syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Massarotti Marco

    2008-07-01

    Full Text Available Abstract Introduction Shoulder-hand syndrome is a relatively rare clinical entity classified as a complex regional pain syndrome type 1 and consisting essentially of a painful 'frozen shoulder' with disability, swelling, vasomotor or dystrophic changes in the homolateral hand. The pathophysiology is not completely clear but a predominant 'sympathetic' factor affecting the neural and vascular supply to the affected parts seems to be involved. Shoulder-hand syndrome has been related to many surgical, orthopedic, neurological and medical conditions; it is more often seen after myocardial infarction, hemiplegia and painful conditions of neck and shoulder, such as trauma, tumors, cervical discogenic or intraforaminal diseases and shoulder calcific tendinopathy, but has also been associated with herpetic infections, brain and lung tumors, thoracoplasty and drugs including phenobarbitone and isoniazid. The diagnosis of shoulder-hand syndrome is primarily clinical, but imaging studies, particularly bone scintigraphy, may be useful to exclude other disorders. Case presentation We report the case of a 67-year-old woman who presented with shoulder-hand syndrome as the initial manifestation of gastric cancer which had metastasized to bone. Conclusion Wider investigations are advisable in patients with atypical shoulder-hand syndrome. To the best of the authors' knowledge this is the first case of shoulder-hand syndrome associated with metastatic gastric cancer.

  5. Correlation between MR imaging and histopathological findings of cystic metastatic brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Fukusumi, Akio [Nara Medical Univ., Kashihara (Japan); Iwasaki, Satoru; Ohkawa, Naosumi [and others

    1996-12-01

    To clarify the correlation between the histopathological findings and MR signal intensity of the cyst wall, fifteen cystic metastatic brain tumors of eleven patients were imaged using a 0.5T MR unit just before surgery, and the MRI findings were correlated with the histopathological findings of resected lesions. On T2-weighted images, all cyst walls showed hypointensity. On T1-weighted images, the intensity of the cyst wall could be classified into three groups, compared with the cerebral cortex. Walls with hyperintensity on T1WI (group H; n=6) consisted of ample tumor cells, blood vessels and connective tissues, suggesting viable tumor cells. Iso-intense walls on T1WI (group I; n=3) had abundant reactive glial tissues. Hypointense walls on T1WI (group L; n=5) revealed hemorrhage and/or hemosiderin in the wall, suggesting hemorrhagic necrosis. Thus a good correlation was demonstrated between the MR signal intensities and histopathological findings of cyst walls of cystic metastatic brain tumors. This may contribute not only to more precise diagnosis on MRI but also to more planning for treatment of cystic brain metastases. (author)

  6. A Case of Brain Metastases from Breast Cancer Treated with Whole-Brain Radiotherapy and Eribulin Mesylate

    Directory of Open Access Journals (Sweden)

    Carsten Nieder

    2012-01-01

    Full Text Available Patients with triple receptor-negative breast cancer often develop aggressive metastatic disease, which also might involve the brain. In many cases, systemic and local treatment is needed. It is important to consider the toxicity of chemo- and radiotherapy, especially when newly approved drugs become available. Randomised studies leading to drug approval often exclude patients with newly diagnosed brain metastases. Here we report our initial experience with eribulin mesylate and whole-brain radiotherapy (WBRT in a heavily pretreated patient with multiple brain, lung, and bone metastases from triple receptor-negative breast cancer. Eribulin mesylate was given after 4 previous lines for metastatic disease. Two weeks after the initial dose, that is, during the first cycle, the patient was diagnosed with 5 brain metastases with a maximum size of approximately 4.5 cm. She continued chemotherapy and received concomitant WBRT with 10 fractions of 3 Gy. After 3 cycles of eribulin mesylate, treatment was discontinued because of newly diagnosed liver metastases and progression in the lungs. No unexpected acute toxicity was observed. The only relevant adverse reactions were haematological events after the third cycle (haemoglobin 9.5 g/dL, leukocytes 3.1×109/L. The patient died from respiratory failure 18.5 months from diagnosis of metastatic disease, and 2.7 months from diagnosis of brain metastases. To the best of our knowledge, this is the first report on combined WBRT and eribulin mesylate.

  7. Outcomes in Patients with Obstructive Jaundice from Metastatic Colorectal Cancer and Implications for Management

    Science.gov (United States)

    Nichols, Shawnn D.; Albert, Scott; Shirley, Lawrence; Schmidt, Carl; Abdel-Misih, Sherif; El-Dika, Samer; Groce, J. Royce; Wu, Christina; Goldberg, Richard M.; Bekaii-Saab, Tanios; Bloomston, Mark

    2016-01-01

    Introduction Patients with metastatic colorectal cancer can develop jaundice from intrahepatic or extrahepatic causes. Currently, there is little data on the underlying causes and overall survival after onset of jaundice. The purpose of this study was to characterize the causes of jaundice and determine outcomes. Methods Six hundred twenty-nine patients treated for metastatic colorectal cancer between 2004 and 2010 were retrospectively reviewed. Those developing jaundice were grouped as having intrahepatic or extrahepatic obstruction. Demographics, clinicopathologic, and outcome data were analyzed. Results Sixty-two patients with metastatic colorectal cancer developed jaundice. Intrahepatic biliary obstruction was most common, occurring in younger patients. Time from metastatic diagnosis to presentation of jaundice was similar between groups, as was the mean number of prior lines of chemotherapy. Biliary decompression was successful 41.7 % of the time and was attempted more commonly for extrahepatic causes. Median overall survival after onset of jaundice was 1.5 months and it was similar between groups, but improved to 9.6 months in patients who were able to receive further chemotherapy. Conclusions Jaundice due to metastatic colorectal cancer is an ominous finding, representing aggressive tumor biology or exhaustion of therapies. Biliary decompression is often difficult and should only be pursued when additional treatment options are available. PMID:25300799

  8. Stable and high expression of Galectin-8 tightly controls metastatic progression of prostate cancer

    Science.gov (United States)

    Gentilini, Lucas Daniel; Pérez, Ignacio González; Kotler, Monica Lidia; Chauchereau, Anne; Laderach, Diego Jose; Compagno, Daniel

    2017-01-01

    Two decades ago, Galectin-8 was described as a prostate carcinoma biomarker since it is only expressed in the neoplastic prostate, but not in the healthy tissue. To date, no biological function has been attributed to Galectin-8 that could explain this differential expression. In this study we silenced Galectin-8 in two human prostate cancer cell lines, PC3 and IGR-CaP1, and designed a pre-clinical experimental model that allows monitoring the pathology from its early steps to the long-term metastatic stages. We show for the first time that the natural and conserved expression of Gal-8 in tumour cells is responsible for the metastatic evolution of prostate cancer. In fact, Gal-8 controls the rearrangement of the cytoskeleton and E-Cadherin expression, with a major impact on anoikis and homotypic aggregation of tumour cells, both being essential processes for the survival of circulating tumour cells during metastasis. While localized prostate cancer can be cured, metastatic and advanced disease remains a significant therapeutic challenge, urging for the identification of prognostic markers of the metastatic process. Collectively, our results highlight Galectin-8 as a potential target for anti-metastatic therapy against prostate cancer. PMID:28591719

  9. Factors influencing choice of chemotherapy in metastatic colorectal cancer (mCRC

    Directory of Open Access Journals (Sweden)

    Rossi L

    2013-11-01

    Full Text Available Luigi Rossi, Foteini Vakiarou, Federica Zoratto, Loredana Bianchi, Anselmo Papa, Enrico Basso, Monica Verrico, Giuseppe Lo Russo, Salvatore Evangelista, Guilia Rinaldi, Francesca Perrone-Congedi, Gian Paolo Spinelli, Valeria Stati, Davide Caruso, Alessandra Prete, Silverio TomaoDepartment of Medico-Surgical Sciences and Biotechnologies, "Sapienza" University of Rome, Rome, Italy; Oncology Unit, ICOT, Latina, ItalyAbstract: Management of metastatic colorectal cancer requires a multimodal approach and must be performed by an experienced, multidisciplinary expert team. The optimal choice of the individual treatment modality, according to disease localization and extent, tumor biology, and patient clinical characteristics, will be one that can maintain quality of life and long-term survival, and even cure selected patients. This review is an overview of the different therapeutic approaches available in metastatic colorectal cancer, for the purpose of defining personalized therapeutic algorithms according to tumor biology and patient clinical features.Keywords: metastatic colorectal cancer, patient clinical features, tumor biology, multidisciplinary approach

  10. Burden of early, advanced and metastatic breast cancer in The Netherlands.

    Science.gov (United States)

    Vondeling, G T; Menezes, G L; Dvortsin, E P; Jansman, F G A; Konings, I R; Postma, M J; Rozenbaum, M H

    2018-03-07

    The aim of this study was to estimate the total economic and health related burden of breast cancer in the Netherlands. Data on incidence, prevalence, mortality and survival were extracted from the Dutch National Cancer Registry and were used to calculate the economic and health related burden of breast cancer for overall, DCIS (stage 0), early- (stage I), locally advanced- (stage II-III) and metastatic- (stage IV) breast cancer by age groups and by year (if applicable). The overall incidence of breast cancer increased from 103.4 up to 153.2 per 100,000 women between 1990 and 2014. The increase was driven by DCIS and early breast cancer as the incidence of locally advanced and metastatic breast cancer remained stable. Between 1990 and 2014, ten-year overall survival rates increased from 87% to 93% for early breast cancer, 41% to 62% for locally advanced- and from 6% to 9% for metastatic disease. Annually, breast cancer in the Netherlands is responsible for approximately 3100 deaths, 26,000 life years lost, 65,000 Disability Adjusted Life Years (DALYs) and an economic burden of €1.27 billion. This study provides a comprehensive assessment of the burden of breast cancer and subsequent trends over time in the Netherlands.

  11. Metabolic Plasticity of Metastatic Breast Cancer Cells: Adaptation to Changes in the Microenvironment

    Directory of Open Access Journals (Sweden)

    Rui V. Simões

    2015-08-01

    Full Text Available Cancer cells adapt their metabolism during tumorigenesis. We studied two isogenic breast cancer cells lines (highly metastatic 4T1; nonmetastatic 67NR to identify differences in their glucose and glutamine metabolism in response to metabolic and environmental stress. Dynamic magnetic resonance spectroscopy of 13C-isotopomers showed that 4T1 cells have higher glycolytic and tricarboxylic acid (TCA cycle flux than 67NR cells and readily switch between glycolysis and oxidative phosphorylation (OXPHOS in response to different extracellular environments. OXPHOS activity increased with metastatic potential in isogenic cell lines derived from the same primary breast cancer: 4T1 > 4T07 and 168FARN (local micrometastasis only > 67NR. We observed a restricted TCA cycle flux at the succinate dehydrogenase step in 67NR cells (but not in 4T1 cells, leading to succinate accumulation and hindering OXPHOS. In the four isogenic cell lines, environmental stresses modulated succinate dehydrogenase subunit A expression according to metastatic potential. Moreover, glucose-derived lactate production was more glutamine dependent in cell lines with higher metastatic potential. These studies show clear differences in TCA cycle metabolism between 4T1 and 67NR breast cancer cells. They indicate that metastases-forming 4T1 cells are more adept at adjusting their metabolism in response to environmental stress than isogenic, nonmetastatic 67NR cells. We suggest that the metabolic plasticity and adaptability are more important to the metastatic breast cancer phenotype than rapid cell proliferation alone, which could 1 provide a new biomarker for early detection of this phenotype, possibly at the time of diagnosis, and 2 lead to new treatment strategies of metastatic breast cancer by targeting mitochondrial metabolism.

  12. Bevacizumab in combination with cetuximab and irinotecan after failure of cetuximab and irinotecan in patients with metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Larsen, Finn Ole; Pfeiffer, Per; Nielsen, Dorte

    2011-01-01

    The efficacy and safety of concurrent administration of irinotecan with the two monoclonal antibodies cetuximab and bevacizumab as fourth line therapy in heavily pretreated patients with metastatic colorectal cancer were evaluated.......The efficacy and safety of concurrent administration of irinotecan with the two monoclonal antibodies cetuximab and bevacizumab as fourth line therapy in heavily pretreated patients with metastatic colorectal cancer were evaluated....

  13. Pembrolizumab in Treating Participants With Metastatic, Recurrent or Locally Advanced Cancer and Genomic Instability

    Science.gov (United States)

    2018-02-05

    BRCA1 Gene Mutation; BRCA2 Gene Mutation; Locally Advanced Solid Neoplasm; Metastatic Malignant Solid Neoplasm; POLD1 Gene Mutation; POLE Gene Mutation; Recurrent Malignant Solid Neoplasm; Recurrent Ovarian Carcinoma; Stage III Breast Cancer AJCC v7; Stage III Ovarian Cancer AJCC v8; Stage IIIA Breast Cancer AJCC v7; Stage IIIA Ovarian Cancer AJCC v8; Stage IIIB Breast Cancer AJCC v7; Stage IIIB Ovarian Cancer AJCC v8; Stage IIIC Breast Cancer AJCC v7; Stage IIIC Ovarian Cancer AJCC v8; Stage IV Breast Cancer AJCC v6 and v7; Stage IV Ovarian Cancer AJCC v8; Stage IVA Ovarian Cancer AJCC v8; Stage IVB Ovarian Cancer AJCC v8

  14. Factors influencing choice of chemotherapy in metastatic colorectal cancer (mCRC)

    International Nuclear Information System (INIS)

    Rossi, Luigi; Vakiarou, Foteini; Zoratto, Federica; Bianchi, Loredana; Papa, Anselmo; Basso, Enrico; Verrico, Monica; Lo Russo, Giuseppe; Evangelista, Salvatore; Rinaldi, Guilia; Perrone-Congedi, Francesca; Spinelli, Gian Paolo; Stati, Valeria; Caruso, Davide; Prete, Alessandra; Tomao, Silverio

    2013-01-01

    Management of metastatic colorectal cancer requires a multimodal approach and must be performed by an experienced, multidisciplinary expert team. The optimal choice of the individual treatment modality, according to disease localization and extent, tumor biology, and patient clinical characteristics, will be one that can maintain quality of life and long-term survival, and even cure selected patients. This review is an overview of the different therapeutic approaches available in metastatic colorectal cancer, for the purpose of defining personalized therapeutic algorithms according to tumor biology and patient clinical features

  15. Metastatic prostate cancer in transsexual diagnosed after three decades of estrogen therapy.

    Science.gov (United States)

    Turo, Rafal; Jallad, Samer; Prescott, Stephen; Cross, William Richard

    2013-01-01

    The incidence of prostate cancer in transsexual patients is very low with only few reported cases. Many years before presenting with prostate cancer, these patients receive hormone ablation as a part of their gender therapy. Their disease is already defined as castrate resistant, and the treatment and follow-up of such patients remains a challenge. We report a case of a male-to-female transgender woman who was diagnosed with metastatic prostate cancer, 31 years post-feminization.

  16. Metastatic prostate cancer in transsexual diagnosed after three decades of estrogen therapy

    OpenAIRE

    Turo, Rafal; Jallad, Samer; Prescott, Stephen; Cross, William Richard

    2013-01-01

    The incidence of prostate cancer in transsexual patients is very low with only few reported cases. Many years before presenting with prostate cancer, these patients receive hormone ablation as a part of their gender therapy. Their disease is already defined as castrate resistant, and the treatment and follow-up of such patients remains a challenge. We report a case of a male-to-female transgender woman who was diagnosed with metastatic prostate cancer, 31 years post-feminization.

  17. Development of Targeted Nanobubbles for Ultrasound Imaging and Ablation of Metastatic Prostate Cancer Lesions

    Science.gov (United States)

    2014-08-01

    matrix, optically transparent fibrin-based gel phantom embedded with a layer of PC-3 and C4-2B of human prostate cancer , and MDA-MB-231 of breast ... Theranostics , 3(11): 802-815, 2013.  O. Aydin, E. Vlaisavljevich, Y. Y. Durmaz, M. ElSayed1, Z. Xu, “Nanodroplet-Mediated Histotripsy Cancer Cell...Ultrasound Imaging and Ablation of Metastatic Prostate Cancer Lesions PRINCIPAL INVESTIGATOR: Mohamed El-Sayed CONTRACTING ORGANIZATION

  18. Metastatic prostate cancer in transsexual diagnosed after three decades of estrogen therapy

    Science.gov (United States)

    Turo, Rafal; Jallad, Samer; Prescott, Stephen; Cross, William Richard

    2013-01-01

    The incidence of prostate cancer in transsexual patients is very low with only few reported cases. Many years before presenting with prostate cancer, these patients receive hormone ablation as a part of their gender therapy. Their disease is already defined as castrate resistant, and the treatment and follow-up of such patients remains a challenge. We report a case of a male-to-female transgender woman who was diagnosed with metastatic prostate cancer, 31 years post-feminization. PMID:24032068

  19. Subcutaneous preconditioning increases invasion and metastatic dissemination in mouse colorectal cancer models

    Directory of Open Access Journals (Sweden)

    Patricia Alamo

    2014-03-01

    Full Text Available Mouse colorectal cancer (CRC models generated by orthotopic microinjection of human CRC cell lines reproduce the pattern of lymphatic, haematological and transcoelomic spread but generate low metastatic efficiency. Our aim was to develop a new strategy that could increase the metastatic efficiency of these models. We used subcutaneous implantation of the human CRC cell lines HCT116 or SW48 prior to their orthotopic microinjection in the cecum of nude mice (SC+ORT. This subcutaneous preconditioning significantly enhanced metastatic dissemination. In the HCT116 model it increased the number and size of metastatic foci in lymph nodes, lung, liver and peritoneum, whereas, in the SW48 model, it induced a shift from non-metastatic to metastatic. In both models the number of apoptotic bodies in the primary tumour in the SC+ORT group was significantly reduced compared with that in the direct orthotopic injection (ORT group. Moreover, in HCT116 tumours the number of keratin-positive tumour buddings and single epithelial cells increased at the invasion front in SC+ORT mice. In the SW48 tumour model, we observed a trend towards a higher number of tumour buds and single cells in the SC+ORT group but this did not reach statistical significance. At a molecular level, the enhanced metastatic efficiency observed in the HCT116 SC+ORT model was associated with an increase in AKT activation, VEGF-A overexpression and downregulation of β1 integrin in primary tumour tissue, whereas, in SW48 SC+ORT mice, the level of expression of these proteins remained unchanged. In summary, subcutaneous preconditioning increased the metastatic dissemination of both orthotopic CRC models by increasing tumour cell survival and invasion at the tumour invasion front. This approach could be useful to simultaneously study the mechanisms of metastases and to evaluate anti-metastatic drugs against CRC.

  20. Prospective Cohort Study Depending on the Use of Palliative Care for Advanced Stage of Cancer Patients

    Science.gov (United States)

    2017-09-05

    Stage IV Breast Cancer; Stage IV Pancreatic Cancer; Stage IV Colon Cancer; Stage IV Gastric Cancer; Stage IV Lung Cancer; Stage IV Liver Cancer; Malignant Hematologic Neoplasm; Biliary Cancer Metastatic; Pediatric Leukemia; Pediatric Lymphoma; Pediatric Brain Tumor; Pediatric Solid Tumor

  1. Comparison of tumor-infiltrating lymphocytes between primary and metastatic tumors in breast cancer patients.

    Science.gov (United States)

    Ogiya, Rin; Niikura, Naoki; Kumaki, Nobue; Bianchini, Giampaolo; Kitano, Shigehisa; Iwamoto, Takayuki; Hayashi, Naoki; Yokoyama, Kozue; Oshitanai, Risa; Terao, Mayako; Morioka, Toru; Tsuda, Banri; Okamura, Takuho; Saito, Yuki; Suzuki, Yasuhiro; Tokuda, Yutaka

    2016-12-01

    The presence of tumor-infiltrating lymphocytes (TILs) is associated with favorable long-term outcome in breast cancer. However, little is known about changes in TILs during metastatic progression. To confirm our hypothesis that malignant tumors escape from the host immune system during metastasis, we evaluated the percentage of TILs in paired samples of primary and metastatic breast tumors. We retrospectively identified 25 patients with human epidermal growth factor receptor-2 (HER2 + , n = 14) and triple negative (TN, n = 11) early breast cancer diagnosed between 1990 and 2009 at Tokai University Hospital (Isehara, Japan) and who subsequently experienced regional or distant recurrence confirmed by tumor biopsy/resection. Hematoxylin-eosin-stained slides of these paired samples were evaluated for stromal TILs. Immunohistochemical staining was carried out using primary antibodies against CD4, CD8, Foxp3, programmed cell death ligand 1 (PD-L1), PD-L2, and HLA class I for characterizing the TILs and breast tumors. The percentage of TILs in the primary tumors was significantly higher (average 34.6%) than that in metastatic tumors (average 15.7%) (paired t-test, P = 0.004) and that of CD8 + and CD4 + T cells significantly decreased from primary to metastatic tumors (paired t-test, P = 0.008 and P = 0.026, respectively). The PD-L1, PD-L2, and HLA class I antibody expression changed from positive to negative and vice versa from the primary to the metastatic tumors. Tumors at first metastatic recurrence in HER2 + and TN breast cancers have a lower percentage of TILs and CD8 + and CD4 + T cells compared to primary tumors, which indicates that immune escape plays a role in tumor progression. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  2. STING ligand c-di-GMP improves cancer vaccination against metastatic breast cancer.

    Science.gov (United States)

    Chandra, Dinesh; Quispe-Tintaya, Wilber; Jahangir, Arthee; Asafu-Adjei, Denise; Ramos, Ilyssa; Sintim, Herman O; Zhou, Jie; Hayakawa, Yoshihiro; Karaolis, David K R; Gravekamp, Claudia

    2014-09-01

    Cancer vaccination may be our best and most benign option for preventing or treating metastatic cancer. However, breakthroughs are hampered by immune suppression in the tumor microenvironment. In this study, we analyzed whether cyclic diguanylate (c-di-GMP), a ligand for stimulator of interferon genes (STING), could overcome immune suppression and improve vaccination against metastatic breast cancer. Mice with metastatic breast cancer (4T1 model) were therapeutically immunized with an attenuated Listeria monocytogenes (LM)-based vaccine, expressing tumor-associated antigen Mage-b (LM-Mb), followed by multiple low doses of c-di-GMP (0.2 μmol/L). This treatment resulted in a striking and near elimination of all metastases. Experiments revealed that c-di-GMP targets myeloid-derived suppressor cells (MDSC) and tumor cells. Low doses of c-di-GMP significantly increased the production of IL12 by MDSCs, in correlation with improved T-cell responses to Mage-b, whereas a high dose of c-di-GMP (range, 0.3-3 mmol/L) activated caspase-3 in the 4T1 tumor cells and killed the tumor cells directly. On the basis of these results, we tested one administration of high-dose c-di-GMP (3 mmol/L) followed by repeated administrations of low-dose c-di-GMP (0.2 μmol/L) in the 4T1 model, and found equal efficacy compared with the combination of LM-Mb and c-di-GMP. This finding correlated with a mechanism of improved CD8 T-cell responses to tumor-associated antigens (TAA) Mage-b and Survivin, most likely through cross-presentation of these TAAs from c-di-GMP-killed 4T1 tumor cells, and through c-di-GMP-activated TAA-specific T cells. Our results demonstrate that activation of STING-dependent pathways by c-di-GMP is highly attractive for cancer immunotherapy. ©2014 American Association for Cancer Research.

  3. Metastatic breast cancer: do current treatments improve quality of life? A prospective study

    Directory of Open Access Journals (Sweden)

    Fernanda Amado

    Full Text Available CONTEXT AND OBJECTIVE: In metastatic breast cancer cases, the currently available therapeutic approaches provide minimal improvement in survival. As such, quality of life (QOL becomes one of the main objectives of treatment. It is not known whether current treatments derived from trials improve QOL. The aim was to evaluate changes in QOL among metastatic breast cancer patients receiving treatment derived from trials. DESIGN AND SETTING: Prospective observational QOL survey in a tertiary cancer center. METHODS: To evaluate the influence of current treatments on patients' QOL, the Medical Outcomes Study Short Form-36 (SF-36 and the Beck Depression Inventory (BDI were applied on three occasions: before starting treatment and at the 6th and 12th weeks, to consecutive metastatic breast cancer patients over a one-year period. RESULTS: We found an improvement in QOL in the sample evaluated (n = 40, expressed by changes in the overall SF-36 score (p = 0.002 and the BDI (p = 0.004. Taken individually, the SF-36 components Pain, Social Functioning and Mental Health also improved significantly. Patients with worse initial performance status and secondary symptoms displayed greater improvement than those with better initial performance status and asymptomatic disease (p < 0.001. Patients who received more than one type of therapy showed larger gains than those given only one type (p = 0.038. CONCLUSIONS: In our environment, current metastatic breast cancer treatments can improve QOL, especially among symptomatic patients and those with low performance status.

  4. Study on medical economic evaluation methods for metastatic brain tumors therapy

    International Nuclear Information System (INIS)

    Takura, Tomoyuki; Hayashi, Motohiro; Muragaki, Yoshihiro; Iseki, Hiroshi; Uetsuka, Yoshio

    2010-01-01

    Treatment design for metastatic brain tumors is required to firstly care about the life and function for which the patient hopes because it is terminal care. Therefore, to discuss the value of the therapy, a viewpoint of the quality of life (QOL) and the socioeconomic factors other than the survival rate is important. However, examination that applies these factors to the therapy needs to be carried out more thoroughly. With this in mind, we discuss cost effectiveness of therapy for metastatic brain tumor, through a pilot study on gamma knife therapy. We studied 18 patients (mean age 61.6 years old) undergoing therapy for metastatic brain tumors. The health rate QOL was assessed by the profile-type measure SF-36 (Short-Form 36-Item Ver1.2) and the preference-based measure EQ-5D (EuroQoL-5D), before and six months after gamma knife therapy. Cost-utility-analysis (yen/Qaly) was carried out from quality adjusted life years (Qalys) and medical fee claims. In addition, we made a correlation analysis of the irradiation procedure and the gains attained. The observation by SF-36 for six months was useful for metastatic brain tumor. As a result, the QOL indicators showed increased mental health (MH: p=0.040) and role emotional (RE: p=0.029) with significant difference. In the measurement of EQ-5D, it was added only for one month based on the significant difference (p=0.022) from the pre-therapy QOL. The utilities that were analyzed became 0.052±0.175 standard deviation (SD) (score), and Qalys were 0.135. Because the cost was 721.4±5.2 SD (thousand yen), the performance of cost-utility-analysis was estimated as 5,330,000 (yen/Qaly). In addition, positive correlation (r=0.845/p=0.034) was found between the EQ-5D utility score and the tumor irradiation energy (mJ), etc. We established a new value over and above mere survival rate concerning metastatic brain tumor therapy. The socioeconomics and efficacy of therapy are more difficult to discuss in this disease than in other

  5. CD44-positive cancer stem cells expressing cellular prion protein contribute to metastatic capacity in colorectal cancer.

    Science.gov (United States)

    Du, Lei; Rao, Guanhua; Wang, Hongyi; Li, Baowei; Tian, Weili; Cui, Jiantao; He, Leya; Laffin, Brian; Tian, Xiuyun; Hao, Chunyi; Liu, Hongmin; Sun, Xin; Zhu, Yushan; Tang, Dean G; Mehrpour, Maryam; Lu, Youyong; Chen, Quan

    2013-04-15

    Cancer stem cells are implicated in tumor progression, metastasis, and recurrence, although the exact mechanisms remain poorly understood. Here, we show that the expression of cellular prion protein (PrPc, PRNP) is positively correlated with an increased risk of metastasis in colorectal cancer. PrPc defines a subpopulation of CD44-positive cancer stem cells that contributes to metastatic capacity. PrPc(+)CD44(+) colorectal cancer stem cells displayed high liver metastatic capability, unlike PrPc(-)CD44(+) stem cells, that was inhibited by RNAi-mediated attenuation of PrPc. Notably, administration of PrPc monoclonal antibodies significantly inhibited tumorigenicity and metastasis of colorectal cancer stem cells in mouse models of orthotopic metastasis. PrPc promoted epithelial to mesenchymal transition (EMT) via the ERK2 (MAPK1) pathway, thereby conferring high metastatic capacity. Our findings reveal the function of PrPc in regulating EMT in cancer stem cells, and they identify PrPc as candidate therapeutic target in metastatic colorectal cancer. ©2013 AACR.

  6. Metastatic Colorectal Cancer in Young Adults: A Study From the South Australian Population-Based Registry.

    Science.gov (United States)

    Vatandoust, Sina; Price, Timothy J; Ullah, Shahid; Roy, Amitesh C; Beeke, Carole; Young, Joanne P; Townsend, Amanda; Padbury, Robert; Roder, David; Karapetis, Christos S

    2016-03-01

    Colorectal cancer (CRC) is a common malignancy. There is growing evidence that CRC incidence is increasing in the younger population. There is controversy surrounding the prognosis of young patients with CRC. In this study we reviewed Australian patients with metastatic CRC (mCRC) who were younger than 40 years of age at the time of diagnosis of metastatic disease. To our knowledge this is the first study to focus on this age group with mCRC. This was a retrospective study using data from the South Australian Metastatic Colorectal Cancer database. We compared patient and disease characteristics, management approaches, and outcomes for age groups Young-onset mCRC patients, when defined as aged younger than 40 years, have equivalent survival compared with their older counterparts. This is despite differences in disease characteristics and management approach between the 2 groups. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2016-08-27

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

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

    Directory of Open Access Journals (Sweden)

    Yo-Han Han

    2016-08-01

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

  9. In Vitro Co-Culture Models of Breast Cancer Metastatic Progression towards Bone

    Directory of Open Access Journals (Sweden)

    Chiara Arrigoni

    2016-08-01

    Full Text Available Advanced breast cancer frequently metastasizes to bone through a multistep process involving the detachment of cells from the primary tumor, their intravasation into the bloodstream, adhesion to the endothelium and extravasation into the bone, culminating with the establishment of a vicious cycle causing extensive bone lysis. In recent years, the crosstalk between tumor cells and secondary organs microenvironment is gaining much attention, being indicated as a crucial aspect in all metastatic steps. To investigate the complex interrelation between the tumor and the microenvironment, both in vitro and in vivo models have been exploited. In vitro models have some advantages over in vivo, mainly the possibility to thoroughly dissect in controlled conditions and with only human cells the cellular and molecular mechanisms underlying the metastatic progression. In this article we will review the main results deriving from in vitro co-culture models, describing mechanisms activated in the crosstalk between breast cancer and bone cells which drive the different metastatic steps.

  10. SPECIFIC CHARACTERISTICS OF BRAIN METASTASIZING IN PATIENTS WITH LUMINAL SUBTYPE OF BREAST CANCER

    Directory of Open Access Journals (Sweden)

    A. S. Balkanov

    2016-01-01

    Full Text Available Background: More than half of female patients with breast cancer are diagnosed with a  luminal subtype of the disease; however, specific characteristics of its metastases to the brain have been not well studied, unlike those of HER2 positive and triple negative subtypes. Aim: A  comparative analysis of characteristics of metastatic brain lesions in patients with luminal breast cancer. Materials and methods: The time from surgery for breast cancer to the first recurrence and to metastatic brain lesions (assessed by contrast-enhanced MRI imaging was measured in 41 patients with luminal subtype of breast cancer (median age, 49.5±9.6  years, depending on a  diameter of the primary tumor and numbers of involved axillary lymph nodes. Results: The time interval to occurrence of brain metastases in luminal subtype of breast cancer is not associated with the size of the tumor. If≥4  axillary lymph nodes are involved (N2–3, brain metastases are identified much earlier (p<0.05 than in patients with N0–1 (34.5±23.9 months and 62.7±50 months, respectively. Neither the size nor the involvement of axillary lymph nodes has any impact on the rates of metastatic lesion to the brain during the first recurrence. Conclusion: Brain metastases occur at a much shorter time in those patients of luminal subtype of breast cancer who have metastases in≥4  axillary lymph nodes. Brain metastases develop in 50% of patients with the first recurrence of the luminal subtype of breast cancer.

  11. WE-EF-BRA-10: Prophylactic Cranial Irradiation Reduces the Incidence of Brain Metastasis in a Mouse Model of Metastatic Breast Cancerr

    Energy Technology Data Exchange (ETDEWEB)

    Smith, D; Debeb, B; Larson, R; Diagaradjane, P; Woodward, W [MD Anderson Cancer Center, Houston, TX (United States)

    2015-06-15

    Purpose: Prophylactic cranial irradiation (PCI) is a clinical technique used to reduce the incidence of brain metastasis and improve overall survival in select patients with acute lymphoblastic leukemia and small-cell lung cancer. We examined whether PCI could benefit breast cancer patients at high risk of developing brain metastases. Methods: We utilized our mouse model in which 500k green fluorescent protein (GFP)-labeled breast cancer cells injected into the tail vein of SCID/Beige mice resulted in brain metastases in approximately two-thirds of untreated mice. To test the efficacy of PCI, one set of mice was irradiated five days after cell injection with a single fraction of 4-Gy (two 2-Gy opposing fields) whole-brain irradiation on the XRAD 225Cx small-animal irradiator. Four controls were included: a non-irradiated group, a group irradiated two days prior to cell injection, and two groups irradiated 3 or 6 weeks after cell injection. Mice were sacrificed four and eight weeks post-injection and were evaluated for the presence of brain metastases on a fluorescent stereomicroscope. Results: The incidence of brain metastasis in the non-irradiated group was 77% and 90% at four and eight weeks, respectively. The PCI group had a significantly lower incidence, 20% and 30%, whereas the other three control groups had incidence rates similar to the non-treated control (70% to 100%). Further, the number of metastases and the metastatic burden were also significantly lower in the PCI group compared to all other groups. Conclusion: The timing of irradiation to treat subclinical disease is critical, as a small dose of whole-brain irradiation given five days after cell injection abrogated tumor burden by greater than 90%, but had no effect when administered twenty-one days after cell injection. PCI is likely to benefit breast cancer patients at high risk of developing brain metastases and should be strongly considered in the clinic.

  12. CD133+CXCR4+ colon cancer cells exhibit metastatic potential and predict poor prognosis of patients

    Directory of Open Access Journals (Sweden)

    Zhang Shan-shan

    2012-08-01

    Full Text Available Abstract Background Colorectal cancer (CRC, which frequently metastasizes to the liver, is one of the three leading causes of cancer-related deaths worldwide. Growing evidence suggests that a subset of cells exists among cancer stem cells. This distinct subpopulation is thought to contribute to liver metastasis; however, it has not been fully explored in CRC yet. Methods Flow cytometry analysis was performed to detect distinct subsets with CD133 and CXCR4 markers in human primary and metastatic CRC tissues. The 'stemness' and metastatic capacities of different subpopulations derived from the colon cancer cell line HCT116 were compared in vitro and in vivo. The roles of epithelial-mesenchymal transition (EMT and stromal-cell derived factor-1 (SDF-1 in the metastatic process were also investigated. A survival curve was used to explore the correlation between the content of CD133+CXCR4+ cancer cells and patient survival. Results In human specimens, the content of CD133+CXCR4+ cells was higher in liver metastases than in primary colorectal tumors. Clonogenic and tumorigenic cells were restricted to CD133+ cells in the HCT116 cell line, with CXCR4 expression having no impact on the 'stemness' properties. We found that CD133+CXCR4+ cancer cells had a high metastatic capacity in vitro and in vivo. Compared with CD133+CXCR4- cells, CD133+CXCR4+ cancer cells experienced EMT, which contributed partly to their metastatic phenotype. We then determined that SDF-1/CXCL12 treatment could further induce EMT in CD133+CXCR4+ cancer cells and enhance their invasive behavior, while this could not be observed in CD133+CXCR4- cancer cells. Blocking SDF-1/CXCR4 interaction with a CXCR4 antagonist, AMD3100 (1,10-[1,4-phenylenebis(methylene]bis-1,4,8,11 -tetraazacyclotetradecane octahydrochloride, inhibited metastatic tumor growth in a mouse hepatic metastasis model. Finally, a high percentage of CD133+CXCR4+ cells in human primary CRC was associated with a reduced two

  13. Efficacy of chemotherapy after hormone therapy for hormone receptor–positive metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Ryutaro Mori

    2014-11-01

    Full Text Available Objective: According to the guidelines for metastatic breast cancer, hormone therapy for hormone receptor–positive metastatic breast cancer without life-threatening metastasis should be received prior to chemotherapy. Previous trials have investigated the sensitivity of chemotherapy for preoperative breast cancer based on the efficacy of neoadjuvant hormone therapy. In this retrospective study, we investigated the efficacy of chemotherapy for metastatic breast cancer in hormone therapy–effective and hormone therapy–ineffective cases. Methods: Patients who received chemotherapy after hormone therapy for metastatic breast cancer between 2006 and 2013 at our institution were investigated. Results: A total of 32 patients received chemotherapy after hormone therapy for metastatic breast cancer. The median patient age was 59 years, and most of the primary tumors exhibited a T2 status. A total of 26 patients had an N(+ status, while 7 patients had human epidermal growth factor receptor 2–positive tumors. A total of 13 patients received clinical benefits from hormone therapy, with a rate of clinical benefit of subsequent chemotherapy of 30.8%, which was not significantly different from that observed in the hormone therapy–ineffective patients (52.6%. A total of 13 patients were able to continue the hormone therapy for more than 1 year, with a rate of clinical benefit of chemotherapy of 38.5%, which was not significantly different from that observed in the short-term hormone therapy patients (47.4%. The luminal A patients were able to continue hormone therapy for a significantly longer period than the non-luminal A patients (median survival time: 17.8 months vs 6.35 months, p = 0.0085. However, there were no significant differences in the response to or duration of chemotherapy. Conclusion: The efficacy of chemotherapy for metastatic breast cancer cannot be predicted based on the efficacy of prior hormone therapy or tumor subtype

  14. Decline in peripheral blood NKG2D+CD3+CD56+ NKT cells in metastatic colorectal cancer patients.

    Science.gov (United States)

    Gharagozloo, M; Rezaei, A; Kalantari, H; Bahador, A; Hassannejad, N; Maracy, M; Nouri, N; Sedghi, M; Ghazanfari, H; Bayat, B

    2018-01-01

    Colorectal cancer (CRC) is one of the main causes of cancer deaths in the world. This cancer can be divided into non-metastatic and metastatic CRC stages. CD3+CD56+ NKT cell subsets are a minor T cell subset in peripheral blood and conduct the killing of tumor cells in direct manner. Little is obvious about levels and surface markers of these cells such as NKG2D in different cancers, especially in CRC. We included 15 non-metastatic (low-grade), 11 non-metastatic (high-grade), 10 metastatic colorectal cancer patients and 18 healthy controls. The percentages of CD3+CD56+ NKT cells and NKG2D+CD56+ NKT cells from samples were analyzed by flow cytometry in peripheral blood mononuclear cells (PBMCs) of samples. We found that there was a significantly lower number of NKG2D+CD3+CD56+ cells in peripheral blood of patients with metastatic colorectal cancer compared with normal controls (77.53 ± 5.79 % vs 90.74 ± 9.84 %; pNKT cells was significantly lower in patients with metastatic colorectal cancer compared to healthy controls strengthens the hypothesis that NKT cells can play a substantial role in the protection against human colorectal cancer, and this opens up avenues for novel studies about elucidating the other aspects of tumor surveillance in CRC progression and immunotherapy (Tab. 2, Fig. 2, Ref. 46).

  15. Brain cancer genomics and epigenomics.

    Science.gov (United States)

    Archer, Tenley C; Sengupta, Soma; Pomeroy, Scott L

    2018-01-01

    Classically, brain cancers have been graded and diagnosed based on histology and risk stratified by clinical criteria. Recent advances in genomics and epigenomics have ushered in an era of defining cancers based on molecular criteria. These advances have increased our precision of identifying oncogenic driving events and, most importantly, increased our precision at predicting clinical outcome. For the first time in its history, the 2016 revision of the WHO Classification of Tumors of the Central Nervous System included molecular features as tumor classification criteria. Brain tumors can develop in the context of genetic cancer predisposition syndromes, such as Li-Fraumeni or Gorlin syndrome, but by far most commonly arise through the acquisition of somatic mutations and chromosome changes in the malignant cells. By taking a survey across this cancer landscape, certain themes emerge as being common events to drive cancer: DNA damage repair, genomic instability, mechanistic target of rapamycin pathway, sonic hedgehog pathway, hypoxia, and epigenetic dysfunction. Understanding these mechanisms is of paramount importance for improving targeted therapies, and for identifying the right patients for those therapies. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Impact of ethnicity on the outcome of men with metastatic, hormone-sensitive prostate cancer.

    Science.gov (United States)

    Bernard, Brandon; Muralidhar, Vinayak; Chen, Yu-Hui; Sridhar, Srikala S; Mitchell, Edith P; Pettaway, Curtis A; Carducci, Michael A; Nguyen, Paul L; Sweeney, Christopher J

    2017-05-01

    Prostate cancer (PCa) outcomes are impacted by socioeconomic and biologic factors. Ethnicity plays a role in the former, but little is known about the responsiveness of metastatic PCa to androgen-deprivation therapy (ADT) among races. The Surveillance, Epidemiology, and End Results (SEER) registry was used to identify men who were diagnosed with distant, de novo, metastatic PCa from 2004 to 2012. Patterns of presentation, overall survival (OS), and PCa-specific mortality (PCSM) were determined for each race. E3805 clinical trial data also were retrospectively reviewed to assess outcomes of ADT and ADT plus docetaxel by race. Of all PCa diagnoses in SEER, distant, de novo, metastatic disease was diagnosed in 4.2% of non-Hispanic whites, 5.8% of Hispanic whites, 5.7% of blacks, 5.5% of Asians/Pacific Islanders, and 8.8% of American Indians/Alaska Natives (P blacks, respectively. Few Asians participated in the E3805 trial. Asian men have superior median OS and PCSM for distant, de novo, metastatic PCa than men of other race. Non-Hispanic whites and blacks who receive treatment with ADT or chemohormonal therapy have comparable outcomes. Cancer 2017;123:1536-1544. © 2017 American Cancer Society. © 2017 American Cancer Society.

  17. Cardiovascular morbidity in long-term survivors of metastatic testicular cancer

    NARCIS (Netherlands)

    Meinardi, MT; Gietema, JA; van der Graaf, WTA; van Veldhuisen, DJ; Runne, MA; Sluiter, WJ; de Vries, EGE; Willemse, PBH; Mulder, NH; van den Berg, MP; Sleijfer, DT; Schraffordt Koops, H.

    Purpose: To determine whether long-term survivors of metastatic testicular cancer have an increased risk of cardiovascular morbidity more than 10 years after chemotherapy. Patients and Methods: Eighty-seven patients treated with cisplatin-containing chemotherapy before 1987 who were in remission for

  18. Metastatic castration-resistant prostate cancer: new therapies, novel combination strategies and implications for immunotherapy

    NARCIS (Netherlands)

    Drake, C.G.; Sharma, P.; Gerritsen, W.R.

    2014-01-01

    For the past decade, docetaxel has remained the global standard of care for frontline treatment of metastatic castration-resistant prostate cancer (mCRPC). Until recently, there were limited options for patients with mCRPC following docetaxel failure or resistance, but now the approved treatment

  19. Targeted delivery of a sialic acid-blocking glycomimetic to cancer cells inhibits metastatic spread

    NARCIS (Netherlands)

    Bull, C.; Boltje, T.J.; Dinther, E.A.W. van; Peters, T.; Graaf, A.M.A. de; Leusen, J.H.W.; Kreutz, M.; Figdor, C.G.; Brok, M.H.M.G.M. den; Adema, G.J.

    2015-01-01

    Sialic acid sugars are overexpressed by cancer cells and contribute to the metastatic cascade at multiple levels. Therapeutic interference of sialic acids, however, has been difficult to pursue because of the absence of dedicated tools. Here we show that a rationally designed sialic acid-blocking

  20. A survival score for patients with metastatic spinal cord compression from prostate cancer

    NARCIS (Netherlands)

    Rades, D.; Douglas, S.; Veninga, T.; Bajrovic, A.; Stalpers, L. J. A.; Hoskin, P. J.; Rudat, V.; Schild, S. E.

    2012-01-01

    This study aimed to develop and validate a survival scoring system for patients with metastatic spinal cord compression (MSCC) from prostate cancer. Of 436 patients, 218 patients were assigned to the test group and 218 patients to the validation group. Eight potential prognostic factors (age,

  1. Low Number of Detectable Circulating Tumor Cells in Non-metastatic Colon Cancer

    DEFF Research Database (Denmark)

    Thorsteinsson, Morten; Söletormos, György; Jess, Per

    2011-01-01

    The aim of the present study was to detect circulating tumor cells (CTCs) in the peripheral blood of patients with non-metastatic colon cancer and to evaluate whether there is a diurnal variation in the CTC counts. Furthermore, the study aimed to examine the correlation between CTCs and TNM stage...

  2. Phase I/II study on docetaxel, gemcitabine and prednisone in castrate refractory metastatic prostate cancer

    DEFF Research Database (Denmark)

    Buch-Hansen, Trine Zeeberg; Bentzen, Lise Nørgaard; Hansen, Steinbjoern

    2010-01-01

    DGP, maximum of eight courses, until progression or unacceptable toxicity. Docetaxel 75 mg/m(2) was administered intravenously day 1, gemcitabine was given day 1 and 8 in doses increasing from 600 to 1,000 mg/m(2) every third week. Patients had castrate refractory metastatic prostate cancer (CRMPC......), adequate function of liver, kidney and bone marrow; ECOG performance status...

  3. Primary tumor location and bevacizumab effectiveness in patients with metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Boisen, M K; Johansen, J S; Dehlendorff, Christian

    2013-01-01

    There is an unmet need for predictive markers for the antiangiogenic agent bevacizumab in metastatic colorectal cancer (mCRC). We aimed to assess whether the location of the primary tumor is associated with bevacizumab effectiveness when combined with capecitabine and oxaliplatin (CAPEOX...

  4. Safety of cabazitaxel in senior adults with metastatic castration-resistant prostate cancer

    DEFF Research Database (Denmark)

    Heidenreich, Axel; Bracarda, Sergio; Mason, Malcolm

    2014-01-01

    BACKGROUND: Cabazitaxel/prednisone has been shown to prolong survival versus mitoxantrone/prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) that has progressed during or after docetaxel. Subsequently, compassionate-use programmes (CUPs) and expanded-access progra...

  5. Influence of the American ODAC Statement on Austrian Bevacizumab Prescribing Practice for Metastatic Breast Cancer

    OpenAIRE

    Preusser, Matthias; Fülöp, Gerhard; Berghoff, Anna Sophie; Heinzl, Harald; Steger, Guenther G.; Greil, Richard; Zielinski, Christoph C.; Bartsch, Rupert

    2012-01-01

    The influence of the discrepancy between the Oncologic Drugs Advisory Committee (ODAC) and European Medicines Agency positions on bevacizumab prescribing practice for metastatic breast cancer in Austria during January 2006 to June 2011 was investigated. The Austrian bevacizumab prescribing practice was found to be significantly influenced by the ODAC statement issued in July 2010.

  6. Abiraterone acetate for patients with metastatic castration-resistant prostate cancer progressing after chemotherapy

    DEFF Research Database (Denmark)

    Sternberg, Cora N; Castellano, Daniel; Daugaard, Gedske

    2014-01-01

    BACKGROUND: In the final analysis of the phase 3 COU-AA-301 study, abiraterone acetate plus prednisone significantly prolonged overall survival compared with prednisone alone in patients with metastatic castration-resistant prostate cancer progressing after chemotherapy. Here, we present the fina...

  7. Quality of life and care needs in women with estrogen positive metastatic breast cancer

    DEFF Research Database (Denmark)

    Lee Mortensen, Gitte; Madsen, Ivan Bredbjerg; Krogsgaard, Randi

    2018-01-01

    BACKGROUND: In recent years, the prognosis of metastatic breast cancer (MBC) has improved with more effective therapies applicable to a wider range of patients. To many patients, a MBC diagnosis thus initiates a prolonged course of illness and treatment. This qualitative study aimed to explore...

  8. Decoy receptor 1 (DCR1) promoter hypermethylation and response to irinotecan in metastatic colorectal cancer

    NARCIS (Netherlands)

    Bosch, Linda J W; Trooskens, Geert; Snaebjornsson, Petur; Coupe, Veerle M. H.; Mongera, Sandra; Haan, Josien C.; Richman, Susan D.; Koopman, Miriam|info:eu-repo/dai/nl/298209640; Tol, Jolien; Meyer, Tim; Louwagie, Joost; Dehaspe, Luc; van Grieken, Nicole C. T.; Ylstra, Bauke; Verheul, Henk M. W.; van Engeland, Manon; Nagtegaal, Iris D; Herman, James G; Quirke, Philip; Seymour, Matthew T; Punt, Cornelis J A; van Criekinge, Wim; Carvalho, Beatriz; Meijer, Gerrit A.

    2017-01-01

    Diversity in colorectal cancer biology is associated with variable responses to standard chemotherapy. We aimed to identify and validate DNA hypermethylated genes as predictive biomarkers for irinotecan treatment of metastatic CRC patients. Candidate genes were selected from 389 genes involved in

  9. Prostate specific antigen: a prognostic marker of survival in good prognosis metastatic prostate cancer? (EORTC 30892)

    NARCIS (Netherlands)

    Collette, Laurence; de Reijke, Theo M.; Schröder, Fritz H.

    2003-01-01

    We study the value of PSA response and PSA progression as prognostic factors for survival in good prognosis metastatic prostate cancer. Data from 257 patients treated with Flutamide or Cyproterone acetate within the EORTC GU Group protocol 30892 have been used and analysis by Cox models. A PSA

  10. Advancements in the Treatment of Metastatic Breast Cancer (MBC: The Role of Ixabepilone

    Directory of Open Access Journals (Sweden)

    Massimo Cristofanilli

    2012-01-01

    Full Text Available Successful management of breast cancer in the metastatic setting is often confounded by resistance to chemotherapeutics, in particular anthracyclines and taxanes. The limited number of effective treatment options for patients with more aggressive biological subtypes, such as triple-negative metastatic breast cancer, is especially concerning. As such, a therapy clinically proven to be effective in this subtype would be of great value. Ixabepilone, a novel synthetic lactam analog of epothilone B, demonstrated better clinical outcomes in metastatic disease, particularly in triple-negative breast cancer. Most recently, studies have shown the activity of ixabepilone in the neoadjuvant setting, suggesting a role for this drug in primary disease. Notably, treating in the neoadjuvant setting might allow clinicians to explore the predictive value of biomarkers and response to treatment, as pharmacogenomic approaches to therapy continue to evolve. In this article, we review the efficacy and safety data of ixabepilone as a monotherapy and as a component of combination therapy for metastatic and primary breast cancer.

  11. Efficacy of HER2-targeted therapy in metastatic breast cancer. Monoclonal antibodies and tyrosine kinase inhibitors

    DEFF Research Database (Denmark)

    Nielsen, Dorte L; Kümler, Iben; Palshof, Jesper Andreas

    2013-01-01

    Therapies targeting the human epidermal growth factor receptor (HER) 2 are effective in metastatic breast cancer (MBC). We review the efficacy of HER2-directed therapies, focussing on monoclonal antibodies and tyrosine kinase inhibitors targeting HER2 that have been tested in phase II-III studies...

  12. The oncologic role of local treatment in primary metastatic prostate cancer

    NARCIS (Netherlands)

    Ghadjar, P.; Briganti, A.; Visschere, P.J. De; Futterer, J.J.; Giannarini, G.; Isbarn, H.; Ost, P.; Sooriakumaran, P.; Surcel, C.I.; Bergh, R.C. van den; Oort, I.M. van; Yossepowitch, O.; Ploussard, G.

    2015-01-01

    PURPOSE: To determine the oncologic benefit or otherwise of local treatment of the prostate in patients with primary metastatic prostate cancer. METHODS: A review of the literature was performed in April 2014 using the Medline/PubMed database. Studies were identified using the search terms "prostate

  13. Prognostic Value of Metastatic Tumoral Caveolin-1 Expression in Patients with Resected Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Der Sheng Sun

    2017-01-01

    Full Text Available Objective. Caveolin-1 (Cav-1, as the main component of caveolae, has complex roles in tumourigenesis in human malignancies. We investigated Cav-1 in primary and metastatic tumor cells of gastric cancer (GC and its association with clinical outcomes. Methods. We retrieved 145 cases of GC who had undergone curative gastrectomy. The expression levels of Cav-1 was evaluated by immunohistochemistry, and its association with clinicopathological parameters and patient survival was analyzed. Results. High expression of Cav-1 protein of the GC in the stomach and metastatic lymph node was 12.4% (18/145 and 16.5% (15/91. In the multivariate analysis, tumoral Cav-1 protein in metastatic lymph node showed prognostic significance for relapse-free survival (RFS, HR, 3.934; 95% CI, 1.882–8.224; P=0.001 and cancer-specific survival outcome (CSS, HR, 2.681; 95% CI, 1.613–8.623; P=0.002. Among the GCs with metastatic lymph node, it remained as a strong indicator of poor prognosis for RFS (HR, 3.136; 95% CI, 1.444–6.810; P=0.004 and CSS (HR, 2.509; 95% CI, 1.078–5.837; P=0.032. Conclusion. High expression of tumoral Cav-1 protein in metastatic lymph node is associated with unfavorable prognosis of curative resected GC, indicating the potential of novel prognostic markers.

  14. Surviving at a distant site: The organotropism of metastatic breast cancer.

    Science.gov (United States)

    Wei, Shi; Siegal, Gene P

    2018-03-01

    Many cancers demonstrate a non-random distribution of sites for distant relapse while others have the propensity to metastasize to multiple organ systems. One of the notable recent findings is that the breast cancer subtypes differ not only in their biological characteristics as primary tumors but also in their capacity for metastatic progression. This information could potentially be utilized in treatment decision making and surveillance strategies. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. An Evaluation of Algorithms for Identifying Metastatic Breast, Lung, or Colorectal Cancer in Administrative Claims Data.

    Science.gov (United States)

    Whyte, Joanna L; Engel-Nitz, Nicole M; Teitelbaum, April; Gomez Rey, Gabriel; Kallich, Joel D

    2015-07-01

    Administrative health care claims data are used for epidemiologic, health services, and outcomes cancer research and thus play a significant role in policy. Cancer stage, which is often a major driver of cost and clinical outcomes, is not typically included in claims data. Evaluate algorithms used in a dataset of cancer patients to identify patients with metastatic breast (BC), lung (LC), or colorectal (CRC) cancer using claims data. Clinical data on BC, LC, or CRC patients (between January 1, 2007 and March 31, 2010) were linked to a health care claims database. Inclusion required health plan enrollment ≥3 months before initial cancer diagnosis date. Algorithms were used in the claims database to identify patients' disease status, which was compared with physician-reported metastases. Generic and tumor-specific algorithms were evaluated using ICD-9 codes, varying diagnosis time frames, and including/excluding other tumors. Positive and negative predictive values, sensitivity, and specificity were assessed. The linked databases included 14,480 patients; of whom, 32%, 17%, and 14.2% had metastatic BC, LC, and CRC, respectively, at diagnosis and met inclusion criteria. Nontumor-specific algorithms had lower specificity than tumor-specific algorithms. Tumor-specific algorithms' sensitivity and specificity were 53% and 99% for BC, 55% and 85% for LC, and 59% and 98% for CRC, respectively. Algorithms to distinguish metastatic BC, LC, and CRC from locally advanced disease should use tumor-specific primary cancer codes with 2 claims for the specific primary cancer >30-42 days apart to reduce misclassification. These performed best overall in specificity, positive predictive values, and overall accuracy to identify metastatic cancer in a health care claims database.

  16. Monitoring treatment response and metastatic relapse in advanced bladder cancer by liquid biopsy analysis

    DEFF Research Database (Denmark)

    Birkenkamp-Demtröder, Karin; Christensen, Emil; Nordentoft, Iver Kristiansen

    2017-01-01

    of circulating tumour DNA (ctDNA) in plasma and urine to detect metastatic relapse after cystectomy and measure treatment efficacy. We exome sequenced tumour and germline DNA from patients with muscle-invasive bladder cancer and monitored ctDNA in 370 liquid biopsies throughout the disease courses by 84......DNA detection in plasma and diagnosis of relapse was 101 d after cystectomy (range 0-932 d). Early detection of metastatic relapse and treatment response using liquid biopsies represents a novel, highly sensitive tool for monitoring patients, supporting clinicians, and guiding treatment decisions. PATIENT...

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

    Science.gov (United States)

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

    2017-06-01

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

  18. STK31 as novel biomarker of metastatic potential and tumorigenicity of colorectal cancer.

    Science.gov (United States)

    Zhong, Lan; Liu, Jing; Hu, Yedong; Wang, Wei; Xu, Fei; Xu, Wen; Han, Junyi; Biskup, Ewelina

    2017-04-11

    Colorectal cancer (CRC) is the fifth most common cause of cancer deaths in China and fourth worldwide. Metastatic dissemination of primary tumors is considered main cause for CRC related mortality. The serine-threonine kinase 31 (STK31) gene is a novel cancer testis (CT) antigen. It was found significantly highly expressed in gastrointestinal cancers. In our study we aimed to analyze the correlation between STK31 expression patterns and metastasization, tumor stage and grade in CRC patients. Relative STK31 expression level was significantly higher in patients with lymph node metastasis. STK31 expression levels in primary tumorous tissues of metastatic patients were significantly higher than in ANCTs and in lymph nodes samples, both at the RNA level and the protein level. Surgical specimens of cancerous tissues, paired with adjacent noncancerous tissues, and lymph nodes from 44 CRC cases with different clinicopathological features were collected. Expression of STK31 was detected and measured by immunohistochemistry and quantitative real-time polymerase chain reaction (QRT-PCR). Our data suggest that STK31 might be a potential biomarker in detecting, monitoring and predicting the metastatic risk of colorectal cancer.

  19. Everolimus-associated acute kidney injury in patients with metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    A Chandra

    2017-01-01

    Full Text Available Recently, everolimus (Evl has been introduced in the management of hormone receptor-positive metastatic breast cancer, in combination with aromatase inhibitors. Evl-induced acute kidney injury has hitherto been described in other malignancies, especially renal cell cancer, but only once before in a patient with breast cancer. We describe two cases of Evl-associated nephrotoxicity in patients with breast cancer, one of whom underwent a renal biopsy showing acute tubular necrosis. Both our patients improved after withdrawal of the offending agent and have normal renal functions on follow-up.

  20. Drug development for metastatic castration-resistant prostate cancer: current status and future perspectives.

    Science.gov (United States)

    Lassi, Kiran; Dawson, Nancy A

    2011-04-01

    Prostate cancer represents a third of all newly diagnosed cancers in men in the USA with an estimated incidence of 192,280 cases and 27,360 deaths in 2009. It continues to be a major cause of cancer-related morbidity and mortality, and there is an urgent need for new treatments. Historically, systemic therapy options were limited after progression on docetaxel-based chemotherapy. This article reviews current data on the novel therapeutics demonstrating activity in metastatic castration-resistant prostate cancer and their future role in the treatment of this disease with a poor prognosis.

  1. Large scale systematic proteomic quantification from non-metastatic to metastatic colorectal cancer

    Science.gov (United States)

    Yin, Xuefei; Zhang, Yang; Guo, Shaowen; Jin, Hong; Wang, Wenhai; Yang, Pengyuan

    2015-07-01

    A systematic proteomic quantification of formalin-fixed, paraffin-embedded (FFPE) colorectal cancer tissues from stage I to stage IIIC was performed in large scale. 1017 proteins were identified with 338 proteins in quantitative changes by label free method, while 341 proteins were quantified with significant expression changes among 6294 proteins by iTRAQ method. We found that proteins related to migration expression increased and those for binding and adherent decreased during the colorectal cancer development according to the gene ontology (GO) annotation and ingenuity pathway analysis (IPA). The integrin alpha 5 (ITA5) in integrin family was focused, which was consistent with the metastasis related pathway. The expression level of ITA5 decreased in metastasis tissues and the result has been further verified by Western blotting. Another two cell migration related proteins vitronectin (VTN) and actin-related protein (ARP3) were also proved to be up-regulated by both mass spectrometry (MS) based quantification results and Western blotting. Up to now, our result shows one of the largest dataset in colorectal cancer proteomics research. Our strategy reveals a disease driven omics-pattern for the metastasis colorectal cancer.

  2. Does Metastatic Lymph Node SUVmax Predict Survival in Patients with Esophageal Cancer?

    Directory of Open Access Journals (Sweden)

    Betül Vatankulu

    2015-10-01

    Full Text Available Objective: We aimed to investigate the SUVmax of primary tumor and metastatic lymph node in predicting survival in patients with esophageal cancer. Methods: We retrospectively analyzed patients with esophageal cancer between 2009 and 2011 who had FDG positronemission tomography (PET/computed tomography (CT. All patients were followed-up to 2013. Clinical staging, SUVmax of primary tumor and metastatic lymph node were evaluated. Results: One hundred seven patients were included in the study. All patients were followed-up between 2 and 49 months. The mean SUVmax of primary tumor and metastatic lymph node were 19.3±8.8 and 10.4±9.1, respectively. Metastatic lymph node SUVmax had an effect in predicting survival whereas primary tumor SUVmax did not have an effect (p=0.014 and p=0.262, respectively. Multivariate Cox regression analysis showed that clinical stage of the disease was the only independent factor predicting survival (p=0.001. Conclusion: Among patients with esophageal cancer, the value of primary tumor SUVmax did not have an effect on survival. Clinical stage assessed with FDG PET/CT imaging was found to predict survival in esophageal carcinoma. Additionally, lymph node SUVmax was identified as a new parameter in predicting survival in the present study

  3. A Case of Metastatic Bladder Cancer in Both Lungs Treated with Korean Medicine Therapy Alone

    Directory of Open Access Journals (Sweden)

    Dong-Hyun Lee

    2014-07-01

    Full Text Available This case report is aimed to investigate the effects of Korean medicine therapy (KMT including oral herbal medicine and herb nebulizer therapy in treating metastatic bladder cancer in the lungs. A 74-year-old man was diagnosed with metastatic bladder cancer in both lungs in August 2013. He refused any chemotherapy and was admitted to our hospital in a much progressed state on January 11, 2014. Since then, he was treated with KMT until May 17, 2014. The main oral herbal medicines were Hyunamdan made of heat-processed ginseng, Hangamdan S made of Cordyceps militaris, Panax ginseng radix, Commiphora myrrha, calculus bovis, margarita, Boswellia carteri, Panax notoginseng radix and Cremastra appendiculata tuber, and nebulizer therapy with Soram nebulizer solution made of wild ginseng and Cordyceps sinensis distillate. Their effect was evaluated considering the change of the main symptoms and using serial chest X-ray. The size and number of multiple metastatic nodules in both lungs were markedly decreased and the symptoms had disappeared. These results suggest that KMT can be an effective method to treat metastatic bladder cancer in the lungs.

  4. Toxicity and profile and objective response of Paclitaxel in metastatic breast cancer

    International Nuclear Information System (INIS)

    Ansari, T.N.; Mahmood, A; Rasul, S.; Syed, A.S.

    2005-01-01

    Objective: To evaluate the efficacy and toxicity of 1-hour weekly Paclitaxel in metastatic breast cancer along with evaluation of overall survival. Patients and Methods: Thirty six patients were enrolled in the study. All patients with histologically confirmed and bi- dimensionally measurable metastatic breast cancer who had received previously either chemotherapy or hormone therapy were included in the study. Paclitaxel was administered in 1-hour weekly infusion in a dose of 100 mg/m/sup 2/ for 12 doses. Results: All patients had received previous chemotherapy with either CAF or CMF. Twenty five patients had also received hormone therapy, 61% had two or more metastatic sites involved, and lung was the common site of involvement. Complete response was observed in 4 (11.1 %) patients, partial response in 14 (38.8%) patients, with an overall response rate of 50.0%. Clinical benefit was 94.4% and median overall survival was 11 months. Treatment was well-tolerated with no grade 3 or 4 toxicity. Common side effects were arthralgias, myalgias and neutropenia. Conclusion: Treatment with 1-hour weekly infusion of Paclitaxel is a well-tolerated chemotherapy with a substantial degree of efficacy in patients with metastatic breast cancer. (author)

  5. Progression criteria for cancer antigen 15.3 and carcinoembryonic antigen in metastatic breast cancer compared by computer simulation of marker data

    DEFF Research Database (Denmark)

    Sölétormos, G; Hyltoft Petersen, P; Dombernowsky, P

    2000-01-01

    BACKGROUND: We investigated the utility of computer simulation models for performance comparisons of different tumor marker assessment criteria to define progression or nonprogression of metastatic breast cancer. METHODS: Clinically relevant values for progressive cancer antigen 15...

  6. First radiotherapy of human metastatic brain tumors delivered by a computerized tomography scanner (CTRx).

    Science.gov (United States)

    Rose, J H; Norman, A; Ingram, M; Aoki, C; Solberg, T; Mesa, A

    1999-12-01

    This Phase I study was designed to evaluate the computed tomography (CT) scanner as a device for radiation therapy of human brain tumors (CTRx). This first use in humans of a modified CT for treatment was founded on extensive research experience with canine tumors. An additional objective was to increase the therapeutic radiation dose to tumors compared to normal tissue by concentration of infused contrast material in tumors, an effect available at diagnostic x-ray energies but not at megavoltage energies. A small metastatic brain tumor in each of eight patients received 3-5-weekly fractions of 5 Gy equivalent per fraction from a CT scanner modified to deliver radiation therapy. In each patient, one additional tumor, lying completely outside the volume treated by CTRx, served as a control. The tumor receiving CTRx was treated after infusion of iodinated x-ray contrast media (CM) for dose enhancement. Many of these patients also received conventional 40 Gy whole brain radiation, before, during, or after CTRx treatment. None of the patients showed adverse reactions to the CM or necrosis of the normal brain from the CTRx boost radiation. Monte Carlo calculations of the radiation dose distributions in a model tumor showed that the CTRx irradiation of tumors carrying 10 mg or more of iodine per gram of tumor was as good or better than the dose distribution from conventional 10-MV X-rays. The treated tumor in two of the patients vanished after four treatments, whereas a control tumor in one patient remained constant and grew 4-fold in another patient. The CTRx concept effectively combines a modified CT scanner as a diagnostic device, as a simulator dedicated to radiotherapy, and as a treatment machine. Thus, CTRx could be very useful for radiation oncologists in controlling CM-enhanced and other small brain tumors.

  7. Tumor Restrictive Gene Therapy for Metastatic Prostate Cancer

    National Research Council Canada - National Science Library

    Gardner, Thomas

    2001-01-01

    ...) to specifically target and lyse cells of an androgen independent prostate cancer osseous metastasis, which account for a majority of the morbidity and mortality experience by men with prostate cancer...

  8. Tumor Restrictive Gene Therapy for Metastatic Prostate Cancer

    National Research Council Canada - National Science Library

    Gardner, Thomas

    2000-01-01

    ...) to specifically target and lyse cells of an androgen independent prostate cancer osseous metastasis, which account for a majority of the morbidity and mortality experience by men with prostate cancer...

  9. Molecular Mechanisms of Metastatic Progression in Breast Cancer

    National Research Council Canada - National Science Library

    Flanagan, Louise A

    2004-01-01

    .... However, recent studies have demonstrated that clusterin expression correlates with tumor grade in prostate cancer and in one retrospective study has been associated with tumor progression in breast cancer...

  10. Palliative hysterectomy for vaginal bleeding from breast cancer metastatic to the uterus.

    Science.gov (United States)

    Berger, Amnon A; Matrai, Cathleen E; Cigler, Tessa; Frey, Melissa K

    2018-01-01

    Breast cancer is the most prevalent cancer in the United States. With an increasing rate of survivorship and extended life span for patients with metastatic disease, the demand for palliative care is increasing. Although uncommon, metastases to gynaecologic organs have been reported and are often present with post-menopausal bleeding. Post-menopausal bleeding can become clinically significant and have a detrimental effect on quality of life. We report the case of a 70-year-old woman with symptomatic vaginal bleeding caused by breast cancer metastatic to her uterus, cervix, fallopian tubes and ovaries. She was successfully treated with minimally invasive hysterectomy, resolving her vaginal bleeding and anemia and allowing her to resume chemotherapy.

  11. Durable response using regorafenib in an elderly patient with metastatic colorectal cancer: case report

    Directory of Open Access Journals (Sweden)

    Tang R

    2015-11-01

    Full Text Available Ronald Tang,1 Tatiana Kain,2 June Herman,2 Tara Seery1 1Division of Hematology-Oncology, 2Division of Nuclear Medicine and Molecular Imaging, University of California, Irvine, Orange, CA, USA Abstract: Regorafenib, an oral multikinase inhibitor, was approved in September 2012 by the US Food and Drug Administration for the treatment of patients with metastatic colorectal cancer. Since this time, however, few case reports outlining real-world usage have been published in the literature. Here, we detail the clinical history of an elderly woman with KRAS wild-type colon cancer who received regorafenib after prior treatment with other agents. We show that by employing dose modification strategies to address adverse events, this patient was able to remain on therapy for 11 months and achieve stable disease. Keywords: regorafenib, metastatic colorectal cancer, oral multikinase inhibitor

  12. Detection and monitoring of hypermethylated RASSF1A in serum from patients with metastatic breast cancer

    DEFF Research Database (Denmark)

    Kristiansen, Søren; Nielsen, Dorte Lisbet; Søletormos, Gyorgy Tamas Pal

    2016-01-01

    BACKGROUND: Circulating hypermethylated RASSF1A could be a novel and potential useful marker for monitoring patients with metastatic breast cancer. Technical obstacles include fragmentation of the circulating DNA, fluctuations in the concentration, low concentrations of circulating tumor DNA...... in circulating non-tumor DNA. As a proof of principle, there was concordance in the kinetics of the RASSF1A and the serological cancer biomarkers CA 15-3, CEA, and TPA. CONCLUSIONS: Methylation-sensitive restriction enzymes may be a useful methodological approach for monitoring circulating hypermethylated RASSF1...... of the rare circulating tumor DNA was initially optimized. By analysis of production of PCR amplicons from HpaII- or BstUI-treated DNA isolated from 24 patients with metastatic breast cancer, we located four regions resulting in sensitivities from 63 to 83 %. When examining samples from 24 control subjects...

  13. FIRST-LINE TREATMENT IN PATIENTS WITH INOPERABLE METASTATIC COLON CANCER

    Directory of Open Access Journals (Sweden)

    M. Yu. Fedyanin

    2014-01-01

    Full Text Available First-line therapy for metastatic colon cancer is most important for a patient. Its median time to progression constitutes the bulk of the patient’s survival. Clearly, it is necessary to choose the most effective combinations of targeted drugs and chemotherapy regimens. The choice of therapy for patients with colon cancer is governed by both the clinical characteristics of the disease and the molecular changes of a tumor. In recent literature, there has been a great deal of evidence for the use of targeted drugs in different clinical situations; the results of comparative trials of different treatment combinations have been published. This all determines the reconsideration of the choice of a treatment regimen in patients with metastatic colon cancer; it is the topic of the present review.

  14. Expression of MAGE-A and NY-ESO-1 in Primary and Metastatic Cancers.

    Science.gov (United States)

    Park, Tristen S; Groh, Eric M; Patel, Krishna; Kerkar, Sid P; Lee, Chyi-Chia Richard; Rosenberg, Steven A

    2016-01-01

    Melanoma-associated antigen-A (MAGE-A) and New York esophageal squamous cell cancer-1 (NY-ESO-1) are 2 cancer testis antigens (CTA) demonstrating potential for use in targeted immunotherapy. Clinical trials in melanoma and synovial sarcomas targeting these antigens in immune-based therapies have demonstrated durable tumor regression. Although protein expression of NY-ESO-1 has been assessed in a variety of cancer types, the expression of MAGE-A has not been studied in depth. In this study we analyzed MAGE-A and NY-ESO-1 expression in 314 melanoma specimens from 301 melanoma patients, 38 patients with squamous cell cancers and 111 patients with adenocarcinomas. Our results demonstrated higher expression of MAGE-A compared with NY-ESO-1 in melanomas (32% vs. 13%) and squamous cell carcinomas (45% vs. 7.9%), and higher expression of both CTAs in metastatic versus primary tumors. CTA expression in adenocarcinomas was low (MAGE-A: 10%, NY-ESO-1: 0.9%). In addition, we looked at concordance of expression among metastatic melanoma lesions within the same patient and found concordant expression in 38 of 47 patients for MAGE-A and 43 of 47 patients for NY-ESO-1. Our study demonstrated that the MAGE-A family may be of greater utility than NY-ESO-1 for targeted immunotherapy in a variety of cancer histologies, in particular metastatic melanomas and squamous cell carcinomas.

  15. Surgical therapy for testicular cancer metastatic to the liver

    OpenAIRE

    Maluccio, Mary; Einhorn, Lawrence H.; Goulet, Robert J.

    2007-01-01

    In recent years improved cure rates have been achieved for testicular cancer. A better understanding of the biology of subtypes of testicular cancer and the introduction of surgical intervention has contributed greatly to how we currently approach a young man with testicular cancer. We describe here experience at our institution of the treatment, results and prognostic factors for testicular cancer metastases to the liver. Careful diagnostic work-up and planning of the therapy are required, i...

  16. Organtropic Metastatic Secretomes and Exosomes in Breast Cancer

    Science.gov (United States)

    2016-10-01

    significantly increase diagnostic options, improve treatment efficacy and survival of breast cancer patients. The objectives of our proposal are to...has tremendous potential to improve the diagnosis, prognosis and treatment of breast cancer . We hypothesized that tumor and stromal cells...organ-tropic metastasis of breast cancer to bone and lung has tremendous potential impact on improving the diagnosis, prognosis and treatment of

  17. Retrospective analysis of metastatic behaviour of breast cancer subtypes

    NARCIS (Netherlands)

    Savci-Heijink, C. Dilara; Halfwerk, Hans; Hooijer, Gerrit K. J.; Horlings, Hugo M.; Wesseling, Jelle; van de Vijver, Marc J.

    2015-01-01

    Among breast cancer patients who develop distant metastases, there is marked variability in the clinical course, including metastasis pattern. Here, we present a retrospective study of breast cancer patients who all developed distant metastases focusing on the association between breast cancer

  18. The CEA−/lo colorectal cancer cell population harbors cancer stem cells and metastatic cells

    Science.gov (United States)

    Zhang, Bo; Mu, Lei; Huang, Kaiyu; Zhao, Hui; Ma, Chensen; Li, Xiaolan; Tao, Deding; Gong, Jianping; Qin, Jichao

    2016-01-01

    Serum carcinoembryonic antigen (CEA) is the most commonly used tumor marker in a variety of cancers including colorectal cancer (CRC) for tumor diagnosis and monitoring. Recent studies have shown that colonic crypt cells expressing little or no CEA may enrich for stem cells. Numerous studies have clearly shown that there exist CRC patients with normal serum CEA levels during tumor progression or even tumor relapse, although CEA itself is considered to promote metastasis and block cell differentiation. These seemingly contradictory observations prompted us to investigate, herein, the biological properties as well as tumorigenic and metastatic capacity of CRC cells that express high (CEA+) versus low CEA (CEA−/lo) levels of CEA. Our findings show that the abundance of CEA−/lo cells correlate with poor differentiation and poor prognosis, and moreover, CEA−/lo cells form more spheres in vitro, generate more tumors and exhibit a higher potential in developing liver and lung metastases than corresponding CEA+ cells. Applying RNAi-mediated approach, we found that IGF1R mediated tumorigenic and capacity of CEA−/lo cells but did not mediate those of CEA+ cells. Notably, our data demonstrated that CEA molecule was capable of protecting CEA−/lo cells from anoikis, implying that CEA+ cells, although themselves possessing less tumorigenic and metastatic capacity, may promote metastasis of CEA−/lo cells via secreting CEA molecule. Our observations suggest that, besides targeting CEA molecule, CEA−/lo cells may represent a critical source of tumor progression and metastasis, and should therefore be the target of future therapies. PMID:27813496

  19. Identification of genes regulating migration and invasion using a new model of metastatic prostate cancer

    International Nuclear Information System (INIS)

    Banyard, Jacqueline; Chung, Ivy; Migliozzi, Matthew; Phan, Derek T; Wilson, Arianne M; Zetter, Bruce R; Bielenberg, Diane R

    2014-01-01

    Understanding the complex, multistep process of metastasis remains a major challenge in cancer research. Metastasis models can reveal insights in tumor development and progression and provide tools to test new intervention strategies. To develop a new cancer metastasis model, we used DU145 human prostate cancer cells and performed repeated rounds of orthotopic prostate injection and selection of subsequent lymph node metastases. Tumor growth, metastasis, cell migration and invasion were analyzed. Microarray analysis was used to identify cell migration- and cancer-related genes correlating with metastasis. Selected genes were silenced using siRNA, and their roles in cell migration and invasion were determined in transwell migration and Matrigel invasion assays. Our in vivo cycling strategy created cell lines with dramatically increased tumorigenesis and increased ability to colonize lymph nodes (DU145LN1-LN4). Prostate tumor xenografts displayed increased vascularization, enlarged podoplanin-positive lymphatic vessels and invasive margins. Microarray analysis revealed gene expression profiles that correlated with metastatic potential. Using gene network analysis we selected 3 significantly upregulated cell movement and cancer related genes for further analysis: EPCAM (epithelial cell adhesion molecule), ITGB4 (integrin β4) and PLAU (urokinase-type plasminogen activator (uPA)). These genes all showed increased protein expression in the more metastatic DU145-LN4 cells compared to the parental DU145. SiRNA knockdown of EpCAM, integrin-β4 or uPA all significantly reduced cell migration in DU145-LN4 cells. In contrast, only uPA siRNA inhibited cell invasion into Matrigel. This role of uPA in cell invasion was confirmed using the uPA inhibitors, amiloride and UK122. Our approach has identified genes required for the migration and invasion of metastatic tumor cells, and we propose that our new in vivo model system will be a powerful tool to interrogate the metastatic

  20. Imaging Nuclear-Cytoplasmic Dynamics in Primary and Metastatic Colon Cancer in Nude Mice.

    Science.gov (United States)

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

    2016-05-01

    Colon cancer frequently results in metastasis to the liver, where it becomes the main cause of death. However, the cell cycle in primary tumors and metastases is poorly understood. We developed a mouse model of liver metastasis using the human colon cancer cell line HCT-116, which expresses green fluorescent protein (GFP) in the nucleus and red fluorescent protein (RFP) in the cytoplasm (HCT-116-GFP-RFP). HCT-116 GFP-RFP cells were injected into the spleen of nu/nu nude mice. HCT-116-GFP-RFP cells subsequently formed primary tumors in the spleen, as well as metastatic colonies in the liver and retroperitoneum by 28 days after cell transplantation. Using an Olympus FV1000 confocal microscope, it was possible to clearly image mitosis of the dual-colored colon cancer cells in the primary tumor as well as liver and other metastases. Multi-nucleate cancer cells, in addition to mono-nucleate cancer cells and their mitosis, were observed in the primary tumor and metastasis. Multi-nucleate HCT-116-GFP-RFP cells were also observed after culture of the primary and metastatic tumors. A similar ratio of mono-nucleate, multi-nucleate, and mitotic cells grew from the primary and metastatic tumors in culture, suggesting similarity of the nuclear-cytoplasmic dynamics of primary and metastatic cancer cells, further emphasizing the stochastic nature of metastasis. Our results demonstrate a similar heterogeneity of nuclear-cytoplasmic dynamics within primary tumors and metastases, which may be an important factor in the stochastic nature of metastasis. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  1. A novel, multimodal theranostic nanoprobe is effectively incorporated into melanoma brain metastatic cells

    Czech Academy of Sciences Publication Activity Database

    Aasen, S. N.; Eichler, T. W.; Hrubý, Martin; Pospíšilová, Aneta; Štěpánek, Petr; Spriet, E.; Jirák, D.; Skaftnesmo, K. O.; Thorsen, F.

    2015-01-01

    Roč. 75, 15 Supplement (2015), Abstract nr. 5195 ISSN 0008-5472. [Annual Meeting of the American Association for Cancer Research /106./. 18.04.2015-22.04.2015, Philadelphia] Institutional support: RVO:61389013 Keywords : melanoma brain metastasis * nanoprobe * theranostics Subject RIV: FR - Pharmacology ; Medidal Chemistry

  2. Re-irradiation of brain metastases and metastatic spinal cord compression: clinical practice suggestions.

    Science.gov (United States)

    Maranzano, Ernesto; Trippa, Fabio; Pacchiarini, Diamante; Chirico, Luigia; Basagni, Maria Luisa; Rossi, Romina; Bellavita, Rita; Schiavone, Concetta; Italiani, Marco; Muti, Marco

    2005-01-01

    The recent improvements of therapeutic approaches in oncology have allowed a certain number of patients with advanced disease to survive much longer than in the past. So, the number of cases with brain metastases and metastatic spinal cord compression has increased, as has the possibility of developing a recurrence in areas of the central nervous system already treated with radiotherapy. Clinicians are reluctant to perform re-irradiation of the brain, because of the risk of severe side effects. The tolerance dose for the brain to a single course of radiotherapy is 50-60 Gy in 2 Gy daily fractions. New metastases appear in 22-73% of the cases after whole brain radiotherapy, but the percentage of reirradiated patients is 3-10%. An accurate selection must be made before giving an indication to re-irradiation. Patients with Karnofsky performance status > 70, age variable associated with an increased risk of unacceptable acute and/or chronic neurotoxicity. Re-treatment of brain metastases can be done with whole brain radiotherapy, stereotactic radiosurgery or fractionated stereotactic radiotherapy. Most patients had no relevant radiation-induced toxicity after a second course of whole brain radiotherapy or stereotactic radiosurgery. There are few data on fractionated stereotactic radiotherapy in the re-irradiation of brain metastases. In general, the incidence of an "in-field" recurrence of spinal metastasis varies from 2.5-11% of cases and can occur 2-40 months after the first radiotherapy cycle. Radiation-induced myelopathy can occur months or years (6 months-7 years) after radiotherapy, and the pathogenesis remains obscure. Higher radiotherapy doses, larger doses per fraction, and previous exposure to radiation could be associated with a higher probability of developing radiation-induced myelopathy. Experimental data indicate that also the total dose of the first and second radiotherapy, interval to re-treatment, length of the irradiated spinal cord, and age of the

  3. RhoC a new target for therapeutic vaccination against metastatic cancer

    DEFF Research Database (Denmark)

    Wenandy, L.; Sorensen, R.B.; Straten, P.T.

    2008-01-01

    moving forward in multiple areas, including the adoptive transfer of anti-tumor-reactive T cells and the use of "therapeutic" vaccines. The over-expression of RhoC in cancer and the fact that immune escape by down regulation or loss of expression of this protein would reduce the morbidity and mortality......Most cancer deaths are due to the development of metastases. Increased expression of RhoC is linked to enhanced metastatic potential in multiple cancers. Consequently, the RhoC protein is an attractive target for drug design. The clinical application of immunotherapy against cancer is rapidly...... of cancer makes RhoC a very attractive target for anti-cancer immunotherapy. Herein, we describe an HLA-A3 restricted epitope from RhoC, which is recognized by cytotoxic T cells. Moreover, RhoC-specific T cells show cytotoxic potential against HLA-matched cancer cells of different origin. Thus, RhoC may...

  4. Potential role of pemetrexed in metastatic breast cancer patients pre-treated with anthracycline or taxane

    Directory of Open Access Journals (Sweden)

    Li-Yan Zhou

    2015-03-01

    Full Text Available Objectives: This article reviews pharmacology, pharmacokinetic properties, clinical efficacy, and safety in metastatic breast cancer patients, as well as the predictive biomarkers for outcome of treatment with pemetrexed-based regimens. Methods: PubMed, Embase, OVID, and the Cochrane Library databases were searched from the beginning of each database without any limitations to the date of publication. Search terms were ‘‘pemetrexed’’ or ‘‘LY231514’’ or “Alimta”, “metastatic breast cancer”, and “advanced breast cancer”. Results: There were 15 studies (n = 1002 meeting our criteria for evaluation. Eight single-agent trials (n = 551 and seven using combinations with other agents (n = 451 were identified that evaluated pemetrexed for use in patients with metastatic breast cancer. Response rates to pemetrexed as a single agent varied from 8% to 31%, and with combination therapy have been reported to be between 15.8% and 55.7%. With routine supplementation of patients with folic acid, dexamethasone, and vitamin B12, the toxicity profile of these patients was mild, including dose-limiting neutropenia and thrombocytopenia, as well as lower grades of reversible hepatotoxicity and gastrointestinal toxicity. Expression of thymidylate synthase (TS and other biomarkers are associated with the prognosis and sensitivity for pemetrexed in breast cancer. Conclusion: Pemetrexed has shown remarkable activity with acceptable toxicities for treatment of metastatic breast cancer patients. Translational research on pemetrexed in breast cancer identified biomarkers as well as additional genes important to its clinical activity and toxicity. Further research is needed to clarify the role of pemetrexed in breast cancer treatment in order to guide oncologists. Keywords: Metastatic breast cancer, Chemotherapy, Pemetrexed, Anthracycline, Taxane

  5. Detecting Metastatic Bladder Cancer Using (18)F-Fluorodeoxyglucose Positron-Emission Tomography/Computed Tomography.

    Science.gov (United States)

    Öztürk, Hakan

    2015-10-01

    The purpose of this study was to retrospectively investigate the contribution of (18)F-fluorodeoxyglucose-positron emission tomography/computed tomography ((18)F-FDG-PET/CT) to detection of metastatic bladder cancer. The present study included 79 patients (69 men and 10 women) undergoing (18)F-FDG-PET/CT upon suspicion of metastatic bladder cancer between July 2007 and April 2013. The mean age was 66.1 years with a standard deviation of 10.7 years (range, 21 to 85 years). Patients were required to fast for 6 hours prior to scanning, and whole-body PET scanning from the skull base to the upper thighs was performed approximately 1 hour after intravenous injection of 555 MBq of (18)F-FDG. Whole body CT scanning was performed in the cranio-caudal direction. FDG-PET images were reconstructed using CT data for attenuation correction. Suspicious recurrent or metastatic lesions were confirmed by histopathology or clinical follow-up. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of (18)F-FDG-PET/CT were 89%, 78%, 90%, 75%, and 86%, respectively. (18)F-FDG-PET/CT can detect metastases with high sensitivity and positive predictive values in patients with metastatic bladder carcinoma.

  6. Limited effect of lymph node status on the metastatic pattern in colorectal cancer

    Science.gov (United States)

    Knijn, Nikki; van Erning, Felice N.; Overbeek, Lucy I.H.; Punt, Cornelis J.A.; Lemmens, Valery E.P.P.; Hugen, Niek; Nagtegaal, Iris D.

    2016-01-01

    Regional lymph node metastases in colorectal cancer (CRC) decrease outcome. Whether nodal metastases function as a biomarker, i.e. as a sign of advanced disease, or are in fact involved in the metastatic process is unclear. We evaluated metastatic patterns of CRC according to the lymph node status of the primary tumor. A retrospective review of 1393 patients with metastatic CRC who underwent autopsy in the Netherlands was performed. Metastatic patterns of regional lymph node positive and negative CRC were compared and validated by population-based data from the Eindhoven Cancer Registry (ECR). Patients with regional lymph node positive CRC more often developed peritoneal metastases (28% vs. 21%, p=0.003) and distant lymph node metastases (25% vs. 15%, p <0.001). Incidences of liver and lung metastases were comparable. Data from the ECR confirmed our findings regarding peritoneal (22.4% vs. 17.0%, p=0.003) and distant lymph node metastases (15.8% vs. 9.7%, p <0.001). Regional lymph node positive CRC show a slightly different dissemination pattern, with higher rates of peritoneal and distant lymph nodes metastases. Comparable incidences of liver and lung metastases support the hypothesis that dissemination to distant organs occurs independently of lymphatic spread. PMID:27145371

  7. Metastatic urinary tract cancers in pap test: Cytomorphologic findings and differential diagnosis.

    Science.gov (United States)

    Allison, Derek B; Olson, Matthew T; Maleki, Zahra; Ali, Syed Z

    2016-12-01

    Although the cervical Pap test was devised for the detection of primary cervical neoplasia, it can provide additional diagnostic information, and in some cases, be diagnostic for noncervical processes. The diagnosis of metastatic extrauterine cervical cancers on the Pap test is extremely rare; and in most cases, it is the result of an ovarian or fallopian tube primary. Further, urinary tract cancers, including renal and urinary primaries are exceedingly rare. To our knowledge, six surgical cases of metastatic clear cell renal cell carcinoma (RCC) have been described. We report the first case of metastatic clear cell RCC detected on the cervical Pap test. Additionally, to our knowledge, we report the second case of metastatic high-grade urothelial carcinoma detected on the cervical Pap test. Both patients had a history of malignancy, which underscore the importance of broadening the differential diagnosis to rule out cytomorphologic features consistent with a patient's primary diagnosis when interpreting the cervical Pap test. Diagn. Cytopathol. 2016;44:1078-1081. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  8. Complete response of metastatic renal cancer with dendritic cell vaccine

    Directory of Open Access Journals (Sweden)

    Dall'Oglio Marcos

    2003-01-01

    Full Text Available INTRODUCTION: We report a case of metastatic renal cell carcinoma that presented involution following therapy with dendritic cells. CASE REPORT: Male, 51-year old patient underwent left radical nephrectomy in September 1999 due to renal cell carcinoma, evolved with recurrence of the neoplasia in January 2002, confirmed by resection of the lesion. A vaccine therapy based on dendritic cells was then performed during 5 months (4 applications. After this period, there was occurrence of new lesions, whose resection revealed areas of necrosis and inflammatory infiltrate. DISCUSSION: The outcome of renal cell carcinoma is influenced by prognostic factors that confer more aggressive tumor characteristics. However, in cases of recurrence, the systemic therapy with dendritic cells-based vaccine can be associated with a better outcome with regression of disease.

  9. uPAR Targeted Radionuclide Therapy with 177Lu-DOTA-AE105 Inhibits Dissemination of Metastatic Prostate Cancer

    DEFF Research Database (Denmark)

    Persson, Morten; Juhl, Karina; Rasmussen, Palle

    2014-01-01

    The urokinase-type plasminogen activator receptor (uPAR) is implicated in cancer invasion and metastatic development in prostate cancer and provides therefore an attractive molecular target for both imaging and therapy. In this study, we provide the first in vivo data on an antimetastatic effect...... of uPAR radionuclide targeted therapy in such lesions and show the potential of uPAR positron emission tomography (PET) imaging for identifying small foci of metastatic cells in a mouse model of disseminating human prostate cancer. Two radiolabeled ligands were generated in high purity and specific...... value of 100 nM in a competitive binding experiment. In vivo, uPAR targeted radionuclide therapy significantly reduced the number of metastatic lesions in the disseminated metastatic prostate cancer model, when compared to vehicle and nontargeted 177Lu groups (p

  10. Phase III trial of bevacizumab in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer

    NARCIS (Netherlands)

    van Cutsem, Eric; Vervenne, Walter L.; Bennouna, Jaafar; Humblet, Yves; Gill, Sharlene; van Laethem, Jean-Luc; Verslype, Chris; Scheithauer, Werner; Shang, Aijing; Cosaert, Jan; Moore, Malcolm J.

    2009-01-01

    Treatment with gemcitabine provides modest benefits in patients with metastatic pancreatic cancer. The addition of erlotinib to gemcitabine shows a small but significant improvement in overall survival (OS) versus gemcitabine alone. Phase II results for bevacizumab plus gemcitabine provided the

  11. Ketone supplementation decreases tumor cell viability and prolongs survival of mice with metastatic cancer.

    Science.gov (United States)

    Poff, A M; Ari, C; Arnold, P; Seyfried, T N; D'Agostino, D P

    2014-10-01

    Cancer cells express an abnormal metabolism characterized by increased glucose consumption owing to genetic mutations and mitochondrial dysfunction. Previous studies indicate that unlike healthy tissues, cancer cells are unable to effectively use ketone bodies for energy. Furthermore, ketones inhibit the proliferation and viability of cultured tumor cells. As the Warburg effect is especially prominent in metastatic cells, we hypothesized that dietary ketone supplementation would inhibit metastatic cancer progression in vivo. Proliferation and viability were measured in the highly metastatic VM-M3 cells cultured in the presence and absence of β-hydroxybutyrate (βHB). Adult male inbred VM mice were implanted subcutaneously with firefly luciferase-tagged syngeneic VM-M3 cells. Mice were fed a standard diet supplemented with either 1,3-butanediol (BD) or a ketone ester (KE), which are metabolized to the ketone bodies βHB and acetoacetate. Tumor growth was monitored by in vivo bioluminescent imaging. Survival time, tumor growth rate, blood glucose, blood βHB and body weight were measured throughout the survival study. Ketone supplementation decreased proliferation and viability of the VM-M3 cells grown in vitro, even in the presence of high glucose. Dietary ketone supplementation with BD and KE prolonged survival in VM-M3 mice with systemic metastatic cancer by 51 and 69%, respectively (p < 0.05). Ketone administration elicited anticancer effects in vitro and in vivo independent of glucose levels or calorie restriction. The use of supplemental ketone precursors as a cancer treatment should be further investigated in animal models to determine potential for future clinical use. © 2014 The Authors Published by Wiley Periodicals, Inc. on behalf of UICC.

  12. Trifluridine/tipiracil and regorafenib: new weapons in the war against metastatic colorectal cancer.

    Science.gov (United States)

    Weinberg, Benjamin A; Marshall, John L; Salem, Mohamed E

    2016-08-01

    Colorectal cancer (CRC) is the second leading cause of cancer-related death in the United States. Approximately 20% of patients have metastatic disease at diagnosis, and a vast number of these patients die within 5 years. The advent of modern chemotherapeutics has improved median overall survival for these patients; nonetheless, we must keep striving for better outcomes. Trifluridine/tipiracil (TAS-102) and regorafenib are agents newly approved by the US Food and Drug Administration that show promise in the treatment of metastatic colorectal cancer. These drugs have the benefit of being formulated for oral administration and have different side effect profiles. These differences are important in the selection of the best therapy for each patient, especially if the patient is prone to a side effect that is unique to just one of the treatments. In this review, we discuss the mechanism of action, side effect profile, and clinical efficacy of trifluridine/tipiracil, and compare them with those of regorafenib. Future trials will evaluate the use of these drugs in earlier lines of therapy, alone and in combination with other agents. We now have 2 more agents in the arsenal against metastatic colorectal cancer and the future is looking brighter for patients, although we still have a long way to go.

  13. Increased autophagic response in a population of metastatic breast cancer cells

    Science.gov (United States)

    LI, YI; LIBBY, EMILY FALK; LEWIS, MONICA J.; LIU, JIANZHONG; SHACKA, JOHN J.; HURST, DOUGLAS R.

    2016-01-01

    Breast cancer cells are heterogeneous in their ability to invade and fully metastasize, and thus also in their capacity to survive the numerous stresses encountered throughout the multiple steps of the metastatic cascade. Considering the role of autophagy as a survival response to stress, the present study hypothesized that distinct populations of breast cancer cells may possess an altered autophagic capacity that influences their metastatic potential. It was observed that a metastatic breast cancer cell line, MDA-MB-231, that was sensitive to autophagic induction additionally possessed the ability to proliferate following nutrient deprivation. Furthermore, a selected subpopulation of these cells that survived multiple exposures to starvation conditions demonstrated a heightened response to autophagic induction compared to their parent cells. Although this subpopulation maintained a more grape-like pattern in three-dimensional culture compared to the extended spikes of the parent population, autophagic induction in this subpopulation elicited an invasive phenotype with extended spikes. Taken together, these results suggest that autophagic induction may contribute to the ability of distinct breast cancer cell populations to survive and invade. PMID:27347175

  14. Survival analysis of stage IV metastatic gastric cancer patients treated with HangAm-Plus.

    Science.gov (United States)

    Park, Jae-Woo; Yoon, Jeungwon; Cho, Chong-Kwan; Lee, Yeon-Weol; Yoo, Hwa-Seung

    2014-01-01

    To evaluate the efficacy of HangAm-Plus (HAP) on stage IV metastatic gastric cancer by analyzing the treated patients' overall survival outcome. Following the study eligibility, overall survival and one year survival rate of 44 stage IV metastatic gastric cancer patients who visited East-West Cancer Center (EWCC) were analyzed. The study consisted of two arms: HAP treatment only (n=18) and combined treatment of concurrent conventional chemotherapy and HAP (n=26). Patient characteristics by gender, age, surgical intervention, Eastern Cooperative Oncology Group (ECOG) score, treatment duration (HAP group (5.1 months). One-year survival rate of combined treatment group and HAP group was 38.5%±9.5% and 33.3%±11.1%, respectively (P>0.05). One-year survival rate of those received more and less than 4-week treatment was 57.1%±18.7% and 8.3%±8.0%, respectively (P=0.001). The study supports the safety and potential efficacy of HAP treatment in prevention of chemo-related side effects for stage IV metastatic gastric cancer treated with conventional chemotherapy. Further studies are needed to investigate and confirm the results before applying the treatment in clinical settings.

  15. The adjuvant value of Andrographis paniculata in metastatic esophageal cancer treatment - from preclinical perspectives.

    Science.gov (United States)

    Li, Lin; Yue, Grace Gar-Lee; Lee, Julia Kin-Ming; Wong, Eric Chun-Wai; Fung, Kwok-Pui; Yu, Jun; Lau, Clara Bik-San; Chiu, Philip Wai-Yan

    2017-04-12

    Esophageal cancer (EC) is the fourth and sixth leading cause of cancer-related deaths in China and United States, respectively. The dismal prognosis of EC is mainly attributed to distant metastases, which may not be overcome by chemotherapy alone. Hence, the use of alternative adjuvant treatments, such as herbal medicines, for metastatic EC remains a great desire of patients. Our previous study demonstrated the in vivo anti-tumor and in vitro anti-invasion activities of Andrographis paniculata (AP) in esophageal cancer. In the present study, the chemical constituents of absorbed AP components through human intestinal Caco-2 cell monolayer were verified for the first time. The anti-migratory activities and suppressive effects on metastasis-related factors such as HER2, MMP2, MMP9, TM4SF3, CXCR4 of the absorbed AP components were revealed in esophageal cancer cells EC-109. The anti-tumor and anti-metastatic effects of AP water extract (1600 mg/kg) were further confirmed in metastatic esophageal xenograft-bearing mice. Besides, AP water extract acted synergistically with cisplatin plus 5-fluorouracil on inhibiting tumor nodule growth (with combination index present findings provide evidence on safety and advantages of the combined use of AP with chemotherapeutics in pre-clinical setting.

  16. Durvalumab, Tremelimumab + Radiotherapy in Gynecologic Cancer

    Science.gov (United States)

    2018-01-30

    Recurrent Gynecological Cancer; Metastatic Cervical Cancer; Metastatic Ovarian Cancer; Metastatic Vaginal Cancer; Metastatic Vulvar Cancer; Metastatic Endometrial Cancer; Recurrent Cervical Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Vaginal Cancer; Recurrent Vulvar Cancer; Recurrent Endometrial Cancer

  17. Bisphosphonate-related osteonecrosis of the jaw in metastatic breast cancer patients: a review of 25 cases

    OpenAIRE

    Kim, Hong-Joon; Park, Tae-Jun; Ahn, Kang-Min

    2016-01-01

    Background Intravenous bisphosphonates have been used in metastatic breast cancer patients to reduce pathologic bone fracture and bone pain. However, necrosis of the jaw has been reported in those who received intravenous bisphosphonates. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is caused by dental extraction, dental implant surgery, and denture wearing; however, it occurs spontaneously. The purpose of this study was to report BRONJ in metastatic breast cancer patients. Methods...

  18. Fusions of Breast Carcinoma and Dendritic Cells as a Vaccine for the Treatment of Metastatic Breast Cancer

    Science.gov (United States)

    2005-07-01

    AD Award Number: DAMD17-03-1-0487 TITLE: Fusions of Breast Carcinoma and Dendritic Cells as a Vaccine for the Treatment of Metastatic Breast Cancer...4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Fusions of Breast Carcinoma and Dendritic Cells as a Vaccine for the Treatment of Metastatic Breast Cancer... Borras -Cuesta, F., and Lasarte, J. J. CD4+/CD25+ regulatory cells inhibit activation of tumor-primed CD4+ T cells with IFN- gamma-dependent

  19. Megestrol acetate in the treatment of metastatic breast cancer

    NARCIS (Netherlands)

    J. Alexieva-Figusch (Jana)

    1984-01-01

    textabstractThere are many non-elucidated questions concerning cancer, especially of the breast, in which hormones are involved. The scope of this particular study is to bring more clarity on the role of the progestin megestrol acetate in the hormonal treatment of breast cancer. It should be kept in

  20. Topoisomerase I copy number alterations as biomarker for irinotecan efficacy in metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Palshof, Jesper Andreas; Hogdall, Estrid Vilma Solyom; Poulsen, Tim Svenstrup

    2017-01-01

    Background No biomarker exists to guide the optimal choice of chemotherapy for patients with metastatic colorectal cancer. We examined the copy numbers (CN) of topoisomerase I (TOP1) as well as the ratios of TOP1/CEN-20 and TOP1/CEN-2 as biomarkers for irinotecan efficacy in patients...... with metastatic colorectal cancer. Methods From a national cohort, we identified 163 patients treated every third week with irinotecan 350 mg/m2 as second-line therapy. Among these 108 were eligible for analyses and thus entered the study. Primary tumors samples were collected and tissue microarray (TMA) blocks...... of the markers TOP1 CN, TOP1/CEN-20-ratio or TOP1/CEN-2-ratio were associated with progression free survival, overall survival or baseline characteristics. Yet, we observed a borderline association for a stepwise increase of the TOP1 CN in relation to objective response as hazard ratio were 1.35 (95% CI 0...

  1. Successful Treatment of Advanced Metastatic Prostate Cancer following Chemotherapy Based on Molecular Profiling

    Directory of Open Access Journals (Sweden)

    Charles E. Myers

    2012-03-01

    Full Text Available After Taxotere fails, treatment options for metastatic prostate cancer are limited. The three drugs with FDA approval in this setting, Jevtana, Provenge and Zytiga, are associated with median survivals of less than 2 years. In part, the impact on survival is the result of low response rates, indicating a significant proportion of patients exhibiting de novo resistance to these agents. An alternate approach is to let treatment selection be governed by gene expression profiling so that the treatment is tailored to the specific patient. Here, we report a case of metastatic prostate cancer with a dramatic response to treatment selected based on molecular profiling. This patient had failed LHRH agonist, bicalutamide, Taxotere, and doxorubicin. Molecular profiling showed overexpression of the androgen receptor and he had a dramatic response of measurable disease to second-line hormonal therapy with ketoconazole, estrogen and Leukine.

  2. Dual Inhibition of EGFR and VEGF in Heavily Pretreated Patients with Metastatic Colorectal Cancer

    DEFF Research Database (Denmark)

    Larsen, Finn Ole; Markussen, Alice; Nielsen, Dorte

    2017-01-01

    Objective: The aim of this study was to evaluate the efficacy and safety of combining irinotecan, bevacizumab, and cetuximab/panitumumab as a 4th-line treatment in patients with metastatic colorectal cancer. Methods: All patients had KRAS wild-type metastatic colorectal cancer and had previously...... received fluoropyrimidine, oxaliplatin, irinotecan, and cetuximab/panitumumab in a 1st, 2nd, and 3rd line setting. Most patients had previously received bevacizumab as well. All patients had progressed within 3 months after the last given treatment before starting the triple combination therapy every...... second week. Results: Sixty-three patients were evaluated. The triple combination therapy was well tolerated. The median progression-free survival was 6.1 months, and the median overall survival was 11.9 months. Four patients (6%) obtained a partial response, and 40 (63%) had stable disease. Conclusion...

  3. Fournier gangrene as a manifestation of undiagnosed metastatic perforated colorectal cancer.

    Science.gov (United States)

    Chan, Cyrus C; Williams, Mallory

    2013-01-01

    Abstract Fournier gangrene is a necrotizing soft tissue infection involving the perineum. We present a case of Fournier gangrene as the clinical presentation of perforated metastatic rectal cancer. The patient is a 78-year-old man in a nursing home who presented to our institution with necrosis and ischemia of the scrotum. After wide debridement of necrotic tissue and bilateral orchiectomy, computed tomography was carried out to investigate abnormal findings seen on his chest X-ray, which revealed multiple pulmonary metastases as well as a mass highly suspicious for a perforated rectal mass. Once stable, a diverting colostomy and biopsies of the rectal mass were performed, confirming the presence of a metastatic, poorly differentiated rectal adenocarcinoma. Albeit an unusual etiology of Fournier gangrene, this case highlights the rare but important causes of this deadly condition and teaches us to be cognizant of the variations in the presentation of colorectal cancer.

  4. Chemotherapy versus best supportive care in stage IV non-small cell lung cancer, non metastatic to the brain Quimioterapia versus melhor tratamento de suporte em câncer de pulmão estádio clínico IV não metastático para o sistema nervoso central

    Directory of Open Access Journals (Sweden)

    Agnaldo Anelli

    2001-04-01

    Full Text Available Stage IV non-small cell lung cancer is a fatal disease, with a median survival of 14 months. Systemic chemotherapy is the most common approach. However the impact in overall survival and quality of life still a controversy. OBJECTIVES: To determine differences in overall survival and quality of life among patients with stage IV non-small cell lung cancer non-metastatic to the brain treated with best supportive care versus systemic chemotherapy. PATIENTS: From February 1990 through December 1995, 78 eligible patients were admitted with the diagnosis of stage IV non-small cell lung cancer . Patients were divided in 2 groups: Group A (n=31 -- treated with best supportive care , and Group B (n=47 -- treated with systemic chemotherapy. RESULTS: The median survival time was 23 weeks (range 5 -- 153 weeks in Group A and 55 weeks (range 7.4 -- 213 weeks in Group B (p=0.0018. In both groups, the incidence of admission for IV antibiotics and need of blood transfusions were similar. Patients receiving systemic chemotherapy were also stratified into those receiving mytomycin, vinblastin, and cisplatinum, n=25 and those receiving other combination regimens (platinum derivatives associated with other drugs, n=22. Patients receiving mytomycin, vinblastin, and cisplatinum, n=25 had a higher incidence of febrile neutropenia and had their cycles delayed for longer periods of time than the other group. These patients also had a shorter median survival time (51 versus 66 weeks, p=0.005. CONCLUSION: In patients with stage IV non-small cell lung cancer, non-metastatic to the brain, chemotherapy significantly increases survival compared with best supportive care.O câncer de pulmão de células não pequenas em estádio IV é uma doença fatal, com uma sobrevida mediana de seis meses. Quimioterapia é a abordagem mais freqüente, apresentando um impacto na sobrevida controverso e questionável alteração na qualidade de vida. OBJETIVOS: Comparar o impacto na

  5. Apoptotic circulating tumor cells in early and metastatic breast cancer patients.

    Science.gov (United States)

    Kallergi, Galatea; Konstantinidis, Georgios; Markomanolaki, Harris; Papadaki, Maria A; Mavroudis, Dimitris; Stournaras, Christos; Georgoulias, Vassilis; Agelaki, Sofia

    2013-09-01

    The detection of circulating tumor cells (CTC) in breast cancer is strongly associated with disease relapse. Since it is unclear whether all CTCs are capable of generating metastasis, we investigated their apoptotic and proliferative status in 56 CTC-positive (29 early and 27 metastatic) patients with breast cancer. Double-staining immunofluorescence experiments were carried out in peripheral blood mononuclear cells (PBMC) cytospins, using the pancytokeratin A45-B/B3 antibody and either M30 (apoptotic marker) or Ki67 (proliferation marker) antibodies. Apoptosis was also evaluated using a polycaspase detection kit. Patients with metastatic disease had significantly lower numbers of apoptotic CTCs compared with patients with early breast cancer (polycaspase kit: 8.1% vs. 47.4% of the total CTC number; P = 0.0001; M30-antibody: 32.1% vs. 76.63%; P = 0.002). The median percentage of apoptotic CTCs per patient was also lower in patients with advanced compared with those with early disease (polycaspase kit: 0% vs. 53.6%; M30-antibody: 15% vs. 80%). Ki67-positive CTCs were identified in 51.7% and 44% of patients with early and metastatic disease, respectively. Adjuvant chemotherapy reduced both the number of CTCs per patient and the number of proliferating CTCs (63.9% vs. 30%). In conclusion, apoptotic CTCs could be detected in patients with breast cancer irrespective of their clinical status, though the incidence of detection is higher in early compared with metastatic patients. The detection of CTCs that survive despite adjuvant therapy implies that CTC elimination should be attempted using agents targeting their distinctive molecular characteristics.

  6. MYC RNAi-PT Combination Nanotherapy for Metastatic Prostate Cancer Treatment

    Science.gov (United States)

    2016-10-01

    combining platinum (Pt) chemotherapy and MYC- targeting RNA interference (RNAi) for more effective treatment of metastatic prostate cancer (PCa). In...project is to develop an innovative nanotherapy modality by combining platinum (Pt) chemotherapy and MYC-targeting RNA interference (RNAi) for more...used to align to the mm10 mouse reference genome mouse genome and generate gene and isoform level expression measures. Tables of estimated

  7. Disseminated Paracoccidioidomycosis (Simulating Metastatic Lung Cancer) and Strongyloides stercoralis Hyperinfestation in a Steroid-Treated Patient▿

    Science.gov (United States)

    Dall Bello, Aline Gehlen; Severo, Cecília Bittencourt; de Mattos Oliveira, Flávio; Severo, Luiz Carlos

    2011-01-01

    We report a case of disseminated paracoccidioidomycosis, initially suggestive of metastatic lung cancer. The infection was associated with strongyloides hyperinfestation as a result of iatrogenic hypercorticoidism. Examination of a smear prepared from aspirated tracheobronchial secretion and stained by Grocott-methenamine-silver revealed structures consistent with Paracoccidioides brasiliensis and Strongyloides stercoralis. At autopsy, the central nervous system and pulmonary paracoccidioidomycosis, as well as pulmonary strongyloidiasis, were confirmed, without evidence of malignant cells. PMID:21430109

  8. Array-based sensing of normal, cancerous, and metastatic cells using conjugated fluorescent polymers.

    Science.gov (United States)

    Bajaj, Avinash; Miranda, Oscar R; Phillips, Ronnie; Kim, Ik-Bum; Jerry, D Joseph; Bunz, Uwe H F; Rotello, Vincent M

    2010-01-27

    A family of conjugated fluorescent polymers was used to create an array for cell sensing. Fluorescent conjugated polymers with pendant charged residues provided multivalent interactions with cell membranes, allowing the detection of subtle differences between different cell types on the basis of cell surface features. Highly reproducible characteristic patterns were obtained from different cell types as well as from isogenic cell lines, enabling the identification of the cell type as well differentiating between normal, cancerous, and metastatic isogenic cell types with high accuracy.

  9. Maintenance treatment with gemcitabine have a promising activity on metastatic bladder cancer survival.

    Science.gov (United States)

    Kuş, Tülay; Aktaş, Gökmen

    2017-09-01

    To investigate the effects of gemcitabine maintenance treatment on survival in patients with metastatic bladder cancer. Gemcitabine maintenance monotherapy was administered following the standard platinum-gemcitabine therapy in patients with metastatic bladder cancer. Patients who had responded to standard treatment received maintenance gemcitabine therapy as 1000 mg/m 2 on days 1 and 8 every three weeks until progression or development of unacceptable toxicity. The following clinical factors were noted: performance status, age, sex, stage, site of metastasis, choice of cisplatin-gemcitabine or carboplatin-gemcitabine, response rates to the initial chemotherapy. Progression-free survival (PFS) and overall survival (OS) for standard treatment, and following gemcitabine monotreatment and for maintenance gemcitabine therapy were calculated using Kaplan-Meier method. A total of 88 patients with metastatic bladder cancer treated between February 2009 to October 2015 were evaluated retrospectively and 23 patients (26.1%) who had responded to six cycles of platinum-gemcitabine treatment were included in this study. Maintenance gamcitabine was administered for a median of 7 times (range 3-14 times). Grade 3 hematotoxicity according to the criteria of the Common Terminology Criteria of Adverse Events was observed in 7 (30.4%) patients. Median PFS of patients was 46 (range: 30-82) weeks for platinum-based treatment plus maintenance gemcitabine therapy. A higher median PFS was obtained in patients who were maintenance therapy in metastatic bladder cancer patients who did not shown progression after the standard platinum-gemcitabine treatment contributes to survival and presents low toxicity profile, when compared to historical controls.

  10. Molecular subtypes of metastatic colorectal cancer are associated with patient response to irinotecan-based therapies.

    Science.gov (United States)

    Del Rio, M; Mollevi, C; Bibeau, F; Vie, N; Selves, J; Emile, J-F; Roger, P; Gongora, C; Robert, J; Tubiana-Mathieu, N; Ychou, M; Martineau, P

    2017-05-01

    Currently, metastatic colorectal cancer is treated as a homogeneous disease and only RAS mutational status has been approved as a negative predictive factor in patients treated with cetuximab. The aim of this study was to evaluate if recently identified molecular subtypes of colon cancer are associated with response of metastatic patients to first-line therapy. We collected and analysed 143 samples of human colorectal tumours with complete clinical annotations, including the response to treatment. Gene expression profiling was used to classify patients in three to six classes using four different molecular classifications. Correlations between molecular subtypes, response to treatment, progression-free and overall survival were analysed. We first demonstrated that the four previously described molecular classifications of colorectal cancer defined in non-metastatic patients also correctly classify stage IV patients. One of the classifications is strongly associated with response to FOLFIRI (P=0.003), but not to FOLFOX (P=0.911) and FOLFIRI + Bevacizumab (P=0.190). In particular, we identify a molecular subtype representing 28% of the patients that shows an exceptionally high response rate to FOLFIRI (87.5%). These patients have a two-fold longer overall survival (40.1 months) when treated with FOLFIRI, as first-line regimen, instead of FOLFOX (18.6 months). Our results demonstrate the interest of molecular classifications to develop tailored therapies for patients with metastatic colorectal cancer and a strong impact of the first-line regimen on the overall survival of some patients. This however remains to be confirmed in a large prospective clinical trial. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. A Unique Case of Muscle Invasive Metastatic Breast Cancer Mimicking Myositis

    Science.gov (United States)

    2017-06-28

    of non-Hispanic white women, diagnosis of metastatic disease as the initial presentation is seen in 6% of patients (1). Breast cancer typically...of widely disseminated disease [3, 4). Extra nodal head and neck metastases are also uncommon with only a few case reports and case series documenting...involvement of the thyroid , mandible, subcutaneous tissues, or pharynx [S- 11]. Thus, metastases to muscles of the neck are almost unheard of, w ith

  12. The Role of Surgery in Metastatic Bladder Cancer: A Systematic Review.

    Science.gov (United States)

    Abufaraj, Mohammad; Dalbagni, Guido; Daneshmand, Siamak; Horenblas, Simon; Kamat, Ashish M; Kanzaki, Ryu; Zlotta, Alexandre R; Shariat, Shahrokh F

    2017-11-06

    The role of surgery in metastatic bladder cancer (BCa) is unclear. In this collaborative review article, we reviewed the contemporary literature on the surgical management of metastatic BCa and factors associated with outcomes to support the development of clinical guidelines as well as informed clinical decision-making. A systematic search of English language literature using PubMed-Medline and Scopus from 1999 to 2016 was performed. The beneficial role of consolidation surgery in metastatic BCa is still unproven. In patients with clinically evident lymph node metastasis, data suggest a survival advantage for patients undergoing postchemotherapy radical cystectomy with lymphadenectomy, especially in those with measurable response to chemotherapy (CHT). Intraoperatively identified enlarged pelvic lymph nodes should be removed. Anecdotal reports of resection of pulmonary metastasis as part of multimodal approach suggest possible improved survival in well-selected patients. Cytoreductive radical cystectomy as local treatment has also been explored in patients with metastatic disease, although its benefits remain to be assessed. Consolidative extirpative surgery may be considered in patients with clinically evident pelvic or retroperitoneal lymph nodal metastases but only if they have had a response to CHT. Surgery for limited pulmonary metastases may also be considered in very selected cases. Best candidates are those with resectable disease who demonstrate measurable response to CHT with good performance status. In the absence of data from prospective randomized studies, each patient should be evaluated on an individual basis and decisions made together with the patient and multidisciplinary teams. Surgical resection of metastases is technically feasible and can be safely performed. It may help improve cancer control and eventually survival in very selected patients with limited metastatic burden. In a patient who is motivated to receive chemotherapy and to undergo

  13. Nanomedicine developments in the treatment of metastatic pancreatic cancer: focus on nanoliposomal irinotecan

    Directory of Open Access Journals (Sweden)

    Ko AH

    2016-03-01

    Full Text Available Andrew H KoDivision of Hematology/Oncology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA Abstract: Nanoliposomal irinotecan (nal-IRI was originally developed using an efficient and high-loading capacity system to encapsulate irinotecan within a liposomal carrier, producing a therapeutic agent with improved biodistribution and pharmacokinetic characteristics compared to free drug. Specifically, administration of nal-IRI results in prolonged exposure of SN-38, the active metabolite of irinotecan, within tumors, while at the same time offering the advantage of less systemic toxicity than traditional irinotecan. These favorable properties of nal-IRI, confirmed in a variety of tumor xenograft models, led to its clinical evaluation in a number of disease indications for which camptothecins have proven activity, including in colorectal, gastric, and pancreatic cancers. The culmination of these clinical trials was the NAPOLI-1 (Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy trial, an international Phase III study evaluating nal-IRI both alone and in combination with 5-fluorouracil and leucovorin in patients with metastatic pancreatic adenocarcinoma following progression on gemcitabine-based chemotherapy. Positive results from NAPOLI-1 led to approval of nal-IRI (with 5-fluorouracil/leucovorin in October 2015 by the US Food and Drug Administration specifically for the treatment of metastatic pancreatic cancer in the second-line setting and beyond, a clinical context in which there had previously been no accepted standard of care. As such, nal-IRI represents an important landmark in cancer drug development, and potentially ushers in a new era where a greater number of patients with advanced pancreatic cancer can be sequenced through multiple lines of therapy translating into meaningful improvements in

  14. Androgen receptor expression on circulating tumor cells in metastatic breast cancer.

    Directory of Open Access Journals (Sweden)

    Takeo Fujii

    Full Text Available Androgen receptor (AR is frequently detected in breast cancers, and AR-targeted therapies are showing activity in AR-positive (AR+ breast cancer. However, the role of AR in breast cancers is still not fully elucidated and the biology of AR in breast cancer remains incompletely understood. Circulating tumor cells (CTCs can serve as prognostic and diagnostic tools, prompting us to measure AR protein expression and conduct genomic analyses on CTCs in patients with metastatic breast cancer.Blood samples from patients with metastatic breast cancer were deposited on glass slides, subjected to nuclear staining with DAPI, and reacted with fluorescent-labeled antibodies to detect CD45, cytokeratin (CK, and biomarkers of interest (AR, estrogen receptor [ER], and HER2 on all nucleated cells. The stained slides were scanned and enumerated by non-enrichment-based non-biased approach independent of cell surface epithelial cell adhesion molecule (EpCAM using the Epic Sciences CTC platform. Data were analyzed using established digital pathology algorithms.Of 68 patients, 51 (75% had at least 1 CTC, and 49 of these 51 (96% had hormone-receptor-positive (HR+/HER2-negative primary tumors. AR was expressed in CK+ CTCs in 10 patients. Of these 10 patients, 3 also had ER expression in CK+ CTCs. Single cell genomic analysis of 78 CTCs from 1 of these 3 patients identified three distinct copy number patterns. AR+ cells had a lower frequency of chromosomal changes than ER+ and HER2+ cells.CTC enumeration and analysis using no enrichment or selection provides a non-biased approach to detect AR expression and chromosomal aberrations in CTCs in patients with metastatic breast cancer. The heterogeneity of intrapatient AR expression in CTCs leads to the new hypothesis that patients with AR+ CTCs have heterogeneous disease with multiple drivers. Further studies are warranted to investigate the clinical applicability of AR+ CTCs and their heterogeneity.

  15. Palliative radiotherapy in patients with a symptomatic pelvic mass of metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Chun Ho Kyung

    2011-05-01

    Full Text Available Abstract Background To evaluate the palliative role of radiotherapy (RT and define the effectiveness of chemotherapy combined with palliative RT (CCRT in patients with a symptomatic pelvic mass of metastatic colorectal cancer. Methods From August 1995 to December 2007, 80 patients with a symptomatic pelvic mass of metastatic colorectal cancer were treated with palliative RT at Samsung Medical Center. Initial presenting symptoms were pain (68 cases, bleeding (18 cases, and obstruction (nine cases. The pelvic mass originated from rectal cancer in 58 patients (73% and from colon cancer in 22 patients (27%. Initially 72 patients (90% were treated with surgery, including 64 complete local excisions; 77% in colon cancer and 81% in rectal cancer. The total RT dose ranged 8-60 Gy (median: 36 Gy with 1.8-8 Gy per fraction. When the α/β for the tumor was assumed to be 10 Gy for the biologically equivalent dose (BED, the median RT dose was 46.8 Gy10 (14.4-78. Twenty one patients (26% were treated with CCRT. Symptom palliation was assessed one month after the completion of RT. Results Symptom palliation was achieved in 80% of the cases. During the median follow-up period of five months (1-44 months, 45% of the cases experienced reappearance of symptoms; the median symptom control duration was five months. Median survival after RT was six months. On univariate analysis, the only significant prognostic factor for symptom control duration was BED ≥40 Gy10 (p Conclusions RT was an effective palliation method in patients with a symptomatic pelvic mass of metastatic colorectal cancer. For improvement of symptom control rate and duration, a BED ≥ 40 Gy10 is recommended when possible. Considering the low morbidity and improved symptom palliation, CCRT might be considered in patients with good performance status.

  16. Palliative radiotherapy in patients with a symptomatic pelvic mass of metastatic colorectal cancer

    International Nuclear Information System (INIS)

    Bae, Sun Hyun; Yun, Seong Hyeon; Kim, Hee Cheol; Park, Won; Choi, Doo Ho; Nam, Heerim; Kang, Won Ki; Park, Young Suk; Park, Joon Oh; Chun, Ho Kyung; Lee, Woo Yong

    2011-01-01

    To evaluate the palliative role of radiotherapy (RT) and define the effectiveness of chemotherapy combined with palliative RT (CCRT) in patients with a symptomatic pelvic mass of metastatic colorectal cancer. From August 1995 to December 2007, 80 patients with a symptomatic pelvic mass of metastatic colorectal cancer were treated with palliative RT at Samsung Medical Center. Initial presenting symptoms were pain (68 cases), bleeding (18 cases), and obstruction (nine cases). The pelvic mass originated from rectal cancer in 58 patients (73%) and from colon cancer in 22 patients (27%). Initially 72 patients (90%) were treated with surgery, including 64 complete local excisions; 77% in colon cancer and 81% in rectal cancer. The total RT dose ranged 8-60 Gy (median: 36 Gy) with 1.8-8 Gy per fraction. When the α/β for the tumor was assumed to be 10 Gy for the biologically equivalent dose (BED), the median RT dose was 46.8 Gy 10 (14.4-78). Twenty one patients (26%) were treated with CCRT. Symptom palliation was assessed one month after the completion of RT. Symptom palliation was achieved in 80% of the cases. During the median follow-up period of five months (1-44 months), 45% of the cases experienced reappearance of symptoms; the median symptom control duration was five months. Median survival after RT was six months. On univariate analysis, the only significant prognostic factor for symptom control duration was BED ≥40 Gy 10 (p < 0.05), and CCRT was a marginally significant factor (p = 0.0644). On multivariate analysis, BED and CCRT were significant prognostic factors for symptom control duration (p < 0.05). RT was an effective palliation method in patients with a symptomatic pelvic mass of metastatic colorectal cancer. For improvement of symptom control rate and duration, a BED ≥ 40 Gy 10 is recommended when possible. Considering the low morbidity and improved symptom palliation, CCRT might be considered in patients with good performance status

  17. Androgen receptor expression on circulating tumor cells in metastatic breast cancer

    Science.gov (United States)

    Fujii, Takeo; Reuben, James M.; Huo, Lei; Espinosa Fernandez, Jose Rodrigo; Gong, Yun; Krupa, Rachel; Suraneni, Mahipal V.; Graf, Ryon P.; Lee, Jerry; Greene, Stephanie; Rodriguez, Angel; Dugan, Lyndsey; Louw, Jessica; Lim, Bora; Barcenas, Carlos H.; Marx, Angela N.; Tripathy, Debu; Wang, Yipeng; Landers, Mark; Dittamore, Ryan

    2017-01-01

    Purpose Androgen receptor (AR) is frequently detected in breast cancers, and AR-targeted therapies are showing activity in AR-positive (AR+) breast cancer. However, the role of AR in breast cancers is still not fully elucidated and the biology of AR in breast cancer remains incompletely understood. Circulating tumor cells (CTCs) can serve as prognostic and diagnostic tools, prompting us to measure AR protein expression and conduct genomic analyses on CTCs in patients with metastatic breast cancer. Methods Blood samples from patients with metastatic breast cancer were deposited on glass slides, subjected to nuclear staining with DAPI, and reacted with fluorescent-labeled antibodies to detect CD45, cytokeratin (CK), and biomarkers of interest (AR, estrogen receptor [ER], and HER2) on all nucleated cells. The stained slides were scanned and enumerated by non-enrichment-based non-biased approach independent of cell surface epithelial cell adhesion molecule (EpCAM) using the Epic Sciences CTC platform. Data were analyzed using established digital pathology algorithms. Results Of 68 patients, 51 (75%) had at least 1 CTC, and 49 of these 51 (96%) had hormone-receptor-positive (HR+)/HER2-negative primary tumors. AR was expressed in CK+ CTCs in 10 patients. Of these 10 patients, 3 also had ER expression in CK+ CTCs. Single cell genomic analysis of 78 CTCs from 1 of these 3 patients identified three distinct copy number patterns. AR+ cells had a lower frequency of chromosomal changes than ER+ and HER2+ cells. Conclusions CTC enumeration and analysis using no enrichment or selection provides a non-biased approach to detect AR expression and chromosomal aberrations in CTCs in patients with metastatic breast cancer. The heterogeneity of intrapatient AR expression in CTCs leads to the new hypothesis that patients with AR+ CTCs have heterogeneous disease with multiple drivers. Further studies are warranted to investigate the clinical applicability of AR+ CTCs and their

  18. Phosphodiesterase type 5 inhibitors increase Herceptin transport and treatment efficacy in mouse metastatic brain tumor models.

    Directory of Open Access Journals (Sweden)

    Jinwei Hu

    2010-04-01

    Full Text Available Chemotherapeutic drugs and newly developed therapeutic monoclonal antibodies are adequately delivered to most solid and systemic tumors. However, drug delivery into primary brain tumors and metastases is impeded by the blood-brain tumor barrier (BTB, significantly limiting drug use in brain cancer treatment.We examined the effect of phosphodiesterase 5 (PDE5 inhibitors in nude mice on drug delivery to intracranially implanted human lung and breast tumors as the most common primary tumors forming brain metastases, and studied underlying mechanisms of drug transport. In vitro assays demonstrated that PDE5 inhibitors enhanced the uptake of [(14C]dextran and trastuzumab (Herceptin, a humanized monoclonal antibody against HER2/neu by cultured mouse brain endothelial cells (MBEC. The mechanism of drug delivery was examined using inhibitors for caveolae-mediated endocytosis, macropinocytosis and coated pit/clathrin endocytosis. Inhibitor analysis strongly implicated caveolae and macropinocytosis endocytic pathways involvement in the PDE5 inhibitor-enhanced Herceptin uptake by MBEC. Oral administration of PDE5 inhibitor, vardenafil, to mice with HER2-positive intracranial lung tumors led to an increased tumor permeability to high molecular weight [(14C]dextran (2.6-fold increase and to Herceptin (2-fold increase. Survival time of intracranial lung cancer-bearing mice treated with Herceptin in combination with vardenafil was significantly increased as compared to the untreated, vardenafil- or Herceptin-treated mice (p0.05.These findings suggest that PDE5 inhibitors may effectively modulate BTB permeability, and enhance delivery and therapeutic efficacy of monoclonal antibodies in hard-to-treat brain metastases from different primary tumors that had metastasized to the brain.

  19. Extracellular vesicles for personalized therapy decision support in advanced metastatic cancers and its potential impact for prostate cancer.

    Science.gov (United States)

    Soekmadji, Carolina; Corcoran, Niall M; Oleinikova, Irina; Jovanovic, Lidija; Ramm, Grant A; Nelson, Colleen C; Jenster, Guido; Russell, Pamela J

    2017-10-01

    The use of circulating tumor cells (CTCs) and circulating extracellular vesicles (EVs), such as exosomes, as liquid biopsy-derived biomarkers for cancers have been investigated. CTC enumeration using the CellSearch based platform provides an accurate insight on overall survival where higher CTC counts indicate poor prognosis for patients with advanced metastatic cancer. EVs provide information based on their lipid, protein, and nucleic acid content and can be isolated from biofluids and analyzed from a relatively small volume, providing a routine and non-invasive modality to monitor disease progression. Our pilot experiment by assessing the level of two subpopulations of small EVs, the CD9 positive and CD63 positive EVs, showed that the CD9 positive EV level is higher in plasma from patients with advanced metastatic prostate cancer with detectable CTCs. These data show the potential utility of a particular EV subpopulation to serve as biomarkers for advanced metastatic prostate cancer. EVs can potentially be utilized as biomarkers to provide accurate genotypic and phenotypic information for advanced prostate cancer, where new strategies to design a more personalized therapy is currently the focus of considerable investigation. © 2017 Wiley Periodicals, Inc.

  20. HER-2, ER, PR status concordance in primary breast cancer and corresponding metastatic lesion in lymph node in Chinese women.

    Science.gov (United States)

    Li, Min Hua; Hou, Chuan Ling; Wang, Cheng; Sun, Ai Jing

    2016-04-01

    To compare the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) in the primary site and the metastatic lesion of lymph nodes in invasive breast cancer for investigating whether the expression of these biomarkers in the primary site could act as a surrogate to the lymphatic metastatic lesion in the same patient. In lymphatic metastatic lesion and corresponding primary lesion of 107 cases of invasive breast cancer, ER and PR statuses were assessed by immunohistochemistry (IHC). HER-2 expression level was evaluated by IHC and/or fluorescence in situ hybridization (FISH). In the primary lesions, 43.9% were ER positive; 46.7% were PR positive; 34.6% were HER-2 positive. In corresponding lymphatic metastatic lesions, the HER-2 status was concordant in 90 patients; 9 patients were diagnosed positive in metastatic lesion while negative in primary lesion; 8 patients were negative in metastatic lesion while positive in primary site (agreement, 84.1%; κ=0.647). A change in ER status was observed in 24 cases: 17 cases positive in metastatic site while negative in primary site; 7 cases negative in metastatic site while positive in primary site (agreement, 77.6%; κ=0.534). PR status discordance between the primary lesion and the metastatic regional lymph nodes was reported in 19 cases (agreement, 82.2%; κ=0.640). This study revealed that there was only a moderate concordance of ER, PR and HER-2 status between primary tumors and metastatic lymph nodes. These results indicate that it was inappropriate to predict the status of ER, PR and HER-2 in metastatic lymph nodes based on the results of evaluation of that in primary lesions. Copyright © 2015 Elsevier GmbH. All rights reserved.

  1. Tumor Restrictive Gene Therapy for Metastatic Prostate Cancer

    National Research Council Canada - National Science Library

    Gardner, Thomas

    2000-01-01

    .... The scope of this project to perform the studies outlined in proposal to prove the hypothesis that conditional replication under the guidance of the osteocalcin promoter can exert a prostate cancer...

  2. Tumor Restrictive Gene Therapy for Metastatic Prostate Cancer

    National Research Council Canada - National Science Library

    Gardner, Thomas

    2001-01-01

    .... The scope of this project to perform the studies outlined in proposal to prove the hypothesis that conditional replication under the guidance of the osteocalcin promoter can exert a prostate cancer...

  3. Trafficking of Metastatic Breast Cancer Cells in Bone

    National Research Council Canada - National Science Library

    Mastro, Andrea M

    2004-01-01

    ... metaphyses. Human breast cancer cells that express green fluorescent protein (GFP-MDA-MB 231) will be inoculated into athymic mice by intracardiac injection and femurs harvested at various times from 1 hour to 6 weeks later...

  4. Development of a Gene Therapy Trial for Metastatic Prostate Cancer

    National Research Council Canada - National Science Library

    Gardner, Thomas A

    2006-01-01

    .... The Phase I trial under development employs a prostate restricted replicative adenovirus (PRRA) with excellent preclinical performance in vitro and in vivo in relevant animal models of human prostate cancer...

  5. Enzalutamide for the treatment of metastatic castration-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Rodriguez-Vida A

    2015-06-01

    Full Text Available Alejo Rodriguez-Vida,1 Myria Galazi,1 Sarah Rudman,1 Simon Chowdhury,1 Cora N Sternberg2 1Medical Oncology Department, Guy’s and St Thomas’ NHS Foundation Trust, London, UK; 2Medical Oncology Department, San Camillo and Forlanini Hospitals, Rome, Italy Abstract: In recent years, several nonhormonal and hormonal agents, including enzalutamide, have been approved for the treatment of metastatic castration-resistant prostate cancer (CRPC on the basis of improved overall survival in prospective clinical trials. The incorporation of these agents has revolutionized the treatment of CRPC but has also raised the question of what is the ideal sequence of administering them. Enzalutamide is a nonsteroidal second-generation antiandrogen that has been approved for the treatment of metastatic CRPC both in the post-docetaxel and chemotherapy-naïve settings. This article reviews the pharmacological characteristics of enzalutamide, the efficacy studies which led to its approval, its safety profile, and quality of life-related parameters as well as its place in the sequential treatment and management of metastatic prostate cancer. Keywords: enzalutamide, antiandrogen, ADT, androgen receptor, castration resistant prostate cancer, overall survival

  6. Identification of 42 Genes Linked to Stage II Colorectal Cancer Metastatic Relapse

    Directory of Open Access Journals (Sweden)

    Rabeah A. Al-Temaimi

    2016-04-01

    Full Text Available Colorectal cancer (CRC is one of the leading causes of cancer mortality. Metastasis remains the primary cause of CRC death. Predicting the possibility of metastatic relapse in early-stage CRC is of paramount importance to target therapy for patients who really need it and spare those with low-potential of metastasis. Ninety-six stage II CRC cases were stratified using high-resolution array comparative genomic hybridization (aCGH data based on a predictive survival algorithm and supervised clustering. All genes included within the resultant copy number aberrations were each interrogated independently at mRNA level using CRC expression datasets available from public repositories, which included 1820 colon cancers, and 167 normal colon tissues. Reduced mRNA expression driven by copy number losses and increased expression driven by copy number gains revealed 42 altered transcripts (29 reduced and 13 increased transcripts associated with metastatic relapse, short disease-free or overall survival, and/or epithelial to mesenchymal transition (EMT. Resultant genes were classified based on gene ontology (GO, which identified four functional enrichment groups involved in growth regulation, genomic integrity, metabolism, and signal transduction pathways. The identified 42 genes may be useful for predicting metastatic relapse in stage II CRC. Further studies are necessary to validate these findings.

  7. Development of nanotheranostics against metastatic breast cancer--A focus on the biology & mechanistic approaches.

    Science.gov (United States)

    Subramanian, Anuradha; Manigandan, Amrutha; Sivashankari, P R; Sethuraman, Swaminathan

    2015-12-01

    Treatment for metastatic breast cancer still remains to be a challenge since the currently available diagnostic and treatment strategies fail to detect the micro-metastasis resulting in higher mortality rate. Moreover, the lack of specificity to target circulating tumor cells is also a factor. In addition, currently available imaging modalities to identify the secondaries vary with respect to various metastatic anatomic areas and size of the tumor. The drawbacks associated with the existing clinical management of the metastatic breast cancer demands the requirement of multifunctional nanotheranostics, which could diagnose at macro- and microscopic level, target the solid as well as circulating tumor cells and control further progression with the simultaneous evaluation of treatment response in a single platform. However, without the understanding of the biology as well as preferential homing ability of circulating tumor cells at distant organs, it is quite impossible to address the existing challenges in the present diagnostics and therapeutics against the breast cancer metastasis. Hence this review outlines the severity of the problem, basic biology and organ specificity with the sequential steps for the secondary progression of disease followed by the various mechanistic approaches in diagnosis and therapy at different stages. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Oral vinorelbine in metastatic breast cancer: a review of current clinical trial results.

    Science.gov (United States)

    Aapro, Matti; Finek, Jindrich

    2012-04-01

    Oral chemotherapy is one of the options for the treatment of endocrine non-responsive metastatic breast cancer. A search of the online PubMed database was undertaken to identify clinical trials evaluating oral vinorelbine in metastatic breast cancer. All the clinically relevant data have been analysed in this article. A total of 31 studies including more than 1000 patients have been included into this analysis. Oral vinorelbine either as a single-agent or in combination has shown consistent efficacy results (response rates between 27% and 85% in first-line). The all-oral combination of oral vinorelbine and capecitabine has shown comparable efficacy to a taxane-based combination in a randomised phase II study. Importantly, activity has also been observed in the subset of patients previously treated with anthracyclines and taxanes. For HER2-positive patients, oral vinorelbine in combination with trastuzumab is among the most active options. Oral vinorelbine presents a manageable tolerance profile. Neutropenia is the most common adverse event and alopecia is not frequently observed. Anti-emetic prophylaxis is recommended. Taken together, these data indicate that oral vinorelbine is a highly effective and well tolerated agent which can be used in first-line and subsequent metastatic breast cancer settings. Moreover, this compound may offer the specific advantages of oral chemotherapy, as fewer and shorter hospital visits, delayed use of central venous access devices and maintained social activities. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Monthly docetaxel and weekly gemcitabine in metastatic breast cancer: a phase II trial.

    Science.gov (United States)

    Laufman, L R; Spiridonidis, C H; Pritchard, J; Roach, R; Zangmeister, J; Larrimer, N; Moore, T; Segal, M; Jones, J; Patel, T; Gutterman, L; Carman, L; Colborn, D; Kuebler, J P

    2001-09-01

    Docetaxel and gemcitabine are active against breast cancer. The purpose of this phase II study was to evaluate the efficacy and safety of monthly docetaxel combined with weekly gemcitabine in patients with chemotherapy-pretreated metastatic breast cancer. Thirty-nine patients were enrolled, of whom thirty had received prior chemotherapy in the adjuvant setting, seven for metastatic disease, and two for both, including prior anthracycline in 33 patients. Treatment was gemcitabine 800 mg/m2 days 1, 8, 15 and docetaxel 100 mg/M2 on day 1, with cycles repeated every four weeks. Response rate was 79% (95% confidence interval (CI): 63%-91%), with 2 complete and 29 partial responses. Twenty-five of the responders remained progression-free for more than six months. Median survival was 24.5 months. Delivered dose intensity of gemcitabine was lower than expected (63% of planned). The predominant hematologic toxicity was grade 4 neutropenia in 36 patients, complicated by fever in three patients. With the exception of asthenia, severe non-hematological toxicities were infrequent. Monthly docetaxel, combined with weekly gemcitabine, has significant but manageable hematologic toxicity. Despite frequent dose adjustments, this doublet is very active in metastatic breast cancer, producing a high proportion of durable responses associated with favorable survival.

  10. New Epigenetic Therapeutic Intervention for Metastatic Breast Cancer

    Science.gov (United States)

    2017-04-01

    11/09/2016 University of Wisconsin-Madison, Cancer Biology Seminar Series, Madison, WI, “From Epigenetic Mechanism to Targeted Therapy” 12/22/2016...Transcription” 02/16/2017 Purdue University Cancer Center, West Lafayette, IN, “From Epigenetic Structural Mechanism to Targeted Therapy” 7 Binhua P...171,284/yr, d.c. “Structure and Mechanism of Protein Modules in Chromatin Biology” This project aims to conduct structural and biochemical analyses

  11. Novel concepts of antiangiogenic therapies in metastatic renal cell cancer.

    Science.gov (United States)

    Pichler, Renate; Heidegger, Isabel

    2017-01-01

    The era of antiangiogenic drugs targeting the vascular endothelial growth factor (VEGF) signaling pathway has become a mainstay in the treatment of metastatic renal cell carcinoma (mRCC), showing primary responses in 65-70% of patients. Nevertheless, most of those patients progress to angiogenesis inhibitors over time due to different modes of resistance (adaptive and intrinsic). Both in vitro and in vivo analyses provided evidence that PD-L1 upregulation in hypoxia conditions is dependent on hypoxia-inducible factor (HIF)-2alpha and is associated with an overexpression of VEGF. Thus, additional blockade of PD-L1 along with inhibition of angiogenesis pathways seems to represent a novel and innovative treatment concept in mRCC. In this short review, we provide an overview on ongoing phase III trials combining antiangiogenic therapies with checkpoint inhibitors in the first-line setting. Moreover, we critically analyze the impact of recently approved therapeutic antiangiogenic agents and checkpoint inhibitors after progression to first-generation tyrosine kinase inhibitors and their mode of action. In addition, response and resistance hypotheses and biomarkers to antiangiogenic therapy in clinical practice are critically discussed.

  12. Isolated lung events following radiation for early stage breast cancer: incidence and predictors for primary lung vs metastatic breast cancer

    International Nuclear Information System (INIS)

    Van Buren, Teresa A; Harris, Jay R; Sugarbaker, David J; Schneider, Lindsey; Healey, Elizabeth A

    1995-01-01

    Purpose: 1) To define the incidence of isolated lung events in a cohort of women treated with conservative surgery (CS) and radiation therapy (RT) for early stage breast cancer. 2) Among such patients, to define the relative distribution of primary lung cancer, metastatic breast cancer, and indeterminate lesions; and to identify any predictors for a diagnosis of lung vs metastatic breast cancer. 3) To examine the cohort with respect to whether a higher than expected incidence of lung cancer is seen following breast irradiation. Materials and Methods: Between 1968 and 1986, 1865 patients with clinical stage I-II breast cancer were treated with CS and RT; the median follow-up for surviving patients is 129 months. The study population was limited to patients who developed a subsequent isolated lung event as the first site of distant disease. Isolated lung event was defined as disease limited to the thoracic cavity, without evidence of either uncontrolled local breast disease or metastatic disease elsewhere. Diagnosis of the lung event as a primary lung cancer, a metastatic breast lesion, or an indeterminate lesion was documented from the viewpoint of 1) the pathologic analysis and 2) the clinical impression at the time of the lung event. Results: Sixty six of the 1865 patients (3.5%) developed an isolated lung event. The relative distribution of the pathologic and clinical diagnoses is shown below: The 66 lung events were characterized either as a solitary pulmonary nodule (27), multiple nodules (23), pleural effusion alone (10), unknown (2), or miscellaneous other findings (4). Among the 47 patients for whom pathology was available, the diagnosis remained indeterminate for 24 (51%). For patients with a definitive pathologic diagnosis, 69% ((9(13))) of smokers had a new lung cancer compared to 20% ((2(10))) of non-smokers (p=0.036), and 67% ((10(15))) of patients with a solitary pulmonary nodule had lung cancer compared to 14% ((1(7))) for other lung presentations (p

  13. Prognostic impact of carcinoembryonic antigen (CEA) on patients with metastatic pancreatic cancer: A retrospective cohort study.

    Science.gov (United States)

    Imaoka, Hiroshi; Mizuno, Nobumasa; Hara, Kazuo; Hijioka, Susumu; Tajika, Masahiro; Tanaka, Tsutomu; Ishihara, Makoto; Hirayama, Yutaka; Hieda, Nobuhiro; Yoshida, Tsukasa; Okuno, Nozomi; Shimizu, Yasuhiro; Niwa, Yasumasa; Yamao, Kenji

    2016-01-01

    Carcinoembryonic antigen (CEA) is one of the most widely used tumor markers, and its level is increased in 30-60% of patients with pancreatic cancer (PC). However, little is known about the implications of CEA as a prognostic marker in metastatic PC. The purpose of this study was to examine the usefulness of CEA levels as a prognostic marker in patients with metastatic PC. We conducted a retrospective cohort study using data from a computerized database. A total of 433 patients with metastatic disease were analyzed. Median overall survival (OS) was significantly shorter for patients with high CEA (>5 ng/ml) than with normal CEA (≤5 ng/ml) (6.8 vs. 10.3 months, respectively; p CEA level was an independent predictive factor for OS (hazard ratio [HR], 1.81; 95% confidence interval [CI], 1.45-2.26). In the high CEA group, OS in patients treated with combination chemotherapy was similar to that with single-agent chemotherapy (median, 7.1 vs. 6.8 months; HR for OS, 0.99; 95% CI, 0.71-1.40). The present results show that CEA level is an independent prognostic factor in patients with metastatic PC. A combination chemotherapy regimen may offer modest survival benefit in patients with high CEA. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  14. Practical consensus recommendations on Her2 +ve breast cancer with solitary brain mets

    Directory of Open Access Journals (Sweden)

    Nitesh Rohatgi

    2018-01-01

    Full Text Available Breast cancer is a common cause of brain metastases, with metastases occurring in at least 10–16% of patients. Longer survival of patients with metastatic breast cancer and the use of better imaging techniques are associated with an increased incidence of brain metastases. Current therapies include surgery, whole-brain radiation therapy, stereotactic radiosurgery, chemotherapy and targeted therapies. However, the timing and appropriate use of these therapies is controversial and careful patient selection by using available prognostic tools is extremely important. Expert oncologist discussed on the mode of treatment to extend the OS and improve the quality of life ofHER2-positivebreast cancer patients with Solitary brain metastases. This expert group used data from published literature, practical experience and opinion of a large group of academic oncologists to arrive at this practical consensus recommendations for the benefit of community oncologists.

  15. Factors affecting the local control of stereotactic body radiotherapy for lung tumors including primary lung cancer and metastatic lung tumors

    International Nuclear Information System (INIS)

    Hamamoto, Yasushi; Kataoka, Masaaki; Yamashita, Motohiro

    2012-01-01

    The purpose of this study was to identify factors affecting local control of stereotactic body radiotherapy (SBRT) for lung tumors including primary lung cancer and metastatic lung tumors. Between June 2006 and June 2009, 159 lung tumors in 144 patients (primary lung cancer, 128; metastatic lung tumor, 31) were treated with SBRT with 48-60 Gy (mean 50.1 Gy) in 4-5 fractions. Higher doses were given to larger tumors and metastatic tumors in principle. Assessed factors were age, gender, tumor origin (primary vs. metastatic), histological subtype, tumor size, tumor appearance (solid vs. ground glass opacity), maximum standardized uptake value of positron emission tomography using 18 F-fluoro-2-deoxy-D-glucose, and SBRT doses. Follow-up time was 1-60 months (median 18 months). The 1-, 2-, and 3-year local failure-free rates of all lesions were 90, 80, and 77%, respectively. On univariate analysis, metastatic tumors (p<0.0001), solid tumors (p=0.0246), and higher SBRT doses (p=0.0334) were the statistically significant unfavorable factors for local control. On multivariate analysis, only tumor origin was statistically significant (p=0.0027). The 2-year local failure-free rates of primary lung cancer and metastatic lung tumors were 87 and 50%, respectively. A metastatic tumor was the only independently significant unfavorable factor for local control after SBRT. (author)

  16. Acute Respiratory Distress Syndrome after Treatment of Metastatic Prostate Cancer with Taxotere: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Ali Raufi

    2015-01-01

    Full Text Available Prostate cancer is the most common cancer in men. Docetaxel is a common chemotherapeutic agent that has proven its efficacy in the treatment of patients with both castration sensitive and resistant metastatic prostate cancer. We report a case of acute respiratory distress syndrome (ARDS in a patient with metastatic prostate cancer treated with docetaxel (Taxotere. ARDS is very rare but life threatening complication of docetaxel which requires aggressive supportive care and close monitoring. Better awareness and prompt diagnosis of this treatment related ARDS will improve the effectiveness and outcome of its management.

  17. Is there a role for antiandrogen monotherapy in patients with metastatic prostate cancer?

    DEFF Research Database (Denmark)

    Kaisary, A V; Iversen, P; Tyrrell, C J

    2001-01-01

    Castration is the most widely used form of androgen ablation employed in the treatment of metastatic (M1) prostate cancer. Non-steroidal antiandrogen monotherapy is a potential alternative treatment option for men for whom castration is unacceptable or not indicated. Of the three non-steroidal...... with a prostate specific antigen (PSA) level 400 ng/ml) may decide that quality of life and symptomatic benefits outweigh the slight survival disadvantage seen in clinical trials and opt for bicalutamide monotherapy as an alternative to castration.Prostate Cancer and Prostatic Diseases (2001) 4, 196-203....

  18. Bone pain induced by metastatic cancer: pathophysiology and treatment

    International Nuclear Information System (INIS)

    Salas-Herrera, Isaias; Huertas-Gabert, Luis Carlos

    2004-01-01

    Cancer patients who develop bone metastases are an estimated 60 to 84% . Of these 79% experienced pain syndromes are difficult to manage, of which 50% die without adequate pain relief and with a poor quality of life. Therefore, it is necessary to have accessible and effective medications for the management of this condition. The pathophysiology of pain in bone is reviewed and the drugs used most frequently in the management of this type of cancer pain are described. Furthermore an algorithm of 6 steps is presented and can guide the physician when making a therapeutic decision. (author) [es

  19. Diarrhoea Caused by Diffuse Metastatic Lobular Breast Cancer

    Directory of Open Access Journals (Sweden)

    Sjoerd F. Bakker

    2016-01-01

    Full Text Available A 70-year-old woman with a history of lobular breast cancer presented to our Outpatient Clinic with diarrhoea for the past 3 years. Clinical examination and laboratory research were normal. Colonoscopy showed diffuse mild erythema and a decreased vascular pattern. Biopsies from the ascending colon, transverse colon, and descending colon showed metastases of lobular breast carcinoma. Although gastrointestinal metastases are rare in breast cancer, our case emphasizes the need for further diagnostic efforts in patients with gastrointestinal symptoms and a history of breast carcinoma.

  20. General Information about Metastatic Squamous Neck Cancer with Occult Primary

    Science.gov (United States)

    ... causes the tissue to light up under a microscope. This type of test may be used to tell the difference between different types of cancer. Light and electron ... and high-powered microscopes to look for certain changes in the cells. ...

  1. Colorectal cancer: prevention and management of metastatic disease.

    Science.gov (United States)

    Sugarbaker, Paul H

    2014-01-01

    This paper compared the similarities and differences of the two most common types of colorectal cancer metastases. The treatment of liver metastases by surgery combined with systemic chemotherapy was explained. The different natural history of liver metastases as compared to peritoneal metastases and the possibility for prevention of peritoneal metastases were emphasized. Perioperative cancer chemotherapy or second-look surgery must be considered as individualized treatments of selected patients who have small volume peritoneal metastases or who are known to be at risk for subsequent disease progression on peritoneal surfaces. However, the fact that peritoneal metastases, when diagnosed in the follow-up of colorectal cancer patients, can be cured with a combination of cytoreductive surgery and hyperthermic perioperative chemotherapy cannot be ignored. Careful follow-up and timely intervention in colorectal cancer patients with progressive disease are a necessary part of the management strategies recommended by the multidisciplinary team. After a critical evaluation of the data currently available, these strategies for prevention and management of colorectal metastases are presented as the author's recommendations for a high standard of care. As more information becomes available, modifications may be necessary.

  2. Current treatment for colorectal cancer metastatic to the liver

    NARCIS (Netherlands)

    Cromheecke, M; de Jong, KP; Hoekstra, HJ

    1999-01-01

    Surgery is currently the only available treatment option which offers the potential for cure for patients with liver metastases from colorectal cancer. Of those who undergo a potentially curative operation for their primary tumour but subsequently recur, almost 80% will develop evidence of

  3. Expression profiling of circulating tumor cells in metastatic breast cancer

    Czech Academy of Sciences Publication Activity Database

    Lang, J.; Scott, J.H.; Wolf, D.M.; Novák, Petr; Punj, V.; Magbanua, M.J.M.; Zhu, W.Z.; Mineyev, N.; Haqq, CH.; Crothers, J.

    2015-01-01

    Roč. 149, č. 1 (2015), s. 121-131 ISSN 0167-6806 Institutional support: RVO:60077344 Keywords : Circulating tumor cells * Micrometastases * Breast cancer * EpCAM Subject RIV: FD - Oncology ; Hematology Impact factor: 4.085, year: 2015

  4. uPAR targeted radionuclide therapy with (177)Lu-DOTA-AE105 inhibits dissemination of metastatic prostate cancer.

    Science.gov (United States)

    Persson, Morten; Juhl, Karina; Rasmussen, Palle; Brandt-Larsen, Malene; Madsen, Jacob; Ploug, Michael; Kjaer, Andreas

    2014-08-04

    The urokinase-type plasminogen activator receptor (uPAR) is implicated in cancer invasion and metastatic development in prostate cancer and provides therefore an attractive molecular target for both imaging and therapy. In this study, we provide the first in vivo data on an antimetastatic effect of uPAR radionuclide targeted therapy in such lesions and show the potential of uPAR positron emission tomography (PET) imaging for identifying small foci of metastatic cells in a mouse model of disseminating human prostate cancer. Two radiolabeled ligands were generated in high purity and specific activity: a uPAR-targeting probe ((177)Lu-DOTA-AE105) and a nonbinding control ((177)Lu-DOTA-AE105mut). Both uPAR flow cytometry and ELISA confirmed high expression levels of the target uPAR in PC-3M-LUC2.luc cells, and cell binding studies using (177)Lu-DOTA-AE105 resulted in a specific binding with an IC50 value of 100 nM in a competitive binding experiment. In vivo, uPAR targeted radionuclide therapy significantly reduced the number of metastatic lesions in the disseminated metastatic prostate cancer model, when compared to vehicle and nontargeted (177)Lu groups (p < 0.05) using bioluminescence imaging. Moreover, we found a significantly longer metastatic-free survival, with 65% of all mice without any disseminated metastatic lesions present at 65 days after first treatment dose (p = 0.047). In contrast, only 30% of all mice in the combined control groups treated with (177)Lu-DOTA-AE105mut or vehicle were without metastatic lesions. No treatment-induced toxicity was observed during the study as evaluated by observing animal weight and H&E staining of kidney tissue (dose-limiting organ). Finally, uPAR PET imaging using (64)Cu-DOTA-AE105 detected all small, disseminated metastatic foci when compared with bioluminescence imaging in a cohort of animals during the treatment study. In conclusion, uPAR targeted radiotherapy resulted in a significant reduction in the number of

  5. Metastatic testicular cancer presenting as lower back pain in a pilot.

    Science.gov (United States)

    Bermudez, Daniela J; Groh, Jonathan

    2014-11-01

    Lower back pain is ubiquitous in the helicopter community and testicular cancer is the most common solid organ tumor that affects approximately 1% of men ages 15 to 35. However, rarely is lower back pain caused by testicular cancer and, in an otherwise healthy male, it is generally low on the differential diagnosis. Literature review discovered the most recent case report where lower back pain was the presenting symptom for testicular cancer was in 1987. A 26-yr-old male helicopter pilot presented to clinic complaining of lower back pain for greater than 1 yr for which conservative treatment had failed. The pain was so severe he was unable to sleep and had to remove himself from the flight schedule. The patient was seen by physical therapy and a chiropractor and treated with NSAIDs and other pain medications, including narcotics. After further investigation, it was discovered that the patient's lower back pain was a result of a retroperitoneal metastatic tumor originating from his right testicle. It is important to consider that, although most aviators in their twenties have been screened for chronic illness, they are still at risk for developing cancer. In this case, the patient never complained of testicular mass or pain and even denied symptoms during review of systems questioning. Proper education regarding the importance of self-examination and reporting of abnormalities is key to early detection and intervention. The 5-yr survival for metastatic testicular cancer is greater than 95%.

  6. Living and dying with metastatic bowel cancer: Serial in-depth interviews with patients.

    Science.gov (United States)

    Carduff, E; Kendall, M; Murray, S A

    2018-01-01

    Colorectal cancer is the second highest cause of cancer deaths. There are significant physical and psycho-social effects on quality of life with advanced disease. Despite this, there are few accounts of the patient experience from advanced illness through to dying. We elicited the longitudinal experiences of living and dying with incurable metastatic colorectal cancer by conducting serial interviews with patients for 12 months or until they died. The interviews were analysed, using a narrative approach, longitudinally as case studies and then together. Thirty-six interviews with 16 patients were conducted. Patients experience metastatic colorectal cancer in three phases; (1) Diagnosis and initial treatment; (2) Deterioration and social isolation and (3) Death and dying. Many patients initially said they hoped to survive, but, as "private" and in-depth accounts of the experience emerged in further interviews, so did the understanding that this hope co-existed with the knowledge that death was near. Palliative chemotherapy and the challenge of accessing private accounts of patient experience can inhibit care planning and prevent patients benefitting from an active holistic palliative care approach earlier in the disease trajectory. This study has immediate clinical relevance for health care professionals in oncology, palliative care and primary care. © 2017 The Authors. European Journal of Cancer Care Published by John Wiley & Sons Ltd.

  7. Analysis of autophagic flux in response to sulforaphane in metastatic prostate cancer cells

    Science.gov (United States)

    Watson, Gregory W; Wickramasekara, Samanthi; Fang, Yufeng; Palomera-Sanchez, Zoraya; Maier, Claudia S; Williams, David E; Dashwood, Roderick H; Perez, Viviana I; Ho, Emily

    2015-01-01

    Scope The phytochemical sulforaphane has been shown to decrease prostate cancer metastases in a genetic mouse model of prostate carcinogenesis, though the mechanism of action is not fully known. Sulforaphane has been reported to stimulate autophagy, and modulation of autophagy has been proposed to influence sulforaphane cytotoxicity; however, no conclusions about autophagy can be drawn without assessing autophagic flux, which has not been characterized in prostate cancer cells following sulforaphane treatment. Methods and Results We conducted an investigation to assess the impact of sulforaphane on autophagic flux in two metastatic prostate cancer cell lines at a concentration shown to decrease metastasis in vivo. Autophagic flux was assessed by multiple autophagy related proteins and substrates. We found that sulforaphane can stimulate autophagic flux and cell death only at high concentrations, above what has been observed in vivo. Conclusion These results suggest that sulforaphane does not directly stimulate autophagy or cell death in metastatic prostate cancer cells under physiologically relevant conditions, but instead supports the involvement of in vivo factors as important effectors of sulforaphane- mediated prostate cancer suppression. PMID:26108801

  8. [Prostate cancer diagnosed through the biopsy of the bone metastatic lesion; a case report].

    Science.gov (United States)

    Ueda, Yasuo; Higuchii, Yoshihide; Hashimoto, Takahiko; Mitsui, Youzou; Maruyamai, Takuo; Kondou, Nobuyuki; Nojima, Michio; Yamamoto, Shingo; Shincho, Mayumi; Hirota, Seiichi; Shima, Hiroki

    2007-05-01

    An 80-year-old man visited our clinic with the chief complaint of asymptomatic macroscopic hematuria secondary to anticoagulant medicine. Although digital rectal examination was normal, a high serum prostate specific antigen (PSA) level (85.9 ng/ml) led us to perform sextant prostate biopsy, resulting in negative for cancer. Three months later, since the serum PSA increased to 169 ng/ml with high serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 levels. Twelve-core prostate biopsy was performed again, but the result was negative. Pelvic magnetic resonance imaging (MRI) showed a metastatic lesion on the right pubic bone, which was biopsied, and turned out to be poorly differentiated prostate cancer in histology. Maximum androgen blockade failed to control PSA. Finally he died of pneumonia 55 days after the bone biopsy. To our knowledge, there were only two case reports diagnosed as prostate cancer by biopsies of the metastatic lesions in Japanese literature, but none in the English literature. These findings suggest that high serum levels of CEA and CA19-9 in patients with prostate cancer are indications of hormone-refractory prostate cancer resulting in poor prognosis.

  9. Docetaxel vs 5-fluorouracil plus vinorelbine in metastatic breast cancer after anthracycline therapy failure

    Science.gov (United States)

    Bonneterre, J; Roché, H; Monnier, A; Guastalla, J P; Namer, M; Fargeot, P; Assadourian, S

    2002-01-01

    This multicentre, randomised phase III study compared docetaxel with 5-fluorouracil+vinorelbine in patients with metastatic breast cancer after failure of neo/adjuvant or one line of palliative anthracycline-based chemotherapy. One hundred and seventy-six metastatic breast cancer patients were randomised to receive docetaxel (100 mg m−2) every 3 weeks or 5-fluorouracil+vinorelbine: 5-fluorouracil (750 mg m−2 per day continuous infusion) D1–5 plus vinorelbine (25 mg m−2) D1 and D5 of each 3-week cycle. Eighty-six patients received 516 cycles of docetaxel; 90 patients received 476 cycles of 5-fluorouracil+vinorelbine. Median time to progression (6.5 vs 5.1 months) and overall survival (16.0 vs 15.0 months) did not differ significantly between the docetaxel and 5-fluorouracil+vinorelbine arms, respectively. Six (7%) complete responses and 31 (36%) partial responses occurred with docetaxel (overall response rate 43%, 95% confidence interval: 32–53%), while 4 (4.4%) complete responses and 31 (34.4%) partial responses occurred with 5-fluorouracil+vinorelbine (overall response rate 38.8%, 95% confidence interval: 29–49%). Main grade 3–4 toxicities were (docetaxel vs 5-fluorouracil+vinorelbine): neutropenia 82% vs 67%; stomatitis 5% vs 40%; febrile neutropenia 13% vs 22%; and infection 2% vs 7%. There was one possible treatment-related death in the docetaxel arm and five with 5-fluorouracil+vinorelbine. In anthracycline-pretreated metastatic breast cancer patients, docetaxel showed comparable efficacy to 5-fluorouracil+vinorelbine, but was less toxic. British Journal of Cancer (2002) 87, 1210–1215. doi:10.1038/sj.bjc.6600645 www.bjcancer.com © 2002 Cancer Research UK PMID:12439707

  10. Metastatic Carcinoma Occurring in a Gastric Hyperplastic Polyp Mimicking Primary Gastric Cancer: The First Reported Case

    Directory of Open Access Journals (Sweden)

    Gabriel M. Groisman

    2014-01-01

    Full Text Available Hyperplastic polyps of the stomach are regarded as benign. However, in rare cases they may contain incipient primary carcinomas. To our knowledge, breast carcinoma metastatic to a gastric hyperplastic polyp has not yet been reported. We describe the case of a 69-year-old woman to whom a gastric polyp was endoscopically excised. The patient had previously undergone a right mastectomy for mixed, invasive ductal and lobular carcinoma 5 years earlier. Histological sections from the gastric lesion showed typical features of hyperplastic polyp with foci of poorly differentiated adenocarcinoma including signet ring cells infiltrating the lamina propria. The histologic findings were consistent with a primary gastric cancer. However, the carcinoma cells were immunopositive for estrogen and progesterone receptors and GATA3 and negative for CDX2, Hep Par 1, and MUC5AC. E-cadherin showed membranous reactivity in some of the carcinoma cells while in others it was negative. Accordingly, metastatic mixed, lobular and ductal breast carcinoma was diagnosed. We conclude that metastatic adenocarcinoma mimicking primary gastric cancer can be rarely encountered in hyperplastic gastric polyps.

  11. Exome Sequencing of Cell-Free DNA from Metastatic Cancer Patients Identifies Clinically Actionable Mutations Distinct from Primary Disease.

    Science.gov (United States)

    Butler, Timothy M; Johnson-Camacho, Katherine; Peto, Myron; Wang, Nicholas J; Macey, Tara A; Korkola, James E; Koppie, Theresa M; Corless, Christopher L; Gray, Joe W; Spellman, Paul T

    2015-01-01

    The identification of the molecular drivers of cancer by sequencing is the backbone of precision medicine and the basis of personalized therapy; however, biopsies of primary tumors provide only a snapshot of the evolution of the disease and may miss potential therapeutic targets, especially in the metastatic setting. A liquid biopsy, in the form of cell-free DNA (cfDNA) sequencing, has the potential to capture the inter- and intra-tumoral heterogeneity present in metastatic disease, and, through serial blood draws, track the evolution of the tumor genome. In order to determine the clinical utility of cfDNA sequencing we performed whole-exome sequencing on cfDNA and tumor DNA from two patients with metastatic disease; only minor modifications to our sequencing and analysis pipelines were required for sequencing and mutation calling of cfDNA. The first patient had metastatic sarcoma and 47 of 48 mutations present in the primary tumor were also found in the cell-free DNA. The second patient had metastatic breast cancer and sequencing identified an ESR1 mutation in the cfDNA and metastatic site, but not in the primary tumor. This likely explains tumor progression on Anastrozole. Significant heterogeneity between the primary and metastatic tumors, with cfDNA reflecting the metastases, suggested separation from the primary lesion early in tumor evolution. This is best illustrated by an activating PIK3CA mutation (H1047R) which was clonal in the primary tumor, but completely absent from either the metastasis or cfDNA. Here we show that cfDNA sequencing supplies clinically actionable information with minimal risks compared to metastatic biopsies. This study demonstrates the utility of whole-exome sequencing of cell-free DNA from patients with metastatic disease. cfDNA sequencing identified an ESR1 mutation, potentially explaining a patient's resistance to aromatase inhibition, and gave insight into how metastatic lesions differ from the primary tumor.

  12. Primary hepatic embryonal sarcoma masquerading as metastatic ovarian cancer

    Directory of Open Access Journals (Sweden)

    Praseedom Raaj

    2009-06-01

    Full Text Available Abstract Background Hepatic embryonal sarcoma (HES is a rare but aggressive primary tumor of the liver occurring most frequently in childhood. Case presentation We report a case of a 52 year old woman having previously undergone treatment for ovarian serous papillary carcinoma who subsequently presented with a large solitary mass in the liver. Initially this was presumed to be metastasis from the ovarian primary however, on further examination it was shown to be a primary hepatic embryonal sarcoma. Conclusion Primary liver tumors should be considered in differential diagnoses in patients with ovarian cancer who subsequently present with liver tumors. This is particularly important when there is no direct evidence of recurrence of ovarian cancer.

  13. Metastatic castration-resistant prostate cancer: time for innovation.

    Science.gov (United States)

    Tucci, Marcello; Scagliotti, Giorgio Vittorio; Vignani, Francesca

    2015-01-01

    Androgen deprivation is the mainstay of advanced prostate cancer treatment. Despite initial responses, almost all patients progress to castration-resistant prostate cancer (CRPC). The understanding of the biology of CRPC and the evidence that CRPC still remains driven by androgen receptor signaling led to the discovery of new therapeutic targets. In the last few years, large Phase III trials showed improvements in survival and outcomes and led to the approval of a CYP17 inhibitor (abiraterone), an androgen receptor antagonist (enzalutamide), the taxane cabazitaxel, an α-emitter (radium-223), the bone resorption-targeting drug denosumab and an immunotherapy (sipuleucel-T). This article describes the molecular mechanisms underlying castration resistance, discusses recent and ongoing trials and offers some insights into identifying the best sequence of new drugs.

  14. Metastatic colorectal cancer responsive to regorafenib for 2 years: a case report.

    Science.gov (United States)

    Yoshino, Kenji; Manaka, Dai; Kudo, Ryo; Kanai, Shunpei; Mitsuoka, Eisei; Kanto, Satoshi; Hamasu, Shinya; Konishi, Sayuri; Nishitai, Ryuta

    2017-08-18

    Regorafenib is an oral multikinase inhibitor that has been demonstrated as clinically effective in patients with metastatic colorectal cancer in phase III studies. Although disease control was achieved in 40% of the pretreated patients with metastatic colorectal cancer in the pivotal studies, radiological response has rarely been reported. Severe adverse events associated with regorafenib are known to occur during the first and second courses of treatment. We present a case of a 62-year-old Japanese patient whose metastatic colorectal cancer has been responding to treatment with regorafenib for 2 years. A 54-year-old Japanese man visited our institute exhibiting general malaise, and he was diagnosed with ascending colon cancer in April 2006. He underwent right hemicolectomy, and the final staging was T3N0M0, stage II. After 19 months, pulmonary metastasis and anastomotic recurrences were detected, and a series of operations were performed to resect both metastatic lesions. After that, liver metastasis, a duodenal metastasis with right renal invasion, right adrenal metastasis, and para-aortic lymph node metastases were observed during follow-up, and chemotherapy and resection were performed. The patient had metastatic para-aortic lymph nodes after the fifth tumor resection and underwent multiple lines of chemotherapy in April 2014. Regorafenib monotherapy was started at 80 mg/day. Then, regorafenib was increased to 120 mg/day in the second cycle. Regorafenib monotherapy led to 60% tumor shrinkage within the initial 2 months, and the tumor further decreased in size over 4 months until it became unrecognizable on imaging studies. The clinical effects of regorafenib monotherapy have shown a partial response according to Response Evaluation Criteria in Solid Tumors criteria. No severe adverse events were observed, except for mild fatigue and hand-foot syndrome. The patient has received 24 courses of regorafenib over 2 years without exhibiting tumor progression. To the

  15. Hyaluronan-Based Therapy for Metastatic Prostate Cancer

    Science.gov (United States)

    2016-09-01

    cancer cell lines (LNCaP) that do not highly express CD44 (Figure 3A). This important finding motivates CD44 targeting by HA-NPs to induce targeted...biotechnology professionals, manufacturing experts, clinicians and entrepreneurs to discuss clinical translation of a lead biologic drug and the development...allowed me to discuss clinical translation with entrepreneurs and professionals in the biotechnology field.  I was selected as one of the top 50 future

  16. New Epigenetic Therapeutic Intervention for Metastatic Breast Cancer

    Science.gov (United States)

    2016-04-01

    possess many epithelial- mesenchymal transition (EMT) characteristics including invasion, resistance to apoptosis, and cancer stem cell-like traits that...ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (Her2/neu), hence the name. The available treatments targeting these...analysis Her2/neu – human epidermal growth factor receptor 2 ITC – isothermal titration calorimetry NMR – nuclear magnetic resonance PR

  17. Prolactin receptor in breast cancer: marker for metastatic risk.

    Science.gov (United States)

    Shemanko, Carrie S

    2016-11-01

    Prolactin and prolactin receptor signaling and function are complex in nature and intricate in function. Basic, pre-clinical and translational research has opened up our eyes to the understanding that prolactin and prolactin receptor signaling function differently within different cellular contexts and microenvironmental conditions. Its multiple roles in normal physiology are subverted in cancer initiation and progression, and gradually we are teasing out the intricacies of function and therapeutic value. Recently, we observed that prolactin has a role in accelerating the time to bone metastasis in breast cancer patients and identified the mechanism by which prolactin stimulated breast cancer cell-mediated lytic osteoclast formation. The possibility that the prolactin receptor is a marker for metastasis, and specifically bone metastasis, is one that may have to be put into the context of the different variants of prolactin, different prolactin receptor isoforms and intricate signaling pathways that are regulated by the microenvironment. The more complete the picture, the better one can test biomarker identity and design clinical trials to test therapeutic intervention. This review will cover the recent advances and highlight the complexity of prolactin receptor biology. © 2016 Society for Endocrinology.

  18. Retrospective study of the effect of disease progression on patient reported outcomes in HER-2 negative metastatic breast cancer patients

    Directory of Open Access Journals (Sweden)

    Yu Elaine

    2011-06-01

    Full Text Available Abstract Background This retrospective study evaluated the impact of disease progression and of specific sites of metastasis on patient reported outcomes (PROs that assess symptom burden and health related quality of life (HRQoL in women with metastatic breast cancer (mBC. Methods HER-2 negative mBC patients (n = 102 were enrolled from 7 U.S. community oncology practices. Demographic, disease and treatment characteristics were abstracted from electronic medical records and linked to archived Patient Care Monitor (PCM assessments. The PCM is a self-report measure of symptom burden and HRQoL administered as part of routine care in participating practices. Linear mixed models were used to examine change in PCM scores over time. Results Mean age was 57 years, with 72% of patients Caucasian, and 25% African American. Median time from mBC diagnosis to first disease progression was 8.8 months. Metastasis to bone (60%, lung (28% and liver (26% predominated at initial metastatic diagnosis. Results showed that PCM items assessing fatigue, physical pain and trouble sleeping were sensitive to either general effects of disease progression or to effects associated with specific sites of metastasis. Progression of disease was also associated with modest but significant worsening of General Physical Symptoms, Treatment Side Effects, Acute Distress and Impaired Performance index scores. In addition, there were marked detrimental effects of liver metastasis on Treatment Side Effects, and of brain metastasis on Acute Distress. Conclusions Disease progression has a detrimental impact on cancer-related symptoms. Delaying disease progression may have a positive impact on patients' HRQoL.

  19. Abiraterone Acetate: A Review in Metastatic Castration-Resistant Prostrate Cancer.

    Science.gov (United States)

    Scott, Lesley J

    2017-09-01

    Oral abiraterone acetate (Zytiga ® ) is a selective inhibitor of CYP17 and thereby inhibits androgen biosynthesis, with androgen signalling crucial in the progression from primary to metastatic prostate cancer (PC) and subsequently, in the development of metastatic castration-resistant PC (mCRPC). In large phase 3 trials and in the clinical practice setting, oral abiraterone acetate in combination with prednisone was an effective treatment and had an acceptable, manageable tolerability and safety profile in chemotherapy-naive and docetaxel-experienced men with mCRPC. In the pivotal global phase 3 trials, relative to placebo (+prednisone), abiraterone acetate (+prednisone) prolonged overall survival (OS) at data maturity (final analysis) and radiographic progression-free survival (rPFS) at all assessed timepoints. Given its efficacy in prolonging OS and its convenient once-daily oral regimen, in combination with prednisone, abiraterone acetate is an important first-line option for the treatment of mCRPC.

  20. Mayo Clinic Cancer Center experience of metastatic extramammary Paget disease 1998-2012

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    Leslie Padrnos

    2016-11-01

    Full Text Available Extramammary Paget disease (EMPD is a rare cutaneous malignancy. The most common presentation of EMPD is the vulva followed by perianal involvement. Most cases are localized to the dermis with treatment focused on surgery, topical treatment or radiotherapy. Recurrence is frequent despite therapies utilized. Metastatic extramammary Paget disease is uncommon and, as such, standard treatment guidelines do not exist. This study sought to evaluate the treatment regimens and outcomes of patients treated at a Mayo Clinic Center from 1998-2012. Cancer registry inquiry revealed 261 patients with report advanced Paget disease during these years. Ten cases of metastatic EPMD were identified with sufficient documentation for review. This review reveals support for utilizing localized radiation therapy for bulky disease sequentially with systemic chemotherapy consisting of carboplatin and paclitaxel or irinotecan. Further studies are necessary to define the optimal treatment regimen.

  1. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Van Cutsem, E; Cervantes, A; Adam, R

    2016-01-01

    for and undergoing surgical resection of their localised metastatic disease but also to a more strategic approach to the delivery of systemic therapy and an expansion in the use of ablative techniques. This reflects the increase in the number of patients that are being managed within a multidisciplinary team...... based on the current available evidence to provide a series of evidence-based recommendations to assist in the treatment and management of patients with mCRC in this rapidly evolving treatment setting.......Colorectal cancer (CRC) is one of the most common malignancies in Western countries. Over the last 20 years, and the last decade in particular, the clinical outcome for patients with metastatic CRC (mCRC) has improved greatly due not only to an increase in the number of patients being referred...

  2. The pioneer factor PBX1 is a novel driver of metastatic progression in ERα-positive breast cancer

    Science.gov (United States)

    Magnani, Luca; Patten, Darren K.; Nguyen, Van T.M.; Hong, Sung-Pil; Steel, Jennifer H.; Patel, Naina; Lombardo, Ylenia; Faronato, Monica; Gomes, Ana R.; Woodley, Laura; Page, Karen; Guttery, David; Primrose, Lindsay; Garcia, Daniel Fernandez; Shaw, Jacqui; Viola, Patrizia; Green, Andrew; Nolan, Christopher; Ellis, Ian O.; Rakha, Emad A.; Shousha, Sami; Lam, Eric W.-F.; Győrffy, Balázs; Lupien, Mathieu; Coombes, R. Charles

    2015-01-01

    Over 30% of ERα breast cancer patients develop relapses and progress to metastatic disease despite treatment with endocrine therapies. The pioneer factor PBX1 translates epigenetic cues and mediates estrogen induced ERα binding. Here we demonstrate that PBX1 plays a central role in regulating the ERα transcriptional response to epidermal growth factor (EGF) signaling. PBX1 regulates a subset of EGF-ERα genes highly expressed in aggressive breast tumours. Retrospective stratification of luminal patients using PBX1 protein levels in primary cancer further demonstrates that elevated PBX1 protein levels correlate with earlier metastatic progression. In agreement, PBX1 protein levels are significantly upregulated during metastatic progression in ERα-positive breast cancer patients. Finally we reveal that PBX1 upregulation in aggressive tumours is partly mediated by genomic amplification of the PBX1 locus. Correspondingly, ERα-positive breast cancer patients carrying PBX1 amplification are characterized by poor survival. Notably, we demonstrate that PBX1 amplification can be identified in tumor derived-circulating free DNA of ERα-positive metastatic patients. Metastatic patients with PBX1 amplification are also characterized by shorter relapse-free survival. Our data identifies PBX1 amplification as a functional hallmark of aggressive ERα-positive breast cancers. Mechanistically, PBX1 amplification impinges on several critical pathways associated with aggressive ERα-positive breast cancer. PMID:26215677

  3. 3D radiation therapy or intensity-modulated radiotherapy for recurrent and metastatic cervical cancer: the Shanghai Cancer Hospital experience.

    Directory of Open Access Journals (Sweden)

    Su-Ping Liu

    Full Text Available We evaluate the outcomes of irradiation by using three-dimensional radiation therapy (3D-RT or intensity-modulated radiotherapy (IMRT for recurrent and metastatic cervical cancer. Between 2007 and 2010, 50 patients with recurrent and metastatic cervical cancer were treated using 3D-RT or IMRT. The median time interval between the initial treatment and the start of irradiation was 12 (6-51 months. Salvage surgery was performed before irradiation in 5 patients, and 38 patients received concurrent chemotherapy. Sixteen patients underwent 3D-RT, and 34 patients received IMRT. Median follow-up for all the patients was 18.3 months. Three-year overall survival and locoregional control were 56.1% and 59.7%, respectively. Three-year progression-free survival and disease-free survival were 65.3% and 64.3%, respectively. Nine patients developed grade 3 leukopenia. Grade 5 acute toxicity was not observed in any of the patients; however, 2 patients developed Grade 3 late toxicity. 3D-RT or IMRT is effective for the treatment of recurrent and metastatic cervical cancer, with the 3-year overall survival of 56.1%, and its complications are acceptable. Long-term follow-up and further studies are needed to confirm the role of 3D-RT or IMRT in the multimodality management of the disease.

  4. Management of elderly patients with prostate cancer without metastatic lesions

    International Nuclear Information System (INIS)

    Sakamoto, Naotaka; Akitake, Masakazu; Ikoma, Saya; Ri, Ken; Masuda, Katsuaki; Yoshikawa, Masahiro; Iguchi, Atsushi

    2010-01-01

    In order to assess the optimal management for elderly patients with localized and locally advanced prostate cancer (clinical stage: T1-T4N0M0), we reviewed the prognoses. From April 2000 to December 2008, we treated and followed up 175 patients aged 75 years, or older. In almost all of the patients above 79 years of age, endocrine therapy was selected. Among the 75 to 79-year-old patients, the proportion of radiation therapy, including external beam radiation therapy (EBRT) and high-dose-rate brachytherapy (HDR-brachytherapy), as well as radical prostatectomy increased. The follow-up period for all the patients was 0 to 106 months (median, 32 months). In the low- and intermediate-risk group, the actuarial biochemical control rate at 60 months for radical prostatectomy and endocrine therapy was 100% and 90%, respectively, and no patients with EBRT combined with endocrine therapy, and HDR-brachytherapy had biochemical failure at 34 and 46 months, respectively. In the high-risk group with 75 to 79-year-old patients, the actuarial biochemical control rate at 60 months for EBRT combined with endocrine therapy, radical prostatectomy and endocrine therapy was 71.4%, 69.0% and 55.7%, respectively, while the actuarial biochemical control rate at 48 months for HDR-brachytherapy was 40.9%. In the high-risk group with patients above 79 years of age, the actuarial biochemical control rate at 60 months for endocrine therapy was 64.5%. Prostate cancer death was recognized only in 1 patient within the high-risk group, treated by endocrine therapy. In all the patients, the overall survival rate at 60 months for EBRT combined with endocrine therapy, HDR-brachytherapy, radical prostatectomy and endocrine therapy was 100%, 100%, 76.4% and 89.5%, respectively. The actuarial biochemical control rate and overall survival rate were not significant among the management options in each risk group. However, the 75 to 79-year-old patients within the high-risk group, who were treated with

  5. Current status of treatment of metastatic colorectal cancer with special reference to cetuximab and elderly patients

    Directory of Open Access Journals (Sweden)

    Per Pfeiffer

    2008-12-01

    Full Text Available Per Pfeiffer, Camilla Qvortrup, Jon K BjerregaardDepartment of Oncology, Odense University Hospital. Institute of Clinical Research, University of Southern Denmark. Odense C, DenmarkPurpose: Elderly cancer patients often have co-morbidities and other characteristics that make the selection of optimal treatment more complex. The introduction of targeted therapies in colorectal cancer has further complicated this problem. This review will focus on the role of the EGFR antibody cetuximab in elderly patients.Methods: We have reviewed the available evidence in the literature to evaluate the results of therapy with cetuximab, alone or in combination with chemotherapy, with a focus on elderly patients with metastatic colorectal cancer (mCRC.Results: In patients with mCRC, combination chemotherapy prolongs median survival to more than 18 months and even around 24 months in combination with cetuximab in selected patients. No prospective studies have evaluated cetuximab in elderly patients. However, subgroup analyses from randomized trials and retrospective analysis suggest that the efficacy of chemotherapy and cetuximab is maintained in fit elderly patients, but with slightly increased but acceptable toxicity.Conclusion: No prospective cetuximab studies have been conducted solely in a population of elderly patients. However, available data suggest that outcomes in the fit elderly mirror results observed in younger patients.Keywords: metastatic colorectal cancer, cetuximab, elderly patients

  6. Hope, optimism and survival in a randomised trial of chemotherapy for metastatic colorectal cancer.

    Science.gov (United States)

    Schofield, Penelope E; Stockler, M R; Zannino, D; Tebbutt, N C; Price, T J; Simes, R J; Wong, N; Pavlakis, N; Ransom, D; Moylan, E; Underhill, C; Wyld, D; Burns, I; Ward, R; Wilcken, N; Jefford, M

    2016-01-01

    Psychological responses to cancer are widely believed to affect survival. We investigated associations between hope, optimism, anxiety, depression, health utility and survival in patients starting first-line chemotherapy for metastatic colorectal cancer. Four hundred twenty-nine subjects with metastatic colorectal cancer in a randomised controlled trial of chemotherapy completed baseline questionnaires assessing the following: hopefulness, optimism, anxiety and depression and health utility. Hazard ratios (HRs) and P values were calculated with Cox models for overall survival (OS) and progression-free survival (PFS) in univariable and multivariable analyses. Median follow-up was 31 months. Univariable analyses showed that OS was associated negatively with depression (HR 2.04, P optimism, anxiety or hopefulness. PFS was not associated with hope, optimism, anxiety or depression in any analyses. Depression and health utility, but not optimism, hope or anxiety, were associated with survival after controlling for known prognostic factors in patients with advanced colorectal cancer. Further research is required to understand the nature of the relationship between depression and survival. If a causal mechanism is identified, this may lead to interventional possibilities.

  7. Emerging combination therapies for metastatic colorectal cancer – impact of trifluridine/tipiracil

    Directory of Open Access Journals (Sweden)

    Puthiamadathil JM

    2017-10-01

    Full Text Available Jeevan M Puthiamadathil,1 Benjamin A Weinberg1,2 1Department of Medicine, 2Ruesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA Abstract: Patients with metastatic colorectal cancer (mCRC are surviving longer now than ever before, but mortality rates are still high and more effective therapies are clearly needed. For patients with disease that is refractory to fluoropyrimidines, oxaliplatin, irinotecan, and biologic agents targeting the vascular endothelial growth factor and epidermal growth factor receptor pathways, novel treatment options trifluridine/tipiracil (TAS-102 and regorafenib can be effective disease stabilizers. However, objective clinical responses are rare and toxicities are manageable but common. In order to tackle poor clinical responses to TAS-102, there is an ongoing effort to effectively combine this drug with other agents, particularly those targeting angiogenesis. Certain subpopulations appear to benefit more than others from TAS-102; those that benefit often have underlying genetic defects in DNA repair pathways and/or develop neutropenia. In this review, we focus on the role of TAS-102 in the treatment of mCRC, including its use in combination with other agents, potential predictive biomarkers of response to TAS-102, and possible future directions. Keywords: metastatic colorectal cancer, trifluridine, tipiracil, TAS-102, regorafenib

  8. A Case of Long Term Survival in Woman with Metastatic Breast Cancer Treated with Trastuzumab

    Directory of Open Access Journals (Sweden)

    Deyan N. Davidov

    2012-02-01

    Full Text Available Intravenous Trastuzumab is an effective treatment for metastatic breast cancer after failure of first- line chemotherapy for patients with human epidermal growth factor 2 (HER- 2 - positive receptor. The aim of this study is to present of case of long time survival woman with metastatic breast cancer. The case is a 55- years old female. She underwent left mastectomy with axillary lymphadenectomy for breast cancer. Histological examination showed invasive ductal carcinoma, grade III, estrogen and progesterone receptor- negative, HER2- positive receptor status. Radiotherapy and six courses with antracyclines were performed as adjuvant chemotherapy. One year after the operation she was diagnosed to have lung metastases. Treatment was initiated with Trastuzumab 8 mg/kg for loading dose and 4 mg/kg maintenance dose every week. Treatment was continued for more than two years. Control computer tomography indicates stable disease. No adverse events were reported for twenty four months of Trastuzumab treatment. Treatment was stopped due to patients withdrawn. Overall survival was 31 months. This case indicate that long term Trastuzumab would be an optimal treatment for HER2- positive breast cancer patients.

  9. Osteonecrosis of the jaw in patients with metastatic breast cancer: ethnic and socio-economic aspects.

    Science.gov (United States)

    Quispe, Dolly; Shi, Runhua; Burton, Gary

    2011-01-01

    Bisphosphonate therapy is an important adjunct to the treatment of patients with bone metastasis. Osteonecrosis of the jaw (ONJ), a complication related to bisphosphonate therapy, is reported in up to 7% of patients with metastatic breast cancer. The objective of this study was to define the prevalence and to identify risk factors associated with development of ONJ in a predominantly low socio-economic population. Medical records of patients with a diagnosis of metastatic breast cancer with bone metastasis seen between 2002 and 2007 were reviewed. All patients received a minimum of four infusions of zolendronic acid. Data on demographics, insurance status, tobacco use, concurrent therapy, body mass index, and number of zolendronic acid infusions were analyzed. Of the 110 patient analyzed, 10 developed ONJ (9%) with the mean number of zolendronic acid infusions in patients with ONJ of 22.9 ± 17. ONJ was seen more frequently in Caucasian than in African Americans patients (15% versus 2%; p = 0.019). ONJ was associated with older age at diagnosis of metastatic breast cancer (p = 0.02), tobacco use (p = 0.049), but was not associated with SES or duration of therapy. After adjusting for SES, Caucasian patients were 9.1 times more likely to have ONJ when compared with African American patients. (95% CI 1.03-81.7). Our results suggest an increase prevalence of ONJ in Caucasian breast cancer patients. However, as our study population is small, additional studies to confirm this finding are needed. © 2011 Wiley Periodicals, Inc.

  10. A case of long term survival with skeletal only metastatic breast cancer.

    Science.gov (United States)

    Kuechle, Joseph B; McGrath, Brian E; Khoury, Thaer; Mindell, Eugene R

    2015-01-01

    The prognosis of patients with metastatic breast cancer is very poor. Because of this, treatment of skeletal metastasis is often palliative with limited goals rather than cure. However, there are those patients, such as presented here, who survive for an extended time. This thirty-six year old female presented with lytic lesions to one ulna and rib five years after mastectomy for breast cancer. Despite radiation and chemotherapy, the ulnar lesion expanded and resulted in an elbow dislocation. The rib lesion was resected and the arm amputated above the elbow. She developed local recurrence in both her above elbow amputation stump and chest wall and a more proximal below shoulder amputation was performed with resection of chest wall lesion. Even though she had locally aggressive disease, she has survived for 31 years after diagnosis without any evidence of disease. Reports of metastatic breast cancer survival indicate the five year survival to be 15%. There have been few reports indicating that those patients with skeletal only or oligometastatic disease have improved prognosis. It is not clear what biological properties of these tumors results in the improved survival. This case highlights the challenges of giving patients the optimal treatment in the light of limited ability to predict prognosis. It also highlights the need to further investigate the phenotypes of breast cancer that can, despite metastatic disease and with modern treatment go on to long survival. In addition this case demonstrates the importance of long term followup. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Overexpression of Oct4 suppresses the metastatic potential of breast cancer cells via Rnd1 downregulation.

    Science.gov (United States)

    Shen, Long; Qin, Kunhua; Wang, Dekun; Zhang, Yan; Bai, Nan; Yang, Shengyong; Luo, Yunping; Xiang, Rong; Tan, Xiaoyue

    2014-11-01

    Although Oct4 is known as a critical transcription factor involved in maintaining "stemness", its role in tumor metastasis is still controversial. Herein, we overexpressed and silenced Oct4 expression in two breast cancer cell lines, MDA-MB-231 and 4T1, separately. Our data showed that ectopic overexpression of Oct4 suppressed cell migration and invasion in vitro and the formation of metastatic lung nodules in vivo. Conversely, Oct4 downregulation increased the metastatic potential of breast cancer cells both in vitro and in vivo. Furthermore, we identified Rnd1 as the downstream target of Oct4 by ribonucleic acid sequencing (RNA-seq) analysis, which was significantly downregulated upon Oct4 overexpression. Chromatin immunoprecipitation assays revealed the binding of Oct4 to the promoter region of Rnd1 by ectopic overexpression of Oct4. Dual luciferase assays indicated that Oct4 overexpression suppressed transcriptional activity of the Rnd1 promoter. Moreover, overexpression of Rnd1 partially rescued the inhibitory effects of Oct4 on the migration and invasion of breast cancer cells. Overexpression of Rnd1 counteracted the influence of Oct4 on the formation of cell adhesion and lamellipodia, which implied a potential underlying mechanism involving Rnd1. In addition, we also found that overexpression of Oct4 led to an elevation of E-cadherin expression, even in 4T1 cells that possess a relatively high basal level of E-cadherin. Rnd1 overexpression impaired the promoting effects of Oct4 on E-cadherin expression in MDA-MB-231 cells. These results suggest that Oct4 affects the metastatic potential of breast cancer cells through Rnd1-mediated effects that influence cell motility and E-cadherin expression. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. T Cells Targeting Carcinoembryonic Antigen Can Mediate Regression of Metastatic Colorectal Cancer but Induce Severe Transient Colitis

    Science.gov (United States)

    Parkhurst, Maria R; Yang, James C; Langan, Russell C; Dudley, Mark E; Nathan, Debbie-Ann N; Feldman, Steven A; Davis, Jeremy L; Morgan, Richard A; Merino, Maria J; Sherry, Richard M; Hughes, Marybeth S; Kammula, Udai S; Phan, Giao Q; Lim, Ramona M; Wank, Stephen A; Restifo, Nicholas P; Robbins, Paul F; Laurencot, Carolyn M; Rosenberg, Steven A

    2011-01-01

    Autologous T lymphocytes genetically engineered to express a murine T cell receptor (TCR) against human carcinoembryonic antigen (CEA) were administered to three patients with metastatic colorectal cancer refractory to standard treatments. All patients experienced profound decreases in serum CEA levels (74–99%), and one patient had an objective regression of cancer metastatic to the lung and liver. However, a severe transient inflammatory colitis that represented a dose limiting toxicity was induced in all three patients. This report represents the first example of objective regression of metastatic colorectal cancer mediated by adoptive T cell transfer and illustrates the successful use of a TCR, raised in human leukocyte antigen (HLA) transgenic mice, against a human tumor associated antigen. It also emphasizes the destructive power of small numbers of highly avid T cells and the limitations of using CEA as a target for cancer immunotherapy. PMID:21157437

  13. Polychlorinated Biphenyls (PCBs) Enhance Metastatic Properties of Breast Cancer Cells by Activating Rho-Associated Kinase (ROCK)

    Science.gov (United States)

    Liu, Sijin; Li, Shitao; Du, Yuguo

    2010-01-01

    Background Polychlorinated biphenyls (PCBs) are a family of structurally related chlorinated aromatic hydrocarbons. Numerous studies have documented a wide spectrum of biological effects of PCBs on human health, such as immunotoxicity, neurotoxocity, estrogenic or antiestrogenic activity, and carcinogensis. The role of PCBs as etiologic agents for breast cancer has been intensively explored in a variety of in vivo, animal and epidemiologic studies. A number of investigations indicated that higher levels of PCBs in mammary tissues or sera correlated to breast cancer risk, and PCBs might be implicated in advancing breast cancer progression. Methodology/Principal Findings In the current study, we for the first time report that PCBs greatly promote the ROCK activity and therefore increase cell motility for both non-metastatic and metastatic human breast cancer cells in vitro. In the in vivo study, PCBs significantly advance disease progression, leading to enhanced capability of metastatic breast cancer cells to metastasize to bone, lung and liver. Additionally, PCBs robustly induce the production of intracellular reactive oxygen species (ROS) in breast cancer cells; ROS mechanistically elevate ROCK activity. Conclusions/Significance PCBs enhance the metastatic propensity of breast cancer cells by activating the ROCK signaling, which is dependent on ROS induced by PCBs. Inhibition of ROCK may stand for a unique way to restrain metastases in breast cancer upon PCB exposure. PMID:20585605

  14. Polychlorinated biphenyls (PCBs enhance metastatic properties of breast cancer cells by activating Rho-associated kinase (ROCK.

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    Sijin Liu

    Full Text Available BACKGROUND: Polychlorinated biphenyls (PCBs are a family of structurally related chlorinated aromatic hydrocarbons. Numerous studies have documented a wide spectrum of biological effects of PCBs on human health, such as immunotoxicity, neurotoxicity, estrogenic or antiestrogenic activity, and carcinogenesis. The role of PCBs as etiologic agents for breast cancer has been intensively explored in a variety of in vivo, animal and epidemiologic studies. A number of investigations indicated that higher levels of PCBs in mammary tissues or sera correlated to breast cancer risk, and PCBs might be implicated in advancing breast cancer progression. METHODOLOGY/PRINCIPAL FINDINGS: In the current study, we for the first time report that PCBs greatly promote the ROCK activity and therefore increase cell motility for both non-metastatic and metastatic human breast cancer cells in vitro. In the in vivo study, PCBs significantly advance disease progression, leading to enhanced capability of metastatic breast cancer cells to metastasize to bone, lung and liver. Additionally, PCBs robustly induce the production of intracellular reactive oxygen species (ROS in breast cancer cells; ROS mechanistically elevate ROCK activity. CONCLUSIONS/SIGNIFICANCE: PCBs enhance the metastatic propensity of breast cancer cells by activating the ROCK signaling, which is dependent on ROS induced by PCBs. Inhibition of ROCK may stand for a unique way to restrain metastases in breast cancer upon PCB exposure.

  15. 2012 European Thyroid Association Guidelines for Metastatic Medullary Thyroid Cancer

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    V V Voskoboynikov

    2013-06-01

    Full Text Available Distant metastases are the main cause of death in patients with medullary thyroid cancer (MTC. These 21 recommendations focus on MTC patients with distant metastases and a detailed followup protocol of patients with biochemical or imaging evidence of disease, selection criteria for treatment, and treatment modalities, including local and systemic treatments based on the results of recent trials. Asymptomatic patients with low tumor burden and stable disease may benefit from local treatment modalities and can be followed up at regular intervals of time. Imaging is usually performed every 6–12 months, or at longer inter vals of time depending on the doubling times of serum calcitonin and carcinoembryonic antigen levels. Patients with symptoms, large tumor burden and progression on imaging should receive systemic treatment. Indeed, major progress has recently been achieved with novel targeted therapies using kinase inhibitors directed against RET and VEGFR, but further research is needed to improve the outcome of these patients.

  16. Identification of extracapsular invasion of the metastatic lymph nodes as a useful prognostic sign in patients with resectable colorectal cancer.

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    Komuta, K; Okudaira, S; Haraguchi, M; Furui, J; Kanematsu, T

    2001-12-01

    The present study was undertaken to evaluate whether the microscopic patterns of distribution and extracapsular invasion of cancer cells in the regional lymph nodes were linked to the survival rates for patients with advanced colorectal cancer who undergo a curative surgical resection. Two hundred ninety-six surgically resected metastatic lymph nodes from 84 patients with node-positive colorectal cancer were microscopically examined. The distribution of cancer cells in the lymph nodes were grouped into two types: type A (> or =50 percent cancer) and type B (cancer). The extracapsular invasion of cancer cells in the nodes were divided into three subgroups: pattern X (no evidence of cancer cell invasion into the adjacent tissue); pattern Y (less than five cancer cells were seen in the adjacent tissue); and pattern Z (more than five cancer cells invaded the adjacent tissue). The patients, based on these microscopic manifestations of metastatic patterns in the nodes, were divided into three groups: Group 1, patients with pattern X nodal metastases only; Group 2, patients with pattern Y and pattern (X + Y) nodal metastases; and Group 3, patients with pattern Z, pattern (X + Z), pattern (Y + Z), and pattern (X + Y + Z) nodal metastases. The survival rates and disease-free survival rates for patients with metastatic lymph nodes showing an extracapsular invasion pattern (Groups 2 and 3) were significantly worse than those for patients with metastatic nodes showing no extracapsular invasion pattern only (Group 1; P thesis of this article that the identification of extracapsular invasion of the metastatic lymph nodes can be taken as a useful prognostic sign in patients with resectable colorectal cancer.

  17. Increased diacylglycerol kinase ζ expression in human metastatic colon cancer cells augments Rho GTPase activity and contributes to enhanced invasion

    International Nuclear Information System (INIS)

    Cai, Kun; Mulatz, Kirk; Ard, Ryan; Nguyen, Thanh; Gee, Stephen H

    2014-01-01

    Unraveling the signaling pathways responsible for the establishment of a metastatic phenotype in carcinoma cells is critically important for understanding the pathology of cancer. The acquisition of cell motility is a key property of metastatic tumor cells and is a prerequisite for invasion. Rho GTPases regulate actin cytoskeleton reorganization and the cellular responses required for cell motility and invasion. Diacylglycerol kinase ζ (DGKζ), an enzyme that phosphorylates diacylglycerol to yield phosphatidic acid, regulates the activity of the Rho GTPases Rac1 and RhoA. DGKζ mRNA is highly expressed in several different colon cancer cell lines, as well as in colon cancer tissue relative to normal colonic epithelium, and thus may contribute to the metastatic process. To investigate potential roles of DGKζ in cancer metastasis, a cellular, isogenic model of human colorectal cancer metastatic transition was used. DGKζ protein levels, Rac1 and RhoA activity, and PAK phosphorylation were measured in the non-metastatic SW480 adenocarcinoma cell line and its highly metastatic variant, the SW620 line. The effect of DGKζ silencing on Rho GTPase activity and invasion through Matrigel-coated Transwell inserts was studied in SW620 cells. Invasiveness was also measured in PC-3 prostate cancer and MDA-MB-231 breast cancer cells depleted of DGKζ. DGKζ protein levels were elevated approximately 3-fold in SW620 cells compared to SW480 cells. There was a concomitant increase in active Rac1 in SW620 cells, as well as substantial increases in the expression and phosphorylation of the Rac1 effector PAK1. Similarly, RhoA activity and expression were increased in SW620 cells. Knockdown of DGKζ expression in SW620 cells by shRNA-mediated silencing significantly reduced Rac1 and RhoA activity and attenuated the invasiveness of SW620 cells in vitro. DGKζ silencing in highly metastatic MDA-MB-231 breast cancer cells and PC-3 prostate cancer cells also significantly attenuated

  18. Mechanisms of CTC Biomarkers in Breast Cancer Brain Metastasis

    Science.gov (United States)

    2015-10-01

    assays are shown on the left). Control, non-invasive/non-BCBM generating MCF7 and invasive/BCBM generating MDA-MB231BR breast cancer cells were...visualized invadopodia formation. We used non-invasive poorly metastatic MCF7 and highly metastatic MDA-MB231BR breast cancer cells as negative and...control MCF7 cell- derived spheroids did not form any protrusions whereas invadopodia formation was noted when employing invasive 231BR spheroids. Of

  19. Nuclear IGF-1R predicts chemotherapy and targeted therapy resistance in metastatic colorectal cancer.

    Science.gov (United States)

    Codony-Servat, Jordi; Cuatrecasas, Miriam; Asensio, Elena; Montironi, Carla; Martínez-Cardús, Anna; Marín-Aguilera, Mercedes; Horndler, Carlos; Martínez-Balibrea, Eva; Rubini, Michele; Jares, Pedro; Reig, Oscar; Victoria, Iván; Gaba, Lydia; Martín-Richard, Marta; Alonso, Vicente; Escudero, Pilar; Fernández-Martos, Carlos; Feliu, Jaime; Méndez, Jose Carlos; Méndez, Miguel; Gallego, Javier; Salud, Antonieta; Rojo, Federico; Castells, Antoni; Prat, Aleix; Rosell, Rafael; García-Albéniz, Xabier; Camps, Jordi; Maurel, Joan

    2017-12-05

    Although chemotherapy is the cornerstone treatment for patients with metastatic colorectal cancer (mCRC), acquired chemoresistance is common and constitutes the main reason for treatment failure. Monoclonal antibodies against insulin-like growth factor-1 receptor (IGF-1R) have been tested in pre-treated mCRC patients, but results have been largely deceiving. We analysed time to progression, overall survival, and the mutational status of RAS, BRAF and nuclear p-IGF-1R expression by immunohistochemistry, in 470 metastatic CRC patients. The effect of IGF-1R activation and distribution was also assessed using cellular models of CRC and RNAi for functional validation. Nuclear IGF-1R increased in metastatic tumours compared to paired untreated primary tumours, and significantly correlated with poor overall survival in mCRC patients. In vitro, chemo-resistant cell lines presented significantly higher levels of IGF-1R expression within the nuclear compartment, and PIAS3, a protein implicated also in the sumoylation process of intranuclear proteins, contributed to IGF-1R nuclear sequestration, highlighting the essential role of PIAS3 in this process. Intriguingly, we observed that ganitumab, an IGF-1R blocking-antibody used in several clinical trials, and dasatinib, an SRC inhibitor, increased the nuclear localisation of IGF-1R. Our study demonstrates that IGF-1R nuclear location might lead to chemotherapy and targeted agent resistance.

  20. Identification of Tetranectin as a Potential Biomarker for Metastatic Oral Cancer

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    Shen Hu

    2010-09-01

    Full Text Available Lymph node involvement is the most important predictor of survival rates in patients with oral squamous cell carcinoma (OSCC. A biomarker that can indicate lymph node metastasis would be valuable to classify patients with OSCC for optimal treatment. In this study, we have performed a serum proteomic analysis of OSCC using 2-D gel electrophoresis and liquid chromatography/tandem mass spectrometry. One of the down-regulated proteins in OSCC was identified as tetranectin, which is a protein encoded by the CLEC3B gene (C-type lectin domain family 3, member B. We further tested the protein level in serum and saliva from patients with lymph-node metastatic and primary OSCC. Tetranectin was found significantly under-expressed in both serum and saliva of metastatic OSCC compared to primary OSCC. Our results suggest that serum or saliva tetranectin may serve as a potential biomarker for metastatic OSCC. Other candidate serum biomarkers for OSCC included superoxide dismutase, ficolin 2, CD-5 antigen-like protein, RalA binding protein 1, plasma retinol-binding protein and transthyretin. Their clinical utility for OSCC detection remains to be further tested in cancer patients.

  1. Molecular changes in pre-metastatic lymph nodes of esophageal cancer patients.

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    Benjamin Otto

    Full Text Available Lymph node metastasis indicates poor prognosis in esophageal cancer. To understand the underlying mechanisms, most studies so far focused on investigating the tumors themselves and/or invaded lymph nodes. However they neglected the potential events within the metastatic niche, which precede invasion. Here we report the first description of these regulations in patients on transcription level. We determined transcriptomic profiles of still metastasis-free regional lymph nodes for two patient groups: patients classified as pN1 (n = 9, metastatic nodes exist or pN0 (n = 5, no metastatic nodes exist. All investigated lymph nodes, also those from pN1 patients, were still metastasis-free. The results show that regional lymph nodes of pN1 patients differ decisively from those of pN0 patients--even before metastasis has taken place. In the pN0 group distinct immune response patterns were observed. In contrast, lymph nodes of the pN1 group exhibited a clear profile of reduced immune response and reduced proliferation, but increased apoptosis, enhanced hypoplasia and morphological conversion processes. DKK1 was the most significant gene associated with the molecular mechanisms taking place in lymph nodes of patients suffering from metastasis (pN1. We assume that the two molecular profiles observed constitute different stages of a progressive disease. Finally we suggest that DKK1 might play an important role within the mechanisms leading to lymph node metastasis.

  2. Evaluation of liquid biopsies for detection of emerging mutated genes in metastatic colorectal cancer.

    Science.gov (United States)

    Furuki, Hiroyasu; Yamada, Takeshi; Takahashi, Goro; Iwai, Takuma; Koizumi, Michihiro; Shinji, Seiichi; Yokoyama, Yasuyuki; Takeda, Kohki; Taniai, Nobuhiko; Uchida, Eiji

    2018-02-02

    Detection of gene mutations is important for planning molecular targeted therapy. Although most gene mutations are concordant between primary colon cancers and their liver metastases, new mutations can emerge in metastases. The liquid biopsy is a newly developed, gene analytic method to detect mutations in metastatic tumors. In this prospective study, we evaluated the applicability of liquid biopsies in the detection of mutations in primary and metastatic tumors. We included 22 patients with liver metastases from colorectal cancer and extracted DNA from primary colorectal tumors, metastatic liver tumors, and peripheral blood (liquid biopsy). Next-generation sequencing (NGS) and digital PCR were performed to detect mutations in these three sample types. We found a total of 36 different mutations in samples from primary tumors, liver metastases, and liquid biopsies using NGS. Twenty-eight of these mutations were found in all three types of samples, whereas liquid biopsy did not identify four mutations that had been found in both primary tumors and liver metastases, but did identify four mutations that were found in liver tumors but not in primary tumors. The sensitivity of liquid biopsies for detecting mutations in liver metastases was 64% (23/36) using NGS and 89% (32/36, P = 0.02) using dPCR. The specificities of NGS and dPCR were 100% (23/23) and 100% (32/32), respectively. Emerging mutations, which are not found in primary tumors, can be detected in their metastases and liquid biopsies. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  3. A cost comparison of biologic treatment regimens for metastatic colorectal cancer in Italy

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    Sergio Iannazzo

    2017-10-01

    Full Text Available IntroductionBevacizumab is a monoclonal antibody, which, in association with combination chemotherapy regimens, has been shown to be active in metastatic colorectal cancer. Other biologic agents active in the same setting are cetuximab and panitumumab, both of which are monoclonal antibodies directed against the antiepidermal growth factor receptor. The objective of this study was to compare treatment costs of first-line regimens for metastatic colorectal cancer in Italy.MethodsA set of first-line regimens was considered, according to the Italian Association of Medical Oncology and the European Society for Medical Oncology guidelines. A targeted review of the literature was undertaken to identify clinical study references for treatment regimens. The total cost of a regimen was calculated in the perspective of the Italian healthcare system summing up drugs, administration, and adverse event costs, based on year 2016 prices and tariffs.ResultsBevacizumab 7.5 mg + capecitabine was the least expensive regimen, with a total cost of €16,754 per patient. When we consider regimens based on FOLFOX, bevacizumab 5 mg + FOLFOX4 was the least expensive (€32,709 per patient, compared to panitumumab + FOLFOX4 (€42,815, cetuximab + FOLFOX4 (€42,725, and cetuximab + FOLFOX (€37,995. If we consider combination regimens based on FOLFIRI, the association of FOLFIRI and bevacizumab was less expensive than regimens that included cetuximab (€28,389 for bevacizumab 5 mg + FOLFIRI and €35,310 for cetuximab + FOLFIRI.ConclusionsFrom the perspective of the Italian health care system, bevacizumab appears to be a convenient option among the first-line regimens for metastatic colorectal cancer. Further study, based on real-world evidence, would be necessary to confirm this result.

  4. New Biomarkers for Selecting the Best Therapy Regimens in Metastatic Castration-Resistant Prostate Cancer.

    Science.gov (United States)

    Heidegger, Isabel; Heidenreich, Axel; Pfister, David

    2017-02-01

    Prostate cancer is the most common cancer in men. In recent years, several new targeted therapeutic agents for the treatment of metastatic castration resistant prostate cancer (mCRPC) have been developed. These include androgen receptor targeting agents, new taxanes, radium-223, and immunotherapies. In this short review, we provide a summary of clinical and preclinical biomarkers for each of these new treatment strategies, also including new markers currently presented in conference papers only. Moreover, we address the role of these biomarkers in clinical routine with the aim to select best-personalized treatment strategies for patients. Finally, we provide a decision tree for selecting the proper therapy for patients with mCRPC according to the discussed biomarkers.

  5. Deformation-driven, lethal damage to cancer cells. Its contribution to metastatic inefficiency.

    Science.gov (United States)

    Weiss, L

    1991-04-01

    Direct and indirect, in vivo and in vitro observations are in accord with the hypothesis that as a consequence of their deformation within capillaries, cancer cells undergo sphere-to-cylinder shape-transformations that create a demand for increased surface area. When this demand cannot be met by apparent increases in surface area accomplished by nonlethal, surface "unfolding," the cell surface membrane is stretched; if expansion results in more than a 4% increase in true surface area, the membrane ruptures, resulting in cancer cell death. It is suggested that this deformation-driven process is an important factor in accounting for the rapid death of circulating cancer cells that have been trapped in the microvasculature. Therefore, this mechanism is thought to make a significant contribution to metastatic inefficiency by acting as a potent rate-regulator for hematogenous metastasis.

  6. Effects of cyclophosphamide on laser immunotherapy for the treatment of metastatic cancer

    Science.gov (United States)

    Bahavar, Cody F.; Acquaviva, Joseph T.; Rabei, Sheyla; Sikes, Allie; Nordquist, Robert E.; Hode, Tomas; Liu, Hong; Chen, Wei R.

    2014-02-01

    Laser immunotherapy (LIT) is an innovative cancer modality that uses laser irradiation and immunological stimulation to treat late-stage, metastatic cancers. The current mode of operation in LIT is through interstitial laser irradiation. Although LIT is still in development, recent clinical trials have shown that it can be used to successfully treat patients with late-stage breast cancer and melanoma. Cyclophosphamide is a chemotherapy drug that suppresses regulatory T cells when used in low doses. In this study tumor-bearing rats were treated with LIT using an 805-nm laser with a power of 2.0 W and low-dose cyclophosphamide. Glycated chitosan was used as an immunological stimulant. The goal was to observe the effects of different doses of cyclophosphamide in addition to LIT on the survival of the tumor-bearing rats.

  7. Targeting Met and VEGFR Axis in Metastatic Castration-Resistant Prostate Cancer: 'Game Over'?

    Science.gov (United States)

    Modena, Alessandra; Massari, Francesco; Ciccarese, Chiara; Brunelli, Matteo; Santoni, Matteo; Montironi, Rodolfo; Martignoni, Guido; Tortora, Giampaolo

    2016-08-01

    Despite recent advances that have been made in the therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC), effective management of bone metastases remains a key goal not yet reached. The receptor tyrosine kinase MET and the vascular endothelial growth factor receptor (VEGFR) seem to play an important role in prostate cancer progression and pathological bone turnover, representing potential targets for improving clinical outcomes in mCRPC. Studies evaluating agents that target one or both these pathways have demonstrated modest activity but no improvement in overall survival. Nevertheless, this therapeutic strategy seems to still be a promising and engaging area of prostate cancer research and the interest in better understanding the MET/VEGFR axis and the mechanism of action of these inhibitors is growing. This review describes the rationale for targeting MET and VEGFR pathway in mCRPC and provides the clinical data available to date and an update on ongoing trials.

  8. Comparison of miRNA and gene expression profiles between metastatic and primary prostate cancer.

    Science.gov (United States)

    Guo, Kaimin; Liang, Zuowen; Li, Fubiao; Wang, Hongliang

    2017-11-01

    The present study aimed to identify the regulatory mechanisms associated with the metastasis of prostate cancer (PC). The microRNA (miRNA/miR) microarray dataset GSE21036 and gene transcript dataset GSE21034 were downloaded from the Gene Expression Omnibus database. Following pre-processing, differentially expressed miRNAs (DEMs) and differentially expressed genes (DEGs) between samples from patients with primary prostate cancer (PPC) and metastatic prostate cancer (MPC) with |log 2 fold change (FC)| >1 and a false discovery rate terms (36 terms), followed by miR-494 (24 terms), miR-30d (18 terms), miR-181a (15 terms), hsa-miR-196a (8 terms), miR-708 (7 terms) and miR-486-5p (2 terms). Therefore, these miRNAs may serve roles in the metastasis of PC cells via downregulation of their corresponding target DEGs.

  9. Numb chin syndrome as a primary presentation of metastatic breast cancer

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    Jasjot Sahni

    2017-01-01

    Full Text Available Numb chin syndrome (NCS is characterized by facial neuropathy along the distribution of the mental branch of the trigeminal nerve. We report a case of NCS in a 65 year old woman who initially presented to her dentist with nonspecific symptoms that she thought were related to a tooth infection. The patient was otherwise healthy and her medical history was significant for breast cancer treated 20 years prior; her cancer was thought to be in complete remission. Upon clinical examination and conventional dental radiography, no pathology was seen such as odontogenic, periodontal, or jawbone infection. Only paresthesia and hypoesthesia was noted unilaterally in her left chin, jaw and lower lip. A computed tomography scan was obtained for further evaluation and revealed lytic metastatic disease involving the right mandible at the level of the mandibular foramen; lytic lesions of the thoracic vertebrae and multiple pulmonary nodules were also noted. Oncologic referral was made immediately which confirmed a diagnosis of metastatic breast cancer. Familiarity with NCS is important for oral health care providers in order to identify etiology and differential diagnosis, as well as to provide appropriate referral and management.

  10. Lapatinib plus transtuzumab for HER-2 positiva metastatic breast cancer: Experience of use

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    C. García-Muñoz

    2014-03-01

    Full Text Available Abstract: Objective: To describe the outcomes produced by concomitant use of HER2-receptor inhibitors Lapatinib and Trastuzumab for the treatment of HER 2-positive metastatic breast cancer. Method: Retrospective observational study. Patients treated with Trastuzumab and Lapatinib between January of 2010 and May of 2012 were selected. Demographical and clinical data were gathered. Results: 23 patients with metastatic breast cancer (mean age 59.3 ± 13.3 years were included. All of them had received an average of 5 treatment lines with at least one of them including Trastuzumab. The median progression-free survival rate with combined Lapatinib + Trastuzumab, with or without associated chemotherapy was 7 months (95% CI: 2.78-11.21 and 3 months for the patients only receiving Lapatinib and Trastuzumab. Seven patients experienced adverse events and in four patients the treatment was stopped due to toxicity. Conclusions: The treatment with HER2-receptor inhibitors in our patients resulted in progression-free survival rates similar to those published in clinical trials with patients receiving Lapatinib + Trastuzumab not combined with any other anti-cancer therapy, with good treatment tolerability.

  11. Functional analysis of prognostic gene expression network genes in metastatic breast cancer models.

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    Thomas R Geiger

    Full Text Available Identification of conserved co-expression networks is a useful tool for clustering groups of genes enriched for common molecular or cellular functions [1]. The relative importance of genes within networks can frequently be inferred by the degree of connectivity, with those displaying high connectivity being significantly more likely to be associated with specific molecular functions [2]. Previously we utilized cross-species network analysis to identify two network modules that were significantly associated with distant metastasis free survival in breast cancer. Here, we validate one of the highly connected genes as a metastasis associated gene. Tpx2, the most highly connected gene within a proliferation network specifically prognostic for estrogen receptor positive (ER+ breast cancers, enhances metastatic disease, but in a tumor autonomous, proliferation-independent manner. Histologic analysis suggests instead that variation of TPX2 levels within disseminated tumor cells may influence the transition between dormant to actively proliferating cells in the secondary site. These results support the co-expression network approach for identification of new metastasis-associated genes to provide new information regarding the etiology of breast cancer progression and metastatic disease.

  12. Impact of modern chemotherapy on the survival of women presenting with de novo metastatic breast cancer

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    Pal Sumanta K

    2012-09-01

    Full Text Available Abstract Background Data that directly associate utilization of novel systemic therapies with survival trends in metastatic breast cancer (MBC are limited. In the setting of de novo MBC, large registry analyses cite positive temporal trends in survival, but the extent to which advances in systemic therapy have contributed to these gains is not clear. Methods The City of Hope Cancer Registry was used to identify a consecutive series of patients with de novo MBC who received their first line of therapy between 1985 and 2004. Comprehensive clinicopathologic and treatment-related data were collected for each patient. Univariate analyses were conducted via Cox regression to identify factors associated with improved survival. Multivariate analysis was also conducted via Cox regression and the stepwise procedure was used to identify independent predictors of survival. Results A total of 324 patients with de novo MBC were identified. After application of exclusion criteria, including the sole presence of supraclavicular node metastasis, 274 patients were retained in the analysis. The treatment-related characteristics associated with improved survival included: use of endocrine therapy (hazard ratio [HR] 0.60, 95%CI 0.47-0.77; P Conclusions The overall survival of women with de novo metastatic breast cancer has improved over the past 20 years. However, the contribution of conventional cytotoxic agents to this improvement is minimal.

  13. Green tea extract selectively targets nanomechanics of live metastatic cancer cells

    Science.gov (United States)

    Cross, Sarah E.; Jin, Yu-Sheng; Lu, Qing-Yi; Rao, JianYu; Gimzewski, James K.

    2011-05-01

    Green tea extract (GTE) is known to be a potential anticancer agent (Yang et al 2009 Nat. Rev. Cancer 9 429-39) with various biological activities (Lu et al 2005 Clin. Cancer Res. 11 1675-83 Yang et al 1998 Carcinogenesis 19 611-6) yet the precise mechanism of action is still unclear. The biomechanical response of GTE treated cells taken directly from patient's body samples was measured using atomic force microscopy (AFM) (Binnig et al 1986 Phys. Rev. Lett. 56 930). We found significant increase in stiffness of GTE treated metastatic tumor cells, with a resulting value similar to untreated normal mesothelial cells, whereas mesothelial cell stiffness after GTE treatment is unchanged. Immunofluorescence analysis showed an increase in cytoskeletal-F-actin in GTE treated tumor cells, suggesting GTE treated tumor cells display mechanical, structural and morphological features similar to normal cells, which appears to be mediated by annexin-I expression, as determined by siRNA analysis of an in vitro cell line model. Our data indicates that GTE selectively targets human metastatic cancer cells but not normal mesothelial cells, a finding that is significantly advantageous compared to conventional chemotherapy agents.

  14. Cabazitaxel: more than a new taxane for metastatic castrate-resistant prostate cancer?

    Science.gov (United States)

    Mita, Alain C; Figlin, Robert; Mita, Monica M

    2012-12-15

    The taxanes are recognized as a major class of chemotherapeutic agents; however, mechanisms of innate and acquired resistance can limit their usefulness. Cabazitaxel, a novel taxane with microtubule-stabilizing potency similar to docetaxel, exhibits activity against tumor cell lines resistant to paclitaxel and docetaxel. Cabazitaxel showed linear pharmacokinetics and a terminal elimination half-life comparable with that of docetaxel, findings which support dosing as a single infusion in three-week treatment cycles. Dose-ranging studies recommended doses of 20 or 25 mg/m(2) every three weeks. Antitumor activity was shown in patients with advanced cancer and chemotherapy failure (including taxane failure). Other early studies investigated the efficacy of cabazitaxel in pretreated metastatic breast cancer, either as a single agent or in combination with capecitabine. Objective antitumor response rates of up to 24% and sustained tumor stabilizations were also observed. The TROPIC phase III study, conducted in patients with metastatic castrate-resistant prostate cancer previously treated with docetaxel, established cabazitaxel as the first chemotherapeutic agent to offer a survival advantage in this patient population. Across these studies, the dose-limiting hematologic toxicity was neutropenia (including febrile neutropenia), usually controllable with colony-stimulating factor/granulocyte-colony stimulating factor support. ©2012 AACR.

  15. Changes of initiation, promotion and metastatic enzyme system in human breast cancer with the proton irradiation

    International Nuclear Information System (INIS)

    Sohn, Y. H.; Kim, S. W.; Lee, K. S.; Mo, J. Y.

    2010-04-01

    Proton irradiations in the cells were significantly decreased cell viability but increased the QR activity in a dose-dependent manner. Cell viability was 92.3%, 88.4%, 81.8%, 72.4%, 68.9% at doses of 0.5, 2, 8, 16, and 32 Gy, respectively. At doses of 2, 8, 16, and 32 Gy, QR activity was increased 1.27-, 1.31-, 1.45- and 2.08-fold. However, negligible GST activity in the cells was detected and the activity was not changed by proton irradiation. Proton irradiation also increased GSH contents by 1.18- and 1.21-fold at doses of 0.5 and 2 Gy. In contrast, the ODC activity, a key enzyme in polyamine biosynthesis and tumor promotion, was decreased in a dose-dependent manner. We also investigated anti-metastatic effects of proton beam irradiation in breast cancer cells. Invasion and wound healing assay showed that metastatic activities in breast cancer cells were significantly decreased in a dose-dependent manner by proton beam irradiation. In zymography of MMP-9, the activity was slightly diminished. These results suggest that breast cancer chemopreventive potential was increased with proton irradiation by increasing the QR activity and the GSH levels and by inhibiting the ODC activity.

  16. Impact of Hypoxia on the Metastatic Potential of Human Prostate Cancer Cells

    International Nuclear Information System (INIS)

    Dai Yao; Bae, Kyungmi; Siemann, Dietmar W.

    2011-01-01

    Purpose: Intratumoral hypoxia is known to be associated with radioresistance and metastasis. The present study examined the effect of acute and chronic hypoxia on the metastatic potential of prostate cancer PC-3, DU145, and LNCaP cells. Methods and Materials: Cell proliferation and clonogenicity were tested by MTT assay and colony formation assay, respectively. 'Wound-healing' and Matrigel-based chamber assays were used to monitor cell motility and invasion. Hypoxia-inducible factor 1 alpha (HIF-1α) expression was tested by Western blot, and HIF-1-target gene expression was detected by real-time polymerase chain reaction. Secretion of matrix metalloproteinases (MMPs) was determined by gelatin zymography. Results: When PC-3 cells were exposed to 1% oxygen (hypoxia) for various periods of time, chronic hypoxia (≥24 h) decreased cell proliferation and induced cell death. In contrast, prostate cancer cells exposed to acute hypoxia (≤6 h) displayed increased motility, clonogenic survival, and invasive capacity. At the molecular level, both hypoxia and anoxia transiently stabilized HIF-1α. Exposure to hypoxia also induced the early expression of MMP-2, an invasiveness-related gene. Treatment with the HIF-1 inhibitor YC-1 attenuated the acute hypoxia-induced migration, invasion, and MMP-2 activity. Conclusions: The length of oxygen deprivation strongly affected the functional behavior of all three prostate cancer cell lines. Acute hypoxia in particular was found to promote a more aggressive metastatic phenotype.

  17. Changes of initiation, promotion and metastatic enzyme system in human breast cancer with the proton irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Sohn, Y. H.; Kim, S. W.; Lee, K. S.; Mo, J. Y. [Dongguk University, Seoul (Korea, Republic of)

    2010-04-15

    Proton irradiations in the cells were significantly decreased cell viability but increased the QR activity in a dose-dependent manner. Cell viability was 92.3%, 88.4%, 81.8%, 72.4%, 68.9% at doses of 0.5, 2, 8, 16, and 32 Gy, respectively. At doses of 2, 8, 16, and 32 Gy, QR activity was increased 1.27-, 1.31-, 1.45- and 2.08-fold. However, negligible GST activity in the cells was detected and the activity was not changed by proton irradiation. Proton irradiation also increased GSH contents by 1.18- and 1.21-fold at doses of 0.5 and 2 Gy. In contrast, the ODC activity, a key enzyme in polyamine biosynthesis and tumor promotion, was decreased in a dose-dependent manner. We also investigated anti-metastatic effects of proton beam irradiation in breast cancer cells. Invasion and wound healing assay showed that metastatic activities in breast cancer cells were significantly decreased in a dose-dependent manner by proton beam irradiation. In zymography of MMP-9, the activity was slightly diminished. These results suggest that breast cancer chemopreventive potential was increased with proton irradiation by increasing the QR activity and the GSH levels and by inhibiting the ODC activity.

  18. Can Biomarker Assessment on Circulating Tumor Cells Help Direct Therapy in Metastatic Breast Cancer?

    Energy Technology Data Exchange (ETDEWEB)

    Turner, Natalie [Sandro Pitigliani Medical Oncology Department, Prato Hospital, Istituto Toscano Tumori, Via Ugo Foscolo, Prato, PO 59100 (Italy); Pestrin, Marta [Sandro Pitigliani Medical Oncology Department, Prato Hospital, Istituto Toscano Tumori, Via Ugo Foscolo, Prato, PO 59100 (Italy); Translational Research Laboratory, Prato Hospital, Via Ugo Foscolo, Prato, PO 59100 (Italy); Galardi, Francesca; De Luca, Francesca [Translational Research Laboratory, Prato Hospital, Via Ugo Foscolo, Prato, PO 59100 (Italy); Malorni, Luca [Sandro Pitigliani Medical Oncology Department, Prato Hospital, Istituto Toscano Tumori, Via Ugo Foscolo, Prato, PO 59100 (Italy); Translational Research Laboratory, Prato Hospital, Via Ugo Foscolo, Prato, PO 59100 (Italy); Di Leo, Angelo, E-mail: adileo@usl4.toscana.it [Sandro Pitigliani Medical Oncology Department, Prato Hospital, Istituto Toscano Tumori, Via Ugo Foscolo, Prato, PO 59100 (Italy)

    2014-03-25

    Circulating tumor cell (CTC) count has prognostic significance in metastatic breast cancer, but the predictive utility of CTCs is uncertain. Molecular studies on CTCs have often been limited by a low number of CTCs isolated from a high background of leukocytes. Improved enrichment techniques are now allowing molecular characterisation of single CTCs, whereby molecular markers on single CTCs may provide a real-time assessment of tumor biomarker status from a blood test or “liquid biopsy”, potentially negating the need for a more invasive tissue biopsy. The predictive ability of CTC biomarker analysis has predominantly been assessed in relation to HER2, with variable and inconclusive results. Limited data exist for other biomarkers, such as the estrogen receptor. In addition to the need to define and validate the most accurate and reproducible method for CTC molecular analysis, the clinical relevance of biomarkers, including gain of HER2 on CTC after HER2 negative primary breast cancer, remains uncertain. This review summarises the currently available data relating to biomarker evaluation on CTCs and its role in directing management in metastatic breast cancer, discusses limitations, and outlines measures that may enable future development of this approach.

  19. Evaluation of KRAS Gene Mutations in Metastatic Colorectal Cancer Patients in Kermanshah Province.

    Science.gov (United States)

    Amirifard, Nasrin; Sadeghi, Edris; Farshchian, Negin; Haghparast, Abbas; Choubsaz, Mansour

    2016-01-01

    Worldwide, colorectal cancer (CRC) is reported to be the fourth most common cancer in men and the third most common in women. KRAS is a protooncogene located on the short arm of chromosome 12. The aim of this study was to evaluate the KRAS oncogene and its relationship it with clinicopathologic features in 33 Kurdish patients. Metastatic CRC between 2012 and 2016 that came to Imam Reza hospital, Kermanshah province, Iran, were analysed for KRAS mutations using allele specific PCR primers and pyrosequencing. Correlations between variables was analyzed in PASW SPSS and overall survival curves were plotted in Graph Pad prism 5. The mean age for them at diagnosis was 51.5±12.6 years (range, 2276 years). Among the 33 patients that were sequenced, 12 samples in the KRAS gene had a nucleotide change, 11 in codon 12 and 1 in codon 13.There was no significant relationship between the mutation and clinical and pathological aspects of the disease. Knowledge of the KRAS status can help in decisionmaking to treat metastatic colorectal cancer patients more efficiently and increase survival. However, many Kurdish people due to economic problems are not able to do this valuable genetic test. In addition, we need more careful research of KRAS oncogene at the molecular level in young populations with more patients.

  20. Matrix rigidity induces osteolytic gene expression of metastatic breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Nazanin S Ruppender

    Full Text Available Nearly 70% of breast cancer patients with advanced disease will develop bone metastases. Once established in bone, tumor cells produce factors that cause changes in normal bone remodeling, such as parathyroid hormone-related protein (PTHrP. While enhanced expression of PTHrP is known to stimulate osteoclasts to resorb bone, the environmental factors driving tumor cells to express PTHrP in the early stages of development of metastatic bone disease are unknown. In this study, we have shown that tumor cells known to metastasize to bone respond to 2D substrates with rigidities comparable to that of the bone microenvironment by increasing expression and production of PTHrP. The cellular response is regulated by Rho-dependent actomyosin contractility mediated by TGF-ß signaling. Inhibition of Rho-associated kinase (ROCK using both pharmacological and genetic approaches decreased PTHrP expression. Furthermore, cells expressing a dominant negative form of the TGF-ß receptor did not respond to substrate rigidity, and inhibition of ROCK decreased PTHrP expression induced by exogenous TGF-ß. These observations suggest a role for the differential rigidity of the mineralized bone microenvironment in early stages of tumor-induced osteolysis, which is especially important in metastatic cancer since many cancers (such as those of the breast and lung preferentially metastasize to bone.

  1. Contemporary Trends and Survival Outcomes After Aborted Radical Prostatectomy in Lymph Node Metastatic Prostate Cancer Patients.

    Science.gov (United States)

    Bandini, Marco; Preisser, Felix; Nazzani, Sebastiano; Marchioni, Michele; Tian, Zhe; Fossati, Nicola; Gandaglia, Giorgio; Gallina, Andrea; Abdollah, Firas; Shariat, Shahrokh F; Montorsi, Francesco; Saad, Fred; Tilki, Derya; Briganti, Alberto; Karakiewicz, Pierre I

    2018-01-20

    Aborted radical prostatectomy (aRP) in lymph node (LN) metastatic (pN1) prostate cancer (PCa) patients showed worse survival in European patients. Contemporary rates of aRP are unknown in North America. To examine the rate of aRP and its effect on cancer-specific mortality (CSM) in contemporary North American patients. Within the Surveillance Epidemiology and End Results database (2004-2014), we identified 3719 pN1 PCa patients. RP. Incidence proportion and median survival of LN metastatic PCa patients who underwent aRP versus completed RP (cRP). Cumulative incidence plots and competing-risks regression (CRR) models tested CSM and other-cause mortality rates according to aRP versus cRP. The effect of selected variables on CSM rate was graphically depicted using LOESS methodology. All analyses were repeated after propensity score matching. Between 2004 and 2014, the rate of aRP decreased from 20.4% to 5.6% (pcontemporary North American patients, 5% are affected by aRP. It confers a significant survival disadvantage that applies to patients with baseline PSA values up to 50ng/ml and in those with up to seven LN metastases. Radical prostatectomy should not be aborted in pN1 prostate cancer individuals. Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  2. Detection of Metastatic Breast and Thyroid Cancer in Lymph Nodes by Desorption Electrospray Ionization Mass Spectrometry Imaging

    Science.gov (United States)

    Zhang, Jialing; Feider, Clara L.; Nagi, Chandandeep; Yu, Wendong; Carter, Stacey A.; Suliburk, James; Cao, Hop S. Tran; Eberlin, Livia S.

    2017-06-01

    Ambient ionization mass spectrometry has been widely applied to image lipids and metabolites in primary cancer tissues with the purpose of detecting and understanding metabolic changes associated with cancer development and progression. Here, we report the use of desorption electrospray ionization mass spectrometry (DESI-MS) to image metastatic breast and thyroid cancer in human lymph node tissues. Our results show clear alterations in lipid and metabolite distributions detected in the mass spectra profiles from 42 samples of metastatic thyroid tumors, metastatic breast tumors, and normal lymph node tissues. 2D DESI-MS ion images of selected molecular species allowed discrimination and visualization of specific histologic features within tissue sections, including regions of metastatic cancer, adjacent normal lymph node, and fibrosis or adipose tissues, which strongly correlated with pathologic findings. In thyroid cancer metastasis, increased relative abundances of ceramides and glycerophosphoinisitols were observed. In breast cancer metastasis, increased relative abundances of various fatty acids and specific glycerophospholipids were seen. Trends in the alterations in fatty acyl chain composition of lipid species were also observed through detailed mass spectra evaluation and chemical identification of molecular species. The results obtained demonstrate DESI-MSI as a potential clinical tool for the detection of breast and thyroid cancer metastasis in lymph nodes, although further validation is needed. [Figure not available: see fulltext.

  3. The impending financial healthcare burden and ethical dilemma of systemic therapy in metastatic cancer.

    Science.gov (United States)

    Riaz, Muhammad Kashif; Bal, Susan; Wise-Draper, Trisha

    2016-09-01

    Metastatic cancer remains a devastating disease that threatens to disrupt entire family structures creating economic and psychosocial stress. Fortunately, great strides have resulted in improved therapies over the years but at a huge social-economic cost. The economic burden has risen greatly and carries with it new ethical concerns when deciding treatment. Here, we discuss the financial and ethical challenges that oncologists and their patients face in the era of novel treatment strategies. J. Surg. Oncol. 2016;114:323-328. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  4. Enzalutamide in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer

    DEFF Research Database (Denmark)

    Beer, Tomasz M; Armstrong, Andrew J; Rathkopf, Dana

    2017-01-01

    Enzalutamide significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) among men with chemotherapy-naïve metastatic castration-resistant prostate cancer at the prespecified interim analysis of PREVAIL, a phase 3, double-blind, randomized study. We evaluated......, back pain, constipation, and arthralgia. This final analysis of PREVAIL provides more complete assessment of the clinical benefit of enzalutamide. PREVAIL is registered on ClinicalTrials.gov as NCT01212991. PATIENT SUMMARY: According to data from longer follow-up, enzalutamide continued to provide...

  5. TH-E-BRF-08: Subpopulations of Similarly-Responding Lesions in Metastatic Prostate Cancer

    International Nuclear Information System (INIS)

    Lin, C; Harmon, S; Perk, T; Jeraj, R

    2014-01-01

    Purpose: In patients with multiple lesions, resistance to cancer treatments and subsequent disease recurrence may be due to heterogeneity of response across lesions. This study aims to identify subpopulations of similarly-responding metastatic prostate cancer lesions in bone using quantitative PET metrics. Methods: Seven metastatic prostate cancer patients treated with AR-directed therapy received pre-treatment and mid-treatment [F-18]NaF PET/CT scans. Images were registered using an articulated CT registration algorithm and transformations were applied to PET segmentations. Midtreatment response was calculated on PET-based texture features. Hierarchical agglomerative clustering was used to form groups of similarly-responding lesions, with the number of natural clusters (K) determined by the inconsistency coefficient. Lesion clustering was performed within each patient, and for the pooled population. The cophenetic coefficient (C) quantified how well the data was clustered. The Jaccard Index (JI) assessed similarity of cluster assignments from patient clustering and from population clustering. Results: 188 lesions in seven patients were identified for analysis (between 6 to 53 lesions per patient). Lesion response was defined as percent change relative to pre-treatment for 23 uncorrelated PET-based feature identifiers. . High response heterogeneity was found across all lesions (i.e. range ΔSUVmax =−95.98% to 775.00%). For intra-patient clustering, K ranged from 1–20. Population-based clustering resulted in 75 clusters, of 1-6 lesions each. Intra-patient clustering resulted in higher quality clusters than population clustering (mean C=0.95, range=0.89 to 1.00). For all patients, cluster assignments from population clustering showed good agreement to intra-patient clustering (mean JI=0.87, range=0.68 to 1.00). Conclusion: Subpopulations of similarly-responding lesions were identified in patients with multiple metastatic lesions. Good agreement was found between

  6. Gemcitabine and capecitabine for heavily pre-treated metastatic colorectal cancer patients

    DEFF Research Database (Denmark)

    Spindler, Karen-Lise G; Pallisgaard, Niels; Andersen, Rikke F

    2014-01-01

    AIM: We investigated the efficacy and safety of capecitabine and gemcitabin (GemCap) in heavily pre-treated, therapy-resistant metastatic colorectal cancer (mCRC) patients and the clinical importance of cell-free DNA (cfDNA) measurement. PATIENTS AND METHODS: Patients' inclusion criteria included...... histopathologically-verified mCRC refractory to standard chemotherapy, adequate organ function and performance status. Treatment included capecitabine (2,000 mg/m(2) day on days 1-7 q2w) and gemcitabine (1,000 mg/m(2) on day 1). The number of DNA alleles was measured in pre-treatment plasma samples using an in...

  7. Interleukin-6 and C-reactive protein as prognostic biomarkers in metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Thomsen, Maria; Kersten, Christian; Sorbye, Halfdan

    2016-01-01

    Objectives: The aim was to explore the prognostic significance of IL-6 and markers of systemic inflammatory response (SIR), in particular C-reactive protein (CRP), in metastatic colorectal cancer (mCRC) patients, in the total study population and according to RAS and BRAF mutation status. Results...... 24.3 months to 12.3 months, (P treatment serum samples...... from 393 patients included in the NORDIC-VII trial, in which patients with mCRC received first line treatment. The effect of serum IL-6 and CRP on progressionfree survival (PFS) and overall survival (OS) was estimated. Conclusions: High baseline serum consentrations of IL-6 or CRP were associated...

  8. Disseminated intravascular coagulation in a patient with metastatic prostate cancer: Fatal outcome following strontium-89 therapy

    Energy Technology Data Exchange (ETDEWEB)

    Leong, C.; McKenzie, R.; Coupland, D.B. [Univ. of British Columbia, (Canada)] [and others

    1994-10-01

    A patient with metastatic prostate cancer was found to have low-grade disseminated intravascular coagulation (DIC). He had significant bone pain despite external-beam radiotherapy and was given {sup 89}Sr with subsequent thrombocytopenia and epistaxis. The patient died from generalized hemorrhage 36 days postinjection. Although it is not possible to establish a causal relationship between {sup 89}Sr and DIC, practitioners should be alert to complications associated with the primary disorder which might occur at a time to raise concern about the intervention. 8 refs., 1 tab.

  9. Molecular biology of breast cancer metastasis: Clinical implications of experimental studies on metastatic inefficiency

    International Nuclear Information System (INIS)

    Chambers, Ann F; Naumov, George N; Vantyghem, Sharon A; Tuck, Alan B

    2000-01-01

    Recent technological advances have led to an increasing ability to detect isolated tumour cells and groups of tumour cells in patients' blood, lymph nodes or bone marrow. However, the clinical significance of these cells is unclear. Should they be considered as evidence of metastasis, necessitating aggressive treatment, or are they in some cases unrelated to clinical outcome? Quantitative experimental studies on the basic biology of metastatic inefficiency are providing clues that may help in understanding the significance of these cells. This understanding will be of use in guiding clinical studies to assess the significance of isolated tumour cells and micrometastases in cancer patients

  10. Hypoxia increases the metastatic ability of breast cancer cells via upregulation of CXCR4

    LENUS (Irish Health Repository)

    Cronin, Patricia A

    2010-05-21

    Abstract Background Chemokine SDF1α and its unique receptor CXCR4 have been implicated in organ-specific metastases of many cancers including breast cancer. Hypoxia is a common feature of solid tumors and is associated with their malignant phenotype. We hypothesized that hypoxia would upregulate CXCR4 expression and lead to increased chemotactic responsiveness to its specific ligand SDF1α. Methods Three breast cancer cell lines MDA-MB-231, MCF7 and 4T1 were subjected to 48 hrs of hypoxia or normoxia. Cell surface receptor expression was evaluated using flow cytometry. An extracellular matrix invasion assay and microporous migration assay was used to assess chemotactic response and metastatic ability. Results CXCR4 surface expression was significantly increased in the two human breast cancer cell lines, MDA-MB-231 and MCF7, following exposure to hypoxia. This upregulation of CXCR4 cell surface expression corresponded to a significant increase in migration and invasion in response to SDF1-α in vitro. The increase in metastatic potential of both the normoxic and the hypoxic treated breast cancer cell lines was attenuated by neutralization of CXCR4 with a CXCR4 neutralizing mAb, MAB172 or a CXCR4 antagonist, AMD3100, showing the relationship between CXCR4 overexpression and increased chemotactic responsiveness. Conclusions CXCR4 expression can be modulated by the tissue microenvironment such as hypoxia. Upregulation of CXCR4 is associated with increased migratory and invasive potential and this effect can be abrogated by CXCR4 inhibition. Chemokine receptor CXCR4 is a potential therapeutic target in the adjuvant treatment of breast cancer.

  11. The Vitamin D Analog, MART-10, Attenuates Triple Negative Breast Cancer Cells Metastatic Potential

    Science.gov (United States)

    Chiang, Kun-Chun; Yeh, Ta-Sen; Chen, Shin-Cheh; Pang, Jong-Hwei S.; Yeh, Chun-Nan; Hsu, Jun-Te; Chen, Li-Wei; Kuo, Sheng-Fong; Takano, Masashi; Kittaka, Atsushi; Chen, Tai C.; Sun, Chi-Chin; Juang, Horng-Heng

    2016-01-01

    Regarding breast cancer treatment, triple negative breast cancer (TNBC) is a difficult issue. Most TNBC patients die of cancer metastasis. Thus, to develop a new regimen to attenuate TNBC metastatic potential is urgently needed. MART-10 (19-nor-2α-(3-hydroxypropyl)-1α,25(OH)2D3), the newly-synthesized 1α,25(OH)2D3 analog, has been shown to be much more potent in cancer growth inhibition than 1α,25(OH)2D3 and be active in vivo without inducing obvious side effect. In this study, we demonstrated that both 1α,25(OH)2D3 and MART-10 could effectively repress TNBC cells migration and invasion with MART-10 more effective. MART-10 and 1α,25(OH)2D3 induced cadherin switching (upregulation of E-cadherin and downregulation of N-cadherin) and downregulated P-cadherin expression in MDA-MB-231 cells. The EMT(epithelial mesenchymal transition) process in MDA-MB-231 cells was repressed by MART-10 through inhibiting Zeb1, Zeb2, Slug, and Twist expression. LCN2, one kind of breast cancer metastasis stimulator, was also found for the first time to be repressed by 1α,25(OH)2D3 and MART-10 in breast cancer cells. Matrix metalloproteinase-9 (MMP-9) activity was also downregulated by MART-10. Furthermore, F-actin synthesis in MDA-MB-231 cells was attenuated as exposure to 1α,25(OH)2D3 and MART-10. Based on our result, we conclude that MART-10 could effectively inhibit TNBC cells metastatic potential and deserves further investigation as a new regimen to treat TNBC. PMID:27110769

  12. The Vitamin D Analog, MART-10, Attenuates Triple Negative Breast Cancer Cells Metastatic Potential

    Directory of Open Access Journals (Sweden)

    Kun-Chun Chiang

    2016-04-01

    Full Text Available Regarding breast cancer treatment, triple negative breast cancer (TNBC is a difficult issue. Most TNBC patients die of cancer metastasis. Thus, to develop a new regimen to attenuate TNBC metastatic potential is urgently needed. MART-10 (19-nor-2α-(3-hydroxypropyl-1α,25(OH2D3, the newly-synthesized 1α,25(OH2D3 analog, has been shown to be much more potent in cancer growth inhibition than 1α,25(OH2D3 and be active in vivo without inducing obvious side effect. In this study, we demonstrated that both 1α,25(OH2D3 and MART-10 could effectively repress TNBC cells migration and invasion with MART-10 more effective. MART-10 and 1α,25(OH2D3 induced cadherin switching (upregulation of E-cadherin and downregulation of N-cadherin and downregulated P-cadherin expression in MDA-MB-231 cells. The EMT(epithelial mesenchymal transition process in MDA-MB-231 cells was repressed by MART-10 through inhibiting Zeb1, Zeb2, Slug, and Twist expression. LCN2, one kind of breast cancer metastasis stimulator, was also found for the first time to be repressed by 1α,25(OH2D3 and MART-10 in breast cancer cells. Matrix metalloproteinase-9 (MMP-9 activity was also downregulated by MART-10. Furthermore, F-actin synthesis in MDA-MB-231 cells was attenuated as exposure to 1α,25(OH2D3 and MART-10. Based on our result, we conclude that MART-10 could effectively inhibit TNBC cells metastatic potential and deserves further investigation as a new regimen to treat TNBC.

  13. Irinotecan, Continuous 5-Fluorouracil, and Low dose of Leucovorin (modified FOLFIRI) as First Line of Therapy in Recurrent or Metastatic Colorectal Cancer

    OpenAIRE

    Lee, Myung-Ah; Byun, Jae-Ho; Shim, Byoung-Young; Woo, In-Sook; Kang, Jin-Hyung; Hong, Young Seon; Lee, Kyung Shik; Choi, Myung Gyu; Chang, Suk Kyun; Oh, Seong Taek; Choi, Sung Il; Lee, Doo Suk

    2005-01-01

    Background Irinotecan, in combination with 5-fluorouracil (5-FU) and a high dose of leucovorin (LV), known as FOLFIRI regimen, has shown activity in recurrent or metastatic colorectal cancer. Therefore, we evaluated the efficacy and safety of irinotecan, 5-FU and a low dose of LV (modified FOLFIRI) as a first line of therapy for patients with relapsed or metastatic colorectal cancer. Methods Between January 2002 and October 2004, 44 patients with histologically confirmed recurrent or metastat...

  14. Association between tumor tissue TIMP-1 levels and objective response to first-line chemotherapy in metastatic breast cancer

    DEFF Research Database (Denmark)

    Klintman, Marie; Würtz, Sidse Ørnbjerg; Christensen, Ib Jarle

    2010-01-01

    In a previous study from our laboratory, high tumor levels of tissue inhibitor of metalloproteinases-1 (TIMP-1) have been associated with an adverse response to chemotherapy in metastatic breast cancer suggesting that TIMP-1, which is known to inhibit apoptosis, may be a new predictive marker...... in this disease. The purpose of this study was to investigate the association between TIMP-1 and objective response to chemotherapy in an independent patient population consisting of patients with metastatic breast cancer from Sweden and Denmark. TIMP-1 was measured using ELISA in 162 primary tumor extracts from...... patients who later developed metastatic breast cancer and these levels were related to the objective response to first-line chemotherapy. Increasing levels of TIMP-1 were associated with a decreasing probability of response to treatment, reaching borderline significance (OR = 1.59, 95% CI: 0.97-2.62, P = 0...

  15. Cancer of the prostate presenting with diffuse osteolytic metastatic bone lesions: a case report

    Directory of Open Access Journals (Sweden)

    Segamwenge Innocent Lule

    2012-12-01

    Full Text Available Abstract Introduction Prostate cancer is the second most common cancer in men and the fifth most common cancer worldwide. In the USA it is more common in African-American men than in Caucasian men. Prostate cancer frequently metastasizes to bone and the lesions appear osteoblastic on radiographs. Presentation with diffuse osteolytic bone lesions is rare. We describe an unusual presentation of metastatic prostate cancer with diffuse osteolytic bone lesions. Case presentation A 65-year-old Namibian man presented with anemia, thrombocytopenia and worsening back pains. In addition he had complaints of effort intolerance, palpitations, dysuria and mild symptoms of bladder outlet obstruction. On examination he was found to be anemic, had a swollen tender right shoulder joint and spine tenderness to percussion. On digital rectal examination he had asymmetrical enlargement of the prostate which felt nodular and hard with diffuse firmness in some parts. His prostate-specific antigen was greater than 100ng/mL and he had diffuse osteolytic lesions involving the right humerus, and all vertebral, femur and pelvic bones. His screen for multiple myeloma was negative and the prostate biopsy confirmed prostate cancer. Conclusion Prostate cancer rarely presents with diffuse osteolytic bone lesions and should be considered in the differential diagnosis when evaluating male patients with osteolytic bone lesions.

  16. A Case Report of Unilateral Severe Visual Loss Along with Bilateral Optic Disc Cupping Secondary to Metastatic Brain Tumor

    Directory of Open Access Journals (Sweden)

    M Mahdavi

    2006-07-01

    Full Text Available Purpose: To report a case of unilateral severe visual loss and bilateral optic disc cupping secondary to brain metastasis of bronchogenic carcinoma Patient and findings: A 48 year-old woman presented with severe visual loss of left eye without redness or pain or any systemic findings .Clinical findings included decreased visual acuity of left eye to 4 m CF and (+3 positive Marcus-Gunn reflex .There was asymmetric optic disc cupping associated with visual field defect in left eye The neurologic investigations showed a secondary metastatic tumor in the brain from bronchogenic carcinoma. Conclusion: Before making a diagnosis of normal -tension glaucoma in asymmetric optic disc cupping and normal intraocular pressure, ophthalmologists should rule out neurologic defects and brain tumors.

  17. Lack of Caudal-Type Homeobox Transcription Factor 2 Expression as a Prognostic Biomarker in Metastatic Colorectal Cancer.

    Science.gov (United States)

    Zhang, Ben Y; Jones, Jeremy C; Briggler, Andrew M; Hubbard, Joleen M; Kipp, Benjamin R; Sargent, Daniel J; Dixon, Jesse G; Grothey, Axel

    2017-06-01

    Although the lack of CDX2 expression has recently been proposed as a potential biomarker for a high risk of relapse in patients with stage II and III colon cancer after complete surgical resection, its prognostic role in metastatic colorectal cancer (CRC) remains unclear and warrants investigation. We identified 145 patients treated at our institution from 2006 to 2016, including 66 patients with CDX2-negative metastatic CRC and a comparison cohort of 79 patients with CDX2-positive metastatic CRC. Overall survival (OS) and progression-free survival (PFS) for first-line systemic therapy were estimated using the Kaplan-Meier method. The associations of CDX2 expression with survival were evaluated using Cox proportional hazards regression models. The prevalence of absent CDX2 expression in our cohort was 5.6%. Patients with CDX2-negative metastatic CRC were significantly more likely to be female, and to have right-sided primary tumors, poorly differentiated histologic features, and distant lymph node metastasis. The median OS for patients with CDX2-negative and -positive metastatic CRC was 8 and 39 months, respectively (hazard ratio [HR], 4.04; 95% confidence interval [CI], 2.49-6.54; P lack of CDX2 expression and OS remained statistically significant (HR, 4.52; 95% CI, 2.50-8.17; P lack of CDX2 expression in metastatic CRC is an adverse prognostic feature and a potential negative predictor of the response to chemotherapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Brain metastases from epithelial ovarian cancer.

    Science.gov (United States)

    Tay, S-K; Rajesh, H

    2005-01-01

    Brain metastasis from epithelial ovarian cancer is uncommon. We studied the presentation, treatment, and prognosis of brain metastasis in a single institution. A retrospective review of clinical details kept in the computer database of gynecologic oncology services in a tertiary institution between 1993 and 2003 was done. A Medline search for English publications on brain metastasis from epithelial ovarian cancer was performed from 1966 to 2003. The study period included 605 patients, and 4 (0.66%) patients developed brain metastases. The patients were usually well, until they presented with hemiparesis. The median primary treatment to brain metastasis interval was 16.5 months. Three out of four cases had multiple brain metastases, and all had small-volume extracranial tumor relapses. Serum CA125 measurement was not reliable in the screening for brain metastasis. The median survival after brain metastasis was 19.5 months. Single brain metastasis can be treated with surgery. Our experience supports the prevalent published opinion that all other cases should be considered for combined radiotherapy and surgery or radiotherapy and chemotherapy. Surveillance of tumor recurrence with serum CA125 monitoring does not predict brain metastasis, which carries a poor prognosis. The best mode of management of these patients is yet to be determined. Large study with multicenter participation to establish the standard treatment is urgently needed.

  19. Actin cytoskeleton regulation of epithelial mesenchymal transition in metastatic cancer cells.

    Directory of Open Access Journals (Sweden)

    Jay Shankar

    Full Text Available Epithelial-mesenchymal transition (EMT is associated with loss of the cell-cell adhesion molecule E-cadherin and disruption of cell-cell junctions as well as with acquisition of migratory properties including reorganization of the actin cytoskeleton and activation of the RhoA GTPase. Here we show that depolymerization of the actin cytoskeleton of various metastatic cancer cell lines with Cytochalasin D (Cyt D reduces cell size and F-actin levels and induces E-cadherin expression at both the protein and mRNA level. Induction of E-cadherin was dose dependent and paralleled loss of the mesenchymal markers N-cadherin and vimentin. E-cadherin levels increased 2 hours after addition of Cyt D in cells showing an E-cadherin mRNA response but only after 10-12 hours in HT-1080 fibrosarcoma and MDA-MB-231 cells in which E-cadherin mRNA level were only minimally affected by Cyt D. Cyt D treatment induced the nuclear-cytoplasmic translocation of EMT-associated SNAI 1 and SMAD1/2/3 transcription factors. In non-metastatic MCF-7 breast cancer cells, that express E-cadherin and represent a cancer cell model for EMT, actin depolymerization with Cyt D induced elevated E-cadherin while actin stabilization with Jasplakinolide reduced E-cadherin levels. Elevated E-cadherin levels due to Cyt D were associated with reduced activation of Rho A. Expression of dominant-negative Rho A mutant increased and dominant-active Rho A mutant decreased E-cadherin levels and also prevented Cyt D induction of E-cadherin. Reduced Rho A activation downstream of actin remodelling therefore induces E-cadherin and reverses EMT in cancer cells. Cyt D treatment inhibited migration and, at higher concentrations, induced cytotoxicity of both HT-1080 fibrosarcoma cells and normal Hs27 fibroblasts, but only induced mesenchymal-epithelial transition in HT-1080 cancer cells. Our studies suggest that actin remodelling is an upstream regulator of EMT in metastatic cancer cells.

  20. Prostate radiation in non-metastatic castrate refractory prostate cancer provides an interesting insight into biology of prostate cancer

    Directory of Open Access Journals (Sweden)

    Pascoe Abigail C

    2012-03-01

    Full Text Available Abstract Background The natural history of non-metastatic castrate refractory prostate cancer is unknown and treatment options are limited. We present a retrospective review of 13 patients with locally advanced or high risk prostate cancer, initially treated with hormone monotherapy and then treated with prostate radiation after becoming castration refractory. Findings Median PSA response following prostate radiation was 67.4%. Median time to biochemical progression following radiotherapy was 15 months and to detection of metastatic disease was 18.5 months. Median survival from castration resistance (to date of death or November 2011 was 60 months, with median survival from RT 42 months. Conclusion Prostate radiation appears to be beneficial even in patients with potential micrometastatic disease, which supports the hypothesis that the primary tumour is important in the progression of prostate cancer. These results are an interesting addition to the literature on the biology of prostate cancer especially as this data is unlikely to be available in the future due to combined prostate radiation and androgen deprivation therapy now being the standard of care.

  1. Higher overall survival in metastatic pancreatic cancer: the impact of where and how treatment is delivered

    Science.gov (United States)

    Usón, Pedro Luiz Serrano; França, Monique Sedlmaier; Rodrigues, Heloisa Veasey; Macedo, Antônio Luiz de Vasconcellos; Goldenberg, Alberto; Smaletz, Oren; Armentano, Daniela Pezzutti Domingues; Simon, Sergio Daniel; Gansl, Rene Claudio

    2015-01-01

    Objective To determine the overall survival of patients with advanced pancreatic cancer and evaluate factors that impact prognosis in a private cancer center. Methods Data from the Hospital Cancer Registry at Hospital Israelita Albert Einstein were retrospectively collected. The patients enrolled had metastatic cancer at diagnosis or earlier staging and subsequent recurrence. Cases of neuroendocrine tumors were excluded. Results A total of 65 patients were evaluated, including 63 with adenocarcinoma. The median overall survival for patients in all stages was 20.7 months (95%CI: 15.6-25.7), while the overall survival of metastatic disease was 13.3 months. Among the 33 cases with stage IV cancer, there was no evidence of a statistically significant association between median survival and CA19-9 dosage (p=0.212), tumor location (p=0.482), first treatment performed (p=0.337), lymphovascular invasion (p=0.286), and age (p=0.152). However, the number of lines of chemotherapy was significantly associated with survival (log-rank p=0.013), with an estimated median survival of 10.2 months for patients who received up to two lines of treatment and 23.5 months for those receiving more than two lines of chemotherapy. Conclusion The survival of patients treated was longer than that reported in the literature. The only statistically significant factor related to increased survival was higher number of lines of chemotherapy received. We believe that the higher socioeconomic status of patients surveyed in this study, as well as their greater access to treatment options, may have influenced their overall survival. PMID:26313433

  2. The Subclonal Architecture of Metastatic Breast Cancer: Results from a Prospective Community-Based Rapid Autopsy Program “CASCADE”

    Science.gov (United States)

    Flensburg, Christoffer; Alsop, Kathryn; Mansour, Mariam; Francis, Prudence A.; Thorne, Heather A.; Silva, Maria Joao; Kanu, Nnennaya; Dietzen, Michelle; Bowtell, David D.; Speed, Terence P.; Swanton, Charles; Loi, Sherene

    2016-01-01

    Background Understanding the cancer genome is seen as a key step in improving outcomes for cancer patients. Genomic assays are emerging as a possible avenue to personalised medicine in breast cancer. However, evolution of the cancer genome during the natural history of breast cancer is largely unknown, as is the profile of disease at death. We sought to study in detail these aspects of advanced breast cancers that have resulted in lethal disease. Methods and Findings Three patients with oestrogen-receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer and one patient with triple negative breast cancer underwent rapid autopsy as part of an institutional prospective community-based rapid autopsy program (CASCADE). Cases represented a range of management problems in breast cancer, including late relapse after early stage disease, de novo metastatic disease, discordant disease response, and disease refractory to treatment. Between 5 and 12 metastatic sites were collected at autopsy together with available primary tumours and longitudinal metastatic biopsies taken during life. Samples underwent paired tumour-normal whole exome sequencing and single nucleotide polymorphism (SNP) arrays. Subclonal architectures were inferred by jointly analysing all samples from each patient. Mutations were validated using high depth amplicon sequencing. Between cases, there were significant differences in mutational burden, driver mutations, mutational processes, and copy number variation. Within each case, we found dramatic heterogeneity in subclonal structure from primary to metastatic disease and between metastatic sites, such that no single lesion captured the breadth of disease. Metastatic cross-seeding was found in each case, and treatment drove subclonal diversification. Subclones displayed parallel evolution of treatment resistance in some cases and apparent augmentation of key oncogenic drivers as an alternative resistance mechanism. We

  3. The Subclonal Architecture of Metastatic Breast Cancer: Results from a Prospective Community-Based Rapid Autopsy Program "CASCADE".

    Directory of Open Access Journals (Sweden)

    Peter Savas

    2016-12-01

    Full Text Available Understanding the cancer genome is seen as a key step in improving outcomes for cancer patients. Genomic assays are emerging as a possible avenue to personalised medicine in breast cancer. However, evolution of the cancer genome during the natural history of breast cancer is largely unknown, as is the profile of disease at death. We sought to study in detail these aspects of advanced breast cancers that have resulted in lethal disease.Three patients with oestrogen-receptor (ER-positive, human epidermal growth factor receptor 2 (HER2-negative breast cancer and one patient with triple negative breast cancer underwent rapid autopsy as part of an institutional prospective community-based rapid autopsy program (CASCADE. Cases represented a range of management problems in breast cancer, including late relapse after early stage disease, de novo metastatic disease, discordant disease response, and disease refractory to treatment. Between 5 and 12 metastatic sites were collected at autopsy together with available primary tumours and longitudinal metastatic biopsies taken during life. Samples underwent paired tumour-normal whole exome sequencing and single nucleotide polymorphism (SNP arrays. Subclonal architectures were inferred by jointly analysing all samples from each patient. Mutations were validated using high depth amplicon sequencing. Between cases, there were significant differences in mutational burden, driver mutations, mutational processes, and copy number variation. Within each case, we found dramatic heterogeneity in subclonal structure from primary to metastatic disease and between metastatic sites, such that no single lesion captured the breadth of disease. Metastatic cross-seeding was found in each case, and treatment drove subclonal diversification. Subclones displayed parallel evolution of treatment resistance in some cases and apparent augmentation of key oncogenic drivers as an alternative resistance mechanism. We also observed the

  4. The Subclonal Architecture of Metastatic Breast Cancer: Results from a Prospective Community-Based Rapid Autopsy Program "CASCADE".

    Science.gov (United States)

    Savas, Peter; Teo, Zhi Ling; Lefevre, Christophe; Flensburg, Christoffer; Caramia, Franco; Alsop, Kathryn; Mansour, Mariam; Francis, Prudence A; Thorne, Heather A; Silva, Maria Joao; Kanu, Nnennaya; Dietzen, Michelle; Rowan, Andrew; Kschischo, Maik; Fox, Stephen; Bowtell, David D; Dawson, Sarah-Jane; Speed, Terence P; Swanton, Charles; Loi, Sherene

    2016-12-01

    Understanding the cancer genome is seen as a key step in improving outcomes for cancer patients. Genomic assays are emerging as a possible avenue to personalised medicine in breast cancer. However, evolution of the cancer genome during the natural history of breast cancer is largely unknown, as is the profile of disease at death. We sought to study in detail these aspects of advanced breast cancers that have resulted in lethal disease. Three patients with oestrogen-receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer and one patient with triple negative breast cancer underwent rapid autopsy as part of an institutional prospective community-based rapid autopsy program (CASCADE). Cases represented a range of management problems in breast cancer, including late relapse after early stage disease, de novo metastatic disease, discordant disease response, and disease refractory to treatment. Between 5 and 12 metastatic sites were collected at autopsy together with available primary tumours and longitudinal metastatic biopsies taken during life. Samples underwent paired tumour-normal whole exome sequencing and single nucleotide polymorphism (SNP) arrays. Subclonal architectures were inferred by jointly analysing all samples from each patient. Mutations were validated using high depth amplicon sequencing. Between cases, there were significant differences in mutational burden, driver mutations, mutational processes, and copy number variation. Within each case, we found dramatic heterogeneity in subclonal structure from primary to metastatic disease and between metastatic sites, such that no single lesion captured the breadth of disease. Metastatic cross-seeding was found in each case, and treatment drove subclonal diversification. Subclones displayed parallel evolution of treatment resistance in some cases and apparent augmentation of key oncogenic drivers as an alternative resistance mechanism. We also observed the role of

  5. Influence of the location and number of metastases in the survival of metastatic prostatic cancer patients.

    Science.gov (United States)

    Guijarro, A; Hernández, V; de la Morena, J M; Jiménez-Valladolid, I; Pérez-Fernández, E; de la Peña, E; Llorente, C

    2017-05-01

    The prognosis of patients diagnosed with metastatic prostate cancer seems to be modulated by factors such as the number and site of metastases. Our objective is to evaluate survival outcomes according to the number and site of metastases in our series of metastatic patients over the last 15 years. A retrospective analysis was performed on patients diagnosed between 1998 and 2014. We analyzed overall survival and progression-free survival, depending on the number and location of metastases on patients with newly diagnosed metastatic prostate cancer. Other potential prognostic factors were also evaluated: age, clinical stage, PSA at diagnosis, Gleason, PSA nadir, time till PSA nadir and first-line or second-line treatment after progression. We analyzed a series of 162 patients. The mean age was 72.7yr (SD: 8.5). The estimated median overall survival was 3.9 yr (95% CI 2.6-5.2). The overall survival in patients with only lymph node metastases was 7 yr (95% CI 4.1-9.7), 3.9 (95%CI 2.3-5.5) in patients with only bone metastases, 2.5 yr (95% CI 2-2.3) in lymph nodes and bone metastases, and 2.2 yr (95% CI 1.4-3) in patients with visceral metastases (Pnumber of metastases showed no association with survival. The site of metastases has a clear impact on both overall survival and progression-free survival. Patients with only lymph node involvement had a better prognosis. The number of metastases showed no significant impact on survival in our series. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. Locoregional symptoms in patients with de novo metastatic prostate cancer: Morbidity, management, and disease outcome.

    Science.gov (United States)

    Patrikidou, Anna; Brureau, Laurent; Casenave, Julien; Albiges, Laurence; Di Palma, Mario; Patard, Jean-Jacques; Baumert, Hervé; Blanchard, Pierre; Bossi, Alberto; Kitikidou, Kyriaki; Massard, Christophe; Fizazi, Karim; Blanchet, Pascal; Loriot, Yohann

    2015-05-01

    The paradigm change observed over the last few years in several solid tumors emphasizes the value of locoregional treatment in the presence of metastatic disease, currently ignored in de novo prostate cancer (CaP). We investigated the effect of the primary tumor that is left untreated on prostate cancer-specific morbidity and mortality, time to castration resistance, and overall survival (OS). We performed a bicentric cohort study. The overall population included de novo metastatic CaP managed at the Genito-Urinary Oncology Unit of the Gustave Roussy Institute and the Urology Clinic of the University Hospital of Pointe-à-Pitre, France. Descriptive statistical and outcome analyses were performed in the overall cohort and also separately in the N+M0 and M+subgroups. The overall cohort included 263 patients. Approximately two-thirds of patients (64%) presented with locoregional symptoms at diagnosis, and 78% throughout the disease. Of the symptomatic patients, 59% required a locoregional procedure. Median OS of patients with locoregional symptoms at diagnosis was shorter than in those who were asymptomatic (47 vs. 86 mo, P = 0.0007); this difference was maintained in the N+M0 and M+subgroups. Median OS and time to castration resistance showed a nonsignificant trend in favor of patients undergoing a locoregional treatment at diagnosis. The presence of symptoms due to locoregional disease in de novo metastatic CaP entails significant morbidity and even mortality and requires active management. Randomized prospective trials are needed to evaluate the role of initial definite locoregional treatment in these patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Peritumoral edema of meningiomas and metastatic brain tumors: differences in diffusion characteristics evaluated with diffusion-tensor MR imaging

    International Nuclear Information System (INIS)

    Toh, Cheng-Hong; Wong, Alex M.-C; Wong, Ho-Fai; Wan, Yung-Liang; Wei, Kuo-Chen; Ng, Shu-Hang

    2007-01-01

    We prospectively compared the fractional anisotropy (FA) and mean diffusivity (MD) of the peritumoral edema of meningiomas and metastatic brain tumors with diffusion-tensor magnetic resonance (MR) imaging. The study protocol was approved by the local ethics committee, and written informed consent was obtained. Preoperative diffusion-tensor MR imaging was performed in 15 patients with meningiomas and 11 patients with metastatic brain tumors. Regions of interest (ROI) were placed in the peritumoral edema and normal-appearing white matter (NAWM) of the contralateral hemisphere to measure the FA and MD. The FA and MD ratios were calculated for each ROI in relation to the NAWM of the contralateral hemisphere. Changes in peritumoral MD and FA, in terms of primary values and ratios, were compared using a two-sample t-test; P -3 mm 2 /s) of the peritumoral edema for metastases and meningiomas, respectively, were 0.902 ± 0.057 and 0.820 ± 0.094, the mean MD ratios were 220.3 ± 22.6 and 193.1 ± 23.4, the mean FA values were 0.146 ± 0.026 and 0.199 ± 0.052, and the mean FA ratios were 32.3 ± 5.9 and 46.0 ± 12.1. All the values were significantly different between metastases and meningiomas (MD values P 0.016, MD ratios P = 0.006, FA values P = 0.005, FA ratios P = 0.002). The peritumoral edema of metastatic brain tumors and meningiomas show different MD and FA on diffusion-tensor MR imaging. (orig.)

  8. Effects of aspirin on small-cell lung cancer mortality and metastatic presentation.

    Science.gov (United States)

    Maddison, Paul

    2017-04-01

    Although meta-analysis data have shown that taking regular aspirin may reduce lung cancer mortality, individual trial data results are conflicting, and the data on the effects of aspirin on different histological subtypes of lung tumours, in particular small-cell lung cancer, are sparse. We conducted a prospective observational study of 313 patients with a new diagnosis of small-cell lung cancer and recorded use of aspirin before and after tumour diagnosis. Seventy-one (23%) patients were taking regular daily aspirin for more than 2 years at the time of tumour diagnosis. We found that regular use of aspirin had no effect on survival nor metastatic presentation compared to data from small-cell lung cancer patients not taking aspirin. The lack of survival benefit in patients with small-cell lung cancer taking long-term aspirin may be due to the low expression of cyclooxygenase-2 in small-cell lung cancer tissue. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Deficient Mismatch Repair and the Role of Immunotherapy in Metastatic Colorectal Cancer.

    Science.gov (United States)

    Quiroga, Dionisia; Lyerly, H Kim; Morse, Michael A

    2016-08-01

    Division of colorectal cancers (CRCs) into molecular subsets yields important consequences for prognosis and therapeutic response. The microsatellite instability (MSI) immune subgroup, accounting for 15 % of early-stage and 3 % of metastatic CRCs, are a result of deficient cellular DNA mismatch repair (dMMR) mechanisms. dMMR CRCs are notable for greater survivability, yet lack of benefit from fluoropyrimidine-based therapy in early-stage disease as compared to proficient DNA mismatch repair (pMMR) CRCs but are substantially lethal when metastatic. The surging interest in cancer immunotherapy, particularly checkpoint blockade, has further led to a focus on MSI tumors, which are notable for their substantial T cell infiltrate. In this review, we will discuss the biologic underpinnings for the immunogenicity of dMMR CRC and the preclinical development of therapies intended to modulate this immune response. Next, we will discuss the previous and ongoing clinical trials specifically designed to evaluate immunotherapeutic treatment of dMMR CRCs. Building on the success of the early immune checkpoint inhibitor clinical trials for dMMR CRC, combinations with other anti-tumor immunotherapies may provide an even more robust response, thereby, creating an alternative treatment regimen for those who have failed standard therapies or possibly resulting in prophylactic therapies for patients with highly oncogenic hereditary mismatch repair deficiencies.

  10. Proactive strategies for regorafenib in metastatic colorectal cancer: implications for optimal patient management

    International Nuclear Information System (INIS)

    Khan, Gazala; Moss, Rebecca A; Braiteh, Fadi; Saltzman, Marc

    2014-01-01

    Regorafenib is a broad-spectrum oral multikinase inhibitor that targets several angiogenic, oncogenic, and stromal receptor tyrosine kinases that support the tumor microenvironment. Results from the pivotal Phase III Patients with Metastatic Colorectal Cancer Treated with Regorafenib or Placebo After Failure of Standard Therapy (CORRECT) trial showed that the addition of regorafenib to best supportive care resulted in a significant improvement in median overall survival and progression-free survival compared with placebo plus best supportive care in patients with metastatic colorectal cancer (mCRC) following all available approved therapies. Thus, regorafenib is the first oral multikinase inhibitor indicated for mCRC; it currently has approval in the USA, EU, Japan, Canada, and Singapore for the treatment of mCRC patients who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-vascular endothelial growth factor therapy, and, if the tumor is KRAS wild-type, an anti-epidermal growth factor receptor therapy. In this review, we highlight regorafenib’s mechanism of action, present key efficacy data from the CORRECT trial, and discuss how to proactively manage common adverse events (eg, hand-foot skin reaction, hypertension, oral mucositis, diarrhea, and fatigue) experienced by patients receiving regorafenib. Increased awareness of potential adverse events associated with regorafenib and the implementation of proactive strategies to prevent, monitor, and manage these events early in the course of treatment will be instrumental in ensuring optimal patient management and continuation of regorafenib therapy

  11. Changes in Water Mobility Measured by Diffusion MRI Predict Response of Metastatic Breast Cancer to Chemotherapy

    Directory of Open Access Journals (Sweden)

    Rebecca J. Theilmann

    2004-11-01

    Full Text Available A goal of oncology is the individualization of patient care to optimize therapeutic responses and minimize toxicities. Achieving this will require noninvasive, quantifiable, and early markers of tumor response. Preclinical data from xenografted tumors using a variety of antitumor therapies have shown that magnetic resonance imaging (MRI-measured mobility of tissue water (apparent diffusion coefficient of water, or ADCw is a biomarker presaging cell death in the tumor. This communication tests the hypothesis that changes in water mobility will quantitatively presage tumor responses in patients with metastatic liver lesions from breast cancer. A total of 13 patients with metastatic breast cancer and 60 measurable liver lesions were monitored by diffusion MRI after initiation of new courses of chemotherapy. MR images were obtained prior to, and at 4, 11, and 39 days following the initiation of therapy for determination of volumes and ADCw values. The data indicate that diffusion MRI can predict response by 4 or 11 days after commencement of therapy, depending on the analytic method. The highest concordance was observed in tumor lesions that were less than 8 cm3 in volume at presentation. These results suggest that diffusion MRI can be useful to predict the response of liver metastases to effective chemotherapy.

  12. Molecular analysis distinguishes metastatic disease from second cancers in patients with retinoblastoma.

    Science.gov (United States)

    Racher, Hilary; Soliman, Sameh; Argiropoulos, Bob; Chan, Helen S L; Gallie, Brenda L; Perrier, Renée; Matevski, Donco; Rushlow, Diane; Piovesan, Beata; Shaikh, Furqan; MacDonald, Heather; Corson, Timothy W

    2016-01-01

    The pediatric ocular tumor retinoblastoma readily metastasizes, but these lesions can masquerade as histologically similar pediatric small round blue cell tumors. Since 98% of retinoblastomas have RB1 mutations and a characteristic genomic copy number "signature", genetic analysis is an appealing adjunct to histopathology to distinguish retinoblastoma metastasis from second primary cancer in retinoblastoma patients. Here, we describe such an approach in two retinoblastoma cases. In patient one, allele-specific (AS)-PCR for a somatic nonsense mutation confirmed that a temple mass was metastatic retinoblastoma. In a second patient, a rib mass shared somatic copy number gains and losses with the primary tumor. For definitive diagnosis, however, an RB1 mutation was needed, but heterozygous promoter→exon 11 deletion was the only RB1 mutation detected in the primary tumor. We used a novel application of inverse PCR to identify the deletion breakpoint. Subsequently, AS-PCR designed for the breakpoint confirmed that the rib mass was metastatic retinoblastoma. These cases demonstrate that personalized molecular testing can confirm retinoblastoma metastases and rule out a second primary cancer, thereby helping to direct the clinical management. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Korean Medicine Therapy as a Substitute for Chemotherapy for Metastatic Breast Cancer: A Case Report

    Directory of Open Access Journals (Sweden)

    Dong-Hyun Lee

    2015-02-01

    Full Text Available A 46-year-old Korean woman was diagnosed with stage III breast cancer and underwent 8 cycles of neoadjuvant chemotherapy, breast conservation surgery and adjuvant radiotherapy. However, the cancer recurred in the right upper lung (RUL and the right pulmonary hilum after 8 months. The RUL nodule was removed through a wedge resection, and the pathologic finding was revealed as a metastatic adenocarcinoma. Adjuvant chemotherapy was recommended, but she refused it because she feared adverse reactions to chemotherapy. Instead, Korean Medicine Therapy with intravenous wild ginseng pharmacopuncture (WGP, Cordyceps sinensis pharmacopuncture, Trichosanthes kirilowii pharmacopuncture, Euonymus alatus pharmacopuncture (EAP and Astragalus membranaceus pharmacopuncture was started. After a month, the disease looked stable, but findings of newly occurring metastatic lymphadenopathies appeared on CT after 6 months. Salvage chemotherapy was recommended, but she also refused it. At this time, Prunella vulgaris pharmacopuncture was started. Finally, a complete resolution was confirmed on PET-CT after 5 months, and she has remained in stable condition for more than 6 months with WGP, EAP, a Soram nebulizer solution inhalation and the oral intake of Soramdan S and Hangamdan S.

  14. Circulating Tumor Cells Predict Occult Metastatic Disease and Prognosis in Pancreatic Cancer.

    Science.gov (United States)

    Court, Colin M; Ankeny, Jacob S; Sho, Shonan; Winograd, Paul; Hou, Shuang; Song, Min; Wainberg, Zev A; Girgis, Mark D; Graeber, Thomas G; Agopian, Vatche G; Tseng, Hsian-Rong; Tomlinson, James S

    2018-04-01

    Occult metastatic tumors, below imaging thresholds, are a limitation of staging systems that rely on cross-sectional imaging alone and are a cause of the routine understaging of pancreatic ductal adenocarcinomas (PDACs). We investigated circulating tumor cells (CTCs) as a preoperative predictor of occult metastatic disease and as a prognostic biomarker for PDAC patients. A total of 126 patients (100 with cancer, 26 with benign disease) were enrolled in our study and CTCs were identified and enumerated from 4 mL of venous blood using the microfluidic NanoVelcro assay. CTC enumeration was correlated with clinicopathologic variables and outcomes following both surgical and systemic therapies. CTCs were identified in 78% of PDAC patients and CTC counts correlated with increasing stage (ρ = 0.42, p < 0.001). Of the 53 patients taken for potentially curative surgery, 13 (24.5%) had occult metastatic disease intraoperatively. Patients with occult disease had significantly more CTCs than patients with local disease only (median 7 vs. 1 CTC, p < 0.0001). At a cut-off of three or more CTCs/4 mL, CTCs correctly identified patients with occult metastatic disease preoperatively (area under the receiver operating characteristic curve 0.82, 95% confidence interval (CI) 0.76-0.98, p < 0.0001). CTCs were a univariate predictor of recurrence-free survival following surgery [hazard ratio (HR) 2.36, 95% CI 1.17-4.78, p = 0.017], as well as an independent predictor of overall survival on multivariate analysis (HR 1.38, 95% CI 1.01-1.88, p = 0.040). CTCs show promise as a prognostic biomarker for PDAC patients at all stages of disease being treated both medically and surgically. Furthermore, CTCs demonstrate potential as a preoperative biomarker for identifying patients at high risk of occult metastatic disease.

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

    Science.gov (United States)

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

    2009-03-01

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

  16. Dendritic cell vaccination in combination with docetaxel for patients with metastatic castration-resistant prostate cancer

    DEFF Research Database (Denmark)

    Kongsted, Per; Borch, Troels Holz; Ellebaek, Eva

    2017-01-01

    Background aims  We investigated whether the addition of an autologous dendritic cell–based cancer vaccine (DCvac) induces an immune response in patients with metastatic castration-resistant prostate cancer treated with docetaxel.  Methods  Forty-three patients were randomized 1:1 to receive up......: 5.5 versus 5.7 months (P = 0.62, log rank) and 21.9 versus 25.1 months (P = 0.60, log rank). Nine (50%) and 14 (78%) patients treated with docetaxel and DCvac had a TAA-specific or vaccine-specific immune response in the ELISpot and DTH analysis, respectively. Vaccine induced toxicity was limited...

  17. Clinical trial enrollment, patient characteristics, and survival differences in prospectively registered metastatic colorectal cancer patients

    DEFF Research Database (Denmark)

    Sorbye, Halfdan; Pfeiffer, Per; Cavalli-Björkman, Nina

    2009-01-01

    BACKGROUND: Trial accrual patterns were examined to determine whether metastatic colorectal cancer (mCRC) patients enrolled in trials are representative of a general cancer population concerning patient characteristics and survival. METHODS: A total of 760 mCRC patients referred for their first...... oncological consideration at 3 hospitals in Scandinavia covering defined populations were registered consecutively during 2003 to 2006. Clinical trial enrollment, patient characteristics, and treatment were recorded prospectively, and the follow-up was complete. RESULTS: Palliative chemotherapy was initiated...... was then only 2.1 months. The median survival for all 760 nonresectable mCRC patients was 10.7 months. CONCLUSIONS: mCRC patients enrolled into clinical trials differ in characteristics from patients receiving chemotherapy outside protocol and have better survival, even when given the same treatment. Although...

  18. Regorafenib-induced retinal and gastrointestinal hemorrhage in a metastatic colorectal cancer patient with liver dysfunction

    Science.gov (United States)

    Tsuchihashi, Kenji; Shimokawa, Hozumi; Takayoshi, Kotoe; Nio, Kenta; Aikawa, Tomomi; Matsushita, Yuzo; Wada, Iori; Arita, Shuji; Ariyama, Hiroshi; Kusaba, Hitoshi; Sonoda, Koh-Hei; Akashi, Koichi; Baba, Eishi

    2017-01-01

    Abstract Rationale: Regorafenib is effective for metastatic colorectal cancer but its toxicity such as hemorrhage should be considered. The safety of regorafenib for the patient with the liver disease is not known. Patient concerns: Seventy-one-year old man of colon cancer had myodesopsia and blood stool after 14 days from the initiation of regorafenib administration with 50% dose reduction due to liver dysfunction. Diagnoses: Fundus examination revealed hemorrhage of the retinal vein. Interventions: Regorafenib treatment was discontinued and observational therapy was pursued. Outcomes: Retinal and gastrointestinal hemorrhage resolved in 1 week. Lessons: Retinal hemorrhage should be considered as the differential diagnosis of myodesopsia in the patient treated by regorafenib. Safety and pharmacokinetic of continuous regorafenib administration for patients with liver dysfunction remains to be clarified. PMID:29049226

  19. Autumn Royal and Ribier Grape Juice Extracts Reduced Viability and Metastatic Potential of Colon Cancer Cells

    Science.gov (United States)

    Valenzuela, Manuel; Bastias, Lorena; Montenegro, Iván; Werner, Enrique; Madrid, Alejandro; Godoy, Patricio

    2018-01-01

    Antioxidants are known to be beneficial to health. This paper evaluates the potential chemopreventive and anticancer properties of phenolic compounds present in grape juice extracts (GJE) from Autumn Royal and Ribier varieties. The effects of these GJE on viability (SRB day assay) and metastatic potential (migration and invasion parameters) of colon cancer cell lines HT-29 and SW-480 were evaluated. The effects of GJE on two matrix metalloproteinase gene expressions (MMP2 and MMP9) were also evaluated via qRT-PCR. In the former, GJE reduced cell viability in both cell lines in a dose-dependent manner. GJE treatment also reduced cell migration and invasion. Moreover, MMP-2 and MMP-9 gene expression diminished depending on extract and on cell type. Conclusions. These results provide novel information concerning anticancer properties of selected GJE by revealing selective cytotoxicity and the ability to reduce invasiveness of colon cancer cells. PMID:29552079

  20. Bevacizumab in the Treatment of Metastatic Breast Cancer: Friend or Foe?

    Science.gov (United States)

    Montero, Alberto J.; Escobar, Mauricio; Lopes, Gilberto; Glück, Stefan; Vogel, Charles

    2011-01-01

    Metastatic breast cancer (MBC) is a major cause of death among women worldwide. Progress has been made in treating MBC with the advent of anti-estrogen therapies, potent cytotoxic agents, and monoclonal antibodies. Bevacizumab is a monoclonal antibody against circulating vascular endothelial growth factor (VEGF), which was approved in 2008 by the US Food and Drug Administration (FDA), for first-line treatment of HER-2 negative MBC in combination with paclitaxel. The FDA then reversed this decision in December 2010 by recommending removal of the MBC indication from bevacizumab, citing primarily safety concerns, and that these risks did not outweigh the ability of bevacizumab to significantly prolong progression-free survival. This decision was unexpected in the oncology community and remains controversial. This review looks at all available phase 3 data with bevacizumab in the MBC setting to determine whether the data support this decision by the FDA, and discusses the future of bevacizumab in breast cancer. PMID:22012632

  1. Improved systemic treatment for early breast cancer improves cure rates, modifies metastatic pattern and shortens post-metastatic survival: 35-year results from the Munich Cancer Registry.

    Science.gov (United States)

    Hölzel, Dieter; Eckel, Renate; Bauerfeind, Ingo; Baier, Bernd; Beck, Thomas; Braun, Michael; Ettl, Johannes; Hamann, Ulrich; Kiechle, Marion; Mahner, Sven; Schindlbeck, Christian; de Waal, Johann; Harbeck, Nadia; Engel, Jutta

    2017-04-20

    Systemic therapies (ATHs) in early breast cancer have improved the survival of breast cancer (BC) patients in recent decades. The magnitude of the changes in overall, metastasis-free (MFS) and post-metastatic (PMS) survival and in the metastasis (MET) pattern will be described. We analysed 60,227 patients with a diagnosis of T-N-M0 BC between 1978 and 2013 and 11,983 patients with metastases (MET) in the Munich Cancer Registry. Patients will be divided into four time periods to identify relationships between BC and METs. Survival was estimated using Kaplan-Meier curves, and Cox proportional hazards models were used to explore the impact of the BC subtype and MET status on survival with the time periods as surrogate markers for ATH evolution. During the observation period, 5-year relative survival has improved from 80.3 to 93.6% with an adjusted hazard ratio of 0.54 (P < 0.0001). Successful implementation of ATH has changed the MET pattern. The percentage of liver and CNS METs has more than doubled, the rate of lung METs remains stable, and the rate of bone METs has been reduced by approximately 50%. MFS has been prolonged with a hazard ratio 0.75 (P < 0.0001), but PMS has declined (hazard ratio 1.36; P < 0.0001); however, effects of adjuvant and palliative treatments cannot be separated. These results do not contradict improvements in advanced BC and do not suggest alterations of MET tumour biology by ATH. Over the past three decades, ATHs have dramatically improved patient survival after BC diagnosis-most likely, by eradicating prevalent micro-METs; as a result, the MET pattern has changed. Eradicating only a portion of the first METs results in delaying the onset of subsequent MET, which leads to an apparently paradoxical effect: an extension of the MET-free interval and a reduction in PMS.

  2. Racial Disparities in Functional Disability among Older Women with Newly Diagnosed Non-metastatic Breast Cancer

    Science.gov (United States)

    Owusu, Cynthia; Schluchter, Mark; Koroukian, Siran M.; Mazhuvanchery, Suzanne; Berger, Nathan A.

    2013-01-01

    Background To assess racial differences in functional disability among older women with non-metastatic breast cancer. Methods This is a cross-sectional study. Between April 2008 and December 2012, women aged ≥65 years with newly diagnosed stage I–III breast cancer were recruited from ambulatory oncology clinics at an academic center. Prior to receiving any adjuvant treatment participants completed a comprehensive geriatric assessment. The primary outcome was functional disability, defined as dependency in any Basic or Instrumental Activity of Daily Living, Yes or No. Logistic regression analyses were undertaken. Results We enrolled 190 women whose mean age was 75.0 years at diagnosis (SD=7.0, range 65–93 years). Thirty-two percent were African-American (AA), and 39 percent had functional disability. Controlling for age, participants with functional disability were more likely to be AA [versus (vs.) non-Hispanic White], Odds ratio (OR) = 4.19, 95% confidence interval (CI) =2.12–8.27. Fifty-nine percent of the racial difference in functional disability was explained by a higher prevalence of lower income and education among AA. Additionally, the higher prevalence of chronic medical conditions and obesity among AA, after accounting for socioeconomic factors, further explained 40% of the Black-White difference in functional disability. Conclusion Among older women with newly diagnosed non-metastatic breast cancer, functional disability is highly prevalent and African-Americans are disproportionately affected. Interventions to optimize the functional status of at-risk individuals, particularly African-Americans, during and after cancer treatment may improve treatment tolerance and overall survival outcomes. PMID:24114615

  3. PIK3CA mutation detection in metastatic biliary cancer using cell-free DNA.

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    Kim, Seung Tae; Lira, Maruja; Deng, Shibing; Lee, Sujin; Park, Young Suk; Lim, Ho Yeong; Kang, Won Ki; Mao, Mao; Heo, Jin Seok; Kwon, Wooil; Jang, Kee-Taek; Lee, Jeeyun; Park, Joon Oh

    2015-11-24

    PIK3CA mutation is considered a good candidate for targeted therapies in cancers, especially biliary tract cancer (BTC). We evaluated the utility of cell free DNA (cfDNA) from serum by using droplet digital PCR (ddPCR) as an alternative source for PIK3CA mutation analysis. To identify matching archival tumour specimens from serum samples of advanced BTC patients, mutation detection using ddPCR with Bio-Rad's PrimePCR mutation and wild type assays were performed for PIK3CA p.E542K, p.E545K, and p.H1047R. Thirty-eight patients with metastatic BTC were enrolled. Only one (BTC 29T) sample (n = 38) was positive for PIK3CA p.E542K and another (BTC 27T) for p.H1047R mutation; none was positive for PIK3CA p.E545K. Matched serum sample (BTC 29P) was positive for PIK3CA p.E542K with 28 mutant copies detected, corresponding to 48 copies/ml of serum and an allelic prevalence of 0.3%. Another matched serum sample (BTC 27P) was positive for PIK3CA p.H1047R with 10 mutant copies detected, i.e. 18 copies/ml and an allelic frequency of 0.2%. High correlation was noted in the PIK3CA mutation status between tumour gDNA and serum cfDNA. Low-level PIK3CA mutations were detectable in the serum indicating the utility of cfDNA as a DNA source to detect cancer-derived mutations in metastatic biliary cancers.

  4. The efficacy and toxicity profile of metronomic chemotherapy for metastatic breast cancer: A meta-analysis.

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    Yangyang Liu

    Full Text Available The current meta-analysis aimed to summarize the available evidence for the efficacy and serious adverse events (AEs associated with use of metronomic chemotherapy (MCT in patients with metastatic breast cancer (MBC.Electronic databases (PubMed, EMBASE database, Web of Knowledge, and the Cochrane database were systematically searched for articles related to the use of MCT in MBC patients. Eligible studies included clinical trials of MBC patients treated with MCT that presented sufficient data related to tumor response, progression-free survival (PFS, overall survival (OS, and grade 3/4 AEs. A meta-analysis was performed using a random effects model.This meta-analysis consists of 22 clinical trials with 1360 patients. The pooled objective response rate and clinical benefit rate of MCT were 34.1% (95% CI 27.4-41.5 and 55.6% (95% CI 49.2-61.9, respectively. The overall 6-month PFS, 12-month OS, and 24-month OS rates were 56.8% (95% CI 48.3-64.9, 70.3% (95% CI 62.6-76.9, and 40.0% (95% CI 30.6-50.2, respectively. The pooled incidence of grade 3/4 AEs was 29.5% (95% CI 21.1-39.5. There was no statistically significant difference observed in any endpoint between subgroups defined by concomitant anti-cancer therapies or chemotherapy regimens. After excluding one controversial study, we observed a trend showing lower toxicity rates with the use of MCT alone compared to use of MCT with other anti-cancer therapies (P = 0.070.Metronomic chemotherapy may be effective for use in patients with metastatic breast cancer. MCT used alone is possibly equally effective and less toxic than combination therapies. Well-designed RCTs are needed to obtain more evidence.

  5. Proactive strategies for regorafenib in metastatic colorectal cancer: implications for optimal patient management

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    Khan G

    2014-03-01

    Full Text Available Gazala Khan,1 Rebecca A Moss,2 Fadi Braiteh,3,4 Marc Saltzman5 1Department of Hematology and Oncology, Henry Ford Hospital, Detroit, MI, USA; 2Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA; 3US Oncology Research, Las Vegas, NV, USA; 4Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA; 5Innovative Medical Research of South Florida, Inc, Aventura, FL, USA Abstract: Regorafenib is a broad-spectrum oral multikinase inhibitor that targets several angiogenic, oncogenic, and stromal receptor tyrosine kinases that support the tumor microenvironment. Results from the pivotal Phase III Patients with Metastatic Colorectal Cancer Treated with Regorafenib or Placebo After Failure of Standard Therapy (CORRECT trial showed that the addition of regorafenib to best supportive care resulted in a significant improvement in median overall survival and progression-free survival compared with placebo plus best supportive care in patients with metastatic colorectal cancer (mCRC following all available approved therapies. Thus, regorafenib is the first oral multikinase inhibitor indicated for mCRC; it currently has approval in the USA, EU, Japan, Canada, and Singapore for the treatment of mCRC patients who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-vascular endothelial growth factor therapy, and, if the tumor is KRAS wild-type, an anti-epidermal growth factor receptor therapy. In this review, we highlight regorafenib's mechanism of action, present key efficacy data from the CORRECT trial, and discuss how to proactively manage common adverse events (eg, hand-foot skin reaction, hypertension, oral mucositis, diarrhea, and fatigue experienced by patients receiving regorafenib. Increased awareness of potential adverse events associated with regorafenib and the implementation of proactive strategies to prevent, monitor, and manage these

  6. The prognostic impact of epidermal growth factor receptor in patients with metastatic gastric cancer

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    Atmaca Akin

    2012-11-01

    Full Text Available Abstract Background The epidermal growth factor receptor (EGFR is a potential target of anticancer therapy in gastric cancer. However, its prognostic role in metastatic gastric or gastroesophageal junction (GE cancer has not been established yet. Methods EGFR status was analyzed by immunohistochemistry (IHC in paraffin-embedded samples from 357 patients who received chemotherapy in 4 first-line trials. Automated RNA extraction from paraffin and RT-quantitative PCR were additionally used to evaluate EGFR mRNA expression in 130 patients. Results EGFR protein expression (any grade and overexpression (3+ were observed in 43% and 11% of patients, respectively. EGFR positivity correlated with intestinal type histology (p = 0.05, but not with other clinicopathologic characteristics. Median follow-up was 18.2 months. Median overall survival (OS was similar in patients with EGFR positive vs. those with EGFR negative tumors, regardless whether positivity was defined as ≥1+ (10.6 vs. 10.9 months, p = 0.463 or as 3+ (8.6 vs. 10.8 months, p = 0.377. The multivariate analysis indicated that EGFR status is not an independent prognostic factor (hazard ratio 0.85, 0.56 to 1.12, p = 0.247. There were also no significant differences in overall survival when patients were categorized according to median (p = 0.116 or quartile (p = 0.767 distribution of EGFR mRNA gene expression. Similar distributions of progression-free survival according to EGFR status were observed. Conclusions Unlike different cancer types where EGFR-positive disease is associated with an adverse prognostic value, EGFR positivity is not prognostic of patient outcome in metastatic gastric or GE cancer.

  7. Outpatient Pain Medication Use: An Electronic Daily Diary Study in Metastatic Breast Cancer.

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    Stephenson, Ellen; DeLongis, Anita; Bruel, Brian; Badr, Hoda

    2018-04-01

    Understanding cancer patients' everyday pain experiences and their concomitant use of pain medication may help identify ways to improve pain management among outpatients. This study examined the between-person and within-person associations between pain intensity and analgesic use in metastatic breast cancer patients. Fifty-three women who were initiating treatment for metastatic breast cancer completed electronic diary assessments six times per day for 14 days. The likelihood of taking medication was found to depend on patients' average pain levels and on whether their pain was better or worse than usual at the time. Patients who typically experienced moderate-to-high pain were more likely to be prescribed and to take analgesics than were patients who typically experienced low pain. However, these patients tended not to vary their medication use based on within-person fluctuations in pain. In contrast, patients who typically experienced low pain tended to increase their medication use at times when their pain was higher than usual but were less likely to use medication than were patients who typically experienced higher levels of pain. Our findings provide some evidence that patients with advanced cancer tend to use their pain medications appropriately. Patients with lower pain appear to be taking medications in response to increases in pain, whereas patients whose pain is typically more intense may be relying on other cues to prompt them to take analgesic medication. Clinicians may need to be sensitive to individual differences in the factors associated with pain medication use in daily life. Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  8. Motivation and preferences of exercise programmes in patients with inoperable metastatic lung cancer: a need assessment.

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    Kartolo, Adi; Cheng, Susanna; Petrella, Teresa

    2016-01-01

    The aim of this study is to investigate the motivation, ability, preferences, and perceived potential facilitating factors/barriers of patients with inoperable metastatic lung cancer towards exercise programmes. This is a cross-sectional study using survey adopting the Theory of Planned Behaviour (TPB) to obtain patients' experience recruited through Odette Cancer Centre, Sunnybrook Health Sciences Complex. Results were expressed in percentages, P value, and Spearman's rho. Sixty patients were recruited from January 2014 to April 2014. Patients generally had a high level across TPB measures, with 63% of them indicating that they have the motivation to exercise. Significant association in relation to motivation was established on attitudes (importance, P = 0.005, rho = 0.326; helpfulness, P = 0.015, rho = 0.348; and easiness, P = 0.001, rho = 0.375) and subjective norm of close members (P = 0.0069, rho = 0.348) and healthcare professionals (P = 0.012, rho = 0.328). Being a non-smoker (P = 0.042, rho = 0.311), having a past exercise history prior to diagnosis (P = 0.000, rho = 0.563), and absence of COPD (P = 0.016, rho = -0.312) were also shown to have a significant association with motivation to exercise. Patients were motivated to participate in an exercise programme despite contrary belief; however, they might have limited ability and preferred light intensity type of exercise such as walking. Their motivation to exercise was driven by different factors when compared to other cancer patient populations. Thus, it is important for healthcare professionals to understand the factors influencing their motivation and increase their awareness (only 26% of patients indicated receiving advice regarding exercise) to better the care towards patients with metastatic lung cancer.

  9. Nanotherapeutic approaches for brain cancer management.

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    Saenz del Burgo, Laura; Hernández, Rosa María; Orive, Gorka; Pedraz, Jose Luis

    2014-07-01

    Around the world, cancer remains one of the most important causes of morbidity and mortality. Worldwide, approximately 238,000 new cases of brain and other central nervous system tumors are diagnosed every year. Nanotherapeutic approaches hold tremendous potential for diagnosis and treatment of brain cancer, including the ability to target complex molecular cargoes to the tumor sites and the capacity of crossing the blood-brain barrier and accessing to the brain after systemic administration. A new generation of "smart" nanoparticles has been designed as novel targeted delivery devices for new therapies including gene therapy, anti-angiogenic and thermotherapy. This review highlights the latest research, opportunities and challenges for developing novel nanotherapeutics for treating brain cancers. This comprehensive review highlights the latest research results, opportunities and challenges for developing novel nanotherapeutics for treating brain cancers, with a special focus on "smart" nanoparticles as novel targeted delivery devices for new therapies including gene therapy, anti-angiogenic therapy and localized thermotherapy. © 2014.

  10. Prognostic implication of the metastatic lesion-to-ovarian cancer standardised uptake value ratio in advanced serous epithelial ovarian cancer

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    Chung, Hyun Hoon; Lee, Maria; Kim, Hee-Seung; Kim, Jae-Weon; Park, Noh-Hyun; Song, Yong Sang [Seoul National University College of Medicine, Department of Obstetrics and Gynaecology, Cancer Research Institute, Seoul (Korea, Republic of); Cheon, Gi Jeong [Seoul National University College of Medicine, Department of Nuclear Medicine, Cancer Research Institute, Seoul (Korea, Republic of)

    2017-11-15

    To evaluate the prognostic value of metabolic activity of metastatic lesions measured by {sup 18}F-flurodeoxyglucose ({sup 18}F-FDG) uptake on preoperative positron emission tomography/computed tomography (PET/CT) in patients with advanced serous epithelial ovarian cancer (EOC). Clinico-pathological variables and PET/CT parameters such as the maximum standardised uptake value of the ovarian cancer (SUV{sub ovary}), metastatic lesions (SUV{sub meta}), and the metastatic lesion-to-ovarian cancer standardised uptake value ratio (SUV{sub meta}/SUV{sub ovary}) were assessed in International Federation of Gynaecology and Obstetrics (FIGO) stage III, IV patients. Clinico-pathological data were retrospectively reviewed for 94 eligible patients. The median progression-free survival (PFS) was 18.5 months (range, 6-90 months), and 57 (60.6%) patients experienced recurrence. Older age [P = 0.017, hazard ratio (HR) 1.036, 95% CI 1.006-1.066], residual disease after surgery (P = 0.024, HR 1.907, 95% CI 1.087-3.346), and high SUV{sub meta}/SUV{sub ovary} (P = 0.019, HR 2.321, 95% CI 1.148-4.692) were independent risk factors of recurrence. Patients with high SUV{sub meta}/SUV{sub ovary} showed a significantly worse PFS than those with low SUV{sub meta}/SUV{sub ovary} (P = 0.007, log-rank test). Preoperative SUV{sub meta}/SUV{sub ovary} was significantly associated with recurrence and has an incremental prognostic value for PFS in patients with advanced serous EOC. (orig.)

  11. FIRST LINE 5-FU-BASED CHEMOTHERAPY WITH/WITHOUT BEVACIZUMAB FOR METASTATIC COLORECTAL CANCER: TISSUE BIOMARKER CANDIDATES

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    Assia Konsoulova

    2016-03-01

    Full Text Available Purpose: Colorectal cancer is the second leading cause of cancer mortality in the USA. According to Bulgarian National Statistics Institute, 2370 colon and 1664 rectal cancer cases were diagnosed in 2012 with total number of patients 29995. Adding bevacizumab to chemotherapy in patients with metastatic disease improves progression-free survival (PFS but no predictive markers have been proven in the clinical practice. In our study we examined two tissue biomarkers that may correlate with response to bevacizumab-containing chemotherapy in patients with metastatic colorectal cancer. Patients and Methods: 54 patients with metastatic colorectal cancer were assigned to first line 5-Fu-based chemotherapy with/without bevacizumab. The primary end point was PFS, with additional determination of response and toxicity. Paraffin-embedded samples from primary tumors were collected from all 54 patients. Expression levels of two tumor biomarkers VEGFR-2 and Neuropilin 1 (NP-1 were evaluated with immunohistochemistry. Results: The median PFS for the group treated with CT/Bev was 8.8 months, compared with 5.4 months for the group with chemotherapy alone (95% CI, log-rank test P =0.003. The corresponding overall response rates were 19.3% and 10.2% respectively (P < 0.05 for CT/Bev vs CT. Patients with low NP-1 had statistically significant prolongation of PFS as compared to those with high NP-1 (95% CI, log rank test p= 0.017. Patients with low NP-1 appeared to experience a larger bevacizumab treatment effect in terms of PFS (p=0,049,HR 0.333, 95% CI, 0.111 to 0.995 than patients with high NP-1. Conclusion: The addition of bevacizumab to 5-Fu based chemotherapy improves PFS for patients with metastatic colorectal cancer. Expression of tumor NP-1 is a potential biomarker candidate for prediction of clinical outcome in patients with metastatic colorectal cancer, treated with first line chemotherapy plus bevacizumab.

  12. Quality of life and its related factors among Iranian patients with metastatic gastrointestinal tract cancer: A cross-sectional study

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    Jabbar Heydari Fard

    2014-01-01

    Full Text Available Context: Quality of life (QoL is an important issue in all cancer patients; especially in patients with metastatic cancer. But there is very little information available about QoL in patients with metastatic gastrointestinal cancer. Aims: The aim of this study was to evaluate the quality of life and its associated factors among Iranian patients with metastatic gastrointestinal tract cancer. Materials and Methods: In this cross-sectional study, a total of 250 patients with metastatic gastrointestinal tract cancer were recruited from the one oncology center related to the Mazandaran University of Medical Sciences, Sari, between March 2012 and August 2013. Their QoL was evaluated using the EORTC QLQ-C30 questionnaire (Persian version. Results: In this study, the overall QoL score of patients with gastrointestinal tract cancer was 57.63, which was relatively optimal. There was a statistically significant relationship between symptoms scale and general health status domains of quality of life with age ( P < 0.05. Also, there was a significant association between patients′ gender and their social functioning ( P = 0.017 and also their emotional functioning ( P = 0.015. Conclusions: The findings suggest that in patients with metastatic gastrointestinal cancers, the most affected functions in their QoL were social and emotional functioning which get worse with age. Thus, providing psychological counseling and psychotherapy services to deliver culturally appropriate mental health care and social support for these patients and their families′ which can lead to the improvement of QoL in these patients is strongly recommended.

  13. Tyrosine kinase receptor inhibitor-targeted combined chemotherapy for metastatic bladder cancer

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    Chia-Lun Wu

    2012-04-01

    Full Text Available Overexpression of hypoxia-inducible factor-1 alpha is noted during the invasive and metastatic process of transitional cell carcinoma. It will upregulate vascular endothelial growth factor (VEGF and drive proliferation, invasiveness, metastasis, and antiapoptotic ability of cancer cells. We proposed that tyrosine kinase receptor inhibitor, sunitinib malate—(Sutent; Pfizer Inc., Taiwan, combined with chemotherapeutic drug may present synergistic cytotoxic enhancement to transitional cell carcinoma cells with subsequent inhibition of their cellular behaviors, including proliferation, invasiveness, and metastatic activity. The contents of VEGF-A in mouse bladder tumor cells (MBT-2 and culture medium were detected by quantification-polymerase chain reaction and Western blot individually. The inhibitory concentrations of various chemotherapeutic drugs, sunitinib, and their combination treatment in MBT-2 were determined by 3-(4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2H-tetrazolium bromide (MTT assay. Microchamber transmembrane migration assay was applied in evaluation of the inhibitory effects of different dosages of sunitinib and combination treatment on tumor cells. The cell cycle and apoptosis were analyzed after combination therapy by flow cytometry. Variation in apoptotic pathway was elucidated by Western blot using specific antibodies with cleaved PARP and caspase-3. Metastatic animal model mimicked by tail vein injection of MBT-2 cells was used to evaluate the treatment efficiency in tumor weight and survival rate. The mRNA and protein level of VEGF-A in MBT-2 cells increased by 70% at 48 hours interval under hypoxia stress condition. In MTT assay, MBT-2 cells had shown the highest sensitivity to epirubicin. Sunitinib combined with epirubicin had shown a synergistic cytotoxic effect to MBT-2 cells. Sunitinib and its combination with epirubicin showed significant inhibition on MBT-2 cells migration in microchambers. G2/M phase arrest and

  14. Concerns about Breast Cancer, Pain, and Fatigue in Non-Metastatic Breast Cancer Patients Undergoing Primary Treatment

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    Chelsea R. Amiel

    2016-08-01

    Full Text Available Women diagnosed with breast cancer often endorse psychosocial concerns prior to treatment, which may influence symptom experiences. Among these, low perceived social support relates to elevated fatigue. Those with low social support perceptions may also experience a greater sense of rejection. We sought to determine if social rejection concerns post-surgery predict fatigue interference 12 months later in women with non-metastatic breast cancer. Depressive symptoms and pain severity after completion of adjuvant therapy (six months post-surgery were examined as potential mediators. Women (N = 240 with non-metastatic breast cancer were recruited 2–10 weeks post-surgery. Multiple regression analyses examined relationships among variables adjusting for relevant covariates. Greater rejection concerns at study entry predicted greater fatigue interference 12 months later (p < 0.01. Pain severity after adjuvant therapy partially mediated the relationship between social rejection concerns and fatigue interference, with significant indirect (β = 0.06, 95% CI (0.009, 0.176 and direct effects (β = 0.18, SE = 0.07, t(146 = 2.78, p < 0.01, 95% CI (0.053, 0.311. Therefore, pain levels post-treatment may affect how concerns of social rejection relate to subsequent fatigue interference. Interventions targeting fears of social rejection and interpersonal skills early in treatment may reduce physical symptom burden during treatment and into survivorship.

  15. MET Activation and Physical Dynamics of the Metastatic Process: The Paradigm of Cancers of Unknown Primary Origin.

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    Stella, Giulia M; Benvenuti, Silvia; Gentile, Alessandra; Comoglio, Paolo M

    2017-10-01

    The molecular and cellular mechanisms which drive metastatic spread are the topic of constant debate and scientific research due to the potential implications for cancer patients' prognosis. In addition to genetics and environmental factors, mechanics of single cells and physical interaction with the surrounding environment play relevant role in defining invasive phenotype. Reconstructing the physical properties of metastatic clones may help to clarify still open issues in disease progression as well as to lead to new diagnostic and therapeutic approaches. In this perspective cancer of unknown primary origin (CUP) identify the ideal model to study physical interactions and forces involved in the metastatic process. We have previously demonstrated that MET oncogene is mutated with unexpected high frequency in CUPs. We here analyze and discuss how the MET activation by somatic mutation may affect physical properties in giving rise to such a highly malignant syndrome, as that defined by CUP. Copyright © 2017. Published by Elsevier B.V.

  16. MicroRNAs as Regulator of Signaling Networks in Metastatic Colon Cancer.

    Science.gov (United States)

    Wang, Jian; Du, Yong; Liu, Xiaoming; Cho, William C; Yang, Yinxue

    2015-01-01

    MicroRNAs (miRNAs) are a class of small, noncoding RNA molecules capable of regulating gene expression translationally and/or transcriptionally. A large number of evidence have demonstrated that miRNAs have a functional role in both physiological and pathological processes by regulating the expression of their target genes. Recently, the functionalities of miRNAs in the initiation, progression, angiogenesis, metastasis, and chemoresistance of tumors have gained increasing attentions. Particularly, the alteration of miRNA profiles has been correlated with the transformation and metastasis of various cancers, including colon cancer. This paper reports the latest findings on miRNAs involved in different signaling networks leading to colon cancer metastasis, mainly focusing on miRNA profiling and their roles in PTEN/PI3K, EGFR, TGFβ, and p53 signaling pathways of metastatic colon cancer. The potential of miRNAs used as biomarkers in the diagnosis, prognosis, and therapeutic targets in colon cancer is also discussed.

  17. MicroRNAs as Regulator of Signaling Networks in Metastatic Colon Cancer

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    Jian Wang

    2015-01-01

    Full Text Available MicroRNAs (miRNAs are a class of small, noncoding RNA molecules capable of regulating gene expression translationally and/or transcriptionally. A large number of evidence have demonstrated that miRNAs have a functional role in both physiological and pathological processes by regulating the expression of their target genes. Recently, the functionalities of miRNAs in the initiation, progression, angiogenesis, metastasis, and chemoresistance of tumors have gained increasing attentions. Particularly, the alteration of miRNA profiles has been correlated with the transformation and metastasis of various cancers, including colon cancer. This paper reports the latest findings on miRNAs involved in different signaling networks leading to colon cancer metastasis, mainly focusing on miRNA profiling and their roles in PTEN/PI3K, EGFR, TGFβ, and p53 signaling pathways of metastatic colon cancer. The potential of miRNAs used as biomarkers in the diagnosis, prognosis, and therapeutic targets in colon cancer is also discussed.

  18. Relationship between preoperative breast MRI and surgical treatment of non-metastatic breast cancer.

    Science.gov (United States)

    Onega, Tracy; Weiss, Julie E; Goodrich, Martha E; Zhu, Weiwei; DeMartini, Wendy B; Kerlikowske, Karla; Ozanne, Elissa; Tosteson, Anna N A; Henderson, Louise M; Buist, Diana S M; Wernli, Karen J; Herschorn, Sally D; Hotaling, Elise; O'Donoghue, Cristina; Hubbard, Rebecca

    2017-12-01

    More extensive surgical treatments for early stage breast cancer are increasing. The patterns of preoperative MRI overall and by stage for this trend has not been well established. Using Breast Cancer Surveillance Consortium registry data from 2010 through 2014, we identified women with an incident non-metastatic breast cancer and determined use of preoperative MRI and initial surgical treatment (mastectomy, with or without contralateral prophylactic mastectomy (CPM), reconstruction, and breast conserving surgery ± radiation). Clinical and sociodemographic covariates were included in multivariable logistic regression models to estimate adjusted odds ratios and 95% confidence intervals. Of the 13 097 women, 2217 (16.9%) had a preoperative MRI. Among the women with MRI, results indicated 32% higher odds of unilateral mastectomy compared to breast conserving surgery and of mastectomy with CPM compared to unilateral mastectomy. Women with preoperative MRI also had 56% higher odds of reconstruction. Preoperative MRI in women with DCIS and early stage invasive breast cancer is associated with more frequent mastectomy, CPM, and reconstruction surgical treatment. Use of more extensive surgical treatment and reconstruction among women with DCIS and early stage invasive cancer whom undergo MRI warrants further investigation. © 2017 Wiley Periodicals, Inc.

  19. MicroRNAs as Regulator of Signaling Networks in Metastatic Colon Cancer

    Science.gov (United States)

    Wang, Jian; Du, Yong; Liu, Xiaoming; Cho, William C.; Yang, Yinxue

    2015-01-01

    MicroRNAs (miRNAs) are a class of small, noncoding RNA molecules capable of regulating gene expression translationally and/or transcriptionally. A large number of evidence have demonstrated that miRNAs have a functional role in both physiological and pathological processes by regulating the expression of their target genes. Recently, the functionalities of miRNAs in the initiation, progression, angiogenesis, metastasis, and chemoresistance of tumors have gained increasing attentions. Particularly, the alteration of miRNA profiles has been correlated with the transformation and metastasis of various cancers, including colon cancer. This paper reports the latest findings on miRNAs involved in different signaling networks leading to colon cancer metastasis, mainly focusing on miRNA profiling and their roles in PTEN/PI3K, EGFR, TGFβ, and p53 signaling pathways of metastatic colon cancer. The potential of miRNAs used as biomarkers in the diagnosis, prognosis, and therapeutic targets in colon cancer is also discussed. PMID:26064956

  20. CHARACTERISTICS OF CLINICAL COURSE OF METASTATIC AND PRIMARY OVARIAN TUMORS IN COLON CANCER

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    I. A. Dzhanyan

    2015-01-01

    Full Text Available The aim of this study was to investigate clinical pecuiliarities of ovarian tumors in colon cancer patients and determination of complex diagnostic methods.Subject and methods. Russian N.N.  Blokhin Cancer Research Center archives were used for retrospective study, patients, who underwent treatment during 1989–2013  were included. Colon cancer patients with ovarian metastases and with synchronous or metachronous tumors were included.Results. 141 patients were included: 91 patients had colon cancer with ovarian metastases (group 1 and 50 patients had synchronous or metachronous ovarian tumours (group 2. Ovarian tumors were diagnosed during the 1 year in 74 (81.3 % patients in group 1 and in 23 (46 % in group 2. Patients in group 2 less frequently had children (9 (18.0 % vs 5 (5.5 + 2.3 %, р < 0.05, family history of cancer (3 (6 % vs 16 (17.6 %, р < 0.05 and concomitant diseases. Median CA 125 level in group 1 was 64.96 ng/ml and 180 ng/ml in group 2. Ovarian tumors had solid and cystic structure during US examination in 66 (73 % patients in group 1 and 31 (62 % patients in group 2 had solid ovarian tumors on US examination.Conclusions. The differential diagnostics of primary and metastatic ovarian tumors must include CEA, CA 19–9 and CA 125 serum levels and pelvic US.

  1. Supportive and palliative care for metastatic breast cancer: resource allocations in low- and middle-income countries. A Breast Health Global Initiative 2013 consensus statement.

    Science.gov (United States)

    Cleary, James; Ddungu, Henry; Distelhorst, Sandra R; Ripamonti, Carla; Rodin, Gary M; Bushnaq, Mohammad A; Clegg-Lamptey, Joe N; Connor, Stephen R; Diwani, Msemo B; Eniu, Alexandru; Harford, Joe B; Kumar, Suresh; Rajagopal, M R; Thompson, Beti; Gralow, Julie R; Anderson, Benjamin O

    2013-10-01

    Many women diagnosed with breast cancer in low- and middle-income countries (LMICs) present with advanced-stage disease. While cure is not a realistic outcome, site-specific interventions, supportive care, and palliative care can achieve meaningful outcomes and improve quality of life. As part of the 5th Breast Health Global Initiative (BHGI) Global Summit, an expert international panel identified thirteen key resource recommendations for supportive and palliative care for metastatic breast cancer. The recommendations are presented in three resource-stratified tables: health system resource allocations, resource allocations for organ-based metastatic breast cancer, and resource allocations for palliative care. These tables illustrate how health systems can provide supportive and palliative care services for patients at a basic level of available resources, and incrementally add services as more resources become available. The health systems table includes health professional education, patient and family education, palliative care models, and diagnostic testing. The metastatic disease management table provides recommendations for supportive care for bone, brain, liver, lung, and skin metastases as well as bowel obstruction. The third table includes the palliative care recommendations: pain management, and psychosocial and spiritual aspects of care. The panel considered pain management a priority at a basic level of resource allocation and emphasized the need for morphine to be easily available in LMICs. Regular pain assessments and the proper use of pharmacologic and non-pharmacologic interventions are recommended. Basic-level resources for psychosocial and spiritual aspects of care include health professional and patient and family education, as well as patient support, including community-based peer support. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. A structured review of health utility measures and elicitation in advanced/metastatic breast cancer

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    Hao Y

    2016-06-01

    Full Text Available Yanni Hao,1 Verena Wolfram,2 Jennifer Cook2 1Novartis Pharmaceuticals, East Hanover, NJ, USA; 2Adelphi Values, Bollington, UK Background: Health utilities are increasingly incorporated in health economic evaluations. Different elicitation methods, direct and indirect, have been established in the past. This study examined the evidence on health utility elicitation previously reported in advanced/metastatic breast cancer and aimed to link these results to requirements of reimbursement bodies. Methods: Searches were conducted using a detailed search strategy across several electronic databases (MEDLINE, EMBASE, Cochrane Library, and EconLit databases, online sources (Cost-effectiveness Analysis Registry and the Health Economics Research Center, and web sites of health technology assessment (HTA bodies. Publications were selected based on the search strategy and the overall study objectives. Results: A total of 768 publications were identified in the searches, and 26 publications, comprising 18 journal articles and eight submissions to HTA bodies, were included in the evidence review. Most journal articles derived utilities from the European Quality of Life Five-Dimensions questionnaire (EQ-5D. Other utility measures, such as the direct methods standard gamble (SG, time trade-off (TTO, and visual analog scale (VAS, were less frequently used. Several studies described mapping algorithms to generate utilities from disease-specific health-related quality of life (HRQOL instruments such as European Organization for Research and Treatment of Cancer Quality of Life Questionnaire – Core 30 (EORTC QLQ-C30, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire – Breast Cancer 23 (EORTC QLQ-BR23, Functional Assessment of Cancer Therapy – General questionnaire (FACT-G, and Utility-Based Questionnaire-Cancer (UBQ-C; most used EQ-5D as the reference. Sociodemographic factors that affect health utilities, such as age, sex

  3. Systemic therapy of brain metastases: non–small cell lung cancer, breast cancer, and melanoma

    Science.gov (United States)

    Baik, Christina S.; Gadi, Vijayakrishna K.; Bhatia, Shailender; Chow, Laura Q.M.

    2017-01-01

    Brain metastases (BM) occur frequently in many cancers, particularly non–small cell lung cancer (NSCLC), breast cancer, and melanoma. The development of BM is associated with poor prognosis and has an adverse impact on survival and quality of life. Commonly used therapies for BM such as surgery or radiotherapy are associated with only modest benefits. However, recent advances in systemic therapy of many cancers have generated considerable interest in exploration of those therapies for treatment of intracranial metastases. This review discusses the epidemiology of BM from the aforementioned primary tumors and the challenges of using systemic therapies for metastatic disease located within the central nervous system. Cumulative data from several retrospective and small prospective studies suggest that molecularly targeted systemic therapies may be an effective option for the treatment of BM from NSCLC, breast cancer, and melanoma, either as monotherapy or in conjunction with other therapies. Larger prospective studies are warranted to further characterize the efficacy and safety profiles of these targeted agents for the treatment of BM. PMID:28031389

  4. Massage Therapy for Patients with Metastatic Cancer: A Pilot Randomized Controlled Trial

    Science.gov (United States)

    Toth, Maria; Marcantonio, Edward R.; Davis, Roger B.; Walton, Tracy; Kahn, Janet R.

    2013-01-01

    Abstract Objectives The study objectives were to determine the feasibility and effects of providing therapeutic massage at home for patients with metastatic cancer. Design This was a randomized controlled trial. Settings/location Patients were enrolled at Oncology Clinics at a large urban academic medical center; massage therapy was provided in patients' homes. Subjects Subjects were patients with metastatic cancer. Interventions There were three interventions: massage therapy, no-touch intervention, and usual care. Outcome measures Primary outcomes were pain, anxiety, and alertness; secondary outcomes were quality of life and sleep. Results In this study, it was possible to provide interventions for all patients at home by professional massage therapists. The mean number of massage therapy sessions per patient was 2.8. A significant improvement was found in the quality of life of the patients who received massage therapy after 1-week follow-up, which was not observed in either the No Touch control or the Usual Care control groups, but the difference was not sustained at 1 month. There were trends toward improvement in pain and sleep of the patients after therapeutic massage but not in patients in the control groups. There were no serious adverse events related to the interventions. Conclusions The study results showed that it is feasible to provide therapeutic massage at home for patients with advanced cancer, and to randomize patients to a no-touch intervention. Providing therapeutic massage improves the quality of life at the end of life for patients and may be associated with further beneficial effects, such as improvement in pain and sleep quality. Larger randomized controlled trials are needed to substantiate these findings. PMID:23368724

  5. Trends in the Treatment of Metastatic Colon and Rectal Cancer in Elderly Patients.

    Science.gov (United States)

    Bradley, Cathy J; Yabroff, K Robin; Warren, Joan L; Zeruto, Christopher; Chawla, Neetu; Lamont, Elizabeth B

    2016-05-01

    Little is known about the use and costs of antineoplastic regimens for elderly patients with metastatic colorectal cancer (mCRC). We report population-based trends over a 10-year period in the treatment, survival, and costs in mCRC patients, stratified by ages 65-74 and 75+. We used Surveillance, Epidemiology, and End Results-Medicare data for persons diagnosed with metastatic colon (N=16117) or rectal cancer (N=4008) between 2000 and 2009. We estimated the adjusted percent of patients who received antineoplastic agents, by type, number, and their costs 12 months following diagnosis. We report the percent of patients who received 3 or more of commonly prescribed agents and estimate survival for the 24-month period following diagnosis by age and treatment. The percentage that received 3 or more agents increased from 3% to 73% in colon patients aged 65-74 and from 2% to 53% in patients 75+. Similar increases were observed in rectal patients. Average 1-year costs per patient in 2009 were $106,461 and $102,680 for colon and rectal cancers, respectively, reflecting an increase of 32% and 20%, for patients who received antineoplastic agents. Median survival increased by about 6 and 10 months, respectively, for colon and rectal patients aged 65-74 who received antineoplastic agents, but an improvement of only 1 month of median survival was observed for patients 75+. Expensive multiple agent regimens are increasingly used in older mCRC patients. For patients aged 64-75 years, these treatments may be associated with several months of additional life, but patients aged 75+ may incur considerable expense without any survival benefit.

  6. The Impacts of Inclusion in Clinical Trials on Outcomes among Patients with Metastatic Breast Cancer (MBC.

    Directory of Open Access Journals (Sweden)

    Ji Yun Lee

    Full Text Available Metastatic breast cancer (MBC remains a devastating and incurable disease. Over the past decade, the implementation of clinical trials both with and without molecular targeted therapeutics has impacted the daily clinical treatment of patients with MBC. In this study, we determine whether including MBC patients in clinical trials affects clinical outcomes.We retrospectively reviewed data for a total of 863 patients diagnosed with initial or recurrent (after receiving adjuvant systemic treatments following surgery metastatic disease between January 2000 and December 2013. Data were obtained from the breast cancer database of Samsung Medical Center.Among the 806 patients selected for inclusion, 188 (23% had participated in clinical trials. A total of 185 clinical trials were conducted from 2000 to 2014. When compared with earlier periods (n = 10 for 2000-2004, clinical trial enrollment significantly increased over time (n = 103 for 2005-2009, P = 0.024; n = 110 for 2010-2014, P = 0.046. Multivariate analyses revealed that biologic subtype, distant recurrence free interval (DRFI, and clinical trial enrollment were independent predictors of overall survival. Patients who participated in clinical trials showed improved survival, with a hazard ratio of 0.75 (95% CI, 0.59-0.95, which was associated with a 25% reduction in the risk of death. However, subgroup analysis showed that this improved survival benefit was not maintained in patients with triple negative breast cancer (TNBC.Although not conclusive, we could speculate that there were differences in the use of newer agents or regimens over time, and these differences appear to be associated with improved survival.

  7. Radiotherapy in the management of non-metastatic prostate cancer: Current standards and future opportunities

    International Nuclear Information System (INIS)

    Forman, Jeffrey D.

    1997-01-01

    Objectives: The intent of this course is to review issues involved in the management of non-metastatic prostate cancer and to clarify the role of external beam radiotherapy, the use of neo-adjuvant and adjuvant hormonal therapy in conjunction with the radiation, the management of patients with regional metastases and recurrent disease following surgery and radiation. At the end of this course, participants should be able to fluently discuss management issues and strategies across the entire spectrum of non-metastatic prostate cancer. - Pre-treatment prognostic factors including clinical stage, grade, and pre-treatment PSA, will be presented and their relative value in determining therapeutic strategies will be discussed. Strategies to be discussed include standard dose radiation, escalated dose radiation, particle radiation and the use of adjuvant and neo-adjuvant hormonal therapy. - The process of simulation and field design will be presented, the value of CT-based treatment planning, beams-eye view design and the relative value of three-dimensional treatment planning will be discussed. - The significance of prostate and patient movement and strategies for dealing with this will also be presented so that what constitutes an adequate simulation and margin of treatment can be clarified. - The management of newly diagnosed patients, covering the range of low stage/low grade to locally advanced prostate cancer will be discussed. - The relative value of increasing dose, the relative value of using neo-adjuvant and/or adjuvant hormone therapy and the indications for escalated dose will be presented. - Strategies for managing post-prostatectomy patients will be reviewed. Data on adjuvant and therapeutic irradiation for biochemical failure will be presented and a strategy for management will be discussed. - How to deal with patients with residual disease post radiation will be discussed and the relative value of cryotherapy, salvage prostatectomy or hormonal therapy will

  8. Bevacizumab treatment in the elderly patient with metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Di Bartolomeo M

    2015-01-01

    Full Text Available Maria Di Bartolomeo,1 Claudia Maggi,1 Francesca Ricchini,1 Filippo Pietrantonio,1 Roberto Iacovelli,1 Filippo de Braud,1 Alessandro Inno2 1Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, 2Department of Medical Oncology, Sacro Cuore-Don Calabria Hospital, Negrar, Italy Abstract: Metastatic colorectal cancer (mCRC, like many cancers, is primarily a disease of elderly people. Despite this prevalence, such patients are often excluded from randomized trials or represent a minority of enrolled patients. Moreover, the criteria for establishing benefit or side effects of treatment strategies in this population are uncertain and not well recognized. Bevacizumab improves the outcome of mCRC when used in combination with standard first-line and second-line chemotherapy and beyond the first disease progression when given with a chemotherapy backbone different from that used in the precedent line. The particular toxicity profile of this antiangiogenesis agent (in particular hypertension, thromboembolic events, hemorrhage, and renal failure may discourage its use in elderly patients with comorbidities. Data from subgroup analyses of randomized trials and the results of recent cohort studies suggest a significant benefit from the addition of bevacizumab to standard chemotherapy for elderly patients comparable with that observed in younger patients, except for the increased risk for thromboembolic events. Age alone should not be a barrier to use of bevacizumab, and further research with a more complete geriatric assessment should investigate the role of bevacizumab in elderly patients with mCRC to avoid undertreatment of this patient population due to a ­historical conservative approach. Keywords: bevacizumab, elderly, metastatic colorectal cancer, antivascular treatment, review

  9. Efficacy and safety of regorafenib in the treatment of metastatic colorectal cancer: A systematic review.

    Science.gov (United States)

    Røed Skårderud, Maria; Polk, Anne; Kjeldgaard Vistisen, Kirsten; Larsen, Finn Ole; Nielsen, Dorte Lisbet

    2018-01-01

    Despite advances in the treatment of colorectal cancer, third-line treatment options are still limited. Regorafenib was approved in 2012 for the treatment of patients with metastatic colorectal cancer previously treated with approved standard therapy. The purpose of this review is to present existing clinical data on regorafenib. We systematically searched the PubMed and Embase databases, as well as ASCO and ESMO conference abstracts, for studies in English including ≥30 patients, evaluating the efficacy and safety of regorafenib in patients with metastatic colorectal cancer. A meta-analysis was conducted on the published, randomized phase III trials. 24 eligible studies were included. In two phase III trials, regorafenib significantly increased overall survival (OS), progression free survival (PFS), and disease control rate when compared to placebo. Survival benefits of 1.4 and 2.5 months were presented. The meta-analysis indicated a significant greater treatment effect on OS (hazard ratio 0.67) and PFS (hazard ratio 0.40), compared to placebo. The non-randomized studies mostly supported these results. The most frequently reported adverse events were hand-foot-skin reaction (25%-86%), hypertension (11%-47%) and fatigue (2%-73%). Large phase III randomized trials indicate that regorafenib provides a benefit in OS and PFS when compared to placebo. Adverse events were common, but manageable and typ