WorldWideScience

Sample records for cancer metastatic clones

  1. Breast cancer (metastatic)

    OpenAIRE

    Stebbing, Justin; Slater, Sarah; Slevin, Maurice

    2007-01-01

    Median survival from metastatic breast cancer is 12 months without treatment, but young people can survive up to 20 years with the disease, whereas in other metastatic cancers this would be considered very unusual.

  2. Metastatic Cancer

    Science.gov (United States)

    ... of recurrent disease and assessment of prognosis. Clinical Radiology 2007; 62(1):28–34. [PubMed Abstract] Talmadge ... your website or other digital platform? Our syndication services page shows you how. National Cancer Institute at ...

  3. Heterogeneity of clones from a human metastatic melanoma detected by autologous cytotoxic T lymphocyte clones

    OpenAIRE

    1986-01-01

    The possibility that a single human tumor may be composed of an heterogeneous population of cells with respect to susceptibility to lysis by autologous CTL clones was investigated by testing six cytolytic clones derived by micromanipulation against the autologous metastatic melanoma, Me28, and against 31 clones derived from Me28 by cloning in soft agar. Highly significant differences in the lysis of many tumor clones were observed by three of the CTL effectors in comparison with the cytotoxic...

  4. Chemotherapy of metastatic colon cancer

    Directory of Open Access Journals (Sweden)

    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. 

  5. 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

  6. Metastatic renal cell cancer treatments.

    Science.gov (United States)

    Sternberg, C N

    2003-01-01

    Metastatic renal cell carcinoma has been considered to be resistant to chemotherapy, with responses observed in only limited numbers of patients. For this reason, therapeutic options have ranged from no treatment, to immunotherapy with cytokines such as IL-2 and interferon-alpha, chemotherapy alone or in combination with cytokines, and to a variety of new investigational approaches. Interferon and interleukin-2 (IL-2) have led to long-term survival in selected patients. Immunotherapy with cytokines, monoclonal antibodies, new agents, dendritic cell therapy, and allotransplantation offer promise. Novel therapeutic strategies include combining cytokines, and antiangiogenic approaches such as thalidomide and antivascular endothelial growth factor therapy. Pathologic, cytogenic and molecular studies have proven that renal cell carcinoma is not a single tumor entity. Efforts to improve results also include the identification of prognostic factors, which allow treatment to be better directed towards those patients most likely to benefit. Increasing understanding of cancer biology is beginning to allow for a more targeted approach to the therapy of metastatic renal cell carcinoma. Adequate positioning of known treatments is essential and many trials of new targeted therapies are underway. PMID:14988745

  7. 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.

  8. TAS-102 for Metastatic Colorectal Cancer

    Science.gov (United States)

    A summary of results from an international phase III trial that compared TAS-102 with placebo in patients with metastatic colorectal cancer whose disease progressed following prior treatments or who had health conditions that prevented the re-administrati

  9. 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 not...... 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<0.001 for all comparisons). Fatigue and hypertension were the...

  10. [Metastatic hormone-sensitive prostate cancer].

    Science.gov (United States)

    Gravis, Gwenaelle; Salem, Naji; Walz, Jochen

    2015-01-01

    The prostate cancer in its hormone-sensitive metastatic presentation is infrequent, it is either an initial presentation of the disease or an evolution after local treatment, without castration of the biological relapse. The surgical or biological castration remains the cornerstone of the treatment. The deadline of castration initiation and its modalities of administration, intermittent or continuous rest debated but consensual on the initiation is the appearance of the symptomatic disease. The chemotherapy by docetaxel in association with the castration increases significantly the survival of the patients having a high tumoral volume. The efficacy on the whole metastatic population requires additional analyses. Clinical prognostic factors as the bone localizations (axial or appendicular), the visceral involvement (liver, lung) are determining for the survival of these patients. Biological prognostic factors are in evaluation. Except the clodronate acid, which showed a survival improvement in the hormone-sensitive metastatic prostate cancer (HSMPC), the other treatments targeting the bone (zoledronic acid, rank-ligand inhibitor) demonstrated a benefit only in castrate resistant metastatic prostate cancer (MCRPC). The management of local disease lets suggest a benefit to at least symptomatic disease, but it requires to be estimated prospectively in clinical trials. The new hormonal treatments targeting the androgen receptor in CPMRC are in evaluation in CPMHS. The objective is to increase the survival and the quality of life of the CPMHS and to delay the evolution towards the castration resistant metastatic disease. PMID:25609491

  11. 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

  12. Surgical management of metastatic differentiated thyroid cancer

    International Nuclear Information System (INIS)

    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

  13. Measuring the metastatic potential of cancer cells

    Science.gov (United States)

    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.

  14. Alpha Particle Therapy in Metastatic Prostate Cancer

    International Nuclear Information System (INIS)

    Metastatic castrate resistant prostate cancer (CRPC) is a leading cause of cancer mortality among men in western countries. Although nearly 85% of patients present with localised disease, up to 40% will eventually develop metastatic disease during the course of illness. Of men dying from prostate cancer, more than 90% have bone metastases many with no other significant metastatic sites. Symptoms related to bone metastases and skeletal related events (SREs) account for the major cause of morbidity in these patients. Bone-seeking radionuclides have been used in the treatment of prostate cancer bone metastases for many years. The first bone seeking radionuclide drug approved by the FDA was Strontium-89. Other agents have also been used including Samarium-153 EDTMP, Rhenium-186 (-188)-HEDP. These radionuclides are all emit shortrange therapeutic beta radiation with bone marrow as the dose limiting toxicity. There is strong clinical trial evidence of benefit for these radionuclides in reducing pain in advanced prostate cancer; however, none of the drugs has been shown to improve survival, albeit none of the clinical trials were powered to detect differences in survival

  15. [Biotherapies in metastatic colorectal cancers in 2014].

    Science.gov (United States)

    Jouinot, Anne; Coriat, Romain; Huillard, Olivier; Goldwasser, François

    2014-10-01

    The treatment of metastatic colorectal cancer has been transformed during the last decade with biotherapies, two of them were marketed in 2013. Four agents are monoclonal antibodies, while the fifth agent is a tyrosine kinase inhibitor. Two agents are inhibitors of the EGF-receptor pathway, cetuximab and panitumumab, and have as class-toxicity, cutaneous toxicity. The other three agents are bevacizumab, aflibercept and regorafenib, and interact with angiogenesis, they are associated with a risk of vascular toxicity, mainly hypertension. These agents participate to an improvement of disease control at the metastatic stage, and in some cases, favour the curative surgical resection of metastases. Their use is discussed in multidisciplinary meetings dedicated to gastrointestinal cancers, in the presence of liver surgeons. PMID:25065664

  16. Immunotherapy for metastatic colorectal cancer

    DEFF Research Database (Denmark)

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

    2012-01-01

    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......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...

  17. Deep Learning for Identifying Metastatic Breast Cancer

    OpenAIRE

    Wang, Dayong; Khosla, Aditya; Gargeya, Rishab; Irshad, Humayun; Beck, Andrew H

    2016-01-01

    The International Symposium on Biomedical Imaging (ISBI) held a grand challenge to evaluate computational systems for the automated detection of metastatic breast cancer in whole slide images of sentinel lymph node biopsies. Our team won both competitions in the grand challenge, obtaining an area under the receiver operating curve (AUC) of 0.925 for the task of whole slide image classification and a score of 0.7051 for the tumor localization task. A pathologist independently reviewed the same...

  18. Colon Cancer Metastatic to the Biliary Tree.

    Science.gov (United States)

    Strauss, Alexandra T; Clayton, Steven B; Markow, Michael; Mamel, Jay

    2016-04-01

    Metastasis of colon adenocarcinoma is commonly found in the lung, liver, or peritoneum. Common bile duct (CBD) tumors related to adenomas from familial adenomatous polyposis metastasizing from outside of the gastrointestinal tract have been reported. We report a case of biliary colic due to metastatic colon adenocarcinoma to the CBD. Obstructive jaundice with signs of acalculous cholecystitis on imaging in a patient with a history of colon cancer should raise suspicion for metastasis to CBD. PMID:27144209

  19. Upfront Chemotherapy for Metastatic Prostate Cancer.

    Science.gov (United States)

    Lam, Elaine T; Flaig, Thomas W

    2015-12-01

    Traditionally, androgen deprivation therapy (ADT) has been the standard initial treatment for metastatic hormone-sensitive prostate cancer (mHSPC), with chemotherapy utilized in the castration-resistant setting. Data reported from three recent clinical trials shed new light on the role of upfront docetaxel in advanced or mHSPC. Two of these studies-CHAARTED and STAMPEDE-showed significant improvement in overall survival, while the third study, GETUG-AFU 15, showed no statistical difference. The CHAARTED study showed a 13.6-month survival improvement and the STAMPEDE study showed a 10-month survival improvement with ADT plus docetaxel, compared with ADT alone, in the hormone-sensitive setting. These numbers are remarkable when compared with the 2.9-month survival benefit from docetaxel in the metastatic castration-resistant setting, which has been the standard setting for the use of docetaxel in advanced prostate cancer. In this review, we describe the historical data for chemotherapy in the perioperative and metastatic prostate cancer settings, and the recent trials that are changing the paradigm in support of docetaxel in the upfront setting. PMID:26676900

  20. 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....... Several studies aiming to define the optimal dose and schedule of combination paclitaxel/doxorubicin have now been completed or are ongoing. Phase I/II studies have yielded encouraging preliminary response rates but quite variable toxicity profiles depending on the schedule used. These clinical trials...

  1. Optimizing initial chemotherapy for metastatic pancreatic cancer.

    Science.gov (United States)

    Mantripragada, Kalyan C; Safran, Howard

    2016-05-01

    The two combination chemotherapy regimens FOLFIRINOX and gemcitabine plus nab-paclitaxel represent major breakthroughs in the management of metastatic pancreatic cancer. Both regimens showed unprecedented survival advantage in the setting of front-line therapy. However, their application for treatment of patients in the community is challenging because of significant toxicities, thus limiting potential benefits to a narrow population of patients. Modifications to the dose intensity or schedule of those regimens improve their tolerability, while likely retaining survival advantage over single-agent chemotherapy. Newer strategies to optimize these two active regimens in advanced pancreatic cancer are being explored that can help personalize treatment to individual patients. PMID:26939741

  2. Establishment of cell clones with different metastatic potential from the metastatic hepatocellular carcinoma cell line MHCC97

    Institute of Scientific and Technical Information of China (English)

    Yan Li; Zhao-You Tang; Sheng-Long Ye; Yin-Kun Liu; Jie Chen; Qiong Xue; Jun Chen; Dong-Mei Gao; Wei-Hua Bao

    2001-01-01

    ALM To establish clone cells with different metastatic potential for the study of metastasis-related mechanisms. METHODS Cloning procedure was performed on parental hepatocellular carcinoma (HCC) cell line MHCC97. andbiological characteristics of the target clones selected by in vivo screening were studied.``RESULTS Two clones with high MHCC97-H and IowMHCC9--L1 metastatic potential were isolated from theparent cell line. Compared with MHCC97-L. MHCC97-H hadsmaller cell size average cell diameter 43 um vs 50 μmand faster in vitro and in vivo growth rate tumor celldoubling time was 34.2 h vs 60.0 h. The main ranges ofchromosomes were 5.5 58 in MHCC97-H and 57 62 inMHCC97-L. Boyden chamber in vitro invasion assay demonstrated that the number of penetrating cells through the artificial basement membrane was 137.5 - 11 .0) cellsfield for MHC_C99--H vs 17.7 - 6.3) field for MHCC97-L.The proportions of cells in GO Gl phase. S phase, and G_ M phase for MHCC97-H MHCC97-L were 0.56 6.65.0.28 0.25 and 0.l6 0.10, respectively, as measured by flow cytometry. The serum AFP levels in nude mice 5 wk after orthotopic implantation of tumor tissue were ( 24666 μg. L for MHCC97-H and (91- 66) μg' L 1 for MHCC97L. The pulmonary metastatic rate was 100% (10-10) vs40% 4- 10).``CONCLUSION Two clones of the same genetic background but with different biological behaviors were established, which could be valuable models for investigation on HCC metastasis.``

  3. Aromatase inhibitor strategies in metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Heather L McArthur

    2009-07-01

    Full Text Available Heather L McArthur, Patrick G MorrisBreast Cancer Medicine Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USAAbstract: Despite ongoing therapeutic innovations, metastatic breast cancer (MBC remains a treatable but incurable disease. In the developed world, a diagnosis of MBC without a preceding diagnosis of early stage disease is a rare event. However, approximately one-third of women with early stage breast cancer ultimately experience a distant recurrence. Because the majority of breast cancers express estrogen and/or progesterone receptors and are accordingly considered hormone-sensitive, therapeutic strategies that interfere with hormone-mediated tumorigenesis have been a cornerstone of the breast cancer management paradigm for decades. Historically, the selective estrogen receptor modulator tamoxifen has been the most extensively studied and widely used hormone maneuver in breast cancer. However, a recent therapeutic innovation, namely the successful development of third-generation aromatase inhibitors (AIs, has had a dramatic impact on the treatment paradigm for women with hormone-sensitive MBC. Because of the demonstrated efficacy in postmenopausal breast cancer patients, the generally favorable side-effect profile, and the convenience of oral administration, AIs are now in widespread clinical use. Currently, there are three clinically available third-generation AIs: two reversible, nonsteroidal AIs, letrozole and anastrozole; and one irreversible, steroidal AI, exemestane. All three agents are at least as efficacious as tamoxifen as monotherapy for postmenopausal women with hormone-sensitive MBC. Current clinical research aims to improve upon existing strategies by evaluating AIs in combination with systemic chemotherapy regimens and/or novel targeted agents. It is hoped that these therapeutic innovations will lead to ongoing improvements in quality of life parameters and ideally survival for women

  4. Intrahepatic therapy for liver-dominant metastatic colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Kerlijne; De; Groote; Hans; Prenen

    2015-01-01

    In patients with metastatic colorectal cancer, the liver is the most common site of metastatic disease. In patients with liver-dominant disease, consideration needs to be given to locoregional treatments such as hepatic arterial infusion chemotherapy, transarterial chemoembolisation and selective internal radiation therapy because hepatic metastases are a major cause of liver failure especially in chemorefractory disease. In this review we provide insights on the published literature for locoregional treatment of liver metastases in metastatic colorectal cancer.

  5. The microcell mediated transfer of human chromosome 8 into highly metastatic rat liver cancer cell line C5F

    Institute of Scientific and Technical Information of China (English)

    Hu Liu; Sheng-Long Ye; Jiong Yang; Zhao-You Tang; Yin-Kun Liu; Lun-Xiu Qin; Shuang-Jian Qiu; Rui-Xia Sun

    2003-01-01

    AIM: Our previous research on the surgical samples of primary liver cancer with CGH showed that the loss of human chromosome 8p had correlation with the metastatic phenotype of liver cancer. In order to seek the functional evidence that there could be a metastatsis suppressor gene (s) for liver cancer on human chromosome 8, we tried to transfer normal human chromosome 8 into rat liver cancer cell line C5F, which had high metastatic potential to lung.METHODS: Human chromosome 8 randomly marked with neo gene was introduced into C5F cell line by MMCT and positive microcell hybrids were screened by double selections of G418 and HAT. Single cell isolation cloning was applied to clone microcell hybrids. Finally, STS-PCR and WCP-FISH were used to confirm the introduction.RESULTS: Microcell hybrids resistant to HAT and G418 were obtained and 15 clones were obtained by single-cell isolation cloning. STS-PCR and WCP-FISH proved that human chromosome 8 had been successfully introduced into rat liver cancer cell line C5F. STS-PCR detected a random loss in the chromosome introduced and WCP-FISH found a consistent recombination of the introduced human chromosome with the rat chromosome.CONCLUSION: The successful introduction of human chromosome 8 into highly metastatic rat liver cancer cell line builds the basis for seeking functional evidence of a metastasis suppressor gene for liver cancer harboring on human chromosome 8 and its subsequent cloning.

  6. 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

  7. Construction of metastatic spinal cancer tissue microarrays

    Institute of Scientific and Technical Information of China (English)

    Yang Xinghai; Chen Huajiang; Xiao Jianru; Yuan Wen; Jia Lianshun

    2009-01-01

    Objective: To explore the construction of metastatic spinal cancer (MSC) tissue microarrays and validate its value in immunohistochemical study of MSC. Methods: Paraffin-embedded specimens from 71 MSC cases and 6 primary tumor cases were selected as donor blocks and prepared into MSC tissue microarrays by tissue array arrangement, the steps of which included location, punching, sampling, sample seeding, and re-diagnosis by hematoxylin-eosin (HE) as well as MMP-9 and MMP-14 immunohistochemical staining. Results: The MSC tissue microarrays thus constructed were intact and crackless, containing 154 complete and well arranged microarray points. None of the sectioned tissue microarrays was lost, and the results of HE staining was consistent with the primary pathologic diagnoses. Immunohistochemical staining was also good without non-specific or marginal effect. Conclusion: The MSC tissue microarrays have a high value in the immunohistochemical study of MSC.

  8. Pharmacoeconomics of Available Treatment Options for Metastatic Prostate Cancer

    OpenAIRE

    Zeliadt, Steven B.; Penson, David F.

    2007-01-01

    The resources devoted to managing metastatic prostate cancer are enormous, yet little attention has been given to directly measuring the economic consequences of treatment alternatives. The purpose of this article was to evaluate the pharmacoeconomics of available treatments for metastatic prostate cancer, including hormone-sensitive disease, androgen-independent prostate cancer and locally advanced/progressive disease. We identified 58 articles addressing economic issues related to metastati...

  9. Metastatic Bladder Cancer: A Review of Current Management

    OpenAIRE

    Andrew Fletcher; Ananya Choudhury; Nooreen Alam

    2011-01-01

    Bladder cancer continues to result in substantial morbidity and mortality for affected individuals. Advances in the management of metastatic bladder cancer have been limited. Chemotherapy with platinum-based regimes remains the mainstay of first-line treatment. Studies investigating alternative regimes have offered no survival advantage. Targeted therapies may offer benefit either as single agent or in combination with chemotherapy. Symptoms due to metastatic bladder cancer impact patients' q...

  10. Role of the neural niche in brain metastatic cancer

    OpenAIRE

    Termini, John; Neman, Josh; Jandial, Rahul

    2014-01-01

    Metastasis is the relenteless pursuit of cancer to escape its primary site and colonize distant organs. This malignant evolutionary process is biologically heterogeneous, yet one unifying element is the critical role of the microenvironment for arriving metastatic cells. Historically brain metastases were rarely investigated since patients with advanced cancer were considered terminal. Fortunately, advances in molecular therapies have led to patients living longer with metastatic cancer. Howe...

  11. Predominance of the metastatic phenotype in hybrids formed by fusion of mouse and human melanoma clones.

    Science.gov (United States)

    van Golen, K L; Risin, S; Staroselsky, A; Berger, D; Tainsky, M A; Pathak, S; Price, J E

    1996-03-01

    The fusion of mouse and human melanoma cells that were tumorigenic but had different metastatic capabilities resulted in hybrids that were metastatic when injected intravenously or subcutaneously into nude mice, regardless of whether it was the mouse or the human melanoma clone that was metastatic. The H7 hybrid line, formed by fusing murine nonmetastatic K1735 C19 cells with human metastatic A375 C15 cells retained high metastatic potential over more than 50 sub-culture passages, suggesting that the dominant metastatic phenotype in these hybrid cells was stable. Using fluorescent in situ hybridization (FISH), human chromosome 17 was consistently identified as the predominant human chromosome in the majority of H7 cells tested between passages 20 and 60. Western blot analysis showed that the hybrid cells expressed human nm23 protein, indicating that at least one gene on the human chromosome 17 was functional. Immunocytochemistry and immunoprecipitation showed that the metastatic A375 C15 and H7 cells expressed p53 protein, but that the nonmetastatic K1735 C19 melanoma cells did not. Sequencing the human p53 gene in A375 C15N and H7 showed mutations in exon 7. Using a bioassay technique, we showed that K1735 C19 cells can spread from subcutaneous tumors to the lungs of nude mice yet fail to form metastases. With the addition of human chromosome 17 from A375 C15 cells, which carries a mutant p53 gene, the cells readily formed lung metastases. In this melanoma hybrid, a mutant p53 gene appears to confer a survival advantage on cells arrested in the lungs of nude mice and thus contributes to the growth of metastatic cells. PMID:8605733

  12. Tracking the origins and drivers of subclonal metastatic expansion in prostate cancer.

    Science.gov (United States)

    Hong, Matthew K H; Macintyre, Geoff; Wedge, David C; Van Loo, Peter; Patel, Keval; Lunke, Sebastian; Alexandrov, Ludmil B; Sloggett, Clare; Cmero, Marek; Marass, Francesco; Tsui, Dana; Mangiola, Stefano; Lonie, Andrew; Naeem, Haroon; Sapre, Nikhil; Phal, Pramit M; Kurganovs, Natalie; Chin, Xiaowen; Kerger, Michael; Warren, Anne Y; Neal, David; Gnanapragasam, Vincent; Rosenfeld, Nitzan; Pedersen, John S; Ryan, Andrew; Haviv, Izhak; Costello, Anthony J; Corcoran, Niall M; Hovens, Christopher M

    2015-01-01

    Tumour heterogeneity in primary prostate cancer is a well-established phenomenon. However, how the subclonal diversity of tumours changes during metastasis and progression to lethality is poorly understood. Here we reveal the precise direction of metastatic spread across four lethal prostate cancer patients using whole-genome and ultra-deep targeted sequencing of longitudinally collected primary and metastatic tumours. We find one case of metastatic spread to the surgical bed causing local recurrence, and another case of cross-metastatic site seeding combining with dynamic remoulding of subclonal mixtures in response to therapy. By ultra-deep sequencing end-stage blood, we detect both metastatic and primary tumour clones, even years after removal of the prostate. Analysis of mutations associated with metastasis reveals an enrichment of TP53 mutations, and additional sequencing of metastases from 19 patients demonstrates that acquisition of TP53 mutations is linked with the expansion of subclones with metastatic potential which we can detect in the blood. PMID:25827447

  13. Tracking the origins and drivers of subclonal metastatic expansion in prostate cancer

    Science.gov (United States)

    Hong, Matthew K.H.; Macintyre, Geoff; Wedge, David C.; Van Loo, Peter; Patel, Keval; Lunke, Sebastian; Alexandrov, Ludmil B.; Sloggett, Clare; Cmero, Marek; Marass, Francesco; Tsui, Dana; Mangiola, Stefano; Lonie, Andrew; Naeem, Haroon; Sapre, Nikhil; Phal, Pramit M.; Kurganovs, Natalie; Chin, Xiaowen; Kerger, Michael; Warren, Anne Y.; Neal, David; Gnanapragasam, Vincent; Rosenfeld, Nitzan; Pedersen, John S.; Ryan, Andrew; Haviv, Izhak; Costello, Anthony J.; Corcoran, Niall M.; Hovens, Christopher M.

    2015-01-01

    Tumour heterogeneity in primary prostate cancer is a well-established phenomenon. However, how the subclonal diversity of tumours changes during metastasis and progression to lethality is poorly understood. Here we reveal the precise direction of metastatic spread across four lethal prostate cancer patients using whole-genome and ultra-deep targeted sequencing of longitudinally collected primary and metastatic tumours. We find one case of metastatic spread to the surgical bed causing local recurrence, and another case of cross-metastatic site seeding combining with dynamic remoulding of subclonal mixtures in response to therapy. By ultra-deep sequencing end-stage blood, we detect both metastatic and primary tumour clones, even years after removal of the prostate. Analysis of mutations associated with metastasis reveals an enrichment of TP53 mutations, and additional sequencing of metastases from 19 patients demonstrates that acquisition of TP53 mutations is linked with the expansion of subclones with metastatic potential which we can detect in the blood. PMID:25827447

  14. Systemic chemotherapy for metastatic breast cancer

    Institute of Scientific and Technical Information of China (English)

    Yannan Zhao; Biyun Wang

    2015-01-01

    Breast cancer is the leading cause of cancer among women worldwide and the most common cancer in China. Many factors influence the treatment strategy for metastatic breast cancer (MBC). Chemotherapy should be administered to patients with hormone receptor-negative tumors, symptomatic visceral metastasis, and a short disease-free interval. Sequential single-agent chemotherapy has similar efficacy as combination agents in terms of overall survival and quality of life. Anthracyclines are the cornerstone of first-line treatment for MBC, and taxanes represent the second treatment option after resistance. When progression or intolerable toxicity occurs after optimal treatment, the alternative treatments include capecitabine, vinorel-bine, and gemcitabine. Ixabepilone and eribulin are relatively new effective single agents. A combination of cytotoxic agents for patients with rapid clinical progression can further improve the overall response rate and time to progression compared to single-agent treatment. For patients with MBC who were pretreated with anthracyclines in the neoadjuvant/adjuvant setting, a taxane-containing regimen such as docetaxel plus capecitabine or gemcitabine plus paclitaxel should be administered. Platinum-based therapies such as cisplatin or carboplatin have a role in the treatment of triple-negative breast cancer. Meanwhile, the efficacy of the addition of targeted drugs such as iniparib, bevacizumab, and cetuximab to chemotherapy remains unproven. Maintenance chemotherapy is routinely recommended in clinical practice at present. Patients who were previously treated with paclitaxel and gemcitabine have better progression-free and overall survival with maintenance chemotherapy according to a Korean phase Ⅲ clinical trial. Sequential maintenance treatment with capecitabine monotherapy after capecitabine-based combination chemotherapy (X-based X) appears favorable based on a series of domestic studies.

  15. A review on metastatic breast cancer in Iran

    OpenAIRE

    Hamidreza Alizadeh Otaghvar; Mostafa Hosseini; Adnan Tizmaghz; Ghazaal Shabestanipour; Hamid Noori

    2015-01-01

    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 t...

  16. 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.

  17. Eribulin Improves Survival of Women with Metastatic Breast Cancer

    Science.gov (United States)

    Treatment with eribulin (Halaven™) improved overall survival in women with metastatic breast cancer whose disease progressed despite multiple rounds of prior chemotherapy, according to the results of a phase III clinical trial called EMBRACE.

  18. Nab-Paclitaxel Plus Gemcitabine for Metastatic Pancreatic Cancer

    Science.gov (United States)

    A summary of results from a phase III trial that compared the combination of albumin-bound paclitaxel (nab-paclitaxel [Abraxane®]) and gemcitabine (Gemzar®) versus gemcitabine alone in patients with metastatic pancreatic cancer.

  19. Management of Metastatic Colorectal Cancer: Defining the Role of Capecitabine

    OpenAIRE

    Lynda R. Wiseman; Katherine A. Lyseng-Williamson

    2005-01-01

    Colorectal cancer (CRC), one of the most common cancers, is associated with significant morbidity, mortality, and medical costs. Treatment options in metastatic CRC are largely palliative, and aim to provide symptom relief, improve health-related quality of life, and prolong survival. Chemotherapy is the mainstay of treatment for metastatic disease. Fluorouracil/leucovorin with or without oxaliplatin or irinotecan is the most widely used regimen. These agents are administered intravenously (b...

  20. BRAF-Directed Therapy in Metastatic Colorectal Cancer.

    Science.gov (United States)

    Korphaisarn, Krittiya; Kopetz, Scott

    2016-01-01

    Activating BRAF (V-raf murine sarcoma viral oncogene homolog B) mutations occur in approximately 5% to 10% of patients with metastatic colorectal cancer, mostly V600E mutation, and it is associated with distinct clinical and pathological features. To date, there are no approved treatments to target this mutation. BRAF inhibitor monotherapy has limited efficacy, in contrast to metastatic melanoma. Combination strategies that block not only BRAF mutated kinase but other alternative pathways are ongoing and have demonstrated improved activity. This review aims to provide data about new strategies to target to BRAF gene mutation in metastatic colorectal cancer. PMID:27341594

  1. Clinical implications of metastatic lymph node ratio in gastric cancer

    Directory of Open Access Journals (Sweden)

    Wang Shubao

    2007-10-01

    Full Text Available Abstract Background The 5-year survival rate in patients with gastric cancer is still poor, and lymph node metastasis is considered one of the most important prognostic factors. However, there are controversies in the classification of lymph node metastasis in gastric cancer. This study was carried out to investigate whether the metastatic lymph node ratio is a reliable classification of lymph node metastasis in gastric cancer in Chinese. Methods 224 cases with gastric cancer with more than D1 dissection were retrospectively reviewed. The association between the total number of resected lymph nodes and the number of metastatic lymph nodes was determined. The prognostic value of the metastastic node ratio, defined as the ratio of the number of metastatic lymph nodes over the total number of resected lymph nodes, and the pN classification was assessed. Results The number of metastatic lymph node increased with the number of total resected lymph nodes. A Cox regression revealed that the metastatic node ratio, the number of metastatic nodes, histological type, and histological growth pattern independently influenced prognosis. The 5-year survival rates were 78%, 61%, 25%, 0% in cases with a metastastic node ratio of 0%, > 0% but 80%, respectively (P P Conclusion The metastatic lymph node ratio is a simple and useful independent prognostic factor. It may obviate possible confounding factors that are related to stage migration, and should be considered as an important component in the lymph node category.

  2. (-)-Gossypol reduces invasiveness in metastatic prostate cancer cells

    Science.gov (United States)

    Acquisition of metastatic ability by prostatic cancer cells is the most lethal aspect of prostatic cancer progression. (-)-Gossypol, a polyphenolic compound present in cottonseeds, possesses anti-proliferation and pro-apoptotic effects in various cancer cells. In this study, the differences betwee...

  3. Metastatic breast cancer and its complications.

    Science.gov (United States)

    Rubens, R D

    1992-12-01

    Tamoxifen is now established for use in premenopausal as well as postmenopausal patients. Recent reports have not shown its activity to be enhanced by the addition of either prednisolone, progestogens, or interferon. Reversible ocular toxicity from tamoxifen appears to be more common than had been previously realized. Different schedules giving the same dose intensity of doxorubicin give markedly different pharmacokinetic profiles. Although this does not lead to differences in responses or physical toxicity, it seems to have important implications for quality of life. Taxol is showing impressive activity in advanced breast cancer, and significant response rates have also been reported for carboplatin and podophyllotoxin derivatives. To achieve maximum effectiveness from the cyclophosphamide, methotrexate, and fluorouracil combination, attention to schedule and dose intensity has been shown to be important. No new effective cytotoxic combinations have been described. High-dose chemotherapy requiring bone marrow support remains experimental. Further progress has been made in monitoring the response of metastatic bone disease to treatment. The precise significance for patients of the results in many of the papers reviewed is often uncertain because they lack quality-of-life measures; the importance of this approach is emphasized. PMID:1457519

  4. The clone wars - revenge of the metastatic rogue state: the sarcoma paradigm

    Directory of Open Access Journals (Sweden)

    Holly Lynn Spraker

    2012-01-01

    Full Text Available Ewing sarcoma (ES is the second most common bone tumor affecting primarily adolescents and young adults. Despite recent advances in biological understanding, intensification of chemotherapeutic treatments, and progress in local control with surgery and/or radiation therapy, patients with metastatic or recurrent ES continue to have a dismal prognosis with less than 20% overall survival. All ES likely is metastatic at diagnosis although our methods of detection and classification may not account for this. Progressive disease may arise via a combination of: 1 selection of chemotherapy-resistant clones, 2 signaling from bone or lung microenvironments that may attract tumor cells to distant locations, and/or 3 genetic changes within the ES cells themselves due to a combination of therapy-related selection and DNA-damaging chemotherapeutic agents. These possibilities and the evidence base to support them are explored.

  5. Fluorescent-Antibody Targeting of Insulin-Like Growth Factor-1 Receptor Visualizes Metastatic Human Colon Cancer in Orthotopic Mouse Models

    OpenAIRE

    Park, Jeong Youp; Murakami, Takashi; Lee, Jin Young; Zhang, Yong; Hoffman, Robert M; Bouvet, Michael

    2016-01-01

    Fluorescent-antibody targeting of metastatic cancer has been demonstrated by our laboratory to enable tumor visualization and effective fluorescence-guided surgery. The goal of the present study was to determine whether insulin-like growth factor-1 receptor (IGF-1R) antibodies, conjugated with bright fluorophores, could enable visualization of metastatic colon cancer in orthotopic nude mouse models. IGF-1R antibody (clone 24–31) was conjugated with 550 nm, 650 nm or PEGylated 650 nm fluoropho...

  6. 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

  7. Serum‐derived exosomes from mice with highly metastatic breast cancer transfer increased metastatic capacity to a poorly metastatic tumor

    OpenAIRE

    Gorczynski, Reginald M.; Erin, Nuray; Zhu, Fang

    2016-01-01

    Abstract Altered interaction between CD200 and CD200R represents an example of “checkpoint blockade” disrupting an effective, tumor‐directed, host response in murine breast cancer cells. In CD200R1KO mice, long‐term cure of EMT6 breast cancer, including metastatic spread to lung and liver, was achieved in BALB/c mice. The reverse was observed with 4THM tumors, an aggressive, inflammatory breast cancer, with increased tumor metastasis in CD200R1KO. We explored possible explanations for this di...

  8. Evaluation of dual energy spectral CT in differentiating metastatic from non-metastatic lymph nodes in rectal cancer: Initial experience

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Huanhuan [Department of Radiology, Ruijin Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai 200025 (China); Department of Radiology, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine (China); Yan, Fuhua; Pan, Zilai; Lin, Xiaozhu; Luo, Xianfu; Shi, Cen [Department of Radiology, Ruijin Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai 200025 (China); Chen, Xiaoyan [Department of Pathology, Ruijin Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai 200025 (China); Wang, Baisong [Department of Biomedical Statistics, Shanghai Jiaotong University, School of Medicine, Shanghai 200025 (China); Zhang, Huan, E-mail: huanzhangy@126.com [Department of Radiology, Ruijin Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai 200025 (China)

    2015-02-15

    Highlights: • Colorectal cancer is the third most prevalent cancer and the status of the regional lymph nodes in rectal cancer is considered to be one of the most powerful prognostic factor in the absence of distant metastatic disease. Detecting LNs metastasis is still a challenging problem due to the presence of microscopic metastasis or inflammatory swelling of LNs. • We investigated the value of dual energy spectral CT in differentiating metastatic from non-metastatic lymph nodes in rectal cancer. Our study demonstrated that the quantitative normalized iodine concentration (nIC) could be useful for differentiating metastatic and non-metastatic lymph nodes. The combination of nIC in portal venous phase and conventional size criterion could improve the diagnostic accuracy, sensitivity, specificity, positive predictive value and negative predictive value of rectal cancer. - Abstract: Objectives: To investigate the value of dual energy spectral CT (DEsCT) imaging in differentiating metastatic from non-metastatic lymph nodes in rectal cancer. Methods: Fifty-five patients with rectal cancer underwent the arterial phase (AP) and portal venous phase (PP) contrast-enhanced DEsCT imaging. The virtual monochromatic images and iodine-based material decomposition images derived from DEsCT imaging were interpreted for lymph nodes (LNs) measurement. The short axis diameter and the normalized iodine concentration (nIC) of metastatic and non-metastatic LNs were measured. The two-sample t test was used to compare the short axis diameters and nIC values of metastatic and non-metastatic LNs. ROC analysis was performed to assess the diagnostic performance. Results: One hundred and fifty two LNs including 92 non-metastatic LNs and 60 metastatic LNs were matched using the radiological-pathological correlation. The mean short axis diameter of metastatic LNs was significantly larger than that of the non-metastatic LNs (7.28 ± 2.28 mm vs. 4.90 ± 1.64 mm, P < 0.001). The mean n

  9. Treatment of Metastatic Prostate Cancer in Older Adults.

    Science.gov (United States)

    Loh, Kah Poh; Mohile, Supriya G; Kessler, Elizabeth; Fung, Chunkit

    2016-10-01

    The aging of the population, along with rising life expectancy, means that increasing numbers of older men will be diagnosed with prostate cancer, and a large proportion of these men will present with metastatic disease. In this paper, we discuss recent advances in prostate cancer treatment. In particular, we review management approaches for older patients with metastatic prostate cancer based on the decision tree developed by the International Society of Geriatric Oncology, which categorized older men as "fit," "vulnerable," and "frail" according to comprehensive geriatric assessment. PMID:27586377

  10. Gamma knife radiosurgery for metastatic brain tumors from lung cancer

    International Nuclear Information System (INIS)

    The purpose of this retrospective study is to evaluate the effectiveness of gamma knife radiosurgery (GKS) alone for metastatic brain tumors from lung cancer. Two hundred thirty-one consecutive patients with metastatic brain tumors from lung cancer filling the following 4 criteria were analyzed for this study; no prior brain tumor treatment, 25 or fewer lesions, a maximum 5 tumors with diameter of 2 cm or more, no surgically inaccessible tumor 3 cm or greater in diameter. According to the same treatment protocol, large tumors (≥ 3 cm) were surgically removed and all the other small lesions (10 brain lesions. This study suggests the results of GKS for metastatic brain tumors from lung cancer are quite satisfactory considering prevention of neurological death and maintenance of QOL. But cases with carcinomatous meningitis and/or >10 brain lesions are not good candidates for GKS alone. (author)

  11. Systemic therapy for metastatic bladder cancer in 2016 and beyond.

    Science.gov (United States)

    Collazo-Lorduy, Ana; Galsky, Matthew D

    2016-05-01

    Metastatic urothelial cancer is generally associated with poor outcomes. In the first-line setting, platinum-based chemotherapy is the standard of care but resistance rapidly develops and the vast majority of patients ultimately experience disease progression. Despite several decades of clinical drug development focused on the treatment of platinum-resistant metastatic urothelial cancer, as of late 2015 there are no standard therapies approved by the US FDA in this setting. However, preliminary results from a series of recent trials exploring innovative approaches forecast a 'sea change' in the management of this difficult to treat malignancy. Herein, we review new approaches for the management of patients with metastatic urothelial cancer focused on three key therapeutic target areas: recurrent somatic alterations, the tumor neovasculature and tumor-associated immune escape. PMID:26922914

  12. Heparanase mediates a novel mechanism in lapatinib-resistant brain metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Lixin Zhang

    2015-01-01

    Full Text Available Heparanase (HPSE is the dominant mammalian endoglycosidase and important tumorigenic, angiogenic, and pro-metastatic molecule. Highest levels of HPSE activity have been consistently detected in cells possessing highest propensities to colonize the brain, emphasizing the therapeutic potential for targeting HPSE in brain metastatic breast cancer (BMBC. Lapatinib (Tykerb is a small-molecule and dual inhibitor of human epidermal growth factor receptor1 and 2 (EGFR and HER2, respectively which are both high-risk predictors of BMBC. It was approved by the US Food and Drug Administration for treatment of patients with advanced or metastatic breast cancer. However, its role is limited in BMBC whose response rates to lapatinib are significantly lower than those for extracranial metastasis. Because HPSE can affect EGFR phosphorylation, we examined Roneparstat, a non-anticoagulant heparin with potent anti-HPSE activity, to inhibit EGFR signaling pathways and BMBC onset using lapatinib-resistant clones generated from HER2-transfected, EGFR-expressing MDA-MB-231BR cells. Cell growth, EGFR pathways, and HPSE targets were assessed among selected clones in the absence or presence of Roneparstat and/or lapatinib. Roneparstat overcame lapatinib resistance by inhibiting pathways associated with EGFR tyrosine residues that are not targeted by lapatinib. Roneparstat inhibited the growth and BMBC abilities of lapatinib-resistant clones. A molecular mechanism was identified by which HPSE mediates an alternative survival pathway in lapatinib-resistant clones and is modulated by Roneparstat. These results demonstrate that the inhibition of HPSE-mediated signaling plays important roles in lapatinib resistance, and provide mechanistic insights to validate the use of Roneparstat for novel BMBC therapeutic strategies.

  13. Stromal targeted therapy in bone metastatic prostate cancer: promise delivered

    Institute of Scientific and Technical Information of China (English)

    Oliver Sartor; William Goeckeler; Oyvind Bruland

    2011-01-01

    The ability of epithelial neoplasms to evade both hormonal and cytotoxic therapies is self-evident as the common carcinomas (lung,stomach,breast,colon and prostate) at their metastatic stage are rarely curable with current therapies.Though the precise reasons for incurability are debated,virtually all agree that tumor genetic heterogeneity makes eradication of the tumor difficult given ‘Darwinian' selection processes that are associated with the emergence of drug-resistant cellular clones.

  14. Personalizing medicine for metastatic colorectal cancer: Current developments

    OpenAIRE

    Marques, Andrea Marin; Turner, Alice; de Mello, Ramon Andrade

    2014-01-01

    Metastatic colorectal cancer (mCRC) is still one of the tumor types with the highest incidence and mortality. In 2012, colorectal cancer was the second most prevalence cancer among males (9%) and the third among females (8%). In this disease, early diagnosis is important to improve treatment outcomes. However, at the time of diagnosis, about one quarter of patients already have metastases, and overall survival of these patients at 5-years survival is very low. Because of these poor statistics...

  15. Takotsubo cardiomyopathy in two men receiving bevacizumab for metastatic cancer

    OpenAIRE

    Thérèse H Franco; Ahmed Khan; Vishal Joshi; Beje Thomas

    2008-01-01

    Thérèse H Franco, Ahmed Khan, Vishal Joshi, Beje ThomasDepartment of Internal Medicine, University of Connecticut, Farmington, CT, USAAbstract: Bevacizumab is a monoclonal antibody that inhibits vascular endothelial growth factor (VEGF). It is a novel chemotherapeutic agent currently approved as part of combination chemotherapy for metastatic colorectal cancer, non-small cell lung cancer, and breast cancer (Hurwitz et al 2004; Sandler et al 2006; Traina et al 2007). Arte...

  16. Enzalutamide for patients with metastatic castration-resistant prostate cancer

    Science.gov (United States)

    Ramadan, Wijdan H; Kabbara, Wissam K; Al Basiouni Al Masri, Hiba S

    2015-01-01

    Objective To review and evaluate current literature on the US Food and Drug Administration (FDA)-approved drug enzalutamide (XTANDI®) in metastatic castration-resistant prostate cancer. Data sources Literature search was done through PubMed using the terms enzalutamide, MDV3100, abiraterone, and castration-resistant prostate cancer. Data from FDA product labels were also used. Study selection and data extraction Recent and relevant studies were included in the review. Collected clinical trials were screened and evaluated. Data synthesis Enzalutamide is an androgen receptor (AR) inhibitor with high selectivity and affinity to the AR. It was approved by the FDA to treat metastatic castration-resistant prostate cancer in patients previously treated with docetaxel, after a Phase III trial (AFFIRM) that showed a 4.8-month survival benefit in this population. Recently, the FDA expanded the approval of enzalutamide as first-line therapy for metastatic castration-resistant prostate cancer (mCRPC) who did not receive chemotherapy. Moreover, enzalutamide is shown to be associated with an acceptable safety profile. Conclusion Enzalutamide has been shown to be both safe and effective in improving overall survival in metastatic castration-resistant prostate cancer postchemotherapy with docetaxel and as a first line treatment before initiation of chemotherapy. However, additional studies and head-to-head trials are needed. PMID:25945058

  17. Treatment of patients with metastatic pancreatic cancer: Experience from a tertiary Indian cancer center

    OpenAIRE

    Sirohi, B; S Dawood; S. Rastogi; Pandey, A.; Bal, M; N Shetty; Shrikhande, S. V.

    2015-01-01

    Background: The aim of this study was to look at the outcome of patients with metastatic pancreatic cancer treated at a tertiary cancer center in India. Patients And Methods: A total of 101 patients with locally advanced and metastatic pancreatic cancer diagnosed between May 2012 and July 2013 were identified from a prospectively maintained database at the tertiary cancer center. Overall survival (OS) was computed using the Kaplan–Meir product limit method and compared across groups using the...

  18. Metastatic colorectal cancer-past, progress and future

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The clinical management of metastatic (stage Ⅳ)colorectal cancer (CRC) is a common challenge faced by surgeons and physicians. The last decade has seen exciting developments in the management of CRC, with significant improvements in prognosis for patients diagnosed with stage Ⅳ disease. Treatment options have expanded from 5-fluorouracil alone to a range of pharmaceutical and interventional therapies,improving survival, and providing a cure in selected cases. Enhanced understanding of the biologic pathways most important in colorectal carcinogenesis has led to a new generation of drugs showing promise in advanced disease. It is hoped that in the near future the treatment paradigm of metastatic CRC will be analogous to that of a chronic illness, rather than a rapidly terminal condition.This overview discusses the epidemiology of advanced CRC and currently available therapeutic options including medical, surgical, ablative and novel modalities in the management of metastatic colorectal cancer.

  19. Pulmonary Hyalinizing Granuloma Mimicking Metastatic Lung Cancer

    OpenAIRE

    Nuri Düzgün; Ercan Kurtipek; Hıdır Esme; Meryem İlkay Eren Karanis; İsmet Tolu

    2015-01-01

    Pulmonary hyalinizing granuloma is a very rare benign condition, which usually manifests as solitary and sometimes as multiple pulmonary nodules. Deposition of immune complexes in the lung parenchyma due to hypersensitivity reactions is implicated in the etiology of pulmonary hyalinizing granuloma. A 59-year-old female patient who presented to our clinic with complaints of chest pain and cough had bilateral, multiple, and rounded lesions with regular margins suggesting metastatic lung disease...

  20. INTRAPLEURAL IMMUNOTHERAPY FOR METASTATIC PLEURISIES IN PATIENTS WITH BREAST CANCER

    OpenAIRE

    K. S. Titov; L. V. Demidov; M. V. Kiselevsky; I. N. Mikhailova; I. Zh. Shubina; A. N. Gritsai; I. E. Sinelnikov; L. M. Rodionova

    2009-01-01

    Intrapleural immunotherapy for metastatic pleurisies demonstrates a high efficiency in the treatment of patients with breast cancer (BC). This immunotherapy modality is regarded as one of the stages of complex treatment in patients with disseminated BC and allows its capabilities to be extended for their further management.

  1. Cancer of unknown primitive metastatic. About two clinical cases

    International Nuclear Information System (INIS)

    This work is about the two clinical cases about the unknown primitive metastatic cancer. The main techniques used for the diagnosis, treatment and monitoring of different s carcinomas are: Electronic microscope, molecular biology and genetics, especially histopathological study, topographic survey, ultrasound, radiography, chemotherapy, radiotherapy

  2. Visualising and quantifying angiogenesis in metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Hansen, Torben Frøstrup; Nielsen, Boye Schnack; Jakobsen, Anders; Sørensen, Flemming Brandt

    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...

  3. Palbociclib in Combination With Tamoxifen as First Line Therapy for Metastatic Hormone Receptor Positive Breast Cancer

    Science.gov (United States)

    2016-07-05

    Hormone Receptor Positive Malignant Neoplasm of Breast; Human Epidermal Growth Factor 2 Negative Carcinoma of Breast; Estrogen Receptor Positive Breast Cancer; Progesterone Receptor Positive Tumor; Metastatic Breast Cancer

  4. Cabozantinib for progressive metastatic medullary thyroid cancer: a review

    OpenAIRE

    Colombo JR; Wein RO

    2014-01-01

    Joshua R Colombo, Richard O Wein Department of Otolaryngology, Head and Neck Surgery, Tufts Medical Center, Boston, MA, USA Abstract: Medullary thyroid cancer is uncommon and patients typically present with advanced disease. Treatment options for patients with progressive, metastatic medullary thyroid cancer had been limited until recently. Tyrosine kinase inhibitors have garnered increasing interest in this subset of patients. The US Food and Drug Administration recently approved cabozantin...

  5. Advances in diagnosis and treatment of metastatic cervical cancer.

    Science.gov (United States)

    Li, Haoran; Wu, Xiaohua; Cheng, Xi

    2016-07-01

    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

  6. Management of hormone-sensitive metastatic prostate cancer.

    Science.gov (United States)

    Agarwal, Neeraj; Hussain, Maha

    2013-12-01

    Targeting gonadal androgen synthesis (often in conjunction with blockade of androgen receptor) is the cornerstone of treatment of hormone-sensitive metastatic prostate cancer (HSPC). Despite the failure of androgen deprivation therapy, most tumors maintain some dependence on androgen or androgen receptor signaling for proliferation. This article reviews the current standard of care for metastatic HSPC, mechanisms of treatment resistance, novel drugs targeting the androgen signaling pathway, biomarkers predicting response to treatment and survival, future directions, and ongoing clinical trials in HSPC. PMID:24188260

  7. 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.

  8. The Complex Function of Hsp70 in Metastatic Cancer

    Directory of Open Access Journals (Sweden)

    Kata Juhasz

    2013-12-01

    Full Text Available Elevated expression of the inducible heat shock protein 70 (Hsp70 is known to correlate with poor prognosis in many cancers. Hsp70 confers survival advantage as well as resistance to chemotherapeutic agents, and promotes tumor cell invasion. At the same time, tumor-derived extracellular Hsp70 has been recognized as a “chaperokine”, activating antitumor immunity. In this review we discuss localization dependent functions of Hsp70 in the context of invasive cancer. Understanding the molecular principles of metastasis formation steps, as well as interactions of the tumor cells with the microenvironment and the immune system is essential for fighting metastatic cancer. Although Hsp70 has been implicated in different steps of the metastatic process, the exact mechanisms of its action remain to be explored. Known and potential functions of Hsp70 in controlling or modulating of invasion and metastasis are discussed.

  9. Anti-angiogenic agents in metastatic colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Colorectal cancer (CRC) is a major public health concernbeing the third leading cause of cancer mortality inthe United States. The availability of better therapeuticoptions has led to a decline in cancer mortality in thesepatients. Surgical resection should be considered in allstages of the disease. The use of conversion therapyhas made surgery a potentially curative option even inpatients with initially unresectable metastatic disease.In this review we discuss the role of various antiangiogenicagents in patients with metastatic CRC(mCRC). We describe the mechanism of action of theseagents, and the rationale for their use in combinationwith chemotherapy. We also review important clinicalstudies that have evaluated the safety and efficacy ofthese agents in mCRC patients. Despite the discoveryof several promising anti-angiogenic agents, mCRCremains an incurable disease with a median overallsurvival of just over 2 years in patients exposed to allavailable treatment regimens. Further insights intotumor biology and tumor microenvironment may helpimprove outcomes in these patients.

  10. Takotsubo cardiomyopathy in two men receiving bevacizumab for metastatic cancer

    Directory of Open Access Journals (Sweden)

    Thérèse H Franco

    2008-10-01

    Full Text Available Thérèse H Franco, Ahmed Khan, Vishal Joshi, Beje ThomasDepartment of Internal Medicine, University of Connecticut, Farmington, CT, USAAbstract: Bevacizumab is a monoclonal antibody that inhibits vascular endothelial growth factor (VEGF. It is a novel chemotherapeutic agent currently approved as part of combination chemotherapy for metastatic colorectal cancer, non-small cell lung cancer, and breast cancer (Hurwitz et al 2004; Sandler et al 2006; Traina et al 2007. Arterial thrombosis, including cerebral infarction, transient ischemic attacks, myocardial infarction, and angina are common, occurring in 4.4% of patients whose regimen includes bevacizumab (versus 1.9% on regimen without bevacizumab (Genetech, Inc. 2008. This series will review two cases of patients exposed to bevacizumab who subsequently developed ST elevations on electrocardiogram (ECG and elevated cardiac biomarkers. Both patients underwent cardiac catheterization, which demonstrated apical ballooning and akinesis in a distribution discordant with the observed (noncritical atherosclerotic lesions. Both patients had recovery of left ventricular function within 30 days. The clinical presentation, including ECGs and findings on catheterization as well as the rapid recovery of ventricular function, is consistent with the diagnosis of takotsubo cardiomyopathy. Takotsubo cardiomyopathy was first described in 1991, but the pathophysiology and exact mechanism of injury remain largely unknown. These two cases are notable for their occurrence in men and the association with treatment of metastatic cancer including bevacizumab.Keywords: vascular endothelial growth factor, bevacizumab, metastatic cancer, chemotherapy, takotsubo, cardiomyopathy

  11. Evaluate Risk/Benefit of Nab Paclitaxel in Combination With Gemcitabine and Carboplatin Compared to Gemcitabine and Carboplatin in Triple Negative Metastatic Breast Cancer (or Metastatic Triple Negative Breast Cancer)

    Science.gov (United States)

    2016-08-24

    Breast Tumor; Breast Cancer; Cancer of the Breast; Estrogen Receptor- Negative Breast Cancer; HER2- Negative Breast Cancer; Progesterone Receptor- Negative Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer; Triple-negative Breast Cancer; Triple-negative Metastatic Breast Cancer; Metastatic Breast Cancer

  12. Metastatic Colorectal Cancer: Review of Diagnosis and Treatment Options

    Directory of Open Access Journals (Sweden)

    Madalina Palaghia

    2015-04-01

    Full Text Available Colorectal cancer (CRC is currently considered the third most common neoplasm in the world according to the World Cancer Research Fund International with 1.4 million cases diagnosed in 2012, and the second malignity as cause of death. Approximately 1/5 of patients present directly with metastatic disease (mCRC, and 30 to 50% develop metastasis after surgical treatment for initially localized disease. The aims of the current study are to review the diagnostic particularities, treatment options and clinical evolution of mCRC. Metastatic process in CRC is long and complex, involving several mechanisms, molecular pathways and cellular types. Advances in medical imaging now allow an early and accurate diagnosis of metastatic lesions no matter their location. The progress of fundamental research in CRC led to understanding the molecular basis of the metastatic process that was further translated into novel chemotherapic and biological agents, thus increasing overall survival and and progression-free survival rates. Resection of liver, lung and brain metastases is crucial for survival when achievable and is more effective when completed by an oncological treatment and rigorous follow-up. All patients with mCRC should be discussed by a multidisciplinary team (surgeon, oncologist, radiologist, and gastroenterologist in order to identify the most appropriate therapeutic management.

  13. The importance of biopsy in clinically diagnosed metastatic lesions in patients with breast cancer

    OpenAIRE

    Qu, Qing; Zong, Yu; Fei, Xiao-Chun; Chen, Xiao-Song; Xu, Cheng; Lou, Gu-yin; Shen, Kun-wei

    2014-01-01

    Background Receptor status discordance, such as estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status between primary breast cancer and metastatic lesions has been reported. The aim of this study was to evaluate the biopsy of clinically diagnosed metastatic lesions and to determine the changes in hormonal receptor and HER2 status of the metastatic lesions. Methods Sixty-three patients with clinically diagnosed metastatic breast cancer un...

  14. Metastatic Breast Cancer to the Common Bile Duct Presenting as Obstructive Jaundice

    OpenAIRE

    Cochrane, Justin; Schlepp, Greg

    2015-01-01

    Metastatic breast cancer is typically identified in the bones, lymph nodes, lungs and liver. Rarely does metastatic breast cancer involve the common bile duct (CBD) without direct extension from liver metastasis into the CBD. We present a woman diagnosed with metastatic breast cancer in the CBD after presenting with obstructive jaundice. Patients with a history of primary breast cancer who present with obstructive jaundice secondary to CBD mass need identification of the mass in order to prov...

  15. 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.

  16. Medical Management of Metastatic Medullary Thyroid Cancer

    OpenAIRE

    Maxwell, Jessica E; Sherman, Scott K.; O’Dorisio, Thomas M.; Howe, James R.

    2014-01-01

    Medullary thyroid cancer (MTC) is an aggressive form of thyroid cancer, which occurs in both heritable and sporadic forms. Discovery that mutations in the RET protooncogene predispose to familial cases of this disease has allowed for presymptomatic identification of gene carriers and prophylactic surgery to improve the prognosis of these patients. A significant number of patients with the sporadic type of MTC and even with familial disease, still present with nodal or distant metastases, maki...

  17. Pneumocystis jirovecii pneumonia following everolimus treatment of metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Kelvin Teck-Hong Kuik

    2014-10-01

    Full Text Available Everolimus is an inhibitor of mammalian target of rapamycin with anti-tumour activity. While everolimus is known to cause drug-induced pneumonitis, it is rarely associated with Pneumocystis jirovecii pneumonia (PJP. We report a patient on everolimus therapy for metastatic breast cancer that developed PJP. Diagnosis was based on clinical features and a quantitative polymerase chain reaction for P. jirovecii DNA. Clinicians should consider PJP as a potential cause of pulmonary infiltrates in patients treated with everolimus.

  18. Pneumocystis jirovecii pneumonia following everolimus treatment of metastatic breast cancer

    OpenAIRE

    Kelvin Teck-Hong Kuik; Jason Trubiano; Worth, Leon J.; Nur-shirin Harun; Daniel Steinfort; Douglas Johnson

    2014-01-01

    Everolimus is an inhibitor of mammalian target of rapamycin with anti-tumour activity. While everolimus is known to cause drug-induced pneumonitis, it is rarely associated with Pneumocystis jirovecii pneumonia (PJP). We report a patient on everolimus therapy for metastatic breast cancer that developed PJP. Diagnosis was based on clinical features and a quantitative polymerase chain reaction for P. jirovecii DNA. Clinicians should consider PJP as a potential cause of pulmonary infiltrates in p...

  19. miR-345 in Metastatic Colorectal Cancer

    DEFF Research Database (Denmark)

    Schou, Jakob V; Rossi, Simona; Jensen, Benny V; Nielsen, Dorte L; Pfeiffer, Per; Høgdall, Estrid; Yilmaz, Mette; Tejpar, Sabine; Delorenzi, Mauro; Kruhøffer, Mogens; Johansen, Julia S

    2014-01-01

    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 for...

  20. Metronomic chemotherapy in metastatic breast cancer Impact on VEGF

    International Nuclear Information System (INIS)

    Background: Anticancer chemotherapy is thought to be effective by means of direct cytotoxicity on tumor cells. Alternative mechanisms of efficacy have been ascribed to several common anticancer agents; including cyclophosphamide (CTX) and capecitabine (Cap) when given at lower doses for prolonged period (metronomic chemotherapy) postulating an antiangiogenic activity as well, Aim of work :To evaluate the action and tolerability of metronomic chemotherapy (MC) and its impact on serum vascular endothetial growth factor (VEGF) levels in metastatic breast cancer (MBC) patients. Patients and methods: In this study we evaluated the clinical efficacy and tolerability of low dose, capecitabine (500 mg twice daily) together with oral cyclophosphamide (CTX) (a dose of 50 mg once daily) in patients with metastatic breast cancer. Vascular endothelial growth factor (VEGF), an angiogenic marker, was measured in the serum samples; at base line, and after 2 and 6 months of therapy. Results: Sixty patients were evaluable. One achieved complete response (CR), 12 partial responses (PR), and 21 stable diseases (SD), while 26 were with progressive disease (PD). The overall response rate was 21.7% with overall disease control (CR, PR, and SD) 56.7%. The median time to progression was 7±2.59 months and overall survival 16 ±8.02 months. Toxicity was mild, Palmar-plantar erythrodythesia was the must common side effect and was observed in 22 patients (37%), leucopenia (Gl + 2) was the most common hematological toxicity, and it was reported in 27% of the cases. The median VEGF level was significantly declined after 2 and 6 months of therapy compared to the base line among the patients with disease control (CR, PR, and SD). In multivariate logisatic regression analysis, patients with post-menopausal, positive hormonal receptors, negative HER-2/Neu, and one, metastatic site, were statistically significant and have a better disease control rate. Coclcusions: MC induced drop in VEGF, and was

  1. 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

  2. Label-Free Quantitative Proteomics and N-terminal Analysis of Human Metastatic Lung Cancer Cells

    OpenAIRE

    Min, Hophil; Han, Dohyun; Kim, Yikwon; Cho, Jee Yeon; Jin, Jonghwa; Kim, Youngsoo

    2014-01-01

    Proteomic analysis is helpful in identifying cancer-associated proteins that are differentially expressed and fragmented that can be annotated as dysregulated networks and pathways during metastasis. To examine meta-static process in lung cancer, we performed a proteomics study by label-free quantitative analysis and N-terminal analysis in 2 human non-small-cell lung cancer cell lines with disparate metastatic potentials—NCI-H1703 (primary cell, stage I) and NCI-H1755 (metastatic cell, stage ...

  3. A review on metastatic breast cancer in Iran

    Institute of Scientific and Technical Information of China (English)

    Hamidreza; Alizadeh; Otaghvar; Mostafa; Hosseini; Adnan; Tizmaghz; Ghazaal; Shabestanipour; Hamid; Noori

    2015-01-01

    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 6 160 breast cancers are diagnosed in the country each year and 1 063 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.

  4. 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.

  5. Her-2 overexpression increases the metastatic outgrowth of breast cancer cells in the brain.

    Science.gov (United States)

    Palmieri, Diane; Bronder, Julie L; Herring, Jeanne M; Yoneda, Toshiyuki; Weil, Robert J; Stark, Andreas M; Kurek, Raffael; Vega-Valle, Eleazar; Feigenbaum, Lionel; Halverson, Douglas; Vortmeyer, Alexander O; Steinberg, Seth M; Aldape, Kenneth; Steeg, Patricia S

    2007-05-01

    Retrospective studies of breast cancer patients suggest that primary tumor Her-2 overexpression or trastuzumab therapy is associated with a devastating complication: the development of central nervous system (brain) metastases. Herein, we present Her-2 expression trends from resected human brain metastases and data from an experimental brain metastasis assay, both indicative of a functional contribution of Her-2 to brain metastatic colonization. Of 124 archival resected brain metastases from breast cancer patients, 36.2% overexpressed Her-2, indicating an enrichment in the frequency of tumor Her-2 overexpression at this metastatic site. Using quantitative real-time PCR of laser capture microdissected epithelial cells, Her-2 and epidermal growth factor receptor (EGFR) mRNA levels in a cohort of 12 frozen brain metastases were increased up to 5- and 9-fold, respectively, over those of Her-2-amplified primary tumors. Co-overexpression of Her-2 and EGFR was also observed in a subset of brain metastases. We then tested the hypothesis that overexpression of Her-2 increases the colonization of breast cancer cells in the brain in vivo. A subclone of MDA-MB-231 human breast carcinoma cells that selectively metastasizes to brain (231-BR) overexpressed EGFR; 231-BR cells were transfected with low (4- to 8-fold) or high (22- to 28-fold) levels of Her-2. In vivo, in a model of brain metastasis, low or high Her-2-overexpressing 231-BR clones produced comparable numbers of micrometastases in the brain as control transfectants; however, the Her-2 transfectants yielded 3-fold greater large metastases (>50 microm(2); P < 0.001). Our data indicate that Her-2 overexpression increases the outgrowth of metastatic tumor cells in the brain in this model system. PMID:17483330

  6. Why Chemotherapy Should be Given Early for Men with Metastatic Prostate Cancer.

    Science.gov (United States)

    Hernandez-Aya, Leonel F; Hussain, Maha

    2015-01-01

    Metastatic hormone-sensitive prostate cancer (mHSPC) is an incurable disease, and despite a high response rate to androgen-deprivation therapy (ADT), outcomes have not significantly changed for many decades. Earlier attempts at multitargeted strategies with the addition of cytotoxic chemotherapy to ADT did not affect survival. As more effective therapies are emerging, including cytotoxic therapy for patients with metastatic castrate-resistant prostate cancer (mCRPC), there is increasing interest for testing these drugs earlier in the disease course. The premise is that agents with clinical benefit in advanced mCRPC may have a better effect if used preemptively before the development of significant resistance and to attack earlier de novo androgen resistant/independent clones. The recent results of the phase III clinical trial E3805 investigating ADT with or without docetaxel in mHSPC provide compelling support for this strategy. Docetaxel combined with ADT significantly improved overall survival from 44 to 57.6 months (p=0.0003), particularly in patients with high-volume disease (from 32.2 to 49.2 months; p=0.0006). Longer follow-up is needed to assess the effect on patients with low disease burden. Further studies are needed to further maximize the antitumor effect in patients with mHSPC and to investigate the effects of advancing therapy to this disease setting on the efficacy of respective agents in the castration-resistant setting. PMID:25993184

  7. Study of angiogenesis induced by metastatic and non-metastatic liver cancer by corneal micropocket model in nude mice

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    AIM To study the angiogenesis induced by liver cancer with different metastatic potentials using corneal micropocket model in nude mice.METHODS Corneal micropockets were created in nude mice. Tumor tissues and liver tissues were implanted into the corneal micropockets. Angiogenesis was observed using a digital camera under slit-lamp biomicroscope, and compared among different grafts and incision alone. Vascular responses were recorded in regard to the range, number and length of new blood vessels toward the grafts or incisions.RESULTS Vascular responses induced by tumor tissues were greater than those by incision alone and liver tissue grafts. LCI-D20 induced more intensive angiogenesis than LCI-D35.CONCLUSION Highly metastatic liver cancer LCI D20 was more angiogenic than low metastatic cancer LCI D35 and liver tissue. Micropocket was a useful model to study dynamic process of angiogenesis in vivo.

  8. Metastatic kidney cancer: Choice of first-line therapy

    Directory of Open Access Journals (Sweden)

    B. Ya. Alekseev

    2014-11-01

    Full Text Available The current practice in prescribing targeted agents for patients with metastatic kidney cancer (KC is based on the results of a few large-scale multicenter randomized trials of the efficacy of different drugs in different clinical situations. Most international and national oncology and urology associations recommend 3 standard treatment options: 1 bevaсizumab in combination with interferon; 2 sunitinib; 3 pazopanib as first-line therapy in patients with good and intermediate risk metastatic KC. The valid choice of a drug for first-line therapy is one of the topical problems of real clinical practice. The criteria for choosing a drug are primarily its efficacy and toxicity profile. In addition, the specific features of a patient’s health status, the presence of different intercurrent diseases, lifestyle, and professional peculiarities also affect the choice of a treatment regimen. The paper comparatively reviews the efficacy and toxicity of bevaсizumab in combination with interferon at different doses, those of sunitinib and pazopanib, on the basis of which the choice of a drug for the therapy of patients with good and intermediate risk metastatic KC may be planned in a specific clinical situation.

  9. PET-CT in the evaluation of metastatic breast cancer

    International Nuclear Information System (INIS)

    A 44-year-old woman underwent two PET-CT scans for the evaluation of metastatic breast cancer. A radical left mastectomy with axillary dissection (1 of 43 nodes positive) followed by chemotherapy, was performed in 1998. She represented in October 2003 with a left supraclavicular fossa mass. This was confirmed to be recurrent breast cancer on FNAB. She was considered for a radical neck dissection and the surgeon requested a PET scan. Other imaging at this time included a normal bone scan and CT brain. CT neck/chest/abdomen/pelvis showed soft tissue thickening in the left lower neck. The PET-CT scan showed multiple glucose avid lesions in the sternum, mediastinum and neck lymph nodes as well as a small lesion in the proximal left femur consistent with extensive metastatic disease. Surgery was cancelled and Femara chemotherapy commenced. Femara was stopped in March 2004 and the patient began alternative therapies. In October 2004 she presented to her surgeon with new back and chest pain. CT of the neck/chest/abdomen/pelvis showed a soft tissue mass in the upper sternum and a lymph node at the base of the neck highly suspicious for metastatic disease. There were also 2 suspicious lung nodules and a lesion in the proximal left femur reported as an osteoid osteoma. Wholebody PET-CT scans were performed on a Siemens LSO Biograph, 60mins after the injection of 350Mbq of Fl 8-Fag, with arms at the patient's side and head in the field-of-view. On both occasions the patient had to pay for the scan. On the 2004 PET-CT scan, the CT brain revealed multiple hyperdense lesions consistent with hemorrhagic metastases. In addition, there were innumerable glucose avid foci involving viscera, nodes and skeleton consistent with disseminated disease. Our case illustrates: (i) the value of PET in the management of metastatic breast cancer; (ii) the improved accuracy of PET-CT in delineating sites of disease; (iii) the issues of head movement in PET-CT and. (iv) the problem with lack of

  10. Novel Combinations for the Treatment of Metastatic Breast Cancer

    Directory of Open Access Journals (Sweden)

    Linda T. Vahdat

    2010-01-01

    Full Text Available Anthracyclines and taxanes represent the mainstay of first-line cytotoxic therapy for metastatic breast cancer (MBC, but most patients eventually develop resistance to these agents. Consequently, alternative combinations for MBC therapy are the subject of much ongoing research. Capecitabine and ixabepilone is the only chemotherapy combination specifically approved for MBC after failure of anthracyclines and taxanes. Other options have limited data to support their use in this setting but are commonly used in practice. Future MBC therapies will likely combine alternative chemotherapies and novel biologic agents, and numerous ongoing trials should help to further define the proper use of these regimens.

  11. 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

  12. Tracking the origins and drivers of subclonal metastatic expansion in prostate cancer

    OpenAIRE

    Hong, Matthew K H; Macintyre, Geoff; Wedge, David C.; Van Loo, Peter; Patel, Keval; Lunke, Sebastian; Alexandrov, Ludmil B.; Sloggett, Clare; Cmero, Marek; Marass, Francesco; Tsui, Dana; Mangiola, Stefano; Lonie, Andrew; Naeem, Haroon; Sapre, Nikhil

    2015-01-01

    Tumour heterogeneity in primary prostate cancer is a well-established phenomenon. However, how the subclonal diversity of tumours changes during metastasis and progression to lethality is poorly understood. Here we reveal the precise direction of metastatic spread across four lethal prostate cancer patients using whole-genome and ultra-deep targeted sequencing of longitudinally collected primary and metastatic tumours. We find one case of metastatic spread to the surgical bed causing local re...

  13. pp-GalNAc-T13 induces high metastatic potential of murine Lewis lung cancer by generating trimeric Tn antigen

    Energy Technology Data Exchange (ETDEWEB)

    Matsumoto, Yasuyuki; Zhang, Qing [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Akita, Kaoru; Nakada, Hiroshi [Department of Molecular Biosciences, Faculty of Life Sciences, Kyoto Sangyo University, Kamigamo-Motoyama, Kita-ku, Kyoto 603-8555 (Japan); Hamamura, Kazunori; Tokuda, Noriyo [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Tsuchida, Akiko [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Noguchi Institute, 1-8-1 Kaga, Itabashi, Tokyo 173-0003 (Japan); Matsubara, Takeshi; Hori, Tomoko; Okajima, Tetsuya [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Furukawa, Keiko [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, 1200 Matsumoto-cho, Kasugai 487-8501 (Japan); Urano, Takeshi [Department of Biochemistry, Shimane University School of Medicine, Izumo 693-8501 (Japan); Furukawa, Koichi, E-mail: koichi@med.nagoya-u.ac.jp [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan)

    2012-03-02

    Highlights: Black-Right-Pointing-Pointer ppGalNAc-T13 was up-regulated in high metastatic sublines of Lewis lung cancer. Black-Right-Pointing-Pointer ppGalNAc-T13 expression enhanced cell invasion activity in low metastatic sublines. Black-Right-Pointing-Pointer Trimeric Tn antigen was induced in the transfectant cells of ppGalNAc-T13 cDNA. Black-Right-Pointing-Pointer A major protein carrying trimeric Tn structure was identified as Syndecan-1. Black-Right-Pointing-Pointer Silencing of ppGalNAc-T13 resulted in the reduction of invasion and of metastasis.. -- Abstract: In order to analyze the mechanisms for cancer metastasis, high metastatic sublines (H7-A, H7-Lu, H7-O, C4-sc, and C4-ly) were obtained by repeated injection of mouse Lewis lung cancer sublines H7 and C4 into C57BL/6 mice. These sublines exhibited increased proliferation and invasion activity in vitro. Ganglioside profiles exhibited lower expression of GM1 in high metastatic sublines than the parent lines. Then, we established GM1-Si-1 and GM1-Si-2 by stable silencing of GM1 synthase in H7 cells. These GM1-knockdown clones exhibited increased proliferation and invasion. Then, we explored genes that markedly altered in the expression levels by DNA microarray in the combination of C4 vs. C4-ly or H7 vs. H7 (GM1-Si). Consequently, pp-GalNAc-T13 gene was identified as up-regulated genes in the high metastatic sublines. Stable transfection of pp-GalNAc-T13 cDNA into C4 (T13-TF) resulted in increased invasion and motility. Then, immunoblotting and flow cytometry using various antibodies and lectins were performed. Only anti-trimeric Tn antibody (mAb MLS128), showed increased expression levels of trimeric Tn antigen in T13-TF clones. Moreover, immunoprecipitation/immunoblotting was performed by mAb MLS128, leading to the identification of an 80 kDa band carrying trimeric Tn antigen, i.e. Syndecan-1. Stable silencing of endogenous pp-GalNAc-T13 in C4-sc (T13-KD) revealed that primary tumors generated by

  14. pp-GalNAc-T13 induces high metastatic potential of murine Lewis lung cancer by generating trimeric Tn antigen

    International Nuclear Information System (INIS)

    Highlights: ► ppGalNAc-T13 was up-regulated in high metastatic sublines of Lewis lung cancer. ► ppGalNAc-T13 expression enhanced cell invasion activity in low metastatic sublines. ► Trimeric Tn antigen was induced in the transfectant cells of ppGalNAc-T13 cDNA. ► A major protein carrying trimeric Tn structure was identified as Syndecan-1. ► Silencing of ppGalNAc-T13 resulted in the reduction of invasion and of metastasis.. -- Abstract: In order to analyze the mechanisms for cancer metastasis, high metastatic sublines (H7-A, H7-Lu, H7-O, C4-sc, and C4-ly) were obtained by repeated injection of mouse Lewis lung cancer sublines H7 and C4 into C57BL/6 mice. These sublines exhibited increased proliferation and invasion activity in vitro. Ganglioside profiles exhibited lower expression of GM1 in high metastatic sublines than the parent lines. Then, we established GM1-Si-1 and GM1-Si-2 by stable silencing of GM1 synthase in H7 cells. These GM1-knockdown clones exhibited increased proliferation and invasion. Then, we explored genes that markedly altered in the expression levels by DNA microarray in the combination of C4 vs. C4-ly or H7 vs. H7 (GM1-Si). Consequently, pp-GalNAc-T13 gene was identified as up-regulated genes in the high metastatic sublines. Stable transfection of pp-GalNAc-T13 cDNA into C4 (T13-TF) resulted in increased invasion and motility. Then, immunoblotting and flow cytometry using various antibodies and lectins were performed. Only anti-trimeric Tn antibody (mAb MLS128), showed increased expression levels of trimeric Tn antigen in T13-TF clones. Moreover, immunoprecipitation/immunoblotting was performed by mAb MLS128, leading to the identification of an 80 kDa band carrying trimeric Tn antigen, i.e. Syndecan-1. Stable silencing of endogenous pp-GalNAc-T13 in C4-sc (T13-KD) revealed that primary tumors generated by subcutaneous injection of T13-KD clones showed lower coalescence to fascia and peritoneum, and significantly reduced lung

  15. Bevacizumab Significantly Improves Survival for Patients with Recurrent and Metastatic Cervical Cancer

    Science.gov (United States)

    ... improves survival for patients with recurrent and metastatic cervical cancer Posted: February 7, 2013 Updated: June 2, 2013 ... 496-6641 Patients with advanced, recurrent, or persistent cervical cancer that was not curable with standard treatment who ...

  16. Management of metastatic hormone-sensitive prostate cancer.

    Science.gov (United States)

    Bernard, Brandon; Sweeney, Christopher J

    2015-03-01

    In 2014, prostate cancer will affect roughly 15 % of American men during their lifetimes with about 230,000 new cases and 29,000 deaths per year. If required, most can be treated with curative surgery or radiotherapy. Upon relapse, androgen deprivation therapy (intermittent or continuous) is the cornerstone of treatment for hormone-sensitive disease. Response is variable and treatment is associated with a significant risk of toxicity. Recently, significant advances in survival have been demonstrated with chemohormonal therapy in men with high-volume disease. In addition, new findings have informed the approach to preventing bone complications in patients on therapy for metastatic hormone-sensitive prostate cancer. Devising clinical prediction tools and biomarkers is needed to select patients most likely to benefit from certain therapies and allow for a personalized approach. PMID:25677237

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

    Science.gov (United States)

    Ehab, Moataz; Elbaz, Mohamad

    2016-01-01

    Breast cancer is the most common cancer diagnosed in women. Each year, thousands die either because of disease progression or failure of treatment. Breast cancer is classified into different subtypes based on the molecular expression of estrogen receptor (ER), progesterone receptor, and/or human epidermal growth factor receptor 2 (HER2). These receptors represent important therapeutic targets either through monoclonal antibodies or through small-molecule inhibitors directed toward them. However, up to 40% of patients develop either a primary or a secondary resistance to the current treatments. Therefore, there is an urgent need for investigating new targets in order to overcome the resistance and/or enhance the current therapies. Cell cycle is altered in many human cancers, especially in breast cancer. Cyclin-dependent kinases (CDKs), especially CDK4 and CDK6, play a pivotal role in cell cycle progression that makes them potential targets for new promising therapies. CDK inhibition has shown strong antitumor activities, ranging from cytostatic antiproliferative effects to synergistic effects in combination with other antitumor drugs. In order to overcome the drawbacks of the first-generation CDK inhibitors, recently, new CDK inhibitors have emerged that are more selective to CDK4 and CDK6 such as palbociclib, which is the most advanced CDK4/6 inhibitor in trials. In preclinical studies, palbociclib has shown a very promising antitumor activity, especially against ERα+ breast cancer subtype. Palbociclib has gained world attention, and US the Food and Drug Administration has accelerated its approval for first-line treatment in combination with letrozole for the first-line systematic 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

  18. MRI of metastatic adenocarcinomas to the brain. Differential diagnosis of colorectal and pulmonary cancer

    International Nuclear Information System (INIS)

    To clarify the characteristic features of MR imagings of metastatic adenocarcinomas to the brain and search for differential points between the lesions from colorectal cancer and those of lung cancer, we evaluated retrospectively intraparenchymal metastatic lesions of 13 colorectal origins and 13 pulmonary origins on MR imagings, compared with resected specimens. Metastatic lesions from colorectal cancer showed marked hypointense solid components on T2WI, which correspond to the dense tumor cells and coagulated necrosis pathologically. Metastatic lesions from lung cancers showed mixed intensity and various components on T2WI, which correspond to various histological components, such as solid tumor cell's nests, hemorrhage, necrosis and cystic fluid collection. Pathological specimens suggested that the low signal intensity on T2WI of MRI derived from concentration of tumor cells and coagulated necrosis including macrophages and lymphocytes. This study may contribute to make the differential diagnosis of metastatic adenocarcinomas to the brain from colorectal and pulmonary cancers. (author)

  19. Pan FGFR Kinase Inhibitor BGJ398 and Combination Chemotherapy in Treating Patients With Untreated Metastatic Pancreatic Cancer

    Science.gov (United States)

    2016-05-19

    Colon Adenocarcinoma; Metastatic Pancreatic Adenocarcinoma; Pancreatic Adenocarcinoma; Pancreatic Ductal Adenocarcinoma; Rectal Adenocarcinoma; Stage III Pancreatic Cancer; Stage IIIA Colon Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer; Stage IV Pancreatic Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

  20. 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.

  1. Docetaxel-related toxicity in metastatic hormone-sensitive and metastatic castration-resistant prostate cancer.

    Science.gov (United States)

    Schweizer, Michael T; Gulati, Roman; Mostaghel, Elahe A; Nelson, Peter S; Montgomery, R Bruce; Yu, Evan Y; Cheng, Heather H

    2016-07-01

    Docetaxel plus androgen deprivation therapy (ADT) offers a survival benefit in metastatic hormone-sensitive prostate cancer (mHSPC). However, one trial evaluating docetaxel in mHSPC (GETUG-AFU15) showed unexpected toxicity; raising concerns that docetaxel may carry increased toxicity when used to treat mHSPC compared to metastatic castration-resistant prostate cancer (mCRPC). We conducted a retrospective analysis evaluating differences in toxicity based on the clinical state (i.e., mHSPC vs. mCRPC) that docetaxel was used. Patients initiating docetaxel between 1/1/2014 and 7/15/2015 were included, with the former date chosen to coincide with the press release for the first mHSPC study that showed a survival benefit with early docetaxel; ensuring contemporary docetaxel-treated cohorts. Thirty-nine mCRPC and 22 mHSPC patients were included. Compared to mCRPC, mHSPC patients were younger (median years: 66.3 vs. 71.8, P = 0.007); had better performance status (ECOG 0-1: 100 vs. 62 %, P < 0.0001); and used opiates less frequently (29 vs. 66 %, P = 0.04). Neutropenic fevers occurred in 9 and 5 % (P = 0.95) of men with mHSPC and mCRPC, respectively. Other toxicities also occurred at similar rates between cohorts. The incidence of any toxic event was 73 and 67 % (P = 0.84) for men with mHSPC and mCRPC, respectively. Within the mHSPC cohort, neutropenic fevers occurred at a similar rate regardless of the time interval between initiating ADT and the start of docetaxel. We did not observe a significant difference in toxicity between mHSPC and mCRPC patients receiving docetaxel. However, the small sample size and retrospective nature of this study limit our ability to draw definitive conclusions. PMID:27300548

  2. 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

  3. Individualized dosimetry in the management of metastatic differentiated thyroid cancer

    International Nuclear Information System (INIS)

    Aim. This paper analyzes the available data on the dosimetric approach and describes the use of dosimetry in the Division of Nuclear Medicine of the National Cancer Institute in Milan. Dosimetry is rarely performed when planning radio-iodine activity, although most of the available guidelines do mention this possibility, without giving any well defined indication. Aim of the present research was to validate the usefulness of dosimetry in the management of metastatic thyroid cancer. Benua (1962) set the limit of blood absorbed dose at 2 Gy to avoid hematological toxicity. Maxon (1983) determined at 80 Gy the dose to achieve complete destruction of a metastatic lesion. Dorn (2003) combined red marrow and lesion dosimetry showing that high activity administrations with less that 3 Gy to the red marrow are a safe and more effective with respect to fixed activities administrations. Lee (2008) reported 50% responses with high activity administrations based on blood dosimetry, in 47 patients which were unsuccessfully previously treated with fixed activities. Sgouros (2005) and Song (2006) introduced key parameters as Biological Effective Dose and Uniform Equivalent Dose in order to describe the effects of continuos low dose rate irradiation and non uniform activity uptake, typical of nuclear medicine treatments. Methods: Red marrow and lesion dosimetry (planar view) were performed during the treatment, without changing the fixed activity schema. Results: This experience demonstrate first of all, that dosimetry is feasible in the clinical routine, and that it can provide the clinician with important information, no matter its often quoted limited numerical accuracy. A total of 17/20 lesion doses below 80 Gy have been detected. Three/17 (doses between 40 and 80 Gy) disappeared in the follow-up scintigram. Two/17 were undetectable at computed tomography or nuclear magnetic resonance. These data suggest that repetition of treatment on a lesion drastically reduces its uptake

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

    International Nuclear Information System (INIS)

    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)

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

    International Nuclear Information System (INIS)

    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)

  6. Validating of the pre-clinical mouse model for metastatic breast cancer to the mandible

    OpenAIRE

    Young Sun HWANG; Han, Sang-Sun; Kim, Ki-Rim; Lee, Ye-Jin; Lee, Sun-Kyung; PARK Kwang-Kyun; Chung, Won-Yoon

    2015-01-01

    Metastatic breast carcinoma has a great tendency to spread to the mandible. It is concomitantly associated with bone destruction, food intake disorder, and a poorer prognosis. Appropriate animal models need to be developed for a better understanding of the mechanisms underlying the metastatic process of breast cancer cells to mandible and to test the effects of potential lead compounds. Here, we assessed the metastasis model of intracardiac injection using luciferase-transfected metastatic br...

  7. State of the art management of metastatic gastroesophageal cancer.

    Science.gov (United States)

    Murphy, Adrian G; Lynch, David; Kelly, Ronan J

    2015-09-01

    The anatomical locations of upper gastrointestinal (GI) tumors have changed remarkably in the western world and reflect the increasing impact of obesity and gastroesophageal (GE) reflux rather than infectious etiologies. Incidence rates of GE tumors are rising rapidly and survival rates for patients with metastatic disease remain poor. Traditionally, cytotoxic chemotherapy has had some survival advantages but increasingly complex combination regimens are limited by toxicities. The advent of molecularly targeted therapy has provided additional options for patients with advanced disease including trastuzumab and ramucirumab. There has also been detailed molecular characterization of upper GI tumors which hopefully will result in improved tailoring of clinical trial design accounting for the heterogeneity inherent in GE tumors. While numerous targeted therapies are currently being studied in clinical trials, there is much excitement regarding the role of immunotherapy in GE cancers. Although further investigation is warranted, it represents a promising avenue for patients with advanced GE tumors. PMID:26539453

  8. Cetuximab in the treatment of metastatic colorectal cancer.

    Science.gov (United States)

    Moosmann, Nicolas; Heinemann, Volker

    2007-02-01

    Cetuximab is a chimeric monoclonal antibody that binds to the epidermal growth factor receptor and thereby inhibits cell proliferation, metastasis and angiogenesis. Preclinical studies indicate that cetuximab induces synergistic antitumor activity when combined with chemotherapy or radiation. This observation is supported by clinical trials demonstrating that cetuximab improves tumor response when used in conjunction with modern chemotherapy in patients with metastatic colorectal cancer. Improved treatment efficacy may help to increase the rate of hepatic metastasis resection after downsizing of initially unresectable lesions. In pretreated patients, cetuximab may restore the sensitivity to irinotecan and, therefore, has been registered in this setting. Ongoing studies are investigating the integration of anti-epidermal growth factor receptor and anti-vascular endothelial growth factor strategies into new treatment regimens. Promising results have already been obtained in a trial combining irinotecan, bevacizumab and cetuximab. PMID:17250462

  9. Tracking metastatic breast cancer: the future of biology in biosensors.

    Science.gov (United States)

    Lim, Y C; Wiegmans, A P

    2016-04-01

    Circulating tumour cells associated with breast cancer (brCTCs) represent cells that have the capability to establish aggressive secondary metastatic tumours. The isolation and characterization of CTCs from blood in a single device is the future of oncology diagnosis and treatment. The methods of enrichment of CTCs have primarily utilized simple biological interactions with bimodal reporting with biased high purity and low numbers or low purity and high background. In this review, we will discuss the advances in microfluidics that has allowed the use of more complex selection criteria and biological methods to identify CTC populations. We will also discuss a potential new method of selection based on the response of the oncogenic DNA repair pathways within brCTCs. This method would allow insight into not only the oncogenic signalling at play but the chemoresistance mechanisms that could guide future therapeutic intervention at any stage of disease progression. PMID:26995223

  10. Efficacy of stereotactic radiotherapy for primary and metastatic liver cancer

    International Nuclear Information System (INIS)

    Twenty patients (30 nodules) with metastatic liver cancer (MLC) and 10 cases with hepatocellular carcinoma (HCC) treated by stereotactic radiotherapy (SRT) were analyzed. SRT was administered at 48.0 or 52.8 Gy/4 Fr/1 wk. The response rate (RR) in MLC patients was 78%, and 11 patients survived longer than 1 year and 9 patients survived as long as 2 years. Clinical analysis suggests that the ideal indications for SRT in MLC are solitary nodules in patients without extrahepatic disease who have undergone systemic chemotherapy. Although RR of SRT for HCC was as high as 85%, intrahepatic recurrence was observed in all patients and 6 patients died within 1 year Further analysis is needed to determine the indication for SRT in HCC patients. (author)

  11. Living with metastatic breast cancer: a qualitative analysis of physical, psychological, and social sequelae.

    Science.gov (United States)

    Mosher, Catherine E; Johnson, Courtney; Dickler, Maura; Norton, Larry; Massie, Mary Jane; DuHamel, Katherine

    2013-01-01

    Women with metastatic breast cancer face a wide range of medical, practical, and emotional challenges that impact their quality of life. Research to date, however, has not focused on the quality-of-life concerns of metastatic breast cancer patients with significant distress. The present study examined a range of concerns among distressed metastatic breast cancer patients, including physical and emotional distress, social functioning, and existential issues. Forty-four distressed women with metastatic breast cancer wrote their deepest thoughts and feelings regarding their illness. These essays were thematically analyzed for effects of the illness on quality of life. Three themes were identified in patients' essays. First, metastatic breast cancer and its treatment may result in a number of quality-of-life concerns, including physical symptom burden, emotional distress, body image disturbance, and disrupted daily activities. Second, social constraints on disclosure of cancer-related concerns may exacerbate patients' distress. Third, many women experience a heightened awareness of life's brevity and search for meaning in their cancer experience. Results highlight a range of quality-of-life concerns following a metastatic breast cancer diagnosis and suggest that addressing social constraints on cancer-related disclosure and the search for meaning may improve patients' psychological adjustment. PMID:23528206

  12. First-Line Treatment of Metastatic Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Mohammed Tokh

    2012-03-01

    Full Text Available Metastatic pancreatic cancer is an aggressive malignancy that is difficult to treat. Gemcitabine monotherapy has been used first line and many contemporary treatment approaches have focused on gemcitabine plus experimental agents. The 2012 ASCO Gastrointestinal Cancers Symposium Abstract #213 is a study of gemcitabine with IPI-926, a novel hedgehog pathway inhibitor. Abstract #227 is a study of gemcitabine with 90Y-hPAM4 radioimmunotherapy with yttrium labeled anti-mucin humanized antibody. Abstract #296 is a study of gemcitabine with temsirolimus, an mTOR inhibitor. Gemcitabine and erlotinib has shown slight advantages to gemcitabine alone. Abstract #253 takes this one step further and evaluates gemcitabine and erlotinib with apricoxib, a COX-2 inhibitor. FOLFIRINOX has shown superiority to gemcitabine; however, doing so at the cost of significantly greater toxicity. Abstract #199, is a study which examines the cost effectiveness of first line FOLFIRINOX approaches. Another cost effective study is portrayed in Abstract #372, a study evaluating the survival of unresectable pancreatic cancer patients treated with gemcitabine and the disease course is followed clinically without radiographic follow-up.

  13. Clinical effects of laser immunotherapy on metastatic cancer patients

    Science.gov (United States)

    Naylor, Mark F.; Lam, Anh K.; Bahavar, Cody F.; Nordquist, Robert E.; Chen, Wei R.

    2016-03-01

    Clinical trials of late-stage breast cancer patients and late-stage melanoma patients treated by laser immunotherapy (LIT) have shown promising results. In a 2010 study of Li et al, eleven late-stage melanoma patients received LIT in one or multiple 6-week treatment cycles applied to a 200-cm2 treatment site, which usually contained multiple cutaneous metastases. Long-term, positive response was observed in six patients. All lesions in the treatment area of the patients responded to LIT, eight of which achieved complete local response (CLR). CLR was observed in the non-treatment site (regional) lesions in four patients. Five patients were still alive at the time of last follow-up. The probability of 12-month overall survival was 70%.2 In 2011, Li et al, treated ten late stage breast cancer patients with LIT.1 In 8 patients available for evaluation, the objective response rate was 62.5% and the clinical beneficial response rate was 75%.1 This review demonstrates that LIT is safe and well tolerated, so it can be easily applied on an outpatient basis and can be combined with other pharmaceutical modalities to improve the therapeutic response of metastatic cancers.

  14. Comparative study of proteome between primary cancer and hepatic metastatic tumor in colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Bo Yu; Shi-Yong Li; Ping An; Ying-Nan Zhang; Zhen-Jia Liang; Shu-Jun Yuan; Hui-Yun Cai

    2004-01-01

    AIM: To identify the differential proteins associated with colorectal cancer genesis and hepatic metastasis. METHODS: Hydrophobic protein samples were extracted from normal colorectal mucosa, primary cancer lesion and hepatic metastatic foci of colorectal cancer. With twodimensional electrophoresis and image analysis, differentially expressed protein spots were detected, and the proteins were identified by matrix assisted laser desorption/ionization-time of flight-mass spectrometry and peptide mass fingerprint analysis.RESULTS: Significant alterations of the proteins in number and expression levels were discovered in primary cancer and hepatic metastatic foci, the expression of a number of proteins was lost in 25-40 ku, but protein spots was increased in 14-21ku, compared with normal mucosa. Nine differentially expressed protein spots were identified. Three proteins expressed in normal mucosa, but lost in primary cancer and hepatic metastasis, were recognized ascalmodulin, ribonuclease 6 precursor and mannosidase-α.Proapolipoprotein was expressed progressively from normal mucosa to primary cancer and hepatic metastasis. The differentially expressed protein of beta-globin was found in normal mucosa and hepatic metastatic tumor, but lost in primary cancer lesion. Cdc 42, a GTP-binding protein, was identified in hepatic metastasis. The protein spots of C4 from primary cancer, M7 and M9 from hepatic metastasis had less homology with the proteins in database. CONCLUSION: Variations of hydrophobic protein expression in colorectal cancer initiation and hepatic metastasis are significant and can be observed with two-dimensionalelectrophoresis. The expression of calmodulin, ribonuclease6 precursor and mannosidase-α is lost but the expression of proapolipoprotein is enhanced which is associated with colorectal cancer genesis and hepatic metastasis. Cdc 42 and beta-globin are expressed abnormally in hepaticmetastasis. Protein C4, M7 and M9 may be associated withcolorectal

  15. Eribulin (Halaven: a new, effective treatment for women with heavily pretreated metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Twelves C

    2011-08-01

    Full Text Available J Menis1, C Twelves21Department of Oncology, University Hospital Santa Maria della Misericordia, Udine, Italy; 2Leeds Cancer Research UK Centre, University of Leeds and St James's Institute of Oncology, Leeds, UKAbstract: Although metastatic breast cancer remains essentially incurable, many patients previously treated with an anthracycline, taxane, and capecitabine are relatively fit and keen to receive further therapy. Several drugs are used in this setting, but with little evidence of clinically relevant benefit, and none have previously shown improved survival. Eribulin (Halaven® is a nontaxane tubulin-binding agent with a novel mode of action, and was recently approved by the European Medicines Agency and US Food and Drug Agency as a single agent for patients with heavily pretreated metastatic breast cancer. This review provides an overview of the discovery, and preclinical and clinical development of eribulin, culminating in the recently published EMBRACE metastatic breast cancer study.Keywords: eribulin, metastatic breast cancer, pretreated

  16. Cell stiffness is a biomarker of the metastatic potential of ovarian cancer cells

    Science.gov (United States)

    Xu, Wenwei; Mezencev, Roman; Kim, Byungkyu; Wang, Lijuan; McDonald, John; Sulchek, Todd; Sulchek Team; McDonald Team

    2013-03-01

    The metastatic potential of cells is an important parameter in the design of optimal strategies for the personalized treatment of cancer. Using atomic force microscopy (AFM), we show that ovarian cancer cells are generally softer and display lower intrinsic variability in cell stiffness than non-malignant ovarian epithelial cells. A detailed study of highly invasive ovarian cancer cells (HEY A8) and their less invasive parental cells (HEY), demonstrates that deformability can serve as an accurate biomarker of metastatic potential. Comparative gene expression profiling indicate that the reduced stiffness of highly metastatic HEY A8 cells is associated with actin cytoskeleton remodeling, microscopic examination of actin fiber structure in these cell lines is consistent with this prediction. Our results indicate that cell stiffness not only distinguishes ovarian cancer cells from non-malignant cells, but may also be a useful biomarker to evaluate the relative metastatic potential of ovarian and perhaps other types of cancer cells.

  17. Validating of the pre-clinical mouse model for metastatic breast cancer to the mandible

    Directory of Open Access Journals (Sweden)

    Young Sun HWANG

    2015-02-01

    Full Text Available Metastatic breast carcinoma has a great tendency to spread to the mandible. It is concomitantly associated with bone destruction, food intake disorder, and a poorer prognosis. Appropriate animal models need to be developed for a better understanding of the mechanisms underlying the metastatic process of breast cancer cells to mandible and to test the effects of potential lead compounds. Here, we assessed the metastasis model of intracardiac injection using luciferase-transfected metastatic breast cancer cells (MDA-MB-231Luc+ by determining the incidences of metastasis, mCT images, and histopathological results. A high bioluminescence signal mainly detected mandibular lesions with less frequent distal femora and proximal tibiae lesions. Extensive mandibular bone destruction occurred in nude mice grafted with metastatic breast cancer cells. This type of animal model might be a useful tool in assessing therapeutic implications and the efficacy of anti-cancer drugs for osteolytic cancers.

  18. Role of ultrasound in detection of metastatic neck nodes in patients with oral cancer

    Directory of Open Access Journals (Sweden)

    P Sureshkannan

    2011-01-01

    Conclusion: USG is a reliable and valuable tool for metastatic lymph node screening in head and neck cancer patients. It is a cheap, noninvasive, easy-to-handle and cost-effective diagnostic method. USG performed better than clinical palpation in detecting cervical metastatic nodes.

  19. Predictive computational modeling to define effective treatment strategies for bone metastatic prostate cancer.

    Science.gov (United States)

    Cook, Leah M; Araujo, Arturo; Pow-Sang, Julio M; Budzevich, Mikalai M; Basanta, David; Lynch, Conor C

    2016-01-01

    The ability to rapidly assess the efficacy of therapeutic strategies for incurable bone metastatic prostate cancer is an urgent need. Pre-clinical in vivo models are limited in their ability to define the temporal effects of therapies on simultaneous multicellular interactions in the cancer-bone microenvironment. Integrating biological and computational modeling approaches can overcome this limitation. Here, we generated a biologically driven discrete hybrid cellular automaton (HCA) model of bone metastatic prostate cancer to identify the optimal therapeutic window for putative targeted therapies. As proof of principle, we focused on TGFβ because of its known pleiotropic cellular effects. HCA simulations predict an optimal effect for TGFβ inhibition in a pre-metastatic setting with quantitative outputs indicating a significant impact on prostate cancer cell viability, osteoclast formation and osteoblast differentiation. In silico predictions were validated in vivo with models of bone metastatic prostate cancer (PAIII and C4-2B). Analysis of human bone metastatic prostate cancer specimens reveals heterogeneous cancer cell use of TGFβ. Patient specific information was seeded into the HCA model to predict the effect of TGFβ inhibitor treatment on disease evolution. Collectively, we demonstrate how an integrated computational/biological approach can rapidly optimize the efficacy of potential targeted therapies on bone metastatic prostate cancer. PMID:27411810

  20. The influence of the pre-metastatic niche on breast cancer metastasis.

    Science.gov (United States)

    Ursini-Siegel, Josie; Siegel, Peter M

    2016-09-28

    The emergence of metastatic disease constitutes a significant life-threatening development during cancer progression. To date, intensive efforts have been focused on understanding the intrinsic properties that confer malignant potential to cancer cells, as well as the role of the primary tumour microenvironment in promoting cancer metastasis. Beyond events occurring at the primary site, the metastatic cascade is composed of numerous barriers that must be overcome in order for disseminating cancer cells to form distal metastases. The most formidable of these is the ability of cancer cells to seed and grow in a completely foreign microenvironment. Interestingly, solid malignancies often display a particular tropism for specific tissue sites. For example, breast patients with metastatic disease will often develop bone, lung, liver or brain metastases. This mini-review will explore aspects of pre-existing and induced metastatic niches and focus on how the unique composition and function of diverse niche components, within common sites of breast cancer metastasis, enable the survival and growth of disseminated cancer cells. These common supportive functions of the niche are provided by a complex array of stromal components and molecular mechanisms that are, in part, reflective of the tissue in which the metastases arise. Finally, the metastatic niche is a dynamic structure that is continually altered and sculpted by the cancer cells during progression of the metastatic lesion. PMID:26577808

  1. Treatment of patients with metastatic pancreatic cancer: Experience from a tertiary Indian cancer center

    Directory of Open Access Journals (Sweden)

    B Sirohi

    2015-01-01

    Full Text Available Background: The aim of this study was to look at the outcome of patients with metastatic pancreatic cancer treated at a tertiary cancer center in India. Patients And Methods: A total of 101 patients with locally advanced and metastatic pancreatic cancer diagnosed between May 2012 and July 2013 were identified from a prospectively maintained database at the tertiary cancer center. Overall survival (OS was computed using the Kaplan–Meir product limit method and compared across groups using the log-rank statistics. Cox proportional hazards model, adjusted for a number of patient and tumor characteristics, was then used to determine factors prognostic for OS. Results: Median age at diagnosis was 55 years (range: 21–81 years. 57.4% (n = 58 of patients were male, 22% (n = 22 had performance status (PS of <2 at diagnosis and 89% received first-line chemotherapy, while the rest received best supportive care. For the whole cohort, 6 month and 1-year OS was 57% (95% confidence interval [CI]: 46–66% and 47% (95% CI: 35–57%, respectively. In a multivariable model, PS <2 and oligometastatic disease were associated with a significantly decreased risk of death. Conclusion: Results from our analysis indicate that the prognostic outcome among Indian patients with metastatic pancreatic cancer is poor with survival outcomes similar to those reported in North America and Europe.

  2. Optical detection of metastatic cancer cells using a scanned laser pico-projection system

    International Nuclear Information System (INIS)

    Metastasis is responsible for 90% of all cancer-related deaths in humans. As a result, reliable techniques for detecting metastatic cells are urgently required. Although various techniques have been proposed for metastasis detection, they are generally capable of detecting metastatic cells only once migration has already occurred. Accordingly, the present study proposes an optical method for physical characterization of metastatic cancer cells using a scanned laser pico-projection system (SLPP). The validity of the proposed method is demonstrated using five pairs of cancer cell lines and two pairs of non-cancer cell lines treated by IPTG induction in order to mimic normal cells with an overexpression of oncogene. The results show that for all of the considered cell lines, the SLPP speckle contrast of the high-metastatic cells is significantly higher than that of the low-metastatic cells. As a result, the speckle contrast measurement provides a reliable means of distinguishing quantitatively between low- and high-metastatic cells of the same origin. Compared to existing metastasis detection methods, the proposed SLPP approach has many advantages, including a higher throughput, a lower cost, a larger sample size and a more reliable diagnostic performance. As a result, it provides a highly promising solution for physical characterization of metastatic cancer cells in vitro. (letter)

  3. Radiotherapy in patients with distant metastatic breast cancer

    International Nuclear Information System (INIS)

    The study evaluates frequency of and indications for disease-related radiotherapy in the palliative breast cancer (BC) situation and analyzes in which phase of the palliative disease course radiotherapy was applied. 340 patients who developed distant metastatic disease (DMD) and died (i.e. patients with completed disease courses) were analyzed. 165 patients (48.5%) received palliative radiotherapy (255 series, 337 planning target volumes) as a part of palliative care. The most common sites for radiotherapy were the bone (217 volumes, 64.4% of all radiated volumes) and the brain (57 volumes, 16.9%). 127 series (49.8%) were performed in the first third of the metastatic disease survival (MDS) period; 84 series (32.8%) were performed in the last third. The median survival after radiotherapy was 10 months. Patients who had received radiation were younger compared to those who had no radiation (61 vs. 68 years, p < 0.001) and had an improved MDS (26 vs. 14 months, p < 0.001). Compared to rapidly progressive disease courses with short survival times, in cases where effective systemic therapy achieved a longer MDS (≥24 months), radiotherapy was significantly more often a part of the multimodal palliative therapy (52.1% vs. 37.1%, p = 0.006). In a cohort of BC patients with DMD, nearly one half of the patients received radiotherapy during the palliative disease course. In a palliative therapy approach, which increasingly allows for treatment according to the principles of a chronic disease, radiotherapy has a clearly established role in the therapy concept

  4. Sleeping Beauty screen reveals Pparg activation in metastatic prostate cancer.

    Science.gov (United States)

    Ahmad, Imran; Mui, Ernest; Galbraith, Laura; Patel, Rachana; Tan, Ee Hong; Salji, Mark; Rust, Alistair G; Repiscak, Peter; Hedley, Ann; Markert, Elke; Loveridge, Carolyn; van der Weyden, Louise; Edwards, Joanne; Sansom, Owen J; Adams, David J; Leung, Hing Y

    2016-07-19

    Prostate cancer (CaP) is the most common adult male cancer in the developed world. The paucity of biomarkers to predict prostate tumor biology makes it important to identify key pathways that confer poor prognosis and guide potential targeted therapy. Using a murine forward mutagenesis screen in a Pten-null background, we identified peroxisome proliferator-activated receptor gamma (Pparg), encoding a ligand-activated transcription factor, as a promoter of metastatic CaP through activation of lipid signaling pathways, including up-regulation of lipid synthesis enzymes [fatty acid synthase (FASN), acetyl-CoA carboxylase (ACC), ATP citrate lyase (ACLY)]. Importantly, inhibition of PPARG suppressed tumor growth in vivo, with down-regulation of the lipid synthesis program. We show that elevated levels of PPARG strongly correlate with elevation of FASN in human CaP and that high levels of PPARG/FASN and PI3K/pAKT pathway activation confer a poor prognosis. These data suggest that CaP patients could be stratified in terms of PPARG/FASN and PTEN levels to identify patients with aggressive CaP who may respond favorably to PPARG/FASN inhibition. PMID:27357679

  5. Radium-223 in metastatic castration resistant prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Winston Vuong; Oliver Sartor; Sumanta K Pal

    2014-01-01

    In 2004, docetaxel was approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). For the next several years, there was a lull in drug approvals. However, from 2010 onwards, 5 additional therapies have been approved on the basis of showing a survival beneift in phase III studies. These agents include sipuleucel-T, cabazitaxel, abiraterone, enzalutamide and (most recently) radium-223. Amongst radiopharmaceuticals currently used for advanced prostate cancer (e.g. samarium-153 and strontium-89), radium-223 possesses several unique properties. As an alpha-emitting compound, the agent produces a high-energy output over a short range, facilitating selective destruction of tissue within the bone in the region of osteoblastic lesions while sparing surrounding normal tissue. The current review will outline biological rationale for radium-223 and also provide an overview of preclinical and clinical development of the agent. Rational sequencing of radium-223 and combinations, in the increasingly complex landscape of mCRPC will be discussed, along with factors inlfuencing clinical implementation.

  6. 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

  7. DIFFERENTIAL DIAGNOSIS OF PRIMARY AND METASTATIC OVARIAN TUMORS IN PATIENTS WITH COLONIC CANCER

    Directory of Open Access Journals (Sweden)

    I. G. Komarov

    2013-01-01

    Full Text Available This report summarizes existing data on differential diagnosis between primary and metastatic ovarian cancer in patients with colorectal cancer (CRC. The results obtained in N.N. Blokhin Russian Cancer Research Center on the management of this malignancy are also presented. The evidence in favour of the need of genetic counseling and monitoring of the patients with aggravated familial history for early diagnosis of synchronous and metachronous ovarian cancer in patients with CRC is produced. A number of clinical, laboratory and diagnostic methods in addition to immunohistology and molecular genetics should be used for differential diagnosis of primary and metastatic ovarian cancer in patients with CRC.

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

    International Nuclear Information System (INIS)

    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

  9. 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

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

    OpenAIRE

    Ocvirk Janja; Moltara Maja Ebert; Mesti Tanja; Boc Marko; Rebersek Martina; Volk Neva; Benedik Jernej; Hlebanja Zvezdana

    2016-01-01

    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.

  11. Body fluid MMP-2 as a putative biomarker in metastatic breast cancer

    OpenAIRE

    NOH, SEWON; Jung, Jae-Joon; Jung, Minkyu; KIM, KI-HYANG; Lee, Ha-young; WANG, BRANDON; CHO, JOANNA; Kim, Tae Soo; Jeung, Hei-Cheul; Rha, Sun Young

    2012-01-01

    In the present study, we investigated the role of matrix metalloproteinase (MMP)-2 and -9 as novel biomarkers in the body fluid of patients with metastatic breast cancer. We measured the expression of MMPs in 37 samples of body fluid (10 peritoneal and 27 pleural fluids) from metastatic breast cancer patients between 2000 and 2009. Zymography and ELISA assays were used to determine the cut-off level and to quantify MMP expression from a positive control, HT-1080 conditioned media. MMP express...

  12. Concomitant parenteral nutrition and systemic cytotoxic therapy in a metastatic colorectal cancer patient

    Directory of Open Access Journals (Sweden)

    A. A. Popov

    2015-02-01

    Full Text Available Pathologic nutrients metabolism presents a severe problem in metastatic colorectal cancer patients, especially those with canceromatosis. A hypermetabolism-catabolism syndrome frequently develops in in patients with progressing canceromatosis. This leads to cachexia anorexia syndrome, which significantly impedes available treatment options. Artificial nutrition allows to improve available treatment in such patients. We present a successful case of concomitant parenteral nutrition and systemic cytotoxic therapy in metastatic colorectal cancer patient with peritoneal canceromatosis.

  13. Treatment of initially metastatic small-cell lung cancer

    International Nuclear Information System (INIS)

    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)

  14. Effect of Proton Beam on Cancer Progressive and Metastatic Enzymes

    International Nuclear Information System (INIS)

    The purpose of this study was to investigate the effect of proton beam on enzymes for promotion/progression of carcinogenesis and metastasis of malignant tumor cells to clarify proton beam-specific biological effects. The changes of cancer chemopreventive enzymes in human colorectal adenocarcinoma HT-29 cells irradiated with proton beams were tested by measuring the activities of quinine reductase (QR), glutathione S-transferase (GST), and ornithine decarboxylase (ODC), glutathione (GSH) levels, and expression of cyclooxygenase-2 (COX-2). We also examined the effect of proton beam on the ODC activity and expression of COX-2 in human breast cancer cell. We then assessed the metastatic capabilities of HT-29 and MDA-MB-231 cells irradiated with proton beam by measuring the invasiveness of cells through Matrigel-coated membrane and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MMP activity in MDA-MB-231 and HT-29 cells. QR activity of irradiated HT-29 cells was slightly increased. Proton irradiation at dose of 32 Gy in HT-29 cells increased GST activity by 1.23-fold. In addition GSH levels in HT-29 cells was significantly increased 1.23- (p<0.05), 1.32- (p<0.01) and 1.34-fold (p<0.01) with the proton irradiation at doses of 8, 16 and 32 Gy, respectively. These results suggest that colon cancer chemopreventive activity was increased with the proton irradiation by increasing QR and GST activities and GSH levels and inhibiting ODC activity. Proton ion irradiation decreased the invasiveness of TPA-treated HT-29 cells and MDA-MB-231 cells through Matrigel-coated membrane. Proton ion irradiation pretreatment decreased TPA-induced MMP activity in MDA-MB-231 and HT-29 cells. Further studies are necessary to investigate if these findings could be translated to in vivo situations

  15. 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.

  16. Correlation of the ratio of metastatic to non-metastatic cancer cases with the degree of socioeconomic deprivation among Texas counties

    Directory of Open Access Journals (Sweden)

    Belasco Eric

    2011-02-01

    Full Text Available Abstract Background Previous studies have demonstrated that cancer registrations and hospital discharge rate are closely correlated with census data-based socioeconomic deprivation indices. We hypothesized that communities with higher degrees of socioeconomic deprivation tend to have a higher ratio of metastatic to non-metastatic cancer cases (lung, breast, prostate, female genital system, colorectal cancers or all types of cancers combined. In this study, we investigate the potential link between this ratio and the Wellbeing Index (WI among Texas counties. Results Cancer data in 2000 were provided by the Texas Cancer Registry, while data on the ten socioeconomic variables among the 254 Texas counties in 2000 for building the WI were obtained from U.S. Census Bureau. The ten socioeconomic status variables were subjected to the principal component analysis, and the first principal component scores were grouped into deciles for the WI (1 to 10 and the 254 Texas counties were classified into 10 corresponding groups. Weighted linear regression analyses and a Cochran-Armitage trend test were performed to determine the relationship between the ratio of age-adjusted metastatic to non-metastatic cancer incidence cases and WI. The ratios of metastatic to non-metastatic cases of female genital system cancer (r2 = 0.84, p = 0.0002, all-type cancers (r2= 0.73, p = 0.0017 and lung cancer (r2= 0.54, p = 0.0156 at diagnosis were positively correlated with WI. Conclusions The ratios of metastatic to non-metastatic cases of all-type, female genital system and lung cancers at diagnosis were statistically correlated with socioeconomic deprivation. Potential mediators for the correlation warrant further investigation in order to reduce health disparities associated with socioeconomic inequality.

  17. Sarcoidosis mimicking metastatic thyroid cancer following radioactive iodine therapy

    Directory of Open Access Journals (Sweden)

    Zin W. Myint

    2015-02-01

    Full Text Available Introduction: Sarcoidosis is an inflammatory disease characterized by non-caseating granulomas that can be present in diverse organ systems. Sarcoidosis can be associated with malignancy, presenting either preceding, during, or after chemotherapy. We herewith report a case of sarcoidosis mimicking cancer recurrence that developed after radioactive iodine therapy for papillary thyroid cancer. Background: A 68-year-old Caucasian woman was found to have an incidental mediastinal lymph node. She underwent biopsy, which revealed sarcoidosis. There was no further treatment or evidence of recurrence over the ensuing 9 years. She was then diagnosed with low-grade papillary thyroid cancer in the right posterior lobe and treated with total thyroidectomy followed by radioactive iodine therapy. Six months later, she was found to have elevated serum thyroglobulin. Post–remnant ablation scan showed increased tracer uptake in the bed of the thyroid. Though two thyroid ultrasound scans were negative, she was treated with I-131 for possible recurrence. She then developed right hip pain, prompting further investigation. Though a skeletal survey was negative, an 18-fluorodeoxyglucose positron emission tomography (PET scan study revealed multiple hypermetabolic skeletal lesions in both humeri and the proximal left femur. In addition, hypermetabolic hilar and mediastinal nodes were noted. As widespread cancer metastasis was suspected, bone biopsy was performed, which showed non-caseating granulomas, consistent with recurrence of sarcoidosis. Conclusion: Sarcoid lesions may mimic metastatic disease or recurrence in oncologic patients. Biopsy and histopathology examination should be performed to confirm the diagnosis. Recurrence or reactivation of sarcoidosis has been proposed to result from altered immunologic milieu because of the presence of either active cancer or its therapy. Teodorovic and colleagues postulated that the radioactive I-131 therapy leads to

  18. Eribulin for the treatment of metastatic breast cancer: an update on its safety and efficacy

    Directory of Open Access Journals (Sweden)

    Doherty MK

    2015-01-01

    Full Text Available Mark K Doherty, Patrick G Morris Department of Medical Oncology, Beaumont Hospital, Dublin, Ireland Abstract: Breast cancer remains a leading cause of cancer-related death internationally. Treatment approaches for metastatic breast cancer have evolved in recent years; however chemotherapy remains a core component for the majority of patients. Agents such as anthracyclines and taxanes have been extensively studied and form standard treatment. Eribulin mesylate is a novel synthetic microtubule-directed chemotherapy, based on a naturally-occurring compound. Through phase I studies, eribulin was found to be tolerable and activity was seen in patients with metastatic breast cancer. Phase II studies in metastatic breast cancer further demonstrated its efficacy, with responses and survival which compare favorably with other studied chemotherapy agents. The phase III EMBRACE study showed superior survival for patients treated with eribulin compared with those who received a physician’s choice control. This led to its approval for use in many countries in this setting. Its toxicity profile is well established and manageable for the most part, with the commonest reported toxicities being alopecia, fatigue, neutropenia and peripheral neuropathy. A second reported phase III study comparing eribulin to capecitabine failed to show an improvement in survival in pretreated patients. This article reviews the clinical pharmacology and mechanism of action of eribulin, and summarizes the results of the major preclinical and clinical studies of eribulin in metastatic breast cancer. Keywords: eribulin, breast cancer, metastatic breast cancer, review, new treatments, chemotherapy

  19. [Treatment of metastatic castration-resistant prostate cancer].

    Science.gov (United States)

    Caffo, Orazio

    2015-01-01

    The treatment of metastatic castration-resistant prostate cancer (mCRPC) represents one of the oncological fields where the most impressive improvements has been observed in the last decades. At the beginning of this century, the expected survival of mCRPC patients was not more than 12 months. After the introduction of docetaxel in the clinical practice in 2004, and the recent availability of new drugs cabazitaxel, abiraterone acetate, enzalutamide, and radium-223 the landscape is dramatically changed with an expected median survival of about three years. The possibility of administering docetaxel, abiraterone acetate, and enzalutamide as first line treatment, and cabazitaxel, abiretone acetate, and enzalutamide as second line, as well as the availability of radium-223 for the treatment of mCRPC patients regardless of chemotherapy administration, changed the natural history of the disease. At the same time, it is probable that also the biology of the disease is changing with the appearance of mechanisms of resistance which are common to all the drugs. This plays a central role in sequencing the available drugs not only in the first and second line setting but also beyond the second line. The future challenges for the oncologists will be to develop new drugs able to overcome the resistances, mainly when they are native, to find the optimal sequence to optimize the use of available drugs, to place at the best place other active drugs, such as vaccines and radiopharmaceuticals, to exploit the new drugs also in a hormone-sensitive phase. PMID:25621779

  20. Severe hypocalcemia after oral ibandronate in a patient with metastatic breast cancer: a case report

    Directory of Open Access Journals (Sweden)

    Fatma AVCI

    2014-01-01

    Full Text Available Bone metastasis is a common finding in patients with metastatic breast cancer. In approximately 25% of breast cancers, bone is commonly the first area of metastasis. Pain, hypercalcemia and bone fractures are the most common complications of bone metastasis. Bisphosphonates effectively reduce and prevent skeletal related complications in breast cancer patients with bone metastases. Although hypocalcemia might occur during bisphosphonate therapy, symptomatic hypocalcemia after oral bisphosphonate therapy is rare and usually occurs several weeks after the initiation of the therapy. In this case report, we present a metastatic breast cancer patient with vitamin D deficiency who developed severe hypocalcemia in the early period following oral ibandronic acid treatment.

  1. Vinorelbine and cisplatin combined with endostatin as the first-line therapy for metastatic pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Objective Systemic chemotherapy for metastatic pancreatic cancer is still a difficult problem in clinical practice.The standard chemotherapy of pancreatic cancer has been gemcitabine,but the response rate is low.Therefore,it is in urgent need to explore an effective clinical therapy for this cancer.This paper,a case report,is aimed at discussing the effectiveness of vinorelbine and cisplatin combined with endostatin as the first-line therapy for metastatic pancreatic cancer.Methods A 52-year-old female pati...

  2. Candidate Antimetastasis Drugs Suppress the Metastatic Capacity of Breast Cancer Cells by Reducing Membrane Fluidity.

    Science.gov (United States)

    Zhao, Weina; Prijic, Sara; Urban, Bettina C; Tisza, Michael J; Zuo, Yan; Li, Lin; Tan, Zhi; Chen, Xiaoling; Mani, Sendurai A; Chang, Jeffrey T

    2016-04-01

    Despite the high mortality from metastatic cancer, therapeutic targets to prevent metastasis are limited. Efforts to identify genetic aberrations that predispose tumors to metastasis have been mostly unsuccessful. To understand the nature of candidate targets for metastatic disease, we performed an in silico screen to identify drugs that can inhibit a gene expression signature associated with epithelial-mesenchymal transition (EMT). Compounds discovered through this method, including those previously identified, appeared to restrict metastatic capacity through a common mechanism, the ability to modulate the fluidity of cell membranes. Treatment of breast cancer cell lines with the putative antimetastasis agents reduced membrane fluidity, resulting in decreased cell motility, stem cell-like properties, and EMT in vitro, and the drugs also inhibited spontaneous metastasis in vivo When fluidity was unchanged, the antimetastasis compounds could no longer restrict metastasis, indicating a causal association between fluidity and metastasis. We further demonstrate that fluidity can be regulated by cellular cholesterol flux, as the cholesterol efflux channel ABCA1 potentiated metastatic behaviors in vitro and in vivo The requirement for fluidity was further supported by the finding in breast cancer patients that ABCA1 was overexpressed in 41% of metastatic tumors, reducing time to metastasis by 9 years. Collectively, our findings reveal increased membrane fluidity as a necessary cellular feature of metastatic potential that can be controlled by many currently available drugs, offering a viable therapeutic opportunity to prevent cancer metastasis. Cancer Res; 76(7); 2037-49. ©2016 AACR. PMID:26825169

  3. 'Charting a new course for prostate cancer' - currying favor for docetaxel in hormone-sensitive metastatic prostate cancer.

    Science.gov (United States)

    Voskoboynik, Mark; Staffurth, John; Malik, Zafar; Sweeney, Christopher; Chowdhury, Simon

    2014-11-01

    Docetaxel has an established role in the treatment of metastatic castrate-resistant prostate cancer. A number of recent treatments have been shown to improve the survival outcomes for this group of patients and many with improved toxicity profiles, bringing the role of docetaxel into question. We discuss the results and implications of the CHAARTED study that demonstrated a significant improvement in overall survival with docetaxel in metastatic hormone-sensitive prostate cancer. PMID:25353342

  4. 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

    To determine the optimal use of chemotherapy in the neoadjuvant, adjuvant, and metastatic setting in patients with advanced urothelial cell carcinoma, a consensus conference was convened by the World Health Organization (WHO) and the Société Internationale d'Urologie (SIU) to critically review 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...

  5. Management of Hormone-Sensitive and Hormone-Refractory Metastatic Prostate Cancer.

    Science.gov (United States)

    Rago

    1998-11-01

    BACKGROUND: Prostate cancer is a significant health problem in the United States and is the focus of increasing attention in our society. With the aging of the US population, it is likely that prostate cancer will continue to grow in importance. The options for systemic therapy of metastatic prostate cancer should be familiar to physicians, including nonspecialists, whose patients seek their advice and counsel. METHODS: Past and recent literature was surveyed to provide an understanding of the systemic treatment of advanced prostate cancer. The author presents a review of the systemic treatment of metastatic prostate cancer in different clinical circumstances and addresses the current status of chemotherapy in the management of advanced prostate cancer. RESULTS: Early androgen deprivation used over prolonged periods appears to be modestly superior to delayed androgen deprivation with a small potential survival advantage and an advantage in delaying disease progression in advanced prostate cancer. Patients with hormone-refractory prostate cancer may benefit from secondary hormonal therapy (eg, adrenal enzyme inhibitors, antiandrogens, glucocorticoids) and chemotherapy. CONCLUSIONS: The choices of therapy for metastatic prostate cancer depend on individual patient preference. Patients and physicians should be aware of the possible side effects associated with the therapeutics options for treatment of metastatic prostate cancer. PMID:10761100

  6. Surrogacy of progression free survival for overall survival in metastatic breast cancer studies: meta-analyses of published studies

    OpenAIRE

    Kundu, Madan G.; Acharyya, Suddhasatta

    2016-01-01

    Purpose: PFS is often used as a surrogate endpoint for OS in metastatic breast cancer studies. We have evaluated the association of treatment effect on PFS with significant HR$_{OS}$ (and how this association is affected by other factors) in published prospective metastatic breast cancer studies. Methods: A systematic literature search in PubMed identified prospective metastatic breast cancer studies. Treatments effects on PFS were determined using hazard ratio (HR$_{PFS}$), increase in media...

  7. 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.

  8. 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.

  9. Treatment Advances in Locally Advanced and Metastatic Non-Small Cell Lung Cancer

    OpenAIRE

    Surmont, Veerle

    2010-01-01

    textabstractLung cancer is the leading cause of cancer mortality in the United States and Europe. Approximately 85% of the patients with lung cancer have non–small cell lung cancer (NSCLC), which can be classified into squamous, adeno, large cell and not otherwise specified (NOS) histologies. The most common histologies are: adenocarcinoma ( 50%), squamous cell ( 20%), and large cell ( 10%). More than two third of the patients have locally advanced or metastatic disease at the time of diagnos...

  10. Potential synergistic implications for stromal-targeted radiopharmaceuticals in bone-metastatic prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Oliver Sartor

    2011-01-01

    Genetic heterogeneity and chemotherapy-resistant 'stem cells' represent two of the most pressing issues in devising new strategies for the treatment of advanced prostate cancer. Though curative strategies have long been present for men with localized disease, metastatic prostate cancer is currently incurable. Though substantial improvements in outcomes are now possible through the utilization of newly approved therapies, novel combinations are clearly needed. Herein we describe potentially synergistic interactions between bone stromal-targeted radiopharmaceuticals and other therapies for treatment of bone-metastatic prostate cancer. Radiation has long been known to synergize with cytotoxic chemotherapies and recent data also suggest the possibility of synergy when combining radiation and immune-based strategies. Combination therapies will be required to substantially improve survival for men with castrate-resistant metastatic prostate cancer and we hypothesize that bone-targeted radiopharmaceuticals will play an important role in this process.

  11. Metastatic squamous cell carcinoma thyroid from functionally cured cancer cervix

    International Nuclear Information System (INIS)

    The authors report a very unusual occurrence of a metastatic squamous carcinoma to thyroid gland from a treated squamous cell carcinoma cervix 12 years before with no recurrence at the primary site. The case also has an additional complexity of rapid progression of the metastatic thyroid carcinoma to wide spread dissemination to lungs and bones while on concurrent chemo radio therapy confirming the aggressiveness of the entity

  12. Mechanisms of resistance to anti-EGFR monoclonal antibody treatment in metastatic colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Zacharenia; Saridaki; Vassilis; Georgoulias; John; Souglakos

    2010-01-01

    Metastatic colorectal cancer (mCRC) continues to be counted as a major health problem. The introduction of newer cytotoxics, irinotecan and oxaliplatin, has achieved a significant improvement in survival rates. Novel targeted therapies (bevacizumab, and cetux-imab) in combination with most efficient chemotherapy regimens have pushed the median survival beyond the 2-year mark and increased the proportion of patients which could benefit from resection of metastatic lesions. In addition, several studies have p...

  13. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer

    OpenAIRE

    E. Van Cutsem; Cervantes, A.; Adam, R.; Sobrero, A; van Krieken, J. H.; Aderka, D; Aranda Aguilar, E; Bardelli, A.; Benson, A; Bodoky, G; Ciardiello, F; D'Hoore, A; Diaz-Rubio, E; Douillard, J-Y; Ducreux, M.

    2016-01-01

    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 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. ...

  14. Immunotherapy of metastatic and autochthonous liver cancer with IL-15/IL-15Rα fusion protein

    OpenAIRE

    Cheng, Liang; Du, Xuexiang; Su, Lishan; Wang, Shengdian

    2014-01-01

    Liver cancer has a poor prognosis. Our recent study demonstrates that hyper-IL-15, composed of IL-15 and the sushi domain of IL-15 receptor α chain, provides an effective therapy against well-established metastatic and autochthonous liver cancers in mouse models by triggering activation and expansion of hepatic CD8+ T cells.

  15. Chronic Stress, Depression and Immunity in Spouses of Metastatic Breast Cancer Patients

    Science.gov (United States)

    Mortimer, Jane S. Blake; Sephton, Sandra E.; Kimerling, Rachel; Butler, Lisa; Bernstein, Aaron S.; Spiegel, David

    2005-01-01

    Objective: The objective of this study was to examine how the chronicity of stress affects psychological stress-responses, depressive symptoms, and "in vivo" immunocompetence in spouses of women with metastatic breast cancer. Methods: Participants were 34 spouses of breast cancer patients. Their wives had been living with a diagnosis of recurrence…

  16. Heterogeneity and clinical significance of ESR1 mutations in ER-positive metastatic breast cancer patients receiving fulvestrant.

    Science.gov (United States)

    Spoerke, Jill M; Gendreau, Steven; Walter, Kimberly; Qiu, Jiaheng; Wilson, Timothy R; Savage, Heidi; Aimi, Junko; Derynck, Mika K; Chen, Meng; Chan, Iris T; Amler, Lukas C; Hampton, Garret M; Johnston, Stephen; Krop, Ian; Schmid, Peter; Lackner, Mark R

    2016-01-01

    Mutations in ESR1 have been associated with resistance to aromatase inhibitor (AI) therapy in patients with ER+ metastatic breast cancer. Little is known of the impact of these mutations in patients receiving selective oestrogen receptor degrader (SERD) therapy. In this study, hotspot mutations in ESR1 and PIK3CA from ctDNA were assayed in clinical trial samples from ER+ metastatic breast cancer patients randomized either to the SERD fulvestrant or fulvestrant plus a pan-PI3K inhibitor. ESR1 mutations are present in 37% of baseline samples and are enriched in patients with luminal A and PIK3CA-mutated tumours. ESR1 mutations are often polyclonal and longitudinal analysis shows distinct clones exhibiting divergent behaviour over time. ESR1 mutation allele frequency does not show a consistent pattern of increases during fulvestrant treatment, and progression-free survival is not different in patients with ESR1 mutations compared with wild-type patients. ESR1 mutations are not associated with clinical resistance to fulvestrant in this study. PMID:27174596

  17. Lapatinib: the evidence for its therapeutic value in metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Andrew Thomson

    2005-06-01

    Full Text Available Andrew ThomsonCore Medical Publishing, Knutsford, UKIntroduction: Breast cancer is the most common cancer affecting women. Many patients ultimately progress to metastatic disease and optimal management of this disease remains a significant therapeutic challenge. Lapatinib, a dual tyrosine kinase inhibitor, is in clinical development for treatment of this disease. Aims: The objective of this article is to review the published evidence for the treatment of metastatic breast cancer with lapatinib, and assess its therapeutic potential.Evidence review: Most evidence has appeared in meeting abstract reports of phase I and II studies in healthy volunteers and cancer patients. Four studies have included patients with exclusively breast cancer. Complete and partial responses and stable disease has been reported in some patients. Emerging evidence indicates that complete and partial responses can be achieved in some patients with metastatic breast cancer. Lapatinib appears to be well tolerated in cancer patients and the maximum tolerated dose is in the region of 1800 mg/day. In addition, it has been used in combination with other cancer treatments. Five ongoing or planned phase II monotherapy and three phase III combination-therapy studies with lapatinib have been identified.Outcomes summary: The phase I and II studies reported to date have provided safety data and preliminary indications regarding efficacy. There is preliminary evidence that lapatinib can achieve objective response rates of 10–38% in patients with metastatic breast cancer. Patients with tumors overexpressing ErbB1 and/or ErbB2 are likely to benefit from lapatinib treatment. Key words: lapatinib, GW572016, metastatic breast cancer, signal transduction, tyrosine kinase inhibition

  18. Muscleblind-like 1 suppresses breast cancer metastatic colonization and stabilizes metastasis suppressor transcripts.

    Science.gov (United States)

    Fish, Lisa; Pencheva, Nora; Goodarzi, Hani; Tran, Hien; Yoshida, Mitsukuni; Tavazoie, Sohail F

    2016-02-15

    Post-transcriptional deregulation is a defining feature of metastatic cancer. While many microRNAs have been implicated as regulators of metastatic progression, less is known about the roles and mechanisms of RNA-binding proteins in this process. We identified muscleblind-like 1 (MBNL1), a gene implicated in myotonic dystrophy, as a robust suppressor of multiorgan breast cancer metastasis. MBNL1 binds the 3' untranslated regions (UTRs) of DBNL (drebrin-like protein) and TACC1 (transforming acidic coiled-coil containing protein 1)-two genes that we implicate as metastasis suppressors. By enhancing the stability of these genes' transcripts, MBNL1 suppresses cell invasiveness. Consistent with these findings, elevated MBNL1 expression in human breast tumors is associated with reduced metastatic relapse likelihood. Our findings delineate a post-transcriptional network that governs breast cancer metastasis through RNA-binding protein-mediated transcript stabilization. PMID:26883358

  19. Highly variable cancer subpopulations that exhibit enhanced transcriptome variability and metastatic fitness.

    Science.gov (United States)

    Nguyen, Alexander; Yoshida, Mitsukuni; Goodarzi, Hani; Tavazoie, Sohail F

    2016-01-01

    Individual cells within a tumour can exhibit distinct genetic and molecular features. The impact of such diversification on metastatic potential is unknown. Here we identify clonal human breast cancer subpopulations that display different levels of morphological and molecular diversity. Highly variable subpopulations are more proficient at metastatic colonization and chemotherapeutic survival. Through single-cell RNA-sequencing, inter-cell transcript expression variability is identified as a defining feature of the highly variable subpopulations that leads to protein-level variation. Furthermore, we identify high variability in the spliceosomal machinery gene set. Engineered variable expression of the spliceosomal gene SNRNP40 promotes metastasis, attributable to cells with low expression. Clinically, low SNRNP40 expression is associated with metastatic relapse. Our findings reveal transcriptomic variability generation as a mechanism by which cancer subpopulations can diversify gene expression states, which may allow for enhanced fitness under changing environmental pressures encountered during cancer progression. PMID:27138336

  20. 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

  1. 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.

  2. Irrefutable evidence for the use of docetaxel in newly diagnosed metastatic prostate cancer: Results from the STAMPEDE and CHAARTED trials

    NARCIS (Netherlands)

    R.J. van Soest (Robert Jan); R. de Wit (Ronald)

    2015-01-01

    textabstractAndrogen deprivation therapy (ADT) has been used in the treatment of metastatic prostate cancer since the first description of its hormonal dependence in 1941. In 2004, docetaxel chemotherapy became the mainstay of treatment in metastatic castration-resistant prostate cancer (mCRPC), fol

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

    OpenAIRE

    Lee, Dong-Hyun; Kim, Sung-Su; Seong, Shin; Woo, Chang-Ryoul; Han, Jae-Bok

    2014-01-01

    Abstract 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 wer...

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

    Science.gov (United States)

    Alamo, Patricia; Gallardo, Alberto; Pavón, Miguel A.; Casanova, Isolda; Trias, Manuel; Mangues, Maria A.; Vázquez, Esther; Villaverde, Antonio; Mangues, Ramon; Céspedes, Maria V.

    2014-01-01

    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. PMID:24487410

  5. 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.

  6. Tumor-infiltrating lymphocytes for the treatment of metastatic cancer

    DEFF Research Database (Denmark)

    Geukes Foppen, M H; Donia, M; Svane, I M;

    2015-01-01

    five years, treatment with immunotherapy (anti CTLA-4, anti PD-1, or the combination of these antibodies) has shown very promising results and was able to improve survival in patients with metastatic melanoma. Adoptive cell therapy using tumor-infiltrating lymphocytes is yet another, but highly...

  7. Aberrant metastatic behavior and particular features of early gastric cancer.

    Science.gov (United States)

    Gurzu, Simona; Jung, Ioan; Kadar, Zoltan

    2015-12-01

    In this paper, we have focused on the metastatic behavior of EGC and its particularities. The main factors that are currently considered as predictors of the metastatic behavior and that are used in the therapeutic decision (endoscopic resection vs surgical removal) are the tumor size (upper or bellow 2 cm), depth of infiltration, angiolymphatic invasion, the presence or absence of ulceration, and histologic type (undifferentiated vs differentiated carcinomas). However, most of the metastatic cases were published as case reports or case series. This is the reason why a proper estimation of metastatic risk in EGC is not well known. To date, 79 cases presenting bone metastases, three reports of brain metastases, and one EGC that was associated with skin metastasis were published. However, occult metastasis, lymph node micrometastasis, and skip metastasis can also occur and should be identified. Making a synthesis of the literature data that is correlated with our experience, we finally proposed the inclusion of the six Japanese subgrouping system, tumor size, angiolymphatic invasion, and micrometastasis as components of the pTNM staging system, which should be particularly adapted for EGC. PMID:26547366

  8. Dietary cholesterol deprivation improves survival and reduces incidence of metastatic colon cancer in dimethylhydrazine-pretreated rats.

    OpenAIRE

    Cruse, J P; Lewin, M. R.; Clark, C G

    1982-01-01

    Cholesterol feeding of rats with colon cancer induced by dimethylhydrazine results in reduced survival and an increased incidence of metastatic colon cancer. As cholesterol may be implicated in the induction or maintenance of the metastatic process, an experiment was designed to determine whether rats with colon cancer would benefit from the removal of cholesterol from the diet. Female Wistar rats were treated with a colon cancer-inducing regimen of dimethylhydrazine (40 mg/kg/week for 10 wee...

  9. iTRAQ identification of candidate serum biomarkers associated with metastatic progression of human prostate cancer.

    Science.gov (United States)

    Rehman, Ishtiaq; Evans, Caroline A; Glen, Adam; Cross, Simon S; Eaton, Colby L; Down, Jenny; Pesce, Giancarlo; Phillips, Joshua T; Yen, Ow Saw; Thalmann, George N; Wright, Phillip C; Hamdy, Freddie C

    2012-01-01

    A major challenge in the management of patients with prostate cancer is identifying those individuals at risk of developing metastatic disease, as in most cases the disease will remain indolent. We analyzed pooled serum samples from 4 groups of patients (n = 5 samples/group), collected prospectively and actively monitored for a minimum of 5 yrs. Patients groups were (i) histological diagnosis of benign prostatic hyperplasia with no evidence of cancer 'BPH', (ii) localised cancer with no evidence of progression, 'non-progressing' (iii) localised cancer with evidence of biochemical progression, 'progressing', and (iv) bone metastasis at presentation 'metastatic'. Pooled samples were immuno-depleted of the 14 most highly abundant proteins and analysed using a 4-plex iTRAQ approach. Overall 122 proteins were identified and relatively quantified. Comparisons of progressing versus non-progressing groups identified the significant differential expression of 25 proteins (pfactor 1 alpha 1 (eEF1A1), one of the candidates identified, was significantly higher in osteoblasts in close proximity to metastatic tumour cells compared with osteoblasts in control bone (p = 0.0353, Mann Whitney U). Our proteomic approach has identified leads for potentially useful serum biomarkers associated with the metastatic progression of prostate cancer. The panels identified, including eEF1A1 warrant further investigation and validation. PMID:22355332

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

    Science.gov (United States)

    Arrigoni, Chiara; Bersini, Simone; Gilardi, Mara; Moretti, Matteo

    2016-01-01

    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. PMID:27571063

  11. The evolving role of cytotoxic chemotherapy in the management of patients with metastatic prostate cancer.

    Science.gov (United States)

    Diamond, Elan; Garcias, María del Carmen; Karir, Beerinder; Tagawa, Scott T

    2015-02-01

    Prostate cancer (PC) is the most common cancer in men in the United States. Although outcomes are excellent for early-stage disease, survival for men with metastatic PC is limited. While older studies did not supported the use of chemotherapy in PC, the efficacy of taxane chemotherapy plus prednisone is now well established in men with metastatic castration resistant PC (CRPC). The results of CHAARTED trial have further expanded the use of chemotherapy to patients with metastatic hormone-sensitive disease. The clinical efficacy of taxanes over other chemotherapeutics may be a result of its ability to inhibit microtubule-dependent trafficking of proteins such as the androgen-receptor (AR). Ongoing research uses chemotherapy earlier in the disease course as well as explores the utility of combining cytotoxic chemotherapy with biologic agents. PMID:25762124

  12. 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.

  13. A meta analysis of cetuximab plus oxaliplatin based chemotherapy regimen for metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Y L Zhu

    2014-01-01

    Full Text Available Background: Oxaliplatin based chemotherapy regimen was one of the most used chemotherapy modality for metastatic colorectal cancer. The purpose of this meta-analysis was to assess the clinical activity and toxicities of cetuximab plus oxaliplatin-based chemotherapy regimen for metastatic colorectal Cancer. Methods: We searched the clinical studies about the cetuximab plus oxaliplatin-based chemotherapy regimen versus oxaliplatin-based chemotherapy alone for metastatic colorectal cancer in the databases of PubMed, EMBASE, Cochran, and CNKI. The data of response and toxicities were extracted and pooled by random or fixed effects model. And publication bias was evaluated by begg′s funnel plot and egger′s regression test. Results: Seven papers were included in this study. Adding cetuximab to oxaliplatin-based chemotherapy regime can significant increase response rate in K-RAS mutation metastatic colorectal patients (odds ratio [OR]: 1.45, 95% confidence interval [CI]: 1.17-1.80, Z = 3.38, P = 0.001 and metastatic colorectal patients without knowing the K-RAS status (OR: 1.36, 95% CI: 1.11-1.65, Z = 1.89, P = 0.003. But for patients with mutated K-RAS, the improvement for objective response rate was not statistical significant (OR: 0.70, 95% CI: 0.49-1.01, Z = 3.00, P = 0.058 when adding cetuximab to oxaliplatin-based chemotherapy regime. The pooled results indicating the rash and diarrhea risk was significantly increased in the combined treatment group (P 0.05. Significant publication bias was found in toxicities evaluation. Conclusion: Cetuximab plus oxaliplatin-based chemotherapy regimen significant increase the response rate for metastatic colorectal cancer. But the some toxicities such rash and diarrhea risk was also increased.

  14. “Unique trend” and “contradictory trend” in discrimination of primary synchronous lung cancer and metastatic lung cancer

    OpenAIRE

    Shen, Cheng; Xu, Huan; Lunxu LIU; Zhou, Yubin; Chen, Dali; Du, Heng; Han, Zhaojie; Che, Guowei

    2013-01-01

    Background Distinguishing between multiple primary lung cancers and metastatic tumors is often difficult when the tumor histology is same. Since genomic instability is a common feature of cancer, we hypothesized that independently arising neoplasms in an individual patient would exhibit measurable genomic variation, enabling discrimination of tumor lineage and relatedness. The feasibility of analyzing genomic instability expression profiles to distinguish multiple primary lung cancers from me...

  15. Bevacizumab for metastatic colorectal cancer: a NICE single technology appraisal.

    Science.gov (United States)

    Whyte, Sophie; Pandor, Abdullah; Stevenson, Matt

    2012-12-01

    The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of bevacizumab (Roche Products) to submit evidence for the clinical and cost effectiveness of this drug for the treatment of patients with metastatic colorectal cancer (mCRC), as part of the Institute's Single Technology Appraisal (STA) process. The School of Health and Related Research (ScHARR) at the University of Sheffield was commissioned to act as the Evidence Review Group (ERG). This paper provides a description of the company submission, the ERG review and NICE's subsequent decisions. The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology provided within the manufacturer's submission to NICE. The ERG also independently searched for relevant evidence and modified the manufacturer's decision analytic model to examine the impact of altering some of the key assumptions. The main clinical effectiveness data were derived from a phase III, multicentre, multinational, two-arm, randomized, open-label study with the primary objective of confirming the non-inferiority of oxaliplatin plus capecitabine (XELOX) compared with oxaliplatin plus 5-fluorouracil and folinic acid (FOLFOX-4) in adult patients with histologically confirmed mCRC who had not previously been treated. The ERG considered that the NO16966 trial was of reasonable methodological quality and demonstrated a significant improvement in both progression-free and overall survival when bevacizumab is added to either XELOX or FOLFOX-4. The ERG considered that the size of the actual treatment effect of bevacizumab was uncertain due to trial design limitations, imbalance of a known prognostic factor, relatively short treatment duration compared with that allowed within the trial protocol, and interpretation of the statistical analyses. The manufacturer's submission included a de novo economic evaluation using a cost-effectiveness model built in Microsoft® Excel. The ERG

  16. Covalent Targeting of Fibroblast Growth Factor Receptor Inhibits Metastatic Breast Cancer.

    Science.gov (United States)

    Brown, Wells S; Tan, Li; Smith, Andrew; Gray, Nathanael S; Wendt, Michael K

    2016-09-01

    Therapeutic targeting of late-stage breast cancer is limited by an inadequate understanding of how tumor cell signaling evolves during metastatic progression and by the currently available small molecule inhibitors capable of targeting these processes. Herein, we demonstrate that both β3 integrin and fibroblast growth factor receptor-1 (FGFR1) are part of an epithelial-mesenchymal transition (EMT) program that is required to facilitate metastatic outgrowth in response to fibroblast growth factor-2 (FGF2). Mechanistically, β3 integrin physically disrupts an interaction between FGFR1 and E-cadherin, leading to a dramatic redistribution of FGFR1 subcellular localization, enhanced FGF2 signaling and increased three-dimensional (3D) outgrowth of metastatic breast cancer cells. This ability of β3 integrin to drive FGFR signaling requires the enzymatic activity of focal adhesion kinase (FAK). Consistent with these mechanistic data, we demonstrate that FGFR, β3 integrin, and FAK constitute a molecular signature capable of predicting decreased survival of patients with the basal-like subtype of breast cancer. Importantly, covalent targeting of a conserved cysteine in the P-loop of FGFR1-4 with our newly developed small molecule, FIIN-4, more effectively blocks 3D metastatic outgrowth as compared with currently available FGFR inhibitors. In vivo application of FIIN-4 potently inhibited the growth of metastatic, patient-derived breast cancer xenografts and murine-derived metastases growing within the pulmonary microenvironment. Overall, the current studies demonstrate that FGFR1 works in concert with other EMT effector molecules to drive aberrant downstream signaling, and that these events can be effectively targeted using our novel therapeutics for the treatment of the most aggressive forms of breast cancer. Mol Cancer Ther; 15(9); 2096-106. ©2016 AACR. PMID:27371729

  17. Metastatic Prostate Cancer to the Urethra Masquerading as Urothelial Carcinoma

    OpenAIRE

    Ibrahim Zardawi; Peter Chong

    2016-01-01

    Tumors of the urethra, whether primary or metastatic, are very rare. The true nature of urethral neoplasm is not always obvious clinically nor in routine histological sections. Immunostains should be performed on such lesions because of management implications. We present a case of multiple metastases to the urethra from a prostatic carcinoma, masquerading as multiple urothelial carcinomas. Pathologists and urologists should be aware of the possibility of metastasis from the prostate.

  18. Current status of primary pharmacotherapy and future perspectives toward upfront therapy for metastatic hormone-sensitive prostate cancer.

    Science.gov (United States)

    Shiota, Masaki; Eto, Masatoshi

    2016-05-01

    Since 1941, androgen deprivation therapy has been the primary treatment for metastatic hormone-sensitive prostate cancer. Androgen deprivation therapy consists of several regimens that vary according to therapeutic modality, as well as treatment schedule. Androgen deprivation therapy initially shows excellent antitumor effects, such as relief of cancer-related symptoms, tumor marker decline and tumor shrinking. However, most metastatic hormone-sensitive prostate cancer cases eventually develop castration resistance and become lethal. Taxanes, such as docetaxel and cabazitaxel, as well as novel androgen receptor-targeting agents, such as abiraterone acetate and enzalutamide, have emerged for metastatic castration-resistant prostate cancer. The concept and principle of primary therapy for metastatic hormone-sensitive prostate cancer has remained unchanged for decades. Recently, upfront docetaxel chemotherapy has been shown to prolong overall survival in men with metastatic hormone-sensitive prostate cancer, and would lead to a paradigm shift in primary pharmacotherapy for metastatic hormone-sensitive prostate cancer. This raises the possibility of upfront use of taxanes, as well as novel androgen receptor-targeting agents combined with androgen deprivation therapy. The present review summarizes the current status of primary pharmacotherapy for metastatic hormone-sensitive prostate cancer, and discusses future perspectives in this field. PMID:27062039

  19. 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...

  20. 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) in the ...

  1. Changes in mutational status during third-line treatment for metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Spindler, Karen-Lise Garm; Pallisgaard, Niels; Andersen, Rikke Fredslund; Jakobsen, Anders

    2014-01-01

    KRAS and BRAF mutations are responsible for primary resistance to epidermal growth factor receptor (EGFR) MoAbs in metastatic colorectal cancer (mCRC), but it is unknown what causes wildtype (wt) patients to develop resistance during treatment. We measured circulating free DNA (cfDNA), KRAS and B...

  2. 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...

  3. Concomitant parenteral nutrition and systemic cytotoxic therapy in a metastatic colorectal cancer patient

    OpenAIRE

    Popov, A.A.; I. L. Chernikovsky; O. L. Fakhrutdinova; E V Tkachenko

    2012-01-01

    Pathologic nutrients metabolism presents a severe problem in metastatic colorectal cancer patients, especially those with canceromatosis. A hypermetabolism-catabolism syndrome frequently develops in in patients with progressing canceromatosis. This leads to cachexia anorexia syndrome, which significantly impedes available treatment options. Artificial nutrition allows to improve available treatment in such patients. We present a successful case of concomitant parenteral nutrition and systemic...

  4. 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; Høyer, Morten; Jensen, Niels Viggo; Saxe, Charlotte; Sengeloev, Lisa

    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...

  5. Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer

    DEFF Research Database (Denmark)

    Brose, Marcia S; Nutting, Christopher M; Jarzab, Barbara;

    2014-01-01

    BACKGROUND: Patients with radioactive iodine ((131)I)-refractory locally advanced or metastatic differentiated thyroid cancer have a poor prognosis because of the absence of effective treatment options. In this study, we assessed the efficacy and safety of orally administered sorafenib in the tre...

  6. 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...... 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...... of CTC to be a prognostic marker of poor disease-free survival. CONCLUSION: The presence of CTC in peripheral blood is a potential marker of poor disease-free survival in patients with non-metastastic colorectal cancer. The low abundance of CTC in non-metastatic colorectal cancer requires very...

  7. Prognostic Relevance of Pretherapeutic Gamma-Glutamyltransferase in Patients with Primary Metastatic Breast Cancer

    OpenAIRE

    Staudigl, Christine; Concin, Nicole; Grimm, Christoph; Pfeiler, Georg; Nehoda, Regina; Singer, Christian F.; Polterauer, Stephan

    2015-01-01

    Background Gamma-glutamyltransferase (GGT) is a known marker for apoptotic balance and cell detoxification. Recently, an association of baseline GGT levels and breast cancer incidence, tumor progression and chemotherapy resistance was shown. The purpose of this study was to evaluate the association of pre-therapeutic GGT levels, clinical-pathological parameters and survival in patients with primary metastatic breast cancer (PMBC). Methods In this multicenter analysis, pre-therapeutic GGT leve...

  8. Korean Medicine Therapy as a Substitute for Chemotherapy for Metastatic Breast Cancer: A Case Report

    OpenAIRE

    Lee, Dong-Hyun; Kim, Sung-Su; Seong, Shin; Kim, Nari; Han, Jae-Bok

    2015-01-01

    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 reac...

  9. Targeted Biomarker Profiling of Matched Primary and Metastatic Estrogen Receptor Positive Breast Cancers

    OpenAIRE

    Schleifman, Erica B; Desai, Rupal; Spoerke, Jill M.; Xiao, Yuanyuan; Wong, Cheryl; Abbas, Ilma; O’Brien, Carol; Patel, Rajesh; Sumiyoshi, Teiko; Fu, Ling; Tam, Rachel N.; Koeppen, Hartmut; Wilson, Timothy R; Raja, Rajiv; Hampton, Garret M.

    2014-01-01

    Patients with newly diagnosed, early stage estrogen receptor positive (ER+) breast cancer often show disease free survival in excess of five years following surgery and systemic adjuvant therapy. An important question is whether diagnostic tumor tissue from the primary lesion offers an accurate molecular portrait of the cancer post recurrence and thus may be used for predictive diagnostic purposes for patients with relapsed, metastatic disease. As the class I phosphatidylinositol 3' kinase (P...

  10. Treatment Algorithms for Patients with Metastatic Non-Small Cell, Non-Squamous Lung Cancer

    OpenAIRE

    Melosky, Barbara

    2014-01-01

    A number of developments have altered the treatment paradigm for metastatic non-small cell, non-squamous lung cancer. These include increasing knowledge of molecular signal pathways, as well as the outcomes of several large-scale trials. As a result, treatments are becoming more efficacious and more personalized, and are changing the management and prognosis of non-small cell lung cancer patients. This is resulting in increased survival in select patient groups. In this paper, a simplified al...

  11. Oxidative stress may cause metastatic disease in patients with colorectal cancer

    DEFF Research Database (Denmark)

    Søndergaard, Edith Smed; Gögenur, Ismail

    2014-01-01

    Despite surgical treatment of stage II colorectal cancer many patients will experience relapse. Inflammatory and immunologic reactions created due to the surgical stress response result in the production of reactive oxygen species. Oxidative stress in turn, may result in the stimulation of cancer...... cells that have not been cleared by the immune system to metastasize. In this paper we present an overview of studies where oxidative stress in relation to surgery has been linked to the development of metastatic disease....

  12. Endometrial Adenocarcinoma Metastatic to the Colon Masquerading as a Primary Colon Cancer

    Directory of Open Access Journals (Sweden)

    Michael J. Anstadt

    2012-04-01

    Full Text Available While the majority of colonic malignancies represent primarytumors, secondary tumors are not uncommon. We present a case ofendometrial cancer metastatic to the colon masquerading as a primarycolonic adenocarcinoma. The clinical and pathologic characteristicsof each disease are discussed. To our knowledge, this is the firstreported case of endometrial cancer metastasis to the colon in theabsence of endometriosis. It demonstrates the importance of usingimmunohistochemistry to distinguish morphologically similar tumorsin a patient who seemingly presents with more than one primarymalignancy.

  13. Role of connexins in metastatic breast cancer and melanoma brain colonization

    OpenAIRE

    Stoletov, Konstantin; Strnadel, Jan; Zardouzian, Erin; Momiyama, Masashi; Park, Frederick D.; Kelber, Jonathan A.; Pizzo, Donald P.; Hoffman, Robert; VandenBerg, Scott R.; Klemke, Richard L.

    2013-01-01

    Breast cancer and melanoma cells commonly metastasize to the brain using homing mechanisms that are poorly understood. Cancer patients with brain metastases display poor prognosis and survival due to the lack of effective therapeutics and treatment strategies. Recent work using intravital microscopy and preclinical animal models indicates that metastatic cells colonize the brain, specifically in close contact with the existing brain vasculature. However, it is not known how contact with the v...

  14. Nomogram for overall survival of Japanese patients with bone-metastatic prostate cancer

    OpenAIRE

    Miyoshi, Yasuhide; Noguchi, Kazumi; Yanagisawa, Masahiro; Taguri, Masataka; Morita, Satoshi; Ikeda, Ichiro; Fujinami, Kiyoshi; Miura, Takeshi; Kobayashi, Kazuki; Uemura, Hiroji

    2015-01-01

    Background We analyzed the relationship between prostate cancer outcomes and pretreatment clinical factors and developed a prognostic nomogram of overall survival (OS) of patients with bone metastasis. Methods From 1993 to 2011, 463 consecutive patients were treated for bone-metastatic prostate cancer. Data sets from 361 patients were used to develop a nomogram (training data), and data sets of 102 patients were used for validation of the nomogram (validation data). Using the external validat...

  15. Advances in Treating Metastatic Bone Cancer: Summary Statement for the First Cambridge Conference

    OpenAIRE

    Lipton, Allan; Berenson, James R; Body, Jean-Jacques; Boyce, Brendan F.; Bruland, Oyvind S.; Carducci, Michael A; Cleeland, Charles S.; Clohisy, Denis R.; Coleman, Robert E.; Cook, Richard J.; Guise, Theresa A.; Pearse, Roger N.; Powles, Trevor J; Rogers, Michael J; Roodman, G. David

    2006-01-01

    The First Cambridge Conference on Advances in Treating Metastatic Bone Cancer, a symposium held in Cambridge, Massachusetts, October 28 to 29, 2005, was convened to discuss recent advances and research related to the natural history of bone metastases and skeletal complications, bone cancer biology, treatment of myeloma and other solid tumors, and treatment-induced bone loss. The conference format combined brief presentations with extended periods of discussion. The conclusions reached during...

  16. In vivo selection for spine-derived highly metastatic lung cancer cells is associated with increased migration, inflammation and decreased adhesion.

    Science.gov (United States)

    Cai, Xiaopan; Luo, Jian; Yang, Xinghai; Deng, Huayun; Zhang, Jishen; Li, Shichang; Wei, Haifeng; Yang, Cheng; Xu, Leqin; Jin, Rongrong; Li, Zhenxi; Zhou, Wang; Ding, JianDong; Chu, Jianjun; Jia, Lianshun; Jia, Qi; Tan, Chengjun; Liu, Mingyao; Xiao, Jianru

    2015-09-01

    We developed a murine spine metastasis model by screening five metastatic non-small cell lung cancer cell lines (PC-9, A549, NCI-H1299, NCI-H460, H2030). A549 cells displayed the highest tendency towards spine metastases. After three rounds of selection in vivo, we isolated a clone named A549L6, which induced spine metastasis in 80% of injected mice. The parameters of the A549L6 cell spinal metastatic mouse models were consistent with clinical spine metastasis features. All the spinal metastatic mice developed symptoms of nerve compression after 40 days. A549L6 cells had increased migration, invasiveness and decreased adhesion compared to the original A549L0 cells. In contrast, there was no significant differences in cell proliferation, apoptosis and sensitivity to chemotherapeutic agents such as cisplatin. Comparative transcriptomic analysis and real-time PCR analysis showed that expression of signaling molecules regulating several tumor properties including migration (MYL9), metastasis (CEACAM6, VEGFC, CX3CL1, CST1, CCL5, S100A9, IGF1, NOTCH3), adhesion (FN1, CEACAM1) and inflammation (TRAF2, NFκB2 and RelB) were altered in A549L6 cells. We suggest that migration, adhesion and inflammation related genes contribute to spine metastatic capacity. PMID:26090868

  17. Clinical impact of FDG PET-CT in patients with potentially operable metastatic colorectal cancer

    International Nuclear Information System (INIS)

    Aim: To assess the clinical impact of 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) positron-emission tomography–computed tomography (PET-CT) in patients with potentially resectable metastatic colorectal cancer. Materials and methods: One hundred and two patients with potentially resectable metastatic colorectal cancer underwent FDG PET-CT in addition to conventional imaging over an 18-month period. The findings were compared to conventional imaging, with histological or clinico-radiological validation. The impact on subsequent management was evaluated using information from clinico-radiological databases. Results: Of 102 patients (mean age 67 years, range 27–85 years), 94 had liver, five had isolated lung, and three had limited peritoneal metastases. In 31 patients (30%) PET-CT had a major impact on subsequent management, by correctly clarifying indeterminate lesions on conventional imaging as inoperable metastatic disease in 16 patients, detecting previously unsuspected metastatic disease in nine patients, identifying occult second primary tumours in three patients, and correctly down-staging three patients. PET-CT had a minor impact in 12 patients (12%), no impact in 49 cases (48%), and a potentially negative impact in 10 cases (10%). Following PET-CT, 36 (35%) patients were no longer considered for surgery. Of those remaining operative 45 of 66 (68%) underwent potentially curative metastatic surgery. In this cohort PET-CT saved 16 futile laparotomies. Conclusion: FDG PET-CT has a valuable role in selected patients with metastatic colorectal cancer by improving staging accuracy and characterizing indeterminate lesions and helps triage patients to the appropriate treatment.

  18. Clinical impact of FDG PET-CT in patients with potentially operable metastatic colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Briggs, R.H. [Department of Radiology, Calderdale and Huddersfield NHS Foundation Trust, Huddersfield (United Kingdom); Chowdhury, F.U. [Departments of Radiology and Nuclear Medicine, St James' s University Hospital, Leeds (United Kingdom); Lodge, J.P.A. [HPB and Transplant Unit, St James' s University Hospital, Leeds (United Kingdom); Scarsbrook, A.F., E-mail: andrew.scarsbrook@leedsth.nhs.uk [Departments of Radiology and Nuclear Medicine, St James' s University Hospital, Leeds (United Kingdom)

    2011-12-15

    Aim: To assess the clinical impact of 2-[{sup 18}F]-fluoro-2-deoxy-D-glucose (FDG) positron-emission tomography-computed tomography (PET-CT) in patients with potentially resectable metastatic colorectal cancer. Materials and methods: One hundred and two patients with potentially resectable metastatic colorectal cancer underwent FDG PET-CT in addition to conventional imaging over an 18-month period. The findings were compared to conventional imaging, with histological or clinico-radiological validation. The impact on subsequent management was evaluated using information from clinico-radiological databases. Results: Of 102 patients (mean age 67 years, range 27-85 years), 94 had liver, five had isolated lung, and three had limited peritoneal metastases. In 31 patients (30%) PET-CT had a major impact on subsequent management, by correctly clarifying indeterminate lesions on conventional imaging as inoperable metastatic disease in 16 patients, detecting previously unsuspected metastatic disease in nine patients, identifying occult second primary tumours in three patients, and correctly down-staging three patients. PET-CT had a minor impact in 12 patients (12%), no impact in 49 cases (48%), and a potentially negative impact in 10 cases (10%). Following PET-CT, 36 (35%) patients were no longer considered for surgery. Of those remaining operative 45 of 66 (68%) underwent potentially curative metastatic surgery. In this cohort PET-CT saved 16 futile laparotomies. Conclusion: FDG PET-CT has a valuable role in selected patients with metastatic colorectal cancer by improving staging accuracy and characterizing indeterminate lesions and helps triage patients to the appropriate treatment.

  19. Fluid biopsy in patients with metastatic prostate, pancreatic and breast cancers

    International Nuclear Information System (INIS)

    Hematologic spread of carcinoma results in incurable metastasis; yet, the basic characteristics and travel mechanisms of cancer cells in the bloodstream are unknown. We have established a fluid phase biopsy approach that identifies circulating tumor cells (CTCs) without using surface protein-based enrichment and presents them in sufficiently high definition (HD) to satisfy diagnostic pathology image quality requirements. This 'HD-CTC' assay finds >5 HD-CTCs mL−1 of blood in 80% of patients with metastatic prostate cancer (n = 20), in 70% of patients with metastatic breast cancer (n = 30), in 50% of patients with metastatic pancreatic cancer (n = 18), and in 0% of normal controls (n = 15). Additionally, it finds HD-CTC clusters ranging from 2 HD-CTCs to greater than 30 HD-CTCs in the majority of these cancer patients. This initial validation of an enrichment-free assay demonstrates our ability to identify significant numbers of HD-CTCs in a majority of patients with prostate, breast and pancreatic cancers

  20. 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.

  1. Bone-Targeted Therapy in Metastatic Breast Cancer – All Well-Established Knowledge?

    Science.gov (United States)

    Gampenrieder, Simon P.; Rinnerthaler, Gabriel; Greil, Richard

    2014-01-01

    Summary Bone-targeted therapies like bisphosphonates (zoledronic acid or pamidronate) or denosumab are recommended in all patients with metastatic breast cancer and bone metastases, whether they are symptomatic or not. The choice between these 2 different agents, however, remains open. In this review, we critically discuss the emerging evidence for direct anti-tumor activity of bone-targeting agents, the utility of bone turnover markers for treatment decision and efficacy prediction, as well as the safety and financial aspects of bisphosphonates and denosumab. Furthermore, we provide a possible therapeutic algorithm, and present new pharmacologic agents which are being investigated for the treatment of metastatic bone disease. PMID:25759612

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

    OpenAIRE

    Ehab M; Elbaz M

    2016-01-01

    Moataz Ehab,1 Mohamad Elbaz2,31Department of Pharmacy Practice, 2Department of Pharmacology, Pharmacy School, Helwan University, Egypt; 3Department of Pathology, The Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH, USAAbstract: Breast cancer is the most common cancer diagnosed in women. Each year, thousands die either because of disease progression or failure of treatment. Breast cancer is classified into different subtypes based on the molecula...

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

    OpenAIRE

    Elbaz, Mohamad

    2016-01-01

    Moataz Ehab,1 Mohamad Elbaz2,31Department of Pharmacy Practice, 2Department of Pharmacology, Pharmacy School, Helwan University, Egypt; 3Department of Pathology, The Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH, USAAbstract: Breast cancer is the most common cancer diagnosed in women. Each year, thousands die either because of disease progression or failure of treatment. Breast cancer is classified into different subtypes based on the mole...

  4. 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...

  5. Critical appraisal of bevacizumab in the treatment of metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Zoratto F

    2012-09-01

    Full Text Available Federica Zoratto,1 Luigi Rossi,1 Angelo Zullo,2 Anselmo Papa,1 Eleonora Zaccarelli,1 Luigi Tomao,3 Erika Giordani,1 Maria Colonna,4 Giovanni Baiano,5 Silverio Tomao11Department of Medico-Surgical Sciences and Biotechnologies, “Sapienza” University, Oncology Unit, “SM Goretti” Hospital, Latina; 2Gastroenterology and Digestive Endoscopy Unit, “Nuovo Regina Margherita” Hospital, Rome; 3Biology Department, “Regina Elena National Cancer Institute”, Rome; 4Oncology Unit, “Don Luigi di Liegro” Hospital, Gaeta, 5Surgery Unit, “San Giovanni di Dio” Hospital, Fondi, ItalyAbstract: Colorectal cancer is one of the most common cancers worldwide. The prognosis of patients with metastatic colorectal cancer in recent years has increased from 5 months with best supportive care to nearly 2 years with chemotherapy combined with bevacizumab, an antivascular endothelial growth factor monoclonal antibody. New prognostic and predictive biomarkers have been identified to guide chemotherapy in metastatic colorectal cancer, such as KRAS and BRAF oncogenes. However, the status of these oncogenes does not affect the efficacy of bevacizumab, and biomarkers predicting response to treatment with bevacizumab are still lacking. Addition of bevacizumab to regimens based on fluoropyrimidines or irinotecan has been shown to improve overall survival in treatment-naïve patients with metastatic colorectal cancer. Similarly, a significant increase in overall survival rate is achieved by adding bevacizumab to fluoropyrimidines and oxaliplatin in patients with disease progression. Bevacizumab has been found to be effective even when used as third-line therapy and later. In addition, cohort studies have shown that bevacizumab improves survival significantly despite disease progression. Finally, bevacizumab therapy in the neoadjuvant setting for the treatment of liver metastasis is well tolerated, safe, and effective.Keywords: metastatic colorectal cancer

  6. A case of metastatic bladder cancer in both lungs treated with korean medicine therapy alone.

    Science.gov (United States)

    Lee, Dong-Hyun; Kim, Sung-Su; Seong, Shin; Woo, Chang-Ryoul; Han, Jae-Bok

    2014-05-01

    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. PMID:25232323

  7. Retinal Targets ALDH Positive Cancer Stem Cell and Alters the Phenotype of Highly Metastatic Osteosarcoma Cells

    Directory of Open Access Journals (Sweden)

    Xiaodong Mu

    2015-01-01

    Full Text Available Aldehyde dehydrogenase (ALDH is a cancer stem cell marker. Retinoic acid has antitumor properties, including the induction of apoptosis and inhibition of proliferation. Retinal, the precursor of retinoic acid, can be oxidized to retinoic acid by dehydrogenases, including ALDH. We hypothesized that retinal could potentially be transformed to retinoic acid with higher efficiency by cancer stem cells, due to the higher ALDH activity. We previously observed that ALDH activity is greater in highly metastatic K7M2 osteosarcoma (OS cells than in nonmetastatic K12 OS cells. We also demonstrated that ALDH activity correlates with clinical metastases in bone sarcoma patients, suggesting that ALDH may be a therapeutic target specific to cells with high metastatic potential. Our current results demonstrated that retinal preferentially affected the phenotypes of ALDH-high K7M2 cells in contrast to ALDH-low K12 cells, which could be mediated by the more efficient transformation of retinal to retinoic acid by ALDH in K7M2 cells. Retinal treatment of highly metastatic K7M2 cells decreased their proliferation, invasion capacity, and resistance to oxidative stress. Retinal altered the expression of metastasis-related genes. These observations indicate that retinal may be used to specifically target metastatic cancer stem cells in OS.

  8. 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.

  9. A multicentric observational trial of pegylated liposomal doxorubicin for metastatic breast cancer

    International Nuclear Information System (INIS)

    Pegylated liposomal doxorubicin (PLD) is active in metastatic breast cancer. This observational study evaluated the efficacy and safety of PLD in patients treated during routine clinical practice. Eligible patients had metastatic breast cancer and were treated with PLD according to the dose and schedule determined by their physician as part of routine practice. The primary objectives were to analyze the efficacy and toxicity of PLD therapy. 125 patients were assessable. Median age was 62 years, 78% had performance status 0-1, and 60% had estrogen-receptor-positive disease. PLD treatment was second- or third-line in 69% of patients. Prior anthracyclines (adjuvant or metastatic) had been used in 56% of patients. The majority of patients (79%) received PLD every 4 weeks at a median dose of 40 mg/m2. Overall response rate was 43% in all patients and 34% in those previously treated with anthracyclines. The most common grade 3/4 adverse events were skin toxicity/hand-foot syndrome (6%), and leukopenia (3%). This observational study supports the activity and tolerability of PLD in metastatic breast cancer as demonstrated in PLD clinical trials

  10. General Information about Metastatic Squamous Neck Cancer with Occult Primary

    Science.gov (United States)

    ... Español 1-800-4-CANCER Live Chat Publications Dictionary Menu Contact Dictionary Search About Cancer Causes and Prevention Risk Factors ... Contacts Other Funding Find NCI funding for small business innovation, technology transfer, and contracts Training Cancer Training ...

  11. A Cancer That Went Up in Smoke: Pulmonary Reaction to e-Cigarettes Imitating Metastatic Cancer

    DEFF Research Database (Denmark)

    Madsen, Lene Margrethe Ring; Vinther Krarup, Niels Henrik; Bergmann, Troels Korshøj;

    2016-01-01

    e-Cigarettes have gained worldwide popularity as a substitute for smoking, but concern has been raised regarding the long-term effects associated with their use. We report a case of a 45-year-old female consumer of e-cigarettes who presented with 4 months of abdominal pain and fever. Initial imag....... Upon cessation of e-cigarette use (known as vaping), the lung nodules disappeared, and the liver lesions regressed. Our case report suggests that vaping can induce an inflammatory reaction mimicking metastatic cancer....... imaging discovered multiple pulmonary nodules and liver lesions suspicious of widespread metastases; however, an extensive evaluation found no evidence of malignancy. Results of a lung biopsy revealed an area with multinucleated giant cells suggestive of a foreign body reaction to a lipophilic material...

  12. [Indoleamine 2,3-Dioxygenase Activity during Fulvestrant Therapy for Aromatase Inhibitor-Resistant Metastatic Breast Cancer].

    Science.gov (United States)

    Sakurai, Kenichi; Fujisaki, Shigeru; Suzuki, Shuhei; Adachi, Keita; Nagashima, Saki; Masuo, Yuki; Tomita, Ryouichi; Gonda, Kenji; Enomoto, Katsuhisa; Amano, Sadao; Matsuo, Sadanori; Umeda, Nao

    2015-10-01

    We evaluated the clinical significance of indoleamine 2,3-dioxygenase (IDO) during fulvestrant therapy for aromatase inhibitor (AI)-resistant metastatic breast cancer. IDO activity can be measured by the tryptophan (Trp)/kynurenine (Kyn) ratio. Trp and Kyn were measured with high performance liquid chromatography (HPLC). Patients with AI resistant metastatic breast cancer had a 28.6% response rate to fulvestrant therapy, and the clinical benefit rate was 76.2%. AI-resistant metastatic breast cancer patients with distant metastases had a lower serum Trp/Kyn level than patients who had local recurrences. During fulvestrant therapy, IDO activity significantly decreased in the fulvestrant responder group compared to that in the fulvestrant non-responder group. During fulvestrant therapy, the IDO activity correlated with the number of metastatic lesions. These results suggest that measuring the Trp/Kyn ratio is useful for evaluating immunological metastatic status during endocrine therapy. PMID:26489554

  13. 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

  14. Metastatic breast cancer to the gastrointestinal tract: A case series and review of the literature

    Institute of Scientific and Technical Information of China (English)

    Jose Nazareno; Donald Taves; Harold G Preiksaitis

    2006-01-01

    Metastatic breast cancer involving the hepatobiliary tract or ascites secondary to peritoneal carcinomatosis has been well described. Luminal gastrointestinal tract involvement is less common and recognition of the range of possible presentations is important for early and accurate diagnosis and treatment. We report 6 patients with a variety of presentations of metastatic breast cancer of the luminal gastrointestinal tract. These include oropharyngeal and esophageal involvement presenting as dysphagia with one case of pseudoachalasia, a linitis plastica-like picture with gastric narrowing and thickened folds, small bowel obstruction and multiple strictures mimicking Crohn's disease, and a colonic neoplasm presenting with obstruction. Lobular carcinoma,representing only 10% of breast cancers is more likely to metastasize to the gastrointestinal tract. These patients presented with gastrointestinal manifestations after an average of 9.5 years and as long as 20 years from initial diagnosis of breast cancer. Given the increased survival of breast cancer patients with current therapeutic regimes, more unusual presentations of metastatic disease, including involvement of the gastrointestinal tract can be anticipated.

  15. 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

    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...... 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...... 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, Rho...

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

    International Nuclear Information System (INIS)

    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

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

    Institute of Scientific and Technical Information of China (English)

    Li-Yan Zhou; Ye-Hui Shi; Yong-Sheng Jia; Zhong-Sheng Tong

    2015-01-01

    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 ¼ 1002) meeting our criteria for evaluation. Eight single-agent trials (n ¼ 551) and seven using combinations with other agents (n ¼ 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. Copyright © 2015, Chinese Medical Association Production. Production and hosting by Elsevier B.V. on behalf of KeAi Com-munications Co., Ltd. This is an open access article under the CC BY-NC-ND license

  18. EVEROLIMUS IN THE TREATMENT FOR METASTATIC RENAL CANCER

    Directory of Open Access Journals (Sweden)

    B. Ya. Alekseyev

    2014-07-01

    Full Text Available Target drugs acting via the HIF/VEGF pathway show a steady-state clinical effect in treating patients with metastatic renal cell carcinoma (RCC. However, to continue therapy in patients with developing resistance in the prolonged use of tyrosine kinase inhibitors remained unsolved, which brought about a search for alternative pathogenetic pathways and new effective appropriate medicines. One of its solutions was the mTOR pathway and everolimus acting via it. Motzer et al. conducted the RECORD-1 phase III international multicenter randomized double-blind placebo-controlled study of the efficiency of everolimus. The study enrolled 410 patients with metastatic RCC that progressed during target therapy with sunitinib and/or sorafenib. The study was interrupted before the appointed time, as recommended by the Independent Data Monitoring Committee since the established effectiveness threshold values and conformity criteria for a positive study result were achieved. According to an independent centralized assessment, everolimus reduced the risk for disease progression by 70% (p < 0.0001. The median progression-free survival was longer in the everolimus group than that in the placebo group, which was 4.9 and 1.9 months, respectively (p < 0.0001. Final double-blind analysis showed a partial response in 5 (2% patients and disease stabilization in 185 (67% patients in the everolimus group; there were no patients by the former indicator and 45 (32% patients by the latter in the placebo group. The final findings showed no statistically significant difference in overall survival rates between the groups: the median overall survival was 14.78 and 14.39 months in the everolimus and placebo groups, respectively (p = 0.177. This might be due to a cross impact because 79 (81% of the 98 patients from the placebo group were switched over to open-labeled everolimus taking after disease progression. Everolimus demonstrated a good tolerability and safety. Grade III

  19. Challenges Associated with Tyrosine Kinase Inhibitor Therapy for Metastatic Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Maria E. Cabanillas

    2011-01-01

    Full Text Available Tyrosine kinase inhibitors (TKIs which target angiogenesis are promising treatments for patients with metastatic medullary and differentiated thyroid cancers. Sorafenib, sunitinib, and pazopanib are commercially available drugs which have been studied in these diseases. Vandetanib is the first drug approved in the United States for treatment of medullary thyroid cancer. These TKIs are used as chronic therapies, and therefore it is imperative to understand the adverse event profile in order to avoid excessive toxicity and maintain patients on therapy as long as it proves beneficial. Here we review common toxicities, management of these, and other challenging situations that arise when using TKIs in patients with thyroid cancer.

  20. Abiraterone plus prednisone improves survival in metastatic castration-resistant prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Scott T Tagawa; Himisha Beltran

    2011-01-01

    In essentially just 1 year's time,we have seen science translated into exciting new therapeutic agents for men with metastatic castration-resistant prostate cancer (CRPC),1 most recently with the United States Food and Drug Administration (FDA) approval of abiraterone acetate in combination with prednisone.2 While prostate cancer has been known to be highly responsive to surgical or medical castration for well over half a century,3 what was once termed 'hormone refractory' prostate cancer inevitably developed,leading to cancerrelated death.Many consider the introduction of chemotherapy for CRPC initially for symptomatic benefit,then with improvements in survival,a substantial step forward.

  1. Locally ablative therapies for primary and metastatic liver cancer.

    Science.gov (United States)

    Li, David; Kang, Josephine; Madoff, David C

    2014-08-01

    Locally ablative therapies have an increasing role in the effective multidisciplinary approach towards the treatment of both primary and metastatic liver tumors. In patients who are not considered surgical candidates and have low volume disease, these therapies have now become established into consensus practice guidelines. A large range of therapeutic options exist including percutaneous ethanol injection (PEI), radiofrequency ablation (RFA), microwave ablation (MWA), cryoablation, percutaneous laser ablation (PLA), irreversible electroporation (IRE), stereotactic body radiation therapy (SBRT) and high intensity focused ultrasound (HIFU); each having benefits and drawbacks. The greatest body of evidence supporting clinical utility in the liver currently exists for RFA, with PEI having fallen out of favor. MWA, IRE, SBRT and HIFU are relatively nascent technologies, and outcomes data supporting their use is promising. Future directions of ablative therapies include tandem approaches to improve efficacy in the treatment of liver tumors. PMID:24746315

  2. 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.

  3. Crosstalk between Metastatic Cancer Cells and Bone Microenvironments

    Institute of Scientific and Technical Information of China (English)

    Toshiyuki YONEDA

    2009-01-01

    @@ Bone is one of the most preferential target sites for cancers such as breast, prostate and lung cancers to metastasize. Although the mechanism under-lying this organ preference still needs to be elucidated, observations that specific inhibitors of osteoclasts such as bisphosphonates inhibit bone metastases suggest a critical role of osteoclasts.

  4. Exome sequencing of contralateral breast cancer identifies metastatic disease.

    Science.gov (United States)

    Klevebring, Daniel; Lindberg, Johan; Rockberg, Julia; Hilliges, Camilla; Hall, Per; Sandberg, Maria; Czene, Kamila

    2015-06-01

    Women with contralateral breast cancer (CBC) have significantly worse prognosis compared to women with unilateral cancer. A possible explanation of the poor prognosis of patients with CBC is that in a subset of patients, the second cancer is not a new primary tumor but a metastasis of the first cancer that has potentially obtained aggressive characteristics through selection of treatment. Exome and whole-genome sequencing of solid tumors has previously been used to investigate the clonal relationship between primary tumors and metastases in several diseases. In order to assess the relationship between the first and the second cancer, we performed exome sequencing to identify somatic mutations in both first and second cancers, and compared paired normal tissue of 25 patients with metachronous CBC. For three patients, we identified shared somatic mutations indicating a common clonal origin thereby demonstrating that the second tumor is a metastasis of the first cancer, rather than a new primary cancer. Accordingly, these patients all developed distant metastasis within 3 years of the second diagnosis, compared with 7 out of 22 patients with non-shared somatic profiles. Genomic profiling of both tumors help the clinicians distinguish between true CBCs and subsequent metastases. PMID:25922084

  5. nab-Paclitaxel in combination with biologically targeted agents for early and metastatic breast cancer.

    Science.gov (United States)

    Megerdichian, Christine; Olimpiadi, Yuliya; Hurvitz, Sara A

    2014-06-01

    Taxanes are highly active chemotherapeutic agents used in the treatment of early-stage and metastatic breast cancer. Novel formulations have been developed to improve efficacy and decrease toxicity associated with these cytotoxic agents. nab-Paclitaxel is a biologically interactive, solvent-free, 130-nm-sized albumin-bound paclitaxel, developed to avoid the Cremophor vehicle used in solvent-based paclitaxel. Based on a pivotal phase 3 study, nab-paclitaxel was shown to be safely infused at a significantly higher dose of paclitaxel than the doses used with standard paclitaxel therapy, and had a shorter infusion time, no premedication, and higher response rates. It is now approved in the United States for treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant therapy, and has demonstrated promising efficacy and favorable tolerability. Recently, several phase 2 and 3 studies have suggested a role for nab-paclitaxel in combination with biologically targeted agents for the treatment of early- and late-stage breast cancer. This review will discuss the findings of clinical trials evaluating nab-paclitaxel in combination with biologically targeted therapeutic agents for breast cancer in the neoadjuvant, adjuvant, and metastatic settings. PMID:24560997

  6. 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. PMID:27487107

  7. Patient-Reported Outcomes in Metastatic Breast Cancer: A Review of Industry-Sponsored Clinical Trials

    Science.gov (United States)

    Krohe, Meaghan; Hao, Yanni; Lamoureux, Roger E.; Galipeau, Nina; Globe, Denise; Foley, Catherine; Mazar, Iyar; Solomon, Jeffrey; Shields, Alan L.

    2016-01-01

    INTRODUCTION Patient-reported outcome (PRO) measures serve to capture vital patient information not otherwise obtained by primary study endpoints. This paper examines how PROs are utilized as endpoints in industry-sponsored metastatic breast cancer clinical trials. METHODS A search was conducted in the clinicaltrials.gov web site for trials involving common treatments for metastatic breast cancer. Thirty-eight clinical trials were identified which included a PRO endpoint in the study, and data were extracted and summarized. RESULTS Overall, 17 unique PRO questionnaires and 14 concepts of measurement were identified as secondary or exploratory endpoints. The Functional Assessment of Cancer Therapy—Breast was the most frequently utilized questionnaire, commonly implemented to assess quality of life. The EORTC QLQ-C30 was also frequently used to measure quality of life or pain. CONCLUSION This review shares insights into the role of PROs in trials for metastatic breast cancer from which treatment developers and other stakeholders can enhance successful implementation of the patient voice into future trials. PMID:27441001

  8. Targeted biomarker profiling of matched primary and metastatic estrogen receptor positive breast cancers.

    Directory of Open Access Journals (Sweden)

    Erica B Schleifman

    Full Text Available Patients with newly diagnosed, early stage estrogen receptor positive (ER+ breast cancer often show disease free survival in excess of five years following surgery and systemic adjuvant therapy. An important question is whether diagnostic tumor tissue from the primary lesion offers an accurate molecular portrait of the cancer post recurrence and thus may be used for predictive diagnostic purposes for patients with relapsed, metastatic disease. As the class I phosphatidylinositol 3' kinase (PI3K pathway is frequently activated in ER+ breast cancer and has been linked to acquired resistance to hormonal therapy, we hypothesized pathway status could evolve over time and treatment. Biomarker analyses were conducted on matched, asynchronous primary and metastatic tumors from 77 patients with ER+ breast cancer. We examined whether PIK3CA and AKT1 alterations or PTEN and Ki67 levels showed differences between primary and metastatic samples. We also sought to look more broadly at gene expression markers reflective of proliferation, molecular subtype, and key receptors and signaling pathways using an mRNA analysis platform developed on the Fluidigm BioMark™ microfluidics system to measure the relative expression of 90 breast cancer related genes in formalin-fixed paraffin-embedded (FFPE tissue. Application of this panel of biomarker assays to matched tumor pairs showed a high concordance between primary and metastatic tissue, with generally few changes in mutation status, proliferative markers, or gene expression between matched samples. The collection of assays described here has been optimized for FFPE tissue and may have utility in exploratory analyses to identify patient subsets responsive to targeted therapies.

  9. S0420, Sorafenib in Treating Patients With Recurrent or Metastatic Head and Neck Cancer

    Science.gov (United States)

    2013-02-27

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

  10. ADAM15 Is Functionally Associated with the Metastatic Progression of Human Bladder Cancer.

    Directory of Open Access Journals (Sweden)

    Guadalupe Lorenzatti Hiles

    Full Text Available ADAM15 is a member of a family of catalytically active disintegrin membrane metalloproteinases that function as molecular signaling switches, shed membrane bound growth factors and/or cleave and inactivate cell adhesion molecules. Aberrant metalloproteinase function of ADAM15 may contribute to tumor progression through the release of growth factors or disruption of cell adhesion. In this study, we utilized human bladder cancer tissues and cell lines to evaluate the expression and function of ADAM15 in the progression of human bladder cancer. Examination of genome and transcriptome databases revealed that ADAM15 ranked in the top 5% of amplified genes and its mRNA was significantly overexpressed in invasive and metastatic bladder cancer compared to noninvasive disease. Immunostaining of a bladder tumor tissue array designed to evaluate disease progression revealed increased ADAM15 immunoreactivity associated with increasing cancer stage and exhibited significantly stronger staining in metastatic samples. About half of the invasive tumors and the majority of the metastatic cases exhibited high ADAM15 staining index, while all low grade and noninvasive cases exhibited negative or low staining. The knockdown of ADAM15 mRNA expression significantly inhibited bladder tumor cell migration and reduced the invasive capacity of bladder tumor cells through MatrigelTM and monolayers of vascular endothelium. The knockdown of ADAM15 in a human xenograft model of bladder cancer inhibited tumor growth by 45% compared to controls. Structural modeling of the catalytic domain led to the design of a novel ADAM15-specific sulfonamide inhibitor that demonstrated bioactivity and significantly reduced the viability of bladder cancer cells in vitro and in human bladder cancer xenografts. Taken together, the results revealed an undescribed role of ADAM15 in the invasion of human bladder cancer and suggested that the ADAM15 catalytic domain may represent a viable

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

    Science.gov (United States)

    2016-05-13

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

  12. 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.

  13. A Comprehensive Review of Clinical Trials on EGFR Inhibitors Such as Cetuximab and Panitumumab as Monotherapy and in Combination for Treatment of Metastatic Colorectal Cancer

    OpenAIRE

    Yazdi, Mohammad Hossein; Faramarzi, Mohammad Ali; Nikfar, Shekoufeh; Abdollahi, Mohammad

    2015-01-01

    Metastatic colorectal cancer is the fourth most common cause of death due to cancer after those of lung, stomach, and liver. Anti epidermal growth factor receptor drugs as a targeting therapy seem to be good candidates for curing metastatic colorectal cancer. Two available anti epidermal growth factor receptor monoclonal antibodies are cetuximab and panitumumab which have been approved for metastatic colorectal cancer treatment. Through the available literature on NCBI and clinical trials, 31...

  14. Irrefutable evidence for the use of docetaxel in newly diagnosed metastatic prostate cancer: results from the STAMPEDE and CHAARTED trials

    OpenAIRE

    Soest, Robert Jan; de Wit, Ronald

    2015-01-01

    textabstractAndrogen deprivation therapy (ADT) has been used in the treatment of metastatic prostate cancer since the first description of its hormonal dependence in 1941. In 2004, docetaxel chemotherapy became the mainstay of treatment in metastatic castration-resistant prostate cancer (mCRPC), following robust, albeit modest, survival benefit in two randomized phase 3 trials. The recently published CHAARTED trial was the first to show that combining ADT with docetaxel in men with hormone-na...

  15. Metastatic renal cell carcinoma presenting as a breast mass in a woman with history of primary breast cancer

    OpenAIRE

    Balliauw, C; Termote, B; Steen, A.; Moerman, P; M. R. Christiaens; Van Ongeval, C

    2011-01-01

    Metastatic extramammary breast tumours are uncommon and differential diagnosis with primary breast carcinoma may prove to be difficult. We report a case of a metastasis of a renal cell cancer in the breast in a woman with a history of primary breast cancer. On follow-up of her breast carcinoma, a lump was detected via mammography and ultrasound. Core needle biopsy revealed a metastatic extramammary lesion originating from an asymptomatic renal cell carcinoma. We conclude that the diagnosis of...

  16. Percutaneous Placement of Self-Expandable Metallic Stents in Patients with Obstructive Jaundice Secondary to Metastatic Gastric Cancer after Gastrectomy

    OpenAIRE

    Hong, Hyun Pyo; Seo, Tae-Seok; Cha, In-Ho; Yu, Jung Rim; Mok, Young Jae; Oh, Joo Hyeong; Kwon, Se Hwan; Kim, Sam Soo; Kim, Seung Kwon

    2013-01-01

    Objective To evaluate the outcomes of patients undergoing percutaneous placements of a biliary stent for obstructive jaundice secondary to metastatic gastric cancer after gastrectomy. Materials and Methods Fifty patients (mean age, 62.4 years; range, 27-86 years) who underwent percutaneous placements of a biliary stent for obstructive jaundice secondary to metastatic gastric cancer after gastrectomy were included. The technical success rate, clinical success rate, complication rate, stent pat...

  17. Circulating HER2 Extracellular Domain and Response to Chemotherapy in Metastatic Breast Cancer

    International Nuclear Information System (INIS)

    The present study was designed to demonstrate the association between HER2 and chemotherapy resistance in patients with metastatic breast cancer. Patients and methods: We performed a prospective assessment of the predictive value of the circulating HER2 extracellular domain (ECD) in patients with metastatic breast carcinoma using paclitaxel and doxorubicin. Serum samples were collected from 45 patients with metastatic breast carcinoma before first-line chemotherapy for metastatic disease and the levels of circulating HER2 ECD were measured using an enzyme immunoassay. Immunohistochemistry with anti-HER2 monoclonal antibody CB 11 was used to assess the expression of HER2 in the primary tumors. Results: When 450 fmol/ml was used as a cutoff, 18 patients (40%) had elevated HER2 ECD levels. Elevated levels of circulating HER2 ECD were associated with the expression of HER2 in the primary tumor tissue and with the metastatic tumor burden (evaluated with the marker CA 15-3; ρ= 0.032 and ρ= 0.002, respectively) but not with variables such as menopausal status. stage at diagnosis, previous adjuvant therapy, or the number of metastatic sites. The levels of circulating HER2 ECD correlated inversely with the response to treatment. The probability of obtaining a complete response to chemotherapy was significantly lower (ρ= 0.021) in patients with elevated HER2 ECD levels (0%; 95% confidence interval. 0-13%) in comparison with patients with non-elevated HER2 (26.9%; 95% confidence interval. ] 2-45%). In addition, the duration of clinical response was significantly shorter in patients with elevated HER2 ECD, in comparison with the cases with non-elevated HER2 (7.5 versus 11 months; ρ= 0.035). Conclusion: In conclusion, elevated levels of circulating HER2 ECD in patients with metastatic breast cancer correlate with reduced efficacy of a paclitaxel-doxorubicin chemotherapy combination. We suggest that the poor response rate associated with HER2 expression in advanced breast

  18. Utility of Surgeon-Performed Ultrasound Assessment of the Lateral Neck for Metastatic Papillary Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Cortney Y. Lee

    2012-01-01

    Full Text Available Ultrasound is the recommended staging modality for papillary thyroid cancer. Surgeons proficient in US assessment of the neck and experienced in the management of papillary thyroid cancer (PTC appear uniquely qualified to assess the lateral cervical lymph nodes for metastatic disease. Of 310 patients treated for PTC between 2000 and 2008, 109 underwent surgeon-performed ultrasound (SUS of the lateral neck preoperatively. Fine needle aspiration was performed on suspicious lateral lymph nodes. SUS findings were compared with FNA cytology and results of postoperative imaging studies. The sensitivity and negative predictive value of SUS were 88% and 97%, respectively. Four patients were found to have missed metastatic disease within 6 months. No patient underwent a nontherapeutic neck dissection. SUS combined with US-guided FNA of suspicious lymph nodes can accurately stage PTC to reliably direct surgical management.

  19. 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

    investigator. Median time to PSA progression was 8·5 months (95% CI 8·3-9·7) and median time to clinical progression was 12·7 months (11·8-13·8). INTERPRETATION: No new safety signals or unexpected adverse events were found in this early-access protocol trial to assess abiraterone acetate for patients with......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 final...... analysis of an early-access protocol trial that was initiated after completion of COU-AA-301 to enable worldwide preapproval access to abiraterone acetate in patients with metastatic castration-resistant prostate cancer progressing after chemotherapy. METHODS: We did a multicentre, open-label, early...

  20. Sarcoidosis mimicking metastatic thyroid cancer following radioactive iodine therapy

    OpenAIRE

    Myint, Zin W.; Chow, Robert D.

    2015-01-01

    Introduction: Sarcoidosis is an inflammatory disease characterized by non-caseating granulomas that can be present in diverse organ systems. Sarcoidosis can be associated with malignancy, presenting either preceding, during, or after chemotherapy. We herewith report a case of sarcoidosis mimicking cancer recurrence that developed after radioactive iodine therapy for papillary thyroid cancer.Background: A 68-year-old Caucasian woman was found to have an incidental mediastinal lymph node. She u...

  1. Altered Sphingolipid Metabolism in Patients with Metastatic Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Todd E. Fox

    2013-07-01

    Full Text Available Although numerous genetic mutations and amplifications have been identified in pancreatic cancer, much of the molecular pathogenesis of the disease remains undefined. While proteomic and transcriptomic analyses have been utilized to probe and characterize pancreatic tumors, lipidomic analyses have not been applied to identify perturbations in pancreatic cancer patient samples. Thus, we utilized a mass spectrometry-based lipidomic approach, focused towards the sphingolipid class of lipids, to quantify changes in human pancreatic cancer tumor and plasma specimens. Subgroup analysis revealed that patients with positive lymph node metastasis have a markedly higher level of ceramide species (C16:0 and C24:1 in their tumor specimens compared to pancreatic cancer patients without nodal disease or to patients with pancreatitis. Also of interest, ceramide metabolites, including phosphorylated (sphingosine- and sphinganine-1-phosphate and glycosylated (cerebroside species were elevated in the plasma, but not the pancreas, of pancreatic cancer patients with nodal disease. Analysis of plasma level of cytokine and growth factors revealed that IL-6, IL-8, CCL11 (eotaxin, EGF and IP10 (interferon inducible protein 10, CXCL10 were elevated in patients with positive lymph nodes metastasis, but that only IP10 and EGF directly correlated with several sphingolipid changes. Taken together, these data indicate that sphingolipid metabolism is altered in human pancreatic cancer and associated with advanced disease. Assessing plasma and/or tissue sphingolipids could potentially risk stratify patients in the clinical setting.

  2. 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.

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

    International Nuclear Information System (INIS)

    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 Gy10 (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 Gy10 (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 Gy10 is recommended when possible. Considering the low morbidity and improved symptom palliation, CCRT might be considered in patients with good performance status

  4. Cetuximab plus FOLFOX6 or FOLFIRI in metastatic colorectal cancer: CECOG trial

    Institute of Scientific and Technical Information of China (English)

    Janja; Ocvirk; Thomas; Brodowicz; Fritz; Wrba; Tudor; E; Ciuleanu; Galina; Kurteva; Semir; Beslija; Ivan; Koza; Zsuzsanna; Pápai; Diethelm; Messinger; Ugur; Yilmaz; Zsolt; Faluhelyi; Suayib; Yalcin; Demetris; Papamichael; Miklós; Wenczl; Zrinka; Mrsic-Krmpotic; Einat; Shacham-Shmueli; Damir; Vrbanec; Regina; Esser; Werner; Scheithauer; Christoph; C; Zie-linski

    2010-01-01

    AIM: To investigate efficacy and safety of cetuximab combined with two chemotherapy regimens in patients with unresectable metastatic colorectal cancer (mCRC). METHODS: Randomized patients received cetuximab with 5-fluorouracil (5-FU), folinic acid (FA) and oxaliplatin (FOLFOX) 6 (arm A, n = 74) or 5-FU, FA and irinotecan (FOLFIRI) (arm B, n = 77). KRAS mutation status was determined retrospectively in a subset of tumors (n = 117). RESULTS: No significant difference was found between treatment arms A and B ...

  5. Predicting Response to Hormonal Therapy and Survival in Men with Hormone Sensitive Metastatic Prostate Cancer

    OpenAIRE

    Grivas, Petros D; Robins, Diane M.; Hussain, Maha

    2012-01-01

    Androgen deprivation is the cornerstone of the management of metastatic prostate cancer. Despite several decades of clinical experience with this therapy there are no standard predictive biomarkers for response. Although several candidate genetic, hormonal, inflammatory, biochemical, metabolic biomarkers have been suggested as potential predictors of response and outcome, none has been prospectively validated nor has proven clinical utility to date. There is significant heterogeneity in the d...

  6. Mathematical and numerical analysis of a model for anti-angiogenic therapy in metastatic cancers

    CERN Document Server

    Benzekry, Sebastien

    2010-01-01

    We introduce and analyze a phenomenological model for anti-angiogenic therapy in the treatment of metastatic cancers. It is a structured transport equation with a nonlocal boundary condition describing the evolution of the density of metastasis that we analyze first at the continuous level. We present the numerical analysis of a lagrangian scheme based on the characteristics whose convergence establishes existence of solutions. Then we prove an error estimate and use the model to perform interesting simulations in view of clinical applications.

  7. Clinical Efficacy of Capecitabine and Cyclophosphamide (XC) in Patients with Metastatic Breast Cancer

    OpenAIRE

    Shien, Tadahiko; Doihara, Hiroyoshi; Nishiyama,Keiko; Masuda, Hiroko; Nogami, Tomohiro; Ikeda, Hirokuni; Taira, Naruto

    2011-01-01

    Combined low-dose therapy of oral capecitabine (Xeloda) and cyclophosphamide (XC) has been demonstrated to be useful for long-term control of lesions in patients with metastatic breast cancer (MBC) and is aimed at symptomatic alleviation and prolongation of survival. Here, a retrospective review was conducted of MBC patients administered XC at the Okayama University Hospital (OUH), to evaluate responses to XC, adverse events and time to progression (TTP). Twenty patients with MBC received XC ...

  8. Willingness to pay to avoid metastatic breast cancer treatment side effects: results from a conjoint analysis

    OpenAIRE

    Lalla, Deepa; Carlton, Rashad; Santos, Eduardo; Bramley, Thomas; D’Souza, Anna

    2014-01-01

    Purpose Metastatic breast cancer (MBC) patients are treated with a variety of regimens with differing side effects that can reduce the patients’ quality of life. This study assessed the willingness to pay (WTP) to avoid side effects related to MBC treatment using conjoint analysis. Methods An online, self-administered conjoint analysis survey of US adult female MBC patients was conducted to elicit preferences for MBC treatment side effects. Attributes included in the analysis were hair loss, ...

  9. 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......-CSF, especially at cycle 1 and in men aged > or =75 years, is important and improves tolerability in senior adults treated with cabazitaxel....

  10. Effects of occupational therapy on quality of life of patients with metastatic prostate cancer

    OpenAIRE

    Huri, Meral; Huri, Emre; Kayihan, Hulya; Altuntas, Onur

    2015-01-01

    Objectives: To evaluate the efficiency of occupational therapy relative to a home program in improving quality of life (QoL) among men who were treated for metastatic prostate cancer (MPC). Methods: Fifty-five men were assigned randomly to either the 12-week cognitive behavioral therapy based occupational therapy (OT-CBSM) intervention (treatment group) or a home program (control group) between March 2012 and August 2014 in the Department of Occupational Therapy, Faculty of Health Sciences, H...

  11. A transgenic mouse model of metastatic prostate cancer originating from neuroendocrine cells

    OpenAIRE

    Garabedian, Emily M.; Humphrey, Peter A.; Jeffrey I Gordon

    1998-01-01

    A transgenic mouse model of metastatic prostate cancer has been developed that is 100% penetrant in multiple pedigrees. Nucleotides −6500 to +34 of the mouse cryptdin-2 gene were used to direct expression of simian virus 40 T antigen to a subset of neuroendocrine cells in all lobes of the FVB/N mouse prostate. Transgene expression is initiated between 7 and 8 weeks of age and leads to development of prostatic intraepithelial neoplasia within a week. Prostatic intraepithelial neoplasia progres...

  12. 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.

  13. Integrated multimodal imaging of dynamic bone-tumor alterations associated with metastatic prostate cancer.

    Science.gov (United States)

    Brisset, Jean-Christophe; Hoff, Benjamin A; Chenevert, Thomas L; Jacobson, Jon A; Boes, Jennifer L; Galbán, Stefanie; Rehemtulla, Alnawaz; Johnson, Timothy D; Pienta, Kenneth J; Galbán, Craig J; Meyer, Charles R; Schakel, Timothy; Nicolay, Klaas; Alva, Ajjai S; Hussain, Maha; Ross, Brian D

    2015-01-01

    Bone metastasis occurs for men with advanced prostate cancer which promotes osseous growth and destruction driven by alterations in osteoblast and osteoclast homeostasis. Patients can experience pain, spontaneous fractures and morbidity eroding overall quality of life. The complex and dynamic cellular interactions within the bone microenvironment limit current treatment options thus prostate to bone metastases remains incurable. This study uses voxel-based analysis of diffusion-weighted MRI and CT scans to simultaneously evaluate temporal changes in normal bone homeostasis along with prostate bone metatastsis to deliver an improved understanding of the spatiotemporal local microenvironment. Dynamic tumor-stromal interactions were assessed during treatment in mouse models along with a pilot prospective clinical trial with metastatic hormone sensitive and castration resistant prostate cancer patients with bone metastases. Longitudinal changes in tumor and bone imaging metrics during delivery of therapy were quantified. Studies revealed that voxel-based parametric response maps (PRM) of DW-MRI and CT scans could be used to quantify and spatially visualize dynamic changes during prostate tumor growth and in response to treatment thereby distinguishing patients with stable disease from those with progressive disease (pprostate tumor-stromal responses to therapies thus demonstrating the potential of multi-modal PRM image-based biomarkers as a novel means for assessing dynamic alterations associated with metastatic prostate cancer. These results establish an integrated and clinically translatable approach which can be readily implemented for improving the clinical management of patients with metastatic bone disease. PMID:25859981

  14. Circulating Tumor Cells in Metastatic Breast Cancer: A Prognostic and Predictive Marker

    Directory of Open Access Journals (Sweden)

    Sayyed Farshid Moussavi-Harami

    2014-05-01

    Full Text Available The role of circulating tumor cells (CTCs as a marker for disease progression in metastatic cancer is controversial. The current review will serve to summarize the evidence on CTCs as a marker of disease progression in patients with metastatic breast cancer. The immunohistochemistry (IHC-based CellSearch® is the only FDA-approved isolation technique for quantifying CTCs in patients with metastatic breast cancer. We searched PubMed and Web of Knowledge for clinical studies that assessed the prognostic and predictive value of CTCs using IHC-based isolation. The patient outcomes reported include median and Cox-proportional hazard ratios for overall survival (OS and progression-free survival (PFS. All studies reported shorter OS for CTC-positive patients versus CTC-negative. A subset of the selected trials reported significant lower median PFS for CTC-positive patients. The reported trials support the utility of CTC enumeration for patient prognosis. But further studies are required to determine the utility of CTC enumeration for guiding patient therapy. There are three clinical trials ongoing to test this hypothesis. These studies, and others, will further establish the role of CTCs in clinical practice.

  15. Clinical observation on docetaxel plus S1 in the treatment of advanced metastatic breast cancer

    Institute of Scientific and Technical Information of China (English)

    Jian Cao; Ping Sun

    2013-01-01

    Objective: The aim of our study was to observe the efficacy and adverse reactions of docetaxel plus S1 in patients with advanced metastatic breast cancer. Methods: Twenty-seven patients with advanced metastatic breast cancer receiving docetaxel plus S1 in our hospital were analyzed. The efficacy and safety were evaluated according to RECIST and NCI CTC 3.0. Results: The clinical efficacy and toxicity were evaluated in all the 27 patients, including 1 case of CR, 12 of PR, 6 of SD, and 8 of PD (ORR = 48.1%, CBR = 70.3%). The median time to tumor progression (mTTP) was 7.3 months. No IV degree of adverse reaction was observed in the observation group. Most adverse reactions were degrees I and II, the most common reactions were neutropenia (59.3%), abnormal liver function (33.3%), gastrointestinal adverse events (29.6 %) and stomatitis (7.4%). Conclusion: With good efficacy and low toxicity, docetaxel plus S1 could be administered in the treatment of advanced metastatic breast cancer.

  16. Tissue engineering a surrogate niche for metastatic cancer cells.

    Science.gov (United States)

    Seib, F Philipp; Berry, Janice E; Shiozawa, Yusuke; Taichman, Russell S; Kaplan, David L

    2015-05-01

    In breast and prostate cancer patients, the bone marrow is a preferred site of metastasis. We hypothesized that we could use tissue-engineering strategies to lure metastasizing cancer cells to tissue-engineered bone marrow. First, we generated highly porous 3D silk scaffolds that were biocompatible and amenable to bone morphogenetic protein 2 functionalization. Control and functionalized silk scaffolds were subcutaneously implanted in mice and bone marrow development was followed. Only functionalized scaffolds developed cancellous bone and red bone marrow, which appeared as early as two weeks post-implantation and further developed over the 16-week study period. This tissue-engineered bone marrow microenvironment could be readily manipulated in situ to understand the biology of bone metastasis. To test the ability of functionalized scaffolds to serve as a surrogate niche for metastasis, human breast cancer cells were injected into the mammary fat pads of mice. The treatment of animals with scaffolds had no significant effect on primary tumor growth. However, extensive metastasis was observed in functionalized scaffolds, and the highest levels for scaffolds that were in situ manipulated with receptor activator of nuclear factor kappa-B ligand (RANKL). We also applied this tissue-engineered bone marrow model in a prostate cancer and experimental metastasis setting. In summary, we were able to use tissue-engineered bone marrow to serve as a target or "trap" for metastasizing cancer cells. PMID:25771021

  17. SB-715992 in Treating Patients With Recurrent or Metastatic Head and Neck Cancer

    Science.gov (United States)

    2013-05-07

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Verrucous Carcinoma of the Larynx; Stage IV Verrucous Carcinoma of the Oral Cavity; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity

  18. Long-Time Survival of a Patient with Metastatic Pancreatic Cancer: A Case Report

    Directory of Open Access Journals (Sweden)

    Željko Soldić

    2011-08-01

    Full Text Available Pancreatic cancer is a malignant neoplasm of the pancreas. It does not cause any symptoms in the early stage, and later symptoms are nonspecific, thus the disease is usually diagnosed when already advanced. In 2008, pancreatic cancer ranked eighth on the list of the 10 most common cancers among men in Croatia and tenth on the list of the most common cancers among Croatian women. Pancreatic cancer has a poor prognosis, with a survival time of only 6–8 months for metastatic disease. Gemcitabine is the standard chemotherapeutic option. Other chemotherapeutic agents include5-fluorouracil and leucovorin. In this paper, we present a case of a patient diagnosed with locally advanced and metastatic pancreatic cancer, who is still alive and currently receives his fourth line of chemotherapy 5 years after the diagnosis. Following disease progression on gemcitabine chemotherapy, he was treated with chemoradiotherapy which, however, had no effect. We then applied cisplatin monochemotherapy which offered excellent disease control, was well tolerated by the patient and, although somewhat obsolete in this form, showed to be a valuable chemotherapeutic option.

  19. Bone pain induced by metastatic cancer: pathophysiology and treatment

    International Nuclear Information System (INIS)

    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)

  20. Systemic therapy for the treatment of hormone-sensitive metastatic prostate cancer: from intermittent androgen deprivation therapy to chemotherapy.

    Science.gov (United States)

    Liaw, Bobby C; Shevach, Jeffrey; Oh, William K

    2015-03-01

    Treatment of advanced prostate cancer has changed considerably in recent years, but the vast majority of advances have been made in patients with metastatic castration-resistant disease. There have been relatively fewer advances in the earlier, hormonally responsive stage of metastatic disease. Since the empiric establishment of androgen deprivation therapy as first-line therapy for metastatic prostate cancer decades ago, there have been multiple studies looking at variations of suppressing testosterone, but the overall paradigm has not been strongly challenged until more recently. In particular, the dramatic results reported by the CHAARTED trial not only bring chemotherapy to an arena historically dominated solely by hormonal therapy but also stimulate renewed efforts into improving upon our management of metastatic hormone-sensitive prostate cancer. PMID:25677235

  1. Advances in Variations of Estrogen Receptor, Progesterone Receptor and Human Epidermal Growth Factor Receptor-2 Status in Metastatic Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    Yuan Yuan; Zhang Lili

    2013-01-01

    Chemotherapy, endocrine therapy and molecular targeted therapy are vital means in the treatment of metastatic breast cancer (MBC), whose reasonable and standard applications are of great importance to prolong patients’ survival and improve the quality of life. The expressions of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2) present signiifcant differences between primary and metastatic breast cancer. However, these differences may affect the selection of MBC patients for therapeutic strategies and judgment on the prognosis. Hence, the relevant researches on variations of hormone receptors and HER-2 in primary and metastatic breast cancer, discordant causes of ER, PR and HER-2 expression in primary and metastatic lesions and clinical value of biopsy to the metastases are reviewed in the study.

  2. Evaluation of the prognosis of cancer patients with metastatic bone tumors based on serial bone scintigrams

    Energy Technology Data Exchange (ETDEWEB)

    Ohmori, Kazuo; Matsui, Hisao; Yasuda, Taketoshi; Kanamori, Masahiko; Yudoh, Kazuo; Seto, Hikaru; Tsuji, Haruo [Toyama Medical and Pharmaceutical University (Japan)

    1997-08-01

    We counted the lesions at the time of detection of bone metastases and calculated the rate of increase in the number of bone metastases from changes in serial bone scintigrams, and investigated the usefulness of serial scintigrams as a prognostic indicator in patients with metastatic bone tumors. Subjects were 112 patients with bone metastases from four types of primary lesion: 21 with prostate cancer, 27 breast cancer, 39 lung cancer and 25 stomach cancer. Of these, 18 (prostate), 19 (breast), nine (lung) and eight (stomach) underwent serial bone scintigrams in which bone metastases were first detected and identified as progressing. The numbers of lesions at the time of detection of bone metastases for prostate and stomach cancers were significantly greater than those for lung cancer. The rate of increase in the number of bone metastases for stomach cancer was significantly higher than that for prostate or breast cancers. There was no correlation between the survival time after the detection of bone metastases and the number of lesions at the time of detection in the four types of cancer. However, in prostate cancer, a negative correlation existed between the survival time after the detection of bone metastases and the rate of increase in the number of bone metastases. Thus, in patients with bone metastases from prostate cancer, it appears that the rate of increase in the number of bone metastases, estimated from serial bone scintigrams, was indicative of prognosis. (author)

  3. 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 metastati

  4. 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: 3.940, year: 2014

  5. Unusual pulmonary metastatic pattern in a case of pancreatic cancer

    OpenAIRE

    Shah, Nirav; Jubber, Akeel; Osman, Marcin; Syed, Imran

    2011-01-01

    The authors report the case of a cystic pancreatic cancer with pulmonary metastasis to illustrate the unusual radiographic halo-sign appearance of nodular/consolidative change with surrounding ground glass pattern and also to highlight the histopathological background underlying this pattern.

  6. Increased Expression of P-Glycoprotein Is Associated with Doxorubicin Chemoresistance in the Metastatic 4T1 Breast Cancer Model

    OpenAIRE

    Bao, Lili; Haque, Aliyya; Jackson, Kamilah; Hazari, Sidhartha; Moroz, Krzysztof; Jetly, Rachna; Dash, Srikanta

    2011-01-01

    Development of drug resistance is one of the major causes of breast cancer treatment failure. The goal of this study was to understand the chemoresistance mechanism using the highly metastatic 4T1 breast cancer model, which emulates stage IV breast cancer in humans. The metastatic 4T1 breast cancer cell line treated with either doxorubicin or 5-FU showed a concentration-dependent reduced cell proliferation, with induced G2-phase growth arrest (doxorubicin) or G1-phase growth arrest (5-FU). Do...

  7. Enhanced detection of metastatic prostate cancer cells in human plasma with lipid bodies staining

    International Nuclear Information System (INIS)

    Reprogramming of energy metabolism of malignant cancer cells confers competitive advantage in growth environments with limited resources. However, not every process of cancer development is associated with competition for resources. During hematogenous transport, cancer cells are exposed to high levels of oxygen and nutrients. Does energy metabolism of cancer cells change as a function of exposure to the bloodstream? Could such changes be exploited to improve the detection of circulating tumor cells (CTC)? These questions have clinical significance, but have not yet been sufficiently examined. The energy metabolism was examined as a function of incubation in nutrient-rich plasma in prostate metastatic cancer cells LNCaP and non-transformed prostate epithelial cells RWPE1. Uptake kinetics of a fluorescent glucose analog (2-NBD) and lipophilic dyes (DiD & Bodipy) were measured in both cell lines, as well as in peripheral blood mononuclear cells (PBMC). LNCaP cells exhibited hyper-acetylation of low molecular weight proteins compared to RWPE1 cells. Following plasma incubation, protein lysine acetylation profile was unchanged for LNCaP cells while significantly altered for RWPE1 cells. O-linked glycosylated protein profiles were different between LNCaP and RWPE1 cells and varied in both cell lines with plasma incubation. Maximal respiration or glycolytic capacities was unchanged in LNCaP cells and impaired in RWPE1 cells following plasma incubation. However, the uptake rates of 2-NBD and DiD were insufficient for discrimination of LNCaP, or RWPE1 cells from PBMC. On the other hand, both RWPE1 and LNCaP cells exhibited intracellular lipid bodies following plasma incubation; whereas, PBMC did not. The presence of lipid bodies in LNCaP cells permitted retention of Bodipy dye and allowed discrimination of LNCaP cells from PBMC with flow cytometry. Despite clear differences in energy metabolism, metastatic prostate cancer cells could not be efficiently distinguished from

  8. 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...... 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....

  9. Overexpression of Bcl-2 enhances metastatic potential of human bladder cancer cells

    OpenAIRE

    Miyake, H; Hara, I.; Yamanaka, K.; Gohji, K.; Arakawa, S; Kamidono, S.

    1999-01-01

    We investigated the effect of Bcl-2 expression on the metastatic process of bladder cancer cells by using the Bcl-2-transfected human bladder cancer cell lines (KoTCC-1/BH) and the control vector only-transfected cell line (KoTCC-1/C), which were generated in our previous study (Miyake et al (1998) Oncogene 16: 933–934). When they were injected intravenously into athymic nude mice, KoTCC-1/BH formed more than three times as many tumour nodules in the lungs as did KoTCC-1/C. In addition, tumou...

  10. 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)

    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 18F-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)

  11. Every Single Cell Clones from Cancer Cell Lines Growing Tumors In Vivo May Not Invalidate the Cancer Stem Cell Concept

    OpenAIRE

    Li, Fengzhi

    2009-01-01

    We present the result of our research on the tumorigenic ability of single cell clones isolated from an aggressive murine breast cancer cell line in a matched allografting mouse model. Tumor formation is basically dependent on the cell numbers injected per location. We argue that in vivo tumor formation from single cell clones, isolated in vitro from cancer cell lines, may not provide conclusive evidence to disprove the cancer stem cell (CSC) theory without additional data.

  12. Relaxins enhance growth of spontaneous murine breast cancers as well as metastatic colonization of the brain.

    Science.gov (United States)

    Binder, Claudia; Chuang, Eugenia; Habla, Christina; Bleckmann, Annalen; Schulz, Matthias; Bathgate, Ross; Einspanier, Almuth

    2014-01-01

    Relaxins are known for their tissue remodeling capacity which is also a hallmark of cancer progression. However, their role in the latter context is still unclear, particularly in breast cancer. In a mouse model with spontaneously arising breast cancer due to erbB2-overexpression we show that exposure to porcine relaxin results in significantly enhanced tumour growth as compared to control animals. This is accompanied by increased serum concentrations of progesterone and estradiol as well as elevated expression of the respective receptors and the relaxin receptor RXFP1 in the tumour tissue. It is also associated with enhanced infiltration by tumour-associated macrophages which are known to promote tumour progression. Additionally, we show in an ex vivo model of metastatic brain colonization that porcine relaxin as well as human brain-specific relaxin-3 promotes invasion into the brain tissue and enhance interaction of breast cancer cells with the resident brain macrophages, the microglia. Relaxin signaling is mediated via RXFP1, since R 3/I5, a specific agonist of the relaxin-3 receptor RXFP3 in the brain, does not significantly enhance invasion. Taken together, these findings strongly support a role of relaxins in the progression of breast cancer where they foster primary tumour growth as well as metastatic colonization by direct and indirect means. PMID:23963762

  13. Outcome of Surgical Treatment for Metastatic Vertebra Bone Tumor in Advanced Lung Cancer

    Directory of Open Access Journals (Sweden)

    Akiko Fukuhara

    2010-03-01

    Full Text Available Background: Spinal metastases of patients with advanced stage lung cancer are an important target for palliative therapy, because their incidence is high, and they often cause severe symptoms and worsen the quality of life. Surgery is one of the most effective treatment options, but the indication of surgery is unclear as the procedure is invasive and patients with spinal metastasis have a rather short life expectancy. Furthermore, there have been few studies that have focused on lung cancer with poor prognosis. Methods: We reviewed all of the cases of lung cancer from January 1999 to July 2007 in the Department of Respiratory Medicine, Kyoto University Hospital, Japan. Thirteen patients with metastatic spinal tumor of lung cancer underwent surgery, and all of them had a poor performance status score (3 or 4. Results: Neurological improvement by at least 1 Frankel grade was seen in 10 of 14 cases (71%. Improvement of the movement capacity was noted in 9 of 14 cases (64%, and pain improvement was noted in 12 of 14 (86%. Median postoperative survival was 5 months (1–25 months. In particular, the group with a good postoperative performance status score (0–2 was shown to have a better median postoperative survival of 13 months. Conclusions: Surgical treatment for symptomatic metastatic spinal tumor of lung cancer can improve quality of life in a substantially high percentage of patients. Surgery should be considered even if preoperative performance status is poor.

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

    OpenAIRE

    Bruce Hough; Adam Brufsky; Suzanne Lentzsch

    2010-01-01

    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...

  15. Capecitabine for locally advanced and metastatic colorectal cancer: A review

    OpenAIRE

    Koukourakis, Georgios V; Zacharias, Georgios; Tsalafoutas, John; Theodoridis, Dimitrios; Kouloulias, Vassilios

    2010-01-01

    Capecitabine (Xeloda®) is an oral fluoropyrimidine which is produced as a pro-drug of fluorouracil, and shows improved tolerability and intratumor drug concentrations following its tumor-specific conversion to the active drug. We have searched the Pubmed and Cochrane databases from 1980 to 2009 with the purpose of reviewing all available information on Capecitabine, focusing on its clinical effectiveness against colorectal cancer. Special attention has been paid to trials that compared Capeci...

  16. Feasibility of capecitabine immunotherapy in a taxane-refractory metastatic breast cancer patient: A rural cancer hospital experience

    Directory of Open Access Journals (Sweden)

    Vivek Tiwari

    2014-05-01

    Full Text Available To manage a metastatic cancer patient in a rural setting is a daunting task owing to the lack of resources and infrastructure. Intravenous chemotherapy (CT, with its debilitating side effects, often causes a decrease in the quality of life (QOL of the patient. When the treatment is of palliative intent, efforts should be made to provide maximum symptom relief to the patient, striking a balance between the patient’s wishes and a sound scientific rationale. We describe our experience with a patient with extensively metastatic breast cancer treated in our rural center with single-agent oral capecitabine, without development of any severe toxicity and with a significant improvement in disease process and patient’s performance status (PS.

  17. Feasibility of capecitabine monotherapy in a taxane refractory metastatic breast cancer patient: A rural cancer hospital experience

    Directory of Open Access Journals (Sweden)

    Vivek Tiwari

    2014-05-01

    Full Text Available To manage a metastatic cancer patient in a rural setting is a daunting task owing to the lack of resources and infrastructure. Intravenous chemotherapy (CT, with its debilitating side effects often causes a decrease in the quality of life (QOL of the patient. When the treatment is of palliative intent, efforts should be made to provide maximum symptom relief to the patient striking a balance between the patient’s wishes and a sound scientific rationale. We describe our experience with a patient with extensively metastatic breast cancer treated in our rural center with single agent oral capecitabine, without development of any severe toxicity and with a significant improvement in disease process and patient’s performance status (PS

  18. Neuromuscular electrical stimulation for a patient with metastatic lung cancer--a case report.

    Science.gov (United States)

    Crevenna, Richard; Marosi, Christine; Schmidinger, Manuela; Fialka-Moser, Veronika

    2006-09-01

    A 47-year-old female patient suffering from advanced lung cancer with metastatic bone and brain disease participated in a passive exercise program, consisting of neuromuscular electrical stimulation (NMES) five times a week, carried out for 4 weeks. After the training period, the results of the 6-min walk (420 m before and 603 m after the training period) have improved by 44%, which demonstrates the increase of physical performance (mobility, endurance capacity). The results of the "Timed up and go" indicate an improvement of mobility and functional health of skeletal muscles. Furthermore, the quality of life (QOL)-scales (assessed by using the SF-36 health survey) "Physical functioning", "Role-physical", "Mental health", "Role-emotional", "Vitality", "Bodily pain", and "General health" showed improvements after the intervention period. Feasibility, safety, and beneficial effects of the NMES program were proven for the patient in this case study. These findings indicate that NMES, initiated and executed with appropriate care, may serve as a useful supportive means of palliative treatment in some patients with advanced cancer and metastatic disease, especially in cases of metastatic involvement of the brain and of the skeletal system with the risk of seizures and pathological fractures where volitional training is not allowed. PMID:16523264

  19. Vascular Differences Detected by MRI for Metastatic Versus Nonmetastatic Breast and Prostate Cancer Xenografts

    Directory of Open Access Journals (Sweden)

    Zaver M. Bhujwalla

    2001-01-01

    Full Text Available Several studies have linked vascular density, identified in histologic sections, to “metastatic risk.” Functional information of the vasculature, not readily available from histologic sections, can be obtained with contrast-enhanced MRI to exploit for therapy or metastasis prevention. Our aims were to determine if human breast and prostate cancer xenograffs preselected for differences in invasive and metastatic characteristics established correspondingly different vascular volume and permeability, quantified here with noninvasive MRI of the intravascular contrast agent albumin-GdDTPA. Tumor vascular volume and permeability of human breast and prostate cancer xenografts were characterized using MRI. Parallel studies confirmed the invasive behavior of these cell lines. Vascular endothelial growth factor (VEGF expression in the cell lines was measured using ELISA and Western blots. Metastasis to the lungs was evaluated with spontaneous as well as experimental assay. Metastatic tumors formed vasculature with significantly higher permeability or vascular volume (P < .05, two-sided unpaired t test. The permeability profile matched VEGF expression. Within tumors, regions of high vascular volume usually exhibited low permeability whereas regions of low vascular volume exhibited high permeability. We observed that although invasion was necessary, without adequate vascularization it was not sufficient for metastasis to occur.

  20. Vertebral compression fractures after spine irradiation using conventional fractionation in patients with metastatic colorectal cancer

    International Nuclear Information System (INIS)

    To evaluate the risk of vertebral compression fracture (VCF) after conventional radiotherapy (RT) for colorectal cancer (CRC) with spine metastasis and to identify risk factors for VCF in metastatic and non-metastatic irradiated spines. We retrospectively reviewed 68 spinal segments in 16 patients who received conventional RT between 2009 and 2012. Fracture was defined as a newly developed VCF or progression of an existing fracture. The target volume included all metastatic spinal segments and one additional non-metastatic vertebra adjacent to the tumor-involved spines. The median follow-up was 7.8 months. Among all 68 spinal segments, there were six fracture events (8.8%) including three new VCFs and three fracture progressions. Observed VCF rates in vertebral segments with prior irradiation or pre-existing compression fracture were 30.0% and 75.0% respectively, compared with 5.2% and 4.7% for segments without prior irradiation or pre-existing compression fracture, respectively (both p < 0.05). The 1-year fracture-free probability was 87.8% (95% CI, 78.2-97.4). On multivariate analysis, prior irradiation (HR, 7.30; 95% CI, 1.31-40.86) and pre-existing compression fracture (HR, 18.45; 95% CI, 3.42-99.52) were independent risk factors for VCF. The incidence of VCF following conventional RT to the spine is not particularly high, regardless of metastatic tumor involvement. Spines that received irradiation and/or have pre-existing compression fracture before RT have an increased risk of VCF and require close observation.

  1. Vertebral compression fractures after spine irradiation using conventional fractionation in patients with metastatic colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ree, Woo Joong; Kim, Kyung Hwan; Chang, Jee Suk; Kim, Hyun Ju; Choi, Seo Hee; Koom, Woong Sub [Dept.of Radiation Oncology, Yonsei Cancer Center, Yonsei University Health System, Seoul (Korea, Republic of)

    2014-12-15

    To evaluate the risk of vertebral compression fracture (VCF) after conventional radiotherapy (RT) for colorectal cancer (CRC) with spine metastasis and to identify risk factors for VCF in metastatic and non-metastatic irradiated spines. We retrospectively reviewed 68 spinal segments in 16 patients who received conventional RT between 2009 and 2012. Fracture was defined as a newly developed VCF or progression of an existing fracture. The target volume included all metastatic spinal segments and one additional non-metastatic vertebra adjacent to the tumor-involved spines. The median follow-up was 7.8 months. Among all 68 spinal segments, there were six fracture events (8.8%) including three new VCFs and three fracture progressions. Observed VCF rates in vertebral segments with prior irradiation or pre-existing compression fracture were 30.0% and 75.0% respectively, compared with 5.2% and 4.7% for segments without prior irradiation or pre-existing compression fracture, respectively (both p < 0.05). The 1-year fracture-free probability was 87.8% (95% CI, 78.2-97.4). On multivariate analysis, prior irradiation (HR, 7.30; 95% CI, 1.31-40.86) and pre-existing compression fracture (HR, 18.45; 95% CI, 3.42-99.52) were independent risk factors for VCF. The incidence of VCF following conventional RT to the spine is not particularly high, regardless of metastatic tumor involvement. Spines that received irradiation and/or have pre-existing compression fracture before RT have an increased risk of VCF and require close observation.

  2. [Medical castration in the treatment of locally advanced or metastatic prostate cancer: an update].

    Science.gov (United States)

    Drouin, S-J; Rouprêt, M; Davin, J-L; Soulié, M

    2009-04-01

    Indications for hormonotherapy in prostate cancer are in deep mutation and are constantly evolving. Used initially (1941) in metastatic stages, hormone therapy is used nowadays in locally advanced prostate cancer and aggressive localized disease. Its prescription in association with radiotherapy or surgery has provided a benefit regarding survival free progression. The place of hormone therapy in localized prostate cancer is not well defined and the debate is still ongoing, especially in case of biochemical recurrence after irradiation or radical prostatectomy and even in neoadjuvant cases. Additional and further studies are ongoing and are strongly needed to establish new guidelines. Nevertheless, hormone therapy is not restricted any more to palliative cases and is part of the current therapeutic arsenal of the urologist for high risk localized and/or locally advanced prostate cancers. PMID:19465332

  3. Improvements in population-based survival of patients presenting with metastatic rectal cancer in the south of the Netherlands, 1992-2008

    NARCIS (Netherlands)

    V.E.P.P. Lemmens (Valery); N. de Haan (N.); H.J.T. Rutten (Harm); H. Martijn (Hendrik); O.J.L. Loosveld (Olaf); R.M.H. Roumen (Rudi); G.J.M. Creemers (Geert-Jan)

    2011-01-01

    textabstractWe analysed population-based treatment and survival data of patientswho presented with metastatic rectal cancer. All patients diagnosed with primary synchronous metastatic rectal cancer between 1992 and 2008 in the Eindhoven Cancer Registry area were included. Date of diagnosis was divid

  4. Lysine-Specific Demethylase 1 in Breast Cancer Cells Contributes to the Production of Endogenous Formaldehyde in the Metastatic Bone Cancer Pain Model of Rats

    OpenAIRE

    Jia Liu; Feng-Yu Liu; Zhi-Qian Tong; Zhi-Hua Li; Wen Chen; Wen-Hong Luo; Hui Li; Hong-Jun Luo; Yan Tang; Jun-Min Tang; Jie Cai; Fei-Fei Liao; You Wan

    2013-01-01

    BACKGROUND: Bone cancer pain seriously affects the quality of life of cancer patients. Our previous study found that endogenous formaldehyde was produced by cancer cells metastasized into bone marrows and played an important role in bone cancer pain. However, the mechanism of production of this endogenous formaldehyde by metastatic cancer cells was unknown in bone cancer pain rats. Lysine-specific demethylase 1 (LSD1) is one of the major enzymes catalyzing the production of formaldehyde. The ...

  5. 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.

  6. Transcatheter hepatic arterial chemoembolization in treatment of GIST with metastatic liver cancer

    International Nuclear Information System (INIS)

    Objective: To observe the clinical curative effect of transcatheter hepatic arterial chemoembolization (TACE) in treatment of gastrointestinal stromal tumors (GIST) with metastatic liver cancer. Methods: Four GIST patients with 19 lesions of liver metastasis were treated with 2-4 times of TACE. The diameters of the metastatic tumor were from 2-5 cm. FuDR, CDDP, EPI-ADM, together with lipiodol ultrafluid and gelatin sponge to from a mirture was prepared for arterial embolization. Results: DSA showed abundant tumor vasculature and tumor stain on hepatoarterial angiography. The size of tumor showed no decrease after TACE and lipiodol was cleared away in a short period. No patient achieved CR or PR until two of them received imatinib. Conclusions: TACE is not effective in treating hepatic metastasis from GIST shown in limited cases. (authors)

  7. Metastatic Breast Cancer Cells Collectively Invade Collagen by Following a Glucose Gradient

    Science.gov (United States)

    Sun, Bo; Austin, Robert; Liu, Liyu; Duclos, Guillaume; Lee, Jeongseog; Wu, Amy; Kam, Yooseok; Sontag, Eduardo; Stone, Howard; Sturm, James; Gatenby, Robert

    2013-03-01

    We show that MDA-MB-231 metastatic breast cancer cells collectively invade a three dimensional collagen matrix by following a glucose gradient. We observe that due to the 3D physical deformation of the matrix, as measured by the displacement of reporter beads within the matrix, there exists a long range deformation mechanical field inside the matrix which serves to couple the motions of the invading metastatic cell. The invasion front of the cells is a dynamic one, with different cells assuming the lead on a time scale of 24 hours due to certain cells having higher speeds of penetration, which are not sustained. The front cell leadership is dynamic presumably due to metabolic costs associated with the long range strain field which proceeds the invading cell front, which we have imaged using confocal imaging and marker beads imbedded in the collagen matrix. Sponsored by the NCI/NIH Physical Sciences Oncology Centers

  8. “Unique trend” and “contradictory trend” in discrimination of primary synchronous lung cancer and metastatic lung cancer

    International Nuclear Information System (INIS)

    Distinguishing between multiple primary lung cancers and metastatic tumors is often difficult when the tumor histology is same. Since genomic instability is a common feature of cancer, we hypothesized that independently arising neoplasms in an individual patient would exhibit measurable genomic variation, enabling discrimination of tumor lineage and relatedness. The feasibility of analyzing genomic instability expression profiles to distinguish multiple primary lung cancers from metastatic tumors was evaluated. This study enrolled 13 patients, with multiple primary lung cancers demonstrating with the histology, who underwent surgery between April 2003 and December 2012 at the Department of the Thoracic Surgery at West China Hospital in Sichuan province of China and 10 patients who were diagnosed as metastasis disease during the same period for comparison purposes. Genomic DNA from lung cancers from individual patients was analyzed by six microsatellites (D2S1363, D6S1056, D7S1824, D10S1239, D15S822, and D22S689) with PCR to identify discordant allelic variation. The experiments were approved by the West China Hospital Ethics committee (No.2013 (33)) and all patients agreed to participate in the study and signed an informed consent form. All of the 10 patients with distant metastasis showed a consistent consequence that we called “unique trend” between primary tumor and distant metastasis. The “trend” is representive in this study, which means that all alleles corresponding to six microsatellite markers were detected in DNA from primary tumors but were reduced or not observed in DNA from metastatic tumors. In the group of synchronous lung tumor with different histological types, the result showed a “contradictory trend”. Some alleles were detected in DNA from primary tumors but were reduced or not observed in DNA from metastatic tumors and other alleles corresponding to six microsatellite markers were detected in DNA from metastatic tumors but were

  9. Exome Sequencing of Cell-Free DNA from Metastatic Cancer Patients Identifies Clinically Actionable Mutations Distinct from Primary Disease.

    Directory of Open Access Journals (Sweden)

    Timothy M Butler

    Full Text Available 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.

  10. 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. PMID:26317216

  11. DEAD-box helicase DP103 defines metastatic potential of human breast cancers.

    Science.gov (United States)

    Shin, Eun Myoung; Hay, Hui Sin; Lee, Moon Hee; Goh, Jen Nee; Tan, Tuan Zea; Sen, Yin Ping; Lim, See Wee; Yousef, Einas M; Ong, Hooi Tin; Thike, Aye Aye; Kong, Xiangjun; Wu, Zhengsheng; Mendoz, Earnest; Sun, Wei; Salto-Tellez, Manuel; Lim, Chwee Teck; Lobie, Peter E; Lim, Yoon Pin; Yap, Celestial T; Zeng, Qi; Sethi, Gautam; Lee, Martin B; Tan, Patrick; Goh, Boon Cher; Miller, Lance D; Thiery, Jean Paul; Zhu, Tao; Gaboury, Louis; Tan, Puay Hoon; Hui, Kam Man; Yip, George Wai-Cheong; Miyamoto, Shigeki; Kumar, Alan Prem; Tergaonkar, Vinay

    2014-09-01

    Despite advancement in breast cancer treatment, 30% of patients with early breast cancers experience relapse with distant metastasis. It is a challenge to identify patients at risk for relapse; therefore, the identification of markers and therapeutic targets for metastatic breast cancers is imperative. Here, we identified DP103 as a biomarker and metastasis-driving oncogene in human breast cancers and determined that DP103 elevates matrix metallopeptidase 9 (MMP9) levels, which are associated with metastasis and invasion through activation of NF-κB. In turn, NF-κB signaling positively activated DP103 expression. Furthermore, DP103 enhanced TGF-β-activated kinase-1 (TAK1) phosphorylation of NF-κB-activating IκB kinase 2 (IKK2), leading to increased NF-κB activity. Reduction of DP103 expression in invasive breast cancer cells reduced phosphorylation of IKK2, abrogated NF-κB-mediated MMP9 expression, and impeded metastasis in a murine xenograft model. In breast cancer patient tissues, elevated levels of DP103 correlated with enhanced MMP9, reduced overall survival, and reduced survival after relapse. Together, these data indicate that a positive DP103/NF-κB feedback loop promotes constitutive NF-κB activation in invasive breast cancers and activation of this pathway is linked to cancer progression and the acquisition of chemotherapy resistance. Furthermore, our results suggest that DP103 has potential as a therapeutic target for breast cancer treatment. PMID:25083991

  12. 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

  13. Real Time Metastatic Route Tracking of Orthotopic PC-3-GFP Human Prostate Cancer Using Intravital Imaging.

    Science.gov (United States)

    Zhang, Yong; Wang, Xiaoen; Hoffman, Robert M; Seki, Naohiko

    2016-04-01

    The cellular basis of metastasis is poorly understood. An important step to understanding this process is to be able to visualize the routes by which cancer cells migrate from the primary tumor to various distant sites to eventually form metastasis. Our laboratory previously developed single-cell in vivo imaging using fluorescent proteins to label cancer cells. In the present study, using PC-3 human prostate cancer cells labeled with green fluorescent protein (GFP) and orthotopic tumor transplantation, we have imaged in live mice various highly diverse routes by which PC-3 cells metastasize superiorly and inferiorly to distant sites, including in the portal area, stomach area, and urogenital system. Imaging began at day 9, at which time distant metastasis had already occurred, and increased at each imaging point at days 10, 13, 14, and 16. Metastatic cells were observed migrating superiorly and inferiorly from the primary tumor as well as in lymphatic channels and trafficking in various organ systems demonstrating that PC-3 has multiple metastatic routes similar to hormone-independent advanced-stage prostate cancer in the clinic. PMID:26515240

  14. 186Re-HEDP for metastatic bone pain in breast cancer patients

    International Nuclear Information System (INIS)

    Two-thirds of patients with metastatic cancer suffer from pain. Pain originating from skeletal metastases is the most common form of cancer-related pain. Bone pain, often exacerbated by pressure or movement, limits the patient's autonomy and social life. Pain palliation with bone-seeking radiopharmaceuticals has proven to be an effective treatment modality in patients with metastatic bone pain. These bone-seeking radiopharmaceuticals are extremely powerful in treating scattered painful bone metastases, for which external beam radiotherapy is impossible because of the large field of irradiation. 186Re-hydroxyethylidene diphosphonate (HEDP) is a potentially useful radiopharmaceutical for this purpose, having numerous advantageous characteristics. Bone marrow toxicity is limited and reversible, which makes repetitive treatment safe. Studies have shown encouraging clinical results of palliative therapy using 186Re-HEDP, with an overall response rate of ca. 70% in painful bone metastases. It is effective for fast palliation of painful bone metastases from various tumours and the effect tends to last longer if patients are treated early in the course of their disease. 186Re-HEDP is at least as effective in breast cancer patients with painful bone metastases as in patients with metastatic prostate cancer. It is to be preferred to radiopharmaceuticals with a long physical half-life in this group of patients, who tend to have more extensive haematological toxicity since they have frequently been pretreated with bone marrow suppressive chemotherapy. This systemic form of radionuclide therapy is simple to administer and complements other treatment options. It has been associated with marked pain reduction, improved mobility in many patients, reduced dependence on analgesics, and improved performance status and quality of life. (orig.)

  15. First-line targeted therapies in the treatment of metastatic colorectal cancer – role of cetuximab

    Directory of Open Access Journals (Sweden)

    Giuseppe Tonini

    2009-04-01

    Full Text Available Giuseppe Tonini, Alice Calvieri, Bruno Vincenzi, Daniele SantiniMedical Oncology, University Campus Bio-Medico, Rome, ItalyAbstract: Worldwide, colorectal cancer (CRC is the fourth most commonly diagnosed malignant disease and the second leading cause of cancer-related death in Western nations. In 2008 there were an estimated 148,810 new cases and 49,960 deaths in the US. For several years different chemotherapeutic regimens, based on floropyrimidines, irinotecan and oxaliplatin, have been used in advanced CRC, but survival is still unsatisfactory. New targeted therapies, including drugs and monoclonal antibodies (MoABs , show great promise in the fight against CRC and have shown activity in different disease settings. Cetuximab, a chimeric IgG1 monoclonal antibody that binds to the extracellular domain of epidermal growth factor receptor (EGFR, is active in metastatic colorectal cancer (mCRC. As an IgG1 antibody, cetuximab may exert its antitumor efficacy through both EGFR antagonism and antibody-dependent cell-mediated cytotoxicity. The combination of this drug with classical chemotherapies has shown better clinical profiles reflected in an improvement in overall and progression-free survival. Clinical trials established the role of cetuximab, particularly with irinotecan, in irinotecan-refractory/heavily pretreated patients. Whereas cetuximab has a clear indication in the salvage setting, its role in first-line therapy remains investigational. It is particularly encouraging that cetuximab may enhance curative opportunities in patients with early metastatic disease, suggesting that adding cetuximab in first-line therapy may downstage disease in some patients, and, as a result, allow potentially curative resection of previously unresectable metastases. In this review we will focus on the main epidermal growth factor receptor inhibitors demonstrating clinical benefit, and the role of cetuximab in first-line treatment of metastatic CRC

  16. Metastatic Urothelial Carcinoma of the Prepuce and Glans Penis: Suspected Implantation of Non-Muscle-Invasive Bladder Cancer via Urine

    Directory of Open Access Journals (Sweden)

    Tomoyuki Makino

    2014-07-01

    Full Text Available Cutaneous metastatic implantation of non-muscle-invasive urothelial carcinoma via urine is a rare finding, and only few cases have been reported in the literature. Here, we present a case of metastatic urothelial carcinoma of the prepuce and glans penis, which was suspected to be an implantation of non-muscle-invasive bladder cancer via urine. The patient had pseudophimosis of the penis, and contact with urine containing urothelial carcinoma cells was considered to be the cause of the metastatic implantation.

  17. Graphene oxide-wrapped PEGylated liquid crystalline nanoparticles for effective chemo-photothermal therapy of metastatic prostate cancer cells.

    Science.gov (United States)

    Thapa, Raj Kumar; Youn, Yu Seok; Jeong, Jee-Heon; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

    2016-07-01

    Here, we report the preparation of PEGylated liquid crystalline nanoparticles (LCN) loaded with docetaxel (DTX) and wrapped with graphene oxide (GO), called PEG-GO/LCN/DTX, for effective chemo-photothermal therapy of metastatic prostate cancer cells. The prepared formulation exhibited a small particle size (prostate cancer cells and exhibited potent apoptotic and antimigration effects, mediated by the combination of the anticancer effects of DTX and the thermal heat induced by exposure of GO to NIR light. Taken together, our findings support that PEG-GO/LCN/DTX may be an effective system for treatment of metastatic prostate cancer. Moreover, the results establish a proof-of-concept for the potential chemo-photothermal functionality of PEG-GO/LCN/DTX. This hybrid system of LCN and GO could provide controlled and targeted drug delivery with enhanced NIR-induced thermal effects for effective treatment of metastatic cancers. PMID:27022866

  18. Gefitinib in Treating Patients With Metastatic or Unresectable Head and Neck Cancer or Non-Small Cell Lung Cancer

    Science.gov (United States)

    2013-01-11

    Anaplastic Thyroid Cancer; Insular Thyroid Cancer; Metastatic Parathyroid Cancer; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Non-small Cell Lung Cancer; Recurrent Parathyroid Cancer; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Thyroid Cancer; Recurrent Verrucous Carcinoma of the Larynx; Stage III Follicular Thyroid Cancer; Stage III Papillary Thyroid Cancer; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Larynx; Stage IIIB Non-small Cell Lung Cancer; Stage IV Lymphoepithelioma of the Nasopharynx; Stage IV Non-small Cell Lung Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Adenoid Cystic Carcinoma of the Oral Cavity; Stage IVA Basal Cell Carcinoma of the Lip; Stage IVA Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Follicular Thyroid Cancer; Stage IVA Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage IVA Lymphoepithelioma of the Oropharynx; Stage IVA Midline Lethal Granuloma of the Paranasal Sinus

  19. Metastatic breast cancer patients: attitudes toward tissue donation for rapid autopsy.

    Science.gov (United States)

    Achkar, Tala; Wilson, John; Simon, Jacqueline; Rosenzweig, Margaret; Puhalla, Shannon

    2016-01-01

    Rapid autopsy (RA) offers a unique opportunity to obtain a large amount of metastatic tissue at death in order to deepen existing understanding of cancer evolution and heterogeneity. In breast cancer, understanding metastasis is particularly valuable given that treatment regimens are based on the traditional hormone and HER2 receptor status as well as evolving genomic data of the primary tumor. We aimed to elucidate the attitudes and interests of patients with metastatic breast cancer (MBC) toward RA, and to identify associated demographic or disease characteristics that may influence patient attitudes and interest. Ninety-seven patients with MBC were surveyed over the course of 12 months at a large, urban comprehensive cancer center's breast cancer outpatient clinic. 93/97 patients completed the survey sufficiently to be included in the analysis. Fisher's exact test was employed for categorical variables, and t test and rank-sum tests for continuous variables. p values ≤0.05 were considered statistically significant. Of the 93 patients with MBC analyzed, 87 % were willing to donate tissue at death. Marital status and younger age were associated with willingness to donate (p = 0.000, p = 0.025, respectively). Race, employment status, religion/spirituality, and cancer subtype were not associated with likelihood of donating. Forty-five percent of patients felt that doctors should ask about RA at diagnosis of early-stage breast cancer rather than during late-stage disease. These data provide evidence that an RA program would be welcomed by patients and requires initiative by providers. PMID:26705147

  20. Metastatic Urothelial Carcinoma of the Prepuce and Glans Penis: Suspected Implantation of Non-Muscle-Invasive Bladder Cancer via Urine

    OpenAIRE

    Makino, Tomoyuki; Kitagawa, Yasuhide; Namiki, Mikio

    2014-01-01

    Abstract Cutaneous metastatic implantation of non-muscle-invasive urothelial carcinoma via urine is a rare finding, and only few cases have been reported in the literature. Here, we present a case of metastatic urothelial carcinoma of the prepuce and glans penis, which was suspected to be an implantation of non-muscle-invasive bladder cancer via urine. The patient had pseudophimosis of the penis, and contact with urine containing urothelial carcinoma cells was considered to be the cause of th...

  1. What Is the Role of Nanotechnology in Diagnosis and Treatment of Metastatic Breast Cancer? Promising Scenarios for the Near Future

    OpenAIRE

    Marta, Truffi; Luca, Sorrentino; Serena, Mazzucchelli; Luisa, Fiandra; Fabio, Corsi

    2016-01-01

    Metastatic breast cancer represents a diagnostic and therapeutic challenge due to tumor heterogeneity and to various physiological barriers that hinder drug delivery to the metastatic sites. To overcome these limitations, nanoformulated drugs have been developed and tested in preclinical studies, and few of them have been successfully translated into clinical practice. In particular, liposomal anthracyclines and nanoformulated albumin-bound paclitaxel have revealed an improved therapeutic ind...

  2. Correlation between MMPs and their inhibitors in breast cancer tumor tissue specimens and in cell lines with different metastatic potential

    OpenAIRE

    Silva Ismael DCG; Silva Fabricio C; Neto João S; Gomes Luciana R; Figueira Rita CS; Sogayar Mari C

    2009-01-01

    Abstract Background The metastatic disease rather than the primary tumor itself is responsible for death in most solid tumors, including breast cancer. The role of matrix metalloproteinases (MMPs), tissue inhibitors of MMPs (TIMPs) and Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) in the metastatic process has previously been established. However, in all published studies only a limited number of MMPs/MMP inhibitors was analyzed in a limited number of cell lines. Here, we ...

  3. Exome Sequencing of Cell-Free DNA from Metastatic Cancer Patients Identifies Clinically Actionable Mutations Distinct from Primary Disease

    OpenAIRE

    Butler, Timothy M.; Johnson-Camacho, Katherine; Peto, Myron; Wang, Nicholas J.; Macey, Tara A.; Korkola, James E.; Koppie, Theresa M.; Corless, Christopher L.; Joe W. Gray; 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, thro...

  4. Enhanced invasion of metastatic cancer cells via extracellular matrix interface.

    Directory of Open Access Journals (Sweden)

    Jiangrui Zhu

    Full Text Available Cancer cell invasion is a major component of metastasis and is responsible for extensive cell diffusion into and major destruction of tissues. Cells exhibit complex invasion modes, including a variety of collective behaviors. This phenomenon results in the structural heterogeneity of the extracellular matrix (ECM in tissues. Here, we systematically investigated the environmental heterogeneity facilitating tumor cell invasion via a combination of in vitro cell migration experiments and computer simulations. Specifically, we constructed an ECM microenvironment in a microfabricated biochip and successfully created a three-dimensional (3D funnel-like matrigel interface inside. Scanning electron microscopy demonstrated that the interface was at the interior defects of the nano-scale molecular anisotropic orientation and the localized structural density variations in the matrigel. Our results, particularly the correlation of the collective migration pattern with the geometric features of the funnel-like interface, indicate that this heterogeneous in vitro ECM structure strongly guides and promotes aggressive cell invasion in the rigid matrigel space. A cellular automaton model was proposed based on our experimental observations, and the associated quantitative analysis indicated that cell invasion was initiated and controlled by several mechanisms, including microenvironment heterogeneity, long-range cell-cell homotype and gradient-driven directional cellular migration. Our work shows the feasibility of constructing a complex and heterogeneous in vitro 3D ECM microenvironment that mimics the in vivo environment. Moreover, our results indicate that ECM heterogeneity is essential in controlling collective cell invasive behaviors and therefore determining metastasis efficiency.

  5. 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)

    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

  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. Integrated multimodal imaging of dynamic bone-tumor alterations associated with metastatic prostate cancer.

    Directory of Open Access Journals (Sweden)

    Jean-Christophe Brisset

    Full Text Available Bone metastasis occurs for men with advanced prostate cancer which promotes osseous growth and destruction driven by alterations in osteoblast and osteoclast homeostasis. Patients can experience pain, spontaneous fractures and morbidity eroding overall quality of life. The complex and dynamic cellular interactions within the bone microenvironment limit current treatment options thus prostate to bone metastases remains incurable. This study uses voxel-based analysis of diffusion-weighted MRI and CT scans to simultaneously evaluate temporal changes in normal bone homeostasis along with prostate bone metatastsis to deliver an improved understanding of the spatiotemporal local microenvironment. Dynamic tumor-stromal interactions were assessed during treatment in mouse models along with a pilot prospective clinical trial with metastatic hormone sensitive and castration resistant prostate cancer patients with bone metastases. Longitudinal changes in tumor and bone imaging metrics during delivery of therapy were quantified. Studies revealed that voxel-based parametric response maps (PRM of DW-MRI and CT scans could be used to quantify and spatially visualize dynamic changes during prostate tumor growth and in response to treatment thereby distinguishing patients with stable disease from those with progressive disease (p<0.05. These studies suggest that PRM imaging biomarkers are useful for detection of the impact of prostate tumor-stromal responses to therapies thus demonstrating the potential of multi-modal PRM image-based biomarkers as a novel means for assessing dynamic alterations associated with metastatic prostate cancer. These results establish an integrated and clinically translatable approach which can be readily implemented for improving the clinical management of patients with metastatic bone disease.

  8. Development of a highly metastatic model that reveals a crucial role of fibronectin in lung cancer cell migration and invasion

    International Nuclear Information System (INIS)

    The formation of metastasis is the most common cause of death in patients with lung cancer. A major implement to understand the molecular mechanisms involved in lung cancer metastasis has been the lack of suitable models to address it. In this study, we aimed at establishing a highly metastatic model of human lung cancer and characterizing its metastatic properties and underlying mechanisms. The human lung adeno-carcinoma SPC-A-1 cell line was used as parental cells for developing of highly metastatic cells by in vivo selection in NOD/SCID mice. After three rounds of selection, a new SPC-A-1sci cell line was established from pulmonary metastatic lesions. Subsequently, the metastatic properties of this cell line were analyzed, including optical imaging of in vivo metastasis, immunofluorescence and immunohistochemical analysis of several epithelial mesenchymal transition (EMT) makers and trans-well migration and invasion assays. Finally, the functional roles of fibronectin in the invasive and metastatic potentials of SPC-A-1sci cells were determined by shRNA analysis. A spontaneously pulmonary metastatic model of human lung adeno-carcinoma was established in NOD/SCID mice, from which a new lung cancer cell line, designated SPC-A-1sci, was isolated. Initially, the highly metastatic behavior of this cell line was validated by optical imaging in mice models. Further analyses showed that this cell line exhibit phenotypic and molecular alterations consistent with EMT. Compared with its parent cell line SPC-A-1, SPC-A-1sci was more aggressive in vitro, including increased potentials for cell spreading, migration and invasion. Importantly, fibronectin, a mesenchymal maker of EMT, was found to be highly expressed in SPC-A-1sci cells and down-regulation of it can decrease the in vitro and in vivo metastatic abilities of this cell line. We have successfully established a new human lung cancer cell line with highly metastatic potentials, which is subject to EMT and possibly

  9. Identification of Tetranectin as a Potential Biomarker for Metastatic Oral Cancer

    Directory of Open Access Journals (Sweden)

    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.

  10. The role and indications of aggressive locoregional therapy in metastatic inflammatory breast cancer.

    Science.gov (United States)

    Yan, Yi; Tang, Lili; Tong, Wei; Zhou, Jingyu

    2016-01-01

    We seek to confirm the effect and explore the indications of aggressive locoregional management in patients with metastatic inflammatory breast cancer (IBC). Between 2003 and 2014, we reviewed the records of 156 patients with metastatic IBC from five large centers of Breast Surgery in the region of central south of China. Clinicopathologic data were collected to access overall survival (OS), prognostic factors and the indications for locoregional treatment. 75 (48%) patients underwent aggressive locoregional therapy. Patients in locoregional therapy group had a median OS of 24 months compared with 17 months of those in no locoregional therapy group. 2-year OS rate of these two groups was 52% and 32%, separately. Locoregional therapy (HR = 0.556; 95% CI 0.385-0.803; p = 0.002) was confirmed to be an independent prognostic factor, which could significantly improve OS of patients with metastatic IBC. For locoregional therapy group, statistical differences were observed in all subgroups stratified by the factors that were significant in univariate analysis except in the subgroups of stable disease, Charlson comorbidity index ≥3 and cerebral metastasis. Therefore, systemic therapy efficacy, Charlson comorbidity index and cerebral metastasis status appeared to be important indexes for choice of locoregional therapy in different individuals. PMID:27174789

  11. Hypoxia increases the metastatic ability of breast cancer cells via upregulation of CXCR4

    Directory of Open Access Journals (Sweden)

    Redmond H Paul

    2010-05-01

    Full Text Available 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.

  12. 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.

  13. Hypoxia increases the metastatic ability of breast cancer cells via upregulation of CXCR4

    International Nuclear Information System (INIS)

    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. 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. 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. 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

  14. Can Biomarker Assessment on Circulating Tumor Cells Help Direct Therapy in Metastatic Breast Cancer?

    International Nuclear Information System (INIS)

    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

  15. Can Biomarker Assessment on Circulating Tumor Cells Help Direct Therapy in Metastatic Breast Cancer?

    Directory of Open Access Journals (Sweden)

    Natalie Turner

    2014-03-01

    Full Text Available 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.

  16. 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.

  17. Functional analysis of prognostic gene expression network genes in metastatic breast cancer models.

    Directory of Open Access Journals (Sweden)

    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.

  18. Role of capecitabine in treating metastatic colorectal cancer in Chinese patients

    Directory of Open Access Journals (Sweden)

    Wang F

    2014-04-01

    Full Text Available Feng Wang,* Feng-Hua Wang,* Long Bai, Rui-Hua XuDepartment of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China *These authors contributed equally to this workAbstract: The China Food and Drug Administration approved the use of capecitabine in patients with metastatic colorectal cancer (mCRC in 2004. This paper reviews the available information of capecitabine in Chinese patients with mCRC, focusing on its effectiveness and safety against mCRC. Identification of all eligible studies was made by searching the PubMed and Wanfang database from 2000 to 2013. Published data examining various aspects of clinical response and tolerability with capecitabine alone or in combination with other chemotherapeutic or biological agents for first- and second-line mCRC were examined. Capecitabine and its combination displayed high efficacy in Chinese patients with mCRC. Toxicities are generally manageable, and elderly patients can tolerate capecitabine well.Keywords: capecitabine, metastatic colorectal cancer, Chinese

  19. Changes of initiation, promotion and metastatic enzyme system in human breast cancer with the proton irradiation

    International Nuclear Information System (INIS)

    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.

  20. A phase II trial of a biweekly combination of paclitaxel and gemcitabine in metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Spinelli Gian

    2006-05-01

    Full Text Available Abstract Background Many emerging new drugs have recently been trialled for treatment of early and advanced breast cancer. Among these new agents paclitaxel and gemcitabine play a crucial role, mostly in patients with relapsed and metastatic disease after failure of chemotherapy with antracyclines. Methods A phase II study was started in order to evaluate the activity and toxicity of a combination of paclitaxel and gemcitabine in a biweekly schedule on metastatic breast cancer patients previously treated with antracyclines. Results Twenty-five patients received paclitaxel (150 mg/mq by 3-hours infusion, followed by gemcitabine (2000 mg/mq given as a 60 min i.v. infusion (day 1–14 for a maximum of eight cycles. In all patients treatment was evaluated for toxicity and efficacy; four patients (16% achieved a complete response, 12 (48% a partial response giving an overall objective response rate of 64%. Stable disease was documented in 5 patients (20% and progressive disease occurred in 4 patients (16%. Conclusion The schedule of treatment was safe and tolerable from a haematological and non-haematological point of view. These data confirm that the combination of gemcitabine and paclitaxel on a biweekly basis is an effective and well-tolerated regimen in breast cancer patients with prior therapeutic exposure to antracyclines.

  1. Green tea extract selectively targets nanomechanics of live metastatic cancer cells

    International Nuclear Information System (INIS)

    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.

  2. 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.

  3. Impact of Hypoxia on the Metastatic Potential of Human Prostate Cancer Cells

    International Nuclear Information System (INIS)

    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.

  4. Metastatic canine mammary carcinomas can be identified by a gene expression profile that partly overlaps with human breast cancer profiles

    International Nuclear Information System (INIS)

    Similar to human breast cancer mammary tumors of the female dog are commonly associated with a fatal outcome due to the development of distant metastases. However, the molecular defects leading to metastasis are largely unknown and the value of canine mammary carcinoma as a model for human breast cancer is unclear. In this study, we analyzed the gene expression signatures associated with mammary tumor metastasis and asked for parallels with the human equivalent. Messenger RNA expression profiles of twenty-seven lymph node metastasis positive or negative canine mammary carcinomas were established by microarray analysis. Differentially expressed genes were functionally characterized and associated with molecular pathways. The findings were also correlated with published data on human breast cancer. Metastatic canine mammary carcinomas had 1,011 significantly differentially expressed genes when compared to non-metastatic carcinomas. Metastatic carcinomas had a significant up-regulation of genes associated with cell cycle regulation, matrix modulation, protein folding and proteasomal degradation whereas cell differentiation genes, growth factor pathway genes and regulators of actin organization were significantly down-regulated. Interestingly, 265 of the 1,011 differentially expressed canine genes are also related to human breast cancer and, vice versa, parts of a human prognostic gene signature were identified in the expression profiles of the metastatic canine tumors. Metastatic canine mammary carcinomas can be discriminated from non-metastatic carcinomas by their gene expression profiles. More than one third of the differentially expressed genes are also described of relevance for human breast cancer. Many of the differentially expressed genes are linked to functions and pathways which appear to be relevant for the induction and maintenance of metastatic progression and may represent new therapeutic targets. Furthermore, dogs are in some aspects suitable as a

  5. Gemcitabine and AMG 479 in Metastatic Adenocarcinoma of the Pancreas

    Science.gov (United States)

    2014-03-28

    Adenocarcinoma of the Pancreas; Advanced Solid Tumors; Cancer; Cancer of Pancreas; Cancer of the Pancreas; Metastases; Metastatic Cancer; Metastatic Pancreatic Cancer; Pancreas Cancer; Pancreatic Cancer; Bone Metastases; Endocrine Cancer; Oncology; Oncology Patients; Solid Tumors; Advanced Malignancy

  6. Experience with S-1 in older Caucasian patients with metastatic colorectal cancer (mCRC)

    DEFF Research Database (Denmark)

    Winther, Stine Braendegaard; Zubcevic, Kanita; Qvortrup, Camilla;

    2016-01-01

    BACKGROUND: An aging population will increase the number of older patients with metastatic colorectal cancer (mCRC). However, there is limited knowledge about treatment in older patients as they are under-represented in clinical trials. The oral fluoropyrimidine S-1 is associated with a lower rate....... In general, therapy was well tolerated; main non-hematological toxicities were fatigue and diarrhea. CONCLUSION: S-1 monotherapy, SOx and IRIS were well tolerated for older patients with mCRC and could become alternative regimens in older mCRC patients. These regimens are now further evaluated...

  7. FCGR polymorphisms and cetuximab efficacy in chemorefractory metastatic colorectal cancer: an international consortium study

    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 of...... patients, respectively. Samples were collected from 1123 mCRC patients from 15 European centres treated with cetuximab alone or in combination with chemotherapy. Fc gamma receptor (FCGR) status was centrally genotyped. Two additional externally genotyped series were included. RESULTS: Incidences of FCGR2A...

  8. A systematic review on topoisomerase 1 inhibition in the treatment of metastatic breast cancer

    DEFF Research Database (Denmark)

    Kümler, Iben; Brünner, Nils; Stenvang, Jan;

    2013-01-01

    Following treatment with anthracyclines and taxanes, few established options exist for the treatment of metastatic breast cancer (MBC). Although the topoisomerase 1 inhibitors irinotecan, etirinotecan, and topotecan have been used in clinical trials on MBC, the drugs have never been introduced...... showed very limited effect. Topotecan was studied in combination with either another chemotherapeutic or a biologic agent in two trials, both studies failing to show any effect of topotecan. The most common grade 3 and 4 adverse events (AE) for irinotecan were neutropenia, diarrhea, and nausea...

  9. Symptom burden & quality of life among patients receiving second-line treatment of metastatic colorectal cancer

    OpenAIRE

    Walker Mark S; Pharm Elaine; Kerr Jiandong; Yim Yeun; Stepanski Edward J; Schwartzberg Lee S

    2012-01-01

    Abstract Background Bevacizumab (B) and cetuximab (C) are both approved for use in the treatment of metastatic colorectal cancer (mCRC) in the second-line. We examined patient reported symptom burden during second-line treatment of mCRC. Methods Adult mCRC patients treated in the second-line setting with a regimen that included B, C, or chemotherapy only (O) and who had completed ≥ 1 Patient Care Monitor (PCM) surveys as part of routine clinical care were drawn from the ACORN Data Warehouse. ...

  10. Molecular biology of breast cancer metastasis: Clinical implications of experimental studies on metastatic inefficiency

    International Nuclear Information System (INIS)

    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

  11. TH-E-BRF-08: Subpopulations of Similarly-Responding Lesions in Metastatic Prostate Cancer

    International Nuclear Information System (INIS)

    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

  12. Intraarticular hemorrhage due to bevacizumab in a patient with metastatic colorectal cancer: a case report

    Directory of Open Access Journals (Sweden)

    Uysal Mukremin

    2012-07-01

    Full Text Available Abstract Introduction Bevacizumab is a monoclonal antibody against vascular endothelial growth factor. It is widely used in the treatment of metastatic colorectal cancer. It has some specific side effects including severe bleeding, wound healing problems, gastrointestinal perforation, proteinuria and hypertension. Case presentation We present the case of a 65-year old Asian man with synovial metastasis of the knee who experienced intraarticular hemorrhage after bevacizumab treatment. He presented with monoarthritis of the left knee. Conclusion Bevacizumab-related hemorrhage can cause serious morbidity and unusual sites of hemorrhage may be seen.

  13. Chemotherapy and Functional Medicine in a Patient With Metastatic Breast Cancer: A Case Report.

    Science.gov (United States)

    Taxman, Elliot T; Conlon, Erin D; Speers, Alex; Dismuke, Kristin L; Heyman, Tonya S; Taxman, Thomas L

    2016-03-01

    More than one-half of all cancer patients use some combination of conventional and complementary medicine, but exactly how this is done and what the outcomes include are poorly understood. This case study reports the successful treatment of metastatic invasive ductal breast carcinoma by 2 physician groups with treatments that combined conventional chemotherapy with nutritional support guided by nutritional and digestive laboratory testing. The goal of minimizing side effects and enhancing outcomes was achieved in this patient who did not receive radiation therapy and is almost 3 y posttreatment with no evidence of recurrence. PMID:27053933

  14. [Management of complications after residual tumor resection for metastatic testicular cancer].

    Science.gov (United States)

    Lusch, A; Zaum, M; Winter, C; Albers, P

    2014-07-01

    Residual tumor resection (RTR) in patients with metastatic testicular cancer plays a pivotal role in a multimodal treatment. It can be performed unilaterally or as an extended bilateral RTR. Additional surgical procedures might be necessary, such as nephrectomy, splenectomy, partial colectomy, or vascular interventions with possible caval resection, cavotomy, or aortic resection with aortic grafting. Consequently, several complications can be seen in the intra- and postoperative course, most common of which are superficial wound infections, intestinal paralysis, lymphocele, and chylous ascites. We sought to describe complication management and how to prevent complications before they arise. PMID:25023235

  15. 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.

  16. Prostate radiation in non-metastatic castrate refractory prostate cancer provides an interesting insight into biology of prostate cancer

    International Nuclear Information System (INIS)

    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. 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. 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

  17. 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...

  18. 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.

  19. Exon-level transcriptome profiling in murine breast cancer reveals splicing changes specific to tumors with different metastatic abilities.

    Directory of Open Access Journals (Sweden)

    Amandine Bemmo

    Full Text Available BACKGROUND: Breast cancer is the second most frequent type of cancer affecting women. We are increasingly aware that changes in mRNA splicing are associated with various characteristics of cancer. The most deadly aspect of cancer is metastasis, the process by which cancer spreads from the primary tumor to distant organs. However, little is known specifically about the involvement of alternative splicing in the formation of macroscopic metastases. Our study investigates transcript isoform changes that characterize tumors of different abilities to form growing metastases. METHODS AND FINDINGS: To identify alternative splicing events (ASEs that are associated with the fully metastatic phenotype in breast cancer, we used Affymetrix Exon Microarrays to profile mRNA isoform variations genome-wide in weakly metastatic (168FARN and 4T07 and highly metastatic (4T1 mammary carcinomas. Statistical analysis identified significant expression changes in 7606 out of 155,994 (4% exons and in 1725 out of 189,460 (1% intronic regions, which affect 2623 out of 16,654 (16% genes. These changes correspond to putative alternative isoforms-several of which are novel-that are differentially expressed between tumors of varying metastatic phenotypes. Gene pathway analysis showed that 1224 of genes expressing alternative isoforms were involved in cell growth, cell interactions, cell proliferation, cell migration and cell death and have been previously linked to cancers and genetic disorders. We chose ten predicted splice variants for RT-PCR validation, eight of which were successfully confirmed (MED24, MFI2, SRRT, CD44, CLK1 and HNRNPH1. These include three novel intron retentions in CD44, a gene in which isoform variations have been previously associated with the metastasis of several cancers. CONCLUSION: Our findings reveal that various genes are differently spliced and/or expressed in association with the metastatic phenotype of tumor cells. Identification of

  20. A case report on efficacy of Abound™ for anti-EGFR antibody-associated skin disorder in metastatic colon cancer

    OpenAIRE

    Matsuhashi, Nobuhisa; Takahashi, Takao; Nonaka,kenichi; ICHIKAWA, KENGO; Yawata, Kazunori; Tanahashi, Toshiyuki; Imai, Hisashi; Sasaki, Yoshiyuki; Tanaka, Yoshihiro; Okumura, Naoki; Yamaguchi, Kazuya; Osada, Shinji; Yoshida, Kazuhiro

    2014-01-01

    Background Panitumumab is a full human epidermal growth factor receptor (EGFR) monoclonal antibody, an agent for metastatic colorectal cancer therapy. One of the most general adverse events of anti-EGFR monoclonal antibody therapy is skin disorder. At the present time, although prophylaxis of skin disorder is important for continuation of cancer therapy, there are no effective precautionary treatments. Case presentation A 73-year-old male with sigmoid colon cancer and synchronous lung metasta...

  1. Decreased Autocrine EGFR Signaling in Metastatic Breast Cancer Cells Inhibits Tumor Growth in Bone and Mammary Fat Pad

    OpenAIRE

    Nickerson, Nicole K.; Mohammad, Khalid S.; Gilmore, Jennifer L.; Crismore, Erin; Bruzzaniti, Angela; Guise, Theresa A.; Foley, John

    2012-01-01

    Breast cancer metastasis to bone triggers a vicious cycle of tumor growth linked to osteolysis. Breast cancer cells and osteoblasts express the epidermal growth factor receptor (EGFR) and produce ErbB family ligands, suggesting participation of these growth factors in autocrine and paracrine signaling within the bone microenvironment. EGFR ligand expression was profiled in the bone metastatic MDA-MB-231 cells (MDA-231), and agonist-induced signaling was examined in both breast cancer and oste...

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

    OpenAIRE

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

    2012-01-01

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

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

    OpenAIRE

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

    2013-01-01

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

  4. Quantitative proteomic study of human prostate cancer cells with different metastatic potentials.

    Science.gov (United States)

    Li, Qun; Li, Yilei; Wang, Yanying; Cui, Zheng; Gong, Lulu; Qu, Zhigang; Zhong, Yanping; Zhou, Jun; Zhou, Ying; Gao, Yong; Li, Yulin

    2016-04-01

    Metastatic dissemination is a feature of most cancers including prostate cancer (PCa), and is the main cause of treatment failure and mortality. The aim of the study is to explore the mechanisms of PCa metastasis and to search for potential prognostic markers using proteomics. Two-dimensional fluorescent differential gel electrophoresis (2D-DIGE) was used to quantify proteins in normal prostate epithelial cells, bone metastasis-derived PC-3 cells, and visceral metastasis-derived PC-3M cells. Metastatic potential was confirmed by flow cytometry, electron microscopy, proliferating cell nuclear antigen assay, and wound healing assay. Differential protein expression was compared between PCa cells with different metastatic potentials (LNcap, DU145, PC-3 and PC-3M) and normal prostate epithelial cells (RWPE-1). Selected candidate proteins in human prostate tissues were analyzed using GOA, UniProt and GeneCards analyses. Eighty-six proteins were differentially expressed between cell lines (>1.5-fold, P<0.05). Among them, twelve proteins were identified by MALDI-TOF-MS. One protein was upregulated in normal prostate epithelial cells, nine proteins were upregulated in PC-3, and two proteins were upregulated in PC-3M. Proteins were divided into five groups according to their functions. The SETDB1 protein was closely associated with the prognosis of PCa. Bioinformatics suggested that SETDB1 might promote PCa bone metastasis through the WNT pathway. In conclusion, SETDB1 might be associated with the development of bone metastases from PCa. Further study is necessary to assess its exact role in PCa. PMID:26846621

  5. Massive portal vein tumor thrombus from colorectal cancer without any metastatic nodules in the liver parenchyma: report of a case

    Directory of Open Access Journals (Sweden)

    Yasushi Rino

    2011-10-01

    Full Text Available Metastatic lesions in the liver derived from colorectal cancer rarely invade the portal vein macroscopically. Portal vein tumor thrombus is commonly associated with hepatocellular carcinoma. Colorectal liver metastases are usually accompanied by microscopic tumor invasion into the intrahepatic portal vein, and the incidence of macroscopic tumor thrombus in the trunk of the portal vein is rare. Here, we provide unique appearance of metastatic colorectal cancer. To the best of our knowledge, macroscopically, the right portal vein filled with the tumor thrombus without any tumor in liver parenchyma has been quite rare.

  6. Proactive strategies for regorafenib in metastatic colorectal cancer: implications for optimal patient management

    International Nuclear Information System (INIS)

    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

  7. Korean medicine therapy as a substitute for chemotherapy for metastatic breast cancer: a case report.

    Science.gov (United States)

    Lee, Dong-Hyun; Kim, Sung-Su; Seong, Shin; Kim, Nari; Han, Jae-Bok

    2015-01-01

    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. PMID:25848354

  8. Administration of cetuximab every 2 weeks in the treatment of metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Tabernero, Josep; Pfeiffer, Per; Cervantes, Andrés

    2008-01-01

    The primary purpose of this paper is to present the available evidence for the administration of cetuximab on an every-2-weeks basis in combination with irinotecan in metastatic colorectal cancer (mCRC). Cetuximab is an epidermal growth factor receptor-targeted IgG(1) monoclonal antibody that is ......The primary purpose of this paper is to present the available evidence for the administration of cetuximab on an every-2-weeks basis in combination with irinotecan in metastatic colorectal cancer (mCRC). Cetuximab is an epidermal growth factor receptor-targeted IgG(1) monoclonal antibody...... that is approved for use in combination with irinotecan or as monotherapy in the treatment of mCRC. The currently approved dosing regimen for cetuximab is a 400-mg/m(2) initial dose followed by 250 mg/m(2) weekly. Many commonly used chemotherapy agents for mCRC (including irinotecan alone or in combination with 5....... The efficacy and safety of the every-2-weeks dosing regimen were similar to those reported for the approved weekly dosing regimen. The indication from these preliminary findings is that every-2-weeks administration of cetuximab (500 mg/m(2)) may be a potentially convenient alternative to the approved weekly...

  9. 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.

  10. Optimal Sequencing of New Drugs in Metastatic Castration-Resistant Prostate Cancer: Dream or Reality?

    Science.gov (United States)

    Caffo, Orazio; Lunardi, Andrea; Trentin, Chiara; Maines, Francesca; Veccia, Antonello; Galligioni, Enzo

    2016-01-01

    The availability of new drugs capable of improving the overall survival of patients with metastatic castration-resistant prostate cancer has led to the possibility of using them sequentially in the hope of obtaining a cumulative survival benefit. The new agents have already been administered as third-line treatments in patients who have previously received them as second line in everyday clinical practice, but the efficacy of this practice is not yet supported by clinical trial data, and evidence of possible cross-resistance has reinforced the debate concerning the best sequence to use in order to maximise the benefit. Furthermore, the situation is further complicated by the possibility of administering new hormonal agents to chemotherapy-naïve patients, and novel chemotherapeutic agents to hormone-sensitive patients. This article critically reviews the available data concerning the sequential use of new drugs, and discusses the real evidence concerning their optimal positioning in the therapeutic strategy of metastatic castration-resistant prostate cancer. PMID:26721408

  11. THE GENE EXPRESSION PROFILE OF HIGHLY METASTATIC HUMAN OVARIAN CANCER CELL LINE BY GENE CHIP

    Institute of Scientific and Technical Information of China (English)

    吕桂泉; 许沈华; 牟瀚舟; 朱赤红; 羊正炎; 高永良; 楼洪坤; 刘祥麟; 杨文; 程勇

    2001-01-01

    To study the gene expression of high metastatic human ovarian carcinoma cell line (HO-8910PM) and to screen for novel metastasis- associated genes by cDNA microarray. Methods: The cDNA was retro-transcribed from equal quantity mRNA derived from tissues of highly metastatic ovarian carcinoma cell line and normal ovarian, and was labeled with Cy5 and Cy3 fluorescence as probes. The mixed probes were hybridized with BioDoor 4096 double dot human whole gene chip. The chip was scanned by scanArray 3000 laser scanner. The acquired image was analyzed by ImaGene 3.0 software. Results: By applying the cDNA microarray we found: A total of 323 genes whose expression level were 3 times higher or lower in HO-8910PM cell than normal ovarian epithelium cell were screened out, with 71 higher and 252 lower respectively. Among these 10 were new genes. 67 genes showed expression difference bigger than 6 times between HO-8910PM cell and normal ovarian epithelium cell, among these genes 12 were higher, 55 lower, and two new genes were found. Conclusion: cDNA microarray technique is effective in screening the differentially expressed genes between human ovarian cancer cell line (HO-8910PM) and normal ovarian epithelium cell. Using the cDNA microarray to analyze of human ovarian cancer cell line gene expression profile difference will help the gene diagnosis, treatment and protection.

  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. PMID:27318443

  13. Automatic FDG-PET-based tumor and metastatic lymph node segmentation in cervical cancer

    Science.gov (United States)

    Arbonès, Dídac R.; Jensen, Henrik G.; Loft, Annika; Munck af Rosenschöld, Per; Hansen, Anders Elias; Igel, Christian; Darkner, Sune

    2014-03-01

    Treatment of cervical cancer, one of the three most commonly diagnosed cancers worldwide, often relies on delineations of the tumour and metastases based on PET imaging using the contrast agent 18F-Fluorodeoxyglucose (FDG). We present a robust automatic algorithm for segmenting the gross tumour volume (GTV) and metastatic lymph nodes in such images. As the cervix is located next to the bladder and FDG is washed out through the urine, the PET-positive GTV and the bladder cannot be easily separated. Our processing pipeline starts with a histogram-based region of interest detection followed by level set segmentation. After that, morphological image operations combined with clustering, region growing, and nearest neighbour labelling allow to remove the bladder and to identify the tumour and metastatic lymph nodes. The proposed method was applied to 125 patients and no failure could be detected by visual inspection. We compared our segmentations with results from manual delineations of corresponding MR and CT images, showing that the detected GTV lays at least 97.5% within the MR/CT delineations. We conclude that the algorithm has a very high potential for substituting the tedious manual delineation of PET positive areas.

  14. Cytotoxic chemotherapy in the contemporary management of metastatic castration-resistant prostate cancer (mCRPC).

    Science.gov (United States)

    Sonpavde, Guru; Wang, Christopher G; Galsky, Matthew D; Oh, William K; Armstrong, Andrew J

    2015-07-01

    For several years, docetaxel was the only treatment shown to improve survival of patients with metastatic castration-resistant prostate cancer (mCRPC). There are now several novel agents available, although chemotherapy with docetaxel and cabazitaxel continues to play an important role. However, the increasing number of available agents will inevitably affect the timing of chemotherapy and therefore it may be important to offer this approach before declining performance status renders patients ineligible for chemotherapy. Patient selection is also important to optimise treatment benefit. The role of predictive biomarkers has assumed greater importance due to the development of multiple agents and resistance to available agents. In addition, the optimal sequence of treatments remains undefined and requires further study in order to maximize long-term outcomes. We provide an overview of the clinical data supporting the role of chemotherapy in the treatment of mCRPC and the emerging role in metastatic castration-sensitive prostate cancer. We review the key issues in the management of patients including selection of patients for chemotherapy, when to start chemotherapy, and how best to sequence treatments to maximise outcomes. In addition, we briefly summarise the promising new chemotherapeutic agents in development in the context of emerging therapies. PMID:25046451

  15. Uncovering cancer cell behavioral phenotype in 3-D in vitro metastatic landscapes

    Science.gov (United States)

    Liu, Liyu; Sun, Bo; Duclos, Guillaume; Kam, Yoonseok; Gatenby, Robert; Stone, Howard; Austin, Robert

    2012-02-01

    One well-known fact is that cancer cell genetics determines cell metastatic potentials. However, from a physics point of view, genetics as cell properties cannot directly act on metastasis. An agent is needed to unscramble the genetics first before generating dynamics for metastasis. Exactly this agent is cell behavioral phenotype, which is rarely studied due to the difficulties of real-time cell tracking in in vivo tissue. Here we have successfully constructed a micro in vitro environment with collagen based Extracellular Matrix (ECM) structures for cell 3-D metastasis. With stable nutrition (glucose) gradient inside, breast cancer cell MDA-MB-231 is able to invade inside the collagen from the nutrition poor site towards the nutrition rich site. Continuous confocal microscopy captures images of the cells every 12 hours and tracks their positions in 3-D space. The micro fluorescent beads pre-mixed inside the ECM demonstrate that invasive cells have altered the structures through mechanics. With the observation and the analysis of cell collective behaviors, we argue that game theory may exist between the pioneering cells and their followers in the metastatic cell group. The cell collaboration may explain the high efficiency of metastasis.

  16. Clinical Response of Metastatic Breast Cancer to Multi-targeted Therapeutic Approach: A Single Case Report

    Directory of Open Access Journals (Sweden)

    Christian Meiners

    2011-03-01

    Full Text Available The present article describes the ongoing (partial remission of a female patient (41 years old from estrogen receptor (ER-positive/progesterone receptor (PR-negative metastatic breast cancer in response to a combination treatment directed towards the revitalization of the mitochondrial respiratory chain (oxidative phosphorylation, the suppression of NF-kappaB as a factor triggering the inflammatory response, and chemotherapy with capecitabine. The reduction of tumor mass was evidenced by a continuing decline of CA15-3 and CEA tumor marker serum levels and 18FDG-PET-CT plus magnetic resonance (MR imaging. It is concluded that such combination treatment might be a useful option for treating already formed metastases and for providing protection against the formation of metastases in ER positive breast cancer. The findings need to be corroborated by clinical trials. Whether similar results can be expected for other malignant tumor phenotypes relying on glycolysis as the main energy source remains to be elucidated.

  17. Clinical Response of Metastatic Breast Cancer to Multi-targeted Therapeutic Approach: A Single Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Meiners, Christian [Gautinger Straße 3b, D-82234 Wessling (Germany)

    2011-03-17

    The present article describes the ongoing (partial) remission of a female patient (41 years old) from estrogen receptor (ER)-positive/progesterone receptor (PR)-negative metastatic breast cancer in response to a combination treatment directed towards the revitalization of the mitochondrial respiratory chain (oxidative phosphorylation), the suppression of NF-kappaB as a factor triggering the inflammatory response, and chemotherapy with capecitabine. The reduction of tumor mass was evidenced by a continuing decline of CA15-3 and CEA tumor marker serum levels and {sup 18}FDG-PET-CT plus magnetic resonance (MR) imaging. It is concluded that such combination treatment might be a useful option for treating already formed metastases and for providing protection against the formation of metastases in ER positive breast cancer. The findings need to be corroborated by clinical trials. Whether similar results can be expected for other malignant tumor phenotypes relying on glycolysis as the main energy source remains to be elucidated.

  18. Challenging chemoresistant metastatic colorectal cancer: therapeutic strategies from the clinic and from the laboratory.

    Science.gov (United States)

    Sartore-Bianchi, A; Loupakis, F; Argilés, G; Prager, G W

    2016-08-01

    As survival has improved for patients with metastatic colorectal cancer (mCRC), there is an increasing need for effective and well-tolerated third-line and subsequent-lines of treatment. Despite recent advances with the development of new-targeted therapies in this setting, there remains an unmet need to exploit oncogenic drivers of colorectal cancer and overcome acquired resistance. Potential treatment strategies include revisiting old targets such as human epidermal growth factor receptor 2, RAS, and BRAF and investigating new targets such as c-MET, the PI3 kinase, and Wnt pathways, and also the use of immune-checkpoint inhibitors. Here, we review recent phase III trials exploring approved agents, early trials investigating new drugs for chemorefractory mCRC, and the potential of capturing tumour dynamics during its evolution by liquid biopsy analysis. PMID:27154421

  19. 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

    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......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...

  20. Clinical Response of Metastatic Breast Cancer to Multi-targeted Therapeutic Approach: A Single Case Report

    International Nuclear Information System (INIS)

    The present article describes the ongoing (partial) remission of a female patient (41 years old) from estrogen receptor (ER)-positive/progesterone receptor (PR)-negative metastatic breast cancer in response to a combination treatment directed towards the revitalization of the mitochondrial respiratory chain (oxidative phosphorylation), the suppression of NF-kappaB as a factor triggering the inflammatory response, and chemotherapy with capecitabine. The reduction of tumor mass was evidenced by a continuing decline of CA15-3 and CEA tumor marker serum levels and 18FDG-PET-CT plus magnetic resonance (MR) imaging. It is concluded that such combination treatment might be a useful option for treating already formed metastases and for providing protection against the formation of metastases in ER positive breast cancer. The findings need to be corroborated by clinical trials. Whether similar results can be expected for other malignant tumor phenotypes relying on glycolysis as the main energy source remains to be elucidated

  1. Ex vivo electrical impedance measurements on excised hepatic tissue from human patients with metastatic colorectal cancer

    International Nuclear Information System (INIS)

    Point-wise ex vivo electrical impedance spectroscopy measurements were conducted on excised hepatic tissue from human patients with metastatic colorectal cancer using a linear four-electrode impedance probe. This study of 132 measurements from 10 colorectal cancer patients, the largest to date, reports that the equivalent electrical conductivity for tumor tissue is significantly higher than normal tissue (p < 0.01), ranging from 2–5 times greater over the measured frequency range of 100 Hz–1 MHz. Difference in tissue electrical permittivity is also found to be statistically significant across most frequencies. Furthermore, the complex impedance is also reported for both normal and tumor tissue. Consistent with trends for tissue electrical conductivity, normal tissue has a significantly higher impedance than tumor tissue (p < 0.01), as well as a higher net capacitive phase shift (33° for normal liver tissue in contrast to 10° for tumor tissue). (paper)

  2. Noninvasive Optical Tracking of Red Fluorescent Protein-Expressing Cancer Cells in a Model of Metastatic Breast Cancer

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    Paul T. Winnard, Jr.

    2006-10-01

    Full Text Available We have evaluated the use of the Xenogen IVIS 200 imaging system for real-time fluorescence protein- based optical imaging of metastatic progression in live animals. We found that green fluorescent protein- expressing cells (100 × 106 were not detectable in a mouse cadaver phantom experiment. However, a 10-fold lower number of tdTomato-expressing cells were easily detected. Mammary fat pad xenografts of stable MDA-MB-231-tdTomato cells were generated for the imaging of metastatic progression. At 2 weeks postinjection, barely palpable tumor burdens were easily detected at the sites of injection. At 8 weeks, a small contralateral mammary fat pad metastasis was imaged and, by 13 weeks, metastases to lymph nodes were detectable. Metastases with nodular composition were detectable within the rib cage region at 15 weeks. 3-D image reconstructions indicated that the detection of fluorescence extended to approximately 1 cm below the surface. A combination of intense tdTomato fluorescence, imaging at ≥ 620 nm (where autofluorescence is minimized, the sensitivity of the Xenogen imager made this possible. This study demonstrates the utility of the noninvasive optical tracking of cancer cells during metastatic progression with endogenously expressed fluorescence protein reporters using detection wavelengths of ≥ 620 nm.

  3. Metastatic Cancer

    Science.gov (United States)

    ... Breast Bone, brain, liver, lung Colorectal Liver, lung, peritoneum Kidney Adrenal gland , bone, brain, liver, lung Lung ... brain, liver, lung, skin/muscle Ovary Liver, lung, peritoneum Pancreas Liver, lung, peritoneum Prostate Adrenal gland, bone, ...

  4. 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

  5. Panitumumab: the evidence for its use in the treatment of metastatic colorectal cancer

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    Rossana Berardi

    2010-09-01

    Full Text Available Rossana Berardi1, Azzurra Onofri2, Mirco Pistelli2, Elena Maccaroni2, Mario Scartozzi1, Chiara Pierantoni1, Stefano Cascinu11Clinica di Oncologia Medica, Università Politecnica delle Marche, Ospedali Riuniti Umberto I-GM Lancisi-G Salesi di Ancona, Italy; 2Scuola di Specializzazione in Oncologia Medica, Università Politecnica delle Marche, Ancona, ItalyAbstract: Panitumumab is the first fully human monoclonal antibody to Epidermal Growth Factor Receptor (EGFR to enter clinical trials for the treatment of solid tumors. The anti-tumor activity of panitumumab has been tested in vitro and in vivo, and inhibition of tumor growth has been observed in numerous cancer models, particularly lung, kidney and colorectal (CRC. Preclinical and clinical studies have established a role for panitumumab in metastatic colorectal cancer (mCRC refractory to multiple chemotherapeutic regimens. Based on these encouraging findings, panitumumab was approved by the US Food and Drug Administration for the treatment of patients with epidermal growth factor receptor-expressing mCRC refractory to fluoropyrimidine-, oxaliplatin-, and/or irinotecan-containing chemotherapeutic regimens. The improvement in progression free survival (PFS and response rate (RR produced by panitumumab monotherapy was significantly greater in patients with non mutated (wild-type K-RAS than in those with mutant K-RAS. Therefore implementing routine K-RAS screening and limiting the use of EGFR inhibitors to patients with wild-type K-RAS appears the better strategy for select only the patients who could benefit from the therapy with panitumumab and also may have the potential for cost savings. The purpose of this review was to evaluate the patient-related, disease-related and economic-related evidence for the use of panitumumab in the treatment of metastatic colorectal cancer in clinical practice.Keywords: colorectal cancer, EGFR; K-RAS, panitumumab 

  6. Can high frequency ultrasound predict metastatic lymph nodes in patients with invasive breast cancer?

    International Nuclear Information System (INIS)

    Purpose: Use high frequency ultrasound to predict the presence of metastatic axillary lymph nodes, with a high specificity and positive predictive value, in patients with invasive breast cancer. The clinical aim is to improve the surgical management and possible survival rate of groups of patients who would not normally have conventional axillary dissections. Materials and methods: The ipsilateral and contralateral axillas of 42 consecutive patients with invasive breast cancer were scanned prior to treatment using a B-mode frequency of 13 MHz and a Doppler frequency of 7 MHz. The presence or absence of an echogenic centre for each lymph node detected was recorded, measurements were also taken to determine the L/S (long axis/short axis) ratio of the node and the widest and narrowest part of the cortex. Power Doppler was also used to determine vascularity. The contralateral axilla was used as a control for each patient. Results: In this study of patients with invasive breast cancer, where ipsilateral lymph nodes had a cortical bulge of ≥3 mm and/or at least two lymph nodes had absent echogenic centres, all had disease spread to the axillary lymph nodes (10 patients). Sensitivity and specificity were 52.6% and 100%, respectively, positive and negative predictive values were 100% and 71.9%, respectively, the P-value was 0.001 and the Kappa score was 0.55. Conclusion: This would indicate that high frequency ultrasound could be used to accurately predict metastatic lymph nodes in a proportion of patients with invasive breast cancer, which may alter patient management

  7. Expression patterns of CEACAM5 and CEACAM6 in primary and metastatic cancers

    International Nuclear Information System (INIS)

    Many breast, pancreatic, colonic and non-small-cell lung carcinoma lines express CEACAM6 (NCA-90) and CEACAM5 (carcinoembryonic antigen, CEA), and antibodies to both can affect tumor cell growth in vitro and in vivo. Here, we compare both antigens as a function of histological phenotype in breast, pancreatic, lung, ovarian, and prostatic cancers, including patient-matched normal, primary tumor, and metastatic breast and colonic cancer specimens. Antigen expression was determined by immunohistochemistry (IHC) using tissue microarrays with MN-15 and MN-3 antibodies targeting the A1B1- and N-domains of CEACAM6, respectively, and the MN-14 antibody targeting the A3B3 domain of CEACAM5. IHC was performed using avidin-biotin-diaminobenzide staining. The average score ± SD (0 = negative/8 = highest) for each histotype was recorded. For all tumors, the amount of CEACAM6 expressed was greater than that of CEACAM5, and reflected tumor histotype. In breast tumors, CEACAM6 was highest in papillary > infiltrating ductal > lobular > phyllodes; in pancreatic tumors, moderately-differentiated > well-differentiated > poorly-differentiated tumors; mucinous ovarian adenocarcinomas had almost 3-fold more CEACAM6 than serous ovarian adenocarcinomas; lung adenocarcinomas > squamous tumors; and liver metastases of colonic carcinoma > primary tumors = lymph nodes metastases > normal intestine. However, CEACAM6 expression was similar in prostate cancer and normal tissues. The amount of CEACAM6 in metastatic colon tumors found in liver was higher than in many primary colon tumors. In contrast, CEACAM6 immunostaining of lymph node metastases from breast, colon, or lung tumors was similar to the primary tumor. CEACAM6 expression is elevated in many solid tumors, but variable as a function of histotype. Based on previous work demonstrating a role for CEACAM6 in tumor cell migration, invasion and adhesion, and formation of distant metastases (Blumenthal et al., Cancer Res 65: 8809–8817, 2005

  8. PIK3CA mutation detection in metastatic biliary cancer using cell-free DNA

    Science.gov (United States)

    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

    2015-01-01

    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. PMID:26498688

  9. Targeting galectin-1 overcomes breast cancer-associated immunosuppression and prevents metastatic disease.

    Science.gov (United States)

    Dalotto-Moreno, Tomás; Croci, Diego O; Cerliani, Juan P; Martinez-Allo, Verónica C; Dergan-Dylon, Sebastián; Méndez-Huergo, Santiago P; Stupirski, Juan C; Mazal, Daniel; Osinaga, Eduardo; Toscano, Marta A; Sundblad, Victoria; Rabinovich, Gabriel A; Salatino, Mariana

    2013-02-01

    Galectin-1 (Gal1), an evolutionarily conserved glycan-binding protein, contributes to the creation of an immunosuppressed microenvironment at sites of tumor growth. In spite of considerable progress in elucidating its role in tumor-immune escape, the mechanisms underlying the inhibitory functions of Gal1 remain obscure. Here, we investigated the contribution of tumor Gal1 to tumor growth, metastasis, and immunosuppression in breast cancer. We found that the frequency of Gal1(+) cells in human breast cancer biopsies correlated positively with tumor grade, while specimens from patients with benign hyperplasia showed negative or limited Gal1 staining. To examine the pathophysiologic relevance of Gal1 in breast cancer, we used the metastatic mouse mammary tumor 4T1, which expresses and secretes substantial amounts of Gal1. Silencing Gal1 expression in this model induced a marked reduction in both tumor growth and the number of lung metastases. This effect was abrogated when mice were inoculated with wild-type 4T1 tumor cells in their contralateral flank, suggesting involvement of a systemic modulation of the immune response. Gal1 attenuation in 4T1 cells also reduced the frequency of CD4(+)CD25(+) Foxp3(+) regulatory T (T(reg)) cells within the tumor, draining lymph nodes, spleen, and lung metastases. Further, it abrogated the immunosuppressive function of T(reg) cells and selectively lowered the expression of the T-cell regulatory molecule LAT (linker for activation of T cells) on these cells, disarming their suppressive activity. Taken together, our results offer a preclinical proof of concept that therapeutic targeting of Gal1 can overcome breast cancer-associated immunosuppression and can prevent metastatic disease. PMID:23204230

  10. 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.

  11. Low Phosphorylated AKT Expression in Laryngeal Cancer: Indications for a Higher Metastatic Risk

    Energy Technology Data Exchange (ETDEWEB)

    Nijkamp, Monique M.; Span, Paul N.; Stegeman, Hanneke [Department of Radiation Oncology, Radboud University Nijmegen Medical Center, Nijmegen (Netherlands); Grénman, Reidar [Departments of Otorhinolaryngology-Head-and-Neck-Surgery and Medical Biochemistry, Turku University Hospital and University of Turku, Turku (Finland); Kaanders, Johannes H.A.M. [Department of Radiation Oncology, Radboud University Nijmegen Medical Center, Nijmegen (Netherlands); Bussink, Johan, E-mail: j.bussink@rther.umcn.nl [Department of Radiation Oncology, Radboud University Nijmegen Medical Center, Nijmegen (Netherlands)

    2013-10-01

    Purpose: To validate the association of phosphorylated (p)AKT with lymph node metastasis in an independent, homogeneous cohort of patients with larynx cancer. Methods and Materials: Seventy-eight patients with laryngeal cancer were included. Epidermal growth factor receptor, pAKT, vimentin, E-cadherin, hypoxia, and blood vessels were visualized in biopsy material using immunohistochemistry. Positive tumor areas and spatial relationships between markers were assessed by automated image analysis. In 6 laryngeal cancer cell lines, E-cadherin and vimentin messenger RNA was quantified by real-time polymerase chain reaction and by immunohistochemistry before and after treatment with the pAKT inhibitor MK-2206. Results: A significant correlation was found between low pAKT in the primary tumor and positive lymph node status (P=.0005). Tumors with lymph node metastases had an approximately 10-fold lower median pAKT value compared with tumors without lymph node metastases, albeit with large intertumor variations, validating our previous results. After inhibition of pAKT in laryngeal cancer cells with MK-2206, up-regulation of vimentin and a downregulation of E-cadherin occurred, consistent with epithelial–mesenchymal transition. Conclusion: Low pAKT expression in larynx tumors is associated with lymph node metastases. Further, inhibition of pAKT in laryngeal cancer induces epithelial–mesenchymal transition, predisposing for an increased metastatic risk.

  12. A Distributed Network for Intensive Longitudinal Monitoring in Metastatic Triple-Negative Breast Cancer

    Science.gov (United States)

    Blau, C. Anthony; Ramirez, Arturo B.; Blau, Sibel; Pritchard, Colin C.; Dorschner, Michael O.; Schmechel, Stephen C.; Martins, Timothy J.; Mahen, Elisabeth M.; Burton, Kimberly A.; Komashko, Vitalina M.; Radenbaugh, Amie J.; Dougherty, Katy; Thomas, Anju; Miller, Christopher P.; Annis, James; Fromm, Jonathan R.; Song, Chaozhong; Chang, Elizabeth; Howard, Kellie; Austin, Sharon; Schmidt, Rodney A.; Linenberger, Michael L.; Becker, Pamela S.; Senecal, Francis M.; Mecham, Brigham H.; Lee, Su-In; Madan, Anup; Ronen, Roy; Dutkowski, Janusz; Heimfeld, Shelly; Wood, Brent L.; Stilwell, Jackie L.; Kaldjian, Eric P.; Haussler, David; Zhu, Jingchun

    2016-01-01

    Accelerating cancer research is expected to require new types of clinical trials. This report describes the Intensive Trial of OMics in Cancer (ITOMIC) and a participant with triple-negative breast cancer metastatic to bone, who had markedly elevated circulating tumor cells (CTCs) that were monitored 48 times over 9 months. A total of 32 researchers from 14 institutions were engaged in the patient’s evaluation; 20 researchers had no prior involvement in patient care and 18 were recruited specifically for this patient. Whole-exome sequencing of 3 bone marrow samples demonstrated a novel ROS1 variant that was estimated to be present in most or all tumor cells. After an initial response to cisplatin, a hypothesis of crizotinib sensitivity was disproven. Leukapheresis followed by partial CTC enrichment allowed for the development of a differential high-throughput drug screen and demonstrated sensitivity to investigational BH3-mimetic inhibitors of BCL-2 that could not be tested in the patient because requests to the pharmaceutical sponsors were denied. The number and size of CTC clusters correlated with clinical status and eventually death. Focusing the expertise of a distributed network of investigators on an intensively monitored patient with cancer can generate high-resolution views of the natural history of cancer and suggest new opportunities for therapy. Optimization requires access to investigational drugs. PMID:26733551

  13. Quality of life and its related factors among Iranian patients with metastatic gastrointestinal tract cancer: A cross-sectional study

    Directory of Open Access Journals (Sweden)

    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.

  14. Metastatic brain cancer: prediction of response to whole-brain helical tomotherapy with simultaneous intralesional boost for metastatic disease using quantitative MR imaging features

    Science.gov (United States)

    Sharma, Harish; Bauman, Glenn; Rodrigues, George; Bartha, Robert; Ward, Aaron

    2014-03-01

    The sequential application of whole brain radiotherapy (WBRT) and more targeted stereotactic radiosurgery (SRS) is frequently used to treat metastatic brain tumors. However, SRS has side effects related to necrosis and edema, and requires separate and relatively invasive localization procedures. Helical tomotherapy (HT) allows for a SRS-type simultaneous infield boost (SIB) of multiple brain metastases, synchronously with WBRT and without separate stereotactic procedures. However, some patients' tumors may not respond to HT+SIB, and would be more appropriately treated with radiosurgery or conventional surgery despite the additional risks and side effects. As a first step toward a broader objective of developing a means for response prediction to HT+SIB, the goal of this study was to investigate whether quantitative measurements of tumor size and appearance (including first- and second-order texture features) on a magnetic resonance imaging (MRI) scan acquired prior to treatment could be used to differentiate responder and nonresponder patient groups after HT+SIB treatment of metastatic disease of the brain. Our results demonstrated that smaller lesions may respond better to this form of therapy; measures of appearance provided limited added value over measures of size for response prediction. With further validation on a larger data set, this approach may lead to a means for prediction of individual patient response based on pre-treatment MRI, supporting appropriate therapy selection for patients with metastatic brain cancer.

  15. 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

    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 bioluminescence imaging...... 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 metastatic lesions in a human metastatic prostate cancer model. Furthermore, we have provided the first evidence of the potential...

  16. A structured review of health utility measures and elicitation in advanced/metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    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

  17. 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

  18. 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.

  19. Can epithermal boron neutron capture therapy treat primary and metastatic liver cancer?

    International Nuclear Information System (INIS)

    Full text: The poor prognosis of metastatic cancer to the liver calls for the investigation of alternative treatment modalities. This paper analyses the possible use of epithermal boron neutron capture therapy for the palliative treatment of these cancers. We examine possible treatment planning scenarios for selected tumour to liver boron ratios, and specifically for the epithermal beam at the HFR, Petten. It is required that a therapeutic ratio> 1 be achieved over the entire organ. Monte Carlo calculations were performed using the radiation transport code MCNP. The geometrical model used a 'variable voxel' technique to reconstruct an anthropomorphic phantom from CT scans. Regions of interest such as the liver were modelled to a resolution of a few millimetres, whereas surrounding regions were modelled with lesser detail thereby facilitating faster computation time. Three dimensional dose distributions were calculated for a frontal beam directed at the liver, and found to be in satisfactory agreement with measurements using bare and cadmium covered gold foils, PIN and MOSFET dosimeters for fast neutron and gamma measurements respectively. Dose distributions were calculated for orthogonal epithermal neutron beams to the front and side, using the parameters of the epithermal beam at Petten, and assumed tumour and normal tissue boron-10 concentrations of 30 ppm and 7.5 ppm boron-10 respectively. The therapeutic ratio (i e the dose to the tumour relative to the maximum dose to normal tissue) was found to be about 1.8, reducing to unity for the limiting condition of a tumour in the posterior liver. This result opens up the possibility of palliative therapy for the management of primary and metastatic liver cancer

  20. Effects of clusterin over-expression on metastatic progression and therapy in breast cancer

    Directory of Open Access Journals (Sweden)

    Chatterjee Namita

    2010-03-01

    Full Text Available Abstract Background Clusterin is a secreted glycoprotein that is upregulated in a variety of cell lines in response to stress, and enhances cell survival. A second nuclear isoform of clusterin that is associated with cell death has also been identified. The aim of this study was to determine the role(s of the secretory isoform in breast tumor progression and metastasis. Methods To investigate the role of secretory clusterin in the biology of breast cancer tumor growth and resistance to therapy we have engineered an MCF-7 cell line (MCF-7CLU that over-expresses clusterin. We have measured the in vitro effects of clusterin over-expression on cell cycle, cell death, and sensitivity to TNFalpha and tamoxifen. Using an orthotopic model of breast cancer, we have also determined the effects of over-expression of clusterin on tumor growth and metastatic progression. Results In vitro, over-expression of secretory clusterin alters the cell cycle kinetics and decreases the rate of cell death, resulting in the enhancement of cell growth. Over-expression of secretory clusterin also blocks the TNFalpha-mediated induction of p21 and abrogates the cleavage of Bax to t-Bax, rendering the MCF-7CLU cells significantly more resistant to the cytokine than the parental cells. Orthotopic primary tumors derived from MCF-7CLU cells grow significantly more rapidly than tumors derived from parental MCF-7 cells and, unlike the parental cells, metastasize frequently to the lungs. Conclusions These data suggest that secretory clusterin, which is frequently up-regulated in breast cancers by common therapies, including anti-estrogens, may play a significant role in tumor growth, metastatic progression and subsequent drug resistance in surviving cells.

  1. Isolation and genomic analysis of circulating tumor cells from castration resistant metastatic prostate cancer

    International Nuclear Information System (INIS)

    The number of circulating tumor cells (CTCs) in metastatic prostate cancer patients provides prognostic and predictive information. However, it is the molecular characterization of CTCs that offers insight into the biology of these tumor cells in the context of personalized treatment. We developed a novel approach to isolate CTCs away from hematopoietic cells with high purity, enabling genomic analysis of these cells. The isolation protocol involves immunomagnetic enrichment followed by fluorescence activated cell sorting (IE/FACS). To evaluate the feasibility of isolation of CTCs by IE/FACS and downstream genomic profiling, we conducted a pilot study in patients with metastatic castration resistant prostate cancer (CRPC). Twenty (20) sequential CRPC patients were assayed using CellSearch™. Twelve (12) patients positive for CTCs were subjected to immunomagnetic enrichment and fluorescence activated cell sorting (IE/FACS) to isolate CTCs. Genomic DNA of CTCs was subjected to whole genome amplification (WGA) followed by gene copy number analysis via array comparative genomic hybridization (aCGH). CTCs from nine (9) patients successfully profiled were observed to have multiple copy number aberrations including those previously reported in primary prostate tumors such as gains in 8q and losses in 8p. High-level copy number gains at the androgen receptor (AR) locus were observed in 7 (78%) cases. Comparison of genomic profiles between CTCs and archival primary tumors from the same patients revealed common lineage. However, high-level copy number gains in the AR locus were observed in CTCs, but not in the matched archival primary tumors. We developed a new approach to isolate prostate CTCs without significant leukocyte admixture, and to subject them to genome-wide copy number analysis. Our assay may be utilized to explore genomic events involved in cancer progression, e.g. development of castration resistance and to monitor therapeutic efficacy of targeted therapies in

  2. Radiotherapy in the management of non-metastatic prostate cancer: Current standards and future opportunities

    International Nuclear Information System (INIS)

    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

  3. Stress sensitivity in metastatic breast cancer: analysis of hypothalamic-pituitary-adrenal axis function.

    Science.gov (United States)

    Spiegel, David; Giese-Davis, Janine; Taylor, C Barr; Kraemer, Helena

    2006-11-01

    The normal diurnal cortisol cycle has a peak in the morning, decreasing rapidly over the day, with low levels during the night, then rising rapidly again to the morning peak. A pattern of flatter daytime slopes has been associated with more rapid cancer progression in both animals and humans. We studied the relationship between the daytime slopes and other daytime cortisol responses to both pharmacological and psychosocial challenges of hypothalamic-pituitary-adrenal (HPA) axis function as well as DHEA in a sample of 99 women with metastatic breast cancer, in hopes of elucidating the dysregulatory process. We found that the different components of HPA regulation: the daytime cortisol slope, the rise in cortisol from waking to 30 min later, and cortisol response to various challenges, including dexamethasone (DEX) suppression, corticotrophin releasing factor (CRF) activation, and the Trier Social Stress Task, were at best modestly associated. Escape from suppression stimulated by 1mg of DEX administered the night before was moderately but significantly associated with flatter daytime cortisol slopes (r=0.28 to .30 at different times of the post DEX administration day, all pSocial Stress Task. The CRF activation test (following 1.5mg of DEX to assure that the effect was due to exogenous CRF) produced ACTH levels that were correlated (r=0.66, presponsiveness to ACTH stimulation. Daytime cortisol slopes were significantly correlated with the slope of DHEA (r=.21, p=.04, N=95). Our general findings suggest that flatter daytime cortisol slopes among metastatic breast cancer patients may be related to disrupted feedback inhibition rather than hypersensitivity in response to stimulation. PMID:17081700

  4. Two cases of bowel perforation in patients with metastatic renal cancer treated with molecular target drug

    International Nuclear Information System (INIS)

    An 82-year-old man started immunotherapy with interferon because of lung metastasis 5 years after he had undergone radical nephrectomy. Three years later, he developed multiple metastases, and was started on sorafenib (400 mg/day) and nonsteroidal anti-inflammatory drug (NSAID) orally. As his cancer-related pain worsened with time, he was administered 30 Gy radiation therapy for bone metastasis of L4. He was then admitted to our hospital for pain control because of ineffective radiation therapy. One day, he suddenly had abdominal pain and vomiting, and was diagnosed as bowel perforation based on computed tomography. He was managed conservatively by nasogastric suction and antibiotic course. A 62-year-old man diagnosed as metastatic renal cell cancer began immunotherapy soon after undergoing radical nephrectomy in Dec., 2006. Although he was started on oral sorafenib (800 mg/day) in July, 2008, metastatic foci enlarged after 18 months. He was then changed to sunitinib (50 mg/day). Sunitinib had immediate and long-lasting effect on the cancer for about 10 months, but he was then admitted to our hospital for pleural effusion. While under treatment for thoracic cavity drainage, he experienced upper abdominal pain and was diagnosis as bowel perforation based on computed tomography. He underwent emergency laparotomy. Molecular target drugs such as sorafenib and sunitinib have serious adverse effects. Bowel perforation is rare, but among those adverse effects. It should be remembered that caution is required for long-term use or combined radiation therapy and NSAIDs with molecular target drug. (author)

  5. A gene transfer comparative study of HSA-conjugated antiangiogenic factors in a transgenic mouse model of metastatic ocular cancer.

    Science.gov (United States)

    Frau, E; Magnon, C; Opolon, P; Connault, E; Opolon, D; Beermann, F; Beerman, F; Abitbol, M; Perricaudet, M; Bouquet, C

    2007-03-01

    Different antiangiogenic and antimetastatic recombinant adenoviruses were tested in a transgenic mouse model of metastatic ocular cancer (TRP1/SV40 Tag transgenic mice), which is a highly aggressive tumor, developed from the pigmented epithelium of the retina. These vectors, encoding amino-terminal fragments of urokinase plasminogen activator (ATF), angiostatin Kringles (K1-3), endostatin (ES) and canstatin (Can) coupled to human serum albumin (HSA) were injected to assess their metastatic and antiangiogenic activities in our model. Compared to AdCO1 control group, AdATF-HSA did not significantly reduce metastatic growth. In contrast, mice treated with AdK1-3-HSA, AdES-HSA and AdCan-HSA displayed significantly smaller metastases (1.19+/-1.19, 0.87+/-1.5, 0.43+/-0.56 vs controls 4.04+/-5.12 mm3). Moreover, a stronger inhibition of metastatic growth was obtained with AdCan-HSA than with AdK1-3-HSA (P=0.04). Median survival was improved by 4 weeks. A close correlation was observed between the effects of these viruses on metastatic growth and their capacity to inhibit tumor angiogenesis. Our study indicates that systemic antiangiogenic factors production by recombinant adenoviruses, particularly Can, might represent an effective way of delaying metastatic growth via inhibition of angiogenesis. PMID:17082795

  6. Phase II trial of temsirolimus alone and in combination with irinotecan for KRAS mutant metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Spindler, Karen-Lise Garm; Sørensen, Morten; Pallisgaard, Niels;

    2013-01-01

    Background. Patients with chemotherapy refractory metastatic colorectal cancer and KRAS mutations have no effective treatment option. The present study evaluated the efficacy of temsirolimus in chemotherapy refractory mCRC with KRAS mutations. Furthermore, we wanted to investigate if resistance t...

  7. Sipuleucel-T: Autologous Cellular Immunotherapy for Men with Asymptomatic or Minimally Symptomatic Metastatic Castrate Resistant Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Robert B. Sims

    2011-01-01

    Full Text Available Sipuleucel T is an autologous cellular immunotherapy designed to stimulate an immune response in men diagnosed with asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory prostate cancer. Sipuleucel T improves overall survival and provides an additional treatment option for this patient population.

  8. Irrefutable evidence for the use of docetaxel in newly diagnosed metastatic prostate cancer: results from the STAMPEDE and CHAARTED trials.

    Science.gov (United States)

    van Soest, Robert J; de Wit, Ronald

    2015-01-01

    Androgen deprivation therapy (ADT) has been used in the treatment of metastatic prostate cancer since the first description of its hormonal dependence in 1941. In 2004, docetaxel chemotherapy became the mainstay of treatment in metastatic castration-resistant prostate cancer (mCRPC), following robust, albeit modest, survival benefit in two randomized phase 3 trials. The recently published CHAARTED trial was the first to show that combining ADT with docetaxel in men with hormone-naïve (hormone-sensitive) metastatic prostate cancer (mHSPC) yielded a remarkable overall survival benefit of 13.6 months as compared with ADT alone. In the current issue of The Lancet, James et al. report results of the STAMPEDE trial in men with high-risk locally advanced or metastatic prostate cancer initiating long-term hormone therapy. The combination of six cycles of docetaxel with ADT in men commencing long-term ADT demonstrated a similar OS benefit compared with standard of care (SOC) by a median of 10 months. Based on the consistency of the data and the firmness of the benefit provided, docetaxel in addition to ADT should be considered SOC for men with newly diagnosed mHSPC. PMID:26695172

  9. Solitary metastatic cancer to the thyroid: a report of five cases with fine-needle aspiration cytology

    Directory of Open Access Journals (Sweden)

    Batoroev Yuri

    2007-01-01

    Full Text Available Abstract Three men and 2 women with ages ranging from 37 to 70 years, clinically and histologically confirmed solitary, palpable metastatic cancers to the thyroid (SMCT and preoperative cytologic investigation of their thyroid lesions by fine-needle aspiration (FNA, were reviewed. Four patients were known to have a solid cancer treated by radical surgery 1 to 4 years prior [1 bronchogenic squamous cell carcinoma, 1 parotid adenoid cystic carcinoma, 1 renal cell carcinoma (RCC and 1 cutaneous melanoma], and 1 patient had no past history of cancer. Direct smears prepared from the patients' thyroid FNAs were fixed in 95% ethanol and stained with the Papanicolaou method. In 3 cases, immunostaining of the aspirated tumor cells with thyroglobulin antibody was performed, and in 1 case an aspiration smear was stained with commercial HMB-45 antibody. A correct cytodiagnosis of metastatic cancer to the thyroid was made in all 5 cases. In 1 patient the thyroid FNA revealed a metastatic RCC that led to the discovery of a clinically occult RCC. All 5 patients died of metastatic disease 27 to 40 months after surgical resection of their SMCTs.

  10. High Throughput Screening of Natural Phenolic Compounds Against Migration of Metastatic Triple-Negative Breast Cancer (TNBC) Cells

    OpenAIRE

    Nasrollahi, Samila

    2013-01-01

    In this report, we hypothesize that natural phenolic compounds may present a new class of chemotherapeutics against migration of metastatic triple-negative breast cancers (TNBC). In this project we will screen a small library of phenolic compounds to test this hypothesis, identify compounds that show efficacy against TNBC cell migration, and elucidate underlying molecular mechanisms.

  11. Approval Summary: Pemetrexed Maintenance Therapy of Advanced/Metastatic Nonsquamous, Non-Small Cell Lung Cancer (NSCLC)

    OpenAIRE

    Cohen, Martin H.; Cortazar, Patricia; Justice, Robert; Pazdur, Richard

    2010-01-01

    The study that led to U.S. Food and Drug Administration approval of pemetrexed injection for maintenance treatment of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer whose disease has not progressed after four cycles of platinum-based doublet induction chemotherapy is reviewed.

  12. Sorafenib in radioactive iodine-refractory well-differentiated metastatic thyroid cancer

    Directory of Open Access Journals (Sweden)

    McFarl

    2014-07-01

    Full Text Available Daniel C McFarland,1 Krzysztof J Misiukiewicz2,31Division of Hematology and Medical Oncology, Mount Sinai Medical Center, New York, NY, USA; 2Division of Hematology and Medical Oncology, 3Department of Otolaryngology, Mount Sinai Medical Center, Ruttenberg Treatment Center, New York, NY, USAAbstract: Recent Phase III data presented at the American Society of Clinical Oncology (ASCO 2013 annual conference by Brose et al led to the US Food and Drug Administration (FDA approval of sorafenib for the treatment of well-differentiated radioactive iodine-resistant metastatic thyroid cancer. This is the second drug in 40 years to be FDA approved for this indication. Recent reviews and a meta-analysis reveal a modest ability to induce a partial remission but substantial ability to halt disease progression. Given the significant activating mutations present in thyroid cancer, many of which are inhibited by sorafenib, the next logical approach may be to combine targeted rational therapies if permitted by collective toxicity profiles. This systematic review aims to summarize the recent Phase II/III data leading to the FDA approval of sorafenib for radioactive iodine therapy differentiated thyroid cancer and highlights recent novel combination therapy trials.Keywords: tyrosine kinase inhibitors, targeted therapy, RAI DTC, novel thyroid cancer treatment

  13. Survival of patients with metastatic breast cancer: twenty-year data from two SEER registries

    International Nuclear Information System (INIS)

    Many researchers are interested to know if there are any improvements in recent treatment results for metastatic breast cancer in the community, especially for 10- or 15-year survival. Between 1981 and 1985, 782 and 580 female patients with metastatic breast cancer were extracted respectively from the Connecticut and San Francisco-Oakland registries of the Surveillance, Epidemiology, and End Results (SEER) database. The lognormal statistical method to estimate survival was retrospectively validated since the 15-year cause-specific survival rates could be calculated using the standard life-table actuarial method. Estimated rates were compared to the actuarial data available in 2000. Between 1991 and 1995, further 752 and 632 female patients with metastatic breast cancer were extracted respectively from the Connecticut and San Francisco-Oakland registries. The data were analyzed to estimate the 15-year cause-specific survival rates before the year 2005. The 5-year period (1981–1985) was chosen, and patients were followed as a cohort for an additional 3 years. The estimated 15-year cause-specific survival rates were 7.1% (95% confidence interval, CI, 1.8–12.4) and 9.1% (95% CI, 3.8–14.4) by the lognormal model for the two registries of Connecticut and San Francisco-Oakland respectively. Since the SEER database provides follow-up information to the end of the year 2000, actuarial calculation can be performed to confirm (validate) the estimation. The Kaplan-Meier calculation for the 15-year cause-specific survival rates were 8.3% (95% CI, 5.8–10.8) and 7.0% (95% CI, 4.3–9.7) respectively. Using the 1991–1995 5-year period cohort and followed for an additional 3 years, the 15-year cause-specific survival rates were estimated to be 9.1% (95% CI, 3.8–14.4) and 14.7% (95% CI, 9.8–19.6) for the two registries of Connecticut and San Francisco-Oakland respectively. For the period 1981–1985, the 15-year cause-specific survival for the Connecticut and the San

  14. Prognostic value of quantitative fluorodeoxyglucose measurements in newly diagnosed metastatic breast cancer

    International Nuclear Information System (INIS)

    The aim of this study was to determine the prognostic value of quantitative fluorodeoxyglucose (FDG) measurements (maximum standardized uptake value [SUVmax], metabolic tumor volume [MTV], and total lesion glycolysis [TLG]) in patients with newly diagnosed metastatic breast cancer (MBC). An IRB-approved retrospective review was performed of patients who underwent FDG positron emission tomography (PET)/computed tomography (CT) from 1/02 to 12/08 within 60 days of diagnosis MBC. Patients with FDG-avid lesions without receiving chemotherapy in the prior 30 days were included. Target lesions in bone, lymph node (LN), liver, and lung were analyzed for SUVmax, MTV, and TLG. Medical records were reviewed for patient characteristics and overall survival (OS). Cox regression was used to test associations between quantitative FDG measurements and OS. A total of 253 patients were identified with disease in bone (n = 150), LN (n = 162), liver (n = 48), and lung (n = 66) at the time of metastatic diagnosis. Higher SUVmax tertile was associated with worse OS in bone metastases (highest vs. lowest tertile hazard ratio [HR] = 3.1, P < 0.01), but not in LN, liver or lung (all P > 0.1). Higher MTV tertile was associated with worse OS in LN (HR = 2.4, P < 0.01) and liver (HR = 3.0, P = 0.02) metastases, but not in bone (P = 0.22) or lung (P = 0.14). Higher TLG tertile was associated with worse OS in bone (HR = 2.2, P = 0.02), LN (HR = 2.3, P < 0.01), and liver (HR = 4.9, P < 0.01) metastases, but not in lung (P = 0.19). We conclude measures of FDG avidity are prognostic biomarkers in newly diagnosed MBC. SUVmax and TLG were both predictors of survival in breast cancer patients with bone metastases. TLG may be a more informative biomarker of OS than SUVmax for patients with LN and liver metastases. Measures of fluorodeoxyglucose (FDG) avidity are prognostic biomarkers in newly diagnosed metastatic breast cancer. Volumetric measurements, such as total lesion glycolysis (TLG), may be

  15. Characterization of metastatic disease in recently diagnosed breast cancer and relapsed breast cancer (after treatment), with PET / CT

    International Nuclear Information System (INIS)

    Purpose. To describe metastatic disease detected by PET/CT in breast cancer (BC), and to evaluate the relative contribution of PET and CT analyzed separately. Patients and Method. We defined two groups of patients with BC: 1) recently diagnosed with no treatment, 2) with relapse after treatment. We described findings which are visible exclusively with CT and exclusively with PET. Results. In recently diagnosed patients (n=17) 88% show lymphadenopathies, 29% bone metastases (BM), 17% lung metastases, 17% hepatic metastases, and 11% other localizations. For relapsed patients (n=35) these percentages were 54%, 62%, 34%, 31% and 28%, respectively. CT detected more lung nodules and sclerotic bone lesions than PET. PET detected more lymphadenopathies, medullary bone and hepatic lesions than CT. There were synchronous cancers in 6% of recently diagnosed patients and in 11% of relapsed patients. Conclusion. BC patients show mainly lymph nodal and bone metastasis. The PET/CT hybrid study detected more lesions than PET and CT analyzed separately

  16. What Is the Role of Nanotechnology in Diagnosis and Treatment of Metastatic Breast Cancer? Promising Scenarios for the Near Future

    Directory of Open Access Journals (Sweden)

    Truffi Marta

    2016-01-01

    Full Text Available Metastatic breast cancer represents a diagnostic and therapeutic challenge due to tumor heterogeneity and to various physiological barriers that hinder drug delivery to the metastatic sites. To overcome these limitations, nanoformulated drugs have been developed and tested in preclinical studies, and few of them have been successfully translated into clinical practice. In particular, liposomal anthracyclines and nanoformulated albumin-bound paclitaxel have revealed an improved therapeutic index when compared to conventional chemotherapy, with significant reduction of drugs toxicity. Several strategies for nanoparticles engineering have more recently been explored to increase selectivity for tumor cells and to reach poorly accessible metastatic districts. Targeted nanoparticles, directed toward tumor markers and tissue-specific metastases, may provide effective devices in case of low-vascularized and small-sized metastases, thus paving the way for a real change in the natural history of metastatic disease. A number of targets have been identified and exploited for surface functionalization of different types of nanoparticles, which are currently undergoing preclinical studies. The aim of this review is to provide an overview of current nanotechnology applied to metastatic breast cancer diagnosis and treatment. Promising results encourage an upcoming translation of this research into clinical practice for an effective management of the disease in the near future.

  17. Combined ipsilateral neck and axillary lymphadenectomy for metastatic skin cancers: a case series and surgical tips.

    Science.gov (United States)

    Goodenough, J; Martin, H; Shaaban, H

    2013-08-01

    In the absence of distant disease simultaneous skin cancer metastasis to neck and axillary lymph nodes necessitates both an axillary and neck en block lymphadenectomy. A combined ipsilateral neck and axillary lymph node dissection should involve an in-continuity dissection through the cervicoaxillary canal for optimal lymphatic and oncological clearance. Review of the literature reveals little published instruction on the procedure since the radical surgery performed by Bowden over 50 years ago. We present 4 cases where ipsilateral axillary and neck lymph node dissections were performed for metastatic melanoma and a case of apical axillary node dissection via a neck incision approach. Our surgical tips include performing apical axillary node dissection via the neck incision and consideration of clavicular osteotomy or clavicular excision. A transclavicular approach was taken in one patient who had an excellent functional outcome after a plate and screw fixation. One elderly patient required a middle third claviculectomy which reduced shoulder elevation but was not associated with functional impairment. We conclude the surgery is safe and associated with the usual morbidity ascribed with either an axillary or neck dissection undertaken in isolation. However, patients have a significant risk of disease relapse as would be expected due to the duel metastatic sites, multiple lymph node and neck involvement which are known to be independent poor prognostic factors on melanoma survival and relapse. PMID:23664381

  18. Metastatic lung cancer presenting with jugular foramen syndrome in a case of von Recklinghausens disease

    Directory of Open Access Journals (Sweden)

    Agarwal Amit

    2010-01-01

    Full Text Available Metastatic carcinomas from a distant primary malignancy involving the temporal bone particularly the jugular foramen are rare tumors. A 57-year-old gentleman had multiple gradually increasing swellings over the body since many years. For last two years, he noticed enlargement of the swelling in left calf and rapidly enlarging painful new swelling over the left chest wall in back for last one year. He had recent involvement of left seventh, eighth and lower cranial nerves. CT scan showed an extensive lesion in left jugular foramen region with bone destruction. The patient underwent decompression of the left jugular foramen mass lesion. The tumor was extremely vascular and a partial decompression could only be performed. Although there was relief in the headache but the neurological deficits were persisting. Histopathology of the tumor showed features of metastatic small ling cancer. In the present case, there was presence of long standing multiple swelling all over the body and the patient had painful enlargement that he perceived as an ongoing process of the von Recklinghausen′s disease and made a delay in seeking the medical advice resulting in a well advanced disease and with poor prognosis.

  19. Development of Raman spectral markers to assess metastatic bone in breast cancer

    Science.gov (United States)

    Ding, Hao; Nyman, Jeffry S.; Sterling, Julie A.; Perrien, Daniel S.; Mahadevan-Jansen, Anita; Bi, Xiaohong

    2014-11-01

    Bone is the most common site for breast cancer metastases. One of the major complications of bone metastasis is pathological bone fracture caused by chronic bone loss and degeneration. Current guidelines for the prediction of pathological fracture mainly rely on radiographs or computed tomography, which are limited in their ability to predict fracture risk. The present study explored the feasibility of using Raman spectroscopy to estimate pathological fracture risk by characterizing the alterations in the compositional properties of metastatic bones. Tibiae with evident bone destruction were investigated using Raman spectroscopy. The carbonation level calculated by the ratio of carbonate/phosphate ν1 significantly increased in the tumor-bearing bone at all the sampling regions at the proximal metaphysis and diaphysis, while tumor-induced elevation in mineralization and crystallinity was more pronounced in the metaphysis. Furthermore, the increased carbonation level is positively correlated to bone lesion size, indicating that this parameter could serve as a unique spectral marker for tumor progression and bone loss. With the promising advances in the development of spatially offset Raman spectroscopy for deep tissue measurement, this spectral marker can potentially be used for future noninvasive evaluation of metastatic bone and prediction of pathological fracture risk.

  20. Ratio of Metastatic to Examined Lymph Nodes, a Helpful Staging System and Independent Prognostic Factor of Esophagogastric Junction Cancer

    OpenAIRE

    Zhang, Hao; Wang, Wei; Dongmei DIAO; Cheng, Yao; SONG, YONGCHUN; Zhu, Kun; DANG, CHENGXUE

    2013-01-01

    Background The incidence of the esophagogastric junction cancer is growing rapidly. The purpose of this study is to clarify the outcome of the ratio between metastatic and examined lymph nodes in esophagogastric junction cancer patients with or without 7 examined lymph nodes. Methods A total of 3,481 patients who underwent operation are identified from the Surveillance, Epidemiology, and End Results database. Different lymph nodes resected groups are analyzed to test the lymph nodes ratio fac...

  1. Has the practice of radiation oncology for locally advanced and metastatic non-small-cell lung cancer changed in Canada?

    OpenAIRE

    Han, K.; Bezjak, A.; Xu, W.; Kane, G.

    2010-01-01

    Aim Previous surveys have revealed wide variations in the management by radiation oncologists of non-small-cell lung cancer (nsclc) in Canada. The aim of the present study was to determine the current patterns of practice for locally advanced and metastatic nsclc among Canadian radiation oncologists. Materials and Methods An online survey was distributed electronically to all members of the Canadian Association of Radiation Oncologists. Those who treat lung cancer were invited to participate....

  2. Whole-genome bisulfite sequencing of cell-free DNA identifies signature associated with metastatic breast cancer

    OpenAIRE

    Legendre, Christophe; Gooden, Gerald C.; Johnson, Kyle; Martinez, Rae Anne; Liang, Winnie S.; Salhia, Bodour

    2015-01-01

    Background A number of clinico-pathological criteria and molecular profiles have been used to stratify patients into high- and low-risk groups. Currently, there are still no effective methods to determine which patients harbor micrometastatic disease after standard breast cancer therapy and who will eventually develop local or distant recurrence. The purpose of our study was to identify circulating DNA methylation changes that can be used for prediction of metastatic breast cancer (MBC). Resu...

  3. Emerging drug discovery approaches for selective targeting of “precursor” metastatic breast cancer cells: highlights and perspectives

    OpenAIRE

    AAlaoui-Jamali, Moulay; Bijian, Krikor; Batist, Gerald

    2011-01-01

    Breast cancer is a prevalent disease and a major cause of morbidity and cancer-related deaths among women worldwide. A significant number of patients at the time of primary diagnosis present metastatic disease, at least to locoregional lymph nodes, which results in somewhat unpredictable prognosis that often prompts adjuvant systemic therapies of various kinds. The time course of distant recurrence is also unpredictable with some patients sustaining a recurrence within months after diagnosis,...

  4. The granulocyte macrophage–colony stimulating factor surface modified MB49 bladder cancer stem cells vaccine against metastatic bladder cancer

    Directory of Open Access Journals (Sweden)

    Yong-tong Zhu

    2014-07-01

    Full Text Available The MB49 bladder cancer cell vaccine was effective against bladder cancer in the mice model in previous studies. However, part of the tumors regrew as the vaccine could not eliminate the cancer stem cells (CSCs. MB49 bladder cancer stem cells (MCSCs were isolated by a combination of the limited dilution method and the serum free culture medium method. MCSCs possessed higher expression of CD133, CD44, OCT4, NANOG, and ABCG2, the ability of differentiation, higher proliferative abilities, lower susceptibility to chemotherapy, greater migration in vitro, and stronger tumorigenic abilities in vivo. Then streptavidin–mouse granulocyte macrophage–colony stimulating factor (SA–mGM–CSF MCSCs vaccine was prepared. SA–mGM–CSF MCSCs vaccine extended the survival of the mice and inhibited the growth of tumor in protective, therapeutic, memorial and specific immune response experiments. The level of immunoglobulin G and the ratio of dendritic cells and CD4+ and CD8+ T cells were highest in the experimental group when compared to those in other four control groups, as well as for the cytotoxicity assay. We demonstrated that SA–mGM–CSF MCSCs vaccine induces an antitumor immune response to metastatic bladder cancer.

  5. Biophysical and morphological effects of nanodiamond/nanoplatinum solution (DPV576) on metastatic murine breast cancer cells in vitro

    International Nuclear Information System (INIS)

    Nanoparticles have recently gained increased attention as drug delivery systems for the treatment of cancer due to their minute size and unique chemical properties. However, very few studies have tested the biophysical changes associated with nanoparticles on metastatic cancer cells at the cellular and sub-cellular scales. Here, we investigated the mechanical and morphological properties of cancer cells by measuring the changes in cell Young’s Modulus using AFM, filopodial retraction (FR) by time lapse optical light microscopy imaging and filopodial disorganization by high resolution AFM imaging of cells upon treatment with nanoparticles. In the current study, nanomechanical changes in live murine metastatic breast cancer cells (4T1) post exposure to a nanodiamond/nanoplatinum mixture dispersed in aqueous solution (DPV576), were monitored. Results showed a decrease in Young’s modulus at two hours post treatment with DPV576 in a dose dependent manner. Partial FR at 20 min and complete FR at 40 min were observed. Moreover, analysis of the retraction distance (in microns) measured over time (minutes), showed that a DPV576 concentration of 15%v/v yielded the highest FR rate. In addition, DPV576 treated cells showed early signs of filopodial disorganization and disintegration. This study demonstrates the changes in cell stiffness and tracks early structural alterations of metastatic breast cancer cells post treatment with DPV576, which may have important implications in the role of nanodiamond/nanoplatinum based cancer cell therapy and sensitization to chemotherapy drugs. (paper)

  6. Carboplatin, Paclitaxel, Cetuximab, and Erlotinib Hydrochloride in Treating Patients With Metastatic or Recurrent Head and Neck Squamous Cell Cancer

    Science.gov (United States)

    2016-03-01

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage IV Salivary Gland Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IV Verrucous Carcinoma of the Larynx; Stage IV Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

  7. Biophysical and morphological effects of nanodiamond/nanoplatinum solution (DPV576) on metastatic murine breast cancer cells in vitro

    Science.gov (United States)

    Ghoneum, Alia; Zhu, Huanqi; Woo, JungReem; Zabinyakov, Nikita; Sharma, Shivani; Gimzewski, James K.

    2014-11-01

    Nanoparticles have recently gained increased attention as drug delivery systems for the treatment of cancer due to their minute size and unique chemical properties. However, very few studies have tested the biophysical changes associated with nanoparticles on metastatic cancer cells at the cellular and sub-cellular scales. Here, we investigated the mechanical and morphological properties of cancer cells by measuring the changes in cell Young’s Modulus using AFM, filopodial retraction (FR) by time lapse optical light microscopy imaging and filopodial disorganization by high resolution AFM imaging of cells upon treatment with nanoparticles. In the current study, nanomechanical changes in live murine metastatic breast cancer cells (4T1) post exposure to a nanodiamond/nanoplatinum mixture dispersed in aqueous solution (DPV576), were monitored. Results showed a decrease in Young’s modulus at two hours post treatment with DPV576 in a dose dependent manner. Partial FR at 20 min and complete FR at 40 min were observed. Moreover, analysis of the retraction distance (in microns) measured over time (minutes), showed that a DPV576 concentration of 15%v/v yielded the highest FR rate. In addition, DPV576 treated cells showed early signs of filopodial disorganization and disintegration. This study demonstrates the changes in cell stiffness and tracks early structural alterations of metastatic breast cancer cells post treatment with DPV576, which may have important implications in the role of nanodiamond/nanoplatinum based cancer cell therapy and sensitization to chemotherapy drugs.

  8. CAPECITABINE IN THE TREATMENT OF BRAIN METASTATIC LESION IN PATIENTS WITH BREAST CANCER

    Directory of Open Access Journals (Sweden)

    E. A. Moskvina

    2012-01-01

    Full Text Available The paper considers the experience with capecitabine in 67 patients with brain metastatic lesion from breast cancer. The immediate efficacy of capecitabine and the results of therapy with the agent were analyzed in the groups of its use alone and in combination with radiotherapy both for therapeutic purposes and as an adjuvant regimen. In the chemoradiation therapy group, the objective effects in the brain were 73 %. The median time to progression was 12.27 months. In the monochemotherapy group, the objective effects were 30 %. The median time to progression was 4 months. The results of the investigation show that capecitabine has pronounced antitumor activity and moderate toxicity. Combination treatment is the method of choice. 

  9. 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...... in MBC. Trastuzumab is an important component of first-line treatment of HER2-positive MBC. New anti-HER2 drugs have the potential to change clinical practice. The potential role of the different drugs and regimens is yet to be determined. The response rate for trastuzumab-DM1 of 26-64% is comparable...... to those obtained for capecitabine plus lapatinib (48%), continuing trastuzumab in combination with capecitabine (48%), pertuzumab plus trastuzumab (24%), and neratinib (24%). Strategies combining multiple HER2-directed therapies might yield additive or synergistic effects and lead to improved...

  10. Radiotherapy associated with concurrent bevacizumab in patients with non-metastatic breast cancer.

    Science.gov (United States)

    Pernin, Victor; Belin, Lisa; Cottu, Paul; Bontemps, Patrick; Lemanski, Claire; De La Lande, Brigitte; Baumann, Pierre; Missohou, Fernand; Levy, Christelle; Peignaux, Karine; Bougnoux, Pierre; Denis, Fabrice; Bollet, Marc; Dendale, Rémi; Vago, Nora Ady; Campana, François; Fourquet, Alain; Kirova, Youlia M

    2014-12-01

    The purpose of this multicenter prospective and descriptive study was to determine late toxicities and outcomes among patients with non-metastatic breast cancer receiving concurrent bevacizumab (BV) and radiation therapy (RT) in the clinical trials. Early and late toxicities were assessed and evaluation was available for 63 patients (pts) at 12 months. Acute radiation dermatitis was observed in 48 (76%): grade 1 for 27, grade 2 for 17 and grade 3 for 4 pts. Grade 2 acute oesophagitis was observed in one patient (2%). Little toxicity was described 1 year after the completion of RT: 7 pts (12%): grade 1-2 pain, 3 (5%) presented grade 1 fibrosis, and 2 pts (4%) - telangiectasia. One patient (2%) experienced grade 1 dyspnoea. Five grade 1-2 lymphoedema occurred. Only one patient experienced a LEVF value less than 50% one year after the end of RT. In conclusion, the concurrent BV with locoregional RT provides acceptable toxicities. PMID:25260760

  11. Plasma TIMP-1 levels and treatment outcome in patients treated with XELOX for metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Frederiksen, C.; Qvortrup, C.; Christensen, I.J.; Glimelius, B.; Berglund, Å.; Jensen, B.V.; Nielsen, S.E.; Keldsen, N.; Nielsen, H.J.; Brunner, Nils; Pfeiffer, P.

    2011-01-01

    associations between baseline TIMP-1 or CEA levels and best response to treatment or progression-free survival (PFS) could be demonstrated. In contrast, high baseline plasma TIMP-1 levels were associated with poor overall survival (OS), P = 0.008, hazard ratio (HR) = 1.80 [95% confidence interval (CI): 1......BACKGROUND: The aim was to evaluate the association between plasma tissue inhibitor of metalloproteinase-1 (TIMP-1) and serum carcinoembryonic antigen (CEA) levels and outcome in patients with metastatic colorectal cancer (mCRC) receiving XELOX (combination chemotherapy with capecitabine and...... oxaliplatin) as first-line treatment. PATIENTS AND METHODS: One hundred and twenty patients were included. Blood samples were collected before treatment and 3 weeks later before the next treatment cycle. Plasma TIMP-1 and serum CEA levels were correlated to treatment outcome. RESULTS: No significant...

  12. A group cognitive behaviour therapy programme with metastatic breast cancer patients.

    Science.gov (United States)

    Edelman, S; Bell, D R; Kidman, A D

    1999-01-01

    One-hundred and twenty-four patients with metastatic breast cancer were randomised to either a group Cognitive Behaviour Therapy (CBT) intervention, or to a no-therapy control group condition. Both groups received standard oncological care; however, therapy recipients also attended eight weekly sessions of group CBT, followed by a family night, and three further monthly sessions. Patients completed the 'Profile of Mood States' (POMS) and the Coopersmith Self-esteem Inventory (CSI) before and after therapy, and at 3 and 6 month follow-up periods. Outcome data in the period following therapy showed reduced depression and total mood disturbance, as well as improved self-esteem amongst therapy participants, relative to a no-therapy control group. These improvements were no longer evident at the 3 or 6 month follow-up assessments. We also report on the difficulties associated with conducting a group intervention with this patient cohort. PMID:10474848

  13. Profile of ramucirumab in the treatment of metastatic non-small-cell lung cancer.

    Science.gov (United States)

    Cooper, Maryann R; Binkowski, Chelsea; Hartung, Jessica; Towle, Jennifer

    2016-01-01

    The interaction between vascular endothelial growth factor and its receptor is an important therapeutic target due to the importance of this pathway in carcinogenesis. In particular, this pathway promotes and regulates angiogenesis as well as increases endothelial cell proliferation, permeability, and survival. Ramucirumab is a fully human monoclonal antibody that specifically targets the vascular endothelial growth factor receptor-2, the key receptor implicated in angiogenesis. Currently, ramucirumab is approved for the second-line treatment of metastatic non-small-cell lung cancer (NSCLC) in combination with docetaxel. In a Phase III clinical trial, ramucirumab was shown to improve the overall survival in patients with disease progression, despite platinum-based chemotherapy for advanced NSCLC. This review describes the pharmacology, pharmacokinetics and dynamics, adverse event profile, and the clinical activity of ramucirumab observed in Phase II and III trials in NSCLC. PMID:27110124

  14. Prostate-Specific Antigen Nadir and Time to Prostate-Specific Antigen Nadir Following Maximal Androgen Blockade Independently Predict Prognosis in Patients with Metastatic Prostate Cancer

    OpenAIRE

    Hong, Seok Young; Cho, Dae Sung; Kim, Sun Il; Ahn, Hyun Soo; Kim, Se Joong

    2012-01-01

    Purpose To evaluate the influence of prostate-specific antigen (PSA) kinetics following maximal androgen blockade (MAB) on disease progression and cancer-specific survival in patients with metastatic, hormone-sensitive prostate cancer. Materials and Methods One hundred thirty-one patients with metastatic, hormone-sensitive prostate cancer treated with MAB at our institution were included in this study. Patients' characteristics, PSA at MAB initiation, PSA nadir, time to PSA nadir (TTN), and P...

  15. Involvement of Cox-2 in the metastatic potential of chemotherapy-resistant breast cancer cells

    International Nuclear Information System (INIS)

    A major problem with the use of current chemotherapy regimens for several cancers, including breast cancer, is development of intrinsic or acquired drug resistance, which results in disease recurrence and metastasis. However, the mechanisms underlying this drug resistance are unknown. To study the molecular mechanisms underlying the invasive and metastatic activities of drug-resistant cancer cells, we generated a doxorubicin-resistant MCF-7 breast cancer cell line (MCF-7/DOX). We used MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays, flow cytometry assays, DNA fragmentation assays, Western blot analysis, cell invasion assays, small interfering RNA (siRNA) transfection, reverse transcription-polymerase chain reaction, experimental lung metastasis models, and gelatin and fibrinogen/plasminogen zymography to study the molecular mechanism of metastatic activities in MCF-7/DOX cells. We found that MCF-7/DOX acquired invasive activities. In addition, Western blot analysis showed increased expression of epidermal growth factor receptor (EGFR) and Cox-2 in MCF-7/DOX cells. Inhibition of Cox-2, phosphoinositide 3-kinase (PI3K)/Akt, or mitogen-activated protein kinase (MAPK) pathways effectively inhibited the invasive activities of MCF-7/DOX cells. Gelatin and fibrinogen/plasminogen zymography analysis showed that the enzymatic activities of matrix metalloproteinase-2 (MMP-2), MMP-9, and urokinase-type plasminogen activator were markedly higher in MCF-7/DOX cells than in the MCF-7 cells. In vitro invasion assays and mouse models of lung metastasis demonstrated that MCF-7/DOX cells acquired invasive abilities. Using siRNAs and agonists specific for prostaglandin E (EP) receptors, we found that EP1 and EP3 played important roles in the invasiveness of MCF-7/DOX cells. We found that the invasive activity of MCF-7/DOX cells is mediated by Cox-2, which is induced by the EGFR-activated PI3K/Akt and MAPK pathways. In addition, EP1 and EP3 are important in

  16. On the development of models in mice of advanced visceral metastatic disease for anti-cancer drug testing.

    Science.gov (United States)

    Man, Shan; Munoz, Raquel; Kerbel, Robert S

    2007-12-01

    It is well known clinically that advanced, bulky visceral metastatic disease is generally much less responsive to most anti-cancer therapies, compared to microscopic metastatic disease. This problem is exacerbated when treating cancers that have been previously exposed to multiple lines of therapy, and which have acquired a 'refractory' phenotype. However, mimicking such clinical treatment situations in preclinical mouse models involving the testing of new or existing cancer therapies is extremely rare. Treatment of 'metastasis', in retrospect, usually involves minimal residual disease and therapy naïve tumors. This could account in many instances for the failure to reproduce highly encouraging preclinical results in subsequent phase I or phase II clinical trials. To that end, we have embarked on an experimental program designed to develop models of advanced, visceral metastatic disease, in some cases involving tumors previously exposed to various therapies. The strategy first involves the orthotopic transplantation of a human cancer cell line, such as breast cancer cell line, into the mammary fat pads of immune deficient mice, followed by surgical resection of the resultant primary tumors that develops. Recovery of distant macroscopic metastases, usually in the lungs, is then undertaken, which can take up to 4 months to visibly form. Cell lines are established from such metastases and the process of orthotopic transplantation, surgical resection, and recovery of distant metastases is undertaken, at least one more time. Using such an approach highly metastatically aggressive variant sublines can be obtained, provided they are once again injected into an orthotopic site and the primary tumors removed by surgery. By waiting sufficient time after removal of the primary tumors, about only 1 month, mice with extensive metastatic disease in sites such as the lungs, liver, and lymph nodes can be obtained. An example of therapy being initiated in an advanced stage of such

  17. Capecitabine maintenance therapy in patients with recurrent or metastatic breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Si, W. [General Hospital of the Chinese People' s Liberation Army, Department of Medical Oncology, Haidian District, Beijing, China, Department of Medical Oncology, General Hospital of the Chinese People’s Liberation Army, Haidian District, Beijing (China); School of Medicine, Nankai University, Tianjin (China); Zhu, Y.Y.; Li, Y.; Gao, P.; Han, C.; You, J.H.; Linghu, R.X.; Jiao, S.C.; Yang, J.L. [General Hospital of the Chinese People' s Liberation Army, Department of Medical Oncology, Haidian District, Beijing, China, Department of Medical Oncology, General Hospital of the Chinese People’s Liberation Army, Haidian District, Beijing (China)

    2013-11-25

    Our objective was to investigate the efficacy and safety of capecitabine maintenance therapy (CMT) after capecitabine-based combination chemotherapy in patients with metastatic breast cancer. The clinical data of 139 metastatic breast cancer patients treated from March 2008 to May 2012 with capecitabine-based combination chemotherapy were retrospectively analyzed. When initial disease control was achieved by the combination chemotherapy, we used CMT for 50 patients, while 37 patients were treated with a different (non-CMT) maintenance therapy. We compared time to progression (TTP), objective response rate, disease control rate, clinical benefit rate, and safety of the two groups, and a sub-group analysis was performed according to pathological characteristics. Sixty-four percent of the patients received a median of six cycles of a docetaxel+capecitabine combination chemotherapy regimen (range 1-45); the median TTP (MTTP) for the complete treatment was 9.43 months (95%CI=8.38-10.48 months) for the CMT group and 4.5 months (95%CI=4.22-4.78 months; P=0.004) for the non-CMT group. The MTTPs for the maintenance therapies administered after the initial capecitabine combined chemotherapy were 4.11 months (95%CI=3.34-4.87 months) for the CMT group and 2.0 months (95%CI=1.63-2.38 months) for the non-CMT group. Gastrointestinal side effects, decreased white blood cells and palmar-plantar erythrodysesthesia were the main adverse reactions experienced with the combination chemotherapies, CMT and non-CMT treatments. No significant differences in the incidence of adverse reactions were detected in the CMT and non-CMT patients. After initial disease control was achieved with the capecitabine-based combination chemotherapy, CMT can significantly prolong TTP rates with a favorable safety profile.

  18. Capecitabine maintenance therapy in patients with recurrent or metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    W. Si

    2013-12-01

    Full Text Available Our objective was to investigate the efficacy and safety of capecitabine maintenance therapy (CMT after capecitabine-based combination chemotherapy in patients with metastatic breast cancer. The clinical data of 139 metastatic breast cancer patients treated from March 2008 to May 2012 with capecitabine-based combination chemotherapy were retrospectively analyzed. When initial disease control was achieved by the combination chemotherapy, we used CMT for 50 patients, while 37 patients were treated with a different (non-CMT maintenance therapy. We compared time to progression (TTP, objective response rate, disease control rate, clinical benefit rate, and safety of the two groups, and a sub-group analysis was performed according to pathological characteristics. Sixty-four percent of the patients received a median of six cycles of a docetaxel+capecitabine combination chemotherapy regimen (range 1-45; the median TTP (MTTP for the complete treatment was 9.43 months (95%CI=8.38-10.48 months for the CMT group and 4.5 months (95%CI=4.22-4.78 months; P=0.004 for the non-CMT group. The MTTPs for the maintenance therapies administered after the initial capecitabine combined chemotherapy were 4.11 months (95%CI=3.34-4.87 months for the CMT group and 2.0 months (95%CI=1.63-2.38 months for the non-CMT group. Gastrointestinal side effects, decreased white blood cells and palmar-plantar erythrodysesthesia were the main adverse reactions experienced with the combination chemotherapies, CMT and non-CMT treatments. No significant differences in the incidence of adverse reactions were detected in the CMT and non-CMT patients. After initial disease control was achieved with the capecitabine-based combination chemotherapy, CMT can significantly prolong TTP rates with a favorable safety profile.

  19. "Resurrection of clinical efficacy" after resistance to endocrine therapy in metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Robertson John FR

    2006-07-01

    Full Text Available Abstract Background In a significant proportion of metastatic breast cancer (MBC patients whose tumour has progressed within 6 months of endocrine therapy (de novo resistance, it is generally believed that the chance of achieving clinical benefit (CB with further endocrine therapy is minimal. Methods Data was retrieved from a prospectively updated database of metastatic breast cancer. Relevant data was exported to SPSS™ software for statistical analysis. Results In oestrogen receptor (ER positive MBC patients with assessable disease, CB was achieved in 159 (71.3% (1st line patients. When these patients were put on further endocrine therapy, the CB rates were 63.2% (on 2nd line, 46.1% (on 3rd line and 20% (on 4th line with a median duration of response (DOR in those with CB of 22, 12, 11 and 15 months respectively. The remaining 64(28.7% patients had de novo resistance on 1st line endocrine therapy. Seventeen of these patients were treated with further endocrine therapy. The CB rates were 29.4% (on 2nd line and 22.2% (on 3rd line with a median DOR in those with CB of 22.7 months and 14 months respectively. Conclusion The chance of further endocrine response continues to decrease with each line of therapy, yet CB is still seen with reasonable duration even with a 4th line agent. In addition, further endocrine response, with long duration, can be seen in a significant proportion of patients who have developed de novo resistance to 1st line endocrine therapy. The use of further endocrine therapy should not be excluded under these circumstances.

  20. Second-line therapy for gemcitabine-pretreated advanced or metastatic pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Romain Altwegg; Marc Ychou; Vanessa Guillaumon; Simon Thezenas; Pierre Senesse; Nicolas Flori; Thibault Mazard

    2012-01-01

    AIM:To investigate second-line chemotherapy in gemcitabine-pretreated patients with advanced or metastatic pancreatic cancer [(frequency,response,outcome,course of carbohydrate antigen 19-9 (CA 19-9)].METHODS:This retrospective study included all patients with advanced or metastatic pancreatic cancer (adenocarcinoma or carcinoma) treated with secondline chemotherapy in our center between 2000 and 2008.All patients received first-line chemotherapy with gemcitabine,and prior surgery or radiotherapy was permitted.We analyzed each chemotherapy protocol for second-line treatment,the number of cycles and the type of combination used.The primary endpoint was overall survival.Secondary endpoints included progression-free survival,response rate,grade 3-4 toxicity,dosage modifications and CA 19-9 course.RESULTS:A total of eighty patients (38%) underwent a second-line therapy among 206 patients who had initially received first-line treatment with a gemcitabine-based regimen.Median number of cycles was 4 (range:1-12) and the median duration of treatment was 2.6 mo (range:0.3-7.4).The overall disease control rate was 40.0%.The median overall survival and progression-free survival from the start of second-line therapy were 5.8 (95% CI:4.1-6.6) and 3.4 mo (95% CI:2.4-4.2),respectively.Toxicity was generally acceptable.Median overall survival of patients with a CA 19-9 level declining by more than 20% was 10.3 mo (95% CI:4.5-11.6) vs 5.2 mo (95% CI:4.0-6.4) for others (P =0.008).CONCLUSION:A large proportion of patients could benefit from second-line therapy,and CA 19-9 allows efficient treatment monitoring both in first and secondline chemotherapy.

  1. Capecitabine maintenance therapy in patients with recurrent or metastatic breast cancer

    International Nuclear Information System (INIS)

    Our objective was to investigate the efficacy and safety of capecitabine maintenance therapy (CMT) after capecitabine-based combination chemotherapy in patients with metastatic breast cancer. The clinical data of 139 metastatic breast cancer patients treated from March 2008 to May 2012 with capecitabine-based combination chemotherapy were retrospectively analyzed. When initial disease control was achieved by the combination chemotherapy, we used CMT for 50 patients, while 37 patients were treated with a different (non-CMT) maintenance therapy. We compared time to progression (TTP), objective response rate, disease control rate, clinical benefit rate, and safety of the two groups, and a sub-group analysis was performed according to pathological characteristics. Sixty-four percent of the patients received a median of six cycles of a docetaxel+capecitabine combination chemotherapy regimen (range 1-45); the median TTP (MTTP) for the complete treatment was 9.43 months (95%CI=8.38-10.48 months) for the CMT group and 4.5 months (95%CI=4.22-4.78 months; P=0.004) for the non-CMT group. The MTTPs for the maintenance therapies administered after the initial capecitabine combined chemotherapy were 4.11 months (95%CI=3.34-4.87 months) for the CMT group and 2.0 months (95%CI=1.63-2.38 months) for the non-CMT group. Gastrointestinal side effects, decreased white blood cells and palmar-plantar erythrodysesthesia were the main adverse reactions experienced with the combination chemotherapies, CMT and non-CMT treatments. No significant differences in the incidence of adverse reactions were detected in the CMT and non-CMT patients. After initial disease control was achieved with the capecitabine-based combination chemotherapy, CMT can significantly prolong TTP rates with a favorable safety profile

  2. Role of cetuximab and sorafenib in treatment of metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    K M Galal

    2011-01-01

    Full Text Available Background: The relationship of epidermal growth factor receptors (EGFR pathway, such as PI3K, K-ras, and B-raf, with response to EGFR-targeted antibodies is less well studied. Aim: To assess sorafenib with cetuximab in treating metastatic colorectal cancer. Settings and Design: Thirty-five patients with metastatic colorectal cancer were randomized to receive cetuximab with or without oral sorafenib. Patients and Methods: Patients received cetuximab IV weekly for four weeks and oral sorafenib twice daily on days 1 - 28, with recycling every four weeks. The primary end point was the response rate (partial and complete, while the secondary end points were the adverse effects, time to progression and overall survival. Statistical Analysis was made using the Statistical Product and Service Solutions, using SPSS 10.0, with estimation of both time to progression and overall survival time by the Kaplan-Meier method and comparing the two groups with the use of a log-rank test. Results: Partial response was higher in cetuximab-sorafenib (EN, which constituted 33.3% compared to 17.6% in the cetuximab group (P = 0.44. Progression-free survival had a statistically higher significant difference in wild K-ras compared to mutant K-ras cases (P = .0001. Median overall survival was seven and five months in the (EN and (E groups respectively (P = 0.49. Conclusion: K-ras and B-raf was a predictor of response, so genotyping of tumors was needed for defining the patient population that was likely to benefit from the targeted therapy. A combination of therapy that simultaneously targets K-ras and B-raf could be a useful approach to increase the number of patients who may benefit from anti-EGFR therapy.

  3. Prognostic Value of Fluoro-D-glucose Uptake of Primary Tumor and Metastatic Lesions in Advanced Nonsmall Cell Lung Cancer

    OpenAIRE

    Nguyen, Xuan Canh; Nguyen, Khoi; Tran, Minh Thong; Maurea, Simone; Salvatore, Marco

    2014-01-01

    To assess the prognostic value of maximum standardized uptake value (maxSUV) of the primary tumor (maxSUVpt), maxSUV of whole-body tumors (maxSUVwb) and sum of maximum standardized uptake value (sumaxSUV) measured by the sum of maxSUVs of the primary tumor, metastatic lymph nodes, and metastatic lesions per each organ on fluoro-D-glucose-positron emission tomography/computed tomography in advanced non-small cell lung cancer (NSCLC). Eighty-three patients (49 male, 34 female) with advanced NSC...

  4. Photo-nano immunotherapy for metastatic breast cancer using synergistic single-walled carbon nanotubes and glycated chitosan

    Science.gov (United States)

    Zhou, Feifan; Hasanjee, Aamr; Doughty, Austin; West, Connor; Liu, Hong; Chen, Wei R.

    2015-03-01

    In our previous work, we constructed a multifunctional nano system, using single-walled carbon nanotube (SWNT) and glycated chitosan (GC), which can synergize photothermal and immunological effects. To further confirm the therapy efficacy, with a metastatic mouse mammary tumor model (4T1), we investigate the therapy effects and immune response induced by SWNT-GC, under laser irradiation. Laser+SWNT-GC treatment not only suppressed the prime tumor, but also induced antitumor immune response. It could be developed into a promising treatment modality for the metastatic breast cancer.

  5. Review of the Interaction Between Body Composition and Clinical Outcomes in Metastatic Renal Cell Cancer Treated With Targeted Therapies

    OpenAIRE

    Steven M Yip; Heng, Daniel Y. C.; Tang, Patricia A.

    2016-01-01

    Treatment of metastatic renal cell cancer (mRCC) currently focuses on inhibition of the vascular endothelial growth factor pathway and the mammalian target of rapamycin (mTOR) pathway. Obesity confers a higher risk of RCC. However, the influence of obesity on clinical outcomes in mRCC in the era of targeted therapy is less clear. This review focuses on the impact of body composition on targeted therapy outcomes in mRCC. The International Metastatic Renal Cell Carcinoma Database Consortium dat...

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

    International Nuclear Information System (INIS)

    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.)

  7. Generation of Organ-conditioned Media and Applications for Studying Organ-specific Influences on Breast Cancer Metastatic Behavior.

    Science.gov (United States)

    Piaseczny, Matthew M; Pio, Graciella M; Chu, Jenny E; Xia, Ying; Nguyen, Kim; Goodale, David; Allan, Alison

    2016-01-01

    Breast cancer preferentially metastasizes to the lymph node, bone, lung, brain and liver in breast cancer patients. Previous research efforts have focused on identifying factors inherent to breast cancer cells that are responsible for this observed metastatic pattern (termed organ tropism), however much less is known about factors present within specific organs that contribute to this process. This is in part because of a lack of in vitro model systems that accurately recapitulate the organ microenvironment. To address this, an ex vivo model system has been established that allows for the study of soluble factors present within different organ microenvironments. This model consists of generating conditioned media from organs (lymph node, bone, lung, and brain) isolated from normal athymic nude mice. The model system has been validated by demonstrating that different breast cancer cell lines display cell-line specific and organ-specific malignant behavior in response to organ-conditioned media that corresponds to their in vivo metastatic potential. This model system can be used to identify and evaluate specific organ-derived soluble factors that may play a role in the metastatic behavior of breast and other types of cancer cells, including influences on growth, migration, stem-like behavior, and gene expression, as well as the identification of potential new therapeutic targets for cancer. This is the first ex vivo model system that can be used to study organ-specific metastatic behavior in detail and evaluate the role of specific organ-derived soluble factors in driving the process of cancer metastasis. PMID:27341354

  8. Rationality and Irrationality in Ryke Geerd Hamer's System for Holistic Treatment of Metastatic Cancer

    Directory of Open Access Journals (Sweden)

    Søren Ventegodt

    2005-01-01

    Full Text Available The aim of this paper is to examine if the “medical laws” found by the German physician Ryke Geerd Hamer are substantiated by contemporary holistic medical theory. He developed a psychosomatic theory after a personal emotional trauma that he believed resulted in his subsequent development of a testicular cancer. From our analysis, it is clear that the two most fundamental principles of Hamer's work, the psychosomatic “iron law of cancer” (Hamer's first “law” and the principle of pathogenesis being reversed into salutogenesis (Hamer's second “law”, are well-established principles of holistic medicine today. Hamer's understanding of symbols in medicine, virus and bacteria, and the evolutionary process itself (Hamer's third, fourth, and fifth “law” differs a great deal from both traditional and contemporary holistic medical theory and we did not find them substantiated. Hamer's understanding of cancer metastasis was built on these failing principles and therefore not substantiated either. Altogether, it seems that Hamer's thinking was basically sound as the most fundamental principles of his work were built on an understanding very similar to holistic medical thinkers of today. We found his postulate that metastatic cancer patients can be healed or their health improved by using his system of holistic medicine likely to be true, at least for some motivated patients. This must be tested scientifically, however, before being accepted. His presentation of his system and work has been idiosyncratic and highly provocative, which has alienated him from the whole medical community.

  9. Ixabepilone: a new treatment option for the management of taxane-resistant metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Marta Vallee Cobham

    2009-06-01

    Full Text Available Marta Vallee Cobham, Diana DonovanWeill Cornell Breast Center, Cornell University/New York-Presbyterian Hospital, New York, NY, USAAbstract: Ixabepilone (Ixempra®; Bristol-Myers Squibb is a novel microtubule stabilizing agent recently approved for the treatment of metastatic breast cancer (MBC. This article focuses on considerations for ixabepilone administration and adverse event (AE management, drawing from the biomedical literature indexed in PubMed, published abstracts from the American Society of Clinical Oncology annual meetings, and the manufacturer’s prescribing information for ixabepilone. Administered as monotherapy or in combination with capecitabine in clinical studies, ixabepilone demonstrated positive clinical response rates, prolonged progression-free survival, and a favorable safety profile in patients with MBC. Treatment-related AEs were predictable and manageable with dose modification, treatment interruption, and active management. As ixabepilone undergoes development in earlier lines of breast cancer therapy and in other solid tumors, oncology nurses will encounter more and more patients receiving ixabepilone therapy. If nurses are acquainted with the unique management strategies associated with ixabepilone treatment, as detailed herein, patients are more likely to receive the full benefit of therapy. Keywords: breast cancer, chemotherapy, microtubule-stabilizing agent, ixabepilone, adverse events, patient management 

  10. The hypoxic cancer secretome induces pre-metastatic bone lesions through lysyl oxidase

    Science.gov (United States)

    Cox, Thomas R.; Rumney, Robin M.H.; Schoof, Erwin M.; Perryman, Lara; Høye, Anette M.; Agrawal, Ankita; Bird, Demelza; Latif, Norain Ab; Forrest, Hamish; Evans, Holly R.; Huggins, Iain D; Lang, Georgina; Linding, Rune

    2016-01-01

    Tumour metastasis is a complex process involving reciprocal interplay between cancer cells and host stroma at both primary and secondary sites, and is strongly influenced by microenvironmental factors such as hypoxia1. Tumour-secreted proteins play a crucial role in these interactions2–5 and present strategic therapeutic potential. Metastasis of breast cancer to the bone affects approximately 85% of patients with advanced disease and renders them largely untreatable6. Specifically, osteolytic bone lesions, where bone is destroyed, lead to debilitating skeletal complications and increased patient morbidity and mortality6,7. The molecular interactions governing the early events of osteolytic lesion formation are currently unclear. Here we show hypoxia to be specifically associated with bone relapse in ER-negative breast cancer patients. Global quantitative analysis of the hypoxic secretome identified Lysyl Oxidase (LOX) as significantly associated with bone-tropism and relapse. High expression of LOX in primary breast tumours or systemic delivery of LOX leads to osteolytic lesion formation whereas silencing or inhibition of LOX activity abrogates tumour-driven osteolytic lesion formation. We identify LOX as a novel regulator of NFATc1-driven osteoclastogenesis, independent of RANK Ligand, which disrupts normal bone homeostasis leading to the formation of focal pre-metastatic lesions. We show that these lesions subsequently provide a platform for circulating tumour cells to colonise and form bone metastases. Our study identifies a novel mechanism of regulation of bone homeostasis and metastasis, opening up opportunities for novel therapeutic intervention with important clinical implications. PMID:26017313

  11. Anti-VEGF agents in metastatic colorectal cancer (mCRC: are they all alike?

    Directory of Open Access Journals (Sweden)

    Saif MW

    2013-06-01

    Full Text Available Muhammad Wasif Saif GI Oncology Program, Tufts University School of Medicine, Boston, MA, USA Abstract: Bevacizumab is a monoclonal antibody that binds and neutralizes vascular endothelial growth factor (VEGF-A, a key player in the angiogenesis pathway. Despite benefits of bevacizumab in cancer therapy, it is clear that the VEGF pathway is complex, involving multiple isoforms, receptors, and alternative ligands such as VEGF-B, and placental growth factor, which could enable escape from VEGF-A-targeted angiogenesis inhibition. Recently developed therapies have targeted other ligands in the VEGF pathway (eg, aflibercept, known as ziv-aflibercept in the United States, VEGF receptors (eg, ramucirumab, and their tyrosine kinase signaling (ie, tyrosine kinase inhibitors. The goal of the current review was to identify comparative preclinical data for the currently available VEGF-targeted therapies. Sources were compiled using PubMed searches (2007 to 2012, using search terms including, but not limited to: “bevacizumab,” “aflibercept,” “ramucirumab,” and “IMC-18F1.” Two preclinical studies were identified that compared bevacizumab and the newer agent, aflibercept. These studies identified some important differences in binding and pharmacodynamic activity, although the potential clinical relevance of these findings is not known. Newer antiangiogenesis therapies should help further expand treatment options for colorectal and other cancers. Comparative preclinical data on these agents is currently lacking. Keywords: aflibercept, antiangiogenesis, metastatic colorectal cancer (mCRC, tyrosine kinase inhibitor (TKI, vascular endothelial growth factor (VEGF

  12. Mechanical properties of metastatic breast cancer cells invading into collagen I matrices

    Science.gov (United States)

    Ros, Robert

    2014-03-01

    Mechanical interactions between cells and the extracellular matrix (ECM) are critical to the metastasis of cancer cells. To investigate the mechanical interplay between the cells and ECM during invasion, we created thin bovine collagen I hydrogels ranging from 0.1-5 kPa in Young's modulus that were seeded with highly metastatic MDA-MB-231 breast cancer cells. Significant population fractions invaded the matrices either partially or fully within 24 h. We then combined confocal fluorescence microscopy and indentation with an atomic force microscope to determine the Young's moduli of individual embedded cells and the pericellular matrix using novel analysis methods for heterogeneous samples. In partially embedded cells, we observe a statistically significant correlation between the degree of invasion and the Young's modulus, which was up to an order of magnitude greater than that of the same cells measured in 2D. ROCK inhibition returned the cells' Young's moduli to values similar to 2D and diminished but did not abrogate invasion. This provides evidence that Rho/ROCK-dependent acto-myosin contractility is employed for matrix reorganization during initial invasion, and suggests the observed cell stiffening is due to an attendant increase in actin stress fibers. This work was supported by the National Cancer Institute under the grant U54 CA143862.

  13. Low-temperature plasma needle effects on cultured metastatic breast cancer cells

    Science.gov (United States)

    Knecht, Sean; Bilen, Sven; Micci, Michael; Brubaker, Timothy; Wilson, Michael; Cook, Ian; Czesak, Nicholas; Hipkins, Garret

    2015-11-01

    The Penn State Low-Temperature Plasma group is presently investigating the applications of low-temperature plasma for biomedical applications, including the effects on MDA-MB-231 metastatic breast cancer cells. A plasma needle system has been designed and constructed that consists of a 22-gauge stainless steel syringe needle, which acts as the high-voltage electrode, covered with PEEK tubing as the dielectric with a ring ground electrode on the outside. The system is driven by a low-frequency AC voltage amplifier, with typical operating conditions of 2-5 kV peak voltage at 5 kHz. Helium is used as the working fluid and produces a plasma jet with ~ cm's visible extent. Cultured breast cancer cells were provided by our collaborator and exposed to the plasma needle for varying doses and detachment of cells was observed. The effects are attributed to reactive oxygen and nitrogen species generation and transport through the cell culture medium. Plasma needle characterization and the results of the breast cancer experiments will be presented.

  14. Metastatic dormancy: a complex network between cancer stem cells and their microenvironment.

    Science.gov (United States)

    Bleau, Anne-Marie; Agliano, Alice; Larzabal, Leyre; de Aberasturi, Arrate Lopez; Calvo, Alfonso

    2014-12-01

    Metastasis represents the major threat of cancer progression and generally emerges years after the detection of the primary tumor. An important rate-limiting step resides in cellular dormancy, where a disseminated tumor cell remains in a quiescent state at a remote organ. Herein we review the molecular mechanisms leading to tumor dormancy, mainly in regards to cellular quiescence and the tumor microenvironment. Based on the current published literature, we provide evidence that links the cancer stem cell (CSC) theory with dormancy and metastasis. Once a disseminated tumor cell reaches a target tissue, a tight regulation imposed by the foreign microenvironment will dictate the fate of these cells, which implies a balance in the secretion of soluble factors, modulation of the extracellular matrix and the angiogenic switch. We investigate thoroughly whether the CSC theory could also apply to metastasis initiation. In fact, the resistance of CSCs to therapy, leading to the minimal residual disease and cellular quiescence phenotypes, predisposes for the development of metastases. Finally, we describe the new technologies available for the identification of circulating tumor cells (CTCs), as well as their clinical relevance in dormancy of metastatic cancer patients. PMID:24887025

  15. Novel esophageal squamous cell carcinoma bone metastatic clone isolated by scintigraphy, X ray and micro PET/CT

    OpenAIRE

    Zhao, Bi-Zeng; Cao, Jie; Shao, Jin-chen; Sun, Yan-Bing; Fan, Li-Min; Wu, Chun-Yu; Liang, Sheng; Guo, Bao-Feng; Yang, Guang; Xie, Wen-Hui; Yang, Qing-cheng; Yang, Shun-Fang

    2014-01-01

    AIM: To establish a Chinese esophageal squamous cell carcinoma (ESCC) cell line with high bone metastasis potency using 99mTc-methylene diphosphonate (99mTc-MDP) micro-pinhole scintigraphy, X ray and micro-positron emission tomography/computed tomography (PET/CT) for exploring the mechanism of occurrence and development in esophageal cancer.

  16. Genome and transcriptome sequencing in prospective metastatic triple-negative breast cancer uncovers therapeutic vulnerabilities.

    Science.gov (United States)

    Craig, David W; O'Shaughnessy, Joyce A; Kiefer, Jeffrey A; Aldrich, Jessica; Sinari, Shripad; Moses, Tracy M; Wong, Shukmei; Dinh, Jennifer; Christoforides, Alexis; Blum, Joanne L; Aitelli, Cristi L; Osborne, Cynthia R; Izatt, Tyler; Kurdoglu, Ahmet; Baker, Angela; Koeman, Julie; Barbacioru, Catalin; Sakarya, Onur; De La Vega, Francisco M; Siddiqui, Asim; Hoang, Linh; Billings, Paul R; Salhia, Bodour; Tolcher, Anthony W; Trent, Jeffrey M; Mousses, Spyro; Von Hoff, Daniel; Carpten, John D

    2013-01-01

    Triple-negative breast cancer (TNBC) is characterized by the absence of expression of estrogen receptor, progesterone receptor, and HER-2. Thirty percent of patients recur after first-line treatment, and metastatic TNBC (mTNBC) has a poor prognosis with median survival of one year. Here, we present initial analyses of whole genome and transcriptome sequencing data from 14 prospective mTNBC. We have cataloged the collection of somatic genomic alterations in these advanced tumors, particularly those that may inform targeted therapies. Genes mutated in multiple tumors included TP53, LRP1B, HERC1, CDH5, RB1, and NF1. Notable genes involved in focal structural events were CTNNA1, PTEN, FBXW7, BRCA2, WT1, FGFR1, KRAS, HRAS, ARAF, BRAF, and PGCP. Homozygous deletion of CTNNA1 was detected in 2 of 6 African Americans. RNA sequencing revealed consistent overexpression of the FOXM1 gene when tumor gene expression was compared with nonmalignant breast samples. Using an outlier analysis of gene expression comparing one cancer with all the others, we detected expression patterns unique to each patient's tumor. Integrative DNA/RNA analysis provided evidence for deregulation of mutated genes, including the monoallelic expression of TP53 mutations. Finally, molecular alterations in several cancers supported targeted therapeutic intervention on clinical trials with known inhibitors, particularly for alterations in the RAS/RAF/MEK/ERK and PI3K/AKT/mTOR pathways. In conclusion, whole genome and transcriptome profiling of mTNBC have provided insights into somatic events occurring in this difficult to treat cancer. These genomic data have guided patients to investigational treatment trials and provide hypotheses for future trials in this irremediable cancer. PMID:23171949

  17. Therapeutic trials to control metastatic cancer with 90Y-DOTA-Lanreotide

    International Nuclear Information System (INIS)

    As Somatostatin-analogue-scintigraphy using 111In labelled ligands could demonstrate a high density of somatostatin-receptors in a variety of cancer types, we tried to use 90Y-DOTA-Lanreotide (= 'MAURITIUS') for therapy in patients with rapidly progressing metastatic disease in whom no other therapy had been effective after uptake of the molecule in metastases was assessed by scanning (including SPECT) with 184 MBq 111In-DOTA-Lanreotide. Fifteen patients were treated so far (carcinoid tumours 8, thyroid cancer 5, oesophagus cancer 1, colon/prostate cancer 1) after dosimetry including estimates of radiation dose to tumour, whole body, marrow, urinary tract and liver. According to these data they received 740-1590 MBq 90Y-Lanreotide at intervals of 2-6 weeks up to 6 times which gave 10-18 Gy to the tumour. Follow-up for up to 12 months showed complete/partial remissions in 2/15, stable disease in 6/15 and no effect in 6/15. A comparison of scan data between 111In-Octreotide and 111In-Lanreotide showed that binding of both tracers was different in 7/17 patients, showing either better Octreotide-uptake or better Lanreotide-uptake. Side effects were only transient thrombocytopenia (5/15) and moderate leukopenia (6/15). Obviously, even with low doses of 90Y-Lanreotide some improvement in the management of patients with cancer types expressing somatostatin receptors can be achieved when rapid progression of metastases occurs. Modifications of the therapy protocol could perhaps improve our preliminary results. (author)

  18. Cloning of HPV16 E2 Gene from a Biopsied Cervical Cancer Sample

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective To clone HPV16 E2 gene from a biopsied cervical cancer sampleMaterials & Methods HPV 1 6 E2 gene was amplified from specimen derived from aHPV 16 positive patient, then cloned and sequenced. Results The full-length of HPV 16 E2 gene was successfully cloned. In comparisonwith the prototype accepted by GenBank, six point mutations in HPV 1 6 E2 nucleotideacid sequence were identified. Of them, three were missense, and one was in the over-lapping E4 gene and was synonymous to E4.Conclusion HPV 16 E2 gene was successfully cloned, and some nucleotide acids in itssequence were different from the prototype.

  19. Revaluation on detection of metastatic cancer of the colorectum with barium enema. Comparison with computed tomography and colonoscopy

    International Nuclear Information System (INIS)

    The findings with barium enema were analyzed and compared to those with computed tomography and colonoscopy in 15 patients with metastatic cancer of the colorectum, which were from 8 gastric, 2 colonic, 2 ovarian, 1 pancreatic, 1 prostatic carcinomas and 1 unknown origin. Primary cancers of intra-abdominal cavity origin tended to make multiple colorectal metastases (91.7%). With barium enema colonic and rectal involvement was mostly expressed as the tethered type and the diffuse type by Ishikawa's classification, respectively. Computed tomography detected direct tumor invasion to the colorectum in 4 cases. Of the other 11 cases, 8 patients (72.3%) showed abnormally thickened colorectal wall. Colonoscopy detected only 3 (37.5%) out of 8 lesions seen in 4 patients who had undergone colonoscopy before barium enema. Many of the lesions missed were the tethered type involvement. Barium enema is the most sensitive method to detect metastatic cancer of the colorectum. (author)

  20. Visualisation of metastatic oesophageal and gastric cancer and prediction of clinical response to palliative chemotherapy using {sup 18}FDG PET

    Energy Technology Data Exchange (ETDEWEB)

    Lorenzen, S.; Peschel, C.; Lordick, F. [Dept. of Internal Medicine, Haematology/Medical Oncology, Technical Univ. Munich (Germany); Herrmann, K.; Wieder, H.; Schwaiger, M. [Dept. of Nuclear Medicine, Technical Univ. Munich (Germany); Weber, W.A.; Hennig, M. [Inst. for Medical Statistics and Epidemiology, Technical Univ. Munich (Germany); Ott, K. [Dept. of Surgery, Technical Univ. of Munich (Germany); Bredenkamp, R. [Munich Centre for Clinical Studies, Munich (Germany)

    2007-07-01

    Aim: This study assessed the value of {sup 18}F-deoxyglucose positron emission tomography (FDG-PET) for visualisation and early metabolic response assessment in metastatic gastro-oesophageal cancer. Patients, methods: Twenty-six patients who were treated for metastatic disease (20 adenocarcinomas, 6 squamous cell cancers) underwent FDG-PET before and two weeks after the onset of palliative chemotherapy with either oxaliplatin + 5-FU/LV or with docetaxel + capecitabine. PET results were validated according to clinical response based on RECIST criteria. Results: Twenty-four tumours (92%) could be visualised by FDG-PET and were also assessable by a second PET scan at 2 weeks. The 2 tumours that were not detectable by PET were both gastric cancers belonging to the non-intestinal subtype according to Lauren. Median time to progression and overall survival were not significantly different for metabolic responders and non-responders (6.3 vs 5.3 months and 14.1 vs 12.5 months, respectively). Conclusion: In this heterogeneous study population, FDG-PET had a limited accuracy in predicting clinical response. However, the metabolic response prediction was particularly good in the subgroup of patients with oesophageal squamous cell cancer. Therefore, FDG-PET and assessment of cancer therapy clearly merits further investigation in circumscribed patient populations with metastatic disease. (orig.)

  1. Cooperative Treatment of Metastatic Breast Cancer Using Host-Guest Nanoplatform Coloaded with Docetaxel and siRNA.

    Science.gov (United States)

    Wang, Dangge; Wang, Tingting; Xu, Zhiai; Yu, Haijun; Feng, Bing; Zhang, Junying; Guo, Chengyue; Yin, Qi; Zhang, Zhiwen; Li, Yaping

    2016-01-27

    Conventional chemotherapy shows moderate efficiency against metastatic cancer since it targets only part of the mechanisms regulating tumor growth and metastasis. Here, gold nanorod (GNR)-based host-guest nanoplatforms loaded with docetaxel (DTX) and small interfering RNA (siRNA)-p65 (referred to as DTX-loaded GNR (GDTX)/p65) for chemo-, RNA interference (RNAi), and photothermal ablation (PTA) cooperative treatment of metastatic breast cancer are reported. To prepare the nanoplatform, GNRs are first coated with cyclodextrin (CD)-grafted polyethylenimine (PEI) and then loaded with DTX and siRNA through host-guest interaction with CD and electrostatic interaction with PEI, respectively. Upon near-infrared laser irradiation, GNRs generate a significant hyperthermia effect to trigger siRNA and DTX release. DTX reduces tumor growth by inhibiting mitosis of cancer cells. Meanwhile, siRNA-p65 suppresses lung metastasis and proliferation of cancer cells by blocking the nuclear factor kappa B (NF-κB) pathway and downregulating the downstream genes matrix metalloproteinase-9 (MMP-9) and B cell lymphoma-2 (Bcl-2). It is demonstrated that GDTX/p65 in combination with laser irradiation significantly inhibits the growth and lung metastasis of 4T1 breast tumors. The antitumor results suggest promising potential of the host-guest nanoplatform for combinational treatment of metastatic cancer by using RNAi, chemotherapy, and PTA. PMID:26662850

  2. Increased B Regulatory Phenotype in Non-Metastatic Lymph Nodes of Node-Positive Breast Cancer Patients.

    Science.gov (United States)

    Mehdipour, F; Razmkhah, M; Hosseini, A; Bagheri, M; Safaei, A; Talei, A-R; Ghaderi, A

    2016-03-01

    Tumour-draining lymph nodes (TDLNs) are centre in orchestrating the immune responses against cancer. The cellularity and lymphocyte subpopulations change in the process of cancer progression and lymph node involvement. B lymphocyte subsets and their function in breast cancer-draining lymph nodes have not been well elucidated. Here, we studied the influence of tumour metastasis on the frequencies of different B cell subsets including naïve and memory B cells as well as those which are known to be enriched in the regulatory pool in TDLNs of 30 patients with breast cancer. Lymphocytes were obtained from a fresh piece of each lymph node and stained for CD19 and other B cell-associated markers and subjected to flow cytometry. Our investigation revealed that metastatic TDLN showed a significant decrease in active, memory and class-switched B cells while the frequencies of B cells with regulatory phenotypes were not changed. However, CD27(hi) CD25(+) and CD1d(hi) CD5(+) B regulatory subsets significantly increased in non-metastatic lymph nodes (nMLNs) of node-positive patients compared with node-negative patients. Our data provided evidence that in breast cancer, metastasis of tumour to axillary lymph nodes altered B cell populations in favour of resting, inactive and unswitched phenotypes. We assume that the lymphatic involvement may cause an increase in a subset of regulatory B cells in non-metastatic lymph nodes. PMID:26708831

  3. Co-evolution of somatic variation in primary and metastatic colorectal cancer may expand biopsy indications in the molecular era.

    Directory of Open Access Journals (Sweden)

    Richard Kim

    Full Text Available Metastasis is thought to be a clonal event whereby a single cell initiates the development of a new tumor at a distant site. However the degree to which primary and metastatic tumors differ on a molecular level remains unclear. To further evaluate these concepts, we used next generation sequencing (NGS to assess the molecular composition of paired primary and metastatic colorectal cancer tissue specimens.468 colorectal tumor samples from a large personalized medicine initiative were assessed by targeted gene sequencing of 1,321 individual genes. Eighteen patients produced genomic profiles for 17 paired primary:metastatic (and 2 metastatic:metastatic specimens.An average of 33.3 mutations/tumor were concordant (shared between matched samples, including common well-known genes (APC, KRAS, TP53. An average of 2.3 mutations/tumor were discordant (unshared among paired sites. KRAS mutational status was always concordant. The overall concordance rate for mutations was 93.5%; however, nearly all (18/19 (94.7% paired tumors showed at least one mutational discordance. Mutations were seen in: TTN, the largest gene (5 discordant pairs, ADAMTS20, APC, MACF1, RASA1, TP53, and WNT2 (2 discordant pairs, SMAD2, SMAD3, SMAD4, FBXW7, and 66 others (1 discordant pair.Whereas primary and metastatic tumors displayed little variance overall, co-evolution produced incremental mutations in both. These results suggest that while biopsy of the primary tumor alone is likely sufficient in the chemotherapy-naïve patient, additional biopsies of primary or metastatic disease may be necessary to precisely tailor therapy following chemotherapy resistance or insensitivity in order to adequately account for tumor evolution.

  4. Leptin receptor (Ob-R) mRNA expression and serum leptin concentration in patients with colorectal and metastatic colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Erkasap, N.; Ozkurt, M. [Department of Physiology, Osmangazi University Medical Faculty, Meselik, Eskisehir (Turkey); Erkasap, S.; Yasar, F. [Department of General Surgery, Osmangazi University Medical Faculty, Meselik, Eskisehir (Turkey); Uzuner, K. [Department of Physiology, Osmangazi University Medical Faculty, Meselik, Eskisehir (Turkey); Ihtiyar, E. [Department of General Surgery, Osmangazi University Medical Faculty, Meselik, Eskisehir (Turkey); Uslu, S.; Kara, M. [Department of Biochemistry, Osmangazi University Medical Faculty, Meselik, Eskisehir (Turkey); Bolluk, O. [Department of Biostatistics, Osmangazi University Medical Faculty, Meselik, Eskisehir (Turkey)

    2013-03-19

    The objective of the present study was to investigate the effect of leptin on the progression of colorectal carcinoma to metastatic disease by analyzing the serum leptin concentration and Ob-R gene expression in colon cancer tissues. Tissue samples were obtained from 31 patients who underwent surgical resection for colon (18 cases) and metastatic colon (13 cases) cancer. Serum leptin concentration was determined by an enzyme-linked immunosorbent assay (ELISA) and Ob-R mRNA expression by real-time polymerase chain reaction (RT-PCR) for both groups. ELISA data were analyzed by the Student t-test and RT-PCR data were analyzed by the Mann-Whitney U-test. RT-PCR results demonstrated that mRNA expression of Ob-R in human metastatic colorectal cancer was higher than in local colorectal cancer tissues. On the other hand, mean serum leptin concentration was significantly higher in local colorectal cancer patients compared to patients with metastatic colorectal cancer. The results of the present study suggest a role for leptin in the progression of colon cancer to metastatic disease without weight loss. In other words, significantly increased Ob-R mRNA expression and decreased serum leptin concentration in patients with metastatic colon cancer indicate that sensitization to leptin activity may be a major indicator of metastasis to the colon tissue and the determination of leptin concentration and leptin gene expression may be used to aid the diagnosis.

  5. Leptin receptor (Ob-R) mRNA expression and serum leptin concentration in patients with colorectal and metastatic colorectal cancer

    International Nuclear Information System (INIS)

    The objective of the present study was to investigate the effect of leptin on the progression of colorectal carcinoma to metastatic disease by analyzing the serum leptin concentration and Ob-R gene expression in colon cancer tissues. Tissue samples were obtained from 31 patients who underwent surgical resection for colon (18 cases) and metastatic colon (13 cases) cancer. Serum leptin concentration was determined by an enzyme-linked immunosorbent assay (ELISA) and Ob-R mRNA expression by real-time polymerase chain reaction (RT-PCR) for both groups. ELISA data were analyzed by the Student t-test and RT-PCR data were analyzed by the Mann-Whitney U-test. RT-PCR results demonstrated that mRNA expression of Ob-R in human metastatic colorectal cancer was higher than in local colorectal cancer tissues. On the other hand, mean serum leptin concentration was significantly higher in local colorectal cancer patients compared to patients with metastatic colorectal cancer. The results of the present study suggest a role for leptin in the progression of colon cancer to metastatic disease without weight loss. In other words, significantly increased Ob-R mRNA expression and decreased serum leptin concentration in patients with metastatic colon cancer indicate that sensitization to leptin activity may be a major indicator of metastasis to the colon tissue and the determination of leptin concentration and leptin gene expression may be used to aid the diagnosis

  6. Leptin receptor (Ob-R mRNA expression and serum leptin concentration in patients with colorectal and metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    N. Erkasap

    Full Text Available The objective of the present study was to investigate the effect of leptin on the progression of colorectal carcinoma to metastatic disease by analyzing the serum leptin concentration and Ob-R gene expression in colon cancer tissues. Tissue samples were obtained from 31 patients who underwent surgical resection for colon (18 cases and metastatic colon (13 cases cancer. Serum leptin concentration was determined by an enzyme-linked immunosorbent assay (ELISA and Ob-R mRNA expression by real-time polymerase chain reaction (RT-PCR for both groups. ELISA data were analyzed by the Student t-test and RT-PCR data were analyzed by the Mann-Whitney U-test. RT-PCR results demonstrated that mRNA expression of Ob-R in human metastatic colorectal cancer was higher than in local colorectal cancer tissues. On the other hand, mean serum leptin concentration was significantly higher in local colorectal cancer patients compared to patients with metastatic colorectal cancer. The results of the present study suggest a role for leptin in the progression of colon cancer to metastatic disease without weight loss. In other words, significantly increased Ob-R mRNA expression and decreased serum leptin concentration in patients with metastatic colon cancer indicate that sensitization to leptin activity may be a major indicator of metastasis to the colon tissue and the determination of leptin concentration and leptin gene expression may be used to aid the diagnosis.

  7. Differential diagnosis of metastasis from non-metastatic lymph nodes in cervical cancers: pilot study of diffusion weighted imaging with background suppression at 3T magnetic resonance

    Institute of Scientific and Technical Information of China (English)

    YU Shen-ping; HE Li; LIU Bo; ZHUANG Xiao-zhao; LIU Ming-juan; HU Xiao-shu

    2010-01-01

    Background Diffusion weighted imaging with background suppression (DWIBS) is potentially useful in detecting metastatic lymph nodes. This study aimed to evaluate the efficacy of DWIBS at 3T magnetic resonance (MR) for diagnosing metastatic lymph nodes in cervical cancer.Methods This retrospective study included 25 patients with cervical cancer who underwent MR examination and were treated by hysterectomy and lymphadenectomy. The metastatic and non-metastatic lymph nodes were histologically proven by operation. Apparent diffusion coefficient (ADC) values, long-axis diameters, short-axis diameters, ratio of short- to long-axis diameters of all the identifiable lymph nodes were measured and compared.Results Twenty-five primary tumor lesions, 17 metastatic lymph nodes and 140 non-metastatic lymph nodes were pathologically confirmed in 25 cases with cervical cancer. The difference of ADC values between primary tumor lesions,metastatic and non-metastatic lymph nodes were statistically significant (F=7.93, P=0.001). There was no statistically significant difference between primary tumor lesions of cervical cancer and metastatic lymph nodes (t=-0.75, P=-0.456),and the difference between primary tumor lesions and non-metastatic lymph nodes was statistically significant (t =4.68, P<0.001). The ADC values, long-axis diameters, short-axis diameters, ratio of short- to long-axis diameters of metastatic and non-metastatic lymph nodes were (0.86±0.36)×10-3 mm2/s vs. (1.12±0.34)×10-3 mm2/s, (1.51±0.41) cm vs.(1.19±0.36) cm, (1.16±0.35) cm vs. (0.77±0.22) cm, 0.78±0.17 vs. 0.68±0.19 respectively, and statistically significant difference existed between two groups.Conclusions DWIBS at 3T MR has the distinct advantages in detecting pelvic lymph nodes of cervical cancer.Quantitative measurement of ADC values could reflect the degree of restriction of diffusion of metastatic and non-metastatic lymph nodes. The combination of size and ADC value would be useful in the

  8. Update on options for treatment of metastatic castration-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Prakash Vishnu

    2010-03-01

    Full Text Available Prakash Vishnu, Winston W TanDivision of Hematology Oncology, Mayo Clinic, Jacksonville, FL, USABackground: Prostate cancer is one of the most common cancers in men in US and European countries. Despite having a favorable prognosis, the incidence of incurable metastatic disease and mortality in the US is about 28,000 per year. Although hormone-based androgen deprivation therapies typically result in rapid responses, nearly all patients eventually develop progressive castration-resistant disease state. With readily available prostate-specific antigen (PSA testing, most of these patients are asymptomatic and manifest progression simply as a rising PSA. In patients with castration-resistant prostate cancer (CRPC, the median survival is about 1–2 years, with improvements in survival seen mostly with docetaxel-based regimens. The purpose of this article is to review the recent developments in the treatment of advanced CRPC.Recent findings: Since the two landmark trials (TAX-327 and Southwest Oncology Group 99–16 in CRPC, several newer cytotoxic drugs (epothilones, satraplatin, targeted agents (abiraterone, MDV3100 and vaccines have been tested in phase II and III setting with promising results.Conclusions: The role of newer agents in the treatment of CRPC still needs to be validated by phase III trials, which are currently ongoing. Whilst the novel biomarkers, ‘circulating tumor cells’, have been shown to provide important prognostic information and are anticipated to be incorporated in future clinical decision-making, their exact utility and relevance calls for a larger prospective validation.Keywords: castration-resistant prostate cancer, novel therapies, mechanisms of resistance, circulating tumor cells

  9. Prognostic factors in a series of 504 breast cancer patients with metastatic spinal cord compression

    International Nuclear Information System (INIS)

    This study was performed to identify new significant prognostic factors in breast cancer patients irradiated for metastatic spinal cord compression (MSCC). The data of 504 patients with breast cancer patients with MSCC were retrospectively analyzed with respect to posttreatment motor function, local control of MSCC, and survival. The investigated potential prognostic factors included age, Eastern Cooperative Oncology Group (ECOG) performance score, number of involved vertebrae, other bone metastases, visceral metastases, pretreatment ambulatory status, interval from cancer diagnosis to radiotherapy of MSCC, time developing motor deficits before radiotherapy, and the radiation schedule. On multivariate analysis, better functional outcome was associated with ambulatory status prior to RT (estimate - 1.29, p < 0.001), no visceral metastases (estimate - 0.52, p = 0.020), and slower development of motor deficits (estimate + 2.47, p < 0.001). Improved local control was significantly associated with no other bone metastases (risk ratio (RR) 4.33, 95% confidence interval (CI) 1.36-14.02, p = 0.013) and no visceral metastases (RR 3.02, 95% CI 1.42-6.40, p = 0.005). Improved survival was significantly associated with involvement of only 1-2 vertebrae (RR 1.27, 95% CI 1.01-1.60, p = 0.044), ambulatory status before radiotherapy (RR 1.75, 95% CI 1.23-2.50, p = 0.002), no other bone metastases (RR 1.93, 95% CI 1.18-3.13, p = 0.009), no visceral metastases (RR 7.60, 95% CI 5.39-10.84, p < 0.001), and time developing motor deficits before radiotherapy (RR 1.55, 95% CI 1.30-1.86, p < 0.001). Several new independent prognostic factors were identified for treatment outcomes. These prognostic factors should be considered in future trials and may be used to develop prognostic scores for breast cancer patients with MSCC. (orig.)

  10. Gastric obstruction secondary to metastatic breast cancer: a case report and literature review

    Directory of Open Access Journals (Sweden)

    Hussain Tasadooq

    2012-08-01

    Full Text Available Abstract Introduction Gastrointestinal tract soft tissues metastasis is a well-known occurrence with invasive lobular breast cancer subtypes. Gastric involvement is more common, with reports of both diffuse and localized involvements. Usually, a gastric localized involvement presents as wall thickening with an appearance similar to that of a gastrointestinal stromal tumour; rarely does a localized metastatic deposit grow aggressively to present as a large tumour causing obstructive symptoms. Our case highlights one such unusual presentation in a patient presenting with non-specific gastrointestinal symptoms. To the best of our knowledge, there have been no previous reports on a similar presentation occurring from a localized metastasis. Case presentation A 65-year-old Caucasian woman awaiting an outpatient oral gastroduodenoscopy for symptoms of intermittent vomiting, epigastric pains and weight loss of six weeks’ duration presented acutely with symptoms of haematemesis and abdominal distension. An initial contrast-enhanced computed tomography scan showed a grossly dilated stomach with a locally advanced stenosing tumour mass at the pylorus. Our patient had a history of left mastectomy and axillary clearance followed by adjuvant endocrine therapy for an oestrogen receptor- and progesterone receptor-positive, grade 2, invasive lobular breast cancer. The oral gastroduodenoscopy confirmed the computed tomography findings; biopsies of the pyloric mass on immunohistochemistry stains were strongly positive for pancytokeratin and gross cystic disease fluid proteins, consistent with an invasive lobular breast cancer metastasis. She received a palliative gastrojejunal bypass and her adjuvant endocrine treatment was switched over to exemestane. Conclusion Our case highlights the aggressive behaviour of a localized gastric metastasis that is unusual and unexpected. Gastrointestinal symptomatology can be non-specific and, at times, non-diagnostic on

  11. Integrated clinical, whole-genome, and transcriptome analysis of multisampled lethal metastatic prostate cancer.

    Science.gov (United States)

    Bova, G Steven; Kallio, Heini M L; Annala, Matti; Kivinummi, Kati; Högnäs, Gunilla; Häyrynen, Sergei; Rantapero, Tommi; Kivinen, Virpi; Isaacs, William B; Tolonen, Teemu; Nykter, Matti; Visakorpi, Tapio

    2016-05-01

    We report the first combined analysis of whole-genome sequence, detailed clinical history, and transcriptome sequence of multiple prostate cancer metastases in a single patient (A21). Whole-genome and transcriptome sequence was obtained from nine anatomically separate metastases, and targeted DNA sequencing was performed in cancerous and noncancerous foci within the primary tumor specimen removed 5 yr before death. Transcriptome analysis revealed increased expression of androgen receptor (AR)-regulated genes in liver metastases that harbored an AR p.L702H mutation, suggesting a dominant effect by the mutation despite being present in only one of an estimated 16 copies per cell. The metastases harbored several alterations to the PI3K/AKT pathway, including a clonal truncal mutation in PIK3CG and present in all metastatic sites studied. The list of truncal genomic alterations shared by all metastases included homozygous deletion of TP53, hemizygous deletion of RB1 and CHD1, and amplification of FGFR1. If the patient were treated today, given this knowledge, the use of second-generation androgen-directed therapies, cessation of glucocorticoid administration, and therapeutic inhibition of the PI3K/AKT pathway or FGFR1 receptor could provide personalized benefit. Three previously unreported truncal clonal missense mutations (ABCC4 p.R891L, ALDH9A1 p.W89R, and ASNA1 p.P75R) were expressed at the RNA level and assessed as druggable. The truncal status of mutations may be critical for effective actionability and merit further study. Our findings suggest that a large set of deeply analyzed cases could serve as a powerful guide to more effective prostate cancer basic science and personalized cancer medicine clinical trials. PMID:27148588

  12. Integrated clinical, whole-genome, and transcriptome analysis of multisampled lethal metastatic prostate cancer

    Science.gov (United States)

    Bova, G. Steven; Kallio, Heini M.L.; Annala, Matti; Kivinummi, Kati; Högnäs, Gunilla; Häyrynen, Sergei; Rantapero, Tommi; Kivinen, Virpi; Isaacs, William B.; Tolonen, Teemu; Nykter, Matti; Visakorpi, Tapio

    2016-01-01

    We report the first combined analysis of whole-genome sequence, detailed clinical history, and transcriptome sequence of multiple prostate cancer metastases in a single patient (A21). Whole-genome and transcriptome sequence was obtained from nine anatomically separate metastases, and targeted DNA sequencing was performed in cancerous and noncancerous foci within the primary tumor specimen removed 5 yr before death. Transcriptome analysis revealed increased expression of androgen receptor (AR)-regulated genes in liver metastases that harbored an AR p.L702H mutation, suggesting a dominant effect by the mutation despite being present in only one of an estimated 16 copies per cell. The metastases harbored several alterations to the PI3K/AKT pathway, including a clonal truncal mutation in PIK3CG and present in all metastatic sites studied. The list of truncal genomic alterations shared by all metastases included homozygous deletion of TP53, hemizygous deletion of RB1 and CHD1, and amplification of FGFR1. If the patient were treated today, given this knowledge, the use of second-generation androgen-directed therapies, cessation of glucocorticoid administration, and therapeutic inhibition of the PI3K/AKT pathway or FGFR1 receptor could provide personalized benefit. Three previously unreported truncal clonal missense mutations (ABCC4 p.R891L, ALDH9A1 p.W89R, and ASNA1 p.P75R) were expressed at the RNA level and assessed as druggable. The truncal status of mutations may be critical for effective actionability and merit further study. Our findings suggest that a large set of deeply analyzed cases could serve as a powerful guide to more effective prostate cancer basic science and personalized cancer medicine clinical trials.

  13. What are we able to achieve in the treatment of metastatic non-small cell lung cancer today?

    International Nuclear Information System (INIS)

    Several meta analyses published in the beginning of the 1990s confirmed effectivity of chemotherapy in comparison with best supportive care in advanced/metastatic non-small cell lung cancer: the median survival time was prolonged by 6 weeks - 2 months, and the number of patients surviving one year increased by about 10%. Influence of these meta analyses on perception of non-small cell lung cancer chemotherapy as an indicated but less effective treatment continues until today in some extend. Image of the advanced non-small cell lung cancer treatment has improved during the last years markedly, mainly due to new treatment possibilities discussed in this case report. (author)

  14. Elevated 68Ga Prostate-Specific Membrane Antigen Activity in Metastatic Non-Small Cell Lung Cancer.

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    Shetty, Deepa; Loh, Han; Bui, Chuong; Mansberg, Robert; Stevanovic, Amanda

    2016-05-01

    A 71-year-old man with a background of treated stage IIIB non-small cell lung cancer was referred for Ga prostate-specific membrane antigen (PSMA) PET/CT for staging of prostate cancer. In addition to the PSMA uptake in the known prostate malignancy, the study also demonstrated increased PSMA uptake in an enlarging left lower lobe lung mass with diffusely increased PSMA uptake in an enlarged thyroid gland and bilateral enlarged supraclavicular lymph nodes. Fine-needle aspiration biopsy of the thyroid gland and a left supraclavicular lymph node demonstrated metastatic adenocarcinoma from a primary lung cancer. PMID:26828144

  15. Comparison of histopathology to gene expression profiling for the diagnosis of metastatic cancer

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    Kulkarni Anand

    2012-08-01

    Full Text Available Abstract Background Determining the primary site of metastatic cancer with confidence can be challenging. Pathologists commonly use a battery of immunohistochemical (IHC stains to determine the primary site. Gene expression profiling (GEP has found increasing use, particularly in the most difficult cases. In this pilot study, a direct comparison between GEP and IHC-guided methods was performed. Methods Ten archived formalin-fixed paraffin embedded metastatic tumor samples for which the primary site had been clinically determined were selected. Five pathologists who were blinded to the diagnosis were asked to determine the primary site using IHC and other stains selected from a panel of 84 stains. Each pathologist was provided patient sex, biopsy site and gross sample description only. Slides were digitized using ScanScope®XT at 0.25 μm/pixel. Each evaluating pathologist was allowed to provide a diagnosis in three stages: initial (after reviewing the H&E image, intermediate (after reviewing images from the first batch of stains and final diagnosis (after the second batch of stains if requested. GEP was performed using the only FDA-cleared test for this intended use, the Pathwork Tissue of Origin Test. No sample information was provided for GEP testing except for patient sex. Results were reported as the tumor tissue type with the highest similarity score. Results In this feasibility study, GEP determined the correct primary site in 9 of the 10 cases (90%, compared to the IHC-guided method which determined the correct primary site for 32 of 50 case evaluations (average 64%, range 50% to 80%. The five pathologists directing the IHC-guided method ordered an average of 8.8 stains per case (range 1 to 18. GEP required an average of 3 slides per case (range 1 to 4. Conclusions Results of the pilot study suggest that GEP provides correct primary site identification in a higher percentage of metastatic cases than IHC-guided methods, and uses less

  16. Abiraterone in the treatment of metastatic castration-resistant prostate cancer

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    Mostaghel EA

    2014-01-01

    Full Text Available Elahe A Mostaghel Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA Abstract: Androgen deprivation therapy remains the single most effective treatment for the initial therapy of advanced prostate cancer, but is uniformly marked by progression to castration-resistant prostate cancer (CRPC. Residual tumor androgens and androgen axis activation are now recognized to play a prominent role in mediating CRPC progression. Despite suppression of circulating testosterone to castrate levels, castration does not eliminate androgens from the prostate tumor microenvironment and residual androgen levels are well within the range capable of activating the androgen receptor (AR and AR-mediated gene expression. Accordingly, therapeutic strategies that more effectively target production of intratumoral androgens are necessary. The introduction of abiraterone, a potent suppressor of cytochrome P450 17 α-hydroxysteroid dehydrogenase-mediated androgen production, has heralded a new era in the hormonal treatment of men with metastatic CRPC. Herein, the androgen and AR-mediated mechanisms that contribute to CRPC progression and establish cytochrome P450 17 α-hydroxysteroid dehydrogenase as a critical therapeutic target are briefly reviewed. The mechanism of action and pharmacokinetics of abiraterone are reviewed and its recently described activity against AR and 3-β-hydroxysteroid dehydrogenase is discussed. The Phase I and II data initially demonstrating the efficacy of abiraterone and Phase III data supporting its approval for patients with metastatic CRPC are reviewed. The safety and tolerability of abiraterone, including the incidence and management of side effects and potential drug interactions, are discussed. The current place of abiraterone in CRPC therapy is reviewed and early evidence regarding cross-resistance of abiraterone with taxane therapy, mechanisms of resistance to abiraterone, and observations of an

  17. Vincristine, cisplatin, teniposide, and cyclophosphamide combination in the treatment of recurrent or metastatic adrenocortical cancer.

    Science.gov (United States)

    Khan, Tanweera S; Sundin, Anders; Juhlin, Claes; Wilander, Erik; Oberg, Kjell; Eriksson, Barbro

    2004-01-01

    The efficacy and tolerability of a combination of vincristine, cisplatin, teniposide, and cyclophosphamide (OPEC) in 11 patients (median age, 45 yr) with recurrent and/or metastatic adrenocortical cancer (ACC) (seven functional and four nonfunctional) were evaluated. All patients received this regimen after the failure of streptozocin and o,p'-DDD (SO) combination therapy. The regimen comprised cyclophosphamide, 600 mg/m2, and vincristine, 1.5 mg/m2, maximum dose 2.0 mg (d 1); cisplatin, 100 mg/m2 (d 2) and teniposide, 150 mg/m2 (d 4). Cycles were repeated every 4 wk. One to eight cycles (median, six cycles) of OPEC were administered to each patient. The median duration of treatment was 6 mo. The overall 2-yr survival rate was 82% and the median survival since diagnosis was 44 mo while it was 21 mo since start of OPEC therapy. Responses were obtained in nine patients: partial response in two patients, and stable disease in seven patients. The median duration of response was 6.75 mo. A total of 60 cycles of chemotherapy were given to all patients; grade 1-2 toxicity occurred in 57 cycles, while grade 3 toxicity was observed only in two cycles, according to NCI's Common Toxicity Criteria. We conclude that the OPEC regimen may be considered in recurrent or metastatic ACC as a second-line medical treatment. However, the combination is accompanied by considerable side effects and dose modifications are necessary in order to be able to recommend the treatment. This regimen needs further evaluation compared with SO therapy preferably in a randomized multicenter trial. PMID:15299189

  18. Type and dose of radiotherapy used for initial treatment of non-metastatic prostate cancer

    International Nuclear Information System (INIS)

    We sought to describe patterns of initial radiotherapy among non-metastatic prostate cancer (PC) patients by recurrence risk groups. Medical records were abstracted for a sample of 9017 PC cases diagnosed in 2004 as a part of the Center for Disease Control and Prevention’s Prostate and Breast Patterns of Care Study in seven states. Non-metastatic PC cases are categorized as low-risk (LR), intermediate-risk (IR) or high-risk (HR) groups based on pretreatment PSA, tumor stage, and Gleason score per 2002 NCCN guidelines. Univariate and multivariate analyses were employed to determine factors associated with the type and dose of radiotherapy by the risk groups. Of the 9,017 patients, 3153 who received definitive radiotherapy either alone or in combination with hormone therapy (HT) were selected for in-depth analysis. Multivariate models showed that LR patients were more likely to receive seed implant brachytherapy (BT) than those in higher risk groups. Those in the IR group were most likely to receive external beam radiotherapy (EBRT) combined with BT or high-dose radiotherapy. Use of HT in combination with radiotherapy was more common in the IR and HR groups than for LR patients. Intensity modulated radiation treatment (IMRT) was used to treat 32.6% of PC patients treated with EBRT, with the majority (60.6%) treated with high-dose radiotherapy. Radiotherapy types and dosage utilization varied by PC risk groups. Patients in IR were more likely than those in LR or HR to receive high-dose radiotherapy. IMRT was used in about one third of patients to deliver high-dose radiotherapy

  19. Use of Palliative Radiotherapy Among Patients With Metastatic Non-Small-Cell Lung Cancer

    International Nuclear Information System (INIS)

    Purpose: Radiotherapy (RT) is known to effectively palliate many symptoms of patients with metastatic non-small-cell lung cancer (NSCLC). Anecdotally, RT is believed to be commonly used in this setting, but limited population-based data are available. The objective of this study was to examine the utilization patterns of palliative RT among elderly patients with Stage IV NSCLC and, in particular, to identify factors associated with its use. Methods and Materials: A retrospective population-based cohort study was performed using linked Surveillance, Epidemiology and End Results (SEER)-Medicare data to identify 11,084 Medicare beneficiaries aged ≥65 years who presented with Stage IV NSCLC in the 11 SEER regions between 1991 and 1996. The primary outcome was receipt of RT. Logistic regression analysis was used to identify factors associated with receipt of RT. Results: A total of 58% of these patients received RT, with its use decreasing over time (p = 0.01). Increasing age was negatively associated with receipt of treatment (p <0.001), as was increasing comorbidities (p <0.001). Factors positively associated with the receipt of RT included income (p = 0.001), hospitalization (p <0.001), and treatment with chemotherapy (p <0.001). Although the use varied across the SEER regions (p = 0.001), gender, race/ethnicity, and distance to the nearest RT facility were not associated with treatment. Conclusions: Elderly patients with metastatic NSCLC frequently receive palliative RT, but its use varies, especially with age and receipt of chemotherapy. Additional research is needed to determine whether this variability reflects good quality care

  20. SU-D-303-01: Spatial Distribution of Bone Metastases In Metastatic Castrate-Resistant Prostate Cancer

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    Perk, T; Bradshaw, T; Harmon, S; Perlman, S; Liu, G; Jeraj, R [University of Wisconsin, Madison, WI (United States)

    2015-06-15

    Purpose: Identification of metastatic bone lesions is critical in prostate cancer, where treatments may be more effective in patients with fewer lesions. This study aims characterize the distribution and spread of bone lesions and create a probability map of metastatic spread in bone. Methods: Fifty-five metastatic castrate-resistant prostate cancer patients received up to 3 whole-body [F-18]NaF PET/CT scans. Lesions were identified by physician on PET/CT and contoured using a threshold of SUV>15. An atlas-based segmentation method was used to create CT regions, which determined skeletal location of lesions. Patients were divided into 3 groups with low (N<40), medium (40100) numbers of lesions. A combination of articulated and deformable registrations was used to register the skeletal segments and lesions of each patient to a single skeleton. All the lesion data was then combined to make a probability map. Results: A total of 4038 metastatic lesions (mean 74, range 2–304) were identified. Skeletal regions with highest occurrence of lesions included ribs, thoracic spine, and pelvis with 21%, 19%, and 15% of the total number lesions and 8%, 18%, and 31 % of the total lesion volume, respectively. Interestingly, patients with fewer lesions were found to have a lower proportion of lesions in the ribs (9% in low vs. 27% in high number of lesions). Additionally, the probability map showed specific areas in the spine and pelvis where over 75% of patients had metastases, and other areas in the skeleton with a less than 2% of metastases. Conclusion: We identified skeletal regions with higher incidence of metastases and specific sub-regions in the skeleton that had high or low probability of occurrence of metastases. Additionally, we found that metastatic lesions in the ribs and skull occur more commonly in advanced disease. These results may have future applications in computer-aided diagnosis. Funding from the Prostate Cancer Foundation.

  1. SU-D-303-01: Spatial Distribution of Bone Metastases In Metastatic Castrate-Resistant Prostate Cancer

    International Nuclear Information System (INIS)

    Purpose: Identification of metastatic bone lesions is critical in prostate cancer, where treatments may be more effective in patients with fewer lesions. This study aims characterize the distribution and spread of bone lesions and create a probability map of metastatic spread in bone. Methods: Fifty-five metastatic castrate-resistant prostate cancer patients received up to 3 whole-body [F-18]NaF PET/CT scans. Lesions were identified by physician on PET/CT and contoured using a threshold of SUV>15. An atlas-based segmentation method was used to create CT regions, which determined skeletal location of lesions. Patients were divided into 3 groups with low (N<40), medium (40100) numbers of lesions. A combination of articulated and deformable registrations was used to register the skeletal segments and lesions of each patient to a single skeleton. All the lesion data was then combined to make a probability map. Results: A total of 4038 metastatic lesions (mean 74, range 2–304) were identified. Skeletal regions with highest occurrence of lesions included ribs, thoracic spine, and pelvis with 21%, 19%, and 15% of the total number lesions and 8%, 18%, and 31 % of the total lesion volume, respectively. Interestingly, patients with fewer lesions were found to have a lower proportion of lesions in the ribs (9% in low vs. 27% in high number of lesions). Additionally, the probability map showed specific areas in the spine and pelvis where over 75% of patients had metastases, and other areas in the skeleton with a less than 2% of metastases. Conclusion: We identified skeletal regions with higher incidence of metastases and specific sub-regions in the skeleton that had high or low probability of occurrence of metastases. Additionally, we found that metastatic lesions in the ribs and skull occur more commonly in advanced disease. These results may have future applications in computer-aided diagnosis. Funding from the Prostate Cancer Foundation

  2. Gemcitabine and Cisplatin Combination Chemotherapy as a First-Line Treatment in Patients with Metastatic Breast Cancer

    International Nuclear Information System (INIS)

    The prospective study were to evaluate the efficacy and toxicity of Gemcitabine plus cisplatin as a first line chemotherapy in female patients with metastatic breast cancer who previously received anthracyclin-based regimen as adjuvant chemotherapy. Patients and Methods: Twenty five patients with metastatic and at least one bi-dimensionally measurable lesion were included in this study. Adequate bone marrow reserve, adequate hepatic and renal functions and performance status $ 2 were required. Patients have previously received anthracyclin based-chemotherapy as adjuvant. Treatment consisted of Gemcitabine 1250 mg/m2 on days I and 8 and cisplatin 75 mg/m2 on day I, cycles were repeated at 3-week intervals. 25 patients were evaluable for toxicity and 22 patients for response. Overall response was 54.5%. Complete response was reported in 13.6% of patients and partial response was reported in 40.9% of patients. Six patients (27.2%) had stable disease and disease progression was reported in (18.2%) of patients. Response was reported in all metastatic sites. Toxicities included grade 3,4 vomiting in 32% and grade 3, 4 neutropenia in 12%, grade 3, 4 thrompocytopenia in 32%. Only one case of neutropenic fever was reported. Renal and neurotoxicity was encountered in 12% and alopecia grade I. 2 in 8% of patients. o treatment related death was reported. The median overall survival was ]4.8 months (range: 2 to 18.5). Gemcitabine and cisplatin combination chemotherapy is active and well tolerated regimen for patients with metastatic breast cancer. This regimen represents a therapeutic option for patients receiving front line therapy for their metastatic breast cancer. Phase III randomized trial is needed for comparison with other 2nd line regimens to define the exact role of this combination

  3. Metastatic prostate cancer with elevated serum levels of CEA and CA19-9

    Directory of Open Access Journals (Sweden)

    Guang-Dar Juang

    2014-03-01

    Full Text Available Prostate-specific antigen (PSA is well known as a specific tumor marker for prostate cancer, but carcinoembryonic antigen (CEA- and carbohydrate antigen 19-9 (CA19-9-elevating adenocarcinomas originating in the prostate gland are rare. We report a case of metastatic adenocarcinoma of the prostate gland with a high serum level of CEA and CA19-9 in a 78-year-old man in whom prostate cancer (T3N1M1 had been diagnosed 2 years ago and who was treated with androgen deprivation therapy. He visited the emergency department because of a loss of appetite and abdominal pain. The serum CEA and CA19-9 levels were increased to 218.9 ng/mL (normal, <5 ng/mL and 212 ng/mL (normal, <27 ng/mL, respectively. The serum PSA level was slightly elevated (4.41 ng/mL. Computed tomography demonstrated multiple liver metastases, para-aortic lymph node enlargement, and lung metastases. A liver biopsy was performed and the specimen showed high-grade adenocarcinoma with focal positive staining for PSA. Despite chemotherapy with docetaxel, the patient died 3 months after treatment. Based on this case and a review of the literature, an aggressive variant of prostatic carcinoma with a high serum level of CEA and CA19-9 and a low PSA level was shown to progress rapidly with a poor prognosis.

  4. Cutaneous lupus erythematosus after treatment with paclitaxel and bevacizumab for metastatic breast cancer: a case report

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    Koulu Leena

    2011-06-01

    Full Text Available Abstract Introduction The monoclonal anti-vascular endothelial growth factor antibody bevacizumab is increasingly used in the treatment of several malignant tumors. The usual side effects of this drug are hypertension and proteinuria. Paclitaxel is widely used in the treatment of breast cancer and head and neck carcinomas. Neither of these two drugs typically causes skin disorders. Paclitaxel-related cutaneous lupus erythematosus has been described before, but in earlier cases patients had a history of autoimmune disease. Case presentation We report a case of a 65-year-old Caucasian woman who presented with cutaneous lupus erythematosus after receiving paclitaxel-bevacizumab combination treatment as first-line therapy for metastatic breast cancer. Her cutaneous symptoms and increased serum anti-SSA and anti-SSB antibodies disappeared shortly after the discontinuation of therapy. Conclusion We conclude that cutaneous lupus erythematosus can also be seen in patients without earlier anamnesis of autoimmune disorders and that, furthermore, bevacizumab might cause atypical cutaneous side effects.

  5. A Meta-Analysis Study of Polychemotherapy versus Monochemotherapy in Patients of Metastatic Breast Cancer

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    Amal Kumar

    2016-05-01

    Full Text Available Polychemotherapy and intermittent monochemotherapy regimens in metastatic breast cancer were examined in a meta analysis that included both tumor response rate and toxicities. Randomized controlled studies (conducted during 1990-2008 comparing monochemotherapy and poly-chemotherapy in advanced breast cancer patients were selected from electronic databases. Meta-analysis for response rate and toxicities [nausea and vomiting, toxic death, alopecia and reduced white cell count (WCC] was performed using the Mantel-Haenszel method. The heterogeneity among the trials was assessed through a χ2 statistic, I2 and visual inspection of the forest plots. Analysis of eligible studies reveals statistical significant difference in response rate (OR 0.72, 95% CI 0.65-0.79, nausea and vomiting (OR 0.80, 95% CI 0.67-0.59, Alopecia (OR 0.75, 95% CI 0.64-0.88 and reduced WCC (OR 0.55, 95% CI 0.48-0.62 which favours polychemotherapy except toxic death (OR 0.87, 95% CI 0.58-1.29. There was marked evidence of heterogeneity in all end points except toxic death. This meta analysis shows the superiority of efficacy but not of safety of polychemotherapy over that of a single agent. However, the choice of treatment should be based on the response to the therapy, toxicity, patient preference, presence of metastases or imminent complications requiring aggressive and rapid tumor control.

  6. Fluorescence diagnostics of metastatic lesion of regional lymph nodes upon surgical treatment of breast cancer

    Science.gov (United States)

    Filonenko, E. V.; Pak, D. D.; Yanikova, A. G.

    2013-06-01

    We have performed intraoperative fluorescence diagnostics of 60 patients for metastases of breast cancer to regional lymph nodes. All the patients were divided into two groups. The first group consisted of 50 patients, which were surgically treated at the first stage. The second group consisted of ten patients, which underwent combined treatment. At the first stage, they received from two to four courses of neoadjuvant chemotherapy, and, at the second stage, the surgical intervention was performed. The intraoperative fluorescence diagnostics was performed using the preparation alasens (precursor of protoporphyrin IX in the human organism). The occurrence of fluorescence of alasens-induced protoporphyrin IX was determined visually and using the local fluorescence spectroscopy method. Altogether, 498 lymph nodes were examined: 408 in the first group and 90 in the second one. For the first group, the sensitivity of the method was found to be 87.2%, and its specificity, 94.8%; in the second group, these parameters were determined to be 77 and 78%, respectively. The first experience of the application of the intraoperative fluorescence diagnostics of metastatic lesion of lymph nodes in patients with breast cancer has shown its high efficiency and application potential.

  7. 3D Raman imaging of systemic endothelial dysfunction in the murine model of metastatic breast cancer.

    Science.gov (United States)

    Pacia, Marta Z; Buczek, Elzbieta; Blazejczyk, Agnieszka; Gregorius, Aleksandra; Wietrzyk, Joanna; Chlopicki, Stefan; Baranska, Malgorzata; Kaczor, Agnieszka

    2016-05-01

    It was recently reported in the murine model of metastatic breast cancer (4T1) that tumor progression and development of metastasis is associated with systemic endothelial dysfunction characterized by impaired nitric oxide (NO) production. Using Raman 3D confocal imaging with the analysis of the individual layers of the vascular wall combined with AFM endothelial surface imaging, we demonstrated that metastasis-induced systemic endothelial dysfunction resulted in distinct chemical changes in the endothelium of the aorta. These changes, manifested as a significant increase in the protein content (18 %) and a slight decrease in the lipid content (4 %), were limited to the endothelium and did not occur in the deeper layers of the vascular wall. The altered lipid to protein ratio in the endothelium, although more pronounced in the fixed vascular wall, was also observed in the freshly isolated unfixed vascular wall samples in the aqueous environment (12 and 7 % change of protein and lipid content, respectively). Our results support the finding that the metastasis induces systemic endothelial dysfunction that may contribute to cancer progression. Graphical Abstract Schematic illustration of methodology of sample preparation and measurement. PMID:26935932

  8. Advantages and Disadvantages of Bone Protective Agents in Metastatic Prostate Cancer: Lessons Learned

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    Christian Thomas

    2016-08-01

    Full Text Available Nine out of ten metastatic prostate cancer (PCa patients will develop osseous metastases. Of these, every second will suffer from skeletal-related events (SRE. SRE are associated with an increased risk for death, which is markedly increased in the presence of pathological fracture. Moreover, health insurance costs nearly double in the presence of SRE. Zoledronic acid and denosumab are both approved drugs for the prevention or delay of SRE in castration-resistant prostate cancer (CRPC patients with osseous metastases. However, long-term treatment with one of these two drugs is associated with the development of medication-related osteonecrosis of the jaw (MRONJ. Routine inspections of the oral cavity before and during treatment are mandatory in these patients. Regarding imaging techniques, bone scintigraphy seems to be a promising tool to detect early stage MRONJ. Zoledronic acid does not reduce the incidence of SRE in hormone-sensitive PCa. First data shows 3-monthly application of zoledronic acid to be equi-effective to monthly application.

  9. Mitomycin-C+fluoropyrimidines in heavily pretreated metastatic colorectal cancer: a systematic review and evidence synthesis.

    Science.gov (United States)

    Petrelli, Fausto; Ghidini, Antonio; Inno, Alessandro; Barni, Sandro

    2016-07-01

    Mitomycin-C (MMC) combined with fluoropyrimidines has historically been used for pretreated patients with some activity in this setting, in particular, as third-line chemotherapy (CT) or beyond. We have evaluated the efficacy and safety of MMC-based therapy as a further line of CT in advanced colorectal cancer. Prospective or retrospective studies of MMC-based CT were included in the pooled analysis. PubMed, EMBASE, SCOPUS, Web of Science, the Cochrane Library database and CINAHL were searched systematically. The outcomes were progression-free survival, overall survival, overall response rate and grades 3-4 drug-related adverse events. Seventeen trials involving 681 patients were included in the analysis. Overall, the pooled average weighted progression-free survival and overall survival were 2.84 [95% confidence interval (CI) 2.5-3.1] and 7.47 (95% CI 6-8.9) months, respectively. The corresponding pooled overall response rate was 7.2% (95% CI 5.2-9.9%) and the pooled disease control rate was 38.7% (95% CI 31.7-46.3%). The G3-4 neutropenia and anaemia were the most frequent haematological toxicities (range 0-20%). Nonhaematological G3-4 toxicities were compatible with the associated agent. MMC with fluoropyrimidines represents a viable and active combination for pretreated metastatic colorectal cancer patients. It is thus an option when other agents have failed, or are unavailable or not indicated. PMID:27186954

  10. In situ vaccination with cowpea mosaic virus nanoparticles suppresses metastatic cancer

    Science.gov (United States)

    Lizotte, P. H.; Wen, A. M.; Sheen, M. R.; Fields, J.; Rojanasopondist, P.; Steinmetz, N. F.; Fiering, S.

    2016-03-01

    Nanotechnology has tremendous potential to contribute to cancer immunotherapy. The ‘in situ vaccination’ immunotherapy strategy directly manipulates identified tumours to overcome local tumour-mediated immunosuppression and subsequently stimulates systemic antitumour immunity to treat metastases. We show that inhalation of self-assembling virus-like nanoparticles from cowpea mosaic virus (CPMV) reduces established B16F10 lung melanoma and simultaneously generates potent systemic antitumour immunity against poorly immunogenic B16F10 in the skin. Full efficacy required Il-12, Ifn-γ, adaptive immunity and neutrophils. Inhaled CPMV nanoparticles were rapidly taken up by and activated neutrophils in the tumour microenvironment as an important part of the antitumour immune response. CPMV also exhibited clear treatment efficacy and systemic antitumour immunity in ovarian, colon, and breast tumour models in multiple anatomic locations. CPMV nanoparticles are stable, nontoxic, modifiable with drugs and antigens, and their nanomanufacture is highly scalable. These properties, combined with their inherent immunogenicity and demonstrated efficacy against a poorly immunogenic tumour, make CPMV an attractive and novel immunotherapy against metastatic cancer.

  11. Anxiety and its time courses during radiotherapy for non-metastatic breast cancer: A longitudinal study

    International Nuclear Information System (INIS)

    Purpose: To our knowledge, no study has specifically assessed the time course of anxiety during radiotherapy (RT). The objective of this study was to assess anxiety time courses in patients with non-metastatic breast cancer. Material and methods: This multicenter, descriptive longitudinal study included 213 consecutive patients with breast cancer who completed visual analog scales (VASs) assessing state anxiety before and after the RT simulation and the first and last five RT sessions. Results: Pre- and post-session anxiety mean levels were highest at the RT simulation (respectively, 2.9 ± 2.9 and 1.6 ± 2.5) and first RT session (respectively, 3.4 ± 2.9 and 2.0 ± 2.4), then declined rapidly. Clinically relevant mean differences (⩾1 cm on the VAS) between pre- and post-simulation/session VAS scores were found only for the RT simulation (−1.3 ± 2.7; p < 0.001) and first RT session (−1.4 ± 2.4; p < 0.001). Five percent to 16% of patients presented clinically relevant anxiety (pre- and post-simulation/session VAS scores ⩾ 4 cm) throughout treatment. Conclusions: To optimize care, RT team members should offer all patients appropriate information about treatment at the simulation, check patients’ understanding, and identify patients with clinically relevant anxiety requiring appropriate support throughout RT

  12. Clinical Significance of Biological Markers at Primary Operation for Metastatic Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    ZHANG Zhenhuan; YAMASHITA Hiroko; TOYAMA Tatsuya; YAMAMOTO Yutaka; IWASE Hirotaka

    2007-01-01

    Purpose: To identify the prognostic value of biological markers at initial operation for metastatic breast cancer, we measured the presence of estrogen receptor-alpha (ERα), progesterone receptor (PgR) and human epidermal growth factor receptor type 2 (HER2),and histological grade (HG) of tumors. Methods: One-hundred and seventy-six patients, aged 29 to 90 (median: 51 years), with recurrent breast cancer underwent primary operation at our department during the period from 1983 to 2000. Clinicopathological factors examined at primary operation included menopausal symptoms, presence of axillary lymph node metastasis, tumor size, HG, HER2, ERα and PgR.Factors examined at recurrence included site of primary recurrence, disease-free interval(DFI) and tumor markers, such as CEA and CA15-3. The relationship between these factors and prognosis following recurrence was assessed. Results: Menopausal status, axillary lymph node metastasis and tumor size at primary operation had no significant effect on prognosis. Patients with low HG, positive expession of ERα and PgR, and low HER2 expression had a good prognosis, similar to those with long DFI and distant metastases. After distant metastases, HER2 was found to be the most important prognostic factor following recurrence and in predicting response to drug therapy.Conclusion: Biological factors indicating tumor malignancy at the time of the first operation are also important prognostic factors following tumor recurrence.

  13. 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.

  14. Aggressive Treatment of Patients with Metastatic Colorectal Cancer Increases Survival: A Scandinavian Single-Center Experience

    Directory of Open Access Journals (Sweden)

    Kristoffer Watten Brudvik

    2013-01-01

    Full Text Available Background. We examined overall and disease-free survivals in a cohort of patients subjected to resection of liver metastasis from colorectal cancer (CRLM in a 10-year period when new treatment strategies were implemented. Methods. Data from 239 consecutive patients selected for liver resection of CRLM during the period from 2002 to 2011 at a single center were used to estimate overall and disease-free survival. The results were assessed against new treatment strategies and established risk factors. Results. The 5-year cumulative overall and disease-free survivals were 46 and 24%. The overall survival was the same after reresection, independently of the number of prior resections and irrespectively of the location of the recurrent disease. The time intervals between each recurrence were similar (11 ± 1 months. Patients with high tumor load given neoadjuvant chemotherapy had comparable survival to those with less extensive disease without neoadjuvant chemotherapy. Positive resection margin or resectable extrahepatic disease did not affect overall survival. Conclusion. Our data support that one still, and perhaps to an even greater extent, should seek an aggressive therapeutic strategy to achieve resectable status for recurrent hepatic and extrahepatic metastases. The data should be viewed in the context of recent advances in the understanding of cancer biology and the metastatic process.

  15. 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

  16. Fracture risk assessment: improved evaluation of vertebral integrity among metastatic cancer patients to aid in surgical decision-making

    Science.gov (United States)

    Augustine, Kurt E.; Camp, Jon J.; Holmes, David R.; Huddleston, Paul M.; Lu, Lichun; Yaszemski, Michael J.; Robb, Richard A.

    2012-03-01

    Failure of the spine's structural integrity from metastatic disease can lead to both pain and neurologic deficit. Fractures that require treatment occur in over 30% of bony metastases. Our objective is to use computed tomography (CT) in conjunction with analytic techniques that have been previously developed to predict fracture risk in cancer patients with metastatic disease to the spine. Current clinical practice for cancer patients with spine metastasis often requires an empirical decision regarding spinal reconstructive surgery. Early image-based software systems used for CT analysis are time consuming and poorly suited for clinical application. The Biomedical Image Resource (BIR) at Mayo Clinic, Rochester has developed an image analysis computer program that calculates from CT scans, the residual load-bearing capacity in a vertebra with metastatic cancer. The Spine Cancer Assessment (SCA) program is built on a platform designed for clinical practice, with a workflow format that allows for rapid selection of patient CT exams, followed by guided image analysis tasks, resulting in a fracture risk report. The analysis features allow the surgeon to quickly isolate a single vertebra and obtain an immediate pre-surgical multiple parallel section composite beam fracture risk analysis based on algorithms developed at Mayo Clinic. The analysis software is undergoing clinical validation studies. We expect this approach will facilitate patient management and utilization of reliable guidelines for selecting among various treatment option based on fracture risk.

  17. Development of Hemolytic Anemia in a Nivolumab-Treated Patient with Refractory Metastatic Squamous Cell Skin Cancer and Chronic Lymphatic Leukemia.

    Science.gov (United States)

    Schwab, K S; Heine, A; Weimann, T; Kristiansen, G; Brossart, P

    2016-01-01

    Management of patients with metastatic squamous cell skin cancer, refractory to initial therapy with standard chemotherapy and radiation protocols, remains difficult with poor overall prognosis and limited therapeutic options. Recently, promising response rates with nivolumab, a programmed death receptor-1-blocking antibody, in squamous cancer of the head and neck have been demonstrated. Considering the similar histological patterns of squamous cell cancer of the skin and squamous cell cancer of the head and neck, we assumed that nivolumab could also be effective in our patients with refractory metastatic squamous cell cancer of the skin. So far, there have been no clinical data on the therapeutic efficacy of nivolumab in squamous cell skin cancer. We here present a case of a patient with metastatic squamous cell skin cancer refractory to previous therapies, who showed a good response to nivolumab over a period of 5 months, but developed a serious hemolytic crisis under nivolumab treatment after eight applications. PMID:27462240

  18. Complete Regression of Metastatic Cervical Cancer After Treatment With Human Papillomavirus–Targeted Tumor-Infiltrating T Cells

    Science.gov (United States)

    Stevanović, Sanja; Draper, Lindsey M.; Langhan, Michelle M.; Campbell, Tracy E.; Kwong, Mei Li; Wunderlich, John R.; Dudley, Mark E.; Yang, James C.; Sherry, Richard M.; Kammula, Udai S.; Restifo, Nicholas P.; Rosenberg, Steven A.; Hinrichs, Christian S.

    2015-01-01

    Purpose Metastatic cervical cancer is a prototypical chemotherapy-refractory epithelial malignancy for which better treatments are needed. Adoptive T-cell therapy (ACT) is emerging as a promising cancer treatment, but its study in epithelial malignancies has been limited. This study was conducted to determine if ACT could mediate regression of metastatic cervical cancer. Patients and Methods Patients enrolled onto this protocol were diagnosed with metastatic cervical cancer and had previously received platinum-based chemotherapy or chemoradiotherapy. Patients were treated with a single infusion of tumor-infiltrating T cells selected when possible for human papillomavirus (HPV) E6 and E7 reactivity (HPV-TILs). Cell infusion was preceded by lymphocyte-depleting chemotherapy and was followed by administration of aldesleukin. Results Three of nine patients experienced objective tumor responses (two complete responses and one partial response). The two complete responses were ongoing 22 and 15 months after treatment, respectively. One partial response was 3 months in duration. The HPV reactivity of T cells in the infusion product (as measured by interferon gamma production, enzyme-linked immunospot, and CD137 upregulation assays) correlated positively with clinical response (P = .0238 for all three assays). In addition, the frequency of HPV-reactive T cells in peripheral blood 1 month after treatment was positively associated with clinical response (P = .0238). Conclusion Durable, complete regression of metastatic cervical cancer can occur after a single infusion of HPV-TILs. Exploratory studies suggest a correlation between HPV reactivity of the infusion product and clinical response. Continued investigation of this therapy is warranted. PMID:25823737

  19. A randomized phase III trial on maintenance treatment with bevacizumab alone or in combination with erlotinib after chemotherapy and bevacizumab in metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Johnsson, Anders; Hagman, H; Frödin, J-E;

    2013-01-01

    The main objective was to study the effect on progression-free survival (PFS) of adding erlotinib to bevacizumab as maintenance treatment following chemotherapy and bevacizumab as first-line treatment of metastatic colorectal cancer (mCRC)....

  20. Cetuximab and Everolimus in Treating Patients With Metastatic or Recurrent Colon Cancer or Head and Neck Cancer

    Science.gov (United States)

    2012-07-06

    Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Colon Cancer; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage IV Adenoid Cystic Carcinoma of the Oral Cavity; Stage IV Basal Cell Carcinoma of the Lip; Stage IV Lymphoepithelioma of the Nasopharynx; Stage IV Lymphoepithelioma of the Oropharynx; Stage IV Mucoepidermoid Carcinoma of the Oral Cavity; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Verrucous Carcinoma of the Larynx; Stage IV Verrucous Carcinoma of the Oral Cavity; Stage IVA Colon Cancer; Stage IVA Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage IVA Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Colon

  1. Anti-epidermal or anti-vascular endothelial growth factor as first-line metastatic colorectal cancer in modified Glasgow prognostic score 2' patients

    OpenAIRE

    Dréanic, Johann; Dhooge, Marion; Barret, Maximilien; Brezault, Catherine; Mir, Olivier; Chaussade, Stanislas; Coriat, Romain

    2015-01-01

    Background In metastatic colorectal cancer, the modified Glasgow prognostic score (mGPS) has been approved as an independent prognostic indicator of survival. No data existed on poor prognosis patients treated with molecular-targeted agents. Methods From January 2007 to February 2012, patients with metastatic colorectal cancer and poor predictive survival score (mGPS = 2), treated with 5-fluorouracil-based chemotherapy in addition to an anti-epidermal growth factor receptor (EGFR) or anti-vas...

  2. A Phase 2 Study of Abiraterone Acetate in Japanese Men with Metastatic Castration-resistant Prostate Cancer Who Had Received Docetaxel-based Chemotherapy

    OpenAIRE

    SATOH, TAKEFUMI; Uemura, Hiroji; Tanabe, Kazunari; Nishiyama, Tsutomu; Terai, Akito; Yokomizo, Akira; Nakatani, Tatsuya; Imanaka, Keiichiro; Ozono, Seiichiro; Akaza, Hideyuki

    2014-01-01

    Objective In this Phase 2 multicenter study the efficacy and safety of oral abiraterone acetate (1000 mg/once daily) plus prednisolone (5 mg/twice daily) was evaluated in metastatic castration-resistant prostate cancer patients from Japan who had previously received docetaxel-based chemotherapy. Methods Men (aged ≥20 years) with metastatic castration-resistant prostate cancer (prostate-specific antigen levels: ≥5 ng/ml), who had received 1 or 2 cytotoxic chemotherapies (with ≥1 regimen being ...

  3. Assessment of circulating tumor cells and serum markers for progression-free survival prediction in metastatic breast cancer: a prospective observational study

    OpenAIRE

    Bidard, François-Clément; Hajage, David; Bachelot, Thomas; Delaloge, Suzette; Brain, Etienne; Campone, Mario; Cottu, Paul; Beuzeboc, Philippe; Rolland, Emilie; Mathiot, Claire; Pierga, Jean-Yves

    2012-01-01

    Introduction Circulating tumor cells (CTC) have been recently proposed as a new dynamic blood marker whose positivity at baseline is a prognostic factor and whose changes under treatment are correlated with progression-free survival (PFS) in metastatic breast cancer patients. However, serum marker levels are also used for the same purpose, and no clear comparison has been reported to date. Methods The IC 2006-04 enrolled prospectively 267 metastatic breast cancer patients treated by first lin...

  4. Tolerability, efficacy and pharmacokinetics of bicalutamide 300 mg, 450 mg or 600 mg as monotherapy for patients with locally advanced or metastatic prostate cancer, compared with castration

    DEFF Research Database (Denmark)

    Tyrrell, Chris J; Iversen, Peter; Tammela, Teuvo; Anderson, John; Björk, Thomas; Kaisary, Amir V; Morris, Thomas

    2006-01-01

    To evaluate the pharmacokinetics, tolerability and effect on endocrinology of bicalutamide given as once-daily monotherapy at doses of >150 mg to patients with locally advanced (M0) or metastatic (M1) prostate cancer, with efficacy as a secondary endpoint.......To evaluate the pharmacokinetics, tolerability and effect on endocrinology of bicalutamide given as once-daily monotherapy at doses of >150 mg to patients with locally advanced (M0) or metastatic (M1) prostate cancer, with efficacy as a secondary endpoint....

  5. Randomised, phase II trial comparing oral capecitabine (Xeloda®) with paclitaxel in patients with metastatic/advanced breast cancer pretreated with anthracyclines

    OpenAIRE

    Talbot, D C; Moiseyenko, V; Van Belle, S; O'Reilly, S. M.; Alba Conejo, E; Ackland, S; Eisenberg, P; Melnychuk, D.; Pienkowski, T; Burger, H-U; Laws, S.; Osterwalder, B

    2002-01-01

    Capecitabine, an oral fluoropyrimidine carbamate, was designed to generate 5-fluorouracil preferentially at the tumour site. This randomised, phase II trial evaluated the efficacy and safety of capecitabine or paclitaxel in patients with anthracycline-pretreated metastatic breast cancer. Outpatients with locally advanced and/or metastatic breast cancer whose disease was unresponsive or resistant to anthracycline therapy were randomised to 3-week cycles of intermittent oral capecitabine (1255 ...

  6. Progression-free survival as a potential surrogate for overall survival in metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Beauchemin C

    2014-06-01

    Full Text Available Catherine Beauchemin,1 Dan Cooper,2 Marie-Ève Lapierre,1 Louise Yelle,3 Jean Lachaine11Université de Montréal, Faculté de pharmacie, Montreal, 2Institut national d'excellence en santé et en services sociaux (INESSS, 3Centre Hospitalier de l'Université de Montréal – Hôpital Notre-Dame, Département de médecine, Université de Montréal, Montreal, QC, CanadaBackground: Progression-free survival (PFS and time to progression (TTP are frequently used to establish the clinical efficacy of anti-cancer drugs. However, the surrogacy of PFS/TTP for overall survival (OS remains a matter of uncertainty in metastatic breast cancer (mBC. This study assessed the relationship between PFS/TTP and OS in mBC using a trial-based approach.Methods: We conducted a systematic literature review according to the PICO method: 'Population' consisted of women with mBC; 'Interventions' and 'Comparators' were standard treatments for mBC or best supportive care; 'Outcomes' of interest were median PFS/TTP and OS. We first performed a correlation analysis between median PFS/TTP and OS, and then conducted subgroup analyses to explore possible reasons for heterogeneity. Then, we assessed the relationship between the treatment effect on PFS/TTP and OS. The treatment effect on PFS/TTP and OS was quantified by the absolute difference of median values. We also conducted linear regression analysis to predict the effects of a new anti-cancer drug on OS on the basis of its effects on PFS/TTP.Results: A total of 5,041 studies were identified, and 144 fulfilled the eligibility criteria. There was a statistically significant relationship between median PFS/TTP and OS across included trials (r=0.428; P<0.01. Correlation coefficient for the treatment effect on PFS/TTP and OS was estimated at 0.427 (P<0.01. The obtained linear regression equation was ΔOS =−0.088 (95% confidence interval [CI] −1.347–1.172 + 1.753 (95% CI 1.307–2.198 × ΔPFS (R2=0.86.Conclusion: Results of

  7. A structured review of health utility measures and elicitation in advanced/metastatic breast cancer

    Science.gov (United States)

    Hao, Yanni; Wolfram, Verena; Cook, Jennifer

    2016-01-01

    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, income, and education, as well as disease progression, choice of utility elicitation method, and country settings, were identified

  8. Two-dimensional electrophoretic comparison of metastatic and non-metastatic human breast tumors using in vitro cultured epithelial cells derived from the cancer tissues

    International Nuclear Information System (INIS)

    Breast carcinomas represent a heterogeneous group of tumors diverse in behavior, outcome, and response to therapy. Identification of proteins resembling the tumor biology can improve the diagnosis, prediction, treatment selection, and targeting of therapy. Since the beginning of the post-genomic era, the focus of molecular biology gradually moved from genomes to proteins and proteomes and to their functionality. Proteomics can potentially capture dynamic changes in protein expression integrating both genetic and epigenetic influences. We prepared primary cultures of epithelial cells from 23 breast cancer tissue samples and performed comparative proteomic analysis. Seven patients developed distant metastases within three-year follow-up. These samples were included into a metastase-positive group, the others formed a metastase-negative group. Two-dimensional electrophoretical (2-DE) gels in pH range 4–7 were prepared. Spot densities in 2-DE protein maps were subjected to statistical analyses (R/maanova package) and data-mining analysis (GUHA). For identification of proteins in selected spots, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed. Three protein spots were significantly altered between the metastatic and non-metastatic groups. The correlations were proven at the 0.05 significance level. Nucleophosmin was increased in the group with metastases. The levels of 2,3-trans-enoyl-CoA isomerase and glutathione peroxidase 1 were decreased. We have performed an extensive proteomic study of mammary epithelial cells from breast cancer patients. We have found differentially expressed proteins between the samples from metastase-positive and metastase-negative patient groups

  9. Human antibodies targeting cell surface antigens overexpressed by the hormone refractory metastatic prostate cancer cells: ICAM-1 is a tumor antigen that mediates prostate cancer cell invasion

    OpenAIRE

    Conrad, Fraser; Zhu, Xiaodong; Zhang, Xin; Chalkley, Robert J.; Burlingame, Alma L; Marks, James D.; Liu, Bin

    2009-01-01

    Transition from hormone-sensitive to hormone-refractory metastatic tumor types poses a major challenge for prostate cancer treatment. Tumor antigens that are differentially expressed during this transition are likely to play important roles in imparting prostate cancer cells with the ability to grow in a hormone-deprived environment and to metastasize to distal sites such as the bone and thus, are likely targets for therapeutic intervention. To identify those molecules and particularly cell s...

  10. Cabazitaxel as second-line or third-line therapy in patients with metastatic castration-resistant prostate cancer

    DEFF Research Database (Denmark)

    Kongsted, Per; Svane, Inge M; Lindberg, Henriette;

    2016-01-01

    To compare treatment outcomes in patients with metastatic castration-resistant prostate cancer treated with cabazitaxel (CA) as second-line or third-line therapy in the everyday clinical setting. Charts from 94 patients treated with CA as second-line (n=28) or third-line therapy (n=66) were...... evaluated. Common Terminology Criteria for Adverse Events were used to register grade 3-4 nonhematological toxicity during treatment with CA. Baseline metastatic castration-resistant prostate cancer-related prognostic factors, duration of therapy, and maximum prostate-specific antigen (PSA) percentage...... change were registered during treatment with CA and previous/subsequent novel androgen receptor targeting therapies. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. A median of 6 versus 5 treatment cycles was administered in patients treated with...

  11. Nab-paclitaxel plus gemcitabine in the treatment of metastatic pancreatic cancer: utility and experience from the clinic

    Directory of Open Access Journals (Sweden)

    Kundranda MN

    2016-01-01

    Full Text Available Madappa N Kundranda, Tomislav Dragovich Division of Hematology and Oncology, Banner MD Anderson Cancer Center, Gilbert, AZ, USA Abstract: Pancreatic ductal adenocarcinoma remains one of the deadliest epithelial cancers, primarily due to late diagnosis, early metastasis and the lack of effective treatments. With recent advances in systemic therapies, the median survival for metastatic disease has essentially doubled to approximately 1 year, and a significant number of patients are receiving multiple lines of therapy. One such first-line therapy is the combination of gemcitabine with nab-paclitaxel, which was approved by the US Food and Drug Administration in 2013. This standard option is now serving as a backbone to other novel combinations. In this review, we focus on the development of this combination, its clinical utility, and real-life experiences of managing patients with metastatic pancreatic ductal adenocarcinoma receiving gemcitabine and nab-paclitaxel. Keywords: pancreatic ductal adenocarcinoma, nab-paclitaxel, MPACT trial, PRODIGE 4/ACCORD 11 trial

  12. Raloxifene inhibits tumor growth and lymph node metastasis in a xenograft model of metastatic mammary cancer

    International Nuclear Information System (INIS)

    The effects of raloxifene, a novel selective estrogen receptor modulator, were studied in a mouse metastatic mammary cancer model expressing cytoplasmic ERα. Mammary tumors, induced by inoculation of syngeneic BALB/c mice with BJMC3879luc2 cells, were subsequently treated with raloxifene at 0, 18 and 27 mg/kg/day using mini-osmotic pumps. In vitro study demonstrated that the ERα in BJMC3879luc2 cells was smaller (between 50 and 64 kDa) than the normal-sized ERα (66 kDa) and showed cytoplasmic localization. A statistically significant but weak estradiol response was observed in this cell line. When BJMC3879luc2 tumors were implanted into mice, the ERα mRNA levels were significantly higher in females than in males. In vitro studies showed that raloxifene induced mitochondria-mediated apoptosis and cell-cycle arrest in the G1-phase and a decrease in the cell population in the S-phase. In animal experiments, tumor volumes were significantly suppressed in the raloxifene-treated groups. The multiplicity of lymph node metastasis was significantly decreased in the 27 mg/kg group. Levels of apoptosis were significantly increased in the raloxifene-treated groups, whereas the levels of DNA synthesis were significantly decreased in these groups. No differences in microvessel density in tumors were observed between the control and raloxifene-treated groups. The numbers of dilated lymphatic vessels containing intraluminal tumor cells were significantly reduced in mammary tumors in the raloxifene-treated groups. The levels of ERα mRNA in mammary tumors tended to be decreased in the raloxifene-treated groups. These results suggest that the antimetastatic activity of raloxifene in mammary cancer expressing cytoplasmic ERα may be a crucial finding with clinical applications and that raloxifene may be useful as an adjuvant therapy and for the chemoprevention of breast cancer development

  13. Raloxifene inhibits tumor growth and lymph node metastasis in a xenograft model of metastatic mammary cancer

    Directory of Open Access Journals (Sweden)

    Li Zhong-Lian

    2010-10-01

    Full Text Available Abstract Background The effects of raloxifene, a novel selective estrogen receptor modulator, were studied in a mouse metastatic mammary cancer model expressing cytoplasmic ERα. Methods Mammary tumors, induced by inoculation of syngeneic BALB/c mice with BJMC3879luc2 cells, were subsequently treated with raloxifene at 0, 18 and 27 mg/kg/day using mini-osmotic pumps. Results In vitro study demonstrated that the ERα in BJMC3879luc2 cells was smaller (between 50 and 64 kDa than the normal-sized ERα (66 kDa and showed cytoplasmic localization. A statistically significant but weak estradiol response was observed in this cell line. When BJMC3879luc2 tumors were implanted into mice, the ERα mRNA levels were significantly higher in females than in males. In vitro studies showed that raloxifene induced mitochondria-mediated apoptosis and cell-cycle arrest in the G1-phase and a decrease in the cell population in the S-phase. In animal experiments, tumor volumes were significantly suppressed in the raloxifene-treated groups. The multiplicity of lymph node metastasis was significantly decreased in the 27 mg/kg group. Levels of apoptosis were significantly increased in the raloxifene-treated groups, whereas the levels of DNA synthesis were significantly decreased in these groups. No differences in microvessel density in tumors were observed between the control and raloxifene-treated groups. The numbers of dilated lymphatic vessels containing intraluminal tumor cells were significantly reduced in mammary tumors in the raloxifene-treated groups. The levels of ERα mRNA in mammary tumors tended to be decreased in the raloxifene-treated groups. Conclusion These results suggest that the antimetastatic activity of raloxifene in mammary cancer expressing cytoplasmic ERα may be a crucial finding with clinical applications and that raloxifene may be useful as an adjuvant therapy and for the chemoprevention of breast cancer development.

  14. Efficacy and safety of levodropropizine and dihydrocodeine on nonproductive cough in primary and metastatic lung cancer.

    Science.gov (United States)

    Luporini, G; Barni, S; Marchi, E; Daffonchio, L

    1998-07-01

    Nonproductive cough is a frequent and distressing symptom in patients with lung cancer, and it is not even relieved by palliative chemotherapy. A double-blind, randomized clinical trial regarding the treatment of nonproductive cough was performed in 140 adults with primary lung cancer or metastatic cancer of the lungs. The therapeutic efficacy and the tolerability of a 7-day treatment with levodropropizine drops (75 mg t.i.d.) were evaluated in comparison with dihydrocodeine drops (10 mg t.i.d.; 7 days). Efficacy was assessed on the basis of cough severity scores, number of night awakenings due to cough, and overall estimate of antitussive efficacy. Tolerability was evaluated by laboratory results, vital signs and any adverse event occurring during the clinical trial, including presence or absence of somnolence. Subjective cough severity was significantly reduced during treatment with either levodropropizine and dihydrocodeine, the antitussive effect and its time-profile being similar for both drugs. Also, according to the investigator's evaluation, both levodropropizine and dihydrocodeine produced a significant decrease in cough severity. Concurrently with the relief of cough, the number of night awakenings was decreased significantly by both drugs, with no difference between the two treatments. No change in laboratory test values was considered clinically relevant, and vital signs were not clinically affected. The number of patients reporting adverse events was similar in the levodropropizine (n=6) and dihydrocodeine (n=4) group. However, the percentage of patients experiencing somnolence in the group receiving levodropropizine (8%) was significantly lower as compared with that of the dihydrocodeine group (22%). These results confirm the antitussive effectiveness of levodropropizine and suggest a more favourable benefit/risk profile when compared to dihydrocodeine. PMID:9701421

  15. Artificial neural network analysis of circulating tumor cells in metastatic breast cancer patients.

    Science.gov (United States)

    Giordano, Antonio; Giuliano, Mario; De Laurentiis, Michelino; Eleuteri, Antonio; Iorio, Francesco; Tagliaferri, Roberto; Hortobagyi, Gabriel N; Pusztai, Lajos; De Placido, Sabino; Hess, Kenneth; Cristofanilli, Massimo; Reuben, James M

    2011-09-01

    A cut-off of 5 circulating tumor cells (CTCs) per 7.5 ml of blood in metastatic breast cancer (MBC) patients is highly predictive of outcome. We analyzed the relationship between CTCs as a continuous variable and overall survival in immunohistochemically defined primary tumor molecular subtypes using an artificial neural network (ANN) prognostic tool to determine the shape of the relationship between risk of death and CTC count and to predict individual survival. We analyzed a training dataset of 311 of 517 (60%) consecutive MBC patients who had been treated at MD Anderson Cancer Center from September 2004 to 2009 and who had undergone pre-therapy CTC counts (CellSearch(®)). Age; estrogen, progesterone receptor, and HER2 status; visceral metastasis; metastatic disease sites; therapy type and line; and CTCs as a continuous value were evaluated using ANN. A model with parameter estimates obtained from the training data was tested in a validation set of the remaining 206 (40%) patients. The model estimates were accurate, with good discrimination and calibration. Risk of death, as estimated by ANN, linearly increased with increasing CTC count in all molecular tumor subtypes but was higher in ER+ and triple-negative MBC than in HER2+. The probabilities of survival for the four subtypes with 0 CTC were as follows: ER+/HER2- 0.947, ER+/HER2+ 0.959, ER-/HER2+ 0.902, and ER-/HER2- 0.875. For patients with 200 CTCs, they were ER+/HER2- 0.439, ER+/HER2+ 0.621, ER-/HER2+ 0.307, ER-/HER2- 0.130. In this large study, ANN revealed a linear increase of risk of death in MBC patients with increasing CTC counts in all tumor subtypes. CTCs' prognostic effect was less evident in HER2+ MBC patients treated with targeted therapy. This study may support the concept that the number of CTCs, along with the biologic characteristics, needs to be carefully taken into account in future analysis. PMID:21710134

  16. Long-term, treatment-free survival in select patients with distant metastatic papillary thyroid cancer

    OpenAIRE

    Kwong, Norra; Marqusee, Ellen; Gordon, Michael S.; Larsen, P. Reed; Garber, Jeffrey R; Kim, Matthew I.; Alexander, Erik K.

    2014-01-01

    Well-differentiated thyroid carcinoma (WDTC) generally has a favorable prognosis. However, patients with distant metastatic disease experience progression of disease with a higher mortality. A subset of patients not previously described may challenge the conventional dogma regarding the progressive nature of all metastatic WDTC. Through analysis of our database, we identified patients with distant metastatic WDTC and persistent, minimally progressive disease. In all patients, persistent metas...

  17. Comparison of PET metabolic indices for the early assessment of tumour response in metastatic colorectal cancer patients treated by polychemotherapy

    OpenAIRE

    Maisonobe, Jacques-Antoine; Garcia, Camilo A.; Necib, Hatem; Vanderlinden, Bruno; Hendlisz, Alain; Flamen, Patrick; Buvat, Irène

    2012-01-01

    Purpose To compare the performance of eight metabolic indices for the early assessment of tumour response in patients with metastatic colorectal cancer (mCRC) treated with chemotherapy. Methods Forty patients with advanced mCRC underwent two FDG PET/CT scans, at baseline and on day 14 after chemotherapy initiation. For each lesion, eight metabolic indices were calculated: four standardized uptake values (SUV) without correction for the partial volume effect (PVE), two SUV with correction for ...

  18. Comparison of treatment patterns and economic outcomes in metastatic breast cancer patients initiated on trastuzumab versus lapatinib: a retrospective analysis

    OpenAIRE

    Guérin, Annie; Lalla, Deepa; Gauthier, Geneviève; Styles, Amy; Wu, Eric Q.; Masaquel, Anthony; Brammer, Melissa G

    2014-01-01

    Few studies have compared treatment patterns, healthcare resource utilization (HRU), and costs in patients with metastatic breast cancer (mBC) receiving HER2 directed therapy. This study evaluated these outcomes in patients receiving trastuzumab or lapatinib. Adult women with mBC, who were initiated on trastuzumab or lapatinib, on or after March 13, 2007, were selected from the US-based PharMetrics® Integrated Database (2000–2011). Patients were required to be continuously enrolled in their h...

  19. Enzalutamide treatment in patients with metastatic castration-resistant prostate cancer progressing after chemotherapy and abiraterone acetate

    DEFF Research Database (Denmark)

    Thomsen, Frederik Birkebaek; Røder, Martin Andreas; Rathenborg, Per;

    2014-01-01

    OBJECTIVE: The aim of this study was to record prostate-specific antigen (PSA) response and overall survival (OS) for a group of metastatic castration-resistant prostate cancer (mCRPC) patients treated with enzalutamide following progression after abiraterone treatment in the post-chemotherapy...... marked fall in PSA following enzalutamide therapy in post-chemotherapy mCRPC patients compared with reported results in randomized trials. Larger prospective studies of sequencing are warranted....

  20. Genomic alterations indicate tumor origin and varied metastatic potential of disseminated cells from prostate-cancer patients

    OpenAIRE

    Holcomb, Ilona N.; Grove, Douglas I.; Kinnunen, Martin; Friedman, Cynthia L.; Gallaher, Ian S.; Todd M. Morgan; Sather, Cassandra L.; Delrow, Jeffrey J; Peter S Nelson; Lange, Paul H.; Ellis, William J; True, Lawrence D.; Janet M Young; Hsu, Li; Trask, Barbara J.

    2008-01-01

    Disseminated epithelial cells can be isolated from the bone marrow of a far greater fraction of prostate-cancer patients than the fraction of patients who progress to metastatic disease. To provide a better understanding of these cells, we have characterized their genomic alterations. We first present an array comparative genomic hybridization method capable of detecting genomic changes in the small number of disseminated cells (10-20) that can typically be obtained from bone-marrow aspirates...