WorldWideScience

Sample records for metastatic colon cancer

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

    Science.gov (United States)

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

    2016-08-01

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

  2. 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. 

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

    Science.gov (United States)

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

    2012-01-01

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

  4. Unsupported off-label chemotherapy in metastatic colon cancer

    Directory of Open Access Journals (Sweden)

    de Souza Jonas A

    2012-12-01

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

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

    Science.gov (United States)

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

    2014-11-01

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

  6. Invasive ductal breast cancer metastatic to the sigmoid colon

    Directory of Open Access Journals (Sweden)

    Zhou Xiao-cong

    2012-11-01

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

  7. 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.

  8. 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...

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

    Directory of Open Access Journals (Sweden)

    M. Yu. Fedyanin

    2014-01-01

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

  10. Chemoembolization Using Irinotecan in Treating Patients With Liver Metastases From Metastatic Colon or Rectal Cancer

    Science.gov (United States)

    2015-09-10

    Liver Metastases; Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IV Colon Cancer; Stage IV Rectal Cancer

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

    Science.gov (United States)

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

    2016-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Zhang Shan-shan

    2012-08-01

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

  13. Metastatic Cancer

    Science.gov (United States)

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

  14. Colon cancer

    Science.gov (United States)

    Colorectal cancer; Cancer - colon; Rectal cancer; Cancer - rectum; Adenocarcinoma - colon; Colon - adenocarcinoma; Colon carcinoma ... eat may play a role in getting colon cancer. Colon cancer may be linked to a high-fat, ...

  15. MicroRNAs as Regulator of Signaling Networks in Metastatic Colon Cancer.

    Science.gov (United States)

    Wang, Jian; Du, Yong; Liu, Xiaoming; Cho, William C; Yang, Yinxue

    2015-01-01

    MicroRNAs (miRNAs) are a class of small, noncoding RNA molecules capable of regulating gene expression translationally and/or transcriptionally. A large number of evidence have demonstrated that miRNAs have a functional role in both physiological and pathological processes by regulating the expression of their target genes. Recently, the functionalities of miRNAs in the initiation, progression, angiogenesis, metastasis, and chemoresistance of tumors have gained increasing attentions. Particularly, the alteration of miRNA profiles has been correlated with the transformation and metastasis of various cancers, including colon cancer. This paper reports the latest findings on miRNAs involved in different signaling networks leading to colon cancer metastasis, mainly focusing on miRNA profiling and their roles in PTEN/PI3K, EGFR, TGFβ, and p53 signaling pathways of metastatic colon cancer. The potential of miRNAs used as biomarkers in the diagnosis, prognosis, and therapeutic targets in colon cancer is also discussed.

  16. MicroRNAs as Regulator of Signaling Networks in Metastatic Colon Cancer

    Directory of Open Access Journals (Sweden)

    Jian Wang

    2015-01-01

    Full Text Available MicroRNAs (miRNAs are a class of small, noncoding RNA molecules capable of regulating gene expression translationally and/or transcriptionally. A large number of evidence have demonstrated that miRNAs have a functional role in both physiological and pathological processes by regulating the expression of their target genes. Recently, the functionalities of miRNAs in the initiation, progression, angiogenesis, metastasis, and chemoresistance of tumors have gained increasing attentions. Particularly, the alteration of miRNA profiles has been correlated with the transformation and metastasis of various cancers, including colon cancer. This paper reports the latest findings on miRNAs involved in different signaling networks leading to colon cancer metastasis, mainly focusing on miRNA profiling and their roles in PTEN/PI3K, EGFR, TGFβ, and p53 signaling pathways of metastatic colon cancer. The potential of miRNAs used as biomarkers in the diagnosis, prognosis, and therapeutic targets in colon cancer is also discussed.

  17. MicroRNAs as Regulator of Signaling Networks in Metastatic Colon Cancer

    Science.gov (United States)

    Wang, Jian; Du, Yong; Liu, Xiaoming; Cho, William C.; Yang, Yinxue

    2015-01-01

    MicroRNAs (miRNAs) are a class of small, noncoding RNA molecules capable of regulating gene expression translationally and/or transcriptionally. A large number of evidence have demonstrated that miRNAs have a functional role in both physiological and pathological processes by regulating the expression of their target genes. Recently, the functionalities of miRNAs in the initiation, progression, angiogenesis, metastasis, and chemoresistance of tumors have gained increasing attentions. Particularly, the alteration of miRNA profiles has been correlated with the transformation and metastasis of various cancers, including colon cancer. This paper reports the latest findings on miRNAs involved in different signaling networks leading to colon cancer metastasis, mainly focusing on miRNA profiling and their roles in PTEN/PI3K, EGFR, TGFβ, and p53 signaling pathways of metastatic colon cancer. The potential of miRNAs used as biomarkers in the diagnosis, prognosis, and therapeutic targets in colon cancer is also discussed. PMID:26064956

  18. Autumn Royal and Ribier Grape Juice Extracts Reduced Viability and Metastatic Potential of Colon Cancer Cells

    Science.gov (United States)

    Valenzuela, Manuel; Bastias, Lorena; Montenegro, Iván; Werner, Enrique; Madrid, Alejandro; Godoy, Patricio

    2018-01-01

    Antioxidants are known to be beneficial to health. This paper evaluates the potential chemopreventive and anticancer properties of phenolic compounds present in grape juice extracts (GJE) from Autumn Royal and Ribier varieties. The effects of these GJE on viability (SRB day assay) and metastatic potential (migration and invasion parameters) of colon cancer cell lines HT-29 and SW-480 were evaluated. The effects of GJE on two matrix metalloproteinase gene expressions (MMP2 and MMP9) were also evaluated via qRT-PCR. In the former, GJE reduced cell viability in both cell lines in a dose-dependent manner. GJE treatment also reduced cell migration and invasion. Moreover, MMP-2 and MMP-9 gene expression diminished depending on extract and on cell type. Conclusions. These results provide novel information concerning anticancer properties of selected GJE by revealing selective cytotoxicity and the ability to reduce invasiveness of colon cancer cells. PMID:29552079

  19. CHARACTERISTICS OF CLINICAL COURSE OF METASTATIC AND PRIMARY OVARIAN TUMORS IN COLON CANCER

    Directory of Open Access Journals (Sweden)

    I. A. Dzhanyan

    2015-01-01

    Full Text Available The aim of this study was to investigate clinical pecuiliarities of ovarian tumors in colon cancer patients and determination of complex diagnostic methods.Subject and methods. Russian N.N.  Blokhin Cancer Research Center archives were used for retrospective study, patients, who underwent treatment during 1989–2013  were included. Colon cancer patients with ovarian metastases and with synchronous or metachronous tumors were included.Results. 141 patients were included: 91 patients had colon cancer with ovarian metastases (group 1 and 50 patients had synchronous or metachronous ovarian tumours (group 2. Ovarian tumors were diagnosed during the 1 year in 74 (81.3 % patients in group 1 and in 23 (46 % in group 2. Patients in group 2 less frequently had children (9 (18.0 % vs 5 (5.5 + 2.3 %, р < 0.05, family history of cancer (3 (6 % vs 16 (17.6 %, р < 0.05 and concomitant diseases. Median CA 125 level in group 1 was 64.96 ng/ml and 180 ng/ml in group 2. Ovarian tumors had solid and cystic structure during US examination in 66 (73 % patients in group 1 and 31 (62 % patients in group 2 had solid ovarian tumors on US examination.Conclusions. The differential diagnostics of primary and metastatic ovarian tumors must include CEA, CA 19–9 and CA 125 serum levels and pelvic US.

  20. Trends in the Treatment of Metastatic Colon and Rectal Cancer in Elderly Patients.

    Science.gov (United States)

    Bradley, Cathy J; Yabroff, K Robin; Warren, Joan L; Zeruto, Christopher; Chawla, Neetu; Lamont, Elizabeth B

    2016-05-01

    Little is known about the use and costs of antineoplastic regimens for elderly patients with metastatic colorectal cancer (mCRC). We report population-based trends over a 10-year period in the treatment, survival, and costs in mCRC patients, stratified by ages 65-74 and 75+. We used Surveillance, Epidemiology, and End Results-Medicare data for persons diagnosed with metastatic colon (N=16117) or rectal cancer (N=4008) between 2000 and 2009. We estimated the adjusted percent of patients who received antineoplastic agents, by type, number, and their costs 12 months following diagnosis. We report the percent of patients who received 3 or more of commonly prescribed agents and estimate survival for the 24-month period following diagnosis by age and treatment. The percentage that received 3 or more agents increased from 3% to 73% in colon patients aged 65-74 and from 2% to 53% in patients 75+. Similar increases were observed in rectal patients. Average 1-year costs per patient in 2009 were $106,461 and $102,680 for colon and rectal cancers, respectively, reflecting an increase of 32% and 20%, for patients who received antineoplastic agents. Median survival increased by about 6 and 10 months, respectively, for colon and rectal patients aged 65-74 who received antineoplastic agents, but an improvement of only 1 month of median survival was observed for patients 75+. Expensive multiple agent regimens are increasingly used in older mCRC patients. For patients aged 64-75 years, these treatments may be associated with several months of additional life, but patients aged 75+ may incur considerable expense without any survival benefit.

  1. A rapid, sensitive, reproducible and cost-effective method for mutation profiling of colon cancer and metastatic lymph nodes

    OpenAIRE

    Fumagalli, Debora; Gavin, Patrick G; Taniyama, Yusuke; Kim, Seung-Il; Choi, Hyun-Joo; Paik, Soonmyung; Pogue-Geile, Katherine L

    2010-01-01

    Abstract Background An increasing number of studies show that genetic markers can aid in refining prognostic information and predicting the benefit from systemic therapy. Our goal was to develop a high throughput, cost-effective and simple methodology for the detection of clinically relevant hot spot mutations in colon cancer. Methods The Maldi-Tof mass spectrometry platform and OncoCarta panel from Sequenom were used to profile 239 colon cancers and 39 metastatic lymph nodes from NSABP clini...

  2. ERCC1 and TS Expression as Prognostic and Predictive Biomarkers in Metastatic Colon Cancer.

    Directory of Open Access Journals (Sweden)

    Michel B Choueiri

    Full Text Available In patients with metastatic colon cancer, response to first line chemotherapy is a strong predictor of overall survival (OS. Currently, oncologists lack diagnostic tests to determine which chemotherapy regimen offers the greatest chance for response in an individual patient. Here we present the results of gene expression analysis for two genes, ERCC1 and TS, measured with the commercially available ResponseDX: Colon assay (Response Genetics, Los Angeles, CA in 41 patients with de novo metastatic colon cancer diagnosed between July 2008 and August 2013 at the University of California, San Diego. In addition ERCC1 and TS expression levels as determined by RNAseq and survival data for patients in TCGA were downloaded from the TCGA data portal. We found that patients with low expression of ERCC1 (n = 33 had significantly longer median OS (36.0 vs. 10.1 mo, HR 0.29, 95% CI .095 to .84, log-rank p = 9.0x10-6 and median time to treatment to failure (TTF following first line chemotherapy (14.1 vs. 2.4 mo, HR 0.17, 95% CI 0.048 to 0.58, log-rank p = 5.3x10-4 relative to those with high expression (n = 4. After accounting for the covariates age, sex, tumor grade and ECOG performance status in a Cox proportional hazard model the association of low ERCC1 with longer OS (HR 0.18, 95% CI 0.14 to 0.26, p = 0.0448 and TTF (HR 0.16, 95% CI 0.14 to 0.21, p = 0.0053 remained significant. Patients with low TS expression (n = 29 had significantly longer median OS (36.0 vs. 14.8 mo, HR 0.25, 95% CI 0.074 to 0.82, log-rank p = 0.022 relative to those with high expression (n = 12. The combined low expression of ERCC1/TS was predictive of response in patients treated with FOLFOX (40% vs. 91%, RR 2.3, Fisher's exact test p = 0.03, n = 27, but not with FOLFIRI (71% vs. 71%, RR 1.0, Fisher's exact test p = 1, n = 14. Overall, these findings suggest that measurement of ERCC1 and TS expression has potential clinical utility in managing patients with metastatic colorectal

  3. Increased diacylglycerol kinase ζ expression in human metastatic colon cancer cells augments Rho GTPase activity and contributes to enhanced invasion

    International Nuclear Information System (INIS)

    Cai, Kun; Mulatz, Kirk; Ard, Ryan; Nguyen, Thanh; Gee, Stephen H

    2014-01-01

    Unraveling the signaling pathways responsible for the establishment of a metastatic phenotype in carcinoma cells is critically important for understanding the pathology of cancer. The acquisition of cell motility is a key property of metastatic tumor cells and is a prerequisite for invasion. Rho GTPases regulate actin cytoskeleton reorganization and the cellular responses required for cell motility and invasion. Diacylglycerol kinase ζ (DGKζ), an enzyme that phosphorylates diacylglycerol to yield phosphatidic acid, regulates the activity of the Rho GTPases Rac1 and RhoA. DGKζ mRNA is highly expressed in several different colon cancer cell lines, as well as in colon cancer tissue relative to normal colonic epithelium, and thus may contribute to the metastatic process. To investigate potential roles of DGKζ in cancer metastasis, a cellular, isogenic model of human colorectal cancer metastatic transition was used. DGKζ protein levels, Rac1 and RhoA activity, and PAK phosphorylation were measured in the non-metastatic SW480 adenocarcinoma cell line and its highly metastatic variant, the SW620 line. The effect of DGKζ silencing on Rho GTPase activity and invasion through Matrigel-coated Transwell inserts was studied in SW620 cells. Invasiveness was also measured in PC-3 prostate cancer and MDA-MB-231 breast cancer cells depleted of DGKζ. DGKζ protein levels were elevated approximately 3-fold in SW620 cells compared to SW480 cells. There was a concomitant increase in active Rac1 in SW620 cells, as well as substantial increases in the expression and phosphorylation of the Rac1 effector PAK1. Similarly, RhoA activity and expression were increased in SW620 cells. Knockdown of DGKζ expression in SW620 cells by shRNA-mediated silencing significantly reduced Rac1 and RhoA activity and attenuated the invasiveness of SW620 cells in vitro. DGKζ silencing in highly metastatic MDA-MB-231 breast cancer cells and PC-3 prostate cancer cells also significantly attenuated

  4. Fatal Acute Liver Failure as a Consequence of Regorafenib Treatment in a Metastatic Colon Cancer

    Directory of Open Access Journals (Sweden)

    Dominique Béchade

    2017-08-01

    Full Text Available Regorafenib is a multikinase inhibitor which showed benefits in pretreated metastatic colorectal cancer patients. Hepatotoxicity has been described as a frequent side effect. We report the case of a 65-year-old patient presenting with jaundice, fever, and hepatocellular insufficiency which led to death of the patient. She had previously been treated with several lines of chemotherapy for sub- and diaphragmatic ganglionic metastases of a colon adenocarcinoma. There were no liver metastases. The fatal liver failure occurred at the beginning of treatment with regorafenib at a dosage of 3 tablets per day. No concomitant treatment was given, and other causes of liver damage were eliminated. The liver biopsy showed hepatocyte necrosis with lymphocyte infiltration. This observation illustrates the risk of severe hepatic involvement typically occurring within the first 2 months of treatment. Monitoring liver biology every 2 weeks is essential during the first 2 months to detect any hepatotoxicity.

  5. Association of methylenetetrahydrofolate reductase gene polymorphisms and sex-specific survival in patients with metastatic colon cancer.

    Science.gov (United States)

    Zhang, Wu; Press, Oliver A; Haiman, Christopher A; Yang, Dong Yun; Gordon, Michael A; Fazzone, William; El-Khoueiry, Anthony; Iqbal, Syma; Sherrod, Andy E; Lurje, Georg; Lenz, Heinz-Josef

    2007-08-20

    Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme regulating intracellular folate levels, which affects DNA synthesis and methylation. Two MTHFR gene polymorphisms, C677T and A1298C, are linked to altered enzyme activity. Several studies have shown these two polymorphisms to be associated with response to fluorouracil (FU) -based treatment in advanced colon cancer patients, but data are inconsistent and contradictory. Meanwhile, epidemiologic studies demonstrated that these MTHFR polymorphisms were associated with cancer risk in a sex-specific manner. We tested the hypothesis of whether these two polymorphisms are associated with sex-specific clinical outcome in metastatic colon cancer patients treated with FU-based chemotherapy. This study included 318 patients (177 men and 141 women) with metastatic colon cancer treated between 1992 and 2003 at the University of Southern California/Norris Comprehensive Cancer Center or Los Angeles County/University of Southern California Medical Center. Peripheral blood samples were collected from each patient, and genomic DNA was extracted from WBCs. Two MTHFR gene polymorphisms (C677T and A1298C) were tested by fluorogenic 5'-nuclease assay. The A1298C polymorphism showed statistically significant differences in overall survival (OS) in female, but not male, patients with metastatic colon cancer (log-rank test, P = .038). Among females, OS was greater for patients with the A/A genotype (n = 67; median OS, 18.4 months) compared with patients with the A/C genotype (n = 50; median OS, 13.9 months) or C/C genotype (n = 10; median OS, 15.6 months). Although preliminary, these data support the role of the A1298C polymorphism in MTHFR as prognostic marker in female patients with metastatic colon cancer. Further studies are needed to confirm these findings.

  6. SN38 conjugated hyaluronic acid gold nanoparticles as a novel system against metastatic colon cancer cells.

    Science.gov (United States)

    Hosseinzadeh, Hosniyeh; Atyabi, Fatemeh; Varnamkhasti, Behrang Shiri; Hosseinzadeh, Reza; Ostad, Seyed Nasser; Ghahremani, Mohammad Hossein; Dinarvand, Rassoul

    2017-06-30

    Combination of chemotherapy and photothermal therapy has been proposed for better treatment of metastatic colon cancer. In this study SN38, a highly potent cytotoxic agent, was conjugated to negatively charged hyaluronic acid (HA), which was deposited on the surface of the positively charged gold nanoparticles via electrostatic interaction. The drug conjugation and its interaction with gold nanoparticles were verified by 1 H NMR and UV-vis spectroscopies, respectively. The prepared SN38-HA gold NPs are negatively charged spherical nanoparticles with an average size of 75±10nm. In vitro release study revealed that drug release in acidic conditions (pH 5.2) was faster than that in physiological pH. Red light emitting diode (LED, 630nm, 30mW) was used as a light source for photothermal experiments. The drug release in acidic conditions was increased up to 30% using red LED illumination (6min) in comparison with experiment carried out indark. The cytotoxicity study on MUC1 positive HT29, SW480 colon cancer cells and MUC1 negative CHO cells, showed higher toxicity of the nanoparticles on HT29 and SW480 cell lines compared to CHO cells. Confocal microscopy images along with flow cytometry analysis confirm the cytotoxicity results. The incubation time for reaching IC50 decreases from 48h to 24h by LED illumination after nanoparticle treatment. Migratory potential of the HT29 and SW480 cell lines was reduced by co-application of SN38-HA gold NPs and LED radiation. Also anti-proliferative study indicates that LED radiation has increased the cytotoxicity of the nanoparticles and this effect is remained up to 8days. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Irinotecan-Eluting Beads in Treating Patients With Refractory Metastatic Colon or Rectal Cancer That Has Spread to the Liver

    Science.gov (United States)

    2018-02-22

    Liver Metastases; Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

  8. Positron emission tomography/computed tomography and biomarkers for early treatment response evaluation in metastatic colon cancer

    DEFF Research Database (Denmark)

    Engelmann, Bodil E.; Loft, Annika; Kjær, Andreas

    2014-01-01

    BACKGROUND: Treatment options for metastatic colon cancer (mCC) are widening. We prospectively evaluated serial 2-deoxy-2-[18F]fluoro-d-glucose positron-emission tomography/computed tomography (PET/CT) and measurements of tissue inhibitor of metalloproteinases-1 (TIMP-1), carcinoembryonic antigen...... evaluated by PET/CT before treatment, after one and four treatment series. Morphological and metabolic response was independently assessed according to Response Evaluation Criteria in Solid Tumors and European Organization for Research and Treatment of Cancer PET criteria. Plasma TIMP-1, plasma u...

  9. Multiplex flow cytometry barcoding and antibody arrays identify surface antigen profiles of primary and metastatic colon cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Kumar Sukhdeo

    Full Text Available Colon cancer is a deadly disease affecting millions of people worldwide. Current treatment challenges include management of disease burden as well as improvements in detection and targeting of tumor cells. To identify disease state-specific surface antigen signatures, we combined fluorescent cell barcoding with high-throughput flow cytometric profiling of primary and metastatic colon cancer lines (SW480, SW620, and HCT116. Our multiplexed technique offers improvements over conventional methods by permitting the simultaneous and rapid screening of cancer cells with reduced effort and cost. The method uses a protein-level analysis with commercially available antibodies on live cells with intact epitopes to detect potential tumor-specific targets that can be further investigated for their clinical utility. Multiplexed antibody arrays can easily be applied to other tumor types or pathologies for discovery-based approaches to target identification.

  10. A Chinese Decoction, Kuan-Sin-Yin, Improves Autonomic Function and Cancer-Related Symptoms of Metastatic Colon Cancer.

    Science.gov (United States)

    Chien, Tsai-Ju; Liu, Chia-Yu; Ko, Pin-Hao; Hsu, Chung-Hua

    2016-03-01

    Kuan-Sin-Yin (KSY) is a traditional Chinese medicine (TCM) decoction, which has been shown to have cytostatic effects on cancer cells and involved in the TCM theory of promoting yin-yang balance.Sonce many cancer patients suffer from autonomic dysfunction (AD), which correspond to yin-yang imbalance in TCM. The aim of this study is to evaluate the possible effect of KSY in metastatic colon cancer (mCRC) patients with AD. We conducted a single-group experiment. Total 52 qualified patients were enrolled. Participants took the KSY daily for 2 weeks. The primary outcome was KSY efficacy as reflected in the heart rate variability (HRV) and electrical conductivity (µA) over 12 meridian points. Autonomic function was examined before and after the KSY intervention. The vagal and sympathetic tone were recorded by HRV; 12 meridian energies were measured using a meridian energy analysis device. Secondary outcomes were cancer-related symptoms and patient quality of life (QoL). The results showed that the KSY intervention improved AD via increasing the vagal tone (HF: P = .041), but not the sympathetic tone (LF: P = .154); total autonomic activity was significantly enhanced (HRV activity: P = .013). Intriguingly, energy increased more over the yin meridian (P = .010) than over the yang meridian (P = .015). Cancer-related symptoms and QoL were significantly improved (P yin-yang concept of energy. © The Author(s) 2015.

  11. Akt Inhibitor MK2206 in Treating Patients With Previously Treated Colon or Rectal Cancer That is Metastatic or Locally Advanced and Cannot Be Removed by Surgery

    Science.gov (United States)

    2017-06-26

    Colon Mucinous Adenocarcinoma; Colon Signet Ring Cell Adenocarcinoma; Rectal Mucinous Adenocarcinoma; Rectal Signet Ring Cell Adenocarcinoma; Recurrent Colon Carcinoma; Recurrent Rectal Carcinoma; 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 IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

  12. Ceramide targets xIAP and cIAP1 to sensitize metastatic colon and breast cancer cells to apoptosis induction to suppress tumor progression

    International Nuclear Information System (INIS)

    Paschall, Amy V; Bielawska, Alicja; Liu, Kebin; Zimmerman, Mary A; Torres, Christina M; Yang, Dafeng; Chen, May R; Li, Xia; Bieberich, Erhard; Bai, Aiping; Bielawski, Jacek

    2014-01-01

    Ceramide is a bioeffector that mediates various cellular processes, including apoptosis. However, the mechanism underlying ceramide function in apoptosis is apparently cell type-dependent and is not well-understood. We aimed at identifying molecular targets of ceramide in metastatic human colon and breast cancer cells, and determining the efficacy of ceramide analog in suppression of colon and breast cancer metastasis. The activity of and mechanism underlying ceramide as a cytotoxic agent, and as a sensitizer for Fas-mediated apoptosis was analyzed in human cell lines established from primary or metastatic colon and breast cancers. The efficacy of ceramide analog LCL85 in suppression of metastasis was examined in preclinical mouse tumor models. Exposure of human colon carcinoma cells to ceramide analog LCL85 results in apoptosis in a dose-dependent manner. Interestingly, a sublethal dose of LCL85 increased C16 ceramide content and overcame tumor cell resistance to Fas-mediated apoptosis. Subsequently, treatment of tumor cells with exogenous C16 ceramide resulted in increased tumor cell sensitivity to Fas-mediated apoptosis. LCL85 resembles Smac mimetic BV6 in sensitization of colon carcinoma cells to Fas-mediated apoptosis by inducing proteasomal degradation of cIAP1 and xIAP proteins. LCL85 also decreased xIAP1 and cIAP1 protein levels and sensitized metastatic human breast cancer cells to Fas-mediated apoptosis. Silencing xIAP and cIAP1 with specific siRNAs significantly increased the metastatic human colon carcinoma cell sensitivity to Fas-mediated apoptosis, suggesting that IAP proteins mediate apoptosis resistance in metastatic human colon carcinoma cells and ceramide induces IAP protein degradation to sensitize the tumor cells to apoptosis induction. Consistent with its apoptosis sensitization activity, subtoxic doses of LCL85 suppressed colon carcinoma cell metastatic potential in an experimental lung metastasis mouse model, as well as breast cancer growth

  13. Metastatic Colon Cancer in an 18-Year-Old without Predisposing Factors

    Directory of Open Access Journals (Sweden)

    Divya Mirchandani

    2016-01-01

    Full Text Available While colorectal carcinoma is a common gastrointestinal cancer in adults, it is rare in pediatrics with an incidence of 1 : 1,000,000 and represents a fraction of neoplasms encountered in children. Malignant neoplasms represent a major cause of mortality in the pediatric age group. While presenting with weight loss, iron deficiency, rectal bleeding, abdominal pain, and change in bowel habits, or symptoms similar to acute appendicitis, the working diagnosis may be considered to be anorexia. This case illustrates the importance of considering colon cancer among other disease entities as a cause of unintentional weight loss in adolescents. While this is a rare occurrence in the pediatric population, significant unintentional weight loss with altered bowel habits should prompt a search for underlying malignancy—even in the absence of a positive family history or predisposing cancer syndromes.

  14. [Right Hemi-Colectomy for a Metastatic Transverse Colon Tumor from Breast Cancer Following Bilateral Breast Cancer Resection - A Case Report].

    Science.gov (United States)

    Okamura, Shu; Yanagisawa, Tetsu; Ohishi, Kazuhito; Murata, Kohei; Nushijima, Yoichiro; Hamano, Rie; Fukuchi, Nariaki; Ebisui, Chikara; Yokouchi, Hideoki; Kinuta, Masakatsu

    2016-11-01

    We herein report the case of a 75-year-old female patient who underwent 4 surgeries for bilateral breast cancer and its recurrence. When she presented at a clinic with an irritable colon, a fist-sized tumor was palpated in the right upper abdomen at her first medical examination. Abdominal CT scan at the clinic revealed a tumor with a maximum diameter of 10 cm on the right side of the transverse colon and multiple swollen mesenteric lymph nodes. Therefore, the patient was referred to our hospital for surgery. Colonoscopy revealed stenosis of the same lesion with an edematous mucosa and sclerosis. Using immunohistochemistry, a biopsy specimen from the lesion tested positive for CK AE1+AE3, and negative for CD20(-)and CD3 (-). As a result, the tumor was diagnosed as a poorly differentiated adenocarcinoma. We performed right hemicolectomy to avoid her intestinal obstruction. Tumor cells were mainly present at the subserosa, according to HEstaining. Using immunostaining, the cells were tested for the following markers: CDX2(-), GCDFP15(weakly positive), CK7(strongly positive), CD20(partially positive), E R(+), PgR(-), and HER2(1+), characterizing the tumor as metastasis of breast cancer. Although gastro-intestinal metastasis from breast cancer is rare, and colon metastasis is even rarer, it might be necessary to rule out the possibility of a metastatic colon tumor from breast cancer when treating patients with a colon tumor who have undergone surgery for breast cancer.

  15. A mechanically-induced colon cancer cell population shows increased metastatic potential

    KAUST Repository

    Tang, Xin

    2014-05-29

    Background: Metastasis accounts for the majority of deaths from cancer. Although tumor microenvironment has been shown to have a significant impact on the initiation and/or promotion of metastasis, the mechanism remains elusive. We previously reported that HCT-8 colon cancer cells underwent a phenotypic transition from an adhesive epithelial type (E-cell) to a rounded dissociated type (R-cell) via soft substrate culture, which resembled the initiation of metastasis. The objective of current study was to investigate the molecular and metabolic mechanisms of the E-R transition.Methods: Global gene expressions of HCT-8 E and R cells were measured by RNA Sequencing (RNA-seq); and the results were further confirmed by real-time PCR. Reactive oxygen species (ROS), anoikis resistance, enzyme activity of aldehyde dehydrogenase 3 family, member A1 (ALDH3A1), and in vitro invasion assay were tested on both E and R cells. The deformability of HCT-8 E and R cells was measured by atomic force microscopy (AFM). To study the in vivo invasiveness of two cell types, athymic nude mice were intra-splenically injected with HCT-8 E or R cells and sacrificed after 9 weeks. Incidences of tumor development and metastasis were histologically evaluated and analyzed with Fisher\\'s exact test.Results: Besides HCT-8, E-R transition on soft substrates was also seen in three other cancer cell lines (HCT116, SW480 colon and DU145 prostate cancer). The expression of some genes, such as ALDH3A1, TNS4, CLDN2, and AKR1B10, which are known to play important roles in cancer cell migration, invasion, proliferation and apoptosis, were increased in HCT-8 R cells. R cells also showed higher ALDH3A1 enzyme activity, higher ROS, higher anoikis resistance, and higher softness than E cells. More importantly, in vitro assay and in vivo animal models revealed that HCT-8 R cells were more invasive than E cells.Conclusions: Our comprehensive comparison of HCT-8 E and R cells revealed differences of molecular

  16. A Preclinical Model of Chronic Alcohol Consumption Reveals Increased Metastatic Seeding of Colon Cancer Cells in the Liver.

    Science.gov (United States)

    Im, Hwi-Jin; Kim, Hyeong-Geug; Lee, Jin-Seok; Kim, Hyo-Seon; Cho, Jung-Hyo; Jo, Il-Joo; Park, Sung-Joo; Son, Chang-Gue

    2016-04-01

    Liver metastasis is the main cause of death from colorectal cancer. Alcohol consumption impacts liver function and is suggested to be an independent risk factor for liver metastasis of colorectal cancer, but no experimental evidence supporting this hypothesis has been demonstrated to date. In this study, we investigated the effect of alcohol intake on liver metastasis. We examined colon cancer cell spread from the spleen in mice provided with water (control group), alcohol for 4 weeks before tumor injection (prealcohol), alcohol for 3 weeks after tumor injection (postalcohol), or alcohol throughout the 7-week study (alcohol). Alcohol intake significantly increased hepatic metastatic burden in the prealcohol (2.4-fold, P < 0.001), postalcohol (2.0-fold, P < 0.01), and alcohol groups (2.2-fold, P < 0.001). A fluorescence-based metastasis tracking assay also confirmed an alcohol-induced increase in the abundance of tumor cells in the liver (2.5-fold, P < 0.001). Investigation of the host microenvironment revealed an alcohol-induced inflammatory response marked by elevated TNFα, IL1β, IL6, and IFNγ protein levels, as well as increased expression of intercellular molecule-1 (ICAM1) in hepatic tissues after 4 weeks of alcohol consumption. Moreover, the peripheral blood of mice provided with alcohol for 4 weeks exhibited reduced natural killer and CD8(+) T-cell counts. Collectively, our findings suggest that chronic alcohol consumption accelerates liver metastasis of colorectal cancer cells through alterations to the liver microenvironment and inactivation of immune surveillance. Cancer Res; 76(7); 1698-704. ©2016 AACR. ©2016 American Association for Cancer Research.

  17. Metastatic mucinous adenocarcinoma of the distal common bile duct, from transverse colon cancer presenting as obstructive jaundice.

    Science.gov (United States)

    Lee, Doo-Ho; Ahn, Young Joon; Shin, Rumi; Lee, Hae Won

    2015-08-01

    The patient was a 70-year-old male whose chief complaints were obstructive jaundice and weight loss. Abdominal imaging studies showed a 2.5 cm sized mass at the distal common bile duct, which was suggestive of bile duct cancer. Eccentric enhancing wall thickening in the transverse colon was also shown, suggesting concomitant colon cancer. A colonoscopy revealed a lumen-encircling ulcerofungating mass in the transverse colon, that was pathologically proven to be adenocarcinoma. The bile duct pathology was also adenocarcinoma. Pylorus-preserving pancreaticoduodenectomy and extended right hemicolectomy were performed under the diagnosis of double primary cancers. Postoperative histopathologic examination revealed moderately differentiated mucinous adenocarcinoma of transverse colon cancer, and mucinous adenocarcinoma of the distal common bile duct. Immunohistochemical staining studies showed that the bile duct cancer had metastasized from the colon cancer. The patient recovered uneventfully from surgery and will be undergoing chemotherapy for three months.

  18. Learning about Colon Cancer

    Science.gov (United States)

    ... What do we know about heredity and colon cancer? Colon cancer, a malignant tumor of the large intestine, ... page Additional Resources for Information on Hereditary Colon Cancer Colon and Rectal Cancer Information [cancer.gov] The most ...

  19. Clinical and demographic characteristics associated with the receipt of chemotherapy treatment among 7951 elderly metastatic colon cancer patients.

    Science.gov (United States)

    Reese, Emily S; Onukwugha, Eberechukwu; Hanna, Nader; Seal, Brian S; Mullins, C Daniel

    2013-12-01

    Among older individuals diagnosed with metastatic colon cancer (mCC) there is limited evidence available that describes the characteristics associated with advancing to second- and subsequent lines of treatment with chemotherapy/biologics. Our objective was to describe the trends and lines of treatment received among elderly mCC patients. Elderly beneficiaries diagnosed with mCC from 2003 to 2007 were identified in the Surveillance, Epidemiology and End Results (SEER)-Medicare dataset. Beneficiaries were followed up until death or censoring. Treatment lines were classified in combinations of chemotherapies and biologics. Modified Poisson regression was used to predict receipt of lines of treatment. Analyses controlled for age, race/ethnicity, gender, marital status, state buy-in during diagnosis year, SEER-registry site, Charlson comorbidity index (CCI), poor performance indicators, surgery of primary site, and surgery of regional/distal sites. Among 7951 Medicare beneficiaries identified with mCC, 3266 initiated therapy. Of these, 1440 advanced to second-line treatment. Of these, 274 advanced to a subsequent-line treatment. Surgeries of the primary tumor site and of the regional/distal sites and marital status were the most significant variables associated with advancing through second- and subsequent-line treatments. Greater than 80 years of age, African American race, SEER-registry area, less than 6 months state buy-in assistance in mCC diagnosis year, and having poor performance indicators were inversely associated with receipt of second- or subsequent-line treatments. Among elderly individuals diagnosed with mCC, we identified demographic, clinical, and regional factors associated with receipt of second- and subsequent-line chemotherapy/biologics. Additional research is warranted to understand the role of physician versus patient preferences as well as geographic differences explaining why patients advance through lines of chemotherapy. © 2013 The Authors

  20. Expression of DIAPH1 is up-regulated in colorectal cancer and its down-regulation strongly reduces the metastatic capacity of colon carcinoma cells.

    Science.gov (United States)

    Lin, Yuan-Na; Izbicki, Jakob R; König, Alexandra; Habermann, Jens K; Blechner, Christine; Lange, Tobias; Schumacher, Udo; Windhorst, Sabine

    2014-04-01

    In most cases, metastatic colorectal cancer is not curable, thus new approaches are necessary to identify novel targets for colorectal cancer therapy. Actin-binding-proteins (ABPs) directly regulate motility of metastasising tumor cells, and for cortactin an association with colon cancer metastasis has been already shown. However, as its depletion only incompletely inhibits metastasis, additional, more suitable cellular targets have to be identified. Here we analyzed expression of the ABPs, DIAPH1, VASP, N-WASP, and fascin in comparison with cortactin and found that, besides cortactin, DIAPH1 was expressed with the highest frequency (63%) in colorectal cancer. As well as cortactin, DIAPH1 was not detectable in normal colon tissue and expression of both proteins was positively correlated with metastasis of colorectal cancer. To analyse the mechanistic role of DIAPH1 for metastasis of colon carcinoma cells in comparison with cortactin, expression of the proteins was stably down-regulated in the human colon carcinoma cell lines HT-29, HROC-24 and HCT-116. Analysis of metastasis of colon carcinoma cells in SCID mice revealed that depletion of DIAPH1 reduced metastasis 60-fold and depletion of cortactin 16-fold as compared with control cells. Most likely the stronger effect of DIAPH1 depletion on colon cancer metastasis is due to the fact that in vitro knock down of DIAPH1 impaired all steps of metastasis; adhesion, invasion and migration while down-regulation of cortactin only reduced adhesion and invasion. This very strong reducing effect of DIAPH1 depletion on colon carcinoma cell metastasis makes the protein a promising therapeutic target for individualized colorectal cancer therapy. © 2013 UICC.

  1. Successful twin pregnancy outcome after in utero exposure to FOLFOX for metastatic colon cancer: a case report and review of the literature

    DEFF Research Database (Denmark)

    Jeppesen, Johanne Bakker; Østerlind, Kell

    2011-01-01

    many dilemmas and concerns for the physician and patient. A delay in treatment may compromise maternal survival; however, therapy for the cancer may be harmful to the fetus. We present a case of a 26-year-old woman pregnant with twins who was diagnosed with metastatic colon cancer and treated with 5......There is limited experience in treating advanced colorectal cancer diagnosed during pregnancy because it is a rare occurrence; however, the incidence of colorectal cancer complicating pregnancy is expected to increase in the future. The combination of cancer and pregnancy is complicated and causes......-fluorouracil, leukovorin, and oxaliplatin (FOLFOX) from 13 weeks gestational age to birth. The patient gave birth to healthy twins without malformations at 33 weeks gestational age. At follow-up examination, the 2-year-old twins are developing normally. The patient herself died 1 year after the initial cancer...

  2. [A Case with Metastatic Huge Ovarian Tumor from Transverse Colon Cancer, Who Underwent Systemic Chemotherapy after Bilateral Oophorectomy and Right Hemi Colectomy].

    Science.gov (United States)

    Miyanari, Shun; Nagasaki, Toshiya; Minami, Hironori; Fukuoka, Hironori; Murahashi, Satoshi; Suzuki, Shinsuke; Ushigome, Hajime; Akiyoshi, Takashi; Konishi, Tsuyoshi; Fujimoto, Yoshiya; Nagayama, Satoshi; Fukunaga, Yosuke; Ueno, Masashi

    2017-11-01

    Metastatic ovarian tumors from colon cancer would be resistant to chemotherapy, and compromising quality of life(QOL) of these patients was caused by acute enlargement of the tumors. A 37-year-old woman with abdominal distension was diagnosed with transverse colon cancer, bilateral ovarian metastases, liver metastases, and peritoneal dissemination at prior hospital. Two courses of chemotherapy(FOLFOX)were administered, but metastaticovarian tumors enlarged. Chemotherapy was discontinued and she was referred to our institution. To achieve symptom relief, improving QOL, and to resume chemotherapy, we planned bilateral oophorectomy and primary tumor resection if other stenotic lesion was not present. As a result, we safely performed open bilateral oophorectomy and right hemi colectomy, and the patient discharged on postoperative day 11 without complications. Chemotherapy was resumed and continued for 7 months up to this time. Even though, curative resection could not be achieved, oophorectomy should be performed in patients with enlarged metastatic ovarian tumor from colon cancer, in spite of administration of chemotherapy.

  3. Metastatic signet ring colon cancer in a Caribbean young adult and review of the literature.

    Science.gov (United States)

    Koczka, Charles Philip; Goodman, Adam

    2012-06-01

    Colorectal cancer is the third most common neoplasm diagnosed in the USA, with less than 3% of patients younger than 40 years. Although most of the literature indicates that younger patients present with a higher stage and grade of cancer, mortality is not clearly correlated. Furthermore, the literature pertaining to colorectal cancer in the nonwhite youth is limited. In this case report, we report a case of aggressive colorectal cancer metastasizing in a young Afro-Caribbean woman with no known risk factors. The aim of this report is to raise awareness of this entity in the younger population, particularly in Afro-Caribbeans, which remains a highly understudied group compared with the rest of the US population.

  4. FOLFIRI and regorafenib combination therapy with dose escalation of irinotecan as fourth-line treatment for patients with metastatic colon cancer according to UGT1A1 genotyping

    Directory of Open Access Journals (Sweden)

    Lu CY

    2014-11-01

    Full Text Available Chien-Yu Lu,1,2 Yung-Sung Yeh,3–5 Ching-Wen Huang,5,6, Cheng-Jen Ma,4,5 Fang-Jung Yu,1,2 Jaw-Yuan Wang4–10 1Division of Gastroenterology, Department of Internal Medicine, 2Department of Internal Medicine, Faculty of Medicine, College of Medicine, 3Department of Emergency Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, 4Graduate Institute of Clinical Medicine, College of Medicine, 5Division of Gastroenterology and General Surgery, Department of Surgery, Kaohsiung Medical University Hospital, 6Graduate Institute of Medicine, College of Medicine, 7Cancer Center, Kaohsiung Medical University Hospital, 8Department of Genomic Medicine, 9Department of Surgery, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 10Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Kaohsiung, Taiwan Abstract: Here we report a case of metastatic colon cancer treated with 5-fluorouracil, leucovorin, and escalated doses of irinotecan (FOLFIRI combined with regorafenib in the fourth-line setting after uridine diphosphate glucuronosyltransferase (UGT1A1 genotyping analysis. A 66-year-old male was initially diagnosed with Union Internationale Contre le Cancer stage III descending colon cancer and underwent curative surgery. He received postoperative adjuvant chemotherapy; however, liver metastasis developed and a partial hepatectomy was performed thereafter. Unfortunately, pulmonary metastases and recurrent liver tumors were found despite a series of systemic treatments with multiple combinations of cytotoxic and biologic agents. Recently, a novel multikinase inhibitor, regorafenib, was approved for the treatment of metastatic colorectal cancer refractory to other therapeutic modalities. As further treatment, we combined regorafenib with FOLFIRI, which included dose escalations of irinotecan, after UGT1A1 genotyping analysis. The therapeutic results were promising, with the improvement in liver and pulmonary metastases being

  5. Trametinib and TAS-102 in Treating Patients With Colon or Rectal Cancer That is Advanced, Metastatic, or Cannot Be Removed by Surgery

    Science.gov (United States)

    2018-04-13

    RAS Family Gene Mutation; Stage III Colon Cancer AJCC v7; Stage III Colorectal Cancer AJCC v7; Stage III Rectal Cancer AJCC v7; Stage IIIA Colon Cancer AJCC v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIA Rectal Cancer AJCC v7; Stage IIIB Colon Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIB Rectal Cancer AJCC v7; Stage IIIC Colon Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7; Stage IIIC Rectal Cancer AJCC v7; Stage IV Colon Cancer AJCC v7; Stage IV Colorectal Cancer AJCC v7; Stage IV Rectal Cancer AJCC v7; Stage IVA Colon Cancer AJCC v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVA Rectal Cancer AJCC v7; Stage IVB Colon Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7; Stage IVB Rectal Cancer AJCC v7

  6. Serum uric acid as a surrogate marker of favorable response to bevacizumab treatment in patients with metastatic colon cancer.

    Science.gov (United States)

    Selcukbiricik, F; Kanbay, M; Solak, Y; Bilici, A; Kanıtez, M; Balık, E; Mandel, N M

    2016-11-01

    Bevacizumab is a monoclonal antibody which is a vascular endothelial growth factor inhibitor. It obscures vascularization of tumor tissue and damages intratumoral microcirculation. The damaged intratumoral microcirculation leads to tissue hypoxia and results in increase of uric acid level. The main aim of our study was to investigate the relationship between uric acid change and response to bevacizumab therapy. This study included a total of 158 patients with metastatic colorectal cancer who had received bevacizumab therapy. The number of male patients was 100 (63.3 %) while female patients number was 58 (37.7 %). The median age was 61 (29-83). There was relationship between increase of uric acid level of third month uric acid level and stable disease (p uric acid level (p uric acid level (p uric acid in patients with metastatic colorectal cancer who favorably responded to chemotherapy with bevacizumab. But further studies are justified to test whether monitoring uric acid levels might predict clinical outcomes of patients with metastatic colorectal cancer.

  7. Circulating plasma MiR-141 is a novel biomarker for metastatic colon cancer and predicts poor prognosis.

    Directory of Open Access Journals (Sweden)

    Hanyin Cheng

    Full Text Available BACKGROUND: Colorectal cancer (CRC remains one of the major cancer types and cancer related death worldwide. Sensitive, non-invasive biomarkers that can facilitate disease detection, staging and prediction of therapeutic outcome are highly desirable to improve survival rate and help to determine optimized treatment for CRC. The small non-coding RNAs, microRNAs (miRNAs, have recently been identified as critical regulators for various diseases including cancer and may represent a novel class of cancer biomarkers. The purpose of this study was to identify and validate circulating microRNAs in human plasma for use as such biomarkers in colon cancer. METHODOLOGY/PRINCIPAL FINDINGS: By using quantitative reverse transcription-polymerase chain reaction, we found that circulating miR-141 was significantly associated with stage IV colon cancer in a cohort of 102 plasma samples. Receiver operating characteristic (ROC analysis was used to evaluate the sensitivity and specificity of candidate plasma microRNA markers. We observed that combination of miR-141 and carcinoembryonic antigen (CEA, a widely used marker for CRC, further improved the accuracy of detection. These findings were validated in an independent cohort of 156 plasma samples collected at Tianjin, China. Furthermore, our analysis showed that high levels of plasma miR-141 predicted poor survival in both cohorts and that miR-141 was an independent prognostic factor for advanced colon cancer. CONCLUSIONS/SIGNIFICANCE: We propose that plasma miR-141 may represent a novel biomarker that complements CEA in detecting colon cancer with distant metastasis and that high levels of miR-141 in plasma were associated with poor prognosis.

  8. The tumor suppressor CDX2 opposes pro-metastatic biomechanical modifications of colon cancer cells through organization of the actin cytoskeleton.

    Science.gov (United States)

    Platet, Nadine; Hinkel, Isabelle; Richert, Ludovic; Murdamoothoo, Devadarssen; Moufok-Sadoun, Ahlam; Vanier, Marie; Lavalle, Philippe; Gaiddon, Christian; Vautier, Dominique; Freund, Jean-Noel; Gross, Isabelle

    2017-02-01

    The vast majority of cancer deaths are caused by the formation of metastases rather than the primary tumor itself. Despite this clinical importance, the molecular and cellular events that support the dissemination of cancer cells are not yet fully unraveled. We have previously shown that CDX2, a homeotic transcription factor essential for gut development, acts as a colon-specific tumor suppressor and opposes metastasis. Here, using a combination of biochemical, biophysical, and immunofluorescence techniques, we further investigated the mechanisms promoted by CDX2 that might antagonize tumor cell dissemination. We found that CDX2 expression regulates the transcription of RHO GEFs, thereby activating RHO signaling cascades that lead to reorganization of the actin cytoskeleton and enhanced adherent junctions. Accordingly, we observed by atomic force microscopy (AFM) that colon cancer cells expressing CDX2 are less deformable, a feature that has been shown to correlate with poor metastatic potential. Thus, this study illustrates how the loss of expression of a transcription factor during colon cancer progression modifies the biomechanical characteristics of tumor cells and hence facilitates invasion and metastasis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Tumor lysis syndrome in a patient with metastatic colon cancer after treatment with oxaliplatin and 5-Fu

    Directory of Open Access Journals (Sweden)

    Ruo-Han Tseng

    2016-12-01

    Full Text Available Tumor lysis syndrome in solid tumors is a rare occurrence, with a poor prognosis. We present the case of a patient of recurrent colon cancer who received chemotherapy with FOLFOX regimen (lencovorin, fluorouracil, and oxaliplatin with subsequent tumor lysis. We present a recurrent rectal cancer patient suffered from tumor lysis syndrome after salvage FOLFOX regimen. After treat with CVVH with improved conscious status. In this case report, we had review the tumor lysis in solid tumor.

  10. Using Naïve Bayesian Analysis to Determine Imaging Characteristics of KRAS Mutations in Metastatic Colon Cancer.

    Science.gov (United States)

    Pershad, Yash; Govindan, Siddharth; Hara, Amy K; Borad, Mitesh J; Bekaii-Saab, Tanios; Wallace, Alex; Albadawi, Hassan; Oklu, Rahmi

    2017-09-02

    Genotype, particularly Ras status, greatly affects prognosis and treatment of liver metastasis in colon cancer patients. This pilot aimed to apply word frequency analysis and a naive Bayes classifier on radiology reports to extract distinguishing imaging descriptors of wild-type colon cancer patients and those with v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations. In this institutional-review-board-approved study, we compiled a SNaPshot mutation analysis dataset from 457 colon adenocarcinoma patients. From this cohort of patients, we analyzed radiology reports of 299 patients (> 32,000 reports) who either were wild-type (147 patients) or had a KRAS (152 patients) mutation. Our algorithm determined word frequency within the wild-type and mutant radiology reports and used a naive Bayes classifier to determine the probability of a given word belonging to either group. The classifier determined that words with a greater than 50% chance of being in the KRAS mutation group and which had the highest absolute probability difference compared to the wild-type group included: "several", "innumerable", "confluent", and "numerous" ( p colon adenocarcinoma. Moreover, likely characteristic imaging traits of mutant tumors make probabilistic word analysis useful in identifying unique characteristics and disease course, with applications ranging from radiology and pathology reports to clinical notes.

  11. Olaparib In Metastatic Breast Cancer

    Science.gov (United States)

    2017-12-17

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

  12. Extracellular matrix mediators of metastatic cell colonization characterized using scaffold mimics of the pre-metastatic niche.

    Science.gov (United States)

    Aguado, Brian A; Caffe, Jordan R; Nanavati, Dhaval; Rao, Shreyas S; Bushnell, Grace G; Azarin, Samira M; Shea, Lonnie D

    2016-03-01

    Metastatic tumor cells colonize the pre-metastatic niche, which is a complex microenvironment consisting partially of extracellular matrix (ECM) proteins. We sought to identify and validate novel contributors to tumor cell colonization using ECM-coated poly(ε-caprolactone) (PCL) scaffolds as mimics of the pre-metastatic niche. Utilizing orthotopic breast cancer mouse models, fibronectin and collagen IV-coated scaffolds implanted in the subcutaneous space captured colonizing tumor cells, showing a greater than 2-fold increase in tumor cell accumulation at the implant site compared to uncoated scaffolds. As a strategy to identify additional ECM colonization contributors, decellularized matrix (DCM) from lungs and livers containing metastatic tumors were characterized. In vitro, metastatic cell adhesion was increased on DCM coatings from diseased organs relative to healthy DCM. Furthermore, in vivo implantations of diseased DCM-coated scaffolds had increased tumor cell colonization relative to healthy DCM coatings. Mass-spectrometry proteomics was performed on healthy and diseased DCM to identify candidates associated with colonization. Myeloperoxidase was identified as abundantly present in diseased organs and validated as a contributor to colonization using myeloperoxidase-coated scaffold implants. This work identified novel ECM proteins associated with colonization using decellularization and proteomics techniques and validated candidates using a scaffold to mimic the pre-metastatic niche. The pre-metastatic niche consists partially of ECM proteins that promote metastatic cell colonization to a target organ. We present a biomaterials-based approach to mimic this niche and identify ECM mediators of colonization. Using murine breast cancer models, we implanted microporous PCL scaffolds to recruit colonizing tumor cells in vivo. As a strategy to modulate colonization, we coated scaffolds with various ECM proteins, including decellularized lung and liver matrix from

  13. Metastatic Small Bowel Tumor from Descending Colon Cancer with Extensive Hematogenous or Lymphogenous Spread: Survey of the Japanese Literature

    Directory of Open Access Journals (Sweden)

    Yutaka Kojima

    2010-09-01

    Full Text Available We present the case of a 68-year-old female patient who was diagnosed with cancer of the descending colon in July 1994 and underwent partial resection of the colon (type 2, moderately to well differentiated adenocarcinoma, se, ly1, v1, n(–. In April 1996, she was admitted to a nearby hospital for symptoms of ileus, which improved at the hospital. However, she was referred to our hospital for melena. In blood test, Hb was 8.7 g/dl, showing anemia, and carcinoembryonic antigen level was elevated to 50.7 ng/ml. Abdominal CT and small bowel series showed only mild expansion of the small bowel, suggesting no obvious occlusion. Abdominal surgery was performed in May 1995 for repeated development of ileus symptoms and suspicion of bleeding from the small bowel. Since the findings of the abdominal surgery showed a circular tumor in the lower ileum, partial resection of the small bowel was performed. Histopathological examination showed type 3, moderately to well differentiated adnocarcinoma, se, ly2, v0, n = 1/13. The principal tumor was located within the subserosa and grew up exclusively through the muscularis propria and the submucosa, into the mucous layer. The mucosa remained slightly on the surface layer. Based on these findings, the patient was diagnosed with metastasis of descending colon cancer to the small bowel. Her prognosis was good, and neither metastasis nor redevelopment of the cancer have been confirmed to date, 11 years and 7 months since the surgery.

  14. Drosophila homologue of Diaphanous 1 (DIAPH1) controls the metastatic potential of colon cancer cells by regulating microtubule-dependent adhesion.

    Science.gov (United States)

    Lin, Yuan-Na; Bhuwania, Ridhirama; Gromova, Kira; Failla, Antonio Virgilio; Lange, Tobias; Riecken, Kristoffer; Linder, Stefan; Kneussel, Matthias; Izbicki, Jakob R; Windhorst, Sabine

    2015-07-30

    Drosophila homologue of Diaphanous 1 (DIAPH1) regulates actin polymerization and microtubule (MT) stabilization upon stimulation with lysophosphatidic acid (LPA). Recently, we showed strongly reduced lung metastasis of DIAPH1-depleted colon cancer cells but we found accumulations of DIAPH1-depleted cells in bone marrow. Here, we analyzed possible organ- or tissue-specific metastasis of DIAPH1-depleted HCT-116 cells. Our data confirmed that depletion of DIAPH1 strongly inhibited lung metastasis and revealed that, in contrast to control cells, DIAPH1-depleted cells did not form metastases in further organs. Detailed mechanistic analysis on cells that were not stimulated with LPA to activate the cytoskeleton-modulating activity of DIAPH1, revealed that even under basal conditions DIAPH1 was essential for cellular adhesion to collagen. In non-stimulated cells DIAPH1 did not control actin dynamics but, interestingly, was essential for stabilization of microtubules (MTs). Additionally, DIAPH1 controlled directed vesicle trafficking and with this, local clustering of the adhesion protein integrin-β1 at the plasma membrane. Therefore, we conclude that under non-stimulating conditions DIAPH1 controls cellular adhesion by stabilizing MTs required for local clustering of integrin-β1 at the plasma membrane. Thus, blockade of DIAPH1-tubulin interaction may be a promising approach to inhibit one of the earliest steps in the metastatic cascade of colon cancer.

  15. Colon cancer screening

    Science.gov (United States)

    Screening for colon cancer; Colonoscopy - screening; Sigmoidoscopy - screening; Virtual colonoscopy - screening; Fecal immunochemical test; Stool DNA test; sDNA test; Colorectal cancer - screening; Rectal ...

  16. CT in colon cancer

    International Nuclear Information System (INIS)

    Fujita, Nobuyuki; Hasegawa, Takashi; Kubo, Kozo; Ogawa, Hajime; Sato, Yukihiko; Tomita, Masayoshi; Hanawa, Makoto; Matsuzawa, Tohru; Nishioka, Ken

    1990-01-01

    CT pictures from 59 lesions of advanced colon cancer including rectal cancer were reviewed to evaluate a role of CT in preoperative staging diagnosis. CT findings were recorded following general rules for clinical and pathological studies on cancer of colon rectum and anus, proposed by Japanese society for cancer of colon and rectum. Tumors were detected in 90% of advanced colon cancers. Sensitivity in local extension (S factor) was 58.0%. Sensitivity in lymphonode involvement (N factor) was 50.0%. Sensitivity in final staging diagnosis, dividing colon cancer into two groups below st II and above st III, was 63.3%. Further study should be necessitated to provide useful information for preoperative staging diagnosis of colon cancer. (author)

  17. High susceptibility of metastatic cells derived from human prostate and colon cancer cells to TRAIL and sensitization of TRAIL-insensitive primary cells to TRAIL by 4,5-dimethoxy-2-nitrobenzaldehyde

    Directory of Open Access Journals (Sweden)

    Lee Jae-Won

    2011-04-01

    Full Text Available Abstract Background Tumor recurrence and metastasis develop as a result of tumors' acquisition of anti-apoptotic mechanisms and therefore, it is necessary to develop novel effective therapeutics against metastatic cancers. In this study, we showed the differential TRAIL responsiveness of human prostate adenocarcinoma PC3 and human colon carcinoma KM12 cells and their respective highly metastatic PC3-MM2 and KM12L4A sublines and investigated the mechanism underlying high susceptibility of human metastatic cancer cells to TRAIL. Results PC3-MM2 and KM12L4A cells with high level of c-Myc and DNA-PKcs were more susceptible to TRAIL than their poorly metastatic primary PC3 and KM12 cells, which was associated with down-regulation of c-FLIPL/S and Mcl-1 and up-regulation of the TRAIL receptor DR5 but not DR4 in both metastatic cells. Moreover, high susceptibility of these metastatic cells to TRAIL was resulted from TRAIL-induced potent activation of caspase-8, -9, and -3 in comparison with their primary cells, which led to cleavage and down-regulation of DNA-PKcs. Knockdown of c-Myc gene in TRAIL-treated PC3-MM2 cells prevented the increase of DR5 cell surface expression, caspase activation and DNA-PKcs cleavage and attenuated the apoptotic effects of TRAIL. Moreover, the suppression of DNA-PKcs level with siRNA in the cells induced the up-regulation of DR5 and active caspase-8, -9, and -3. We also found that 4,5-dimethoxy-2-nitrobenzaldehyde (DMNB, a specific inhibitor of DNA-PK, potentiated TRAIL-induced cytotoxicity and apoptosis in relatively TRAIL-insensitive PC3 and KM12 cells and therefore functioned as a TRAIL sensitizer. Conclusion This study showed the positive relationship between c-Myc expression in highly metastatic human prostate and colon cancer cells and susceptibility to TRAIL-induced apoptosis and therefore indicated that TRAIL might be used as an effective therapeutic modality for advanced metastatic cancers overexpressing c-Myc and

  18. CXCL12 gene silencing down-regulates metastatic potential via blockage of MAPK/PI3K/AP-1 signaling pathway in colon cancer.

    Science.gov (United States)

    Ma, J; Su, H; Yu, B; Guo, T; Gong, Z; Qi, J; Zhao, X; Du, J

    2018-01-05

    To investigate the effect of CXCL12 gene silencing on proliferation,invasion, angiogenesis and the relationship of MAPK/PI3K/AP-1 signaling pathway in colon cancer cells. RT-PCR and Western-blot were used to detect the expression of CXCL12 mRNA and protein in four colon cancer cell lines. Human colon cancer cells were transfected with CXCL12 siRNA carrying by Lipofectamine 2000. The expression of CXCL12 protein was confirmed by immunoblotting. WST-1, invasion and angiogenesis assay were used to examine the effect on proliferation, invasion and angiogenesis in colon cancer cells after CXCL12 siRNA silence, respectively. The phosphorylation of MAPK/PI3K/AP-1 protein levels was detected by Western blotting in CXCL12 siRNA suppression DLD-1 cell. CXCL12 mRNA and proteins were only expressed in DLD-1 colon cancer cell lines. CXCL12 siRNA were transfected into DLD-1 cells, the expression CXCL12 proteins was significantly inhibited (P colon cancer cell. The silencing CXCL12 gene significantly inhibits the proliferation, invasion and angiogenesis ability of some types colon carcinoma cells through down-regulation of MAPK/PI3K/AP-1 signaling pathway.

  19. Understanding your colon cancer risk

    Science.gov (United States)

    Colon cancer - prevention; Colon cancer - screening ... We do not know what causes colon cancer, but we do know some of the things that may increase the risk of getting it, such as: Age. Your risk increases ...

  20. Phase II trial of yttrium-90-DOTA-biotin pretargeted by NR-LU-10 antibody/streptavidin in patients with metastatic colon cancer

    International Nuclear Information System (INIS)

    Knox, S J.; Goris, M L.; Tempero, M.; Weiden, P L.; Gentner, L.; Breitz, H.; Adams, G. P.; Axworthy, D.; Gaffigan, S.; Bryan, K.; Fisher, Darrell R.; Colcher, D; Horak, I D.; Weiner, L M.

    1999-01-01

    A Phase II study of yttrium-90-tetra-azacyclododecanetetra-acetic acid-biotin (Y-90-DOTA-biotin) pretargeted by NR-LU-10 antibody/streptavidin (SA) was performed. The primary objectives of the study were to evaluate the efficacy and safety of this therapy in patients with metastatic colon cancer. Twenty-five patients were treated with a single dose of 110 mCi/m 2 (mean administered dose, 106.5-10.3 mCi/m 2 ) of Y-90-DOTA-biotin. There were three components of the therapy. Patients first received NR-LU-10/SA on day 1. A clearing agent (biotin-galactose-human serum albumin) was administered 48 h after the NR-LU-10/SA to remove residual circulating unbound NR-LU-10/SA. Lastly, 24 h after administration of clearing agent, patients received biotin-DOTA-labeled with 110 mCi/m 2 Y-90. All three components of the therapy were administered i.v. Both hematological and nonhematological toxicities were observed. Diarrhea was the most frequent grade 4 nonhematological toxicity (16%; with 16% grade 3 diarrhea). Hematological toxicity was less severe with 8% grade 3 and 8% grade 4 neutropenia and 8% grade 3 and 16% grade 4 thrombocytopenia. The overall response rate was 8%. Two partial responders had freedom from progression of 16 weeks. Four patients (16%) had stable disease with freedom from progression of 10-20 weeks. Despite the relatively disappointing results of this study in terms of therapeutic efficacy and toxicity, proof of principle was obtained for the pretargeting approach. In addition, valuable new information was obtained about normal tissue tolerance to low-dose-rate irradiation that will help to provide useful guidelines for future study designs

  1. 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.

  2. Control of Metastatic Colonization in Prostate Cancer: The Functional Mechanism of Metastasis Suppression by JNKK1/MKK4

    Science.gov (United States)

    2012-09-01

    19a. NAME OF RESPONSIBLE PERSON USAMRMC a. REPORT U b. ABSTRACT U c. THIS PAGE U UU 2 19b. TELEPHONE NUMBER (include area code ...prostate. Clin Cancer Res 1997;3: 249–56. 4. Cher ML, de Oliveira JG, Beaman AA, Nemeth JA, Hussain M, Wood DP, Jr. Cellular proliferation and prevalence

  3. Colon and rectal cancer

    International Nuclear Information System (INIS)

    Saldombide, L.; Cordoba, A.

    2010-01-01

    This study is about the diagnosis, therapy and monitoring of colon cancer. The techniques used are the endoscopy with biopsy in the pre and post operative colon surgery, abdominal ultrasound, chest X-ray studies of hemogram as well as liver and renal function

  4. Colon cancer - slideshow

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/presentations/100157.htm Colon cancer - Series—Normal anatomy To use the sharing features on this page, please enable JavaScript. Go to slide 1 out of 5 Go to slide 2 out of ... to slide 5 out of 5 Overview The colon, or large intestine, is a muscular tube that ...

  5. The Impact of Primary Tumor Location on Long-Term Survival in Patients Undergoing Hepatic Resection for Metastatic Colon Cancer.

    Science.gov (United States)

    Creasy, John M; Sadot, Eran; Koerkamp, Bas Groot; Chou, Joanne F; Gonen, Mithat; Kemeny, Nancy E; Saltz, Leonard B; Balachandran, Vinod P; Peter Kingham, T; DeMatteo, Ronald P; Allen, Peter J; Jarnagin, William R; D'Angelica, Michael I

    2018-02-01

    The impact of primary tumor location on overall survival (OS), recurrence-free survival (RFS), and long-term outcomes has not been well established in patients undergoing potentially curative resection of colorectal liver metastases (CRLM). A single-institution database was queried for initial resections for CRLM 1992-2004. Primary tumor location determined by chart review (right = cecum to transverse; left = splenic flexure to sigmoid). Rectal cancer (distal 16 cm), multiple primaries, and unknown location were excluded. Kaplan-Meier and Cox regression methods were used. Cure was defined as actual 10-year survival with either no recurrence or resected recurrence with at least 3 years of disease-free follow-up. A total of 907 patients were included with a median follow-up of 11 years; 578 patients (64%) had left-sided and 329 (36%) right-sided primaries. Median OS for patients with a left-sided primary was 5.2 years (95% confidence interval [CI] 4.6-6.0) versus 3.6 years (95% CI 3.2-4.2) for right-sided (p = 0.004). On multivariable analysis, the hazard ratio for right-sided tumors was 1.22 (95% CI 1.02-1.45, p = 0.028) after adjusting for common clinicopathologic factors. Median RFS was marginally different stratified by primary location (1.3 vs. 1.7 years; p = 0.065). On multivariable analysis, location of primary was not significantly associated with RFS (p = 0.105). Observed cure rates were 22% for left-sided and 20% for right-sided tumors. Among patients undergoing resection of CRLM, left-sided primary tumors were associated with improved median OS. However, long-term survival and recurrence-free survival were not significantly different stratified by primary location. Patients with left-sided primary tumors displayed a prolonged clinical course suggestive of more indolent biology.

  6. Stages of Colon Cancer

    Science.gov (United States)

    ... types of surgery : Local excision or simple polypectomy . Resection and anastomosis . This is done when the tumor is too ... stage I colon cancer usually includes the following: Resection and anastomosis . Use our clinical trial search to find NCI- ...

  7. Metastasis of Colon Cancer to the Breast

    Directory of Open Access Journals (Sweden)

    Swei H. Tsung

    2017-01-01

    Full Text Available Breast metastases from extramammary neoplasms are extremely rare, and even more so is metastasis of colon cancer to the breast. Despite its rarity, metastatic disease to the breast is an important diagnostic issue because its treatment differs greatly from that of primary cancer. Proper diagnosis of this rare event requires an accurate clinical history, proper immunohistochemical workup, and a high level of suspicion.

  8. Metastatic breast carcinoma uncovered in an otherwise unremarkable “random colon biopsy”

    Directory of Open Access Journals (Sweden)

    Mike Black

    2016-06-01

    Full Text Available Breast cancer is one of the most devastating cancers afflicting women, being a main cause of cancer related death. Approximately 50% of these patients have developed regional or distant metastases at the time of diagnosis; hence, an early diagnosis and surgery with indicated neoadjuvant therapy are crucial in eradicating this disease and improving patient survival. A significant percentage of patients, even after initial satisfactory tumor removal, still face the threat of metastatic diseases which could plague a wide spectrum of body sites such as bones, lungs, central nervous system, liver and gastrointestinal tract (mostly upper gastrointestinal locations. Colonic and anorectal involvement by metastatic breast cancer has been less frequently reported in disseminated diseases. Typically, metastatic disease presents as a mass, enteric stenosis, or obstruction. Rare cases, however, may not form an endoscopically or radiologically recognizable lesion, and thus could be overlooked. Here we report a unique case of random colon biopsies in a patient presenting with epigastric pain, whose stomach biopsy showed Helicobacter pylori-associated chronic active gastritis. No colonoscopic lesion was present; however, microscopic examination of the “random biopsy” revealed scattered single and small clusters of tumor cells involving the lamina propria of the colonic mucosa, morphologically and immunophenotypically consistent with metastatic disease from breast carcinoma. The clinical presentation and histopathology of the case were reviewed and compared with limited cases reported in the literature. We conclude that high levels of suspicion and alertness are essential to identify occult microscopic gastrointestinal metastatic breast cancer in the absence of a grossly appreciable lesion.

  9. Rectal and colon cancer: Not just a different anatomic site.

    Science.gov (United States)

    Tamas, K; Walenkamp, A M E; de Vries, E G E; van Vugt, M A T M; Beets-Tan, R G; van Etten, B; de Groot, D J A; Hospers, G A P

    2015-09-01

    Due to differences in anatomy, primary rectal and colon cancer require different staging procedures, different neo-adjuvant treatment and different surgical approaches. For example, neoadjuvant radiotherapy or chemoradiotherapy is administered solely for rectal cancer. Neoadjuvant therapy and total mesorectal excision for rectal cancer might be responsible in part for the differing effect of adjuvant systemic treatment on overall survival, which is more evident in colon cancer than in rectal cancer. Apart from anatomic divergences, rectal and colon cancer also differ in their embryological origin and metastatic patterns. Moreover, they harbor a different composition of drug targets, such as v-raf murine sarcoma viral oncogene homolog B (BRAF), which is preferentially mutated in proximal colon cancers, and the epidermal growth factor receptor (EGFR), which is prevalently amplified or overexpressed in distal colorectal cancers. Despite their differences in metastatic pattern, composition of drug targets and earlier local treatment, metastatic rectal and colon cancer are, however, commonly regarded as one entity and are treated alike. In this review, we focused on rectal cancer and its biological and clinical differences and similarities relative to colon cancer. These aspects are crucial because they influence the current staging and treatment of these cancers, and might influence the design of future trials with targeted drugs. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Vasohibin-1 suppresses colon cancer

    OpenAIRE

    Liu, Shuai; Han, Bing; Zhang, Qunyuan; Dou, Jie; Wang, Fang; Lin, Wenli; Sun, Yuping; Peng, Guangyong

    2015-01-01

    Vasohibin-1 (VASH1) is an endogenous angiogenesis inhibitor. However, the clinical relevance of VASH1 in colon cancer and its regulations on cancer angiogenesis and cancer cell biological characteristics are still unknown. Here we showed that stromal VASH1 levels were negatively correlated with tumor size, advanced clinical stage and distant metastases in colon cancer patients. Overexpression of VASH1 in colon cancer cells induced apoptosis and senescence, inhibiting cancer cell growth and co...

  11. 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

  12. Metastatic Colonic Adenocarcinoma in Breast: Report of Two Cases and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Jiten P. Kothadia

    2015-01-01

    Full Text Available Metastatic adenocarcinoma to the breast from an extramammary site is extremely rare. In the literature, the most current estimate is that extramammary metastases account for only 0.43% of all breast malignancies and that, of these extramammary sites, colon cancer metastases form a very small subset. Most commonly seen metastasis in breast is from a contralateral breast carcinoma, followed by metastasis from hematopoietic neoplasms, malignant melanoma, sarcoma, lung, prostate, and ovary and gastric neoplasms. Here we present two rare cases, in which colonic adenocarcinomas were found to metastasize to the breast. In both cases, core biopsies were obtained from the suspicious areas identified on mammogram. Histopathology revealed neoplastic proliferation of atypical glandular components within benign breast parenchyma which were morphologically consistent with metastatic adenocarcinoma. By immunohistochemical staining, it was confirmed that the neoplastic components were immunoreactive to colonic markers and nonreactive to breast markers, thus further supporting the morphologic findings. It is extremely important to make this distinction between primary breast cancer and a metastatic process, in order to provide the most effective and appropriate treatment for the patient and to avoid any harmful or unnecessary surgical procedures.

  13. Vectors for Treatment of Metastatic Breast Cancer

    National Research Council Canada - National Science Library

    Deisseroth, Albert B

    2005-01-01

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

  14. Vectors for Treatment of Metastatic Breast Cancer

    National Research Council Canada - National Science Library

    Deisseroth, Albert

    2004-01-01

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

  15. Current treatment of metastatic endometrial cancer.

    Science.gov (United States)

    Temkin, Sarah M; Fleming, Gini

    2009-01-01

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

  16. Comparative molecular analyses of left-sided colon, right-sided colon, and rectal cancers.

    Science.gov (United States)

    Salem, Mohamed E; Weinberg, Benjamin A; Xiu, Joanne; El-Deiry, Wafik S; Hwang, Jimmy J; Gatalica, Zoran; Philip, Philip A; Shields, Anthony F; Lenz, Heinz-Josef; Marshall, John L

    2017-10-17

    Tumor sidedness has emerged as an important prognostic and predictive factor in the treatment of colorectal cancer. Recent studies demonstrate that patients with advanced right-sided colon cancers have a worse prognosis than those with left-sided colon or rectal cancers, and these patient subgroups respond differently to biological therapies. Historically, management of patients with metastatic colon and rectal cancers has been similar, and colon and rectal cancer patients have been grouped together in large clinical trials. Clearly, the differences in molecular biology among right-sided colon, left-sided colon, and rectal cancers should be further studied in order to account for disparities in clinical outcomes. We profiled 10,570 colorectal tumors (of which 2,413 were identified as arising from the left colon, right colon, or rectum) using next-generation sequencing, immunohistochemistry, chromogenic in-situ hybridization, and fragment analysis (Caris Life Sciences, Phoenix, AZ). Right-sided colon cancers had higher rates of microsatellite instability, more frequent aberrant activation of the EGFR pathway including higher BRAF and PIK3CA mutation rates, and increased mutational burden compared to left-sided colon and rectal cancers. Rectal cancers had higher rates of TOPO1 expression and Her2/neu amplification compared to both left- and right-sided colon cancers. Molecular variations among right-sided colon, left-sided colon, and rectal tumors may contribute to differences in clinical behavior. The site of tumor origin (left colon, right colon, or rectum) should certainly be considered when selecting treatment regimens and stratifying patients for future clinical trials.

  17. Vasohibin-1 suppresses colon cancer

    Science.gov (United States)

    Liu, Shuai; Han, Bing; Zhang, Qunyuan; Dou, Jie; Wang, Fang; Lin, Wenli; Sun, Yuping; Peng, Guangyong

    2015-01-01

    Vasohibin-1 (VASH1) is an endogenous angiogenesis inhibitor. However, the clinical relevance of VASH1 in colon cancer and its regulations on cancer angiogenesis and cancer cell biological characteristics are still unknown. Here we showed that stromal VASH1 levels were negatively correlated with tumor size, advanced clinical stage and distant metastases in colon cancer patients. Overexpression of VASH1 in colon cancer cells induced apoptosis and senescence, inhibiting cancer cell growth and colony formation in vitro and tumor growth in vivo. In addition, knockdown of VASH1 in cancer cells promoted cell growth, adhesion and migration in vitro, and enhanced tumorigenesis and metastasis in vivo. PMID:25797264

  18. Vasohibin-1 suppresses colon cancer.

    Science.gov (United States)

    Liu, Shuai; Han, Bing; Zhang, Qunyuan; Dou, Jie; Wang, Fang; Lin, Wenli; Sun, Yuping; Peng, Guangyong

    2015-04-10

    Vasohibin-1 (VASH1) is an endogenous angiogenesis inhibitor.However, the clinical relevance of VASH1 in colon cancer and its regulations on cancer angiogenesis and cancer cell biological characteristics are still unknown. Here we showed that stromal VASH1 levels were negatively correlated with tumor size, advanced clinical stage and distant metastases in colon cancer patients. Overexpression of VASH1 in colon cancer cells induced apoptosis and senescence, inhibiting cancer cell growth and colony formation in vitro and tumor growth in vivo. In addition, knockdown of VASH1 in cancer cells promoted cell growth, adhesion and migration in vitro, and enhanced tumorigenesis and metastasis in vivo.

  19. Genome-wide in vivo screen identifies novel host regulators of metastatic colonization

    Science.gov (United States)

    van der Weyden, Louise; Arends, Mark J.; Campbell, Andrew D.; Bald, Tobias; Wardle-Jones, Hannah; Griggs, Nicola; Velasco-Herrera, Martin Del Castillo; Tüting, Thomas; Sansom, Owen J.; Karp, Natasha A.; Clare, Simon; Gleeson, Diane; Ryder, Edward; Galli, Antonella; Tuck, Elizabeth; Cambridge, Emma L.; Voet, Thierry; Macaulay, Iain C.; Wong, Kim; Spiegel, Sarah; Speak, Anneliese O.; Adams, David J.

    2017-01-01

    Metastasis is the leading cause of death for cancer patients. This multi-stage process requires tumour cells to survive in the circulation, extravasate at distant sites, then proliferate; it involves contributions from both the tumour cell and tumour microenvironment (‘host’, which includes stromal cells and the immune system1). Studies suggest the early steps of the metastatic process are relatively efficient, with the post-extravasation regulation of tumour growth (‘colonization’) being critical in determining metastatic outcome2. Here we show the results of screening 810 mutant mouse lines using an in vivo assay to identify microenvironmental regulators of metastatic colonization. We identify 23 genes that, when disrupted in mouse, modify the ability of tumour cells to establish metastatic foci, with 19 of these genes not previously demonstrated to play a role in host control of metastasis. The largest reduction in pulmonary metastasis was observed in sphingosine-1-phosphate (S1P) transporter spinster homologue 2 (Spns2)-deficient mice. We demonstrate a novel outcome of S1P-mediated regulation of lymphocyte trafficking, whereby deletion of Spns2, either globally or in a lymphatic endothelial-specific manner, creates a circulating lymphopenia and a higher percentage of effector T cells and natural killer (NK) cells present in the lung. This allows for potent tumour cell killing, and an overall decreased metastatic burden. PMID:28052056

  20. 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.

  1. CT Findings of Colonic Complications Associated with Colon Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sang Won; Shin, Hyeong Cheol; Kim, Il Young; Kim, Young Tong; Kim, Chang Jin [Cheonan Hospital, Soonchunhyang University, Cheonan (Korea, Republic of)

    2010-04-15

    A broad spectrum of colonic complications can occur in patients with colon cancer. Clinically, some of these complications can obscure the presence of underlying malignancies in the colon and these complications may require emergency surgical management. The complications of the colon that can be associated with colon cancer include obstruction, perforation, abscess formation, acute appendicitis, ischemic colitis and intussusception. Although the majority of these complications only rarely occur, familiarity with the various manifestations of colon cancer complications will facilitate making an accurate diagnosis and administering prompt management in these situations. The purpose of this pictorial essay is to review the CT appearance of the colonic complications associated with colon cancer.

  2. CT Findings of Colonic Complications Associated with Colon Cancer

    International Nuclear Information System (INIS)

    Kim, Sang Won; Shin, Hyeong Cheol; Kim, Il Young; Kim, Young Tong; Kim, Chang Jin

    2010-01-01

    A broad spectrum of colonic complications can occur in patients with colon cancer. Clinically, some of these complications can obscure the presence of underlying malignancies in the colon and these complications may require emergency surgical management. The complications of the colon that can be associated with colon cancer include obstruction, perforation, abscess formation, acute appendicitis, ischemic colitis and intussusception. Although the majority of these complications only rarely occur, familiarity with the various manifestations of colon cancer complications will facilitate making an accurate diagnosis and administering prompt management in these situations. The purpose of this pictorial essay is to review the CT appearance of the colonic complications associated with colon cancer

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

    Science.gov (United States)

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

    2014-05-15

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

  4. Human bone perivascular niche-on-a-chip for studying metastatic colonization.

    Science.gov (United States)

    Marturano-Kruik, Alessandro; Nava, Michele Maria; Yeager, Keith; Chramiec, Alan; Hao, Luke; Robinson, Samuel; Guo, Edward; Raimondi, Manuela Teresa; Vunjak-Novakovic, Gordana

    2018-02-06

    Eight out of 10 breast cancer patients die within 5 years after the primary tumor has spread to the bones. Tumor cells disseminated from the breast roam the vasculature, colonizing perivascular niches around blood capillaries. Slow flows support the niche maintenance by driving the oxygen, nutrients, and signaling factors from the blood into the interstitial tissue, while extracellular matrix, endothelial cells, and mesenchymal stem cells regulate metastatic homing. Here, we show the feasibility of developing a perfused bone perivascular niche-on-a-chip to investigate the progression and drug resistance of breast cancer cells colonizing the bone. The model is a functional human triculture with stable vascular networks within a 3D native bone matrix cultured on a microfluidic chip. Providing the niche-on-a-chip with controlled flow velocities, shear stresses, and oxygen gradients, we established a long-lasting, self-assembled vascular network without supplementation of angiogenic factors. We further show that human bone marrow-derived mesenchymal stem cells, which have undergone phenotypical transition toward perivascular cell lineages, support the formation of capillary-like structures lining the vascular lumen. Finally, breast cancer cells exposed to interstitial flow within the bone perivascular niche-on-a-chip persist in a slow-proliferative state associated with increased drug resistance. We propose that the bone perivascular niche-on-a-chip with interstitial flow promotes the formation of stable vasculature and mediates cancer cell colonization.

  5. Metastatic adenocarcinoma of the colon presenting as a monarthritis of the hip in a young patient

    Directory of Open Access Journals (Sweden)

    Cobiella Carlos

    2006-12-01

    Full Text Available Abstract Background Malignant arthritis is a rare manifestation of metastatic disease. We describe the case of a previously well 28 year old man in whom hip pain was the presenting symptom of disease. We describe the case and discuss the aetiology of colorectal cancer in young patients. We then review the literature and discuss the investigation and management of malignant joint arthritis. Case presentation We present the case of a 28 year old man who presented to the emergency department with an acute monoarthritis of the hip. He had an unremarkable past medical history and was systemically well. A diagnosis of malignant joint effusion was reached after a heightened index of clinical suspicion, magnetic resonance imaging and cytological evaluation of the synovial fluid. Computed tomography and bone scan confirmed widespread metastatic disease from a primary colonic adenocarcinoma. The patient tolerated three cycles of oxaliplatin and capecitabine but died 4 months after presentation. Conclusion The metastatic spread of cancer to the joint and the synovium is one of the rarest manifestations of malignant disease and has not been previously reported as the presenting symptom of disease. The diagnosis is a difficult one to reach and is associated with a poor prognosis. This case illustrates the importance of thorough investigation in reaching this diagnosis and entertaining the possibility in individuals who do not respond to conventional management of acute monoarthritis, even in young patients and individuals who do not display any other symptoms of disease.

  6. Colon cancer associated transcripts in human cancers.

    Science.gov (United States)

    Chen, Yincong; Xie, Haibiao; Gao, Qunjun; Zhan, Hengji; Xiao, Huizhong; Zou, Yifan; Zhang, Fuyou; Liu, Yuchen; Li, Jianfa

    2017-10-01

    Long non-coding RNAs serve as important regulators in complicated cellular activities, including cell differentiation, proliferation and death. Dysregulation of long non-coding RNAs occurs in the formation and progression of cancers. The family of colon cancer associated transcripts, long non-coding RNAs colon cancer associated transcript-1 and colon cancer associated transcript-2 are known as oncogenes involved in various cancers. Colon cancer associated transcript-1 is a novel lncRNA located in 8q24.2, and colon cancer associated transcript-2 maps to the 8q24.21 region encompassing rs6983267. Colon cancer associated transcripts have close associations with clinical characteristics, such as lymph node metastasis, high TNM stage and short overall survival. Knockdown of them can reverse the malignant phenotypes of cancer cells, including proliferation, migration, invasion and apoptosis. Moreover, they can increase the expression level of c-MYC and oncogenic microRNAs via activating a series of complex mechanisms. In brief, the family of colon cancer associated transcripts may serve as potential biomarkers or therapeutic targets for human cancers. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  7. Enzalutamide in metastatic prostate cancer before chemotherapy

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  8. Targeted photodynamic therapy as potential treatment modality for the eradication of colon cancer and colon cancer stem cells.

    Science.gov (United States)

    Hodgkinson, Natasha; Kruger, Cherie A; Abrahamse, Heidi

    2017-10-01

    Colorectal cancer is commonly treated by tumour resection, as chemotherapy and radiation have proven to be less effective, especially if the tumour has metastasized. Resistance to therapies occurs in almost all patients with colorectal cancer, especially in those with metastatic tumours. Cancer stem cells have the ability to self-renew, and their slow rate of cycling enhances resistance to treatment and increases the likelihood of tumour recurrence. Most metastatic tumours are unable to be surgically removed, thus creating a need for treatment modalities that target cancers directly and destroy cancer stem cells. Photodynamic therapy involves a photosensitizer that when exposed to a light source of a particular wavelength becomes excited and produces a form of oxygen that kills cancer cells. Photodynamic therapy is currently being investigated as a treatment modality for colorectal cancer, and new studies are exploring enhancing photodynamic therapy efficacy with the aid of drug carriers and immune conjugates. These modifications could prove effective in targeting cancer stem cells that are thought to be resistant to photodynamic therapy. In order for photodynamic therapy to be an effective treatment in colorectal cancer, it requires treatment of both primary tumours and the metastatic secondary disease that is caused by colon cancer stem cells. This review focuses on current photodynamic therapy treatments available for colorectal cancer and highlights proposed actively targeted photosynthetic drug uptake mechanisms specifically mediated towards colon cancer stem cells, as well as identify the gaps in research which need to be investigated in order to develop a combinative targeted photodynamic therapy regime that can effectively control colorectal cancer primary and metastatic tumour growth by eliminating colon cancer stem cells.

  9. Treatment Option Overview (Colon Cancer)

    Science.gov (United States)

    ... types of surgery : Local excision or simple polypectomy . Resection and anastomosis . This is done when the tumor is too ... stage I colon cancer usually includes the following: Resection and anastomosis . Use our clinical trial search to find NCI- ...

  10. General Information about Colon Cancer

    Science.gov (United States)

    ... types of surgery : Local excision or simple polypectomy . Resection and anastomosis . This is done when the tumor is too ... stage I colon cancer usually includes the following: Resection and anastomosis . Use our clinical trial search to find NCI- ...

  11. 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.

  12. Spontaneous regression of colon cancer.

    Science.gov (United States)

    Kihara, Kyoichi; Fujita, Shin; Ohshiro, Taihei; Yamamoto, Seiichiro; Sekine, Shigeki

    2015-01-01

    A case of spontaneous regression of transverse colon cancer is reported. A 64-year-old man was diagnosed as having cancer of the transverse colon at a local hospital. Initial and second colonoscopy examinations revealed a typical cancer of the transverse colon, which was diagnosed as moderately differentiated adenocarcinoma. The patient underwent right hemicolectomy 6 weeks after the initial colonoscopy. The resected specimen showed only a scar at the tumor site, and no cancerous tissue was proven histologically. The patient is alive with no evidence of recurrence 1 year after surgery. Although an antitumor immune response is the most likely explanation, the exact nature of the phenomenon was unclear. We describe this rare case and review the literature pertaining to spontaneous regression of colorectal cancer. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  14. Cetuximab in treatment of metastatic colorectal cancer

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  15. Sorafenib makes headway on metastatic thyroid cancer.

    Science.gov (United States)

    2013-07-01

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

  16. 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

  17. Surgical management of metastatic differentiated thyroid cancer

    International Nuclear Information System (INIS)

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

    1999-01-01

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

  18. A Case of Sigmoid Colon Tuberculosis Mimicking Colon Cancer

    OpenAIRE

    Yu, Seong-Min; Park, Jong-Hwan; Kim, Min-Dae; Lee, Hee-Ryong; Jung, Peel; Ryu, Tae-Hyun; Choi, Seung-Ho; Lee, Il-Seon

    2012-01-01

    Tuberculosis of the sigmoid colon is a rare disorder. An 80-year-old man visited Bongseng Memorial Hospital for medical examination. A colonoscopy was performed, and a lesion in the sigmoid colon that was suspected to be colon cancer was found. A biopsy was performed, and tuberculous enteritis with chronic granulomatous inflammation was diagnosed. Intestinal tuberculosis is most frequent in the ileocecal area, followed by the ascending colon, transverse colon, duodenum, stomach, and sigmoid c...

  19. The Economics of Colon Cancer.

    Science.gov (United States)

    Orangio, Guy R

    2018-04-01

    The economic burden of cancer on the national health expenditure is billions of dollars. The economic cost is measured on direct and indirect medical costs, which vary depending on stage at diagnosis, patient age, type of medical services, and site of service. Costs vary by region, physician behavior, and patient preferences. When analyzing the economic burden of survivors of colon cancer, we cannot forget the societal burden. Post-acute care and readmissions are major economic burdens. People with colon cancer have to be followed for their lifetime. Economic models are being studied to give cost-effective solutions to this problem. Copyright © 2017 Elsevier Inc. All rights reserved.

  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 explored. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has been demonstrated to be highly effective in treating patients with advanced breast cancer, including those with anthracycline-resistant breast cancer, a fact that has led to efforts to combine paclitaxel and anthracyclines...

  1. Preventing Second Cancers in Colon Cancer Survivors

    Science.gov (United States)

    In this phase III trial, people who have had curative surgery for colon cancer will be randomly assigned to take sulindac and a placebo, eflornithine and a placebo, both sulindac and eflornithine, or two placebo pills for 36 months.

  2. Sentinel node in colon cancer

    International Nuclear Information System (INIS)

    Andreoni, B.; Crosta, C.; Chiappa, A.; Bianchi, P. P.; Sonzogni, A.; Misitano, P.; Corbellini, C.; Veronesi, U.; Andreoni, B.; Chiappa, A.; Misitano, P.; Corbellini, C.; Senore, C.

    2009-01-01

    Treatment after 'complete' endoscopic polypectomy of a malignant polyp varies. The patient may undergo colon resection and lymphadenectomy with no evidence of disease at the final diagnosis (overtreatment?) or be offered the possibility of endoscopic surveillance only with a diagnosis of disease persistence after some time, which entails an apparent therapeutic 'delay' (undertreatment?). The choice between surgical radicalization and endoscopic follow-up after complete polypectomy of a malignant polyp is not based on scientifically-validated clinico-pathological proofs. The aim of this paper is to present the outlines of two studies: one on the choice between intensive surveillance or surgery after complete polypectomy of a malignant colorectal polyp (SEC=GISCoR) and one on the predictive value of sentinel node in staging early colorectal cancer. Should the studies prove the good predictive value of sentinel nodes in colon cancer and a satisfactory reproducibility of the technique, new management perspectives would open for patients with colon cancer. (authors)

  3. Propensity Score Analysis of Regorafenib Versus Trifluridine/Tipiracil in Patients with Metastatic Colorectal Cancer Refractory to Standard Chemotherapy (REGOTAS): A Japanese Society for Cancer of the Colon and Rectum Multicenter Observational Study.

    Science.gov (United States)

    Moriwaki, Toshikazu; Fukuoka, Shota; Taniguchi, Hiroya; Takashima, Atsuo; Kumekawa, Yusuke; Kajiwara, Takeshi; Yamazaki, Kentaro; Esaki, Taito; Makiyama, Chinatsu; Denda, Tadamichi; Satake, Hironaga; Suto, Takeshi; Sugimoto, Naotoshi; Enomoto, Masanobu; Ishikawa, Toshiaki; Kashiwada, Tomomi; Sugiyama, Masahiko; Komatsu, Yoshito; Okuyama, Hiroyuki; Baba, Eishi; Sakai, Daisuke; Watanabe, Tomoki; Tamura, Takao; Yamashita, Kimihiro; Gosho, Masahiko; Shimada, Yasuhiro

    2018-01-01

    This study compared the efficacy of regorafenib and trifluridine/tipiracil (TFTD) in patients with metastatic colorectal cancer (mCRC) who are refractory to standard chemotherapy, because despite their clinical approval, it still remains unclear which of these two drugs should be used as initial treatment. The clinical data of patients with mCRC who were treated with regorafenib or TFTD and those of drug-naive patients, between June 2014 and September 2015, were retrospectively collected from 24 institutions in Japan. Overall survival (OS) was evaluated using the Cox's proportional hazard models based on propensity score adjustment for baseline characteristics. A total of 550 patients (223 patients in the regorafenib group and 327 patients in the TFTD group) met all criteria. The median OS was 7.9 months (95% confidence interval [CI], 6.8-9.2) in the regorafenib group and 7.4 months (95% CI, 6.6-8.3) in the TFTD group. The propensity score adjusted analysis showed that OS was similar between the two groups (adjusted hazard ratio [HR], 0.96; 95% CI, 0.78-1.18). In the subgroup analysis, a significant interaction with age was observed. Regorafenib showed favorable survival in patients aged regorafenib and TFTD was observed in patients with mCRC. Although the choice of the drug by age might affect survival, a clearly predictive biomarker to distinguish the two drugs should be identified in further studies. Previous studies of patients with metastatic colorectal cancer refractory to standard chemotherapy had demonstrated that both regorafenib and trifluridine/tipiracil could result in increased overall survival compared with placebo, but there are no head-to-head trials. This large, multicenter, observational study retrospectively compared the efficacy of regorafenib and trifluridine/tipiracil in 550 patients with metastatic colorectal cancer refractory to standard chemotherapy who had access to both drugs. Although no difference in overall survival was found between

  4. Theranostics Targeting Metastatic Breast Cancer

    Science.gov (United States)

    2016-10-01

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

  5. Robotic adrenalectomy for sigmoid colon cancer oligometastasis.

    Science.gov (United States)

    Pai, Vishwas D; Bhandare, Manish; Deodhar, Kedar; Yuvaraja, Thyavihally Boregowda; Saklani, Avanish P

    2015-12-01

    Solitary adrenal metastasis from colorectal cancer is rare with reported incidence from 3.1% to 14.4% in the literature. Conventionally, adrenal metastasis is considered as indicative of widespread systemic disease and hence treated with palliative intent. Surgical resection remains controversial although a median survival of 32 months was found in the largest reported case series. It has been postulated that surgical resection should be offered when the adrenal metastasis develops more than 6 months after the treatment of the primary tumor. For the metastatic lesions and potentially malignant lesions, role of minimally invasive surgery is still considered controversial. We are presenting a case of metachronous, solitary adrenal metastasis from sigmoid colon carcinoma treated surgically with curative intent.

  6. Immunotherapy for metastatic colorectal cancer

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  7. Immunotherapy in metastatic prostate cancer

    Directory of Open Access Journals (Sweden)

    Susan F Slovin

    2016-01-01

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

  8. Radioisotopes in management of metastatic prostate cancer.

    Science.gov (United States)

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

    2016-01-01

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

  9. Pertuzumab and Cetuximab in Treating Patients With Previously Treated Locally Advanced or Metastatic Colorectal Cancer

    Science.gov (United States)

    2015-03-11

    Adenocarcinoma of the Colon; Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage III Colon Cancer; Stage III Rectal Cancer; Stage IV Colon Cancer; Stage IV Rectal Cancer

  10. Outcome of Colonic Surgery in Elderly Patients with Colon Cancer

    OpenAIRE

    Hermans, E.; van Schaik, P. M.; Prins, H. A.; Ernst, M. F.; Dautzenberg, P. J. L.; Bosscha, K.

    2010-01-01

    Introduction. Colonic cancer is one of the most commonly diagnosed malignancies and most often occurs in patients aged 65 years or older. Aim. To evaluate the outcome of colonic surgery in the elderly in our hospital and to compare five-year survival rates between the younger and elderly patients. Methods. 207 consecutive patients underwent surgery for colon cancer. Patients were separated in patients younger than 75 and older than 75 years. Results. Elderly patients presented significantly m...

  11. Metastatic Malignancy to the Colon and Rectum: A Report of 14 Cases from One Single Institute.

    Science.gov (United States)

    Lin, Chi-Chun; Lin, Chun-Chi; Chen, Wei-Shone; Lin, Tzu-Chen; Lin, Jen-Kou; Jiang, Jeng-Kai

    2017-10-31

    Metastatic malignancy occurs rarely in the colon or rectum. We presented 14 patients with colorectal metastasis (CRM). A retrospective review was conducted on a computerized colorectal tumor database at the Taipei Veterans General Hospital from January 2000 to June 2013. The incidence of CRM was 0.19% (14 in 7,524 patients). There were 6 males and 8 females with a mean age of 66.9 ± 13.6 years. Origins of the CRM included lung cancers (n = 3), prostate cancers (n = 2), and others (n = 1, respectively). Clinical presentations were not specific and colonoscopic pictures were indistinguishable from primary colorectal cancers; 5 of the 9 biopsies identified metastasis. Eight patients had extracolonic metastasis and 6 patients had CRM only. Significantly better survival was observed in the CRM-only group (p = 0.037). The mean interval from the treatment of primary tumor to the diagnosis of CRM was 30.2 ± 49.0 months. The mean survival time after CRM was 24.9 ± 30.8 months. Clinical features and colonoscopic findings of CRM were indistinguishable from primary colorectal cancer. Histopathological review of the biopsy could be helpful in identifying the primary lesion. Surgical resection with curative intent provided longer survival in CRM-only patients. © 2017 S. Karger AG, Basel.

  12. Leptin receptor (Ob-R) mRNA expression and serum leptin concentration in patients with colorectal and metastatic colorectal cancer

    International Nuclear Information System (INIS)

    Erkasap, N.; Ozkurt, M.; Erkasap, S.; Yasar, F.; Uzuner, K.; Ihtiyar, E.; Uslu, S.; Kara, M.; Bolluk, O.

    2013-01-01

    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

  13. Phase I Study of Cetuximab With RO4929097 in Metastatic Colorectal Cancer

    Science.gov (United States)

    2015-05-15

    Colon Mucinous Adenocarcinoma; Colon Signet Ring Cell Adenocarcinoma; Rectal Mucinous Adenocarcinoma; Rectal Signet Ring Cell Adenocarcinoma; Recurrent Colon Carcinoma; Recurrent Rectal Carcinoma; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

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

    African Journals Online (AJOL)

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

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

    African Journals Online (AJOL)

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

  16. [A Case of Transverse Colon Cancer Metastasized to the Spermatic Cord after Resection of Peritoneal Dissemination].

    Science.gov (United States)

    Kikuchi, Isao; Kimura, Tomoaki; Azuma, Saya; Shimbo, Tomonori; Wakabayashi, Toshiki; Ota, Sakae; Sato, Tsutomu; Itoh, Seiji; Ishida, Toshiya; Sageshima, Masato

    2017-11-01

    We report a rare case of spermatic cord metastasis from colon cancer. A man in his 50s underwent extended right hemicolectomy for transverse colon cancer followed by resection of a peritoneal recurrence. After receiving adjuvant chemotherapy for 6 months, he became aware of a right inguinal mass. A spermatic cord tumor was noted on computed tomography(CT) and FDG/PET-CT. He underwent radical orchiectomy. The resected tumor was histologically compatible with the colon cancer. Although he received additional chemotherapy, right inguinal recurrence was resected 6 months after orchiectomy. Colon cancer is the second most common origin, after gastric cancer, of metastatic spermatic tumor. As several metastatic routes have been reported, peritoneal seeding is mostly suspected in this case.

  17. Drugs Approved for Colon and Rectal Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for use in colon cancer and rectal cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  18. PET-MRI in Diagnosing Patients With Colon or Rectal Cancer

    Science.gov (United States)

    2015-11-25

    Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage IIA Colon Cancer; Stage IIA Rectal Cancer; Stage IIB Colon Cancer; Stage IIB Rectal Cancer; Stage IIC Colon Cancer; Stage IIC Rectal 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 IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

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

    National Research Council Canada - National Science Library

    Bhujwalla, Zaver

    1999-01-01

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

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

    National Research Council Canada - National Science Library

    Bhujwalla, Zaver

    1998-01-01

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

  1. SOLITARY SPLENIC METASTASIS OF COLON CANCER: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Sh. Hashemzadeh M. Safari

    2004-11-01

    Full Text Available Although splenic metastasis is fairly common in disseminated cancer, solitary splenic metastasis in the absence of diffuse dissemination is rare. We report a case of 44 year-old man who developed isolated splenic metastasis of colon cancer. The patient had undergone right sided hemicolectomy for colon cancer in 1988. In 2001, he underwent reoperation because of local recurrence of tumor in the anastomotic site. The patient was admitted to our hospital on Sep 2003 with abdominal pain. Chest X-ray was normal. Abdominal CT scan showed a large cystic lesion in the spleen. Splenectomy was performed for the patient. The spleen was enlarged, firm and irregular. Histological examination showed metastatic mucinous adenocarcinoma. Based on this case, we recommend that clinicians consider possibility of metastasis in cystic lesions of spleen, especially in patients with a history of a malignant disease.

  2. Differential Impact of Anastomotic Leak in Patients With Stage IV Colonic or Rectal Cancer

    DEFF Research Database (Denmark)

    Nordholm-Carstensen, Andreas; Rolff, Hans Christian; Krarup, Peter-Martin

    2017-01-01

    cancer (p = 0.04) but not on those with rectal cancer (p = 0.91). Anastomotic leak was followed by the decreased administration of adjuvant chemotherapy in patients with colon cancer (p = 0.007) but not in patients with rectal cancer (p = 0.47). Finally, anastomotic leak had a detrimental impact...... on metastasectomy rates after colon cancer but not on resection rates of rectal cancer. LIMITATIONS: Retrospective data on the selection criteria for primary tumor resection and metastatic tumor load were unavailable. CONCLUSIONS: The impact of anastomotic leak on patients differed between stage IV colon and rectal...... cancers. Survival and eligibility to receive chemotherapy and metastasectomy differed between patients with colon and rectal cancers. When planning for primary tumor resection, these factors should be considered....

  3. Relapsed Colon Cancer Patient Presenting With Hematuria 13 Years After Primary Tumor Resection: A Case Report

    Directory of Open Access Journals (Sweden)

    Yu-Ho Huang

    2010-04-01

    Full Text Available We report a rare case of postoperative colon cancer recurrence who presented with hematuria 13 years after resection of the primary colonic cancer. The patient was 72 years of age and underwent surgical resection of sigmoid colon cancer at another regional hospital in 1994. Since June 2007, this patient has complained of hematuria and bloody stool. On physical examination, tenderness and a hard, indurated mass was palpable in the lower mid-abdomen. Abdominal computed tomography showed a metastatic tumor at the lower midline peritoneum with invasion of the adjacent abdominal wall. Her serum carcinoembryonic antigen level was elevated to 32 ng/dL. Histopathology revealed metastatic colonic adenocarcinoma in the jejunum and abdominal wall.

  4. 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

  5. Right colon cancer: Left behind.

    Science.gov (United States)

    Gervaz, P; Usel, M; Rapiti, E; Chappuis, P; Neyroud-Kaspar, I; Bouchardy, C

    2016-09-01

    Prognosis of colon cancer (CC) has steadily improved during the past three decades. This trend, however, may vary according to proximal (right) or distal (left) tumor location. We studied if improvement in survival was greater for left than for right CC. We included all CC recorded at the Geneva population-based registry between 1980 and 2006. We compared patients, tumor and treatment characteristics between left and right CC by logistic regression and compared CC specific survival by Cox models taking into account putative confounders. We also compared changes in survival between CC location in early and late years of observation. Among the 3396 CC patients, 1334 (39%) had right-sided and 2062 (61%) left-sided tumors. In the early 1980s, 5-year specific survival was identical for right and left CCs (49% vs. 48%). During the study period, a dramatic improvement in survival was observed for patients with left-sided cancers (Hazard ratio [HR]: 0.42, 95% confidence interval [CI]: 0.29-0.62, p colon cancer patients, those with right-sided lesions have by far the worse prognosis. Change of strategic management in this subgroup is warranted. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Mesenchymal Cells in Colon Cancer.

    Science.gov (United States)

    Koliaraki, Vasiliki; Pallangyo, Charles K; Greten, Florian R; Kollias, George

    2017-04-01

    Mesenchymal cells in the intestine comprise a variety of cell types of diverse origins, functions, and molecular markers. They provide mechanical and structural support and have important functions during intestinal organogenesis, morphogenesis, and homeostasis. Recent studies of the human transcriptome have revealed their importance in the development of colorectal cancer, and studies from animal models have provided evidence for their roles in the pathogenesis of colitis-associated cancer and sporadic colorectal cancer. Mesenchymal cells in tumors, called cancer-associated fibroblasts, arise via activation of resident mesenchymal cell populations and the recruitment of bone marrow-derived mesenchymal stem cells and fibrocytes. Cancer-associated fibroblasts have a variety of activities that promote colon tumor development and progression; these include regulation of intestinal inflammation, epithelial proliferation, stem cell maintenance, angiogenesis, extracellular matrix remodeling, and metastasis. We review the intestinal mesenchymal cell-specific pathways that regulate these processes, with a focus on their roles in mediating interactions between inflammation and carcinogenesis. We also discuss how increasing our understanding of intestinal mesenchymal cell biology and function could lead to new strategies to identify and treat colitis-associated cancers. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  7. A case of leptospirosis simulating colon cancer with liver metastases.

    Science.gov (United States)

    Granito, Alessandro; Ballardini, Giorgio; Fusconi, Marco; Volta, Umberto; Muratori, Paolo; Sambri, Vittorio; Battista, Giuseppe; Bianchi, Francesco-B

    2004-08-15

    We report a case of a 61-year-old man who presented with fatigue, abdominal pain and hepatomegaly. Computed tomography (CT) of the abdomen showed hepatomegaly and multiple hepatic lesions highly suggestive of metastatic diseases. Due to the endoscopic finding of colon ulcer, colon cancer with liver metastases was suspected. Biochemically a slight increase of transaminases, alkaline phosphatase and gammaglutamyl transpeptidase were present; alpha-fetoprotein, carcinoembryogenic antigen and carbohydrate 19-9 antigen serum levels were normal. Laboratory and instrumental investigations, including colon and liver biopsies revealed no signs of malignancy. In the light of spontaneous improvement of symptoms and CT findings, his personal history was reevaluated revealing direct contact with pigs and their tissues. Diagnosis of leptospirosis was considered and confirmed by detection of an elevated titer of antibodies to leptospira. After two mo, biochemical data, CT and colonoscopy were totally normal.

  8. IL33 Promotes Colon Cancer Cell Stemness via JNK Activation and Macrophage Recruitment

    Science.gov (United States)

    Fang, Min; Li, Yongkui; Huang, Kai; Qi, Shanshan; Zhang, Jian; Zgodzinski, Witold; Majewski, Marek; Wallner, Grzegorz; Gozdz, Stanislaw; Macek, Pawel; Kowalik, Artur; Pasiarski, Marcin; Grywalska, Ewelina; Vatan, Linda; Nagarsheth, Nisha; Li, Wei; Zhao, Lili; Kryczek, Ilona; Wang, Guobin; Wang, Zheng; Zou, Weiping; Wang, Lin

    2018-01-01

    The expression and biological role of IL33 in colon cancer is poorly understood. In this study, we show that IL33 is expressed by vascular endothelial cells and tumor cells in the human colon cancer microenvironment. Administration of human IL33 and overexpression of murine IL33 enhanced human and murine colon cancer cell growth in vivo, respectively. IL33 stimulated cell sphere formation and prevented chemotherapy-induced tumor apoptosis. Mechanistically, IL33 activated core stem cell genes NANOG, NOTCH3, and OCT3/4 via the ST2 signaling pathway, and induced phosphorylation of c-Jun N terminal kinase (JNK) activation and enhanced binding of c-Jun to the promoters of the core stem cell genes. Moreover, IL33 recruited macrophages into the cancer microenvironment and stimulated them to produce prostaglandin E2, which supported colon cancer stemness and tumor growth. Clinically, tumor IL33 expression associated with poor survival in patients with metastatic colon cancer. Thus, IL33 dually targets tumor cells and macrophages and endows stem-like qualities to colon cancer cells to promote carcinogenesis. Collectively, our work reveals an immune-associated mechanism that extrinsically confers cancer cell stemness properties. Targeting the IL33 signaling pathway may offer an opportunity to treat patients with metastatic cancer. PMID:28249897

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

    Science.gov (United States)

    2015-11-01

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

  10. Carcinoembryonic antigen in multifocal colon cancer

    International Nuclear Information System (INIS)

    Vladanov, I.P.; Kuznetsova, L.F.; Anan'ev, V.S.

    1988-01-01

    The paper is concerned with analysis of CEA indices in 43 patients with multifocal colon cancer (22 with synchronous and 21 with metachronous colon cancer). The level of CEA was elevated in the group of patients with metachronous cancer in 85.7 % in the group of patients with synchronous cancer in 90.9 %, and in the entire group of colon cancer patients in 88.4 %. No correlation between the level of CEA and the presence of the second (third of more) tumor simultaneously was not revealed. CEA can be used as a test for diagnosis of recurrences and metachronous colon cancer during a follow-up of patients subjected to radical treatment for a primary colon tumor

  11. Reconstructing metastatic seeding patterns of human cancers

    Science.gov (United States)

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

    2017-01-01

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

  12. Muscarinic Receptor Signaling in Colon Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Rosenvinge, Erik C. von, E-mail: evonrose@medicine.umaryland.edu; Raufman, Jean-Pierre [University of Maryland School of Medicine, Division of Gastroenterology & Hepatology, 22 S. Greene Street, N3W62, Baltimore, MD 21201 (United States); Department of Veterans Affairs, VA Maryland Health Care System, 10 North Greene Street, Baltimore, MD 21201 (United States)

    2011-03-02

    According to the adenoma-carcinoma sequence, colon cancer results from accumulating somatic gene mutations; environmental growth factors accelerate and augment this process. For example, diets rich in meat and fat increase fecal bile acids and colon cancer risk. In rodent cancer models, increased fecal bile acids promote colon dysplasia. Conversely, in rodents and in persons with inflammatory bowel disease, low-dose ursodeoxycholic acid treatment alters fecal bile acid composition and attenuates colon neoplasia. In the course of elucidating the mechanism underlying these actions, we discovered that bile acids interact functionally with intestinal muscarinic receptors. The present communication reviews muscarinic receptor expression in normal and neoplastic colon epithelium, the role of autocrine signaling following synthesis and release of acetylcholine from colon cancer cells, post-muscarinic receptor signaling including the role of transactivation of epidermal growth factor receptors and activation of the ERK and PI3K/AKT signaling pathways, the structural biology and metabolism of bile acids and evidence for functional interaction of bile acids with muscarinic receptors on human colon cancer cells. In murine colon cancer models, deficiency of subtype 3 muscarinic receptors attenuates intestinal neoplasia; a proof-of-concept supporting muscarinic receptor signaling as a therapeutic target for colon cancer.

  13. Muscarinic Receptor Signaling in Colon Cancer

    International Nuclear Information System (INIS)

    Rosenvinge, Erik C. von; Raufman, Jean-Pierre

    2011-01-01

    According to the adenoma-carcinoma sequence, colon cancer results from accumulating somatic gene mutations; environmental growth factors accelerate and augment this process. For example, diets rich in meat and fat increase fecal bile acids and colon cancer risk. In rodent cancer models, increased fecal bile acids promote colon dysplasia. Conversely, in rodents and in persons with inflammatory bowel disease, low-dose ursodeoxycholic acid treatment alters fecal bile acid composition and attenuates colon neoplasia. In the course of elucidating the mechanism underlying these actions, we discovered that bile acids interact functionally with intestinal muscarinic receptors. The present communication reviews muscarinic receptor expression in normal and neoplastic colon epithelium, the role of autocrine signaling following synthesis and release of acetylcholine from colon cancer cells, post-muscarinic receptor signaling including the role of transactivation of epidermal growth factor receptors and activation of the ERK and PI3K/AKT signaling pathways, the structural biology and metabolism of bile acids and evidence for functional interaction of bile acids with muscarinic receptors on human colon cancer cells. In murine colon cancer models, deficiency of subtype 3 muscarinic receptors attenuates intestinal neoplasia; a proof-of-concept supporting muscarinic receptor signaling as a therapeutic target for colon cancer

  14. Muscarinic Receptor Signaling in Colon Cancer

    Directory of Open Access Journals (Sweden)

    Jean-Pierre Raufman

    2011-03-01

    Full Text Available According to the adenoma-carcinoma sequence, colon cancer results from accumulating somatic gene mutations; environmental growth factors accelerate and augment this process. For example, diets rich in meat and fat increase fecal bile acids and colon cancer risk. In rodent cancer models, increased fecal bile acids promote colon dysplasia. Conversely, in rodents and in persons with inflammatory bowel disease, low-dose ursodeoxycholic acid treatment alters fecal bile acid composition and attenuates colon neoplasia. In the course of elucidating the mechanism underlying these actions, we discovered that bile acids interact functionally with intestinal muscarinic receptors. The present communication reviews muscarinic receptor expression in normal and neoplastic colon epithelium, the role of autocrine signaling following synthesis and release of acetylcholine from colon cancer cells, post-muscarinic receptor signaling including the role of transactivation of epidermal growth factor receptors and activation of the ERK and PI3K/AKT signaling pathways, the structural biology and metabolism of bile acids and evidence for functional interaction of bile acids with muscarinic receptors on human colon cancer cells. In murine colon cancer models, deficiency of subtype 3 muscarinic receptors attenuates intestinal neoplasia; a proof-of-concept supporting muscarinic receptor signaling as a therapeutic target for colon cancer.

  15. Peculiarities of radiodiagnosis of minor colon cancer

    International Nuclear Information System (INIS)

    Mushnikova, V.N.; Arablinskij, V.M.; Strekalovskij, V.P.; Markova, E.V.

    1985-01-01

    Basing on an analysis of the results of a multimodality study of 40 patients with minor (under 3 cm) colonic cancer the authors described in detail a method of its detection and classified its X-ray symptoms with relation to the tumor type and the degree of colon wall invasion. They showed the difficulty of radiodiagnosis of minor colonic cancer and its possibility in combination with endoscopic and morphological studies. For a better detection of the X-ray signs of minor colonic cancer one should successively use a number of methods including a polypositional study, pharmacological tests, spot roentgenography of the suspect parts of the colon using tight and semitight filling with barium meal and double contrast examination. The X-ray appearance of colonic cancer does not depend on its size: the smaller tumor size the less noticeable X-ray signs not only of malignancy but also of the tumor itself

  16. Colon Cancer Risk Assessment - Gauss Program

    Science.gov (United States)

    An executable file (in GAUSS) that projects absolute colon cancer risk (with confidence intervals) according to NCI’s Colorectal Cancer Risk Assessment Tool (CCRAT) algorithm. GAUSS is not needed to run the program.

  17. Outcome of colonic surgery in elderly patients with colon cancer.

    Science.gov (United States)

    Hermans, E; van Schaik, P M; Prins, H A; Ernst, M F; Dautzenberg, P J L; Bosscha, K

    2010-01-01

    Introduction. Colonic cancer is one of the most commonly diagnosed malignancies and most often occurs in patients aged 65 years or older. Aim. To evaluate the outcome of colonic surgery in the elderly in our hospital and to compare five-year survival rates between the younger and elderly patients. Methods. 207 consecutive patients underwent surgery for colon cancer. Patients were separated in patients younger than 75 and older than 75 years. Results. Elderly patients presented significantly more (P younger group was 62% compared with 36% in the elderly (P younger patients compared with 32% in the elderly (P < .05). Conclusion. Curative resection of colonic carcinoma in the elderly is well tolerated and age alone should not be an indication for less aggressive therapy. However, the type and number of co-morbidities influence post-operative mortality and morbidity.

  18. Role of neutral ceramidase in colon cancer

    Science.gov (United States)

    García-Barros, Mónica; Coant, Nicolas; Kawamori, Toshihiko; Wada, Masayuki; Snider, Ashley J.; Truman, Jean-Philip; Wu, Bill X.; Furuya, Hideki; Clarke, Christopher J.; Bialkowska, Agnieszka B.; Ghaleb, Amr; Yang, Vincent W.; Obeid, Lina M.; Hannun, Yusuf A.

    2016-01-01

    Alterations in sphingolipid metabolism, especially ceramide and sphingosine 1-phosphate, have been linked to colon cancer, suggesting that enzymes of sphingolipid metabolism may emerge as novel regulators and targets in colon cancer. Neutral ceramidase (nCDase), a key enzyme in sphingolipid metabolism that hydrolyzes ceramide into sphingosine, is highly expressed in the intestine; however, its role in colon cancer has not been defined. Here we show that molecular and pharmacological inhibition of nCDase in colon cancer cells increases ceramide, and this is accompanied by decreased cell survival and increased apoptosis and autophagy, with minimal effects on noncancerous cells. Inhibition of nCDase resulted in loss of β-catenin and inhibition of ERK, components of pathways relevant for colon cancer development. Furthermore, inhibition of nCDase in a xenograft model delayed tumor growth and increased ceramide while decreasing proliferation. It is noteworthy that mice lacking nCDase treated with azoxymethane were protected from tumor formation. Taken together, these studies show that nCDase is pivotal for regulating initiation and development of colon cancer, and these data suggest that this enzyme is a suitable and novel target for colon cancer therapy.—García-Barros, M., Coant, N., Kawamori, T., Wada, M., Snider, A. J., Truman, J.-P., Wu, B. X., Furuya, H., Clarke, C. J., Bialkowska, A. B., Ghaleb, A., Yang, V. W., Obeid, L. M., Hannun, Y. A. Role of neutral ceramidase in colon cancer. PMID:27609772

  19. Role of neutral ceramidase in colon cancer.

    Science.gov (United States)

    García-Barros, Mónica; Coant, Nicolas; Kawamori, Toshihiko; Wada, Masayuki; Snider, Ashley J; Truman, Jean-Philip; Wu, Bill X; Furuya, Hideki; Clarke, Christopher J; Bialkowska, Agnieszka B; Ghaleb, Amr; Yang, Vincent W; Obeid, Lina M; Hannun, Yusuf A

    2016-12-01

    Alterations in sphingolipid metabolism, especially ceramide and sphingosine 1-phosphate, have been linked to colon cancer, suggesting that enzymes of sphingolipid metabolism may emerge as novel regulators and targets in colon cancer. Neutral ceramidase (nCDase), a key enzyme in sphingolipid metabolism that hydrolyzes ceramide into sphingosine, is highly expressed in the intestine; however, its role in colon cancer has not been defined. Here we show that molecular and pharmacological inhibition of nCDase in colon cancer cells increases ceramide, and this is accompanied by decreased cell survival and increased apoptosis and autophagy, with minimal effects on noncancerous cells. Inhibition of nCDase resulted in loss of β-catenin and inhibition of ERK, components of pathways relevant for colon cancer development. Furthermore, inhibition of nCDase in a xenograft model delayed tumor growth and increased ceramide while decreasing proliferation. It is noteworthy that mice lacking nCDase treated with azoxymethane were protected from tumor formation. Taken together, these studies show that nCDase is pivotal for regulating initiation and development of colon cancer, and these data suggest that this enzyme is a suitable and novel target for colon cancer therapy.-García-Barros, M., Coant, N., Kawamori, T., Wada, M., Snider, A. J., Truman, J.-P., Wu, B. X., Furuya, H., Clarke, C. J., Bialkowska, A. B., Ghaleb, A., Yang, V. W., Obeid, L. M., Hannun, Y. A. Role of neutral ceramidase in colon cancer. © FASEB.

  20. Colon and rectal cancer survival by tumor location and microsatellite instability: the Colon Cancer Family Registry.

    Science.gov (United States)

    Phipps, Amanda I; Lindor, Noralane M; Jenkins, Mark A; Baron, John A; Win, Aung Ko; Gallinger, Steven; Gryfe, Robert; Newcomb, Polly A

    2013-08-01

    Cancers in the proximal colon, distal colon, and rectum are frequently studied together; however, there are biological differences in cancers across these sites, particularly in the prevalence of microsatellite instability. We assessed the differences in survival by colon or rectal cancer site, considering the contribution of microsatellite instability to such differences. This is a population-based prospective cohort study for cancer survival. This study was conducted within the Colon Cancer Family Registry, an international consortium. Participants were identified from population-based cancer registries in the United States, Canada, and Australia. Information on tumor site, microsatellite instability, and survival after diagnosis was available for 3284 men and women diagnosed with incident invasive colon or rectal cancer between 1997 and 2002, with ages at diagnosis ranging from 18 to 74. Cox regression was used to calculate hazard ratios for the association between all-cause mortality and tumor location, overall and by microsatellite instability status. Distal colon (HR, 0.59; 95% CI, 0.49-0.71) and rectal cancers (HR, 0.68; 95% CI, 0.57-0.81) were associated with lower mortality than proximal colon cancer overall. Compared specifically with patients with proximal colon cancer exhibiting no/low microsatellite instability, patients with distal colon and rectal cancers experienced lower mortality, regardless of microsatellite instability status; patients with proximal colon cancer exhibiting high microsatellite instability had the lowest mortality. Study limitations include the absence of stage at diagnosis and cause-of-death information for all but a subset of study participants. Some patient groups defined jointly by tumor site and microsatellite instability status are subject to small numbers. Proximal colon cancer survival differs from survival for distal colon and rectal cancer in a manner apparently dependent on microsatellite instability status. These

  1. TNFα cooperates with IFN-γ to repress Bcl-xL expression to sensitize metastatic colon carcinoma cells to TRAIL-mediated apoptosis.

    Directory of Open Access Journals (Sweden)

    Feiyan Liu

    Full Text Available BACKGROUND: TNF-related apoptosis-inducing ligand (TRAIL is an immune effector molecule that functions as a selective anti-tumor agent. However, tumor cells, especially metastatic tumor cells often exhibit a TRAIL-resistant phenotype, which is currently a major impediment in TRAIL therapy. The aim of this study is to investigate the synergistic effect of TNFα and IFN-γ in sensitizing metastatic colon carcinoma cells to TRAIL-mediated apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: The efficacy and underlying molecular mechanism of cooperation between TNFα and IFN-γ in sensitizing metastatic colon carcinoma cells to TRAIL-mediated apoptosis were examined. The functional significance of TNFα- and IFN-γ-producing T lymphocyte immunotherapy in combination with TRAIL therapy in suppression of colon carcinoma metastasis was determined in an experimental metastasis mouse model. We observed that TNFα or IFN-γ alone exhibits minimal sensitization effects, but effectively sensitized metastatic colon carcinoma cells to TRAIL-induced apoptosis when used in combination. TNFα and IFN-γ cooperate to repress Bcl-xL expression, whereas TNFα represses Survivin expression in the metastatic colon carcinoma cells. Silencing Bcl-xL expression significantly increased the metastatic colon carcinoma cell sensitivity to TRAIL-induced apoptosis. Conversely, overexpression of Bcl-xL significantly decreased the tumor cell sensitivity to TRAIL-induced apoptosis. Furthermore, TNFα and IFN-γ also synergistically enhanced TRAIL-induced caspase-8 activation. TNFα and IFN-γ was up-regulated in activated primary and tumor-specific T cells. TRAIL was expressed in tumor-infiltrating immune cells in vivo, and in tumor-specific cytotoxic T lymphocytes (CTL ex vivo. Consequently, TRAIL therapy in combination with TNFα/IFN-γ-producing CTL adoptive transfer immunotherapy effectively suppressed colon carcinoma metastasis in vivo. CONCLUSIONS/SIGNIFICANCE: TNFα and IFN

  2. Enzalutamide Improves Survival in Patients with Metastatic Prostate Cancer

    Science.gov (United States)

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

  3. Cytoreductive surgery for men with metastatic prostate cancer

    Directory of Open Access Journals (Sweden)

    Nikolas Katelaris

    2016-09-01

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

  4. miR-155, identified as anti-metastatic by global miRNA profiling of a metastasis model, inhibits cancer cell extravasation and colonization in vivo and causes significant signaling alterations

    DEFF Research Database (Denmark)

    Gravgaard, Karina Hedelund; Terp, Mikkel G; Lund, Rikke R

    2015-01-01

    To gain insight into miRNA regulation in metastasis formation, we used a metastasis cell line model that allows investigation of extravasation and colonization of circulating cancer cells to lungs in mice. Using global miRNA profiling, 28 miRNAs were found to exhibit significantly altered...... in lungs when injected intravenously in immunodeficient mice. Our experiments addressing the underlying mechanism of the altered tumor burden revealed that miR-155-overexpressing CL16 cells were less invasive than CL16 control cells in vitro, while miR-155 overexpression had no effect on cancer cell...... proliferation or apoptosis in established lung tumors. To identify proteins regulated by miR-155 and thus delineate its function in our cell model, we compared the proteome of xenograft tumors derived from miR-155-overexpressing CL16 cells and CL16 control cells using mass spectrometry-based proteomics. >4...

  5. 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

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

    African Journals Online (AJOL)

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

  7. Targeting Siah2 as Novel Therapy for Metastatic Prostate Cancer

    Science.gov (United States)

    2015-10-01

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

  8. Small invasive colon cancer with systemic metastasis: A case report

    Directory of Open Access Journals (Sweden)

    Sakamoto Taku

    2011-05-01

    Full Text Available ABSTRACT Background Recently, especially in Japan, several researchers have suggested that colorectal cancer can develop not only through an adenoma-carcinoma sequence but also from normal mucosa via a de novo pathway, and that these de novo cancers have more aggressive malignant potential. We report a case of aggressive colon cancer resulting in systemic metastasis despite small tumour size. Case Presentation A 35-year-old woman presented at the referring hospital with swelling of the left cervical lymph node. Biopsy of the lymph node revealed metastatic adenocarcinoma; however, CT scan and mammography were unable to identify the site of the primary lesion. She was diagnosed with unknown primary cancer and referred to our hospital for further examination. Immunohistochemical reevaluation showed the cervical lymph node biopsy specimen to be positive for CDX2 and CK20 and negative for CK7 expression, leading us to suspect the presence of a primary colorectal cancer. We performed a total colonoscopy, and detected a small protruding lesion in the transverse colon. The tumour was only 12 mm in diameter, with a central depressed component and a severely thickened stalk, which suggested direct cancer invasion of the deep submucosa. We concluded that this lesion was the site of origin of the metastasis despite the small tumour size, and performed diagnostic endoscopic mucosal resection. The lesion was found to have an intramucosal cancer component, demonstrating that this lesion represented primary colon cancer. The patient was referred to the gastrointestinal oncology division for systemic chemotherapy. Conclusions In this case, immunohistochemical findings strongly suggested the existence of a colorectal cancer. The non-polypoid gross appearance of the tumour suggested that it can originate de novo , thus providing a valuable case in support of the aggressive malignant potential of a de novo colorectal cancer pathway.

  9. Nutrients and Risk of Colon Cancer

    International Nuclear Information System (INIS)

    Hu, Jinfu; La Vecchia, Carlo; Negri, Eva; Mery, Les

    2010-01-01

    Dietary fats are thought to be important in the etiology of colon cancer. However, the evidence linking them is inconclusive. Studies on dietary protein, cholesterol and carbohydrate and the risk of colon cancer are also inconsistent. This study examined the association between dietary intake of protein, fats, cholesterol and carbohydrates, and the risk of colon cancer. Mailed questionnaires were completed by 1731 individuals with histologically confirmed cases of colon cancer and 3097 population controls between 1994 and 1997 in seven Canadian provinces. Measurements included socio-economic status, lifestyle habits and diet. A 69-item food frequency questionnaire was used to provide data on eating habits from two years before the study. Odds ratios (OR) and 95% confidence intervals (CI) were computed using unconditional logistic regression. The nutrients were categorized by quartiles based on the distributions among the controls. Intake of polyunsaturated fat, trans-fat and cholesterol were significantly associated with the risk of colon cancer; the ORs for the highest quartiles were 1.36 (95% CI, 1.02–1.80), 1.37 (95% CI, 1.10–1.71) and 1.42 (95% CI, 1.10–1.84), respectively. The association was stronger with proximal colon cancer (PCC). An increased risk was also observed with increasing intake of sucrose for both proximal and distal colon cancers; the ORs for the highest quartiles were 1.67 (95% CI, 1.22–2.29) for PCC and 1.58 (95% CI, 1.18–2.10) for distal colon cancer (DCC). An elevated risk of PCC was also found with increased lactose intake. Our findings provide evidence that a diet low in fat and sucrose could reduce the risk of various colon cancers

  10. 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.

  11. A study of gene expression markers for predictive significance for bevacizumab benefit in patients with metastatic colon cancer: a translational research study of the Hellenic Cooperative Oncology Group (HeCOG)

    International Nuclear Information System (INIS)

    Pentheroudakis, George; Samantas, Epaminontas; Papakostas, Pavlos; Bafaloukos, Dimitrios; Razis, Evangelia; Christodoulou, Christos; Varthalitis, Ioannis; Pavlidis, Nicholas; Fountzilas, George; Kotoula, Vassiliki; Fountzilas, Elena; Kouvatseas, George; Basdanis, George; Xanthakis, Ioannis; Makatsoris, Thomas; Charalambous, Elpida; Papamichael, Demetris

    2014-01-01

    Bevacizumab, an antibody neutralizing Vascular Endothelial Growth Factor (VEGF), is licensed for the management of patients with advanced colon cancer. However, tumor biomarkers identifying the molecular tumor subsets most amenable to angiogenesis modulation are lacking. We profiled expession of 24526 genes by means of whole genome 24 K DASL (c-DNA-mediated, Annealing, Selection and Ligation) arrays, (Illumina, CA) in 16 bevacizumab-treated patients with advanced colon cancer (Test set). Genes with correlation to 8-month Progression-free status were studied by means of qPCR in two independent colon cancer cohorts: 49 patients treated with bevacizumab + chemotherapy (Bevacizumab qPCR set) and 72 patients treated with chemotherapy only (Control qPCR set). Endpoints were best tumor response before metastasectomy (ORR) and progression-free survival (PFS). Five genes were significantly correlated to 8-month progression-free status in the Test set: overexpression of KLF12 and downregulation of AGR2, ALDH6A1, MCM5, TFF2. In the two independent datasets, irinotecan- or oxaliplatin-based chemotherapy was administered as first-line treatment and metastasectomies were subsequently applied in 8-14% of patients. No prognostically significant gene classifier encompassing all five genes could be validated in the Bevacizumab or Control qPCR sets. The complex gene expression profile of all-low tumor (ALDH6A1 + TFF2 + MCM5) was strongly associated with ORR in the Bevacizumab qPCR set (ORR 85.7%, p = 0.007), but not in the Control set (ORR 36.4%, p = 0.747). The Odds Ratio for response for the all-low tumor (ALDH6A1 + TFF2 + MCM5) profile versus any other ALDH6A1 + TFF2 + MCM5 profile was 15 (p = 0.018) in the Bevacizumab qPCR set but only 0.72 (p = 0.63) in the Control set. The tumor expression profile of (KLF12-high + TFF2-low) was significantly associated with PFS only in the Bevacizumab qPCR set: bevacizumab-treated patients with (KLF12-high + TFF2-low) tumors had superior PFS

  12. Treatment Options (by Stage) for Colon Cancer

    Science.gov (United States)

    ... types of surgery : Local excision or simple polypectomy . Resection and anastomosis . This is done when the tumor is too ... stage I colon cancer usually includes the following: Resection and anastomosis . Use our clinical trial search to find NCI- ...

  13. Redefining Adjuvant Therapy for Colon Cancer

    Science.gov (United States)

    In this trial, patients with resected stage III colon cancer are being randomly assigned to receive FOLFOX chemotherapy for either 3 or 6 months and to take either a pill called celecoxib or a matching placebo pill for 3 years.

  14. Colon Cancer After Acute Diverticulitis Treatment

    OpenAIRE

    Oh, Kwang Hoon; Han, Koon Hee; Kim, Eun Jung; Lee, Je Hoon; Choi, Kyu Un; Han, Myung Sik; Ahn, Jae Hong; Cheon, Gab Jin

    2013-01-01

    Diverticulitis is the most common clinical complication of diverticular disease, affecting 10-25% of the patients with diverticula. The prevalences of diverticulitis and colon cancer tend to increase with age and are higher in industrialized countries. Consequently, diverticulitis and colon cancer have been reported to have similar epidemiological characteristics. However, the relationship between these diseases remains controversial, as is the performance of routine colonoscopy after an epis...

  15. 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

  16. Curative resection of transverse colon cancer via minilaparotomy.

    Science.gov (United States)

    Ishida, Hideyuki; Ishiguro, Tohru; Ishibashi, Keiichiro; Ohsawa, Tomonori; Okada, Norimichi; Kumamoto, Kensuke; Haga, Norihiro

    2011-01-01

    Minilaparotomy has been reported to be a minimally invasive alternative to laparoscopically assisted surgery. We retrospectively evaluated the usefulness of minilaparotomy for the resection of transverse colon cancer, which has generally been considered difficult to resect laparoscopically. Patients for whom curative resection was attempted for transverse colon cancer (n = 21) or sigmoid colon cancer (n = 81) via minilaparotomy (skin incision, transverse colon cancer as well as those with sigmoid colon cancer.

  17. Multifaceted Interpretation of Colon Cancer Stem Cells.

    Science.gov (United States)

    Hatano, Yuichiro; Fukuda, Shinya; Hisamatsu, Kenji; Hirata, Akihiro; Hara, Akira; Tomita, Hiroyuki

    2017-07-05

    Colon cancer is one of the leading causes of cancer-related deaths worldwide, despite recent advances in clinical oncology. Accumulating evidence sheds light on the existence of cancer stem cells and their role in conferring therapeutic resistance. Cancer stem cells are a minor fraction of cancer cells, which enable tumor heterogeneity and initiate tumor formation. In addition, these cells are resistant to various cytotoxic factors. Therefore, elimination of cancer stem cells is difficult but essential to cure the malignant foci completely. Herein, we review the recent evidence for intestinal stem cells and colon cancer stem cells, methods to detect the tumor-initiating cells, and clinical significance of cancer stem cell markers. We also describe the emerging problems of cancer stem cell theory, including bidirectional conversion and intertumoral heterogeneity of stem cell phenotype.

  18. Targeting Siah2 as Novel Therapy for Metastatic Prostate Cancer

    Science.gov (United States)

    2017-12-01

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

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

    Science.gov (United States)

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

    2016-12-01

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

  20. 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.

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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

  2. Colorectal (Colon) Cancer: What Are the Risk Factors?

    Science.gov (United States)

    ... The CDC Cancel Submit Search The CDC Colorectal (Colon) Cancer Note: Javascript is disabled or is not supported ... Risk Assessment Tool (National Cancer Institute) Learning About Colon Cancer Stay Informed Language: English Español (Spanish) File Formats ...

  3. Melanosis coli in patients with colon cancer

    Directory of Open Access Journals (Sweden)

    Dorota Biernacka-Wawrzonek

    2016-12-01

    Full Text Available Intoduction: Melanosis coli is a benign lesion affecting the mucosa of the large intestine. There is a relationship between the presence of melanosis and anthraquinone laxative use. Melanosis coli is also observed in patients with colon cancer, but there is doubt whether these two conditions are related. Aim : To analyze the correlation between melanosis and colon cancer. Material and methods: We analyzed retrospectively 436 patients undergoing colon cancer surgery. There were 246 women and 190 men. Patients were divided into three age groups: under 50 years, between 51 and 65 years, and over 66 years. We analyzed sections of the cancer and intestinal mucosa from the tumor’s proximal (2–5 cm and distal (8–10 cm zone. Results : Melanosis coli was present in 52 patients, which represents 11.9% of patients with colon cancer. More often it was present in women. The most common location of melanosis and colon cancer was the terminal part of the large intestine. In patients below 50 years of age in both sexes melanosis coli did not occur. In men, melanosis was more common in the age group over 66 years. Intensity of pigmentation was higher in the tumor’s distal zone. Conclusions : The incidence of melanosis coli increases with age, similar to that of colon cancer. Melanosis was not present inside tumors, in almost half of the cases it was not present in the proximal zone, and the degree of pigmentation increased in distal zone. The cause-effect relationship between melanosis coli and colon cancer remains uncertain.

  4. Revaluation on detection of metastatic cancer of the colorectum with barium enema. Comparison with computed tomography and colonoscopy

    International Nuclear Information System (INIS)

    Watari, Jiro; Mizukami, Yusuke; Tanabe, Hirotaka

    1996-01-01

    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)

  5. Predictive utility of cyclo-oxygenase-2 expression by colon and rectal cancer.

    Science.gov (United States)

    Lobo Prabhu, Kristel C; Vu, Lan; Chan, Simon K; Phang, Terry; Gown, Allen; Jones, Steven J; Wiseman, Sam M

    2014-05-01

    Cyclo-oxygenase-2 (COX-2), an inducible enzyme expressed in areas of inflammation, is a target of interest for colorectal cancer therapy. Currently, the predictive significance of COX-2 in colorectal cancer remains unclear. Tissue microarrays were constructed using 118 colon cancer and 85 rectal cancer specimens; 44 synchronous metastatic colon cancer and 22 rectal cancer lymph nodes were also evaluated. COX-2 expression was assessed by immunohistochemistry. Univariate analysis was used to determine the predictive significance of clinicopathologic variables. Overall survival, disease-specific survival, and disease-free survival were the main outcomes examined. COX-2 was found to be expressed in 93% of colon cancers and 87% of rectal cancers. Decreased COX-2 expression was related to decreased disease-specific survival (P = .016) and decreased disease-free survival (P = .019) in the rectal cancer cohort but not in the colon cancer cohort. COX-2 expression has predictive utility for management of rectal but not colon cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Maric G

    2013-07-01

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

  7. Fetal microchimerism in breast and colon cancer

    DEFF Research Database (Denmark)

    Kamper-Jørgensen, M; Biggar, R J; Stamper, Casey L

    2011-01-01

    1574 Background: Cells acquired by a woman from her baby that durably persist in her blood and tissues is known as fetal microchimerism (FMc). In women with breast cancer, frequency and quantity of FMc in blood and breast tissue is reduced compared to healthy women. Whether the absence of fetal...... microchimerism predicts risk for developing breast cancer is unknown. FMc was evaluated in buffy coat cells from presumed healthy women who later developed breast cancer or colon cancer, a cancer in which prior pregnancy appears protective but has different associations with endocrine risk factors. METHODS....... DNA from repository buffy coat specimens was tested for male FMc with quantitative PCR targeting the DYS14gene on the Y chromosome. For this analysis, 89 women who developed breast cancer and 67 women who developed colon cancer were evaluable for FMc. Results were compared to 272 women who remained...

  8. Fetal microchimerism in breast and colon cancer

    DEFF Research Database (Denmark)

    Kamper-Jørgensen, M; Biggar, R J; Stamper, Casey L

    2011-01-01

    microchimerism predicts risk for developing breast cancer is unknown. FMc was evaluated in buffy coat cells from presumed healthy women who later developed breast cancer or colon cancer, a cancer in which prior pregnancy appears protective but has different associations with endocrine risk factors. METHODS......1574 Background: Cells acquired by a woman from her baby that durably persist in her blood and tissues is known as fetal microchimerism (FMc). In women with breast cancer, frequency and quantity of FMc in blood and breast tissue is reduced compared to healthy women. Whether the absence of fetal....... DNA from repository buffy coat specimens was tested for male FMc with quantitative PCR targeting the DYS14gene on the Y chromosome. For this analysis, 89 women who developed breast cancer and 67 women who developed colon cancer were evaluable for FMc. Results were compared to 272 women who remained...

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

    Science.gov (United States)

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

    2015-02-01

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

  10. Use of capecitabine in management of early colon cancer

    Directory of Open Access Journals (Sweden)

    Cassidy J

    2011-08-01

    Full Text Available H Hameed, J CassidyBeatson West of Scotland Cancer Centre, Glasgow, Scotland, UKAbstract: Capecitabine (Xeloda®, Roche, Basel, Switzerland is a pro-drug of 5-fluorouracil (5-FU, and it is converted to 5-FU in the cancer cell by enzymatic degradation. The role of capecitabine in colorectal cancer has evolved in the last 15 years. In early trials in the metastatic setting, capecitabine has shown superior response rates compared with those achieved with 5-FU (Mayo Clinic regimen (26% vs 17%, with equivalent progression-free survival and overall survival. In the adjuvant setting, the Xeloda in Adjuvant Colon Cancer Therapy (X-ACT trial demonstrated that capecitabine as a single agent led to improvement in relapse-free survival (hazard ratio: 0.86, 95% confidence interval: 0.74–0.99, P = 0.04 and was associated with significantly fewer adverse events than 5-FU plus leucovorin (LV, folinic acid. On the basis of the X-ACT trial, capecitabine was approved by the United States Food and Drug Administration, the National Institute for Clinical Excellence, and the Scottish Medicines Consortium as monotherapy for the adjuvant treatment of stage III colon cancer. The next step was to incorporate capecitabine into combination therapy. The XELOXA trial studied the combination of capecitabine and oxaliplatin (XELOX vs 5-FU/LV and demonstrated 5-year disease-free survival of 66% for XELOX, compared with 60% for 5-FU/LV. The toxicity profile was also quite comparable in the two arms. So both the single agent use of capecitabine as well as in combination with oxaliplatin can be considered as part of the standard of care in management of early colon cancer in appropriately selected patient groups.Keywords: 5-fluorouracil, 5-FU, leucovorin, folinic acid, LV, XELOX, oxaliplatin, FOLFOX

  11. Colon cancer metastasis to the mandibular gingiva with partial occult squamous differentiation: A case report and literature review.

    Science.gov (United States)

    Ren, Quan-Guang; Huang, Tao; Yang, Sheng-Li; Hu, Jian-Li

    2017-02-01

    Metastasis is the primary cause of death among patients with colon cancer. However, the number of available studies regarding oral cavity metastases from colon cancer is currently limited. We herein report an unusual case of a 60-year-old male patient who developed an oral cavity metastasis from colon cancer. A total of 12 clinical case studies reporting colon cancer metastases to the mandibular gingival region were also reviewed, with the aim to elucidate the clinical and pathological characteristics of this disease entity in order to improve clinical diagnosis and treatment. It was demonstrated that patients with oral cavity metastases from colon cancer were predominantly in the sixth or seventh decades of life. The mandible was the main site of metastatic tumors to the oral cavity, while the occurrence of gingival metastases was comparatively rare. Moreover, the diagnoses of an oral metastatic tumor and primary colon cancer were often synchronous and were frequently accompanied with metastases to other organs. Several key aspects were suggested that should be accounted for when diagnosing colon cancer patients, including focusing attention to oral symptoms when examining cancer patients, utilizing a multidisciplinary approach for differential diagnosis and utilizing postoperative pathological examination to accurately diagnose the type of tumor and optimize the efficacy of treatment.

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

    Science.gov (United States)

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

    2015-06-01

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

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2007-10-24

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

  15. Chemotherapeutic Treatment of Priapism in Metastatic Rectal Cancer

    Directory of Open Access Journals (Sweden)

    Y. Kitai

    2008-12-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Mian Wang

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

  18. Current immunotherapeutic strategies in colon cancer.

    Science.gov (United States)

    Morse, Michael; Langer, Lee; Starodub, Alexander; Hobeika, Amy; Clay, Timothy; Lyerly, H Kim

    2007-10-01

    Because chemotherapy is standard in the treatment of colorectal cancer, it is important to demonstrate whether immunizations may be given to patients receiving systemic chemotherapy. Although some studies have demonstrated immune responses in patients with metastatic colorectal carcinoma who failed standard chemotherapy, the setting of minimal residual disease may be the preferred setting for cancer vaccines. It may be important to choose antigens that have functions important to the cancer cell. The best adjuvant is not well established and may depend on the type of immune response desired. The immune system is "programmed" to down-regulate immune responses once they have become activated to avoid the development of autoimmune disease.

  19. Generation of an inducible colon-specific Cre enzyme mouse line for colon cancer research

    NARCIS (Netherlands)

    Tetteh, Paul W; Kretzschmar, Kai; Begthel, Harry; van den Born, Maaike; Korving, Jeroen; Morsink, Folkert H M; Farin, Henner; van Es, Johan H; Offerhaus, G Johan A; Clevers, Hans

    2016-01-01

    Current mouse models for colorectal cancer often differ significantly from human colon cancer, being largely restricted to the small intestine. Here, we aim to develop a colon-specific inducible mouse model that can faithfully recapitulate human colon cancer initiation and progression. Carbonic

  20. The Association of Anisakiasis in the Ascending Colon with Sigmoid Colon Cancer: CT Colonography Findings

    International Nuclear Information System (INIS)

    Yoo, Hye Jin; Kim, Se Hyung; Lee, Jeong Min; Kim, Min A; Han, Joon Koo; Choi, Byung Ihn

    2008-01-01

    The association of anisakiasis of the colon with colon cancer is rare and difficult to diagnose. Only one case of this type has been reported to date. In this study, we report a case of synchronous colon cancer and colonic anisakiasis. A 50- year-old woman was admitted for abdominal pain, and a volume-rendered surface- shaded image of CT colonography (CTC) revealed a concentric narrowing in the sigmoid colon and a segmental fold thickening in the ascending colon. A total colectomy was performed and the diagnosis of synchronous sigmoid colon cancer and anisakiasis of the ascending colon was confirmed. This case is the first reported visualization of synchronous colon cancer and colonic anisakiasis on a CTC

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

    Science.gov (United States)

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

    2015-04-01

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

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

    African Journals Online (AJOL)

    1991-03-02

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    NARCIS (Netherlands)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2015-11-10

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

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

    International Nuclear Information System (INIS)

    Arai, Yasuaki; Kido, Choichiro

    1987-01-01

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

  7. Optimal duration of systemic treatment in metastatic colorectal cancer

    NARCIS (Netherlands)

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

    2014-01-01

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

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

    African Journals Online (AJOL)

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

  9. Diarrhoea Caused by Diffuse Metastatic Lobular Breast Cancer

    Directory of Open Access Journals (Sweden)

    Sjoerd F. Bakker

    2016-01-01

    Full Text Available A 70-year-old woman with a history of lobular breast cancer presented to our Outpatient Clinic with diarrhoea for the past 3 years. Clinical examination and laboratory research were normal. Colonoscopy showed diffuse mild erythema and a decreased vascular pattern. Biopsies from the ascending colon, transverse colon, and descending colon showed metastases of lobular breast carcinoma. Although gastrointestinal metastases are rare in breast cancer, our case emphasizes the need for further diagnostic efforts in patients with gastrointestinal symptoms and a history of breast carcinoma.

  10. Proton pumps, angiogenesis, and metastatic breast cancer

    Science.gov (United States)

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

    2000-04-01

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

  11. Asian and Hispanic Americans' cancer fatalism and colon cancer screening.

    Science.gov (United States)

    Jun, Jungmi; Oh, Kyeung Mi

    2013-03-01

    To explore fatalistic attributions of colon cancer development among Asian and Hispanic Americans in comparison with non-Hispanic whites; also to examine the impacts of fatalism on adherence to the colon cancer screening guideline. For the analysis, the 2005 Health Information National Trends Survey data were employed. Both Asian and Hispanic Americans were more likely to make fatalistic attribution and were less likely to follow the guideline than whites. Particularly for Asians, fatalism was a significant predictor for not adhering to the guideline. These findings emphasize the need for cultural interventions to disrupt fatalistic attitudes towards colon cancer preventions.

  12. Clinicopathologic factors identify sporadic mismatch repair-defective colon cancers

    DEFF Research Database (Denmark)

    Halvarsson, Britta; Anderson, Harald; Domanska, Katarina

    2008-01-01

    Identification of sporadic mismatch repair (MMR)-defective colon cancers is increasingly demanded for decisions on adjuvant therapies. We evaluated clinicopathologic factors for the identification of these prognostically favorable tumors. Histopathologic features in 238 consecutive colon cancers...

  13. Lack of Caudal-Type Homeobox Transcription Factor 2 Expression as a Prognostic Biomarker in Metastatic Colorectal Cancer.

    Science.gov (United States)

    Zhang, Ben Y; Jones, Jeremy C; Briggler, Andrew M; Hubbard, Joleen M; Kipp, Benjamin R; Sargent, Daniel J; Dixon, Jesse G; Grothey, Axel

    2017-06-01

    Although the lack of CDX2 expression has recently been proposed as a potential biomarker for a high risk of relapse in patients with stage II and III colon cancer after complete surgical resection, its prognostic role in metastatic colorectal cancer (CRC) remains unclear and warrants investigation. We identified 145 patients treated at our institution from 2006 to 2016, including 66 patients with CDX2-negative metastatic CRC and a comparison cohort of 79 patients with CDX2-positive metastatic CRC. Overall survival (OS) and progression-free survival (PFS) for first-line systemic therapy were estimated using the Kaplan-Meier method. The associations of CDX2 expression with survival were evaluated using Cox proportional hazards regression models. The prevalence of absent CDX2 expression in our cohort was 5.6%. Patients with CDX2-negative metastatic CRC were significantly more likely to be female, and to have right-sided primary tumors, poorly differentiated histologic features, and distant lymph node metastasis. The median OS for patients with CDX2-negative and -positive metastatic CRC was 8 and 39 months, respectively (hazard ratio [HR], 4.04; 95% confidence interval [CI], 2.49-6.54; P lack of CDX2 expression and OS remained statistically significant (HR, 4.52; 95% CI, 2.50-8.17; P lack of CDX2 expression in metastatic CRC is an adverse prognostic feature and a potential negative predictor of the response to chemotherapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Breast Cancer Cell Colonization of the Human Bone Marrow Adipose Tissue Niche

    Directory of Open Access Journals (Sweden)

    Zach S. Templeton

    2015-12-01

    Full Text Available BACKGROUND/OBJECTIVES: Bone is a preferred site of breast cancer metastasis, suggesting the presence of tissue-specific features that attract and promote the outgrowth of breast cancer cells. We sought to identify parameters of human bone tissue associated with breast cancer cell osteotropism and colonization in the metastatic niche. METHODS: Migration and colonization patterns of MDA-MB-231-fLuc-EGFP (luciferase-enhanced green fluorescence protein and MCF-7-fLuc-EGFP breast cancer cells were studied in co-culture with cancellous bone tissue fragments isolated from 14 hip arthroplasties. Breast cancer cell migration into tissues and toward tissue-conditioned medium was measured in Transwell migration chambers using bioluminescence imaging and analyzed as a function of secreted factors measured by multiplex immunoassay. Patterns of breast cancer cell colonization were evaluated with fluorescence microscopy and immunohistochemistry. RESULTS: Enhanced MDA-MB-231-fLuc-EGFP breast cancer cell migration to bone-conditioned versus control medium was observed in 12/14 specimens (P = .0014 and correlated significantly with increasing levels of the adipokines/cytokines leptin (P = .006 and IL-1β (P = .001 in univariate and multivariate regression analyses. Fluorescence microscopy and immunohistochemistry of fragments underscored the extreme adiposity of adult human bone tissues and revealed extensive breast cancer cell colonization within the marrow adipose tissue compartment. CONCLUSIONS: Our results show that breast cancer cells migrate to human bone tissue-conditioned medium in association with increasing levels of leptin and IL-1β, and colonize the bone marrow adipose tissue compartment of cultured fragments. Bone marrow adipose tissue and its molecular signals may be important but understudied components of the breast cancer metastatic niche.

  15. Enterobacter Strains Might Promote Colon Cancer.

    Science.gov (United States)

    Yurdakul, Dilşad; Yazgan-Karataş, Ayten; Şahin, Fikrettin

    2015-09-01

    Many studies have been performed to determine the interaction between bacterial species and cancer. However, there has been no attempts to demonstrate a possible relationship between Enterobacter spp. and colon cancer so far. Therefore, in the present study, it is aimed to investigate the effects of Enterobacter strains on colon cancer. Bacterial proteins were isolated from 11 Enterobacter spp., one Morganella morganii, and one Escherichia coli strains, and applied onto NCM460 (Incell) and CRL1790 (ATCC) cell lines. Cell viability and proliferation were determined in MTS assay. Flow Cytometry was used to detect CD24 level and apoptosis. Real-Time PCR studies were performed to determine NFKB and Bcl2 expression. Graphpad Software was used for statistical analysis. The results showed that proteins, isolated from the Enterobacter spp., have significantly increased cell viability and proliferation, while decreasing the apoptosis of the cell lines tested. The data in the present study indicated that Enterobacter strains might promote colon cancer. Moreover, Enterobacter spp. could be a clinically important factor for colon cancer initiation and progression. Studies can be extended on animal models in order to develop new strategies for treatment.

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

    Science.gov (United States)

    2016-10-01

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

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

    Science.gov (United States)

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

    2017-05-01

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

  18. Medical image of the week: metastatic testicular cancer

    Directory of Open Access Journals (Sweden)

    Debo M

    2014-06-01

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

  19. Advances in diagnosis and treatment of metastatic cervical cancer

    Science.gov (United States)

    2016-01-01

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

  20. Promising oncolytic agents for metastatic breast cancer treatment

    Directory of Open Access Journals (Sweden)

    Cody JJ

    2015-06-01

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

  1. Colon cancer stem cells: Controversies and perspectives

    Science.gov (United States)

    Puglisi, Maria Ausiliatrice; Tesori, Valentina; Lattanzi, Wanda; Gasbarrini, Giovanni Battista; Gasbarrini, Antonio

    2013-01-01

    Tumors have long been viewed as a population in which all cells have the equal propensity to form new tumors, the so called conventional stochastic model. The cutting-edge theory on tumor origin and progression, tends to consider cancer as a stem cell disease. Stem cells are actively involved in the onset and maintenance of colon cancer. This review is intended to examine the state of the art on colon cancer stem cells (CSCs), with regard to the recent achievements of basic research and to the corresponding translational consequences. Specific prominence is given to the hypothesized origin of CSCs and to the methods for their identification. The growing understanding of CSC biology is driving the optimization of novel anti-cancer targeted drugs. PMID:23716979

  2. Clinicopathologic factors identify sporadic mismatch repair-defective colon cancers

    DEFF Research Database (Denmark)

    Halvarsson, Britta; Anderson, Harald; Domanska, Katarina

    2008-01-01

    Identification of sporadic mismatch repair (MMR)-defective colon cancers is increasingly demanded for decisions on adjuvant therapies. We evaluated clinicopathologic factors for the identification of these prognostically favorable tumors. Histopathologic features in 238 consecutive colon cancers...... and excluded 61.5% of the tumors from MMR testing. This clinicopathologic index thus successfully selects MMR-defective colon cancers. Udgivelsesdato: 2008-Feb...

  3. The study of serum folate in patients with colon cancer

    International Nuclear Information System (INIS)

    Xu Sumei; Li Long

    2002-01-01

    Serum folate concentration was measured by radioimmunoassay in 36 patients with colon cancer. Folate concentration in the patients was lower than that in controls (P<0.05). Serum folate concentration was closely related to colon cancer. Regulating food and drink structure to improve lower folate condition could play a active part in preventing colon cancer

  4. Metabolic Syndrome X and Colon Cancer

    Czech Academy of Sciences Publication Activity Database

    Matoulek, M.; Svobodová, S.; Svačina, Š.; Plavcová, Marie; Zvárová, Jana; Visokai, V.; Lipská, M.

    2003-01-01

    Roč. 27, suppl. 1 (2003), s. 86 ISSN 0307-0565. [European Congress on Obesity /12./. 29.05.2003-01.06.2003, Helsinki] R&D Projects: GA MZd NB6635; GA MŠk LN00B107 Keywords : metabolic syndrome X * colon cancer Subject RIV: BB - Applied Statistics, Operational Research

  5. [Postoperative intraperitoneal complications in colon cancer surgery].

    Science.gov (United States)

    Erokhina, E A; Topuzov, É G; Topuzov, É É

    2014-01-01

    The authors studied the clinical characteristics and terms of the development of postoperative intraperitoneal complications in patients undergoing colon cancer surgery. It was stated, that the diversity of clinical data depended on complication characteristics. Results of investigation allowed defining of the most dangerous terms of intraperitoneal complications and risk factors.

  6. Therapeutic considerations in Dukes C colon cancer

    NARCIS (Netherlands)

    Bleeker, Willem Aldert

    2001-01-01

    Colon cancer is one of the main health issues in the western world. In the Netherlands more than 7000 patients are diagnosed yearly with this disease and half of them will die from it. Prognosis largely depends on tumor stage, which is estimated by radiological, clinical and histological

  7. Cell-Free DNA in Metastatic Colorectal Cancer

    DEFF Research Database (Denmark)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Goldenberg David M

    2007-01-01

    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusion 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

  9. Promising oncolytic agents for metastatic breast cancer treatment

    Science.gov (United States)

    Cody, James J; Hurst, Douglas R

    2015-01-01

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

  10. Patient Beliefs About Colon Cancer Screening.

    Science.gov (United States)

    Ely, John W; Levy, Barcey T; Daly, Jeanette; Xu, Yinghui

    2016-03-01

    Only about half of eligible individuals undergo colon cancer screening. We have limited knowledge about the patient beliefs that adversely affect screening decisions and about which beliefs might be amenable to change through education. As part of a clinical trial, 641 rural Iowans, aged 52 to 79 years, reported their beliefs about colon cancer screening in response to a mailed questionnaire. Consenting subjects were randomized into four groups, which were distinguished by four levels of increasingly intensive efforts to promote screening. Two of the groups received mailed educational materials and completed a follow-up questionnaire, which allowed us to determine whether their beliefs about screening changed following the education. We also completed a factor analysis to identify underlying (latent) factors that might explain the responses to 33 questions about readiness, attitudes, and perceived barriers related to colon cancer screening. The strongest predictors of a patient's stated readiness to be screened were a physician's recommendation to be screened (1 point difference on 10-point Likert scale, 95 % confidence interval [CI], 0.5 to 1.6 point difference), a family history of colon cancer (0.85-point Likert scale difference, 95 % CI, 0.1 to 1.6), and a belief that health-care decisions should be mostly left to physicians rather than patients (Spearman correlation coefficient 0.21, P < .001). Of the 33 questionnaire items about screening beliefs, 11 (33 %) changed favorably following the educational intervention. In the factor analysis, the 33 items were reduced to 8 underlying factors, such as being too busy to undergo screening and worries about screening procedures. We found a limited number of underlying factors that may help explain patient resistance to colon cancer screening.

  11. Complement 5a stimulates macrophage polarization and contributes to tumor metastases of colon cancer.

    Science.gov (United States)

    Piao, Chunmei; Zhang, Wen-Mei; Li, Tao-Tao; Zhang, Cong-Cong; Qiu, Shulan; Liu, Yan; Liu, Sa; Jin, Ming; Jia, Li-Xin; Song, Wen-Chao; Du, Jie

    2018-05-15

    Inflammatory cells such as macrophages can play a pro-tumorigenic role in the tumor stroma. Tumor-associated macrophages (TAMs) generally display an M2 phenotype with tumor-promoting activity; however, the mechanisms regulating the TAM phenotype remain unclear. Complement 5a (C5a) is a cytokine-like polypeptide that is generated during complement system activation and is known to promote tumor growth. Herein, we investigated the role of C5a on macrophage polarization in colon cancer metastasis in mice. We found that deficiency of the C5a receptor (C5aR) severely impairs the metastatic ability of implanted colon cancer cells. C5aR was expressed on TAMs, which exhibited an M2-like functional profile in colon cancer liver metastatic lesions. Furthermore, C5a mediated macrophage polarization and this process relied substantially on activation of the nuclear factor-kappa B (NF-κB) pathway. Finally, analysis of human colon carcinoma indicated that C5aR expression is negatively associated with tumor differentiation grade. Our results demonstrate that C5aR has a central role in regulating the M2 phenotype of TAMs, which in turn, contributes to hepatic metastasis of colon cancer through NF-κB signaling. C5a is a potential novel marker for cancer prognosis and drugs targeting complement system activation, specifically the C5aR pathway, may offer new therapeutic opportunities for colon cancer management. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. Metastasis of sigmoid colon cancer in cryptorchid testis: report of a case.

    Science.gov (United States)

    Rampa, Mario; Battaglia, Luigi; Caprotti, Andrea; Gazzano, Giacomo; Prestianni, Pierpaolo; Muscarà, Cecilia; Vannelli, Alberto

    2012-01-01

    Isolated testicular metastasis from colorectal cancer is considered an unusual event. In this case report we describe for the first time a metastasis from an adenocarcinoma of the sigmoid colon to a cryptorchid testis. The patient developed a painless testicular nodule three years after the diagnosis of primary sigmoid colon cancer. Recent reports have suggested that the incidence of genitourinary abnormalities in human males has increased over the past 50 years; in particular, cryptorchid testes increase the clinical risk factors for primary or metastatic testicular cancer. In conclusion, there should be awareness of the risk of metastasis of colorectal cancer to the testis in the workup of patients with testicular symptoms. Furthermore, patients with colorectal cancer and cryptorchidism should be managed with a single surgical intervention: when the primary colorectal tumor is removed, the cryptorchid testicle should also be removed to reduce the risk of late metastases.

  13. Role of microsatellite instability in colon cancer

    Directory of Open Access Journals (Sweden)

    M. Yu. Fedyanin

    2012-01-01

    Full Text Available Coloncancer is among leading causes of cancer morbidity and mortality both inRussiaand worldwide. Development of molecular biology lead to decoding of carcinogenesis and tumor progression mechanisms. These processes require accumulation of genetic and epigenetic alterations in a tumor cell.Coloncancer carcinogenesis is characterized by mutations cumulation in genes controlling growth and differentiation of epithelial cells, which leads to their genetic instability. Microsatellite instability is a type of genetic instability characterized by deterioration of mismatch DNA repair. This leads to faster accumulation of mutations in DNA. Loss of mismatch repair mechanism can easily be diagnosed by length of DNA microsatellites. These alterations are termed microsatellite instability. They can be found both in hereditary and sporadic colon cancers. This review covers the questions of microsatellite instability, its prognostic and predictive value in colon cancer.

  14. Colon cancer: a civilization disorder.

    Science.gov (United States)

    Watson, Alastair J M; Collins, Paul D

    2011-01-01

    Colorectal cancer arises in individuals with acquired or inherited genetic predisposition who are exposed to a range of risk factors. Many of these risk factors are associated with affluent Western societies. More than 95% of colorectal cancers are sporadic, arising in individuals without a significant hereditary risk. Geographic variation in the incidence of colorectal cancer is considerable with a higher incidence observed in the West. Environmental factors contribute substantially to this variation. A number of these risk factors are associated with a Western lifestyle and could be considered a product of 'civilization'. Recently, smoking has been recognized as a risk factor. Energy consumption also influences colorectal cancer risk, with obesity increasing risk and exercise reducing risk. However, the strongest contribution to environmental risk for colorectal cancer is dietary. Consumption of fat, alcohol and red meat is associated with an increased risk. Fresh fruit and vegetables and dietary fibre may be protective. Much has been learnt recently about the molecular pathogenesis of colorectal cancer. Colorectal cancer always arises in the context of genomic instability. There is inactivation of the tumour suppressor genes adenomatous polyposis coli, p53, transforming growth factor-β, activation of oncogene pathways including K-ras, and activation of the cyclooxygenase-2, epidermal growth factor receptor and vascular endothelial growth factor pathways. The mechanisms by which some environmental factors modify the mutation risk in these pathways have been described. Copyright © 2011 S. Karger AG, Basel.

  15. Unusual presentation of metastatic gall bladder cancer

    Directory of Open Access Journals (Sweden)

    Piyush Shukla

    2014-01-01

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

  16. Coffee, colon function and colorectal cancer.

    Science.gov (United States)

    Vitaglione, Paola; Fogliano, Vincenzo; Pellegrini, Nicoletta

    2012-09-01

    For several years the physiological effects of coffee have been focused on its caffeine content, disregarding the hundreds of bioactive coffee components, such as polyphenols, melanoidins, carbohydrates, diterpenes, etc. These compounds may exert their protection against colorectal cancer (CRC), the third most common cancer worldwide. However, the amount and type of compounds ingested with the beverage may be highly different depending on the variety of coffee used, the roasting degree, the type of brewing method as well as the serving size. In this frame, this paper reviews the mechanisms by which coffee may influence the risk of CRC development focusing on espresso and filtered coffee, as well as on the components that totally or partially reach the colon i.e. polyphenols and dietary fiber, including melanoidins. In particular the effects of coffee on some colon conditions whose deregulation may lead to cancer, namely microbiota composition and lumen reducing environment, were considered. Taken together the discussed studies indicated that, due to their in vivo metabolism and composition, both coffee chlorogenic acids and dietary fiber, including melanoidins, may reduce CRC risk, increasing colon motility and antioxidant status. Further studies should finally assess whether the coffee benefits for colon are driven through a prebiotic effect.

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

    Science.gov (United States)

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

    2016-01-01

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

  18. A Study of Clinicopathological Differences Between Right-sided and Left-sided Colon Cancers

    OpenAIRE

    芳賀, 駿介; 遠藤, 俊吾; 加藤, 博之; 高橋, 直樹; 吉松, 和彦; 橋本, 雅彦; 石橋, 敬一郎; 梅原, 有弘; 横溝, 肇; 梶原, 哲郎; Shunsuke, HAGA; Shungo, ENDO; Hiroyuki, KATO; Naoki, TAKAHASHI; Kazuhiko, YOSHIMATSU

    1996-01-01

    The present study was aimed to determine the clinicopathological features of cancers of the right-sided colon (cecum, ascending colon, transverse colon) and left-sided colon (descending colon, sigmoid colon) in order to help improve the efficacy of their treatment. Excluding multiple cancer cases, 364 patients with primary colon cancer underwent surgey at our department between 1974 and 1994; they comprised 171 individuals with right-sided colon cancer and 193 with left-sided colon cancer. A ...

  19. Study of endothelin-1 and vascular endothelial growth factor in patients with cancer colon.

    Science.gov (United States)

    Abdel-Gawad, Iman A; Hassanein, Hala M R; Bahgat, Nahla A; Abdel Sattar, Mona A; El-Sissy, Azza H; Altaweel, Maha A; Helal, Amany M

    2008-09-01

    The levels of endothelin-1 and VEGF were evaluated in the sera of newly diagnosed patients with cancer colon and were compared with the routinely used tumor markers; CEA and CA19.9. Their relations with some prognostic factors of cancer colon were also investigated. The study included 48 patients with cancer colon and 20 apparently healthy volunteers as a control group. Patients were 23 males and 25 females with age range from 18 to 71 years (mean = 47 +/- 1.8). Both serum and plasma samples were obtained from patients and controls. Six percent of patients had grade 1 tumors, 77 % had grade 2 and 17 % had grade 3 disease. As regard to the stage, 52 % of patients were stage II, 35.5 % were stage III, while 12.5 % were stage IV. Liver metastasis was present in 12.5 %, while 35 % showed lymph node metastasis. The VEGF, endothelin-1, CA19.9 and CEA were significantly higher in the cancer colon patients than in control groups (p-value < 0.001,0.006, < 0.001 and <0.001; respectively). Plasma level of endothelin-1 and serum level of VEGF showed significantly higher levels in advanced stages of the disease (p value < 0.001) and in presence of liver metastasis (p value <0.00l and 0.002 respectively), while VEGF showed significant result when compared with the grade (p value = 0.032). In this study, when comparing the levels of plasma endothelin-1 and serum VEGF between the metastatic, non-metastatic liver patients of the cancer colon group and the control group, the comparison was statistically significant for both markers (p < 0.001). Endothelin-1 and VEGF showed significant positive correlation (r=0.77 and p-value < 0.0001). Serum VEGF and CA19.9 showed good sensitivities which were not different (97.9 % and 87.5 % ,respectively), while there was no significant difference between VEGF, CA19.9 and CEA with respect to specificities (100 %, 90 % and 100 % respectively). Both endothelin-1 and VEGF may be used for early detection of liver metastasis in cancer colon and VEGF

  20. Cytoreductive prostatectomy in metastatic prostate cancer

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  1. Pancreatoduodenectomy with colon resection for cancer: A nationwide retrospective analysis

    NARCIS (Netherlands)

    Marsman, E. Madelief; de Rooij, Thijs; van Eijck, Casper H.; Boerma, Djamila; Bonsing, Bert A.; van Dam, Ronald M.; van Dieren, Susan; Erdmann, Joris I.; Gerhards, Michael F.; de Hingh, Ignace H.; Kazemier, Geert; Klaase, Joost; Molenaar, I. Quintus; Patijn, Gijs A.; Scheepers, Joris J.; Tanis, Pieter J.; Busch, Olivier R.; Besselink, Marc G.

    2016-01-01

    Microscopically radical (R0) resection of pancreatic, periampullary, or colon cancer may occasionally require a pancreatoduodenectomy with colon resection (PD-colon), but the benefits of this procedure have been disputed, and multicenter studies on morbidity and oncologic outcomes after PD-colon are

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

    Directory of Open Access Journals (Sweden)

    Brendan Corkery

    2008-09-01

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

  3. Combination Drug Delivery Approaches in Metastatic Breast Cancer

    Directory of Open Access Journals (Sweden)

    Jun H. Lee

    2012-01-01

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

  4. 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.

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

    Science.gov (United States)

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

    2012-08-01

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

  6. Eating patterns and risk of colon cancer.

    Science.gov (United States)

    Slattery, M L; Boucher, K M; Caan, B J; Potter, J D; Ma, K N

    1998-07-01

    Colon cancer has been associated with several nutrients and foods. The authors used data from a population-based study conducted in Northern California, Utah, and Minnesota to examine associations between dietary eating patterns and risk of developing colon cancer. Through factor analysis, detailed dietary intake data obtained from 1,993 cases (diagnosed in 1991-1994) and 2,410 controls were grouped into factors that were evaluated for relations with lifestyle characteristics and colon cancer risk. Several dietary patterns emerged. The dietary patterns with the most variation were labeled "Western," "prudent," "high fat/sugar dairy," "substituters," and "drinkers." The "Western" dietary pattern was associated with a higher body mass index and a greater intake of total energy and dietary cholesterol. The "prudent" pattern was associated with higher levels of vigorous leisure time physical activity, smaller body size, and higher intakes of dietary fiber and folate. Persons who had high scores on the "drinker" pattern were also more likely to smoke cigarettes. The "Western" dietary pattern was associated with an increased risk of colon cancer in both men and women. The association was strongest among people diagnosed prior to age 67 years (for men, odds ratio (OR)=1.96, 95% confidence interval (CI) 1.22-3.15; for women, OR=2.02, 95% CI 1.21-3.36) and among men with distal tumors (OR=2.25, 95% CI 1.47-3.46). The "prudent" diet was protective, with the strongest associations being observed among people diagnosed prior to age 67 years (men: OR=0.63, 95% CI 0.43-0.92; women: OR=0.58, 95% CI 0.38-0.87); associations with this dietary pattern were also strong among persons with proximal tumors (men: OR=0.55, 95% CI 0.38-0.80; women: OR=0.64, 95% CI 0.45-0.92). Although "substituters" (people who substituted low fat dairy products for high fat dairy products, margarine for butter, poultry for red meat, and whole grains for refined grains) were at reduced risk of colon cancer

  7. Targeting Mitochondrial Inhibitors for Metastatic Castrate Resistant Prostate Cancer

    Science.gov (United States)

    2017-09-01

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

  8. Visualising and quantifying angiogenesis in metastatic colorectal cancer

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  9. Salvage Lenvatinib Therapy in Metastatic Anaplastic Thyroid Cancer.

    Science.gov (United States)

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

    2017-07-01

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

  10. Isolated metachronous splenic metastasis from synchronous colon cancer

    Directory of Open Access Journals (Sweden)

    Aker Fugen

    2006-07-01

    Full Text Available Abstract Background Isolated splenic metastases from colorectal cancer are very rare and there are only 13 cases reported in the English literature so far. Most cases are asymptomatic and the diagnosis is usually made by imaging studies during the evaluation of rising CEA level postoperatively. Case presentation A 76-year-old man underwent an extended left hemicolectomy for synchronous colon cancers located at the left flexure and the sigmoid colon. The tumors were staged as IIIC (T3N2M0 clinically and the patient received adjuvant chemotherapy. During the first year follow-up period, the patient remained asymptomatic with normal levels of laboratory tests including CEA measurement. However, a gradually rising CEA level after the 14th postoperative month necessitated further imaging studies including computed tomography of the abdomen which revealed a mass in the spleen that was subsequently confirmed by 18FDG- PET scanning to be an isolated metastasis. The patient underwent splenectomy 17 months after his previous cancer surgery. Histological diagnosis confirmed a metastatic adenocarcinoma with no capsule invasion. After an uneventful postoperative period, the patient has been symptom-free during the one-year of follow-up with normal blood CEA levels, although he did not accept to receive any further adjuvant therapy. To the best of our knowledge, this 14th case of isolated splenic metastasis from colorectal carcinoma is also the first reported case of splenic metastasis demonstrated preoperatively by 18FDG PET-CT fusion scanning which revealed its solitary nature as well. Conclusion Isolated splenic metastasis is a rare finding in the follow-up of colorectal cancer patients and long-term survival can be achieved with splenectomy.

  11. Gene Delivery for Metastatic Prostate Cancer Cells

    National Research Council Canada - National Science Library

    Pang, Shen

    2001-01-01

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

  12. FIRST LINE 5-FU-BASED CHEMOTHERAPY WITH/WITHOUT BEVACIZUMAB FOR METASTATIC COLORECTAL CANCER: TISSUE BIOMARKER CANDIDATES

    Directory of Open Access Journals (Sweden)

    Assia Konsoulova

    2016-03-01

    Full Text Available Purpose: Colorectal cancer is the second leading cause of cancer mortality in the USA. According to Bulgarian National Statistics Institute, 2370 colon and 1664 rectal cancer cases were diagnosed in 2012 with total number of patients 29995. Adding bevacizumab to chemotherapy in patients with metastatic disease improves progression-free survival (PFS but no predictive markers have been proven in the clinical practice. In our study we examined two tissue biomarkers that may correlate with response to bevacizumab-containing chemotherapy in patients with metastatic colorectal cancer. Patients and Methods: 54 patients with metastatic colorectal cancer were assigned to first line 5-Fu-based chemotherapy with/without bevacizumab. The primary end point was PFS, with additional determination of response and toxicity. Paraffin-embedded samples from primary tumors were collected from all 54 patients. Expression levels of two tumor biomarkers VEGFR-2 and Neuropilin 1 (NP-1 were evaluated with immunohistochemistry. Results: The median PFS for the group treated with CT/Bev was 8.8 months, compared with 5.4 months for the group with chemotherapy alone (95% CI, log-rank test P =0.003. The corresponding overall response rates were 19.3% and 10.2% respectively (P < 0.05 for CT/Bev vs CT. Patients with low NP-1 had statistically significant prolongation of PFS as compared to those with high NP-1 (95% CI, log rank test p= 0.017. Patients with low NP-1 appeared to experience a larger bevacizumab treatment effect in terms of PFS (p=0,049,HR 0.333, 95% CI, 0.111 to 0.995 than patients with high NP-1. Conclusion: The addition of bevacizumab to 5-Fu based chemotherapy improves PFS for patients with metastatic colorectal cancer. Expression of tumor NP-1 is a potential biomarker candidate for prediction of clinical outcome in patients with metastatic colorectal cancer, treated with first line chemotherapy plus bevacizumab.

  13. Red meat and colon cancer : a possible role for heme

    NARCIS (Netherlands)

    Sesink, Aloysius Lambertus Antonia

    2000-01-01

    Sporadic colon cancer is a multifactorial aging disease affected by long-term exposure to environmental risk factors. Epidemiological studies have shown that risk for colon cancer is associated with diets high in red meat and/or animal fat. The mechanisms by which colonic tumors arise are, however,

  14. Right sided colon cancer at Olabisi Onabanjo University Teaching ...

    African Journals Online (AJOL)

    Recent studies suggest that right sided colon cancer may have a different clinicopathological behaviour and prognosis from carcinoma in the rest of the colon and especially the rectum. Reports in the Nigerian literature had usually considered colon and rectal cancer together, thereby masking these differences. This study is ...

  15. Regorafenib-induced retinal and gastrointestinal hemorrhage in a metastatic colorectal cancer patient with liver dysfunction

    Science.gov (United States)

    Tsuchihashi, Kenji; Shimokawa, Hozumi; Takayoshi, Kotoe; Nio, Kenta; Aikawa, Tomomi; Matsushita, Yuzo; Wada, Iori; Arita, Shuji; Ariyama, Hiroshi; Kusaba, Hitoshi; Sonoda, Koh-Hei; Akashi, Koichi; Baba, Eishi

    2017-01-01

    Abstract Rationale: Regorafenib is effective for metastatic colorectal cancer but its toxicity such as hemorrhage should be considered. The safety of regorafenib for the patient with the liver disease is not known. Patient concerns: Seventy-one-year old man of colon cancer had myodesopsia and blood stool after 14 days from the initiation of regorafenib administration with 50% dose reduction due to liver dysfunction. Diagnoses: Fundus examination revealed hemorrhage of the retinal vein. Interventions: Regorafenib treatment was discontinued and observational therapy was pursued. Outcomes: Retinal and gastrointestinal hemorrhage resolved in 1 week. Lessons: Retinal hemorrhage should be considered as the differential diagnosis of myodesopsia in the patient treated by regorafenib. Safety and pharmacokinetic of continuous regorafenib administration for patients with liver dysfunction remains to be clarified. PMID:29049226

  16. Oral bisphosphonates and colon cancer

    DEFF Research Database (Denmark)

    Eiken, Pia; Vestergaard, Peter

    2015-01-01

    Bisphosphonates (BPs) are widely used as the main treatment for osteoporosis. In vitro and animal studies suggest that use of BPs may have a potential for colorectal cancer (CRC) prevention. Safety and efficacy in terms of osteoporosis prevention have only been evaluated in randomized controlled...

  17. Acquired resistance to HSP90 inhibitor 17-AAG and increased metastatic potential are associated with MUC1 expression in colon carcinoma cells.

    Science.gov (United States)

    Liu, Xin; Ban, Li-Li; Luo, Gang; Li, Zhi-Yao; Li, Yun-Feng; Zhou, Yong-Chun; Wang, Xi-Cai; Jin, Cong-Guo; Ye, Jia-Gui; Ma, Ding-Ding; Xie, Qing; Huang, You-Guang

    2016-06-01

    Heat shock protein 90 (HSP90) is a molecular chaperone required for the stability and function of many proteins. The chaperoning of oncoproteins by HSP90 enhances the survival, growth, and invasive potential of cancer cells. HSP90 inhibitors are promising new anticancer agents, in which the benzoquinone ansamycin 17-allylamino-17-demethoxygeldanamycin (17-AAG) is currently in clinical evaluation. However, the implications of acquired resistance to this class of drug remain largely unexplored. In the present study, we have generated isogenic human colon cancer cell lines that are resistant to 17-AAG by continued culturing in the compound. Cross-resistance was found with another HSP90 inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin. The resistant cells showed obvious morphology changes with a metastatic phenotype and significant increases in migration and adhesion to collagens. Western blotting analysis of epithelial-mesenchymal transition molecular markers found that expression of E-cadherin downregulated, whereas expression of N-cadherin and β-catenin upregulated in the resistant cells. Mucin 1 (MUC1) has been reported to mediate metastasis as well as chemical resistance in many cancers. Here, we found that MUC1 expression was significantly elevated in the acquired drug resistance cells. 17-AAG treatment could decrease MUC1 more in parental cells than in acquired 17-AAG-resistant cells. Further study found that knockdown of MUC1 expression by small interfering RNA could obviously re-sensitize the resistant cells to 17-AAG treatment, and decrease the cell migration and adhesion. These were coupled with a downregulation in N-cadherin and β-catenin. The results indicate that HSP90 inhibitor therapies in colon carcinomas could generate resistance and increase metastatic potential that might mediated by upregulation of MUC1 expression. Findings from this study further our understanding of the potential clinical effects of HSP90-directed therapies in

  18. Localised perforation of locally advanced transverse colon cancer with spontaneous colocutaneous fistula formation: a clinical challenge.

    Science.gov (United States)

    Wadhwani, Nikita; Diwakar, Deepak Kumar

    2018-04-19

    Colon cancer can present with complications such as obstruction, perforation and bleeding. The clinical presentation has been recognised as an independent prognostic factor for morbidity and mortality. 1 We present a rare case of localised perforation of a locally advanced colon cancer arising from mid-transverse colon in an elderly woman in the absence of widely metastatic disease with eventual cutaneous involvement of the overlying skin by direct extension, resulting in formation of colocutaneous fistula. The management of such cases is complex as usually tailored to the situation encountered. 2 This case was a clinical challenge to choose between initial palliative resection and curative R0 resection following neoadjuvant chemotherapy. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  19. Suppressor of cytokine signaling 1 modulates invasion and metastatic potential of colorectal cancer cells.

    Science.gov (United States)

    David, Muriel; Naudin, Cécile; Letourneur, Martine; Polrot, Mélanie; Renoir, Jack-Michel; Lazar, Vladimir; Dessen, Philippe; Roche, Serge; Bertoglio, Jacques; Pierre, Josiane

    2014-07-01

    Suppressor of cytokine signaling (SOCS) 1 is an inducible negative regulator of cytokine signaling but its role in human cancer is not completely established. Here we report that, while SOCS1 is expressed in normal colonic epithelium and colon adenocarcinomas, its level decreases during progression of colon adenocarcinomas, the lowest level being found in the most aggressive stage and least differentiated carcinomas. Forced expression of SOCS1 in metastatic colorectal SW620 cells reverses many characteristics of Epithelial-Mesenchymal Transition (EMT), as highlighted by the disappearance of the transcription factor ZEB1 and the mesenchymal form of p120ctn and the re-expression of E-cadherin. Furthermore, miRNA profiling indicated that SOCS1 also up-regulates the expression of the mir-200 family of miRNAs, which can promote the mesenchymal-epithelial transition and reduce tumor cell migration. Accordingly, overexpression of SOCS1 induced cell morphology changes and dramatically reduced tumor cell invasion in vitro. When injected in nude mice, SOCS1-expressing SW620 cells induced metastases in a smaller number of animals than parental SW620 cells, and did not generate any adrenal gland or bone metastasis. Overall, our results suggest that SOCS1 controls metastatic progression of colorectal tumors by preventing the mesenchymal-epithelial transition (MET), including E-cadherin expression. This pathway may be associated with survival to colorectal cancer by reducing the capacity of generating metastases. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  20. Directory of Colon and Rectal Cancer Specialist Teams

    OpenAIRE

    Department of Health; Social Services and Public Safety

    2004-01-01

    The Directory of Colon and Rectal Cancer Specialist Teams has been produced under the auspices of the Northern Ireland Regional Advisory Committee on Cancer. It contains details of the full membership of the clinical teams providing care for colon and rectal cancer in each of Health and Social Services Board Area. Lead Clinicians For Colon and Rectal Cancer Services (PDF 74 KB) EHSSB (PDF 198 KB) NHSSB (PDF 107 KB) SHSSB (PDF 130 KB) WHSSB (PDF 131 KB)

  1. Suppress orthotopic colon cancer and its metastasis through exact targeting and highly selective drug release by a smart nanomicelle.

    Science.gov (United States)

    Zhu, Chunqi; Zhang, Hanbo; Li, Wei; Luo, Lihua; Guo, Xiaomeng; Wang, Zuhua; Kong, Fenfen; Li, Qingpo; Yang, Jie; Du, Yongzhong; You, Jian

    2018-04-01

    The treatment of metastatic cancer is a huge challenge at the moment. Highly precise targeting delivery and drug release in tumor have always been our pursuit in cancer therapy, especially to advance cancer with metastasis, for increasing the efficacy and biosafety. We established a smart nanosized micelle, formed by tocopherol succinate (TOS) conjugated hyaluronic acid (HA) using a disulfide bond linker. The micelle (HA-SS-TOS, HSST) can highly specifically bind with CD44 receptor over-expressed tumor, and response selectively to high GSH level in the cells, inducing disulfide bond breakage and the release of the payload (paclitaxel, PTX). To predict the antitumor efficacy of the micelles more clinically, we established an orthotopic colon cancer model with high metastasis rate, which could be visualized by the luciferase bioluminescence. Our data confirmed CD44 high expression in the colon cancer cells. Highly matching between the micellar fluorescence and bioluminescence of cancer cells in intestines demonstrated an exact recognition of our micelles to orthotopic colon tumor and its metastatic cells, attributing to the mediation of CD44 receptors. Furthermore, the fluorescence of the released Nile Red from the micelles was found only in the tumor and its metastatic cells, and almost completely overlapped with the bioluminescence of the cancer cells, indicating a highly selective drug release. Our micelles presented an excellent therapeutic effect against metastatic colon cancer, and induced significantly prolonged survival time for the mice, which might become a promising nanomedicine platform for the future clinical application against advanced cancers with high CD44 receptor expression. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. A prognostic analysis of 895 cases of stage III colon cancer in different colon subsites.

    Science.gov (United States)

    Zhang, Yan; Ma, Junli; Zhang, Sai; Deng, Ganlu; Wu, Xiaoling; He, Jingxuan; Pei, Haiping; Shen, Hong; Zeng, Shan

    2015-09-01

    Stage III colon cancer is currently treated as an entity with a unified therapeutic principle. The aim of the retrospective study is to explore the clinicopathological characteristics and outcomes of site-specific stage III colon cancers and the influences of tumor location on prognosis. Eight hundred ninety-five patients with stage III colon cancer treated with radical operation and subsequent adjuvant chemotherapy (5-fluorouracil/oxaliplatin) were divided into seven groups according to colon segment (cecum, ascending colon, hepatic flexure, transverse colon, splenic flexure, descending colon, and sigmoid colon). Expression of excision repair cross-complementing group 1 (ERCC1) and thymidylate synthase (TS) was examined by immunohistochemistry. We assessed if differences exist in patient characteristics and clinic outcomes between the seven groups. There were significant differences in tumor differentiation (P Cancer (AJCC) tumor-node-metastasis (TNM) stage (P colon. Cox regression analyses identified that tumor location was an independent prognostic factor for RFS and OS. Stage III colon cancer located proximally carried a poorer survival than that located distally. Different efficacies of FOLFOX adjuvant chemotherapy may be an important factor affecting survival of site-specific stage III colon cancers.

  3. Human Colon Cancer Cells Cultivated in Space

    Science.gov (United States)

    1995-01-01

    Within five days, bioreactor cultivated human colon cancer cells (shown) grown in Microgravity on the STS-70 mission in 1995, had grown 30 times the volume of the control specimens on Earth. The samples grown in space had a higher level of cellular organization and specialization. Because they more closely resemble tumors found in the body, microgravity grown cell cultures are ideal for research purposes.

  4. miR-345 in Metastatic Colorectal Cancer

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  5. Comparative effectiveness of primary tumor resection in patients with stage IV colon cancer.

    Science.gov (United States)

    Alawadi, Zeinab; Phatak, Uma R; Hu, Chung-Yuan; Bailey, Christina E; You, Y Nancy; Kao, Lillian S; Massarweh, Nader N; Feig, Barry W; Rodriguez-Bigas, Miguel A; Skibber, John M; Chang, George J

    2017-04-01

    Although the safety of combination chemotherapy without primary tumor resection (PTR) in patients with stage IV colon cancer has been established, questions remain regarding a potential survival benefit with PTR. The objective of this study was to compare mortality rates in patients who had colon cancer with unresectable metastases who did and did not undergo PTR. An observational cohort study was conducted among patients with unresectable metastatic colon cancer identified from the National Cancer Data Base (2003-2005). Multivariate Cox regression analyses with and without propensity score weighting (PSW) were performed to compare survival outcomes. Instrumental variable analysis, using the annual hospital-level PTR rate as the instrument, was used to account for treatment selection bias. To account for survivor treatment bias, in situations in which patients might die soon after diagnosis from different reasons, a landmark method was used. In the total cohort, 8641 of 15,154 patients (57%) underwent PTR, and 73.8% of those procedures (4972 of 6735) were at landmark. PTR was associated with a significant reduction in mortality using Cox regression (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.44-0.47) or PSW (HR, 0.46; 95% CI, 0. 44-0.49). However, instrumental variable analysis revealed a much smaller effect (relative mortality rate, 0.91; 95% CI, 0.87-0.96). Although a smaller benefit was observed with the landmark method using Cox regression (HR, 0.6; 95% CI, 0.55-0.64) and PSW (HR, 0.59; 95% CI, 0.54-0.64), instrumental variable analysis revealed no survival benefit (relative mortality rate, 0.97; 95% CI, 0.87-1.06). Among patients with unresectable metastatic colon cancer, after adjustment for confounder effects, PTR was not associated with improved survival compared with systemic chemotherapy; therefore, routine noncurative PTR is not recommended. Cancer 2017;123:1124-1133. © 2016 American Cancer Society. © 2016 American Cancer Society.

  6. Metastatic colorectal cancer responsive to regorafenib for 2 years: a case report.

    Science.gov (United States)

    Yoshino, Kenji; Manaka, Dai; Kudo, Ryo; Kanai, Shunpei; Mitsuoka, Eisei; Kanto, Satoshi; Hamasu, Shinya; Konishi, Sayuri; Nishitai, Ryuta

    2017-08-18

    Regorafenib is an oral multikinase inhibitor that has been demonstrated as clinically effective in patients with metastatic colorectal cancer in phase III studies. Although disease control was achieved in 40% of the pretreated patients with metastatic colorectal cancer in the pivotal studies, radiological response has rarely been reported. Severe adverse events associated with regorafenib are known to occur during the first and second courses of treatment. We present a case of a 62-year-old Japanese patient whose metastatic colorectal cancer has been responding to treatment with regorafenib for 2 years. A 54-year-old Japanese man visited our institute exhibiting general malaise, and he was diagnosed with ascending colon cancer in April 2006. He underwent right hemicolectomy, and the final staging was T3N0M0, stage II. After 19 months, pulmonary metastasis and anastomotic recurrences were detected, and a series of operations were performed to resect both metastatic lesions. After that, liver metastasis, a duodenal metastasis with right renal invasion, right adrenal metastasis, and para-aortic lymph node metastases were observed during follow-up, and chemotherapy and resection were performed. The patient had metastatic para-aortic lymph nodes after the fifth tumor resection and underwent multiple lines of chemotherapy in April 2014. Regorafenib monotherapy was started at 80 mg/day. Then, regorafenib was increased to 120 mg/day in the second cycle. Regorafenib monotherapy led to 60% tumor shrinkage within the initial 2 months, and the tumor further decreased in size over 4 months until it became unrecognizable on imaging studies. The clinical effects of regorafenib monotherapy have shown a partial response according to Response Evaluation Criteria in Solid Tumors criteria. No severe adverse events were observed, except for mild fatigue and hand-foot syndrome. The patient has received 24 courses of regorafenib over 2 years without exhibiting tumor progression. To the

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

    Science.gov (United States)

    2016-12-01

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

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

    DEFF Research Database (Denmark)

    Sölétormos, G; Nielsen, D; Schiøler, V

    1992-01-01

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

  9. Nutraceuticals as potential therapeutic agents for colon cancer: a review

    Directory of Open Access Journals (Sweden)

    Palaniselvam Kuppusamy

    2014-06-01

    Full Text Available Colon cancer is a world-wide health problem and the second-most dangerous type of cancer, affecting both men and women. The modern diet and lifestyles, with high meat consumption and excessive alcohol use, along with limited physical activity has led to an increasing mortality rate for colon cancer worldwide. As a result, there is a need to develop novel and environmentally benign drug therapies for colon cancer. Currently, nutraceuticals play an increasingly important role in the treatment of various chronic diseases such as colon cancer, diabetes and Alzheimer׳s disease. Nutraceuticals are derived from various natural sources such as medicinal plants, marine organisms, vegetables and fruits. Nutraceuticals have shown the potential to reduce the risk of colon cancer and slow its progression. These dietary substances target different molecular aspects of colon cancer development. Accordingly, this review briefly discusses the medicinal importance of nutraceuticals and their ability to reduce the risk of colorectal carcinogenesis.

  10. Nutraceuticals as potential therapeutic agents for colon cancer: a review.

    Science.gov (United States)

    Kuppusamy, Palaniselvam; Yusoff, Mashitah M; Maniam, Gaanty Pragas; Ichwan, Solachuddin Jauhari Arief; Soundharrajan, Ilavenil; Govindan, Natanamurugaraj

    2014-06-01

    Colon cancer is a world-wide health problem and the second-most dangerous type of cancer, affecting both men and women. The modern diet and lifestyles, with high meat consumption and excessive alcohol use, along with limited physical activity has led to an increasing mortality rate for colon cancer worldwide. As a result, there is a need to develop novel and environmentally benign drug therapies for colon cancer. Currently, nutraceuticals play an increasingly important role in the treatment of various chronic diseases such as colon cancer, diabetes and Alzheimer׳s disease. Nutraceuticals are derived from various natural sources such as medicinal plants, marine organisms, vegetables and fruits. Nutraceuticals have shown the potential to reduce the risk of colon cancer and slow its progression. These dietary substances target different molecular aspects of colon cancer development. Accordingly, this review briefly discusses the medicinal importance of nutraceuticals and their ability to reduce the risk of colorectal carcinogenesis.

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

    Science.gov (United States)

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

    2013-02-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

    Wei, Shi; Siegal, Gene P

    2017-03-01

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

  14. Colorectal (Colon) Cancer: Questions to Ask Your Doctor

    Science.gov (United States)

    ... The CDC Cancel Submit Search The CDC Colorectal (Colon) Cancer Note: Javascript is disabled or is not supported ... Cancer Home Questions to Ask Your Doctor About Colorectal Cancer Language: English Español (Spanish) Recommend on Facebook Tweet ...

  15. 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

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

    DEFF Research Database (Denmark)

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

    1993-01-01

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

  17. Surgical resection of synchronously metastatic adrenocortical cancer.

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

    2018-03-05

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

  19. Study of Endothelin-1 and Vascular Endothelial Growth Factor in Patients with Cancer Colon

    International Nuclear Information System (INIS)

    ABDEL-GAWAD, I.A.; HASSANEIN, H.M.R.; BAHGAT, N.A.; ABDEL SATTAR, M.A.; EL-SISSY, A.H.; ALTAWEEL, M.A.; HELAL, A.M.

    2008-01-01

    Purpose: The levels of endothelin-1 and VEGF were evaluated in the sera of newly diagnosed patients with cancer colon and were compared with the routinely used tumor markers; CEA and CA19.9. Their relations with some prognostic factors of cancer colon were also investigated. Subjects and Methods: The study included 48 patients with cancer colon and 20 apparently healthy volunteers as a control group. Patients were 23 males and 25 females with age range from 18 to 71 years (mean = 47±1.8). Both serum and plasma samples were obtained from patients and controls. Results: Six percent of patients had grade 1 tumors, 77% had grade 2 and 17% had grade 3 disease. As regard to the stage, 52% of patients were stage II, 35.5% were stage III, while 12.5% were stage IV. Liver metastasis was present in 12.5%, while 35% showed lymph node metastasis. The VEGF, endothelin-1, CA 19.9 and CEA were significantly higher in the cancer colon patients than in control groups (p-value <0.001, 0.006, <0.001 and <0.001; respectively). Plasma level of endothelin-1 and serum level of VEGF showed significantly higher levels in advanced stages of the disease (p value <0 .001) and in presence of liver metastasis (p value <0.001 and 0.002 respectively), while VEGF showed significant result when compared with the grade (p value=0.032). In this study, when comparing the levels of plasma endothelin-1 and serum VEGF between the metastatic, non-metastatic liver patients of the cancer colon group and the control group, the comparison was statistically significant for both markers (p<0.001). Endothelin-1 and VEGF showed significant positive correlation (r=0.77 and p-value <0.0001). Serum VEGF and CA 19.9 showed good sensitivities which were not different (97.9% and 87.5%; respectively), while there was no significant difference between VEGF, CA 19.9 and CEA with respect to specificities (100%, 90% and 100% respectively). Conclusion: Both endothelin-1 and VEGF may be used for early detection of liver

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

    Science.gov (United States)

    Zhou, Feifan

    2016-03-01

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

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

    Science.gov (United States)

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

    2017-08-01

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

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

    Science.gov (United States)

    Garg, Shivani; Mulki, Ramzi; Sher, Daniel

    2016-03-08

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

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

    Directory of Open Access Journals (Sweden)

    Abdolhassan Talaiezadeh

    2015-06-01

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

  4. Evaluation of liquid biopsies for detection of emerging mutated genes in metastatic colorectal cancer.

    Science.gov (United States)

    Furuki, Hiroyasu; Yamada, Takeshi; Takahashi, Goro; Iwai, Takuma; Koizumi, Michihiro; Shinji, Seiichi; Yokoyama, Yasuyuki; Takeda, Kohki; Taniai, Nobuhiko; Uchida, Eiji

    2018-02-02

    Detection of gene mutations is important for planning molecular targeted therapy. Although most gene mutations are concordant between primary colon cancers and their liver metastases, new mutations can emerge in metastases. The liquid biopsy is a newly developed, gene analytic method to detect mutations in metastatic tumors. In this prospective study, we evaluated the applicability of liquid biopsies in the detection of mutations in primary and metastatic tumors. We included 22 patients with liver metastases from colorectal cancer and extracted DNA from primary colorectal tumors, metastatic liver tumors, and peripheral blood (liquid biopsy). Next-generation sequencing (NGS) and digital PCR were performed to detect mutations in these three sample types. We found a total of 36 different mutations in samples from primary tumors, liver metastases, and liquid biopsies using NGS. Twenty-eight of these mutations were found in all three types of samples, whereas liquid biopsy did not identify four mutations that had been found in both primary tumors and liver metastases, but did identify four mutations that were found in liver tumors but not in primary tumors. The sensitivity of liquid biopsies for detecting mutations in liver metastases was 64% (23/36) using NGS and 89% (32/36, P = 0.02) using dPCR. The specificities of NGS and dPCR were 100% (23/23) and 100% (32/32), respectively. Emerging mutations, which are not found in primary tumors, can be detected in their metastases and liquid biopsies. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  5. Soluble interleukin 6 receptor (sIL-6R) mediates colonic tumor cell adherence to the vascular endothelium: a mechanism for metastatic initiation?

    LENUS (Irish Health Repository)

    Dowdall, J F

    2012-02-03

    The mechanisms by which surgery increases metastatic proliferation remain poorly characterized, although endotoxin and immunocytes play a role. Recent evidence suggests that endothelial adherence of tumor cells may be important in the formation of metastases. Soluble receptors of interleukin-6 (sIL-6R) shed by activated neutrophils exert IL-6 effects on endothelial cells, which are unresponsive under normal circumstances. This study examined the hypothesis that sIL-6R released by surgical stress increases tumor cell adherence to the endothelium. Neutrophils (PMN) were stimulated with lipopolysaccharide, C-reactive protein (CRP), and tumor necrosis factor-alpha. Soluble IL-6R release was measured by enzyme-linked immunosorbent assay. Colonic tumor cells transfected with green fluorescent protein and endothelial cells were exposed to sIL-6R, and tumor cell adherence and transmigration were measured by fluorescence microscopy. Basal release of sIL-6R from PMN was 44.7 +\\/- 8.2 pg\\/ml at 60 min. This was significantly increased by endotoxin and CRP (131 +\\/- 16.8 and 84.1 +\\/- 5.3, respectively; both P < 0.05). However, tumor necrosis factor-alpha did not significantly alter sIL-6R release. Endothelial and tumor cell exposure to sIL-6R increased tumor cell adherence by 71.3% within 2 h but did not significantly increase transmigration, even at 6 h. Mediators of surgical stress induce neutrophil release of a soluble receptor for IL-6 that enhances colon cancer cell endothelial adherence. Since adherence to the endothelium is now considered to be a key event in metastatic genesis, these findings have important implications for colon cancer treatment strategies.

  6. [A case of transverse colon cancer mimicking urachal cancer].

    Science.gov (United States)

    Nishimura, Taku; Inoue, Ryo; Kondo, Junya; Nagashima, Yukiko; Okada, Toshimasa; Nakamura, Mitsuo; Sakata, Koichiro; Yamaguchi, Shiro; Setoguchi, Mihoko

    2013-11-01

    A 55-year-old man was admitted to our hospital because of abdominal distension. Computed tomography revealed an abscess in the anterior abdominal wall and invasion of the large intestine. Biopsy of the large intestine revealed adenocarcinoma. Immunohistochemically, the antigen expression profile of the tumor was positive for cytokeratin 7, cytokeratin 903 (34βE12), and cytokeratin 20. We diagnosed the tumor as urachal cancer and performed surgery. Examination of the resected specimen showed that the tumor was located in the transverse colon. Finally, the patient was diagnosed as having transverse colon cancer with urachal abscess.

  7. 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.

  8. Hormone therapy in metastatic prostate cancer

    Directory of Open Access Journals (Sweden)

    Jebelameli P

    1997-09-01

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

  9. Increased colon cancer risk after severe Salmonella infection

    OpenAIRE

    Mughini-Gras, Lapo; Schaapveld, Michael; Kramers, Jolanda; Mooij, Sofie; Neefjes-Borst, E. Andra; van Pelt, Wilfrid; Neefjes, Jacques

    2018-01-01

    Background Colon cancer constitutes one of the most frequent malignancies. Previous studies showed that Salmonella manipulates host cell signaling pathways and that Salmonella Typhimurium infection facilitates colon cancer development in genetically predisposed mice. This epidemiological study examined whether severe Salmonella infection, usually acquired from contaminated food, is associated with increased colon cancer risk in humans. Methods and findings We performed a nationwide registry-b...

  10. Transverse colon cancer with Krukenberg tumor : A case report

    OpenAIRE

    東門, 敦子; 松原, 洋孝; 下地, 英明; 伊佐, 勉; 濱安, 俊吾; 仲地, 厚; 宮里, 浩; 白石, 祐之; 武藤, 良弘; Tomon, Atsuko; Matsubara, Hirotaka; Shimoji, Hideaki; Isa, Tsutomu; Nakachi, Atsushi; Miyazato, Hiroshi

    1999-01-01

    A case of Krukenberg tumor in a 30-year-old woman with transverse colon cancer is reported herein. The patient was found to have bilateral ovarian tumors and abnormal elevation of serum CEA at a community hospital. Subsequently, she was referred to the University Hospital for further work. Diagnostic examinations including US, CT and colonoscopy demonstrated transverse colon cancer and bilateral ovarian tumors. Exploratory laparotomy showed the growth of transverse colon cancer over the perit...

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

    Science.gov (United States)

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

    2017-09-01

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

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

    Directory of Open Access Journals (Sweden)

    Chung-Chen Wang

    2014-12-01

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

  13. Hereditary colon Cancer: Recommendations for prevention

    International Nuclear Information System (INIS)

    Sarroca, C.

    2004-01-01

    Prevention in individuals with hereditary risk of colon cancer, is subject to clinical and molecular facts because their behavior differs to sporadic cancer. Hereditary cancer diseases affecting the colon in particular linked to other locations or that are associated with pre-cancer (polyps, osteoma s, lentigines) phenotypic markers represent a dissimilar to those who present directly in colorectal cancer status or associated conditions. In the first, the presence of previous injury (phenotypes) allows us to identify, while the latter is essential to have other diagnostic pathway (genotypes) .The location of genomic alterations manages to delve into the problem and identify those who will develop disease. The perspective will be different in the general population and those who do not carry mutations in terms suggestions for prevention, both primary and secondary. Not always the mutation is detected and in these high-risk situations, the clinic is sovereign and agrees to keep all members of these events surveillance strict about not being able to characterize those who are carriers of alterations and our condition is different in the proposition of preventive attitudes: set from when control about which organs and often starts, suffer because of accelerated carcinogenesis. The presentation is focused on populations at increased risk of cancer colorectal, regarding the management of the suggestions for primary prevention, secondary prevention while analyzing the early diagnosis of the disease and the suggestion of treatment, compared to the general population management. Primary prevention, including chemo prevention are described. While in secondary prevention is emphasized to management time tracking, optimization diagnostics according to the pathology suspected, the most common therapeutic approaches and findings relating prophylactic surgery

  14. Photodynamic therapy for metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    E. V. Horanskaya

    2014-01-01

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

  15. Radioembolization for primary and metastatic liver cancer.

    Science.gov (United States)

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

    2011-10-01

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

  16. Depression in older women with metastatic breast cancer.

    Science.gov (United States)

    D'Ambruoso, Sarah F

    2014-12-01

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

  17. Third-line therapy for metastatic colorectal cancer

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  18. Prognostic significance of unintentional body weight loss in colon cancer patients.

    Science.gov (United States)

    Kuo, Yi-Hung; Shi, Chung-Sheng; Huang, Cheng Yi; Huang, Yun-Ching; Chin, Chih-Chien

    2018-04-01

    The aim of the present study was to investigate whether unintentional body weight loss (BWL) provides additional clinical information in terms of tumor progression and prognosis in non-metastatic colon cancer. In the present study, a total of 2,406 consecutive colon cancer patients without metastasis were retrospectively enrolled. Unintentional BWL was defined as loss of >5% of body weight within the last 6-12 months, or defined subjectively upon fulfillment of at least two of the following: Evidence of change in clothing size and corroboration of the reported weight loss by family or friend. This category was recorded as present ('with') or absent ('without'). Logistic regression analysis was performed to determine the correlation between BWL and the tumor characteristics and post-operative outcomes of patients with colon cancer. The Cox regression model was used to determine the association of BWL with long-term survival of colon cancer patients. A significant association between BWL and tumor location [right vs. left: Odds ratio (OR)=1.62; Pcolon cancer is not just a symptom, but it is also correlated with tumor location, size and depth, and is a prognostic factor for poor outcomes including overall survival and tumor relapse.

  19. Characterization of KRAS Rearrangements in Metastatic Prostate Cancer

    Science.gov (United States)

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

    2011-01-01

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

  20. Identification of a Novel TGFβ/PKA Signaling Transduceome in Mediating Control of Cell Survival and Metastasis in Colon Cancer

    Science.gov (United States)

    Rajput, Ashwani; Teggart, Carol A.; Brattain, Lisa E.; Weber, Hannah R.; Chowdhury, Aparajita; Brattain, Michael G.

    2011-01-01

    Background Understanding drivers for metastasis in human cancer is important for potential development of therapies to treat metastases. The role of loss of TGFβ tumor suppressor activities in the metastatic process is essentially unknown. Methodology/Principal Findings Utilizing in vitro and in vivo techniques, we have shown that loss of TGFβ tumor suppressor signaling is necessary to allow the last step of the metastatic process - colonization of the metastatic site. This work demonstrates for the first time that TGFβ receptor reconstitution leads to decreased metastatic colonization. Moreover, we have identified a novel TGFβ/PKA tumor suppressor pathway that acts directly on a known cell survival mechanism that responds to stress with the survivin/XIAP dependent inhibition of caspases that effect apoptosis. The linkage between the TGFβ/PKA transduceome signaling and control of metastasis through induction of cell death was shown by TGFβ receptor restoration with reactivation of the TGFβ/PKA pathway in receptor deficient metastatic colon cancer cells leading to control of aberrant cell survival. Conclusion/Significance This work impacts our understanding of the possible mechanisms that are critical to the growth and maintenance of metastases as well as understanding of a novel TGFβ function as a metastatic suppressor. These results raise the possibility that regeneration of attenuated TGFβ signaling would be an effective target in the treatment of metastasis. Our work indicates the clinical potential for developing anti-metastasis therapy based on inhibition of this very important aberrant cell survival mechanism by the multifaceted TGFβ/PKA transduceome induced pathway. Development of effective treatments for metastatic disease is a pressing need since metastases are the major cause of death in solid tumors. PMID:21559296

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

    International Nuclear Information System (INIS)

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

    1983-01-01

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

  2. Treatment of metastatic colorectal cancer: focus on panitumumab

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  3. Dietary Patterns and Colon Cancer Risk in Whites and African Americans in the North Carolina Colon Cancer Study

    OpenAIRE

    Satia, Jessie A.; Tseng, Marilyn; Galanko, Joseph A.; Martin, Christopher; Sandler, Robert S.

    2009-01-01

    We examined associations of dietary patterns with colon cancer risk in African Americans and Whites from a case-control study in North Carolina. Incident colon cancer cases, 40 to 80 yr (n = 636), and matched controls (n = 1,042) were interviewed in person to elicit information on potential colon cancer risk factors. A validated food frequency questionnaire adapted to include regional foods captured diet over the year prior to diagnosis (cases) or interview date (controls). Three meaningful i...

  4. Diet, Genes, and Microbes: Complexities of Colon Cancer Prevention

    Science.gov (United States)

    Birt, Diane F.; Phillips, Gregory J.

    2013-01-01

    Colorectal cancer is one of the leading causes of cancer-related deaths in the United States, and generally, as countries climb the economic ladder, their rates of colon cancer increase. Colon cancer was an early disease where key genetic mutations were identified as important in disease progression, and there is considerable interest in determining whether specific mutations sensitize the colon to cancer prevention strategies. Epidemiological studies have revealed that fiber- and vegetable-rich diets and physical activity are associated with reduced rates of colon cancer, while consumption of red and processed meat, or alcoholic beverages, and overconsumption as reflected in obesity are associated with increased rates. Animal studies have probed these effects and suggested directions for further refinement of diet in colon cancer prevention. Recently a central role for the microorganisms in the gastrointestinal tract in colon cancer development is being probed, and it is hypothesized that the microbes may integrate diet and host genetics in the etiology of the disease. This review provides background on dietary, genetic, and microbial impacts on colon cancer and describes an ongoing project using rodent models to assess the ability of digestion-resistant starch in the integration of these factors with the goal of furthering colon cancer prevention. PMID:24129759

  5. Diet, genes, and microbes: complexities of colon cancer prevention.

    Science.gov (United States)

    Birt, Diane F; Phillips, Gregory J

    2014-01-01

    Colorectal cancer is one of the leading causes of cancer-related deaths in the United States, and generally, as countries climb the economic ladder, their rates of colon cancer increase. Colon cancer was an early disease where key genetic mutations were identified as important in disease progression, and there is considerable interest in determining whether specific mutations sensitize the colon to cancer prevention strategies. Epidemiological studies have revealed that fiber- and vegetable-rich diets and physical activity are associated with reduced rates of colon cancer, while consumption of red and processed meat, or alcoholic beverages, and overconsumption as reflected in obesity are associated with increased rates. Animal studies have probed these effects and suggested directions for further refinement of diet in colon cancer prevention. Recently a central role for the microorganisms in the gastrointestinal tract in colon cancer development is being probed, and it is hypothesized that the microbes may integrate diet and host genetics in the etiology of the disease. This review provides background on dietary, genetic, and microbial impacts on colon cancer and describes an ongoing project using rodent models to assess the ability of digestion-resistant starch in the integration of these factors with the goal of furthering colon cancer prevention.

  6. 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

  7. Cost-utility analysis of adjuvant chemotherapy in patients with stage III colon cancer in Thailand.

    Science.gov (United States)

    Lerdkiattikorn, Panattharin; Chaikledkaew, Usa; Lausoontornsiri, Wirote; Chindavijak, Somjin; Khuhaprema, Thirawud; Tantai, Narisa; Teerawattananon, Yot

    2015-01-01

    In Thailand, there has been no economic evaluation study of adjuvant chemotherapy for stage III colon cancer patients after resection. This study aims to evaluate the cost-utility of all chemotherapy regimens currently used in Thailand compared with the adjuvant 5-fluorouracil/leucovorin (5-FU/LV) plus capecitabine as the first-line therapy for metastatic disease in patients with stage III colon cancer after resection. A cost-utility analysis was performed to estimate the relevant lifetime costs and health outcomes of chemotherapy regimens based on a societal perspective using a Markov model. The results suggested that the adjuvant 5-FU/LV plus capecitabine as the first-line therapy for metastatic disease would be the most cost-effective chemotherapy. The adjuvant FOLFOX and FOLFIRI as the first-line treatment for metastatic disease would be cost-effective with an incremental cost-effectiveness ratio of 299,365 Thai baht per QALY gained based on a societal perspective if both prices of FOLFOX and FOLFIRI were decreased by 40%.

  8. Endoscopic Localization of Colon Cancer Is Frequently Inaccurate.

    Science.gov (United States)

    Nayor, Jennifer; Rotman, Stephen R; Chan, Walter W; Goldberg, Joel E; Saltzman, John R

    2017-08-01

    Colonoscopic location of a tumor can influence both the surgical procedure choice and overall treatment strategy. To determine the accuracy of colonoscopy in determining the location of colon cancer compared to surgical localization and to elucidate factors that predict discordant colon cancer localization. We conducted a retrospective cross-sectional study of colon cancers diagnosed on colonoscopy at two academic tertiary-care hospitals and two affiliated community hospitals from 2012 to 2014. Colon cancer location was obtained from the endoscopic and surgical pathology reports and characterized by colon segment. We collected data on patient demographics, tumor characteristics, endoscopic procedure characteristics, surgery planned, and surgery performed. Univariate analyses using Chi-squared test and multivariate analysis using forward stepwise logistic regression were performed to determine factors that predict discordant colon cancer localization. There were 110 colon cancer cases identified during the study period. Inaccurate endoscopic colon cancer localization was found in 29% (32/110) of cases. These included 14 cases (12.7%) that were discordant by more than one colonic segment and three cases where the presurgical planned procedure was significantly changed at the time of surgery. On univariate analyses, right-sided colon lesions were associated with increased inaccuracy (43.8 vs 24.4%, p = 0.04). On multivariate analysis, right-sided colon lesions remained independently associated with inaccuracy (OR 1.74, 95% CI 1.03-2.93, p = 0.04). Colon cancer location as determined by colonoscopy is often inaccurate, which can result in intraoperative changes to surgical management, particularly in the right colon.

  9. Inhibitory effect of gene combination in a mouse model of colon cancer with liver metastasis.

    Science.gov (United States)

    DU, Tong; Niu, Hongxin

    2014-09-01

    The aim of the present study was to establish an animal liver metastasis model with human colon cancer and investigate the inhibitory effect of the wild type (WT) p53 gene combined with thymidine kinase/ganciclovir (TK/GCV) and cytosine deaminase/5-fluorocytosine (CD/5-FC) systems on liver metastasis of colon cancer. A nude mouse liver metastasis model with human colon cancer was established via a spleen cultivation method. A total of 32 nude mice were randomly divided into four groups, each group with eight mice. Group 1 mice received splenic injections of SW480 cells (control group), while group 2 mice were injected with SW480/p53 cells in the spleen. Group 3 mice were administered splenic injections of SW480/TK-CD cells, and GCV and 5-FC were injected into the abdominal cavity. Finally, group 4 mice received splenic injections of SW480/p53 cells mixed in equal proportion with SW480/TK-CD cells, as well as GCV and 5-FC injections in the abdominal cavity. These cells described were constructed in our laboratory and other laboratories. The number of liver metastatic tumors, the liver metastasis rate, conventional pathology, electron microscopy and other indicators in the nude mice of each group were compared and observed. The nude mouse liver metastasis model with human colon cancer was successfully established; the liver metastasis rate of the control group was 100%. The results demonstrated that the rate of liver metastasis in the nude mice in each treatment group decreased, as well as the average number of liver metastatic tumors. Furthermore, the effect of the treatment group with genetic combination (group 4) was the most effective, demonstrating that WTp53 had a synergistic effect with TK/GCV and CD/5-FC. Therefore, the present study successfully established a mouse model of liver metastasis with colon cancer by injecting human colon cancer cells in the spleen. Combined gene therapy was shown to have a synergistic effect, which effectively inhibited the

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

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

    OpenAIRE

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

    2015-01-01

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

  12. Safety and Efficacy of Combined Yttrium 90 Resin Radioembolization with Aflibercept and FOLFIRI in a Patient with Metastatic Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Andre De Souza

    2015-01-01

    Full Text Available Background. When associated with isolated four or fewer liver foci, metastatic colorectal cancer is amenable to surgical resection. Alternative therapeutic methods for isolated liver metastases include radioembolization with yttrium 90 (Y90 and transarterial chemoembolization (TACE. We present here a case of a patient with two sites of liver metastatic disease from colorectal cancer who underwent Y90 radioembolization combined with aflibercept and FOLFIRI. Case Report. A 56-year-old female with history of bilateral breast cancer and metastatic colon cancer with prior hemicolectomy and 4 previous chemotherapy regimens developed liver metastasis. She was started on aflibercept and FOLFIRI and concurrently underwent two treatments of radioembolization with Y90, initially targeting the largest right lobe tumor, and then a subsequent treatment targeting the smaller left lobe tumor with retreatment of the right lobe tumor. Her liver metastases exhibited partial response on imaging utilizing the modified RECIST criteria. Interestingly, the patient CEA levels decreased after the procedure. Discussion. This is the first reported case of a patient managed with radioembolization with Y90 combined with aflibercept, an anti-VEGF treatment, and FOLFIRI. An ongoing randomized clinical trial aims to define the role of combined targeted therapy and chemotherapy with radioembolization with Y90.

  13. Metastatic carcinoma of the urinary bladder in a 67-year-old female with underlying triple primary cancers

    Directory of Open Access Journals (Sweden)

    Chia-Yen Hung

    2016-06-01

    A 67-year-old Taiwanese female presented to our institution in November 1997 with gastric signet ring cell carcinoma, pT2N0M0, status post subtotal gastrectomy. In February 2003 she was diagnosed with left breast invasive lobular carcinoma status post modified radical mastectomy, pT2N2M0. Further examination in January 2005 revealed proximal transverse colon cancer, Dukes' C2, with status post right hemicolectomy. She achieved disease-free status from all three malignancies after surgical resection and adjuvant chemotherapy for breast and colon cancers sequentially. In November 2011, she complained about sudden onset of gross hematuria for several days. Diagnostic cystoscopy showed a mass lesion over her urinary bladder. Cystoscope-assisted biopsy showed metastatic poorly differentiated adenocarcinoma with signet ring appearance. Herein we have discussed the pathologic role in the diagnosis of metastatic tumor involving a patient with multiple primary cancers. We also explored the epidemiologic risk and potential causal mechanism of patients with multiple primary cancers.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2018-04-01

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

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

    Science.gov (United States)

    2017-09-05

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

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

    National Research Council Canada - National Science Library

    Thiagalingam, Sam

    2004-01-01

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

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

    DEFF Research Database (Denmark)

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

    1991-01-01

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

  19. Opposite effects of microchimerism on breast and colon cancer

    DEFF Research Database (Denmark)

    Kamper-Jørgensen, Mads; Biggar, Robert J; Tjønneland, Anne

    2012-01-01

    data were obtained during 1993-1997 when all women were cancer-free. In 2006 all women were followed up for incident breast and colon cancer in national registers. In blinded analyses, we analysed buffy coat DNA for Y chromosome (DYS14) as a marker of male microchimerism. RESULTS: We detected male...... microchimerism in 70% of 272 cancer-free women, 40% of 89 women who later developed breast cancer, and 90% of 67 women who later developed colon cancer. The corresponding odds ratios were 0.30 (95% confidence interval (CI) 0.17-0.52) for breast, and 3.9 (95%CI 1.6-9.5) for colon cancer. CONCLUSION: Detection...... of male microchimerism was strongly associated with reduced risk of developing breast cancer and also the increased risk of developing colon cancer. Confirmatory findings based on an improved study design, failure to identify important confounders and the strength of the associations lead us to believe...

  20. Microchimerism and survival after breast and colon cancer diagnosis

    DEFF Research Database (Denmark)

    Kamper-Jørgensen, Mads

    2012-01-01

    Recently, we reported microchimerism to be oppositely associated with maternal breast and colon cancer. In women with a blood test positive for male microchimerism the risk of breast cancer development was reduced to one third, whereas the risk of colon cancer was elevated 4-fold. In this article...... addendum, I report the survival of cases in the original study after being diagnosed with cancer. Despite small numbers, the analysis suggests that microchimerism may be positively associated with survival after breast and maybe colon cancer diagnosis. Despite the findings on colon cancer in our original...... report, I speculate whether microchimerism could have a general beneficial role in cancer, which in some sites may not be evident because an allogeneic maternal immune reaction hastens cancer development....

  1. Rectal and colon cancer : Not just a different anatomic site

    NARCIS (Netherlands)

    Tamas, K.; Walenkamp, A. M. E.; de Vries, E. G. E.; van Vugt, M. A. T. M.; Beets-Tan, R. G.; van Etten, B.; de Groot, D. J. A.; Hospers, G. A. P.

    Due to differences in anatomy, primary rectal and colon cancer require different staging procedures, different neo-adjuvant treatment and different surgical approaches. For example, neoadjuvant radiotherapy or chemoradiotherapy is administered solely for rectal cancer. Neoadjuvant therapy and total

  2. Activating transcription factor-3 (ATF3) functions as a tumor suppressor in colon cancer and is up-regulated upon heat-shock protein 90 (Hsp90) inhibition

    International Nuclear Information System (INIS)

    Hackl, Christina; Stoeltzing, Oliver; Lang, Sven A; Moser, Christian; Mori, Akira; Fichtner-Feigl, Stefan; Hellerbrand, Claus; Dietmeier, Wolfgang; Schlitt, Hans J; Geissler, Edward K

    2010-01-01

    Activating transcription factor-3 (ATF3) is involved in the complex process of cellular stress response. However, its exact role in cancer is discussed controversially because both tumor suppressive and oncogenic effects have been described. Here we followed-up on our previous observation that inhibition of Hsp90 may increase ATF3 expression and sought to determine the role of ATF3 in colon cancer. Regulation of ATF3 was determined in cancer cells using signaling inhibitors and a heat-shock protein-90 (Hsp90) antagonist. Human HCT116 cancer cells were stably transfected with an ATF3-shRNA or a luciferase-shRNA expression plasmid and alterations in cell motility were assessed in migration assays. The impact of ATF3 down-regulation on cancer growth and metastasis were investigated in a subcutaneous tumor model, a model of hepatic tumor growth and in a model of peritoneal carcinomatosis. Human colon cancer tissues were analyzed for ATF3 expression. The results show that therapeutic Hsp90 inhibition substantially up-regulates the expression of ATF3 in various cancer cells, including colon, gastric and pancreatic cancer. This effect was evident both in vitro and in vivo. RNAi mediated knock-down of ATF3 in HCT116 colon cancer cells significantly increased cancer cell migration in vitro. Moreover, in xenogenic mouse models, ATF3 knock-down promoted subcutaneous tumor growth and hepatic metastasis, as well as peritoneal carcinomatosis. Importantly, ATF3 expression was lower in human colon cancer specimens, as compared to corresponding normal surrounding tissues, suggesting that ATF3 may represent a down-regulated tumor suppressor in colon cancer. In conclusion, ATF3 down-regulation in colon cancer promotes tumor growth and metastasis. Considering that blocking Hsp90 induces ATF3 expression, Hsp90 inhibition may represent a valid strategy to treat metastatic colon cancer by up-regulating this anti-metastatic transcription factor

  3. Gene Signature in Sessile Serrated Polyps Identifies Colon Cancer Subtype

    Science.gov (United States)

    Kanth, Priyanka; Bronner, Mary P.; Boucher, Kenneth M.; Burt, Randall W.; Neklason, Deborah W.; Hagedorn, Curt H.; Delker, Don A.

    2016-01-01

    Sessile serrated colon adenoma/polyps (SSA/Ps) are found during routine screening colonoscopy and may account for 20–30% of colon cancers. However, differentiating SSA/Ps from hyperplastic polyps (HP) with little risk of cancer is challenging and complementary molecular markers are needed. Additionally, the molecular mechanisms of colon cancer development from SSA/Ps are poorly understood. RNA sequencing was performed on 21 SSA/Ps, 10 HPs, 10 adenomas, 21 uninvolved colon and 20 control colon specimens. Differential expression and leave-one-out cross validation methods were used to define a unique gene signature of SSA/Ps. Our SSA/P gene signature was evaluated in colon cancer RNA-Seq data from The Cancer Genome Atlas (TCGA) to identify a subtype of colon cancers that may develop from SSA/Ps. A total of 1422 differentially expressed genes were found in SSA/Ps relative to controls. Serrated polyposis syndrome (n=12) and sporadic SSA/Ps (n=9) exhibited almost complete (96%) gene overlap. A 51-gene panel in SSA/P showed similar expression in a subset of TCGA colon cancers with high microsatellite instability (MSI-H). A smaller seven-gene panel showed high sensitivity and specificity in identifying BRAF mutant, CpG island methylator phenotype high (CIMP-H) and MLH1 silenced colon cancers. We describe a unique gene signature in SSA/Ps that identifies a subset of colon cancers likely to develop through the serrated pathway. These gene panels may be utilized for improved differentiation of SSA/Ps from HPs and provide insights into novel molecular pathways altered in colon cancer arising from the serrated pathway. PMID:27026680

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

    Science.gov (United States)

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

    2017-04-01

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

  5. Collaborative Model for Acceleration of Individualized Therapy of Colon Cancer

    Science.gov (United States)

    2015-12-01

    Award Number: W81XWH-11-1-0527 TITLE: Collaborative Model for Acceleration of Individualized Therapy of Colon Cancer PRINCIPAL INVESTIGATOR: Aik...AND SUBTITLE 5a. CONTRACT NUMBER Collaborative Model for Acceleration of Individualized Therapy of Colon Cancer 5b. GRANT NUMBER W81XWH-11-1-0527 5c...neck, lung, breast and colon malignancies, among others. In this preclinical study we assessed the antitumor effects of the novel Plk inhibitor, TAK

  6. Prophylactic effects of triptolide on colon cancer development in ...

    African Journals Online (AJOL)

    Colon cancer is one of the most commonly diagnosed causes of premature mortality in people of developed countries [1-3]. Tumors present in the lining of the colon are the main cause of deaths associated with cancer in the. United States [4]. Adoption of westernized dietary patterns has greatly increased the incidence of ...

  7. Mechanisms of oncogenesis in colon versus rectal cancer.

    NARCIS (Netherlands)

    Kapiteijn, E.; Liefers, G.J.; Los, L.C.; Meershoek-Klein Kranenbarg, E.; Hermans, J.; Tollenaar, R.A.E.M.; Moriya, Y.; Veld, C.J.H. van de; Krieken, J.H.J.M. van

    2001-01-01

    Observations support the theory that development of left- and right-sided colorectal cancers may involve different mechanisms. This study investigated different genes involved in oncogenesis of colon and rectal cancers and analysed their prognostic value. The study group comprised 35 colon and 42

  8. Screening and Management of Colon Polyp as Colorectal Cancer Prevention

    Directory of Open Access Journals (Sweden)

    Gratcia Ayundini

    2016-09-01

    Full Text Available Colon polyp is a term used for abnormality from bulging tissue above surrounding colonic mucosal layer. Adenoma polyp was the commonly found polyp that progress to colorectal cancer. Most of those patients was asymptomatic. Undetected and unmanaged polyp was a risk factors of colorectal cancer event.

  9. Prophylactic effects of triptolide on colon cancer development in ...

    African Journals Online (AJOL)

    Purpose: To investigate effects of triptolide on colon cancer cell growth and its capacity to prevent tumor development in an azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model of colon cancer. Methods: HCT116 cell viability and migration potential were assessed. Control and AOM/DSS-treated mice (with and ...

  10. Clinical issues in the surgical treatment of colon cancer

    NARCIS (Netherlands)

    Amri, R.

    2015-01-01

    More than half of colon cancer patients will eventually die of their disease. Early detection is crucial to maximize chances of cure, as five-year survival can range from 97% to as low as 8% depending on disease stage at diagnosis. Since colon cancer is associated with both old age and obesity,

  11. Short-term outcomes following laparoscopic resection for colon cancer.

    LENUS (Irish Health Repository)

    Kavanagh, Dara O

    2011-03-01

    Laparoscopic resection for colon cancer has been proven to have a similar oncological efficacy compared to open resection. Despite this, it is performed by a minority of colorectal surgeons. The aim of our study was to evaluate the short-term clinical, oncological and survival outcomes in all patients undergoing laparoscopic resection for colon cancer.

  12. Combination of capecitabine and ludartin inhibits colon cancer ...

    African Journals Online (AJOL)

    Purpose: To investigate the efficacy of capecitabine and ludartin in the treatment of colon cancer in mice. Methods: Mice model of colon cancer was used in this study. Quantitative real-time polymerase chain reaction (Qrt-PCR) was used to quantify the expression of vascular endothelial growth factor (VEGF) mRNA.

  13. Role of phytochemicals in colon cancer prevention. A nutrigenomics approach

    NARCIS (Netherlands)

    Erk, van M.J.

    2004-01-01

    Specific food compounds, especially from fruits and vegetables, may protect against development of colon cancer. In this thesis effects and mechanisms of various phytochemicals in relation to colon cancer prevention were studied through application of large-scale gene expression profiling.

  14. Circulating cell-free DNA mutation patterns in early and late stage colon and pancreatic cancer.

    Science.gov (United States)

    Vietsch, Eveline E; Graham, Garrett T; McCutcheon, Justine N; Javaid, Aamir; Giaccone, Giuseppe; Marshall, John L; Wellstein, Anton

    2017-12-01

    Cancer is a heterogeneous disease harboring diverse subclonal populations that can be discriminated by their DNA mutations. Environmental pressure selects subclones that ultimately drive disease progression and tumor relapse. Circulating cell-free DNA (ccfDNA) can be used to approximate the mutational makeup of cancer lesions and can serve as a marker for monitoring disease progression at the molecular level without the need for invasively acquired samples from primary or metastatic lesions. This potential for molecular analysis makes ccfDNA attractive for the study of clonal evolution and for uncovering emerging therapeutic resistance or sensitivity. We assessed ccfDNA from colon and pancreatic adenocarcinoma patients using next generation sequencing of 56 cancer-associated genes at the time of primary resectable disease and metastatic progression and compared this to the mutational patterns of the primary tumor. 28%-47% of non-synonymous mutations in the primary tumors were also detected in the ccfDNA while 71%-78% mutations found in ccfDNA were not detected in the primary tumors. ccfDNA collected at the time of progression harbored 3-5 new mutations not detected in ccfDNA at the earlier collection time points. We conclude that incorporation of ccfDNA analysis provides crucial insights into the changing molecular makeup of progressive colon and pancreatic cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Australian contemporary management of synchronous metastatic colorectal cancer.

    Science.gov (United States)

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

    2018-01-01

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

  16. Differences in telomerase activity between colon and rectal cancer.

    Science.gov (United States)

    Ayiomamitis, Georgios D; Notas, George; Zaravinos, Apostolos; Zizi-Sermpetzoglou, Adamantia; Georgiadou, Maria; Sfakianaki, Ourania; Kouroumallis, Elias

    2014-06-01

    Colorectal cancer is one of the most common cancers and the third leading cause of cancer death in both sexes. The disease progresses as a multistep process and is associated with genetic alterations. One of the characteristic features of cancer is telomerase activation. We sought to evaluate the differences in telomerase activity between colon cancer and adjacent normal tissue and to correlate the differences in telomerase activity between different locations with clinicopathological factors and survival. Matched colon tumour samples and adjacent normal mucosa samples 10 cm away from the tumour were collected during colectomy. We assessed telomerase activity using real time polymerase chain reaction. Several pathological characteristics of tumours, including p53, Ki-67, p21, bcl2 and MLH1 expression were also studied. We collected samples from 49 patients. There was a significantly higher telomerase activity in colon cancer tissue than normal tissue. Adenocarcinomas of the right colon express significantly higher telomerase than left-side cancers. Colon cancers and their adjacent normal tissue had significantly more telomerase and were more positive to MLH1 than rectal cancers. The expression of p53 negatively correlated to telomerase activity and was linked to better patient survival. Colon and rectal cancers seem to have different telomerase and MLH1 profiles, and this could be another factor for their different biologic and clinical behaviour and progression. These results support the idea that the large bowel cannot be considered a uniform organ, at least in the biology of cancer.

  17. RACK1 downregulates levels of the pro-apoptotic protein Fem1b in apoptosis-resistant colon cancer cells.

    Science.gov (United States)

    Subauste, M Cecilia; Ventura-Holman, Tereza; Du, Liqin; Subauste, Jose S; Chan, Shing-Leng; Yu, Victor C; Maher, Joseph F

    2009-12-01

    Evasion of apoptosis plays an important role in colon cancer progression. Following loss of the Apc tumor suppressor gene in mice, the gene encoding Fem1b is upregulated early in neoplastic intestinal epithelium. Fem1b is a pro-apoptotic protein that interacts with Fas, TNFR1 and Apaf-1, and increased expression of Fem1b induces apoptosis of cancer cells. Fem1b is a homolog of FEM-1, a protein in Caenorhabditis elegans that is negatively regulated by ubiquitination and proteasomal degradation. To study Fem1b regulation in colon cancer progression, we used apoptotis-sensitive SW480 cells, derived from a primary colon cancer, and their isogenic, apoptosis-resistant counterparts SW620 cells, derived from a subsequent metastatic lesion in the same patient. Treatment with proteasome inhibitor increased Fem1b protein levels in SW620 cells, but not in SW480 cells. In SW620 cells we found that endogenous Fem1b co-immunoprecipitates in complexes with RACK1, a protein known to mediate ubiquitination and proteasomal degradation of other pro-apoptotic proteins and to be upregulated in colon cancer. Full-length Fem1b, or the N-terminal region of Fem1b, associated with RACK1 when co-expressed in HEK293T cells, and RACK1 stimulated ubiquitination of Fem1b. RACK1 overexpression in SW620 cells led to downregulation of Fem1b protein levels. Conversely, downregulation of RACK1 led to upregulation of Fem1b protein levels, associated with induction of apoptosis, and this apoptosis was inhibited by blocking Fem1b protein upregulation. In conclusion, RACK1 downregulates levels of the pro-apoptotic protein Fem1b in metastatic, apoptosis-resistant colon cancer cells, which may promote apoptosis-resistance during progression of colon cancer.

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

    International Nuclear Information System (INIS)

    Coughlin, Mark F; Fredberg, Jeffrey J

    2013-01-01

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

  19. Increased colon cancer risk after severe Salmonella infection.

    Directory of Open Access Journals (Sweden)

    Lapo Mughini-Gras

    Full Text Available Colon cancer constitutes one of the most frequent malignancies. Previous studies showed that Salmonella manipulates host cell signaling pathways and that Salmonella Typhimurium infection facilitates colon cancer development in genetically predisposed mice. This epidemiological study examined whether severe Salmonella infection, usually acquired from contaminated food, is associated with increased colon cancer risk in humans.We performed a nationwide registry-based study to assess colon cancer risk after diagnosed Salmonella infection. National infectious disease surveillance records (1999-2015 for Dutch residents aged ≥20 years when diagnosed with salmonellosis (n = 14,264 were linked to the Netherlands Cancer Registry. Salmonella-infected patients were laboratory-confirmed under medical consultation after 1-2 weeks of illness. These datasets also contained information on Salmonella serovar and type of infection. Colon cancer risk (overall and per colon subsite among patients with a diagnosed Salmonella infection was compared with expected colon cancer risk in the general population. Data from the nationwide registry of histo- and cytopathology (PALGA and Statistics Netherlands (CBS allowed assessing potential effects of age, gender, latency, socioeconomic status, genetic predisposition, inflammatory bowel disease (IBD, and tumor features. We found that compared to the general population, colon cancer risk was significantly increased (standardized incidence ratio [SIR] 1.54; 95%CI 1.09-2.10 among patients with Salmonella infection diagnosed <60 years of age. Such increased risk concerned specifically the ascending/transverse colon (SIR 2.12; 95%CI 1.38-3.09 after S. Enteritidis infection (SIR 2.97; 95%CI 1.73-4.76. Salmonellosis occurred more frequently among colon cancer patients with pre-infectious IBD, a known risk factor for colon cancer. Colon tumors of patients with a history of Salmonella infection were mostly of low grade

  20. Increased colon cancer risk after severe Salmonella infection

    Science.gov (United States)

    Mooij, Sofie; Neefjes-Borst, E. Andra; van Pelt, Wilfrid; Neefjes, Jacques

    2018-01-01

    Background Colon cancer constitutes one of the most frequent malignancies. Previous studies showed that Salmonella manipulates host cell signaling pathways and that Salmonella Typhimurium infection facilitates colon cancer development in genetically predisposed mice. This epidemiological study examined whether severe Salmonella infection, usually acquired from contaminated food, is associated with increased colon cancer risk in humans. Methods and findings We performed a nationwide registry-based study to assess colon cancer risk after diagnosed Salmonella infection. National infectious disease surveillance records (1999–2015) for Dutch residents aged ≥20 years when diagnosed with salmonellosis (n = 14,264) were linked to the Netherlands Cancer Registry. Salmonella-infected patients were laboratory-confirmed under medical consultation after 1–2 weeks of illness. These datasets also contained information on Salmonella serovar and type of infection. Colon cancer risk (overall and per colon subsite) among patients with a diagnosed Salmonella infection was compared with expected colon cancer risk in the general population. Data from the nationwide registry of histo- and cytopathology (PALGA) and Statistics Netherlands (CBS) allowed assessing potential effects of age, gender, latency, socioeconomic status, genetic predisposition, inflammatory bowel disease (IBD), and tumor features. We found that compared to the general population, colon cancer risk was significantly increased (standardized incidence ratio [SIR] 1.54; 95%CI 1.09–2.10) among patients with Salmonella infection diagnosed transverse colon (SIR 2.12; 95%CI 1.38–3.09) after S. Enteritidis infection (SIR 2.97; 95%CI 1.73–4.76). Salmonellosis occurred more frequently among colon cancer patients with pre-infectious IBD, a known risk factor for colon cancer. Colon tumors of patients with a history of Salmonella infection were mostly of low grade. Conclusions Patients diagnosed with severe

  1. Relation between Carcinoembryonic Antigen Levels in Colon Cancer Tissue and Serum Carcinoembryonic Antigen Levels at Initial Surgery and Recurrence.

    Science.gov (United States)

    Saito, Gota; Sadahiro, Sotaro; Okada, Kazutake; Tanaka, Akira; Suzuki, Toshiyuki; Kamijo, Akemi

    2016-01-01

    Carcinoembryonic antigen (CEA) is widely used for postoperative surveillance of colon cancer. Even if serum CEA is negative at initial surgery, it may turn positive at recurrence. We investigated the relation between serum CEA levels and the immunohistochemical staining status of CEA in the primary and resected metastatic tissues. Out of 224 patients with recurrent colon cancer between 1998 and 2012, we studied 46 patients in whom serum CEA levels were measured and immunohistochemical staining for CEA was possible in the primary and metastatic tissues. The positive rate of serum CEA did not differ between initial surgery and recurrence, regardless of whether the cutoff value was set at 5 or 10 ng/ml (p = 0.829, p = 0.671). There was no relation between the CEA staining status and serum CEA level at initial surgery. However, the CEA staining status of metastatic tissue was significantly related to the serum CEA level at recurrence (p = 0.0046 and p = 0.0026). The immunohistochemical staining status of CEA in metastatic tissue is closely related to the serum CEA level. This finding suggests that serum CEA levels are influenced not only by the CEA production capacity of cancer cells but also by the ability of the surrounding tissue to release CEA into the blood. © 2016 The Author(s) Published by S. Karger AG, Basel.

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

    Science.gov (United States)

    Lee, James J; Sun, Weijing

    2016-01-01

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

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

    Science.gov (United States)

    Alberts, Steven R

    2008-12-01

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

  4. Synchronous colon and renal cancer - case report

    International Nuclear Information System (INIS)

    Luczynska, E.; Pawlik, T.; Aniol, J.; Chwalibog, A.

    2008-01-01

    Primary cancer may occur synchronously in two different organs. We present an example of pathologically proven, coexistent renal and colony double malignant tumors. A 59 year old man, was admitted to the Institute of Oncology due to left renal lesion, discovered during a routine abdominal ultrasound examination. The CT exam was performed before surgery. The CT scans reveled a second abnormality, presenting irregular shaped and thickened to 20 mm intestinal wall within a patient's large bowel. As a next diagnostic step a CT-colonoscopy was undertaken, which confirmed the presence of an exophytic sigmoid lesion, eccentrically affecting the colonic wall and protruding into the lumen moderately narrowing it, placed about 50 cm from the external rectal sphincter. Patient underwent simultaneous radical left nephrectomy and sigmoidectomy. Both tumors were confirmed in pathologic evaluation, reveling renal clear cell carcinoma (Fuhrman G II) and colonic adenocarcinoma (Astler-Coller B2). Preoperative careful imaging studies reveled neoplastic tumors in two different organs, allowing for radical resection at the same surgical procedure. (author)

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

  6. 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

  7. [Expression and significance of CK7 and CK19 in colon cancer].

    Science.gov (United States)

    Zhang, Xin; Zheng, Peng-sheng

    2010-02-01

    To detect the cytokeratin (CK) genes expression in the colon cancer, and investigate the expression variability in different pathological types and clinical stages. The CK gene expression pattern in normal colon, colon cancer tissues and colon cancer cell lines were analyzed by using Immunohistochemical, Immunocytochemical and Western blot ways. CK7 and CK19 didn't express in normal colon tissues. CK7 was low or not expressed in the colon cancer, and CK19 was highly expressed in the colon cancer. There were significant deviation (Pcolon cancer, and CK7-)/CK19+ may be one of the expression characteristics in colon cancer.

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

    Science.gov (United States)

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

    2015-05-28

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

  9. Near-infrared Mueller matrix imaging for colonic cancer detection

    Science.gov (United States)

    Wang, Jianfeng; Zheng, Wei; Lin, Kan; Huang, Zhiwei

    2016-03-01

    Mueller matrix imaging along with polar decomposition method was employed for the colonic cancer detection by polarized light in the near-infrared spectral range (700-1100 nm). A high-speed (colonic tissues (i.e., normal and caner) were acquired. Polar decomposition was further implemented on the 16 images to derive the diattentuation, depolarization, and the retardance images. The decomposed images showed clear margin between the normal and cancerous colon tissue samples. The work shows the potential of near-infrared Mueller matrix imaging for the early diagnosis and detection of malignant lesions in the colon.

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

    OpenAIRE

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

    2017-01-01

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

  11. Colon cancer with unresectable synchronous metastases: the AAAP scoring system for predicting the outcome after primary tumour resection.

    Science.gov (United States)

    Li, Z M; Peng, Y F; Du, C Z; Gu, J

    2016-03-01

    The aim of this study was to develop a prognostic scoring system to predict the outcome of patients with unresectable metastatic colon cancer who received primary colon tumour resection. Patients with confirmed metastatic colon cancer treated at the Peking University Cancer Hospital between 2003 and 2012 were reviewed retrospectively. The correlation of clinicopathological factors with overall survival was analysed using the Kaplan-Meier method and the log-rank test. Independent prognostic factors were identified using a Cox proportional hazards regression model and were then combined to form a prognostic scoring system. A total of 110 eligible patients were included in the study. The median survival time was 10.4 months and the 2-year overall survival (OS) rate was 21.8%. Age over 70 years, an alkaline phosphatase (ALP) level over 160 IU/l, ascites, a platelet/lymphocyte ratio (PLR) above 162 and no postoperative therapy were independently associated with a shorter OS in multivariate analysis. Age, ALP, ascites and PLR were subsequently combined to form the so-called AAAP scoring system. Patients were classified into high, medium and low risk groups according to the score obtained. There were significant differences in OS between each group (P colonic cancer who underwent primary tumour resection. The AAAP scoring system may be a useful tool for surgical decision making. Colorectal Disease © 2015 The Association of Coloproctology of Great Britain and Ireland.

  12. Locally aggressive colonic and rectal cancer ,clinical trial

    OpenAIRE

    Radu, V; Ion, D; şerban, MB; Ciurea, M

    2010-01-01

    This clinical trial studies local invasions from primary colonic and rectal cancers (urinary bladder, abdominal wall, small bowls, uterus, vagina, stomach, bile tract, spleen, duodenum, pancreas, ureters, kidneys), with or without undiscovered metastasis. Primary locally aggressive colonic and rectal cancers include tumors that are staged T4N1–2Mx on diagnosis, and are often associated with a lower prognosis than earlier cancers. [2] Diagnosis is based on thorough clinical evaluation, imagist...

  13. Differential expression of colon cancer associated transcript1 (CCAT1) along the colonic adenoma-carcinoma sequence

    International Nuclear Information System (INIS)

    Alaiyan, Bilal; Trink, Barry; Gure, Ali O; Nissan, Aviram; Ilyayev, Nadia; Stojadinovic, Alexander; Izadjoo, Mina; Roistacher, Marina; Pavlov, Vera; Tzivin, Victoria; Halle, David; Pan, Honguang

    2013-01-01

    The transition from normal epithelium to adenoma and, to invasive carcinoma in the human colon is associated with acquired molecular events taking 5-10 years for malignant transformation. We discovered CCAT1, a non-coding RNA over-expressed in colon cancer (CC), but not in normal tissues, thereby making it a potential disease-specific biomarker. We aimed to define and validate CCAT1 as a CC-specific biomarker, and to study CCAT1 expression across the adenoma-carcinoma sequence of CC tumorigenesis. Tissue samples were obtained from patients undergoing resection for colonic adenoma(s) or carcinoma. Normal colonic tissue (n = 10), adenomatous polyps (n = 18), primary tumor tissue (n = 22), normal mucosa adjacent to primary tumor (n = 16), and lymph node(s) (n = 20), liver (n = 8), and peritoneal metastases (n = 19) were studied. RNA was extracted from all tissue samples, and CCAT1 expression was analyzed using quantitative real time-PCR (qRT-PCR) with confirmatory in-situ hybridization (ISH). Borderline expression of CCAT1 was identified in normal tissue obtained from patients with benign conditions [mean Relative Quantity (RQ) = 5.9]. Significant relative CCAT1 up-regulation was observed in adenomatous polyps (RQ = 178.6 ± 157.0; p = 0.0012); primary tumor tissue (RQ = 64.9 ± 56.9; p = 0.0048); normal mucosa adjacent to primary tumor (RQ = 17.7 ± 21.5; p = 0.09); lymph node, liver and peritoneal metastases (RQ = 11,414.5 ± 12,672.9; 119.2 ± 138.9; 816.3 ± 2,736.1; p = 0.0001, respectively). qRT-PCR results were confirmed by ISH, demonstrating significant correlation between CCAT1 up-regulation measured using these two methods. CCAT1 is up-regulated across the colon adenoma-carcinoma sequence. This up-regulation is evident in pre-malignant conditions and through all disease stages, including advanced metastatic disease suggesting a role in both tumorigenesis and the metastatic process

  14. Assessment of cognitive function in patients with metastatic cancer

    DEFF Research Database (Denmark)

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

    2018-01-01

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

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

    Science.gov (United States)

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

    2016-03-01

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

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  17. [Liver metastases from colon and rectal cancer in terms of differences in their clinical parameters].

    Science.gov (United States)

    Liška, V; Emingr, M; Skála, M; Pálek, R; Troup, O; Novák, P; Vyčítal, O; Skalický, T; Třeška, V

    2016-02-01

    From the clinical point of view, rectal cancer and colon cancer are clearly different nosological units in their progress and treatment. The aim of this study was to analyse and clarify the differences between the behaviour of liver metastases from colon and rectal cancer. The study of these factors is important for determining an accurate prognosis and indication of the most effective surgical therapy and oncologic treatment of colon and rectal cancer as a systemic disease. 223 patients with metastatic disease of colorectal carcinoma operated at the Department of Surgery, University Hospital in Pilsen between January 1, 2006 and January 31, 2012 were included in our study. The group of patients comprised 145 men (65%) and 117 women (35%). 275 operations were performed. Resection was done in 177 patients and radiofrequency ablation (RFA) in the total of 98 cases. Our sample was divided into 3 categories according to the location of the primary tumor to C (colon), comprising 58 patients, S (c. sigmoideum) in 61 patients, and R (rectum), comprising 101 patients. Significance analysis of the studied factors (age, gender, staging [TNM classification], grading, presence of mucinous carcinoma, type of operation) was performed using ANOVA test. Overall survival (OS), disease-free interval (DFI) or no evidence of disease (NED) were estimated using Kaplan-Meier curves, which were compared with the log-rank and Wilcoxon tests. As regards the comparison of primary origin of colorectal metastases in liver regardless of their treatment (resection and RFA), our study indicated that rectal liver metastases showed a significantly earlier recurrence than colon liver metastases (shorter NED/DFI). Among other factors, a locally advanced finding, further R2 resection of liver metastases and positivity of lymph node metastases were statistically significant for the prognosis of an early recurrence of the primary colon and sigmoid tumor. Furthermore, we proved that in patients with

  18. Anti-angiogenic therapy and radioimmunotherapy in colon cancer xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Kinuya, Seigo; Yokoyama, Kunihiko; Michigishi, Takatoshi; Tonami, Norihisa [Dept. of Nuclear Medicine, Kanazawa Univ. (Japan); Kawashima, Atsuhiro [Dept. of Pathology (I), Kanazawa Univ. School of Medicine, Kanazawa, Ishikawa (Japan); Kudo, Miho; Kasahara, Yoshihito [Dept. of Pediatrics, Kanazawa University School of Medicine, Kanazawa, Ishikawa (Japan); Watanabe, Naoto [Dept. of Radiology, Toyama Medical and Pharmaceutical University, Toyama (Japan); Shuke, Noriyuki [Dept. of Radiology, Asahikawa Medical College, Asahikawa (Japan); Bunko, Hisashi [Medical Informatics, Kanazawa University Hospital, Kanazawa (Japan)

    2001-09-01

    Angiogenesis is critical to the growth and metastatic process of malignant tumors. An endogenous estrogen metabolite, 2-methoxyestradiol (2-ME), displays anti-angiogenic and anti-tumorigenic effects. The purpose of this investigation was to determine whether exogenously administered 2-ME would enhance the efficacy of radioimmunotherapy (RIT). Experimental RIT with 4.63 MBq of {sup 131}I-A7, an IgG1 anti-colorectal monoclonal antibody, was conducted in mice xenografted with LS180 human colon cancer cells. 2-ME suspended in 0.5% carboxymethylcellulose was administered daily at a dose of 75 mg/kg per day. 2-ME administration suppressed tumor growth and improved the efficacy of RIT in comparison to RIT alone. Tumor volumes on day 13, expressed as a ratio relative to the initial volume, were 12.7{+-}2.95 in the nontreated control, 4.73{+-}0.89 with 2-ME, 3.05{+-}0.37 with RIT and 0.97{+-}0.20 with RIT+2-ME. Immunohistochemistry of tumor sections stained with an antibody against factor VIII demonstrated a decrease in microvessel number within tumors treated with 2-ME (7.9{+-}0.8/200 x field) as compared with that in control tumors (29.9{+-}2.5). Cell proliferation assay at increasing concentrations of 2-ME showed direct cytotoxicity of 2-ME in vitro at 5 {mu}M and greater. In conclusion, 2-ME enhanced the efficacy of RIT with {sup 131}I-A7 via inhibition of angiogenesis within the xenografts. The direct cytotoxicity of 2-ME appears to have contributed to this improvement. Anti-angiogenic therapy may prolong the dormancy of microscopic metastases while RIT may exterminate this population of cells. Therefore, the combined treatment may improve the therapeutic outcome of patients with disseminated cancer. (orig.)

  19. Dietary patterns and colon cancer risk in Whites and African Americans in the North Carolina Colon Cancer Study.

    Science.gov (United States)

    Satia, Jessie A; Tseng, Marilyn; Galanko, Joseph A; Martin, Christopher; Sandler, Robert S

    2009-01-01

    We examined associations of dietary patterns with colon cancer risk in African Americans and Whites from a case-control study in North Carolina. Incident colon cancer cases, 40 to 80 yr (n = 636), and matched controls (n = 1,042) were interviewed in person to elicit information on potential colon cancer risk factors. A validated food frequency questionnaire adapted to include regional foods captured diet over the year prior to diagnosis (cases) or interview date (controls). Three meaningful intake patterns were identified in both Whites and African Americans: "Western-Southern," "fruit-vegetable," and "metropolitan." Compared to the Western-Southern pattern, the fruit-vegetable and metropolitan patterns were associated with more healthful dietary behaviors (e.g., higher vegetable intake and lower red meat consumption), and demographic/lifestyle characteristics typically correlated with low colon cancer risk, for example, lower BMI, higher education, and higher NSAID use. The fruit-vegetable pattern was significantly inversely associated with colon cancer risk in Whites (OR = 0.4, 95% CI = 0.3-0.6) and the metropolitan pattern with a nonsignificant 30% risk reduction in both Whites and African Americans after adjustment for education. The Western-Southern pattern was not associated with colon cancer risk. These findings may explain some of the racial differences in colon cancer incidence and underscore the importance of examining diet-cancer associations in different population subgroups.

  20. Personalizing colon cancer adjuvant therapy: selecting optimal treatments for individual patients.

    Science.gov (United States)

    Dienstmann, Rodrigo; Salazar, Ramon; Tabernero, Josep

    2015-06-01

    For more than three decades, postoperative chemotherapy-initially fluoropyrimidines and more recently combinations with oxaliplatin-has reduced the risk of tumor recurrence and improved survival for patients with resected colon cancer. Although universally recommended for patients with stage III disease, there is no consensus about the survival benefit of postoperative chemotherapy in stage II colon cancer. The most recent adjuvant clinical trials have not shown any value for adding targeted agents, namely bevacizumab and cetuximab, to standard chemotherapies in stage III disease, despite improved outcomes in the metastatic setting. However, biomarker analyses of multiple studies strongly support the feasibility of refining risk stratification in colon cancer by factoring in molecular characteristics with pathologic tumor staging. In stage II disease, for example, microsatellite instability supports observation after surgery. Furthermore, the value of BRAF or KRAS mutations as additional risk factors in stage III disease is greater when microsatellite status and tumor location are taken into account. Validated predictive markers of adjuvant chemotherapy benefit for stage II or III colon cancer are lacking, but intensive research is ongoing. Recent advances in understanding the biologic hallmarks and drivers of early-stage disease as well as the micrometastatic environment are expected to translate into therapeutic strategies tailored to select patients. This review focuses on the pathologic, molecular, and gene expression characterizations of early-stage colon cancer; new insights into prognostication; and emerging predictive biomarkers that could ultimately help define the optimal adjuvant treatments for patients in routine clinical practice. © 2015 by American Society of Clinical Oncology.

  1. [A Case of Sigmoid Colon Cancer with Metastasis to the Uterus].

    Science.gov (United States)

    Tokoro, Yukinari; Tonooka, Toru; Souda, Hiroaki; Takiguchi, Nobuhiro; Chibana, Tomofumi; Kobayashi, Ryosuke; Arimitsu, Hidehito; Yanagibashi, Hiroo; Chou, Akihiro; Ikeda, Atsushi; Nabeya, Nobuhiro; Kainuma, Osamu; Yamamoto, Hiroshi; Nagata, Matsuo

    2015-11-01

    A 65-year-old woman complaining of fetor ex vagina was diagnosed with endometrial adenocarcinoma of the uterus based on the pathological findings of an endometrial biopsy. Sigmoid colon cancer was found on a pre-operative CT scan. Diagnosis of double cancer was made and we performed sigmoidectomy and panhysterectomy with associated resection of both adnexa. Histopathological examination found that the tumor accounted for almost all of the uterine mucosa and over half of the muscular layer. Immunostaining showed CK7 (-), CK20 (+), CDX2 (+), ER (-), and PgR (-), and we diagnosed it as a metastasis to the uterus of the sigmoid colon cancer. The pathological diagnosis was a moderately differentiated adenocarcinoma, pT4b (SI: urinary bladder), pN0 (0/12), H0, P1,M1a (uterus), pStage Ⅳ. As adjuvant chemotherapy, she was administered XELOX for 6 months. Although colorectal cancer rarely metastasizes to the uterus, due to the increase in the prevalence of colorectal cancer, it may be also increase. To choose the best treatment course, it is necessary to diagnose whether it is a primary uterine cancer or a metastatic uterine cancer.

  2. Lower or Standard Dose Regorafenib in Treating Patients With Refractory Metastatic Colorectal Cancer

    Science.gov (United States)

    2018-03-22

    Colon Adenocarcinoma; Rectal Adenocarcinoma; Stage III Colorectal Cancer AJCC v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7; Stage IV Colorectal Cancer AJCC v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7

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

    Science.gov (United States)

    2017-12-04

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

  4. Radiation-associated colon cancer: A case report.

    Science.gov (United States)

    Sasaki, Kazuhito; Ishihara, Soichiro; Hata, Keisuke; Kiyomatsu, Tomomichi; Nozawa, Hiroaki; Kawai, Kazushige; Tanaka, Toshiaki; Nishikawa, Takeshi; Otani, Kensuke; Yasuda, Koji; Kaneko, Manabu; Murono, Koji; Abe, Hiroyuki; Morikawa, Teppei; Watanabe, Toshiaki

    2017-06-01

    Radiation-associated colon cancer is a rare clinical entity. We herein describe the case of a patient with radiation-associated colon cancer who had undergone low anterior resection for rectal cancer following preoperative radiotherapy. Certain characteristics of radiation-associated colon cancer are highlighted. The patient was a 48-year-old man who had undergone low anterior resection for rectal cancer following preoperative radiotherapy at a total dose of 50 Gy, at the age of 29 years. When the patient presented at the University of Tokyo Hospital, 19 years after the surgery, he complained of severe anal pain and frequent defecation. Colonoscopy revealed two flat tumors in the sigmoid colon, located 10 cm to the oral side of the anastomosis site, which were diagnosed as well-differentiated adenocarcinomas. In addition, colonoscopy identified five flat polyps near the tumors, which were resected endoscopically. Computed tomography and magnetic resonance imaging revealed a mass in the sigmoid colon and no evidence of distant metastasis. Laparoscopic-assisted intersphincteric resection of the rectum and sigmoid colon with diverting ileostomy was performed. There were no specific postoperative complications and the patient was discharged from the hospital on the 20th postoperative day. On pathological examination, the resected rectum and sigmoid colon contained two separate tumors and six flat polyps. The two tumors were diagnosed as well-differentiated adenocarcinomas with invasion of the subserosa and submucosa, respectively. A total of 17 regional lymph nodes without metastasis were resected. The six flat polyps were diagnosed as tubular adenomas. We herein present a case of a radiation-associated colon cancer in a patient who had undergone low anterior resection for rectal cancer following preoperative radiotherapy 19 years prior. Colonoscopic surveillance of radiation-associated colon cancer may be indicated for rectal cancer patients treated with preoperative

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

    NARCIS (Netherlands)

    Kuijpers, A.M.J.

    2015-01-01

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

  6. Differential Impact of Anastomotic Leak in Patients With Stage IV Colonic or Rectal Cancer: A Nationwide Cohort Study.

    Science.gov (United States)

    Nordholm-Carstensen, Andreas; Rolff, Hans Christian; Krarup, Peter-Martin

    2017-05-01

    Anastomotic leak has a negative impact on the prognosis of patients who undergo colorectal cancer resection. However, data on anastomotic leak are limited for stage IV colorectal cancers. The purpose of this study was to investigate the impact of anastomotic leak on survival and the decision to administer chemotherapy and/or metastasectomy after elective surgery for stage IV colorectal cancer. This was a nationwide, retrospective cohort study. Data were obtained from the Danish Colorectal Cancer Group, the Danish Pathology Registry, and the National Patient Registry. Patients who were diagnosed with stage IV colorectal cancer between 2009 and 2013 and underwent elective resection of their primary tumors were included. The primary outcome was all-cause mortality depending on the occurrence of anastomotic leak. Secondary outcomes were the administration of and time to adjuvant chemotherapy, metastasectomy rate, and risk factors for leak. Of the 774 patients with stage IV colorectal cancer who were included, 71 (9.2%) developed anastomotic leaks. Anastomotic leak had a significant impact on the long-term survival of patients with colon cancer (p = 0.04) but not on those with rectal cancer (p = 0.91). Anastomotic leak was followed by the decreased administration of adjuvant chemotherapy in patients with colon cancer (p = 0.007) but not in patients with rectal cancer (p = 0.47). Finally, anastomotic leak had a detrimental impact on metastasectomy rates after colon cancer but not on resection rates of rectal cancer. Retrospective data on the selection criteria for primary tumor resection and metastatic tumor load were unavailable. The impact of anastomotic leak on patients differed between stage IV colon and rectal cancers. Survival and eligibility to receive chemotherapy and metastasectomy differed between patients with colon and rectal cancers. When planning for primary tumor resection, these factors should be considered.

  7. Differences between right- and left-sided colon cancer in patient characteristics, cancer morphology and histology.

    Science.gov (United States)

    Nawa, Toru; Kato, Jun; Kawamoto, Hirofumi; Okada, Hiroyuki; Yamamoto, Hiroshi; Kohno, Hiroyuki; Endo, Hisayuki; Shiratori, Yasushi

    2008-03-01

    Recently, the clinical and biological differences between right- and left-sided colon cancers have been widely debated. However, close analyses of these clinical differences, based on large-scale studies, have been scarcely reported. A total of 3552 consecutive Japanese colorectal cancer cases were examined and the clinical differences between right- and left-sided colon cancer cases were investigated. The proportion of right-sided colon cancer was relatively high in patients aged less than 40 years (33%) and more than 80 years (43%). The proportion of right-sided colon cancer in patients aged 40-59 years was relatively low (male 22% and female 29%). In male patients the proportion increased in the 70-79 years age group (30%), while in female patients the proportion increased in the 60-69 years age group (39%). Right-sided colon cancer was more likely to be detected at an advanced stage (T1 stage; left 22%, right 15%) (P cancer was dominant in the left colon (left 59%; right 40%) (P cancer in the right colon was significantly higher than that in the left colon (left 25%; right 44%) (P colon cancer was observed and the difference between male and female patients was highlighted. Other clinical features also differed between right- and left-sided colon cancer, suggesting that different mechanisms may be at work during right and left colon carcinogenesis.

  8. Cryptogenic pyogenic liver abscess as the herald of colon cancer.

    Science.gov (United States)

    Jeong, Soung Won; Jang, Jae Young; Lee, Tae Hee; Kim, Hyun Gun; Hong, Sung Wook; Park, Seung Hoon; Kim, Sang Gyune; Cheon, Young Koog; Kim, Young Seok; Cho, Young Deok; Kim, Jin-Oh; Kim, Boo Sung; Lee, Eun Jung; Kim, Tae Hyong

    2012-02-01

    Colonic mucosal defects might be a route for bacterial invasion into the portal system, with subsequent hematogenous spread to the liver. We retrospectively investigated the results of colonoscopy and the clinical characteristics of patients with pyogenic liver abscess of colonic origin. A total of 230 consecutive patients with pyogenic liver abscess were reviewed between 2003 and 2010. The 230 patients were categorized into three groups (pancreatobiliary [n = 135], cryptogenic [n = 81], and others [n = 14]). Of the 81 cryptogenic patients, 37 (45.7%) underwent colonoscopy. Colonic lesions with mucosal defects were considered colonic causes of abscess. In the 37 colonoscopic investigations, colon cancer was found in six patients (16.2%), laterally-spreading tumor (LST) in two patients (5.4%), multiple colon ulcers in one patient (2.7%), colon polyps in 17 patients (45.9%), and diverticula in four patients (10.8%). Nine (11%) of 81 cryptogenic abscesses were therefore reclassified as being of colonic origin (colon cancer = 6, LST = 2, ulcer = 1). Three cases were stage III colon cancer, and the others were stage I. Two LST were high-grade dysplasia. The percentage of patients with Klebsiella pneumoniae (K. pneumoniae) and diabetes mellitus (DM) of colonic origin was 66.7%, which was significantly higher than the 8.6% for other causes (P colonic cause. Colonoscopy should be considered for the detection of hidden colonic malignant lesions in patients with cryptogenic pyogenic liver abscess, especially for patients with K. pneumoniae and DM. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

  9. EZH2 depletion blocks the proliferation of colon cancer cells.

    Directory of Open Access Journals (Sweden)

    Bettina Fussbroich

    Full Text Available The Enhancer of Zeste 2 (EZH2 protein has been reported to stimulate cell growth in some cancers and is therefore considered to represent an interesting new target for therapeutic intervention. Here, we investigated a possible role of EZH2 for the growth control of colon cancer cells. RNA interference (RNAi-mediated intracellular EZH2 depletion led to cell cycle arrest of colon carcinoma cells at the G1/S transition. This was associated with a reduction of cell numbers upon transient transfection of synthetic EZH2-targeting siRNAs and with inhibition of their colony formation capacity upon stable expression of vector-borne siRNAs. We furthermore tested whether EZH2 may repress the growth-inhibitory p27 gene, as reported for pancreatic cancer. However, expression analyses of colon cancer cell lines and colon cancer biopsies did not reveal a consistent correlation between EZH2 and p27 levels. Moreover, EZH2 depletion did not re-induce p27 expression in colon cancer cells, indicating that p27 repression by EZH2 may be cell- or tissue-specific. Whole genome transcriptome analyses identified cellular genes affected by EZH2 depletion in colon cancer cell lines. They included several cancer-associated genes linked to cellular proliferation or invasion, such as Dag1, MageD1, SDC1, Timp2, and Tob1. In conclusion, our results demonstrate that EZH2 depletion blocks the growth of colon cancer cells. These findings might provide benefits for the treatment of colon cancer.

  10. Prostate and Colon Cancer Screening Messages in Popular Magazines

    Science.gov (United States)

    Katz, Mira L; Sheridan, Stacey; Pignone, Michael; Lewis, Carmen; Battle, Jamila; Gollop, Claudia; O'Malley, Michael

    2004-01-01

    OBJECTIVES To 1) compare the number of articles published about prostate, colon, and breast cancer in popular magazines during the past 2 decades, and 2) evaluate the content of in-depth prostate and colon cancer screening articles identified from 1996 to 2001. DESIGN We used a searchable database to identify the number of prostate, colon, and breast cancer articles published in three magazines with the highest circulation from six categories. In addition, we performed a systematic review on the in-depth (≥2 pages) articles on prostate and colon cancer screening that appeared from 1996 through 2001. RESULTS Although the number of magazine articles on prostate and colon cancer published in the 1990s increased compared to the 1980s, the number of articles is approximately one third of breast cancer articles. There were 36 in-depth articles from 1996 to 2001 in which prostate or colon cancer screening were mentioned. Over 90% of the articles recommended screening. However, of those articles, only 76% (25/33; 95% confidence interval [CI], 58% to 89%) cited screening guidelines. The benefits of screening were mentioned in 89% (32/36; 95% CI, 74% to 97%) but the harms were only found in 58% (21/36; 95% CI, 41% to 75%). Only 28% (10/36; 95% CI, 14% to 45%) of the articles provided all the necessary information needed for the reader to make an informed decision. CONCLUSIONS In-depth articles about prostate and colon cancer in popular magazines do not appear as frequently as articles about breast cancer. The available articles on prostate and colon cancer screening often do not provide the information necessary for the reader to make an informed decision about screening. PMID:15242469

  11. Hyper-IL-15 suppresses metastatic and autochthonous liver cancer by promoting tumour-specific CD8+ T cell responses.

    Science.gov (United States)

    Cheng, Liang; Du, Xuexiang; Wang, Zheng; Ju, Jianqi; Jia, Mingming; Huang, Qibin; Xing, Qiao; Xu, Meng; Tan, Yi; Liu, Mingyue; Du, Peishuang; Su, Lishan; Wang, Shengdian

    2014-12-01

    Liver cancer has a very dismal prognosis due to lack of effective therapy. Here, we studied the therapeutic effects of hyper-interleukin15 (hyper-IL-15), which is composed of IL-15 and the sushi domain of the IL-15 receptor α chain, on metastatic and autochthonous liver cancers. Liver metastatic tumour models were established by intraportally injecting syngeneic mice with murine CT26 colon carcinoma cells or B16-OVA melanoma cells. Primary hepatocellular carcinoma (HCC) was induced by diethylnitrosamine (DEN). A hydrodynamics-based gene delivery method was used to achieve sustained hyper-IL-15 expression in the liver. Liver gene delivery of hyper-IL-15 robustly expanded CD8(+) T and NK cells, leading to a long-term (more than 40 days) accumulation of CD8(+) T cells in vivo, especially in the liver. Hyper-IL-15 treatment exerted remarkable therapeutic effects on well-established liver metastatic tumours and even on DEN-induced autochthonous HCC, and these effects were abolished by depletion of CD8(+) T cells but not NK cells. Hyper-IL-15 triggered IL-12 and interferon-γ production and reduced the expression of co-inhibitory molecules on dendritic cells in the liver. Adoptive transfer of T cell receptor (TCR) transgenic OT-1 cells showed that hyper-IL-15 preferentially expanded tumour-specific CD8(+) T cells and promoted their interferon-γ synthesis and cytotoxicity. Liver delivery of hyper-IL-15 provides an effective therapy against well-established metastatic and autochthonous liver cancers in mouse models by preferentially expanding tumour-specific CD8(+) T cells and promoting their anti-tumour effects. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  12. Tumor initiating cells and chemoresistance: which is the best strategy to target colon cancer stem cells?

    Science.gov (United States)

    Paldino, Emanuela; Tesori, Valentina; Casalbore, Patrizia; Gasbarrini, Antonio; Puglisi, Maria Ausiliatrice

    2014-01-01

    There is an emerging body of evidence that chemoresistance and minimal residual disease result from selective resistance of a cell subpopulation from the original tumor that is molecularly and phenotypically distinct. These cells are called "cancer stem cells" (CSCs). In this review, we analyze the potential targeting strategies for eradicating CSCs specifically in order to develop more effective therapeutic strategies for metastatic colon cancer. These include induction of terminal epithelial differentiation of CSCs or targeting some genes expressed only in CSCs and involved in self-renewal and chemoresistance. Ideal targets could be cell regulators that simultaneously control the stemness and the resistance of CSCs. Another important aspect of cancer biology, which can also be harnessed to create novel broad-spectrum anticancer agents, is the Warburg effect, also known as aerobic glycolysis. Actually, little is yet known with regard to the metabolism of CSCs population, leaving an exciting unstudied avenue in the dawn of the emerging field of metabolomics.

  13. Diverticular Bleeding of the Colon during Combination Chemotherapy with Bevacizumab and Paclitaxel for Recurrent Breast Cancer

    Directory of Open Access Journals (Sweden)

    Yoshie Nakayama

    2013-01-01

    Full Text Available Background: Bevacizumab has been increasingly used in combination chemotherapy with paclitaxel for treatment of metastatic or recurrent breast cancer. The aim of this report is to underline possible risks associated with the new combination chemotherapy. Case Presentation: A 39-year-old woman with recurrent breast cancer was treated with bevacizumab and paclitaxel. Positron emission tomography revealed breast cancer metastasis to the left supraclavicular lymph nodes and right axillary lymph nodes, with no distant metastasis. Results: After the third cycle of bevacizumab and paclitaxel, the patient developed a bloody bowel discharge. Emergent colonoscopy demonstrated diverticular bleeding on one of the multiple diverticula in the ascending colon. The bleeding point was successfully clipped colonoscopically. Conclusion: The factors for diverticular bleeding are believed to be non-steroidal anti-inflammatory drugs, constipation, and bevacizumab. We recommend reviewing anamneses for diverticulitis, multiple prior abdominal surgeries, peritoneal carcinomatosis, and regular use of certain drugs.

  14. Explanation of colon cancer pathophysiology through analyzing the ...

    African Journals Online (AJOL)

    Background: The colon plays a key role in regulating the homeostasis of bile acids. Aim: The present study aims to evaluate the influence of colon cancer towards the homeostasis of bile acids. Methods: The free and conjugated bile acids were determined using ultraperformance LC (UPLC) coupled with ABI 4000 QTRAP ...

  15. Explanation of colon cancer pathophysiology through analyzing the ...

    African Journals Online (AJOL)

    Abstract. Background: The colon plays a key role in regulating the homeostasis of bile acids. Aim: The present study aims to evaluate the influence of colon cancer towards the homeostasis of bile acids. Methods: The free and conjugated bile acids were determined using ultraperformance LC (UPLC) coupled with ABI 4000.

  16. Combination of capecitabine and ludartin inhibits colon cancer ...

    African Journals Online (AJOL)

    Purpose: To investigate the efficacy of capecitabine and ludartin in the treatment of colon cancer in mice. Methods: Mice model of ... inhibits colon tumor growth and angiogenesis in mice via a mechanism involving suppression of VEGF expression. Thus ..... Clinical pathological features and survival rate of 116 cases of ...

  17. Red meat and colon cancer : how dietary heme initiates hyperproliferation

    NARCIS (Netherlands)

    IJssennagger, N.

    2012-01-01

    Colorectal cancer is a leading cause of cancer deaths in Western countries. The risk to develop colorectal cancer is associated with the intake of red meat. Red meat contains the porphyrin pigment heme. Heme is an irritant for the colonic wall and it is previously shown that the addition of heme

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

    Directory of Open Access Journals (Sweden)

    Carolyn G Marsden

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

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

    Directory of Open Access Journals (Sweden)

    Ioannis Kapelakis

    2017-05-01

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

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

    Science.gov (United States)

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

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

    DEFF Research Database (Denmark)

    Thorsteinsson, M; Jess, Per

    2011-01-01

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

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

    National Research Council Canada - National Science Library

    Bussard, Karen M

    2008-01-01

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

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

    National Research Council Canada - National Science Library

    Selvamurugan, Nagarajan

    2003-01-01

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

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-03-15

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

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

    Directory of Open Access Journals (Sweden)

    Rogers JE

    2017-04-01

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

  7. Fuzzy neural approach for colon cancer prediction | Obi | Scientia ...

    African Journals Online (AJOL)

    fuzzy inference procedure. The proposed system which is self-learning and adaptive is able to handle the uncertainties often associated with the diagnosis and analysis of colon cancer. Keywords: Neural Network, Fuzzy logic, Neuro Fuzzy System, ...

  8. High mortality rates after non-elective colon cancer resection

    DEFF Research Database (Denmark)

    Bakker, I S; Snijders, H S; Grossmann, Irene

    2016-01-01

    AIM: Colon cancer resection in a non-elective setting is associated with high rates of morbidity and mortality. The aim of this retrospective study is to identify risk factors for overall mortality after colon cancer resection with a special focus on non-elective resection. METHOD: Data were...... obtained from the Dutch Surgical Colorectal Audit. Patients undergoing colon cancer resection in the Netherlands between January 2009 and December 2013 were included. Patient, treatment and tumour factors were analyzed in relation to the urgency of surgery. The primary outcome was the thirty day...... postoperative mortality. RESULTS: The study included 30,907 patients. In 5934 (19.2%) of patients, a non-elective colon cancer resection was performed. There was a 4.4% overall mortality rate, with significantly more deaths after non-elective surgery (8.5% vs 3.4%, P

  9. Efficient and reproducible identification of mismatch repair deficient colon cancer

    DEFF Research Database (Denmark)

    Joost, Patrick; Bendahl, Pär-Ola; Halvarsson, Britta

    2013-01-01

    BACKGROUND: The identification of mismatch-repair (MMR) defective colon cancer is clinically relevant for diagnostic, prognostic and potentially also for treatment predictive purposes. Preselection of tumors for MMR analysis can be obtained with predictive models, which need to demonstrate ease...... of application and favorable reproducibility. METHODS: We validated the MMR index for the identification of prognostically favorable MMR deficient colon cancers and compared performance to 5 other prediction models. In total, 474 colon cancers diagnosed ≥ age 50 were evaluated with correlation between...... and efficiently identifies MMR defective colon cancers with high sensitivity and specificity. The model shows stable performance with low inter-observer variability and favorable performance when compared to other MMR predictive models....

  10. Local staging of sigmoid colon cancer using MRI

    DEFF Research Database (Denmark)

    Dam, Claus; Lindebjerg, Jan; Jakobsen, Anders

    2017-01-01

    BACKGROUND: An accurate radiological staging of colon cancer is crucial to select patients who may benefit from neoadjuvant chemotherapy. PURPOSE: To evaluate the diagnostic accuracy of preoperative magnetic resonance imaging (MRI) in identifying locally advanced sigmoid colon cancer, poor...... prognostic factors, and the inter-observer variation of the tumor apparent diffusion coefficient (ADC) values of diffusion-weighted imaging (DWI). MATERIAL AND METHODS: Using 1.5 T MRI with high resolution T2-weighted (T2W) imaging, DWI, and no contrast enhancement, 35 patients with sigmoid colon cancer were...... the measured mean ADC values were below 1.0 × 10(-3) mm(2)/s with an intra-class correlation coefficient in T3cd-T4 tumors of 0.85. CONCLUSION: Preoperative MRI can identify locally advanced sigmoid colon cancer and has potential as the imaging of choice to select patients for neoadjuvant chemotherapy. Initial...

  11. Outcome of Laparoscopic Versus Open Resection for Transverse Colon Cancer.

    Science.gov (United States)

    Zeng, Wei-Gen; Liu, Meng-Jia; Zhou, Zhi-Xiang; Hou, Hui-Rong; Liang, Jian-Wei; Wang, Zheng; Zhang, Xing-Mao; Hu, Jun-Jie

    2015-10-01

    Laparoscopic resection for transverse colon cancer remains controversial. The aim of this study is to investigate the short- and long-term outcomes of laparoscopic surgery for transverse colon cancer. A total of 278 patients with transverse colon cancer from a single institution were included. All patients underwent curative surgery, 156 patients underwent laparoscopic resection (LR), and 122 patients underwent open resection (OR). The short- and long-term results were compared between two groups. Baseline demographic and clinical characteristics were comparable between two groups. Conversions were required in eight (5.1 %) patients. LR group was associated with significantly longer median operating time (180 vs. 140 min; P colon cancer is associated with better short-term outcomes and equivalent long-term oncologic outcomes.

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

    Science.gov (United States)

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

    2015-08-28

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

  13. [A case of transverse colon cancer without a recurrence lesion after five years from resection of hepatic metastasis].

    Science.gov (United States)

    Ami, Katsunori; Nakamura, Masahiro; Takasaki, Jun; Watayou, Yoshihisa; Amagasa, Hidetoshi; Ganno, Hideaki; Kurokawa, Toshiaki; Fukuda, Akira; Nagahama, Takeshi; Ando, Masayuki; Tei, Shikofumi; Okada, Youichi; Arai, Kuniyoshi

    2011-11-01

    The treatment of hepatic metastasis of colon cancer was in progress by new biochemical agents. Generally, a resection was the first alternative treatment against hepatic metastasis of colon cancer, but new antitumor agents were more effective than conventional antitumor agents. Disappearance of metastasis for colon cancer treated with only antitumor agents was commenced to report. We were experienced a case of transverse colon cancer without a recurrence lesion after five years from the resection of hepatic metastasis. A case was a 77-year-old man. He was operated against transverse colon cancer in February 2003. Pathological stage was ss, n0, Stage II. In April 2004, serum CEA was increased. CT examination was not detected a hepatic metastasis but ultrasound examination and MRI detected the metastasis at S7 lesion in the liver. In July 2004, he was admitted to S-1 and PSK until October 2004. In December 2004, the lesion of hepatic metastasis was reduced and serum CEA was decreased. But in September 2005, the metastatic lesion was re-grown. A resection for hepatic metastasis was executed in November 2005. After the resection for hepatic metastasis, he was admitted to UFT/ UZEL from January 2006 to October 2006. Present time( June 2011), the lesion of recurrence was not detected by several examinations (CT, MRI, Ultrasound etc).

  14. 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.

  15. Survival after elective surgery for colonic cancer in Denmark

    DEFF Research Database (Denmark)

    Perdawid, S K; Hemmingsen, L; Boesby, S

    2012-01-01

    AIM: Total mesorectal excision (TME) has been shown to improve the outcome for patients with rectal cancer. In contrast, there are fewer data on complete mesocolic excision (CME) for colonic cancer. METHOD: Data from the National Colorectal Cancer Database were analysed. This includes about 95......% of all patients with colorectal cancer in Denmark. Only patients having elective surgery for colonic cancer in the period 2001-2008 were included. Overall and relative survival analyses were carried out. The study period was divided into the periods 2001-2004 and 2005-2008. RESULTS: 9149 patients were...... included for the final analysis. The overall 5-year survival rates were 0.65 in 2001-2004 and 0.66 in 2005-2008. The relative 5-year survival rates were also within 1% of each other. None of these comparisons was statistically significant. CONCLUSION: Survival following elective colon cancer surgery has...

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

    Science.gov (United States)

    2016-09-01

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

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

    DEFF Research Database (Denmark)

    Iversen, P; Rasmussen, F; Asmussen, C

    1997-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Ocvirk Janja

    2016-06-01

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

  19. Role of phytochemicals in colon cancer prevention : a nutrigenomics approach

    OpenAIRE

    Erk M.J. van

    2004-01-01

    Specific food compounds, especially from fruits and vegetables, may protect against development of colon cancer. In this thesis effects and mechanisms of various phytochemicals in relation to colon cancer prevention were studied through application of large-scale gene expression profiling. Expression measurement of thousands of genes can yield a more complete and in-depth insight into the mode of action of the compounds. Effects of quercetin (a flavonoid present in e.g. apples and onions), cu...

  20. 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.

  1. Curcumin synergizes with resveratrol to inhibit colon cancer.

    Science.gov (United States)

    Majumdar, Adhip P N; Banerjee, Sanjeev; Nautiyal, Jyoti; Patel, Bhaumik B; Patel, Vaishali; Du, Jianhua; Yu, Yingjie; Elliott, Althea A; Levi, Edi; Sarkar, Fazlul H

    2009-01-01

    Development and progression of many malignancies, including colorectal cancer, are associated with activation of multiple signaling pathways. Therefore, inhibition of these signaling pathways with noncytotoxic natural products represents a logical preventive and/or therapeutic approach for colon cancer. Curcumin and resveratrol, both of which inhibit the growth of transformed cells and colon carcinogenesis, were selected to examine whether combining them would be an effective preventive and/or therapeutic strategy for colon cancer. Indeed, the combination of curcumin and resveratrol was found to be more effective in inhibiting growth of p53-positive (wt) and p53-negative colon cancer HCT-116 cells in vitro and in vivo in SCID xenografts of colon cancer HCT-116 (wt) cells than either agent alone. Analysis by Calcusyn software showed synergism between curcumin and resveratrol. The inhibition of tumors in response to curcumin and/or resveratrol was associated with the reduction in proliferation and stimulation of apoptosis accompanied by attenuation of NF-kappaB activity. In vitro studies have further demonstrated that the combinatorial treatment caused a greater inhibition of constitutive activation of EGFR and its family members as well as IGF-1R. Our current data suggest that the combination of curcumin and resveratrol could be an effective preventive/therapeutic strategy for colon cancer.

  2. Idelalisib induces PUMA-dependent apoptosis in colon cancer cells.

    Science.gov (United States)

    Yang, Shida; Zhu, Zhiyong; Zhang, Xiaobing; Zhang, Ning; Yao, Zhicheng

    2017-01-24

    Idelalisib, a PI3K inhibitor, specifically targeting p110δ, has been approved for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma and follicular lymphoma. However, the mechanisms of action of idelalisib in colon cancer cells are not well understood. We investigated how idelalisib suppresses colon cancer cells growth and potentiates effects of other chemotherapeutic drugs. In this study, we found that idelalisib treatment induces PUMA in colon cancer cells irrespective of p53 status through the p65 pathway following AKT inhibition and glycogen synthase kinase 3β (GSK3β) activation. PUMA is necessary for idelalisib-induced apoptosis in colon cancer cells. Idelalisib also synergized with 5-FU or regorafenib to induce marked apoptosis via PUMA in colon cancer cells. Furthermore, PUMA deficiency suppressed apoptosis and antitumor effect of idelalisib in xenograft model. These results demonstrate a critical role of PUMA in mediating the anticancer effects of idelalisib in colon cancer cells and suggest that PUMA induction can be used as an indicator of idelalisib sensitivity, and also have important implications for it clinical applications.

  3. Early colon cancer : findings on double contrast barium enema

    International Nuclear Information System (INIS)

    Kim, Seung Kwon; Lim, Jae Hoon; Lee, Soon Jin; Lim, Hyo Keun

    1998-01-01

    The purpose of this study is to describe the radiologic findings of early colon cancer on double-contrast barium enema. We retrospectively reviewed the double-contrast barium enemas of eight patients (M:F = 6:2; mean age : 67 yrs; range : 48-77 yrs) who were pathologically proven to be early colon cancer. The location, size and gross morphology of lesions was evaluated using double-contrast barium enema, while depth of invasion, degree of differentiation, precancerous lesions and lymph node metastasis were evaluated histopathologically. Early colon cancer was found in the rectum (n=4), sigmoid colon (n=3) and ascending colon (n=1). The size of mass ranged from 2.3 ∼ 8.3 (mean, 4.6) cm. And the polypoid type was most common (n=7); this was subdivided into sessile (Is, n=5), semipedunculated (Isp, n=1) and pedunculated type (Ip, n=1). Another mass was a sessile polypoid combined with a flat depressed lesion. In eight cases, four cancers were confined to the mucosa, while the remaining four had infiltrated the submucosa. Most cancers arose from villous and villotubular adenoma. All cases were well-differentiated adenocarcinoma and no metastasis to lymph nodes had occurred. In early colon cancer, lesions were mainly polypoid and large. Most arose from villous and villotubular adenoma. (author). 19 refs., 1 tab., 3 figs

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

    Science.gov (United States)

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

    2017-12-19

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

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

    Science.gov (United States)

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

    2017-01-01

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

  6. Lymphogenous metastasis to the transverse colon that originated from signet-ring cell gastric cancer: A case report and review of the literature.

    Science.gov (United States)

    Sonoda, Hirofumi; Kawai, Kazushige; Yamaguchi, Hironori; Murono, Koji; Kaneko, Manabu; Nishikawa, Takeshi; Otani, Kensuke; Sasaki, Kazuhito; Yasuda, Koji; Tanaka, Toshiaki; Kiyomatsu, Tomomichi; Hata, Keisuke; Nozawa, Hiroaki; Ishihara, Soichiro; Aikou, Susumu; Yamashita, Hiroharu; Ushiku, Tetsuo; Seto, Yasuyuki; Fukayama, Masashi; Watanabe, Toshiaki

    2017-12-01

    Metastases to the colon are rare and a high-frequency primary region is the stomach. In cases of metastases to the colon, the morphological type of the metastatic region is mostly the infiltrating type of poorly differentiated or undifferentiated adenocarcinoma with lymph and blood vessel invasion. A case of cancer metastasis to the transverse colon that originated from advanced gastric cancer, which shows the difficulties in the precise diagnosis of metastases to the colon, is presented. In the present case, the gastric carcinoma was determined to be an advanced infiltrative ulcerative adenocarcinoma and the colon carcinoma was determined to be a superficial depressed adenocarcinoma. After surgery, the colon carcinoma was diagnosed as a metastatic adenocarcinoma from gastric adenocarcinoma with high invasion of vessels, by immunohistopathological analysis of CK7, CK20, p53 and HER-2. In this report, previously reported cases of metastases to the colon from gastric cancer were reviewed and their morphological characteristics were analyzed. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  7. Cancer of the colon spleen angle. Presentation of a case

    International Nuclear Information System (INIS)

    Martinez Sanchez, Yariana; De la Rosa Perez, Nereida; Barcelo Casanova, Renato E

    2010-01-01

    The colon cancer is currently an important public health problem in developed countries. It is the fourth most common cancer in the world. We report the case of a 65-years-old, black, female patient, assisting our consultation with dyspeptic disturbances as the unique symptom, without known risk factors. We indicated a colon by enema and a distal narrowing was observed at the colon spleen angle, at the same zone of the physiologic narrowing at that level. A colonoscopy was carried out diagnosing a left colon tumor near the spleen angle. It was operated with segmental resection of the spleen angle and a biopsy was made. Pathologic anatomy informed a well-differentiated colon adenocarcinoma

  8. Treatment of initially metastatic small-cell lung cancer

    International Nuclear Information System (INIS)

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

    2013-01-01

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

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

    Science.gov (United States)

    2017-11-20

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

  10. Regorafenib-induced retinal and gastrointestinal hemorrhage in a metastatic colorectal cancer patient with liver dysfunction: A case report.

    Science.gov (United States)

    Tsuchihashi, Kenji; Shimokawa, Hozumi; Takayoshi, Kotoe; Nio, Kenta; Aikawa, Tomomi; Matsushita, Yuzo; Wada, Iori; Arita, Shuji; Ariyama, Hiroshi; Kusaba, Hitoshi; Sonoda, Koh-Hei; Akashi, Koichi; Baba, Eishi

    2017-10-01

    Regorafenib is effective for metastatic colorectal cancer but its toxicity such as hemorrhage should be considered. The safety of regorafenib for the patient with the liver disease is not known. Seventy-one-year old man of colon cancer had myodesopsia and blood stool after 14 days from the initiation of regorafenib administration with 50% dose reduction due to liver dysfunction. Fundus examination revealed hemorrhage of the retinal vein. Regorafenib treatment was discontinued and observational therapy was pursued. Retinal and gastrointestinal hemorrhage resolved in 1 week. Retinal hemorrhage should be considered as the differential diagnosis of myodesopsia in the patient treated by regorafenib. Safety and pharmacokinetic of continuous regorafenib administration for patients with liver dysfunction remains to be clarified.

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

    Science.gov (United States)

    Rimbun, S.; Siregar, Y.

    2018-03-01

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

  12. Special Section: New Ways to Detect Colon Cancer 3-D virtual screening now being used

    Science.gov (United States)

    ... Special Section: Colorectal Cancer New Ways to Detect Colon Cancer 3-D virtual screening now being used Past ... and techniques for 3-D virtual colonoscopy for colon cancer screening. "Things click in the life of an ...

  13. Two distinct expression patterns of urokinase, urokinase receptor and plasminogen activator inhibitor-1 in colon cancer liver metastases

    DEFF Research Database (Denmark)

    Illemann, Martin; Bird, Nigel; Majeed, Ali

    2009-01-01

    Metastatic growth and invasion by colon cancer cells in the liver requires the ability of the cancer cells to interact with the new tissue environment. Plasmin(ogen) is activated on cell surfaces by urokinase-type PA (uPA), and is regulated by uPAR and plasminogen activator inhibitor-1 (PAI-1......). To compare the expression patterns of uPA, uPAR and PAI-1 in colon cancer with that in their liver metastases, we analysed matched samples from 14 patients. In all 14 primary colon cancers, we found upregulation of uPAR, uPA mRNA and PAI-1 in primarily stromal cells at the invasive front. In 5 of the 14......, whereas 8 of the remaining 9 showed direct contact between the cancer cells and the liver parenchyma. We conclude that there are 2 distinct patterns of expression of uPAR, uPA and PAI-1 in colon cancer liver metastases and that these correlate closely with 2 morphological growth patterns. These findings...

  14. Improved survival for rectal cancer compared to colon cancer: the four cohort study.

    Science.gov (United States)

    Buchwald, Pamela; Hall, Claire; Davidson, Callum; Dixon, Liane; Dobbs, Bruce; Robinson, Bridget; Frizelle, Frank

    2018-03-01

    Colorectal cancer (CRC) is the third most common cancer worldwide. This study was undertaken to evaluate survival outcomes and changes of disease outcomes of CRC patients over the last decades. A retrospective analysis of CRC patients in Christchurch was performed in four patient cohorts at 5 yearly intervals; 1993-94, 1998-99, 2004-05 and 2009. Data on cancer location, stage, surgical and oncological treatment and survival were collected. Univariate, multivariate and Kaplan-Meier survival analysis were performed. There were 1391 patients (355, 317, 419 and 300 per cohort), 1037 colon and 354 rectal cancers, respectively. For colon cancer, right-sided cancers appeared more common in later cohorts (P = 0.01). There was a significant decrease in the number of permanent stomas for colon cancer patients (P = 0.001). There was an analogous trend for rectal cancers (P = 0.075). More CRC patients with stage IV disease were treated surgically (P = 0.001) and colon cancer stages I and II tended to have increased survival if operated by a colorectal surgeon (P = 0.06). Oncology referrals have increased remarkably (P = 0.001). Overall 56% of patients were alive at 5 years however rectal cancer patients had significantly better 5-year survival than those with colon cancer (P rectal cancer patients have a better 5-year survival than colon cancer patients. The improved survival with early stage colon cancers operated on by specialist colorectal surgeons needs further exploration. © 2016 Royal Australasian College of Surgeons.

  15. [Evaluation of knowledge about colon cancer prevention versus other tumors].

    Science.gov (United States)

    Sanguinetti, José María; Henry, Nicolás; Ocaña, Domingo; Polesel, Julio Lotero

    2015-06-01

    In Argentina almost 7% of deaths are due to different cancers with screening strategies. Evaluate knowledge about cancer prevention compared with other tumors. Materials. A descriptive and comparative study. A survey between April and June 2013 in Salta City, province of Salta, Argentina. Correct answers were considered. Statistical analysis: Descriptive (mean and percentage), comparative Chi square Test (significance level Pmama and cervix. 20% (CI 0,13-0,28) knew that colon cancer has a genetic predisposition and 58% (CI 0,48-0,67) about mama. 73% (CI 0,63-0,8) received information about cancer prevention. The main source of information was the physician. 46% (CI 0,36-0,55) received medical care in private institutions. Those who had social security, higher educational levels and medical care in private institutions had better knowledge about cancer prevention except in colon cancer. The global results showed levels below 70% in general but extremely low in colon cancer. Not having social security, receiving medical care in public institutions and having a low educational level are related with poor knowledge about cancer prevention except for colon and prostate cancer.

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

    Science.gov (United States)

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

    2017-07-14

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

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

    Science.gov (United States)

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

    2010-02-15

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

  18. The prognostic value of microRNA-126 and microvessel density in patients with stage II colon cancer

    DEFF Research Database (Denmark)

    Hansen, Torben Frøstrup; Kjær-Frifeldt, Sanne; Morgenthaler, Søren

    2014-01-01

    BACKGROUND: Angiogenesis plays a pivotal role in malignant tumour growth and the metastatic process. We analysed the prognostic value of two angiogenesis parameters, microRNA-126 (miRNA-126) and microvessel density (MVD), in a population based cohort of patients operated for stage II colon cancer...... = 0.051. The MVD estimate was not associated with either RF-CSS, p = 0.49, or OS, p = 0.94. CONCLUSION: The current population based study of patients operated for stage II colon cancer demonstrated correlations between several prognostic unfavourable characteristics and miRNA-126 and argues...... were correlated with recurrence-free cancer specific survival (RF-CSS) and overall survival (OS). RESULTS: Low miRNA-126 expression was significantly correlated to T4, high malignancy grade, tumour perforation, fixation, and the presence of microsatellite instability. A prognostic impact on OS...

  19. Multimodal nonlinear optical microscopy used to discriminate human colon cancer

    Science.gov (United States)

    Adur, Javier; Pelegati, Vitor B.; Bianchi, Mariana; de Thomaz, André A.; Baratti, Mariana O.; Carvalho, Hernandes F.; Casco, Víctor H.; Cesar, Carlos L.

    2013-02-01

    Colon cancer is one of the most diffused cancers in the Western World, ranking third worldwide in frequency of incidence after lung and breast cancers. Even if it is curable when detected and treated early, a more accurate premature diagnosis would be a suitable aim for both cancer prognostic and treatment. Combined multimodal nonlinear optical (NLO) microscopies, such as two-photon excitation fluorescence (TPEF), second-harmonic generation (SHG), third harmonic generation (THG), and fluorescence lifetime imaging microscopy (FLIM) can be used to detect morphological and metabolic changes associated with stroma and epithelial transformation in colon cancer disease. NLO microscopes provide complementary information about tissue microstructure, showing distinctive patterns between normal and malignant human colonic mucosa. Using a set of scoring methods significant differences both in the content, distribution and organization of stroma collagen fibrils, and lifetime components of NADH and FAD cofactors of human colon mucosa biopsies were found. Our results provide a framework for using NLO techniques as a clinical diagnostic tool for human colon cancer, and also suggest that the SHG and FLIM metrics could be applied to other intestinal disorders, which are characterized by abnormal cell proliferation and collagen assembly.

  20. Characterization of global microRNA expression reveals oncogenic potential of miR-145 in metastatic colorectal cancer

    International Nuclear Information System (INIS)

    Arndt, Greg M; Retzlaff, Kathy; Bittner, Anton; Raponi, Mitch; Dossey, Lesley; Cullen, Lara M; Lai, Angela; Druker, Riki; Eisbacher, Michael; Zhang, Chunyan; Tran, Nham; Fan, Hongtao

    2009-01-01

    MicroRNAs (MiRNAs) are short non-coding RNAs that control protein expression through various mechanisms. Their altered expression has been shown to be associated with various cancers. The aim of this study was to profile miRNA expression in colorectal cancer (CRC) and to analyze the function of specific miRNAs in CRC cells. MirVana miRNA Bioarrays were used to determine the miRNA expression profile in eight CRC cell line models, 45 human CRC samples of different stages, and four matched normal colon tissue samples. SW620 CRC cells were stably transduced with miR-143 or miR-145 expression vectors and analyzed in vitro for cell proliferation, cell differentiation and anchorage-independent growth. Signalling pathways associated with differentially expressed miRNAs were identified using a gene set enrichment analysis. The expression analysis of clinical CRC samples identified 37 miRNAs that were differentially expressed between CRC and normal tissue. Furthermore, several of these miRNAs were associated with CRC tumor progression including loss of miR-133a and gain of miR-224. We identified 11 common miRNAs that were differentially expressed between normal colon and CRC in both the cell line models and clinical samples. In vitro functional studies indicated that miR-143 and miR-145 appear to function in opposing manners to either inhibit or augment cell proliferation in a metastatic CRC model. The pathways targeted by miR-143 and miR-145 showed no significant overlap. Furthermore, gene expression analysis of metastatic versus non-metastatic isogenic cell lines indicated that miR-145 targets involved in cell cycle and neuregulin pathways were significantly down-regulated in the metastatic context. MiRNAs showing altered expression at different stages of CRC could be targets for CRC therapies and be further developed as potential diagnostic and prognostic analytes. The identified biological processes and signalling pathways collectively targeted by co-expressed miRNAs in

  1. Role of dietary fiber in diverticular disease and colon cancer.

    Science.gov (United States)

    Talbot, J M

    1981-07-01

    This paper reviews recent research on the characterization, properties, and definition of dietary fiber as well as its possible role in colonic carcinogenesis and diverticulosis. Despite progress in analytic methods and characterization, an accepted definition and terminology for fiber are lacking as is an accurate, rapid method for measurement of total dietary fiber or fiber in foods. Mechanisms of effects of fiber in the gut and the significant of interactions between fiber, nutrients gut flora and associated metabolites, and enteric secretions are unclear. Epidemiologic and experimental data indicate an increased risk of diverticular disease and colonic cancer with low-fiber intakes; however, genetic, environmental, cultural, dietary, and other variables were often uncontrolled in the epidemiologic studies. Thus, conclusive evidence for a causal relationship between low intake of fiber and diverticulosis or colonic cancer is not available, and the question whether first protects against human colonic cancer and/or diverticulosis is not completely resolved. Clinical trials in which symptomatic diverticular disease was treated with supplementary dietary fiber have generally had favorable results. Numerous specific questions require additional study before a role for dietary fiber in the prevention of human colonic diverticulosis and cancer of the colon can be established. Suggestions for possible future investigation are provided.

  2. Use of nonsteroidal antiinflamatory drugs for chemoprevention of colon cancer

    Directory of Open Access Journals (Sweden)

    Milić Aleksandra

    2013-01-01

    Full Text Available Colorectal cancer is in the third most frequent cancer among malignant tumors of both sexes in developed countries. It is predominantly a disease of older persons and occurs mostly after the age of 60. Although the etiology of colon cancer is unknown, it is assumed to arise as a result of unclear and complex interactions between genetic and environmental factors. The main element in the etiology of colorectal cancer is the process of genetic changes in epithelial cells of colon mucosa. It is believed that specific epidemiological factors such as stress, hypoxia, reduced intake of glucose and other nutrients, a hereditary predisposition to mutagenic effects, the meat in the diet, bile acids, reduced intake of minerals and vitamins as well as changes in pH of feces lead to initiation of the process of carcinogenesis in mucosa of the colon. Cancer chemoprevention is defined as the use of chemical agents in order to block, prevent or delay the reversal development or progress of cancer. It is believed that chemoprevention is a key component of cancer control, and numerous studies indicate potential role of NSAIDs in chemoprevention of colon cancer.

  3. The influence of hormone therapies on colon and rectal cancer

    DEFF Research Database (Denmark)

    Mørch, Lina Steinrud; Lidegaard, Øjvind; Keiding, Niels

    2016-01-01

    followed 1995–2009. Information on HT exposures was from the National Prescription Register and updated daily, while information on colon (n = 8377) and rectal cancers (n = 4742) were from the National Cancer Registry. Potential confounders were obtained from other national registers. Poisson regression...

  4. Mucin expression patterns in histological grades of colonic cancers ...

    African Journals Online (AJOL)

    Pathological expression of mucins has been noted in cancer development and progression. This study sought to identify and quantify the types of mucins produced during various histological grades of colon cancer and to assess the diagnostic significance. Methods: Formalin fixed, paraffin-embedded tissue blocks, ...

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

    Science.gov (United States)

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

    2017-03-01

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

  6. Incisional hernias after open versus laparoscopic surgery for colonic cancer

    DEFF Research Database (Denmark)

    Jensen, Kristian K.; Krarup, Peter-Martin; Scheike, Thomas

    2016-01-01

    patients operated on electively for colonic cancer with primary anastomosis in Denmark from 2001 to 2008. Patient data were obtained from the database of the Danish Colorectal Cancer Group and merged with data from the National Patient Registry. Multivariable Cox regression and competing risks analysis......, fascial dehiscence, anastomotic leak, and body mass index >25 kg/m(2). CONCLUSIONS: This nationwide analysis demonstrated that laparoscopic as compared with open access for curative resection of colonic cancer was associated with a decreased risk of incisional hernia formation....

  7. A nationwide study on anastomotic leakage after colonic cancer surgery

    DEFF Research Database (Denmark)

    Krarup, Peter-Martin; Jorgensen, L N; Andreasen, A H

    2012-01-01

    Aim: Anastomotic leakage (AL) is a major challenge in colorectal cancer surgery due to increased morbidity and mortality. Possible risk factors should be investigated differentially, distinguishing between rectal and colonic surgery in large-scale studies to avoid selection bias and confounding....... Method: The incidence and risk factors associated with AL were analysed in an unselected nation-wide prospective cohort of patient subjected to curative colonic cancer surgery with primary anastomosis and entered into The Danish Colorectal Cancer Group database between May 2001 and December 2008. Results...

  8. Limitations of tissue micro array in Duke's B colon cancer

    DEFF Research Database (Denmark)

    Kjær-Frifeldt, Sanne; Lindebjerg, Jan; Brunner, Nils

    2012-01-01

    Tissue micro array (TMA) is widely used in cancer research in search of new predictive and prognostic markers. Colon cancer is known to be heterogeneous and the present study addresses some methodological aspects using cores of different size and analysing markers with different cellular...... distribution. We selected 61 paraffin-embedded tissue blocks representing patients diagnosed with Dukes B colon cancer. Two 1 mm and two 2 mm cores were taken from both the centre and the invasive front of the tumour respectively. The immunostaining included MLH1, MSH2, PMS2, p53, COX-2, TIMP and Betacatenin...... moderate to high agreement (kappa = 0.54-0.9) whereas TIMP-1 had the lowest score (kappa 0.19-0.25). The application of TMA in Dukes B colon cancer has several pitfalls and depends substantially on the immunohistochemical marker in question. Therefore a validation study seems justified before applying...

  9. A metastatic colon adenocarcinoma harboring BRAF V600E has a durable major response to dabrafenib/trametinib and chemotherapy

    Directory of Open Access Journals (Sweden)

    Williams CB

    2015-12-01

    Full Text Available Casey B Williams,1,* Caitlin McMahon,2,* Siraj M Ali,2 Mark Abramovitz,1 Kirstin A Williams,1 Jessica Klein,1 Heidi McKean,1 Roman Yelensky,2 Thomas J George Jr,3 Julia A Elvin,2 Salil Soman,4 Doron Lipson,2 Juliann Chmielecki,2 Deborah Morosini,2 Vincent A Miller,2 Philip J Stephens,2 Jeffrey S Ross,2,5 Brian Leyland-Jones1 1Avera Cancer Institute, Sioux Falls, SD, USA; 2Foundation Medicine, Inc., Cambridge, MA, USA; 3University of Florida College of Medicine, Gainesville, FL, USA; 4Beth Israel Deaconess Medical Center, Boston, MA, USA; 5Albany Medical College, Albany, NY, USA *These authors contributed equally to this work Abstract: The subset of metastatic colorectal adenocarcinomas that harbor BRAF V600E mutations are aggressive tumors with significantly shortened survival and limited treatment options. Here we present a colorectal cancer patient whose disease progressed through standard chemotherapy and who developed liver metastasis. Comprehensive genomic profiling (FoundationOne® identified a BRAF V600E mutation in the liver lesion, as well as other genomic alterations consistent with colorectal cancers. Combination therapy of dabrafenib and trametinib with standard cytotoxic chemotherapy resulted in a durable major ongoing response for the patient. This report illustrates the utility of comprehensive genomic profiling with personalized targeted therapy for aggressive metastatic colorectal adenocarcinomas. Keywords: oxaliplatin, colorectal adenocarcinoma, combination targeted therapy, BRAF mutations

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

    Directory of Open Access Journals (Sweden)

    Hadi Danaee

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

  11. Factors associated with the efficiency of maintenance therapy in patients with metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    M. Yu. Fedyanin

    2016-01-01

    Full Text Available Objective: to evaluate tolerability and efficacy of maintenance treatment in the absence of progression after 16 weeks of first-line therapy in patients with unresectable metastatic colon cancer.Materials and methods. We have analyzed medical case histories of patients with metastatic colorectal cancer who underwent treatment in the department of clinical pharmacology and chemotherapy of N. N. Blokhin Russian Cancer Research Center from 2007 to 2015 years. Inclusion criteria were the following: 16–24 weeks of first-line chemotherapy with no signs of progression and the inability to perform metastasectomy. Progression-free survival was the main criterion for effectiveness in our study.Results. 160 (44.5 % of 359 treated patients met the inclusion criteria. 102 (63.7 % patients were followed up, while the other 58 (36.3 % – comparison group patients underwent maintenance chemotherapy. Grade I–II toxic reactions and grade III complications associated with first-line chemotherapy were insignificantly more common in the group of patients left on maintenance chemotherapy: 72.4 % and 37.9 % versus 57.8 % and 24.5 % in the comparison group, p = 0.07 and p = 0.07 respectively. The frequency of grade I–II toxic reactions and grade III complications in the second-line treatment did not differ between treatment groups (p = 0.9 and p = 0.8. The median of progression-free survival in observation group and comparison group was 4, and 6 months (odds ratio (OR 0.6; p = 0.009, and life expectancy – 23 and 31 months (OR 0.75; p = 0.1, respectively. Statistically significant differences between groups with respect to achieving the objective response and/or normalization of carcinoembryonic antigen level were revealed: median of progression-free survival was 13 (n = 26 of 57; 45.6 % and 4 months (n = 31 of 57, 54.4 %, respectively (HR 0.38; p = 0.002, median of life expectancy – 34 months versus 26 months (OR 0.37; p = 0.3.

  12. Bevacizumab for Metastatic Colorectal Cancer: A Global Cost-Effectiveness Analysis.

    Science.gov (United States)

    Goldstein, Daniel A; Chen, Qiushi; Ayer, Turgay; Chan, Kelvin K W; Virik, Kiran; Hammerman, Ariel; Brenner, Baruch; Flowers, Christopher R; Hall, Peter S

    2017-06-01

    In the U.S., the addition of bevacizumab to first-line chemotherapy in metastatic colorectal cancer (mCRC) has been demonstrated to provide 0.10 quality-adjusted life years (QALYs) at an incremental cost-effectiveness ratio (ICER) of $571,000/QALY. Due to variability in pricing, value for money may be different in other countries. Our objective was to establish the cost-effectiveness of bevacizumab in mCRC in the U.S., U.K., Canada, Australia, and Israel. We performed the analysis using a previously established Markov model for mCRC. Input data for efficacy, adverse events, and quality of life were considered to be generalizable and therefore identical for all countries. We used country-specific prices for medications, administration, and other health service costs. All costs were converted from local currency to U.S. dollars at the exchange rates in March 2016. We conducted one-way and probabilistic sensitivity analyses (PSA) to assess the model robustness across parameter uncertainties. Base case results demonstrated that the highest ICER was in the U.S. ($571,000/QALY) and the lowest was in Australia ($277,000/QALY). In Canada, the U.K., and Israel, ICERs ranged between $351,000 and $358,000 per QALY. PSA demonstrated 0% likelihood of bevacizumab being cost-effective in any country at a willingness to pay threshold of $150,000 per QALY. The addition of bevacizumab to first-line chemotherapy for mCRC consistently fails to be cost-effective in all five countries. There are large differences in cost-effectiveness between countries. This study provides a framework for analyzing the value of a cancer drug from the perspectives of multiple international payers. The cost-effectiveness of bevacizumab varies significantly between multiple countries. By conventional thresholds, bevacizumab is not cost-effective in metastatic colon cancer in the U.S., the U.K., Australia, Canada, and Israel. © AlphaMed Press 2017.

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  14. Survival advantages conferred to colon cancer cells by E-selectin-induced activation of the PI3K-NFκB survival axis downstream of Death receptor-3

    International Nuclear Information System (INIS)

    Porquet, Nicolas; Huot, Jacques; Poirier, Andrée; Houle, François; Pin, Anne-Laure; Gout, Stéphanie; Tremblay, Pierre-Luc; Paquet, Éric R; Klinck, Roscoe; Auger, François A

    2011-01-01

    Extravasation of circulating cancer cells is a key event of metastatic dissemination that is initiated by the adhesion of cancer cells to endothelial cells. It requires interactions between adhesion receptors on endothelial cells and their counter-receptors on cancer cells. Notably, E-selectin, a major endothelial adhesion receptor, interacts with Death receptor-3 present on metastatic colon carcinoma cells. This interaction confers metastatic properties to colon cancer cells by promoting the adhesion of cancer cells to endothelial cells and triggering the activation of the pro-migratory p38 and pro-survival ERK pathways in the cancer cells. In the present study, we investigated further the mechanisms by which the E-selectin-activated pathways downstream of DR3 confer a survival advantage to colon cancer cells. Cell survival has been ascertained by using the WST-1 assay and by evaluating the activation of the PI3 kinase/NFκB survival axis. Apoptosis has been assayed by determining DNA fragmentation by Hoechst staining and by measuring cleavage of caspases-8 and -3. DR3 isoforms have been identified by PCR. For more precise quantification, targeted PCR reactions were carried out, and the amplified products were analyzed by automated chip-based microcapillary electrophoresis on an Agilent 2100 Bioanalyzer instrument. Interaction between DR3-expressing HT29 colon carcinoma cells and E-selectin induces the activation of the PI3K/Akt pathway. Moreover, p65/RelA, the anti-apoptotic subunit of NFκB, is rapidly translocated to the nucleus in response to E-selectin. This translocation is impaired by the PI3K inhibitor LY294002. Furthermore, inhibition of the PI3K/Akt pathway increases the cleavage of caspase 8 in colon cancer cells treated with E-selectin and this effect is still further increased when both ERK and PI3K pathways are concomitantly inhibited. Intriguingly, metastatic colon cancer cell lines such as HT29 and SW620 express higher levels of a splice variant of

  15. Sixth nerve palsy as the presenting symptom of metastatic colon carcinoma.

    Science.gov (United States)

    Kinori, Michael; Ben Bassat, Iris; Huna-Baron, Ruth

    2011-02-01

    Isolated cranial mononeuropathies in patients over 50 years of age most commonly result from microvascular ischemic demyelination. A 51-year-old female without vasculopathic risk factors presented with isolated sixth nerve palsy. Magnetic resonance imaging (MRI) of the brain and orbits revealed a cavernous sinus lesion that was diagnosed as a meningioma. Laboratory tests showed abnormal liver function, and an abdominal computerized tomogram demonstrated an obstructive colonic mass with liver metastasis. The pathology tests of specimens taken during a laparotomy diagnosed colon adenocarcinoma. The MRI interpretation was changed to cavernous sinus metastasis from a primary adenocarcinoma of the colon. This case had common cranial nerve symptoms but with a very rare etiology, emphasizing the importance of a high index of suspicion of remote origins in patients with isolated sixth nerve palsy and no atherosclerotic risk factors.

  16. EMT is the dominant program in human colon cancer

    Directory of Open Access Journals (Sweden)

    Tollenaar Rob AEM

    2011-01-01

    Full Text Available Abstract Background Colon cancer has been classically described by clinicopathologic features that permit the prediction of outcome only after surgical resection and staging. Methods We performed an unsupervised analysis of microarray data from 326 colon cancers to identify the first principal component (PC1 of the most variable set of genes. PC1 deciphered two primary, intrinsic molecular subtypes of colon cancer that predicted disease progression and recurrence. Results Here we report that the most dominant pattern of intrinsic gene expression in colon cancer (PC1 was tightly correlated (Pearson R = 0.92, P -135 with the EMT signature-- both in gene identity and directionality. In a global micro-RNA screen, we further identified the most anti-correlated microRNA with PC1 as MiR200, known to regulate EMT. Conclusions These data demonstrate that the biology underpinning the native, molecular classification of human colon cancer--previously thought to be highly heterogeneous-- was clarified through the lens of comprehensive transcriptome analysis.

  17. Variation in positron emission tomography use after colon cancer resection.

    Science.gov (United States)

    Bailey, Christina E; Hu, Chung-Yuan; You, Y Nancy; Kaur, Harmeet; Ernst, Randy D; Chang, George J

    2015-05-01

    Colon cancer surveillance guidelines do not routinely include positron emission tomography (PET) imaging; however, its use after surgical resection has been increasing. We evaluated the secular patterns of PET use after surgical resection of colon cancer among elderly patients and identified factors associated with its increasing use. We used the SEER-linked Medicare database (July 2001 through December 2009) to establish a retrospective cohort of patients age ≥ 66 years who had undergone surgical resection for colon cancer. Postoperative PET use was assessed with the test for trends. Patient, tumor, and treatment characteristics were analyzed using univariable and multivariable logistic regression analyses. Of the 39,221 patients with colon cancer, 6,326 (16.1%) had undergone a PET scan within 2 years after surgery. The use rate steadily increased over time. The majority of PET scans had been performed within 2 months after surgery. Among patients who had undergone a PET scan, 3,644 (57.6%) had also undergone preoperative imaging, and 1,977 (54.3%) of these patients had undergone reimaging with PET within 2 months after surgery. Marriage, year of diagnosis, tumor stage, preoperative imaging, postoperative visit to a medical oncologist, and adjuvant chemotherapy were significantly associated with increased PET use. PET use after colon cancer resection is steadily increasing, and further study is needed to understand the clinical value and effectiveness of PET scans and the reasons for this departure from guideline-concordant care. Copyright © 2015 by American Society of Clinical Oncology.

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

    Science.gov (United States)

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

    2013-01-01

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

  19. 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.

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

    African Journals Online (AJOL)

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    OpenAIRE

    Park, Geon-Tae; Choi, Kyung-Chul

    2016-01-01

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

  3. Influence of dietary protein sources on putative in vitro and in vivo colon cancer biomarkers

    NARCIS (Netherlands)

    Vis, E.H.

    2002-01-01

    Colon cancer (cancer of the large intestine) is a worldwide problem in especially Western countries. The diet might be responsible for up to 90% of these colon cancer cases. This means that decreasing colon cancer risk should be possible by changing the diet. The research presented in this

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

    Science.gov (United States)

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

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

    NARCIS (Netherlands)

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

    2017-01-01

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

  6. Physical mapping of chromosome 8p22 markers and their homozygous deletion in a metastatic prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bova, G.S.; Pin, S.S.; Isaacs, W.B. [Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States)]|[Brady Urological Institute, Baltimore, MD (United States)] [and others

    1996-07-01

    Numerous studies have implicated the short arm of chromosome 8 as the site of one or more tumor suppressor genes inactivated in carcinogenesis of the prostate, colon, lung, and liver. Previously, we identified a homozygous deletion on chromosome 8p22 in a metastatic prostate cancer. To map this homozygous deletion physically, long-range restriction mapping was performed using yeast artificial chromosomes (YACs) spanning approximately 2 Mb of chromosome band 8p22. Subcloned genomic DNA and cDNA probes isolated by hybrid capture from these YACs were mapped in relation to one another, reinforcing map integrity. Mapped single-copy probes from the region were then applied to DNA isolated from a metastatic prostate cancer containing a chromosome 8p22 homozygous deletion and indicated that its deletion spans 730-970 kb. Candidate genes PRLTS (PDGF-receptor {beta}-like tumor suppressor) and CTSB (cathepsin B) are located outside the region of homozygous deletion. Genethon marker D8S549 is located approximately at the center of this region of homozygous deletion. Two new microsatellite polymorphisms, D8S1991 and D8S1992, also located within the region of homozygous deletion on chromosome 8p22, are described. Physical mapping places cosmid CI8-2644 telomeric to MSR (macrophage scavenger receptor), the reverse of a previously published map, altering the interpretation of published deletion studies. This work should prove helpful in the identification of candidate tumor suppressor genes in this region. 47 refs., 5 figs., 1 tab.

  7. Colon-available raspberry polyphenols exhibit anti-cancer effects on in vitro models of colon cancer

    Directory of Open Access Journals (Sweden)

    McDougall Gordon

    2007-01-01

    Full Text Available Abstract Background There is a probable association between consumption of fruit and vegetables and reduced risk of cancer, particularly cancer of the digestive tract. This anti-cancer activity has been attributed in part to anti-oxidants present in these foods. Raspberries in particular are a rich source of the anti-oxidant compounds, such as polyphenols, anthocyanins and ellagitannins. Methods A "colon-available" raspberry extract (CARE was prepared that contained phytochemicals surviving a digestion procedure that mimicked the physiochemical conditions of the upper gastrointestinal tract. The polyphenolic-rich extract was assessed for anti-cancer properties in a series of in vitro systems that model important stages of colon carcinogenesis, initiation, promotion and invasion. Results The phytochemical composition of CARE was monitored using liquid chromatography mass spectrometry. The colon-available raspberry extract was reduced in anthocyanins and ellagitannins compared to the original raspberry juice but enriched in other polyphenols and polyphenol breakdown products that were more stable to gastrointestinal digestion. Initiation – CARE caused significant protective effects against DNA damage induced by hydrogen peroxide in HT29 colon cancer cells measured using single cell microgelelectrophoresis. Promotion – CARE significantly decreased the population of HT29 cells in the G1 phase of the cell cycle, effectively reducing the number of cells entering the cell cycle. However, CARE had no effect on epithelial integrity (barrier function assessed by recording the trans-epithelial resistance (TER of CACO-2 cell monolayers. Invasion – CARE caused significant inhibition of HT115 colon cancer cell invasion using the matrigel invasion assay. Conclusion The results indicate that raspberry phytochemicals likely to reach the colon are capable of inhibiting several important stages in colon carcinogenesis in vitro.

  8. [A case of sigmoid colon cancer with abdominal wall abscess].

    Science.gov (United States)

    Yamamoto, Yuji; Shimizu, Shinichiro; Maruyama, Takashi; Tanaka, Hajime; Matsuzaki, Hiroshi; Natsume, Toshiyuki; Miyazaki, Akinari; Satoh, Yayoi; Satsuka, Tetsutaro; Yoshioka, Takafumi; Kanada, Yoko; Otsuka, Ryota; Yanagihara, Akitoshi; Yokoyama, Masaya; Kobayashi, Takushi

    2014-11-01

    A 63-year-old man was admitted for an abdominal mass. Computed tomography revealed an abscess (21 × 20 cm) in the abdominal wall and a tumor in the sigmoid colon. Thus, cancer of the sigmoid colon complicated by an abscess of the abdominal wall was diagnosed. The abscess was drained and transverse colostomy was performed with curative intent. After the intervention, chemotherapy (XELOX×3) was administered. Three months later, sigmoidectomy was performed and the stoma was closed. Macroscopic and microscopic examination of the resected specimen detected no remnants of cancer. In patients with advanced colon cancer and abdominal wall involvement, a two-stage operation and preoperative chemotherapy may be considered essential when curative resection is performed.

  9. TNF Receptor-2 Facilitates an Immunosuppressive Microenvironment in the Liver to Promote the Colonization and Growth of Hepatic Metastases

    DEFF Research Database (Denmark)

    Ham, Boram; Wang, Ni; D'Costa, Zarina

    2015-01-01

    Successful colonization by a cancer cell of a distant metastatic site requires immune escape in the new microenvironment. TNF signaling has been implicated broadly in the suppression of immune surveillance that prevents colonization at the metastatic site and therefore must be blocked...... chemotherapy-naïve colon cancer patients confirmed the presence of CD33(+)HLA-DR(-)TNFR2(+) myeloid cells in the periphery of hepatic metastases. Overall, our findings implicate TNFR2 in supporting MDSC-mediated immune suppression and metastasis in the liver, suggesting the use of TNFR2 inhibitors...... as a strategy to prevent metastatic progression to liver in colon, lung, and various other types of cancer....

  10. Pitfalls in diagnosing colon cancer on abdominal CT.

    Science.gov (United States)

    Klang, E; Eifer, M; Kopylov, U; Belsky, V; Raskin, S; Konen, E; Amitai, M M

    2017-10-01

    To assess the frequency of undetected colon cancer on conventional abdominal CT and to evaluate the imaging features that are characteristic of those cancers. The present study included consecutive patients diagnosed with colorectal cancer at colonoscopy (2006-2015) who also underwent abdominal computed tomography (CT) performed for various reasons within a year prior to the colonoscopy. The frequency of undetected lesions was evaluated for the original CT interpretations ("original readers"). Two radiologists ("study readers"), blinded to the tumour location, independently performed interpretations oriented for colon cancer detection. The study readers analysed the imaging features of detected tumours (tumour shape, length, maximal wall thickness, free fluid, fat stranding, vascular engorgement, stenosis, and lymphadenopathy). Imaging features of the cancers undetected by the original readers were evaluated. The study included 127 patients. The original readers' frequency of undetected cancer was 25/127 (19.7%). Each study reader could not identify the cancer in 8/127 (6.3%) patients. Imaging features associated with undetected cancers by the original readers included the absence of fat stranding (p=0.007, p=0.003), absence of vascular engorgement (pColon cancer is undetected in 20% of abdominal CT examinations in patients subsequently proven to have colon cancer at colonoscopy. The absence of fat stranding, vascular engorgement, or lymphadenopathy, and an average tumour length of 3.3 cm are contributing factors for failure of detection. Radiologists' training should emphasis these findings as it may improve cancer detection, and clinicians should be aware of the limitations of abdominal CT. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  11. Locally advanced colon cancer with cutaneous invasion: case report.

    Science.gov (United States)

    Tenreiro, Nádia; Ferreira, Cátia; Silva, Silvia; Marques, Rita; Ribeiro, Artur; Sousa, Paulo Jorge; Luís, Fernando Próspero

    2017-03-01

    Locally advanced colon cancer with direct abdominal wall and skin invasion is an extremely rare finding with most data being derived from case reports, historical autopsy-based or single-center retrospective studies. We present a unique case of a colon cancer with direct cutaneous invasion and colocutaneous fistulization. Eighty-six year old Caucasian female with multiple comorbidities, referred to Surgical Consultation due to ulcerated skin lesion in the abdomen. She had a long-standing large umbilical hernia but with no previous episodes of incarceration or occlusive symptoms. She denied any digestive or constitutional symptoms. Physical examination showed a large non-reducible umbilical hernia, with an associated painless firm mass within the hernia sac and cutaneous ulcerated growth. Colonoscopy revealed transverse colon cancer (endoscopic biopsy of the tumor and skin punch biopsy confirmed adenocarcinoma of the colon). Computed tomography showed a tumoral mass within the umbilical hernia, with cutaneous infiltration and enlarged regional lymph nodes. Rapid local progression led to colocutaneous fistula with total fecal diversion. We performed an extended right hemicolectomy with en bloc excision of the hernia sac and infiltrating cutaneous mass. In the current era of widespread use of screening colonoscopies, initial diagnosis of locally advanced colon cancer is decreasing. However, this unique case presented an opportunity to recall the advantages of multivisceral resections.

  12. Time- and dose-dependent effects of curcumin on gene expression in human colon cancer cells

    NARCIS (Netherlands)

    Erk, M.J. van; Teuling, E.; Staal, Y.C.M.; Huybers, S.; Bladeren, P.J. van; Aarts, J.M.M.J.G.; Ommen, B. van

    2004-01-01

    Background. Curcumin is a spice and a coloring food compound with a promising role in colon cancer prevention. Curcumin protects against development of colon tumors in rats treated with a colon carcinogen, in colon cancer cells curcumin can inhibit cell proliferation and induce apoptosis, it is an

  13. Time- and dose-dependent effects of curcumin on gene expression in human colon cancer cells

    NARCIS (Netherlands)

    Van Erk, Marjan J; Teuling, Eva; Staal, Yvonne C. M.; Huybers, Sylvie; Van Bladeren, Peter J; Aarts, Jac MMJG; Van Ommen, Ben

    2004-01-01

    BACKGROUND: Curcumin is a spice and a coloring food compound with a promising role in colon cancer prevention. Curcumin protects against development of colon tumors in rats treated with a colon carcinogen, in colon cancer cells curcumin can inhibit cell proliferation and induce apoptosis, it is an

  14. Time- and dose-dependent effects of curcumin on gene expression in human colon cancer cells

    NARCIS (Netherlands)

    Erk, van M.J.; Teuling, E.; Staal, Y.C.M.; Huybers, S.; Bladeren, van P.J.; Aarts, J.M.M.J.G.; Ommen, van B.

    2004-01-01

    Background: Curcumin is a spice and a coloring food compound with a promising role in colon cancer prevention. Curcumin protects against development of colon tumors in rats treated with a colon carcinogen, in colon cancer cells curcumin can inhibit cell proliferation and induce apoptosis, it is an

  15. Predicting opportunities to increase utilization of laparoscopy for colon cancer.

    Science.gov (United States)

    Keller, Deborah S; Parikh, Niraj; Senagore, Anthony J

    2017-04-01

    Despite proven safety and efficacy, rates of minimally invasive approaches for colon cancer remain low in the USA. Given the known benefits, investigating the root causes of underutilization and methods to increase laparoscopy is warranted. Our goal was to develop a predictive model of factors impacting use of laparoscopic surgery for colon cancer. The Premier Hospital Database was reviewed for elective colorectal resections for colon cancer (2009-2014). Patients were identified by ICD-9-CM diagnosis code and then stratified into open or laparoscopic approaches by ICD-9-CM procedure codes. An adjusted multivariate logistic regression model identified variables predictive of use of laparoscopy for colon cancer. A total of 24,245 patients were included-12,523 (52 %) laparoscopic and 11,722 (48 %) open. General surgeons performed the majority of all procedures (77.99 % open, 71.60 % laparoscopic). Overall use of laparoscopy increased from 48.94 to 52.03 % over the study period (p colon cancer laparoscopically. Colorectal surgeons were 32 % more likely to approach a case laparoscopically than general surgeons (OR 1.315, 95 % CI [1.222, 1.415], p characteristics that can be identified preoperatively to predict who will undergo surgery for colon cancer using laparoscopy. However, additional patients may be eligible for laparoscopy based on patient-level characteristics. These results have implications for regionalization and increasing teaching of MIS. Recognizing and addressing these variables with training and recruiting could increase use of minimally invasive approaches, with the associated clinical and financial benefits.

  16. [A case of long-term survival due to combined modality therapy for liver metastasis of colon cancer].

    Science.gov (United States)

    Hasegawa, Hirofumi; Hashimoto, Takashi; Nakamura, Toshihiko; Kitagawa, Masaru; Kudo, Kensuke; Shoji, Fumihiro; Kabashima, Akira; Teramoto, Seiichi; Kitamura, Masayuki

    2012-11-01

    The patient was a 68-year-old man. Because sigmoid colon cancer and metastatic liver cancer was diagnosed in August 2009, an indwelling central venous port and sigmoid colon resection were implemented. The metastatic liver cancer was a huge tumor occupying the right hepatic lobe and caudate lobe. In consideration of the risk associated with the resection and the possibility of early recurrence, the postoperative chemotherapy was selected. He underwent 9 courses of bevacizumab (Bev)+FOLFOX. The tumor was observed to reduce but continued to occupy the right lobe and caudate lobe. At this point, the surgical treatment was selected because the tumor has been shrunk and there is no appearance of new metastases. In order to preserve residual liver function, he underwent percutaneous transhepatic portal embolization and then resection of the right lobe of the liver in February 2010. Although the Bev+FOLFOX treatment was started again after surgery as adjuvant chemotherapy, the metastatic liver cancer recurred in the remnant liver in August 2010. Because it was about 6 months from the first recurrence of liver resection, we decided to continue chemotherapy immediately without resection. However, the chemotherapy was insufficient to shrink the tumor, which increased because it was present at 3 locations in the liver. Therefore, partial hepatectomy at the 3 locations with positron-emission tomography was performed in February 2011. Since then, chemotherapy has not been performed in patients, and there is no recurrence as of March 2012. In the guideline for the treatment of liver metastasis of colorectal cancer, even though chemotherapy is currently developed, the surgical procedure is recommended for patients who are responsive to local therapy. If the cancer recur immediately after resection, it is difficult to decide whether to re-resect. We report the case in which the tumor-free status can be observed as a result of a combination of systemic chemotherapy and local

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

    Directory of Open Access Journals (Sweden)

    Hui Miao

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

  18. Complement 5a Enhances Hepatic Metastases of Colon Cancer via Monocyte Chemoattractant Protein-1-mediated Inflammatory Cell Infiltration.

    Science.gov (United States)

    Piao, Chunmei; Cai, Lun; Qiu, Shulan; Jia, Lixin; Song, Wenchao; Du, Jie

    2015-04-24

    Complement 5a (C5a), a potent immune mediator generated by complement activation, promotes tumor growth; however, its role in tumor metastasis remains unclear. We demonstrate that C5a contributes to tumor metastases by modulating tumor inflammation in hepatic metastases of colon cancer. Colon cancer cell lines generate C5a under serum-free conditions, and C5a levels increase over time in a murine syngeneic colon cancer hepatic metastasis model. Furthermore, in the absence of C5a receptor or upon pharmacological inhibition of C5a production with an anti-C5 monoclonal antibody, tumor metastasis is severely impaired. A lack of C5a receptor in colon cancer metastatic foci reduces the infiltration of macrophages, neutrophils, and dendritic cells, and the role for C5a receptor on these cells were further verified by bone marrow transplantation experiments. Moreover, C5a signaling increases the expression of the chemokine monocyte chemoattractant protein-1 and the anti-inflammatory molecules arginase-1, interleukin 10, and transforming growth factor β, but is inversely correlated with the expression of pro-inflammatory molecules, which suggests a mechanism for the role of C5a in the inflammatory microenvironment required for tumor metastasis. Our results indicate a new and potentially promising therapeutic application of complement C5a inhibitor for the treatment of malignant tumors. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Complement 5a Enhances Hepatic Metastases of Colon Cancer via Monocyte Chemoattractant Protein-1-mediated Inflammatory Cell Infiltration*

    Science.gov (United States)

    Piao, Chunmei; Cai, Lun; Qiu, Shulan; Jia, Lixin; Song, Wenchao; Du, Jie

    2015-01-01

    Complement 5a (C5a), a potent immune mediator generated by complement activation, promotes tumor growth; however, its role in tumor metastasis remains unclear. We demonstrate that C5a contributes to tumor metastases by modulating tumor inflammation in hepatic metastases of colon cancer. Colon cancer cell lines generate C5a under serum-free conditions, and C5a levels increase over time in a murine syngeneic colon cancer hepatic metastasis model. Furthermore, in the absence of C5a receptor or upon pharmacological inhibition of C5a production with an anti-C5 monoclonal antibody, tumor metastasis is severely impaired. A lack of C5a receptor in colon cancer metastatic foci reduces the infiltration of macrophages, neutrophils, and dendritic cells, and the role for C5a receptor on these cells were further verified by bone marrow transplantation experiments. Moreover, C5a signaling increases the expression of the chemokine monocyte chemoattractant protein-1 and the anti-inflammatory molecules arginase-1, interleukin 10, and transforming growth factor β, but is inversely correlated with the expression of pro-inflammatory molecules, which suggests a mechanism for the role of C5a in the inflammatory microenvironment required for tumor metastasis. Our results indicate a new and potentially promising therapeutic application of complement C5a inhibitor for the treatment of malignant tumors. PMID:25739439

  20. A novel double-enhanced suicide gene therapy in a colon cancer cell line mediated by gef and apoptin.

    Science.gov (United States)

    Boulaiz, Houria; Aránega, Antonia; Cáceres, Blanca; Blanca, Cáceres; Alvarez, Pablo; Pablo, Alvarez; Serrano-Rodríguez, Fernando; Fernando, Rodríguez-Serrano; Carrillo, Esmeralda; Esmeralda, Carrillo; Melguizo, Consolación; Consolación, Melguizo; Prados, Jose; Jose, Prados

    2014-02-01

    Double-suicide gene therapy is a promising strategy for the treatment of advanced cancer. It has become an important research line in the development of gene therapy to overcome the drawbacks of single-gene therapy. The aim of this study was to investigate the usefulness of double-suicide gene therapy with the two suicide genes, gef and apoptin, in colon carcinoma. gef and apoptin genes were cloned into a doxycycline-regulated retrovirus-mediated gene expression system. Expression of both genes in the DLD-1 cell line was confirmed by reverse transcriptase polymerase chain reaction (RT-PCR). Cell viability was determined with the sulforhodamine B colorimetric assay, and the cell cycle was studied by propidium iodide (PI) staining. Annexin V-FITC and PI assays were used to evaluate apoptosis, and the results were confirmed by electron microscopy. The mitochondrial membrane potential was measured by JC-1 assay. Our results showed that the combined expression of gef and apoptin genes was strikingly more effective than the expression of either gene alone. Co-expression of gef and apoptin synergistically enhanced the decrease in cell viability, increasing necrosis and inducing apoptosis in colon cancer cells via the mitochondrial pathway, which can be deficient in advanced or metastatic colon cancer. Double-suicide gene therapy based on gef and apoptin genes may be a candidate for the development of new colon cancer strategies, and further studies are warranted to establish the usefulness of double-suicide gene therapy in vivo.

  1. Regorafenib in combination with silybin as a novel potential strategy for the treatment of metastatic colorectal cancer.

    Science.gov (United States)

    Belli, Valentina; Sforza, Vincenzo; Cardone, Claudia; Martinelli, Erika; Barra, Giusi; Matrone, Nunzia; Napolitano, Stefania; Morgillo, Floriana; Tuccillo, Concetta; Federico, Alessandro; Dallio, Marcello; Loguercio, Carmelina; Gravina, Antonietta Gerarda; De Palma, Raffaele; Ciardiello, Fortunato; Troiani, Teresa

    2017-09-15

    Regorafenib, an oral multikinase inhibitor, has demonstrated survival benefit in metastatic colorectal cancer (mCRC) patients that have progressed after all standard therapies. However, novel strategies to improve tolerability and enhance anti-cancer efficacy are needed. We have evaluated in vitro the effects of regorafenib in combination with silybin, a biologically active component extracted from the seeds of Silybum marianum, in a panel of human colon cancer cells. Furthermore, we have prospectively treated a cohort of 22 refractory mCRC patients with regorafenib plus silybin. Treatment with regorafenib determined a dose-dependent growth inhibition whereas treatment with silybin had no anti-proliferative effects among all cancer cells tested. The combined treatment with regorafenib and silybin induced synergistic anti-proliferative and apoptotic effects by blocking PI3K/AKT/mTOR intracellular pathway. Moreover, combined treatment with regorafenib and silybin increased the production of reactive oxygen species levels within cells. In an exploratory proof of concept clinical study in a cohort of 22 mCRC patients after failure of all standard therapies, the clinical activity of regorafenib in combination with silybin was assessed. A median progression-free survival of 10.0 months and a median overall survival of 17.6 months were observed in these patients. These results suggest that the combined treatment potentially increases the clinical efficacy of regorafenib. Moreover, due to its anti-oxidative properties, silybin could protect patients from drug-induced liver damages, allowing to continue an effective anti-cancer therapy. The present study suggests that silybin in combination with regorafenib is a promising strategy for treatment of metastatic colorectal patients.

  2. Metastases of transverse colon cancer to bilateral ovaries (Krukenberg tumor) and the left breast: A case report.

    Science.gov (United States)

    Luo, Xin-Yu; Wang, Jue; Zhao, Jia; Chen, Rui; Zha, Xiao-Ming

    2017-07-01

    Breast cancer has the highest rate of incidence among all types of cancer in women. Only ~0.43% of breast malignancies occur as a result of metastatic lesions from extramammary tumors. The present study reports an extremely rare case of transverse colon cancer metastasizing to the bilateral ovaries and the left breast. The patient was a 47-year old female, who had a lump in the left breast without axillary lymphadenopathy. Specimens obtained by core needle biopsy were submitted for hematoxylin and eosin examination, and results revealed that the lump was a poorly differentiated adenocarcinoma. Since the patient had elevated levels of the carcinoembryonic antigen and a medical history of a Krukenberg tumor metastasized from colon cancer, immunohistochemical examinations were applied. Results identified that caudal-related homeobox protein 2 and cytokeratin 20 were positively stained, whilst cytokeratin 7 was negatively stained. Therefore, this patient was diagnosed as having colon cancer that had metastasized to the bilateral ovaries and the left breast. As the life expectancy of patients with cancer is increasing, types of metastases that used to be seen as rare are increasingly becoming more common. For clinicians, diagnosis should be cautious, and differential diagnosis should always be kept in mind.

  3. 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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Rossi L

    2013-11-01

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

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

    Science.gov (United States)

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

    2013-01-28

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

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

    Directory of Open Access Journals (Sweden)

    Riihimäki Matias

    2013-01-01

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

  8. Epsin is required for Dishevelled stability and Wnt signaling activation in colon cancer development

    Science.gov (United States)

    Chang, Baojun; Tessneer, Kandice L.; McManus, John; Liu, Xiaolei; Hahn, Scott; Pasula, Satish; Wu, Hao; Song, Hoogeun; Chen, Yiyuan; Cai, Xiaofeng; Dong, Yunzhou; Brophy, Megan L.; Rahman, Ruby; Ma, Jian-Xing; Xia, Lijun; Chen, Hong

    2015-01-01

    Uncontrolled canonical Wnt signaling supports colon epithelial tumor expansion and malignant transformation. Understanding the regulatory mechanisms involved is crucial for elucidating the pathogenesis of and will provide new therapeutic targets for colon cancer. Epsins are ubiquitin-binding adaptor proteins upregulated in several human cancers; however, epsins’ involvement in colon cancer is unknown. Here we show that loss of intestinal epithelial epsins protects against colon cancer by significantly reducing the stability of the crucial Wnt signaling effector, dishevelled (Dvl2), and impairing Wnt signaling. Consistently, epsins and Dvl2 are correspondingly upregulated in colon cancer. Mechanistically, epsin binds Dvl2 via its epsin N-terminal homology domain and ubiquitin-interacting motifs and prohibits Dvl2 polyubiquitination and degradation. Our findings reveal an unconventional role for epsins in stabilizing Dvl2 and potentiating Wnt signaling in colon cancer cells to ensure robust colon cancer progression. Epsins’ pro-carcinogenic role suggests they are potential therapeutic targets to combat colon cancer. PMID:25871009

  9. Analysis on misdiagnosed cases of right colon cancer as appendicitis

    Directory of Open Access Journals (Sweden)

    Sijia Liu

    2016-08-01

    Full Text Available The aim of this case report is to investigate the causes of misdiagnosing right colon cancer as appendicitis, in order to reduce the misdiagnosis rate. The process of diagnosing and treating 44 misdiagnosed right colon cancer cases was analyzed. It was found that the right colonic lumen in these patients was thick, and their cancer consisted mostly of the ulcerative type or of a cauliflower-like tumor that protruded into the intestinal cavity. Moreover, ring-shaped and structured cancer was rarely observed, which suggested a decreased likelihood of obstruction. The patients showed limited peritoneal irritation signs in their right lower abdomen, which was also a potential cause for misdiagnosis. Right colon cancer associated with appendicitis is easily misdiagnosed as simple appendicitis, chronic appendicitis, or appendiceal abscess. Therefore, it is necessary to raise general awareness on the manifestations of the disease in order to exclude other common complications during diagnosis and to reduce the misdiagnosis rate. An accurate early diagnosis and treatment will improve patient prognosis.

  10. Unusual abscesses associated with colon cancer. Report of three cases

    International Nuclear Information System (INIS)

    Okita, Atsushi; Kubo, Yoshiro; Tanada, Minoru; Kurita, Akira; Takashima, Shigemitsu

    2007-01-01

    Three cases of colon cancer accompanied by unusual abscess formation are reported. Case I: A 77-year-old man was diagnosed with a paracolic abscess formation behind the cecum and a swollen appendix by computed tomography (CT) scan. Case II: An 85-year-old woman was diagnosed with an abscess formation of the right iliopsoas muscle, a swollen appendix, and a thickened right colon wall by CT scan. After antibiotic therapy failed, both patients underwent ileocecal resection urgently under suspicion of appendicitis, but cecal cancer around the entrance to the appendix caused secondary appendicitis in both cases. Case III: A 50-year-old woman was diagnosed with sigmoid colon cancer with an abscess formation in the pelvic cavity concomitant with ovarian tumor. A Hartmann procedure was performed, and a pathological examination revealed that a subserosal abscess behind the sigmoid colon cancer perforated the rectum with abscess formation. All cases were definitively diagnosed intraoperatively. The cancer recurred in cases I and III. We emphasize that precise surgical evaluation has an important role in the diagnosis of these complicated diseases. In addition, surgery affords the patient the best chance of recovery, and in these advanced cases radical treatment is recommended as early as possible. (author)

  11. Spontaneous regression of transverse colon cancer: a case report.

    Science.gov (United States)

    Chida, Keigo; Nakanishi, Kazuaki; Shomura, Hiroki; Homma, Shigenori; Hattori, Atsuo; Kazui, Keizo; Taketomi, Akinobu

    2017-12-01

    Spontaneous regression (SR) of many malignant tumors has been well documented, with an approximate incidence of one per 60,000-100,000 cancer patients. However, SR of colorectal cancer (CRC) is very rare, accounting for less than 2% of such cases. We report a case of SR of transverse colon cancer in an 80-year-old man undergoing outpatient follow-up after surgical treatment of early gastric cancer. Colonoscopy (CS) revealed a Borrmann type II tumor in the transverse colon measuring 30 × 30 mm. Because the patient underwent anticoagulant therapy, we did not perform a biopsy at that time. A second CS was performed 1 week after the initial examination and revealed tumor shrinkage to a diameter of 20 mm and a shift to the Borrmann type III morphology. Biopsy revealed a poorly differentiated adenocarcinoma. One week after the second CS, we performed a partial resection of the transverse colon and D2 lymph node dissection. Histopathology revealed inflammatory cell infiltration and fibrosis from the submucosal to muscularis propria layers in the absence of cancer cells, leading to pathological staging of pStage 0 (T0N0). The patient had an uneventful recovery, and CS performed at 5 months postoperatively revealed the absence of a tumor in the colon and rectum. The patient continues to be followed up as an outpatient at 12 months postoperatively, and no recurrence has been observed.

  12. Current management of liver metastases of colon cancer

    International Nuclear Information System (INIS)

    Mainieri Breedy, Giovanna

    2010-01-01

    Colon cancer has been one of the major tumors in the world, both men and women; and it is constituted the third most commonly diagnosed tumor, with approximately 1.2 million of new cases per year. This cancer type is considered of great importance in Costa Rica and has occupied the fifth place. Age is the main risk factor, followed by environmental, diabetic and genetic factors. An IV colon cancer has been manifested with any T, with any N and metastases. Metastases from colon cancer to liver can be classified according to whether have been synchronous (20 to 25%) or metachronous (15 to 29%). In turn, they can be synchronous, resectable or unresectable or mechanical resectable or unresectable. The liver has been the most common site of metastases, and the status of this organ has been an important determinant of overall survival in patients with advanced disease. Half of the patients developed metastases during the course of the disease. Metastases has represented the leading cause of death from this tumor. With the advent of new surgical techniques, new anesthetic care, new chemotherapeutic and molecular agents, together with new radiofrequency modalities and ablative treatment, the approach of metastases from colon cancer to the liver has been shown to be decisive in the prolongation of survival of the patient, who in the past was considered a terminal patient [es

  13. Validation of methylation biomarkers that distinguish normal colon mucosa from cancer patients from normal colon mucosa of patients without cancer

    Science.gov (United States)

    Cesaroni, Matteo; Powell, Jasmine; Sapienza, Carmen

    2014-01-01

    We have validated differences in DNA methylation levels of candidate genes previously reported to discriminate between normal colon mucosa of colon cancer patients and normal colon mucosa of individuals without cancer. Here, we report that CpG sites in 16 of the 30 candidate genes selected show significant differences in mean methylation level in normal colon mucosa of 24 cancer patients and 24 controls. A support vector machine trained on these data and data for an additional 66 CpGs yielded an 18-gene signature, composed of 10 of the validated candidate genes plus eight additional candidates. This model exhibited 96% sensitivity and 100% specificity in a 40-sample training set and classified all eight samples in the test set correctly. Moreover, we found a moderate-strong correlation (Pearson coefficients r=0.253-0.722) between methylation levels in colon mucosa and methylation levels in peripheral blood for seven of the 18 genes in the support vector model. These seven genes, alone, classified 44 of the 48 patients in the validation set correctly and five CpGs selected from only two of the seven genes classified 41 of the 48 patients in the discovery set correctly. These results suggest that methylation biomarkers may be developed that will, at minimum, serve as useful objective and quantitative diagnostic complements to colonoscopy as a cancer-screening tool. These data also suggest that it may be possible to monitor biomarker methylation levels in tissues collected much less invasively than by colonoscopy. PMID:24806665

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

    Science.gov (United States)

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

    2018-03-07

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

  15. Bile acid: a potential inducer of colon cancer stem cells.

    Science.gov (United States)

    Farhana, Lulu; Nangia-Makker, Pratima; Arbit, Evan; Shango, Kathren; Sarkar, Sarah; Mahmud, Hamidah; Hadden, Timothy; Yu, Yingjie; Majumdar, Adhip P N

    2016-12-01

    Although the unconjugated secondary bile acids, specifically deoxycholic acid (DCA) and lithocholic acid (LCA), are considered to be risk factors for colorectal cancer, the precise mechanism(s) by which they regulate carcinogenesis is poorly understood. We hypothesize that the cytotoxic bile acids may promote stemness in colonic epithelial cells leading to generation of cancer stem cells (CSCs) that play a role in the development and progression of colon cancer. Normal human colonic epithelial cells (HCoEpiC) were used to study bile acid DCA/LCA-mediated induction of CSCs. The expression of CSC markers was measured by real-time qPCR. Flow cytometry was used to isolate CSCs. T-cell factor/lymphoid-enhancing factor (TCF/LEF) luciferase assay was employed to examine the transcriptional activity of β-catenin. Downregulation of muscarinic 3 receptor (M3R) was achieved through transfection of corresponding siRNA. We found DCA/LCA to induce CSCs in normal human colonic epithelial cells, as evidenced by the increased proportion of CSCs, elevated levels of several CSC markers, as well as a number of epithelial-mesenchymal transition markers together with increased colonosphere formation, drug exclusion, ABCB1 and ABCG2 expression, and induction of M3R, p-EGFR, matrix metallopeptidases, and c-Myc. Inhibition of M3R signaling greatly suppressed DCA/LCA induction of the CSC marker ALDHA1 and also c-Myc mRNA expression as well as transcriptional activation of TCF/LEF. Our results suggest that bile acids, specifically DCA and LCA, induce cancer stemness in colonic epithelial cells by modulating M3R and Wnt/β-catenin signaling and thus could be considered promoters of colon cancer.

  16. 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.

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

    Science.gov (United States)

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

    2010-12-01

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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

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

    Science.gov (United States)

    2018-02-05

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

  20. Sinusoidal obstruction syndrome (veno-occlusive disease in a patient receiving bevacizumab for metastatic colorectal cancer: a case report

    Directory of Open Access Journals (Sweden)

    Agarwal Vijay

    2008-07-01

    Full Text Available Abstract Introduction We present the case of a patient with colon cancer who, while receiving bevacizumab, developed sinusoidal obstruction syndrome (veno-occlusive disease (SOSVOD. Certain antitumour agents such as 6-mercaptopurine and 6-thioguanine have also been reported to initiate hepatic SOSVOD in isolated cases. There have been no reports so far correlating bevacizumab with SOSVOD. Case presentation A 77-year-old man was being treated with oxaliplatin and a modified de Gramont regimen of 5-fluorouracil for metastatic colon cancer. Bevacizumab (7.5 mg/kg was added from the seventh cycle onwards. Protracted neutropenia and thrombocytopenia led to discontinuation of oxaliplatin after the ninth cycle. A computed tomography scan showed complete response and bevacizumab was continued for another 3 months, after which time the patient developed right hypochondrial pain, transudative ascites, splenomegaly and abnormal liver function tests. Upper gastrointestinal endoscopy showed oesophageal varices. Liver biopsy showed features considered to be consistent with SOSVOD. Bevacizumab was stopped and a policy of watchful waiting was adopted. He tolerated the acute damage to his liver and subsequently the ascites resolved and liver function tests normalised. Conclusion We need to be aware that bevacizumab can cause sinusoidal obstruction syndrome (veno-occlusive disease and that the occurrence of ascites should not be attributed to progressive disease without appropriate evaluation.

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

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

    OpenAIRE

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

    2013-01-01

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

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

    Science.gov (United States)

    2014-08-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

  6. 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.

  7. Positive expression of LSD1 and negative expression of E-cadherin correlate with metastasis and poor prognosis of colon cancer.

    Science.gov (United States)

    Jie, Ding; Zhongmin, Zhang; Guoqing, Liao; Sheng, Liu; Yi, Zhang; Jing, Wen; Liang, Zeng

    2013-06-01

    The first identified lysine-specific demethylase, LSD1, plays an important role in the metastatic progression of several types of cancer. The aim of this study was to investigate LSD1, E-cadherin, and N-cadherin expression in colon cancer specimens and their clinical significance. The expression of LSD1, E-cadherin, and N-cadherin in colon cancer specimens was determined by immunohistochemistry, and the relationship between the expression of the respective molecules and clinicopathological characteristics was analyzed. The positive expression rates of LSD1, E-cadherin, and N-cadherin in colon cancer specimens were 66.7 % (72/108), 85.2 % (92/108), and 41.7 % (45/108), respectively. LSD1 was significantly more highly expressed in colon cancer specimens classified as high TNM stage lesions and with distant metastasis (P colon cancer specimens classified as high TNM stage lesions and with distant metastasis (P clinical and pathological characteristics (P > 0.05). Correlation analysis revealed that LSD1 expression was negatively correlated with E-cadherin expression (r s = -0.318, P = 0.001), but not evidently correlated with N-cadherin expression (r s = 0.182, P = 0.06). Colon cancer specimens with positive LSD1 expression and negative E-cadherin expression were correlated with significantly lower overall survival. LSD1 showed a significantly higher expression, in contrast to the significantly lower expression of E-cadherin, in colon cancer specimens classified as high TNM stage lesions and with distant metastasis. Positive expression of LSD1 and negative expression of E-cadherin may be predictors of a worse colon cancer prognosis.

  8. Green vegetables and colon cancer: the mechanism of a protective effect by chlorophyll

    NARCIS (Netherlands)

    Vogel, de J.

    2006-01-01

    One of the important environmental determinants of the risk of colon cancer is the composition of the diet. Regular consumption of high amounts of red meat increases colon cancer risk. In contrast, consumption of green vegetables decreases the risk of colon cancer. This thesis provides a molecular

  9. File list: Unc.Dig.50.AllAg.Colon_cancer [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Dig.50.AllAg.Colon_cancer hg19 Unclassified Digestive tract Colon cancer SRX115...0169,SRX1150170,SRX124703 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Dig.50.AllAg.Colon_cancer.bed ...

  10. File list: Oth.Dig.50.AllAg.Colon_cancer [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Dig.50.AllAg.Colon_cancer hg19 TFs and others Digestive tract Colon cancer SRX1...55772,SRX155775,SRX155773,SRX155776 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Dig.50.AllAg.Colon_cancer.bed ...

  11. File list: InP.Dig.05.AllAg.Colon_cancer [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Dig.05.AllAg.Colon_cancer hg19 Input control Digestive tract Colon cancer SRX12...124693,SRX124695,SRX124694 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Dig.05.AllAg.Colon_cancer.bed ...

  12. File list: Unc.Dig.05.AllAg.Colon_cancer [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Dig.05.AllAg.Colon_cancer hg19 Unclassified Digestive tract Colon cancer SRX115...0169,SRX1150170,SRX124703 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Dig.05.AllAg.Colon_cancer.bed ...

  13. File list: InP.Dig.50.AllAg.Colon_cancer [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Dig.50.AllAg.Colon_cancer hg19 Input control Digestive tract Colon cancer SRX12...155774,SRX124693,SRX124698 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Dig.50.AllAg.Colon_cancer.bed ...

  14. File list: Unc.Dig.20.AllAg.Colon_cancer [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Dig.20.AllAg.Colon_cancer hg19 Unclassified Digestive tract Colon cancer SRX115...0169,SRX1150170,SRX124703 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Dig.20.AllAg.Colon_cancer.bed ...

  15. File list: InP.Dig.10.AllAg.Colon_cancer [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Dig.10.AllAg.Colon_cancer hg19 Input control Digestive tract Colon cancer SRX12...155774,SRX625671,SRX155777 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Dig.10.AllAg.Colon_cancer.bed ...

  16. File list: InP.Dig.20.AllAg.Colon_cancer [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Dig.20.AllAg.Colon_cancer hg19 Input control Digestive tract Colon cancer SRX12...124693,SRX124697,SRX124698 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Dig.20.AllAg.Colon_cancer.bed ...

  17. File list: Oth.Dig.20.AllAg.Colon_cancer [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Dig.20.AllAg.Colon_cancer hg19 TFs and others Digestive tract Colon cancer SRX1...55772,SRX155773,SRX155775,SRX155776 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Dig.20.AllAg.Colon_cancer.bed ...

  18. File list: Unc.Dig.10.AllAg.Colon_cancer [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Dig.10.AllAg.Colon_cancer hg19 Unclassified Digestive tract Colon cancer SRX115...0169,SRX124703,SRX1150170 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Dig.10.AllAg.Colon_cancer.bed ...

  19. File list: Oth.Dig.05.AllAg.Colon_cancer [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Dig.05.AllAg.Colon_cancer hg19 TFs and others Digestive tract Colon cancer SRX1...55772,SRX155773,SRX155775,SRX155776 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Dig.05.AllAg.Colon_cancer.bed ...

  20. File list: Oth.Dig.10.AllAg.Colon_cancer [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Dig.10.AllAg.Colon_cancer hg19 TFs and others Digestive tract Colon cancer SRX1...55772,SRX155775,SRX155773,SRX155776 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Dig.10.AllAg.Colon_cancer.bed ...

  1. Identification of colonic fibroblast secretomes reveals secretory factors regulating colon cancer cell proliferation.

    Science.gov (United States)

    Chen, Sun-Xia; Xu, Xiao-En; Wang, Xiao-Qing; Cui, Shu-Jian; Xu, Lei-Lei; Jiang, Ying-Hua; Zhang, Yang; Yan, Hai-Bo; Zhang, Qian; Qiao, Jie; Yang, Peng-Yuan; Liu, Feng

    2014-10-14

    Stromal microenvironment influences tumor cell proliferation and migration. Fibroblasts represent the most abundant stromal constituents. Here, we established two pairs of normal fibroblast (NF) and cancer-associated fibroblast (CAF) cultures from colorectal adenocarcinoma tissues and the normal counterparts. The NFs and CAFs were stained positive for typical fibroblast markers and inhibited colon cancer (CC) cell proliferation in in vitro cocultures and in xenograft mouse models. The fibroblast conditioned media were analyzed using LC-MS and 227 proteins were identified at a false discovery rate of 1.3%, including 131 putative secretory and 20 plasma membrane proteins. These proteins were enriched for functional categories of extracellular matrix, adhesion, cell motion, inflammatory response, redox homeostasis and peptidase inhibitor. Secreted protein acidic and rich in cysteine, transgelin, follistatin-related protein 1 (FSTL1) and decorin was abundant in the fibroblast secretome as confirmed by Western blot. Silencing of FSTL1 and transgelin in colonic fibroblast cell line CCD-18Co induced an accelerated proliferation of CC cells in cocultures. Exogenous FSTL1 attenuates CC cell proliferation in a negative fashion. FSTL1 was upregulated in CC patient plasma and cancerous tissues but had no implication in prognosis. Our results provided novel insights into the molecular signatures and modulatory role of CC associated fibroblasts. In this study, a label-free LC-MS was performed to analyze the secretomes of two paired primary fibroblasts, which were isolated from fresh surgical specimen of colorectal adenocarcinoma and adjacent normal colonic tissues and exhibited negative modulatory activity for colon cancer cell growth in in vitro cocultures and in vivo xenograph mouse models. Follistatin-related protein 1 was further revealed to be one of the stroma-derived factors of potential suppression role for colon cancer cell proliferation. Our results provide novel

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

    Science.gov (United States)

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

    2016-12-01

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

  3. Urotensin-II receptor is over-expressed in colon cancer cell lines and in colon carcinoma in humans.

    Science.gov (United States)

    Federico, Alessandro; Zappavigna, Silvia; Romano, Marco; Grieco, Paolo; Luce, Amalia; Marra, Monica; Gravina, Antonietta Gerarda; Stiuso, Paola; D'Armiento, Francesco Paolo; Vitale, Giovanni; Tuccillo, Concetta; Novellino, Ettore; Loguercio, Carmela; Caraglia, Michele

    2014-01-01

    Urotensin (U)-II receptor (UTR) has been previously reported to be over-expressed in a number of tumours. Whether UTR-related pathway plays a role in colon carcinogenesis is unknown. We evaluated UTR protein and mRNA expression in human epithelial colon cancer cell lines and in normal colon tissue, adenomatous polyps and colon cancer. U-II protein expression was assessed in cancer cell lines. Moreover, we evaluated the effects of U-II(4-11) (an UTR agonist), antagonists and knockdown of UTR protein expression through a specific shRNA, on proliferation, invasion and motility of human colon cancer cells. Cancer cell lines expressed U-II protein and UTR protein and mRNA. By immunohistochemistry, UTR was expressed in 5-30% of epithelial cells in 45 normal controls, in 30-48% in 21 adenomatous polyps and in 65-90% in 48 colon adenocarcinomas. UTR mRNA expression was increased by threefold in adenomatous polyps and eightfold in colon cancer, compared with normal colon. U-II(4-11) induced a 20-40% increase in cell growth while the blockade of the receptor with specific antagonists caused growth inhibition of 20-40%. Moreover, the knock down of UTR with a shRNA or the inhibition of UTR with the antagonist urantide induced an approximately 50% inhibition of both motility and invasion. UTR appears to be involved in the regulation of colon cancer cell invasion and motility. These data suggest that UTR-related pathway may play a role in colon carcinogenesis and that UTR may function as a target for therapeutic intervention in colon cancer. © 2013 Stichting European Society for Clinical Investigation Journal Foundation.

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

    Science.gov (United States)

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

    2014-09-01

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

  5. Mechanisms linking dietary fiber, gut microbiota and colon cancer prevention

    Science.gov (United States)

    Many epidemiological and experimental studies have suggested that dietary fiber plays an important role in colon cancer prevention. These findings may relate to the ability of fiber to reduce the contact time of carcinogens within the intestinal lumen and to promote healthy gut microbiota, which mod...

  6. diet, bowel motility, faeces composition and colonic cancer

    African Journals Online (AJOL)

    1970-07-20

    Jul 20, 1970 ... The commonness of colonic cancer in privileged popula- tions compared with its rarity in those pursuing a primitive manner of life suggests that environmental factors are primarily responsible. In this study, differences in diet and their ramificarions are discussed in relation to popu- lations prone and less ...

  7. Effects of 5-fluorouracil adjuvant treatment of colon cancer

    NARCIS (Netherlands)

    Kelder, Wendy; Hospers, Geke A. P.; Plukker, John T. M.

    Since the late 1980s and early 1990s, 5-fluorouracil-based chemotherapy has been the standard adjuvant treatment for Stage III colon cancer. After the initial introduction of 5-fluorouracil in standard treatment protocols, several changes have been made based on results of randomized studies on

  8. Diet, bowel motility, faeces composition and colonic cancer | Walker ...

    African Journals Online (AJOL)

    The commonness of colonic cancer in privileged populations compared with its rarity in those pursuing a primitive manner of life suggests that environmental factors are primarily responsible. In this study, differences in diet and their ramificarions are discussed in relation to populations prone and less prone to the disease.

  9. Gene expression profiles in stages II and III colon cancers

    DEFF Research Database (Denmark)

    Thorsteinsson, Morten; Kirkeby, Lene T; Hansen, Raino

    2012-01-01

    were retrieved from the Gene Expression Omnibus (GEO) (n¿=¿111) in addition to a Danish data set (n¿=¿37). All patients had stages II and III colon cancers. A Prediction Analysis of Microarray classifier, based on the 128-gene signature and the original training set of stage I (n¿=¿65) and stage IV (n......¿=¿76) colon cancers, was reproduced. The stages II and III colon cancers were subsequently classified as either stage I-like (good prognosis) or stage IV-like (poor prognosis) and assessed by the 36 months cumulative incidence of relapse. RESULTS: In the GEO data set, results were reproducible in stage...... correctly predicted as stage IV-like, and the remaining patients were predicted as stage I-like and unclassifiable, respectively. Stage II patients could not be stratified. CONCLUSIONS: The 128-gene signature showed reproducibility in stage III colon cancer, but could not predict recurrence in stage II...

  10. Bitter Melon Component and Colon Cancer Prevention | Division of Cancer Prevention

    Science.gov (United States)

    Despite the best screening efforts to identify and remove colon polyps, colon cancer remains a leading cause of cancer related morbidity and mortality, both in the US and around the world. Also, current therapeutics while good in removing most cancer cells are not adequate because they leave some cells behind. This is because these cells can reemerge and develop a fresh tumor, which in many cases can manifest in a different organ due to metastasis. |

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

    Directory of Open Access Journals (Sweden)

    Fernanda Amado

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

  12. BAGE hypomethylation, a new epigenetic biomarker for colon cancer detection.

    Science.gov (United States)

    Grunau, Christoph; Brun, Marie-Elisabeth; Rivals, Isabelle; Selves, Janick; Hindermann, Winfried; Favre-Mercuret, Magali; Granier, Guillaume; De Sario, Albertina

    2008-06-01

    Early detection of colorectal cancer is a decisive step in the successful and complete cure of the disease. Epigenetic markers, in particular, those based on aberrant DNA methylation, can be used to diagnose cancer. B melanoma antigens (BAGE) are a family of genes and truncated genes located in the heterochromatic regions of several human chromosomes. Our previous work showed that BAGE loci (i.e., genes and truncated genes) were hypermethylated in normal tissues and hypomethylated in 98% of human cancers. In the present study, we analyzed DNA methylation of the BAGE loci in 54 colon cancers and in neighboring histopathologic normal tissue samples. Using a combined bisulfite restriction assay, we showed that BAGE loci were hypomethylated in 81% of carcinoma samples. Colon cancer could be diagnosed with 94% specificity, 83% sensitivity, and 89% accuracy. No correlation was found between DNA methylation of BAGE loci and age, gender of patients, nor with the tumor stage or site. Based on the hypothesis that during neoplastic transformation, hypomethylation occurs in juxtacentromeric CpG islands, we suggest that other genes located in the heterochromatic compartment should be tested. These new markers enrich the list of currently studied epigenetic alterations in colon cancer and could be associated with hypermethylation markers to develop reliable diagnostic tests.

  13. Modulation of intracellular calcium levels by calcium lactate affects colon cancer cell motility through calcium-dependent calpain.

    Directory of Open Access Journals (Sweden)

    Pasupathi Sundaramoorthy

    Full Text Available Cancer cell motility is a key phenomenon regulating invasion and metastasis. Focal adhesion kinase (FAK plays a major role in cellular adhesion and metastasis of various cancers. The relationship between dietary supplementation of calcium and colon cancer has been extensively investigated. However, the effect of calcium (Ca2+ supplementation on calpain-FAK-motility is not clearly understood. We sought to identify the mechanism of FAK cleavage through Ca2+ bound lactate (CaLa, its downstream signaling and role in the motility of human colon cancer cells. We found that treating HCT116 and HT-29 cells with CaLa immediately increased the intracellular Ca2+ (iCa2+ levels for a prolonged period of time. Ca2+ influx induced cleavage of FAK into an N-terminal FAK (FERM domain in a dose-dependent manner. Phosphorylated FAK (p-FAK was also cleaved in to its p-N-terminal FAK. CaLa increased colon cancer cells motility. Calpeptin, a calpain inhibitor, reversed the effects of CaLa on FAK and pFAK cleavage in both cancer cell lines. The cleaved FAK translocates into the nucleus and modulates p53 stability through MDM2-associated ubiquitination. CaLa-induced Ca2+ influx increased the motility of colon cancer cells was mediated by calpain activity through FAK and pFAK protein destabilization. In conclusion, these results suggest that careful consideration may be given in deciding dietary Ca2+ supplementation to patient undergoing treatment for metastatic cancer.

  14. Improvements in 5-year outcomes of stage II/III rectal cancer relative to colon cancer.

    Science.gov (United States)

    Renouf, Daniel J; Woods, Ryan; Speers, Caroline; Hay, John; Phang, P Terry; Fitzgerald, Catherine; Kennecke, Hagen

    2013-12-01

    Stage for stage, rectal cancer has historically been associated with inferior survival compared with colon cancer. Randomized trials of rectal cancer have generally demonstrated improvements in locoregional relapse but not survival. We compared therapy and outcomes of colon versus rectal cancer in 2 time cohorts to determine if relative improvements have occurred. Patients with resected stage II/III colorectal cancer referred to the British Columbia Cancer Agency in 1989/1990 and 2001/2002 were identified. The higher of clinical or pathologic stage was used for patients receiving preoperative chemoradiation. Disease-specific survival (DSS) and overall survival (OS) were compared for rectal and colon cancer between the 2 cohorts. Kaplan-Meier method was used for survival analysis. A total of 1427 patients were included, with 375 from 1989/1990 and 1052 from 2001/2002. Between 1989/1990 and 2001/2002 there were significant increases in the use of perioperative chemotherapy for both rectal and colon cancer (Prectal cancer. DSS significantly improved for rectal (Pcolon cancer (P=0.069). Five-year OS was significantly inferior for rectal versus colon cancer in 1989/1990 (46.1% vs. 57.2%, P=0.023) and was similar to that of colon cancer in 2001/2002 (63.7% vs. 66.2%, P=0.454). Advances in locoregional and systemic therapy significantly improved survival among patients with rectal cancer. DSS and OS are now similar between colon and rectal cancer for both stage II and III disease.

  15. Risk of metachronous colon cancer following surgery for rectal cancer in mismatch repair gene mutation carriers.

    Science.gov (United States)

    Win, Aung Ko; Parry, Susan; Parry, Bryan; Kalady, Matthew F; Macrae, Finlay A; Ahnen, Dennis J; Young, Graeme P; Lipton, Lara; Winship, Ingrid; Boussioutas, Alex; Young, Joanne P; Buchanan, Daniel D; Arnold, Julie; Le Marchand, Loïc; Newcomb, Polly A; Haile, Robert W; Lindor, Noralane M; Gallinger, Steven; Hopper, John L; Jenkins, Mark A

    2013-06-01

    Despite regular surveillance colonoscopy, the metachronous colorectal cancer risk for mismatch repair (MMR) gene mutation carriers after segmental resection for colon cancer is high and total or subtotal colectomy is the preferred option. However, if the index cancer is in the rectum, management decisions are complicated by considerations of impaired bowel function. We aimed to estimate the risk of metachronous colon cancer for MMR gene mutation carriers who underwent a proctectomy for index rectal cancer. This retrospective cohort study comprised 79 carriers of germline mutation in a MMR gene (18 MLH1, 55 MSH2, 4 MSH6, and 2 PMS2) from the Colon Cancer Family Registry who had had a proctectomy for index rectal cancer. Cumulative risks of metachronous colon cancer were calculated using the Kaplan-Meier method. During median 9 years (range 1-32 years) of observation since the first diagnosis of rectal cancer, 21 carriers (27 %) were diagnosed with metachronous colon cancer (incidence 24.25, 95 % confidence interval [CI] 15.81-37.19 per 1,000 person-years). Cumulative risk of metachronous colon cancer was 19 % (95 % CI 9-31 %) at 10 years, 47 (95 % CI 31-68 %) at 20 years, and 69 % (95 % CI 45-89 %) at 30 years after surgical resection. The frequency of surveillance colonoscopy was 1 colonoscopy per 1.16 years (95 % CI 1.01-1.31 years). The AJCC stages of the metachronous cancers, where available, were 72 % stage I, 22 % stage II, and 6 % stage III. Given the high metachronous colon cancer risk for MMR gene mutation carriers diagnosed with an index rectal cancer, proctocolectomy may need to be considered.

  16. Combination hyperthermia and intraarterial 5-FU for metastatic colon carcinoma to liver

    International Nuclear Information System (INIS)

    Moseley, H.S.; Palmquist, M.

    1984-01-01

    Metastatic colorectal carcinoma to the liver remains a formidable challenge. Responses to chemotherapy are brief and the number of effective drugs is very limited. A phase II trial of hepatic hyperthermia and intraarterial chemotherapy was undertaken to attempt to improve response rates and duration. Patients were given a 10 day course of IA 5-FU at 15 mg/kg. During the infusion hyperthermia was given five times using the BSD Annular Phased Array (APA). Thermistors were placed percutaneously into normal liver and tumor using ultrasound or CT scan guidance. Six patients have been treated. Significant problems in positioning ill patients in the APA were encountered, and there was difficulty also in preventing heating throughout the abdominal cavity. Four patients, all with poor performance status, failed to benefit. One patient had improvement in liver function studies for two months and failed to respond on a repeat course. One patient had a complete response which is continuing over 18 months with a liver scan reverting to normal and CEA returning to normal. These preliminary results are promising and warrant further trials

  17. Impact of diabetes on oncologic outcome of colorectal cancer patients: colon vs. rectal cancer.

    Directory of Open Access Journals (Sweden)

    Justin Y Jeon

    Full Text Available BACKGROUND: To evaluate the impact of diabetes on outcomes in colorectal cancer patients and to examine whether this association varies by the location of tumor (colon vs. rectum. PATIENTS AND METHODS: This study includes 4,131 stage I-III colorectal cancer patients, treated between 1995 and 2007 (12.5% diabetic, 53% colon, 47% rectal in South Korea. Cox proportional hazards modeling was used to determine the prognostic influence of DM on survival endpoints. RESULTS: Colorectal cancer patients with DM had significantly worse disease-free survival (DFS [hazard ratio (HR 1.17, 95% confidence interval (CI: 1.00-1.37] compared with patients without DM. When considering colon and rectal cancer independently, DM was significantly associated with worse overall survival (OS (HR: 1.46, 95% CI: 1.11-1.92, DFS (HR: 1.45, 95% CI: 1.15-1.84 and recurrence-free survival (RFS (HR: 1.32, 95% CI: 0.98-1.76 in colon cancer patients. No association for OS, DFS or RFS was observed in rectal cancer patients. There was significant interaction of location of tumor (colon vs. rectal cancer with DM on OS (P = 0.009 and DFS (P = 0.007. CONCLUSIONS: This study suggests that DM negatively impacts survival outcomes of patients with colon cancer but not rectal cancer.

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

    Science.gov (United States)

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

    2013-04-15

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

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

    Science.gov (United States)

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

    2016-03-01

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

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

    Science.gov (United States)

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

    2016-08-27

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