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Sample records for colon cancer tumor

  1. 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...

  2. 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

  3. 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, ...

  4. [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.

  5. Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4

    NARCIS (Netherlands)

    Todaro, Matilde; Alea, Mileidys Perez; Di Stefano, Anna B.; Cammareri, Patrizia; Vermeulen, Louis; Iovino, Flora; Tripodo, Claudio; Russo, Antonio; Gulotta, Gaspare; Medema, Jan Paul; Stassi, Giorgio

    2007-01-01

    A novel paradigm in tumor biology suggests that cancer growth is driven by stem-like cells within a tumor. Here, we describe the identification and characterization of such cells from colon carcinomas using the stem cell marker CD133 that accounts around 2% of the cells in human colon cancer. The

  6. Tumor-stroma ratio predicts recurrence in patients with colon cancer treated with neoadjuvant chemotherapy

    DEFF Research Database (Denmark)

    Hansen, Torben Frøstrup; Kjær-Frifeldt, Sanne; Lindebjerg, Jan

    2017-01-01

    BACKGROUND: Neoadjuvant chemotherapy represents a new treatment approach to locally advanced colon cancer. The aim of this study was to analyze the ability of tumor-stroma ratio (TSR) to predict disease recurrence in patients with locally advanced colon cancer treated with neoadjuvant chemotherapy....... MATERIAL AND METHODS: This study included 65 patients with colon cancer treated with neoadjuvant chemotherapy in a phase II trial. All patients were planned for three cycles of capecitabine and oxaliplatin before surgery. Hematoxylin and eosin stained tissue sections from surgically resected primary tumors...... was 55%, compared to 94% in the group of patients with a high TSR. CONCLUSIONS: TSR assessed in the surgically resected primary tumor from patients with locally advanced colon cancer treated with neoadjuvant chemotherapy provides prognostic value and may serve as a relevant parameter in selecting...

  7. Intraoperative Tumor Perforation is Associated with Decreased 5-Year Survival in Colon Cancer

    DEFF Research Database (Denmark)

    Bundgaard, N S; Bendtsen, V O; Ingeholm, P

    2017-01-01

    BACKGROUND: It is a widely held belief that intraoperative tumor perforation in colon cancer impairs survival and causes local recurrence, although the prognostic importance remains unclear. AIM: The aim of this study was to assess the effect of unintended intraoperative tumor perforation...... on postoperative mortality and long-term survival. MATERIAL AND METHODS: This national cohort study was based on data from a prospectively maintained nationwide colorectal cancer database. We included 16,517 colon cancer patients who were resected with curative intent from 2001 to 2012. RESULTS: Intraoperative...... tumor perforation produced a significantly impaired 5-year survival of 40% compared to 64% in non-perforated colon cancer. Intraoperative tumor perforation was an independent risk factor for death, hazard ratio 1.63 (95% confidence interval: 1.4-1.94), with a significantly increased 90-day postoperative...

  8. [A case of polymyositis associated with transverse colon cancer that responded to tumor resection and chemotherapy].

    Science.gov (United States)

    Uchida, Yuichiro; Okabe, Michio; Kawamoto, Yusuke; Tsukumo, Yuta; Ito, Tadashi

    2015-04-01

    A 72-year-old woman was admitted to our hospital because of muscle weakness and was diagnosed as having polymyositis. Whole-body evaluation revealed advanced transverse colon cancer, and we therefore considered it likely that the patient had paraneoplastic myositis. We performed a curative surgical resection for colon cancer, after which her serum creatine phosphokinase(CPK)level greatly decreased. Steroid therapy was administered postoperatively. However, her CPK levels remained persistently high, even after steroid pulse therapy, and we considered that this was due to steroid-resistance myositis. We administered chemotherapy for colon cancer using 5-fluorouracil plus Leucovorin(5-FU/LV), after which the CPK levels gradually decreased. There have been few previous reports of polymyositis associated with colon cancer and a standard treatment for paraneoplastic myositis has not been established. Most clinicians believe that treatment of the primary tumor may contribute to an improvement of myositis, and in our case, tumor resection and chemotherapy were effective.

  9. Elderly patients with colon cancer have unique tumor characteristics and poor survival.

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    Patel, Supriya S; Nelson, Rebecca; Sanchez, Julian; Lee, Wendy; Uyeno, Lori; Garcia-Aguilar, Julio; Hurria, Arti; Kim, Joseph

    2013-02-15

    The incidence of colon cancer increases with age, and colon cancer predominantly affects individuals >65 years old. However, there are limited data regarding clinical and pathologic factors, treatment characteristics, and survival of older patients with colon cancer. The objective of this study was to determine the effects of increasing age on colon cancer. Patients diagnosed with colon cancer between 1988 and 2006 were identified through the Los Angeles County Cancer Surveillance Program, in Southern California. Patients were stratified into 4 age groups: 18-49, 50-64, 65-79, and ≥80 years. Clinical and pathologic characteristics and disease-specific and overall survival were compared between patients from different age groups. A total of 32,819 patients were assessed. Patients aged 18 to 49 and 65 to 79 years represented the smallest and largest groups, respectively. A near equal number of males and females were diagnosed with colon cancer in the 3 youngest age groups, whereas patients who were ≥80 years old were more commonly white and female. Tumor location was different between groups, and the frequency of larger tumors (>5 cm) was greatest in youngest patients (18-49 years). The oldest patients (≥80 years) were administered chemotherapy at the lowest frequency, and disease-specific and overall survival rates decreased with increasing age. This investigation demonstrates that older age is associated with alterations in clinical and pathologic characteristics and decreased survival. This suggests that the phenotype of colon cancer and the efficacy of colon cancer therapies may be dependent on the age of patients. Copyright © 2012 American Cancer Society.

  10. Transcription factor Runx2 knockdown regulates colon cancer transplantation tumor growth in vitro: an experimental study

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    Bin Xu1

    2017-05-01

    Full Text Available Objective: To study the effect of transcription factor Runx2 knockdown on colon cancer transplantation tumor growth in vitro. Methods: Colon cancer cell lines HT29 were cultured and transfected with negative control (NC - shRNA plasmids and Runx2-shRNA plasmids respectively, the colon cancer cells transfected with shRNA were subcutaneously injected into C57 nude mice, and they were included in NC group and Runx2 knockdown group respectively. 1 week, 2 weeks and 3 weeks after model establishment, serum was collected to determine the contents of tumor markers, and tumor lesions were collected to determine proliferation and apoptosis gene expression. Results: CCSA-2, CEA and CA19-9 levels in serum as well as Rac1, Wnt3a, PLD2 and FAM96B protein expression in transplantation tumor lesions of Runx2 knockdown group were significantly lower than those of NC group while MS4A12, ASPP2 and Fas protein expression in transplantation tumor lesions of Runx2 knockdown group were significantly higher than those of NC group. Conclusion: Transcription factor Runx2 knockdown could inhibit the colon cancer transplantation tumor growth in vitro.

  11. Exosomes from human colorectal cancer induce a tumor-like behavior in colonic mesenchymal stromal cells.

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    Lugini, Luana; Valtieri, Mauro; Federici, Cristina; Cecchetti, Serena; Meschini, Stefania; Condello, Maria; Signore, Michele; Fais, Stefano

    2016-08-02

    Cancer cells, including colorectal cancer ones (CRC), release high amounts of nanovesicles (exosomes), delivering biochemical messages for paracrine or systemic crosstalk. Mesenchymal stromal cells (MSCs) have been shown to play contradicting roles in tumor progression. CRC exosomes induce in cMSCs: i) atypical morphology, higher proliferation, migration and invasion; ii) formation of spheroids; iii) an acidic extracellular environment associated with iv) a plasma membrane redistribution of vacuolar H+-ATPase and increased expression of CEA. Colon cancer derived MSCs, which were isolated from tumor masses, produce umbilicated spheroids, a future frequently observed in the inner core of rapidly growing tumors and recapitulate the changes observed in normal colonic MSCs exposed to CRC exosomes. Tissue specific colonic (c)MSCs were exposed to primary or metastatic CRC exosomes and analysed by light and electron microscopy, proliferation in 2D and 3D cultures, migration and invasion assays, Western blot and confocal microscopy for vacuolar H+-ATPase expression. CRC exosomes are able to induce morphological and functional changes in colonic MSCs, which may favour tumor growth and its malignant progression. Our results suggest that exosomes are actively involved in cancer progression and that inhibiting tumor exosome release may represent a way to interfere with cancer.

  12. CysLT(1)R antagonists inhibit tumor growth in a xenograft model of colon cancer.

    Science.gov (United States)

    Savari, Sayeh; Liu, Minghui; Zhang, Yuan; Sime, Wondossen; Sjölander, Anita

    2013-01-01

    The expression of the inflammatory G-protein coupled receptor CysLT1R has been shown to be upregulated in colon cancer patients and associated with poor prognosis. The present study investigated the correlation between CysLT1R and colon cancer development in vivo using CysLT1R antagonists (ZM198,615 or Montelukast) and the nude mouse xenograft model. Two drug administration regimens were established. The first regimen was established to investigate the importance of CysLT1R in tumor initiation. Nude mice were inoculated with 50 µM CysLT1R antagonist-pretreated HCT-116 colon cancer cells and received continued treatment (5 mg/kg/day, intraperitoneally). The second regimen aimed to address the role of CysLT1R in tumor progression. Nude mice were inoculated with non-pretreated HCT-116 cells and did not receive CysLT1R antagonist treatment until recordable tumor appearance. Both regimens resulted in significantly reduced tumor size, attributed to changes in proliferation and apoptosis as determined by reduced Ki-67 levels and increased levels of p21(WAF/Cip1) (Pcolon cancer cell line HCT-116 and CysLT1R antagonists. In addition to significant reductions in cell proliferation, adhesion and colony formation, we observed induction of cell cycle arrest and apoptosis in a dose-dependent manner. The ability of Montelukast to inhibit growth of human colon cancer xenograft was further validated by using two additional colon cancer cell lines, SW-480 and HT-29. Our results demonstrate that CysLT1R antagonists inhibit growth of colon cancer xenografts primarily by reducing proliferation and inducing apoptosis of the tumor cells.

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

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    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.

  14. 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.

  15. Overexpression of GRK3, Promoting Tumor Proliferation, Is Predictive of Poor Prognosis in Colon Cancer

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    Tao Jiang

    2017-01-01

    Full Text Available Deregulation of G protein-coupled receptor kinase 3 (GRK3, which belongs to a subfamily of kinases called GRKs, acts as a promoter mechanism in some cancer types. Our study found that GRK3 was significantly overexpressed in 162 pairs of colon cancer tissues than in the matched noncancerous mucosa (P<0.01. Based on immunohistochemistry staining of TMAs, GRK3 was dramatically stained positive in primary colon cancer (130/180, 72.22%, whereas it was detected minimally or negative in paired normal mucosa specimens (50/180, 27.78%. Overexpression of GRK3 was closely correlated with AJCC stage (P=0.001, depth of tumor invasion (P<0.001, lymph node involvement (P=0.004, distant metastasis (P=0.016, and histologic differentiation (P=0.004. Overexpression of GRK3 is an independent prognostic indicator that correlates with poor survival in colon cancer patients. Consistent with this, downregulation of GRK3 exhibited decreased cell growth index, reduction in colony formation ability, elevated cell apoptosis rate, and impaired colon tumorigenicity in a xenograft model. Hence, a specific overexpression of GRK3 was observed in colon cancer, GRK3 potentially contributing to progression by mediating cancer cell proliferation and functions as a poor prognostic indicator in colon cancer and potentially represent a novel therapeutic target for the disease.

  16. Translating tumor biology into personalized treatment planning: analytical performance characteristics of the Oncotype DX? Colon Cancer Assay

    OpenAIRE

    Clark-Langone, Kim M; Sangli, Chithra; Krishnakumar, Jayadevi; Watson, Drew

    2010-01-01

    Abstract Background The Oncotype DX® Colon Cancer Assay is a new diagnostic test for determining the likelihood of recurrence in stage II colon cancer patients after surgical resection using fixed paraffin embedded (FPE) primary colon tumor tissue. Like the Oncotype DX Breast Cancer Assay, this is a high complexity, multi-analyte, reverse transcription (RT) polymerase chain reaction (PCR) assay that measures the expression levels of specific cancer-related genes. By capturing the biology unde...

  17. Comparative Study of Carcinoembryonic Antigen Tumor Marker in Stomach and Colon Cancer Patients in Khyber Pakhtunkhwa.

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    Ahmad, Bashir; Gul, Bushra; Ali, Sajid; Bashir, Shumaila; Mahmood, Nourin; Ahmad, Jamshed; Nawaz, Seema

    2015-01-01

    Due to the increase in morbidity and mortality rate, cancer has become an alarming threat to the human population worldwide. Since cancer is a progressive disorder, timely diagnosis would be helpful to prevent/stop cancer from progressing to severe stage. In Khyber Pakhtunkhwa, Pakistan, most of the time, tumors are diagnosed with endoscopy and biopsy; therefore rare studies exist regarding the diagnosis of gastrointestinal (GIT) carcinomas based on tumor markers, especially CEA. This study made a comparative analysis of CEA in admitted hospitalized stomach and colon cancer patients diagnosed as GIT with biopsy. In this study, a total of 66 cases were included. The level of CEA was determined in the blood of these patients using ELISA technique. Out of 66 patients, the level of CEA was high in 59.1% of the total, 60.7% in colon cancer patients and 57.9 % in stomach cancer patients. Moreover, the incidence of colorectal and stomach cancer was greater in males as compared to females. Patients were more of the age group of 40- 60 and the level of CEA was comparatively higher in patients (51.5%) with histology which was moderately differentiated, than patients with well differentiated and poorly differentiated tumor histology. CEA level was high in more than 50% of the total patients. Moreover, CEA exhibited higher sensitivity for colon than stomach cancer.

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

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    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.

  19. Targeting tumor multicellular aggregation through IGPR-1 inhibits colon cancer growth and improves chemotherapy.

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    Woolf, N; Pearson, B E; Bondzie, P A; Meyer, R D; Lavaei, M; Belkina, A C; Chitalia, V; Rahimi, N

    2017-09-18

    Adhesion to extracellular matrix (ECM) is crucially important for survival of normal epithelial cells as detachment from ECM triggers specific apoptosis known as anoikis. As tumor cells lose the requirement for anchorage to ECM, they rely on cell-cell adhesion 'multicellular aggregation' for survival. Multicellular aggregation of tumor cells also significantly determines the sensitivity of tumor cells to the cytotoxic effects of chemotherapeutics. In this report, we demonstrate that expression of immunoglobulin containing and proline-rich receptor-1 (IGPR-1) is upregulated in human primary colon cancer. Our study demonstrates that IGPR-1 promotes tumor multicellular aggregation, and interfering with its adhesive function inhibits multicellular aggregation and, increases cell death. IGPR-1 supports colon carcinoma tumor xenograft growth in mouse, and inhibiting its activity by shRNA or blocking antibody inhibits tumor growth. More importantly, IGPR-1 regulates sensitivity of tumor cells to the chemotherapeutic agent, doxorubicin/adriamycin by a mechanism that involves doxorubicin-induced AKT activation and phosphorylation of IGPR-1 at Ser220. Our findings offer novel insight into IGPR-1's role in colorectal tumor growth, tumor chemosensitivity, and as a possible novel anti-cancer target.

  20. Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4.

    Science.gov (United States)

    Todaro, Matilde; Alea, Mileidys Perez; Di Stefano, Anna B; Cammareri, Patrizia; Vermeulen, Louis; Iovino, Flora; Tripodo, Claudio; Russo, Antonio; Gulotta, Gaspare; Medema, Jan Paul; Stassi, Giorgio

    2007-10-11

    A novel paradigm in tumor biology suggests that cancer growth is driven by stem-like cells within a tumor. Here, we describe the identification and characterization of such cells from colon carcinomas using the stem cell marker CD133 that accounts around 2% of the cells in human colon cancer. The CD133(+) cells grow in vitro as undifferentiated tumor spheroids, and they are both necessary and sufficient to initiate tumor growth in immunodeficient mice. Xenografts resemble the original human tumor maintaining the rare subpopulation of tumorigenic CD133(+) cells. Further analysis revealed that the CD133(+) cells produce and utilize IL-4 to protect themselves from apoptosis. Consistently, treatment with IL-4Ralpha antagonist or anti-IL-4 neutralizing antibody strongly enhances the antitumor efficacy of standard chemotherapeutic drugs through selective sensitization of CD133(+) cells. Our data suggest that colon tumor growth is dictated by stem-like cells that are treatment resistant due to the autocrine production of IL-4.

  1. 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)

  2. Hepatoduodenal lymph node metastasis mimicking Klatskin tumor in a patient with sigmoid colon mucinous cancer

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    Hovhannes Vardevanyan, PhD

    2017-09-01

    Full Text Available We report a case of a 48-year-old female patient, who presented with abdominal pain, jaundice, and lack of appetite. Ultrasound showed intrahepatic biliary dilatation with retroperitoneal lymphadenopathy. Further magnetic resonance cholangiopancreatography detected Klatskin tumor. Computed tomography (CT confirmed the Klatskin tumor with liver metastases and retroperitoneal lymphadenopathy. Biopsy from the hepatic lesion identified mucinous adenocarcinoma, likely originating from bile ducts. Endoscopic retrograde cholangiopancreatography was performed 3 times with stents placed in the left and right hepatic bile ducts. Later the patient had hematochezia and was referred to colonoscopy. Tubulovillous adenoma with dysplasia was diagnosed with signs of in situ cancer. Preoperative CT was done for further staging: new pulmonary metastases were discovered. Sigmoid colon was resected. Histopathology verified a poorly differentiated mucinous adenocarcinoma within the tubulovillous adenoma. Intraoperative biopsies of porta hepatis mass resembled metastatic lymph nodes in hepatoduodenal ligament, mimicking Klatskin tumor. Retrospective analysis of CT data demonstrated presence of sigmoid colon tumor.

  3. A Ketogenic Formula Prevents Tumor Progression and Cancer Cachexia by Attenuating Systemic Inflammation in Colon 26 Tumor-Bearing Mice

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    Kentaro Nakamura

    2018-02-01

    Full Text Available Low-carbohydrate, high-fat diets (ketogenic diets might prevent tumor progression and could be used as supportive therapy; however, few studies have addressed the effect of such diets on colorectal cancer. An infant formula with a ketogenic composition (ketogenic formula; KF is used to treat patients with refractory epilepsy. We investigated the effect of KF on cancer and cancer cachexia in colon tumor-bearing mice. Mice were randomized into normal (NR, tumor-bearing (TB, and ketogenic formula (KF groups. Colon 26 cells were inoculated subcutaneously into TB and KF mice. The NR and TB groups received a standard diet, and the KF mice received KF ad libitum. KF mice preserved their body, muscle, and carcass weights. Tumor weight and plasma IL-6 levels were significantly lower in KF mice than in TB mice. In the KF group, energy intake was significantly higher than that in the other two groups. Blood ketone body concentrations in KF mice were significantly elevated, and there was a significant negative correlation between blood ketone body concentration and tumor weight. Therefore, KF may suppress the progression of cancer and the accompanying systemic inflammation without adverse effects on weight gain, or muscle mass, which might help to prevent cancer cachexia.

  4. Surgical resection of locally advanced primary transverse colon cancer--not a worse outcome in stage II tumor.

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    Hung, Hsin-Yuan; Yeh, Chien-Yuh; Changchien, Chung-Rong; Chen, Jinn-Shiun; Fan, Chung-Wei; Tang, Reiping; Hsieh, Pao-Shiu; Tasi, Wen-Sy; You, Yau-Tong; You, Jeng-Fu; Wang, Jeng-Yi; Chiang, Jy-Ming

    2011-07-01

    In locally advanced primary transverse colon cancer, a tumor may cause perforation or invade adjacent organs. Extensive resection is the best choice of treatment, but such procedures must be weighed against the potential survival benefits. This study was performed to identify the clinicopathological features and treatment outcomes of such tumors. We retrospectively reviewed the database of the Colorectal Cancer Registry of Chang Gung Memorial Hospital between February 1995 and December 2005. Patients with colon cancer sited between the hepatic and splenic flexure that involved an adjacent organ without distant metastasis were defined as having locally advanced transverse colon cancer. A total of 827 patients who underwent surgery for transverse primary colon cancer were enrolled in the study. Stage II and stage III colon cancer were diagnosed in 548 patients. Thirty-two (5.8%) patients were diagnosed with locally advanced tumors. Multivariate analysis revealed that stage III, preoperative carcinoembryonic antigen ≥5 ng/mL, a tumor with perforation or obstruction, and the presence of a locally advanced tumor were significant prognostic factors for both overall and cancer-specific survival. Postoperative morbidity rates differed significantly between the locally advanced and non-locally advanced tumor groups (22.7% vs. 12.3%, P transverse colon tumors (P = 0.21). Surgical resection of locally advanced transverse colon tumors resulted in a higher morbidity and mortality than that of non-locally advanced tumors, but the benefit of extensive surgery in the case of locally advanced tumors cannot be underestimated. Furthermore, this benefit is more pronounced in the case of stage II tumors.

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

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    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. Functional heterogeneity of cancer-associated fibroblasts from human colon tumors shows specific prognostic gene expression signature.

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    Herrera, Mercedes; Islam, Abul B M M K; Herrera, Alberto; Martín, Paloma; García, Vanesa; Silva, Javier; Garcia, Jose M; Salas, Clara; Casal, Ignacio; de Herreros, Antonio García; Bonilla, Félix; Peña, Cristina

    2013-11-01

    Cancer-associated fibroblasts (CAF) actively participate in reciprocal communication with tumor cells and with other cell types in the microenvironment, contributing to a tumor-permissive neighborhood and promoting tumor progression. The aim of this study is the characterization of how CAFs from primary human colon tumors promote migration of colon cancer cells. Primary CAF cultures from 15 primary human colon tumors were established. Their enrichment in CAFs was evaluated by the expression of various epithelial and myofibroblast specific markers. Coculture assays of primary CAFs with different colon tumor cells were performed to evaluate promigratory CAF-derived effects on cancer cells. Gene expression profiles were developed to further investigate CAF characteristics. Coculture assays showed significant differences in fibroblast-derived paracrine promigratory effects on cancer cells. Moreover, the association between CAFs' promigratory effects on cancer cells and classic fibroblast activation or stemness markers was observed. CAF gene expression profiles were analyzed by microarray to identify deregulated genes in different promigratory CAFs. The gene expression signature, derived from the most protumorogenic CAFs, was identified. Interestingly, this "CAF signature" showed a remarkable prognostic value for the clinical outcome of patients with colon cancer. Moreover, this prognostic value was validated in an independent series of 142 patients with colon cancer, by quantitative real-time PCR (qRT-PCR), with a set of four genes included in the "CAF signature." In summary, these studies show for the first time the heterogeneity of primary CAFs' effect on colon cancer cell migration. A CAF gene expression signature able to classify patients with colon cancer into high- and low-risk groups was identified.

  7. Use of a combination of CEA and tumor budding to identify high-risk patients with stage II colon cancer.

    Science.gov (United States)

    Du, Changzheng; Xue, Weicheng; Dou, Fangyuan; Peng, Yifan; Yao, Yunfeng; Zhao, Jun; Gu, Jin

    2017-07-24

    High-risk patients with stage II colon cancer may benefit from adjuvant chemotherapy, but identifying this patient population can be difficult. We assessed the prognosis value for predicting tumor progression in patients with stage II colon cancer, of a panel of 2 biomarkers for colon cancer: tumor budding and preoperative carcinoembryonic antigen (CEA). Consecutive patients (N = 134) with stage II colon cancer who underwent curative surgery from 2000 to 2007 were included. Multivariate analysis was used to evaluate the association of CEA and tumor budding grade with 5-year disease-free survival (DFS). The prognostic accuracy of CEA, tumor budding grade and the combination of both (CEA-budding panel) was determined. The study found that both CEA and tumor budding grade were associated with 5-year DFS. The prognostic accuracy for disease progression was higher for the CEA-budding panel (82.1%) than either CEA (70.9%) or tumor budding grade (72.4%) alone. The findings indicate that the combination of CEA levels and tumor budding grade has greater prognostic value for identifying patients with stage II colon cancer who are at high-risk for disease progression, than either marker alone.

  8. Persistent STAT3 Activation in Colon Cancer Is Associated with Enhanced Cell Proliferation and Tumor Growth

    Directory of Open Access Journals (Sweden)

    Florian M. Corvinus

    2005-06-01

    Full Text Available Colorectal carcinoma (CRC is a major cause of morbidity and mortality in Western countries. It has so far been molecularly defined mainly by alterations of the Wnt pathway. We show here for the first time that aberrant activities of the signal transducer and activator of transcription STAT3 actively contribute to this malignancy and, thus, are a potential therapeutic target for CRC. Constitutive STAT3 activity was found to be abundant in dedifferentiated cancer cells and infiltrating lymphocytes of CRC samples, but not in non-neoplastic colon epithelium. Cell lines derived from malignant colorectal tumors lost persistent STAT3 activity in culture. However, implantation of colon carcinoma cells into nude mice resulted in restoration of STAT3 activity, suggesting a role of an extracellular stimulus within the tumor microenvironment as a trigger for STAT activation. STAT3 activity in CRC cells triggered through interleukin-6 or through a constitutively active STAT3 mutant promoted cancer cell multiplication, whereas STAT3 inhibition through a dominant-negative variant impaired IL-6-driven proliferation. Blockade of STAT3 activation in CRCderived xenograft tumors slowed down their development, arguing for a contribution of STAT3 to colorectal tumor growth.

  9. 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...

  10. The prognostic value of simultaneous tumor and serum RAS/RAF mutations in localized colon cancer

    DEFF Research Database (Denmark)

    Brenner Thomsen, Caroline Emilie; Appelt, Ane Lindegaard; Andersen, Rikke Fredslund

    2017-01-01

    The impact of RAS/RAF mutations in localized colon cancer needs clarification. Based on analysis of tumor-specific DNA, this study aimed at elucidating the prognostic influence of mutational status in tumor and serum using an extended panel of mutations. The study retrospectively included 294.......0057), and disease-free survival (DFS) (HR = 2.18, 95%CI = 1.26-3.77, P = 0.0053). BRAF mutation in the serum and proficient mismatch repair (pMMR) protein in tumor also indicated significantly worse prognosis, OS (HR = 3.45, 95% CI = 1.52-7.85, P = 0.0032) and DFS (HR = 3.61, 95% CI = 1.70-7.67, P = 0...

  11. 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.

  12. Positive detection of exfoliated colon cancer cells on linear stapler cartridges was associated with depth of tumor invasion and preoperative bowel preparation in colon cancer.

    Science.gov (United States)

    Ikehara, Kishiko; Endo, Shungo; Kumamoto, Kensuke; Hidaka, Eiji; Ishida, Fumio; Tanaka, Jun-Ichi; Kudo, Shin-Ei

    2016-08-31

    The aim of this study was to investigate exfoliated cancer cells (ECCs) on linear stapler cartridges used for anastomotic sites in colon cancer. We prospectively analyzed ECCs on linear stapler cartridges used for anastomosis in 100 colon cancer patients who underwent colectomy. Having completed the functional end-to-end anastomosis, the linear stapler cartridges were irrigated with saline, which was collected for cytological examination and cytological diagnoses were made by board-certified pathologists based on Papanicolaou staining. The detection rate of ECCs on the linear stapler cartridges was 20 %. Positive detection of ECCs was significantly associated with depth of tumor invasion (p = 0.012) and preoperative bowel preparation (p = 0.003). There were no marked differences between ECC-positive and ECC-negative groups in terms of the operation methods, tumor location, histopathological classification, and surgical margins. Since ECCs were identified on the cartridge of the linear stapler used for anastomosis, preoperative mechanical bowel preparation using polyethylene glycol solution and cleansing at anastomotic sites using tumoricidal agents before anastomosis may be necessary to decrease ECCs in advanced colon cancer.

  13. 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

  14. 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.

  15. Translating tumor biology into personalized treatment planning: analytical performance characteristics of the Oncotype DX® Colon Cancer Assay

    International Nuclear Information System (INIS)

    Clark-Langone, Kim M; Sangli, Chithra; Krishnakumar, Jayadevi; Watson, Drew

    2010-01-01

    The Oncotype DX ® Colon Cancer Assay is a new diagnostic test for determining the likelihood of recurrence in stage II colon cancer patients after surgical resection using fixed paraffin embedded (FPE) primary colon tumor tissue. Like the Oncotype DX Breast Cancer Assay, this is a high complexity, multi-analyte, reverse transcription (RT) polymerase chain reaction (PCR) assay that measures the expression levels of specific cancer-related genes. By capturing the biology underlying each patient's tumor, the Oncotype DX Colon Cancer Assay provides a Recurrence Score (RS) that reflects an individualized risk of disease recurrence. Here we describe its analytical performance using pre-determined performance criteria, which is a critical component of molecular diagnostic test validation. All analytical measurements met pre-specified performance criteria. PCR amplification efficiency for all 12 assays was high, ranging from 96% to 107%, while linearity was demonstrated over an 11 log 2 concentration range for all assays. Based on estimated components of variance for FPE RNA pools, analytical reproducibility and precision demonstrated low SDs for individual genes (0.16 to 0.32 C T s), gene groups (≤0.05 normalized/aggregate C T s) and RS (≤1.38 RS units). Analytical performance characteristics shown here for both individual genes and gene groups in the Oncotype DX Colon Cancer Assay demonstrate consistent translation of specific biology of individual tumors into clinically useful diagnostic information. The results of these studies illustrate how the analytical capability of the Oncotype DX Colon Cancer Assay has enabled clinical validation of a test to determine individualized recurrence risk after colon cancer surgery

  16. Translating tumor biology into personalized treatment planning: analytical performance characteristics of the Oncotype DX® Colon Cancer Assay

    Directory of Open Access Journals (Sweden)

    Krishnakumar Jayadevi

    2010-12-01

    Full Text Available Abstract Background The Oncotype DX® Colon Cancer Assay is a new diagnostic test for determining the likelihood of recurrence in stage II colon cancer patients after surgical resection using fixed paraffin embedded (FPE primary colon tumor tissue. Like the Oncotype DX Breast Cancer Assay, this is a high complexity, multi-analyte, reverse transcription (RT polymerase chain reaction (PCR assay that measures the expression levels of specific cancer-related genes. By capturing the biology underlying each patient's tumor, the Oncotype DX Colon Cancer Assay provides a Recurrence Score (RS that reflects an individualized risk of disease recurrence. Here we describe its analytical performance using pre-determined performance criteria, which is a critical component of molecular diagnostic test validation. Results All analytical measurements met pre-specified performance criteria. PCR amplification efficiency for all 12 assays was high, ranging from 96% to 107%, while linearity was demonstrated over an 11 log2 concentration range for all assays. Based on estimated components of variance for FPE RNA pools, analytical reproducibility and precision demonstrated low SDs for individual genes (0.16 to 0.32 CTs, gene groups (≤0.05 normalized/aggregate CTs and RS (≤1.38 RS units. Conclusions Analytical performance characteristics shown here for both individual genes and gene groups in the Oncotype DX Colon Cancer Assay demonstrate consistent translation of specific biology of individual tumors into clinically useful diagnostic information. The results of these studies illustrate how the analytical capability of the Oncotype DX Colon Cancer Assay has enabled clinical validation of a test to determine individualized recurrence risk after colon cancer surgery.

  17. Translating tumor biology into personalized treatment planning: analytical performance characteristics of the Oncotype DX Colon Cancer Assay.

    Science.gov (United States)

    Clark-Langone, Kim M; Sangli, Chithra; Krishnakumar, Jayadevi; Watson, Drew

    2010-12-23

    The Oncotype DX Colon Cancer Assay is a new diagnostic test for determining the likelihood of recurrence in stage II colon cancer patients after surgical resection using fixed paraffin embedded (FPE) primary colon tumor tissue. Like the Oncotype DX Breast Cancer Assay, this is a high complexity, multi-analyte, reverse transcription (RT) polymerase chain reaction (PCR) assay that measures the expression levels of specific cancer-related genes. By capturing the biology underlying each patient's tumor, the Oncotype DX Colon Cancer Assay provides a Recurrence Score (RS) that reflects an individualized risk of disease recurrence. Here we describe its analytical performance using pre-determined performance criteria, which is a critical component of molecular diagnostic test validation. All analytical measurements met pre-specified performance criteria. PCR amplification efficiency for all 12 assays was high, ranging from 96% to 107%, while linearity was demonstrated over an 11 log2 concentration range for all assays. Based on estimated components of variance for FPE RNA pools, analytical reproducibility and precision demonstrated low SDs for individual genes (0.16 to 0.32 CTs), gene groups (≤ 0.05 normalized/aggregate CTs) and RS (≤ 1.38 RS units). Analytical performance characteristics shown here for both individual genes and gene groups in the Oncotype DX Colon Cancer Assay demonstrate consistent translation of specific biology of individual tumors into clinically useful diagnostic information. The results of these studies illustrate how the analytical capability of the Oncotype DX Colon Cancer Assay has enabled clinical validation of a test to determine individualized recurrence risk after colon cancer surgery.

  18. Overexpression of UbcH10 alternates the cell cycle profile and accelerate the tumor proliferation in colon cancer

    Directory of Open Access Journals (Sweden)

    Hatoh Shinji

    2009-03-01

    Full Text Available Abstract Background UbcH10 participates in proper metaphase to anaphase transition, and abrogation of UbcH10 results in the premature separation of sister chromatids. To assess the potential role of UbcH10 in colon cancer progression, we analyzed the clinicopathological relevance of UbcH10 in colon cancer. Methods We firstly screened the expression profile of UbcH10 in various types of cancer tissues as well as cell lines. Thereafter, using the colon cancer cells line, we manipulated the expression of UbcH10 and evaluated the cell cycle profile and cellular proliferations. Furthermore, the clinicopathological significance of UbcH10 was immunohistologically evaluated in patients with colon cancer. Statistical analysis was performed using the student's t-test and Chi-square test. Results Using the colon cancer cells, depletion of UbcH10 resulted in suppression of cellular growth whereas overexpression of UbcH10 promoted the cellular growth and oncogenic cellular growth. Mitotic population was markedly alternated by the manipulation of UbcH10 expression. Immunohistochemical analysis indicated that UbcH10 was significantly higher in colon cancer tissue compared with normal colon epithelia. Furthermore, the clinicopathological evaluation revealed that UbcH10 was associated with high-grade histological tumors. Conclusion The results show the clinicopathological significance of UbcH10 in the progression of colon cancer. Thus UbcH10 may act as a novel biomarker in patients with colon cancer.

  19. Study shows colon and rectal tumors constitute a single type of cancer

    Science.gov (United States)

    The pattern of genomic alterations in colon and rectal tissues is the same regardless of anatomic location or origin within the colon or the rectum, leading researchers to conclude that these two cancer types can be grouped as one, according to The Cancer

  20. Stage dependent expression and tumor suppressive function of FAM134B (JK1) in colon cancer.

    Science.gov (United States)

    Islam, Farhadul; Gopalan, Vinod; Wahab, Riajul; Smith, Robert A; Qiao, Bin; Lam, Alfred King-Yin

    2017-01-01

    The aims of the present study are to investigate sub-cellular location, differential expression in different cancer stages and functional role of FAM134B in colon cancer development. FAM134B expression was studied and quantified at protein and mRNA levels in cell lines using immunocytochemistry, Western blot and real-time PCR. In vitro functional assays and an in vivo xenotransplantation mouse models were used to investigate the molecular role of FAM134B in cancer cell biology in response to FAM134B silencing with shRNA lentiviral particles. FAM134B protein was noted in both cytoplasm and nuclei of cancer cells. In cancer cells derived from stage IV colon cancer, FAM134B expression was remarkably reduced when compared to non-cancer colon cells and cancer cells derived from stage II colon cancer. FAM134B knockdown significantly (P colon cancer cells following lentiviral transfection. Furthermore, FAM134B suppression significantly increased (34-52%; P cancer suppressor gene in colon cancer. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  1. [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.

  2. [A Case of Transverse Colon Cancer with Liver Metastasis and Tumor Thrombosis of Portal Vein Effectively Treated with Chemotherapy].

    Science.gov (United States)

    Aida, Toshiaki; Shiobara, Masayuki; Wakatsuki, Kazuo; Arai, Shuka; Suda, Kosuke; Miyazawa, Kotaro; Miyoshi, Tetsutaro; Takahashi, Yoshihisa; Yoshioka, Shigeru

    2018-02-01

    The patient was a 70-year-old man. He was diagnosed with advanced transverse colon cancer. A computed tomography (CT)revealed liver metastasis and tumor thrombosis of portal vein. We started combination chemotherapy with capecita- bine/oxaliplatin(CapeOX). Perforation of the tumor was observed 5 days after CapeOX therapy was started. Treatment with abscess drainage and ileostmy, infection was controlled and general condition was improved. After 9 courses of CapeOX, we changed chemotherapy regimen to irinotecan/tegafur-gimeracil-oteracilpotassium (IRIS)due to strong side effects. In CT and FDG-PET examination after 8 courses of IRIS, the tumor of transverse colon, liver metastasis, and the tumor thrombosis of portalvein became unclear. A year and 6 months have passed since chemotherapy was started, recurrence was not observed. For the patients with unresectable colorectal cancer, it is necessary to consider multidisciplinary treatments including chemotherapy while considering the general condition of them.

  3. MUC1-specific immune therapy generates a strong anti-tumor response in a MUC1-tolerant colon cancer model.

    Science.gov (United States)

    Mukherjee, P; Pathangey, L B; Bradley, J B; Tinder, T L; Basu, G D; Akporiaye, E T; Gendler, S J

    2007-02-19

    A MUC1-based vaccine was used in a preclinical model of colon cancer. The trial was conducted in a MUC1-tolerant immune competent host injected with MC38 colon cancer cells expressing MUC1. The vaccine included: MHC class I-restricted MUC1 peptides, MHC class II-restricted pan-helper-peptide, unmethylated CpG oligodeoxynucleotide, and granulocyte macrophage-colony stimulating factor. Immunization was successful in breaking MUC1 self-tolerance, and in eliciting a robust anti-tumor response. The vaccine stimulated IFN-gamma-producing CD4(+) helper and CD8(+) cytotoxic T cells against MUC1 and other undefined MC38 tumor antigens. In the prophylactic setting, immunization caused complete rejection of tumor cells, while in the therapeutic regimen, tumor burden was significantly reduced.

  4. Tumor Initiating Cells and Chemoresistance: Which Is the Best Strategy to Target Colon Cancer Stem Cells?

    Directory of Open Access Journals (Sweden)

    Emanuela Paldino

    2014-01-01

    Full Text Available 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.

  5. Chemo prevention of Tea Polyphenols against Tumor Growth of Hepato-Colon Cancer Induced by Azoxy methane in Rats

    International Nuclear Information System (INIS)

    Heibashy, M.I.A.; Mazen, G.M.A.

    2008-01-01

    This investigation was conducted to evaluate the chemo prevention of tea polyphenols as anticancer agent in rats which were injected with azoxy methane (AOM) which is a potent hepato-colon carcinogen agents in rodents. The obtained data revealed a significant elevation in serum tumor markers, carcino-embryonic antigen (CEA), alpha-fetoprotein (AFP) and cancer antigen (CA 1 9.9) in carcinogenic rats in comparison to their corresponding normal control ones. Also, there was a significant increase in the content of cytochrome P 4 50 and the activity of alcohol dehydrogenase (ADH) in both liver and colon as well as a significant elevation in the activities of methoxyresorufin-O-dealkylase (MRD), ethoxyresorutin-O-dealkylase (ERD) and pentoxyresorufin-O- dealkylase (PRD) in liver microsomes. While, glutathione content (GSH) and glutathione peroxidase (Gp x ) activity were decreased significantly in liver and colon as a result of cancer induction. On the other hand, the supplementation of black or green tea before induction of cancer in rats led to a considerable correction in all previous parameters studied. These amelioration effects dependent on magic biochemical properties of flavanols (catechins) and type of tea. In conclusion, tea polyphenols have appreciable anti-cancer efficacy on hepato colon cancer in rats. The underlying mechanisms of through which tea counteracted hepato-colon cancer were discussed

  6. Carotenoids and colon cancer.

    Science.gov (United States)

    Slattery, M L; Benson, J; Curtin, K; Ma, K N; Schaeffer, D; Potter, J D

    2000-02-01

    Carotenoids have numerous biological properties that may underpin a role for them as chemopreventive agents. However, except for beta-carotene, little is known about how dietary carotenoids are associated with common cancers, including colon cancer. The objective of this study was to evaluate associations between dietary alpha-carotene, beta-carotene, lycopene, lutein, zeaxanthin, and beta-cryptoxanthin and the risk of colon cancer. Data were collected from 1993 case subjects with first primary incident adenocarcinoma of the colon and from 2410 population-based control subjects. Dietary data were collected from a detailed diet-history questionnaire and nutrient values for dietary carotenoids were obtained from the US Department of Agriculture-Nutrition Coordinating Center carotenoid database (1998 updated version). Lutein was inversely associated with colon cancer in both men and women [odds ratio (OR) for upper quintile of intake relative to lowest quintile of intake: 0.83; 95% CI: 0.66, 1.04; P = 0.04 for linear trend]. The greatest inverse association was observed among subjects in whom colon cancer was diagnosed when they were young (OR: 0.66; 95% CI: 0.48, 0.92; P = 0.02 for linear trend) and among those with tumors located in the proximal segment of the colon (OR: 0.65; 95% CI: 0.51, 0.91; P lettuce, tomatoes, oranges and orange juice, carrots, celery, and greens. These data suggest that incorporating these foods into the diet may help reduce the risk of developing colon cancer.

  7. [Synchronous Double Cancer Involving Gastric Cancer Resembling a Submucosal Tumor with Stenosis in the Pylorus and Ascending Colon Cancer - A Case Report].

    Science.gov (United States)

    Miyauchi, Tatsuomi; Miyaki, Akira; Ida, Arika; Kishibe, Saki; Yamaguchi, Kentaro; Shiozawa, Shunichi; Usui, Takebumi; Kuhara, Kotaro; Kono, Teppei; Naritaka, Yoshihiko

    2016-11-01

    An 82-year-old woman presented to our hospital with a complaint of frequent vomiting. She was admitted for intensive examination and treatment. Abdominal computed tomography revealed that her stomach was severely expanded, and the wall of the ascending colon was thickened throughout its circumference. Upper gastrointestinal endoscopy uncovered severe stenosis in the pylorus and an elevated lesion resembling a submucosal tumor on the posterior wall of the pylorus. Biopsies of the lesion revealed that it was of Group 1. On colonoscopy, type 2 cancer was found in the ascending colon throughout the circumference, and the biopsies revealed that it was of Group 5. Upper gastrointestinal endoscopy was repeated, and the same result was obtained. The possibility of malignancy could not be excluded; therefore, distal gastrectomy and right colectomy were performed. In terms of histopathology, both resected specimens displayed poorly differentiated adenocarcinoma; however, immunohistochemical studies revealed differences in staining at the two sites. The case was diagnosed as synchronous double cancer involving gastric cancer resembling a submucosal tumor with stenosis in the pylorus and ascending colon cancer. Gastric cancer resembling a submucosal tumor is usually difficult to diagnose on biopsy. If the endoscopic findings reveal an elevated lesion resembling a submucosal tumor with stenosis, then the possibility of carcinoma should be considered, and the most suitable treatment should be selected.

  8. 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

  9. 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.

  10. Human Colon Tumors Express a Dominant-Negative Form of SIGIRR That Promotes Inflammation and Colitis-Associated Colon Cancer in Mice.

    Science.gov (United States)

    Zhao, Junjie; Bulek, Katarzyna; Gulen, Muhammet F; Zepp, Jarod A; Karagkounis, Georgio; Martin, Bradley N; Zhou, Hao; Yu, Minjia; Liu, Xiuli; Huang, Emina; Fox, Paul L; Kalady, Matthew F; Markowitz, Sanford D; Li, Xiaoxia

    2015-12-01

    Single immunoglobulin and toll-interleukin 1 receptor (SIGIRR), a negative regulator of the Toll-like and interleukin-1 receptor (IL-1R) signaling pathways, controls intestinal inflammation and suppresses colon tumorigenesis in mice. However, the importance of SIGIRR in human colorectal cancer development has not been determined. We investigated the role of SIGIRR in development of human colorectal cancer. We performed RNA sequence analyses of pairs of colon tumor and nontumor tissues, each collected from 68 patients. Immunoblot and immunofluorescence analyses were used to determine levels of SIGIRR protein in primary human colonic epithelial cells, tumor tissues, and colon cancer cell lines. We expressed SIGIRR and mutant forms of the protein in Vaco cell lines. We created and analyzed mice that expressed full-length (control) or a mutant form of Sigirr (encoding SIGIRR(N86/102S), which is not glycosylated) specifically in the intestinal epithelium. Some mice were given azoxymethane (AOM) and dextran sulfate sodium to induce colitis-associated cancer. Intestinal tissues were collected and analyzed by immunohistochemical and gene expression profile analyses. RNA sequence analyses revealed increased expression of a SIGIRR mRNA isoform, SIGIRR(ΔE8), in colorectal cancer tissues compared to paired nontumor tissues. SIGIRR(ΔE8) is not modified by complex glycans and is therefore retained in the cytoplasm-it cannot localize to the cell membrane or reduce IL1R signaling. SIGIRR(ΔE8) interacts with and has a dominant-negative effect on SIGIRR, reducing its glycosylation, localization to the cell surface, and function. Most SIGIRR detected in human colon cancer tissues was cytoplasmic, whereas in nontumor tissues it was found at the cell membrane. Mice that expressed SIGIRR(N86/102S) developed more inflammation and formed larger tumors after administration of azoxymethane and dextran sulfate sodium than control mice; colon tissues from these mutant mice expressed

  11. Assessment of serum tumor markers, tumor cell apoptosis and immune response in patients with advanced colon cancer after DC-CIK combined with intravenous chemotherapy

    Directory of Open Access Journals (Sweden)

    Lei-Fan Li

    2016-12-01

    Full Text Available Objective: To study the effect of DC-CIK combined with intravenous chemotherapy on serum tumor markers, tumor cell apoptosis and immune response in patients with advanced colon cancer. Methods: A total of 79 patients with advanced colon cancer conservatively treated in our hospital between May 2012 and October 2015 were retrospectively studied and divided into DC-CIK group and intravenous chemotherapy group according to different therapeutic regimens, DC-CIK group received DC-CIK combined with intravenous chemotherapy and intravenous chemotherapy group received conventional intravenous chemotherapy. After three cycles of chemotherapy, the content of tumor markers in serum, expression levels of apoptotic molecules in tumor lesions as well as immune function indexes were determined. Results: After 3 cycles of chemotherapy, CEA, CA199, CA242, HIF-1α, IL-4, IL-5 and IL-10 content in serum of DC-CIK group were significantly lower than those of intravenous chemotherapy group; p53, FAM96B, PTEN, PHLPP, ASPP2 and RASSF10 mRNA content in tumor lesions of DC-CIK group were significantly higher than those of intravenous chemotherapy group; the fluorescence intensity of CD3, CD4 and CD56 on peripheral blood mononuclear cell surface of DC-CIK group were significantly higher than those of intravenous chemotherapy group while the fluorescence intensity of CD8 and CD25 were significantly lower than those of intravenous chemotherapy group; IL-2 and IFN-γ content in serum of DC-CIK group were significantly higher than those of intravenous chemotherapy group while IL-4, IL-5 and IL-10 content were significantly lower than those of intravenous chemotherapy group. Conclusions: DC-CIK combined with intravenous chemotherapy has better effect on killing colon cancer cells and inducing colon cancer cell apoptosis than conventional intravenous chemotherapy, and can also improve the body's anti-tumor immune response.

  12. Patient and tumor characteristics and BRAF and KRAS mutations in colon cancer, NCCTG/Alliance N0147.

    Science.gov (United States)

    Gonsalves, Wilson I; Mahoney, Michelle R; Sargent, Daniel J; Nelson, Garth D; Alberts, Steven R; Sinicrope, Frank A; Goldberg, Richard M; Limburg, Paul J; Thibodeau, Stephen N; Grothey, Axel; Hubbard, Joleen M; Chan, Emily; Nair, Suresh; Berenberg, Jeffrey L; McWilliams, Robert R

    2014-07-01

    KRAS and BRAF (V600E) mutations are important predictive and prognostic markers, respectively, in colon cancer, but little is known about patient and clinical factors associated with them. Two thousand three hundred twenty-six of 3397 patients in the N0147 phase III adjuvant trial for stage III colon cancer completed a patient questionnaire. Primary tumors were assessed for KRAS and BRAF (V600E) mutations and defective mismatch repair (dMMR) status. Logistic regression models and categorical data analysis were used to identify associations of patient and tumor characteristics with mutation status. All statistical tests were two-sided. KRAS (35%) and BRAF (V600E) (14%) mutations were nearly mutually exclusive. KRAS mutations were more likely to be present in patients without a family history of colon cancer and never smokers. Tumors with KRAS mutations were less likely to have dMMR (odds ratio [OR] = 0.21; 95% confidence interval [CI] = 0.15 to 0.31; P characteristics are associated with KRAS and BRAF (V600E) mutations. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. Clinical significance of MCM-2 and MCM-5 expression in colon cancer: association with clinicopathological parameters and tumor proliferative capacity.

    Science.gov (United States)

    Giaginis, Constantinos; Georgiadou, Maria; Dimakopoulou, Konstantina; Tsourouflis, Gerasimos; Gatzidou, Elisavet; Kouraklis, Gregorios; Theocharis, Stamatios

    2009-02-01

    Minichromosome maintenance (MCM) proteins are essential components of DNA replication, being related to cell proliferation, and serve as useful markers for cancer screening, surveillance, and prognosis. Our aim was to examine the clinical significance of MCM-2 and MCM-5 protein expression in colon cancer and to evaluate the association with various clinicopathological characteristics and tumor proliferative capacity. Immunohistochemical expression of MCM-2 and MCM-5 was performed on paraffin-embedded malignant tissue sections obtained from 96 patients with colon cancer. MCM-2 and MCM-5 expression was correlated with different clinicopathological characteristics, proliferative capacity (Ki-67 labeling index), and p53 cell-cycle regulator expression. MCM-2 and Ki-67 expression was significantly associated with the tumors' histological grade (P = 0.003), existence of nodular metastases (N) (P = 0.003 and P = 0.030, respectively), malignancy on adenoma (P = 0.029 and P = 0.024, respectively), and vascular invasion (P = 0.010 and P = 0.011, respectively). MCM-2 expression was additionally associated with Dukes' stage (P = 0.005). Significant positive relationships were found between the expression of MCM-2 or MCM-5 proteins and that of Ki-67 protein (r = 0.963, P-value characteristics examined. The current data suggest that MCM-2 protein expression is significantly associated with important clinicopathological characteristics for patients' management, being correlated with the cell proliferation state in colon cancer.

  14. Tumor associated macrophages protect colon cancer cells from TRAIL-induced apoptosis through IL-1beta-dependent stabilization of Snail in tumor cells.

    Directory of Open Access Journals (Sweden)

    Pawan Kaler

    2010-07-01

    Full Text Available We recently reported that colon tumor cells stimulate macrophages to release IL-1beta, which in turn inactivates GSK3beta and enhances Wnt signaling in colon cancer cells, generating a self-amplifying loop that promotes the growth of tumor cells.Here we describe that macrophages protect HCT116 and Hke-3 colon cancer cells from TRAIL-induced apoptosis. Inactivation of IL-1beta by neutralizing IL-1beta antibody, or silencing of IL-1beta in macrophages inhibited their ability to counter TRAIL-induced apoptosis. Accordingly, IL-1beta was sufficient to inhibit TRAIL-induced apoptosis. TRAIL-induced collapse of the mitochondrial membrane potential (Delta psi and activation of caspases were prevented by macrophages or by recombinant IL-1beta. Pharmacological inhibition of IL-1beta release from macrophages by vitamin D(3, a potent chemopreventive agent for colorectal cancer, restored the ability of TRAIL to induce apoptosis of tumor cells cultured with macrophages. Macrophages and IL-1beta failed to inhibit TRAIL-induced apoptosis in HCT116 cells expressing dnIkappaB, dnAKT or dnTCF4, confirming that they oppose TRAIL-induced cell death through induction of Wnt signaling in tumor cells. We showed that macrophages and IL-1beta stabilized Snail in tumor cells in an NF-kappaB/Wnt dependent manner and that Snail deficient tumor cells were not protected from TRAIL-induced apoptosis by macrophages or by IL-1beta, demonstrating a crucial role of Snail in the resistance of tumor cells to TRAIL.We have identified a positive feedback loop between tumor cells and macrophages that propagates the growth and promotes the survival of colon cancer cells: tumor cells stimulate macrophages to secrete IL-1beta, which in turn, promotes Wnt signaling and stabilizes Snail in tumor cells, conferring resistance to TRAIL. Vitamin D(3 halts this amplifying loop by interfering with the release of IL-1beta from macrophages. Accordingly, vitamin D(3 sensitizes tumor cells to TRAIL

  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. Clinical impact of tumor location on the colon cancer survival and recurrence: analyses of pooled data from three large phase III randomized clinical trials.

    Science.gov (United States)

    Aoyama, Toru; Kashiwabara, Kosuke; Oba, Koji; Honda, Michitaka; Sadahiro, Sotaro; Hamada, Chikuma; Maeda, Hiromichi; Mayanagi, Shuhei; Kanda, Mitsuro; Sakamoto, Junichi; Saji, Shigetoyo; Yoshikawa, Takaki

    2017-11-01

    The aim of the present study was to determine whether or not the overall survival (OS) and disease-free survival (DFS) were affected by the tumor location in patients who underwent curative resection for colon cancer in a pooled analysis of three large phase III studies performed in Japan. In total, 4029 patients were included in the present study. Patients were classified as having right-side colon cancer (RC) if the primary tumor was located in the cecum, ascending colon, hepatic flexure or transverse colon, and left-side colon cancer (LCC) if the tumor site was within the splenic flexure, descending colon, sigmoid colon or recto sigmoid junction. The risk factors for the OS and DFS were analyzed. In the present study, 1449 patients were RC, and 2580 were LCC. The OS rates at 3 and 5 years after surgery were 87.6% and 81.6% in the RC group and 91.5% and 84.5% in the LCC group, respectively. Uni- and multivariate analyses showed that RRC increased the risk of death by 19.7% (adjusted hazard ratio = 1.197; 95% confidence interval, 1.020-1.408; P = 0.0272). In contrast, the DFS was similar between the two locations. The present study confirmed that the tumor location was a risk factor for the OS in patients who underwent curative treatment for colon cancer. Tumor location may, therefore, need to be considered a stratification factor in future phase III trials of colon cancer. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  17. PLK1 has tumor-suppressive potential in APC-truncated colon cancer cells.

    Science.gov (United States)

    Raab, Monika; Sanhaji, Mourad; Matthess, Yves; Hörlin, Albrecht; Lorenz, Ioana; Dötsch, Christina; Habbe, Nils; Waidmann, Oliver; Kurunci-Csacsko, Elisabeth; Firestein, Ron; Becker, Sven; Strebhardt, Klaus

    2018-03-16

    The spindle assembly checkpoint (SAC) acts as a molecular safeguard in ensuring faithful chromosome transmission during mitosis, which is regulated by a complex interplay between phosphatases and kinases including PLK1. Adenomatous polyposis coli (APC) germline mutations cause aneuploidy and are responsible for familial adenomatous polyposis (FAP). Here we study the role of PLK1 in colon cancer cells with chromosomal instability promoted by APC truncation (APC-ΔC). The expression of APC-ΔC in colon cells reduces the accumulation of mitotic cells upon PLK1 inhibition, accelerates mitotic exit and increases the survival of cells with enhanced chromosomal abnormalities. The inhibition of PLK1 in mitotic, APC-∆C-expressing cells reduces the kinetochore levels of Aurora B and hampers the recruitment of SAC component suggesting a compromised mitotic checkpoint. Furthermore, Plk1 inhibition (RNAi, pharmacological compounds) promotes the development of adenomatous polyps in two independent Apc Min/+ mouse models. High PLK1 expression increases the survival of colon cancer patients expressing a truncated APC significantly.

  18. Role of blood tumor markers in predicting metastasis and local recurrence after curative resection of colon cancer

    Science.gov (United States)

    Peng, Yifan; Zhai, Zhiwei; Li, Zhongmin; Wang, Lin; Gu, Jin

    2015-01-01

    Aim: To investigate the prognostic value of carcinoembryonic antigen (CEA), CA199, CA724 and CA242 in peripheral blood and local draining venous blood in colon cancer patients after curative resection. Methods: 92 colon cancer patients who received curative resection were retrospectively analyzed. The CEA, CA199, CA724 and CA242 were detected in peripheral blood and local draining venous blood. Results: Metastasis or local recurrence was found in 29 (29/92, 31.5%) patients during follow-up period. 92 patients were divided into two groups: metastasis/local recurrence group (n = 29) and non-metastasis/local recurrence group (n = 63). Peripheral venous CEA, CA199, CA724 and CA242 (p-CEA, p-CA199, p-CA724 and p-CA242) were comparable between two groups (P > 0.05). The median draining venous CEA (d-CEA) in metastases/local recurrence group (23.7 ± 6.9 ng/ml) was significantly higher than that in non-metastases/local recurrence group (18.1 ± 6.3 ng/ml; P 0.05). The optimal cut-off value of d-CEA was 2.76 ng/ml, with the sensitivity and specificity of 90% and 40% in the prediction of metastasis or local recurrence, respectively. d-CEA correlated with tumor differentiation, T stage, TNM stage, metastasis and local recurrence. Subgroup analysis showed that, of 41 patients with stage II colon cancer, the optimal cut-off value of d-CEA was 8.78 ng/mL, and the sensitivity and specificity were 87.5% and 69.7% in the prediction of metastasis or local recurrence, respectively. Conclusion: d-CEA may be a prognostic factor for stage II colon cancer patients. PMID:25785084

  19. Negligible colon cancer risk from food-borne acrylamide exposure in male F344 rats and nude (nu/nu mice-bearing human colon tumor xenografts.

    Directory of Open Access Journals (Sweden)

    Jayadev Raju

    Full Text Available Acrylamide, a possible human carcinogen, is formed in certain carbohydrate-rich foods processed at high temperature. We evaluated if dietary acrylamide, at doses (0.5, 1.0 or 2.0 mg/kg diet reflecting upper levels found in human foods, modulated colon tumorigenesis in two rodent models. Male F344 rats were randomized to receive diets without (control or with acrylamide. 2-weeks later, rats in each group received two weekly subcutaneous injections of either azoxymethane (AOM or saline, and were killed 20 weeks post-injections; colons were assessed for tumors. Male athymic nude (nu/nu mice bearing HT-29 human colon adenocarcinoma cells-derived tumor xenografts received diets without (control or with acrylamide; tumor growth was monitored and mice were killed 4 weeks later. In the F344 rat study, no tumors were found in the colons of the saline-injected rats. However, the colon tumor incidence was 54.2% and 66.7% in the control and the 2 mg/kg acrylamide-treated AOM-injected groups, respectively. While tumor multiplicity was similar across all diet groups, tumor size and burden were higher in the 2 mg/kg acrylamide group compared to the AOM control. These results suggest that acrylamide by itself is not a "complete carcinogen", but acts as a "co-carcinogen" by exacerbating the effects of AOM. The nude mouse study indicated no differences in the growth of human colon tumor xenografts between acrylamide-treated and control mice, suggesting that acrylamide does not aid in the progression of established tumors. Hence, food-borne acrylamide at levels comparable to those found in human foods is neither an independent carcinogen nor a tumor promoter in the colon. However, our results characterize a potential hazard of acrylamide as a colon co-carcinogen in association with known and possibly other environmental tumor initiators/promoters.

  20. CD133 expression is not restricted to stem cells, and both CD133+ and CD133– metastatic colon cancer cells initiate tumors

    Science.gov (United States)

    Shmelkov, Sergey V.; Butler, Jason M.; Hooper, Andrea T.; Hormigo, Adilia; Kushner, Jared; Milde, Till; St. Clair, Ryan; Baljevic, Muhamed; White, Ian; Jin, David K.; Chadburn, Amy; Murphy, Andrew J.; Valenzuela, David M.; Gale, Nicholas W.; Thurston, Gavin; Yancopoulos, George D.; D’Angelica, Michael; Kemeny, Nancy; Lyden, David; Rafii, Shahin

    2008-01-01

    Colon cancer stem cells are believed to originate from a rare population of putative CD133+ intestinal stem cells. Recent publications suggest that a small subset of colon cancer cells expresses CD133, and that only these CD133+ cancer cells are capable of tumor initiation. However, the precise contribution of CD133+ tumor-initiating cells in mediating colon cancer metastasis remains unknown. Therefore, to temporally and spatially track the expression of CD133 in adult mice and during tumorigenesis, we generated a knockin lacZ reporter mouse (CD133lacZ/+), in which the expression of lacZ is driven by the endogenous CD133 promoters. Using this model and immunostaining, we discovered that CD133 expression in colon is not restricted to stem cells; on the contrary, CD133 is ubiquitously expressed on differentiated colonic epithelium in both adult mice and humans. Using Il10–/–CD133lacZ mice, in which chronic inflammation in colon leads to adenocarcinomas, we demonstrated that CD133 is expressed on a full gamut of colonic tumor cells, which express epithelial cell adhesion molecule (EpCAM). Similarly, CD133 is widely expressed by human primary colon cancer epithelial cells, whereas the CD133– population is composed mostly of stromal and inflammatory cells. Conversely, CD133 expression does not identify the entire population of epithelial and tumor-initiating cells in human metastatic colon cancer. Indeed, both CD133+ and CD133– metastatic tumor subpopulations formed colonospheres in in vitro cultures and were capable of long-term tumorigenesis in a NOD/SCID serial xenotransplantation model. Moreover, metastatic CD133– cells form more aggressive tumors and express typical phenotypic markers of cancer-initiating cells, including CD44 (CD44+CD24–), whereas the CD133+ fraction is composed of CD44lowCD24+ cells. Collectively, our data suggest that CD133 expression is not restricted to intestinal stem or cancer-initiating cells, and during the metastatic

  1. Intrabiliary growth of recurrent tumor after percutaneous RF ablation for treating liver metastasis from colon cancer: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Youn Kyung; Kim, Seung Kwon; Hong, Hyun Pyo [Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2007-12-15

    A 64-year-old man who underwent right hemicolectomy 3.5 years ago for ascending colon cancer and then RF ablation for two metastatic nodules in the liver was admitted to our hospital with a new metastatic nodule in the S6/7 segment of the liver. The CT scan showed a low attenuating metastatic nodule 2.2 cm in diameter in the S6/7 segment of the liver, and the liver showed peripheral bile duct dilatation. This nodule was treated with percutaneous RF ablation. A follow-up CT seven months after RF ablation showed the presence of a viable tumor in the RF ablation zone, with tumor extension along the dilated bile duct. These findings were confirmed on the resected specimen.

  2. Regulation of APC and AXIN2 expression by intestinal tumor suppressor CDX2 in colon cancer cells

    DEFF Research Database (Denmark)

    Olsen, Anders Krüger; Coskun, Mehmet; Bzorek, Michael

    2013-01-01

    was associated with endogenous downregulation of APC and AXIN2 expression in Caco-2 cells but did not affect GSK3β expression. Furthermore, elevated levels of nuclear β-catenin and reduced levels of cytoplasmic APC were correlated to a low CDX2 expression in migrating colon cancer cells in vivo. These results......Wnt signaling is often constitutively active in colorectal cancer cells. The expression of the intestinal specific transcription factor CDX2 is found to be transiently decreased in invasive cells at the tumor/stroma interface. A recent ChIP-Seq study has indicated that several Wnt signaling......-related genes are regulated by CDX2. The aim was to investigate the role of decreased CDX2 level on the expression of APC, AXIN2 and GSK3β in migrating colon cancer cells at the invasive front. CDX2-bound promoter and enhancer regions from APC, AXIN2 and GSK3β were analyzed for gene regulatory activity...

  3. 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...

  4. Inactivation of Adenomatous Polyposis Coli Reduces Bile Acid/Farnesoid X Receptor Expression through Fxr gene CpG Methylation in Mouse Colon Tumors and Human Colon Cancer Cells.

    Science.gov (United States)

    Selmin, Ornella I; Fang, Changming; Lyon, Adam M; Doetschman, Tom C; Thompson, Patricia A; Martinez, Jesse D; Smith, Jeffrey W; Lance, Peter M; Romagnolo, Donato F

    2016-02-01

    The farnesoid X receptor (FXR) regulates bile acid (BA) metabolism and possesses tumor suppressor functions. FXR expression is reduced in colorectal tumors of subjects carrying inactivated adenomatous polyposis coli (APC). Identifying the mechanisms responsible for this reduction may offer new molecular targets for colon cancer prevention. We investigated how APC inactivation influences the regulation of FXR expression in colonic mucosal cells. We hypothesized that APC inactivation would epigenetically repress nuclear receptor subfamily 1, group H, member 4 (FXR gene name) expression through increased CpG methylation. Normal proximal colonic mucosa and normal-appearing adjacent colonic mucosa and colon tumors were collected from wild-type C57BL/6J and Apc-deficient (Apc(Min) (/+)) male mice, respectively. The expression of Fxr, ileal bile acid-binding protein (Ibabp), small heterodimer partner (Shp), and cyclooxygenase-2 (Cox-2) were determined by real-time polymerase chain reaction. In both normal and adjacent colonic mucosa and colon tumors, we measured CpG methylation of Fxr in bisulfonated genomic DNA. In vitro, we measured the impact of APC inactivation and deoxycholic acid (DCA) treatment on FXR expression in human colon cancer HCT-116 cells transfected with silencing RNA for APC and HT-29 cells carrying inactivated APC. In Apc(Min) (/+) mice, constitutive CpG methylation of the Fxrα3/4 promoter was linked to reduced (60-90%) baseline Fxr, Ibabp, and Shp and increased Cox-2 expression in apparently normal adjacent mucosa and colon tumors. Apc knockdown in HCT-116 cells increased cellular myelocytomatosis (c-MYC) and lowered (∼50%) FXR expression, which was further reduced (∼80%) by DCA. In human HCT-116 but not HT-29 colon cancer cells, DCA induced FXR expression and lowered CpG methylation of FXR. We conclude that the loss of APC function favors the silencing of FXR expression through CpG hypermethylation in mouse colonic mucosa and human colon cells

  5. Computer-assisted stereology and automated image analysis for quantification of tumor infiltrating lymphocytes in colon cancer.

    Science.gov (United States)

    Eriksen, Ann C; Andersen, Johnnie B; Kristensson, Martin; dePont Christensen, René; Hansen, Torben F; Kjær-Frifeldt, Sanne; Sørensen, Flemming B

    2017-08-29

    Precise prognostic and predictive variables allowing improved post-operative treatment stratification are missing in patients treated for stage II colon cancer (CC). Investigation of tumor infiltrating lymphocytes (TILs) may be rewarding, but the lack of a standardized analytic technique is a major concern. Manual stereological counting is considered the gold standard, but digital pathology with image analysis is preferred due to time efficiency. The purpose of this study was to compare manual stereological estimates of TILs with automatic counts obtained by image analysis, and at the same time investigate the heterogeneity of TILs. From 43 patients treated for stage II CC in 2002 three paraffin embedded, tumor containing tissue blocks were selected one of them representing the deepest invasive tumor front. Serial sections from each of the 129 blocks were immunohistochemically stained for CD3 and CD8, and the slides were scanned. Stereological estimates of the numerical density and area fraction of TILs were obtained using the computer-assisted newCAST stereology system. For the image analysis approach an app-based algorithm was developed using Visiopharm Integrator System software. For both methods the tumor areas of interest (invasive front and central area) were manually delineated by the observer. Based on all sections, the Spearman's correlation coefficients for density estimates varied from 0.9457 to 0.9638 (p heterogeneity, intra-class correlation coefficients (ICC) for CD3+ TILs varied from 0.615 to 0.746 in the central area, and from 0.686 to 0.746 in the invasive area. ICC for CD8+ TILs varied from 0.724 to 0.775 in the central area, and from 0.746 to 0.765 in the invasive area. Exact objective and time efficient estimates of numerical densities and area fractions of CD3+ and CD8+ TILs in stage II colon cancer can be obtained by image analysis and are highly correlated to the corresponding estimates obtained by the gold standard based on stereology

  6. Biologic determinants of tumor recurrence in stage II colon cancer: validation study of the 12-gene recurrence score in cancer and leukemia group B (CALGB) 9581.

    Science.gov (United States)

    Venook, Alan P; Niedzwiecki, Donna; Lopatin, Margarita; Ye, Xing; Lee, Mark; Friedman, Paula N; Frankel, Wendy; Clark-Langone, Kim; Millward, Carl; Shak, Steven; Goldberg, Richard M; Mahmoud, Najjia N; Warren, Robert S; Schilsky, Richard L; Bertagnolli, Monica M

    2013-05-10

    A greater understanding of the biology of tumor recurrence should improve adjuvant treatment decision making. We conducted a validation study of the 12-gene recurrence score (RS), a quantitative assay integrating stromal response and cell cycle gene expression, in tumor specimens from patients enrolled onto Cancer and Leukemia Group B (CALGB) 9581. CALGB 9581 randomly assigned 1,713 patients with stage II colon cancer to treatment with edrecolomab or observation and found no survival difference. The analysis reported here included all patients with available tissue and recurrence (n = 162) and a random (approximately 1:3) selection of nonrecurring patients. RS was assessed in 690 formalin-fixed paraffin-embedded tumor samples with quantitative reverse transcriptase polymerase chain reaction by using prespecified genes and a previously validated algorithm. Association of RS and recurrence was analyzed by weighted Cox proportional hazards regression. Continuous RS was significantly associated with risk of recurrence (P = .013) as was mismatch repair (MMR) gene deficiency (P = .044). In multivariate analyses, RS was the strongest predictor of recurrence (P = .004), independent of T stage, MMR, number of nodes examined, grade, and lymphovascular invasion. In T3 MMR-intact (MMR-I) patients, prespecified low and high RS groups had average 5-year recurrence risks of 13% (95% CI, 10% to 16%) and 21% (95% CI, 16% to 26%), respectively. The 12-gene RS predicts recurrence in stage II colon cancer in CALGB 9581. This is consistent with the importance of stromal response and cell cycle gene expression in colon tumor recurrence. RS appears to be most discerning for patients with T3 MMR-I tumors, although markers such as grade and lymphovascular invasion did not add value in this subset of patients.

  7. Proteomic profiling of antibody-inducing immunogens in tumor tissue identifies PSMA1, LAP3, ANXA3, and maspin as colon cancer markers

    Science.gov (United States)

    Yang, Qian; Roehrl, Michael H.; Wang, Julia Y.

    2018-01-01

    We hypothesized that cancer tissue immunogens – antigens capable of inducing specific antibody production in patients – are promising targets for development of precision diagnostics and humoral immunotherapies. We developed an innovative immuno-proteomic strategy and identified new immunogenic markers of colon cancer. Proteins from cancers and matched normal tissues were separated by 2D gel electrophoresis and blotted with serum antibodies from the same patients. Antibody-reactive proteins were sequenced by mass spectrometry and validated by Western blotting and immunohistochemistry. 170 serum antibody-reactive proteins were identified only in cancerous but not matched normal. Among these, proteasome subunit alpha type 1 (PSA1), leucine aminopeptidase 3 (LAP3), annexin A3 (ANXA3), and maspin (serpin B5) were reproducibly found in tissues from three patients. Differential expression patterns were confirmed in samples from eight patients with various stages of colon adenocarcinoma and liver metastases. These tumor-resident proteins and/or their associated serum antibodies may be promising markers for colon cancer screening and early diagnosis. Furthermore, tumor tissue-specific antibodies could potentially be exploited as immunotherapeutic targets against cancer. More generally, proteomic profiling of antibody-inducing cancer-associated immunogens represents a powerful generic method for uncovering the tumor antigen-ome, i.e., the totality of immunogenic tumor-associated proteins. PMID:29423100

  8. 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...

  9. 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

  10. Involvement of FFA1 and FFA4 in the regulation of cellular functions during tumor progression in colon cancer cells.

    Science.gov (United States)

    Takahashi, Kaede; Fukushima, Kaori; Onishi, Yuka; Minami, Kanako; Otagaki, Shiho; Ishimoto, Kaichi; Fukushima, Nobuyuki; Honoki, Kanya; Tsujiuchi, Toshifumi

    2018-08-01

    Free fatty acid receptor 1 (FFA1) and FFA4 mediate a variety of biological responses through binding of medium- and long-chain free fatty acids. The aim of this study was to investigate an involvement of FFA1 and FFA4 in the regulation of cellular functions during tumor progression in colon cancer cells. The long-term fluorouracil (5-FU) and cisplatin (CDDP) treated cells were generated from DLD1 cells (DLD-5FU and DLD-CDDP cells, respectively). FFAR1 expressions were lower in DLD-5FU and DLD-CDDP cells than in DLD1 cells. In contrast, DLD-5FU and DLD-CDDP cells showed the high FFAR4 expressions, compared with DLD1 cells. The cell motile activities of DLD-5FU and DLD-CDDP cells were reduced by GW9508 which is an agonist of FFA1 and FFA4. Moreover, GW1100, an antagonist of FFA1, inhibited the cell motile activities of DLD-5FU and DLD-CDDP cells. To evaluate whether FFA1 and FFA4 regulate the enhancement of cell motility, invasion and colony formation, highly migratory (hmDLD1) cells were established from DLD1 cells. FFAR1 expression was significantly higher in hmDLD1 cells than in DLD1 cells, but no change of FFAR4 expression was observed. The elevated cell motile and invasive activities and colony formation of hmDLD1 cells were suppressed by FFA1 inhibition. These results suggest that FFA1 and FFA4 are involved in the regulation of cellular functions during tumor progression in colon cancer DLD1 cells. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Overexpression of long non-coding RNA colon cancer-associated transcript 2 is associated with advanced tumor progression and poor prognosis in patients with colorectal cancer.

    Science.gov (United States)

    Zhang, Junling; Jiang, Yong; Zhu, Jing; Wu, Tao; Ma, Ju; Du, Chuang; Chen, Shanwen; Li, Tengyu; Han, Jinsheng; Wang, Xin

    2017-12-01

    The aim of the present study was to explore the clinicopathological and prognostic significance of long non-coding RNA (lncRNA) colon cancer-associated transcript 2 (CCAT2) expression in human colorectal cancer (CRC). Expression levels of lncRNA CCAT2 in CRC, adjacent non-tumor and healthy colon mucosa tissues were detected by quantitative polymerase chain reaction. The disease-free survival and overall survival rates were evaluated using the Kaplan-Meier method, and multivariate analysis was performed using Cox proportional hazard analysis. The expression level of lncRNA CCAT2 in CRC tissues was increased significantly compared with adjacent normal tissues or non-cancerous tissues. CCAT2 expression was observed to be progressively increased between tumor-node-metastasis (TNM) stages I and IV. A high level of CCAT2 expression was revealed to be associated with poor cell differentiation, deeper tumor infiltration, lymph node metastasis, distance metastasis, vascular invasion and advanced TNM stage. Compared with patients with low levels of CCAT2 expression, patients with high levels of CCAT2 expression had shorter disease-free survival and overall survival times. Multivariate analyses indicated that high CCAT2 expression was an independent poor prognostic factor. Therefore, increased lncRNA CCAT2 expression maybe a potential diagnostic biomarker for CRC, and an independent predictor of prognosis in patients with CRC.

  12. Absceso de pared abdominal por tumor maligno de colon transverso.

    OpenAIRE

    Morales Polanco, Sergio; Díaz Rosales, Juan de Dios; Arenas Valles, Jorge

    2017-01-01

    Introduction: Colon cancer is one of the most frequent and mortal digestive tumors. Complications of this disease could be several and in a few cases, could be rare and infrequent. This article present a case of patient with an abdominal wall abscess due to a malignant transverse colonic tumor. Clinic presentation: Male 56 years-old patient with sepsis and a mass in left superior quadrant on abdomen. The patient was underwent to exploratory laparotomy and findings were a large tumor in transv...

  13. [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.

  14. 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.

  15. 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.

  16. Resection of pulmonary metastases from colon and rectal cancer: factors to predict survival differ regarding to the origin of the primary tumor.

    Science.gov (United States)

    Meimarakis, G; Spelsberg, F; Angele, M; Preissler, G; Fertmann, J; Crispin, A; Reu, S; Kalaitzis, N; Stemmler, M; Giessen, C; Heinemann, V; Stintzing, S; Hatz, R; Winter, H

    2014-08-01

    The purpose of the present study was to determine differences in prognostic factors for survival of patients with pulmonary metastases resected in curative intent from colon or rectum cancer. Between 1980 and 2006, prognostic factors after resection of pulmonary metastases in 171 patients with primary rectum or colon tumor were evaluated. Survival of patients after surgical metastasectomy was compared with that of patients receiving standard chemotherapy by matched-pair analysis. Median survival after pulmonary resection was 35.2 months (confidence interval 27.3-43.2). One-, 3-, and 5-year survival for patients following R0 resection was 88.8, 52.1, and 32.9 % respectively. Complete metastasectomy (R0), UICC stage of the primary tumor, pleural infiltration, and hilar or mediastinal lymph node metastases are independent prognostic factors for survival. Matched-pair analysis confirmed that pulmonary metastasectomy significantly improved survival. Although no difference in survival for patients with pulmonary metastases from lower rectal compared to upper rectal or colon cancer was observed, factors to predict survival are different for patients with lower and middle rectal cancer (R0, mediastinal and/or hilar lymph nodes, gender, UICC stage) compared with patients with upper rectal or colon cancer (R0, number of metastases). Our results indicate that distinct prognostic factors exist for patients with pulmonary metastases from lower rectal compared with upper rectal or colon cancer. This supports the notion that colorectal cancer should not be considered as a single-tumor entity. Metastasectomy, especially after complete resection resulted in a dramatic improvement of survival compared with patients treated with chemotherapy alone.

  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. [Using cancer case identification algorithms in medico-administrative databases: Literature review and first results from the REDSIAM Tumors group based on breast, colon, and lung cancer].

    Science.gov (United States)

    Bousquet, P-J; Caillet, P; Coeuret-Pellicer, M; Goulard, H; Kudjawu, Y C; Le Bihan, C; Lecuyer, A I; Séguret, F

    2017-10-01

    The development and use of healthcare databases accentuates the need for dedicated tools, including validated selection algorithms of cancer diseased patients. As part of the development of the French National Health Insurance System data network REDSIAM, the tumor taskforce established an inventory of national and internal published algorithms in the field of cancer. This work aims to facilitate the choice of a best-suited algorithm. A non-systematic literature search was conducted for various cancers. Results are presented for lung, breast, colon, and rectum. Medline, Scopus, the French Database in Public Health, Google Scholar, and the summaries of the main French journals in oncology and public health were searched for publications until August 2016. An extraction grid adapted to oncology was constructed and used for the extraction process. A total of 18 publications were selected for lung cancer, 18 for breast cancer, and 12 for colorectal cancer. Validation studies of algorithms are scarce. When information is available, the performance and choice of an algorithm are dependent on the context, purpose, and location of the planned study. Accounting for cancer disease specificity, the proposed extraction chart is more detailed than the generic chart developed for other REDSIAM taskforces, but remains easily usable in practice. This study illustrates the complexity of cancer detection through sole reliance on healthcare databases and the lack of validated algorithms specifically designed for this purpose. Studies that standardize and facilitate validation of these algorithms should be developed and promoted. Copyright © 2017. Published by Elsevier Masson SAS.

  19. Neoadjuvant chemotherapy in locally advanced colon cancer

    DEFF Research Database (Denmark)

    Jakobsen, Anders; Andersen, Fahimeh; Fischer, Anders

    2015-01-01

    BACKGROUND: Neoadjuvant chemotherapy has proven valuable in several tumors, but it has not been elucidated in colon cancer. The present phase II trial addressed the issue in high-risk patients selected by computed tomography (CT) scan. MATERIAL AND METHODS: Patients with resectable colon cancer...... 32% (p = 0.005) translating into a three-year DFS of 94% versus 63% (p = 0.005). CONCLUSION: Neoadjuvant chemotherapy in colon cancer is feasible and the results suggest that a major part of the patients can be spared adjuvant chemotherapy. Validation in a randomized trial is warranted....

  20. Genistein inhibits proliferation of colon cancer cells by attenuating a negative effect of epidermal growth factor on tumor suppressor FOXO3 activity

    International Nuclear Information System (INIS)

    Qi, Wentao; Weber, Christopher R; Wasland, Kaarin; Savkovic, Suzana D

    2011-01-01

    Soy consumption is associated with a lower incidence of colon cancer which is believed to be mediated by one of its of components, genistein. Genistein may inhibit cancer progression by inducing apoptosis or inhibiting proliferation, but mechanisms are not well understood. Epidermal growth factor (EGF)-induced proliferation of colon cancer cells plays an important role in colon cancer progression and is mediated by loss of tumor suppressor FOXO3 activity. The aim of this study was to assess if genistein exerts anti-proliferative properties by attenuating the negative effect of EGF on FOXO3 activity. The effect of genistein on proliferation stimulated by EGF-mediated loss of FOXO3 was examined in human colonic cancer HT-29 cells. EGF-induced FOXO3 phosphorylation and translocation were assessed in the presence of genistein. EGF-mediated loss of FOXO3 interactions with p53 (co-immunoprecipitation) and promoter of p27kip1 (ChIP assay) were examined in presence of genistein in cells with mutated p53 (HT-29) and wild type p53 (HCT116). Silencing of p53 determined activity of FOXO3 when it is bound to p53. Genistein inhibited EGF-induced proliferation, while favoring dephosphorylation and nuclear retention of FOXO3 (active state) in colon cancer cells. Upstream of FOXO3, genistein acts via the PI3K/Akt pathway to inhibit EGF-stimulated FOXO3 phosphorylation (i.e. favors active state). Downstream, EGF-induced disassociation of FOXO3 from mutated tumor suppressor p53, but not wild type p53, is inhibited by genistein favoring FOXO3-p53(mut) interactions with the promoter of the cell cycle inhibitor p27kip1 in colon cancer cells. Thus, the FOXO3-p53(mut) complex leads to elevated p27kip1 expression and promotes cell cycle arrest. These novel anti-proliferative mechanisms of genistein suggest a possible role of combining genistein with other chemoreceptive agents for the treatment of colon cancer

  1. 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.

  2. Middle-preserving pancreatectomy for advanced transverse colon cancer invading the duodenun and non-functioning endocrine tumor in the pancreatic tail.

    Science.gov (United States)

    Noda, Hiroshi; Kato, Takaharu; Kamiyama, Hidenori; Toyama, Nobuyuki; Konishi, Fumio

    2011-02-01

    A 73-year-old female was referred to our hospital with a diagnosis of advanced transverse colon cancer with severe anemia and body weight loss. Preoperative evaluations, including colonoscopy, gastroduodenoscopy, and computed tomography, revealed not only a transverse colon cancer massively invading the duodenum, but also a non-functioning endocrine tumor in the pancreatic tail. We performed middle-preserving pancreatectomy (MPP) with right hemicolectomy for these tumors with a curative intent. After the resection, about 6 cm of the body of the pancreas was preserved, and signs of diabetes mellitus have not appeared. The postoperative course was complicated by a grade B pancreatic fistula, but this was successfully treated with conservative management. After a 33-day hospital stay, the patient returned to daily life without signs of pancreatic exocrine insufficiency. Although the long-term follow-up of the patient is indispensable, in this case, MPP might be able to lead to the curative resection of transverse colon cancer massively invading the duodenum and non-functioning endocrine tumor in the pancreatic tail with preservation of pancreatic function.

  3. Studies on colon cancer prone rats. Spontaneous small intestinal carcinomas and tumor induction of small intestine by x-irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Maeura, Y [Osaka Univ. (Japan). Faculty of Medicine

    1979-12-01

    Histological investigation was carried out for Wister-Furth (WF) rats, prone to cancers of the colon and small intestine. Gastric cancer was observed in about 1/4 of the rats with the cancers of the colon and the small intestine, indicating that these rats could be the model animals of the cancer family syndrome with multi-cancers in the gastrointestinal tracts. The small intestine of WF and SD (Sprague-Dowley) rats as exposed to 1000, 2 x 1000, 1500, and 2000 R of x-rays at a dose rate of 157 R/min. In each group the stomach, small intestine, cecum, and colon were histologically investigated, immediately and 15, 25, and 35 weeks after irradiation. The rates of cancer occurrence in 15, 25, and 35 weeks were 5/17, 9/19, and 9/14 for WF strain and 1/8, 2/7, and 2/8 for SD strain, respectively. The rate increased with the increment of the days after irradiation. It was suggested that the atypical epithelium of the gastrointestinal tracts induced the cancer in high rates when some trigger was added.

  4. KRAS Genotype Correlates with Proteasome Inhibitor Ixazomib Activity in Preclinical In Vivo Models of Colon and Non-Small Cell Lung Cancer: Potential Role of Tumor Metabolism.

    Directory of Open Access Journals (Sweden)

    Nibedita Chattopadhyay

    Full Text Available In non-clinical studies, the proteasome inhibitor ixazomib inhibits cell growth in a broad panel of solid tumor cell lines in vitro. In contrast, antitumor activity in xenograft tumors is model-dependent, with some solid tumors showing no response to ixazomib. In this study we examined factors responsible for ixazomib sensitivity or resistance using mouse xenograft models. A survey of 14 non-small cell lung cancer (NSCLC and 6 colon xenografts showed a striking relationship between ixazomib activity and KRAS genotype; tumors with wild-type (WT KRAS were more sensitive to ixazomib than tumors harboring KRAS activating mutations. To confirm the association between KRAS genotype and ixazomib sensitivity, we used SW48 isogenic colon cancer cell lines. Either KRAS-G13D or KRAS-G12V mutations were introduced into KRAS-WT SW48 cells to generate cells that stably express activated KRAS. SW48 KRAS WT tumors, but neither SW48-KRAS-G13D tumors nor SW48-KRAS-G12V tumors, were sensitive to ixazomib in vivo. Since activated KRAS is known to be associated with metabolic reprogramming, we compared metabolite profiling of SW48-WT and SW48-KRAS-G13D tumors treated with or without ixazomib. Prior to treatment there were significant metabolic differences between SW48 WT and SW48-KRAS-G13D tumors, reflecting higher oxidative stress and glucose utilization in the KRAS-G13D tumors. Ixazomib treatment resulted in significant metabolic regulation, and some of these changes were specific to KRAS WT tumors. Depletion of free amino acid pools and activation of GCN2-eIF2α-pathways were observed both in tumor types. However, changes in lipid beta oxidation were observed in only the KRAS WT tumors. The non-clinical data presented here show a correlation between KRAS genotype and ixazomib sensitivity in NSCLC and colon xenografts and provide new evidence of regulation of key metabolic pathways by proteasome inhibition.

  5. KRAS Genotype Correlates with Proteasome Inhibitor Ixazomib Activity in Preclinical In Vivo Models of Colon and Non-Small Cell Lung Cancer: Potential Role of Tumor Metabolism.

    Science.gov (United States)

    Chattopadhyay, Nibedita; Berger, Allison J; Koenig, Erik; Bannerman, Bret; Garnsey, James; Bernard, Hugues; Hales, Paul; Maldonado Lopez, Angel; Yang, Yu; Donelan, Jill; Jordan, Kristen; Tirrell, Stephen; Stringer, Bradley; Xia, Cindy; Hather, Greg; Galvin, Katherine; Manfredi, Mark; Rhodes, Nelson; Amidon, Ben

    2015-01-01

    In non-clinical studies, the proteasome inhibitor ixazomib inhibits cell growth in a broad panel of solid tumor cell lines in vitro. In contrast, antitumor activity in xenograft tumors is model-dependent, with some solid tumors showing no response to ixazomib. In this study we examined factors responsible for ixazomib sensitivity or resistance using mouse xenograft models. A survey of 14 non-small cell lung cancer (NSCLC) and 6 colon xenografts showed a striking relationship between ixazomib activity and KRAS genotype; tumors with wild-type (WT) KRAS were more sensitive to ixazomib than tumors harboring KRAS activating mutations. To confirm the association between KRAS genotype and ixazomib sensitivity, we used SW48 isogenic colon cancer cell lines. Either KRAS-G13D or KRAS-G12V mutations were introduced into KRAS-WT SW48 cells to generate cells that stably express activated KRAS. SW48 KRAS WT tumors, but neither SW48-KRAS-G13D tumors nor SW48-KRAS-G12V tumors, were sensitive to ixazomib in vivo. Since activated KRAS is known to be associated with metabolic reprogramming, we compared metabolite profiling of SW48-WT and SW48-KRAS-G13D tumors treated with or without ixazomib. Prior to treatment there were significant metabolic differences between SW48 WT and SW48-KRAS-G13D tumors, reflecting higher oxidative stress and glucose utilization in the KRAS-G13D tumors. Ixazomib treatment resulted in significant metabolic regulation, and some of these changes were specific to KRAS WT tumors. Depletion of free amino acid pools and activation of GCN2-eIF2α-pathways were observed both in tumor types. However, changes in lipid beta oxidation were observed in only the KRAS WT tumors. The non-clinical data presented here show a correlation between KRAS genotype and ixazomib sensitivity in NSCLC and colon xenografts and provide new evidence of regulation of key metabolic pathways by proteasome inhibition.

  6. Betulinic acid inhibits colon cancer cell and tumor growth and induces proteasome-dependent and -independent downregulation of specificity proteins (Sp transcription factors

    Directory of Open Access Journals (Sweden)

    Pathi Satya

    2011-08-01

    Full Text Available Abstract Background Betulinic acid (BA inhibits growth of several cancer cell lines and tumors and the effects of BA have been attributed to its mitochondriotoxicity and inhibition of multiple pro-oncogenic factors. Previous studies show that BA induces proteasome-dependent degradation of specificity protein (Sp transcription factors Sp1, Sp3 and Sp4 in prostate cancer cells and this study focused on the mechanism of action of BA in colon cancer cells. Methods The effects of BA on colon cancer cell proliferation and apoptosis and tumor growth in vivo were determined using standardized assays. The effects of BA on Sp proteins and Sp-regulated gene products were analyzed by western blots, and real time PCR was used to determine microRNA-27a (miR-27a and ZBTB10 mRNA expression. Results BA inhibited growth and induced apoptosis in RKO and SW480 colon cancer cells and inhibited tumor growth in athymic nude mice bearing RKO cells as xenograft. BA also decreased expression of Sp1, Sp3 and Sp4 transcription factors which are overexpressed in colon cancer cells and decreased levels of several Sp-regulated genes including survivin, vascular endothelial growth factor, p65 sub-unit of NFκB, epidermal growth factor receptor, cyclin D1, and pituitary tumor transforming gene-1. The mechanism of action of BA was dependent on cell context, since BA induced proteasome-dependent and proteasome-independent downregulation of Sp1, Sp3 and Sp4 in SW480 and RKO cells, respectively. In RKO cells, the mechanism of BA-induced repression of Sp1, Sp3 and Sp4 was due to induction of reactive oxygen species (ROS, ROS-mediated repression of microRNA-27a, and induction of the Sp repressor gene ZBTB10. Conclusions These results suggest that the anticancer activity of BA in colon cancer cells is due, in part, to downregulation of Sp1, Sp3 and Sp4 transcription factors; however, the mechanism of this response is cell context-dependent.

  7. Betulinic acid inhibits colon cancer cell and tumor growth and induces proteasome-dependent and -independent downregulation of specificity proteins (Sp) transcription factors

    International Nuclear Information System (INIS)

    Chintharlapalli, Sudhakar; Papineni, Sabitha; Lei, Ping; Pathi, Satya; Safe, Stephen

    2011-01-01

    Betulinic acid (BA) inhibits growth of several cancer cell lines and tumors and the effects of BA have been attributed to its mitochondriotoxicity and inhibition of multiple pro-oncogenic factors. Previous studies show that BA induces proteasome-dependent degradation of specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 in prostate cancer cells and this study focused on the mechanism of action of BA in colon cancer cells. The effects of BA on colon cancer cell proliferation and apoptosis and tumor growth in vivo were determined using standardized assays. The effects of BA on Sp proteins and Sp-regulated gene products were analyzed by western blots, and real time PCR was used to determine microRNA-27a (miR-27a) and ZBTB10 mRNA expression. BA inhibited growth and induced apoptosis in RKO and SW480 colon cancer cells and inhibited tumor growth in athymic nude mice bearing RKO cells as xenograft. BA also decreased expression of Sp1, Sp3 and Sp4 transcription factors which are overexpressed in colon cancer cells and decreased levels of several Sp-regulated genes including survivin, vascular endothelial growth factor, p65 sub-unit of NFκB, epidermal growth factor receptor, cyclin D1, and pituitary tumor transforming gene-1. The mechanism of action of BA was dependent on cell context, since BA induced proteasome-dependent and proteasome-independent downregulation of Sp1, Sp3 and Sp4 in SW480 and RKO cells, respectively. In RKO cells, the mechanism of BA-induced repression of Sp1, Sp3 and Sp4 was due to induction of reactive oxygen species (ROS), ROS-mediated repression of microRNA-27a, and induction of the Sp repressor gene ZBTB10. These results suggest that the anticancer activity of BA in colon cancer cells is due, in part, to downregulation of Sp1, Sp3 and Sp4 transcription factors; however, the mechanism of this response is cell context-dependent

  8. Concomitant consumption of lycopene and fish oil inhibits tumor growth and progression in a mouse xenograft model of colon cancer

    Science.gov (United States)

    Our previous report showed that concomitant supplementation of lycopene and eicosa-pentaenoic acid synergistically inhibited the proliferation of human colon cancer HT-29 cells in vitro. To validate our findings, the present study investigated whether consumption of lycopene and fish oil would help ...

  9. CRH promotes human colon cancer cell proliferation via IL-6/JAK2/STAT3 signaling pathway and VEGF-induced tumor angiogenesis.

    Science.gov (United States)

    Fang, Xianjun; Hong, Yali; Dai, Li; Qian, Yuanyuan; Zhu, Chao; Wu, Biao; Li, Shengnan

    2017-11-01

    Corticotrophin-releasing hormone (CRH) has been demonstrated to participate in various diseases. Our previous study showed that its receptor CRHR1 mediated the development of colitis-associated cancer in mouse model. However, the detailed mechanisms remain unclear. In this study, we explored the oncogenetic role of CRH/CRHR1 signaling in colon cancer cells. Cell proliferation and colony formation assays revealed that CRH contributed to cell proliferation. Moreover, tube formation assay showed that CRH-treated colon cancer cell supernatant significantly promoted tube formation of human umbilical vein endothelial cells (HUVECs). And these effects could be reversed by the CRHR1 specific antagonist Antalarmin. Further investigation showed that CRH significantly upregulated the expressions of interlukin-6 (IL-6) and vascular endothelial growth factor (VEGF) through activating nuclear factor-kappa B (NF-κB). The CRH-induced IL-6 promoted phosphorylation of janus kinase 2 (JAK2) and signal transducers and activators of transcription 3 (STAT3). STAT3 inhibition by Stattic significantly inhibited the CRH-induced cell proliferation. In addition, silence of VEGF resulted in declined tube formation induced by CRH. Taken together, CRH/CRHR1 signaling promoted human colon cancer cell proliferation via NF-κB/IL-6/JAK2/STAT3 signaling pathway and tumor angiogenesis via NF-κB/VEGF signaling pathway. Our results provide evidence to support a critical role for the CRH/CRHR1 signaling in colon cancer progression and suggest its potential utility as a new therapeutic target for colon cancer. © 2017 Wiley Periodicals, Inc.

  10. 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,

  11. 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.

  12. The intraportal injection model: A practical animal model for hepatic metastases and tumor cell dissemination in human colon cancer

    International Nuclear Information System (INIS)

    Thalheimer, Andreas; Waaga-Gasser, Ana M; Otto, Christoph; Bueter, Marco; Illert, Bertram; Gattenlohner, Stefan; Gasser, Martin; Meyer, Detlef; Fein, Martin; Germer, Christoph T

    2009-01-01

    The development of new therapeutic strategies for treatment of metastasized colorectal carcinoma requires biologically relevant and adequate animal models that generate both reproducible metastasis and the dissemination of tumor cells in the form of so-called minimal residual disease (MRD), an expression of the systemic character of neoplastic disease. We injected immunoincompetent nude mice intraportally with different numbers (1 × 10 5 , 1 × 10 6 and 5 × 10 6 cells) of the human colon carcinoma cell lines HT-29 and SW-620 and investigated by histological studies and CK-20 RT-PCR the occurrence of hematogenous metastases and the dissemination of human tumor cells in bone marrow. Only the injection of 1 × 10 6 cells of each colon carcinoma cell line produced acceptable perioperative mortality with reproducible induction of hepatic metastases in up to 89% of all animals. The injection of 1 × 10 6 cells also generated tumor cell dissemination in the bone marrow in up to 63% of animals with hepatic metastases. The present intraportal injection model in immunoincompetent nude mice represents a biologically relevant and adequate animal model for the induction of both reproducible hepatic metastasis and tumor cell dissemination in the bone marrow as a sign of MRD

  13. A multifactorial likelihood model for MMR gene variant classification incorporating probabilities based on sequence bioinformatics and tumor characteristics: a report from the Colon Cancer Family Registry.

    Science.gov (United States)

    Thompson, Bryony A; Goldgar, David E; Paterson, Carol; Clendenning, Mark; Walters, Rhiannon; Arnold, Sven; Parsons, Michael T; Michael D, Walsh; Gallinger, Steven; Haile, Robert W; Hopper, John L; Jenkins, Mark A; Lemarchand, Loic; Lindor, Noralane M; Newcomb, Polly A; Thibodeau, Stephen N; Young, Joanne P; Buchanan, Daniel D; Tavtigian, Sean V; Spurdle, Amanda B

    2013-01-01

    Mismatch repair (MMR) gene sequence variants of uncertain clinical significance are often identified in suspected Lynch syndrome families, and this constitutes a challenge for both researchers and clinicians. Multifactorial likelihood model approaches provide a quantitative measure of MMR variant pathogenicity, but first require input of likelihood ratios (LRs) for different MMR variation-associated characteristics from appropriate, well-characterized reference datasets. Microsatellite instability (MSI) and somatic BRAF tumor data for unselected colorectal cancer probands of known pathogenic variant status were used to derive LRs for tumor characteristics using the Colon Cancer Family Registry (CFR) resource. These tumor LRs were combined with variant segregation within families, and estimates of prior probability of pathogenicity based on sequence conservation and position, to analyze 44 unclassified variants identified initially in Australasian Colon CFR families. In addition, in vitro splicing analyses were conducted on the subset of variants based on bioinformatic splicing predictions. The LR in favor of pathogenicity was estimated to be ~12-fold for a colorectal tumor with a BRAF mutation-negative MSI-H phenotype. For 31 of the 44 variants, the posterior probabilities of pathogenicity were such that altered clinical management would be indicated. Our findings provide a working multifactorial likelihood model for classification that carefully considers mode of ascertainment for gene testing. © 2012 Wiley Periodicals, Inc.

  14. Extravirgin olive oil up-regulates CB₁ tumor suppressor gene in human colon cancer cells and in rat colon via epigenetic mechanisms.

    Science.gov (United States)

    Di Francesco, Andrea; Falconi, Anastasia; Di Germanio, Clara; Micioni Di Bonaventura, Maria Vittoria; Costa, Antonio; Caramuta, Stefano; Del Carlo, Michele; Compagnone, Dario; Dainese, Enrico; Cifani, Carlo; Maccarrone, Mauro; D'Addario, Claudio

    2015-03-01

    Extravirgin olive oil (EVOO) represents the typical lipid source of the Mediterranean diet, an eating habit pattern that has been associated with a significant reduction of cancer risk. Diet is the more studied environmental factor in epigenetics, and many evidences suggest dysregulation of epigenetic pathways in cancer. The aim of our study was to investigate the effects of EVOO and its phenolic compounds on endocannabinoid system (ECS) gene expression via epigenetic regulation in both human colon cancer cells (Caco-2) and rats exposed to short- and long-term dietary EVOO. We observed a selective and transient up-regulation of CNR1 gene - encoding for type 1 cannabinoid receptor (CB₁) - that was evoked by exposure of Caco-2 cells to EVOO (100 ppm), its phenolic extracts (OPE, 50 μM) or authentic hydroxytyrosol (HT, 50 μM) for 24 h. None of the other major elements of the ECS (i.e., CB₂; GPR55 and TRPV1 receptors; and NAPE-PLD, DAGL, FAAH and MAGL enzymes) was affected at any time point. The stimulatory effect of OPE and HT on CB₁ expression was inversely correlated to DNA methylation at CNR1 promoter and was associated with reduced proliferation of Caco-2 cells. Interestingly, CNR1 gene was less expressed in Caco-2 cells when compared to normal colon mucosa cells, and again this effect was associated with higher level of DNA methylation at CNR1. Moreover, in agreement with the in vitro studies, we also observed a remarkable (~4-fold) and selective increase in CB₁ expression in the colon of rats receiving dietary EVOO supplementation for 10 days. Consistently, CpG methylation of rat Cnr1 promoter, miR23a and miR-301a, previously shown to be involved in the pathogenesis of colorectal cancer and predicted to target CB₁ mRNA, was reduced after EVOO administration down to ~50% of controls. Taken together, our findings demonstrating CB₁ gene expression modulation by EVOO or its phenolic compounds via epigenetic mechanism, both in vitro and in vivo, may

  15. "Cancer tumor".

    Science.gov (United States)

    Bronshtehn, V. A.

    The title is a phrase borrowed from a speech by a Leningrad pressman, V. E. Lvov, who called upon those attending a theoretical conference on ideological issues in astronomy held by the Leningrad Branch of the All-Union Astronomic and Geodetic Society (13 - 4 December 1948), "to make a more radical emphasis on the negative role of relativistic cosmology which is a cancer tumor disintegrating the contemporary astronomy theory, and a major ideological enemy of a materialist astronomy".

  16. Protein-bound polysaccharide from Phellinus linteus inhibits tumor growth, invasion, and angiogenesis and alters Wnt/β-catenin in SW480 human colon cancer cells

    Directory of Open Access Journals (Sweden)

    Park Hae-Duck

    2011-07-01

    Full Text Available Abstract Background Polysaccharides extracted from the Phellinus linteus (PL mushroom are known to possess anti-tumor effects. However, the molecular mechanisms responsible for the anti-tumor properties of PL remain to be explored. Experiments were carried out to unravel the anticancer effects of PL. Methods The anti-cancer effects of PL were examined in SW480 colon cancer cells by evaluating cell proliferation, invasion and matrix metallo-proteinase (MMP activity. The anti-angiogenic effects of PL were examined by assessing human umbilical vein endothelial cell (HUVEC proliferation and capillary tube formation. The in vivo effect of PL was evaluated in an athymic nude mouse SW480 tumor engraft model. Results PL (125-1000 μg/mL significantly inhibited cell proliferation and decreased β-catenin expression in SW480 cells. Expression of cyclin D1, one of the downstream-regulated genes of β-catenin, and T-cell factor/lymphocyte enhancer binding factor (TCF/LEF transcription activity were also significantly reduced by PL treatment. PL inhibited in vitro invasion and motility as well as the activity of MMP-9. In addition, PL treatment inhibited HUVEC proliferation and capillary tube formation. Tumor growth of SW480 cells implanted into nude mice was significantly decreased as a consequence of PL treatment, and tumor tissues from treated animals showed an increase in the apoptotic index and a decrease in β-catenin expression. Moreover, the proliferation index and microvessel density were significantly decreased. Conclusions These data suggest that PL suppresses tumor growth, invasion, and angiogenesis through the inhibition of Wnt/β-catenin signaling in certain colon cancer cells.

  17. Occlusive stenosis – atypical presentation of right colon cancer

    Directory of Open Access Journals (Sweden)

    Petrişor Banu

    2018-05-01

    Full Text Available Colorectal cancers are one of the most frequent malignancies worldwide. Significant differences are described in relation to the location of tumors within the colon. Thus, between right and left colon cancer there are epidemiological, clinical, genetic, evolutionary and prognostic differences. Considering these premises, right and left colon cancers can be seen as distinct pathological entities. In right colon cancer the initial phases are often asymptomatic and the presence of symptoms is in relation to advanced phases and complications. We report the case of a 64-year-old man with no significant medical history who was admitted and operated as an emergency for stenotic and perforated tumor of the right colon. Operative exploration revealed distended small bowel loops and caecum up to the ascending colon where a stenosing tumor is found. The tumor extends to a small bowel loop and also exhibit a perforation. Right hemicolectomy was performed, with favorable postoperative evolution and discharge on 7th day.

  18. 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

  19. 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.

  20. Emergency management of acute colonic cancer obstruction.

    Science.gov (United States)

    Gainant, A

    2012-02-01

    Emergency management of obstructing colonic cancer depends on both tumor location and stage, general condition of the patient and surgeon's experience. Right sided or transverse colon obstructing cancers are usually treated by right hemicolectomy-extended if necessary to the transverse colon-with primary anastomosis. For left-sided obstructing cancer, in patients with low surgical risk, primary resection and anastomosis associated with on-table irrigation or manual decompression can be performed. It prevents the confection of a loop colostomy but presents the risk of anastomotic leakage. Subtotal or total colectomy allows the surgeon to encompass distended and fecal-loaded colon, and to perform one-stage resection and anastomosis. Its disadvantage is an increased daily frequency of stools. It must be performed only in cases of diastatic colon perforation or synchronous right colonic cancer. In patients with high surgical risk, Hartmann procedure must be preferred. It allows the treatment of both obstruction and cancer, and prevents anastomotic leakage but needs a second operation to reverse the colostomy. Colonic stenting is clinically successful in up to 90% in specialized groups. It is used as palliation in patients with disseminated disease or bridge to surgery in the others. If stent insertion is not possible, loop colostomy is still indicated in patients at high surgical risk. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  1. Lebein, a snake venom disintegrin, suppresses human colon cancer cells proliferation and tumor-induced angiogenesis through cell cycle arrest, apoptosis induction and inhibition of VEGF expression.

    Science.gov (United States)

    Zakraoui, Ons; Marcinkiewicz, Cezary; Aloui, Zohra; Othman, Houcemeddine; Grépin, Renaud; Haoues, Meriam; Essafi, Makram; Srairi-Abid, Najet; Gasmi, Ammar; Karoui, Habib; Pagès, Gilles; Essafi-Benkhadir, Khadija

    2017-01-01

    Lebein, is an heterodimeric disintegrin isolated from Macrovipera lebetina snake venom that was previously characterized as an inhibitor of ADP-induced platelet aggregation. In this study, we investigated the effect of Lebein on the p53-dependent growth of human colon adenocarcinoma cell lines. We found that Lebein significantly inhibited LS174 (p53wt), HCT116 (p53wt), and HT29 (p53mut) colon cancer cell viability by inducing cell cycle arrest through the modulation of expression levels of the tumor suppression factor p53, cell cycle regulating proteins cyclin D1, CDK2, CDK4, retinoblastoma (Rb), CDK1, and cyclin-dependent kinase inhibitors p21 and p27. Interestingly, Lebein-induced apoptosis of colon cancer cells was dependent on their p53 status. Thus, in LS174 cells, cell death was associated with PARP cleavage and the activation of caspases 3 and 8 while in HCT116 cells, Lebein induced caspase-independent apoptosis through increased expression of apoptosis inducing factor (AIF). In LS174 cells, Lebein triggers the activation of the MAPK ERK1/2 pathway through induction of reactive oxygen species (ROS). It also decreased cell adhesion and migration to fibronectin through down regulation of α5β1 integrin. Moreover, Lebein significantly reduced the expression of two angiogenesis stimulators, Vascular Endothelial Growth Factor (VEGF) and Neuropilin 1 (NRP1). It inhibited the VEGF-induced neovascularization process in the quail embryonic CAM system and blocked the development of human colon adenocarcinoma in nude mice. Overall, our work indicates that Lebein may be useful to design a new therapy against colon cancer. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  2. Procedural difficulty differences according to tumor location do not compromise the clinical outcome of laparoscopic complete mesocolic excision for colon cancer: a retrospective analysis.

    Science.gov (United States)

    Kim, Min Ki; Lee, In Kyu; Kye, Bong-Hyeon; Kim, Jun-Gi

    2017-09-08

    Laparoscopic colectomy procedures and their corresponding difficulty levels may vary depending on the tumor location within the colon, and a laparoscopic complete mesocolic excision (CME) with central vascular ligation (CVL) would require more proficiency than a conventional laparoscopic colectomy. We aimed to report our laparoscopic CME with CVL data and to investigate the clinical outcome differences of laparoscopic CME with CVL by various tumor sub-site locations. Prospectively collected clinical data of consecutive patients who received laparoscopic colectomy for primary colon cancer between April 1995 and December 2010 from single surgeon were retrospectively reviewed. All of the included surgery was performed on the basis of CME with CVL principle with no-touch isolation technique. Data were analyzed and compared among three groups; patients who received right or extended right hemicolectomy (group A, n = 142), transverse colectomy or left or extended left hemicolectomy (group B, n = 59), and sigmoidectomy or anterior resection (group C, n = 210). Female patients were more common in group A (53.5% vs. 37.3% vs. 39.5%, p = 0.020). Other baseline characteristics were comparable. Operative time was shorter in group C than the other groups (309.0 ± 74.7 vs. 324.3 ± 89.1 vs. 280.1 ± 93.1 min, p = 0.000). There was no significant difference among groups in perioperative complication and patient recovery. Five-year overall survival, disease-free survival and local recurrence rate showed no difference for a median follow up period of 73 (1-120) months. In conclusion, laparoscopic tumor-specific CME and CVL for colon cancer can be performed with comparable short- and long-term outcomes regardless of tumor sub-site location except for the operative time.

  3. [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.

  4. Accuracy of colonoscopy in localizing colonic cancer.

    Science.gov (United States)

    Stanciu, C; Trifan, Anca; Khder, Saad Alla

    2007-01-01

    It is important to establish the precise localization of colonic cancer preoperatively; while colonoscopy is regarded as the diagnostic gold standard for colorectal cancer, its ability to localize the tumor is less reliable. To define the accuracy of colonoscopy in identifying the location of colonic cancer. All of the patients who had a colorectal cancer diagnosed by colonoscopy at the Institute of Gastroenterology and Hepatology, Iaşi and subsequently received a surgical intervention at three teaching hospitals in Iaşi, between January 2001 and December 2005, were included in this study. Endoscopic records and operative notes were carefully reviewed, and tumor localization was recorded. There were 161 patients (89 men, 72 women, aged 61.3 +/- 12.8 years) who underwent conventional surgery for colon cancer detected by colonoscopy during the study period. Twenty-two patients (13.66%) had erroneous colonoscopic localization of the tumors. The overall accuracy of preoperative colonoscopic localization was 87.58%. Colonoscopy is an accurate, reliable method for locating colon cancer, although additional techniques (i.e., endoscopic tattooing) should be performed at least for small lesions.

  5. Inhibition of colon cancer growth by methylselenocysteine-induced angiogenic chemomodulation is influenced by histologic characteristics of the tumor.

    Science.gov (United States)

    Bhattacharya, Arup; Tóth, Károly; Sen, Arindam; Seshadri, Mukund; Cao, Shousong; Durrani, Farukh A; Faber, Erik; Repasky, Elizabeth A; Rustum, Youcef M

    2009-07-01

    Despite an armamentarium that is wide in range, scope of action, and target, chemotherapy has limited success in colorectal cancer (CRC). Novel approaches are needed to overcome tumor barriers to chemotherapy that includes an abnormal tumor vasculature constituting a poor drug delivery system. We have previously shown that 5-methylselenocysteine (MSC) enhances therapeutic efficacy of irinotecan in various human tumor xenografts. We have recently demonstrated that MSC through vascular normalization leads to better tumor vascular function in vivo. In this study, we examined the role of MSC on tumor vasculature, interstitial fluid pressure (IFP) and drug delivery in 2 histologically distinct CRC xenografts, HCT-8 (uniformly poorly differentiated) and HT-29 (moderately differentiated tumor with avascular glandular regions). The presence of specific histologic structures as a barrier to therapy in these xenografts and their clinical relevance was studied using tissue microarray of human surgical samples of CRC. MSC led to a significant tumor growth inhibition, a reduced microvessel density, and a more normalized vasculature in both colorectal xenografts. While IFP was found to be significantly improved in HCT-8, an improved intratumoral doxorubicin delivery seen in both xenografts could explain the observed increase in therapeutic efficacy. Differentiated, glandular, avascular and hypoxic regions that contribute to tumor heterogeneity in HT-29 were also evident in the majority of surgical samples of CRC. Such regions constitute a physical barrier to chemotherapy and can confer drug resistance. Our results indicate that MSC could enhance chemotherapeutic efficacy in human CRC, especially in CRC with few or no hypoxic regions.

  6. An Immune-Modulating Diet in Combination with Chemotherapy Prevents Cancer Cachexia by Attenuating Systemic Inflammation in Colon 26 Tumor-Bearing Mice.

    Science.gov (United States)

    Nakamura, Kentaro; Sasayama, Akina; Takahashi, Takeshi; Yamaji, Taketo

    2015-01-01

    Cancer cachexia is characterized by muscle wasting caused partly by systemic inflammation. We previously demonstrated an immune-modulating diet (IMD), an enteral diet enriched with immunonutrition and whey-hydrolyzed peptides, to have antiinflammatory effects in some experimental models. Here, we investigated whether the IMD in combination with chemotherapy could prevent cancer cachexia in colon 26 tumor-bearing mice. Forty tumor-bearing mice were randomized into 5 groups: tumor-bearing control (TB), low dose 5-fluorouracil (5-FU) and standard diet (LF/ST), low dose 5-FU and IMD (LF/IMD), high dose 5-FU and standard diet (HF/ST) and high dose 5-FU and IMD (HF/IMD). The ST and IMD mice received a standard diet or the IMD ad libitum for 21 days. Muscle mass in the IMD mice was significantly higher than that in the ST mice. The LF/IMD in addition to the HF/ST and HF/IMD mice preserved their body and carcass weights. Plasma prostaglandin E2 levels were significantly lower in the IMD mice than in the ST mice. A combined effect was also observed in plasma interleukin-6, glucose, and vascular endothelial growth factor levels. Tumor weight was not affected by different diets. In conclusion, the IMD in combination with chemotherapy prevented cancer cachexia without suppressing chemotherapeutic efficacy.

  7. 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

  8. Effects of Tumor Necrosis Factor-α on Morphology and Mechanical Properties of HCT116 Human Colon Cancer Cells Investigated by Atomic Force Microscopy.

    Science.gov (United States)

    Liu, Huiqing; Wang, Nan; Zhang, Zhe; Wang, Hongda; Du, Jun; Tang, Jilin

    2017-01-01

    Chronic inflammation orchestrates the tumor microenvironment and is strongly associated with cancer. Tumor necrosis factor- α (TNF α ) is involved in tumor invasion and metastasis by inducing epithelial to mesenchymal transition (EMT). This process is defined by the loss of epithelial characteristics and gain of mesenchymal traits. The mechanisms of TNF α -induced EMT in cancer cells have been well studied. However, mechanical properties have not yet been probed. In this work, atomic force microscopy (AFM) was applied to investigate the morphology and mechanical properties of EMT in HCT116 human colon cancer cells. A remarkable morphological change from cobblestone shape to spindle-like morphology was observed. In parallel, AFM images showed that the cellular cytoskeleton was rearranged from a cortical to a stress-fiber pattern. Moreover, cell stiffness measurements indicated that Young's modulus of cells gradually reduced from 1 to 3 days with TNF α -treatment, but it has an apparent increase after 4 days of treatment compared with that for 3 days. Additionally, Young's modulus of the cells treated with TNF α for 4 days is slightly larger than that for 1 or 2 days, but still less than that of the untreated cells. Our work contributes to a better understanding of colorectal cancer metastasis induced by inflammation.

  9. Effects of Tumor Necrosis Factor-α on Morphology and Mechanical Properties of HCT116 Human Colon Cancer Cells Investigated by Atomic Force Microscopy

    Directory of Open Access Journals (Sweden)

    Huiqing Liu

    2017-01-01

    Full Text Available Chronic inflammation orchestrates the tumor microenvironment and is strongly associated with cancer. Tumor necrosis factor-α (TNFα is involved in tumor invasion and metastasis by inducing epithelial to mesenchymal transition (EMT. This process is defined by the loss of epithelial characteristics and gain of mesenchymal traits. The mechanisms of TNFα-induced EMT in cancer cells have been well studied. However, mechanical properties have not yet been probed. In this work, atomic force microscopy (AFM was applied to investigate the morphology and mechanical properties of EMT in HCT116 human colon cancer cells. A remarkable morphological change from cobblestone shape to spindle-like morphology was observed. In parallel, AFM images showed that the cellular cytoskeleton was rearranged from a cortical to a stress-fiber pattern. Moreover, cell stiffness measurements indicated that Young’s modulus of cells gradually reduced from 1 to 3 days with TNFα-treatment, but it has an apparent increase after 4 days of treatment compared with that for 3 days. Additionally, Young’s modulus of the cells treated with TNFα for 4 days is slightly larger than that for 1 or 2 days, but still less than that of the untreated cells. Our work contributes to a better understanding of colorectal cancer metastasis induced by inflammation.

  10. Differences Between Colon Cancer Primaries and Metastases Using a Molecular Assay for Tumor Radiation Sensitivity Suggest Implications for Potential Oligometastatic SBRT Patient Selection

    International Nuclear Information System (INIS)

    Ahmed, Kamran A.; Fulp, William J.; Berglund, Anders E.; Hoffe, Sarah E.; Dilling, Thomas J.; Eschrich, Steven A.; Shridhar, Ravi; Torres-Roca, Javier F.

    2015-01-01

    Purpose: We previously developed a multigene expression model of tumor radiation sensitivity index (RSI) with clinical validation in multiple independent cohorts (breast, rectal, esophageal, and head and neck patients). The purpose of this study was to assess differences between RSI scores in primary colon cancer and metastases. Methods and Materials: Patients were identified from our institutional review board–approved prospective observational protocol. A total of 704 metastatic and 1362 primary lesions were obtained from a de-identified metadata pool. RSI was calculated using the previously published rank-based algorithm. An independent cohort of 29 lung or liver colon metastases treated with 60 Gy in 5 fractions stereotactic body radiation therapy (SBRT) was used for validation. Results: The most common sites of metastases included liver (n=374; 53%), lung (n=116; 17%), and lymph nodes (n=40; 6%). Sixty percent of metastatic tumors, compared with 54% of primaries, were in the RSI radiation-resistant peak, suggesting metastatic tumors may be slightly more radiation resistant than primaries (P=.01). In contrast, when we analyzed metastases based on anatomical site, we uncovered large differences in RSI. The median RSIs for metastases in descending order of radiation resistance were ovary (0.48), abdomen (0.47), liver (0.43), brain (0.42), lung (0.32), and lymph nodes (0.31) (P<.0001). These findings were confirmed when the analysis was restricted to lesions from the same patient (n=139). In our independent cohort of treated lung and liver metastases, lung metastases had an improved local control rate compared to that in patients with liver metastases (2-year local control rate of 100% vs 73.0%, respectively; P=.026). Conclusions: Assessment of radiation sensitivity between primary and metastatic tissues of colon cancer histology revealed significant differences based on anatomical location of metastases. These initial results warrant validation in a larger

  11. Differences Between Colon Cancer Primaries and Metastases Using a Molecular Assay for Tumor Radiation Sensitivity Suggest Implications for Potential Oligometastatic SBRT Patient Selection

    Energy Technology Data Exchange (ETDEWEB)

    Ahmed, Kamran A. [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Fulp, William J.; Berglund, Anders E. [Department of Biostatistics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Hoffe, Sarah E.; Dilling, Thomas J. [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Eschrich, Steven A. [Department of Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Shridhar, Ravi [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Torres-Roca, Javier F., E-mail: javier.torresroca@moffitt.org [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States)

    2015-07-15

    Purpose: We previously developed a multigene expression model of tumor radiation sensitivity index (RSI) with clinical validation in multiple independent cohorts (breast, rectal, esophageal, and head and neck patients). The purpose of this study was to assess differences between RSI scores in primary colon cancer and metastases. Methods and Materials: Patients were identified from our institutional review board–approved prospective observational protocol. A total of 704 metastatic and 1362 primary lesions were obtained from a de-identified metadata pool. RSI was calculated using the previously published rank-based algorithm. An independent cohort of 29 lung or liver colon metastases treated with 60 Gy in 5 fractions stereotactic body radiation therapy (SBRT) was used for validation. Results: The most common sites of metastases included liver (n=374; 53%), lung (n=116; 17%), and lymph nodes (n=40; 6%). Sixty percent of metastatic tumors, compared with 54% of primaries, were in the RSI radiation-resistant peak, suggesting metastatic tumors may be slightly more radiation resistant than primaries (P=.01). In contrast, when we analyzed metastases based on anatomical site, we uncovered large differences in RSI. The median RSIs for metastases in descending order of radiation resistance were ovary (0.48), abdomen (0.47), liver (0.43), brain (0.42), lung (0.32), and lymph nodes (0.31) (P<.0001). These findings were confirmed when the analysis was restricted to lesions from the same patient (n=139). In our independent cohort of treated lung and liver metastases, lung metastases had an improved local control rate compared to that in patients with liver metastases (2-year local control rate of 100% vs 73.0%, respectively; P=.026). Conclusions: Assessment of radiation sensitivity between primary and metastatic tissues of colon cancer histology revealed significant differences based on anatomical location of metastases. These initial results warrant validation in a larger

  12. Cathelicidin suppresses colon cancer development by inhibition of cancer associated fibroblasts

    Directory of Open Access Journals (Sweden)

    Cheng M

    2014-12-01

    Full Text Available Michelle Cheng,1,* Samantha Ho,1,* Jun Hwan Yoo,1,2,* Deanna Hoang-Yen Tran,1,* Kyriaki Bakirtzi,1 Bowei Su,1 Diana Hoang-Ngoc Tran,1 Yuzu Kubota,1 Ryan Ichikawa,1 Hon Wai Koon1 1Center for Inflammatory Bowel Diseases, Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA; 2Digestive Disease Center, CHA University Bundang Medical Center, Seongnam, Republic of Korea *These authors share co-first authorship Background: Cathelicidin (LL-37 in humans and mCRAMP in mice represents a family of endogenous antimicrobial and anti-inflammatory peptides. Cancer-associated fibroblasts can promote the proliferation of colon cancer cells and growth of colon cancer tumors. Methods: We examined the role of cathelicidin in the development of colon cancer, using subcutaneous human HT-29 colon-cancer-cell-derived tumor model in nude mice and azoxymethane- and dextran sulfate-mediated colon cancer model in C57BL/6 mice. We also determined the indirect antitumoral mechanism of cathelicidin via the inhibition of epithelial–mesenchymal transition (EMT of colon cancer cells and fibroblast-supported colon cancer cell proliferation. Results: Intravenous administration of cathelicidin expressing adeno-associated virus significantly reduced the size of tumors, tumor-derived collagen expression, and tumor-derived fibroblast expression in HT-29-derived subcutaneous tumors in nude mice. Enema administration of the mouse cathelicidin peptide significantly reduced the size and number of colonic tumors in azoxymethane- and dextran sulfate-treated mice without inducing apoptosis in tumors and the adjacent normal colonic tissues. Cathelicidin inhibited the collagen expression and vimentin-positive fibroblast expression in colonic tumors. Cathelicidin did not directly affect HT-29 cell viability, but did significantly reduce tumor growth factor-ß1-induced EMT of colon cancer cells. Media conditioned by the

  13. 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.

  14. Imaging analysis of colonic villous tumors

    International Nuclear Information System (INIS)

    Lee, Choon Hyeong; Lim, Joo Won; Lee, Dong Ho; Ko, Yung Tae; Yang, Ik

    1996-01-01

    To evaluate the CT and US features of the colonic villous tumors. We retrospectively reviewed the CT findings of 11 cases with histologically proved colonic villous tumor. CT parameters evaluated were morphological appearances and enhancing pattern (size, shape, margin, presence or absence of fronds, bowel wall thickening). CT features of six cases with malignant change were compared with five tumors without malignant change. US features available in 10 patients were also analyzed. On CT, the tumors showed irregular margin(n=9), presence of fronds(n=6), lobulated shape(n=11), with pericolonic invasion(n=1). Six cases with malignant change were larger(mean, 6.8 cm in diameter) than those without malignant change(mean, 3.3cm). US features in 10 cases were intraluminal mass(n=5), colonic wall thickening(n=5), with variable echogenicity. Colonic villous tumor appeared as a nonspecific mass on CT and US with a difficulty in distinguishing from colon carcinoma

  15. PREOPERATIVE ENDOSCOPIC MARKING OF UNPALPABLE COLONIC TUMORS

    Directory of Open Access Journals (Sweden)

    A. L. Goncharov

    2013-01-01

    Full Text Available The identification of small colon lesions is one of the major problems in laparoscopic colonic resection.Research objective: to develop a technique of visualization of small tumors of a colon by preoperative endoscopic marking of a tumor.Materials and methods. In one day prior to operation to the patient after bowel preparation the colonoscopy is carried out. In the planned point near tumor on antimesentery edge the submucous infiltration of marking solution (Micky Sharpz blue tattoo pigment, UK is made. The volume of entered solution of 1–3 ml. In only 5 months of use of a technique preoperative marking to 14 patients with small (the size of 1–3 cm malignant tumors of the left colon is performed.Results. The tattoo mark was well visualized by during operation at 13 of 14 patients. In all cases we recorded no complications. Time of operation with preoperative marking averaged 108 min, that is significantly less in comparison with average time of operation with an intra-operative colonoscopy – 155 min (р < 0.001.Conclusions. The first experience of preoperative endoscopic marking of non palpable small tumors of a colon is encouraging. Performance of a technique wasn't accompanied by complications and allowed to reduce significantly time of operation and to simplify conditions of performance of operation.

  16. 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 ...

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

    African Journals Online (AJOL)

    Methods: Mice model of colon cancer was used in this study. Quantitative ... mRNA. Micro-vessel density was assessed using immunohistochemical analysis. ... increase in white blood cell (WBC) count, and increased median survival time of colon cancer mice from ..... tumor cells is associated with the development of.

  18. Long-lasting complete response status of advanced stage IV gall bladder cancer and colon cancer after combined treatment including autologous formalin-fixed tumor vaccine: two case reports.

    Science.gov (United States)

    Imaoka, Yuki; Kuranishi, Fumito; Miyazaki, Tsubasa; Yasuda, Hiroko; Ohno, Tadao

    2017-09-11

    The prognosis of advanced (stage IV) cancer of the digestive organs is very poor. We have previously reported a case of advanced breast cancer with bone metastasis that was successfully treated with combined treatments including autologous formalin-fixed tumor vaccine (AFTV). Herein, we report the success of this approach in advanced stage IV (heavily metastasized) cases of gall bladder cancer and colon cancer. Case 1: A 61-year-old woman with stage IV gall bladder cancer (liver metastasis and lymph node metastasis) underwent surgery in May 2011, including partial resection of the liver. She was treated with AFTV as the first-line adjuvant therapy, followed by conventional chemotherapy. This patient is still alive without any recurrence, as confirmed with computed tomography, for more than 5 years. Case 2: A 64-year-old man with stage IV colon cancer (multiple para-aortic lymph node metastases and direct abdominal wall invasion) underwent non-curative surgery in May 2006. Following conventional chemotherapy, two courses of AFTV and radiation therapy were administered sequentially. This patient has had no recurrence for more than 5 years. We report the success of combination therapy including AFTV in cases of liver-metastasized gall bladder cancer and abdominal wall-metastasized colon cancer. Both patients experienced long-lasting, complete remission. Therefore, combination therapies including AFTV should be considered in patients with advanced cancer of the digestive organs.

  19. Stages of Colon Cancer

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... VEGF inhibitors and angiogenesis inhibitors . Epidermal growth factor receptor (EGFR) inhibitor therapy: EGFRs are proteins found on ...

  20. 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.

  1. 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.

  2. Understanding your colon cancer risk

    Science.gov (United States)

    ... for women and 2 drinks per day for men DO NOT smoke You can also have genetic testing done to assess your risk for colon cancer. If you have a strong family history of the disease, talk with your ...

  3. Study protocol of the B-CAST study: a multicenter, prospective cohort study investigating the tumor biomarkers in adjuvant chemotherapy for stage III colon cancer

    International Nuclear Information System (INIS)

    Ishiguro, Megumi; Mori, Masaki; Kakeji, Yoshihiro; Kanazawa, Akiyoshi; Kobayashi, Michiya; Okajima, Masazumi; Hyodo, Ichinosuke; Miyakoda, Keiko; Sugihara, Kenichi; Kotake, Kenjiro; Nishimura, Genichi; Tomita, Naohiro; Ichikawa, Wataru; Takahashi, Keiichi; Watanabe, Toshiaki; Furuhata, Tomohisa; Kondo, Ken

    2013-01-01

    Adjuvant chemotherapy for stage III colon cancer is internationally accepted as standard treatment with established efficacy. Several oral fluorouracil (5-FU) derivatives with different properties are available in Japan, but which drug is the most appropriate for each patient has not been established. Although efficacy prediction of 5-FU derivatives using expression of 5-FU activation/metabolism enzymes in tumors has been studied, it has not been clinically applied. The B-CAST study is a multicenter, prospective cohort study aimed to identify the patients who benefit from adjuvant chemotherapy with each 5-FU regimen, through evaluating the relationship between tumor biomarker expression and treatment outcome. The frozen tumor specimens of patients with stage III colon cancer who receives postoperative adjuvant chemotherapy are examined. Protein expression of thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), epidermal growth factor receptor (EGFR), and vascular endothelial growth factor (VEGF) are evaluated using enzyme-linked immunosorbent assay (ELISA). mRNA expression of TP, DPD, thymidylate synthase (TS) and orotate phosphoribosyl transferase (OPRT) are evaluated using reverse transcription polymerase chain reaction (RT-PCR). The patients’ clinical data reviewed are as follow: demographic and pathological characteristics, regimen, drug doses and treatment duration of adjuvant therapy, types and severity of adverse events, disease free survival, relapse free survival and overall survival. Then, relationships among the protein/mRNA expression, clinicopathological characteristics and the treatment outcomes are analyzed for each 5-FU derivative. A total of 2,128 patients from the 217 institutions were enrolled between April 2009 and March 2012. The B-CAST study demonstrated that large-scale, multicenter translational research using frozen samples was feasible when the sample shipment and Web-based data collection were well organized. The results

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

    Science.gov (United States)

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

    2016-10-18

    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 anhydrase I (Car1) is a gene expressed uniquely in colonic epithelial cells. We generated a colon-specific inducible Car1 CreER knock-in (KI) mouse with broad Cre activity in epithelial cells of the proximal colon and cecum. Deletion of the tumor suppressor gene Apc using the Car1 CreER KI caused tumor formation in the cecum but did not yield adenomas in the proximal colon. Mutation of both Apc and Kras yielded microadenomas in both the cecum and the proximal colon, which progressed to macroadenomas with significant morbidity. Aggressive carcinomas with some invasion into lymph nodes developed upon combined induction of oncogenic mutations of Apc, Kras, p53, and Smad4 Importantly, no adenomas were observed in the small intestine. Additionally, we observed tumors from differentiated Car1-expressing cells with Apc/Kras mutations, suggesting that a top-down model of intestinal tumorigenesis can occur with multiple mutations. Our results establish the Car1 CreER KI as a valuable mouse model to study colon-specific tumorigenesis and metastasis as well as cancer-cell-of-origin questions.

  5. Colonic macrophage polarization in homeostasis, inflammation, and cancer

    Science.gov (United States)

    Appleyard, Caroline B.

    2016-01-01

    Our review focuses on the colonic macrophage, a monocyte-derived, tissue-resident macrophage, and the role it plays in health and disease, specifically in inflammatory conditions such as inflammatory bowel disease and cancer of the colon and rectum. We give special emphasis to macrophage polarization, or phenotype, in these different states. We focus on macrophages because they are one of the most numerous leukocytes in the colon, and because they normally contribute to homeostasis through an anti-inflammatory phenotype. However, in conditions such as inflammatory bowel disease, proinflammatory macrophages are increased in the colon and have been linked to disease severity and progression. In colorectal cancer, tumor cells may employ anti-inflammatory macrophages to promote tumor growth and dissemination, whereas proinflammatory macrophages may antagonize tumor growth. Given the key roles that this cell type plays in homeostasis, inflammation, and cancer, the colonic macrophage is an intriguing therapeutic target. As such, potential macrophage-targeting strategies are discussed. PMID:27229123

  6. 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

  7. 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

  8. 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

  9. 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...

  10. Managing Potentially Resectable Metastatic Colon Cancer

    OpenAIRE

    Marshall, John L.

    2008-01-01

    For patients with metastatic colon cancer, management has evolved from resecting a single liver metastasis and having only one chemotherapy medicine, to resecting multiple metastases including those outside the liver as well as using combination chemotherapy (based on recent supportive trials) to improve outcomes. This success has also raised many questions, including the role of adjuvant chemotherapy to downstage borderline resectable tumors, whether patients who receive preoperative chemoth...

  11. Which FDG/PET parameters of the primary tumors in colon or sigmoid cancer provide the best correlation with the pathological findings?

    International Nuclear Information System (INIS)

    Chen, Shang-Wen; Chen, William Tzu-Liang; Wu, Yi-Chen; Yen, Kuo-Yang; Hsieh, Te-Chun; Lin, Tze-Yi; Kao, Chia-Hung

    2013-01-01

    Background To compare 18 F-fluoro-2-deoxdeoxyglucose (FDG) positron emission tomography (PET) related parameters of primary colon or sigmoid cancer (CSC) with pathological findings. Methods Seventy-seven CSC patients who have undergone preoperative PET computed tomograms (PET/CT) are included in this study. Maximum PET-based tumor length (TL) and tumor width (TW) are determined using several auto-segmentation methods, and various thresholds of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) are measured. The PET-based TL and TW are compared with maximum pathological length and width on the pathological specimen. Results Using a 30% threshold level for maximum uptake of TL (TL30%) and TW (TW30%) yield results that provide an optimal match with maximum pathological length (R = 0.81, p < 0.001) and width (R = 0.70, p < 0.001). TW30% was an independent factor for predicting pathological T3 or T4 stages (OR = 1.26, 95% CI = 1.07–1.47, p = 0.01). The receiver-operating characteristic curves show MTV at a fixed threshold of 40% maximum uptake (MTV40%), and TW30% achieved better correlation with the advanced pathological T stage. No associations with positive N stage were observed. Conclusion Pretreatment PET/CT is a useful tool for predicting the final pathological findings for CSC patients requiring surgical procedures

  12. 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.

  13. 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.

  14. 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.

  15. Impact of MLH1 expression on tumor evolution after curative surgical tumor resection in a murine orthotopic xenograft model for human MSI colon cancer.

    Science.gov (United States)

    Meunier, Katy; Ferron, Marianne; Calmel, Claire; Fléjou, Jean-François; Pocard, Marc; Praz, Françoise

    2017-09-01

    Colorectal cancers (CRCs) displaying microsatellite instability (MSI) most often result from MLH1 deficiency. The aim of this study was to assess the impact of MLH1 expression per se on tumor evolution after curative surgical resection using a xenograft tumor model. Transplantable tumors established with the human MLH1-deficient HCT116 cell line and its MLH1-complemented isogenic clone, mlh1-3, were implanted onto the caecum of NOD/SCID mice. Curative surgical resection was performed at day 10 in half of the animals. The HCT116-derived tumors were more voluminous compared to the mlh1-3 ones (P = .001). Lymph node metastases and peritoneal carcinomatosis occurred significantly more often in the group of mice grafted with HCT116 (P = .007 and P = .035, respectively). Mlh1-3-grafted mice did not develop peritoneal carcinomatosis or liver metastasis. After surgical resection, lymph node metastases only arose in the group of mice implanted with HCT116 and the rate of cure was significantly lower than in the mlh1-3 group (P = .047). The murine orthotopic xenograft model based on isogenic human CRC cell lines allowed us to reveal the impact of MLH1 expression on tumor evolution in mice who underwent curative surgical resection and in mice whose tumor was left in situ. Our data indicate that the behavior of MLH1-deficient CRC is not only governed by mutations arising in genes harboring microsatellite repeated sequences but also from their defect in MLH1 as such. © 2017 Wiley Periodicals, Inc.

  16. Detection of circulating tumor cells with CK20 RT-PCR is an independent negative prognostic marker in colon cancer patients - a prospective study.

    Science.gov (United States)

    Hinz, Sebastian; Hendricks, Alexander; Wittig, Amke; Schafmayer, Clemens; Tepel, Jürgen; Kalthoff, Holger; Becker, Thomas; Röder, Christian

    2017-01-13

    Detection of circulating (CTC) or disseminated tumor cells (DTC) has been associated with negative prognosis and outcome in patients with colorectal cancer, though testing for these cells is not yet part of clinical routine. There are several different methodological approaches to detect tumor cells but standardized detection assays are not implemented so far. In this prospective monocentric study 299 patients with colon cancer were included. CTC and DTC were detected using CK20 RT-PCR as well as immunocytochemistry staining with anti-pan-keratin and anti-EpCAM antibodies. The primary endpoints were: Evaluation of CTC and DTC at the time of surgery and correlation with main tumor characteristics and overall (OS) and disease free survival (DFS). Patients with detectable CTC had a 5-year OS rate of 68% compared to a 5-year OS rate of 85% in patients without detectable CTC in the blood (p = 0.002). Detection of DTC in the bone marrow with CK20 RT-PCR was not associated with a worse OS or DFS. Detection of pan-cytokeratin positive DTC in the bone marrow correlated with a significantly reduced 5-year OS rate (p = 0.048), but detection of DTC in the bone marrow with the anti-EpCAM antibody did not significantly influence the 5-year OS rate (p = 0.958). By multivariate analyses only detection of CTC with CK20 RT-PCR in the blood was revealed to be an independent predictor of worse OS (HR1.94; 95% CI 1.0-3.7; p = 0.04) and DFS (HR 1.94; 95% CI 1.1-3.7; p = 0.044). Detection of CTC with CK20 RT-PCR is a highly specific and independent prognostic marker in colon cancer patients. Detection of DTC in the bone marrow with CK20 RT-PCR or immunohistochemistry with anti-EpCAM antibody is not associated with a negative prognostic influence.

  17. Additional prognostic factors in right colon cancer staging.

    Science.gov (United States)

    Parmeggiani, Domenico; Avenia, Nicola; Gubitosi, Adelmo; Gilio, Francesco; Atelli, Pietro Francesco; Agresti, Massimo

    2011-09-01

    Based on the theory--which is now acknowledged-of a clinical difference between proximal and distal colon cancer and on the results of recent genetic and microbiological studies, a minority of authors have assumed that also in the sphere of right-sided colon cancer, tumors at three different locations, namely, the cecum and ascending and transverse colon, can be considered to be biologically different. These studies have provided the basis for a retrospective study carried out on 50 patients admitted to our department from 1996 to 2008 for tumor pathology of the right colon. The tumor was considered to be a unified biological entity and assessed in relation to the three above-mentioned locations. The results verify that the aggressive of the tumor increases from the cecum to the transverse, with a higher percentage of cecal tumors being in I stage, more tumors in the ascending colon being in II stage, and more transverse tumors, with the largest percentage of N+ and M+, in stages III and IV. This difference in biological behavior for the three tumor locations has been also found in terms of sensitiveness, both pre- and post-operation, of tumor markers CEA, TPA, and CA19-9. Clinical data revealed a binary relationship between the transverse, cecum, and ascending tumors, which ultimately affects patient mortality, which increases in a directly proportional way from the cecum to the transverse-in the case of a tumor at one of these locations.

  18. 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

  19. 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.

  20. Inhibition of Epidermal Growth Factor Receptor and Vascular Endothelial Growth Factor Receptor Phosphorylation on Tumor-Associated Endothelial Cells Leads to Treatment of Orthotopic Human Colon Cancer in Nude Mice

    Directory of Open Access Journals (Sweden)

    Takamitsu Sasaki

    2007-12-01

    Full Text Available The purpose of our study was to determine whether the dual inhibition of epidermal growth factor receptor (EGFR and vascular endothelial growth factor receptor (VEGFR signaling pathways in tumor-associated endothelial cells can inhibit the progressive growth of human colon carcinoma in the cecum of nude mice. SW620CE2 human colon cancer cells growing in culture and orthotopically in the cecum of nude mice expressed a high level of transforming growth factor alpha (TGF-α and vascular endothelial growth factor (VEGF but were negative for EGFR, human epidermal growth factor receptor 2 (HER2, VEGFR. Double immunofluorescence staining revealed that tumorassociated endothelial cells expressed EGFR, VEGFR2, phosphorylated EGFR (pEGFR, phosphorylated VEGFR (pVEGFR. Treatment of mice with either 7H-pyrrolo [2,3-d]-pyrimidine lead scaffold (AEE788; an inhibitor of EGFR and VEGFR tyrosine kinase or CPT-11 as single agents significantly inhibited the growth of cecal tumors (P < .01; this decrease was even more pronounced with AEE788 combined with CPT-11 (P < .001. AEE788 alone or combined with CPT-11 also inhibited the expression of pEGFR and pVEGFR on tumor-associated endothelial cells, significantly decreased vascularization and tumor cell proliferation, increased the level of apoptosis in both tumorassociated endothelial cells and tumor cells. These data demonstrate that targeting EGFR and VEGFR signaling on tumor-associated endothelial cells provides a viable approach for the treatment of colon cancer.

  1. CALCIUM AND THE PREVENTION OF COLON CANCER

    NARCIS (Netherlands)

    WELBERG, JWM; KLEIBEUKER, JH; VANDERMEER, R; MULDER, NH; DEVRIES, EGE

    1991-01-01

    Diet is a major determinant of colon cancer risk. Calcium may protect against colon cancer, presumably by binding cytotoxic bile acids and fatty acids. Numerous studies support this proposition. In subjects at risk for colon cancer oral calcium supplementation has been shown to reduce rectal

  2. 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...

  3. 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

  4. 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

  5. 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

  6. Clinical significance of adiponectin expression in colon cancer patients

    Directory of Open Access Journals (Sweden)

    Mustafa Canhoroz

    2014-01-01

    Conclusion: Adiponectin, which is secreted by adipose tissue, may have a role in the development and progression of cancer via its pro-apoptotic and/or anti-proliferative effects. Adiponectin expression in tumor tissues is likely to have a negative effect on disease - free survival in patients with stage II/III colon cancer; however, no statistically significant effect was demonstrated.

  7. Sigmoid colon cancer arising in a diverticulum of the colon with involvement of the urinary bladder: a case report and review of the literature.

    Science.gov (United States)

    Yagi, Yasumichi; Shoji, Yasuhiro; Sasaki, Shozo; Yoshikawa, Akemi; Tsukioka, Yuji; Fukushima, Wataru; Hirosawa, Hisashi; Izumi, Ryohei; Saito, Katsuhiko

    2014-05-13

    Colon cancer can arise from the mucosa in a colonic diverticulum. Although colon diverticulum is a common disease, few cases have been previously reported on colon cancer associated with a diverticulum. We report a rare case of sigmoid colon cancer arising in a diverticulum with involvement of the urinary bladder, which presented characteristic radiographic images. A 73-year-old man was admitted to our hospital for macroscopic hematuria. Computed tomography and magnetic resonance imaging revealed a sigmoid colon tumor that protruded into the urinary bladder lumen. The radiographs showed a tumor with a characteristic dumbbell-shaped appearance. Colonoscopy showed a type 1 cancer and multiple diverticula in the sigmoid colon. A diagnosis of sigmoid colon cancer with involvement of the urinary bladder was made based on the pathological findings of the biopsied specimens. We performed sigmoidectomy and total resection of the urinary bladder with colostomy and urinary tract diversion. Histopathological findings showed the presence of a colovesical fistula due to extramurally growing colon cancer. Around the colon cancer, the normal colon mucosa was depressed sharply with lack of the muscular layer, suggesting that the colon cancer was arising from a colon diverticulum. The present case is the first report of sigmoid colon cancer arising in a diverticulum with involvement of the urinary bladder. Due to an accurate preoperative radiological diagnosis, we were able to successfully perform a curative resection for sigmoid colon cancer arising in a diverticulum with involvement of the urinary bladder.

  8. CT staging of colon cancer

    Energy Technology Data Exchange (ETDEWEB)

    Dighe, S. [Department of Radiology, Royal Marsden Hospital, Sutton SM5 2TT (United Kingdom); Swift, I. [Department of Surgery, Mayday University Hospital, Croydon CR7 7YE (United Kingdom); Brown, G. [Department of Radiology, Royal Marsden Hospital, Sutton SM5 2TT (United Kingdom)], E-mail: gina.brown@rmh.nhs.uk

    2008-12-15

    Computer tomography (CT) has been the principal investigation in the staging of colon cancers. The information obtained with routine CT has been limited to identifying the site of the tumour, size of the tumour, infiltration into surrounding structures and metastatic spread. The Foxtrot trial National Cancer Research Institute (NCRI) has been specifically designed to evaluate the efficacy of neoadjuvant treatment in colon cancers by using preoperative chemotherapy with or without an anti-Epidermal Growth Factor Receptor (EGFR) monoclonal antibody to improve outcome in high-risk operable colon cancer. Patients are selected based on their staging CT examination. The criteria for poor prognosis are T4 and T3 tumours with more than 5 mm extramural depth. Thus the success of the trial would depend upon the confidence of the radiologist to identify the patients that would receive the neoadjuvant treatment. The aim of this review is to explain the process of identifying high-risk features seen on the staging CT images. This will help to identify a cohort of patients that could truly benefit from neoadjuvant strategies.

  9. CT staging of colon cancer

    International Nuclear Information System (INIS)

    Dighe, S.; Swift, I.; Brown, G.

    2008-01-01

    Computer tomography (CT) has been the principal investigation in the staging of colon cancers. The information obtained with routine CT has been limited to identifying the site of the tumour, size of the tumour, infiltration into surrounding structures and metastatic spread. The Foxtrot trial National Cancer Research Institute (NCRI) has been specifically designed to evaluate the efficacy of neoadjuvant treatment in colon cancers by using preoperative chemotherapy with or without an anti-Epidermal Growth Factor Receptor (EGFR) monoclonal antibody to improve outcome in high-risk operable colon cancer. Patients are selected based on their staging CT examination. The criteria for poor prognosis are T4 and T3 tumours with more than 5 mm extramural depth. Thus the success of the trial would depend upon the confidence of the radiologist to identify the patients that would receive the neoadjuvant treatment. The aim of this review is to explain the process of identifying high-risk features seen on the staging CT images. This will help to identify a cohort of patients that could truly benefit from neoadjuvant strategies

  10. BAY61-3606 potentiates the anti-tumor effects of TRAIL against colon cancer through up-regulating DR4 and down-regulating NF-κB.

    Science.gov (United States)

    Du, Jipei; Wang, Yufang; Chen, Degao; Ji, Guangyu; Ma, Qizhao; Liao, Shiping; Zheng, Yanjiang; Zhang, Ji; Hou, Yiping

    2016-12-28

    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is well known for its ability to preferentially induce apoptosis in malignant cells without causing damage to most normal cells. However, inherent and acquired resistance of tumor to TRAIL-induced apoptosis limits its therapeutic applicability. Here we show that the orally available tyrosine kinase inhibitor, BAY61-3606, enhances the sensitivity of human colon cancer cells, especially those harboring active mutations in Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) gene, to TRAIL-induced apoptosis in vitro and in vivo. The sensitization was achieved by up-regulating death receptor 4 (DR4) and the tumor suppressor p53. BAY61-3606-induced the up-regulation of DR4 is p53-dependent. Knockout of p53 decreased BAY61-3606-induced DR4 expression and inhibited the effect of BAY61-3606 on TRAIL-induced apoptosis. In addition, BAY61-3606 suppressed activity of NF-κB and regulated its gene products, which might also contribute to TRAIL-induced apoptosis. In conclusion, our results showed that BAY61-3606 sensitizes colon cancer cells to TRAIL-induced apoptosis via up-regulating DR4 expression in p53-dependent manner and inhibiting NF-κB activity, suggesting that the combination of TRAIL and BAY61-3606 may be a promising therapeutic approach in the treatment of colon cancer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. 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...... clinicopathologic variables and immunohistochemical MMR protein expression. RESULTS: Female sex, age ≥60 years, proximal tumor location, expanding growth pattern, lack of dirty necrosis, mucinous differentiation and presence of tumor-infiltrating lymphocytes significantly correlated with MMR deficiency. Presence...

  12. Real-time detection system for tumor localization during minimally invasive surgery for gastric and colon cancer removal: In vivo feasibility study in a swine model.

    Science.gov (United States)

    Choi, Won Jung; Moon, Jin-Hee; Min, Jae Seok; Song, Yong Keun; Lee, Seung A; Ahn, Jin Woo; Lee, Sang Hun; Jung, Ha Chul

    2018-03-01

    During minimally invasive surgery (MIS), it is impossible to directly detect marked clips around tumors via palpation. Therefore, we developed a novel method and device using Radio Frequency IDentification (RFID) technology to detect the position of clips during minimally invasive gastrectomy or colectomy. The feasibility of the RFID-based detection system was evaluated in an animal experiment consisting of seven swine. The primary outcome was to successfully detect the location of RFID clips in the stomach and colon. The secondary outcome measures were to detect time (time during the intracorporeal detection of the RFID clip), and accuracy (distance between the RFID clip and the detected site). A total of 25 detection attempts (14 in the stomach and 11 in the colon) using the RFID antenna had a 100% success rate. The median detection time was 32.5 s (range, 15-119 s) for the stomach and 28.0 s (range, 8-87 s) for the colon. The median detection distance was 6.5 mm (range, 4-18 mm) for the stomach and 6.0 mm (range, 3-13 mm) for the colon. We demonstrated favorable results for a RFID system that detects the position of gastric and colon tumors in real-time during MIS. © 2017 Wiley Periodicals, Inc.

  13. Z-505 hydrochloride, an orally active ghrelin agonist, attenuates the progression of cancer cachexia via anabolic hormones in Colon 26 tumor-bearing mice.

    Science.gov (United States)

    Yoshimura, Makoto; Shiomi, Yoshihiro; Ohira, Yuta; Takei, Mineo; Tanaka, Takao

    2017-09-15

    Cancer cachexia is a progressive wasting syndrome characterized by anorexia and weight loss, specifically muscle wasting and fat depletion. There is no therapeutic agent for treatment of this syndrome. We investigated the anti-cachexia effects of Z-505 hydrochloride (Z-505), a new oral growth hormone secretagogue receptor 1a (GHSR1a) agonist, using a mouse model of cancer cachexia. We performed a calcium flux assay in Chinese hamster ovary (CHO-K1) cells stably expressing human GHSR1a to quantify the agonistic activity of Z-505. In Colon 26 tumor-bearing mice, Z-505 (300mg/kg, p.o., twice daily) was administered for 7 days to assess its anti-cachexia effects. Body weight and food intake were monitored during the period, and the skeletal muscle and epididymal fat weights were measured. Serum levels of insulin, insulin-like growth factor 1 (IGF-1), interleukin-6 (IL-6), and corticosterone were measured to confirm the mechanism of the anti-cachexia action of Z-505. Z-505 showed strong agonistic activity similar to that of human ghrelin, with a half maximal effective concentration (EC 50 ) value of 0.45nM. Z-505 treatment significantly increased food intake and inhibited the progression of weight loss. Z-505 also significantly attenuated muscle wasting and fat loss, and increased circulating levels of anabolic factors such as insulin and IGF-1, but not catabolic factors such as IL-6 and corticosterone. These findings suggest that Z-505 might be effective in the treatment of cachexia via the increased anabolic hormone levels stimulated by the activation of the ghrelin receptor, GHSR1a. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Personalized Proteome Profiles of Healthy and Tumor Human Colon Organoids Reveal Both Individual Diversity and Basic Features of Colorectal Cancer.

    Science.gov (United States)

    Cristobal, Alba; van den Toorn, Henk W P; van de Wetering, Marc; Clevers, Hans; Heck, Albert J R; Mohammed, Shabaz

    2017-01-03

    Diseases at the molecular level are complex and patient dependent, necessitating development of strategies that enable precision treatment to optimize clinical outcomes. Organoid technology has recently been shown to have the potential to recapitulate the in vivo characteristics of the original individual's tissue in a three-dimensional in vitro culture system. Here, we present a quantitative mass-spectrometry-based proteomic analysis and a comparative transcriptomic analysis of human colorectal tumor and healthy organoids derived, in parallel, from seven patients. Although gene and protein signatures can be derived to distinguish the tumor organoid population from healthy organoids, our data clearly reveal that each patient possesses a distinct organoid signature at the proteomic level. We demonstrate that a personalized patient-specific organoid proteome profile can be related to the diagnosis of a patient and with future development contribute to the generation of personalized therapies. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  15. 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.

  16. Synchronous hepatic metastasis and metachronous Krukenberg tumor from advanced colon cancer. A case report with an unexpected disease-free survival

    Directory of Open Access Journals (Sweden)

    Giovanni Li Destri

    2017-01-01

    Conclusion: The authors emphasize that the long term survival in colon cancer with hepatic and ovarian metastases is possible as long as it has an adequate surgical approach, a tailored chemotherapy and an intensive follow-up. Most likely new prognostic markers will have to be identified.

  17. Potentialities of computed tomography and ultrasonography in colonic cancer

    International Nuclear Information System (INIS)

    Gorshkov, A.N.

    2001-01-01

    Data of examination of 59 patients with colonic cancer were used to consider the potentialities of transabdominal, transrectal ultrasonography and X-ay compound tomography and to assess their value in diagnosing colonic cancer, including its minor forms. Ultrasound and computed tomographic semiotics of colonic cancer and determines a place of the above techniques in the algorithm of radiation and instrumental studies are described. Inclusion of these techniques into the diagnostic algorithm may solve a range of differentially diagnostic problems and allows a preliminary analysis to be made in a tumor lesion according to the International TNM classification. Ultrasonography and X-ray computed tomography should be included into a range of basic methods for diagnosis of colonic cancer [ru

  18. Prognostic and predictive potential molecular biomarkers in colon cancer.

    Science.gov (United States)

    Nastase, A; Pâslaru, L; Niculescu, A M; Ionescu, M; Dumitraşcu, T; Herlea, V; Dima, S; Gheorghe, C; Lazar, V; Popescu, I

    2011-01-01

    An important objective in nowadays research is the discovery of new biomarkers that can detect colon tumours in early stages and indicate with accuracy the status of the disease. The aim of our study was to identify potential biomarkers for colon cancer onset and progression. We assessed gene expression profiles of a list of 10 candidate genes (MMP-1, MMP-3, MMP-7, DEFA 1, DEFA-5, DEFA-6, IL-8, CXCL-1, SPP-1, CTHRC-1) by quantitative real time PCR in triplets of colonic mucosa (normal, adenoma, tumoral tissue) collected from the same patient during surgery for a group of 20 patients. Additionally we performed immunohistochemistry for DEFA1-3 and SPP1. We remarked that DEFA5 and DEFA6 are key factors in adenoma formation (p<0.05). MMP7 is important in the transition from a benign to a malignant status (p <0.01) and further in metastasis being a prognostic indicator for tumor transformation and for the metastatic potential of cancer cells. IL8, irrespective of tumor stage, has a high mRNA level in adenocarcinoma (p< 0.05). The level of expression for SPP1 is correlated with tumor level. We suggest that high levels of DEFAS, DEFA6 (key elements in adenoma formation), MMP7 (marker of colon cancer onset and progression to metastasis), SPP1 (marker of progression) and IL8 could be used to diagnose an early stage colon cancer and to evaluate the prognostic of progression for colon tumors. Further, if DEFA5 and DEFA6 level of expression are low but MMP7, SPP1 and IL8 level are high we could point out that the transition from adenoma to adenocarcinoma had already occurred. Thus, DEFA5, DEFA6, MMP7, IL8 and SPP1 consist in a valuable panel of biomarkers, whose detection can be used in early detection and progressive disease and also in prognostic of colon cancer.

  19. 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

  20. Colon cancer modulation by a diabetic environment: A single institutional experience.

    Science.gov (United States)

    Prieto, Isabel; Del Puerto-Nevado, Laura; Gonzalez, Nieves; Portal-Nuñez, Sergio; Zazo, Sandra; Corton, Marta; Minguez, Pablo; Gomez-Guerrero, Carmen; Arce, Jose Miguel; Sanz, Ana Belen; Mas, Sebastian; Aguilera, Oscar; Alvarez-Llamas, Gloria; Esbrit, Pedro; Ortiz, Alberto; Ayuso, Carmen; Egido, Jesus; Rojo, Federico; Garcia-Foncillas, Jesus

    2017-01-01

    Multiple observational studies suggest an increased risk of colon cancer in patients with diabetes mellitus (DM). This can theoretically be the result of an influence of the diabetic environment on carcinogenesis or the tumor biologic behavior. To gain insight into the influence of a diabetic environment on colon cancer characteristics and outcomes. Retrospective analysis of clinical records in an academic tertiary care hospital with detailed analysis of 81 diabetic patients diagnosed of colon cancer matched with 79 non-diabetic colon cancer patients. The impact of streptozotocin-induced diabetes on the growth of colon cancer xenografts was studied in mice. The incidence of DM in 1,137 patients with colorectal cancer was 16%. The diabetic colon cancer cases and non-diabetic colon cancer controls were well matched for demographic and clinical variables. The ECOG Scale Performance Status was higher (worse) in diabetics (ECOG ≥1, 29.1% of controls vs 46.9% of diabetics, p = 0.02), but no significant differences were observed in tumor grade, adjuvant therapy, tumor site, lymphovascular invasion, stage, recurrence, death or cancer-related death. Moreover, no differences in tumor variables were observed between patients treated or not with metformin. In the xenograft model, tumor growth and histopathological characteristics did not differ between diabetic and nondiabetic animals. Our findings point towards a mild or negligible effect of the diabetes environment on colon cancer behavior, once cancer has already developed.

  1. Up-regulation of CNDP2 facilitates the proliferation of colon cancer.

    Science.gov (United States)

    Xue, Conglong; Zhang, Zhenwei; Yu, Honglan; Yu, Miao; Yuan, Kaitao; Yang, Ting; Miao, Mingyong; Shi, Hanping

    2014-05-21

    Cytosolic nonspecific dipetidase (CN2) belongs to the family of M20 metallopeptidases. It was stated in previous articles that higher expression levels of CN2 were observed in renal cell carcinoma and breast cancer. Our study explored the correlation between CN2 and colon carcinogenesis. We analysed the relationship between 183 patients clinicopathological characteristics and its CN2 expression. To detect the levels of CN2 in colon cancer cell lines and colon cancer tissues by western blot. To verify cell proliferation in colon cancer cells with knockdown of CNDP2 and explore the causes of these phenomena. The expression levels of CN2 in clinical colon tumors and colon cancer cell lines were significantly higher than that in normal colon mucosa and colon cell lines. The difference in CN2 levels was associated with tumor location (right- and left-sided colon cancer), but there was no significant association with age, gender, tumor size, tumor grade, tumor stage or serum carcinoembryonic antigen (CEA). Knockdown of CNDP2 inhibited cell proliferation, blocked cell cycle progression and retarded carcinogenesis in an animal model. The signaling pathway through which knockdown of CNDP2 inhibited cell proliferation and tumorigenesis involved in EGFR, cyclin B1 and cyclin E. Knockdown of CNDP2 can inhibit the proliferation of colon cancer in vitro and retarded carcinogenesis in vivo.

  2. 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)

  3. [Colorectal cancer the importance of primary tumor location].

    Science.gov (United States)

    Ryska, M; Bauer, J

    2017-01-01

    Retrospective evaluations of the relevance of primary colorectal cancer (CRC) location consistently indicate that right-sided tumors, arising in the cecum, ascending colon, hepatic bend, transverse colon and splenic flexure, are clinically, biologically and genetically different from left-sided tumors - those located in the descending colon, sigmoid colon or rectum. Location in the right-sided colon represents a negative prognostic indicator, particularly for stage III and IV carcinomas. Irrespective of treatment, the rightward location is associated with a significantly increased risk of death when compared to the left side.Key words: colorectal cancer - location - therapy - prognosis.

  4. 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

  5. Evaluation of tumor suppressor gene expressions and aberrant methylation in the colon of cancer-induced rats: a pilot study

    Czech Academy of Sciences Publication Activity Database

    Vymetálková, Veronika; Vannucci, Luca; Korenková, Vlasta; Procházka, Pavel; Slyšková, Jana; Vodičková, Ludmila; Rusňáková, Vendula; Bielik, Ludovít; Burocziová, Monika; Rossmann, Pavel; Vodička, Pavel

    2013-01-01

    Roč. 40, č. 10 (2013), s. 5921-5929 ISSN 0301-4851 R&D Projects: GA AV ČR IAA500200917; GA ČR GPP304/11/P715 Institutional research plan: CEZ:AV0Z50390703; CEZ:AV0Z50520701; CEZ:AV0Z50390512 Institutional support: RVO:61388971 ; RVO:68378041 ; RVO:86652036 Keywords : colorectal cancer * rats * mRNA expression Subject RIV: EB - Genetics ; Molecular Biology; EB - Genetics ; Molecular Biology (BU-J); EB - Genetics ; Molecular Biology (MBU-M) Impact factor: 1.958, year: 2013

  6. 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.

  7. Three-Dimensional Spatiotemporal Modeling of Colon Cancer Organoids Reveals that Multimodal Control of Stem Cell Self-Renewal is a Critical Determinant of Size and Shape in Early Stages of Tumor Growth.

    Science.gov (United States)

    Yan, Huaming; Konstorum, Anna; Lowengrub, John S

    2018-05-01

    We develop a three-dimensional multispecies mathematical model to simulate the growth of colon cancer organoids containing stem, progenitor and terminally differentiated cells, as a model of early (prevascular) tumor growth. Stem cells (SCs) secrete short-range self-renewal promoters (e.g., Wnt) and their long-range inhibitors (e.g., Dkk) and proliferate slowly. Committed progenitor (CP) cells proliferate more rapidly and differentiate to produce post-mitotic terminally differentiated cells that release differentiation promoters, forming negative feedback loops on SC and CP self-renewal. We demonstrate that SCs play a central role in normal and cancer colon organoids. Spatial patterning of the SC self-renewal promoter gives rise to SC clusters, which mimic stem cell niches, around the organoid surface, and drive the development of invasive fingers. We also study the effects of externally applied signaling factors. Applying bone morphogenic proteins, which inhibit SC and CP self-renewal, reduces invasiveness and organoid size. Applying hepatocyte growth factor, which enhances SC self-renewal, produces larger sizes and enhances finger development at low concentrations but suppresses fingers at high concentrations. These results are consistent with recent experiments on colon organoids. Because many cancers are hierarchically organized and are subject to feedback regulation similar to that in normal tissues, our results suggest that in cancer, control of cancer stem cell self-renewal should influence the size and shape in similar ways, thereby opening the door to novel therapies.

  8. Induction of KIAA1199/CEMIP is associated with colon cancer phenotype and poor patient survival.

    Science.gov (United States)

    Fink, Stephen P; Myeroff, Lois L; Kariv, Revital; Platzer, Petra; Xin, Baozhong; Mikkola, Debra; Lawrence, Earl; Morris, Nathan; Nosrati, Arman; Willson, James K V; Willis, Joseph; Veigl, Martina; Barnholtz-Sloan, Jill S; Wang, Zhenghe; Markowitz, Sanford D

    2015-10-13

    Genes induced in colon cancer provide novel candidate biomarkers of tumor phenotype and aggressiveness. We originally identified KIAA1199 (now officially called CEMIP) as a transcript highly induced in colon cancer: initially designating the transcript as Colon Cancer Secreted Protein 1. We molecularly characterized CEMIP expression both at the mRNA and protein level and found it is a secreted protein induced an average of 54-fold in colon cancer. Knockout of CEMIPreduced the ability of human colon cancer cells to form xenograft tumors in athymic mice. Tumors that did grow had increased deposition of hyaluronan, linking CEMIP participation in hyaluronan degradation to the modulation of tumor phenotype. We find CEMIP mRNA overexpression correlates with poorer patient survival. In stage III only (n = 31) or in combined stage II plus stage III colon cancer cases (n = 73), 5-year overall survival was significantly better (p = 0.004 and p = 0.0003, respectively) among patients with low CEMIP expressing tumors than those with high CEMIP expressing tumors. These results demonstrate that CEMIP directly facilitates colon tumor growth, and high CEMIP expression correlates with poor outcome in stage III and in stages II+III combined cohorts. We present CEMIP as a candidate prognostic marker for colon cancer and a potential therapeutic target.

  9. 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.

  10. Patients with Acromegaly Presenting with Colon Cancer: A Case Series

    Directory of Open Access Journals (Sweden)

    Murray B. Gordon

    2016-01-01

    Full Text Available Introduction. Frequent colonoscopy screenings are critical for early diagnosis of colon cancer in patients with acromegaly. Case Presentations. We performed a retrospective analysis of the incidental diagnoses of colon cancer from the ACCESS trial (ClinicalTrials.gov identifier: NCT01995734. Colon cancer was identified in 2 patients (4.5%. Case  1 patient was a 36-year-old male with acromegaly who underwent transsphenoidal surgery to remove the pituitary adenoma. After surgery, the patient underwent routine colonoscopy screening, which revealed a 40 mm tubular adenoma in the descending colon. A T1N1a carcinoma was surgically removed, and 1 of 22 lymph nodes was positive for metastatic disease, leading to a diagnosis of stage 3 colon cancer. Case  2 patient was a 50-year-old male with acromegaly who underwent transsphenoidal surgery to remove a 2 cm pituitary adenoma. The patient reported severe cramping and lower abdominal pain, and an invasive 8.1 cm3 grade 2 adenocarcinoma with signet rings was identified in the ascending colon and removed. Of the 37 lymph nodes, 34 were positive for the presence of tumor cells, and stage 3c colon cancer was confirmed. Conclusion. Current guidelines for colonoscopy screening at the time of diagnosis of acromegaly and at appropriate follow-up intervals should be followed.

  11. Regional and systemic distribution of anti-tumor x anti-CD3 heteroaggregate antibodies and cultured human peripheral blood lymphocytes in a human colon cancer xenograft

    International Nuclear Information System (INIS)

    Nelson, H.; Ramsey, P.S.; Kerr, L.A.; McKean, D.J.; Donohue, J.H.

    1990-01-01

    Anti-tumor antibody (317G5) covalently coupled to an anti-CD3 antibody (OKT3) produces a heteroaggregate (HA) antibody that can target PBL to lyse tumor cells expressing the appropriate tumor Ag. The i.v. and i.p. distribution of radiolabeled HA antibody 317G5 x OKT3 and of radiolabeled cultured human PBL were studied in athymic nude mice bearing solid intraperitoneal tumor established from the human colon tumor line, LS174T. Mice were injected with 125I-labeled HA antibody, 125I-labeled anti-tumor mAb, or 111In-labeled PBL, and at designated timepoints tissues were harvested and measured for radioactivity. 125I-317G5 x OKT3 localized specifically to tumor sites. Tumor radioactivity levels (percent injected dose/gram) were lower with 125I-317G5 x OKT3 HA antibody than with 125I-317G5 anti-tumor mAb, but were similar to levels reported for other anti-tumor mAb. The major difference in radioactivity levels observed between i.v. and i.p. administration of 125I-317G5 x OKT3 was an increase in hepatic radioactivity after i.v. HA antibody administration. HA antibodies produced from F(ab')2 fragments, which exhibit decreased m. w. and decreased Fc receptor-mediated binding, demonstrated improved tumor:tissue ratios as compared to intact antibody HA. 125I-317G5 F(ab')2 x OKT3 F(ab')2 antibody levels were equivalent to intact HA antibody levels in tumor, but were lower than intact HA antibody levels in the blood, bowel, and liver. Tumor:bowel ratios (20:1 at 48 h) were highest when 317G5 F(ab')2 x OKT3 F(ab')2 was injected i.p. Autoradiography confirmed that anti-tumor x anti-CD3 HA antibodies localized specifically to intraperitoneal tumor; that i.p. administered HA antibodies penetrated tumor directly; and that i.v. administered HA antibodies distributed along tumor vasculature

  12. RET is a potential tumor suppressor gene in colorectal cancer

    Science.gov (United States)

    Luo, Yanxin; Tsuchiya, Karen D.; Park, Dong Il; Fausel, Rebecca; Kanngurn, Samornmas; Welcsh, Piri; Dzieciatkowski, Slavomir; Wang, Jianping; Grady, William M.

    2012-01-01

    Cancer arises as the consequence of mutations and epigenetic alterations that activate oncogenes and inactivate tumor suppressor genes. Through a genome-wide screen for methylated genes in colon neoplasms, we identified aberrantly methylated RET in colorectal cancer. RET, a transmembrane receptor tyrosine kinase and a receptor for the GDNF-family ligands, was one of the first oncogenes to be identified and has been shown to be an oncogene in thyroid cancer and pheochromocytoma. However, unexpectedly, we found RET is methylated in 27% of colon adenomas and in 63% of colorectal cancers, and now provide evidence that RET has tumor suppressor activity in colon cancer. The aberrant methylation of RET correlates with decreased RET expression, whereas the restoration of RET in colorectal cancer cell lines results in apoptosis. Furthermore, in support of a tumor suppressor function of RET, mutant RET has also been found in primary colorectal cancer. We now show that these mutations inactivate RET, which is consistent with RET being a tumor suppressor gene in the colon. These findings suggest that the aberrant methylation of RET and the mutational inactivation of RET promote colorectal cancer formation and that RET can serve as a tumor suppressor gene in the colon. Moreover, the increased frequency of methylated RET in colon cancers compared to adenomas suggests RET inactivation is involved in the progression of colon adenomas to cancer. PMID:22751117

  13. Advanced colonic cancer associated with radiation colitis, report of a case

    Energy Technology Data Exchange (ETDEWEB)

    Moriyama, Tomohiko; Sato, Tomoo; Iwai, Keiichirou; Yao, Takashi; Mibu, Ryuichi; Iida, Mitsuo [Kyushu Univ., Fukuoka (Japan). Graduate School of Medical Sciences; Matsumoto, Takayuki [Kyushu Univ., Fukuoka (Japan). Hospital

    2002-07-01

    A 68-year-old woman with a history of irradiation for uterine cervical cancer was admitted to our institute, because of abdominal distension. Barium enema examination and total colonoscopy revealed narrowing, irregular mucosa and an ulcerating tumor in the sigmoid colon and a flat elevation in the transverse colon. Biopsy specimens from these tumors contained adenocarcinoma. Histological examination of the resected colon revealed the tumor in the sigmoid colon to be a well-differentiated adenocarcinoma invading the subserosa and that in the transverse colon to be an intramucosal adenocarcinoma. There were also areas of low or high grade dysplasia in the sigmoid colon. Histological findings compatible with radiation colitis were found in the sigmoid colon. These clinicopathologic features suggested a diagnosis of colonic cancer associated with radiation colitis. (author)

  14. Advanced colonic cancer associated with radiation colitis, report of a case

    International Nuclear Information System (INIS)

    Moriyama, Tomohiko; Sato, Tomoo; Iwai, Keiichirou; Yao, Takashi; Mibu, Ryuichi; Iida, Mitsuo; Matsumoto, Takayuki

    2002-01-01

    A 68-year-old woman with a history of irradiation for uterine cervical cancer was admitted to our institute, because of abdominal distension. Barium enema examination and total colonoscopy revealed narrowing, irregular mucosa and an ulcerating tumor in the sigmoid colon and a flat elevation in the transverse colon. Biopsy specimens from these tumors contained adenocarcinoma. Histological examination of the resected colon revealed the tumor in the sigmoid colon to be a well-differentiated adenocarcinoma invading the subserosa and that in the transverse colon to be an intramucosal adenocarcinoma. There were also areas of low or high grade dysplasia in the sigmoid colon. Histological findings compatible with radiation colitis were found in the sigmoid colon. These clinicopathologic features suggested a diagnosis of colonic cancer associated with radiation colitis. (author)

  15. [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.

  16. Antibody-linked drug destroys tumor cells and tumor blood vessels in many types of cancer | Center for Cancer Research

    Science.gov (United States)

    A team led by Brad St. Croix, Ph.D., Senior Associate Scientist, Mouse Cancer Genetics Program, has developed an antibody-drug conjugate (ADC) that destroys both tumor cells and the blood vessels that nourish them. The drug significantly shrank breast tumors, colon tumors and several other types of cancer and prolonged survival. Learn more...  

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. Locally advanced transverse colon cancer with Trousseau’s syndrome

    Directory of Open Access Journals (Sweden)

    V. A. Aliyev

    2012-01-01

    Full Text Available Migratory venous thrombosis is a manifestation of the rare paraneoplastic syndrome in patients with malignant neoplasms. The paper describes successful surgical treatment in a young patient with a colon tumor associated with Trousseau’s syndrome. The latter manifesting itself as ischemia forced urgent surgeons to amputate the lower third of the left leg. Locally advanced transverse colon cancer spreading to the great vessels was subsequently diagnosed. All paraneoplastic manifestations disappeared after tumor removal. The patient was professionally given surgical, anesthesiological, and resuscitative aids that not only improved his quality of life, but also gave the chance to prolong it.

  5. Activin and TGFβ use diverging mitogenic signaling in advanced colon cancer

    OpenAIRE

    Bauer, Jessica; Ozden, Ozkan; Akagi, Naomi; Carroll, Timothy; Principe, Daniel R.; Staudacher, Jonas J.; Spehlmann, Martina E.; Eckmann, Lars; Grippo, Paul J.; Jung, Barbara

    2015-01-01

    Background Understanding cell signaling pathways that contribute to metastatic colon cancer is critical to risk stratification in the era of personalized therapeutics. Here, we dissect the unique involvement of mitogenic pathways in a TGFβ or activin-induced metastatic phenotype of colon cancer. Method Mitogenic signaling/growth factor receptor status and p21 localization were correlated in primary colon cancers and intestinal tumors from either AOM/DSS treated ACVR2A (activin receptor 2) −/−...

  6. 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.

  7. Prognostic impact of Metadherin-SND1 interaction in colon cancer.

    Science.gov (United States)

    Wang, Nan; Du, Xilin; Zang, Li; Song, Nuan; Yang, Tao; Dong, Rui; Wu, Tao; He, Xianli; Lu, Jianguo

    2012-12-01

    The interaction between Metadherin (MTDH) and Staphylococcal nuclease homology domain containing 1 (SND1) is involved in tumorigenesis and tumor progression of several human malignancies. However, its roles in colon cancer are still unclear. To investigate the clinical value of MTDH and SND1 expression in colon cancer. Immunohistochemical staining was performed to detect the expression of MTDH and SND1 using human colon cancer and their corresponding non-cancerous colon tissues from 196 patients' biopsies. Positive expression of MTDH and SND1 were both increased in colon cancer tissues compared to paired non-cancerous colon tissues. There was a positive correlation between MTDH and SND1 expression in colon cancer tissues (r = 0.86, p colon cancer patients with positive expression of MTDH and SND1 were significantly shorter than those without their expression (both p = 0.01). Furthermore, multivariate Cox regression analysis suggested that positive expression of MTDH and SND1 was an independent poor prognostic predictor in colon cancer. Our data suggest that the increased expression of MTDH and/or SND1 is closely related to carcinogenesis, progression, and prognosis of colon cancer. The co-expression of MTDH/SND1 may be a novel distinctive marker to benefit us in prediction of the prognosis in colon cancer.

  8. 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.

  9. Treatment of colon cancer with oncolytic herpes simplex virus in preclinical models.

    Science.gov (United States)

    Yang, H; Peng, T; Li, J; Wang, Y; Zhang, W; Zhang, P; Peng, S; Du, T; Li, Y; Yan, Q; Liu, B

    2016-05-01

    Cancer stem cells (CSCs), which are a rare population in any type of cancer, including colon cancer, are tumorigenic and responsible for cancer recurrence and metastasis. CSCs have been isolated from a number of different solid tumors recently, although the isolation of CSCs in colon cancer is still challenging. We cultured colon cancer cells in stem cell medium to obtain colonosphere cells. These cells possessed the characteristics of CSCs, with a high capacity of tumorigenicity, migration and invasion in vitro and in vivo. The isolation and identification of CSCs have provided new targets for the therapeutics. Oncolytic herpes simplex viruses (oHSV) are an effective strategy for killing colon cancer cells in preclinical models. Here, we examined the efficacy of an oncolytic herpes simplex virus type 2 (oHSV2) in killing colon cancer cells and colon cancer stem-like cells (CSLCs). oHSV2 was found to be highly cytotoxic to the adherent and sphere cells in vitro, and oHSV2 treatment in vivo significantly inhibited tumor growth. This study demonstrates that oHSV2 is effective against colon cancer cells and colon CSLCs and could be a promising strategy for treating colon cancer patients.

  10. Relationship between tumor gene expression and recurrence in four independent studies of patients with stage II/III colon cancer treated with surgery alone or surgery plus adjuvant fluorouracil plus leucovorin.

    Science.gov (United States)

    O'Connell, Michael J; Lavery, Ian; Yothers, Greg; Paik, Soonmyung; Clark-Langone, Kim M; Lopatin, Margarita; Watson, Drew; Baehner, Frederick L; Shak, Steven; Baker, Joffre; Cowens, J Wayne; Wolmark, Norman

    2010-09-01

    These studies were conducted to determine the relationship between quantitative tumor gene expression and risk of cancer recurrence in patients with stage II or III colon cancer treated with surgery alone or surgery plus fluorouracil (FU) and leucovorin (LV) to develop multigene algorithms to quantify the risk of recurrence as well as the likelihood of differential treatment benefit of FU/LV adjuvant chemotherapy for individual patients. We performed quantitative reverse transcription polymerase chain reaction (RT-qPCR) on RNA extracted from fixed, paraffin-embedded (FPE) tumor blocks from patients with stage II or III colon cancer who were treated with surgery alone (n = 270 from National Surgical Adjuvant Breast and Bowel Project [NSABP] C-01/C-02 and n = 765 from Cleveland Clinic [CC]) or surgery plus FU/LV (n = 308 from NSABP C-04 and n = 508 from NSABP C-06). Overall, 761 candidate genes were studied in C-01/C-02 and C-04, and a subset of 375 genes was studied in CC/C-06. A combined analysis of the four studies identified 48 genes significantly associated with risk of recurrence and 66 genes significantly associated with FU/LV benefit (with four genes in common). Seven recurrence-risk genes, six FU/LV-benefit genes, and five reference genes were selected, and algorithms were developed to identify groups of patients with low, intermediate, and high likelihood of recurrence and benefit from FU/LV. RT-qPCR of FPE colon cancer tissue applied to four large independent populations has been used to develop multigene algorithms for estimating recurrence risk and benefit from FU/LV. These algorithms are being independently validated, and their clinical utility is being evaluated in the Quick and Simple and Reliable (QUASAR) study.

  11. 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.

  12. COX-2 gene expression in colon cancer tissue related to regulating factors and promoter methylation status

    International Nuclear Information System (INIS)

    Asting, Annika Gustafsson; Carén, Helena; Andersson, Marianne; Lönnroth, Christina; Lagerstedt, Kristina; Lundholm, Kent

    2011-01-01

    Increased cyclooxygenase activity promotes progression of colorectal cancer, but the mechanisms behind COX-2 induction remain elusive. This study was therefore aimed to define external cell signaling and transcription factors relating to high COX-2 expression in colon cancer tissue. Tumor and normal colon tissue were collected at primary curative operation in 48 unselected patients. COX-2 expression in tumor and normal colon tissue was quantified including microarray analyses on tumor mRNA accounting for high and low tumor COX-2 expression. Cross hybridization was performed between tumor and normal colon tissue. Methylation status of up-stream COX-2 promoter region was evaluated. Tumors with high COX-2 expression displayed large differences in gene expression compared to normal colon. Numerous genes with altered expression appeared in tumors of high COX-2 expression compared to tumors of low COX-2. COX-2 expression in normal colon was increased in patients with tumors of high COX-2 compared to normal colon from patients with tumors of low COX-2. IL1β, IL6 and iNOS transcripts were up-regulated among external cell signaling factors; nine transcription factors (ATF3, C/EBP, c-Fos, Fos-B, JDP2, JunB, c-Maf, NF-κB, TCF4) showed increased expression and 5 (AP-2, CBP, Elk-1, p53, PEA3) were decreased in tumors with high COX-2. The promoter region of COX-2 gene did not show consistent methylation in tumor or normal colon tissue. Transcription and external cell signaling factors are altered as covariates to COX-2 expression in colon cancer tissue, but DNA methylation of the COX-2 promoter region was not a significant factor behind COX-2 expression in tumor and normal colon tissue

  13. COX-2 gene expression in colon cancer tissue related to regulating factors and promoter methylation status

    Directory of Open Access Journals (Sweden)

    Lagerstedt Kristina

    2011-06-01

    Full Text Available Abstract Background Increased cyclooxygenase activity promotes progression of colorectal cancer, but the mechanisms behind COX-2 induction remain elusive. This study was therefore aimed to define external cell signaling and transcription factors relating to high COX-2 expression in colon cancer tissue. Method Tumor and normal colon tissue were collected at primary curative operation in 48 unselected patients. COX-2 expression in tumor and normal colon tissue was quantified including microarray analyses on tumor mRNA accounting for high and low tumor COX-2 expression. Cross hybridization was performed between tumor and normal colon tissue. Methylation status of up-stream COX-2 promoter region was evaluated. Results Tumors with high COX-2 expression displayed large differences in gene expression compared to normal colon. Numerous genes with altered expression appeared in tumors of high COX-2 expression compared to tumors of low COX-2. COX-2 expression in normal colon was increased in patients with tumors of high COX-2 compared to normal colon from patients with tumors of low COX-2. IL1β, IL6 and iNOS transcripts were up-regulated among external cell signaling factors; nine transcription factors (ATF3, C/EBP, c-Fos, Fos-B, JDP2, JunB, c-Maf, NF-κB, TCF4 showed increased expression and 5 (AP-2, CBP, Elk-1, p53, PEA3 were decreased in tumors with high COX-2. The promoter region of COX-2 gene did not show consistent methylation in tumor or normal colon tissue. Conclusions Transcription and external cell signaling factors are altered as covariates to COX-2 expression in colon cancer tissue, but DNA methylation of the COX-2 promoter region was not a significant factor behind COX-2 expression in tumor and normal colon tissue.

  14. 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

  15. ER-Stress-Induced Differentiation Sensitizes Colon Cancer Stem Cells to Chemotherapy

    NARCIS (Netherlands)

    Wielenga, Mattheus C. B.; Colak, Selcuk; Heijmans, Jarom; van Lidth de Jeude, Jooske F.; Rodermond, Hans M.; Paton, James C.; Paton, Adrienne W.; Vermeulen, Louis; Medema, Jan Paul; van den Brink, Gijs R.

    2015-01-01

    Colon cancer stem cells (colon-CSCs) are more resistant to conventional chemotherapy than differentiated cancer cells. This subset of therapy refractory cells is therefore believed to play an important role in post-therapeutic tumor relapse. In order to improve the rate of sustained response to

  16. SOX9 Expression Predicts Relapse of Stage II Colon Cancer Patients

    DEFF Research Database (Denmark)

    Espersen, Maiken Lise Marcker; Linnemann, Dorte; Christensen, Ib Jarle

    2016-01-01

    The aim of this study was to investigate if the protein expression of Sex-determining region y-box 9 (SOX9) in primary tumors could predict relapse of stage II colon cancer patients.144 patients with stage II primary colon cancer were retrospectively enrolledin the study. SOX9 expression...

  17. Is There a Proximal Migration of Colon Cancers? An Experience from Regional Cancer Center

    Directory of Open Access Journals (Sweden)

    Gouda YG

    2016-01-01

    Full Text Available Colorectal cancers stands 3rd in males and 2nd in females in order of frequency of most common cancers worldwide and in developed countries. And is 4th common in males and 5th common in females in developing countries. Colonic tumors located at the caecum, ascending colon, hepatic flexure, transverse colon, and splenic flexure were defined as right sided colon cancer and tumors located at the descending colon, sigmoid, rectosigmoid and rectum were defined as left sided colorectal cancer. The difference in percentage deviation is statistically not significant and present study concludes that there is no actual migration of colon cancers towards right side. In the present study there is higher proportion of males being affected with Right colon cancers group which is significant and doesn’t go in accordance with the literature published, where females are more affected. Since this is institutional based study there is further need for studies based on population. As the mean age at presentation was very earlier than in the developed countries, the thrust is in us to have an effective screening programs.

  18. Identifying colon cancer risk modules with better classification performance based on human signaling network.

    Science.gov (United States)

    Qu, Xiaoli; Xie, Ruiqiang; Chen, Lina; Feng, Chenchen; Zhou, Yanyan; Li, Wan; Huang, Hao; Jia, Xu; Lv, Junjie; He, Yuehan; Du, Youwen; Li, Weiguo; Shi, Yuchen; He, Weiming

    2014-10-01

    Identifying differences between normal and tumor samples from a modular perspective may help to improve our understanding of the mechanisms responsible for colon cancer. Many cancer studies have shown that signaling transduction and biological pathways are disturbed in disease states, and expression profiles can distinguish variations in diseases. In this study, we integrated a weighted human signaling network and gene expression profiles to select risk modules associated with tumor conditions. Risk modules as classification features by our method had a better classification performance than other methods, and one risk module for colon cancer had a good classification performance for distinguishing between normal/tumor samples and between tumor stages. All genes in the module were annotated to the biological process of positive regulation of cell proliferation, and were highly associated with colon cancer. These results suggested that these genes might be the potential risk genes for colon cancer. Copyright © 2013. Published by Elsevier Inc.

  19. 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.

  20. Engineered Resistant-Starch (ERS) Diet Shapes Colon Microbiota Profile in Parallel with the Retardation of Tumor Growth in In Vitro and In Vivo Pancreatic Cancer Models

    Science.gov (United States)

    Panebianco, Concetta; Adamberg, Kaarel; Adamberg, Signe; Saracino, Chiara; Jaagura, Madis; Kolk, Kaia; Di Chio, Anna Grazia; Graziano, Paolo; Vilu, Raivo; Pazienza, Valerio

    2017-01-01

    Background/aims: Pancreatic cancer (PC) is ranked as the fourth leading cause of cancer-related deaths worldwide. Despite recent advances in treatment options, a modest impact on the outcome of the disease is observed so far. We have previously demonstrated that short-term fasting cycles have the potential to improve the efficacy of chemotherapy against PC. The aim of this study was to assess the effect of an engineered resistant-starch (ERS) mimicking diet on the growth of cancer cell lines in vitro, on the composition of fecal microbiota, and on tumor growth in an in vivo pancreatic cancer mouse xenograft model. Materials and Methods: BxPC-3, MIA PaCa-2 and PANC-1 cells were cultured in the control, and in the ERS-mimicking diet culturing condition, to evaluate tumor growth and proliferation pathways. Pancreatic cancer xenograft mice were subjected to an ERS diet to assess tumor volume and weight as compared to mice fed with a control diet. The composition and activity of fecal microbiota were further analyzed in growth experiments by isothermal microcalorimetry. Results: Pancreatic cancer cells cultured in an ERS diet-mimicking medium showed decreased levels of phospho-ERK1/2 (extracellular signal-regulated kinase proteins) and phospho-mTOR (mammalian target of rapamycin) levels, as compared to those cultured in standard medium. Consistently, xenograft pancreatic cancer mice subjected to an ERS diet displayed significant retardation in tumor growth. In in vitro growth experiments, the fecal microbial cultures from mice fed with an ERS diet showed enhanced growth on residual substrates, higher production of formate and lactate, and decreased amounts of propionate, compared to fecal microbiota from mice fed with the control diet. Conclusion: A positive effect of the ERS diet on composition and metabolism of mouse fecal microbiota shown in vitro is associated with the decrease of tumor progression in the in vivo PC xenograft mouse model. These results suggest that

  1. Nutrients and Risk of Colon Cancer

    Directory of Open Access Journals (Sweden)

    Les Mery

    2010-02-01

    Full Text Available 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.

  2. Nutrients and Risk of Colon Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Jinfu, E-mail: Jinfu.hu@phac-aspc.gc.ca [Evidence and Risk Assessment Division, Centre for Chronic Disease Prevention and Control, Public Health Agency of Canada, 785 Carling Avenue, AL: 6807B, Ottawa, Ontario K1A 0K9 (Canada); La Vecchia, Carlo [Istituto di Ricerche Farmacologiche “Mario Negri,” Via La Masa, 19-20156 Milan (Italy); Istituto di Statistica Medica e Biometria, Università degli Studi di Milano, Via Venezian, 1, 20133 Milan (Italy); Negri, Eva [Istituto di Ricerche Farmacologiche “Mario Negri,” Via La Masa, 19-20156 Milan (Italy); Mery, Les [Evidence and Risk Assessment Division, Centre for Chronic Disease Prevention and Control, Public Health Agency of Canada, 785 Carling Avenue, AL: 6807B, Ottawa, Ontario K1A 0K9 (Canada)

    2010-02-10

    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.

  3. 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

  4. Diet-induced obesity promotes colon tumor development in azoxymethane-treated mice.

    Directory of Open Access Journals (Sweden)

    Iina Tuominen

    Full Text Available Obesity is an important risk factor for colon cancer in humans, and numerous studies have shown that a high fat diet enhances colon cancer development. As both increased adiposity and high fat diet can promote tumorigenesis, we examined the effect of diet-induced obesity, without ongoing high fat diet, on colon tumor development. C57BL/6J male mice were fed regular chow or high fat diet for 8 weeks. Diets were either maintained or switched resulting in four experimental groups: regular chow (R, high fat diet (H, regular chow switched to high fat diet (RH, and high fat diet switched to regular chow (HR. Mice were then administered azoxymethane to induce colon tumors. Tumor incidence and multiplicity were dramatically smaller in the R group relative to all groups that received high fat diet at any point. The effect of obesity on colon tumors could not be explained by differences in aberrant crypt foci number. Moreover, diet did not alter colonic expression of pro-inflammatory cytokines tumor necrosis factor-α, interleukin-6, interleukin-1β, and interferon-γ, which were measured immediately after azoxymethane treatment. Crypt apoptosis and proliferation, which were measured at the same time, were increased in the HR relative to all other groups. Our results suggest that factors associated with obesity - independently of ongoing high fat diet and obesity - promote tumor development because HR group animals had significantly more tumors than R group, and these mice were fed the same regular chow throughout the entire carcinogenic period. Moreover, there was no difference in the number of aberrant crypt foci between these groups, and thus the effect of obesity appears to be on subsequent stages of tumor development when early preneoplastic lesions transition into adenomas.

  5. CD133+CD24lo defines a 5-Fluorouracil-resistant colon cancer stem cell-like phenotype

    Science.gov (United States)

    Paschall, Amy V.; Yang, Dafeng; Lu, Chunwan; Redd, Priscilla S.; Choi, Jeong-Hyeon; Heaton, Christopher M.; Lee, Jeffrey R.; Nayak-Kapoor, Asha; Liu, Kebin

    2016-01-01

    The chemotherapeutic agent 5-Fluorouracil (5-FU) is the most commonly used drug for patients with advanced colon cancer. However, development of resistance to 5-FU is inevitable in almost all patients. The mechanism by which colon cancer develops 5-FU resistance is still unclear. One recently proposed theory is that cancer stem-like cells underlie colon cancer 5-FU resistance, but the phenotypes of 5-FU-resistant colon cancer stem cells are still controversial. We report here that 5-FU treatment selectively enriches a subset of CD133+ colon cancer cells in vitro. 5-FU chemotherapy also increases CD133+ tumor cells in human colon cancer patients. However, sorted CD133+ colon cancer cells exhibit no increased resistance to 5-FU, and CD133 levels exhibit no correlation with colon cancer patient survival or cancer recurrence. Genome-wide analysis of gene expression between sorted CD133+ colon cancer cells and 5-FU-selected colon cancer cells identifies 207 differentially expressed genes. CD24 is one of the genes whose expression level is lower in the CD133+ and 5-FU-resistant colon cancer cells as compared to CD133+ and 5-FU-sensitive colon cancer cells. Consequently, CD133+CD24lo cells exhibit decreased sensitivity to 5-FU. Therefore, we determine that CD133+CD24lo phenotype defines 5-FU-resistant human colon cancer stem cell-like cells. PMID:27659530

  6. Clinical investigation of TROP-2 as an independent biomarker and potential therapeutic target in colon cancer.

    Science.gov (United States)

    Zhao, Peng; Yu, Hai-Zheng; Cai, Jian-Hui

    2015-09-01

    Colon cancer is associated with a severe demographic and economic burden worldwide. The pathogenesis of colon cancer is highly complex and involves sequential genetic and epigenetic mechanisms. Despite extensive investigation, the pathogenesis of colon cancer remains to be elucidated. As the third most common type of cancer worldwide, the treatment options for colon cancer are currently limited. Human trophoblast cell‑surface marker (TROP‑2), is a cell‑surface transmembrane glycoprotein overexpressed by several types of epithelial carcinoma. In addition, TROP‑2 has been demonstrated to be associated with tumorigenesis and invasiveness in solid types of tumor. The aim of the present study was to investigate the protein expression of TROP‑2 in colon cancer tissues, and further explore the association between the expression of TROP‑2 and clinicopathological features of patients with colon cancer. The expression and localization of the TROP‑2 protein was examined using western blot analysis and immunofluorescence staining. Finally, the expression of TROP‑2 expression was correlated to conventional clinicopathological features of colon cancer using a χ2 test. The results revealed that TROP‑2 protein was expressed at high levels in the colon cancer tissues, which was associated with the development and pathological process of colon cancer. Therefore, TROP‑2 may be used as a biomarker to determine the clinical prognosis, and as a potential therapeutic target in colon cancer.

  7. General Information about Colon Cancer

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... VEGF inhibitors and angiogenesis inhibitors . Epidermal growth factor receptor (EGFR) inhibitor therapy: EGFRs are proteins found on ...

  8. Treatment Option Overview (Colon Cancer)

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... VEGF inhibitors and angiogenesis inhibitors . Epidermal growth factor receptor (EGFR) inhibitor therapy: EGFRs are proteins found on ...

  9. Oncogenetic tree model of somatic mutations and DNA methylation in colon tumors.

    Science.gov (United States)

    Sweeney, Carol; Boucher, Kenneth M; Samowitz, Wade S; Wolff, Roger K; Albertsen, Hans; Curtin, Karen; Caan, Bette J; Slattery, Martha L

    2009-01-01

    Our understanding of somatic alterations in colon cancer has evolved from a concept of a series of events taking place in a single sequence to a recognition of multiple pathways. An oncogenetic tree is a model intended to describe the pathways and sequence of somatic alterations in carcinogenesis without assuming that tumors will fall in mutually exclusive categories. We applied this model to data on colon tumor somatic alterations. An oncogenetic tree model was built using data on mutations of TP53, KRAS2, APC, and BRAF genes, methylation at CpG sites of MLH1 and TP16 genes, methylation in tumor (MINT) markers, and microsatellite instability (MSI) for 971 colon tumors from a population-based series. Oncogenetic tree analysis resulted in a reproducible tree with three branches. The model represents methylation of MINT markers as initiating a branch and predisposing to MSI, methylation of MHL1 and TP16, and BRAF mutation. APC mutation is the first alteration in an independent branch and is followed by TP53 mutation. KRAS2 mutation was placed a third independent branch, implying that it neither depends on, nor predisposes to, the other alterations. Individual tumors were observed to have alteration patterns representing every combination of one, two, or all three branches. The oncogenetic tree model assumptions are appropriate for the observed heterogeneity of colon tumors, and the model produces a useful visual schematic of the sequence of events in pathways of colon carcinogenesis.

  10. 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

  11. Overexpression of Long Non-Coding RNA TUG1 Promotes Colon Cancer Progression.

    Science.gov (United States)

    Zhai, Hui-Yuan; Sui, Ming-Hua; Yu, Xiao; Qu, Zhen; Hu, Jin-Chen; Sun, Hai-Qing; Zheng, Hai-Tao; Zhou, Kai; Jiang, Li-Xin

    2016-09-16

    BACKGROUND Colon cancer is one of the most prevalent and deadly cancers worldwide. It is still necessary to further define the mechanisms and explore therapeutic targets of colon cancer. Dysregulation of long noncoding RNAs (lncRNAs) has been shown to be correlated with diverse biological processes, including tumorigenesis. This study aimed to characterize the biological mechanism of taurine-upregulated gene 1 (TUG1) in colon cancer. MATERIAL AND METHODS qRT-PCR was used to analyze the expression level of TUG1 and p63 in 75 colon cancer tissues and the matched adjacent non-tumor tissue. In vitro, cultured colon cancer cell lines HCT-116 and LoVo were used as cell models. TUG1 and p63 were silenced via transferring siRNA into HCT-116 or LoVo. The effects of TUG1 were investigated by examining cell proliferation, apoptosis, and migration. RESULTS Among the 75 colon cancer cases, the expression of TUG1 was significantly higher in colon cancer tissues compared with the matched adjacent non-tumor tissue, while p63 expression was lower in the tumor tissue. In HCT-116 and LoVo, the expression of TUG1 was significantly increased by p63 siRNA transfection. Furthermore, down-regulation of TUG1 by siRNA significantly inhibited the cell proliferation and promoted colon cancer cell apoptosis. In addition, inhibition of TUG1 expression significantly blocked the cell migration ability of colon cancer cells. CONCLUSIONS LncRNA TUG1 may serve as a potential oncogene for colon cancer. Overexpressed TUG1 may contribute to promoting cell proliferation and migration in colon cancer cells.

  12. 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.

  13. The prognostic significance of extramural deposits and extracapsular lymph node invasion in colon cancer.

    LENUS (Irish Health Repository)

    Al Sahaf, Osama

    2011-08-01

    The status of resected lymph nodes in colon cancer determines prognosis and further treatment. The American Joint Committee on Cancer staging system has designated extramural nodules as nonnodal disease and classified them as extensions of the T category in the sixth edition and as site-specific tumor deposits in the seventh edition. Extracapsular lymph node extension is an established poor prognostic indicator in many cancers. Its significance in colon cancer has not been extensively investigated.

  14. Expression and clinical significance of tyrosine phosphatase SHP-2 in colon cancer.

    Science.gov (United States)

    Cai, Peifen; Guo, Wenjie; Yuan, Huaqin; Li, Qian; Wang, Weicheng; Sun, Yang; Li, Xiaomin; Gu, Yanhong

    2014-04-01

    Protein-tyrosine phosphatase SHP-2, encoded by gene PTPN11, has been identified as a tumor-promoting factor in several types of leukemia and is hyper-activated by other mechanisms in some solid tumors including gastric cancer, breast cancer, non-small cell lung cancer (NSCLC), etc. But few were reported on the expression and significances of SHP-2 in colon cancer. Here, we detect SHP-2 expression in colon cancer cells, colon cancer-induced by AOM+DSS in mice and 232 human colon cancer specimens, including 58 groups of self-matched adjacent peritumor tissues and normal tissues. We found that compared to the normal colon tissues, SHP-2 significantly decreased in tumor tissues (Pcolon tumor cells as well as mice colon tumors. And in humans samples, low SHP-2 expression showed a significantly correlation with poor tumor differentiation (P<0.05), late TNM stage (P=0.1666) and lymph node metastasis (P<0.05). Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  15. 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...

  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. [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.

  18. Cell Transformation by PTP1B Truncated Mutants Found in Human Colon and Thyroid Tumors.

    Science.gov (United States)

    Mei, Wenhan; Wang, Kemin; Huang, Jian; Zheng, Xinmin

    2016-01-01

    Expression of wild-type protein tyrosine phosphatase (PTP) 1B may act either as a tumor suppressor by dysregulation of protein tyrosine kinases or a tumor promoter through Src dephosphorylation at Y527 in human breast cancer cells. To explore whether mutated PTP1B is involved in human carcinogenesis, we have sequenced PTP1B cDNAs from human tumors and found splice mutations in ~20% of colon and thyroid tumors. The PTP1BΔE6 mutant expressed in these two tumor types and another PTP1BΔE5 mutant expressed in colon tumor were studied in more detail. Although PTP1BΔE6 revealed no phosphatase activity compared with wild-type PTP1B and the PTP1BΔE5 mutant, its expression induced oncogenic transformation of rat fibroblasts without Src activation, indicating that it involved signaling pathways independent of Src. The transformed cells were tumourigenic in nude mice, suggesting that the PTP1BΔE6 affected other molecule(s) in the human tumors. These observations may provide a novel therapeutic target for colon and thyroid cancer.

  19. Correlation between the methylation of APC gene promoter and colon cancer.

    Science.gov (United States)

    Li, Bing-Qiang; Liu, Peng-Peng; Zhang, Cai-Hua

    2017-08-01

    The present study was planned to explore the correlation between the methylation of APC (adenomatous polyposis coli) and colon carcinogenesis. Colon cancer tissues and tumor-adjacent normal tissues of 60 colon cancer patients (who received surgical operation in our hospital from January 2012 to December 2014) were collected. SW1116 cells in human colon cancer tissues were selected for culturing. 5-aza-2c-deoxycytidine (5-aza-dC) was utilized as an inhibitor of the methylation for APC gene. Methylation specific PCR (MSP) was utilized for detection of APC methylation in SW1116 cells. The MTT and Transwell assays were performed to detect the effect of the methylation of APC gene on the proliferation and invasive abilities of SW1116 cells. The correlation between the methylation of APC gene and pathological parameters of colon cancer patients was analyzed. MSP results revealed that 41 cases (68.33%) showed methylation of APC gene in colon cancer tissues. No methylation of APC gene was found in tumor-adjacent normal tissues. 5-aza-dC was able to inhibit the methylation of APC gene in SW1116 cells. APC gene methylation was correlated with tumor size, differentiation degree, lymph node metastasis and Dukes staging. In conclusion, the levels of the methylation of APC in colon cancer tissues and SW1116 cells are relatively high. The methylation of APC promoted the proliferation and invasion abilities of SW1116 cells. Furthermore, methylation is correlated with a variety of clinicopathological features of colon cancer patients.

  20. Colorectal cancer: genetic abnormalities, tumor progression, tumor heterogeneity, clonal evolution and tumor-initiating cells.

    Science.gov (United States)

    Testa, Ugo; Pelosi, Elvira; Castelli, Germana

    2018-04-13

    Colon cancer is the third most common cancer worldwide. Most colorectal cancer occurrences are sporadic, not related to genetic predisposition or family history; however, 20-30% of patients with colorectal cancer have a family history of colorectal cancer and 5% of these tumors arise in the setting of a Mendelian inheritance syndrome. In many patients, the development of a colorectal cancer is preceded by a benign neoplastic lesion: either an adenomatous polyp or a serrated polyp. Studies carried out in the last years have characterized the main molecular alterations occurring in colorectal cancers, showing that the tumor of each patient displays from two to eight driver mutations. The ensemble of molecular studies, including gene expression studies, has led to two proposed classifications of colorectal cancers, with the identification of four/five non-overlapping groups. The homeostasis of the rapidly renewing intestinal epithelium is ensured by few stem cells present at the level of the base of intestinal crypts. Various experimental evidence suggests that colorectal cancers may derive from the malignant transformation of intestinal stem cells or of intestinal cells that acquire stem cell properties following malignant transformation. Colon cancer stem cells seem to be involved in tumor chemoresistance, radioresistance and relapse.

  1. 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 ...

  2. Oncogenic KRAS activates an embryonic stem cell-like program in human colon cancer initiation.

    Science.gov (United States)

    Le Rolle, Anne-France; Chiu, Thang K; Zeng, Zhaoshi; Shia, Jinru; Weiser, Martin R; Paty, Philip B; Chiu, Vi K

    2016-01-19

    Colorectal cancer is the third most frequently diagnosed cancer worldwide. Prevention of colorectal cancer initiation represents the most effective overall strategy to reduce its associated morbidity and mortality. Activating KRAS mutation (KRASmut) is the most prevalent oncogenic driver in colorectal cancer development, and KRASmut inhibition represents an unmet clinical need. We apply a systems-level approach to study the impact of KRASmut on stem cell signaling during human colon cancer initiation by performing gene set enrichment analysis on gene expression from human colon tissues. We find that KRASmut imposes the embryonic stem cell-like program during human colon cancer initiation from colon adenoma to stage I carcinoma. Expression of miR145, an embryonic SC program inhibitor, promotes cell lineage differentiation marker expression in KRASmut colon cancer cells and significantly suppresses their tumorigenicity. Our data support an in vivo plasticity model of human colon cancer initiation that merges the intrinsic stem cell properties of aberrant colon stem cells with the embryonic stem cell-like program induced by KRASmut to optimize malignant transformation. Inhibition of the embryonic SC-like program in KRASmut colon cancer cells reveals a novel therapeutic strategy to programmatically inhibit KRASmut tumors and prevent colon cancer.

  3. 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.

  4. [A Case of Huge Colon Cancer Accompanied with Severe Hypoproteinemia].

    Science.gov (United States)

    Hiraki, Sakurao; Kanesada, Kou; Harada, Toshio; Tada, Kousuke; Fukuda, Shintaro

    2017-11-01

    We report a case of huge colon cancer accompanied with severe hypoproteinemia. A7 4-year-old woman was referred to our hospital because of abdominal fullness. Blood examinations revealed anemia(hemoglobin 8.8 g/dL)and sever hypopro- teinemia(total protein 4.5 g/dL, albumin 1.1 g/dL). Computed tomography examination of abdomen revealed ascites and large tumor(12.5×10.5 cm)at the right side colon. By further examinations ascending colon cancer without distant metastasis was diagnosed, then we performed right hemicolectomy and primary intestinal anastomosis by open surgery. Ahuge type 1 tumor(18×12 cm)was observed in the excised specimen, which invaded to terminal ileum directly. The tumor was diagnosed moderately differentiated adenocarcinoma without lymph node metastasis(pT3N0M0, fStage II ). Postoperative course was uneventful and serum protein concentration recovered gradually to normal range. Protein leakage from the tumor cannot be proved by this case, so we can't diagnose as protein-losing enteropathy, but we strongly doubt this etiology from postoperative course in this case.

  5. Colon cancer proliferating desulfosinigrin in wasabi (Wasabia japonica).

    Science.gov (United States)

    Weil, Marvin J; Zhang, Yanjun; Nair, Muraleedharan G

    2004-01-01

    A reduced incidence of different types of cancer has been linked to consumption of Brassica vegetables, and there is evidence that glucosinolates (GSLs) and their hydrolysis products play a role in reducing cancer risk. Wasabi (Wasabia japonica) and horseradish (Armoracia rusticana), both Brassica vegetables, are widely used condiments both in Japanese cuisine and in the United States. Desulfosinigrin (DSS) (1) was isolated from a commercially available wasabi powder and from fresh wasabi roots. Sinigrin (2) was isolated from horseradish roots. DSS and sinigrin were evaluated for their inhibitory effects on cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes, on lipid peroxidation, and on the proliferation of human colon (HCT-116), breast (MCF-7), lung (NCIH460), and central nervous system (CNS, SF-268) cancer cell lines. DSS did not inhibit COX enzymes or lipid peroxidation at 250 microg/ml. Sinigrin inhibited lipid peroxidation by 71% at 250 microg/ml. However, DSS promoted the growth of HCT-116 (colon) and NCI H460 (lung) human cancer cells as determined by the MTT assay in a concentration-dependent manner. At 3.72 microg/ml, a 27% increase in the number of viable human HCT-116 colon cancer cells was observed; the corresponding increases at 7.50 and 15 microg/ml were 42 and 69%, respectively. At 60 microg/ml, DSS doubled the number of HCT-16 colon cancer cells. For NCI H460 human lung cancer cells, DSS at 60 microg/ml increased the cell number by 20%. Sinigrin showed no proliferating effect on the tumor cells tested. This is the first report of the tumor cell-proliferating activity by a desulfoglucosinolate, the biosynthetic precursor of GSLs found in Brassica spp.

  6. Combinatorial nanomedicines for colon cancer therapy.

    Science.gov (United States)

    Anitha, A; Maya, S; Sivaram, Amal J; Mony, U; Jayakumar, R

    2016-01-01

    Colon cancer is one of the major causes of cancer deaths worldwide. Even after surgical resection and aggressive chemotherapy, 50% of colorectal carcinoma patients develop recurrent disease. Thus, the rationale of developing new therapeutic approaches to improve the current chemotherapeutic regimen would be highly recommended. There are reports on the effectiveness of combination chemotherapy in colon cancer and it has been practiced in clinics for long time. These approaches are associated with toxic side effects. Later, the drug delivery research had shown the potential of nanoencapsulation techniques and active targeting as an effective method to improve the effectiveness of chemotherapy with less toxicity. This current focus article provides a brief analysis of the ongoing research in the colon cancer area using the combinatorial nanomedicines and its outcome. © 2015 Wiley Periodicals, Inc.

  7. Surgical and pathological outcomes of laparoscopic surgery for transverse colon cancer.

    Science.gov (United States)

    Lee, Y S; Lee, I K; Kang, W K; Cho, H M; Park, J K; Oh, S T; Kim, J G; Kim, Y H

    2008-07-01

    Several multi-institutional prospective randomized trials have demonstrated short-term benefits using laparoscopy. Now the laparoscopic approach is accepted as an alternative to open surgery for colon cancer. However, in prior trials, the transverse colon was excluded. Therefore, it has not been determined whether laparoscopy can be used in the setting of transverse colon cancer. This study evaluated the peri-operative clinical outcomes and oncological quality by pathologic outcomes of laparoscopic surgery for transverse colon cancer. Analysis of the medical records of patients who underwent laparoscopic colorectal resection from August 2004 to November 2007 was made. Computed tomography, barium enema, and colonoscopy were performed to localize the tumor preoperatively. Extended right hemicolectomy, transverse colectomy, and extended left hemicolectomy were performed for transverse colon cancer. Surgical outcomes and pathologic outcomes were compared between transverse colon cancer (TCC) and other site colon cancer (OSCC). Of the 312 colorectal cancer patients, 94 patients underwent laparoscopic surgery for OSCC, and 34 patients underwent laparoscopic surgery for TCC. Patients with TCC were similar to patients with OSCC in age, gender, body mass index, operating time, blood loss, time to pass flatus, start of diet, hospital stay, tumor size, distal resection margin, proximal resection margin, number of lymph nodes, and radial margin. One case in TCC and three cases in OSCC were converted to open surgery. Laparoscopic surgery for transverse colon cancer and OSCC had similar peri-operative clinical and acceptable pathological outcomes.

  8. c9t11-Conjugated linoleic acid-rich oil fails to attenuate wasting in colon-26 tumor-induced late-stage cancer cachexia in male CD2F1 mice.

    Science.gov (United States)

    Tian, Min; Kliewer, Kara L; Asp, Michelle L; Stout, Michael B; Belury, Martha A

    2011-02-01

    Cancer cachexia is characterized by muscle and adipose tissue wasting caused partly by chronic, systemic inflammation. Conjugated linoleic acids (CLAs) are a group of fatty acids with various properties including anti-inflammatory cis9, trans11 (c9t11)-CLA and lipid-mobilizing trans10, cis12 (t10c12)-CLA. The purpose of this study was to test whether dietary supplementation of a c9t11-CLA-rich oil (6:1 c9t11:t10c12) could attenuate wasting of muscle and adipose tissue in colon-26 adenocarcinoma-induced cachexia in mice. Loss of body weight, muscle and adipose tissue mass caused by tumors were not rescued by supplementation with the c9t11-CLA-rich oil. In quadriceps muscle, c9t11-CLA-rich oil exacerbated tumor-induced gene expression of inflammatory markers tumor necrosis factor-α, IL-6 receptor and the E3 ligase MuRF-1 involved in muscle proteolysis. In epididymal adipose tissue, tumor-driven delipidation and atrophy was aggravated by the c9,t11-CLA-rich oil, demonstrated by further reduced adipocyte size and lower adiponectin expression. However, expression of inflammatory cytokines and macrophage markers were not altered by tumors, or CLA supplementation. These data suggest that addition of c9t11-CLA-rich oil (0.6% c9t11, 0.1% t10c12) in diet did not ameliorate wasting in mice with cancer cachexia. Instead, it increased expression of inflammatory markers in the muscle and increased adipose delipidation. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. 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.

  10. 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; 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

  11. Control of Colon Cancer Progression by the Colon Microbiome

    Science.gov (United States)

    2015-08-01

    Award  Number:    W81XWH-­14-­1-­0235   TITLE:      Control of Colon Cancer Progression by the Colon Microbiome PRINCIPAL  INVESTIGATOR:    Frank  J... Microbiome Table  of  Contents   Page   1. Introduction………………………………………………………….4 2. Keywords…………………………………………………………….5 3. Accomplishments………..…………………………………………5

  12. Combination of aging and dimethylhydrazine treatment causes an increase in cancer-stem cell population of rat colonic crypts.

    Science.gov (United States)

    Levi, Edi; Misra, Sandhya; Du, Jianhua; Patel, Bhaumik B; Majumdar, Adhip P N

    2009-07-31

    Aging is associated with increased incidence of colon cancers. It is also becoming evident that cancer stem cells (CSC) play a vital role in the pathogenesis and prognosis of colon cancer. Recently, we reported the presence of colon cancer stem-like cells in macroscopically normal mucosa in patients with adenomatous polyps and that they increase with aging, suggesting that aging may predispose the colon to carcinogenesis. In the current study we have examined the combined effects of aging and carcinogen exposure on the status of colon CSCs in an experimental model. We used young (4-6 months) and aged (22-24 months) rats and exposed them to the carcinogen, dimethylhydroxide (DMH). We investigated the expression of colon cancer stem cell markers, CD44, CD166, EpCam, and ALDH1 as well as EGFR expression in normal colonic crypt epithelium following carcinogen treatment. Our results demonstrate that aging per se or carcinogen treatment alone causes an increase in the number of colon cancer stems cells, as evidenced by increased immunoreactive-CSC-markers positive cells in the colonic mucosa. In aged rats, carcinogen exposure results in a more pronounced increase in colon cancer stem cells. Our study shows that in aging colon the effects of carcinogens are more pronounced, and an increase in colon CSCs is one of the earliest changes preceding tumor development. Moreover, the current investigation of the use of a panel of immunohistochemical markers of colon CSC can potentially serve as a prognostic marker during screening for colon cancer.

  13. γδ T cells as a potential tool in colon cancer immunotherapy.

    Science.gov (United States)

    Ramutton, Thiranut; Buccheri, Simona; Dieli, Francesco; Todaro, Matilde; Stassi, Giorgio; Meraviglia, Serena

    2014-01-01

    γδ T cells are capable of recognizing tumor cells and exert potent cellular cytotoxicity against a large range of tumors, including colon cancer. However, tumors utilize numerous strategies to escape recognition or killing by patrolling γδ T cells, such a downregulation of NKG2D ligands, MICA/B and ULBPs. Therefore, the combined upregulation of T-cell receptorand NKG2D ligands on tumor cells and induction of NKG2D expression on γδ T cells may greatly enhance tumor killing and unlock the functions of γδ T cells. Here, we briefly review current data on the mechanisms of γδ T-cell recognition and killing of colon cancer cells and propose that γδ T cells may represent a promising target for the design of novel and highly innovative immunotherapy in patients with colon cancer.

  14. External Beam Radiotherapy for Colon Cancer: Patterns of Care

    International Nuclear Information System (INIS)

    Dunn, Emily F.; Kozak, Kevin R.; Moody, John S.

    2010-01-01

    Purpose: Despite its common and well characterized use in other gastrointestinal malignancies, little is known about radiotherapy (RT) use in nonmetastatic colon cancer in the United States. To address the paucity of data regarding RT use in colon cancer management, we examined the RT patterns of care in this patient population. Methods and Materials: Patients with nonmetastatic colon cancer, diagnosed between 1988 and 2005, were identified in the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate methods were used to identify factors associated with RT use. Results: On univariate analysis, tumor location, age, sex, race, T stage, N stage, and geographic location were each associated with differences in RT use (all p < 0.01). In general, younger patients, male patients, and patients with more advanced disease were more likely to receive RT. On multivariate analysis, tumor location, age, gender, T and N stage, time of diagnosis and geographic location were significantly associated with RT use (all p < 0.001). Race, however, was not associated with RT use. On multivariate analysis, patients diagnosed in 1988 were 2.5 times more likely to receive RT than those diagnosed in 2005 (p = 0.001). Temporal changes in RT use reflect a responsiveness to evolving evidence related to the therapeutic benefits of adjuvant RT. Conclusions: External beam RT is infrequently used for colon cancer, and its use varies according to patient and tumor characteristics. RT use has declined markedly since the late 1980s; however, it continues to be used for nonmetastatic disease in a highly individualized manner.

  15. Excluding Lynch syndrome in a female patient with metachronous DNA mismatch repair deficient colon- and ovarian cancer

    NARCIS (Netherlands)

    S. Crobach (Stijn); Jansen, A.M.L. (Anne M. L.); Ligtenberg, M.J.L. (Marjolein J. L.); Koopmans, M. (Marije); M. Nielsen (Maartje); F.J. Hes (Frederik); J.T. Wijnen (Juul); W.N.M. Dinjens (Winand); T. van Wezel (Tom); H. Morreau (Hans)

    2017-01-01

    textabstractPatients synchronously or metachronously presenting with ovarian and colon cancer can pose diagnostic challenges. A primary colon carcinoma can metastasize to one or both ovaries, two independent primary tumors can arise or an ovarian carcinoma can metastasize to the colon. Clinical and

  16. Prognostic values of tumor endothelial markers in patients with colorectal cancer

    OpenAIRE

    Rmali, KA; Puntis, MCA; Jiang, WG

    2005-01-01

    AIM: Tumor endothelial markers (TEMs) are a newly discovered family of endothelial markers associated with tumor specific angiogenesis. This study sought to examine the levels of expression (qualitatively and quantitatively) for TEMs in human colon cancer.

  17. 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

  18. Proteogenomic characterization of human colon and rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Bing; Wang, Jing; Wang, Xiaojing; Zhu, Jing; Liu, Qi; Shi, Zhiao; Chambers, Matthew C.; Zimmerman, Lisa J.; Shaddox, Kent F.; Kim, Sangtae; Davies, Sherri; Wang, Sean; Wang, Pei; Kinsinger, Christopher; Rivers, Robert; Rodriguez, Henry; Townsend, Reid; Ellis, Matthew; Carr, Steven A.; Tabb, David L.; Coffey, Robert J.; Slebos, Robbert; Liebler, Daniel

    2014-09-18

    We analyzed proteomes of colon and rectal tumors previously characterized by the Cancer Genome Atlas (TCGA) and performed integrated proteogenomic analyses. Protein sequence variants encoded by somatic genomic variations displayed reduced expression compared to protein variants encoded by germline variations. mRNA transcript abundance did not reliably predict protein expression differences between tumors. Proteomics identified five protein expression subtypes, two of which were associated with the TCGA "MSI/CIMP" transcriptional subtype, but had distinct mutation and methylation patterns and associated with different clinical outcomes. Although CNAs showed strong cis- and trans-effects on mRNA expression, relatively few of these extend to the protein level. Thus, proteomics data enabled prioritization of candidate driver genes. Our analyses identified HNF4A, a novel candidate driver gene in tumors with chromosome 20q amplifications. Integrated proteogenomic analysis provides functional context to interpret genomic abnormalities and affords novel insights into cancer biology.

  19. Mast Cell Targeted Chimeric Toxin Can Be Developed as an Adjunctive Therapy in Colon Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Shan Wang

    2016-03-01

    Full Text Available The association of colitis with colorectal cancer has become increasingly clear with mast cells being identified as important inflammatory cells in the process. In view of the relationship between mast cells and cancer, we studied the effect and mechanisms of mast cells in the development of colon cancer. Functional and mechanistic insights were gained from ex vivo and in vivo studies of cell interactions between mast cells and CT26 cells. Further evidence was reversely obtained in studies of mast cell targeted Fcε-PE40 chimeric toxin. Experiments revealed mast cells could induce colon tumor cell proliferation and invasion. Cancer progression was found to be related to the density of mast cells in colonic submucosa. The activation of MAPK, Rho-GTPase, and STAT pathways in colon cancer cells was triggered by mast cells during cell-to-cell interaction. Lastly, using an Fcε-PE40 chimeric toxin we constructed, we confirmed the promoting effect of mast cells in development of colon cancer. Mast cells are a promoting factor of colon cancer and thus also a potential therapeutic target. The Fcε-PE40 chimeric toxin targeting mast cells could effectively prevent colon cancer in vitro and in vivo. Consequently, these data may demonstrate a novel immunotherapeutic approach for the treatment of tumors.

  20. Ectopic fascioliasis mimicking a colon tumor

    Science.gov (United States)

    Makay, Ozer; Gurcu, Baris; Caliskan, Cemil; Nart, Deniz; Tuncyurek, Muge; Korkut, Mustafa

    2007-01-01

    Fasciola hepatica, a leaf shaped trematode that is common in cattle, sheep and goats, is acquired by eating raw water plants like watercress or drinking water infected with the encysted form of the parasite. The varied clinical presentations of fascioliasis still make a high index of suspicion mandatory. Besides having a wide spectrum of hepatobiliary symptoms like obstructive jaundice, cholangitis and liver cirrhosis, the parasitic infection also has extrabiliary manifestations. Until recently, extrahepatic fascioliasis has been reported in the subcutaneous tissue, brain, lungs, epididymis, inguinal lymph nodes, stomach and the cecum. In this report, a strange manifestation of the fasciola infection in a site other than the liver, a colonic fascioliasis, is presented. PMID:17552017

  1. 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.

  2. Colonic cancer cell polyamine synthesis after photodynamic therapy

    International Nuclear Information System (INIS)

    Briand, G.; Foultier, M.T.; Patrice, T.; Perret, C.; Combre, A.; Etourneau, M.J.

    1992-01-01

    PhotoDynamic Therapy is a new concept for cancer treatment based on the interaction between light and a sensitizer, hematoporphyrin derivative (HPD) selectively retained by tumor cells which becomes toxic after light exposure. This effect decreases cell growth, through complex pathways. The aim of this study was to determine whether cellular polyamines, Put (Putrescine), Spd (Spermidine) and Spm (Spermine) were modified after PDT or not. These cations of small molecular weight are essential for cell growth and differentiation of normal and neoplastic cells. In this study intracellular contents of Put, Spd and Spm were determined on 2 sublines of rat colonic cancer cells cloned from the same rat cancer and forming progressive (PROb) and regressive (REGb) tumors. (author). 12 refs., 2 figs

  3. Dietary fat and risk of colon and rectal cancer with aberrant MLH1 expression, APC or KRAS genes.

    NARCIS (Netherlands)

    Weijenberg, M.P.; Luchtenborg, M.; Goeij, A.F. de; Brink, M.; Muijen, G.N.P. van; Bruine, A.P. de; Goldbohm, R.A.; Brandt, P.A. van den

    2007-01-01

    OBJECTIVE: To investigate baseline fat intake and the risk of colon and rectal tumors lacking MLH1 (mutL homolog 1, colon cancer, nonpolyposis type 2) repair gene expression and harboring mutations in the APC (adenomatous polyposis coli) tumor suppressor gene and in the KRAS (v-Ki-ras2 Kirsten rat

  4. Multiple Cutaneous Metastases as Initial Presentation in Advanced Colon Cancer

    Directory of Open Access Journals (Sweden)

    Sudheer Nambiar

    2018-01-01

    Full Text Available Skin metastases from advanced colorectal cancer are relatively rare and occur most often when the cancer is advanced, following the spread to other organs. Cutaneous metastases occur in about 3% of advanced colorectal cancers. We present an extremely rare case of a 68-year-old woman with advanced ascending colon adenocarcinoma that presented with multiple rapidly progressing painless cutaneous metastatic lesions with no other distant metastases. Of all the tumors, breast cancer most commonly spreads as cutaneous metastasis is followed by lung, colorectal, renal, ovarian, and bladder cancers. Cutaneous metastases can present in a variety of clinical manifestations, such as a rapidly growing painless dermal or subcutaneous nodule with intact overlying epidermis or as ulcers. In cases where the cutaneous deposit is isolated, as in visceral metastasis, there is a role for radical management such as wide local excision and reconstruction. In our patient, since she had multiple cutaneous metastases she began treatment with palliative systemic combination chemotherapy.

  5. FXR silencing in human colon cancer by DNA methylation and KRAS signaling.

    Science.gov (United States)

    Bailey, Ann M; Zhan, Le; Maru, Dipen; Shureiqi, Imad; Pickering, Curtis R; Kiriakova, Galina; Izzo, Julie; He, Nan; Wei, Caimiao; Baladandayuthapani, Veerabhadran; Liang, Han; Kopetz, Scott; Powis, Garth; Guo, Grace L

    2014-01-01

    Farnesoid X receptor (FXR) is a bile acid nuclear receptor described through mouse knockout studies as a tumor suppressor for the development of colon adenocarcinomas. This study investigates the regulation of FXR in the development of human colon cancer. We used immunohistochemistry of FXR in normal tissue (n = 238), polyps (n = 32), and adenocarcinomas, staged I-IV (n = 43, 39, 68, and 9), of the colon; RT-quantitative PCR, reverse-phase protein array, and Western blot analysis in 15 colon cancer cell lines; NR1H4 promoter methylation and mRNA expression in colon cancer samples from The Cancer Genome Atlas; DNA methyltransferase inhibition; methyl-DNA immunoprecipitation (MeDIP); bisulfite sequencing; and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) knockdown assessment to investigate FXR regulation in colon cancer development. Immunohistochemistry and quantitative RT-PCR revealed that expression and function of FXR was reduced in precancerous lesions and silenced in a majority of stage I-IV tumors. FXR expression negatively correlated with phosphatidylinositol-4, 5-bisphosphate 3 kinase signaling and the epithelial-to-mesenchymal transition. The NR1H4 promoter is methylated in ~12% colon cancer The Cancer Genome Atlas samples, and methylation patterns segregate with tumor subtypes. Inhibition of DNA methylation and KRAS silencing both increased FXR expression. FXR expression is decreased early in human colon cancer progression, and both DNA methylation and KRAS signaling may be contributing factors to FXR silencing. FXR potentially suppresses epithelial-to-mesenchymal transition and other oncogenic signaling cascades, and restoration of FXR activity, by blocking silencing mechanisms or increasing residual FXR activity, represents promising therapeutic options for the treatment of colon cancer.

  6. Cell surface fucosylation does not affect development of colon tumors in mice with germline Smad3 mutation

    Science.gov (United States)

    Domino, Steven E.; Karnak, David M.; Hurd, Elizabeth A.

    2006-01-01

    Background/Aims: Neoplasia-related alterations in cell surface α(1,2)fucosylated glycans have been reported in multiple tumors including colon, pancreas, endometrium, cervix, bladder, lung, and choriocarcinoma. Spontaneous colorectal tumors from mice with a germline null mutation of transforming growth factor-β signaling gene Smad3 (Madh3) were tested for α(1,2)fucosylated glycan expression. Methods: Ulex Europaeus Agglutinin-I lectin staining, fucosyltransferase gene northern blot analysis, and a cross of mutant mice with Fut2 and Smad3 germline mutations were performed. Results: Spontaneous colorectal tumors from Smad3 (-/-) homozygous null mice were found to express α(1,2)fucosylated glycans in an abnormal pattern compared to adjacent nonneoplastic colon. Northern blot analysis of α(1,2)fucosyltransferase genes Fut1 and Fut2 revealed that Fut2, but not Fut1, steady-state mRNA levels were significantly increased in tumors relative to adjacent normal colonic mucosa. Mutant mice with a Fut2-inactivating germline mutation were crossed with Smad3 targeted mice. In Smad3 (-/-)/Fut2 (-/-) double knock-out mice, UEA-I lectin staining was eliminated from colon and colon tumors, however, the number and size of tumors present by 24 weeks of age did not vary regardless of the Fut2 genotype. Conclusions: In this model of colorectal cancer, cell surface α(1,2)fucosylation does not affect development of colon tumors. PMID:17264540

  7. Prognostic value of microscopic peritoneal dissemination: comparison between colon and gastric cancer.

    Science.gov (United States)

    Vogel, P; Rüschoff, J; Kümmel, S; Zirngibl, H; Hofstädter, F; Hohenberger, W; Jauch, K W

    2000-01-01

    We evaluated the incidence and prognostic relevance of microscopic intraperitoneal tumor cell dissemination of colon cancer in comparison with dissemination of gastric cancer as a rational for additive intraperitoneal therapy. Peritoneal washouts of 90 patients with colon and 111 patients with gastric cancer were investigated prospectively. Sixty patients with benign diseases and 8 patients with histologically proven gross visible peritoneal carcinomatosis served as controls. Intraoperatively, 100 ml of warm NaCl 0.9 percent were instilled and 20 ml were reaspirated. In all patients hematoxylin and eosin staining (conventional cytology) was performed. Additionally, in 36 patients with colon cancer and 47 patients with gastric cancer, immunostaining with the HEA-125 antibody (immunocytology) was prepared. The results of cytology were assessed for an association with TNM category and cancer grade, based on all patients, and with patient survival, among the R0 resected patients. In conventional cytology 35.5 percent (32/90) of patients with colon cancer and 42.3 percent (47/111) of patients with gastric cancer had a positive cytology. In immunocytology 47.2 percent (17/36) of patients with colon cancer and 46.8 percent (22/47) of patients with gastric cancer were positive. In colon cancer, positive conventional cytology was associated with pT and M category (P = 0.044 and P = 0.0002), whereas immunocytology was only associated with M category (P = 0.007). No association was found between nodal status and immunocytology in colon cancer and with the grading. There was a statistically significant correlation between pT M category and conventional and immunocytology in gastric cancer (P influences survival time after R0 resections only in patients with gastric but not with colon cancer, our results may provide a basis for a decision on additive, prophylactic (intraperitoneal) therapy in gastric but not colon cancer.

  8. Triptolide downregulates Rac1 and the JAK/STAT3 pathway and inhibits colitis-related colon cancer progression

    DEFF Research Database (Denmark)

    Wang, Zhipeng; Jin, Haifeng; Xu, Ruodan

    2009-01-01

    ability to block progress of colitis to colon cancer, and its molecular mechanism of action are investigated. A mouse model for colitis-induced colorectal cancer was used to test the effect of triptolide on cancer progression. Treatment of mice with triptolide decreased the incidence of colon cancer...... formation, and increased survival rate. Moreover, triptolide decreased the incidence of tumors in nude mice inoculated with cultured colon cancer cells dose-dependently. In vitro, triptolide inhibited the proliferation, migration and colony formation of colon cancer cells. Secretion of IL6 and levels of JAK....... This suggests that triptolide might be a candidate for prevention of colitis induced colon cancer because it reduces inflammation and prevents tumor formation and development....

  9. 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

  10. 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

  11. [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.

  12. Colon cancer: it's CIN or CIMP.

    Science.gov (United States)

    Issa, Jean-Pierre

    2008-10-01

    Combined genetic and epigenetic analysis of sporadic colon cancer suggest that it can no longer be viewed as a single disease. There are at least three different subsets with distinct clinico-pathologic features, with important implications for preventions, screening, and therapy.

  13. Colon cancer modulation by a diabetic environment: A single institutional experience

    OpenAIRE

    Prieto, Isabel; del Puerto-Nevado, Laura; Gonzalez, Nieves; Portal-Nu?ez, Sergio; Zazo, Sandra; Corton, Marta; Minguez, Pablo; Gomez-Guerrero, Carmen; Arce, Jose Miguel; Sanz, Ana Belen; Mas, Sebastian; Aguilera, Oscar; Alvarez-Llamas, Gloria; Esbrit, Pedro; Ortiz, Alberto

    2017-01-01

    Background Multiple observational studies suggest an increased risk of colon cancer in patients with diabetes mellitus (DM). This can theoretically be the result of an influence of the diabetic environment on carcinogenesis or the tumor biologic behavior. Aim To gain insight into the influence of a diabetic environment on colon cancer characteristics and outcomes. Material and methods Retrospective analysis of clinical records in an academic tertiary care hospital with detailed analysis of 81...

  14. The Innate Immune Receptor NLRX1 Functions as a Tumor Suppressor by Reducing Colon Tumorigenesis and Key Tumor-Promoting Signals

    Directory of Open Access Journals (Sweden)

    A. Alicia Koblansky

    2016-03-01

    Full Text Available NOD-like receptor (NLR proteins are intracellular innate immune sensors/receptors that regulate immunity. This work shows that NLRX1 serves as a tumor suppressor in colitis-associated cancer (CAC and sporadic colon cancer by keeping key tumor promoting pathways in check. Nlrx1−/− mice were highly susceptible to CAC, showing increases in key cancer-promoting pathways including nuclear factor κB (NF-κB, mitogen-activated protein kinase (MAPK, signal transducer and activator of transcription 3 (STAT3, and interleukin 6 (IL-6. The tumor-suppressive function of NLRX1 originated primarily from the non-hematopoietic compartment. This prompted an analysis of NLRX1 function in the Apcmin/+ genetic model of sporadic gastrointestinal cancer. NLRX1 attenuated Apcmin/+ colon tumorigenesis, cellular proliferation, NF-κB, MAPK, STAT3 activation, and IL-6 levels. Application of anti-interleukin 6 receptor (IL6R antibody therapy reduced tumor burden, increased survival, and reduced STAT3 activation in Nlrx1−/−Apcmin/+ mice. As an important clinical correlate, human colon cancer samples expressed lower levels of NLRX1 than healthy controls in multiple patient cohorts. These data implicate anti-IL6R as a potential personalized therapy for colon cancers with reduced NLRX1.

  15. Screening for colorectal cancer in defunctioned colons.

    Science.gov (United States)

    Akbar, Fayyaz; Quyn, Aaron; Steele, Robert

    2018-01-01

    Objectives Population-based colorectal (bowel) cancer screening using faecal occult blood tests leads to a reduction in cause-specific mortality. However, in people where the colon is defunctioned, the use of standard faecal occult blood test is not appropriate. The aim of this study was to examine the current trends of clinical practice for colorectal cancer screening in people with defunctioned colons. Methods An online survey was performed using SurveyMonkey. All members of the Association of Coloproctology of Great Britain and Ireland were invited by email to participate. Reminders were sent to non-responders and partial responders till six weeks. All responses were included in our analysis. Results Of the 206 (34.59%) questionnaires completed, all questions were answered in 110 (55.8%). Among responders, 94 (85.4%) were colorectal consultant surgeons, 72% had worked in their current capacity for more than five years, and 105 (50.9%) had encountered colorectal cancer in defunctioned colons during their career. Some 72.2% of responders stated that a screening test for colorectal cancer in patients with defunctioned colons was currently not offered, or that they did not know whether or not it was offered in their area. Conclusions Bowel screening in the United Kingdom is currently not offered to 72.2% of the age appropriate population with defunctioned colons. Among responding colorectal surgeons, 50% had encountered colorectal cancer in such patients. There is considerable variability in clinical practice regarding the optimal age for onset of screening, time interval, and the optimal modality to offer for screening in such cases.

  16. Differential diagnosis and cancer staging of a unique case with multiple nodules in the lung - lung adenocarcinoma, metastasis of colon adenocarcinoma, and colon adenocarcinoma metastasizing to lung adenocarcinoma.

    Science.gov (United States)

    Bai, Yun; Qiu, Jianxing; Shang, Xueqian; Liu, Ping; Zhang, Ying; Wang, Ying; Xiong, Yan; Li, Ting

    2015-05-01

    Lung cancer is the most common cancer in the world. Despite this, there have been few cases of simultaneous primary and metastatic cancers in the lung reported, let alone coexisting with tumor-to-tumor metastasis. Herein, we describe an extremely unusual case. A 61-year-old man with a history of colon adenocarcinoma was revealed as having three nodules in the lung 11 months after colectomy. The nodule in the left upper lobe was primary lung adenocarcinoma, the larger one in the right upper lobe was a metastasis of colon adenocarcinoma, and the smaller one in the right upper lobe was colon adenocarcinoma metastasizing to lung adenocarcinoma. Our paper focused on the differential diagnosis and cancer staging of this unique case, and discussed the uncommon phenomenon of the lung acting as a recipient in tumor-to-tumor metastasis.

  17. Stage III & IV colon and rectal cancers share a similar genetic profile: a review of the Oregon Colorectal Cancer Registry.

    Science.gov (United States)

    Gawlick, Ute; Lu, Kim C; Douthit, Miriam A; Diggs, Brian S; Schuff, Kathryn G; Herzig, Daniel O; Tsikitis, Vassiliki L

    2013-05-01

    Determining the molecular profile of colon and rectal cancers offers the possibility of personalized cancer treatment. The purpose of this study was to determine whether known genetic mutations associated with colorectal carcinogenesis differ between colon and rectal cancers and whether they are associated with survival. The Oregon Colorectal Cancer Registry is a prospectively maintained, institutional review board-approved tissue repository with associated demographic and clinical information. The registry was queried for any patient with molecular analysis paired with clinical data. Patient demographics, tumor characteristics, microsatellite instability status, and mutational analysis for p53, AKT, BRAF, KRAS, MET, NRAS, and PIK3CA were analyzed. Categorical variables were compared using chi-square tests. Continuous variables between groups were analyzed using Mann-Whitney U tests. Kaplan-Meier analysis was used for survival studies. Comparisons of survival were made using log-rank tests. The registry included 370 patients: 69% with colon cancer and 31% with rectal cancer. Eighty percent of colon cancers and 68% of rectal cancers were stages III and IV. Mutational analysis found no significant differences in detected mutations between colon and rectal cancers, except that there were significantly more BRAF mutations in colon cancers compared with rectal cancers (10% vs 0%, P colon versus rectal cancers when stratified by the presence of KRAS, PIK3CA, and BRAF mutations. Stage III and IV colon and rectal cancers share similar molecular profiles, except that there were significantly more BRAF mutations in colon cancers compared with rectal cancers. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Chemopreventive effect of chalcone derivative, L2H17, in colon cancer development

    International Nuclear Information System (INIS)

    Xu, Shanmei; Chen, Minxiao; Chen, Wenbo; Hui, Junguo; Ji, Jiansong; Hu, Shuping; Zhou, Jianmin; Wang, Yi; Liang, Guang

    2015-01-01

    Colon cancer is the third most commonly diagnosed cancer and the second leading cause of cancer mortality worldwide. Chalcone and its derivatives are reported to exhibit anti-cancer effects in several cancer cell lines, including colon cancer cells. In addition, chalcones have advantages such as poor interaction with DNA and low risk of mutagenesity. In our previous study, a group of chalcone derivatives were synthesized and exhibited strong anti-inflammatory activities. In this study, we evaluated the anti-cancer effects of the chalcone derivative, L2H17, in colon cancer cells. The cytotoxicities of L2H17 on various colon cancer cell lines were investigated by MTT and clonogenic assay. Cell cycle and apoptosis analysis were performed to evaluate the molecular mechanism of L2H17-mediated inhibition of tumor growth. Also, scratch wound and matrigel invasion experiments were performed to estimate the cell migration and invasion after L2H17 treatment. Finally, we observed the anti-colon cancer effects of L2H17 in vivo. Our data show that compound L2H17 exhibited selective cytotoxic effect on colon cancer cells, via inducing G0/G1 cell cycle arrest and apoptosis in CT26.WT cells. Furthermore, L2H17 treatment decreased cell migration and invasion of CT26.WT cells. In addition, L2H17 possessed marked anti-tumor activity in vivo. The molecular mechanism of L2H17-mediated inhibition of tumor promotion and progression were function through inactivated NF-κB and Akt signaling pathways. All these findings show that L2H17 might be a potential growth inhibitory chalcones derivative for colon cancer cells

  19. ZEB1 Promotes Oxaliplatin Resistance through the Induction of Epithelial - Mesenchymal Transition in Colon Cancer Cells.

    Science.gov (United States)

    Guo, Cao; Ma, Junli; Deng, Ganlu; Qu, Yanlin; Yin, Ling; Li, Yiyi; Han, Ying; Cai, Changjing; Shen, Hong; Zeng, Shan

    2017-01-01

    Background: Oxaliplatin (OXA) chemotherapy is widely used in the clinical treatment of colon cancer. However, chemo-resistance is still a barrier to effective chemotherapy in cases of colon cancer. Accumulated evidence suggests that the epithelial mesenchymal transition (EMT) may be a critical factor in chemo-sensitivity. The present study investigated the effects of Zinc finger E-box binding homeobox 1 (ZEB1) on OXA-sensitivity in colon cancer cells. Method: ZEB1expression and its correlation with clinicopathological characteristics were analyzed using tumor tissue from an independent cohort consisting of 118 colon cancer (CC) patients who receiving OXA-based chemotherapy. ZEB1 modulation of OXA-sensitivity in colon cancer cells was investigated in a OXA-resistant subline of HCT116/OXA cells and the parental colon cancer cell line: HCT116. A CCK8 assay was carried out to determine OXA-sensitivity. qRT-PCR, Western blot, Scratch wound healing and transwell assays were used to determine EMT phenotype of colon cells. ZEB1 knockdown using small interfering RNA (siRNA) was used to determine the ZEB1 contribution to OXA-sensitivity in vitro and in vivo (in a nude mice xenograft model). Result: ZEB1 expression was significantly increased in colon tumor tissue, and was correlated with lymph node metastasis and the depth of invasion. Compared with the parental colon cancer cells (HCT116), HCT116/OXA cells exhibited an EMT phenotype characterized by up-regulated expression of ZEB1, Vimentin, MMP2 and MMP9, but down-regulated expression of E-cadherin. Transfection of Si-ZEB1 into HCT116/OXA cells significantly reversed the EMT phenotype and enhanced OXA-sensitivity in vitro and in vivo . Conclusion: HCT116/OXA cells acquired an EMT phenotype. ZEB1 knockdown effectively restored OXA-sensitivity by reversing EMT. ZEB1 is a potential therapeutic target for the prevention of OXA-resistance in colon cancer.

  20. 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 ...

  1. 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.

  2. Rectal prolapse as initial clinical manifestation of colon cancer.

    Science.gov (United States)

    Chen, C-W; Hsiao, C-W; Wu, C-C; Jao, S-W

    2008-04-01

    Rectal prolapse as the initial clinical manifestation of colorectal cancer is uncommon. We describe the case of a 75-year-old woman who was diagnosed as having adenocarcinoma of the sigmoid colon after presenting with complete rectal prolapse. The tumor caused rectosigmoid intussusception and then it prolapsed out through the anus. She underwent rectosigmoidectomy and rectopexy. The postoperative course was uneventful. The relationship between colorectal cancer and rectal prolapse has not been clearly established. This case report describes an unusual presentation of colorectal cancer. It suggests that rectal prolapse can present as the initial symptom of colorectal cancer and may also be a presenting feature of the occult intra-abdominal pathology. The importance of adequate investigation such as colonoscopy should be emphasized in patients who develop a new onset of rectal prolapse.

  3. Excluding Lynch syndrome in a female patient with metachronous DNA mismatch repair deficient colon- and ovarian cancer

    OpenAIRE

    Crobach, Stijn; Jansen, A.M.L. (Anne M. L.); Ligtenberg, M.J.L. (Marjolein J. L.); Koopmans, M. (Marije); Nielsen, Maartje; Hes, Frederik; Wijnen, Juul; Dinjens, Winand; Wezel, Tom; Morreau, Hans

    2017-01-01

    textabstractPatients synchronously or metachronously presenting with ovarian and colon cancer can pose diagnostic challenges. A primary colon carcinoma can metastasize to one or both ovaries, two independent primary tumors can arise or an ovarian carcinoma can metastasize to the colon. Clinical and immunohistochemical characterization can aid the diagnosis. Recently, we reported that in difficult cases finding pathogenic APC variants supports a colonic origin. In this case report we describe ...

  4. 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

  5. Role of a Cyclooxygenase Inhibitor and Luteolin in the Regression of Colon Tumors in Irradiated Rats

    International Nuclear Information System (INIS)

    Ahmed, E.S.A.

    2015-01-01

    Colon carcinogenesis is a devastating problem leading to morbidity and mortality in developed countries. Colon cancer is a complex multi-step process involving progressive disruption of homeostatic mechanisms controlling intestinal epithelial proliferation/inflammation, differentiation and programmed cell death. Colon cancer is the third most common malignant neoplasm worldwide. Its incidence strongly varies globally and is closely linked to elements of a so-called western lifestyle. In Egypt reports showed that colon cancer was detected in 11–15% of patients who underwent colonoscopy and diagnosed in 29–31% of patients aged 40 years or younger. The present study was planned to evaluate the effect of a cyclooxygenase inhibitor (aspirin) and a natural product (luteolin) and on colon cancer induced by 1, 2 dimethylhydrazine (DMH), beside studying the effects of luteolin and aspirin either alone or combined with fractionated low doses of γ- irradiation as a route of cancer therapy. Seventy adult male Wistar rats were divided into seven groups 10 animals each and treated as follows: 1. Control group (G1): rats of this group received distilled water via gavages for 15 weeks. 2. Colon tumor induction group (G2): rats of this group were injected subcutaneously with DMH (20 mg/kg body weight) once a week for 15 weeks. 3. Colon tumor + irradiation group (G3): these rats were injected subcutaneously with DMH (20 mg/kg body weight) once a week for 15 weeks then at the beginning of the 8th week they were exposed to γ-radiation at a dose level of 0.5 Gy/week x 8 and continued during DMH treatment. 4. Colon tumor + aspirin treatment group (G4): rats of this group gavaged aspirin (50 mg/kg/ week) and injected subcutaneously with DMH for 15 weeks. 5. Colon tumor + luteolin treatment group (G5): these rats were treated orally with LUT (0.2 mg/kg body weight/ day) and injected subcutaneously with DMH (20 mg/kg body weight/ week) for 15 weeks. 6. Colon tumor + aspirin

  6. PGE2-induced colon cancer growth is mediated by mTORC1

    International Nuclear Information System (INIS)

    Dufour, Marc; Faes, Seraina; Dormond-Meuwly, Anne; Demartines, Nicolas; Dormond, Olivier

    2014-01-01

    Highlights: • PGE 2 activates mTORC1 in colon cancer cells. • Inhibition of mTORC1 blocks PGE 2 induced colon cancer cell growth. • mTORC1 is a signaling intermediary in PGE 2 induced colon cancer cell responses. - Abstract: The inflammatory prostaglandin E 2 (PGE 2 ) cytokine plays a key role in the development of colon cancer. Several studies have shown that PGE 2 directly induces the growth of colon cancer cells and furthermore promotes tumor angiogenesis by increasing the production of the vascular endothelial growth factor (VEGF). The signaling intermediaries implicated in these processes have however not been fully characterized. In this report, we show that the mechanistic target of rapamycin complex 1 (mTORC1) plays an important role in PGE 2 -induced colon cancer cell responses. Indeed, stimulation of LS174T cells with PGE 2 increased mTORC1 activity as observed by the augmentation of S6 ribosomal protein phosphorylation, a downstream effector of mTORC1. The PGE 2 EP 4 receptor was responsible for transducing the signal to mTORC1. Moreover, PGE 2 increased colon cancer cell proliferation as well as the growth of colon cancer cell colonies grown in matrigel and blocking mTORC1 by rapamycin or ATP-competitive inhibitors of mTOR abrogated these effects. Similarly, the inhibition of mTORC1 by downregulation of its component raptor using RNA interference blocked PGE 2 -induced LS174T cell growth. Finally, stimulation of LS174T cells with PGE 2 increased VEGF production which was also prevented by mTORC1 inhibition. Taken together, these results show that mTORC1 is an important signaling intermediary in PGE 2 mediated colon cancer cell growth and VEGF production. They further support a role for mTORC1 in inflammation induced tumor growth

  7. Circulating tumor cells in lung cancer.

    Science.gov (United States)

    Young, Rachel; Pailler, Emma; Billiot, Fanny; Drusch, Françoise; Barthelemy, Amélie; Oulhen, Marianne; Besse, Benjamin; Soria, Jean-Charles; Farace, Françoise; Vielh, Philippe

    2012-01-01

    Circulating tumor cells (CTCs) have emerged as potential biomarkers in several cancers such as colon, prostate, and breast carcinomas, with a correlation between CTC number and patient prognosis being established by independent research groups. The detection and enumeration of CTCs, however, is still a developing field, with no universal method of detection suitable for all types of cancer. CTC detection in lung cancer in particular has proven difficult to perform, as CTCs in this type of cancer often present with nonepithelial characteristics. Moreover, as many detection methods rely on the use of epithelial markers to identify CTCs, the loss of these markers during epithelial-to-mesenchymal transition in certain metastatic cancers can render these methods ineffective. The development of personalized medicine has led to an increase in the advancement of molecular characterization of CTCs. The application of techniques such as FISH and RT-PCR to detect EGFR, HER2, and KRAS abnormalities in lung, breast, and colon cancer, for example, could be used to characterize CTCs in real time. The use of CTCs as a 'liquid biopsy' is therefore an exciting possibility providing information on patient prognosis and treatment efficacy. This review summarizes the state of CTC detection today, with particular emphasis on lung cancer, and discusses the future applications of CTCs in helping the clinician to develop new strategies in patient treatment. Copyright © 2012 S. Karger AG, Basel.

  8. Single-cell cloning of colon cancer stem cells reveals a multi-lineage differentiation capacity

    NARCIS (Netherlands)

    Vermeulen, L.; Todaro, M.; de Sousa E Melo, F.; Sprick, M. R.; Kemper, K.; Alea, M. Perez; Richel, D. J.; Stassi, G.; Medema, J. P.

    2008-01-01

    Colon carcinoma is one of the leading causes of death from cancer and is characterized by a heterogenic pool of cells with distinct differentiation patterns. Recently, it was reported that a population of undifferentiated cells from a primary tumor, so-called cancer stem cells (CSC), can

  9. Rhein induces apoptosis of HCT-116 human colon cancer cells via ...

    African Journals Online (AJOL)

    Rhein, a major compound in rhubarb, has been found to have anti-tumor properties in many human cancer cells. However, the details about rhein suppressing the growth of human colon cancer cells remained elusive. In this paper, we explored the potential of rhein as a chemotherapeutic agent on HCT- 116 cells and ...

  10. Differential expression of carbohydrate antigen 19-9 in human colorectal cancer: A comparison with colon and rectal cancers

    Science.gov (United States)

    ZHANG, SHUAI; CHEN, YIJUN; ZHU, ZHANMENG; DING, YUNLONG; REN, SHUANGYI; ZUO, YUNFEI

    2013-01-01

    Colorectal cancer is one of the leading causes of cancer-related mortality, being the third most commonly diagnosed cancer among men and the second among women. Accumulating evidence regarding carbohydrate antigen (CA) demonstrated that tumor-associated antigens are clinically useful for the diagnosis, staging and monitoring of human gastrointestinal cancers, particularly colorectal cancer. There has been an extensive investigation for sensitive and specific markers of this disease. Currently, the gastrointestinal cancer-associated carbohydrate antigen 19-9 (CA19-9) is the most widely applied tumor marker in cancer diagnosis. Despite a similar etiology and cancer incidence rates, there are anatomical and clinical differences between colon and rectal cancer, as well as differences regarding tumor progression and adjuvant treatments. To investigate whether CA19-9 is differentially expressed between colon and rectal cancer, we conducted a differential analysis of serum CA19-9 levels among 227 cases of colorectal cancer, analyzing gender, age, Dukes’ stage and distant metastasis for human colon and rectal cancer as a single entity, separately and as matched pairs. We demonstrated that the serum CA19-9 levels in colorectal cancer were upregulated in advanced stages with distant metastasis. By contrast, the serum CA19-9 levels in colon cancer displayed a differential and upregulated behavior in advanced stages with distant metastasis. By analyzing as matched pairs, the upregulated serum CA19-9 levels in rectal cancer during the early stages without distant metastasis further supported our hypothesis that the expression of CA19-9 displays a site-specific differential behavior. The integrative analysis suggested a significant difference between human colon and rectal cancer, justifying individualized therapy for these two types of cancer. PMID:24649295

  11. Fatty acid and lipidomic data in normal and tumor colon tissues of rats fed diets with and without fish oil

    Directory of Open Access Journals (Sweden)

    Zora Djuric

    2017-08-01

    Full Text Available Data is provided to show the detailed fatty acid and lipidomic composition of normal and tumor rat colon tissues. Rats were fed either a Western fat diet or a fish oil diet, and half the rats from each diet group were treated with chemical carcinogens that induce colon cancer (azoxymethane and dextran sodium sulfate. The data show total fatty acid profiles of sera and of all the colon tissues, namely normal tissue from control rats and both normal and tumor tissues from carcinogen-treated rats, as obtained by gas chromatography with mass spectral detection. Data from lipidomic analyses of a representative subset of the colon tissue samples is also shown in heat maps generated from hierarchical cluster analysis. These data display the utility lipidomic analyses to enhance the interpretation of dietary feeding studies aimed at cancer prevention and support the findings published in the companion paper (Effects of fish oil supplementation on prostaglandins in normal and tumor colon tissue: modulation by the lipogenic phenotype of colon tumors, Djuric et al., 2017 [1].

  12. Induction of cancer stem cell properties in colon cancer cells by defined factors.

    Directory of Open Access Journals (Sweden)

    Nobu Oshima

    Full Text Available Cancer stem cells (CSCs are considered to be responsible for the dismal prognosis of cancer patients. However, little is known about the molecular mechanisms underlying the acquisition and maintenance of CSC properties in cancer cells because of their rarity in clinical samples. We herein induced CSC properties in cancer cells using defined factors. We retrovirally introduced a set of defined factors (OCT3/4, SOX2 and KLF4 into human colon cancer cells, followed by culture with conventional serum-containing medium, not human embryonic stem cell medium. We then evaluated the CSC properties in the cells. The colon cancer cells transduced with the three factors showed significantly enhanced CSC properties in terms of the marker gene expression, sphere formation, chemoresistance and tumorigenicity. We designated the cells with CSC properties induced by the factors, a subset of the transduced cells, as induced CSCs (iCSCs. Moreover, we established a novel technology to isolate and collect the iCSCs based on the differences in the degree of the dye-effluxing activity enhancement. The xenografts derived from our iCSCs were not teratomas. Notably, in contrast to the tumors from the parental cancer cells, the iCSC-based tumors mimicked actual human colon cancer tissues in terms of their immunohistological findings, which showed colonic lineage differentiation. In addition, we confirmed that the phenotypes of our iCSCs were reproducible in serial transplantation experiments. By introducing defined factors, we generated iCSCs with lineage specificity directly from cancer cells, not via an induced pluripotent stem cell state. The novel method enables us to obtain abundant materials of CSCs that not only have enhanced tumorigenicity, but also the ability to differentiate to recapitulate a specific type of cancer tissues. Our method can be of great value to fully understand CSCs and develop new therapies targeting CSCs.

  13. Colon cancer information as a source of exercise motivation for relatives of patients with colon cancer.

    Science.gov (United States)

    McGowan, Erin L; Prapavessis, Harry

    2010-12-01

    Using a Protection Motivation Theory (PMT) framework, this study examined whether factual colon cancer information is a meaningful source of exercise motivation for relatives of patients with colon cancer. One hundred sixty-six inactive relatives were randomly assigned to one of two treatment conditions: PMT group (intervention); and non-PMT group (attention control). At baseline (T1) participants completed demographic information, a questionnaire designed to assess their beliefs toward exercise and colon cancer as well as their exercise intentions. At T2 (one week following T1) participants watched one of two DVD videos that were created for the study. The intervention DVD contained exercise and colon cancer information that was yoked within the four major components of PMT: perceived vulnerability (PV); perceived severity (PS); response efficacy (RE); and self-efficacy (SE), while the attention control DVD contained general diet and cancer information. Immediately following watching the DVD, participants completed the same measures as in T1. Participants assigned to the PMT intervention group showed significant improvement in PV, RE, SE and exercise intentions, whereas participants assigned to the attention control group showed significant improvement only in RE. RE, SE, and PS made significant and unique contributions to prediction of exercise intention. Overall, the results of the present study demonstrate that a single exposure media intervention grounded in a PMT framework can change individuals' exercise and colon cancer beliefs, as well as change their exercise intentions. Implications of these findings and direction for future research are discussed.

  14. The Akt inhibitor ISC-4 synergizes with cetuximab in 5-FU-resistant colon cancer.

    Directory of Open Access Journals (Sweden)

    Joshua E Allen

    Full Text Available Phenylbutyl isoselenocyanate (ISC-4 is an Akt inhibitor with demonstrated preclinical efficacy against melanoma and colon cancer. In this study, we sought to improve the clinical utility of ISC-4 by identifying a synergistic combination with FDA-approved anti-cancer therapies, a relevant and appropriate disease setting for testing, and biomarkers of response. We tested the activity of ISC-4 and 19 FDA-approved anticancer agents, alone or in combination, against the SW480 and RKO human colon cancer cell lines. A synergistic interaction with cetuximab was identified and validated in a panel of additional colon cancer cell lines, as well as the kinetics of synergy. ISC-4 in combination with cetuximab synergistically reduced the viability of human colon cancer cells with wild-type but not mutant KRAS genes. Further analysis revealed that the combination therapy cooperatively decreased cell cycle progression, increased caspase-dependent apoptosis, and decreased phospho-Akt in responsive tumor cells. The synergism between ISC-4 and cetuximab was retained independently of acquired resistance to 5-FU in human colon cancer cells. The combination demonstrated synergistic anti-tumor effects in vivo without toxicity and in the face of resistance to 5-FU. These results suggest that combining ISC-4 and cetuximab should be explored in patients with 5-FU-resistant colon cancer harboring wild-type KRAS.

  15. Prognostic Importance of Bcl-2 Expression in Colon Cancer

    Directory of Open Access Journals (Sweden)

    Arsenal Alikanoðlu

    2012-09-01

    Full Text Available Aim: TNM classification, that had been established according to pathologic and anatomic characteristics of the lesion , is the most important factor in decision of adjuvant therapy in colon cancer. Despite curative resection, recurrence can ocur with a rate of 20-30% in early stage disease. Therefore efficieny of TNM classification is controversial. In recent years ,significance of molecular characteristics of the tumors besides their anatomic and pathologic characteristics in determining the biological behaviour and response to treatment have been discussed. In our study, relation between expression of Bcl-2 and the other known prognostic factors in colon cancer had been searched. Material and Method: Patients who had been followed up in our clinic were enrolled in this study. Expression of Bcl-2 was searched by immunohistochemical method. Results: A total of 52, 19 (%36.5 female and 33 (%63.5 male patients were enrolled in this study. Bcl-2 expression was found positive in 7 (%13.5 and negative in 45 (%86.5 patients. Statistically no significant relationship was found between Bcl-2 expression and sex, stage, regional lymph node involvement, presence of distant metastasis and histologic grade. Discussion: In our study, although not in a statistical significance, we found that Bcl-2 expression is related to early stage disease. Bcl-2 is a low-priced and easily accessible prognostic marker. We think that establishing expression of Bcl-2 by immunohistohemistry may play a role in determining prognosis of patients with colon cancer.

  16. Hydroquinone analog 4-[(Tetrahydro-2H-pyran-2‑yl) oxy] phenol induces C26 colon cancer cell apoptosis and inhibits tumor growth in vivo.

    Science.gov (United States)

    Du, Qigen; Xin, Guang; Niu, Hai; Huang, Wen

    2015-06-01

    The 4[(Tetrahydro‑2H‑pyran‑2‑yl) oxy] phenol (XG‑d) hydroquinone analog, is found in Vaccinium vitis‑idaea  L. Although it is known for its antioxidant properties and high level of safety, its antitumor activity remains to be elucidated. In the present study, the anticancer effect of XG‑d was determined in vitro and in vivo. The cytotoxicity of XG‑d against C26 murine colon carcinoma cells was found to occur in a time‑ and concentration‑dependent manner, whereas little effect was observed in the two normal cell lines (HK‑2 and L02) investigated. Oral administration of XG‑d (100 mg/kg) had effects on the tumor growth of tumor‑bearing mice. Furthermore, marked apoptosis was observed using Hoechst 33258 staining and flow cytometric analysis with annexin V/propidium iodide double staining. XG‑d also downregulated the expression of B‑cell lymphoma 2 (Bcl‑2), increased the expression levels of Bcl‑2‑associated X protein and activated caspase‑9, caspase‑3 and poly(adenosine diphosphate‑ribose) polymerase. The present study demonstrated for the first time, to the best of our knowledge, that XG‑d inhibited cancer cell growth via the induction of apoptosis and was also able to inhibit tumor growth in vivo. These results demonstrated that XG‑d may be used as a potential natural agent for cancer therapy with low toxicity.

  17. [Clinical significance of signal transduction and activators of transcription 3, E-cadherin and vimentin in colon cancer].

    Science.gov (United States)

    Zhang, Chao; Xu, Jian-Hua; Liu, Tao; Cui, Hao

    2011-03-01

    To evaluate the clinical significance of STAT3, E-cadherin and vimentin in colon cancer. Samples of colon cancer tissue and adjacent normal tissue were procured from 70 patients with colon cancer. The expressions of STAT3, E-cadherin and vimentin were detected by immunohistochemistry. Associations of clinicopathological characteristics and these three factors were evaluated. STAT3, E-cadherin, vimentin were positive in 74.3%,32.9%, and 78.6% in the colon cancer tissues, respectively, and were 15.7%, 82.9%, and 12.9% in normal colon mucosa tissues, respectively. They were correlated with tumor differentiation, depth of invasion, lymph node metastasis, and TNM staging(Pcolon cancer. The expressions of STAT3, E-cadherin and vimentin may serve as prognostic indicators for patients with colon cancer.

  18. Differentiation between benign and malignant colon tumors using fast dynamic gadolinium-enhanced MR colonography; a feasibility study

    Energy Technology Data Exchange (ETDEWEB)

    Achiam, M.P., E-mail: achiam1@dadlnet.d [Department of Diagnostic Radiology, Copenhagen University Hospital Herlev, Herlev Ringvej, DK-2730 Herlev (Denmark); Department of Surgical Gastroenterology D, Copenhagen University Hospital Herlev, Herlev Ringvej, DK-2730 Herlev (Denmark); Department of Diagnostic Sciences, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3C, DK-2200 Copenhagen (Denmark); Andersen, L.P.H.; Klein, M. [Department of Surgical Gastroenterology D, Copenhagen University Hospital Herlev, Herlev Ringvej, DK-2730 Herlev (Denmark); Department of Diagnostic Sciences, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3C, DK-2200 Copenhagen (Denmark); Logager, V.; Chabanova, E.; Thomsen, H.S. [Department of Diagnostic Radiology, Copenhagen University Hospital Herlev, Herlev Ringvej, DK-2730 Herlev (Denmark); Department of Diagnostic Sciences, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3C, DK-2200 Copenhagen (Denmark); Rosenberg, J. [Department of Surgical Gastroenterology D, Copenhagen University Hospital Herlev, Herlev Ringvej, DK-2730 Herlev (Denmark); Department of Diagnostic Sciences, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3C, DK-2200 Copenhagen (Denmark)

    2010-06-15

    Background: Colorectal cancer will present itself as a bowel obstruction in 16-23% of all cases. However, not all obstructing tumors are malignant and the differentiation between a benign and a malignant tumor can be difficult. The purpose of our study was to determine whether fast dynamic gadolinium-enhanced MR imaging combined with MR colonography could be used to differentiate a benign from a malignant obstructing colon tumor. Methods: Patients with benign colon tumor stenosis, based on diverticulitis, were asked to participate in the study. The same number of patients with verified colorectal cancer was included. Both groups had to be scheduled for surgery to be included. Two blinded observers analyzed the tumors on MR by placing a region of interest in the tumor and a series of parameters were evaluated, e.g. wash-in, wash-out and time-to-peak. Results: 14 patients were included. The wash-in and wash-out rates were significantly different between the benign and malignant tumors, and a clear distinction between benign and malignant disease was therefore possible by looking only at the MR data. Furthermore, MR colography evaluating the rest of the colon past the stenosis was possible with all patients. Conclusion: The results showed the feasibility of using fast dynamic gadolinium-enhanced MR imaging to differentiate between benign and malignant colonic tumors. With a high intra-class correlation and significant differences found on independent segments of the tumor, the method appears to be reproducible. Furthermore, the potential is big in performing a full preoperative colon evaluation even in patients with obstructing cancer. Trial number: (NCT00114829).

  19. Differentiation between benign and malignant colon tumors using fast dynamic gadolinium-enhanced MR colonography; a feasibility study

    International Nuclear Information System (INIS)

    Achiam, M.P.; Andersen, L.P.H.; Klein, M.; Logager, V.; Chabanova, E.; Thomsen, H.S.; Rosenberg, J.

    2010-01-01

    Background: Colorectal cancer will present itself as a bowel obstruction in 16-23% of all cases. However, not all obstructing tumors are malignant and the differentiation between a benign and a malignant tumor can be difficult. The purpose of our study was to determine whether fast dynamic gadolinium-enhanced MR imaging combined with MR colonography could be used to differentiate a benign from a malignant obstructing colon tumor. Methods: Patients with benign colon tumor stenosis, based on diverticulitis, were asked to participate in the study. The same number of patients with verified colorectal cancer was included. Both groups had to be scheduled for surgery to be included. Two blinded observers analyzed the tumors on MR by placing a region of interest in the tumor and a series of parameters were evaluated, e.g. wash-in, wash-out and time-to-peak. Results: 14 patients were included. The wash-in and wash-out rates were significantly different between the benign and malignant tumors, and a clear distinction between benign and malignant disease was therefore possible by looking only at the MR data. Furthermore, MR colography evaluating the rest of the colon past the stenosis was possible with all patients. Conclusion: The results showed the feasibility of using fast dynamic gadolinium-enhanced MR imaging to differentiate between benign and malignant colonic tumors. With a high intra-class correlation and significant differences found on independent segments of the tumor, the method appears to be reproducible. Furthermore, the potential is big in performing a full preoperative colon evaluation even in patients with obstructing cancer. Trial number: (NCT00114829).

  20. Circulating exosomal microRNAs as biomarkers of colon cancer.

    Directory of Open Access Journals (Sweden)

    Hiroko Ogata-Kawata

    Full Text Available PURPOSE: Exosomal microRNAs (miRNAs have been attracting major interest as potential diagnostic biomarkers of cancer. The aim of this study was to characterize the miRNA profiles of serum exosomes and to identify those that are altered in colorectal cancer (CRC. To evaluate their use as diagnostic biomarkers, the relationship between specific exosomal miRNA levels and pathological changes of patients, including disease stage and tumor resection, was examined. EXPERIMENTAL DESIGN: Microarray analyses of miRNAs in exosome-enriched fractions of serum samples from 88 primary CRC patients and 11 healthy controls were performed. The expression levels of miRNAs in the culture medium of five colon cancer cell lines were also compared with those in the culture medium of a normal colon-derived cell line. The expression profiles of miRNAs that were differentially expressed between CRC and control sample sets were verified using 29 paired samples from post-tumor resection patients. The sensitivities of selected miRNAs as biomarkers of CRC were evaluated and compared with those of known tumor markers (CA19-9 and CEA using a receiver operating characteristic analysis. The expression levels of selected miRNAs were also validated by quantitative real-time RT-PCR analyses of an independent set of 13 CRC patients. RESULTS: The serum exosomal levels of seven miRNAs (let-7a, miR-1229, miR-1246, miR-150, miR-21, miR-223, and miR-23a were significantly higher in primary CRC patients, even those with early stage disease, than in healthy controls, and were significantly down-regulated after surgical resection of tumors. These miRNAs were also secreted at significantly higher levels by colon cancer cell lines than by a normal colon-derived cell line. The high sensitivities of the seven selected exosomal miRNAs were confirmed by a receiver operating characteristic analysis. CONCLUSION: Exosomal miRNA signatures appear to mirror pathological changes of CRC patients and

  1. Yttrium-90 used to treat colon cancer: Awaiting investigational new drug approval

    International Nuclear Information System (INIS)

    Anon.

    1991-01-01

    A new radiation treatment takes just 14 to 21 days to shrink colorectal tumors in laboratory mice, is under review for clinical trials with human cancer patients. The treatment has succeeded in reducing the size of tumors by up to 95%. Colon cancer, the second leading cause of cancer deaths in the US, is extremely difficult to treat unless it is detected early enough for surgical procedures. In laboratory tests over the last 5 years, a team of researchers has developed the treatment using yttrium-90. The yttrium-90 is transported to the tumors by attaching it to monoclonal antibodies that seek out the cancer cells. Once the radioisotope has been targeted to the tumor, the radiation destroys many of the cells, dramatically reducing the size of the tumor. Since this treatment usually does not completely eliminate all the cancer cells, it cannot be called a cure, but it does seem to be an effective method of shrinking colorectal tumors

  2. SIRT1/PGC1α-Dependent Increase in Oxidative Phosphorylation Supports Chemotherapy Resistance of Colon Cancer

    NARCIS (Netherlands)

    Vellinga, Thomas T.; Borovski, Tijana; de Boer, Vincent C. J.; Fatrai, Szabolcs; van Schelven, Susanne; Trumpi, Kari; Verheem, Andre; Snoeren, Nikol; Emmink, Benjamin L.; Koster, Jan; Rinkes, Inne H. M. Borel; Kranenburg, Onno

    2015-01-01

    Chemotherapy treatment of metastatic colon cancer ultimately fails due to development of drug resistance. Identification of chemotherapy-induced changes in tumor biology may provide insight into drug resistance mechanisms. We studied gene expression differences between groups of liver metastases

  3. Case of a sigmoid colon cancer with metachronous metastases to the mesorectum and the abdominal wall

    Directory of Open Access Journals (Sweden)

    Hadjimarcou Andreas

    2010-03-01

    Full Text Available Abstract Backround Sigmoid colon cancer metachronous metastases commonly occur in the liver and lungs with sporadic reports also to the spleen, stomach, thyroid gland, abdominal wall and upper urinary tract. This is a rare case of metachronous metastases invading the mesorectum and the abdominal wall. Case presentation A 72-year-old female underwent sigmoidectomy for stage I (T2N0 M0 sigmoid colon cancer in May 2008. In June 2009, an abdominal computed tomography scan revealed a tumor 2 cm in size at the lower anterior mesorectum and a second mass 2 cm in size at the anterior abdominal wall midline. Total colonoscopy showed no mucosal lesion. The serum carcinoembryonic antigen level was normal. A biopsy of the mesorectum tumor showed similar histologic characteristics with the primary tumor. Since no other site of recurrence was identified, an abdominoperineal resection was attempted. During the operation and after the removal of the incision recurrence, sinus bradycardia and signs of myocardial ischemia were noticed. A loop transverse colostomy was immediately perfomed and the operation was terminated. Postoperative cardiologic examination revealed an acute myocardium infract. Chemo-radiation of the mesorectum tumor and re-evaluation for surgical excision was decided. Conclusion Metachronous metastasis of the mesorectum from sigmoid colon cancer is extremely rare. Although patterns of lymphatic spread from rectal cancer to sigmoid colon have recently been demonstrated, there is no evidence of metachronous mesorectum invasion from sigmoid colon cancer. This could be the issue for future trials.

  4. Radiosensitization effects of sorafenib on colon cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun Ho; Kim, Mi-Sook; Jung, Won-Gyun; Jeong, Youn Kyoung [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2014-11-15

    Radiotherapy is a standard therapy in the adjuvant treatment of resected colon and rectum cancers, and its combination with chemotherapy has been shown to reduce local failure and distant metastasis still further, thereby improving the outcome of treatment. One potential chemotherapeutic agent for this, sorafenib (Nexavar, BAY43-9006), is an oral multikinase inhibitor that blocks tumor cell proliferation and angiogenesis, and induces tumor cell apoptosis by inhibiting serine/threonine kinases (c-RAF and mutant and wild-type BRAF) as well as the receptor tyrosine kinases vascular endothelial growth factor receptor 2 and 3 (VEGFR2 and VEGFR3), platelet- derived growth factor receptor , FLT3, and c-KIT. Sorafenib is currently used in clinics to treat patients with advanced renal cell carcinoma, hepatocellular carcinoma, and thyroid cancer. These findings provide a molecular evidence base for the use of chemoradiation to treat colon cancer, and in vivo modeling should be used to further assess its suitability for clinical applications.

  5. Dietary fat and risk of colon and rectal cancer with aberrant MLH1 expression, APC or KRAS genes.

    Science.gov (United States)

    Weijenberg, Matty P; Lüchtenborg, Margreet; de Goeij, Anton F P M; Brink, Mirian; van Muijen, Goos N P; de Bruïne, Adriaan P; Goldbohm, R Alexandra; van den Brandt, Piet A

    2007-10-01

    To investigate baseline fat intake and the risk of colon and rectal tumors lacking MLH1 (mutL homolog 1, colon cancer, nonpolyposis type 2) repair gene expression and harboring mutations in the APC (adenomatous polyposis coli) tumor suppressor gene and in the KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) oncogene. After 7.3 years of follow-up of the Netherlands Cohort Study (n = 120,852), adjusted incidence rate ratios (RR) and 95% confidence intervals (CI) were computed, based on 401 colon and 130 rectal cancer patients. Total, saturated and monounsaturated fat were not associated with the risk of colon or rectal cancer, or different molecular subgroups. There was also no association between polyunsaturated fat and the risk of overall or subgroups of rectal cancer. Linoleic acid, the most abundant polyunsaturated fatty acid in the diet, was associated with increased risk of colon tumors with only a KRAS mutation and no additional truncating APC mutation or lack of MLH1 expression (RR = 1.41, 95% CI 1.18-1.69 for one standard deviation (i.e., 7.5 g/day) increase in intake, p-trend over the quartiles of intake colon tumors without any of the gene defects, or with tumors harboring aberrations in either MLH1 or APC. Linoleic acid intake is associated with colon tumors with an aberrant KRAS gene, but an intact APC gene and MLH1 expression, suggesting a unique etiology of tumors with specific genetic aberrations.

  6. Could JC virus provoke metastasis in colon cancer?

    Science.gov (United States)

    Sinagra, Emanuele; Raimondo, Dario; Gallo, Elena; Stella, Mario; Cottone, Mario; Orlando, Ambrogio; Rossi, Francesca; Orlando, Emanuele; Messina, Marco; Tomasello, Giovanni; Lo Monte, Attilio Ignazio; La Rocca, Ennio; Rizzo, Aroldo Gabriele

    2014-01-01

    AIM: To evaluate the prevalence of John Cunningham virus (JC virus) in a small cohort of patients with colon cancer and to assess its presence in hepatic metastasis. METHODS: Nineteen consecutive patients with histologically diagnosed colon cancer were included in our study, together with ten subjects affected by histologically and serologically diagnosed hepatitis C virus infection. In the patients included in the colon cancer group, JC virus was searched for in the surgical specimen; in the control group, JC virus was searched for in the hepatic biopsy. The difference in the prevalence of JC virus in the hepatic biopsy between the two groups was assessed through the χ2 test. RESULTS: Four out of 19 patients with colon cancer had a positive polymerase chain reaction (PCR) test for JC virus, and four had liver metastasis. Among the patients with liver metastasis, three out of four had a positive PCR test for JC virus in the surgical specimen and in the liver biopsy; the only patient with liver metastasis with a negative test for JC virus also presented a negative test for JC virus in the surgical specimen. In the control group of patients with hepatitis C infection, none of the ten patients presented JC virus infection in the hepatic biopsy. The difference between the two groups regarding JC virus infection was statistically significant (χ2 = 9.55, P = 0.002). CONCLUSION: JC virus may play a broader role than previously thought, and may be mechanistically involved in the late stages of these tumors. PMID:25400458

  7. Radioimmunotoxin Therapy of Experimental Colon and Ovarian Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Buchsbaum, Donald J.; Vallera, Daniel A.

    2006-02-09

    mixed with the EpCam sFv that was synthesized without any toxin attached. The proliferation studies showed that EpCam sFv was able to block the killing of the EpCam expressing cells by DTEpCam. An irrelevant control protein, 1D10Fc was unable to block. Together, these studies indicated that EpCam was exquisitely selective. In order to produce an IT of even greater potency, we used a toxin containing the Golgi retention sequence KDEL. The same EpCam sFv was spliced to truncated PE containing the terminal KDEL sequence. The addition of KDEL enhanced the potency of the EpCam sFv IT at least 6 logs or 1000-fold with an IC50 of 2 to 7 x 10-8 nM. This conjugate was also shown to be highly selective. Taken together, all of these studies indicate that in vitro experiments have shown that we have a highly potent IT that selectively kills colon cancer cells. The next step was to show that the EpCam IT had the ability to inhibit the growth of flank tumors in vivo in nude mice. The same human colon tumor cells, HT29 used in the in vitro studies were injected into the flank of nude mice. Tumor cells were injected into groups of mice and when tumors reached the size of 0.5 cm3, we injected our best-performing EpCam IT called EpCamKDEL intratumorally. There was a significant drop in tumor size indicating that this agent was very effective against human colon cancer. Since the EpCamKDEL was injected intratumorally, it did not have to travel through the systemic circulation to find its target. Our next step will be to inject EpCamKDEL intravenously into mice with flank tumors to determine if EpCamKDEL has the ability to migrate to the tumor systemically. The next step was to radiolabel EpCamKDEL to see whether it could serve as an RIT. We radiolabeled EpCam with 111In as a surrogate for 90Y and then incubated it with HT29. The labeling efficiency was over 90% indicating that a high percentage of the protein molecules could be readily radiolabeled. However, the immunoreactivity was only

  8. Radioimmunotoxin Therapy of Experimental Colon and Ovarian Cancer

    International Nuclear Information System (INIS)

    Buchsbaum, Donald J.; Vallera, Daniel A.

    2006-01-01

    mixed with the EpCam sFv that was synthesized without any toxin attached. The proliferation studies showed that EpCam sFv was able to block the killing of the EpCam expressing cells by DTEpCam. An irrelevant control protein, 1D10Fc was unable to block. Together, these studies indicated that EpCam was exquisitely selective. In order to produce an IT of even greater potency, we used a toxin containing the Golgi retention sequence KDEL. The same EpCam sFv was spliced to truncated PE containing the terminal KDEL sequence. The addition of KDEL enhanced the potency of the EpCam sFv IT at least 6 logs or 1000-fold with an IC50 of 2 to 7 x 10-8 nM. This conjugate was also shown to be highly selective. Taken together, all of these studies indicate that in vitro experiments have shown that we have a highly potent IT that selectively kills colon cancer cells. The next step was to show that the EpCam IT had the ability to inhibit the growth of flank tumors in vivo in nude mice. The same human colon tumor cells, HT29 used in the in vitro studies were injected into the flank of nude mice. Tumor cells were injected into groups of mice and when tumors reached the size of 0.5 cm3, we injected our best-performing EpCam IT called EpCamKDEL intratumorally. There was a significant drop in tumor size indicating that this agent was very effective against human colon cancer. Since the EpCamKDEL was injected intratumorally, it did not have to travel through the systemic circulation to find its target. Our next step will be to inject EpCamKDEL intravenously into mice with flank tumors to determine if EpCamKDEL has the ability to migrate to the tumor systemically. The next step was to radiolabel EpCamKDEL to see whether it could serve as an RIT. We radiolabeled EpCam with 111In as a surrogate for 90Y and then incubated it with HT29. The labeling efficiency was over 90% indicating that a high percentage of the protein molecules could be readily radiolabeled. However, the immunoreactivity was only

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

    OpenAIRE

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

    2014-01-01

    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 o...

  10. 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)

  11. Bone Marrow Cell Therapy on 1,2-Dimethylhydrazine (DMH)-Induced Colon Cancer in Rats.

    Science.gov (United States)

    El-Khadragy, Manal F; Nabil, Heba M; Hassan, Basmaa N; Tohamy, Amany A; Waaer, Hanaa F; Yehia, Hany M; Alharbi, Afra M; Moneim, Ahmed Esmat Abdel

    2018-01-01

    Stem cell based therapies are being under focus due to their possible role in treatment of various tumors. Bone marrow stem cells believed to have anticancer potential and are preferred for their activities by stimulating the immune system, migration to the site of tumor and ability for inducting apoptosis in cancer cells. The current study was aimed to investigate the tumor suppressive effects of bone marrow cells (BMCs) in 1,2-dimethylhydrazine (DMH)-induced colon cancer in rats. The rats were randomly allocated into four groups: control, BMCs alone, DMH alone and BMCs with DMH. BMCs were injected intrarectally while DMH was injected subcutaneously at 20 mg/kg body weight once a week for 15 weeks. Histopathological examination and gene expression of survivin, β-catenin and multidrug resistance-1 (MDR-1) by real-time reverse transcription-polymerase chain reaction (RT-PCR) in rat colon tissues. This is in addition to oxidative stress markers in colon were performed across all groups. The presence of aberrant crypt foci was reordered once histopathological examination of colon tissue from rats which received DMH alone. Administration of BMCs into rats starting from zero-day of DMH injection improved the histopathological picture which showed a clear improvement in mucosal layer, few inflammatory cells infiltration periglandular and in the lamina propria. Gene expression in rat colon tissue demonstrated that BMCs down-regulated survivin, β-catenin, MDR-1 and cytokeratin 20 genes expression in colon tissues after colon cancer induction. Amelioration of the colon status after administration of MSCs has been evidenced by a major reduction of lipid peroxidation, nitric oxide, and increasing of glutathione content and superoxide dismutase along with catalase activities. Our findings demonstrated that BMCs have tumor suppressive effects in DMH-induced colon cancer as evidenced by down-regulation of survivin, β-catenin, and MDR-1 genes and enhancing the antioxidant

  12. Circumvention and reactivation of the p53 oncogene checkpoint in mouse colon tumors.

    Science.gov (United States)

    Aizu, Wataru; Belinsky, Glenn S; Flynn, Christopher; Noonan, Emily J; Boes, Colleen C; Godman, Cassandra A; Doshi, Bindi; Nambiar, Prashant R; Rosenberg, Daniel W; Giardina, Charles

    2006-10-16

    The p53 tumor suppressor protein is sequence-normal in azoxymethane (AOM)-induced mouse colon tumors, making them a good model for human colon cancers that retain a wild type p53 gene. Cellular localization and co-immunoprecipitation experiments using a cell line derived from an AOM-induced colon tumor (AJ02-NM(0) cells) pointed to constitutively expressed Mdm2 as being an important negative regulator of p53 in these cells. Although the Mdm2 inhibitory protein p19/ARF was expressed in AJ02-NM(0) cells, its level of expression was not sufficient for p53 activation. We tested the response of AJ02-NM(0) cells to the recently developed Mdm2 inhibitor, Nutlin-3. Nutlin-3 was found to activate p53 DNA binding in AJ02-NM(0) cells, to a level comparable to doxorubicin and 5-fluorouracil (5-FU). In addition, Nutlin-3 increased expression of the p53 target genes Bax and PERP to a greater extent than doxorubicin or 5-FU, and triggered a G2/M phase arrest in these cells, compared to a G1 arrest triggered by doxorubicin and 5-FU. The differences in the cellular response may be related to differences in the kinetics of p53 activation and/or its post-translational modification status. In an ex vivo experiment, Nutlin-3 was found to activate p53 target gene expression and apoptosis in AOM-induced tumor tissue, but not in normal adjacent mucosa. Our data indicate that Mdm2 inhibitors may be an effective means of selectively targeting colon cancers that retain a sequence-normal p53 gene while sparing normal tissue and that the AOM model is an appropriate model for the preclinical development of these drugs.

  13. The Role of Curcumin in Modulating Colonic Microbiota During Colitis and Colon Cancer Prevention

    Science.gov (United States)

    McFadden, Rita-Marie T.; Larmonier, Claire B.; Shehab, Kareem W.; Midura-Kiela, Monica; Ramalingam, Rajalakshmy; Harrison, Christy A.; Besselsen, David G.; Chase, John H.; Caporaso, J. Gregory; Jobin, Christian; Ghishan, Fayez K.; Kiela, Pawel R.

    2015-01-01

    Background Intestinal microbiota influences the progression of colitis-associated colorectal cancer (CAC). With diet being a key determinant of the gut microbial ecology, dietary interventions are an attractive avenue for the prevention of CAC. Curcumin is the most active constituent of the ground rhizome of the Curcuma Longa plant, which has been demonstrated to have anti-inflammatory, anti-oxidative and anti-proliferative properties. Methods Il10−/− mice on 129/SvEv background were used as a model of CAC. Starting at 10 weeks of age, WT or Il10−/− mice received six weekly i.p. injections of azoxymethane (AOM) or saline, and were started on either a control or curcumin-supplemented diet. Stools were collected every 4 weeks for microbial community analysis. Mice were sacrificed at 30 weeks of age. Results Curcumin-supplemented diet increased survival, decreased colon weight/length ratio, and at 0.5%, entirely eliminated tumor burden. Although colonic histology indicated improvement with curcumin, no effects of mucosal immune responses have been observed in PBS/Il10−/− mice, and limited effects were seen in AOM/Il10−/− mice. In WT and in Il10−/− mice, curcumin increased bacterial richness, prevented age-related decrease in alpha diversity, increased the relative abundance of Lactobacillales, and decreased Coriobacterales order. Taxonomic profile of AOM/Il10−/− mice receiving curcumin was more similar to those of wild-type mice than those fed control diet. Conclusions In AOM/Il10−/− model, curcumin reduced or eliminated colonic tumor burden with limited effects on mucosal immune responses. The beneficial effect of curcumin on tumorigenesis was associated with the maintenance of a more diverse colonic microbial ecology. PMID:26218141

  14. CacyBP/SIP promotes the proliferation of colon cancer cells.

    Directory of Open Access Journals (Sweden)

    Huihong Zhai

    Full Text Available CacyBP/SIP is a component of the ubiquitin pathway and is overexpressed in several transformed tumor tissues, including colon cancer, which is one of the most common cancers worldwide. It is unknown whether CacyBP/SIP promotes the proliferation of colon cancer cells. This study examined the expression level, subcellular localization, and binding activity of CacyBP/SIP in human colon cancer cells in the presence and absence of the hormone gastrin. We found that CacyBP/SIP was expressed in a high percentage of colon cancer cells, but not in normal colonic surface epithelium. CacyBP/SIP promoted the cell proliferation of colon cancer cells under both basal and gastrin stimulated conditions as shown by knockdown studies. Gastrin stimulation triggered the translocation of CacyBP/SIP to the nucleus, and enhanced interaction between CacyBP/SIP and SKP1, a key component of ubiquitination pathway which further mediated the proteasome-dependent degradation of p27kip1 protein. The gastrin induced reduction in p27kip1 was prevented when cells were treated with the proteasome inhibitor MG132. These results suggest that CacyBP/SIP may be promoting growth of colon cancer cells by enhancing ubiquitin-mediated degradation of p27kip1.

  15. MiR-30a-5p suppresses tumor growth in colon carcinoma by targeting DTL

    DEFF Research Database (Denmark)

    Baraniskin, Alexander; Birkenkamp-Demtröder, Karin; Maghnouj, Abdelouahid

    2012-01-01

    MicroRNAs (miRNAs) are small non-coding RNAs that are involved in different biological processes by suppressing target gene expression. Altered expression of miR-30a-5p has been reported in colon carcinoma. To elucidate its potential biological role in colon cancer, miR-30a-5p was overexpressed via...... with in silico miRNA target prediction, we identified the denticleless protein homolog (DTL) as a potential miRNA-30a-5p target. Subsequent reporter gene assays confirmed the predicted miR-30a-5p binding site in the 3'untranslated region of DTL. Importantly, overexpression of DTL in HCT116 cells partially...... is frequently overexpressed in colorectal cancer. Thus, our data suggest that restoring miR-30a-5p function may prove useful as therapeutic strategy for tumors with reduced miR-30a-5p expression....

  16. [The trends in clinical characteristics of colon cancer in last two decades].

    Science.gov (United States)

    Li, Jing-nan; Zhao, Li; Zheng, Wei-yang; Miao, Zheng; Tang, Xiao-yan; Qian, Jia-ming

    2010-03-01

    To explore the changing of clinical features of colon cancer within 20 years, in order to help early diagnosis and screening of colon cancer in China. A total of 1233 cases of colon cancer in Peking Union Medical College Hospital during 1989 - 2008 were retrospectively studied. All patients were divided into two groups according to the date of onset (1989 - 1998 and 1999 - 2008), the demographic features, clinical manifestations, laboratory examination, colonoscopy characteristics and pathological stage were analyzed. Comparing with 1989 - 1998, in recently 10 years, the morbidity of colon cancer increased, more female and old patients appeared; hematochezia significant less (51.8% vs 31.7%, P colon in 1989 - 1998 (44.6%) shift to sigmoid colon (38.7%) and descending colon (22.7%) up to now. Operation was the first choice of treatment, the early stage (Duke A) patients significant increased (9.3% vs 23.8%, P colon cancer obviously increased, the age was become elder and female patients were increased. The clinical manifestation became more nonspecific. According with the improvement of stool occult blood, serum CEA and colonoscopy detective method and wild spread using, more and more early stage patients were diagnosed. The location of tumor shift from right side to left side, and coincidence with west countries gradually.

  17. 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.

  18. 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.

  19. 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.

  20. PPARδ deficiency disrupts hypoxia-mediated tumorigenic potential of colon cancer cells.

    Science.gov (United States)

    Jeong, Eunshil; Koo, Jung Eun; Yeon, Sang Hyeon; Kwak, Mi-Kyoung; Hwang, Daniel H; Lee, Joo Young

    2014-11-01

    Peroxisome proliferator-activated receptor (PPAR) δ is highly expressed in colon epithelial cells and closely linked to colon carcinogenesis. However, the role of PPARδ in colon cancer cells in a hypoxic tumor microenvironment is not fully understood. We found that expression of the tumor-promoting cytokines, IL-8 and VEGF, induced by hypoxia (colon cancer cells. Consequently, PPARδ-knockout colon cancer cells exposed to hypoxia and deferoxamine failed to stimulate endothelial cell vascularization and macrophage migration/proliferation, whereas wild-type cells were able to induce angiogenesis and macrophage activation in response to hypoxic stress. Hypoxic stress induced transcriptional activation of PPARδ, but not its protein expression, in HCT116 cells. Exogenous expression of p300 potentiated deferoxamine-induced PPARδ transactivation, while siRNA knockdown of p300 abolished hypoxia- and deferoxamine-induced PPARδ transactivation. PPARδ associated with p300 upon hypoxic stress as demonstrated by coimmunoprecipitation studies. PI3K inhibitors or siRNA knockdown of Akt suppressed the PPARδ transactivation induced by hypoxia and deferoxamine in HCT116 cells, leading to decreased expression of IL-8 and VEGF. Collectively, these results reveal that PPARδ is required for hypoxic stress-mediated cytokine expression in colon cancer cells, resulting in promotion of angiogenesis, macrophage recruitment, and macrophage proliferation in the tumor microenvironment. p300 and the PI3K/Akt pathway play a role in the regulation of PPARδ transactivation induced by hypoxic stress. Our results demonstrate the positive crosstalk between PPARδ in tumor cells and the hypoxic tumor microenvironment and provide potential therapeutic targets for colon cancer. © 2014 Wiley Periodicals, Inc.

  1. Physical activity counteracts tumor cell growth in colon carcinoma C26-injected muscles: an interim report

    Directory of Open Access Journals (Sweden)

    Charlotte Hiroux

    2016-06-01

    Full Text Available Skeletal muscle tissue is a rare site of tumor metastasis but is the main target of the degenerative processes occurring in cancer-associated cachexia syndrome. Beneficial effects of physical activity in counteracting cancer-related muscle wasting have been described in the last decades. Recently it has been shown that, in tumor xeno-transplanted mouse models, physical activity is able to directly affect tumor growth by modulating inflammatory responses in the tumor mass microenvironment. Here, we investigated the effect of physical activity on tumor cell growth in colon carcinoma C26 cells injected tibialis anterior muscles of BALB/c mice. Histological analyses revealed that 4 days of voluntary wheel running significantly counteracts tumor cell growth in C26-injected muscles compared to the non-injected sedentary controls. Since striated skeletal muscle tissue is the site of voluntary contraction, our results confirm that physical activity can also directly counteract tumor cell growth in a metabolically active tissue that is usually not a target for metastasis.

  2. Decorin in Human Colon Cancer: Localization In Vivo and Effect on Cancer Cell Behavior In Vitro.

    Science.gov (United States)

    Nyman, Marie C; Sainio, Annele O; Pennanen, Mirka M; Lund, Riikka J; Vuorikoski, Sanna; Sundström, Jari T T; Järveläinen, Hannu T

    2015-09-01

    Decorin is generally recognized as a tumor suppressing molecule. Nevertheless, although decorin has been shown to be differentially expressed in malignant tissues, it has often remained unclear whether, in addition to non-malignant stromal cells, cancer cells also express it. Here, we first used two publicly available databases to analyze the current information about decorin expression and immunoreactivity in normal and malignant human colorectal tissue samples. The analyses demonstrated that decorin expression and immunoreactivity may vary in cancer cells of human colorectal tissues. Therefore, we next examined decorin expression in normal, premalignant and malignant human colorectal tissues in more detail using both in situ hybridization and immunohistochemistry for decorin. Our results invariably demonstrate that malignant cells within human colorectal cancer tissues are devoid of both decorin mRNA and immunoreactivity. Identical results were obtained for cells of neuroendocrine tumors of human colon. Using RT-qPCR, we showed that human colon cancer cell lines are also decorin negative, in accordance with the above in vivo results. Finally, we demonstrate that decorin transduction of human colon cancer cell lines causes a significant reduction in their colony forming capability. Thus, strategies to develop decorin-based adjuvant therapies for human colorectal malignancies are highly rational. © The Author(s) 2015.

  3. Up-regulation of CHAF1A, a poor prognostic factor, facilitates cell proliferation of colon cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Zehua; Cui, Feifei; Yu, Fudong; Peng, Xiao; Jiang, Tao; Chen, Dawei [Department of General Surgery, Shanghai Jiaotong University Affiliated First People’s Hospital, 85 Wujin Road, Shanghai 200080 (China); Lu, Su [Department of Pathology, Shanghai Jiaotong University Affiliated First People’s Hospital, 85 Wujin Road, Shanghai 200080 (China); Tang, Huamei, E-mail: tanghuamei@gmail.com [Department of Pathology, Shanghai Jiaotong University Affiliated First People’s Hospital, 85 Wujin Road, Shanghai 200080 (China); Peng, Zhihai, E-mail: zhihai.peng@hotmail.com [Department of General Surgery, Shanghai Jiaotong University Affiliated First People’s Hospital, 85 Wujin Road, Shanghai 200080 (China)

    2014-06-27

    Highlights: • We identified that CHAF1A was up-regulated in colon tumor mucosa in TMA. • The expression pattern of CHAF1A was validated with qPCR and western-blot. • CHAF1A overexpression is an independent indicator for poor colon cancer survival. • CHAF1A facilitates cell proliferation of colon cancer both in vitro and in vivo. - Abstract: Deregulation of chromatin assembly factor 1, p150 subunit A (CHAF1A) has recently been reported to be involved in the development of some cancer types. In this study, we identified that the frequency of positive CHAF1A staining in primary tumor mucosa (45.8%, 93 of 203 samples) was significantly elevated compared to that in paired normal mucosa (18.7%, 38 of 203 samples). The increased expression was strongly associated with cancer stage, tumor invasion, and histological grade. The five-year survival rate of patients with CHAF1A-positive tumors was remarkably lower than that of patients with CHAF1A-negative tumors. Colon cancer cells with CHAF1A knockdown exhibited decreased cell growth index, reduction in colony formation ability, elevated cell apoptosis rate as well as impaired colon tumorigenicity in nude mice. Hence, CHAF1A upregulation functions as a poor prognostic indicator of colon cancer, potentially contributing to its progression by mediating cancer cell proliferation.

  4. Up-regulation of CHAF1A, a poor prognostic factor, facilitates cell proliferation of colon cancer

    International Nuclear Information System (INIS)

    Wu, Zehua; Cui, Feifei; Yu, Fudong; Peng, Xiao; Jiang, Tao; Chen, Dawei; Lu, Su; Tang, Huamei; Peng, Zhihai

    2014-01-01

    Highlights: • We identified that CHAF1A was up-regulated in colon tumor mucosa in TMA. • The expression pattern of CHAF1A was validated with qPCR and western-blot. • CHAF1A overexpression is an independent indicator for poor colon cancer survival. • CHAF1A facilitates cell proliferation of colon cancer both in vitro and in vivo. - Abstract: Deregulation of chromatin assembly factor 1, p150 subunit A (CHAF1A) has recently been reported to be involved in the development of some cancer types. In this study, we identified that the frequency of positive CHAF1A staining in primary tumor mucosa (45.8%, 93 of 203 samples) was significantly elevated compared to that in paired normal mucosa (18.7%, 38 of 203 samples). The increased expression was strongly associated with cancer stage, tumor invasion, and histological grade. The five-year survival rate of patients with CHAF1A-positive tumors was remarkably lower than that of patients with CHAF1A-negative tumors. Colon cancer cells with CHAF1A knockdown exhibited decreased cell growth index, reduction in colony formation ability, elevated cell apoptosis rate as well as impaired colon tumorigenicity in nude mice. Hence, CHAF1A upregulation functions as a poor prognostic indicator of colon cancer, potentially contributing to its progression by mediating cancer cell proliferation

  5. CIMP status of interval colon cancers: another piece to the puzzle.

    Science.gov (United States)

    Arain, Mustafa A; Sawhney, Mandeep; Sheikh, Shehla; Anway, Ruth; Thyagarajan, Bharat; Bond, John H; Shaukat, Aasma

    2010-05-01

    Colon cancers diagnosed in the interval after a complete colonoscopy may occur due to limitations of colonoscopy or due to the development of new tumors, possibly reflecting molecular and environmental differences in tumorigenesis resulting in rapid tumor growth. In a previous study from our group, interval cancers (colon cancers diagnosed within 5 years of a complete colonoscopy) were almost four times more likely to demonstrate microsatellite instability (MSI) than non-interval cancers. In this study we extended our molecular analysis to compare the CpG island methylator phenotype (CIMP) status of interval and non-interval colorectal cancers and investigate the relationship between the CIMP and MSI pathways in the pathogenesis of interval cancers. We searched our institution's cancer registry for interval cancers, defined as colon cancers that developed within 5 years of a complete colonoscopy. These were frequency matched in a 1:2 ratio by age and sex to patients with non-interval cancers (defined as colon cancers diagnosed on a patient's first recorded colonoscopy). Archived cancer specimens for all subjects were retrieved and tested for CIMP gene markers. The MSI status of subjects identified between 1989 and 2004 was known from our previous study. Tissue specimens of newly identified cases and controls (between 2005 and 2006) were tested for MSI. There were 1,323 cases of colon cancer diagnosed over the 17-year study period, of which 63 were identified as having interval cancer and matched to 131 subjects with non-interval cancer. Study subjects were almost all Caucasian men. CIMP was present in 57% of interval cancers compared to 33% of non-interval cancers (P=0.004). As shown previously, interval cancers were more likely than non-interval cancers to occur in the proximal colon (63% vs. 39%; P=0.002), and have MSI 29% vs. 11%, P=0.004). In multivariable logistic regression model, proximal location (odds ratio (OR) 1.85; 95% confidence interval (CI) 1

  6. Can the localization of primary colonic tumors be improved by staging CT without specific bowel preparation compared to optical colonoscopy?

    International Nuclear Information System (INIS)

    Feuerlein, Sebastian; Grimm, Lars J.; Davenport, Matthew S.; Haystead, Clare M.; Miller, Chad M.; Neville, Amy M.; Jaffe, Tracy A.

    2012-01-01

    Objectives: To investigate the ability of staging computed tomography (CT) without bowel preparation to accurately localize colonic tumors compared to optical colonoscopy. Methods: The local institutional review board approved this retrospective and HIPAA-compliant study. Forty-six patients with colonic adenocarcinoma, preoperative colonoscopy, and staging CT within 60 days of resection were included. Patients underwent contrast enhanced CT imaging without bowel preparation or oral contrast. The colon was divided into four segments with the operative reports used as the standard. Rectal and cecal cancers were excluded. CT scans were reviewed by 5 readers in a segmental binary fashion using a 5-point confidence scale in two sessions blinded and unblinded to the colonoscopy report. Results: At surgery 49 tumors were found in 46 patients. Readers detected 86.1%, 74.3%, and 66.9% of lesions with 92.0%, 94.1%, and 95.4% accuracy for confidence scores of ≥3, ≥4, and 5. CT interobserver agreement was good (κ = 0.82) for the unblinded and moderate (κ = 0.60) for the blinded read. Colonoscopic localization was only 78.7% accurate with 2 tumors undiscovered. Colonoscopic accuracy was low in the descending colon (57.1%) and the transverse colon (55.6%). Conclusions: Preoperative staging CT is more accurate than colonoscopy in the localization of colonic tumors

  7. Butyrate Inhibits Cancerous HCT116 Colon Cell Proliferation but to a Lesser Extent in Noncancerous NCM460 Colon Cells.

    Science.gov (United States)

    Zeng, Huawei; Taussig, David P; Cheng, Wen-Hsing; Johnson, LuAnn K; Hakkak, Reza

    2017-01-01

    Butyrate, an intestinal microbiota metabolite of dietary fiber, exhibits chemoprevention effects on colon cancer development. However, the mechanistic action of butyrate remains to be determined. We hypothesize that butyrate inhibits cancerous cell proliferation but to a lesser extent in noncancerous cells through regulating apoptosis and cellular-signaling pathways. We tested this hypothesis by exposing cancerous HCT116 or non-cancerous NCM460 colon cells to physiologically relevant doses of butyrate. Cellular responses to butyrate were characterized by Western analysis, fluorescent microscopy, acetylation, and DNA fragmentation analyses. Butyrate inhibited cell proliferation, and led to an induction of apoptosis, genomic DNA fragmentation in HCT116 cells, but to a lesser extent in NCM460 cells. Although butyrate increased H3 histone deacetylation and p21 tumor suppressor expression in both cell types, p21 protein level was greater with intense expression around the nuclei in HCT116 cells when compared with that in NCM460 cells. Furthermore, butyrate treatment increased the phosphorylation of extracellular-regulated kinase 1/2 (p-ERK1/2), a survival signal, in NCM460 cells while it decreased p-ERK1/2 in HCT116 cells. Taken together, the activation of survival signaling in NCM460 cells and apoptotic potential in HCT116 cells may confer the increased sensitivity of cancerous colon cells to butyrate in comparison with noncancerous colon cells.

  8. 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...

  9. [Comparison of clinicopathological features and prognosis between left-sided colon cancer and right-sided colon cancer].

    Science.gov (United States)

    Gao, Xianhua; Yu, Guanyu; Liu, Peng; Hao, Liqiang; Liu, Lianjie; Zhang, Wei

    2017-06-25

    To compare the clinicopathological features and prognosis between left-sided colon cancer (LC) and right-sided colon cancer (RC). Clinicopathological and follow-up data of 2 174 colon carcinoma cases undergoing resection at Shanghai Changhai Hospital of The Second Military Medical University from January 2000 to December 2010 were retrospectively analyzed. Patients with transverse colon cancer, overlapping position, unknown location, recurrent cancer, multiple primary cancer, concomitant malignant tumors, preoperative chemotherapy, local resection, incomplete clinical data and missed follow up were excluded. Finally, a total of 1 036 patients, whose primary tumors were radically removed, were enrolled, with 563 patients in LC group (including carcinoma in cecum, ascending colon and hepatic flexure) and 473 in RC group (including carcinoma in splenic flexure, descending colon and sigmoid colon). The clinicopathological features and survival, including median overall survival, 5-year overall survival rate, tumor specific median overall survival, cancer specific 5-year overall survival rate, were compared between LC and RC groups. Tumor specific overall survival was defined as the period between operation date to the date of death caused by cancer progression. Multivariate Cox regression analysis was used to analyze the influencing factors of survival. Propensity score matching was carried out to balance the clinicopathological factors between the two groups with the SAS 9.3, taking the following parameters into consideration (age, gender, gross appearance, tumor diameter, invasion depth, lymph node metastasis, distant metastasis, TNM stages, differentiation, CEA and CA199-9). Patients in RC group and LC group were matched according to the propensity scores and the clinicopathological characteristics and prognosis of two groups were compared again. No significant differences were identified between the two groups in age, distant metastasis and serum CEA level

  10. Review article: loss of the calcium-sensing receptor in colonic epithelium is a key event in the pathogenesis of colon cancer.

    LENUS (Irish Health Repository)

    Rogers, Ailín C

    2012-03-01

    The calcium-sensing receptor (CaSR) is expressed abundantly in normal colonic epithelium and lost in colon cancer, but its exact role on a molecular level and within the carcinogenesis pathway is yet to be described. Epidemiologic studies show that inadequate dietary calcium predisposes to colon cancer; this may be due to the ability of calcium to bind and upregulate the CaSR. Loss of CaSR expression does not seem to be an early event in carcinogenesis; indeed it is associated with late stage, poorly differentiated, chemo-resistant tumors. Induction of CaSR expression in neoplastic colonocytes arrests tumor progression and deems tumors more sensitive to chemotherapy; hence CaSR may be an important target in colon cancer treatment. The CaSR has a complex role in colon cancer; however, more investigation is required on a molecular level to clarify its exact function in carcinogenesis. This review describes the mechanisms by which the CaSR is currently implicated in colon cancer and identifies areas where further study is needed.

  11. DPEP1, expressed in the early stages of colon carcinogenesis, affects cancer cell invasiveness.

    Science.gov (United States)

    Toiyama, Yuji; Inoue, Yasuhiro; Yasuda, Hiromi; Saigusa, Susumu; Yokoe, Takeshi; Okugawa, Yoshinaga; Tanaka, Koji; Miki, Chikao; Kusunoki, Masato

    2011-02-01

    We investigated changes in the gene expression profile in colon cancer in order to identify gene markers that may be useful in the management of this disease. The Cancer Genome Anatomy Project was used to detect differences in gene expression between normal and cancer tissue. The overexpression of dipeptidase-1 (DPEP1) in cancer tissue was confirmed in a sample of 76 patients by real-time PCR. To identify the function of DPEP1, RNA interference (RNAi) was used to inactivate this gene in the colon cancer cell line. Immunohistochemical analysis was performed to characterize the pattern of DPEP1 expression in colon cancer. DPEP1 expression in cancer was significantly higher than that in normal tissue. However, DPEP1 expression decreased with pathological differentiation, lymph-node and distant metastasis. Patients with tumors with decreased DPEP1 expression showed a poorer prognosis, and this was also true of patients with tumors who are treated with curative intent. RNAi-mediated DPEP1 reduction in the colon cancer cell line did not result in cell proliferation or apoptosis, but was associated with an increased invasive ability. DPEP1 protein was observed on the apical side of the cancer cells, and is expressed in the early stages of carcinogenesis, even in adenomas of both sporadic colorectal cancer and familial adenomatous polyposis patients. DPEP1 expression in normal colonic mucosa is very low, but it is highly expressed in colorectal adenoma and cancer specimens and is negatively correlated with parameters of pathological aggressiveness and poor prognosis. DPEP1 is expressed in the early stages of colon carcinogenesis and affects cancer cell invasiveness.

  12. 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...

  13. Different effects of ERβ and TROP2 expression in Chinese patients with early-stage colon cancer.

    Science.gov (United States)

    Fang, Yu-Jing; Wang, Guo-Qiang; Lu, Zhen-Hai; Zhang, Lin; Li, Ji-Bin; Wu, Xiao-Jun; Ding, Pei-Rong; Ou, Qing-Jian; Zhang, Mei-Fang; Jiang, Wu; Pan, Zhi-Zhong; Wan, De-Sen

    2012-12-01

    Estrogen receptor beta (ERβ) and TROP2 expressed in colon carcinoma and might play an important role there. We explored the relationship of ERβ and TROP2 expression with the prognosis of early-stage colon cancer. ERβ and TROP2 levels were assessed by immunohistochemistry in normal mucosa and tumoral tissues from 220 Chinese patients with T(3)N(0)M(0) (stage IIa) and T(4)N(0)M(0) (stage IIb) colon cancer in the Cancer Center, Sun Yat-sen University, who underwent curative surgical resection between 1995 and 2003. The Cox proportional hazards regression model was applied to analyze the overall survival (OS) data, and the ROC curve, Kaplan-Meier estimate, log rank test, and Jackknife method were used to show the effect of ERβ and TROP2 expression at different stages of cancer. The 5-year survival rates were not significantly different between the patients with stage IIa and stage IIb colon cancer (83 vs. 80 %, respectively). The high expression of ERβ was related to decreasing OS in stage IIa and stage IIb colon cancer, while the high expression of TROP2 was related to decreasing OS in stage IIb colon cancer. The expression of ERβ and TROP2 has tumor-suppressive and tumor-promoting effect in stage IIa and stage IIb colon cancer, respectively.

  14. 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.

  15. Differences in patterns of allelic loss between two common types of adult cancer, breast and colon carcinoma, and Wilms' tumor of childhood

    NARCIS (Netherlands)

    Devilee, P.; van den Broek, M.; Mannens, M.; Slater, R.; Cornelisse, C. J.; Westerveld, A.; Khan, P. M.

    1991-01-01

    Several chromosomal regions exhibit loss of heterozygosity (LOH) in different types of human tumor, and on this basis are presumed to carry-suppressor genes. We studied 7 of such chromosome regions, including 3p, 5q, 11p, 13q, 17p, 18q and 22q, using a selected set of DNA markers in 44 Wilms'

  16. 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

  17. MAP kinase genes and colon and rectal cancer

    Science.gov (United States)

    Slattery, Martha L.

    2012-01-01

    Mitogen-activated protein kinase (MAPK) pathways regulate many cellular functions including cell proliferation, differentiation, migration and apoptosis. We evaluate genetic variation in the c-Jun-N-terminal kinases, p38, and extracellular regulated kinases 1/2 MAPK-signaling pathways and colon and rectal cancer risk using data from population-based case-control studies (colon: n = 1555 cases, 1956 controls; rectal: n = 754 cases, 959 controls). We assess 19 genes (DUSP1, DUSP2, DUSP4, DUSP6, DUSP7, MAP2K1, MAP3K1, MAP3K2, MAP3K3, MAP3K7, MAP3K9, MAP3K10, MAP3K11, MAPK1, MAPK3, MAPK8, MAPK12, MAPK14 and RAF1). MAP2K1 rs8039880 [odds ratio (OR) = 0.57, 95% confidence interval (CI) = 0.38, 0.83; GG versus AA genotype] and MAP3K9 rs11625206 (OR = 1.41, 95% CI = 1.14, 1.76; recessive model) were associated with colon cancer (P adj value rectal cancer (P adj cancer risk. Genetic variants had unique associations with KRAS, TP53 and CIMP+ tumors. DUSP2 rs1724120 [hazard rate ratio (HRR) = 0.72, 95%CI = 0.54, 0.96; AA versus GG/GA), MAP3K10 rs112956 (HRR = 1.40, 95% CI = 1.10, 1.76; CT/TT versus CC) and MAP3K11 (HRR = 1.76, 95% CI 1.18, 2.62 TT versus GG/GT) influenced survival after diagnosis with colon cancer; MAP2K1 rs8039880 (HRR = 2.53, 95% CI 1.34, 4.79 GG versus AG/GG) and Raf1 rs11923427 (HRR = 0.59 95% CI = 0.40, 0.86; AA versus TT/TA) were associated with rectal cancer survival. These data suggest that genetic variation in the MAPK-signaling pathway influences colorectal cancer risk and survival after diagnosis. Associations may be modified by lifestyle factors that influence inflammation and oxidative stress. PMID:23027623

  18. The nonfermentable dietary fiber lignin alters putative colon cancer risk factors but does not protect against DMH-induced colon cancer in rats.

    Science.gov (United States)

    Cameron, I L; Hardman, W E; Heitman, D W

    1997-01-01

    The effect of supplementation of the diet with autohydrolyzed lignin on 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis was studied using 112 male Sprague-Dawley rats. Rats received eight weekly injections of DMH (9.5 mg/kg s.c.) or the saline vehicle solution and then were maintained on a basal AIN-76 fiber-free diet or the basal fiber-free diet plus 5% or 10% (wt/wt) lignin for 24 weeks. Rats were killed 32 weeks after the start of the experiment. Colon tumor incidence, location, and multiplicity were determined. Body weight, caloric intake, fecal dry weight, gut transit time, pH of cecal contents, and total fecal bile acid excretion were measured. Supplementation of the diet with 5% or 10% lignin resulted in increased fecal dry weight and total fecal bile acid excretion and in decreased gut transit time, colon pH, and fecal bile acid concentration. Dietary lignin did not significantly affect colon tumor incidence or multiplicity compared with the fiber-free diet. Thus dietary supplementation with autohydrolyzed lignin, a food fiber with good bulking characteristics, had a significant effect on several factors that have previously been linked to reduction of colon cancer risk, but the consumption of high levels of lignin did not decrease the risk for colon cancer.

  19. Colon cancer chemoprevention with ginseng and other botanicals.

    OpenAIRE

    Wargovich, M J

    2001-01-01

    Colorectal cancer is becoming increasingly common in Asian countries and still remains the second leading cause of cancer deaths in the United States. Efforts to prevent colon cancer have targeted early detection through screening and chemoprevention. For the last ten years our laboratory has utilized an in vivo screening assay for the testing of potential cancer preventives for colon cancer. We have conducted investigations on over 150 compounds including many with botanical or herbal origin...

  20. 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...

  1. MicroRNA classifier and nomogram for metastasis prediction in colon cancer.

    Science.gov (United States)

    Goossens-Beumer, Inès J; Derr, Remco S; Buermans, Henk P J; Goeman, Jelle J; Böhringer, Stefan; Morreau, Hans; Nitsche, Ulrich; Janssen, Klaus-Peter; van de Velde, Cornelis J H; Kuppen, Peter J K

    2015-01-01

    Colon cancer prognosis and treatment are currently based on a classification system still showing large heterogeneity in clinical outcome, especially in TNM stages II and III. Prognostic biomarkers for metastasis risk are warranted as development of distant recurrent disease mainly accounts for the high lethality rates of colon cancer. miRNAs have been proposed as potential biomarkers for cancer. Furthermore, a verified standard for normalization of the amount of input material in PCR-based relative quantification of miRNA expression is lacking. A selection of frozen tumor specimens from two independent patient cohorts with TNM stage II-III microsatellite stable primary adenocarcinomas was used for laser capture microdissection. Next-generation sequencing was performed on small RNAs isolated from colorectal tumors from the Dutch cohort (N = 50). Differential expression analysis, comparing in metastasized and nonmetastasized tumors, identified prognostic miRNAs. Validation was performed on colon tumors from the German cohort (N = 43) using quantitative PCR (qPCR). miR25-3p and miR339-5p were identified and validated as independent prognostic markers and used to construct a multivariate nomogram for metastasis risk prediction. The nomogram showed good probability prediction in validation. In addition, we recommend combination of miR16-5p and miR26a-5p as standard for normalization in qPCR of colon cancer tissue-derived miRNA expression. In this international study, we identified and validated a miRNA classifier in primary cancers, and propose a nomogram capable of predicting metastasis risk in microsatellite stable TNM stage II-III colon cancer. In conjunction with TNM staging, by means of a nomogram, this miRNA classifier may allow for personalized treatment decisions based on individual tumor characteristics. ©2014 American Association for Cancer Research.

  2. Complex of MUC1, CIN85 and Cbl in Colon Cancer Progression and Metastasis

    International Nuclear Information System (INIS)

    Cascio, Sandra; Finn, Olivera J.

    2015-01-01

    We previously reported that CIN85, an 85 KDa protein known to be involved in tumor cell migration and metastasis through its interaction with Cbl, associates with MUC1 in tumor cells. MUC1/CIN85 complex also regulates migration and invasion of tumor cells in vitro. Here, we examined specifically human colon carcinoma tissue microarrays (TMA) by immunohistochemistry for the expression of MUC1 and CIN85 and their potential role in cancer progression and metastasis. We detected a significant increase in expression of both MUC1 and CIN85 associated with advanced tumor stage and lymph node metastasis. We further investigated if Cbl could also be present in the MUC1/CIN85 complex. Co-immunoprecipitation assay showed that Cbl co-localized both with CIN85 and with MUC1 in a human colon cancer cell line. To begin to investigate the in vivo relevance of MUC1 overexpression and association with CIN85 and Cbl in cancer development and progression, we used human MUC1 transgenic mice that express MUC1 on the colonic epithelial cells, treated with azoxymethane to initiate and dextran sulfate sodium (AOM/DSS) to promote colorectal carcinogenesis. MUC1.Tg mice showed higher tumor incidence and decreased survival when compared with wild-type mice. Consistent with the in vitro data, the association of MUC1, CIN85 and Cbl was detected in colon tissues of AOM/DSS-treated MUC1 transgenic mice. MUC1/CIN85/Cbl complex appears to contribute to promotion and progression of colon cancer and thus increased expression of MUC1, CIN85 and Cbl in early stage colon cancer might be predictive of poor prognosis

  3. Complex of MUC1, CIN85 and Cbl in Colon Cancer Progression and Metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Cascio, Sandra, E-mail: sac131@pitt.edu [Department of Immunology, University of Pittsburgh School of Medicine, E1040 Biomedical Science Tower, Pittsburgh, PA 15261 (United States); Fondazione Ri.Med, via Bandiera, Palermo 90133 (Italy); Finn, Olivera J., E-mail: sac131@pitt.edu [Department of Immunology, University of Pittsburgh School of Medicine, E1040 Biomedical Science Tower, Pittsburgh, PA 15261 (United States)

    2015-02-10

    We previously reported that CIN85, an 85 KDa protein known to be involved in tumor cell migration and metastasis through its interaction with Cbl, associates with MUC1 in tumor cells. MUC1/CIN85 complex also regulates migration and invasion of tumor cells in vitro. Here, we examined specifically human colon carcinoma tissue microarrays (TMA) by immunohistochemistry for the expression of MUC1 and CIN85 and their potential role in cancer progression and metastasis. We detected a significant increase in expression of both MUC1 and CIN85 associated with advanced tumor stage and lymph node metastasis. We further investigated if Cbl could also be present in the MUC1/CIN85 complex. Co-immunoprecipitation assay showed that Cbl co-localized both with CIN85 and with MUC1 in a human colon cancer cell line. To begin to investigate the in vivo relevance of MUC1 overexpression and association with CIN85 and Cbl in cancer development and progression, we used human MUC1 transgenic mice that express MUC1 on the colonic epithelial cells, treated with azoxymethane to initiate and dextran sulfate sodium (AOM/DSS) to promote colorectal carcinogenesis. MUC1.Tg mice showed higher tumor incidence and decreased survival when compared with wild-type mice. Consistent with the in vitro data, the association of MUC1, CIN85 and Cbl was detected in colon tissues of AOM/DSS-treated MUC1 transgenic mice. MUC1/CIN85/Cbl complex appears to contribute to promotion and progression of colon cancer and thus increased expression of MUC1, CIN85 and Cbl in early stage colon cancer might be predictive of poor prognosis.

  4. Combined adenocarcinoma-carcinoid tumor of transverse colon

    Directory of Open Access Journals (Sweden)

    Prosanta Kumar Bhattacharjee

    2013-01-01

    Full Text Available A 65-year-old male presented with painless hematochezia associated with episodic cramps in upper abdomen, watery diarrhea, and a slowly growing mass in upper abdomen. Examination revealed a firm 6 x 5 cm, intra-abdominal, epigastric mass. Colonoscopy up to 90 cm showed a stenosing, ulcero-proliferative lesion in the transverse colon. No synchronous lesion was detected. Biopsy revealed mucin secreting adenocarcinoma. Exploration showed the growth involving the transverse colon proximal to the splenic flexure with a part of ileum, approximately three feet proximal to ileo-caecal junction, adherent to it. No significant mesenteric lymph node enlargement was evident. The patient underwent resection of the growth along with the segment of adherent ileum. Continuity was re-established by a colo-colic and ileo-ileal anastomosis respectively. Patient received adjuvant chemotherapy. Post-operative histopathology demonstrated a composite histological pattern with an admixture of carcinoid tumor and adenocarcinoma, invasion of ileal serosa and adenocarcinomatous deposits in mesocolic lymph nodes, the tumor staging being (T4, N0, M0/Stage II for carcinoid and (T4, N1, M0/Stage III for adenocarcinoma. Patient was followed-up for a year and was doing well without any evidence of recurrence.

  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. Colon Cancer Tumorigenesis Initiated by the H1047R Mutant PI3K.

    Directory of Open Access Journals (Sweden)

    Alexander E Yueh

    Full Text Available The phosphoinositide 3-kinase (PI3K signaling pathway is critical for multiple important cellular functions, and is one of the most commonly altered pathways in human cancers. We previously developed a mouse model in which colon cancers were initiated by a dominant active PI3K p110-p85 fusion protein. In that model, well-differentiated mucinous adenocarcinomas developed within the colon and initiated through a non-canonical mechanism that is not dependent on WNT signaling. To assess the potential relevance of PI3K mutations in human cancers, we sought to determine if one of the common mutations in the human disease could also initiate similar colon cancers. Mice were generated expressing the Pik3caH1047R mutation, the analog of one of three human hotspot mutations in this gene. Mice expressing a constitutively active PI3K, as a result of this mutation, develop invasive adenocarcinomas strikingly similar to invasive adenocarcinomas found in human colon cancers. These tumors form without a polypoid intermediary and also lack nuclear CTNNB1 (β-catenin, indicating a non-canonical mechanism of tumor initiation mediated by the PI3K pathway. These cancers are sensitive to dual PI3K/mTOR inhibition indicating dependence on the PI3K pathway. The tumor tissue remaining after treatment demonstrated reduction in cellular proliferation and inhibition of PI3K signaling.

  7. A simple, quantitative method using alginate gel to determine rat colonic tumor volume in vivo.

    Science.gov (United States)

    Irving, Amy A; Young, Lindsay B; Pleiman, Jennifer K; Konrath, Michael J; Marzella, Blake; Nonte, Michael; Cacciatore, Justin; Ford, Madeline R; Clipson, Linda; Amos-Landgraf, James M; Dove, William F

    2014-04-01

    Many studies of the response of colonic tumors to therapeutics use tumor multiplicity as the endpoint to determine the effectiveness of the agent. These studies can be greatly enhanced by accurate measurements of tumor volume. Here we present a quantitative method to easily and accurately determine colonic tumor volume. This approach uses a biocompatible alginate to create a negative mold of a tumor-bearing colon; this mold is then used to make positive casts of dental stone that replicate the shape of each original tumor. The weight of the dental stone cast correlates highly with the weight of the dissected tumors. After refinement of the technique, overall error in tumor volume was 16.9% ± 7.9% and includes error from both the alginate and dental stone procedures. Because this technique is limited to molding of tumors in the colon, we utilized the Apc(Pirc/+) rat, which has a propensity for developing colonic tumors that reflect the location of the majority of human intestinal tumors. We have successfully used the described method to determine tumor volumes ranging from 4 to 196 mm³. Alginate molding combined with dental stone casting is a facile method for determining tumor volume in vivo without costly equipment or knowledge of analytic software. This broadly accessible method creates the opportunity to objectively study colonic tumors over time in living animals in conjunction with other experiments and without transferring animals from the facility where they are maintained.

  8. Influence of race on microsatellite instability and CD8+ T cell infiltration in colon cancer.

    Directory of Open Access Journals (Sweden)

    John M Carethers

    Full Text Available African American patients with colorectal cancer show higher mortality than their Caucasian counterparts. Biology might play a partial role, and prior studies suggest a higher prevalence for microsatellite instability (MSI among cancers from African Americans, albeit patients with MSI cancers have improved survival over patients with non-MSI cancers, counter to the outcome observed for African American patients. CD8+ T cell infiltration of colon cancer is postively correlated with MSI tumors, and is also related to improved outcome. Here, we utilized a 503-person, population-based colon cancer cohort comprising 45% African Americans to determine, under blinded conditions from all epidemiological data, the prevalence of MSI and associated CD8+ T cell infiltration within the cancers. Among Caucasian cancers, 14% were MSI, whereas African American cancers demonstrated 7% MSI (P = 0.009. Clinically, MSI cancers between races were similar; among microsatellite stable cancers, African American patients were younger, female, and with proximal cancers. CD8+ T cells were higher in MSI cancers (88.0 vs 30.4/hpf, P<0.0001, but was not different between races. Utilizing this population-based cohort, African American cancers show half the MSI prevalence of Caucasians without change in CD8+ T cell infiltration which may contribute towards their higher mortality from colon cancer.

  9. Adjuvant chemotherapy is associated with improved survival in patients with stage II colon cancer.

    Science.gov (United States)

    Casadaban, Leigh; Rauscher, Garth; Aklilu, Mebea; Villenes, Dana; Freels, Sally; Maker, Ajay V

    2016-11-15

    The role of adjuvant chemotherapy in patients with stage II colon cancer remains to be elucidated and its use varies between patients and institutions. Currently, clinical guidelines suggest discussing adjuvant chemotherapy for patients with high-risk stage II disease in the absence of conclusive randomized controlled trial data. To further investigate this relationship, the objective of the current study was to determine whether an association exists between overall survival (OS) and adjuvant chemotherapy in patients stratified by age and pathological risk features. Data from the National Cancer Data Base were analyzed for demographics, tumor characteristics, management, and survival of patients with stage II colon cancer who were diagnosed from 1998 to 2006 with survival information through 2011. Pearson Chi-square tests and binary logistic regression were used to analyze disease and demographic data. Survival analysis was performed with the log-rank test and Cox proportional hazards regression modeling. Propensity score weighting was used to match cohorts. Among 153,110 patients with stage II colon cancer, predictors of receiving chemotherapy included age clinically relevant OS was associated with the receipt of adjuvant chemotherapy in all patient subgroups regardless of high-risk tumor pathologic features (poor or undifferentiated histology, colon cancer evaluated to date, improved OS was found to be associated with adjuvant chemotherapy regardless of treatment regimen, patient age, or high-risk pathologic risk features. Cancer 2016;122:3277-3287. © 2016 American Cancer Society. © 2016 American Cancer Society.

  10. Trypanosomiasis-induced megacolon illustrates how myenteric neurons modulate the risk for colon cancer in rats and humans.

    Directory of Open Access Journals (Sweden)

    Vinicius Kannen

    2015-04-01

    Full Text Available Trypanosomiasis induces a remarkable myenteric neuronal degeneration leading to megacolon. Very little is known about the risk for colon cancer in chagasic megacolon patients. To clarify whether chagasic megacolon impacts on colon carcinogenesis, we investigated the risk for colon cancer in Trypanosoma cruzi (T. cruzi infected patients and rats.Colon samples from T. cruzi-infected and uninfected patients and rats were histopathologically investigated with colon cancer biomarkers. An experimental model for chemical myenteric denervation was also performed to verify the myenteric neuronal effects on colon carcinogenesis. All experiments complied the guidelines and approval of ethical institutional review boards.No colon tumors were found in chagasic megacolon samples. A significant myenteric neuronal denervation was observed. Epithelial cell proliferation and hyperplasia were found increased in chagasic megacolon. Analyzing the argyrophilic nucleolar organiser regions within the cryptal bottom revealed reduced risk for colon cancer in Chagas' megacolon patients. T. cruzi-infected rats showed a significant myenteric neuronal denervation and decreased numbers of colon preneoplastic lesions. In chemical myenteric denervated rats preneoplastic lesions were reduced from the 2nd wk onward, which ensued having the colon myenteric denervation significantly induced.Our data suggest that the trypanosomiasis-related myenteric neuronal degeneration protects the colon tissue from carcinogenic events. Current findings highlight potential mechanisms in tropical diseases and cancer research.

  11. Transverse colon cancer occurring at a colostomy site 35 years after colostomy: a case report.

    Science.gov (United States)

    Maeda, Chiyo; Hidaka, Eiji; Shimada, Mari; Shimada, Shoji; Nakahara, Kenta; Takayanagi, Daisuke; Takehara, Yusuke; Mukai, Shumpei; Sawada, Naruhiko; Ishida, Fumio; Kudo, Shin-ei

    2015-05-06

    Carcinomas occurring at colostomy sites are rare, and most of these are metachronous colorectal cancers. The median time between colostomy and development of a carcinoma at a colostomy site is 22 years, which exceeds the length of the recommended follow-up period. We report a rare case of a carcinoma of the transverse colon occurring at a colostomy site in a patient without a history of colorectal cancer. An 89-year-old woman presented with a tumor occurring at a colostomy site. Thirty-five years previously, she had undergone a transverse loop colostomy for an iatrogenic colon perforation that occurred during left ureteral lithotomy. Upon physical examination, the patient had a hard nodule measuring 3 cm at the colostomy site. A biopsy of the nodule suggested adenocarcinoma, and the preoperative diagnosis was transverse colon cancer. A laparotomy was performed via a peristomal incision with 5-mm skin margins, and the tumor was covered by a surgical glove to avoid any tumor seeding. The colon was separated from the tumor by 5-cm margins, and the specimen was removed en bloc. An end colostomy was constructed to a new site on the right side of the abdomen. The deficit in the abdominal wall was repaired, and the skin was closed via a purse-string suture. The final diagnosis of the stoma tumor was transverse colon cancer (T2, N0, M0, stage I). One year and five months after surgery, there was no evidence of recurrence. The occurrence of carcinomas at colostomy sites in patients without a history of colorectal cancer is rare. It is important to train ostomates to monitor the stoma for possible tumor recurrence.

  12. A Case of Advanced Descending Colon Cancer in an Adult Patient with Intestinal Malrotation

    Directory of Open Access Journals (Sweden)

    Yoshifumi Nakayama

    2016-01-01

    Full Text Available This report presents an operative case of advanced descending colon cancer in an adult patient with intestinal malrotation. A 63-year-old Japanese male was suffering from left side abdominal pain, abdominal distension, and constipation. An endoscopic examination revealed an advanced tumor in the descending colon. Computed tomography (CT of the abdomen revealed the thickening of the descending colon wall and superior mesenteric vein rotation. An opaque enema detected severe stenosis of the descending colon. An abdominal X-ray examination revealed the dilation of the colon and small intestine with niveau. At the insertion of an ileus tube, the C-loop of the duodenum was observed to be absent and the small intestine was located on the right side of the abdomen. After the decompression of the bowel contents, laparotomy was performed. Descending colon cancer was observed to have directly invaded the left side of the transverse colon. Left hemicolectomy, lymph node dissection, and appendectomy were performed. The patient had an uneventful recovery and was discharged from the hospital on the 16th day after surgery. This report presents a rare operative case of descending colon cancer in an adult patient with intestinal malrotation.

  13. Synthesis and characterization of near IR fluorescent albumin nanoparticles for optical detection of colon cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, Sarit; Pellach, Michal [Department of Chemistry, Bar-Ilan Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat-Gan 52900 (Israel); Kam, Yossi [Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, P.O. Box 12065, Jerusalem 91120 (Israel); Grinberg, Igor; Corem-Salkmon, Enav [Department of Chemistry, Bar-Ilan Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat-Gan 52900 (Israel); Rubinstein, Abraham [Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, P.O. Box 12065, Jerusalem 91120 (Israel); Margel, Shlomo, E-mail: shlomo.margel@mail.biu.ac.il [Department of Chemistry, Bar-Ilan Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat-Gan 52900 (Israel)

    2013-03-01

    Near IR (NIR) fluorescent human serum albumin (HSA) nanoparticles hold great promise as contrast agents for tumor diagnosis. HSA nanoparticles are considered to be biocompatible, non-toxic and non-immunogenic. In addition, NIR fluorescence properties of these nanoparticles are important for in vivo tumor diagnostics, with low autofluorescence and relatively deep penetration of NIR irradiation due to low absorption of biomatrices. The present study describes the synthesis of new NIR fluorescent HSA nanoparticles, by entrapment of a NIR fluorescent dye within the HSA nanoparticles, which also significantly increases the photostability of the dye. Tumor-targeting ligands such as peanut agglutinin (PNA) and anti-carcinoembryonic antigen antibodies (anti-CEA) were covalently conjugated to the NIR fluorescent albumin nanoparticles, increasing the potential fluorescent signal in tumors with upregulated corresponding receptors. Specific colon tumor detection by the NIR fluorescent HSA nanoparticles was demonstrated in a chicken embryo model and a rat model. In future work we also plan to encapsulate cancer drugs such as doxorubicin within the NIR fluorescent HSA nanoparticles for both colon cancer imaging and therapy. - Highlights: Black-Right-Pointing-Pointer Near IR human serum albumin nanoparticles were synthesized and characterized. Black-Right-Pointing-Pointer Nanoparticles were shown to be physically and chemically stable and photostable. Black-Right-Pointing-Pointer Tumor-targeting ligands were covalently conjugated to the nanoparticles. Black-Right-Pointing-Pointer Specific colon cancer tumor detection was demonstrated in chicken-embryo and rat models.

  14. Synthesis and characterization of near IR fluorescent albumin nanoparticles for optical detection of colon cancer

    International Nuclear Information System (INIS)

    Cohen, Sarit; Pellach, Michal; Kam, Yossi; Grinberg, Igor; Corem-Salkmon, Enav; Rubinstein, Abraham; Margel, Shlomo

    2013-01-01

    Near IR (NIR) fluorescent human serum albumin (HSA) nanoparticles hold great promise as contrast agents for tumor diagnosis. HSA nanoparticles are considered to be biocompatible, non-toxic and non-immunogenic. In addition, NIR fluorescence properties of these nanoparticles are important for in vivo tumor diagnostics, with low autofluorescence and relatively deep penetration of NIR irradiation due to low absorption of biomatrices. The present study describes the synthesis of new NIR fluorescent HSA nanoparticles, by entrapment of a NIR fluorescent dye within the HSA nanoparticles, which also significantly increases the photostability of the dye. Tumor-targeting ligands such as peanut agglutinin (PNA) and anti-carcinoembryonic antigen antibodies (anti-CEA) were covalently conjugated to the NIR fluorescent albumin nanoparticles, increasing the potential fluorescent signal in tumors with upregulated corresponding receptors. Specific colon tumor detection by the NIR fluorescent HSA nanoparticles was demonstrated in a chicken embryo model and a rat model. In future work we also plan to encapsulate cancer drugs such as doxorubicin within the NIR fluorescent HSA nanoparticles for both colon cancer imaging and therapy. - Highlights: ► Near IR human serum albumin nanoparticles were synthesized and characterized. ► Nanoparticles were shown to be physically and chemically stable and photostable. ► Tumor-targeting ligands were covalently conjugated to the nanoparticles. ► Specific colon cancer tumor detection was demonstrated in chicken-embryo and rat models.

  15. Imaging Matrix Metalloproteases in Spontaneous Colon Tumors: Validation by Correlation with Histopathology.

    Science.gov (United States)

    Hensley, Harvey; Cooper, Harry S; Chang, Wen-Chi L; Clapper, Margie L

    2017-01-01

    The use of fluorescent probes in conjunction with white-light colonoscopy is a promising strategy for improving the detection of precancerous colorectal lesions, in particular flat (sessile) lesions that do not protrude into the lumen of the colon. We describe a method for determining the sensitivity and specificity of an enzymatically activated near-infrared probe (MMPSense680) for the detection of colon lesions in a mouse model (APC +/Min-FCCC ) of spontaneous colorectal cancer. Fluorescence intensity correlates directly with the activity of matrix metalloproteinases (MMPs). Overexpression of MMPs is an early event in the development of colorectal lesions. Although the probe employed serves as a reporter of the activity of MMPs, our method can be applied to any fluorescent probe that targets an early molecular event in the development of colorectal tumors.

  16. [Progress in the early diagnosis of cancer of the colon and rectum].

    Science.gov (United States)

    Canessa, N; Roset, J; Boffi, A; Ferrara, J B; Galano, A; Albertengo, J C

    1978-09-01

    Our experience with the air contrast examination in the cancer of colon and rectum diagnoses is showed. The colaboration among radiologist, endoscopist, pathologist and surgeon is important. In the large bowel tumors diagnosis, the radiologic and endoscopic prodedures should be evaluated together. The double colonic contrast has showed in our experience, better results than with the barium enema. Over 31 patients with both studies, we obtained 13 false negatives (with barium enema, doing then the double colonic contrast became positive 12 (92.4%).

  17. Crucial role of interleukin-4 in the survival of colon cancer stem cells

    NARCIS (Netherlands)

    Francipane, Maria Giovanna; Alea, Mileidys Perez; Lombardo, Ylenia; Todaro, Matilde; Medema, J. P.; Stassi, Giorgio

    2008-01-01

    Colon tumors may be maintained by a rare fraction of cancer stem-like cells (CSC) that express the cell surface marker CD133. Self-renewing CSCs exhibit relatively greater resistance to clinical cytotoxic therapies and recent work suggests that this resistance may be mediated in part by an autocrine

  18. 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

  19. 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

  20. MicroRNA-98 Suppress Warburg Effect by Targeting HK2 in Colon Cancer Cells.

    Science.gov (United States)

    Zhu, Weimin; Huang, Yijiao; Pan, Qi; Xiang, Pei; Xie, Nanlan; Yu, Hao

    2017-03-01

    Warburg effect is a hallmark of cancer cells. Accumulating evidence suggests that microRNAs (miRs) could regulate such metabolic reprograming. Aberrant expression of miR-98 has been observed in many types of cancers. However, its functions and significance in colon cancer remain largely elusive. To investigate miR-98 expression and the biological functions in colon cancer progression. miR-98 expression levels were determined by quantitative RT-PCR in 215 cases of colon cancer samples. miR-98 mimic or inhibitor was used to test the biological functions in SW480 and HCT116 cells, followed by cell proliferation assay, lactate production, glucose uptake, and cellular ATP levels assay and extracellular acidification rates measurement. Western blot and luciferase assay were used to identify the target of miR-98. miR-98 was significantly down-regulated in colon cancer tissues compared to adjacent colon tissues and acted as a suppressor for Warburg effect in cancer cells. miR-98 inhibited glycolysis by directly targeting hexokinase 2, or HK2, illustrating a novel pathway to mediate Warburg effect of cancer cells. In vitro experiments further indicated that HK2 was involved in miR-98-mediated suppression of glucose uptake, lactate production, and cell proliferation. In addition, we detected HK2 expression in colon cancer tissues and found that the expressions of miR-98 and HK2 were negatively correlated. miR-98 acts as tumor suppressor gene and inhibits Warburg effect in colon cancer cells, which provided potential targets for clinical treatments.

  1. Tumor location and patient characteristics of colon and rectal adenocarcinomas in relation to survival and TNM classes

    International Nuclear Information System (INIS)

    Hemminki, Kari; Santi, Irene; Weires, Marianne; Thomsen, Hauke; Sundquist, Jan; Bermejo, Justo Lorenzo

    2010-01-01

    Old age at diagnosis is associated with poor survival in colorectal cancer (CRC) for unknown reasons. Recent data show that colonoscopy is efficient in preventing left-sided cancers only. We examine the association of Tumor Node Metastasis (TNM) classes with diagnostic age and patient characteristics. The Swedish Family-Cancer Database has data on TNM classes on 6,105 CRC adenocarcinoma patients. Ordinal logistic regression analysis was performed to model tumor characteristics according to age at diagnosis, tumor localization, gender, socioeconomic status, medical region and family history. The results were compared to results from survival analysis. The only parameters systematically associated with TNM classes were age and tumor localization. Young age at diagnosis was a risk factor for aggressive CRC, according to stage, N and M with odds ratios (ORs) ranging from 1.80 to 1.93 for diagnosis before age 50 years compared to diagnosis at 80+ years. All tumor characteristics, particularly T, were worse for colon compared to rectal tumors. Right-sided tumors showed worse characteristics for all classifiers but M. The survival analysis on patients diagnosed since 2000 showed a hazard ratio of 0.55 for diagnosis before age 50 years compared to diagnosis at over 80 years and a modestly better prognosis for left-sided compared to right-sided tumors. The results showed systematically more aggressive tumors in young compared to old patients. The poorer survival of old patients in colon cancer was not related to the available tumor characteristics. However, these partially agreed with the limited colonoscopic success with right-sided tumors

  2. 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,

  3. Reproductive and hormonal factors in male and female colon cancer

    NARCIS (Netherlands)

    Kampman, E.; Bijl, A.J.; Kok, C.; Veer, P. van 't

    1994-01-01

    We analysed data from a case-control study in the Netherlands in order to investigate whether reproductive events and hormonal factors are similarly related to colon cancer risk in men and women after adjustment for dietary factors. In total, 232 colon cancer cases (102 women, 130 men) and 259

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. Cáncer de colon recurrente: diagnóstico y tratamiento Recurrent colon cancer: diagnosis and treatment

    Directory of Open Access Journals (Sweden)

    Roswell Enrique GonzálezRodiles Heredia

    2009-03-01

    Full Text Available INTRODUCCIÓN. El cáncer recurrente es aquel que reaparece luego de un período de tiempo durante el cual no podía ser detectado. El objetivo del presente estudio fue identificar los elementos diagnósticos más relevantes del cáncer de colon recurrente, así como las opciones más adecuadas de tratamiento. MÉTODOS. Se realizó un estudio observacional, descriptivo, longitudinal y retrospectivo sobre el diagnóstico y los resultados del tratamiento de la recurrencia tumoral en 68 pacientes operados por cáncer de colon en un período de 16 años. RESULTADOS. Predominaron los pacientes mayores de 60 años, del sexo femenino; entre las localizaciones, el tumor primario en el colon sigmoides y ascendente, con estadificación en etapa II después de la operación inicial. Las recurrencias más frecuentes fueron la locorregional y la hepática, y su forma de presentación predominante, el tumor palpable. El método clínico y la ecografía abdominal fueron determinantes para el diagnóstico. El tratamiento quirúrgico con quimioterapia adyuvante fue el más efectivo en general, y en particular en la localización locorregional. La supervivencia alcanzó 2 años en el 30,9 % de los pacientes, con predominio de los que habían recibido tratamiento quirúrgico. A los 5 años había fallecido el 85,3 % de la serie. CONCLUSIONES. El diagnóstico precoz y el tratamiento adecuado de la recurrencia tumoral requieren la actuación de un equipo médico multidisciplinario pues es la causa de muerte preponderante en los operados de cáncer de colon con intención curativa. Los 2 primeros años de seguimiento posoperatorio constituyen el período de mayor riesgo de recurrencias.INTRODUCTION. Recurrent cancer is that that reappears after a period of time during which it could not be detected. The objective of this study was to identify the most important diagnostic elements of recurrent colon cancer, as well as the most adequate treatment options. METHODS. An

  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. Right Versus Left Colon Cancer Biology: Integrating the Consensus Molecular Subtypes.

    Science.gov (United States)

    Lee, Michael S; Menter, David G; Kopetz, Scott

    2017-03-01

    Although clinical management of colon cancer generally has not accounted for the primary tumor site, left-sided and right-sided colon cancers harbor different clinical and biologic characteristics. Right-sided colon cancers are more likely to have genome-wide hypermethylation via the CpG island methylator phenotype (CIMP), hypermutated state via microsatellite instability, and BRAF mutation. There are also differential exposures to potential carcinogenic toxins and microbiota in the right and left colon. Gene expression analyses further shed light on distinct biologic subtypes of colorectal cancers (CRCs), with 4 consensus molecular subtypes (CMSs) identified. Importantly, these subtypes are differentially distributed between right- and left-sided CRCs, with greater proportions of the "microsatellite unstable/immune" CMS1 and the "metabolic" CMS3 subtypes found in right-sided colon cancers. This review summarizes important biologic distinctions between right- and left-sided CRCs that likely impact prognosis and may predict for differential responses to biologic therapy. Given the inferior prognosis of stage III-IV right-sided CRCs and emerging data suggesting that anti-epidermal growth factor receptor antibody therapy is associated with worse survival in right-sided stage IV CRCs compared with left-sided cancers, these biologic differences between right- and left-sided CRCs provide critical context and may provide opportunities to personalize therapy. Copyright © 2017 by the National Comprehensive Cancer Network.

  11. Comparison of oncological outcomes of right-sided colon cancer versus left-sided colon cancer after curative resection: Which side is better outcome?

    Science.gov (United States)

    Lim, Dae Ro; Kuk, Jung Kul; Kim, Taehyung; Shin, Eung Jin

    2017-10-01

    There are embryological origins, anatomical, histological, genetic, and immunological differences between right-sided colon cancer (RCC) and left-sided colon cancer (LCC). Many studies have sought to determine the survival and prognosis according to tumor location. This study aimed to analyze outcomes between RCC and LCC. Between January 2000 and December 2012, data on 414 patients who underwent curative resection for RCC and LCC were retrieved from a retrospective database. Propensity score matching (1:1) was performed and RCC was identified in 207 and LCC in 207 patients. On average, RCC exhibited a more advanced N stage, increased tumor size, more frequently poorly differentiated tumors, more harvested lymph nodes, and more positivity of lymphovascular invasion than LCC. With a median follow-up of 66.7 months, the 5-year overall survival (OS) rates for RCC and LCC were 82.1% and 88.7%, respectively, (P cancers, the DFS rates were 61.1% (RCC) and 81.9% (LCC; P colon cancer is needed.

  12. Differential expression of nanog1 and nanogp8 in colon cancer cells

    International Nuclear Information System (INIS)

    Ishiguro, Tatsuya; Sato, Ai; Ohata, Hirokazu; Sakai, Hiroaki; Nakagama, Hitoshi; Okamoto, Koji

    2012-01-01

    Highlights: ► Nanog is expressed in a majority of colon cancer cell lines examined. ► Both nanog1 and nanogp8 are expressed in colon cancer cells with varying ratios. ► Nanog mediates cell proliferation of colon cancer cells. ► Nanog predominantly localizes in cytoplasm of colon cancer cells. -- Abstract: Nanog, a homeodomain transcription factor, is an essential regulator for promotion of self-renewal of embryonic stem cells and inhibition of their differentiation. It has been demonstrated that nanog1 as well as nanogp8, a retrogene of nanog1, is preferentially expressed in advanced stages of several types of cancer, suggesting their involvement during cancer progression. Here, we investigated the expression of Nanog in well-characterized colon cancer cell lines. Expression of Nanog was detectable in 5 (HCT116, HT29, RKO, SW48, SW620) out of seven cell lines examined. RNA expression analyses of nanog1 and nanogp8 indicated that, while nanog1 was a major form in SW620 as well as in teratoma cells Tera-2, nanogp8 was preferentially expressed in HT29 and HCT116. In accordance with this, shRNA-mediated knockdown of nanog1 caused the reduction of Nanog in SW620 but not in HT29. Inhibition of Nanog in SW620 cells negatively affected cell proliferation and tumor formation in mouse xenograft. Biochemical subcellular fractionation and immunostaining analyses revealed predominant localization of Nanog in cytoplasm in SW620 and HT29, while it was mainly localized in nucleus in Tera-2. Our data indicate that nanog1 and nanogp8 are differentially expressed in colon cancer cells, and suggest that their expression contributes to proliferation of colon cancer cells.

  13. Differential expression of nanog1 and nanogp8 in colon cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Ishiguro, Tatsuya; Sato, Ai; Ohata, Hirokazu; Sakai, Hiroaki [Division of Cancer Differentiation, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Nakagama, Hitoshi, E-mail: hnakagam@ncc.go.jp [Division of Cancer Development System, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Okamoto, Koji, E-mail: kojokamo@ncc.go.jo [Division of Cancer Differentiation, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan)

    2012-02-10

    Highlights: Black-Right-Pointing-Pointer Nanog is expressed in a majority of colon cancer cell lines examined. Black-Right-Pointing-Pointer Both nanog1 and nanogp8 are expressed in colon cancer cells with varying ratios. Black-Right-Pointing-Pointer Nanog mediates cell proliferation of colon cancer cells. Black-Right-Pointing-Pointer Nanog predominantly localizes in cytoplasm of colon cancer cells. -- Abstract: Nanog, a homeodomain transcription factor, is an essential regulator for promotion of self-renewal of embryonic stem cells and inhibition of their differentiation. It has been demonstrated that nanog1 as well as nanogp8, a retrogene of nanog1, is preferentially expressed in advanced stages of several types of cancer, suggesting their involvement during cancer progression. Here, we investigated the expression of Nanog in well-characterized colon cancer cell lines. Expression of Nanog was detectable in 5 (HCT116, HT29, RKO, SW48, SW620) out of seven cell lines examined. RNA expression analyses of nanog1 and nanogp8 indicated that, while nanog1 was a major form in SW620 as well as in teratoma cells Tera-2, nanogp8 was preferentially expressed in HT29 and HCT116. In accordance with this, shRNA-mediated knockdown of nanog1 caused the reduction of Nanog in SW620 but not in HT29. Inhibition of Nanog in SW620 cells negatively affected cell proliferation and tumor formation in mouse xenograft. Biochemical subcellular fractionation and immunostaining analyses revealed predominant localization of Nanog in cytoplasm in SW620 and HT29, while it was mainly localized in nucleus in Tera-2. Our data indicate that nanog1 and nanogp8 are differentially expressed in colon cancer cells, and suggest that their expression contributes to proliferation of colon cancer cells.

  14. A novel NSAID derivative, phospho-ibuprofen, prevents AOM-induced colon cancer in rats

    Science.gov (United States)

    OUYANG, NENGTAI; JI, PING; WILLIAMS, JENNIE L.

    2013-01-01

    The cancer chemopreventive properties and gastrointestinal toxicity of ibuprofen are well documented. Modification of existing NSAIDs has improved on the chemopreventive efficacy of this agent and reduced its toxicity. In this study, ibuprofen and a modified derivative (phospho-modified ibuprofen or p-ibuprofen) were used in a chemically induced model of colon cancer. Fisher 344 rats were injected with azoxymethane then treated with either ibuprofen (500 ppm) or p-ibuprofen (900 ppm) for 20 weeks to observe aberrant crypt foci (ACF) or 40 weeks to evaluate tumor incidence and multiplicity. β-catenin and p65 were measured in colonic tissues by immunofluorescence staining. Equal molar doses of ibuprofen (75 and 670 mg/kg) and p-ibuprofen (135 and 1,215 mg/kg) were administered to rats for 7 days to assess acute toxicity. The in vitro effect of p-ibuprofen on COX-2 and PGE2 synthesis, β-catenin expression and NF-κB activity were examined in RAW 264.7 macrophage and HCT 116 colon cancer cells. At week 20, p-ibuprofen and ibuprofen significantly reduced the multiplicity of ACF compared with control (pibuprofen and ibuprofen reduced the multiplicity of colon tumors compared with control (pibuprofen (670 mg/kg) and p-ibuprofen (1,215 mg/kg) resulted in stomach ulceration in 85.7% (6 out of 7) and 14.3% (1 out of 7) of rats, respectively, with pibuprofen and p-ibuprofen suppressed β-catenin nuclear translocation in colon cancer cells. In addition, p-ibuprofen but not ibuprofen inhibited NF-κB activation in colon cancer cells. Collectively, these results suggest that p-ibuprofen is a potential effective novel drug for long-term use in colon cancer prevention. PMID:23291777

  15. 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.

  16. Tumor markers in colorectal cancer

    OpenAIRE

    Fernandes, Luís César [UNIFESP; Matos, Delcio [UNIFESP

    2002-01-01

    Colorectal cancer is a clinical entity of a persistent relevance in clinical practice and its early diagnosis is a determinant factor to obtain better therapeutic results. Tumor markers are helpful means for a better approach to individuals with such neoplasm. In the present review, the authors analyze the phases in which surgical-clinical treatment markers must be used: diagnosis, determination of tumor stage, establishment of prognosis and detection of recurrence. Current and future markers...

  17. HMG-CoA reductase regulates CCL17-induced colon cancer cell migration via geranylgeranylation and RhoA activation

    International Nuclear Information System (INIS)

    Al-Haidari, Amr A.; Syk, Ingvar; Thorlacius, Henrik

    2014-01-01

    Highlights: • Simvastatin blocked CCL17-induced and CCR4-dependent RhoA activation in HT29 cells. • CCL17/CCR4-mediated migration of colon cancer cells was antagonised by simvastatin. • Cell migration recovered by adding Mevalonate and geranylgeranyl pyrophosphate. • Targeting HMG-CoA reductase might be useful to inhibit colon cancer metastasis. - Abstract: Background: Simvastatin is widely used to lower cholesterol levels in patients with cardiovascular diseases, although accumulating evidence suggests that statins, such as simvastatin, also exert numerous anti-tumoral effects. Aim: The aim of this study was to examine the effect of simvastatin on colon cancer cell migration. Methods: Migration assays were performed to evaluate CCL17-induced colon cancer cell (HT-29) chemotaxis. In vitro tumor growth and apoptosis were assessed using a proliferation assay and annexin V assay, respectively. Active RhoA protein levels in CCL17-stimulated colon cancer cells were quantified using a G-LISA assay. Results: We found that simvastatin dose-dependently decreased CCL17-induced colon cancer cell migration. Simvastatin had no effect on colon cancer cell proliferation or apoptosis. Inhibition of beta chemokine receptor 4, CCR4, reduced CCL17-evoked activation of RhoA in colon cancer cells. Moreover, administration of mevalonate reversed the inhibitory effect of simvastatin on CCL17-induced colon cancer cell migration. Interestingly, co-incubation with geranylgeranyl pyrophosphate (GGPP) antagonized the inhibitory impact of simvastatin on colon cancer cell migration triggered by CCL17. Moreover, we observed that simvastatin decreased CCL17-induced activation of RhoA in colon cancer cells. Administration of mevalonate and GGPP reversed the inhibitory effect of simvastatin on CCL17-provoked RhoA activation in colon cancer cells. Conclusions: Taken together, our findings show for the first time that HMG-CoA reductase regulates CCL17-induced colon cancer cell migration via

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

    African Journals Online (AJOL)

    tumor development in an azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model of colon ... pancreas, the expression levels of peroxisome ... diterpenoid molecule [16-18]. Biological investigations of triptolide have revealed its.

  19. Benefit of adjuvant chemotherapy in patients with T4 UICC II colon cancer.

    Science.gov (United States)

    Teufel, Andreas; Gerken, Michael; Hartl, Janine; Itzel, Timo; Fichtner-Feigl, Stefan; Stroszczynski, Christian; Schlitt, Hans Jürgen; Hofstädter, Ferdinand; Klinkhammer-Schalke, Monika

    2015-05-20

    Colorectal cancer is the third most common cancer and a major cause of morbidity and mortality worldwide. Adjuvant chemotherapy is considered the standard of care in patients with UICC stage III colon cancer after R0 resection. Adjuvant therapy was not shown to be beneficial in patients with UICC stage II colon cancer. However, there is an ongoing discussion as to whether adjuvant chemotherapy may be beneficial for a subgroup of UICC II patients in a "high-risk situation" (such as T4). We investigated a Bavarian population-based (2.1 million inhabitants) cohort of 1937 patients with UICC II CRC treated between 2002 and 2012 in regard of the benefit of adjuvant chemotherapy for large (T4) tumors. Patients older than 80 years of age were excluded. Of 1937 patients, 240 had a T4 tumor (12%); 77 of all T4 patients received postoperative chemotherapy (33%). Kaplan-Meier analysis and Cox regression models were used for survival analyses. Patients with a T4 tumor who received postoperative chemotherapy had a highly significant survival benefit in respect of overall survival (pbenefit from adjuvant treatment. Chemotherapy, age at diagnosis, and tumor grading remained independent risk factors in the multivariate cox regression analysis. Our retrospective study demonstrated the significant benefit of adjuvant chemotherapy in the T4 subgroup of patients with UICC II colon cancer. Our data suggest that adjuvant chemotherapy should be seriously considered in these patients.

  20. Genetic variation in bone morphogenetic protein (BMP) and colon and rectal cancer

    Science.gov (United States)

    Slattery, Martha L.; Lundgreen, Abbie; Herrick, Jennifer S.; Kadlubar, Susan; Caan, Bette J.; Potter, John D.; Wolff, Roger K.

    2011-01-01

    Bone morphogenetic proteins (BMP) are part of the TGF-β-signaling pathway; genetic variation in these genes may be involved in colorectal cancer. In this study we evaluated the association between genetic variation in BMP1 (11 tagSNPs), BMP2 (5 tagSNPs), BMP4 (3 tagSNPs), BMPR1A (9 tagSNPs), BMPR1B (21 tagSNPs), BMPR2 (11 tagSNPs), and GDF10 (7 tagSNPs) with risk of colon and rectal cancer and tumor molecular phenotype. We used data from population-based case-control studies (colon cancer n=1574 cases, 1970 controls; rectal cancer n=791 cases, 999 controls). We observed that genetic variation in BMPR1A, BMPR1B, BMPR2, BMP2, and BMP4 was associated with risk of developing colon cancer, with 20 to 30% increased risk for most high-risk genotypes. A summary of high-risk genotypes showed over a twofold increase in colon cancer risk at the upper risk category (OR 2.49 95% CI 1.95, 3.18). BMPR2, BMPR1B, BMP2, and GDF10 were associated with rectal cancer. BMPR2 rs2228545 was associated with an almost twofold increased risk of rectal cancer. The risk associated with the highest category of the summary score for rectal cancer was 2.97 (95% CI 1.87, 4.72). Genes in the BMP-signaling pathway were consistently associated with CIMP+ status in combination with both KRAS-mutated and MSI tumors. BMP genes interacted statistically significantly with other genes in the TGF-β-signaling pathway, including TGFβ1, TGFβR1, Smad 3, Smad 4, and Smad 7. Our data support a role for genetic variation in BMP-related genes in the etiology of colon and rectal cancer. One possible mechanism is via the TGF-β-signaling pathway. PMID:21387313

  1. [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.

  2. Inflammasomes and Cancer: The Dynamic Role of the Inflammasome in Tumor Development

    Directory of Open Access Journals (Sweden)

    Melvin Kantono

    2017-09-01

    Full Text Available Chronic Inflammation in tumor microenvironments is not only associated with various stages of tumor development, but also has significant impacts on tumor immunity and immunotherapy. Inflammasome are an important innate immune pathway critical for the production of active IL-1β and interleukin 18, as well as the induction of pyroptosis. Although extensive studies have demonstrated that inflammasomes play a vital role in infectious and autoimmune diseases, their role in tumor progression remains elusive. Multiple studies using a colitis-associated colon cancer model show that inflammasome components provide protection against the development of colon cancer. However, very recent studies demonstrate that inflammasomes promote tumor progression in skin and breast cancer. These results indicate that inflammasomes can promote and suppress tumor development depending on types of tumors, specific inflammasomes involved, and downstream effector molecules. The complicated role of inflammasomes raises new opportunities and challenges to manipulate inflammasome pathways in the treatment of cancer.

  3. Peroxireduxin-4 is Over-Expressed in Colon Cancer and its Down-Regulation Leads to Apoptosis

    Directory of Open Access Journals (Sweden)

    Sandra M. Leydold

    2011-01-01

    Full Text Available The objective of this study was to gain insight into the biological basis of colon cancer progression by characterizing gene expression differences between normal colon epithelium, corresponding colorectal primary tumors and metastases. We found a close similarity in gene expression patterns between primary tumors and metastases, indicating a correlation between gene expression and morphological characteristics. PRDX4 was identified as highly expressed both in primary colon tumors and metastases, and selected for further characterization. Our study revealed that “Prdx4” (PrxIV, AOE372 shows functional similarities to other Prx family members by negatively affecting apoptosis induction in tumor cells. In addition, our study links Prdx4 with Hif-1α, a key regulatory factor of angiogenesis. Targeting Prdx4 may be an attractive approach in cancer therapy, as its inhibition is expected to lead to induction of apoptosis and blockage of Hif-1α-mediated tumor angiogenesis.

  4. 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.

  5. MicroRNA-215 suppresses cell proliferation, migration and invasion of colon cancer by repressing Yin-Yang 1

    International Nuclear Information System (INIS)

    Chen, Zehong; Han, Siqi; Huang, Wensheng; Wu, Jialin; Liu, Yuyi; Cai, Shirong; He, Yulong; Wu, Suijing; Song, Wu

    2016-01-01

    Colorectal cancer is one of the most common malignant tumors worldwide with rising incidence. MicroRNAs are small non-coding RNAs that implicate in multiple physiological or pathological processes. The aberrant expression of miRNA-215 (miR-215) has been illustrated in various types of cancers. However, the expression of miR-215 in human colon cancer and the biological roles of it remain largely unknown. We conducted this study to explore the expression and the function of miR-215 in human colon cancer. The results showed that miR-215 was remarkably downregulated in colon cancer tissues and cell lines. Overexpression of miR-215 by miR-215 mimic significantly inhibited colon cancer cell proliferation, migration and invasion while knockdown of miR-215 by miR-215 inhibitor exerted reverse effects. Furthermore, we newly identified Yin-Yang 1(YY1) as a direct target of miR-215 which could rescue the effects of miR-215 on colon cancer cells. In summary, our investigation revealed that miR-215 was downregulated in colon cancer and it suppressed colon cancer cell proliferation, migration and invasion by directly targeting YY1. - Highlights: • MiR-215 expression was decreased in colon cancer tissues and cell lines. • Mir-215 inhibited colon cancer cell proliferation, migration and invasion. • MiR-215 targeted YY1 directly. • The effects of miR-215 on colon cancer cells were mediated by YY1.

  6. MicroRNA-145 targets YES and STAT1 in colon cancer cells

    DEFF Research Database (Denmark)

    Gregersen, Lea H; Jacobsen, Anders B; Frankel, Lisa

    2010-01-01

    miRNA overexpression. Gene Ontology analysis showed an overrepresentation of genes involved in cell death, cellular growth and proliferation, cell cycle, gene expression and cancer. A number of the identified miRNA targets have previously been implicated in cancer, including YES, FSCN1, ADAM17, BIRC2......, VANGL1 as well as the transcription factor STAT1. Both YES and STAT1 were verified as direct miR-145 targets. CONCLUSIONS/SIGNIFICANCE: The study identifies and validates new cancer-relevant direct targets of miR-145 in colon cancer cells and hereby adds important mechanistic understanding of the tumor......BACKGROUND: MicroRNAs (miRNAs) have emerged as important gene regulators and are recognized as key players in tumorigenesis. miR-145 is reported to be down-regulated in several cancers, but knowledge of its targets in colon cancer remains limited. METHODOLOGY/PRINCIPAL FINDINGS: To investigate...

  7. 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.

  8. [Treatment reality with respect to laparoscopic surgery of colonic cancer in Germany].

    Science.gov (United States)

    Ptok, H; Gastinger, I; Bruns, C; Lippert, H

    2014-07-01

    Prospective randomized studies and meta-analyses have shown that laparoscopic resection for colonic cancer is equivalent to open resection with respect to the oncological results and has short-term advantages in the early postoperative outcome. The aim of this study was to investigate whether laparoscopic colonic resection has become established as the standard in routine treatment. Data from the multicenter observational study "Quality assurance colonic cancer (primary tumor)" from the time period from 1 January 2009 to 21 December 2011 were evaluated with respect to the total proportion of laparoscopic colonic cancer resections and tumor localization and specifically for laparoscopic sigmoid colon cancer resections. A comparison between low and high volume clinics (< 30 versus ≥ 30 colonic cancer resections/year) was carried out. Laparoscopic colonic cancer resections were carried out in 12 % versus 21.4 % of low and high volume clinics, respectively (p < 0.001) with a significant increase for low volume clinics (from 8.0 % to 15.6 %, p < 0.001) and a constant proportion in high volume clinics (from 21.7 % to 21.1 %, p = 0.905). For sigmoid colon cancer laparoscopic resection was carried out in 49.7 % versus 47.6 % (p = 0.584). Differences were found between low volume and high volume clinics in the conversion rates (17.3 % versus 6.6 %, p < 0.001), the length of the resected portion (Ø 23.6 cm versus 36.0 cm, p < 0.001) and the lymph node yield (Ø n = 15.7 versus 18.2, p = 0.008). There were no differences between the two groups of clinics regarding postoperative morbidity and mortality. The postoperative morbidity and length of stay were significantly lower for laparoscopic sigmoid resection than for conventional sigmoid resection. The laparoscopic access route for colonic cancer resection is not the standard approach in the participating clinics. The laparoscopic access route has the highest proportion for sigmoid colon resection. The differences in the

  9. Elevated serum levels of MMP-11 correlate with poor prognosis in colon cancer patients.

    Science.gov (United States)

    Pang, Li; Wang, Da-Wei; Zhang, Nan; Xu, Da-Hai; Meng, Xiang-Wei

    2016-03-11

    Matrix metalloproteinase 11 (MMP11) has been shown to play a key role in human tumor progression and indicates poor clinical outcome in cancer patients. The current study aimed to evaluate the relationship between serum levels of MMP-11 and prognosis in colon cancer patients. Serum levels of MMP-11 were determined in 92 colon cancer patients and 92 healthy individuals using an enzyme-linked immunosorbent assay (ELISA). Associations between serum MMP-11 levels and clinicopathological characteristics of the patients and their outcomes were investigated. Survival analyses were performed to measure the 5-year overall survival (OS) and disease-free survival (DFS). Serum MMP-11 levels were substantially higher in colon cancer patients than in healthy controls. Moreover, serum MMP-11 levels were significantly higher in patients with advanced T status, lymph node metastasis, distant metastasis, and a higher TNM stage. Elevated serum levels of MMP-11 were identified as an independent prognostic factor for 5-year mortality and adverse events associated with colon cancer. Multivariate Cox regression analysis identified the serum MMP-11 level as an independent predictor of OS and DFS. Our study established that high serum levels of MMP-11 are associated with poor clinical outcome and may serve as a prognostic biomarker in colon cancer patients.

  10. Coated metal stents installation for the treatment of malignant tumors complicated with colonic and rectal fistula

    International Nuclear Information System (INIS)

    Mao Aiwu; Fang Shiming; Liu Shiyi; Lin Qing; Jiang Haosheng; Jia Yiping; Gao Zhongdu

    2007-01-01

    Objective: To probe the clinical features of malignant colonic and rectal tumors together with coated metal stent placement. Methods: 24 cases of colonic fistula with late stage malignant tumors including 16 cases of intestinal cancer(66.7%), 2 cases of gastric and cervical cancers respectively(8.3%); 1 case of bladder, 1 case of prostate, 1 case of ovary and 1 case of gallbladder cancer(4.2%). The cause for the fistulas were direct invasion (37.5% )and radiotherapy (62.5%). The KPS was 30-60, and the median value was 40. CT were done preoperatively and followed by radiography of canulation contrast medium enema to ensure the location of the orifice of the fistula, the route of intestinal canal or complicated with obstruction and the condition with nearby tissues. Stents were finally implanted specifically according to the different situations of intestines. The sites of implanted stents and the occlusion of fistula should be strictly scrutinized; and then with careful follow up of patients complications and general condition. The procedure was carried out practically in 23 cases. Results: The successful rate of technique reached 96%(22/23), the failed one was due to the curve over sharpness of intestinal lock and resulting in non-expansion of the stent. The clinical successful rate was 91.3%. The two failed cased included the one with improper coherence to the intestinal wall leading to the stent migration and the other with a mild leakage after stent placement. The follow-up duration were 28-365 days, average 109 days, and the median value was 92 days. The average surviving period of 3 months and 6 months were 51% and 11% respectively. Conclusion: Intestinal fistula is the common complication after intestinal tumor operation and radiotherapy with poor prognosis. Metal covered stents provide a therapy of choice to improve the life quality and prolong the life span. (authors)

  11. β-Catenin promotes colitis and colon cancer through imprinting of proinflammatory properties in T cells.

    Science.gov (United States)

    Keerthivasan, Shilpa; Aghajani, Katayoun; Dose, Marei; Molinero, Luciana; Khan, Mohammad W; Venkateswaran, Vysak; Weber, Christopher; Emmanuel, Akinola Olumide; Sun, Tianjao; Bentrem, David J; Mulcahy, Mary; Keshavarzian, Ali; Ramos, Elena M; Blatner, Nichole; Khazaie, Khashayarsha; Gounari, Fotini

    2014-02-26

    The density and type of lymphocytes that infiltrate colon tumors are predictive of the clinical outcome of colon cancer. High densities of T helper 17 (T(H)17) cells and inflammation predict poor outcome, whereas infiltration by T regulatory cells (Tregs) that naturally suppress inflammation is associated with longer patient survival. However, the role of Tregs in cancer remains controversial. We recently reported that Tregs in colon cancer patients can become proinflammatory and tumor-promoting. These properties were directly linked with their expression of RORγt (retinoic acid-related orphan receptor-γt), the signature transcription factor of T(H)17 cells. We report that Wnt/β-catenin signaling in T cells promotes expression of RORγt. Expression of β-catenin was elevated in T cells, including Tregs, of patients with colon cancer. Genetically engineered activation of β-catenin in mouse T cells resulted in enhanced chromatin accessibility in the proximity of T cell factor-1 (Tcf-1) binding sites genome-wide, induced expression of T(H)17 signature genes including RORγt, and promoted T(H)17-mediated inflammation. Strikingly, the mice had inflammation of small intestine and colon and developed lesions indistinguishable from colitis-induced cancer. Activation of β-catenin only in Tregs was sufficient to produce inflammation and initiate cancer. On the basis of these findings, we conclude that activation of Wnt/β-catenin signaling in effector T cells and/or Tregs is causatively linked with the imprinting of proinflammatory properties and the promotion of colon cancer.

  12. 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.

  13. Deficient expression of DNA repair enzymes in early progression to sporadic colon cancer

    Science.gov (United States)

    2012-01-01

    crypts near cancers and TVAs suggests that the tumors arose in field defects that were deficient in DNA repair and that deficiencies in Pms2, Ercc1 and Xpf are early steps, often occurring together, in progression to colon cancer. PMID:22494821

  14. Promoter hypermethylation mediated downregulation of FBP1 in human hepatocellular carcinoma and colon cancer.

    Directory of Open Access Journals (Sweden)

    Mingquan Chen

    Full Text Available FBP1, fructose-1,6-bisphosphatase-1, a gluconeogenesis regulatory enzyme, catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and inorganic phosphate. The mechanism that it functions to antagonize glycolysis and was epigenetically inactivated through NF-kappaB pathway in gastric cancer has been reported. However, its role in the liver carcinogenesis still remains unknown. Here, we investigated the expression and DNA methylation of FBP1 in primary HCC and colon tumor. FBP1 was lowly expressed in 80% (8/10 human hepatocellular carcinoma, 66.7% (6/9 liver cancer cell lines and 100% (6/6 colon cancer cell lines, but was higher in paired adjacent non-tumor tissues and immortalized normal cell lines, which was well correlated with its promoter methylation status. Methylation was further detected in primary HCCs, gastric and colon tumor tissues, but none or occasionally in paired adjacent non-tumor tissues. Detailed methylation analysis of 29 CpG sites at a 327-bp promoter region by bisulfite genomic sequencing confirmed its methylation. FBP1 silencing could be reversed by chemical demethylation treatment with 5-aza-2'-deoxycytidine (Aza, indicating direct epigenetic silencing. Restoring FBP1 expression in low expressed cells significantly inhibited cell growth and colony formation ability through the induction of G2-M phase cell cycle arrest. Moreover, the observed effects coincided with an increase in reactive oxygen species (ROS generation. In summary, epigenetic inactivation of FBP1 is also common in human liver and colon cancer. FBP1 appears to be a functional tumor suppressor involved in the liver and colon carcinogenesis.

  15. [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

  16. Integrin α6Bβ4 inhibits colon cancer cell proliferation and c-Myc activity

    International Nuclear Information System (INIS)

    Dydensborg, Anders Bondo; Teller, Inga C; Groulx, Jean-François; Basora, Nuria; Paré, Fréderic; Herring, Elizabeth; Gauthier, Rémy; Jean, Dominique; Beaulieu, Jean-François

    2009-01-01

    Integrins are known to be important contributors to cancer progression. We have previously shown that the integrin β4 subunit is up-regulated in primary colon cancer. Its partner, the integrin α6 subunit, exists as two different mRNA splice variants, α6A and α6B, that differ in their cytoplasmic domains but evidence for distinct biological functions of these α6 splice variants is still lacking. In this work, we first analyzed the expression of integrin α6A and α6B at the protein and transcript levels in normal human colonic cells as well as colorectal adenocarcinoma cells from both primary tumors and established cell lines. Then, using forced expression experiments, we investigated the effect of α6A and α6B on the regulation of cell proliferation in a colon cancer cell line. Using variant-specific antibodies, we observed that α6A and α6B are differentially expressed both within the normal adult colonic epithelium and between normal and diseased colonic tissues. Proliferative cells located in the lower half of the glands were found to predominantly express α6A, while the differentiated and quiescent colonocytes in the upper half of the glands and surface epithelium expressed α6B. A relative decrease of α6B expression was also identified in primary colon tumors and adenocarcinoma cell lines suggesting that the α6A/α6B ratios may be linked to the proliferative status of colonic cells. Additional studies in colon cancer cells showed that experimentally restoring the α6A/α6B balance in favor of α6B caused a decrease in cellular S-phase entry and repressed the activity of c-Myc. The findings that the α6Bβ4 integrin is expressed in quiescent normal colonic cells and is significantly down-regulated in colon cancer cells relative to its α6Aβ4 counterpart are consistent with the anti-proliferative influence and inhibitory effect on c-Myc activity identified for this α6Bβ4 integrin. Taken together, these findings point out the importance of integrin

  17. A comparison of 12-gene colon cancer assay gene expression in African American and Caucasian patients with stage II colon cancer

    International Nuclear Information System (INIS)

    Govindarajan, Rangaswamy; Posey, James; Chao, Calvin Y.; Lu, Ruixiao; Jadhav, Trafina; Javed, Ahmed Y.; Javed, Awais; Mahmoud, Fade A.; Osarogiagbon, Raymond University; Manne, Upender

    2016-01-01

    African American (AA) colon cancer patients have a worse prognosis than Caucasian (CA) colon cancer patients, however, reasons for this disparity are not well understood. To determine if tumor biology might contribute to differential prognosis, we measured recurrence risk and gene expression using the Oncotype DX® Colon Cancer Assay (12-gene assay) and compared the Recurrence Score results and gene expression profiles between AA patients and CA patients with stage II colon cancer. We retrieved demographic, clinical, and archived tumor tissues from stage II colon cancer patients at four institutions. The 12-gene assay and mismatch repair (MMR) status were performed by Genomic Health (Redwood City, California). Student’s t-test and the Wilcoxon rank sum test were used to compare Recurrence Score data and gene expression data from AA and CA patients (SAS Enterprise Guide 5.1). Samples from 122 AA and 122 CA patients were analyzed. There were 118 women (63 AA, 55 CA) and 126 men (59 AA, 67 CA). Median age was 66 years for AA patients and 68 for CA patients. Age, gender, year of surgery, pathologic T-stage, tumor location, the number of lymph nodes examined, lymphovascular invasion, and MMR status were not significantly different between groups (p = 0.93). The mean Recurrence Score result for AA patients (27.9 ± 12.8) and CA patients (28.1 ± 11.8) was not significantly different and the proportions of patients with high Recurrence Score values (≥41) were similar between the groups (17/122 AA; 15/122 CA). None of the gene expression variables, either single genes or gene groups (cell cycle group, stromal group, BGN1, FAP, INHBA1, Ki67, MYBL2, cMYC and GADD45B), was significantly different between the racial groups. After controlling for clinical and pathologic covariates, the means and distributions of Recurrence Score results and gene expression profiles showed no statistically significant difference between patient groups. The distribution of Recurrence Score

  18. A comparison of 12-gene colon cancer assay gene expression in African American and Caucasian patients with stage II colon cancer.

    Science.gov (United States)

    Govindarajan, Rangaswamy; Posey, James; Chao, Calvin Y; Lu, Ruixiao; Jadhav, Trafina; Javed, Ahmed Y; Javed, Awais; Mahmoud, Fade A; Osarogiagbon, Raymond U; Manne, Upender

    2016-06-18

    African American (AA) colon cancer patients have a worse prognosis than Caucasian (CA) colon cancer patients, however, reasons for this disparity are not well understood. To determine if tumor biology might contribute to differential prognosis, we measured recurrence risk and gene expression using the Oncotype DX® Colon Cancer Assay (12-gene assay) and compared the Recurrence Score results and gene expression profiles between AA patients and CA patients with stage II colon cancer. We retrieved demographic, clinical, and archived tumor tissues from stage II colon cancer patients at four institutions. The 12-gene assay and mismatch repair (MMR) status were performed by Genomic Health (Redwood City, California). Student's t-test and the Wilcoxon rank sum test were used to compare Recurrence Score data and gene expression data from AA and CA patients (SAS Enterprise Guide 5.1). Samples from 122 AA and 122 CA patients were analyzed. There were 118 women (63 AA, 55 CA) and 126 men (59 AA, 67 CA). Median age was 66 years for AA patients and 68 for CA patients. Age, gender, year of surgery, pathologic T-stage, tumor location, the number of lymph nodes examined, lymphovascular invasion, and MMR status were not significantly different between groups (p = 0.93). The mean Recurrence Score result for AA patients (27.9 ± 12.8) and CA patients (28.1 ± 11.8) was not significantly different and the proportions of patients with high Recurrence Score values (≥41) were similar between the groups (17/122 AA; 15/122 CA). None of the gene expression variables, either single genes or gene groups (cell cycle group, stromal group, BGN1, FAP, INHBA1, Ki67, MYBL2, cMYC and GADD45B), was significantly different between the racial groups. After controlling for clinical and pathologic covariates, the means and distributions of Recurrence Score results and gene expression profiles showed no statistically significant difference between patient groups. The distribution of

  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. PGE{sub 2}-induced colon cancer growth is mediated by mTORC1

    Energy Technology Data Exchange (ETDEWEB)

    Dufour, Marc, E-mail: Marc.dufour@chuv.ch; Faes, Seraina, E-mail: Seraina.faes@chuv.ch; Dormond-Meuwly, Anne, E-mail: Anne.meuwly-Dormond@chuv.ch; Demartines, Nicolas, E-mail: Demartines@chuv.ch; Dormond, Olivier, E-mail: Olivier.dormond@chuv.ch

    2014-09-05

    Highlights: • PGE{sub 2} activates mTORC1 in colon cancer cells. • Inhibition of mTORC1 blocks PGE{sub 2} induced colon cancer cell growth. • mTORC1 is a signaling intermediary in PGE{sub 2} induced colon cancer cell responses. - Abstract: The inflammatory prostaglandin E{sub 2} (PGE{sub 2}) cytokine plays a key role in the development of colon cancer. Several studies have shown that PGE{sub 2} directly induces the growth of colon cancer cells and furthermore promotes tumor angiogenesis by increasing the production of the vascular endothelial growth factor (VEGF). The signaling intermediaries implicated in these processes have however not been fully characterized. In this report, we show that the mechanistic target of rapamycin complex 1 (mTORC1) plays an important role in PGE{sub 2}-induced colon cancer cell responses. Indeed, stimulation of LS174T cells with PGE{sub 2} increased mTORC1 activity as observed by the augmentation of S6 ribosomal protein phosphorylation, a downstream effector of mTORC1. The PGE{sub 2} EP{sub 4} receptor was responsible for transducing the signal to mTORC1. Moreover, PGE{sub 2} increased colon cancer cell proliferation as well as the growth of colon cancer cell colonies grown in matrigel and blocking mTORC1 by rapamycin or ATP-competitive inhibitors of mTOR abrogated these effects. Similarly, the inhibition of mTORC1 by downregulation of its component raptor using RNA interference blocked PGE{sub 2}-induced LS174T cell growth. Finally, stimulation of LS174T cells with PGE{sub 2} increased VEGF production which was also prevented by mTORC1 inhibition. Taken together, these results show that mTORC1 is an important signaling intermediary in PGE{sub 2} mediated colon cancer cell growth and VEGF production. They further support a role for mTORC1 in inflammation induced tumor growth.

  1. 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.

  2. Colorectal cancer with venous tumor thrombosis

    OpenAIRE

    Kensuke Otani; Soichiro Ishihara; Keisuke Hata; Koji Murono; Kazuhito Sasaki; Koji Yasuda; Takeshi Nishikawa; Toshiaki Tanaka; Tomomichi Kiyomatsu; Kazushige Kawai; Hiroaki Nozawa; Hironori Yamaguchi; Toshiaki Watanabe

    2018-01-01

    Summary: Colorectal cancer is seldom accompanied by venous tumor thrombosis, and little is known about the features of venous tumor thrombosis in colorectal cancer. However, some reports show that colorectal cancer patients can develop venous tumor thrombosis and warn clinicians not to overlook this complication. In this report, we perform a review of 43 previously reported cases and investigate the characteristics of colorectal cancer accompanied by venous tumor thrombosis. The histological ...

  3. 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.

  4. Treatment Options (by Stage) for Colon Cancer

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... VEGF inhibitors and angiogenesis inhibitors . Epidermal growth factor receptor (EGFR) inhibitor therapy: EGFRs are proteins found on ...

  5. Keratin23 (KRT23) knockdown decreases proliferation and affects the DNA damage response of colon cancer cells

    DEFF Research Database (Denmark)

    Birkenkamp-Demtröder, Karin; Hahn, Stephan; Mansilla, Francisco

    2013-01-01

    correlated with absent expression, while increased KRT23 expression in tumor samples correlated with promoter hypomethylation, as confirmed by bisulfite sequencing. Demethylation induced KRT23 expression in vitro. Expression profiling of shRNA mediated stable KRT23 knockdown in colon cancer cell lines showed...... response, mainly molecules of the double strand break repair homologous recombination pathway. KRT23 knockdown decreased the transcript and protein expression of key molecules as e.g. MRE11A, E2F1, RAD51 and BRCA1. Knockdown of KRT23 rendered colon cancer cells more sensitive to irradiation and reduced......Keratin 23 (KRT23) is strongly expressed in colon adenocarcinomas but absent in normal colon mucosa. Array based methylation profiling of 40 colon samples showed that the promoter of KRT23 was methylated in normal colon mucosa, while hypomethylated in most adenocarcinomas. Promoter methylation...

  6. 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

  7. Synuclein gamma predicts poor clinical outcome in colon cancer with normal levels of carcinoembryonic antigen

    Directory of Open Access Journals (Sweden)

    Xing Xiaofang

    2010-07-01

    Full Text Available Abstract Background Synuclein gamma (SNCG, initially identified as a breast cancer specific gene, is aberrantly expressed in many different malignant tumors but rarely expressed in matched nonneoplastic adjacent tissues. In this study, we investigated the prognostic potential of SNCG in colon cancer particularly in the patients with normal carcinoembryonic antigen (CEA levels. Methods SNCG levels were assessed immunohistochemically in cancer tissues from 229 colon adenocarcinoma patients with a mean follow-up of 44 months. Correlations between SNCG levels and clinicopathologic features, preoperative serum CEA level, and clinical outcome were analyzed statistically using SPSS. Results SNCG levels in colon adenocarcinoma were closely associated with intravascular embolus and tumor recurrence but independent of preoperative serum CEA levels. SNCG expression was an independent prognostic factor of a shorter disease-free survival (DFS and overall survival (OS (P P = 0.001, P = 0.001, 0.002 for 97 patients with normal preoperative serum CEA level. Conclusions Our results suggest for the first time that SNCG is a new independent predicator for poor prognosis in patients with colon adenocarcinoma, including those with normal CEA levels. Combination of CEA with SNCG improves prognostic evaluation for patients with colon adenocarcinoma.

  8. The prognosis significance and application value of peritoneal elastic lamina invasion in colon cancer.

    Science.gov (United States)

    Lu, Jun; Hu, Xiumei; Meng, Yutong; Zhao, Hongying; Cao, Qing; Jin, Mulan

    2018-01-01

    The aims of this study were to evaluate the associations between peritoneal elastic lamina invasion (ELI) and the clinicopathological prognostic factors of colon cancer, to evaluate the feasibility of ELI with use of an elastic stain to help diagnose serosal invasion of colon cancer in routine practice, so as to help us to provide a more accurate estimate for prognosis and stage of patients and a marker for postoperative treatment. 254 cases with colon cancer were included in the study. According to the presence of elastic lamina (EL) and elastic lamina invasion (ELI), all cases were divided into four groups: pT3 EL negative (pT3 EL (-)), pT3 ELI positive (pT3 ELI (+)), pT3 ELI negative (pT3 ELI (-)) and pT4a. Statistical analysis was used to analyze the relationship between elastic lamina invasion and other established adverse histologic features. The EL and ELI positive rates were 81.5% and 42.1% respectively. There were significant differences in mph node metastasis, venous invasion and tumor buds between pT3 ELI (-) and pT3 ELI (+), pT3 ELI (-) and pT4a. There was no significant difference in same factors between pT3 ELI (+) and pT4a. In pT3 stage, there were significant differences in lymph node metastasis, perineural invasion and tumor buds between EL (-) and ELI (+). There were no significant differences in same factors between EL (-) and ELI (-). EL was detected less frequently in right-sided tumors compared with left-sided tumors. ELI might be the prognostic factors of colon cancer with II stage and might be the marker of postoperative adjuvant chemotherapy. Patients with pT3 ELI (+) might have similar prognosis to patients with pT4a. For patients with pT3 colon cancer, EL(-) might have similar prognosis as ELI (-) and might take the same therapy. In addition, the right half colon EL positive rate was lower than the left colon. Elastic staining might be a useful tool to help determine the invasive depth and stage of colon cancer.

  9. 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.

  10. Laparoscopic resection of transverse colon cancer at splenic flexure: technical aspects and results.

    Science.gov (United States)

    Okuda, Junji; Yamamoto, Masashi; Tanaka, Keitaro; Masubuchi, Shinsuke; Uchiyama, Kazuhisa

    2016-03-01

    Laparoscopic resection of transverse colon cancer at splenic flexure is technical demanding and its efficacy remains controversial. The aim of this study was to investigate its technical aspects such as pitfalls and overcoming them, and to demonstrate the short-term and oncologic long-term outcomes. To overcome the difficulty in laparoscopic resection of transverse colon cancer at splenic flexure, we recognized the following technical tips as essential. First of all, we have to precisely identify major vessels variations feeding tumor. Secondary, anatomical dissection of mesocolon through medial approach is indispensible. Third, safe takedown of splenic flexure to fully mobilization of left hemicolon is mandatory. This cohort study analyzed 95 patients with stage II (43) and III (52) underwent resection of transverse colon cancer at splenic flexure. 61 laparoscopic surgeries (LAC) and 34 conventional open surgeries (OC) from December 1996 to December 2009 were evaluated. Short-term and oncologic long-term outcomes were recorded. Operative time was longer in LAC. However, blood loss was less, recovery of bowel function and hospital stay were shorter in LAC. There was no conversion in LAC and no significant difference in the postoperative complications. Regarding oncologic long-term outcomes, there were no significant differences between OC and LAC. Laparoscopic resection of transverse colon cancer at splenic flexure resulted in acceptable short-term and oncologic long-term outcomes. Once technical tips acquired, laparoscopic resection of transverse colon cancer at splenic flexure could be feasible as minimally invasive surgery.

  11. 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.

  12. 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

  13. Intestinal helminth infection drives carcinogenesis in colitis-associated colon cancer.

    Directory of Open Access Journals (Sweden)

    Eva Pastille

    2017-09-01

    Full Text Available Inflammatory bowel diseases (IBD are chronic inflammatory disorders of the gastrointestinal tract, strongly associated with an increased risk of colorectal cancer development. Parasitic infections caused by helminths have been shown to modulate the host's immune response by releasing immunomodulatory molecules and inducing regulatory T cells (Tregs. This immunosuppressive state provoked in the host has been considered as a novel and promising approach to treat IBD patients and alleviate acute intestinal inflammation. On the contrary, specific parasite infections are well known to be directly linked to carcinogenesis. Whether a helminth infection interferes with the development of colitis-associated colon cancer (CAC is not yet known. In the present study, we demonstrate that the treatment of mice with the intestinal helminth Heligmosomoides polygyrus at the onset of tumor progression in a mouse model of CAC does not alter tumor growth and distribution. In contrast, H. polygyrus infection in the early inflammatory phase of CAC strengthens the inflammatory response and significantly boosts tumor development. Here, H. polygyrus infection was accompanied by long-lasting alterations in the colonic immune cell compartment, with reduced frequencies of colonic CD8+ effector T cells. Moreover, H. polygyrus infection in the course of dextran sulfate sodium (DSS mediated colitis significantly exacerbates intestinal inflammation by amplifying the release of colonic IL-6 and CXCL1. Thus, our findings indicate that the therapeutic application of helminths during CAC might have tumor-promoting effects and therefore should be well-considered.

  14. Inulin based glutathione-responsive delivery system for colon cancer treatment.

    Science.gov (United States)

    Wang, Dongdong; Sun, Feifei; Lu, Chunbo; Chen, Peng; Wang, Zhaojie; Qiu, Yuanhao; Mu, Haibo; Miao, Zehong; Duan, Jinyou

    2018-05-01

    Colorectal cancer is one of the most common types of tumor in the world. Here we developed a lipoic acid esterified polysaccharide (inulin) delivery system for tanshinone IIA to treat colorectal cancer in vitro. The release of tanshinone IIA in the system was highly responsive to glutathione, which is commonly abundant in cancer cells. In addition, this drug delivery system was proliferative to Bifidobacterium longum, the common inhabitant of human intestine. Thus, this strategy might be useful to improve colon cancer therapy efficacy of anticancer drugs and meanwhile promote the growth of beneficial commensal flora in the gut. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. The differential impact of microsatellite instability as a marker of prognosis and tumour response between colon cancer and rectal cancer.

    Science.gov (United States)

    Hong, Sung Pil; Min, Byung So; Kim, Tae Il; Cheon, Jae Hee; Kim, Nam Kyu; Kim, Hoguen; Kim, Won Ho

    2012-05-01

    Microsatellite instability (MSI) is a distinct molecular phenotype of colorectal cancer related to prognosis and tumour response to 5-fluorouracil (5-FU)-based chemotherapy. We investigated the differential impact of MSI between colon and rectal cancers as a marker of prognosis and chemotherapeutic response. PCR-based MSI assay was performed on 1125 patients. Six hundred and sixty patients (58.7%) had colon cancer and 465 patients (41.3%) had rectal cancer. Among 1125 patients, 106 (9.4%) had high-frequency MSI (MSI-H) tumours. MSI-H colon cancers (13%) had distinct phenotypes including young age at diagnosis, family history of colorectal cancer, early Tumor, Node, Metastasis (TNM) stage, proximal location, poor differentiation, and high level of baseline carcinoembryonic antigen (CEA), while MSI-H rectal cancers (4.3%) showed similar clinicopathological characteristics to MSS/MSI-L tumours except for family history of colorectal cancer. MSI-H tumours were strongly correlated with longer disease free survival (DFS) (P=0.005) and overall survival (OS) (P=0.009) than MSS/MSI-L tumours in colon cancer, while these positive correlations were not observed in rectal cancers. The patients with MSS/MSI-L tumours receiving 5-FU-based chemotherapy showed good prognosis (P=0.013), but this positive association was not observed in MSI-H (P=0.104). These results support the use of MSI status as a marker of prognosis and response to 5-FU-based chemotherapy in patients with colon cancers. Further study is mandatory to evaluate the precise role of MSI in patients with rectal cancers and the effect of 5-FU-based chemotherapy in MSI-H tumours. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Prognostic analysis and comparison of colon cancer in Han and Hui patients.

    Science.gov (United States)

    Zhang, Mei; Zhao, Qu-Chuan; Liu, Yan-Peng; Yang, Lei; Zhu, Hong-Ming; Chhetri, Jagadish K

    2014-05-07

    To investigate the relevant prognostic factors and their differences between colorectal cancer (CRC) patients of Chinese Han and Hui ethnicities in the Beijing region. A retrospective analysis of 880 patients diagnosed with CRC at Xuanwu Hospital, Capital Medical University between September 2001 and September 2011 was performed. Among the 880 patients, 398 and 482 were Hui and Han, respectively. Characteristics including sex, age, diet, tumor size, primary tumor site, Dukes' stage and degree of differentiation were analyzed for their influence on prognosis. Data on dietary structures were recorded through a questionnaire survey conducted during the patient's first visit, return visit or follow-up checkups. Among patients with colon cancer, the 5-year survival rate for patients of Hui ethnicity was lower than that for Han patients (P = 0.025). Six risk factors (age of onset, dietary structure, tumor size, Dukes' stage, location of cancer and degree of differentiation) in both Han and Hui patients were identified as prognostic factors (P dietary structure was a statistically significant factor, and diet varied significantly between the two ethnic groups. Dietary structure has a significant influence on colon cancer prognosis among Han and Hui patients with colon cancer in Beijing, which may cause a difference in their survival rates.

  17. 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.

  18. 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 ...

  19. REDOX IMAGING OF THE p53-DEPENDENT MITOCHONDRIAL REDOX STATE IN COLON CANCER EX VIVO

    Science.gov (United States)

    XU, HE N.; FENG, MIN; MOON, LILY; DOLLOFF, NATHAN; EL-DEIRY, WAFIK; LI, LIN Z.

    2015-01-01

    The mitochondrial redox state and its heterogeneity of colon cancer at tissue level have not been previously reported. Nor has how p53 regulates mitochondrial respiration been measured at (deep) tissue level, presumably due to the unavailability of the technology that has sufficient spatial resolution and tissue penetration depth. Our prior work demonstrated that the mitochondrial redox state and its intratumor heterogeneity is associated with cancer aggressiveness in human melanoma and breast cancer in mouse models, with the more metastatic tumors exhibiting localized regions of more oxidized redox state. Using the Chance redox scanner with an in-plane spatial resolution of 200 μm, we imaged the mitochondrial redox state of the wild-type p53 colon tumors (HCT116 p53 wt) and the p53-deleted colon tumors (HCT116 p53−/−) by collecting the fluorescence signals of nicotinamide adenine dinucleotide (NADH) and oxidized flavoproteins [Fp, including flavin adenine dinucleotide (FAD)] from the mouse xenografts snap-frozen at low temperature. Our results show that: (1) both tumor lines have significant degree of intratumor heterogeneity of the redox state, typically exhibiting a distinct bi-modal distribution that either correlates with the spatial core–rim pattern or the “hot/cold” oxidation-reduction patches; (2) the p53−/− group is significantly more heterogeneous in the mitochondrial redox state and has a more oxidized tumor core compared to the p53 wt group when the tumor sizes of the two groups are matched; (3) the tumor size dependence of the redox indices (such as Fp and Fp redox ratio) is significant in the p53−/− group with the larger ones being more oxidized and more heterogeneous in their redox state, particularly more oxidized in the tumor central regions; (4) the H&E staining images of tumor sections grossly correlate with the redox images. The present work is the first to reveal at the submillimeter scale the intratumor heterogeneity pattern

  20. Mesenchymal Stem Cells Induce Epithelial to Mesenchymal Transition in Colon Cancer Cells through Direct Cell-to-Cell Contact

    Directory of Open Access Journals (Sweden)

    Hidehiko Takigawa

    2017-05-01

    Full Text Available We previously reported that in an orthotopic nude mouse model of human colon cancer, bone marrow–derived mesenchymal stem cells (MSCs migrated to the tumor stroma and promoted tumor growth and metastasis. Here, we evaluated the proliferation and migration ability of cancer cells cocultured with MSCs to elucidate the mechanism of interaction between cancer cells and MSCs. Proliferation and migration of cancer cells increased following direct coculture with MSCs but not following indirect coculture. Thus, we hypothesized that direct contact between cancer cells and MSCs was important. We performed a microarray analysis of gene expression in KM12SM colon cancer cells directly cocultured with MSCs. Expression of epithelial-mesenchymal transition (EMT–related genes such as fibronectin (FN, SPARC, and galectin 1 was increased by direct coculture with MSCs. We also confirmed the upregulation of these genes with real-time polymerase chain reaction. Gene expression was not elevated in cancer cells indirectly cocultured with MSCs. Among the EMT-related genes upregulated by direct coculture with MSCs, we examined the immune localization of FN, a well-known EMT marker. In coculture assay in chamber slides, expression of FN was seen only at the edges of cancer clusters where cancer cells directly contacted MSCs. FN expression in cancer cells increased at the tumor periphery and invasive edge in orthotopic nude mouse tumors and human colon cancer tissues. These results suggest that MSCs induce EMT in colon cancer cells via direct cell-to-cell contact and may play an important role in colon cancer metastasis.

  1. The role of the CpG island methylator phenotype on survival outcome in colon cancer.

    Science.gov (United States)

    Kang, Ki Joo; Min, Byung Hoon; Ryu, Kyung Ju; Kim, Kyoung Mee; Chang, Dong Kyung; Kim, Jae J; Rhee, Jong Chul; Kim, Young Ho

    2015-03-01

    CpG island methylator phenotype (CIMP)- high colorectal cancers (CRCs) have distinct clinicopathologi-cal features from their CIMP-low/negative CRC counterparts. However, controversy exists regarding the prognosis of CRC according to the CIMP status. Therefore, this study examined the prognosis of Korean patients with colon cancer according to the CIMP status. Among a previous cohort pop-ulation with CRC, a total of 154 patients with colon cancer who had available tissue for DNA extraction were included in the study. CIMP-high was defined as ≥3/5 methylated mark-ers using the five-marker panel (CACNA1G, IGF2, NEUROG1, RUNX3, and SOCS1). CIMP-high and CIMP-low/neg-ative cancers were observed in 27 patients (17.5%) and 127 patients (82.5%), respectively. Multivariate analysis adjust-ing for age, gender, tumor location, tumor stage and CIMP and microsatellite instability (MSI) statuses indicated that CIMP-high colon cancers were associated with a significant increase in colon cancer-specific mortality (hazard ratio [HR], 3.23; 95% confidence interval [CI], 1.20 to 8.69; p=0.02). In microsatellite stable cancers, CIMP-high cancer had a poor survival outcome compared to CIMP-low/negative cancer (HR, 2.91; 95% CI, 1.02 to 8.27; p=0.04). Re-gardless of the MSI status, CIMP-high cancers had poor sur-vival outcomes in Korean patients. (Gut Liver, 2015;9202-207).

  2. Comparative Study of Histopathologic Characterization of Azoxymethane-induced Colon Tumors in Three Inbred Rat Strains

    DEFF Research Database (Denmark)

    Kobæk Larsen, Morten; Fenger, Claus; Hansen, Ket

    2002-01-01

    To obtain controlled genetic variation, colon cancer was chemically induced by use of four subcutaneous injections of azoxymethane (15 mg/kg of body weight/wk) to rats of 3 inbred strains (BDIX/OrlIco, F344/NHsd, WAG/Rij). The selection was based on the availability of established colon cancer cell...

  3. Palliative Care Use Among Patients With Solid Cancer Tumors: A National Cancer Data Base Study.

    Science.gov (United States)

    Osagiede, Osayande; Colibaseanu, Dorin T; Spaulding, Aaron C; Frank, Ryan D; Merchea, Amit; Kelley, Scott R; Uitti, Ryan J; Ailawadhi, Sikander

    2018-01-01

    Palliative care has been increasingly recognized as an important part of cancer care but remains underutilized in patients with solid cancers. There is a current gap in knowledge regarding why palliative care is underutilized nationwide. To identify the factors associated with palliative care use among deceased patients with solid cancer tumors. Using the 2016 National Cancer Data Base, we identified deceased patients (2004-2013) with breast, colon, lung, melanoma, and prostate cancer. Data were described as percentages. Associations between palliative care use and patient, facility, and geographic characteristics were evaluated through multivariate logistic regression. A total of 1 840 111 patients were analyzed; 9.6% received palliative care. Palliative care use was higher in the following patient groups: survival >24 months (17% vs 2%), male (54% vs 46%), higher Charlson-Deyo comorbidity score (16% vs 8%), treatment at designated cancer programs (74% vs 71%), lung cancer (76% vs 28%), higher grade cancer (53% vs 24%), and stage IV cancer (59% vs 13%). Patients who lived in communities with a greater percentage of high school degrees had higher odds of receiving palliative care; Central and Pacific regions of the United States had lower odds of palliative care use than the East Coast. Patients with colon, melanoma, or prostate cancer had lower odds of palliative care than patients with breast cancer, whereas those with lung cancer had higher odds. Palliative care use in solid cancer tumors is variable, with a preference for patients with lung cancer, younger age, known insurance status, and higher educational level.

  4. 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

  5. Capecitabine treatment of HCT-15 colon cancer cells induces ...

    African Journals Online (AJOL)

    HCT-15 cells caused condensation of DNA and induced apoptosis in a concentration- ... Conclusion: Capecitabine treatment causes inhibition of colon cancer growth via the mitochondrial ... fluoropyrimidine aimed to selectively transfer 5-.

  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 ... salient differences in environmental factors concern diet. physical activity .... how well known are the risk factors for coronary heart disease; yet ...

  7. Staging with computed tomography of patients with colon cancer

    DEFF Research Database (Denmark)

    Malmstrom, M. L.; Brisling, S.; Klausen, T. W.

    2018-01-01

    Purpose Accurate staging of colonic cancer is important for patient stratification. We aimed to correlate the diagnostic accuracy of preoperative computed tomography (CT) with final histopathology as reference standard. Methods Data was collected retrospectively on 615 consecutive patients operated...

  8. 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.

  9. IGF-II transgenic mice display increased aberrant colon crypt multiplicity and tumor volume after 1,2-dimethylhydrazine treatment

    Directory of Open Access Journals (Sweden)

    Oesterle Doris

    2006-01-01

    Full Text Available Abstract In colorectal cancer insulin-like growth factor II (IGF-II is frequently overexpressed. To evaluate, whether IGF-II affects different stages of tumorigenesis, we induced neoplastic alterations in the colon of wild-type and IGF-II transgenic mice using 1,2-dimethylhydrazine (DMH. Aberrant crypt foci (ACF served as markers of early lesions in the colonic mucosa, whereas adenomas and carcinomas characterized the endpoints of tumor development. DMH-treatment led initially to significantly more ACF in IGF-II transgenic than in wild-type mice. This increase in ACF was especially prominent for those consisting of ≥three aberrant crypts (AC. Nevertheless, adenomas and adenocarcinomas of the colon, present after 34 weeks in both genetic groups, were not found at different frequency. Tumor volumes, however, were significantly higher in IGF-II transgenic mice and correlated with serum IGF-II levels. Immunohistochemical staining for markers of proliferation and apoptosis revealed increased cell proliferation rates in tumors of IGF-II transgenic mice without significant affection of apoptosis. Increased proliferation was accompanied by elevated localization of β-catenin in the cytosol and cell nuclei and reduced appearance at the inner plasma membrane. In conclusion, we provide evidence that IGF-II, via activation of the β-catenin signaling cascade, promotes growth of ACF and tumors without affecting tumor numbers.

  10. [Analysis of prognostic factors after radical resection in 628 patients with stage II or III colon cancer].

    Science.gov (United States)

    Qin, Qiong; Yang, Lin; Zhou, Ai-ping; Sun, Yong-kun; Song, Yan; DU, Feng; Wang, Jin-wan

    2013-03-01

    To analyze the clinicopathologic factors related to recurrence and metastasis of stage II or III colon cancer after radical resection. The clinical and pathological data of 628 patients with stage II or III colon cancer after radical resection from Jan. 2005 to Dec. 2008 in our hospital were retrospectively reviewed and analyzed. The overall recurrence and metastasis rate was 28.5% (179/628). The 5-year disease-free survival (DFS) rate was 70.3% and 5-year overall survival (OS) rate was 78.5%. Univariate analysis showed that age, smoking intensity, depth of tumor invasion, lymph node metastasis, TNM stage, gross classification, histological differentiation, blood vessel tumor embolus, tumor gross pathology, multiple primary tumors, preoperative and postoperative serum concentration of CEA and CA19-9, and the regimen of adjuvant chemotherapy were correlated to recurrence and metastasis of colon cancer after radical resection. Multivariate analysis showed that regional lymph node metastasis, TNM stage, the regimen of postoperative adjuvant chemotherapy, and preoperative serum concentration of CEA and CA19-9 were independent factors affecting the prognosis of colon cancer patients. Regional lymph node metastasis, TNM stage, elevated preoperative serum concentration of CEA and CA19-9, the regimen of postoperative adjuvant chemotherapy with single fluorouracil type drug are independent risk factors of recurrence and metastasis in patients with stage II-III colon cancer after radical resection.

  11. Lack of efficacy of blueberry in nutritional prevention of azoxymethane-initiated cancers of rat small intestine and colon

    Directory of Open Access Journals (Sweden)

    Wu Xianli

    2009-09-01

    Full Text Available Abstract Background Blueberries may lower relative risk for cancers of the gastrointestinal tract. Previous work indicated an inhibitory effect of consumed blueberry (BB on formation of aberrant crypt foci (ACF in colons of male Fisher F344 rats (inbred strain. However, effects of BB on colon tumors and in both genders are unknown. Methods We examined efficacy of BB in inhibition of azoxymethane (AOM-induced colon ACF and intestine tumors in male and female Sprague-Dawley rats (outbred strain. Pregnant rats were fed a diet with or without 10% BB powder; progeny were weaned to the same diet as their dam and received AOM as young adults. Results Male and female rats on control diet had similar numbers of ACF at 6 weeks after AOM administration. BB increased (P P P > 0.05 to reduce overall gastrointestinal tract tumor incidence in males, however, tumor incidence in females was unaffected (P > 0.1 by BB. There was a tendency (0.1 > P > 0.05 for fewer adenocarcinomas (relative to total of adenomatous polyps plus adenocarcinomas in colons of female than male tumor-bearing rats; in small intestine, this gender difference was significant (P P Conclusion Results did not indicate robust cancer-preventive effects of BB. Blueberry influenced ACF occurrence in distal colon and tumor progression in duodenum, in gender-specific fashion. Data indicate the potential for slowing tumor progression (adenomatous polyp to adenocarcinoma by BB.

  12. shRNA-Mediated XRCC2 Gene Knockdown Efficiently Sensitizes Colon Tumor Cells to X-ray Irradiation in Vitro and in Vivo

    Directory of Open Access Journals (Sweden)

    Qin Wang

    2014-01-01

    Full Text Available Colon cancer is one of the most common tumors of the digestive tract. Resistance to ionizing radiation (IR decreased therapeutic efficiency in these patients’ radiotherapy. XRCC2 is the key protein of DNA homologous recombination repair, and its high expression is associated with enhanced resistance to DNA damage induced by IR. Here, we investigated the effect of XRCC2 silencing on colon tumor cells’ growth and sensitivity to X-radiation in vitro and in vivo. Colon tumor cells (T84 cell line were cultivated in vitro and tumors originated from the cell line were propagated as xenografts in nude mice. The suppression of XRCC2 expression was achieved by using vector-based short hairpin RNA (shRNA in T84 cells. We found that the knockdown of XRCC2 expression effectively decreased T84 cellular proliferation and colony formation, and led to cell apoptosis and cell cycle arrested in G2/M phase induced by X-radiation in vitro. In addition, tumor xenograft studies suggested that XRCC2 silencing inhibited tumorigenicity after radiation treatment in vivo. Our data suggest that the suppression of XRCC2 expression rendered colon tumor cells more sensitive to radiation therapy in vitro and in vivo, implying XRCC2 as a promising therapeutic target for the treatment of radioresistant human colon cancer.

  13. Isolated metastasis of colon cancer to the scapula: is surgical resection warranted?

    Directory of Open Access Journals (Sweden)

    Onesti Jill K

    2011-10-01

    Full Text Available Abstract Background Distant metastases from colon cancer spread most frequently to the liver and the lung. Risk factors include positive lymph nodes and high grade tumors. Isolated metastases to the appendicular skeleton are very rare, particularly in the absence of identifiable risk factors. Case report The patient was a 55 year old male with no previous personal or family history of colon cancer. Routine screening revealed a sigmoid adenocarcinoma. He underwent resection with primary anastomosis and was found to have Stage IIA colon cancer. He declined chemotherapy as part of a clinical trial, and eight months later was found to have an isolated metastasis in his right scapula. This was treated medically, but grew to 12 × 15 cm. The patient underwent a curative forequarter amputation and is now more than four years from his original colon surgery. Discussion Stage IIA colon cancers are associated with a high five year survival rate, and chemotherapy is not automatically given. If metastases occur, they are likely to arise from local recurrence or follow lymphatic dissemination to the liver or lungs. Isolated skeletal metastases are quite rare and are usually confined to the axial skeleton. To our knowledge, this is the first reported case of an isolated scapular metastasis in a patient with node negative disease. The decision to treat the recurrence with radiation and chemotherapy did not reduce the tumor, and a forequarter amputation was eventually required. Conclusion This case highlights the importance of adequately analyzing the stage of colon cancer and offering appropriate treatment. Equally important is the early involvement of a surgeon in discussing the timing of the treatment for recurrence. Perhaps if the patient had received chemotherapy or earlier resection, he could have been spared the forequarter amputation. The physician must also be aware of the remote possibility of an unusual presentation of metastasis in order to pursue

  14. Calcitriol Supplementation Causes Decreases in Tumorigenic Proteins and Different Proteomic and Metabolomic Signatures in Right versus Left-Sided Colon Cancer.

    Science.gov (United States)

    Schroll, Monica M; Ludwig, Katelyn R; Bauer, Kerry M; Hummon, Amanda B

    2018-01-11

    Vitamin D deficiency is a common problem worldwide. In particular, it is an issue in the Northern Hemisphere where UVB radiation does not penetrate the atmosphere as readily. There is a correlation between vitamin D deficiency and colorectal cancer incidence and mortality. Furthermore, there is strong evidence that cancer of the ascending (right side) colon is different from cancer of the descending (left side) colon in terms of prognosis, tumor differentiation, and polyp type, as well as at the molecular level. Right-side tumors have elevated Wnt signaling and are more likely to relapse, whereas left-side tumors have reduced expression of tumor suppressor genes. This study seeks to understand both the proteomic and metabolomic changes resulting from treatment of the active metabolite of vitamin D, calcitriol, in right-sided and left-sided colon cancer. Our results show that left-sided colon cancer treated with calcitriol has a substantially greater number of changes in both the proteome and the metabolome than right-sided colon cancer. We found that calcitriol treatment in both right-sided and left-sided colon cancer causes a downregulation of ribosomal protein L37 and protein S100A10. Both of these proteins are heavily involved in tumorigenesis, suggesting a possible mechanism for the correlation between low vitamin D levels and colon cancer.

  15. Calcitriol Supplementation Causes Decreases in Tumorigenic Proteins and Different Proteomic and Metabolomic Signatures in Right versus Left-Sided Colon Cancer

    Directory of Open Access Journals (Sweden)

    Monica M. Schroll

    2018-01-01

    Full Text Available Vitamin D deficiency is a common problem worldwide. In particular, it is an issue in the Northern Hemisphere where UVB radiation does not penetrate the atmosphere as readily. There is a correlation between vitamin D deficiency and colorectal cancer incidence and mortality. Furthermore, there is strong evidence that cancer of the ascending (right side colon is different from cancer of the descending (left side colon in terms of prognosis, tumor differentiation, and polyp type, as well as at the molecular level. Right-side tumors have elevated Wnt signaling and are more likely to relapse, whereas left-side tumors have reduced expression of tumor suppressor genes. This study seeks to understand both the proteomic and metabolomic changes resulting from treatment of the active metabolite of vitamin D, calcitriol, in right-sided and left-sided colon cancer. Our results show that left-sided colon cancer treated with calcitriol has a substantially greater number of changes in both the proteome and the metabolome than right-sided colon cancer. We found that calcitriol treatment in both right-sided and left-sided colon cancer causes a downregulation of ribosomal protein L37 and protein S100A10. Both of these proteins are heavily involved in tumorigenesis, suggesting a possible mechanism for the correlation between low vitamin D levels and colon cancer.

  16. 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.

  17. 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...

  18. Engineering of near IR fluorescent albumin nanoparticles for in vivo detection of colon cancer

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    Cohen Sarit

    2012-08-01

    Full Text Available Abstract Background The use of near-infrared (NIR fluorescence imaging techniques has gained great interest for early detection of cancer because water and other intrinsic biomolecules display negligible absorption or autofluorescence in this region. Novel fluorescent nanoparticles with potential to improve neoplasm detection sensitivity may prove to be a valuable tool in early detection of colon tumors. Methods The present study describes the synthesis and use of NIR fluorescent albumin nanoparticles as a diagnostic tool for detection of colon cancer. These fluorescent nanoparticles were prepared by a precipitation process of human serum albumin (HSA in aqueous solution in the presence of a carboxylic acid derivative of the NIR dye IR-783 (CANIR. Tumor-targeting ligands such as peanut agglutinin (PNA, anti-carcinoembryonic antigen antibodies (anti-CEA and tumor associated glycoprotein-72 monoclonal antibodies (anti-TAG-72 were covalently conjugated to the albumin nanoparticles via the surface carboxylate groups by using the carbodiimide activation method. Results and discussion Leakage of the encapsulated dye into PBS containing 4% HSA or human bowel juice was not detected. This study also demonstrates that the encapsulation of the NIR fluorescent dye within the HSA nanoparticles reduces the photobleaching of the dye significantly. Specific colon tumor detection in a mouse model was demonstrated for PNA, anti-CEA and anti-TAG-72 conjugated NIR fluorescent HSA nanoparticles. These bioactive NIR fluorescent albumin nanoparticles also detected invisible tumors that were revealed as pathological only subsequent to histological analysis. Conclusions These results may suggest a significant advantage of NIR fluorescence imaging using NIR fluorescent nanoparticles over regular colonoscopy. In future work we plan to broaden this study by encapsulating cancer drugs, such as paclitaxel and doxorubicin, within these biodegradable NIR fluorescent HSA

  19. Engineering of near IR fluorescent albumin nanoparticles for in vivo detection of colon cancer.

    Science.gov (United States)

    Cohen, Sarit; Margel, Shlomo

    2012-08-14

    The use of near-infrared (NIR) fluorescence imaging techniques has gained great interest for early detection of cancer because water and other intrinsic biomolecules display negligible absorption or autofluorescence in this region. Novel fluorescent nanoparticles with potential to improve neoplasm detection sensitivity may prove to be a valuable tool in early detection of colon tumors. The present study describes the synthesis and use of NIR fluorescent albumin nanoparticles as a diagnostic tool for detection of colon cancer. These fluorescent nanoparticles were prepared by a precipitation process of human serum albumin (HSA) in aqueous solution in the presence of a carboxylic acid derivative of the NIR dye IR-783 (CANIR). Tumor-targeting ligands such as peanut agglutinin (PNA), anti-carcinoembryonic antigen antibodies (anti-CEA) and tumor associated glycoprotein-72 monoclonal antibodies (anti-TAG-72) were covalently conjugated to the albumin nanoparticles via the surface carboxylate groups by using the carbodiimide activation method. Leakage of the encapsulated dye into PBS containing 4% HSA or human bowel juice was not detected. This study also demonstrates that the encapsulation of the NIR fluorescent dye within the HSA nanoparticles reduces the photobleaching of the dye significantly. Specific colon tumor detection in a mouse model was demonstrated for PNA, anti-CEA and anti-TAG-72 conjugated NIR fluorescent HSA nanoparticles. These bioactive NIR fluorescent albumin nanoparticles also detected invisible tumors that were revealed as pathological only subsequent to histological analysis. These results may suggest a significant advantage of NIR fluorescence imaging using NIR fluorescent nanoparticles over regular colonoscopy. In future work we plan to broaden this study by encapsulating cancer drugs, such as paclitaxel and doxorubicin, within these biodegradable NIR fluorescent HSA nanoparticles, in order to use them for both detection as well as therapy of colon

  20. 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

  1. 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

  2. Double primary malignancies associated with colon cancer in patients with situs inversus totalis: two case reports

    Directory of Open Access Journals (Sweden)

    Kim Dae

    2011-09-01

    Full Text Available Abstract Situs inversus totalis (SIT is not itself a premalignant condition, however, rare synchronous or metachronous multiple primary malignancies have been reported. Herein we present a case of synchronous transverse and sigmoid colon cancers and a case of metachronous rectosigmoid colon and gastric cancers in patients with SIT. A 66-year-old male with SIT was referred for a two-month history of hematochezia. Synchronous colonic tumors were found on the proximal transverse and sigmoid colon. The patient underwent open total colectomy and was discharged without incident. A 71-year-old female with rectosigmoid colon cancer and SIT underwent laparoscopy-assisted low anterior resection. Fourteen months after the surgery, the patient developed a single hepatic metastasis and underwent hepatic segmentectomy (S6. Forty-six months after laparoscopy-assisted low anterior resection, the patient developed metachronous early gastric cancer on the antrum and underwent radical subtotal gastrectomy with gastroduodenostomy. The patient is doing well without recurrence for 28 months.

  3. mTOR inhibition elicits a dramatic response in PI3K-dependent colon cancers.

    Directory of Open Access Journals (Sweden)

    Dustin A Deming

    Full Text Available The phosphatidylinositide-3-kinase (PI3K signaling pathway is critical for multiple cellular functions including metabolism, proliferation, angiogenesis, and apoptosis, and is the most commonly altered pathway in human cancers. Recently, we developed a novel mouse model of colon cancer in which tumors are initiated by a dominant active PI3K (FC PIK3ca. The cancers in these mice are moderately differentiated invasive mucinous adenocarcinomas of the proximal colon that develop by 50 days of age. Interestingly, these cancers form without a benign intermediary or aberrant WNT signaling, indicating a non-canonical mechanism of tumorigenesis. Since these tumors are dependent upon the PI3K pathway, we investigated the potential for tumor response by the targeting of this pathway with rapamycin, an mTOR inhibitor. A cohort of FC PIK3ca mice were treated with rapamycin at a dose of 6 mg/kg/day or placebo for 14 days. FDG dual hybrid PET/CT imaging demonstrated a dramatic tumor response in the rapamycin arm and this was confirmed on necropsy. The tumor tissue remaining after treatment with rapamycin demonstrated increased pERK1/2 or persistent phosphorylated ribosomal protein S6 (pS6, indicating potential resistance mechanisms. This unique model will further our understanding of human disease and facilitate the development of therapeutics through pharmacologic screening and biomarker identification.

  4. Fem1b, a proapoptotic protein, mediates proteasome inhibitor-induced apoptosis of human colon cancer cells.

    Science.gov (United States)

    Subauste, M Cecilia; Sansom, Owen J; Porecha, Nehal; Raich, Natacha; Du, Liqin; Maher, Joseph F

    2010-02-01

    In the treatment of colon cancer, the development of resistance to apoptosis is a major factor in resistance to therapy. New molecular approaches to overcome apoptosis resistance, such as selectively upregulating proapoptotic proteins, are needed in colon cancer therapy. In a mouse model with inactivation of the adenomatous polyposis coli (Apc) tumor suppressor gene, reflecting the pathogenesis of most human colon cancers, the gene encoding feminization-1 homolog b (Fem1b) is upregulated in intestinal epithelium following Apc inactivation. Fem1b is a proapoptotic protein that interacts with apoptosis-inducing proteins Fas, tumor necrosis factor receptor-1 (TNFR1), and apoptotic protease activating factor-1 (Apaf-1). Increasing Fem1b expression induces apoptosis of cancer cells, but effects on colon cancer cells have not been reported. Fem1b is a homolog of feminization-1 (FEM-1), a protein in Caenorhabditis elegans that is regulated by proteasomal degradation, but whether Fem1b is likewise regulated by proteasomal degradation is unknown. Herein, we found that Fem1b protein is expressed in primary human colon cancer specimens, and in malignant SW620, HCT-116, and DLD-1 colon cancer cells. Increasing Fem1b expression, by transfection of a Fem1b expression construct, induced apoptosis of these cells. We found that proteasome inhibitor treatment of SW620, HCT-116, and DLD-1 cells caused upregulation of Fem1b protein levels, associated with induction of apoptosis. Blockade of Fem1b upregulation with morpholino antisense oligonucleotide suppressed the proteasome inhibitor-induced apoptosis of these cells. In conclusion, the proapoptotic protein Fem1b is downregulated by the proteasome in malignant colon cancer cells and mediates proteasome inhibitor-induced apoptosis of these cells. Therefore, Fem1b could represent a novel molecular target to overcome apoptosis resistance in therapy of colon cancer.

  5. Vaccine Therapy in Treating Patients With Colon, Pancreatic, or Lung Cancer

    Science.gov (United States)

    2015-04-27

    Recurrent Colon Cancer; Extensive Stage Small Cell Lung Cancer; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Limited Stage Small Cell Lung Cancer; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Stage III Non-small Cell Lung Cancer; Stage I Pancreatic Cancer; Stage II Non-small Cell Lung Cancer; Stage IVB Pancreatic Cancer; Stage II Pancreatic Cancer; Stage III Colon Cancer; Stage IVA Pancreatic Cancer

  6. 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

  7. Prognostic value of stem cell quantification in stage II colon cancer.

    Directory of Open Access Journals (Sweden)

    Maria Angeles Vaz

    Full Text Available BACKGROUND: Cancer stem cells (CSCs are a subset of tumor cells with capacity to self-renew and generate the diverse cells that make up the tumor. The aim of this study is to evaluate the prognostic value of CSCs in a highly homogeneous population of stage II colon cancer. METHODS: One hundred stage II colon cancer patients treated by the same surgical team between 1977 and 2005 were retrospectively analyzed. None of the patients received adjuvant chemotherapy. Inmunohistochemistry expression of CD133, NANOG and CK20 was scored, using four levels: 50% positivity. Kaplan-Meier analysis and log rank test were used to compare survival. RESULTS: The average patient age was 68 years (patients were between 45-92 years of age and median follow up was 5.8 years. There was recurrent disease in 17 (17%; CD133 expression (defined by >10% positivity was shown in 60% of the tumors, in 95% for NANOG and 78% for CK20. No correlation was found among expression levels of CD133, NANOG or CK20 and relapse-free survival (RFS or overall survival (OS. However, a statistical significant correlation was found between established pathological prognostic factors and RFS and OS. CONCLUSIONS: Stem Cell quantification defined by CD133 and NANOG expression has no correlation with RFS or OS in this cohort of Stage II colon cancer.

  8. Colon cancer: association of histopathological parameters and patients' survival with clinical presentation.

    Science.gov (United States)

    Alexiusdottir, Kristin K; Snaebjornsson, Petur; Tryggvadottir, Laufey; Jonasson, Larus; Olafsdottir, Elinborg J; Björnsson, Einar Stefan; Möller, Pall Helgi; Jonasson, Jon G

    2013-10-01

    Available data correlating symptoms of colon cancer patients with the severity of the disease are very limited. In a population-based setting, we correlated information on symptoms of colon cancer patients with several pathological tumor parameters and survival. Information on all patients diagnosed with colon cancer in Iceland in 1995-2004 for this retrospective, population-based study was obtained from the Icelandic Cancer Registry. Information on symptoms of patients and blood hemoglobin was collected from patients' files. Pathological parameters were obtained from a previously performed standardized tumor review. A total of 768 patients entered this study; the median age was 73 years. Tumors in patients presenting at diagnosis with visible blood in stools were significantly more likely to be of lower grade, having pushing border, conspicuous peritumoral lymphocytic infiltration, and lower frequency of vessel invasion. Patients with abdominal pain and anemia were significantly more likely to have vessel invasion. Logistic regression showed that visible blood in stools was significantly associated with protecting pathological factors (OR range 0.38-0.83, p characteristics and adverse outcome for patients. © 2013 APMIS Published by Blackwell Publishing Ltd.

  9. 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 distribu......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...

  10. MicroRNA-320a suppresses human colon cancer cell proliferation by directly targeting {beta}-catenin

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Jian-Yong [State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi' an (China); State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 710032 Xi' an (China); Huang, Yi [Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, 710032 Xi' an (China); Li, Ji-Peng [State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 710032 Xi' an (China); Zhang, Xiang; Wang, Lei [State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi' an (China); Meng, Yan-Ling [Department of Immunology, Fourth Military Medical University, 710032 Xi' an (China); Yan, Bo [State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi' an (China); Bian, Yong-Qian [State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 710032 Xi' an (China); Zhao, Jing [State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi' an (China); Wang, Wei-Zhong, E-mail: weichang@fmmu.edu.cn [State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 710032 Xi' an (China); and others

    2012-04-20

    Highlights: Black-Right-Pointing-Pointer miR-320a is downregulated in human colorectal carcinoma. Black-Right-Pointing-Pointer Overexpression of miR-320a inhibits colon cancer cell proliferation. Black-Right-Pointing-Pointer {beta}-Catenin is a direct target of miR-320a in colon cancer cells. Black-Right-Pointing-Pointer miR-320a expression inversely correlates with mRNA expression of {beta}-catenin's target genes in human colon carcinoma. -- Abstract: Recent profile studies of microRNA (miRNA) expression have documented a deregulation of miRNA (miR-320a) in human colorectal carcinoma. However, its expression pattern and underlying mechanisms in the development and progression of colorectal carcinoma has not been elucidated clearly. Here, we performed real-time PCR to examine the expression levels of miR-320a in colon cancer cell lines and tumor tissues. And then, we investigated its biological functions in colon cancer cells by a gain of functional strategy. Further more, by the combinational approaches of bioinformatics and experimental validation, we confirmed target associations of miR-320a in colorectal carcinoma. Our results showed that miR-320a was frequently downregulated in cancer cell lines and colon cancer tissues. And we demonstrated that miR-320a restoration inhibited colon cancer cell proliferation and {beta}-catenin, a functionally oncogenic molecule was a direct target gene of miR-320a. Finally, the data of real-time PCR showed the reciprocal relationship between miR-320a and {beta}-catenin's downstream genes in colon cancer tissues. These findings indicate that miR-320a suppresses the growth of colon cancer cells by directly targeting {beta}-catenin, suggesting its application in prognosis prediction and cancer treatment.

  11. MicroRNA-320a suppresses human colon cancer cell proliferation by directly targeting β-catenin

    International Nuclear Information System (INIS)

    Sun, Jian-Yong; Huang, Yi; Li, Ji-Peng; Zhang, Xiang; Wang, Lei; Meng, Yan-Ling; Yan, Bo; Bian, Yong-Qian; Zhao, Jing; Wang, Wei-Zhong

    2012-01-01

    Highlights: ► miR-320a is downregulated in human colorectal carcinoma. ► Overexpression of miR-320a inhibits colon cancer cell proliferation. ► β-Catenin is a direct target of miR-320a in colon cancer cells. ► miR-320a expression inversely correlates with mRNA expression of β-catenin’s target genes in human colon carcinoma. -- Abstract: Recent profile studies of microRNA (miRNA) expression have documented a deregulation of miRNA (miR-320a) in human colorectal carcinoma. However, its expression pattern and underlying mechanisms in the development and progression of colorectal carcinoma has not been elucidated clearly. Here, we performed real-time PCR to examine the expression levels of miR-320a in colon cancer cell lines and tumor tissues. And then, we investigated its biological functions in colon cancer cells by a gain of functional strategy. Further more, by the combinational approaches of bioinformatics and experimental validation, we confirmed target associations of miR-320a in colorectal carcinoma. Our results showed that miR-320a was frequently downregulated in cancer cell lines and colon cancer tissues. And we demonstrated that miR-320a restoration inhibited colon cancer cell proliferation and β-catenin, a functionally oncogenic molecule was a direct target gene of miR-320a. Finally, the data of real-time PCR showed the reciprocal relationship between miR-320a and β-catenin’s downstream genes in colon cancer tissues. These findings indicate that miR-320a suppresses the growth of colon cancer cells by directly targeting β-catenin, suggesting its application in prognosis prediction and cancer treatment.

  12. Diet-Induced Obesity Is Associated with an Impaired NK Cell Function and an Increased Colon Cancer Incidence

    Directory of Open Access Journals (Sweden)

    Ina Bähr

    2017-01-01

    Full Text Available Obesity is associated with an increased colon cancer incidence, but underlying mechanisms remained unclear. Previous studies showed altered Natural killer (NK cell functions in obese individuals. Therefore, we studied the impact of an impaired NK cell functionality on the increased colon cancer risk in obesity. In vitro investigations demonstrated a decreased IFN-γ secretion and cytotoxicity of human NK cells against colon tumor cells after NK cell preincubation with the adipokine leptin. In addition, leptin incubation decreased the expression of activating NK cell receptors. In animal studies, colon cancer growth was induced by injection of azoxymethane (AOM in normal weight and diet-induced obese rats. Body weight and visceral fat mass were increased in obese animals compared to normal weight rats. AOM-treated obese rats showed an increased quantity, size, and weight of colon tumors compared to the normal weight tumor group. Immunohistochemical analyses demonstrated a decreased number of NK cells in spleen and liver in obesity. Additionally, the expression levels of activating NK cell receptors were lower in spleen and liver of obese rats. The results show for the first time that the decreased number and impaired NK cell function may be one cause for the higher colon cancer risk in obesity.

  13. [A case of recurrent transverse colon cancer invading the pancreas and duodenum successfully treated with biliary and duodenal stenting].

    Science.gov (United States)

    Tonooka, Toru; Yoshioka, Shigeru; Shiobara, Masayuki; Wakatsuki, Kazuo; Kataoka, Masaaki; Arai, Shuka; Miyazawa, Kotaro; Nakada, Shinichiro; Kita, Kazuhiko; Saito, Hirofumi; Nomoto, Hiromasa; Usui, Masatoshi; Yabiki, Masashi; Ota, Yuki; Oeda, Yoshio

    2013-11-01

    We report a case of recurrent transverse colon cancer invading the pancreas and duodenum that was successfully treated with biliary and duodenal stenting. A 46-year-old man underwent ascending colostomy for the treatment of obstructive transverse colon cancer with hepatic metastasis. Chemotherapy achieved a partial response, but the levels of tumor markers later began to rise again. He then underwent right hemicolectomy and partial hepatectomy. Post-operative chemotherapy was administered, but the recurrent tumor caused obstructive jaundice and duodenal obstruction. These were successfully treated with biliary and duodenal stenting, and the patient was able to remain at home and maintain his quality of life.

  14. Crucial role of interleukin-4 in the survival of colon cancer stem cells.

    Science.gov (United States)

    Francipane, Maria Giovanna; Alea, Mileidys Perez; Lombardo, Ylenia; Todaro, Matilde; Medema, J P; Stassi, Giorgio

    2008-06-01

    Colon tumors may be maintained by a rare fraction of cancer stem-like cells (CSC) that express the cell surface marker CD133. Self-renewing CSCs exhibit relatively greater resistance to clinical cytotoxic therapies and recent work suggests that this resistance may be mediated in part by an autocrine response to the immune cytokine interleukin 4 (IL-4). Blocking IL-4 signaling can sensitize CSCs to apoptotic stimuli and increase the in vivo efficacy of cytotoxic therapy. These findings suggest that inhibitors of IL-4 signaling may offer a new therapeutic tool in colon carcinoma.

  15. Noscapine induces mitochondria-mediated apoptosis in human colon cancer cells in vivo and in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Zi-Rong; Liu, Meng; Peng, Xiu-Lan; Lei, Xiao-Fei; Zhang, Ji-Xiang [Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province (China); Dong, Wei-Guo, E-mail: dongwg1966@yahoo.com.cn [Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province (China)

    2012-05-11

    Highlights: Black-Right-Pointing-Pointer Noscapine inhibited cell viability of colon cancer in a time- and dose- dependent manner. Black-Right-Pointing-Pointer G{sub 2}/M phase arrest and chromatin condensation and nuclear fragmentation were induced. Black-Right-Pointing-Pointer Noscapine promoted apoptosis via mitochondrial pathways. Black-Right-Pointing-Pointer Tumorigenicity was inhibited by noscapine. -- Abstract: Noscapine, a phthalide isoquinoline alkaloid derived from opium, has been widely used as a cough suppressant for decades. Noscapine has recently been shown to potentiate the anti-cancer effects of several therapies by inducing apoptosis in various malignant cells without any detectable toxicity in cells or tissues. However, the mechanism by which noscapine induces apoptosis in colon cancer cells remains unclear. The signaling pathways by which noscapine induces apoptosis were investigated in colon cancer cell lines treated with various noscapine concentrations for 72 h, and a dose-dependent inhibition of cell viability was observed. Noscapine effectively inhibited the proliferation of LoVo cells in vitro (IC{sub 50} = 75 {mu}M). This cytotoxicity was reflected by cell cycle arrest at G{sub 2}/M and subsequent apoptosis, as indicated by increased chromatin condensation and fragmentation, the upregulation of Bax and cytochrome c (Cyt-c), the downregulation of survivin and Bcl-2, and the activation of caspase-3 and caspase-9. Moreover, in a xenograft tumor model in mice, noscapine injection clearly inhibited tumor growth via the induction of apoptosis, which was demonstrated using a TUNEL assay. These results suggest that noscapine induces apoptosis in colon cancer cells via mitochondrial pathways. Noscapine may be a safe and effective chemotherapeutic agent for the treatment of human colon cancer.

  16. Noscapine induces mitochondria-mediated apoptosis in human colon cancer cells in vivo and in vitro

    International Nuclear Information System (INIS)

    Yang, Zi-Rong; Liu, Meng; Peng, Xiu-Lan; Lei, Xiao-Fei; Zhang, Ji-Xiang; Dong, Wei-Guo

    2012-01-01

    Highlights: ► Noscapine inhibited cell viability of colon cancer in a time- and dose- dependent manner. ► G 2 /M phase arrest and chromatin condensation and nuclear fragmentation were induced. ► Noscapine promoted apoptosis via mitochondrial pathways. ► Tumorigenicity was inhibited by noscapine. -- Abstract: Noscapine, a phthalide isoquinoline alkaloid derived from opium, has been widely used as a cough suppressant for decades. Noscapine has recently been shown to potentiate the anti-cancer effects of several therapies by inducing apoptosis in various malignant cells without any detectable toxicity in cells or tissues. However, the mechanism by which noscapine induces apoptosis in colon cancer cells remains unclear. The signaling pathways by which noscapine induces apoptosis were investigated in colon cancer cell lines treated with various noscapine concentrations for 72 h, and a dose-dependent inhibition of cell viability was observed. Noscapine effectively inhibited the proliferation of LoVo cells in vitro (IC 50 = 75 μM). This cytotoxicity was reflected by cell cycle arrest at G 2 /M and subsequent apoptosis, as indicated by increased chromatin condensation and fragmentation, the upregulation of Bax and cytochrome c (Cyt-c), the downregulation of survivin and Bcl-2, and the activation of caspase-3 and caspase-9. Moreover, in a xenograft tumor model in mice, noscapine injection clearly inhibited tumor growth via the induction of apoptosis, which was demonstrated using a TUNEL assay. These results suggest that noscapine induces apoptosis in colon cancer cells via mitochondrial pathways. Noscapine may be a safe and effective chemotherapeutic agent for the treatment of human colon cancer.

  17. A comparison of laparoscopic and open D3 lymphadenectomy for transverse colon cancer.

    Science.gov (United States)

    Kwak, Han Deok; Ju, Jae Kyun; Lee, Soo Young; Kim, Chang Hyun; Kim, Young Jin; Kim, Hyeong Rok

    2017-12-01

    The type of surgery or surgical approach for transverse colon cancer treatment largely depends on the tumor location or surgeon's preference. However, extensive lymphadenectomy appears to improve the long-term outcomes of locally advanced colon cancers. This study was designed to compare the short- and long-term outcomes after surgery via the laparoscopic or open approach with radical D3 lymph node dissection in patients with stage II and III transverse colon cancer. Patients were treated for stage II and III transverse colon cancer between May 2006 and December 2014. This retrospective study evaluated data collected prospectively at a tertiary teaching hospital. Radical D3 lymphadenectomy included the principal middle colic artery nodes. The study included 144 patients among whom 118 (81.9%) underwent laparoscopic surgery. Significantly more patients in the laparoscopic group underwent extended right hemicolectomy compared with the open group (90.7 vs. 65.4%, p = 0.005). The operative time was longer in the laparoscopic group (151.3 vs. 131.2 min, p = 0.021), and the open group had a greater estimated blood loss volume (160.8 vs. 289.3 ml, p = 0.011). Although the groups differed in terms of tumor size (5.8 vs 7.9 cm, p = 0.007), other pathologic outcomes did not differ. The groups did not differ regarding postoperative parameters or disease-free, overall, and cancer-specific survivals. Despite differences in surgical methods and related factors, no long-term differences in outcomes were observed between laparoscopic and open approaches to radical D3 lymphadenectomy in patients with stage II and III transverse colon cancer.

  18. Clinical Significance of Lymph Node Metastasis in the Mesentery of the Terminal Ileum in Patients With Right-sided Colon Tumors at Different Locations.

    Science.gov (United States)

    Kang, Sung Il; Kim, Duck-Woo; Shin, Eun; Kim, Myung Jo; Son, Il Tae; Oh, Heung-Kwon; Kang, Sung-Bum

    2018-06-01

    There are limited reports on peri-ileal lymph node metastasis in patients with right-sided colon cancer, and little is known about their clinical significance. This study aimed to examine the role of tumor location in the prevalence and clinical significance of peri-ileal lymph node metastasis in patients with right-sided colon cancer. This is a retrospective study from a prospective cohort database. The study was conducted at a tertiary referral hospital. Patients with right-sided colon cancer treated with radical surgery in a hospital between May 2006 and September 2016 were included. The frequency of peri-ileal lymph node metastasis in the study cohort and the role of tumor location and the clinical characteristics of patients with peri-ileal lymph node metastasis were determined. We examined 752 cases with right-sided colon cancer including 82 cecal, 554 ascending colon, and 116 hepatic flexure cancer. Twenty patients (2.7%) had peri-ileal lymph node metastasis. The incidence of metastasis to peri-ileal lymph nodes was 7.3% (6/82) in patients with cecal cancer, 2.2% (12/554) in patients with ascending colon cancer, and 1.7% (2/116) in patients with hepatic flexure cancer. Three patients had stage III cancer and 17 had stage IV. All 3 patients with positive peri-ileal lymph nodes and stage III cancer had cecal tumors. In contrast, all patients with ascending colon or hepatic flexure cancer and positive peri-ileal lymph nodes had stage IV cancer. The results were limited by the retrospective design of the study and the small number of patients with peri-ileal lymph node metastasis. Peri-ileal lymph node metastasis was rare even in right-sided colon cancer and occurred mainly in stage IV. However, it occurred in some patients with locally advanced cecal cancer. These results suggest that optimal resection of the mesentery of the terminal ileum might have clinical benefit, especially in curative surgery for cecal cancer. See Video Abstract at http

  19. Follow on colon cancer: how and when to?

    International Nuclear Information System (INIS)

    Sarroca, C.; Della Valle, A.; Leites, A.; Denis, M.; Alonso, J.; Fresco, R.; Simonet, F.; Rodriguez, A.

    2010-01-01

    There is no consensus on how monitoring should be performed curatively operated patients of colon cancer (C C). It is often it is comprehensive, causing unnecessary and considerable cost surveillance. health. The objective of this study is guidance tracking patients D C operated, making an evidence-based protocol and experience of our working group. Methods: All patients undergoing C C were retrospectively analyzed in the Central Hospital of the Armed Forces (Uruguay) between 1988 and 2003. everyone clinical control, CEA, abdominal-pelvic CT, Rx: monitoring was performed with ray, liver ultrasound, CBC, liver gram enzyme. Events interest were: local recurrence, distant polyps nat ors machi cancers, death. Results: In patients with stage I tumors detected a single event (hyperplastic polyp). In stages II-III, the majority of events were detected CEA elevation or clinically, with the imaging methods of scarce contribution. Only allowed earlier detection of 22.7% of patients with hepatic relapse, not being able to perform in most curative treatment. Special events were exceeded 5 years. Conclusions: 5 years after surgery propose to limit tracking control clinical and endoscopic every 3-5 years. In patients with polyps frequency endoscopy should conform to the characteristics thereof. We consider it unnecessary to performing imaging studies during follow-up and after CEA exceeded 5 years

  20. Exosomes promote cetuximab resistance via the PTEN/Akt pathway in colon cancer cells.

    Science.gov (United States)

    Zhang, S; Zhang, Y; Qu, J; Che, X; Fan, Y; Hou, K; Guo, T; Deng, G; Song, N; Li, C; Wan, X; Qu, X; Liu, Y

    2017-11-13

    Cetuximab is widely used in patients with metastatic colon cancer expressing wildtype KRAS. However, acquired drug resistance limits its clinical efficacy. Exosomes are nanosized vesicles secreted by various cell types. Tumor cell-derived exosomes participate in many biological processes, including tumor invasion, metastasis, and drug resistance. In this study, exosomes derived from cetuximab-resistant RKO colon cancer cells induced cetuximab resistance in cetuximab-sensitive Caco-2 cells. Meanwhile, exosomes from RKO and Caco-2 cells showed different levels of phosphatase and tensin homolog (PTEN) and phosphor-Akt. Furthermore, reduced PTEN and increased phosphorylated Akt levels were found in Caco-2 cells after exposure to RKO cell-derived exosomes. Moreover, an Akt inhibitor prevented RKO cell-derived exosome-induced drug resistance in Caco-2 cells. These findings provide novel evidence that exosomes derived from cetuximab-resistant cells could induce cetuximab resistance in cetuximab-sensitive cells, by downregulating PTEN and increasing phosphorylated Akt levels.